Eight medical centers to study urologic pelvic pain disorders

Eight academic medical centers have been selected by the National Institute of Digestive and Kidney Disease (NIDDK) to study urologic chronic pelvic pain disorders (including prostatitis) by looking for clues outside the bladder and prostate. The total investment for the five-year project is estimated to be up to $37.5 million.

The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network includes six Discovery Sites at which studies will be conducted and two Core Sites at which data collection will be coordinated, tissue samples analyzed, and technical support provided. The Discovery Sites are Northwestern University, the University of California at Los Angeles, the University of Iowa, the University of Michigan, the University of Washington, and Washington University. The Core Sites are the University of Colorado and the University of Pennsylvania.

The innovative research focus is supported by recent epidemiological studies showing that interstitial cystitis/painful bladder syndrome symptoms and chronic prostatitis/chronic pelvic pain syndrome are frequently associated with other chronic pain disorders.

“The bladder was assumed to be the origin of the interstitial cystitis/painful bladder syndrome symptoms and the prostate was assumed to be the source of chronic prostatitis/chronic pelvic pain syndrome symptoms,” explained Leroy M. Nyberg, Jr., M.D., Ph.D., the NIDDK urologist who is heading the program. “However, in spite of intense study funded by NIDDK, no organ-specific cause has been identified for either disorder.”

The prostatitis Foundation hopes this will lead to a better understanding of prostatitis and result in both successful treatments for patients who have the disease and better approaches to prevent new infections.

Prostatitis Foundation

Experts explore link between allergies and interstitial cystitis

Allergy testing and treatment may offer a new therapeutic option for many patients with interstitial cystitis (IC). IC is a severely painful bladder condition affecting as many as 8 million women and 1.5 million men in the United States. Patients and the providers who treat them have long noticed a correlation between allergies and IC.
Recently, a urologist and allergist in Louisville, Kentucky, began to explore the link between these two chronic ailments to provide patients with more effective treatment. The story of their discoveries is featured in the ICA Update, the quarterly magazine of the Interstitial Cystitis Association (ICA).

"Until now, the evidence linking IC and allergies has been circumstantial," said Barbara Gordon, executive director of the ICA, an organization providing advocacy, research funding, and education to ensure early diagnosis and optimal care with dignity for people affected by IC. "Epidemiologic studies show the prevalence of allergies in IC patients to be higher than in people in general. Anti-allergy medications seem to ease IC symptoms, especially when patients have seasonal allergies. And during allergy seasons, doctors report an upswing in IC-related calls and patient visits."

That suggests that there is a correlation between allergies and IC, but can allergies cause bladder symptoms? A clearer answer comes from actual allergy testing and treatment of patients. After holding several discussions on this subject, John Hubbard, M.D., a urologist, and C. Steven Smith, M.D., an allergist/immunologist, partnered to study this phenomenon in a more formal way.

These doctors found they were referring patients to each other. Hubbard was sending IC patients with seasonal allergies to Smith, and Smith had allergy patients who also had bladder symptoms. Then, they found that Smith's allergy testing and treatment was helping to resolve IC symptoms, sometimes dramatically.

Foods Fingered

Although IC patients' seasonal allergy miseries are what gave the clue to the connection, Smith is finding that food allergies are common in IC patients. He estimates that 35 to 40 percent of the IC patients he sees have bona fide allergies to foods, based on the results of their skin prick tests and elimination-challenge diets, and that their IC gets better when they remove those foods from their diet. "We've been able to identify a lot of food allergies that IC patients didn't even know they had," noted Heather Lange, ARNP, the nurse practitioner who works with urologist Hubbard's IC patients.

Stimulants, such as coffee and tea, and the acid and spicy foods that have long been known to cause problems for IC patients may be bladder irritants even without allergy. "Put those on already irritated bladder tissue, and you probably are going to see a response," Smith said. But he's also finding allergic reactions to some of these items in IC patients. Positive skin prick tests for cayenne (a hot pepper) seem to be common.

