Sign-in to Ask A Doctor - 24x7
OR
Sign in with Google
Can Minor Myocardial Fibrosis Impair The Functioning Of The Heart?
Question: Good afternoon Doctor/ Dr Tryelaar,
My question is about myo cardial fibrosis.
In a recent Post Mortem investigation minor myocardial fibrosis (1cm) was found in the heart of a 95 year old female and was described as "there is a small focus of subendocardial scarring in the lateral wall of the left ventricle about 1 cm in diameter."
I would like to know;
1) Whether the minor myo cardial fibrosis could have impaired the functioning of the heart and if so to what possible extent?
2) Possible origins of the cardial fibrosis; for example could it be consequentially related to coronary artery atheroma with moderate stenosis a condition the deceased suffered from?
3) Whether it might be consequentialy related to the prescription of the antibiotic "nitrofurantoin" known for its posible adverse effect of pulmonary fibrosis and especially contraindicated for elderly people by the British Medcial Journal 1982 and the Beers Report 2012?
Thanking you.
My question is about myo cardial fibrosis.
In a recent Post Mortem investigation minor myocardial fibrosis (1cm) was found in the heart of a 95 year old female and was described as "there is a small focus of subendocardial scarring in the lateral wall of the left ventricle about 1 cm in diameter."
I would like to know;
1) Whether the minor myo cardial fibrosis could have impaired the functioning of the heart and if so to what possible extent?
2) Possible origins of the cardial fibrosis; for example could it be consequentially related to coronary artery atheroma with moderate stenosis a condition the deceased suffered from?
3) Whether it might be consequentialy related to the prescription of the antibiotic "nitrofurantoin" known for its posible adverse effect of pulmonary fibrosis and especially contraindicated for elderly people by the British Medcial Journal 1982 and the Beers Report 2012?
Thanking you.
Brief Answer:
Please find detailed answer below
Detailed Answer:
Hi XXXXXX,
Thanks for writing in to us.
Myocardial fibrosis is increasingly recognized as a substrate for arrhythmias and sudden cardiac death (SCD), but has also been described in Congestive Heart Failure, Hypertension, and normal aging. It can cause arrhythmias or non co ordinated heart beats and sudden cardiac arrest.
Two types of fibrosis are recognized: (1) scarring, the fibrotic replacement of lost myocardium, usually of vascular origin; and (2) interstitial, in which a delicate fibrotic net encircles single myocardial fibers. The morphologic findings were correlated with the following clinical findings: hypertension, congestive heart failure, emphysema, cor pulmonale, and coronary artery disease. The results support the hypothesis that interstitial fibrosis develops independently of the above-mentioned clinical conditions and may be considered as a true aging process.
Research on pulmonary adverse effects of nitrofurantion says that:
Pulmonary toxicity with nitrofurantoin is rare with an estimated incidence of 1 in 5,000 first administrations for acute severe disease. Chronic pulmonary reactions are 10-20 times less frequent than acute reactions. However, pulmonary adverse reactions are among those most frequently reported for nitrofurantoin and cover a spectrum ranging from acute to chronic forms.
Acute pulmonary reactions typically have hypersensitivity-type features, and usually affect women aged 40-50 years. They occur 1-2 weeks after initiation of nitrofurantoin, and can recur within minutes to hours of subsequent use.
Chronic pulmonary reactions mainly involve older persons, are often insidious in onset and associated with therapy of six months or longer. Interstitial lung disease and pulmonary fibrosis may develop. The insidious onset can result in an erroneous diagnosis of cardiac failure.
I have read through the XXXXXXX Geriatrics Society Updated Beers Criteria for
Potentially Inappropriate Medication Use in Older Adults
There is no direct link between nitrofurantoin and myocardial fibrosis to the best of my knowledge.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Please find detailed answer below
Detailed Answer:
Hi XXXXXX,
Thanks for writing in to us.
Myocardial fibrosis is increasingly recognized as a substrate for arrhythmias and sudden cardiac death (SCD), but has also been described in Congestive Heart Failure, Hypertension, and normal aging. It can cause arrhythmias or non co ordinated heart beats and sudden cardiac arrest.
Two types of fibrosis are recognized: (1) scarring, the fibrotic replacement of lost myocardium, usually of vascular origin; and (2) interstitial, in which a delicate fibrotic net encircles single myocardial fibers. The morphologic findings were correlated with the following clinical findings: hypertension, congestive heart failure, emphysema, cor pulmonale, and coronary artery disease. The results support the hypothesis that interstitial fibrosis develops independently of the above-mentioned clinical conditions and may be considered as a true aging process.
Research on pulmonary adverse effects of nitrofurantion says that:
Pulmonary toxicity with nitrofurantoin is rare with an estimated incidence of 1 in 5,000 first administrations for acute severe disease. Chronic pulmonary reactions are 10-20 times less frequent than acute reactions. However, pulmonary adverse reactions are among those most frequently reported for nitrofurantoin and cover a spectrum ranging from acute to chronic forms.
Acute pulmonary reactions typically have hypersensitivity-type features, and usually affect women aged 40-50 years. They occur 1-2 weeks after initiation of nitrofurantoin, and can recur within minutes to hours of subsequent use.
Chronic pulmonary reactions mainly involve older persons, are often insidious in onset and associated with therapy of six months or longer. Interstitial lung disease and pulmonary fibrosis may develop. The insidious onset can result in an erroneous diagnosis of cardiac failure.
I have read through the XXXXXXX Geriatrics Society Updated Beers Criteria for
Potentially Inappropriate Medication Use in Older Adults
There is no direct link between nitrofurantoin and myocardial fibrosis to the best of my knowledge.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Above answer was peer-reviewed by :
Dr. Vinay Bhardwaj
Thank you for your reply Dr XXXXXXX
I would appreciate your attention to some points:
1) It is mentioned that myo cardial fibrosis is a substrate for various conditions but also can be a product of aging. Besides aging what might be the causes of the condition?
2) Two types of fibrosis are mentioned. Does "scarring" also occur in interstitial fibrosis? Is it possible that interstitial fibrosis can be visually undetectable at the Post Mortem? Or even the early stages of the first scarring type? I have read that fibrosis can be undetected by X rays and so require high resolution CT technology.
3) Is toxicity synonymous with adverse reactions? It is stated that toxicity is rare and statistically given by your reply as 1 in 5000 cases for severe acute first administrations. The figure for less severe cases is not given and it might be noted again that the British Medical Journal 1982 and the Beers Report 2012 seem to ban the use of the medication for elderly people and the description "rare" might not apply to this specific group? I suppose it might be expected that chronic cases are statistically less than acute cases due to the relative frequency of the condition in the different sampling groups and might not be that meaningful in relation to its possible danger? Perhaps you might have further comments about the danger of the prescription of nitrofurantoin and the value of the contraindication for elderly people given by the Beers Report/ British Medical Journal?
3) I have also read if I recall correctly that even in first administration hyper sensitive reactions may occur in the first three hours?
4) The deceased person relevant to this discussion had repeated UTI infections over the last two and a half years and I presume was given this medication for a week to ten days each time. Do you consider that sufficent time to expose the patient to the risk of developing pulmonary fibrosis in some form perhaps in its early stages? As mentioned before might this be difficult to detect depending on the type of fibrosis and stage of development?
5) Would it be correct to say that the presence of minor myo cardial fibrosis might be the subject of further research to establish a possible link with nitrofurantoin?
Thanking you for your consideration of these questions.
Brief Answer:
Please find detailed answer below
Detailed Answer:
Hi XXXXXX,
Thanks for writing back with an update.
1) It is mentioned that myocardial fibrosis is a substrate for various conditions but also can be a product of aging. Besides aging what might be the causes of the condition?
The various conditions might include the following:
Scarring or replacement myocardial fibrosis is due to miscellaneous inflammatory disease, acute/ chronic ischemia, infarction, chronic renal insufficiency, myocarditis, sarcodosis, genetic and toxic causes.
Reactive interstitial fibrosis is due to hypertension, valvular disorders, diabetes, genetic and aging.
Infiltrative interstitial fibrosis is due to amyloidosis and Andersen Fabry disease
2) Two types of fibrosis are mentioned. Does "scarring" also occur in interstitial fibrosis? Is it possible that interstitial fibrosis can be visually undetectable at the Post Mortem? Or even the early stages of the first scarring type? I have read that fibrosis can be undetected by X rays and so require high resolution CT technology.
The scarring which we were discussing earlier involves replacement of injured myocardium by scarring. In interstitial fibrosis, there is altered biochemical properties of the heart muscle fibers due to change in composition of biomolecules like collagen. At thr Post Mortem, it may not be all that evident in every individual. The collagen content may be known after detailed microscopic evaluation. Recent research has shown that interstitial collagen content is increased in hearts with dilated left ventricles but no clinical or pathological evidence of ischaemic heart disease. Similar results have been reported in patients with dilated cardiomyopathy. Imaging by cardiac MRI is the latest in evaluation of myocardial fibrosis.
3) Is toxicity synonymous with adverse reactions? It is stated that toxicity is rare and statistically given by your reply as 1 in 5000 cases for severe acute first administrations. The figure for less severe cases is not given and it might be noted again that the British Medical Journal 1982 and the Beers Report 2012 seem to ban the use of the medication for elderly people and the description "rare" might not apply to this specific group? I suppose it might be expected that chronic cases are statistically less than acute cases due to the relative frequency of the condition in the different sampling groups and might not be that meaningful in relation to its possible danger? Perhaps you might have further comments about the danger of the prescription of nitrofurantoin and the value of the contraindication for elderly people given by the Beers Report/ British Medical Journal?
Toxicity refers to any expected or unexpected events of a negative nature which may occur with considerable higher doses of drug intake and such medications have a narrow margin of safety.
Adverse reactions are usually expected or unexpected events with even a small dose of the drug in question.
Peer reviews show that in patients with renal impairment, including elderly patients, nitrofurantoin excretion is decreased, and it may not reach adequate urinary minimum inhibitory concentrations. Thus, a primary reason that nitrofurantoin is on the Beers List of medications to avoid in the elderly is inadequate drug concentration in the urine when creatinine clearance falls below 60 mL/min. Besides the potential subtherapeutic effect of nitrofurantoin in patients with renal impairment, patients may be at increased risk for adverse events secondary to drug accumulation. This is the potential for development of toxicity.
A retrospective chart review of 356 patients was conducted in 2009 that assessed the efficacy and safety of nitrofurantoin in patients with renal impairment. The study concluded that nitrofurantoin cure rates for UTI and adverse events were similar between those with and those without renal impairment. It is generally accepted that nitrofurantoin may be ineffective for UTIs in the elderly because age-related declines in renal function result in subtherapeutic concentrations in the urinary tract.
It is possible that the pulmonary fibrosis may occur doe to secondary drug accumulation and hence this must be avoided in the elderly.
3) I have also read if I recall correctly that even in first administration hyper sensitive reactions may occur in the first three hours?
It is possible that adverse reactions may occur in the first three hours in some patients. A study done shows acute pulmonary reactions appeared a mean of 8.7 days after the start of nitrofurantoin treatment. Typical for these were high fever, dyspnoea, cough, blood eosinophilia, bilateral pneumonic or pleuro-pneumonic infiltrations, a reduced transfer factor of the lung and, as revealed in pulmonary biopsy specimens, vasculitis, interstitial inflammation and alveolar exudation.
4) The deceased person relevant to this discussion had repeated UTI infections over the last two and a half years and I presume was given this medication for a week to ten days each time. Do you consider that sufficent time to expose the patient to the risk of developing pulmonary fibrosis in some form perhaps in its early stages? As mentioned before might this be difficult to detect depending on the type of fibrosis and stage of development?
In the treatment of the deceased person, it might have been that there was secondary lung changes due to drug accumulation each time she was given nitrofurantoin. The renal function details are not known and we can at best only make an assumption. There are certain lung changes that would have been expected in the lungs of a 95 year old person and make such findings difficult to detect in early stages.
5) Would it be correct to say that the presence of minor myo cardial fibrosis might be the subject of further research to establish a possible link with nitrofurantoin?
There is little chance of linking nitrofurantoin intake with mild myocardial fibrosis keeping in mind the available medical literature on the topic of discussion.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Please find detailed answer below
Detailed Answer:
Hi XXXXXX,
Thanks for writing back with an update.
1) It is mentioned that myocardial fibrosis is a substrate for various conditions but also can be a product of aging. Besides aging what might be the causes of the condition?
The various conditions might include the following:
Scarring or replacement myocardial fibrosis is due to miscellaneous inflammatory disease, acute/ chronic ischemia, infarction, chronic renal insufficiency, myocarditis, sarcodosis, genetic and toxic causes.
Reactive interstitial fibrosis is due to hypertension, valvular disorders, diabetes, genetic and aging.
Infiltrative interstitial fibrosis is due to amyloidosis and Andersen Fabry disease
2) Two types of fibrosis are mentioned. Does "scarring" also occur in interstitial fibrosis? Is it possible that interstitial fibrosis can be visually undetectable at the Post Mortem? Or even the early stages of the first scarring type? I have read that fibrosis can be undetected by X rays and so require high resolution CT technology.
The scarring which we were discussing earlier involves replacement of injured myocardium by scarring. In interstitial fibrosis, there is altered biochemical properties of the heart muscle fibers due to change in composition of biomolecules like collagen. At thr Post Mortem, it may not be all that evident in every individual. The collagen content may be known after detailed microscopic evaluation. Recent research has shown that interstitial collagen content is increased in hearts with dilated left ventricles but no clinical or pathological evidence of ischaemic heart disease. Similar results have been reported in patients with dilated cardiomyopathy. Imaging by cardiac MRI is the latest in evaluation of myocardial fibrosis.
3) Is toxicity synonymous with adverse reactions? It is stated that toxicity is rare and statistically given by your reply as 1 in 5000 cases for severe acute first administrations. The figure for less severe cases is not given and it might be noted again that the British Medical Journal 1982 and the Beers Report 2012 seem to ban the use of the medication for elderly people and the description "rare" might not apply to this specific group? I suppose it might be expected that chronic cases are statistically less than acute cases due to the relative frequency of the condition in the different sampling groups and might not be that meaningful in relation to its possible danger? Perhaps you might have further comments about the danger of the prescription of nitrofurantoin and the value of the contraindication for elderly people given by the Beers Report/ British Medical Journal?
Toxicity refers to any expected or unexpected events of a negative nature which may occur with considerable higher doses of drug intake and such medications have a narrow margin of safety.
Adverse reactions are usually expected or unexpected events with even a small dose of the drug in question.
Peer reviews show that in patients with renal impairment, including elderly patients, nitrofurantoin excretion is decreased, and it may not reach adequate urinary minimum inhibitory concentrations. Thus, a primary reason that nitrofurantoin is on the Beers List of medications to avoid in the elderly is inadequate drug concentration in the urine when creatinine clearance falls below 60 mL/min. Besides the potential subtherapeutic effect of nitrofurantoin in patients with renal impairment, patients may be at increased risk for adverse events secondary to drug accumulation. This is the potential for development of toxicity.
A retrospective chart review of 356 patients was conducted in 2009 that assessed the efficacy and safety of nitrofurantoin in patients with renal impairment. The study concluded that nitrofurantoin cure rates for UTI and adverse events were similar between those with and those without renal impairment. It is generally accepted that nitrofurantoin may be ineffective for UTIs in the elderly because age-related declines in renal function result in subtherapeutic concentrations in the urinary tract.
It is possible that the pulmonary fibrosis may occur doe to secondary drug accumulation and hence this must be avoided in the elderly.
3) I have also read if I recall correctly that even in first administration hyper sensitive reactions may occur in the first three hours?
It is possible that adverse reactions may occur in the first three hours in some patients. A study done shows acute pulmonary reactions appeared a mean of 8.7 days after the start of nitrofurantoin treatment. Typical for these were high fever, dyspnoea, cough, blood eosinophilia, bilateral pneumonic or pleuro-pneumonic infiltrations, a reduced transfer factor of the lung and, as revealed in pulmonary biopsy specimens, vasculitis, interstitial inflammation and alveolar exudation.
4) The deceased person relevant to this discussion had repeated UTI infections over the last two and a half years and I presume was given this medication for a week to ten days each time. Do you consider that sufficent time to expose the patient to the risk of developing pulmonary fibrosis in some form perhaps in its early stages? As mentioned before might this be difficult to detect depending on the type of fibrosis and stage of development?
In the treatment of the deceased person, it might have been that there was secondary lung changes due to drug accumulation each time she was given nitrofurantoin. The renal function details are not known and we can at best only make an assumption. There are certain lung changes that would have been expected in the lungs of a 95 year old person and make such findings difficult to detect in early stages.
5) Would it be correct to say that the presence of minor myo cardial fibrosis might be the subject of further research to establish a possible link with nitrofurantoin?
There is little chance of linking nitrofurantoin intake with mild myocardial fibrosis keeping in mind the available medical literature on the topic of discussion.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Above answer was peer-reviewed by :
Dr. Yogesh D
Thank you Doctor Chail for your much appreciated thorough and informative advice.
Regarding points 3 and 4 and your answer in which the possibility of renal impairment in the elderly is a factor.
The patient (my mother actually) had post mortem kidneys described as having granular external surfaces with cut surfaces showing diffuse cortical narrowing of a moderate degree together with moderate congestion.
My questions are;
1) Are the kidneys therefore functionally impaired to an extent? if so to what extent?
Another question is interstitial inflammation.
2) Can interstitial inflammation bring about fragility or friability in the tissues of the lungs?
3) Is it possible that signs such as reactive inflammation that might belong to interstitial inflammation can be confused with broncho pneumonia reactive inflammation?
4) Could a sudden problem in breathing/shortness of breath be a possible hyper reaction to nitrofurantoin? If so are the specific antibodies connected with that adverse reaction possible to identify?
Thanks
Brief Answer:
Please find detailed answer below
Detailed Answer:
Hi XXXXXX,
Thanks for writing back with an update.
1) Are the kidneys therefore functionally impaired to an extent? if so to what extent?
When we are discussing about nitrofurantoin in the elderly, the problems arise due to decreased creatinine clearance. The drug is in no way going to affect the kidneys causing nephrotoxicity but will cause secondary rise in drug levels that affects other organs like the lungs. It is not clear if she had a decreased creatinine clearance although the effects of aging are noted in the kidneys.
Latest research (2013) says that data supporting the contraindication of nitrofurantoin for patients with a CrCl less than 60 mL/min are nonexistent. Further research on effects of nitrofurantoin in kidneys in the elderly is needed to make more accurate guidelines. Until such a study becomes available, the limited data available would support considering using this drug in patients with a CrCl of 40 mL/min or higher.
Please find complete article at this link
http://www.ncbi.nlm.nih.gov/pubmed/0000
Another question is interstitial inflammation.
2) Can interstitial inflammation bring about fragility or friability in the tissues of the lungs?
In discussing interstitial inflammation of the lungs, fragile or friable lungs can be seen commonly in asbestos associated interstitial lung disease though extensive interstitial inflammation due to some other conditions may also show a similar picture. Friable lungs are also seen in pneumonia.
3) Is it possible that signs such as reactive inflammation that might belong to interstitial inflammation can be confused with broncho pneumonia reactive inflammation?
In bronchopneumonia cytokines such as tumour necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-beta), interleukin-6 (IL-6), and interleukin-8 (IL-8), secreted to destroy the invading pathogens.
In interstitial lung disease the release of cytokines, such as TNF-α, IFN-α, IL-6, and IL-8, has been postulated as the mechanism responsible. Other possible mechanisms of induction include complement activation or indirect cytotoxic T lymphocyte (CTL) activation.
So we see the same triggers in the immune system working in both cases and that can be confusing if the history and sequence of lung injury is not known.
4) Could a sudden problem in breathing/shortness of breath be a possible hyper reaction to nitrofurantoin? If so are the specific antibodies connected with that adverse reaction possible to identify?
We cannot single out antibodies connected to that adverse reaction.
The most likely cause of pulmonary complications of nitrofurantoin therapy is a hypersensitivity reaction. The interstitial pneumonitis induced by nitrofurantoin is now classified as a non-cytotoxic pneumonitis. Non-cytotoxic drugs, including nitrofurantoin, can activate lymphocytes. Those lymphocytes produce mediators that cause the release of many cytokines, resulting in a lymphocytic alveolitis. Another mechanism described in patients using nitrofurantoin is the disturbance of the equilibrium between oxidants and anti-oxidants in the lung. Nitrofurantoin induces an increased production of oxidants in the lung, resulting in the activation of several inflammatory responses. In vitro experiments revealed the production of toxic metabolic products of nitrofurantoin in the presence of oxygen and lung microsomes. The toxic products may cause lung injury and thus result in diffuse interstitial lung fibrosis.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Please find detailed answer below
Detailed Answer:
Hi XXXXXX,
Thanks for writing back with an update.
1) Are the kidneys therefore functionally impaired to an extent? if so to what extent?
