Question: Dear Dr XXXXXXX

Many thanks for the reply and information given.

Most of my general questions have been answered, the idea being to gain an overview of the medical situation.

My subscription ends 26 May so I will probably find a question every day or two until then.

In a reply you write;

"Urosepsis 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 have "minor" urosepsis? What does "minor" mean? Early stages, under control of antibiotics? Can it be easily misdiagnosed as cystitis? What toxins are specifically associated with urosepsis?

Thanks again.

XXXX


Hello Dr XXXXXXX

I've contacted your colleague and I await his reply with interest.

I'll read the article link for your colleague that you gave me and will no doubt make a comment.

Thank you very much for your referral.

XXXX

Hello Dr XXXXXXX

My e-mail sent to Dr Madani was returned for technical problems? Could you check it?

Thanks.

Hello Dr XXXXXXX

I haven't heard from you for 3 days so there must be a problem..

I've checked the internet given address for Dr Madani and it is the same as the one given by yourself so I don't understand the problem. My letter should have reached him today and I hope to get a reply in the near future.

I've read the didactic article by Dr Madani and note that it is focused on longer term use of nitrofurantoin. Perhaps the shorter term adverse effects might also be of research interest though a longer term preventive use can't be ruled out I presume without doing High Resolution CT.

If I don't receive a reply from you before 26 May when my subscription expires (I suppose that I will have no reason to renew it...) I thank you for your excellent service. My XXXXX XXXXXXX e-mail address is YYYY@YYYY .

Thanking you again.

XXXXXX XXXXXXX (XXXXX)

Hello again Dr XXXXXXX

The communication got interrupted last time without saying than you but I gave you an excellent rating and comment.

I contacted Dr Madani but I haven't received a reply as yet.

You may recall that I was asking about nitrofurantoin and I also read Dr Madani's didactic article which was most useful.

I would like to ask about the possibility of extracting and testing blood post mortem.

Is it normal to have only 0.1 mL of blood for testing after five months at low temperature in the mortuary which I am told is insufficient for testing? After 1 month however the blood was 2 mL.

What does 0.1 mL mean?

Why is there less blood now than 5 months ago?

Is it still possible at 0.1 mL to test the enzyme tryptase for antibody reactions or high performance liquid chromatography for the concentration of this medication?

If not, are there any other more sensitive methods to suggest which are effective for testing nitrofurantoin at that concentration of blood?

Is it possible to test as above at the higher concentration of 2 mL?

Who are the world experts in this field?


I would much appreciate your thorough investigation as in the past of this question.

XXXXX


I would like to ask about the possibility of extracting and testing blood post mortem. Is it normal to have only 0.1 mL of blood for testing after five months at low temperature in the mortuary which I am told is insufficient for testing? After 1 month however the blood was 2 mL. What does 0.1 mL mean? Why is there less blood now than 5 months ago? Is it still possible at 0.1 mL to test the enzyme tryptase for antibody reactions or high performance liquid chromatography for the concentration of this medication? If not, are there any other more sensitive methods to suggest which are effective for testing nitrofurantoin at that concentration of blood? Is it possible to test as above at the higher concentration of 2 mL?

Hello again Dr XXXXXXX

Thanks for the reply and information.

It is not necessarily the nitrofurantoin "concentration" that I wish to test but the presence of an antibody reaction so as to establish an adverse reaction last January which was very probable in this case.

The question I suppose is how long do antibodies exist in the blood after decease? Another healthcare doctor mentioned 3 months as being okay to trace an antibody reaction. Perhaps 5 months is okay too? Perhaps the doctor was referring to another enzyme than tryptase or another more advanced and sensitive method?

Also, is it possible to use the liquid chromatography test for nitrofurantoin with blood plasma and not just urine?

If the problem is not with the amount of blood but with the time why would a doctor make such a statement? The problem of time wasn't mentioned but the quantity of blood?

I would appreciate a prompt reply if possible because I have to discuss this matter.

Thanks.

Hello Dr XXXXXXX

Thank you for your information.

I have writtten to the doctor about this and will discuss this question with you when I have a reply.