The effect on IC of treating environmental allergies with shots or medications is less obvious, said Smith, but still seems to be beneficial. About half to a third of the IC patients he sees have proven environmental allergies or symptoms, such as hay fever, asthma, recurrent ear infections, or chronic urticaria (hives).

Hubbard and Smith are collaborating on a more formal study of the link. One goal is to find a marker that will help urologists decide which patients may benefit from allergy testing and treatment. Like many urologists, Hubbard uses cystoscopy and hydrodistention under anesthesia as part of his workup to exclude other conditions that may cause IC-like symptoms. But he is reviving an older practice of taking a biopsy specimen during the procedure and sending it to a pathologist to look for mast cells because, when mast cells reach a certain density, patients seem to benefit from allergy testing and treatment. Mast cells elsewhere in the body are key players in allergic reactions, but their role in the bladder tissue of IC patients has not been clear.

Dr. Smith and Dr. Hubbard plan to conduct more research and hope to spark the interest of additional IC and allergy researchers. Meanwhile, these doctors are continuing to help IC patients get better. Not everyone responds, said Smith, "But for the high percentage who do improve with allergy management, it's well worth the effort. It's one of the most rewarding patient care experiences I have ever had."

Diet and IC

Future research will reveal more about the role of food allergy in IC patients' symptoms. Meanwhile, whether patients have "true" allergies or sensitivity to foods, the treatment is the same -- an elimination challenge diet. Elimination diets remove the potential problem foods from the patient's diet and add them back one at a time to see if the food really causes a problem.

ICA offers the following advice to patients when modifying their diets: -- The effect of food and drinks on IC symptoms varies greatly from individual to individual. It's important to note the type of food or beverage, as well as how much, how often and the specific combination of food and beverages ingested. Give yourself plenty of time to discover your ideal diet. It may require several weeks of trial and error. -- Eat a healthy, varied, balanced diet -- most patients can do this if they work to identify problem items first.

Interstitial Cystitis Association

Common treatment for chronic prostatitis fails to reduce symptoms

Alfuzosin, a drug commonly prescribed for men with chronic prostatitis, a painful disorder of the prostate and surrounding pelvic area, failed to significantly reduce symptoms in recently diagnosed men who had not been previously treated with this drug, according to a clinical trial sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health (NIH). The study is to be published in the New England Journal of Medicine.

"Although these results are disappointing, it is just as important to find out what doesn't work as it is to know what does," said NIDDK Director Griffin P. Rodgers, M.D. "We have conclusively shown that a drug commonly prescribed for men with chronic prostatitis did not significantly reduce symptoms compared to a placebo."

Chronic prostatitis, which has no known cause and no uniformly effective therapy, is the most common type of prostatitis seen by physicians. Men with this condition experience pain in the genital and urinary tract areas, lower urinary tract symptoms such as pain in the bladder area and during urination, and sexual problems that can severely affect their quality of life. Population-based surveys estimate that 6 percent to 12 percent of men have prostatitis-like symptoms.

A total of 272 men diagnosed with chronic prostatitis were randomly assigned to take either alfuzosin or an identical-looking placebo. Of these, 233 men completed the trial. The primary outcome was a decrease (improvement) in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) of at least four points over 12 weeks of treatment. A 4-point decrease in the NIH-CPSI score has been shown to be the minimal clinically significant difference perceived by patients as beneficial. The index measures the three most important symptoms of chronic prostatitis — pain, problems with urination, and negative effects on quality of life.

The rates of response of the NIH-CPSI in the alfuzosin group and placebo groups were the same — 49.4 percent. In addition, there were no significant differences between the two groups in the changes over time in most of the secondary outcomes, including the total NIH-CPSI score and a global response assessment.

Despite a lack of rigorous evidence supporting the use of antibiotics or alpha blockers for chronic prostatitis, more than three-fourths of primary care physicians often prescribe antibiotics and more than one-half regularly prescribe alpha blockers such as alfuzosin for the condition, according to a recent survey supported by NIDDK. Alpha blockers are a class of drugs that relax the smooth muscle of the bladder and prostate.