When we are discussing about nitrofurantoin in the elderly, the problems arise due to decreased creatinine clearance. The drug is in no way going to affect the kidneys causing nephrotoxicity but will cause secondary rise in drug levels that affects other organs like the lungs. It is not clear if she had a decreased creatinine clearance although the effects of aging are noted in the kidneys.
Latest research (2013) says that data supporting the contraindication of nitrofurantoin for patients with a CrCl less than 60 mL/min are nonexistent. Further research on effects of nitrofurantoin in kidneys in the elderly is needed to make more accurate guidelines. Until such a study becomes available, the limited data available would support considering using this drug in patients with a CrCl of 40 mL/min or higher.
Please find complete article at this link
http://www.ncbi.nlm.nih.gov/pubmed/0000
Another question is interstitial inflammation.
2) Can interstitial inflammation bring about fragility or friability in the tissues of the lungs?
In discussing interstitial inflammation of the lungs, fragile or friable lungs can be seen commonly in asbestos associated interstitial lung disease though extensive interstitial inflammation due to some other conditions may also show a similar picture. Friable lungs are also seen in pneumonia.
3) Is it possible that signs such as reactive inflammation that might belong to interstitial inflammation can be confused with broncho pneumonia reactive inflammation?
In bronchopneumonia cytokines such as tumour necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-beta), interleukin-6 (IL-6), and interleukin-8 (IL-8), secreted to destroy the invading pathogens.
In interstitial lung disease the release of cytokines, such as TNF-α, IFN-α, IL-6, and IL-8, has been postulated as the mechanism responsible. Other possible mechanisms of induction include complement activation or indirect cytotoxic T lymphocyte (CTL) activation.
So we see the same triggers in the immune system working in both cases and that can be confusing if the history and sequence of lung injury is not known.
4) Could a sudden problem in breathing/shortness of breath be a possible hyper reaction to nitrofurantoin? If so are the specific antibodies connected with that adverse reaction possible to identify?
We cannot single out antibodies connected to that adverse reaction.
The most likely cause of pulmonary complications of nitrofurantoin therapy is a hypersensitivity reaction. The interstitial pneumonitis induced by nitrofurantoin is now classified as a non-cytotoxic pneumonitis. Non-cytotoxic drugs, including nitrofurantoin, can activate lymphocytes. Those lymphocytes produce mediators that cause the release of many cytokines, resulting in a lymphocytic alveolitis. Another mechanism described in patients using nitrofurantoin is the disturbance of the equilibrium between oxidants and anti-oxidants in the lung. Nitrofurantoin induces an increased production of oxidants in the lung, resulting in the activation of several inflammatory responses. In vitro experiments revealed the production of toxic metabolic products of nitrofurantoin in the presence of oxygen and lung microsomes. The toxic products may cause lung injury and thus result in diffuse interstitial lung fibrosis.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Above answer was peer-reviewed by :
Dr. Raju A.T
Thank you very much for your reply which I shall study and perhaps ask another question
Focusing on the liver now: if the cut surfaces are recticular and described as consistent with right heart failure does that mean that heart failure has caused a recticular pattern or vice versa (i.e. that liver damage may have caused heart failure?) or both?
What signs might show up from X ray/ high resolution CT for possible damage to the liver from nitrofurantoin?
Why can high resolution CT identify interstitial fibrosis when X rays can't ?
Brief Answer:
Please find detailed answer below
Detailed Answer:
Hi XXXXXX,
Thanks for writing back with an update.
Focusing on the liver now: if the cut surfaces are recticular and described as consistent with right heart failure does that mean that heart failure has caused a recticular pattern or vice versa (i.e. that liver damage may have caused heart failure?) or both?
In right-sided heart failure, the right ventricle (one of the chambers of the heart) loses its pumping function, and blood may pool up into other areas of the body, producing congestion. Congestion affects the liver, the gastrointestinal tract, and the limbs. In addition, the right ventricle may be unable to pump blood efficiently to the lungs and to the left ventricle. This congestion causes changes in the liver are caused due to heart disease.
What signs might show up from X ray/ high resolution CT for possible damage to the liver from nitrofurantoin?
X ray is not much specific an investigation when dealing with suspected lung damage due to nitrfurantoin. I mean that the fibrosis will be seen on X ray but you cannot differentiate it from fibrosis due to other causes on X ray. A HRCT gives finer detail and the patterns in the lung need to be studied and a diagnosis is made by excluding other interstitial disease patterns.
Why can high resolution CT identify interstitial fibrosis when X rays can't ?
A high resolution CT is a method in which approximately 1 mm thin sections of the lung are acquired and this is taken over intervals of 10 mm from the lung apex till the base. This gives the lung architecture in greater detail. A CT scan is high intensity X rays and one CT scan is equivalent to about 200 – 300 chest X rays. But X rays are still the initial tools used to pick up gross findings in any patient.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Please find detailed answer below
Detailed Answer:
Hi XXXXXX,
Thanks for writing back with an update.
Focusing on the liver now: if the cut surfaces are recticular and described as consistent with right heart failure does that mean that heart failure has caused a recticular pattern or vice versa (i.e. that liver damage may have caused heart failure?) or both?
In right-sided heart failure, the right ventricle (one of the chambers of the heart) loses its pumping function, and blood may pool up into other areas of the body, producing congestion. Congestion affects the liver, the gastrointestinal tract, and the limbs. In addition, the right ventricle may be unable to pump blood efficiently to the lungs and to the left ventricle. This congestion causes changes in the liver are caused due to heart disease.
What signs might show up from X ray/ high resolution CT for possible damage to the liver from nitrofurantoin?
X ray is not much specific an investigation when dealing with suspected lung damage due to nitrfurantoin. I mean that the fibrosis will be seen on X ray but you cannot differentiate it from fibrosis due to other causes on X ray. A HRCT gives finer detail and the patterns in the lung need to be studied and a diagnosis is made by excluding other interstitial disease patterns.
Why can high resolution CT identify interstitial fibrosis when X rays can't ?
A high resolution CT is a method in which approximately 1 mm thin sections of the lung are acquired and this is taken over intervals of 10 mm from the lung apex till the base. This gives the lung architecture in greater detail. A CT scan is high intensity X rays and one CT scan is equivalent to about 200 – 300 chest X rays. But X rays are still the initial tools used to pick up gross findings in any patient.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Above answer was peer-reviewed by :
Dr. Chakravarthy Mazumdar
Good morning Dr XXXXXXX
Thank you again for your helpful information.
Turning now if I may to radiology scans.
I would like to request a "second level" investigation MRI scan use for the confirmation of a recent Post Mortem diagnosis of vascular dementia that seems to be a first level clinical medical impression but useful as such for discussion....
Firstly, what is the specific medical definition of vascular dementia?
Post Mortem statements relevant to the brain are that a) the cerebral arteries show extensive atheroma and have a markedly tortuous outline with several sites of stenosis.
b) Some shrinkage of the right temporal lobe.
c) Very minor narrowing of teh gyri consistent with generalised cerebral atrophy.
Is it scientifically reasonable to request further tests (MRI) to confirm the first level diagnosis or is that information diagnostically conclusive in your opinion?
Another question is that "vascular dementia" was substituted for a previous pre-PM report diagnosis given for death certificate purposes of "atherosclerotic dementia".
Is there a difference between vascular dementia and atherosclerotic dementia?
You might note that I have been authorised by the Coroner to open medical discussion with third parties regarding the first level PM report if I wish to do so.
Reply 2
Good afternoon Dr XXXXXXX
As you might have suspected before my last reply I would like to gain a second opinion to legally request a second specialised post mortem investigation.
If you are in agreement I would appreciate your specific comments and more so a formal written and official sounding second medical opinion by yourself (perhaps about a page long?) if that is possible?
I do have authorisation from the Coroner to release PM information but I suppose it is still confidential and sensitive so I would cancel names in it and just leave the medical information.
If you would like to send me your e-mail address I could send you the scanned reports and you could reply by giving information on-line and to my e-mail address perhaps with the official heading letter from your Medical Institute if that is possible?
My concern is that the first autopsy report regarding my mother's recent decease is like a clinical impression of signs given but perhaps requires a lung/liver biopsy; X rays-HRCT; MRI scan etc to confirm or disregard first level medical signs. If I can persuade the Coroner then the expense is paid for by the Coroner's Office.
I don't know how you might consider the situation/written second opinion report requested, as work done for applied teaching medical research purposes ( or to be paid for time if not given through Healthcare on-line services or considered as an exchange for the opportunity in the pursuit of knowledge?
Appreciating your advice and further assistance in any event...
XXXXXXX
Brief Answer:
Please find detailed answer below
Detailed Answer:
Hi XXXXXX,
Thanks for writing in with updates.
Please find replies to your queries below
Firstly, what is the specific medical definition of vascular dementia?
The condition vascular dementia is not a single disease; it is a group of syndromes relating to different vascular mechanisms, the common clinical feature being that of dementia.
Is it scientifically reasonable to request further tests (MRI) to confirm the first level diagnosis or is that information diagnostically conclusive in your opinion?
In my experience, the MRI findings are conclusive and pointing to several changes that can be expected in a patient aged 95 years and having clinical features of dementia. Dementia is a diagnosis made mainly on clinical examination and the MRI has given insight to the possible structural changes in the brain.
Is there a difference between vascular dementia and atherosclerotic dementia?
Vascular dementia is a group and many subtypes of vascular dementia have been described to date. Athrosclerotic dementia is a sub type of vascular dementia in which the primary problem is formation of atheromatous plaques in the arteries supplying the brain which may cause infarcts distally.
The spectrum of vascular dementia includes
(1) mild vascular cognitive impairment,
(2) multi-infarct dementia,
(3) vascular dementia due to a strategic single infarct,
(4) vascular dementia due to lacunar lesions,
(5) vascular dementia due to hemorrhagic lesions,
(6) Binswanger disease,
(7) subcortical vascular dementia, and
(8) mixed dementia (combination of AD and vascular dementia).
I do support you in trying to know the exact cause of death of the deceased but there are few areas which do not appear clear to me at the moment and we could discuss those areas before taking things further concerning a second post mortem.
It is important to know the sequence of events recorded clinically during the last few days or weeks leading to death. Subsequently the details recorded on the death certificate issued by the Coroner must also be reviewed. Once that is over, you may match the events leading to death with the post mortem findings. I agree that certain details remain confidential as per laws in your country.
I am not authorised to give out any formal statements as I am not a forensic specialist, please excuse me for that. However I can try giving you the most appropriate medical information which can be helpful in getting things done formally at your end. I can also give you medical research articles published in peer journals and that can be discussed at your end.
I appreciate the exchange of information for the quest of knowledge. I suppose we need to look at the complete sequence of events leading to death of the deceased and integrate the various liver, lung, heart, brain conditions and any other clinical pathology which may give us a better understanding at what you are looking for.
We must keep in mind that certain tests and investigations can be done and may provide valuable information only when a person is alive. This cannot be effectively repeated in the deceased.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek.
Please find detailed answer below
Detailed Answer:
Hi XXXXXX,
Thanks for writing in with updates.
Please find replies to your queries below
Firstly, what is the specific medical definition of vascular dementia?
The condition vascular dementia is not a single disease; it is a group of syndromes relating to different vascular mechanisms, the common clinical feature being that of dementia.
Is it scientifically reasonable to request further tests (MRI) to confirm the first level diagnosis or is that information diagnostically conclusive in your opinion?
In my experience, the MRI findings are conclusive and pointing to several changes that can be expected in a patient aged 95 years and having clinical features of dementia. Dementia is a diagnosis made mainly on clinical examination and the MRI has given insight to the possible structural changes in the brain.
Is there a difference between vascular dementia and atherosclerotic dementia?
Vascular dementia is a group and many subtypes of vascular dementia have been described to date. Athrosclerotic dementia is a sub type of vascular dementia in which the primary problem is formation of atheromatous plaques in the arteries supplying the brain which may cause infarcts distally.
The spectrum of vascular dementia includes
(1) mild vascular cognitive impairment,
(2) multi-infarct dementia,
(3) vascular dementia due to a strategic single infarct,
(4) vascular dementia due to lacunar lesions,
(5) vascular dementia due to hemorrhagic lesions,
(6) Binswanger disease,
(7) subcortical vascular dementia, and
(8) mixed dementia (combination of AD and vascular dementia).
I do support you in trying to know the exact cause of death of the deceased but there are few areas which do not appear clear to me at the moment and we could discuss those areas before taking things further concerning a second post mortem.
It is important to know the sequence of events recorded clinically during the last few days or weeks leading to death. Subsequently the details recorded on the death certificate issued by the Coroner must also be reviewed. Once that is over, you may match the events leading to death with the post mortem findings. I agree that certain details remain confidential as per laws in your country.
I am not authorised to give out any formal statements as I am not a forensic specialist, please excuse me for that. However I can try giving you the most appropriate medical information which can be helpful in getting things done formally at your end. I can also give you medical research articles published in peer journals and that can be discussed at your end.
I appreciate the exchange of information for the quest of knowledge. I suppose we need to look at the complete sequence of events leading to death of the deceased and integrate the various liver, lung, heart, brain conditions and any other clinical pathology which may give us a better understanding at what you are looking for.
We must keep in mind that certain tests and investigations can be done and may provide valuable information only when a person is alive. This cannot be effectively repeated in the deceased.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek.
Above answer was peer-reviewed by :
Dr. Chakravarthy Mazumdar
Good evening Dr XXXXXXX
Thank you for your reply and information support.
Just to clarify and state the task an overview /summary is given incorporating some of the discussions from before..
The objective is to assess the arguments for a second opinion with the intention if appropriate to request “second level” scientific objective tests.
The causes of death given;
1 a Bronchopneumonia
History; the subject although reported as having a chest infection at the time of ambulance transport had no noticeable signs of bronchopneumonia in the week before. Minor UTI was treated (Uro-sepsis reported as being confirmed by an earlier microscopy test) with the antibiotic nitrofurantoin and the PM report states that “Although urinary antiseptics would not represent adequate treatment of a chest infection, they might modify the clinical signs, effectively camouflaging the findings.”
Any comments?
Signs; “the right lower lobe shows more diffuse firmness and is very soft and friable on compression consistent with bronchopneumonia.”
You state that lung friability may also be caused by interstitial reactive inflammation and pleuro – pneumonic infiltrations?
Can pneumonic infiltration refer to the cause of purulent membrane. The PM report states that “there are prominent areas of purulent membrane over the base of the left lower lobe.”
I believe that after a fatal cardiac arrest it is normal for there to be fluid in the lungs.
It is also mentioned if I am not incorrect in your reply that cytokines produced by the body to destroy pathogens are similar in pneumonia and interstitial inflammation reactions.
A few hours to a mean of 8.7 days is given for possible hyper sensitive reactions.
Could a short term hyper sensitive reactive caused by nitrofurantoin have produced friability or does this possibility refer to extensive and long term use of the drug?
Clinical history ; the subject has been reported to have had UTI infections at least five times over the last two years or so and certainly over the last week before decease the subject was on nitrofurantoin and possibly on the other occasions too..
It is also stated; “both lungs show oedema of the lower lobes together with a rather firm texture to the left lower lobe though I cannot express pus on compression.”
Possibly justified request for tests such as lung biopsy; X rays / HR CT ?
Any comments or other suggestions?
1b vascular dementia
History; the subject had been very independent in her nineties, able to cook, clean and shop for herself etc. No signs of abnormal cognitive impairment was noticed. After a fall about two years ago and a hip replacement she was diagnosed as having vascular dementia but no MRI scan was done or any change in cognitive state. The autopsy report confirmed vascular dementia s but again there was no scan used. No stroke has ever been reported or noticed.
PM report; “The cut surfaces show an area of softening at the right tip of the right temporal lobe measuring about 3 cm in diameter, and softening at the lower pole of the left basal ganglia about 2 cm in diameter. Both of these foci are consistent with established infarction.
Does “established” mean before the cardiac arrest. A cardiac arrest would produce “cerebral infarction” so in that case there should be other infarction signs? No previous stroke has been noticed or reported.
Tests; X rays; MRI image scan; HRCT and Angiogram?
Any comments?
Liver; “The cut surfaces have a prominent reticular pattern consistent with terminal right heart failure. There is no focal lesion.”
Is there evidence of liver failure causing or contributing to the cardiac failure?
Test suggested; liver biopsy?
Kidneys; Granular external surfaces and the cut surfaces show diffuse cortical narrowing of a moderate degree together with moderate congestion.
Test; Kidney biopsy?
Any comments?
Heart; As mentioned before 1 cm of myo cardial fibrosis was found. You comment that there is no direct link between the condition and the use of nitrofurantoin according to the medical l literature to date. Could there be an indirect link?
Toxicology report
a) Paracetamol (38 mg) “is present in the blood at a concentration marginally above the therapeutic range (10-35 mg/l) and is unlikely to be of significance.”
What does “unlikely” mean in this medical context? Unlikely to bring about death?
Is there a combination of medication danger? Nitrofurantoin plus bisoprolol plus parcetamol?
How many parcetamol/dosage a day would be necessary to produce such a high level as 38 mg?
b) “Nitrofurantoin is generally regarded as a substance of low toxicity and may not be detectable in toxicology screens after therapeutic use. Measurement of blood concentrations is only undertaken as part of research studies.”
Possible tests; a) creatinine level from urine 40-60 ml/min?
b) Assay for antibodies or metabolites of nitrofurantoin? Origin of hyper sensitive adverse reaction of malaise etc?
c) Routine blood test and blood and urine culture for residual bacterial infection?
Any comments?
Are there different recommended dosages for long term preventative or chronic use or acute short term therapeutic acute use?
d) History; Adrenalin was administered in the ambulance on the way to hospital. It was injected into the upper left arm.
PM report; “Adrenalin is rapidly removed from the blood in life and is not stable in the blood in vitro unless plasma is separated within 15 minutes in blood collection. Post mortem blood is not suitable for adrenalin measurement.”
However, I have been medically informed that post mortem adrenalin can be measured in serum both peripheral and intra cardiac blood? Any comments?
CPR/DNR
A “down time of 1 hour" is mentioned as being reported to the Pathologist.
Is that possible? What does "down time" mean exactly in precise medical terms?
How long does it take for brain damage to occur and a CPR/DNR choice having to be made?
In conclusion;
Is the request for a second medical opinion justified?
What tests from those mentioned might be reasonable and necessary to advise for a second and specific post mortem investigation considering the information given?
Thanking you for your time and attention.
Thank you for your reply and information support.
Just to clarify and state the task an overview /summary is given incorporating some of the discussions from before..
The objective is to assess the arguments for a second opinion with the intention if appropriate to request “second level” scientific objective tests.
The causes of death given;
1 a Bronchopneumonia
History; the subject although reported as having a chest infection at the time of ambulance transport had no noticeable signs of bronchopneumonia in the week before. Minor UTI was treated (Uro-sepsis reported as being confirmed by an earlier microscopy test) with the antibiotic nitrofurantoin and the PM report states that “Although urinary antiseptics would not represent adequate treatment of a chest infection, they might modify the clinical signs, effectively camouflaging the findings.”
Any comments?
Signs; “the right lower lobe shows more diffuse firmness and is very soft and friable on compression consistent with bronchopneumonia.”
You state that lung friability may also be caused by interstitial reactive inflammation and pleuro – pneumonic infiltrations?
Can pneumonic infiltration refer to the cause of purulent membrane. The PM report states that “there are prominent areas of purulent membrane over the base of the left lower lobe.”
I believe that after a fatal cardiac arrest it is normal for there to be fluid in the lungs.
It is also mentioned if I am not incorrect in your reply that cytokines produced by the body to destroy pathogens are similar in pneumonia and interstitial inflammation reactions.
A few hours to a mean of 8.7 days is given for possible hyper sensitive reactions.
Could a short term hyper sensitive reactive caused by nitrofurantoin have produced friability or does this possibility refer to extensive and long term use of the drug?
Clinical history ; the subject has been reported to have had UTI infections at least five times over the last two years or so and certainly over the last week before decease the subject was on nitrofurantoin and possibly on the other occasions too..
It is also stated; “both lungs show oedema of the lower lobes together with a rather firm texture to the left lower lobe though I cannot express pus on compression.”
Possibly justified request for tests such as lung biopsy; X rays / HR CT ?
Any comments or other suggestions?
1b vascular dementia
History; the subject had been very independent in her nineties, able to cook, clean and shop for herself etc. No signs of abnormal cognitive impairment was noticed. After a fall about two years ago and a hip replacement she was diagnosed as having vascular dementia but no MRI scan was done or any change in cognitive state. The autopsy report confirmed vascular dementia s but again there was no scan used. No stroke has ever been reported or noticed.
PM report; “The cut surfaces show an area of softening at the right tip of the right temporal lobe measuring about 3 cm in diameter, and softening at the lower pole of the left basal ganglia about 2 cm in diameter. Both of these foci are consistent with established infarction.