Another question concerns the doubt over a diagnosis of broncho-pneumonia made from two clinical impressions/signs.

a) The friability/fragility of one lobe.

b) purulent fluid in the lower lungs.

It seems that friability can be caused by other sources of infection other than pneumonia and fluid in the lungs is normal after a fatal cardiac arrest so I have been informed.

I visited my mother just a few hours before her decease and she was perfectly normal and she exhibited no signs of a chest infection in the days before that.

Just to check the diagnosis I asked the Coroner to do second level scientific tests - a biopsy etc but have not succeeded in this request up to now.

Given the five months that have passed since my mother's decease would a lung biopsy etc be able to confirm or not by scientific tesing the clinical impression/opinion of bronchpneumona ?

The same question might be asked of a brain tissue biopsy?

If so what tests would you recommend?

Thanks.

XXXX

Good morning Dr XXXXXXX

Thanks for the reply.

Would a blood test perhaps show up bacterial/antibody reaction to the broncho-pneumonia infection last January?

XXXXX

Hello Dr XXXXXXX

Thanks for the information.

I haven't heard from the microbiologist about the 1 mL blood question/ nitrofurantoin test yet.

I have a practical question.

Dr Madani didn't contact me.

The Coroner belives the test are not in his remit.

Time is running out now and anything is worth a try.

I would appreciate it if you could recommend another doctor (or ask your hospital for a contact in the Manchester/Lancashire UK area if possible or anywhere in the UK) who might be able to extract some blood from my mother and and tissue for a lung biopsy and mediate the nitrofurantoin/biopsy analysis.

Thanks.

XXXXX

Good afternoon Dr XXXXXXX

Thanks for the information.

I am in contact with the doctors again and hope to link some last minute research.

Do you know anything about that Swedish company test you mentioned? Is it more sensive than the standard assay tests to detect tryptase for example?

What happens in time to blood that reduces the optimum conditions for such testing?

Do the antibodies just disappear gradually? Does it depend on the blood consititution of the deceased therefore changing from person to person?

Thanks.

XXXX

Hello Dr XXXXXXX

Thanks for the information.

With regard to a possible allergic or adverse reaction to the medication nitrofurantoin is "anaphyslaxis" a common symptom/condition?

What is this condition?

What tests are available to identify this reaction/condition-anaphyslaxis?

What does this sentence mean "the appearances at the post mortem were those of bronchopneumonia and the changes I saw would not suggest anaphyslaxis".

What is the doctor specifically referring to medically when he uses the word "changes"?

Thanks

XXXXX

I'm not sure that I have another follow up question after your next reply so if I don't contact you again (which I might) thank you for your excellent and punctual service which has given me a bit of a specialised medical education helping me to deal with "medicospeak" .

Hello Dr XXXXXXX

Thanks for the reply and information.

You state, "the tryptase test is useful in knowing whether a person has had an anaphylaxis reaction".

What result specifically would give the confirmation of such a reaction? How is it measured for example? What does it measure precisely?

Thanks.

XXXXX

Hello Dr XXXXXXX

Thanks for the information.

Does anaphylactic mean an extreme allergic reaction?

For example an adverse reaction to nitrofurantoin such as chest discomfort, some respiratory distress, malaise and anxiety when becoming more elevated and distressing can then be termed medically as anaphylactic ?

So in my mother's case if there had been an anaphylactic reaction- an extreme reaction if that is correct as a description, the blood collected in March or recently taken blood after 5 months wouldn't show that particular tryptase reaction?

Is tryptase an enzyme that is a marker for antibodies? Can antibodies be detected in other ways if the tryptase is so short lived?

As far as detecting antibodies to a possible adverse reaction to nitrofurantoin is concerned I have been led to believe by various medical opinion that this may still be possible after a few months and that each individual is unique in thsi respect..

Thanks.

XXXXX

Hello Dr XXXXXXX

Thanks for the information.

Now I would like you to evaluate a diagnostic decisional process.

Please study the clinical case study below and answer (with reasons of course) why you believe scientific tests should or should not done to confirm or not the diagnostic "opinion" based on the symptoms, impressions and signs given;

The patient/the deceased was 95 at the point of death and died after a cardiac arrest. She had been physically healthy for her age.