"Our findings do not support the use of alpha blockers for treating new cases of chronic prostatitis," said J. Curtis Nickel, M.D., of Queen's University in Kingston, Ontario, Canada, and lead author of the study. "But the results of our study will inform future clinical trials of alpha blockers and other potential therapies."

NIH/National Institute of Diabetes and Digestive and Kidney Diseases

New Minimally Invasive Surgery For Chronic Prostatitis

The Krongrad Institute for Minimally Invasive Prostate Surgery is launching a first-of-kind IRBapproved prospective, longitudinal, non-randomized, single-arm Phase II study of patients with a diagnosis of chronic prostatitis before and after laparoscopic radical prostatectomy, a form of minimally invasive surgery. "Individual clinical cases have shown that surgery using laparoscopic radical prostatectomy can eliminate the symptoms associated with chronic prostatitis. This represents a conceptual revolution for men who otherwise have no effective treatment option. The study -- the first of its kind -- aims to better characterize and quantify the effects of minimally invasive surgery on the symptoms of chronic prostatitis," said the study's principal investigator Arnon Krongrad, MD.

Surgery is (and should remain) a treatment of last resort for patients with severe, chronic prostatitis.

Read full story at Medical News Today.

The pepperoni pizza hypothesis

What's the worst that could happen after eating a slice of pepperoni pizza? A little heartburn, for most people. But for up to a million women in the U.S., enjoying that piece of pizza has painful consequences. They have a chronic bladder condition that causes pelvic pain. Spicy food -- as well as citrus, caffeine, tomatoes and alcohol-- can cause a flare in their symptoms and intensify the pain. It was thought that the spike in their symptoms was triggered when digesting the foods produced chemicals in the urine that irritated the bladder.

However, researchers from Northwestern University's Feinberg School of Medicine believe the symptoms -- pain and an urgent need to frequently urinate -- are actually being provoked by a surprise perpetrator. Applying their recent animal study to humans, the scientists believe the colon, irritated by the spicy food, is to blame.

Read full story at Machines Like Us.

The pepperoni pizza hypothesis

What's the worst that could happen after eating a slice of pepperoni pizza? A little heartburn, for most people.

But for up to a million women in the U.S., enjoying that piece of pizza has painful consequences. They have a chronic bladder condition that causes pelvic pain. Spicy food -- as well as citrus, caffeine, tomatoes and alcohol-- can cause a flare in their symptoms and intensify the pain. Researchers had long believed the spike in their symptoms was triggered when digesting the foods produced chemicals in the urine that irritated the bladder.

A surprising new discovery from Northwestern University's Feinberg School of Medicine reveals the symptoms -- pain and an urgent need to frequently urinate -- are actually being provoked a surprise perpetrator. It's the colon, irritated by the spicy food, that's responsible. The finding provides an explanation for how the body actually "hears" pelvic pain.

The discovery also opens up new treatment possibilities for "painful bladder syndrome," or interstitial cystitis, a condition that primarily affects women (only 10 percent of sufferers are men.) During a flare up, the pelvic pain is so intense some women inject anesthetic lidocaine directly into their bladders to get relief. Patients typically also feel an urgent need to urinate up to 50 times a day and are afraid to leave their homes in case they can't find a bathroom.

"This disease has a devastating effect on people's lives," said David Klumpp, principal investigator and assistant professor of urology at the Feinberg School. "It affects people's relationships with family and friends." Klumpp said some women who suffer from this become so depressed, they attempt suicide.

Klumpp conducted the study with postdoctoral fellow Charles Rudick. The paper is published in the September issue of Nature Clinical Practice Urology.

The Northwestern researchers discovered the colon's central role in the pain is caused by the wiring of pelvic organ nerves. Nerves from this region -- the bladder, colon and prostate -- are bunched together like telephone wires and plug into the same region of the spinal cord near the tailbone.