Does “established” mean before the cardiac arrest. A cardiac arrest would produce “cerebral infarction” so in that case there should be other infarction signs? No previous stroke has been noticed or reported.
Tests; X rays; MRI image scan; HRCT and Angiogram?
Any comments?
Liver; “The cut surfaces have a prominent reticular pattern consistent with terminal right heart failure. There is no focal lesion.”
Is there evidence of liver failure causing or contributing to the cardiac failure?
Test suggested; liver biopsy?
Kidneys; Granular external surfaces and the cut surfaces show diffuse cortical narrowing of a moderate degree together with moderate congestion.
Test; Kidney biopsy?
Any comments?
Heart; As mentioned before 1 cm of myo cardial fibrosis was found. You comment that there is no direct link between the condition and the use of nitrofurantoin according to the medical l literature to date. Could there be an indirect link?
Toxicology report
a) Paracetamol (38 mg) “is present in the blood at a concentration marginally above the therapeutic range (10-35 mg/l) and is unlikely to be of significance.”
What does “unlikely” mean in this medical context? Unlikely to bring about death?
Is there a combination of medication danger? Nitrofurantoin plus bisoprolol plus parcetamol?
How many parcetamol/dosage a day would be necessary to produce such a high level as 38 mg?
b) “Nitrofurantoin is generally regarded as a substance of low toxicity and may not be detectable in toxicology screens after therapeutic use. Measurement of blood concentrations is only undertaken as part of research studies.”
Possible tests; a) creatinine level from urine 40-60 ml/min?
b) Assay for antibodies or metabolites of nitrofurantoin? Origin of hyper sensitive adverse reaction of malaise etc?
c) Routine blood test and blood and urine culture for residual bacterial infection?
Any comments?
Are there different recommended dosages for long term preventative or chronic use or acute short term therapeutic acute use?
d) History; Adrenalin was administered in the ambulance on the way to hospital. It was injected into the upper left arm.
PM report; “Adrenalin is rapidly removed from the blood in life and is not stable in the blood in vitro unless plasma is separated within 15 minutes in blood collection. Post mortem blood is not suitable for adrenalin measurement.”
However, I have been medically informed that post mortem adrenalin can be measured in serum both peripheral and intra cardiac blood? Any comments?
CPR/DNR
A “down time of 1 hour" is mentioned as being reported to the Pathologist.
Is that possible? What does "down time" mean exactly in precise medical terms?
How long does it take for brain damage to occur and a CPR/DNR choice having to be made?
In conclusion;
Is the request for a second medical opinion justified?
What tests from those mentioned might be reasonable and necessary to advise for a second and specific post mortem investigation considering the information given?
Thanking you for your time and attention.
Brief Answer:
Please find detailed answer below
Detailed Answer:
Hi XXXXXX,
Thanks for writing in with updates.
Bronchopneumonia is bacterial infection involving the lungs. It can start as a flu and within days the symptoms can worsen following uncontrolled bacterial proliferation if not controlled with medicines. Purulent areas refer to the bacterial proliferation, more in the left lower lobe as mentioned.
The friability of interstitial reactive inflammation is of chronic duration but the presence of infiltrates point at bronchopneumonia.
Cytokines are the basis of immune reactions and the persons immune system to fight the disease. I do not think there is possibility of hypersensitivity reaction considering that she was on the medication for 2 years on and off on many occasions. As no lung fibrosis is mentioned, the possibility of adverse reaction to nirtofurantoin use is less likely.
Established infarction means complete brain tissue damage in those areas due to absent blood supply (?after cardiac arrest). If there was infarction during the lifetime of the patient, it would have been mentioned as gliosis which is a long term change in areas of brain with permanent loss of blood supply. A cardiac arrest will produce brain damage to various degrees. Finally in any human being, the events leading to death are cardiac arrest and brain infarction. X rays for the study of brain are obsolete. CT scan, MRI scan and Angiogram are used mainly in the live patient to see for imaging features in the brain which can highlight certain conditions. HRCT is not used for brain imaging.
It is almost always cardiac failure leading to liver signs. As it is a diffuse condition involving the liver, biopsy will only confirm damage to hepatocytes.
The most important tests for kidney function are serum creatinine and blood urea. Then we do the creatinine clearance and glomerular filtration rate. Biopsy is done only to diagnose the cellular basis of any possible condition that might affect the kidney tissues.
I do not find any indirect link between myocardial fibrosis and nitrofurantoin either.
Unlikely to be of significance refers to a finding which has no influence on the deteriorating condition of the patient leading to death. It did not have any role and did not account for the death in any manner. Nitrofurantoin with bisoprolol and paracetamol cause no drug interactions as per medical literature. A dosage around 3 grams in 24 hours can lead to levels in the range of 38 mg.
Creatinine clearance test can indicate the possible accumulation of nitrofurantoin should it be below 40 – 60ml/ min or less.
High-performance liquid chromatographic assay has been used for the study metabolites of nitrofurantoin in plasma and urine can be done for research purposes.
The peak blood concentration of nitrofurantoin following an oral dose of nitrofurantoin 100 mg, is less than 1 μg/mL and may be undetectable; tissue penetration is negligible; the drug is well concentrated in the urine: 75% of the dose is rapidly metabolised by the liver, but 25% of the dose is excreted in the urine unchanged, reliably achieving levels of 200 μg/ml or more. For this reason, nitrofurantoin cannot be used to treat anything other than simple cystitis.
At the concentrations achieved in urine (>100 microgm/mL), nitrofurantoin is bacteriocidal. It is bacteriostatic against most susceptible organisms at concentrations less than 32 micrograms per milliliter.
Routine urine tests may show presence of bacteria if persistent. Bacteria are seen in blood only when the infection is severe.
Are there different recommended dosages for long term preventative or chronic use or acute short term therapeutic acute use?
For long term prevention the prophylactic dose is 50 mg once daily. For Acute short term therapy the dose is 20 to 100 mg 4 times a day for a week or two days after urine becomes sterile.
It is true that levels of adrenaline are highest until 15 minutes after death and then there is a decline phase. Also the human body starts secreting adrenaline immediately after death and that also declines after 15 minutes. These make it difficult to exactly measure the level of adrenaline in post mortem blood as it has half life of 2 minutes. It is agreed upon that measurement of adrenaline can be made after death within the time frame before it gets destroyed.
"Down Time" is the amount of time between the patient becoming unresponsive, and receiving care. This duration has been recorded as 1 hour in your case. The brain damage starts approximately after 3 minutes from complete cessation of blood supply. After about 10 minutes of complete absence of blood supply to the brain at normal temperature the chances of recovery are thin. CPR/ DNR choice must be made within 5 minutes after a person collapses.
In my impartial opinion a second medical review may not give a better picture than the one we already have. I understand it is a personal loss to you and pray to Almighty to XXXXXXX eternal peace to the deceased. Doing a second post mortem may not help you mush because certain tests and investgations can only be done when the patient is alive. You have not mentioned to me about any prior abnormal kidney functions tests that might have avoided prescribing nitrofurantoin should you still think that is the culprit. There is no mention of any lung fibrosis in X rays following intake of nitrofurantoin in the last two years which again might have been an alarm to stop the medication.
I also note that this particular reply is extensively long and I have had to refer to a lot of material to come to certain conclusions. If you feel that some points are not clear and need further attention, I will be glad to clarify it.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Please find detailed answer below
Detailed Answer:
Hi XXXXXX,
Thanks for writing in with updates.
Bronchopneumonia is bacterial infection involving the lungs. It can start as a flu and within days the symptoms can worsen following uncontrolled bacterial proliferation if not controlled with medicines. Purulent areas refer to the bacterial proliferation, more in the left lower lobe as mentioned.
The friability of interstitial reactive inflammation is of chronic duration but the presence of infiltrates point at bronchopneumonia.
Cytokines are the basis of immune reactions and the persons immune system to fight the disease. I do not think there is possibility of hypersensitivity reaction considering that she was on the medication for 2 years on and off on many occasions. As no lung fibrosis is mentioned, the possibility of adverse reaction to nirtofurantoin use is less likely.
Established infarction means complete brain tissue damage in those areas due to absent blood supply (?after cardiac arrest). If there was infarction during the lifetime of the patient, it would have been mentioned as gliosis which is a long term change in areas of brain with permanent loss of blood supply. A cardiac arrest will produce brain damage to various degrees. Finally in any human being, the events leading to death are cardiac arrest and brain infarction. X rays for the study of brain are obsolete. CT scan, MRI scan and Angiogram are used mainly in the live patient to see for imaging features in the brain which can highlight certain conditions. HRCT is not used for brain imaging.
It is almost always cardiac failure leading to liver signs. As it is a diffuse condition involving the liver, biopsy will only confirm damage to hepatocytes.
The most important tests for kidney function are serum creatinine and blood urea. Then we do the creatinine clearance and glomerular filtration rate. Biopsy is done only to diagnose the cellular basis of any possible condition that might affect the kidney tissues.
I do not find any indirect link between myocardial fibrosis and nitrofurantoin either.
Unlikely to be of significance refers to a finding which has no influence on the deteriorating condition of the patient leading to death. It did not have any role and did not account for the death in any manner. Nitrofurantoin with bisoprolol and paracetamol cause no drug interactions as per medical literature. A dosage around 3 grams in 24 hours can lead to levels in the range of 38 mg.
Creatinine clearance test can indicate the possible accumulation of nitrofurantoin should it be below 40 – 60ml/ min or less.
High-performance liquid chromatographic assay has been used for the study metabolites of nitrofurantoin in plasma and urine can be done for research purposes.
The peak blood concentration of nitrofurantoin following an oral dose of nitrofurantoin 100 mg, is less than 1 μg/mL and may be undetectable; tissue penetration is negligible; the drug is well concentrated in the urine: 75% of the dose is rapidly metabolised by the liver, but 25% of the dose is excreted in the urine unchanged, reliably achieving levels of 200 μg/ml or more. For this reason, nitrofurantoin cannot be used to treat anything other than simple cystitis.
At the concentrations achieved in urine (>100 microgm/mL), nitrofurantoin is bacteriocidal. It is bacteriostatic against most susceptible organisms at concentrations less than 32 micrograms per milliliter.
Routine urine tests may show presence of bacteria if persistent. Bacteria are seen in blood only when the infection is severe.
Are there different recommended dosages for long term preventative or chronic use or acute short term therapeutic acute use?
For long term prevention the prophylactic dose is 50 mg once daily. For Acute short term therapy the dose is 20 to 100 mg 4 times a day for a week or two days after urine becomes sterile.
It is true that levels of adrenaline are highest until 15 minutes after death and then there is a decline phase. Also the human body starts secreting adrenaline immediately after death and that also declines after 15 minutes. These make it difficult to exactly measure the level of adrenaline in post mortem blood as it has half life of 2 minutes. It is agreed upon that measurement of adrenaline can be made after death within the time frame before it gets destroyed.
"Down Time" is the amount of time between the patient becoming unresponsive, and receiving care. This duration has been recorded as 1 hour in your case. The brain damage starts approximately after 3 minutes from complete cessation of blood supply. After about 10 minutes of complete absence of blood supply to the brain at normal temperature the chances of recovery are thin. CPR/ DNR choice must be made within 5 minutes after a person collapses.
In my impartial opinion a second medical review may not give a better picture than the one we already have. I understand it is a personal loss to you and pray to Almighty to XXXXXXX eternal peace to the deceased. Doing a second post mortem may not help you mush because certain tests and investgations can only be done when the patient is alive. You have not mentioned to me about any prior abnormal kidney functions tests that might have avoided prescribing nitrofurantoin should you still think that is the culprit. There is no mention of any lung fibrosis in X rays following intake of nitrofurantoin in the last two years which again might have been an alarm to stop the medication.
I also note that this particular reply is extensively long and I have had to refer to a lot of material to come to certain conclusions. If you feel that some points are not clear and need further attention, I will be glad to clarify it.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Above answer was peer-reviewed by :
Dr. Chakravarthy Mazumdar
Good afternoon Dr XXXXXXX
Thank you for your informative comments and I reply with some more questions refining I hope the points explored.
.
Bronchopneumonia
The relevant clinical/personal history is that ;
a) The subject showed no signs of developing broncho-pneumonia in the week before the decease. I personally visited her just a few hours before and she was perfectly fine. I had been told that she was on medication for UTI but there was no mention of a chest infection if I recall correctly. I noticed no signs of any chest infection.
b) It is stated in the PM report that the probable reason for the absence of broncho pneumonia signs might be the effect of nitrofurantoin.
c) The on-call doctor at the Care Home in the early hours of the morning informed me that there was nothing to worry about and wanted my opinion on whether the patient should be moved to hospital. UTI had been reported, blood pressure up and a bit of a chest infection which in retrospect certainly doesn’t sound like bronchopneumonia in an elderly person.
d) One lobe in the PM report is described as being in a state of healing which means that time had passed and the symptoms should have been noticed I presume.
I would appreciate your attention to the following questions;
1) Does that clinical history mentioned above represent the likely medical condition and symptoms of a person in a state of bronchopneumonia?
2) Is it likely in your opinion that the explanation for not noticing the onset or developed condition of the development of broncho pneumonia was the effects of the use of nitrofurantoin as mentioned in the PM report? Are there any sicientifc facts to support thes claim of the PM report ?
Regarding the clinical report (and your comments);
The primary causes of death are 1 a bronchopneumonia ( and 1 b vascular dementia).
An internet taken definition
"Acute inflammation of the walls of the smaller bronchial tubes, with varying amounts of pulmonary consolidation due to spread of the inflammation into peribronchiolar alveoli and the alveolar ducts; may become confluent or may be hemorrhagic".
3) What does “1 a“ in “1 a broncho pneumonia” mean? Does the definition include a specific bacteria that is traceable by blood/urine tests?
4) Is the cause of death due to the increased stress on the heart as more blood is required for the organs or other causes?
5) Friability is noted in your comments as being stated as a chronic condition with the infiltrates pointing to broncho pneumonia. What else could have caused friability? One possible cause for exampke a sdiscussed is interstitial fibrosis but no test was done and a form of interstitial fibrosis might not be noticed visually or by X ray and HRCT is required. The duration of the prescription of nitrofurantoin for the elderly subject (my mother) still has to be clarified? It might have been only days, repeated intermittent dosages over a couple of years or even in preventative form continuous use over this time.
6) In the PM report the term “consolidation” is also used, “This subject has died with evidence of consolidation in both lower pulmonary lobe...” What does “consolidation” mean? Does “consolidation” mean fluid in the plural sacs or purulence in the fluid caused by bacterial infiltrates?
7) Can bacterial infiltrates cause purulence in the lung fluid after death so allowing the possibility that the “consolidation” if it means fluid in the lungs might have occurred consequentially after death/ terminal cardiac failure?
8) Are those signs / observations scientifically sufficient for a conclusive diagnosis of broncho pneumonia and the standard of care adequate enough to exclude the necessity of tests to confirm the initial clinical impressions?
The diagnosis is in fact introduced with the preamble “ in my opinion...
9) No creatinine clearance test was administered before the very elderly subject (95) was prescribed the medication.
Perhaps as the prescription facts are not so clear HRCT etc testing is justified?
10) If there has not been a long term use but an “acute” short term use of nitrofurantoin then the bacteria produced by the medication in a possible adverse reaction in an elderly person should be identified as discussed before. In this case would “ high-performance liquid chromatographic assay used for the study metabolites of nitrofurantoin in plasma and urine” as you mention be appropriate to use?
1b vascular dementia
Clinical/personal history; it seemed that there was no cognitive impairment as the subject was able to remain independent looking after herself until she had a fall two years ago. After a hip replacement and three weeks convalescence, vascular dementia was diagnosed but no scan was used to confirm this?
11) What is vascular dementia? What is 1 b dementia?
12) Vascular dementia was substituted for a previous pre-PM report diagnosis given for death certificate purposes of "atherosclerotic dementia". Is there a difference between vascular dementia and atherosclerotic dementia?
13) How can vascular dementia be a primary cause of death? In this case causing a cardiac arrest?
14) Is "vascular dementia" to be noted as an unusual diagnosis in the circumstances given above considering the extent of the clinical aspects and personal profile impressions?
Regarding the clinical definition and diagnosis of vascular dementia
After decease brain relevant statements in the PM report are that a) the cerebral arteries show extensive atheroma and have a markedly tortuous outline with several sites of stenosis.
b) Some shrinkage of the right temporal lobe.
c) Very minor narrowing of the gyri consistent with generalised cerebral atrophy.
15) Is it scientifically reasonable to request further tests (MRI etc ) to confirm the first level diagnosis? What is the most reliable scan test to use?
Thanks.
Thank you for your informative comments and I reply with some more questions refining I hope the points explored.
.
Bronchopneumonia
The relevant clinical/personal history is that ;
a) The subject showed no signs of developing broncho-pneumonia in the week before the decease. I personally visited her just a few hours before and she was perfectly fine. I had been told that she was on medication for UTI but there was no mention of a chest infection if I recall correctly. I noticed no signs of any chest infection.
b) It is stated in the PM report that the probable reason for the absence of broncho pneumonia signs might be the effect of nitrofurantoin.
c) The on-call doctor at the Care Home in the early hours of the morning informed me that there was nothing to worry about and wanted my opinion on whether the patient should be moved to hospital. UTI had been reported, blood pressure up and a bit of a chest infection which in retrospect certainly doesn’t sound like bronchopneumonia in an elderly person.
d) One lobe in the PM report is described as being in a state of healing which means that time had passed and the symptoms should have been noticed I presume.
I would appreciate your attention to the following questions;
1) Does that clinical history mentioned above represent the likely medical condition and symptoms of a person in a state of bronchopneumonia?
2) Is it likely in your opinion that the explanation for not noticing the onset or developed condition of the development of broncho pneumonia was the effects of the use of nitrofurantoin as mentioned in the PM report? Are there any sicientifc facts to support thes claim of the PM report ?
Regarding the clinical report (and your comments);
The primary causes of death are 1 a bronchopneumonia ( and 1 b vascular dementia).
An internet taken definition
"Acute inflammation of the walls of the smaller bronchial tubes, with varying amounts of pulmonary consolidation due to spread of the inflammation into peribronchiolar alveoli and the alveolar ducts; may become confluent or may be hemorrhagic".
3) What does “1 a“ in “1 a broncho pneumonia” mean? Does the definition include a specific bacteria that is traceable by blood/urine tests?
4) Is the cause of death due to the increased stress on the heart as more blood is required for the organs or other causes?
5) Friability is noted in your comments as being stated as a chronic condition with the infiltrates pointing to broncho pneumonia. What else could have caused friability? One possible cause for exampke a sdiscussed is interstitial fibrosis but no test was done and a form of interstitial fibrosis might not be noticed visually or by X ray and HRCT is required. The duration of the prescription of nitrofurantoin for the elderly subject (my mother) still has to be clarified? It might have been only days, repeated intermittent dosages over a couple of years or even in preventative form continuous use over this time.
6) In the PM report the term “consolidation” is also used, “This subject has died with evidence of consolidation in both lower pulmonary lobe...” What does “consolidation” mean? Does “consolidation” mean fluid in the plural sacs or purulence in the fluid caused by bacterial infiltrates?
7) Can bacterial infiltrates cause purulence in the lung fluid after death so allowing the possibility that the “consolidation” if it means fluid in the lungs might have occurred consequentially after death/ terminal cardiac failure?
8) Are those signs / observations scientifically sufficient for a conclusive diagnosis of broncho pneumonia and the standard of care adequate enough to exclude the necessity of tests to confirm the initial clinical impressions?
The diagnosis is in fact introduced with the preamble “ in my opinion...
9) No creatinine clearance test was administered before the very elderly subject (95) was prescribed the medication.
Perhaps as the prescription facts are not so clear HRCT etc testing is justified?
10) If there has not been a long term use but an “acute” short term use of nitrofurantoin then the bacteria produced by the medication in a possible adverse reaction in an elderly person should be identified as discussed before. In this case would “ high-performance liquid chromatographic assay used for the study metabolites of nitrofurantoin in plasma and urine” as you mention be appropriate to use?
1b vascular dementia
Clinical/personal history; it seemed that there was no cognitive impairment as the subject was able to remain independent looking after herself until she had a fall two years ago. After a hip replacement and three weeks convalescence, vascular dementia was diagnosed but no scan was used to confirm this?
11) What is vascular dementia? What is 1 b dementia?
12) Vascular dementia was substituted for a previous pre-PM report diagnosis given for death certificate purposes of "atherosclerotic dementia". Is there a difference between vascular dementia and atherosclerotic dementia?
13) How can vascular dementia be a primary cause of death? In this case causing a cardiac arrest?
14) Is "vascular dementia" to be noted as an unusual diagnosis in the circumstances given above considering the extent of the clinical aspects and personal profile impressions?
