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 Sterile Pyuria – significant or not? Could this warrant further research?

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Andi2016

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PostSubject: Sterile Pyuria – significant or not? Could this warrant further research?   Sun May 22, 2016 2:51 pm

Sterile Pyuria – significant or not?

Most of us with IC/PBS symptoms show white blood cells (leucocytes), aka pus cells, in our urine. If there is no foreign invader in the urinary tract, why would the body keep sending pus cells there? Despite what’s currently believed and accepted about white blood cells in urine, wouldn’t it help to be looking into why they are there? Could any number of white blood cells in the urine of symptomatic people be something that deserves more attention and research?

A little bit of background about white blood cells and the currently accepted threshold. When testing urine samples, lab technicians (or their automated machines), abide by a universal threshold (established in 1928) to determine if these pus cells are linked to infection or not.

The threshold was first set by Dukes after studying 300 asymptomatic males and females. He concluded that a count of 10 or more white blood cells/mm3 is considered ‘abnormal’. If there are 9 white blood cells or less, the urine is considered ‘normal’. This threshold has since been repeatedly refuted by research teams who have criticised the technique used in this study and those that followed and repeated Dukes’ critical mistake.

Unfortunately, labs routinely ignore elevated counts of pus cells in a urine sample if the culture doesn’t produce a PURE growth of a SINGLE KNOWN urinary pathogen. Hence, the term ‘sterile pyuira’. This means you have pus cells in your urine, but the tests haven’t been able to identify bacteria responsible that fits their existing criteria (ie type of species, number of species and colony count), so therefore nothing’s wrong with you. Absence of proof is not proof of absence! Could the delay in GPs treating symptomatic patients for possible infection, based on the above lab criteria, allow unidentified bacteria to become established into a chronic embedded biofilm/intracellular infection state, which is then almost impossible to diagnose and even harder to treat? We know biofilm/intracellular infection of the urinary tract is absolutely possible according to research in the US by Scott Hultgren’s team (Hultgren S., 2013).

Another important thing about pus cells as an indication of infections is how long they survive once outside the bladder. Studies have shown that white blood cells die off quickly, decreasing to 60% in the first 2 hours when stored at room temperature, and decreasing to 80% in the first 2 hours when refrigerated (Khan S., 2008) This means by the time the average sample gets to the lab, it’s no longer accurately reflecting the true numbers of white blood cells by a long shot.

My own example: I tried for several days to flush my UTI through with water. I ended up producing a very diluted sample at my doctor’s office. This sample wasn’t collected by the courier until the following afternoon and then did not arrive at the lab until over 24 hours after it was first produced at the clinic. My test highlighted elevated pus cells, but no significant growth, so therefore it was ignored by the lab and the doctor. The same with the second test. And so on, and so on, and so on…

Information found online says the following about white blood cells found in urine:

Sterile pyuria is the presence of elevated numbers of white cells (>10 white cells/mm3) in urine which appears sterile using standard culture techniques.

• Sterile pyuria is not an uncommon laboratory finding.
• Sterile pyuria is often found in female patients with symptoms of urinary tract infection (UTI). However, these results may be misleading for various reasons:
- Standard laboratory culture conditions may not be optimal for growth of atypical organisms.
- Laboratory may not report significant growth either because it was not a single organism or a recognised urinary pathogen.
- Fewer than 100,000 colony-forming units (cfu) per mL reported - eg, it may be that urine was diluted by high fluid intake or an organism may be slow-growing. Studies have shown that approximately half of women presenting with symptoms and counts of 100-10,000 cfu/mL have genuine bladder infections.
• The presence of pyuria increases the significance of a low bacterial count in the urine.
• Cell count per high power field is inaccurate and use of a counting chamber or similar gives more accurate results.

So my questions are:
1) Do white blood cells in urine of symptomatic people warrant further research?

2) Could ANY NUMBER of white blood cells in urine be worth exploring further as a diagnostic measure?

3) Should elevated white blood cells accompanied by a finding of no growth, no significant growth, or mixed growth of no significance, actually be significant?

4) How can we seriously use white blood cells as an indication of infection in the current approach, knowing that their lifespan outside the bladder is so short lived and the samples take so long to reach the lab and be tested?
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barjammar

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PostSubject: Sterile Pyuria - Significant or not   Thu Jun 02, 2016 12:47 pm

Thank you for a thoughtful letter.  In answer to your four questions... Yes, Yes, Yes and Yes (Immediate microscopy or transport in a validated preservative separate from the culture is required).
I have asked Dr Volikova and our master's students to look into the points you have raised.  I am searching for a way to ABSOLUTELY EXCLUDE an infectious cause of cases of IC-BPS.  So we are validating old standards for detecting various agents.  I enjoyed seeing Scott Hultgren's Youtube video at the ICS conference 2015.  Not directly related to IC-BPS but pleasing to see real science being done on the way bacteria might stick to the wall of the bladder.
Cool
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Andi2016

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PostSubject: Re: Sterile Pyuria – significant or not? Could this warrant further research?   Fri Jun 03, 2016 7:39 am

Thanks for the youtube interview. That’s Alan Wolfe asking Scott Hultgren questions in the second half. Alan Wolfe and Linda Braubaker's team have discovered the female urinary microbiota (FUM) which Scott Hulgren sounds excited about in that interview. http://www.europeanurology.com/article/S0302-2838(15)00206-7/fulltext/-sterile-urine-and-the-presence-of-bacteria

Since the discovery of FUM, can existing lab testing techniques/criteria for detecting UTIs still hold up? Is this what you mean by validating old standards for detecting various agents? When I first came across this article, I sent it (with some questions) to a couple of lab microbiologists I’d been trying to communicate with. They wouldn't have a bar of it and didn’t want to discuss the findings further. Why??