People with interstitial cystitis have bladder nerves that are constantly transmitting pain signals to the spinal cord: a steady beep, beep, beep.

But when the colon is irritated by pepperoni pizza or another type of food, colon nerves also send a pain signal to the same area on the spinal chord. This new signal is the tipping point. It ratchets up the pain message to a chorus of BEEPEEPBEEPBEEP!

"It was known that there was cross talk between organs, but until now no one had applied the idea to how pain signals affect this real world disease, how the convergence of these two information streams could make these bladder symptoms worse," said Klumpp, who also is an assistant professor of microbiology-immunology at the Feinberg School.

The findings suggest the bladder pain can be treated rectally with an anesthetic in a suppository or gel. Another possibility is an anesthetic patch applied to pelvic skin. Studies in back pain show anesthetic patches applied to the skin can reduce back pain, Klumpp said.

"We imagine a similar kind of patch might be used to relieve pelvic pain, which might be the best solution of all," he noted.

HOW THEY "CAUGHT" THE COLON

For the study, Klumpp and Rudnick created a model of a mouse that mimicked an inflamed bladder with pelvic pain. Then they injected lidocaine into the bladder. The pain vanished. Next they injected lidocaine into the uterus. There was no diminishment of the pain. Lastly, they tried lidocaine in the colon.

"In the colon it knocked down pain just as effectively as if we put it in the bladder. We thought if the colon can suppress bladder-associated pain, maybe it can make it worse in the way that foods irritate bladder symptoms," Klumpp explained.

So, Klumpp injected a small dose of red pepper into the colon of a normal mouse. The injection didn't provoke any pain. But then he injected a small dose into a mouse with pelvic pain. The pelvic pain worsened.

"We likened it to what happens to humans," Klumpp said. "Pepperoni pizza does nothing to most people other than heartburn, but when you give it to a person with an inflamed bladder, that will cause their symptoms to flare because the nerves from the bladder and bowel are converging on the same part of the spinal cord."

Northwestern University

Overview of AUA Interstitial Cystitis/Painful Bladder Syndrome Session

For the first time in memory, the session devoted to interstitial cystitis at the annual meeting of the AUA was a podium session rather than a poster session. A mix of basic science and clinical presentations resulted in a compelling presentation.

Yokoyama and colleagues from Matsumoto Japan and Pittsburgh examined the antinociceptive effects of systemically administered enkephalin, a d-opiod receptor agonist as well as gene therapy using herpes simplex virus vectors expressing preproenkephalin, the precursor of enkephalin, using a rat model of bladder pain. Their data indicated that both types of enkephalin treatments via systemic administration or herpes simplex virus-mediated gene transfer are effective to suppress bladder pain induced by bladder irritation. Enkephalin gene therapy could be a potential treatment of bladder pain.

Ustinova and co-workers from Pittsburgh and Durham hypothesized that chronic mast cell infiltration of pelvic organs following an acute pelvic organ insult may play a role in chronic pelvic organ sensitization and cross-sensitization. They hypothesized that pelvic organ mastocytosis maintains increased epithelial permeability leading to direct afferent activation by physiologic stimuli. In an animal model they presented data indicating that neurogenic sensitization of bladder afferents by colonic irritation of divergent afferents that innervate both colon and bladder and dorsal root reflexes results in simultaneous mast cell attraction and urothelial barrier breakdown (based on potassium and fluorescein absorption). Further sensitization of submucosal afferents then causes a vicious cycle, attracting more mast cells and resulting in increased breakdown of barrier function.

Liu and Luo from Iowa City showed that interrupting mast cell function in a mouse model of bladder inflammation effectively alleviates autoantigen-mediated bladder inflammation. They went on to hypothesize that mast cell targeting may be a useful approach for treating bladder inflammation with an autoimmune component such as IC. Rudick and co-workers from Chicago used a pseudorabies virus induced neurogenic cystitis model to examine the underlying molecular basis of pelvic pain. Their data in a mouse model suggested that mast cells cause cystitis pain and bladder inflammation through the separable actions of histamine and tumor necrosis factor. They believe that histamine receptors may be valid therapeutic targets for pelvic pain therapy.