Regarding the clinical definition and diagnosis of vascular dementia
After decease brain relevant statements in the PM report are that a) the cerebral arteries show extensive atheroma and have a markedly tortuous outline with several sites of stenosis.
b) Some shrinkage of the right temporal lobe.
c) Very minor narrowing of the gyri consistent with generalised cerebral atrophy.
15) Is it scientifically reasonable to request further tests (MRI etc ) to confirm the first level diagnosis? What is the most reliable scan test to use?
Thanks.
Brief Answer:
Please find detailed answer below
Detailed Answer:
Hi XXXXXX,
Thanks for writing in with updates.
1) Does that clinical history mentioned above represent the likely medical condition and symptoms of a person in a state of bronchopneumonia?
Bronchopneumonia is common in the elderly and complications are usually seen in those with dementia. This is because the person may not be able to express their problems and symptoms and this can further delay treatment. The clinical history may represent such a condition that went unnoticed in initial stages due to inability of the patient to communicate.
2) Is it likely in your opinion that the explanation for not noticing the onset or developed condition of the development of broncho pneumonia was the effects of the use of nitrofurantoin as mentioned in the PM report? Are there any sicientifc facts to support thes claim of the PM report ?
The explanation for not noticing the onset looks more due to the dementia and the person not reporting her symptoms in the early stages. Though the onset and progress in development of pneumonia due to effects of nitrofurantoin cannot be ruled out in its entirety.
3) What does “1 a“ in “1 a broncho pneumonia” mean? Does the definition include a specific bacteria that is traceable by blood/urine tests?
The bronchopneumonia does include the presence of a bacteria or virus (can be mixed infections too) that is traceable by blood tests when proliferation in such quantities to cause severe pneumonia.
4) Is the cause of death due to the increased stress on the heart as more blood is required for the organs or other causes?
In pneumonia the primary cause of death is toxins released by the bacteria which proliferates and affects the vital organs in the body including heart and brain.
5) Friability is noted in your comments as being stated as a chronic condition with the infiltrates pointing to broncho pneumonia. What else could have caused friability? One possible cause for exampke a sdiscussed is interstitial fibrosis but no test was done and a form of interstitial fibrosis might not be noticed visually or by X ray and HRCT is required. The duration of the prescription of nitrofurantoin for the elderly subject (my mother) still has to be clarified? It might have been only days, repeated intermittent dosages over a couple of years or even in preventative form continuous use over this time.
In a patient on nitrofurantoin with nor previous adverse reaction in the time frame mentioned by you, this point gets debatable as interstial lung disease due to nitrofurantoin has not been confirmed or investigated in the past. Again in pneumonia itself we find certain rare types which are associated with nitrofurantoin use like granulomatous interstitial pneumonia but such occurrances are difficult to establish without proper tests and investigations and uncommon.
6) In the PM report the term “consolidation” is also used, “This subject has died with evidence of consolidation in both lower pulmonary lobe...” What does “consolidation” mean? Does “consolidation” mean fluid in the plural sacs or purulence in the fluid caused by bacterial infiltrates?
Lung consolidation is a medical term used for the lungs retaining fluid as a result of tissue injury. The lung contains many tiny air filled sacs which get fluid filled in consolidation. This is almost always due to an underlying infective cause.
7) Can bacterial infiltrates cause purulence in the lung fluid after death so allowing the possibility that the “consolidation” if it means fluid in the lungs might have occurred consequentially after death/ terminal cardiac failure?
The bacterial infiltrates cause purulence and consolidation and when uncontrolled causes death.
8) Are those signs / observations scientifically sufficient for a conclusive diagnosis of broncho pneumonia and the standard of care adequate enough to exclude the necessity of tests to confirm the initial clinical impressions?
The signs and observations in post mortem analysis are indicative of bronchopneumonia. As you say the patient was normal few hours before her death and the care home doctor had ruled out any adversity, I assume the patient was not able to communicate her state of health and this might have been one of the main reasons for the sudden deterioration in condition.
9) No creatinine clearance test was administered before the very elderly subject (95) was prescribed the medication.
Perhaps as the prescription facts are not so clear HRCT etc testing is justified?
Creatinine clearance should have been done when considering repeated treatments with nitrofurantoin in an elderly patient. HRCT is an investigation that follows chest X ray. I feel a chest X ray should also have been done for her.
10) If there has not been a long term use but an “acute” short term use of nitrofurantoin then the bacteria produced by the medication in a possible adverse reaction in an elderly person should be identified as discussed before. In this case would “ high-performance liquid chromatographic assay used for the study metabolites of nitrofurantoin in plasma and urine” as you mention be appropriate to use?
The liquid performance chromatographic technique was used in research earlier and with further developments rapid immunochromatographic assay may be used presently for detection of 1-aminohydantoin (AHD) metabolite of nitrofurantoin in urine specimens. These are highly specialised tests and the concerned laboratory technologist might be able to tell details on the commercial utility of these tests. This is because the tests are done using kits.
11) What is vascular dementia? What is 1 b dementia?
Vascular dementia is dementia due to any cause having vascular (blood supply) related causative factors. Dementia is a group of disorders having congnitive impairment as the presenting feature. It can appear as a wide range of cognitive impairment and is not the same in every patient.
12) Vascular dementia was substituted for a previous pre-PM report diagnosis given for death certificate purposes of "atherosclerotic dementia". Is there a difference between vascular dementia and atherosclerotic dementia?
Vascular dementia is a bigger group and atherosclerotic dementia is a sub type of vascular dementia.
13) How can vascular dementia be a primary cause of death? In this case causing a cardiac arrest?
I suppose the deterioration of the patient condition was a consequence of dementia and she was not able to state her difficulties on time to enable a quicker and more aggressive management of the bronchopneumonia.
14) Is "vascular dementia" to be noted as an unusual diagnosis in the circumstances given above considering the extent of the clinical aspects and personal profile impressions?
Vascular dementia is a contributing diagnosis and a condition which added to the intensity of bronchopneumonia attack leading to an uncontrolled infection.
Regarding the clinical definition and diagnosis of vascular dementia
After decease brain relevant statements in the PM report are that a) the cerebral arteries show extensive atheroma and have a markedly tortuous outline with several sites of stenosis.
b) Some shrinkage of the right temporal lobe.
c) Very minor narrowing of the gyri consistent with generalised cerebral atrophy.
15) Is it scientifically reasonable to request further tests (MRI etc ) to confirm the first level diagnosis? What is the most reliable scan test to use?
After post mortem, the chemical fixation and tissue decomposition may have various effects on the brain and these techniques may not be validated for use in regular medical practice.
You may go in for a second opinion of pathological samples and microscopy.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Please find detailed answer below
Detailed Answer:
Hi XXXXXX,
Thanks for writing in with updates.
1) Does that clinical history mentioned above represent the likely medical condition and symptoms of a person in a state of bronchopneumonia?
Bronchopneumonia is common in the elderly and complications are usually seen in those with dementia. This is because the person may not be able to express their problems and symptoms and this can further delay treatment. The clinical history may represent such a condition that went unnoticed in initial stages due to inability of the patient to communicate.
2) Is it likely in your opinion that the explanation for not noticing the onset or developed condition of the development of broncho pneumonia was the effects of the use of nitrofurantoin as mentioned in the PM report? Are there any sicientifc facts to support thes claim of the PM report ?
The explanation for not noticing the onset looks more due to the dementia and the person not reporting her symptoms in the early stages. Though the onset and progress in development of pneumonia due to effects of nitrofurantoin cannot be ruled out in its entirety.
3) What does “1 a“ in “1 a broncho pneumonia” mean? Does the definition include a specific bacteria that is traceable by blood/urine tests?
The bronchopneumonia does include the presence of a bacteria or virus (can be mixed infections too) that is traceable by blood tests when proliferation in such quantities to cause severe pneumonia.
4) Is the cause of death due to the increased stress on the heart as more blood is required for the organs or other causes?
In pneumonia the primary cause of death is toxins released by the bacteria which proliferates and affects the vital organs in the body including heart and brain.
5) Friability is noted in your comments as being stated as a chronic condition with the infiltrates pointing to broncho pneumonia. What else could have caused friability? One possible cause for exampke a sdiscussed is interstitial fibrosis but no test was done and a form of interstitial fibrosis might not be noticed visually or by X ray and HRCT is required. The duration of the prescription of nitrofurantoin for the elderly subject (my mother) still has to be clarified? It might have been only days, repeated intermittent dosages over a couple of years or even in preventative form continuous use over this time.
In a patient on nitrofurantoin with nor previous adverse reaction in the time frame mentioned by you, this point gets debatable as interstial lung disease due to nitrofurantoin has not been confirmed or investigated in the past. Again in pneumonia itself we find certain rare types which are associated with nitrofurantoin use like granulomatous interstitial pneumonia but such occurrances are difficult to establish without proper tests and investigations and uncommon.
6) In the PM report the term “consolidation” is also used, “This subject has died with evidence of consolidation in both lower pulmonary lobe...” What does “consolidation” mean? Does “consolidation” mean fluid in the plural sacs or purulence in the fluid caused by bacterial infiltrates?
Lung consolidation is a medical term used for the lungs retaining fluid as a result of tissue injury. The lung contains many tiny air filled sacs which get fluid filled in consolidation. This is almost always due to an underlying infective cause.
7) Can bacterial infiltrates cause purulence in the lung fluid after death so allowing the possibility that the “consolidation” if it means fluid in the lungs might have occurred consequentially after death/ terminal cardiac failure?
The bacterial infiltrates cause purulence and consolidation and when uncontrolled causes death.
8) Are those signs / observations scientifically sufficient for a conclusive diagnosis of broncho pneumonia and the standard of care adequate enough to exclude the necessity of tests to confirm the initial clinical impressions?
The signs and observations in post mortem analysis are indicative of bronchopneumonia. As you say the patient was normal few hours before her death and the care home doctor had ruled out any adversity, I assume the patient was not able to communicate her state of health and this might have been one of the main reasons for the sudden deterioration in condition.
9) No creatinine clearance test was administered before the very elderly subject (95) was prescribed the medication.
Perhaps as the prescription facts are not so clear HRCT etc testing is justified?
Creatinine clearance should have been done when considering repeated treatments with nitrofurantoin in an elderly patient. HRCT is an investigation that follows chest X ray. I feel a chest X ray should also have been done for her.
10) If there has not been a long term use but an “acute” short term use of nitrofurantoin then the bacteria produced by the medication in a possible adverse reaction in an elderly person should be identified as discussed before. In this case would “ high-performance liquid chromatographic assay used for the study metabolites of nitrofurantoin in plasma and urine” as you mention be appropriate to use?
The liquid performance chromatographic technique was used in research earlier and with further developments rapid immunochromatographic assay may be used presently for detection of 1-aminohydantoin (AHD) metabolite of nitrofurantoin in urine specimens. These are highly specialised tests and the concerned laboratory technologist might be able to tell details on the commercial utility of these tests. This is because the tests are done using kits.
11) What is vascular dementia? What is 1 b dementia?
Vascular dementia is dementia due to any cause having vascular (blood supply) related causative factors. Dementia is a group of disorders having congnitive impairment as the presenting feature. It can appear as a wide range of cognitive impairment and is not the same in every patient.
12) Vascular dementia was substituted for a previous pre-PM report diagnosis given for death certificate purposes of "atherosclerotic dementia". Is there a difference between vascular dementia and atherosclerotic dementia?
Vascular dementia is a bigger group and atherosclerotic dementia is a sub type of vascular dementia.
13) How can vascular dementia be a primary cause of death? In this case causing a cardiac arrest?
I suppose the deterioration of the patient condition was a consequence of dementia and she was not able to state her difficulties on time to enable a quicker and more aggressive management of the bronchopneumonia.
14) Is "vascular dementia" to be noted as an unusual diagnosis in the circumstances given above considering the extent of the clinical aspects and personal profile impressions?
Vascular dementia is a contributing diagnosis and a condition which added to the intensity of bronchopneumonia attack leading to an uncontrolled infection.
Regarding the clinical definition and diagnosis of vascular dementia
After decease brain relevant statements in the PM report are that a) the cerebral arteries show extensive atheroma and have a markedly tortuous outline with several sites of stenosis.
b) Some shrinkage of the right temporal lobe.
c) Very minor narrowing of the gyri consistent with generalised cerebral atrophy.
15) Is it scientifically reasonable to request further tests (MRI etc ) to confirm the first level diagnosis? What is the most reliable scan test to use?
After post mortem, the chemical fixation and tissue decomposition may have various effects on the brain and these techniques may not be validated for use in regular medical practice.
You may go in for a second opinion of pathological samples and microscopy.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Above answer was peer-reviewed by :
Dr. Chakravarthy Mazumdar
Good afternoon Dr XXXXXXX
Thank you very much for your prompt and informative reply.
I also thank you for your previous personal mention of my mother and your good wishes to her.
My questions relating to the last two of your replies are;
1) Is 1a broncho pneumonia a classification of the most serious and severe type of bronchopneumonia? Your reply mentions the associated bacteria as "when proliferation in such quantities to cause severe pneumonia".
2) Regarding the dosage of nitrofurantoin I recall reading that 200mg was the maximum dosage for short term acute use. Do you have an authority to cite for the referred dosage which you mention can be as high as 400mg in a previous reply? How does the urine become sterile and how is this measured?
3) How do the toxins affect the heart in bronchopneumonia? Is it by forcing the necessity of more blood and so stressing the heart or another death inducing effect in this case?
4) Can the fluid retained in the lungs known medically as consolidation and due to tissue injury be distinguished from the fluid that normally accumulates after decease by cardiac failure? Can purulence be caused by bacteria after decease?
5) Regarding the measurement of adrenalin it seems that the time frame has been exceeded for measurement making measurement impossible? If that is the case then does adrenalin produce any bodies that might still exist and can still be identified and measured after three months?
6) Just to confirm the reply to question 15) Samples and microscopy tests might be more effective as tests rather than a MRI scan to establish clinical vascular dementia? It is stated that "After post mortem, the chemical fixation and tissue decomposition may have various effects on the brain and these techniques may not be validated for use in regular medical practice". What are these various effects and what does regular medical practice mean exactly in this case?
7) What might "established" mean in "established cerebral infarction" in the absence of the mention of gliosis. The subject had no previous reported major (or noticeable minor) infarction. Perhaps it means "significant" as might be expected after such a cardiac failure?
Thanking you.
Brief Answer:
Please find detailed answer below
Detailed Answer:
Hi XXXXXX,
Thanks for writing in with updates.
1) Is 1a broncho pneumonia a classification of the most serious and severe type of bronchopneumonia? Your reply mentions the associated bacteria as "when proliferation in such quantities to cause severe pneumonia".
Pneumonia (or bronchopneumonia) severity is graded by CURB-65 score ie confusion, urea, respiration, blood pressure and age above 65 years which is a simple method. There is another slightly complicated term known as pneumonia severity index. method. There is another slightly complicated term known as pneumonia severity index. You may read more using the given link.
https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&ved=0CDcQFjAB&url=http%3A%2F%2Fwww.rmh.mh.org.au%2Fsecure%2Fdownloadfile.asp%3Ffileid%3D0000&ei=M9NlU5uRHoyjugSrn4LgCA&usg=AFQjCNFfENUbArLqHHQwzVhhRDfLuB6gUw&sig2=obw8a27usOPaTygv9bxFEw&bvm=bv.0000,d.c2E&cad=rja
2) Regarding the dosage of nitrofurantoin I recall reading that 200mg was the maximum dosage for short term acute use. Do you have an authority to cite for the referred dosage which you mention can be as high as 400mg in a previous reply? How does the urine become sterile and how is this measured?
Regarding authority on nitrofurantoin dosage in your country we have the British National Formulary and I request you to please follow the given link
http://www.evidence.nhs.uk/formulary/bnf/current/5-infections/51-antibacterial-drugs/5113-urinary-tract-infections/nitrofurantoin
Urine becomes sterile because the growth and proliferation is controlled by medications (nitrofurantoin). This is tested using urine cultures and a sterile specimen is supposed to not show growth of any organisms.
3) How do the toxins affect the heart in bronchopneumonia? Is it by forcing the necessity of more blood and so stressing the heart or another death inducing effect in this case?
Death in pneumonia is multifactorial and not due to one particular element. The toxins vary with the infective agent. There are as many types of bacteria as are toxins. These toxins cause a chemical cascade in the internal environment of our body which can mean temporarily or permanently damaging the cells in various organs and leading to multiorgan failure when the body is not able to sustain its functions, including the most essentials.
4) Can the fluid retained in the lungs known medically as consolidation and due to tissue injury be distinguished from the fluid that normally accumulates after decease by cardiac failure? Can purulence be caused by bacteria after decease?
Yes we have mainly two types of fluids based on their composition. The exudates are the fluids seen in bacterial infections and pneumonias and transudates are the ones seen in cardiac failure due to non infective causes. Purulence can be caused at any time by the bacteria.
5) Regarding the measurement of adrenalin it seems that the time frame has been exceeded for measurement making measurement impossible? If that is the case then does adrenalin produce any bodies that might still exist and can still be identified and measured after three months?
Adrenaline uptake and breakdown takes place in minutes and after certain time its not traceable in the system. It is not possible to search for any metabolites of adrenaline after three months from the day of death.
6) Just to confirm the reply to question 15) Samples and microscopy tests might be more effective as tests rather than a MRI scan to establish clinical vascular dementia? It is stated that "After post mortem, the chemical fixation and tissue decomposition may have various effects on the brain and these techniques may not be validated for use in regular medical practice". What are these various effects and what does regular medical practice mean exactly in this case?
The brain is usually preserved in a chemical environment which is much different from the natural environment in a human being. Also after death the brain stops functioning. Preservation delays decomposition and MRI appearance of brain tissue may only be partially conclusive in such a situation. Therefore a microscopic analysis can give better insight.
When a particular investigation is not satisfactorily conclusive, it cannot be applied to interpret certain conditions with authority and such findings cannot be taken for granted. Validation is required so that there is no room for ambiguity in findings.
7) What might "established" mean in "established cerebral infarction" in the absence of the mention of gliosis. The subject had no previous reported major (or noticeable minor) infarction. Perhaps it means "significant" as might be expected after such a cardiac failure?
Established brain infarction means confirmed brain tissue permanent irreversible damage. Cardiac failure is a supply failure which can have serious consequences on brain blood supply. The brain tissues are very sensitive to decrease in oxygen levels and are among the first cells in the body to get irreversibly damaged in cardiac arrest.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Please find detailed answer below
Detailed Answer:
Hi XXXXXX,
Thanks for writing in with updates.
1) Is 1a broncho pneumonia a classification of the most serious and severe type of bronchopneumonia? Your reply mentions the associated bacteria as "when proliferation in such quantities to cause severe pneumonia".
Pneumonia (or bronchopneumonia) severity is graded by CURB-65 score ie confusion, urea, respiration, blood pressure and age above 65 years which is a simple method. There is another slightly complicated term known as pneumonia severity index. method. There is another slightly complicated term known as pneumonia severity index. You may read more using the given link.
https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&ved=0CDcQFjAB&url=http%3A%2F%2Fwww.rmh.mh.org.au%2Fsecure%2Fdownloadfile.asp%3Ffileid%3D0000&ei=M9NlU5uRHoyjugSrn4LgCA&usg=AFQjCNFfENUbArLqHHQwzVhhRDfLuB6gUw&sig2=obw8a27usOPaTygv9bxFEw&bvm=bv.0000,d.c2E&cad=rja
2) Regarding the dosage of nitrofurantoin I recall reading that 200mg was the maximum dosage for short term acute use. Do you have an authority to cite for the referred dosage which you mention can be as high as 400mg in a previous reply? How does the urine become sterile and how is this measured?
Regarding authority on nitrofurantoin dosage in your country we have the British National Formulary and I request you to please follow the given link
http://www.evidence.nhs.uk/formulary/bnf/current/5-infections/51-antibacterial-drugs/5113-urinary-tract-infections/nitrofurantoin
Urine becomes sterile because the growth and proliferation is controlled by medications (nitrofurantoin). This is tested using urine cultures and a sterile specimen is supposed to not show growth of any organisms.
3) How do the toxins affect the heart in bronchopneumonia? Is it by forcing the necessity of more blood and so stressing the heart or another death inducing effect in this case?
Death in pneumonia is multifactorial and not due to one particular element. The toxins vary with the infective agent. There are as many types of bacteria as are toxins. These toxins cause a chemical cascade in the internal environment of our body which can mean temporarily or permanently damaging the cells in various organs and leading to multiorgan failure when the body is not able to sustain its functions, including the most essentials.
4) Can the fluid retained in the lungs known medically as consolidation and due to tissue injury be distinguished from the fluid that normally accumulates after decease by cardiac failure? Can purulence be caused by bacteria after decease?
Yes we have mainly two types of fluids based on their composition. The exudates are the fluids seen in bacterial infections and pneumonias and transudates are the ones seen in cardiac failure due to non infective causes. Purulence can be caused at any time by the bacteria.