Scott Hultgren’s popular published papers are focused on intracellular bacteria communities (IBC) in those with recurrent UTIs, which seems to be his main area of interest. However, on the website for Center for Women's Infectious Disease Research (cWIDR), which he is a Director, IC/PBS is listed as an infectious disease under their study. http://biomed21.wustl.edu/ircs/cwidr

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Andi2016

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PostSubject: Re: Sterile Pyuria – significant or not? Could this warrant further research?   Fri Jun 03, 2016 10:47 am

This is the paper the widely accepted understanding about WBCs is based on. It has been criticised that in this study Dukes used the mean and not the median to summarise the data. Other researchers have since argued the significance of the current threshold hat distinguishes between normal and abnormal.

Cuthbert Dukes – ‘Some Observations on Pyuria’.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2102297/pdf/procrsmed01186-0051.pdf


This study talks about the limitations of using pyuria as a marker for UTI because of cell loss due to storage and handling of urine samples.

‘Discrediting microscopic pyuria and leucocyte esterase as diagnostic surrogates for infection in patients with lower urinary tract symptoms: results from a clinical and laboratory evaluation.’
http://www.ncbi.nlm.nih.gov/pubmed/23305196


This study looks at the breakdown of WBCs during storage and handling and highlights the importance of microscopy at the time of collection to avoid underestimating the inflammatory response.
‘The Time Course of White Cell Destruction in urine Samples and the Necessity of Immediate Analysis’
http://www.ics.org/Abstracts/Publish/46/000300.pdf


This study talks about immediate microscopy of white blood cells being an important assessment tool and experiments using boric acid to help preserve cells during transit.

‘Preservation of Urinary White Cells to Enable Adoption of Microscopy of Unspun Urine for Pyuria into Ordinary Clinical Assessment Protocols of Lower Urinary Tract Symptoms’
http://www.ics.org/Abstracts/Publish/47/000156.pdf
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summerly



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PostSubject: Re: Sterile Pyuria – significant or not? Could this warrant further research?   Tue Jun 14, 2016 12:58 pm

Hi Andi2016,

Thanks for posting this. Lots of good information here. And thanks to Barjammer for the video.
I agree that pathology testing of urine needs to be re-examined. I can't even count the numbers of times I left the dr's office in agony after being told that yet another urine culture has come back negative because they are just below the cfu threshold, or been discarded because of "no significant growth" or "mixed-growth/contamination". Since I've been able to take antibiotics and hiprex, my wbc's are right down - along with the pain levels. I know that correlation does not equal causation, but for me this indicates an area that desperately needs to be fixed.
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Helen W



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PostSubject: Re: Sterile Pyuria – significant or not? Could this warrant further research?   Thu Jun 16, 2016 12:07 am

I’m so pleased to have found this forum. I was especially interested to read the comment about the need for immediate mircroscopy of urine to look for white blood cells as a marker of infection.
I have two friends who live in the Netherlands and they tell me that doctors there look under a microscope in the clinic and if they see white blood cells and a patient describes symptoms, then the diagnosis of infection is definite and you are treated with antibiotics. If they see white blood cells with no symptoms, then they assume there may be infection, but they don't necessarily treat it because the body may well be dealing with it. This all sounds so logical - and immediate microscopy seems to be common practice in the Netherlands.
I’m in Britain and it certainly doesn’t happen here! We give samples that are left in boxes in the GPs surgery and then sent to a laboratory – and I’ve no idea what condition they are then kept in. I had continual negative tests, despite getting more and more ill. After four months I was in terrible pain and really in trouble and still the tests were negative - with no-one offering any ideas about what could be wrong. I was offered no help other than ramped up pain killers and anti-depressants. I feel very fortunate to have found a specialist myself who did look under a microscope and immediately detected an infection, but my local GPs are still unconvinced despite seeing me improve so much.
How can it be so different in another country? I’d like to know what happens elsewhere.
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Andi2016

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PostSubject: Re: Sterile Pyuria – significant or not? Could this warrant further research?   Thu Jun 16, 2016 11:43 am

Helen W, that's interesting to know about GPs basing a diagnosis on white blood cells and symptoms in the Netherlands. If a common trigger for IC/PBS is an acute UTI (which you'll hear time and time again in chat rooms etc), and in the Netherlands a UTI is treated immediately based on white blood cells showing under the surgery microscope, I wonder if there's any notable difference in the number of people who go on to develop IC/PBS in that country, compared to other countries?


Summerly, this is what's disturbing about the whole process. Somewhere along the way (after a negative test or two) our symptoms are no longer relevant. The test results are given more credence than the symptoms, and that's usually the end of the story.

I remember meeting with a really nice young urologist a couple of years ago when this began. I liked him and he was respectful and didn't treat me like I was clueless. We discussed my UTI history and what had happened recently with these negative tests. He told me he'd probably diagnose me with painful bladder syndrome (PBS), but he could only do that after a cystocsopy, which he then went on to explain and then to organise a date. It was at this stage of the appointment I asked if he was interested to know what my symptoms were. He stopped, turned to look at me and said "yes, tell me about your symptoms"..... When and why did symptoms stop being relevant?






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dantheman



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PostSubject: Re: Sterile Pyuria – significant or not? Could this warrant further research?   Thu Jun 16, 2016 3:18 pm

Study shows IC possibly caused by a virus

http://www.ncbi.nlm.nih.gov/pubmed/24973060
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