Three presentations examined intravesical lidocaine treatment of the painful bladder. Srinivasan and colleagues from New York observed the effect of 20cc of 2% intravesical lidocaine 10 minute exposure on urodynamic parameters in 8 patients. Bladder capacity, peak flow rate, and first urge to void showed improvement. Nickel and colleagues from Kingston, Ontario and Kent, UK reported the results of a phase 2 trial of an intravesical alkalinized lidocaine solution in IC/PBS. Five consecutive daily instillations were compared to placebo instillations at 19 North American centers with 102 patients randomized. Interval follow-up to day 29 was performed. At 8 days after the 5 day treatment course, 30% of active patients rated their improvement as moderately or markedly improved vs 9.6% on placebo. Welk and Teichman from Vancouver reported on female sexual function in IC patients. Their data in 32 consecutive IC patients with dyspareunia treated with intravesical alkalinized lidocaine and heparin compared multiple sexual domains before and 4 weeks after a course of therapy. 50% of subjects had resolution of dyspareunia and corresponding improvement over several sexual domains. Those with tenderness of the bladder neck alone prior to therapy had the best outcomes.

Jonathan Kaufman from Pittsburgh studied the pharmacokinetics of liposomes after intravesical administration. He concluded that intravesical delivery of empty liposomes provides a significant bladder urothelium targeting advantage with long bladder residence time of 24 hours. These pharmacokinetic studies support the use of empty liposomes as a potential local therapy for painful bladder/interstitial cystitis.

Chuang and colleagues from Taiwan and Pittsburgh presented a paper on the mechanism of analgesia and anti-inflammatory properties of botulinum toxin A in a rat model. They concluded that botulinum toxin A intravesically decreased SNAP-25 level in the bladder, but not in the spinal cord. It inhibited cyclophosphamide induced bladder inflammation and hyperactive bladder. This suggests a local neuromodulation of botulinum toxin A on the bladder without compromise of central neurotransmission.

Wang and co-workers from Wisconsin studied altered urinary bladder function and impaired nociception in mice lacking estrogen receptor-a. The absence of estrogen receptor-a prevented increased peripheral pain perception associated with cystitis, and may help to explain patient differences in perception of pain associated with cystitis.

Diagnosis received attention at this meeting. Ueda and colleagues from Kyoto and Pittsburgh showed that a flexible cystoscope with a narrow band imaging system can detect mucosal angiogenic lesions. In a study of 52 patients, 37 cases were found to have ulcers by conventional cystoscopy under anesthesia. All cases were identified without hydrodistention by the narrow band imaging flexible cystoscopy, and were found to be associated with platelet derived endothelial growth factor on biopsy specimens. The group concluded that this new endoscopic system will make it unnecessary to do cystoscopy with anesthesia to discover the typical Hunner’s lesion. Buffington in Columbus, Ohio assessed the feasibility of using infrared microspectrosopic analysis (IRMS) of dry serum films for diagnosis of IC in cats and humans. Specific infrared bands discriminated IC from healthy subjects in both species. His data suggested that intermediate compounds in the metabolism of tryptophan might be associated with the pathophysiology of IC.

UroToday

Prostatitis May Effect Up To One-half of All Males During Their Lifetimes

Estimates on the number of males in the United States who will experience prostatitis during their lifetimes range up to 50 percent. Many urologic disease experts feel that from 5 to 10 percent of males are experiencing prostatitis at a particular time, making it one of the most common urologic diseases in the U.S.

Prostatitis is an infection or inflammation of the prostate gland that causes intense pain, urinary complications, sexual dysfunction, infertility, and a significant reduction in the quality of life Prior to the mid-1990s, very little research had occurred that could lead to improved diagnostic techniques and a cure.

Prostatitis is difficult to diagnose and treat, and has a wide range of debilitating and troublesome side affects. Unlike prostate cancer and benign prostatic hyperplasia (BPH), prostatitis often affects the lives of young and middle-aged men.