5) Regarding the measurement of adrenalin it seems that the time frame has been exceeded for measurement making measurement impossible? If that is the case then does adrenalin produce any bodies that might still exist and can still be identified and measured after three months?
Adrenaline uptake and breakdown takes place in minutes and after certain time its not traceable in the system. It is not possible to search for any metabolites of adrenaline after three months from the day of death.
6) Just to confirm the reply to question 15) Samples and microscopy tests might be more effective as tests rather than a MRI scan to establish clinical vascular dementia? It is stated that "After post mortem, the chemical fixation and tissue decomposition may have various effects on the brain and these techniques may not be validated for use in regular medical practice". What are these various effects and what does regular medical practice mean exactly in this case?
The brain is usually preserved in a chemical environment which is much different from the natural environment in a human being. Also after death the brain stops functioning. Preservation delays decomposition and MRI appearance of brain tissue may only be partially conclusive in such a situation. Therefore a microscopic analysis can give better insight.
When a particular investigation is not satisfactorily conclusive, it cannot be applied to interpret certain conditions with authority and such findings cannot be taken for granted. Validation is required so that there is no room for ambiguity in findings.
7) What might "established" mean in "established cerebral infarction" in the absence of the mention of gliosis. The subject had no previous reported major (or noticeable minor) infarction. Perhaps it means "significant" as might be expected after such a cardiac failure?
Established brain infarction means confirmed brain tissue permanent irreversible damage. Cardiac failure is a supply failure which can have serious consequences on brain blood supply. The brain tissues are very sensitive to decrease in oxygen levels and are among the first cells in the body to get irreversibly damaged in cardiac arrest.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Above answer was peer-reviewed by :
Dr. Chakravarthy Mazumdar
Hello Dr XXXXXXX
Thank you for your reply and information.
You have answered most of the overview questions and I now continue if I may with a few more questions...
In one of your previous replies you mention that;
"The peak blood concentration of nitrofurantoin following an oral dose of nitrofurantoin 100 mg, is less than 1 μg/mL and may be undetectable; tissue penetration is negligible; the drug is well concentrated in the urine: 75% of the dose is rapidly metabolised by the liver, but 25% of the dose is excreted in the urine unchanged, reliably achieving levels of 200 μg/ml or more. For this reason, nitrofurantoin cannot be used to treat anything other than simple cystitis."
I note that the Post Mortem report states that cystitis was "acute" not "simple".
What does "simple" mean in this specific medical context?
From the information given above nitrofurantoin should not have been given to the deceased as the cystitis was acute not simple. Could you explain exactly why that is the case in acute conditions and what detrimental effects if any might occur?
Reply 2
Good evening Dr XXXXXXX
Just pondering another medical question and so had to send another reply.
I am considering the tests that might identify two adverse reactions to nitrofurantoin and with reference to your previous information. 1) Acute reactions such as malaise, chest discomfort etc and 2) adverse reactions produced from longer term use of nitrofurantoin such as pulmonary fibrosis.
1) If I understand correctly, if one wants to identify an adverse reaction in "acute" form having take place then liquid performance chromoatographic technique and immunochromatographic assays may be used.
a) Would those assays just establish the presence of nitrofurantoin or also that an acute adverse reaction had taken place?
b) What is a metabolite? Is this the substance that a creatinine test would identity to measure the possible nitrofurantoin accumulation level?
c) Is it possible to identify exactly what adverse reaction might have occurred in some cases? You mentioned that shortness of breath wasn't possible. What about malaise, nausea, dry coughing, chest discomfort etc or
d) Can it be stated that if a certain substance x at a certain level is found then some form of unpleasant adverse reaction is bound to follow?
e) Is interstitial pneumonitus an "acute" hyper sensitive reaction to nitrofurantoin or associated with long term induced adverse reactions? Similarly lympocytic alveolitis?
f) Is indirect cytotoxic T lympocyte (CTL) activation associated with short or long term use of nitrofurantoin? What is the specific test for this?
2) Can the oxidant toxic metabolic product of nitrofurantoin producing various inflammatory responses be responsible for both short (acute hyper sensitive ) and long term lung injury producing adverse reactions? What is the test for these oxidants?
2) In relation to more serious adverse reactions over time
a) What is the test to establish cytokines such as TNF a, IFN a, IL-6 and IL-8 to establish the presence of interstitial fibrosis?
b) What is the test to identify the specific pathogins that are targeted by the cytokines?
3) Regarding tests for kidney function and the following a) serum creatinine; b) blood urea; c) creatinine clearance and d) glomerular filtration are these tests done in combination? What distinguishes them from each other?
Thank you.
Brief Answer:
Please find detailed answers below
Detailed Answer:
Hi XXXXXX,
Thanks for writing in with updates.
What does "simple" mean in this specific medical context?
Acute is sudden onset and simple is without any other significant premorbid medical conditions which may complicate the infection. As mentioned acute is the duration of symptoms, in the deceased perhaps it was just over a few days. If not treated, an acute infection may spread to the rest or the urinary system including kidneys.
1) If I understand correctly, if one wants to identify an adverse reaction in "acute" form having take place then liquid performance chromoatographic technique and immunochromatographic assays may be used.
a) Would those assays just establish the presence of nitrofurantoin or also that an acute adverse reaction had taken place?
No, any assay will only tell us the presence of a particular chemical compound and not the consequences of the molecule.
b) What is a metabolite? Is this the substance that a creatinine test would identity to measure the possible nitrofurantoin accumulation level?
A metabolite is a breakdown product of a molecule into other molecules which can be traced to the parent molecule. A creatinine test will not identify such a metabolite of nitrofurantoin. Creatinine test measures the filtering capacity of kidneys.
c) Is it possible to identify exactly what adverse reaction might have occurred in some cases? You mentioned that shortness of breath wasn't possible. What about malaise, nausea, dry coughing, chest discomfort etc or
Adverse reactions are unpredictable and idiosyncratic reactions. They occur due to a cascade of reactions and it is very difficult to identify the magnitude of adverse reaction when such a reaction is mild in intensity. Severe reactions can be related to the time of drug intake. Basically there is tissue inflammation of various degrees as a reaction to the particular offending agent. The events occurring must be correlated and it is not the same in each patient.
d) Can it be stated that if a certain substance x at a certain level is found then some form of unpleasant adverse reaction is bound to follow?
This is known as toxicity reaction. This is a dose dependent reaction. Every molecule has a margin of toxicity and toxic levels need careful survillence.
e) Is interstitial pneumonitus an "acute" hyper sensitive reaction to nitrofurantoin or associated with long term induced adverse reactions? Similarly lympocytic alveolitis?
The interstitial lung changes are very often seen after 6 weeks after commencement of treatment and usually an outcome of long term treatment. Chronic nitrofurantoin reaction associated with T-lymphocyte alveolitis.
f) Is indirect cytotoxic T lympocyte (CTL) activation associated with short or long term use of nitrofurantoin? What is the specific test for this?
It is associated with long term use of nitrofurantoin and is not an isolated mechanism. There are other mechanisms that occur like complement activation system. No specific test is there to single out this mechanism.
2) Can the oxidant toxic metabolic product of nitrofurantoin producing various inflammatory responses be responsible for both short (acute hyper sensitive) and long term lung injury producing adverse reactions? What is the test for these oxidants?
The alteration of the injury to cells in laboratory tests in the presence of antioxidants provides evidence that nitrofurantoin causes oxidant induced lung injury.
2) In relation to more serious adverse reactions over time
a) What is the test to establish cytokines such as TNF a, IFN a, IL-6 and IL-8 to establish the presence of interstitial fibrosis?
These are researched by doing standardised laboratory tests at the biomolecular level and since these cytokines can be associated with multiple factors testing is done by inclusion or exclusion with a scientific basis.
b) What is the test to identify the specific pathogins that are targeted by the cytokines?
Transformation of lymphocytes from peripheral blood into blast-like cells in vitro in patients with certain drug eruptions in the presence of the appropriate drug has been used as a test for hypersensitivity.
3) Regarding tests for kidney function and the following a) serum creatinine; b) blood urea; c) creatinine clearance and d) glomerular filtration are these tests done in combination? What distinguishes them from each other?
These tests are done as per requirement. Serum creatinine and blood urea are basic investigations. Creatinine clearance and glomerular filtration rate are more functional investigation. The parameters evaluate differentiate the tests from each other. Blood urea and serum creatinine are present in a normal range which shows the ability of kidneys to keep these substances under control. Creatinine clearance shows the ability of kidneys to clear creatinine from blood and glomerular filtration rate is the amount of filtration that occurs in the glomerulus of kidneys.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Please find detailed answers below
Detailed Answer:
Hi XXXXXX,
Thanks for writing in with updates.
What does "simple" mean in this specific medical context?
Acute is sudden onset and simple is without any other significant premorbid medical conditions which may complicate the infection. As mentioned acute is the duration of symptoms, in the deceased perhaps it was just over a few days. If not treated, an acute infection may spread to the rest or the urinary system including kidneys.
1) If I understand correctly, if one wants to identify an adverse reaction in "acute" form having take place then liquid performance chromoatographic technique and immunochromatographic assays may be used.
a) Would those assays just establish the presence of nitrofurantoin or also that an acute adverse reaction had taken place?
No, any assay will only tell us the presence of a particular chemical compound and not the consequences of the molecule.
b) What is a metabolite? Is this the substance that a creatinine test would identity to measure the possible nitrofurantoin accumulation level?
A metabolite is a breakdown product of a molecule into other molecules which can be traced to the parent molecule. A creatinine test will not identify such a metabolite of nitrofurantoin. Creatinine test measures the filtering capacity of kidneys.
c) Is it possible to identify exactly what adverse reaction might have occurred in some cases? You mentioned that shortness of breath wasn't possible. What about malaise, nausea, dry coughing, chest discomfort etc or
Adverse reactions are unpredictable and idiosyncratic reactions. They occur due to a cascade of reactions and it is very difficult to identify the magnitude of adverse reaction when such a reaction is mild in intensity. Severe reactions can be related to the time of drug intake. Basically there is tissue inflammation of various degrees as a reaction to the particular offending agent. The events occurring must be correlated and it is not the same in each patient.
d) Can it be stated that if a certain substance x at a certain level is found then some form of unpleasant adverse reaction is bound to follow?
This is known as toxicity reaction. This is a dose dependent reaction. Every molecule has a margin of toxicity and toxic levels need careful survillence.
e) Is interstitial pneumonitus an "acute" hyper sensitive reaction to nitrofurantoin or associated with long term induced adverse reactions? Similarly lympocytic alveolitis?
The interstitial lung changes are very often seen after 6 weeks after commencement of treatment and usually an outcome of long term treatment. Chronic nitrofurantoin reaction associated with T-lymphocyte alveolitis.
f) Is indirect cytotoxic T lympocyte (CTL) activation associated with short or long term use of nitrofurantoin? What is the specific test for this?
It is associated with long term use of nitrofurantoin and is not an isolated mechanism. There are other mechanisms that occur like complement activation system. No specific test is there to single out this mechanism.
2) Can the oxidant toxic metabolic product of nitrofurantoin producing various inflammatory responses be responsible for both short (acute hyper sensitive) and long term lung injury producing adverse reactions? What is the test for these oxidants?
The alteration of the injury to cells in laboratory tests in the presence of antioxidants provides evidence that nitrofurantoin causes oxidant induced lung injury.
2) In relation to more serious adverse reactions over time
a) What is the test to establish cytokines such as TNF a, IFN a, IL-6 and IL-8 to establish the presence of interstitial fibrosis?
These are researched by doing standardised laboratory tests at the biomolecular level and since these cytokines can be associated with multiple factors testing is done by inclusion or exclusion with a scientific basis.
b) What is the test to identify the specific pathogins that are targeted by the cytokines?
Transformation of lymphocytes from peripheral blood into blast-like cells in vitro in patients with certain drug eruptions in the presence of the appropriate drug has been used as a test for hypersensitivity.
3) Regarding tests for kidney function and the following a) serum creatinine; b) blood urea; c) creatinine clearance and d) glomerular filtration are these tests done in combination? What distinguishes them from each other?
These tests are done as per requirement. Serum creatinine and blood urea are basic investigations. Creatinine clearance and glomerular filtration rate are more functional investigation. The parameters evaluate differentiate the tests from each other. Blood urea and serum creatinine are present in a normal range which shows the ability of kidneys to keep these substances under control. Creatinine clearance shows the ability of kidneys to clear creatinine from blood and glomerular filtration rate is the amount of filtration that occurs in the glomerulus of kidneys.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Above answer was peer-reviewed by :
Dr. Prasad
Dear Dr XXXXXXX
Thank you for the prompt and informative reply which I shall study and without doubt have a question to ask.
Regarding a previous reply of yours you write;
"I suppose we need to look at the complete sequence of events leading to death of the deceased and integrate the various liver, lung, heart, brain conditions and any other clinical pathology which may give us a better understanding at what you are looking for".
I can give you an outline of the clinical history of this unexpected event.
Two and half years ago my mother in her early nineties had a fall which left her immobile. She had been very independent up to then and had done her shopping, cooking light cleaning etc for herself as she wanted.
Her cognitive state seemed normal in the sense of dealing with everyday affairs though she did seem to have had a bit of a change of personality and behaviour. I thought it might be the electric pylons and the magnetic resonance which is quite an issue in the UK these days. She did convalescence and then moved to a Nursing Home.
She was also healthy for age. She had been prescribed medication for controlling blood pressure and paracetamol. When I returned home from working abroad I found the cupboards full of unopened cartons and she had not taken the medicine. She was also prescribed clopidogrel but that stopped a few years ago together with the prescription of paracetamol if I am not incorrect but may have been represcribed.
She rarely got colds or flu taking a preventative jab each year and had no history of having heart disease or a stroke.
During her last years in the Nursing Home I was informed that she was taking vitamin D for osteoporosis, paracetamol and bisoprolol for the preventative control of blood pressure. I was also informed that she suffered from diverticulitis but no medication was necessary only when it flared up.
Three months ago I received a call in the early hours of the morning. The on- call doctor informed me that there was nothing to worry about but he had been called because my mother had some chest discomfort, her blood pressure was bit up though her blood saturation level was normal and that was important he added. He asked me whether my mother was taking medication and I informed him that she had UTI and was taking an antibiotic but no medication for her chest.
He asked me whether I was of the opinion that my mother should be moved to hospital. I replied not if that was merely routine and because of the possible trauma. I asked could there be a risk of death having a chest infection and he replied that in elderly people there can be a connection between death and a chest infection and so I agreed.
Not long after that conversation an ambulance was called and after 15 or so minutes in journey my mother had a cardiac arrest and deceased either in the ambulance or the entrance of the hospital.
It seems that no CPR resuscitation was done in the ambulance or hospital though adrenalin is reported as having been administered in the ambulance. It is also stated that a cardiac arrest took place for more than 5 minutes before the ambulance arrived but this has been contradicted by several people.
An initial diagnosis of a cause of death was Urosepsis (stated in the PM report as being diagnosed by a microscopy test a few days before the decease) though this was described as only a minor infection by medical personnel and an autopsy was done which changed the cause of death from Urosepsis to bronchopneumonia and vascular dementia. I visited my mother a few hours before the decease and she was normal and seemed in good health. I visited my mother six days before and the physical health impression was the same.
She was able to communicate and did not mention anything to do with bronchitus or UTI on these two occasions.
The UTI infection had been treated with nitrofurantoin I was later informed.
As mentioned before, the UTI condition had been reported to me four/five times before over the last two years or so and I presume an antibiotic had been given each time.
I wonder whether nitrofurantoin would have had an effect on the reported UTI condition (Urosepsis not nominated as a condition in the PM report) and cystitis is given as being acute. It seems that nitrofurantoin should only be given for simple cystitis?
Considering the facts I contacted the Pathologist and then wrote to the Coroner again for a second level request for tests and the further specialised autopsy.
I have no news of the outcome of this request yet but the interim death certificate recently received now states that the cause of death is to be ascertained and I presume that an inquest date shall soon be set to establish the facts.
The decease of my mother was unexpected and I had believe that she would make a hundred at least. Despite being so elderly she did not want to die and tried to find simple pleasures everday and a reason to be. Her phase with me had not ended and I was considering the situation, the nursing home and even home care to organise in the not too distant future so that some quality time could be salvaged in that difficult last phase.
No end phase decisions were ever discussed with me other than a simple question of whether I wished my mother to pass at home or in hospital.
As mentioned I am considering a second medical opinion and a possible further request to the Coroner and perhaps a further specialised autopsy in any event.
Thanks.
XXXXXXX
P.S. There is another question there I note. What does blood saturation level mean?
Brief Answer:
Please find detailed answer below
Detailed Answer:
Hi XXXXX,
Thanks for writing in with updates.
Medical literature says the following:
Amoxicillin or ampicillin remains the therapy of choice for susceptible enterococci and group B streptococcal infection. Nitrofurantoin is effective for the treatment of lower tract infections, including vancomycin-resistant enterococci. This agent is, however, not effective for the treatment of upper tract infection, or for infection with Klebsiella pneumoniae, P mirabilis or P aeruginosa, and should be avoided in patients with renal failure.
What does blood saturation level mean?
The red blood cells must carry sufficient oxygen through your arteries to all of your internal organs to keep you alive. Normally, when red blood cells pass through the lungs, 95%-100% of them are loaded, or "saturated," with oxygen to carry. If there is lung disease or other types of medical conditions, fewer of your red blood cells may be carrying their usual load of oxygen, and your oxygen saturation might be lower than 95%.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Please find detailed answer below
Detailed Answer:
Hi XXXXX,
Thanks for writing in with updates.
Medical literature says the following:
Amoxicillin or ampicillin remains the therapy of choice for susceptible enterococci and group B streptococcal infection. Nitrofurantoin is effective for the treatment of lower tract infections, including vancomycin-resistant enterococci. This agent is, however, not effective for the treatment of upper tract infection, or for infection with Klebsiella pneumoniae, P mirabilis or P aeruginosa, and should be avoided in patients with renal failure.
What does blood saturation level mean?
The red blood cells must carry sufficient oxygen through your arteries to all of your internal organs to keep you alive. Normally, when red blood cells pass through the lungs, 95%-100% of them are loaded, or "saturated," with oxygen to carry. If there is lung disease or other types of medical conditions, fewer of your red blood cells may be carrying their usual load of oxygen, and your oxygen saturation might be lower than 95%.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Above answer was peer-reviewed by :
Dr. Prasad
Good afternoon Dr XXXXXXX
Thanks for the quick reply and information.
Do you know what the renal functionality of a 95 year old person might expected to be on the creatinine level of measurement?
If the medication nitofurantoin is not effective ( but in a person with no renal functionality below creatinine 40 ml/min) because the upper tract is infected or the condition is "acute" does that mean it can do damage or is just ineffective?
Another question is; I have just read the "Plavix" (clopidogrel) leaflet advice and it states two necessary conditions for the prescription. the patient should have both
1) Atherothrombosis
and
2) a) Had a previous heart attack or
b) stroke or
c) peripheral heart disease or
d) unstable angina (myo cardial infarction)
My medical concern is for the prescription to a person who does not have thrombosis (a medical examination revealing "extensive atheroma with several sites of minor stenosis.... no thrombosis" ) or any of the other conditions (a-d) stated to be necessary for prescription.
Is the concern justified?
Thanks.
Brief Answer:
Please find detailed answer below
Detailed Answer:
Hi XXXXX,
Thanks for writing in with updates.
Do you know what the renal functionality of a 95 year old person might expected to be on the creatinine level of measurement?
In a sample of 608 patients in the 95 – 100 years ages group (women) the following results for creatinine clearance were obtained.
Less than 10 mL/min 6 patients
10 to less than 30 mL/min 368 patients
30 to less than 50 mL/min 197 patients
More than 50 mL/min 37 patients
Average Creatinine Clearance in age group 95 – 100 years (women) is 28 +1.5 mL/min
Please fine reference article in given link
http://osteoporosislongtermcare.ca/2011/PDFs/Estimation-of-Creatinine-Clearance-nov2001.pdf
If the medication nitofurantoin is not effective ( but in a person with no renal functionality below creatinine 40 ml/min) because the upper tract is infected or the condition is "acute" does that mean it can do damage or is just ineffective?
It means that the nitrofurantoin concentration in such patients with acute upper tract infection, the medication is in suboptimal concentrations for control of infection.
Another question is; I have just read the "Plavix" (clopidogrel) leaflet advice and it states two necessary conditions for the prescription. the patient should have both
1) Atherothrombosis
and
2) a) Had a previous heart attack or
b) stroke or
c) peripheral heart disease or
d) unstable angina (myo cardial infarction)
My medical concern is for the prescription to a person who does not have thrombosis (a medical examination revealing "extensive atheroma with several sites of minor stenosis.... no thrombosis" ) or any of the other conditions (a-d) stated to be necessary for prescription.
