Notes on this page: See about
to learn how these notes were prepared. I did not bother to make every note a complete sentence here. I hope you can tell what the speakers meant. Each of these speakers has an entry at the attendees page. I have not provided direct links from each appearance of a speakers name to their listing on the page...you can get there on your own. —Ken Smith.
Remarks with the speaker symbol  are available at the audio archive Dr. Nyberg
Mike Hennenfent
We basically try to distribute this material to the patients, we use entirely volunteer unpaid help. We get letters from patients...patient says "I turned to
this group hoping to glean information on painful condition threatening my job and causing misery at home...please can anyone answer me some questions" [to doctors]...I think that's why you're here.
Dr. Nickel
Here we are again...
In 1995 we were told by TPF there's a problem out there. NIH became convinced after that that in fact it was a problem. But we didn't know how to
define prostatitis, we didn't know the etiology, we didn't know how to do a good diagnosis, didn't know how to follow paints, but mainly did not know
how to treat the disease. NIH decided in their wisdom it was a major health care problem for men.
Last year, first Network...grewout of our feeling 6 sites was not enough...so
much out in the world, so many good researchers we could tie in with, a collaborative network. That's what's happening today. Investigaros and
researchers from Greece, Japan, Bulgaria, Russia, Germany, in this room 80 per cent of researchers who have published in the last decade are in this room.
This afternoon, will be overwhelmed (by poster presentations).
Last year, about 20 of us met, about 10 researchers, companies and patients.
what came out was much more than what we would expect, because of the enthusiasm of the people involved.
- John Krieger, published in JAMA the official consensus definition and classification of prostatitis. Was better than what we were using traditionally.
- Symptom index -- Journal of Urology 162:369-375, 1999. This is still to be validated in clinical trials, but it is a wonderful beginning.
- Published research guidelines, Urol 54:229-233, 1999. Listed priorities of treatment methods.
- A number of us doing histopathological studies, we have to talk the same language. When I'm looking at a patient, I have to be able to determine whether it compares with Krieger, Weidner. We
amalgamated and put together the two systems, have sent around to members for further advice. Manuscript on the way. [Modern up-to-date Textbook of Prostattits, Isis medical media, Oxford, 1999.
Every reference in prostatitis for last 100 years. [ISIS Medical Media, despite its name, appears not to have a website. I have the following
information: Address: 58 St Aldates Oxford Oxfordshire OX1 1ST Phone: 01865 202939 FAX: 01865 202940 E-Mail:
100306.3122@compuserve.com Info: Isis is a medical publisher of
books, journals and CD-ROMS for International markets]
We're not here for our own purpose...not own agendas,... improve our
approach to our patients with prostatitis. No field more important, this is all patient-based and patient-oriented. We must remember: the patient is a
reliable witness. To try to improve our clinical approach. what the patient tells is reliable, we have to take it as the truth, if we take that as our premise we'll accomplish a lot.
Dr. John Kusak:
(Directs research network) [works from slides]
Goals:
- to better define the condition chronic prostatitis or chronic pelvic pain syndrome
- develop techniques to aid in the diagnosis
- To characterize patients with chronic prostatitis
- to study the rtreated natural history and prognosis of patients with chronic prostatitis
Currently meetin our recruitment goals without any difficulty. Currently recruiting a control popullation, 20 at each site, and there will be a Spanish translation of the symptom index.
Future Goals:
- Expand the lab based study
- Conduct randomized, controlled clinical trials within the network in 2000
- Foster international collaboration.
Dr. Nickel
Dr. Barbalias:
Dr. John Kusak:
Dr. Nickel
Dr. John Kusak:
That's in fact one of the objectives, to compare with diagnosed patients, see if there's a difference between these two groups. That's category 4, that's going to be an important category.
Dr. Tim Moon
Dr. Nickel
Thats the reason for #3, CPPS.
?????
Dr. Nyberg
We have a very similar study on IC. Trying to define that. In addition we have a BPH study. We have a large bank of tissue, over 1000 men biopsied
multiple times. Following them and looking at their symptoms. Finally, in this fiscal year,going to start epidemioligical study of demographics of chronic
pelvic pain. I think this will be significant, havnen't put out the RFA yet.
????
Dr. Nyberg
If you feel more should be spent, let your Congressman know.
Patient "Jim "
I was deferred because I was taking antibiotics. in finding the right naieve patients. Is the Internet not a good recruiting tool?