According to The Prostatitis Foundation, prostatitis can result in four significant symptoms: pain, urination problems, sexual dysfunction, and general health problems, such as feeling tired and depressed.

The prostate is a reproductive gland located just below the bladder and in front of the rectum. It wraps around the urethra, a tube that carries urine from the bladder. The prostate produces most of a male’s semen.

To diagnose prostatitis, a physician will collect a patient’s urine and thoroughly exam his prostate gland. To check the prostate gland, a physician will carry out a digital rectal examination, which involves inserting a well lubricated gloved finger into the rectum to check for any abnormalities of the gland. The physician also may collect a sample of prostate fluid so that it can be analyzed.

Some physicians also may want to carry out a prostate specific antigen test to measure the amount of this chemical in a person’s blood. Both prostatitis and prostate cancer can increase a patient’s PSA level.

Over the years, prostatitis has been subdivided into a number of categories, but today commonly accepted variations of the disease include nonbacterial, acute, and chronic.

By far, the most common type of prostatitis is nonbacterial prostatitis. Symptoms may include frequent urination and pain in the lower abdomen or lower back area. Causes may be stress and irregular sexual activity.

According to Dr. Leroy Nyberg, Jr., director of Urology Programs at the National Institutes of Health, treatments for nonbacterial prostatitis may include anti-inflammatory medications or muscle relaxants, taking hot baths, drinking extra fluids, learning to relax when urinating, and ejaculating frequently. “Some physicians also may recommend some changes in a patient’s diet,” Dr. Nyberg said.

Acute bacterial prostatitis can be the result of bacteria, a virus, or a sexually transmitted disease. Symptoms may include fever and chills, low back pain, frequent and painful urination, weak stream urination, and infrequent urination.

Dr. Nyberg explained that these infections often are treated with antibiotics, bed rest, stool softener, and increased fluid intake.

Chronic prostatitis may be bacterial or the result of an inflammation of the prostate. Symptoms may include frequent bladder infections, frequent urination, and persistent pain in the lower abdomen or back.

This form of prostatitis often is treated with medications (often antibiotics), changes in the diet, biofeedback, and nonprescription supplements, according to Dr. Nyberg. Additional information about prostatitis can be found at the Foundation's web site--http://www.prostatitis.org.

Prostatitis Foundation

Cranberry sauce: good for what ails you

Cranberry sauce is not the star of the traditional Thanksgiving Day meal, but when it comes to health benefits, the lowly condiment takes center stage. In fact, researchers at Worcester Polytechnic Institute (WPI) have found that compounds in cranberries are able to alter E. coli bacteria, which are responsible for a host of human illnesses (from kidney infections to gastroenteritis to tooth decay), in ways that render them unable to initiate an infection.

The findings are the result of research by Terri Camesano, associate professor of chemical engineering at WPI, and a team that includes graduate students Yatao Liu and Paola Pinzon-Arango. Funded, in part, by the National Science Foundation and the Cranberry Institute and Wisconsin Cranberry Board, the work has been reported in a number of publications and presentations, including FAV Health 2007 (The 2nd Annual Symposium on Human Health Effects of Fruits and Vegetables), the annual meeting of the American Chemical Society in September 2006, and the January/February 2007 issue of the Italian publication AgroFOOD industry hi-tech.

For the first time, the research has begun to reveal the biochemical and biophysical mechanisms that appear to underlie a number of beneficial health effects that have long been ascribed to cranberries and cranberry juice—in particular, the ability of cranberry juice to prevent urinary tract infections (UTIs). The mechanism by which cranberry juice prevents such infections has not been clear, though scientists have suspected that compounds in the juice somehow prevent bacteria from adhering to the lining of the urinary tract.

Camesano and her students have used the atomic force microscope and other sophisticated tools to study how a group of tannins (called proanthocyanidins or PACs) found primarily in cranberries interact with bacteria at the molecular level. They have found that the compounds prevent E. coli from adhering to cells in the body (a necessary first step in infections) in several ways:

The chemical changes caused by cranberry juice create an energy barrier that keeps the bacteria from getting close to the urinary tract lining.