Is the concern justified?
Plavix prevents the platetlets in blood from clotting abnormally and leading to thrombosis and is a prescription medicine used to treat people who have any of the following:
chest pain due to heart problems, poor circulation in their legs (peripheral arterial disease), heart attack, a stroke
Any bleeding tendency must be ruled out is a patient on Plavix. There need not be thrombosis to start a person on Plavix. The tendency to form thrombosis is sufficient reason to start the medication.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Please find detailed answer below
Detailed Answer:
Hi XXXXX,
Thanks for writing in with updates.
Do you know what the renal functionality of a 95 year old person might expected to be on the creatinine level of measurement?
In a sample of 608 patients in the 95 – 100 years ages group (women) the following results for creatinine clearance were obtained.
Less than 10 mL/min 6 patients
10 to less than 30 mL/min 368 patients
30 to less than 50 mL/min 197 patients
More than 50 mL/min 37 patients
Average Creatinine Clearance in age group 95 – 100 years (women) is 28 +1.5 mL/min
Please fine reference article in given link
http://osteoporosislongtermcare.ca/2011/PDFs/Estimation-of-Creatinine-Clearance-nov2001.pdf
If the medication nitofurantoin is not effective ( but in a person with no renal functionality below creatinine 40 ml/min) because the upper tract is infected or the condition is "acute" does that mean it can do damage or is just ineffective?
It means that the nitrofurantoin concentration in such patients with acute upper tract infection, the medication is in suboptimal concentrations for control of infection.
Another question is; I have just read the "Plavix" (clopidogrel) leaflet advice and it states two necessary conditions for the prescription. the patient should have both
1) Atherothrombosis
and
2) a) Had a previous heart attack or
b) stroke or
c) peripheral heart disease or
d) unstable angina (myo cardial infarction)
My medical concern is for the prescription to a person who does not have thrombosis (a medical examination revealing "extensive atheroma with several sites of minor stenosis.... no thrombosis" ) or any of the other conditions (a-d) stated to be necessary for prescription.
Is the concern justified?
Plavix prevents the platetlets in blood from clotting abnormally and leading to thrombosis and is a prescription medicine used to treat people who have any of the following:
chest pain due to heart problems, poor circulation in their legs (peripheral arterial disease), heart attack, a stroke
Any bleeding tendency must be ruled out is a patient on Plavix. There need not be thrombosis to start a person on Plavix. The tendency to form thrombosis is sufficient reason to start the medication.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Above answer was peer-reviewed by :
Dr. Chakravarthy Mazumdar
Good morning Dr XXXXXXX
Thank you for your informative reply.
In relation to a previous reply and the question/answer
"Is it possible to identify exactly what adverse reaction might have occurred in some cases? You mentioned that shortness of breath wasn't possible. What about malaise, nausea, dry coughing, chest discomfort etc or
Adverse reactions are unpredictable and idiosyncratic reactions. They occur due to a cascade of reactions and it is very difficult to identify the magnitude of adverse reaction when such a reaction is mild in intensity. Severe reactions can be related to the time of drug intake. Basically there is tissue inflammation of various degrees as a reaction to the particular offending agent. The events occurring must be correlated and it is not the same in each patient".
Just to check and specify again, if the possible adverse reactions to establish are for example malaise, chest discomfort, breathing problems etc then after the test to identify nitrofurantoin is the appropriate test an antibody reaction blood test so as to confirm the hyper sensitive reaction? Would a urine test be useful too?
If so has research yet been able to correlate different antibody reactions to specific adverse reactions if that is the expected complex reaction of the human body?
Another two questions.
1) In cardiac failure what is the medical guideline for the use of adrenalin and electro cardiac intervention and specifically....
a) Can they be used together in succession?
b) Is there a reason not to use electro cardiac intervention but only adrenalin?
2) Is it possible to establish the number of heart attacks (terminal) within a time frame for example an hour? Perhaps from the number of cerebral infarcts?
Thanks.
Thank you for your informative reply.
In relation to a previous reply and the question/answer
"Is it possible to identify exactly what adverse reaction might have occurred in some cases? You mentioned that shortness of breath wasn't possible. What about malaise, nausea, dry coughing, chest discomfort etc or
Adverse reactions are unpredictable and idiosyncratic reactions. They occur due to a cascade of reactions and it is very difficult to identify the magnitude of adverse reaction when such a reaction is mild in intensity. Severe reactions can be related to the time of drug intake. Basically there is tissue inflammation of various degrees as a reaction to the particular offending agent. The events occurring must be correlated and it is not the same in each patient".
Just to check and specify again, if the possible adverse reactions to establish are for example malaise, chest discomfort, breathing problems etc then after the test to identify nitrofurantoin is the appropriate test an antibody reaction blood test so as to confirm the hyper sensitive reaction? Would a urine test be useful too?
If so has research yet been able to correlate different antibody reactions to specific adverse reactions if that is the expected complex reaction of the human body?
Another two questions.
1) In cardiac failure what is the medical guideline for the use of adrenalin and electro cardiac intervention and specifically....
a) Can they be used together in succession?
b) Is there a reason not to use electro cardiac intervention but only adrenalin?
2) Is it possible to establish the number of heart attacks (terminal) within a time frame for example an hour? Perhaps from the number of cerebral infarcts?
Thanks.
Brief Answer:
Please find detailed answer below
Detailed Answer:
Hi XXXXXX,
Thanks for writing in with updates.
In relation to a previous reply and the question/answer
"Is it possible to identify exactly what adverse reaction might have occurred in some cases? You mentioned that shortness of breath wasn't possible. What about malaise, nausea, dry coughing, chest discomfort etc or
Adverse reactions are unpredictable and idiosyncratic reactions. They occur due to a cascade of reactions and it is very difficult to identify the magnitude of adverse reaction when such a reaction is mild in intensity. Severe reactions can be related to the time of drug intake. Basically there is tissue inflammation of various degrees as a reaction to the particular offending agent. The events occurring must be correlated and it is not the same in each patient".
Just to check and specify again, if the possible adverse reactions to establish are for example malaise, chest discomfort, breathing problems etc then after the test to identify nitrofurantoin is the appropriate test an antibody reaction blood test so as to confirm the hyper sensitive reaction? Would a urine test be useful too?
Acute adverse hypersensitivity reactions usually appear in the first or second instances of drug intake. The confirmation may be done by doing skin hypersensitivity tests but are not done frequently. Very limited research has been done in this area. There has been a study published in British Journal of Dermatology in 2005 on adverse reactions due to multiple drugs. This study has used techniques that are not widely standardised. An urine test is not useful in this.
If so has research yet been able to correlate different antibody reactions to specific adverse reactions if that is the expected complex reaction of the human body?
Drug hypersensitivity is a very big and complex area of research. It is such that the skin tests help to replicate the possibility of adverse reactions when the drug is injected below the skin in very small quantities. Then signs of local inflammation are looked for. Correlating different antibody reactions to specific adverse reactions is still unexplored.
1) In cardiac failure what is the medical guideline for the use of adrenalin and electro cardiac intervention and specifically....
a) Can they be used together in succession?
At first attempts are made to diagnose a shockable from a non shockable heart rhythm. Shockable rhythms are ventricular fibrillation and ventricular tachycardia with no cardiac output and these benefit the most from a electro cardiac intervention along with adrenalin subsequently. There are defined protocols for sequencing and administering these procedures.
b) Is there a reason not to use electro cardiac intervention but only adrenalin?
Non shockable cardiac rhythms like asystole and pulseless electrical activity in the heart are not responsive to defibrillation.
2) Is it possible to establish the number of heart attacks (terminal) within a time frame for example an hour? Perhaps from the number of cerebral infarcts?
It is not possible to establish the number of heart attacks from the number of cerebral infarcts.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Please find detailed answer below
Detailed Answer:
Hi XXXXXX,
Thanks for writing in with updates.
In relation to a previous reply and the question/answer
"Is it possible to identify exactly what adverse reaction might have occurred in some cases? You mentioned that shortness of breath wasn't possible. What about malaise, nausea, dry coughing, chest discomfort etc or
Adverse reactions are unpredictable and idiosyncratic reactions. They occur due to a cascade of reactions and it is very difficult to identify the magnitude of adverse reaction when such a reaction is mild in intensity. Severe reactions can be related to the time of drug intake. Basically there is tissue inflammation of various degrees as a reaction to the particular offending agent. The events occurring must be correlated and it is not the same in each patient".
Just to check and specify again, if the possible adverse reactions to establish are for example malaise, chest discomfort, breathing problems etc then after the test to identify nitrofurantoin is the appropriate test an antibody reaction blood test so as to confirm the hyper sensitive reaction? Would a urine test be useful too?
Acute adverse hypersensitivity reactions usually appear in the first or second instances of drug intake. The confirmation may be done by doing skin hypersensitivity tests but are not done frequently. Very limited research has been done in this area. There has been a study published in British Journal of Dermatology in 2005 on adverse reactions due to multiple drugs. This study has used techniques that are not widely standardised. An urine test is not useful in this.
If so has research yet been able to correlate different antibody reactions to specific adverse reactions if that is the expected complex reaction of the human body?
Drug hypersensitivity is a very big and complex area of research. It is such that the skin tests help to replicate the possibility of adverse reactions when the drug is injected below the skin in very small quantities. Then signs of local inflammation are looked for. Correlating different antibody reactions to specific adverse reactions is still unexplored.
1) In cardiac failure what is the medical guideline for the use of adrenalin and electro cardiac intervention and specifically....
a) Can they be used together in succession?
At first attempts are made to diagnose a shockable from a non shockable heart rhythm. Shockable rhythms are ventricular fibrillation and ventricular tachycardia with no cardiac output and these benefit the most from a electro cardiac intervention along with adrenalin subsequently. There are defined protocols for sequencing and administering these procedures.
b) Is there a reason not to use electro cardiac intervention but only adrenalin?
Non shockable cardiac rhythms like asystole and pulseless electrical activity in the heart are not responsive to defibrillation.
2) Is it possible to establish the number of heart attacks (terminal) within a time frame for example an hour? Perhaps from the number of cerebral infarcts?
It is not possible to establish the number of heart attacks from the number of cerebral infarcts.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Above answer was peer-reviewed by :
Dr. Chakravarthy Mazumdar
Dear Dr XXXXXXX
Thank you for your reply.
If possible I would be grateful if you could give the exact medical literature reference authority you referred to (preferably internet) for;
1) The dermatological possibility to identify an adverse reaction (Is the authority the British Journal of Dermatology 2005 as mentioned?) and any other useful references. Now three months have passed..
2) a) The non responsiveness of electro cardiac treatment to a certain type of heart failure. I suppose in ordinary man's language there is is a difference between a faint heart rhythm situation and a major heart attack. Is a person having a major heart attack leading to death in a pulseless state during that time? Electro shock intervention should be used in any event I presume in such a case unless there is a CPR/DNR decision to make
b) Administration and sequencing protocol for defibrillation.
3) The dosage of adrenalin that can be used to help a faint heart in danger of passing. Is there any danger at that point between an elderly person's heart (95) and the effect of the adrenalin shock as it reaches it? How long does it take for the adrenalin to reach the heart? Where is the adrenalin injected? Directly into the heart or another part of the body?
Although adrenaline may not be traceable in itself after the short time frame described is there another tracer substance that might have been consequentially produced three months ago but is identifiable now?
If a patient is suspected to be experiencing an acute hyper reaction to nitrofurantoin such as chest discomfort, breathing problems and malaise/anxiety what should be done to alleviate the symptoms?
Thanks.
Thank you for your reply.
If possible I would be grateful if you could give the exact medical literature reference authority you referred to (preferably internet) for;
1) The dermatological possibility to identify an adverse reaction (Is the authority the British Journal of Dermatology 2005 as mentioned?) and any other useful references. Now three months have passed..
2) a) The non responsiveness of electro cardiac treatment to a certain type of heart failure. I suppose in ordinary man's language there is is a difference between a faint heart rhythm situation and a major heart attack. Is a person having a major heart attack leading to death in a pulseless state during that time? Electro shock intervention should be used in any event I presume in such a case unless there is a CPR/DNR decision to make
b) Administration and sequencing protocol for defibrillation.
3) The dosage of adrenalin that can be used to help a faint heart in danger of passing. Is there any danger at that point between an elderly person's heart (95) and the effect of the adrenalin shock as it reaches it? How long does it take for the adrenalin to reach the heart? Where is the adrenalin injected? Directly into the heart or another part of the body?
Although adrenaline may not be traceable in itself after the short time frame described is there another tracer substance that might have been consequentially produced three months ago but is identifiable now?
If a patient is suspected to be experiencing an acute hyper reaction to nitrofurantoin such as chest discomfort, breathing problems and malaise/anxiety what should be done to alleviate the symptoms?
Thanks.
Brief Answer:
Please find detailed answer below
Detailed Answer:
Hi XXXXX,
Thanks for writing in with updates.
1) The dermatological possibility to identify an adverse reaction (Is the authority the British Journal of Dermatology 2005 as mentioned?) and any other useful references. Now three months have passed..
There is no dermatological possibility to know any possibility of an adverse reaction in the deceased. References are as follows.
Dtsch Med Wochenschr. 1972 Feb 18;97(7):256-7.
[Anaphylactic shock following oral administration of nitrofurantoin and demonstration of reagins using the heterologous intracutaneous test (Prausnitz-Küstner)]. [Article in German]
Tykal P, Wilms H.
The usefulness of skin tests to prove drug hypersensitivity
K. Lammintausta. British Journal of Dermatology, Volume 152, Issue 5, pages 968–974, May 2005.
2) a) The non responsiveness of electro cardiac treatment to a certain type of heart failure. I suppose in ordinary man's language there is a difference between a faint heart rhythm situation and a major heart attack. Is a person having a major heart attack leading to death in a pulseless state during that time? Electro shock intervention should be used in any event I presume in such a case unless there is a CPR/DNR decision to make
The cause of heart attack is abnormal electrical activity in the heart. This abnormal rhythm may be correctable or non correctable, what we call shoackable or non shockable. Even to know this, a defibrillator must be connected and then a decision to be made.
b) Administration and sequencing protocol for defibrillation.
Please find the protocol followed for defibrillation and CPR in the UK as given in the link below
https://www.resus.org.uk/pages/als.pdf
3) The dosage of adrenalin that can be used to help a faint heart in danger of passing. Is there any danger at that point between an elderly person's heart (95) and the effect of the adrenalin shock as it reaches it? How long does it take for the adrenalin to reach the heart? Where is the adrenalin injected? Directly into the heart or another part of the body?
Adrenaline is given as 1 mg initial dose intravenously and repeated subsequently as mentioned in the protocol. There is no danger of adrenaline shock in a 95 years old patient. It reaches the heart in few seconds. Intracardiac administration should be used only during open cardiac massage or when other routes of administration are unavailable.
Although adrenaline may not be traceable in itself after the short time frame described is there another tracer substance that might have been consequentially produced three months ago but is identifiable now?
I am sorry there is no such substance which might help to trace adrenaline at this time.
If a patient is suspected to be experiencing an acute hyper reaction to nitrofurantoin such as chest discomfort, breathing problems and malaise/anxiety what should be done to alleviate the symptoms?
The best treatment is to call medical services and go to the emergency room at the earliest. Till then try and keep the patient calm and make them take deep breaths. Loosen any tight clothing be alert in case the patient is collapsing.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Please find detailed answer below
Detailed Answer:
Hi XXXXX,
Thanks for writing in with updates.
1) The dermatological possibility to identify an adverse reaction (Is the authority the British Journal of Dermatology 2005 as mentioned?) and any other useful references. Now three months have passed..
There is no dermatological possibility to know any possibility of an adverse reaction in the deceased. References are as follows.
Dtsch Med Wochenschr. 1972 Feb 18;97(7):256-7.
[Anaphylactic shock following oral administration of nitrofurantoin and demonstration of reagins using the heterologous intracutaneous test (Prausnitz-Küstner)]. [Article in German]
Tykal P, Wilms H.
The usefulness of skin tests to prove drug hypersensitivity
K. Lammintausta. British Journal of Dermatology, Volume 152, Issue 5, pages 968–974, May 2005.
2) a) The non responsiveness of electro cardiac treatment to a certain type of heart failure. I suppose in ordinary man's language there is a difference between a faint heart rhythm situation and a major heart attack. Is a person having a major heart attack leading to death in a pulseless state during that time? Electro shock intervention should be used in any event I presume in such a case unless there is a CPR/DNR decision to make
The cause of heart attack is abnormal electrical activity in the heart. This abnormal rhythm may be correctable or non correctable, what we call shoackable or non shockable. Even to know this, a defibrillator must be connected and then a decision to be made.
b) Administration and sequencing protocol for defibrillation.
Please find the protocol followed for defibrillation and CPR in the UK as given in the link below
https://www.resus.org.uk/pages/als.pdf
3) The dosage of adrenalin that can be used to help a faint heart in danger of passing. Is there any danger at that point between an elderly person's heart (95) and the effect of the adrenalin shock as it reaches it? How long does it take for the adrenalin to reach the heart? Where is the adrenalin injected? Directly into the heart or another part of the body?
Adrenaline is given as 1 mg initial dose intravenously and repeated subsequently as mentioned in the protocol. There is no danger of adrenaline shock in a 95 years old patient. It reaches the heart in few seconds. Intracardiac administration should be used only during open cardiac massage or when other routes of administration are unavailable.
Although adrenaline may not be traceable in itself after the short time frame described is there another tracer substance that might have been consequentially produced three months ago but is identifiable now?
I am sorry there is no such substance which might help to trace adrenaline at this time.
If a patient is suspected to be experiencing an acute hyper reaction to nitrofurantoin such as chest discomfort, breathing problems and malaise/anxiety what should be done to alleviate the symptoms?
The best treatment is to call medical services and go to the emergency room at the earliest. Till then try and keep the patient calm and make them take deep breaths. Loosen any tight clothing be alert in case the patient is collapsing.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Above answer was peer-reviewed by :
Dr. Prasad
Hello Dr Viney,
Thank you for the reply
1. You write, "There is no dermatological possibility to know any possibility of an adverse reaction in the deceased". Is that because three months have passed?
2. I presume that a "major heart attack" requires immediate cardio-electric intervention?
3. I suppose there must a reactive substance to the introduction of adrenalin in the blood? Perhaps research can find it?
4. Would you give adrenalin to a very old person just because the heart rhythm is faint or the person appears to be drifting off? Couldn't it cause a dangerous shock to the heart? A heart that hadn't arrested? Another doctor had the opinion that this wasn't advisable in that situation and that this might cause a cardiac arrest? So the very old patient has to be in cardiac arrest in that case? Is it a question of medical opinion or is there clear right and wrong procedure in specified situations such as the elderly or people with pre-existing heart conditions?
5. What would hospital emergency do to a person in a hyper sensitive adverse reactive state to nitrofurantoin? How long does it last and can the symptoms return again if untreated within a short time frame (for example 3-4 hours)? Couldn't such an adverse reaction reaction to that medication, breathing difficulties malaise and anxiety actually induce a heart attack in an elderly person?
Thanks
Brief Answer:
Please find detailed answer below
Detailed Answer:
Hi XXXXXX,
Thanks for writing in with updates.
1. You write, "There is no dermatological possibility to know any possibility of an adverse reaction in the deceased". Is that because three months have passed?
When we talk of dermatological tests, its difficult to perform it on the deceased.
2. I presume that a "major heart attack" requires immediate cardio-electric intervention?
When a major heart attack is suspected, always electro cardiac intervention is the first choice to get the heart back to its normal rhythm. If its non shockable then the other components of resuscitation are given more importance.
3. I suppose there must a reactive substance to the introduction of adrenalin in the blood? Perhaps research can find it?
Adrenaline is also normally produced in the body in small quantities. As discussed earlier the adrenaline acts on receptors and that is where the changes take place. This happens very fast and then the adrenaline is degraded. You might be right that higher research needs to be done.
4. Would you give adrenalin to a very old person just because the heart rhythm is faint or the person appears to be drifting off? Couldn't it cause a dangerous shock to the heart? A heart that hadn't arrested? Another doctor had the opinion that this wasn't advisable in that situation and that this might cause a cardiac arrest? So the very old patient has to be in cardiac arrest in that case? Is it a question of medical opinion or is there clear right and wrong procedure in specified situations such as the elderly or people with pre-existing heart conditions?
Use of adrenaline is to be with caution in elderly and patients that have:
Hyperthyroidism
Diabetes
Hypertension
Cardiovascular disease (angina, arrhythmias)
Stroke
Prostatic enlargement
Rapid intravenous infusion can cause death from cerebrovascular hemorrhage or cardiac arrhythmias.