Dr. Nickel
The first 50 patients were waiting, through the Internet. We have about 200 patients now, with about 300 in line to be assessed. Most have come from
local communities and referred from family practitioners. We're not getting most ofthe patients self-selecting themselves. Internet self selection is basically over.
Nyberg:
It's more effective if you deal with the pleople who give us money. Hennenfent can help you with that.
Dr. Richard Alexander:
[This is his scheduled presentation] What we have focused on, and interest in, the clinical burden. The man with chronic symptoms non responsive to antibiotics. That's the burden. Relapsing
symptoms, characterized by pain. If you have pain, you have prostatitis. That's how we define it, it may be 10 different diseases, these are human begins with chronic pelvic pain.
Problem of autoimmunity. Tends to be chronic relapsing. Can prostatitis be an auto-immune disease? We try to understand lymphocytes, recognize foreign
cells. This could be induced by infection. Which can serve as an adjuvant.
We look at secretions of the prostate: Can any of these proteins be antigens
for the T-cells.? If look at semen, 1/2 cc of protein from prostate as an antigen. Took T cells from blood, co cultured for 5 days, too see if
proliferated in response. Controls were tetanus and candida. Some men had a response to seminal plasma. The mean was enough different to be significant.
Normal men did not respond to seminal plasma, suggest a difference we're looking for. Some component can be an antigen. PSA may be antigen. Inflammation does not happen for no reason.
Mediated by cytokines. Secreted by immune cells. TNF alpha and IL-1beta are cytokines in rheumatoid arthritis, can find in joint fluid. Blocking TNF is a
way to improve symptoms of rheumatoid arthritis. Looked at 18 patients, median 38 years, compared to 8 controlled men, measured by ELISA, levels
were different. Levels were higher, for both cytokines. These cytokines are made by monocytes. Levels correlated strongly. Didn't correlate with white
cells in EPS. We have begun to develop this as a diagnostic test.
There are theapies that can block cytokines. One is recombinant human TNF
alpha receptor1 and heavy chain of IgG, this came right off immunex's website, they're sponsoring our trial.
Embrel. Will measure cytokine levels. Study coordinator, shamelss attempt to
recruit patiens, 50 per cent chance will get placebo.
Dr. Weidner
Dr. Alexander
We spun the cells out of the sample. Could prostatic fluid be immunosuppresive? I'm familiar that prostatic fluid may be immunosppressive. But we have not looked at that. It's a very interesting idea.
Dr. Wheeler:
Dr. Alexander
In our hands 80 to 90 per cent will have some fluid obtained. But these studies are done on semen, not EPS. Semen and ejaculate over lap in terms of materials.
Dr. Neal
Dr. Wheeler
Dr. Ruggeri
[Begins his presentation] We asked if patients may have blockage in their glands?
First, we looked at seminal volume. Prostatitis patients had significantly less
semen volume. That's one important difference.
We also measured seminal plasma protein concentrations -- no difference.
We looked at markers for what organ was the source [such as] PSA, Zinc and citric acid which indicate it came from the prostate gland, whereas if fluids
came from the seminal vesicals [you find] fructose, prostataglandin, [and] Alpha glucosidase is produced by the epidydimis.
Not statisticallysignificant different on prostate markers. There may be somedisregulation of these markers. Seminal vesicle markers were not
statiscially different. The epidydiamal marker was significantly higher in patients than controls.
We looked at cytokines: Found no difference on TNFalpha , in contrast to Dr.
Alexander's data. IL-8 was only cytokine measured that was elevated in prostatitis patients.
Dr. Shoskes
[Begins his presentation]
First focus, was to find the molecular id of unique microorganisms in men, we used ribosomal RNA id of microrganisms.
Most do not grow in culture, there are those that will not. Because all microorganisms have to make protein, they need ribosomes. There is an area
encoding the ribosome which is very well conserved. Can use molecular techniques to detect and sequence that and place it on phylogentic tree. All of our work is done on EPS.
We found, with Norman Pace of Stanford, a different degeree of micro organisms in men with prostatitis, versus controls. Do have different patterns.
Corynebacteria we find only in men with CPPS, we are in the process of validating this from banked prostate specimens, to see whether this holds true.
Fact that they are there does not prove they are the cause of illness, however..
The difference between commensual and pathogens is elicit an injury response.
As we develop more sensitive culturing, techniques, we are losing specificity as what can be a true pathogen.