Every few months a mild UTI infection was noted and treated with antibiotics.

The cause of death after an autopsy examination was determined as 1a bronchopneumonia (and 1b vascular dementia).

The signs of possible bronchopneumonia from the report are the firmness of the right lower lobe and its friableness.

However, the following pre-autopsy findings may be taken into account.

1) The deceased showed no signs of chest discomfort, pneumonia or bronchopneumonia in the period leading up to the day of decease.

2) No medication for a chest infection was therefore given in the week before the decease.

3) At 4 pm the day before the day of decease the next of kin reports that the deceased seemed perfectly normal.

4) Chest discomfort and breathing problems were noted in the early hours of the morning before the decease at 06.50.

5) The out-of-hours doctor at 03.00 the morning of the decease noted the following;

a) No abnormal signs were given by the stethoscope examination of the chest-no wheezing sound or harder to hear places of breathing.

b) the blood/saturation level was verbally reported at 03.00 as being normal. A later written report of the same time noted the blood/oxygen saturation level as 92% (normal is 95%-while sleeping 94% the literature consulted reports).

Given the information available should scientific testing be done - lung biopsy and blood testing to confirm or not the clinical impression of bronchopneumonia as being the primary cause of death?

Thanks.

XXXXX

Hello Dr XXXXXXX

Thanks for the infomation.

The deceased was diagnosed not only with pneumonia but with broncho-pneumonia.

What are the signs of "broncho" in bronchopneumonia?

No pus on compression of the lung was noticed and noted as such?

No signs of a chest complaint up until the early hours of the day of decease. No medication. No auscultation abnormality. Deceased appeared in good health a few hours before decease. The deceased was actually able to speak about how she felt to an extent. Blood/oxygen saturation level normal three hours before the decease.


The full clinical signs on which the opinion is based in the PM report are;

1) Larynx and trachea are remarkable.
2) Small amount of pus in the airways to the left lower lobe.
3) Firm texture to the left lower lobe though no pus on expression.
4) Oedema in the lower lobes.
5) The right lobe lower lobe shows more diffuse firmness and is very soft and friable on compression.
6) Prominent areas of purulent membrane over the base of the left lower lobe.

Which of those signs might be consistent with bronchpneumonia? Can the signs mentioned be caused by another condition -signs such as firmness or friability or the amount of fluid in the lungs mentioned?

Is the medical OPINION of the pathologist (stated as such in the PM report ) and based on one or two signs scientifically INDUBITABLE in your OPINION reaching the reasonable standard of care expected of investigative medical science without the necessity scientific clinical testing and given the information provided?

In addition to the clinical impressions revealed should a scientific test such as a lung biopsy be authorised in these clinically reported circumstances?

Thanks.

XXXXX XXXXXXX

Hello Dr XXXXXXX

re; definitive and conclusive diagnosis criteria that do not necessitate clinical scientific tests question/circumstantial findings

Thanks for the reply and information.

I would be very grateful if you could comment on.

1) Blood/oxygen saturation being normal three hours before the decease.

2) Auscultation result being normal.

3) The membrane identiflied and the normal occurance of fluid in the lungs post-fatal cardiac arrest which may have become infected. The autopsy was three weeks after the decease.


4) Can broncho-pneumonia develop from what appears to be a normal healthy state to the clinical condition itself in five and half hours or from the moment of some sort of activation/reaction? A change must have occurred in the body at about 1 am leading to decease at about 6.50 am.

and the last two important questions

5) Whether the four signs above that you mention in your reply are DEFINITIVE in the diagnosis that the cause of death was broncho-pneumonia? Could the signs be the result of another cause?

6) Are scientific tests necessary to conclude the expected steps in a scientific diagnosis that can be considered as definitive?

7) Could you specify what you mean by "the findings are circumstantial"?


What I would like to know is not whether a scientific clinical test COULD be done but whether the scientific test SHOULD be done ( perhaps because "the findings are circumstantial" as you state) as it is necessary in the scientific diagnostic process given the few clinical impressions given i.e. some fluid in the lungs, friableness of one lobe etc .

Thanks.

XXXXX XXXXXXX