5. What would hospital emergency do to a person in a hyper sensitive adverse reactive state to nitrofurantoin? How long does it last and can the symptoms return again if untreated within a short time frame (for example 3-4 hours)? Couldn't such an adverse reaction reaction to that medication, breathing difficulties malaise and anxiety actually induce a heart attack in an elderly person?
The first priorities in any hypersensitivity reaction are to prevent life threatening events. This can initially mean the respiratory and cardiac systems. If the heart is functioning properly then the patient may be treated with steroids and antihistamines. Further the patient is put on monitoring and then a systematic management protocol is followed. Such reactions last a few minutes and may not appear if the offending agent is stopped immediately. The heart attack is one of the last events in the situation of an adverse reaction. If an acute adverse reaction had to take place, it would have occurred within the first two occasions of the medication. A chronic adverse reaction will not induce a heart attack if the patient was stable.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Please find detailed answer below
Detailed Answer:
Hi XXXXXX,
Thanks for writing in with updates.
1. You write, "There is no dermatological possibility to know any possibility of an adverse reaction in the deceased". Is that because three months have passed?
When we talk of dermatological tests, its difficult to perform it on the deceased.
2. I presume that a "major heart attack" requires immediate cardio-electric intervention?
When a major heart attack is suspected, always electro cardiac intervention is the first choice to get the heart back to its normal rhythm. If its non shockable then the other components of resuscitation are given more importance.
3. I suppose there must a reactive substance to the introduction of adrenalin in the blood? Perhaps research can find it?
Adrenaline is also normally produced in the body in small quantities. As discussed earlier the adrenaline acts on receptors and that is where the changes take place. This happens very fast and then the adrenaline is degraded. You might be right that higher research needs to be done.
4. Would you give adrenalin to a very old person just because the heart rhythm is faint or the person appears to be drifting off? Couldn't it cause a dangerous shock to the heart? A heart that hadn't arrested? Another doctor had the opinion that this wasn't advisable in that situation and that this might cause a cardiac arrest? So the very old patient has to be in cardiac arrest in that case? Is it a question of medical opinion or is there clear right and wrong procedure in specified situations such as the elderly or people with pre-existing heart conditions?
Use of adrenaline is to be with caution in elderly and patients that have:
Hyperthyroidism
Diabetes
Hypertension
Cardiovascular disease (angina, arrhythmias)
Stroke
Prostatic enlargement
Rapid intravenous infusion can cause death from cerebrovascular hemorrhage or cardiac arrhythmias.
5. What would hospital emergency do to a person in a hyper sensitive adverse reactive state to nitrofurantoin? How long does it last and can the symptoms return again if untreated within a short time frame (for example 3-4 hours)? Couldn't such an adverse reaction reaction to that medication, breathing difficulties malaise and anxiety actually induce a heart attack in an elderly person?
The first priorities in any hypersensitivity reaction are to prevent life threatening events. This can initially mean the respiratory and cardiac systems. If the heart is functioning properly then the patient may be treated with steroids and antihistamines. Further the patient is put on monitoring and then a systematic management protocol is followed. Such reactions last a few minutes and may not appear if the offending agent is stopped immediately. The heart attack is one of the last events in the situation of an adverse reaction. If an acute adverse reaction had to take place, it would have occurred within the first two occasions of the medication. A chronic adverse reaction will not induce a heart attack if the patient was stable.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Above answer was peer-reviewed by :
Dr. Chakravarthy Mazumdar
Hello Dr Vinek,
Thank you for your reply and information.
I am just going to scan the notes given so far and ask for clarification where necessary.
The notes mention;
"The peak blood concentration of nitrofurantoin following an oral dose of nitrofurantoin 100 mg, is less than 1 μg/mL and may be undetectable; tissue penetration is negligible; the drug is well concentrated in the urine: 75% of the dose is rapidly metabolised by the liver, but 25% of the dose is excreted in the urine unchanged, reliably achieving levels of 200 μg/ml or more. For this reason, nitrofurantoin cannot be used to treat anything other than simple cystitis".
What is simple cystitis?
Could you explain in more simple terms what this section means?
Thanks.
Brief Answer:
Please find detailed answer below
Detailed Answer:
Hi XXXXX,
Thanks for writing in with updates.
To be able to fight the bacteria in the urinary tract, the medication (nitrofurantoin) should be present in a concentration at which the bacteria might be eliminated. This concentration is mentioned as 200 μg/ml or more which makes nitrofurantoin specifically the drug of first choice.
Simple cystitis is a urinary infection confined to the bladder. If the infection reaches the kidneys then we call it pyelonehritis.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Please find detailed answer below
Detailed Answer:
Hi XXXXX,
Thanks for writing in with updates.
To be able to fight the bacteria in the urinary tract, the medication (nitrofurantoin) should be present in a concentration at which the bacteria might be eliminated. This concentration is mentioned as 200 μg/ml or more which makes nitrofurantoin specifically the drug of first choice.
Simple cystitis is a urinary infection confined to the bladder. If the infection reaches the kidneys then we call it pyelonehritis.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Above answer was peer-reviewed by :
Dr. Chakravarthy Mazumdar
Good morning Dr XXXXXXX
Still trying to follow the medical reasoning ...
Some more questions.
1. What does "simple" mean in simple cystitis?
2. What does "acute" mean in acute cystitis?
3. What does the measurement code "ug/ml" mean in 200 ug/ml?
4. It is stated, "This concentration is mentioned as 200 μg/ml or more which makes nitrofurantoin specifically the drug of first choice".
a) Does "first choice" refer to comparable concentration levels of other antibiotics on the market?
b) Your reply states that in a bladder infection such unchanged high concentration is effective for neutralising the bacteria that is causing the UTI infection if I am not wrong. The factor of age I suppose has to be taken into account and the problem of kidney impairment so that the concentration figure of 200 ug/ml is not applicable when there is kidney impairment and nitrofurantoin accumulation? This might be pharmaceutical type advertising without specifying other influencing factors? Other medication might be preferable in this case as the nitrofurantoin accumulation in the kidneys is less? That is if nitrofurantoin passes through the kidneys before the antibiotic reaches the bladder?
5) In a previous reply you mention that nitrofurantoin is suitable for treating the upper urinary tract? What is the urinary tract? Is the bladder the upper part of the tract?
6) You state; "....but 25% of the dose is excreted in the urine unchanged, reliably achieving levels of 200 μg/ml or more. For this reason, nitrofurantoin cannot be used to treat anything other than simple cystitis". This seems to imply that the concentration of 200 ug/ml (or its usual high concentration level in comparison with other medications) is only suitable for simple cystitis and therefore not "acute" cystitis? Is that interpretation correct? If so, why is the medication not suitable for acute cystitis?
7) Without clarification I understand "simple" to mean long term usage. A dose of 100g a day of nitrofurantoin would be too high even for young people perhaps and 50g would be preferred?
8) Is "Urosepsis" similar to "cystitis"?
9) In 1989 if I am not incorrect the medication "nitrofurantoin" was completely withdrawn from the US market because of testing/brand name issues to resolve. Do you know anything about that and what happened and the effect on marketing and medical research thereafter?
Thanks
Brief Answer:
Please find detailed answer below
Detailed Answer:
Hi XXXXX,
Thanks for writing in with updates.
1. What does "simple" mean in simple cystitis?
The word simple means uncomplicated. In simple cystitis, the infection is confined to the urinary bladder. There are no clinical features to say that the infection has involved the kidneys.
2. What does "acute" mean in acute cystitis?
Acute is a term used to indicate a sudden onset. The other type of infection is long standing and termed chronic.
3. What does the measurement code "ug/ml" mean in 200 ug/ml?
It is microgram per millilitre and is the concentration of the medication.
4. It is stated, "This concentration is mentioned as 200 μg/ml or more which makes nitrofurantoin specifically the drug of first choice".
a) Does "first choice" refer to comparable concentration levels of other antibiotics on the market?
The first-choice agents for treatment of uncomplicated acute cystitis in women include nitrofurantoin monohydrate/macrocrystals, trimethoprim-sulfamethoxazole (TMP-SMX), or fosfomycin. Beta-lactam antibiotics may be used when other recommended agents cannot be used.
b) Your reply states that in a bladder infection such unchanged high concentration is effective for neutralising the bacteria that is causing the UTI infection if I am not wrong. The factor of age I suppose has to be taken into account and the problem of kidney impairment so that the concentration figure of 200 ug/ml is not applicable when there is kidney impairment and nitrofurantoin accumulation? This might be pharmaceutical type advertising without specifying other influencing factors? Other medication might be preferable in this case as the nitrofurantoin accumulation in the kidneys is less? That is if nitrofurantoin passes through the kidneys before the antibiotic reaches the bladder?
There are regular updates and guidelines made to chalk out protocols for the treatment of medical conditions based on clinical studies. One of the latest among them is given in the link below.
http://cid.oxfordjournals.org/content/52/5/561.full
You may please go through the article and find that there is more than pharmaceutical advertising when recommending a certain medication.
5) In a previous reply you mention that nitrofurantoin is suitable for treating the upper urinary tract? What is the urinary tract? Is the bladder the upper part of the tract?
I think that I have mentioned it as nitrofurantoin is suitable for treating LOWER urinary tract especially simple cystitis. Sorry if there was a confusion on that. The urinary tract consists of the kidneys, ureters, urinary bladder and urethra. The bladder is in the lower urinary tract.
6) You state; "....but 25% of the dose is excreted in the urine unchanged, reliably achieving levels of 200 μg/ml or more. For this reason, nitrofurantoin cannot be used to treat anything other than simple cystitis". This seems to imply that the concentration of 200 ug/ml (or its usual high concentration level in comparison with other medications) is only suitable for simple cystitis and therefore not "acute" cystitis? Is that interpretation correct? If so, why is the medication not suitable for acute cystitis?
Let me clarify that acute is meant to indicate the duration of symptoms. In acute cystitis, the patient was free from the problem till recently. So an uncomplicated acute cystitis still remains “simple” because it is confined to the bladder. On the other hand complicated UTIs are defined as UTIs that are associated with metabolic disorders, that are secondary to anatomic or functional abnormalities that impair urinary tract drainage, or that involve unusual pathogens (eg, yeast), which increases the risk of therapeutic failure
7) Without clarification I understand "simple" to mean long term usage. A dose of 100g a day of nitrofurantoin would be too high even for young people perhaps and 50g would be preferred?;
Simple is a term reserved when there are no complications as mentioned earlier. The doses are in milligrams and nor grams. Recent literature says
nitrofurantoin monohydrate/macrocrystals 100 mg orally twice daily for 5-7days or
nitrofurantoin macrocrystals 50-100 mg orally four times daily for 7days
8) Is "Urosepsis" similar to "cystitis"?
Urosepsis implies clinically evident severe infection of the urinary tract with features consistent with systemic inflammatory response syndrome. It may be associated with multi-organ dysfunction, hypo-perfusion or hypo-tension.
9) In 1989 if I am not incorrect the medication "nitrofurantoin" was completely withdrawn from the US market because of testing/brand name issues to resolve. Do you know anything about that and what happened and the effect on marketing and medical research thereafter?
I do not attach much importance to the complete withdrawal of nirtiofurantoin in the US as it is a medication which is in use for urinary infections since 1953 and even till date being used in treatment as we have seen from the several articles published.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Please find detailed answer below
Detailed Answer:
Hi XXXXX,
Thanks for writing in with updates.
1. What does "simple" mean in simple cystitis?
The word simple means uncomplicated. In simple cystitis, the infection is confined to the urinary bladder. There are no clinical features to say that the infection has involved the kidneys.
2. What does "acute" mean in acute cystitis?
Acute is a term used to indicate a sudden onset. The other type of infection is long standing and termed chronic.
3. What does the measurement code "ug/ml" mean in 200 ug/ml?
It is microgram per millilitre and is the concentration of the medication.
4. It is stated, "This concentration is mentioned as 200 μg/ml or more which makes nitrofurantoin specifically the drug of first choice".
a) Does "first choice" refer to comparable concentration levels of other antibiotics on the market?
The first-choice agents for treatment of uncomplicated acute cystitis in women include nitrofurantoin monohydrate/macrocrystals, trimethoprim-sulfamethoxazole (TMP-SMX), or fosfomycin. Beta-lactam antibiotics may be used when other recommended agents cannot be used.
b) Your reply states that in a bladder infection such unchanged high concentration is effective for neutralising the bacteria that is causing the UTI infection if I am not wrong. The factor of age I suppose has to be taken into account and the problem of kidney impairment so that the concentration figure of 200 ug/ml is not applicable when there is kidney impairment and nitrofurantoin accumulation? This might be pharmaceutical type advertising without specifying other influencing factors? Other medication might be preferable in this case as the nitrofurantoin accumulation in the kidneys is less? That is if nitrofurantoin passes through the kidneys before the antibiotic reaches the bladder?
There are regular updates and guidelines made to chalk out protocols for the treatment of medical conditions based on clinical studies. One of the latest among them is given in the link below.
http://cid.oxfordjournals.org/content/52/5/561.full
You may please go through the article and find that there is more than pharmaceutical advertising when recommending a certain medication.
5) In a previous reply you mention that nitrofurantoin is suitable for treating the upper urinary tract? What is the urinary tract? Is the bladder the upper part of the tract?
I think that I have mentioned it as nitrofurantoin is suitable for treating LOWER urinary tract especially simple cystitis. Sorry if there was a confusion on that. The urinary tract consists of the kidneys, ureters, urinary bladder and urethra. The bladder is in the lower urinary tract.
6) You state; "....but 25% of the dose is excreted in the urine unchanged, reliably achieving levels of 200 μg/ml or more. For this reason, nitrofurantoin cannot be used to treat anything other than simple cystitis". This seems to imply that the concentration of 200 ug/ml (or its usual high concentration level in comparison with other medications) is only suitable for simple cystitis and therefore not "acute" cystitis? Is that interpretation correct? If so, why is the medication not suitable for acute cystitis?
Let me clarify that acute is meant to indicate the duration of symptoms. In acute cystitis, the patient was free from the problem till recently. So an uncomplicated acute cystitis still remains “simple” because it is confined to the bladder. On the other hand complicated UTIs are defined as UTIs that are associated with metabolic disorders, that are secondary to anatomic or functional abnormalities that impair urinary tract drainage, or that involve unusual pathogens (eg, yeast), which increases the risk of therapeutic failure
7) Without clarification I understand "simple" to mean long term usage. A dose of 100g a day of nitrofurantoin would be too high even for young people perhaps and 50g would be preferred?;
Simple is a term reserved when there are no complications as mentioned earlier. The doses are in milligrams and nor grams. Recent literature says
nitrofurantoin monohydrate/macrocrystals 100 mg orally twice daily for 5-7days or
nitrofurantoin macrocrystals 50-100 mg orally four times daily for 7days
8) Is "Urosepsis" similar to "cystitis"?
Urosepsis implies clinically evident severe infection of the urinary tract with features consistent with systemic inflammatory response syndrome. It may be associated with multi-organ dysfunction, hypo-perfusion or hypo-tension.
9) In 1989 if I am not incorrect the medication "nitrofurantoin" was completely withdrawn from the US market because of testing/brand name issues to resolve. Do you know anything about that and what happened and the effect on marketing and medical research thereafter?
I do not attach much importance to the complete withdrawal of nirtiofurantoin in the US as it is a medication which is in use for urinary infections since 1953 and even till date being used in treatment as we have seen from the several articles published.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Above answer was peer-reviewed by :
Dr. Chakravarthy Mazumdar
Good morning Dr XXXXXXX
Thank you for the detailed reply.
In a reply (1 day ago) you mention; "simple cystitis is a urinary infection confined to the bladder. If the infection reaches the kidneys then we call it pyelonehritis".
1) Is Uro-sepsis preceded by simple cystitis then pylonehritis and in effect is a more severe infection than cystitis though similar to it in pathology?
2) Is Urosepsis an infection of the kidneys?
3) In the PM report Urosepsis was originally diagnosed from a microscopy test. Though though this fact is mentioned in the introductory Clinical History section of the Post Mortem report, only acute cystitis is mentioned in the autopsy summary findings. Any comments?
ust an associated question to my last reply.
Is it possible to diagnose cystitis in a Post Mortem examination without a microscopy test?
Just another question.
Is the report of a normal blood saturation level consistent with bronchopneumonia?
Thanks.
XXXXXXX
Thank you for the detailed reply.
In a reply (1 day ago) you mention; "simple cystitis is a urinary infection confined to the bladder. If the infection reaches the kidneys then we call it pyelonehritis".
1) Is Uro-sepsis preceded by simple cystitis then pylonehritis and in effect is a more severe infection than cystitis though similar to it in pathology?
2) Is Urosepsis an infection of the kidneys?
3) In the PM report Urosepsis was originally diagnosed from a microscopy test. Though though this fact is mentioned in the introductory Clinical History section of the Post Mortem report, only acute cystitis is mentioned in the autopsy summary findings. Any comments?
ust an associated question to my last reply.
Is it possible to diagnose cystitis in a Post Mortem examination without a microscopy test?
Just another question.
Is the report of a normal blood saturation level consistent with bronchopneumonia?
Thanks.
XXXXXXX
Brief Answer:
Please find detailed answer below
Detailed Answer:
Hi XXXXX,
Thanks for writing in with updates.
1) Is Uro-sepsis preceded by simple cystitis then pylonehritis and in effect is a more severe infection than cystitis though similar to it in pathology?
Yes, first it is usually a cystitis and then when kidneys are involved, it is pyelonephritis and thereafter if the toxins affect other organ systems then it is urosepsis.
2) Is Urosepsis an infection of the kidneys?
Urosepsis is full blown infection originating in the urinary system and spreading to other areas.
3) In the PM report Urosepsis was originally diagnosed from a microscopy test. Though though this fact is mentioned in the introductory Clinical History section of the Post Mortem report, only acute cystitis is mentioned in the autopsy summary findings. Any comments?
All I can say is urosepesis is an end result of uncontrolled cystitis and happens when the toxins have spread through blood to other areas and the patient shows generalized fever and sickness.
Is it possible to diagnose cystitis in a Post Mortem examination without a microscopy test?
Yes, cystitis can be diagnosed without microscopy.
Is the report of a normal blood saturation level consistent with bronchopneumonia?
Bronchopneumonia is a condition and blood saturation is a variable, The patient can still show normal blood saturation when suffering from bronchopneumonia.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Please find detailed answer below
Detailed Answer:
Hi XXXXX,
Thanks for writing in with updates.
1) Is Uro-sepsis preceded by simple cystitis then pylonehritis and in effect is a more severe infection than cystitis though similar to it in pathology?
Yes, first it is usually a cystitis and then when kidneys are involved, it is pyelonephritis and thereafter if the toxins affect other organ systems then it is urosepsis.
2) Is Urosepsis an infection of the kidneys?
Urosepsis is full blown infection originating in the urinary system and spreading to other areas.
3) In the PM report Urosepsis was originally diagnosed from a microscopy test. Though though this fact is mentioned in the introductory Clinical History section of the Post Mortem report, only acute cystitis is mentioned in the autopsy summary findings. Any comments?
All I can say is urosepesis is an end result of uncontrolled cystitis and happens when the toxins have spread through blood to other areas and the patient shows generalized fever and sickness.
Is it possible to diagnose cystitis in a Post Mortem examination without a microscopy test?
Yes, cystitis can be diagnosed without microscopy.
Is the report of a normal blood saturation level consistent with bronchopneumonia?
Bronchopneumonia is a condition and blood saturation is a variable, The patient can still show normal blood saturation when suffering from bronchopneumonia.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Above answer was peer-reviewed by :
Dr. Prasad
Dear Dr XXXXXXX
Thank you for the reply.
How long does it take for cystitis to develop into Urosepsis if untreated?
How long does it take to reach the intermediary stage of pyelonephritis?
In your reply 4 May regarding the grading of bronchopneumonai the web reference that you gave was scrambled in the transmission. Could you send the web reference again?
Thanks.
XXXXXX
Thank you for the reply.
How long does it take for cystitis to develop into Urosepsis if untreated?
How long does it take to reach the intermediary stage of pyelonephritis?
In your reply 4 May regarding the grading of bronchopneumonai the web reference that you gave was scrambled in the transmission. Could you send the web reference again?
Thanks.
XXXXXX
Brief Answer:
Please find detailed answers below
Detailed Answer:
Hi XXXXX,
Thanks for writing in with updates.
How long does it take for cystitis to develop into Urosepsis if untreated?
Cystitis can progress to urosepsis in few days if left untreated, especially in the elderly.
How long does it take to reach the intermediary stage of pyelonephritis?
Symptoms of acute pyelonephritis usually develop over hours or over the course of a day but may not occur at the same time. In chronic pyelonephritis the symptoms may develop over a period of weeks to months mainly due to lower urinary tract obstruction.
In your reply 4 May regarding the grading of bronchopneumonai the web reference that you gave was scrambled in the transmission. Could you send the web reference again?
www.rmh.mh.org.au/secure/downloadfile.asp?fileid=0000
Regards,
Dr Vivek
Please find detailed answers below
Detailed Answer:
Hi XXXXX,
Thanks for writing in with updates.