We focued on injury response to areas of oxidant stress. This refers to the
presence of reactive oxygen species , which one can overcome with antioxidants. Men with CPPS, much higher level of oxidant stress in their
fluids. In men who have successful therapy through whatever means, the levels of oxidant stress drops dramatically, [but we]found no correlations between
white cells in EPS and oxidant stress. We have had some clinical success with bioflavinoids, so we are asking, what is the clinical action. We found that
treatment with bioflavinoids, have some induction of natural magnesium based sod compounds, increase in level of beta endorphins, in EPS of these men.
Whether or not improved by the therapy. If not improved, may be that mechanism of pain is completely different.
Dr. Rodney Anderson
When a patient has chronic prostatitis with bacteria, there are antibodies to certain bacteria for years. When no classic evidence of bacteria, what happens to specific immunoglobulins?
Shoskes
We haven't looked at that. Effect of bacteria may not be direct. Certain T-cell actions are only seen in autoimmunity. Presence of microrganisms may be
causing different forms of injury response, resulting in local inflammation.
Dr. Nickel
What we're doing in Kingston. We have a Canadian collaborative effort. We're looking at chlamydia, mycoplasma and anaerobes such as
cornebacteria.. Using special culture techniques. All our specimens checked with PCR. Looking for cryptic non-culturable microorganism,, using the
gastritis model. [helicobacter pylori --Ed.] Also viruses.
We'v'e had exciting news, we have identified a potential candidate of cause for
inflammation. Bug first id'd in UK this year. Cannot be cultured. Very small, impossible to culture gram-positive rod. That will soon be published. [Dr.
Nickel declines to name the bacterium despite pleas, citing the need for confidentiality prior to publication]
Prostate is a virtual microbiological jungle. Some microbial genes kept
recurring in every single patient. Only by luck we hooked up with UK group, found their markers in every prostatitis patient, in one control patient we checked did not have it.
Completed epidemiologic study of a county near Kingston, using cpps symptom index. Would have diagnosed prostatitis in 9 per cent of the men there, this is a major helath care problem.
We looked at antibiotic use., analysis on 102 patients, see how CPPS performs in a clinical trial.
Looking at afferent nerve stimulation (works on voiding symptoms)
Using electromotive drug delivery with Pentosan polysulfate, on category 3 patients, successful enough to do placebo controlled study.
Also looking at finesteride [proscar], and also cox-2 inhibitors, and Vioxx. Re bug: preparing a probe for finding this bug. UK group is going to publish this in Nature
. They've asked us not to tell the name of the bug. It has a long name that starts with "P" .
Dr. Schaeffer
At Northwestern we are focusing on infection, cytokines and novel therapies. No one really knows what normal prostate has in it. How do you know
bacteria found in tissues not introduced by biopsy...We study prostates from organ donors. (Hachreiter).
Cytokines -- are present in Eps, seem to correlate with 3a and 4. Are
elevated. Looking at cyclical changes, there are cytokines that change over time, seem to correlate with patients' symptoms.
[We are looking at] novel therapies -- biofeedback, bladder training, we've studied 19 patients for a year and a half. Seem to have a favorable and durable response.
Looking at microwave therapy...heat may help these patients...they can taylor and modify the heat generated to very specific parameters. We can tailor to specific conditions in the prostate.
[Editor's note: Dr. Schaeffer and others made clear that the use of microwave thermotherapies for prostatitis is quite different than the use of the same
devices to induce tissue shrinkage in cases of EPS. The protocols for prostatitis still have to be worked out, but they generally involve much lower temperatures.]
Dr. Nickel
[Thermotherapy is] one of the few treatments with critical analysis have shown some clinical benefits. 4 studies for thermal therapy showing efficacy over
sham. We need a committment for research funding from the companies that make the microwave therapy machines.
Schaeffer
Use a modification of the machine and protocol to treat prostatitis, rather than BPH. In Switzerland, using the traditional approach, [high temperature] [in
prostatitis patients it brught about a] heightened pain response. But we can modify the program in the machine to change the heat profiles. There is a fair
amount of science behind these machines, and they're not the same, they may be able to positively affect outcome.
Dr. Wheeler
The microwave machines target the transition zone, prostatitis is a disease of the entire prostate, not transition zone.
Dr. Nickel
It also might be more than just the prostate in some patients. We have to go on beyond the prostate.
Dr. Vega.
Biopsies sample only a very limited area, while the entire prostate needs to be looked at. In tissue samples from men who have had a total prostatectomy,
there is evidence of prostatitis in 86 per cent of men.
Dr. Potts
We need to be careful about selection bias of the patients [in research studies]. Within myown practice, we're selecting out down to a minority of
prostatitis patients, because patient compliance is a big issue. Then you find a different motivation in a select group who travel to see doctors and who are very determined.
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