How long does it take for cystitis to develop into Urosepsis if untreated?
Cystitis can progress to urosepsis in few days if left untreated, especially in the elderly.
How long does it take to reach the intermediary stage of pyelonephritis?
Symptoms of acute pyelonephritis usually develop over hours or over the course of a day but may not occur at the same time. In chronic pyelonephritis the symptoms may develop over a period of weeks to months mainly due to lower urinary tract obstruction.
In your reply 4 May regarding the grading of bronchopneumonai the web reference that you gave was scrambled in the transmission. Could you send the web reference again?
www.rmh.mh.org.au/secure/downloadfile.asp?fileid=0000
Regards,
Dr Vivek
Above answer was peer-reviewed by :
Dr. Chakravarthy Mazumdar
Good morning Dr XXXXXXX
Thank you for the reply.
According to the Beers Report 2012 “here may be cases in which the healthcare provider determines that a drug on the list is the only reasonable alternative (e.g., end-of-life or palliative care).
Any comment on the human and legal context of possible bio-medical ethical decisions/ protocol and the decisional process of the "health care provider"?
XXXXXXX
Thank you for the reply.
According to the Beers Report 2012 “here may be cases in which the healthcare provider determines that a drug on the list is the only reasonable alternative (e.g., end-of-life or palliative care).
Any comment on the human and legal context of possible bio-medical ethical decisions/ protocol and the decisional process of the "health care provider"?
XXXXXXX
Brief Answer:
Please find detailed answer below
Detailed Answer:
Hi XXXXXX,
Thanks for writing in with updates.
The term health care provider refers to a broad spectrum of individuals who are authorised to provide adequate XXXXXXX provisions to the people seeking it. Under federal regulations, a "health care provider" is defined as: a doctor of medicine or osteopathy, podiatrist, dentist, chiropractor, clinical psychologist, optometrist, nurse practitioner, nurse-midwife, or a clinical social worker who is authorized to practice by the State and performing within the scope of their practice as defined by State law, or a Christian Science practitioner. A health care provider also is any provider from whom the University or the employee's group health plan will accept medical certification to substantiate a claim for benefits.
I found an article detailing “Ethical and Legal Implications of Managed Care” and I suggest you too read the same to have a more clear perspective to the query raised by you. I feel the author has dealt with the topic in a clear manner. I agree to his views.
Please find the article using link given
http://www.drrichardhall.com/ethical.htm
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Please find detailed answer below
Detailed Answer:
Hi XXXXXX,
Thanks for writing in with updates.
The term health care provider refers to a broad spectrum of individuals who are authorised to provide adequate XXXXXXX provisions to the people seeking it. Under federal regulations, a "health care provider" is defined as: a doctor of medicine or osteopathy, podiatrist, dentist, chiropractor, clinical psychologist, optometrist, nurse practitioner, nurse-midwife, or a clinical social worker who is authorized to practice by the State and performing within the scope of their practice as defined by State law, or a Christian Science practitioner. A health care provider also is any provider from whom the University or the employee's group health plan will accept medical certification to substantiate a claim for benefits.
I found an article detailing “Ethical and Legal Implications of Managed Care” and I suggest you too read the same to have a more clear perspective to the query raised by you. I feel the author has dealt with the topic in a clear manner. I agree to his views.
Please find the article using link given
http://www.drrichardhall.com/ethical.htm
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Above answer was peer-reviewed by :
Dr. Chakravarthy Mazumdar
Hello Dr XXXXXXX
Thank you for your reply and information.
My medical questions today are;
Is there any reason why there seems to be no research on identifying individuated antibodies produced by the adverse acute effects of nitrofurantoin such as breathing problems or chills as opposed to fever for example? Presumably the nitrofurantoin antibodies won't be just generic but possible to individuate in a laboratory and so possible to identify post mortem?
If for example there is a breathing problem symptom and it is hypothosised to have originated from an adverse reaction of nitrofurantoin what procedure might a medical researcher use to establish a link between that problem and the antibiotic medication?
Referring to breathing problems again and your reply 29 April.
1. Do interstitial pneumonitus and lymphocytic alveolitis refer to acute hyper sensitivity from short term dosage of nitrofurantoin or can the clinical conditions only be induced from a longer term dosage (in the elderly)?
2. Can the possible excess production of oxidants as a consequence of taking nitrofurantoin be a) consequential on a short term dosage and b) can the resulting inflammatory response ( perhaps only in this case (b) ) from longer term use) be responsible for a "friable"/soft condition of a part of the lung?
You might like to know why I am asking these specific questions? This is because I am wondering whether I could interest a medical researcher/ group to do a micro-specialised research project.
Just one more related question today if I may
Referring to your replies 29 April (point 3) and 5 May point 1f...
1. It seems that in both bronchopneumonia and interstitial fibrosis, cytokines such as TNF-alpha are secreted to destroy pathogens and can be responsible for a reactive inflammation in the lung? The reactive inflammation and the similar cytokines are reasons why there can be a misdiagnosis of bronchopneumonia?
2. Another mechanism to induce the production of cytokines in interstitial fibrosis is stated as "complement activation/indirect cytoxic T lympocyte (CTL) activation".
In the reply 5 May 1f and regarding indirect cytoxic T lympocyte (CTL) activation, it is stated that there is no specific test to identify this mechanism.
Is that a possible research question?
Just one more question before the day is over...
The 1-aminohydantoin (AHD) metabolite of nitrofurantoin can be traced to its parent molecule and is a sign of its presence.
Are all the metabolites of nitrofurantoin known and identifiable by assay tests?
If not the case how do you look for new metabolites? How did the metabolite AHD become known and then subject to testing and identification?
How do establish the concentration of nitrofurantoin? The quantity of antibodies for example?
Thanks.
Thank you for your reply and information.
My medical questions today are;
Is there any reason why there seems to be no research on identifying individuated antibodies produced by the adverse acute effects of nitrofurantoin such as breathing problems or chills as opposed to fever for example? Presumably the nitrofurantoin antibodies won't be just generic but possible to individuate in a laboratory and so possible to identify post mortem?
If for example there is a breathing problem symptom and it is hypothosised to have originated from an adverse reaction of nitrofurantoin what procedure might a medical researcher use to establish a link between that problem and the antibiotic medication?
Referring to breathing problems again and your reply 29 April.
1. Do interstitial pneumonitus and lymphocytic alveolitis refer to acute hyper sensitivity from short term dosage of nitrofurantoin or can the clinical conditions only be induced from a longer term dosage (in the elderly)?
2. Can the possible excess production of oxidants as a consequence of taking nitrofurantoin be a) consequential on a short term dosage and b) can the resulting inflammatory response ( perhaps only in this case (b) ) from longer term use) be responsible for a "friable"/soft condition of a part of the lung?
You might like to know why I am asking these specific questions? This is because I am wondering whether I could interest a medical researcher/ group to do a micro-specialised research project.
Just one more related question today if I may
Referring to your replies 29 April (point 3) and 5 May point 1f...
1. It seems that in both bronchopneumonia and interstitial fibrosis, cytokines such as TNF-alpha are secreted to destroy pathogens and can be responsible for a reactive inflammation in the lung? The reactive inflammation and the similar cytokines are reasons why there can be a misdiagnosis of bronchopneumonia?
2. Another mechanism to induce the production of cytokines in interstitial fibrosis is stated as "complement activation/indirect cytoxic T lympocyte (CTL) activation".
In the reply 5 May 1f and regarding indirect cytoxic T lympocyte (CTL) activation, it is stated that there is no specific test to identify this mechanism.
Is that a possible research question?
Just one more question before the day is over...
The 1-aminohydantoin (AHD) metabolite of nitrofurantoin can be traced to its parent molecule and is a sign of its presence.
Are all the metabolites of nitrofurantoin known and identifiable by assay tests?
If not the case how do you look for new metabolites? How did the metabolite AHD become known and then subject to testing and identification?
How do establish the concentration of nitrofurantoin? The quantity of antibodies for example?
Thanks.
Brief Answer:
Please find detailed answer below
Detailed Answer:
Hi XXXXX,
Thanks for writing in with updates.
1. Do interstitial pneumonitus and lymphocytic alveolitis refer to acute hyper sensitivity from short term dosage of nitrofurantoin or can the clinical conditions only be induced from a longer term dosage (in the elderly)?
Interstitial pneumonitis and lymphocytic alveolitis are usually manesfestations from long term use of nitrofurantoin.
2. Can the possible excess production of oxidants as a consequence of taking nitrofurantoin be a) consequential on a short term dosage and b) can the resulting inflammatory response ( perhaps only in this case (b) ) from longer term use) be responsible for a "friable"/soft condition of a part of the lung?
The imbalance between oxidants and anti oxidants happens over a period of time and long term use. The end result of such a continuous oxidant antioxidant imbalance may lead to a friable lung on prolonged effects.
1. It seems that in both bronchopneumonia and interstitial fibrosis, cytokines such as TNF-alpha are secreted to destroy pathogens and can be responsible for a reactive inflammation in the lung? The reactive inflammation and the similar cytokines are reasons why there can be a misdiagnosis of bronchopneumonia?
They are slightly different , in bronchopneumonia there is lung inflammation due to bacterial growth and lung injury due to interstitial fibrosis is easily differentiated from that due to pneumonia in most cases. The chemical responsible for inflammatory response might be same but the triggers are different.
2. Another mechanism to induce the production of cytokines in interstitial fibrosis is stated as "complement activation/indirect cytoxic T lympocyte (CTL) activation".
In the reply 5 May 1f and regarding indirect cytoxic T lympocyte (CTL) activation, it is stated that there is no specific test to identify this mechanism.
Is that a possible research question?
The complement system is a multi step process in the immune mechanism. A lot of research has been done and is still continuing in the direction. Most of the research is at the micro level and involves many disease conditions. So a test to study complement system in a single entity like interstitial fibrosis may still take time.
The 1-aminohydantoin (AHD) metabolite of nitrofurantoin can be traced to its parent molecule and is a sign of its presence.
Are all the metabolites of nitrofurantoin known and identifiable by assay tests?
Nitrofurantoin is a synthetic nitrofuran derivative which is produced by the condensation of 5-Nitro-2-furaldehyde with 1-aminohydantoin
If not the case how do you look for new metabolites? How did the metabolite AHD become known and then subject to testing and identification?
How do establish the concentration of nitrofurantoin? The quantity of antibodies for example?
Research has been done to study polyclonal antibodies to a derivative of 1-aminohydantoin (AHD) and development of an indirect competitive ELISA for the detection of nitrofurantoin residue in water. This is mainly to see the residues of nitrofurantoin in drinking water for animals.
Please find more information from link given
http://www.ncbi.nlm.nih.gov/pubmed/0000
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Please find detailed answer below
Detailed Answer:
Hi XXXXX,
Thanks for writing in with updates.
1. Do interstitial pneumonitus and lymphocytic alveolitis refer to acute hyper sensitivity from short term dosage of nitrofurantoin or can the clinical conditions only be induced from a longer term dosage (in the elderly)?
Interstitial pneumonitis and lymphocytic alveolitis are usually manesfestations from long term use of nitrofurantoin.
2. Can the possible excess production of oxidants as a consequence of taking nitrofurantoin be a) consequential on a short term dosage and b) can the resulting inflammatory response ( perhaps only in this case (b) ) from longer term use) be responsible for a "friable"/soft condition of a part of the lung?
The imbalance between oxidants and anti oxidants happens over a period of time and long term use. The end result of such a continuous oxidant antioxidant imbalance may lead to a friable lung on prolonged effects.
1. It seems that in both bronchopneumonia and interstitial fibrosis, cytokines such as TNF-alpha are secreted to destroy pathogens and can be responsible for a reactive inflammation in the lung? The reactive inflammation and the similar cytokines are reasons why there can be a misdiagnosis of bronchopneumonia?
They are slightly different , in bronchopneumonia there is lung inflammation due to bacterial growth and lung injury due to interstitial fibrosis is easily differentiated from that due to pneumonia in most cases. The chemical responsible for inflammatory response might be same but the triggers are different.
2. Another mechanism to induce the production of cytokines in interstitial fibrosis is stated as "complement activation/indirect cytoxic T lympocyte (CTL) activation".
In the reply 5 May 1f and regarding indirect cytoxic T lympocyte (CTL) activation, it is stated that there is no specific test to identify this mechanism.
Is that a possible research question?
The complement system is a multi step process in the immune mechanism. A lot of research has been done and is still continuing in the direction. Most of the research is at the micro level and involves many disease conditions. So a test to study complement system in a single entity like interstitial fibrosis may still take time.
The 1-aminohydantoin (AHD) metabolite of nitrofurantoin can be traced to its parent molecule and is a sign of its presence.
Are all the metabolites of nitrofurantoin known and identifiable by assay tests?
Nitrofurantoin is a synthetic nitrofuran derivative which is produced by the condensation of 5-Nitro-2-furaldehyde with 1-aminohydantoin
If not the case how do you look for new metabolites? How did the metabolite AHD become known and then subject to testing and identification?
How do establish the concentration of nitrofurantoin? The quantity of antibodies for example?
Research has been done to study polyclonal antibodies to a derivative of 1-aminohydantoin (AHD) and development of an indirect competitive ELISA for the detection of nitrofurantoin residue in water. This is mainly to see the residues of nitrofurantoin in drinking water for animals.
Please find more information from link given
http://www.ncbi.nlm.nih.gov/pubmed/0000
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Above answer was peer-reviewed by :
Dr. Chakravarthy Mazumdar
Good morning Drr XXXXXXX
Thank you for the reply and information.
Regarding "How do you establish the concentration of nitrofurantoin? The quantity of antibodies for example?" and your reply below;
"Research has been done to study polyclonal antibodies to a derivative of 1-aminohydantoin (AHD) and development of an indirect competitive ELISA for the detection of nitrofurantoin residue in water. This is mainly to see the residues of nitrofurantoin in drinking water for animals".
I suppose that the various possible assay tests will indicate the dosage of nitrofurantoin? Which is the most effective and state of the art assay now? What is an "assay" exactly? What is a metabolite in relation to a parent molecule? A copy of it for some reason? Are there many different metabolites connected to many different molecules? What does "derivative" of 1-aminohydantoin (AHD) mean, the unique metabolite of just one parent molecule called 1-aminohydantoin? ? What does "polyclonal" mean in "polyclonal antibodies"?
Thanks.
XXXXXX
Thank you for the reply and information.
Regarding "How do you establish the concentration of nitrofurantoin? The quantity of antibodies for example?" and your reply below;
"Research has been done to study polyclonal antibodies to a derivative of 1-aminohydantoin (AHD) and development of an indirect competitive ELISA for the detection of nitrofurantoin residue in water. This is mainly to see the residues of nitrofurantoin in drinking water for animals".
I suppose that the various possible assay tests will indicate the dosage of nitrofurantoin? Which is the most effective and state of the art assay now? What is an "assay" exactly? What is a metabolite in relation to a parent molecule? A copy of it for some reason? Are there many different metabolites connected to many different molecules? What does "derivative" of 1-aminohydantoin (AHD) mean, the unique metabolite of just one parent molecule called 1-aminohydantoin? ? What does "polyclonal" mean in "polyclonal antibodies"?
Thanks.
XXXXXX
Brief Answer:
Please find detailed answer below
Detailed Answer:
Hi XXXXXX,
Thanks for writing in with updates.
I know of two tests which can indicate the presence of nitrofurantoin residue.
The cELISA Competitive Enzyme-Linked Immunosorbent Assay test which I shared with you earlier in the day.
Immunochromatographic assay for rapid detection of 1-Aminohydantoin in urine specimens
Both the above tests detect 1-aminohydantoin by which the presence of nitrofurantoin can be confirmed.
The immunochromatography assay can detect with a visual detection limit of 10 ng mL−1 and high specificity.
The cELISA can detect levels of 0.2 ppb.
The Immunochromatography is easier and recent than the cELISA from the references that I have.
An assay is the determination of the content or quality of a particular substance.
The term metabolite is usually restricted to small molecule which form from a bigger molecule and not essentially a copy of it.
1-AHD and 5-Nitro-2-furaldehyde are condensed to form nitrofurantoin.
Derivative means derived from. Nitrofurantoin is derived from 1-AHD and hence its derivative.
Polyclonal means consisting of or derived from many clones and in this context from many clones of B cell lineage.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Please find detailed answer below
Detailed Answer:
Hi XXXXXX,
Thanks for writing in with updates.
I know of two tests which can indicate the presence of nitrofurantoin residue.
The cELISA Competitive Enzyme-Linked Immunosorbent Assay test which I shared with you earlier in the day.
Immunochromatographic assay for rapid detection of 1-Aminohydantoin in urine specimens
Both the above tests detect 1-aminohydantoin by which the presence of nitrofurantoin can be confirmed.
The immunochromatography assay can detect with a visual detection limit of 10 ng mL−1 and high specificity.
The cELISA can detect levels of 0.2 ppb.
The Immunochromatography is easier and recent than the cELISA from the references that I have.
An assay is the determination of the content or quality of a particular substance.
The term metabolite is usually restricted to small molecule which form from a bigger molecule and not essentially a copy of it.
1-AHD and 5-Nitro-2-furaldehyde are condensed to form nitrofurantoin.
Derivative means derived from. Nitrofurantoin is derived from 1-AHD and hence its derivative.
Polyclonal means consisting of or derived from many clones and in this context from many clones of B cell lineage.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Above answer was peer-reviewed by :
Dr. Chakravarthy Mazumdar
Good afternoon Dr XXXXXXX
Thanks for the prompt reply and information.
I note from one of your earlier replies the mention of liquid performance chromatographic technique which is I believe is now superseded by "the cELISA Competitive Enzyme-Linked Immunosorbent Assay test and Immunochromatographic assay for rapid detection of 1-Aminohydantoin in urine specimens".
Another question I would like to ask is whether you have contacts (or would like to find inter-state medical links) in Britain and maybe at a teaching University Hospital who might be interested in doing research on the detection of interstitial fibrosis etc and the possible adverse effects of nitrofurantoin in the short and long term? A micro-project for a Professor and a few students?
The conditions of this on-line service don't disallow such a service but merely protect themselves legally from liability.
I shall try to persuade the Coroner for further PM investigative second level confirmation tests of bronchopneumonia/vascular dementia but such details as discussed in our exchange seem possibly not to be within the remit as cause of death. My mother is still in the mortuary. Or you might know private Medical Consultant/researchers to recommend? I am from the XXXXXXX UK area but a teaching hospital outside the area would be okay too?
Thanks again.
XXXXXX
Brief Answer:
Please find detailed answer below
Detailed Answer:
Hi XXXXX,
Thanks for writing in with updates.
I do not have any contacts in XXXXXXX or surrounding area who I can suggest to do a research study in the area concerning nitrofurantoin and interstitial lung diseases.
However, I can surely give you details of a doctor who has been doing research in this field at West Middlesex University Hospital, Isleworth, Middlesex, London,
Contact details are:
Dr Yasser Madani, Department of Respiratory Medicine, West Middlesex University Hospital, Isleworth, Middlesex, London,
TW7 6AF, UK. Tel: +44 (0)208 560 2121 ext 5337 Fax: +44 (0)208 321 5581 E-mail: YYYY@YYYY
He has recently published an article on Nitrofurantoin-induced lung disease and prophylaxis of urinary tract infections. Link to the article is given below.
http://www.thepcrj.org/journ/aop/pcrj-2012-02-0032-R2.pdf
I suppose if you really think a second PM is essential then please have a detailed discussion with the Coroner putting your views in to perspective.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Please find detailed answer below
Detailed Answer:
Hi XXXXX,
Thanks for writing in with updates.
I do not have any contacts in XXXXXXX or surrounding area who I can suggest to do a research study in the area concerning nitrofurantoin and interstitial lung diseases.
However, I can surely give you details of a doctor who has been doing research in this field at West Middlesex University Hospital, Isleworth, Middlesex, London,
Contact details are:
Dr Yasser Madani, Department of Respiratory Medicine, West Middlesex University Hospital, Isleworth, Middlesex, London,
TW7 6AF, UK. Tel: +44 (0)208 560 2121 ext 5337 Fax: +44 (0)208 321 5581 E-mail: YYYY@YYYY
He has recently published an article on Nitrofurantoin-induced lung disease and prophylaxis of urinary tract infections. Link to the article is given below.
http://www.thepcrj.org/journ/aop/pcrj-2012-02-0032-R2.pdf
I suppose if you really think a second PM is essential then please have a detailed discussion with the Coroner putting your views in to perspective.
Hope your query is answered.
Do write back if you have any doubts.
Regards,
Dr Vivek
Above answer was peer-reviewed by :
Dr. Chakravarthy Mazumdar
Answered by
Get personalised answers from verified doctor in minutes across 80+ specialties