Direct measurements show that the adhesive forces between E. coli and cells of the urinary tract are greatly reduced when at least a 5 percent solution of cranberry juice cocktail is present.

Cranberry juice causes tiny tendrils (known as fimbriae) on the surface of the type of E. coli bacteria responsible for the most serious types of UTIs to become compressed, reducing the bacteria’s ability to latch onto the lining of the urinary tract.
E. coli grown in cranberry juice or the isolated PACs are unable to form biofilms. Biofilms, clusters containing high concentrations of bacteria, are required for infections to develop. Biofilms are the source of infections associated with indwelling catheters and other biomedical devices.

When E. coli are cultured over extended periods in solutions containing various concentrations of either cranberry juice or PACs, their cell membranes undergo changes that hinder the bacteria’s ability to attach to cells of the urinary tract.
Camesano and her team have also noticed that cranberry juice inhibits the ability of E. coli to produce IAA, a molecule involved in a phenomenon known as quorum sensing. Bacteria produce IAA to let other bacteria know they are there. Quorum sensing enables bacteria to sense that their population is large enough to initiate an infection, or to form a biofilm. Keeping bacteria from producing IAA may be another way that cranberry compounds can hinder their ability to cause serious infections.

Some of Camesano’s current work is aimed at assessing the minimum effective dose of cranberry juice (or tannins) and the optimum frequency to ward off infections. In addition, she is working to test whether the urine of patients who have consumed cranberry juice still contains anti-adhesive properties. The clinical portion of the work is being done in collaboration with Amy Howell, associate research scientist at the Philip E. Marucci Center for Blueberry and Cranberry Research at Rutgers University.

Camesano says her work to date indicates that the benefits increase the more juice or cranberry products one consumes. So when it comes to this year’s Thanksgiving feast, don’t spare the cranberry sauce.

Worcester Polytechnic Institute

Treatment of Prostatitis

The term prostatitis is applied to a series of disorders, ranging from acute bacterial infection to chronic pain syndromes, in which the prostate gland is inflamed. Patients present with a variety of symptoms, including urinary obstruction, fever, myalgias, decreased libido or impotence, painful ejaculation and low-back and perineal pain. Physical examination often fails to clarify the cause of the pain. Cultures and microscopic examination of urine and prostatic secretions before and after prostatic massage may help differentiate prostatitis caused by infection from prostatitis with other causes. Because the rate of occult infection is high, a therapeutic trial of antibiotics is often in order even when patients do not appear to have bacterial prostatitis. If the patient responds to therapy, antibiotics are continued for at least three to four weeks, although some men require treatment for several months. A patient who does not respond might be evaluated for chronic nonbacterial prostatitis, in which nonsteroidal anti-inflammatory drugs, alpha-blocking agents, anticholinergic agents or other therapies may provide symptomatic relief.

Read complete article in American Family Physician.

Therapy Aimed at Treating Nanobacteria Proven Effective in Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome

Category III chronic prostatitis/chronic pelvic pain syndrome (CPPS) is a common debilitating condition of unclear etiology. Patients often have prostatic calcifications seen on transrectal ultrasound (TRUS) but their link to symptoms is controversial. Nanobacteria are implicated in stone formation in the urinary tract, thus, therapy aimed at eliminating them and the stones that nanobacteria produce might have an impact on CPPS symptoms. Nanobacteria are gram-negative, small size, slow growing and have the ability to form calcium phosphate crystals at neutral pH. Their growth in vitro is best inhibited by tetracycline.

A total of 16 men with recalcitrant CPPS refractory to multiple prior therapies and who had prostatic calculi seen on TRUS were chosen to be included in a study whose aim was to examine the effectiveness of therapy aimed at nanobacteria. The study was performed by D. A. Shoskes and colleagues from Cleveland Clinic of Florida and the results reported in the February, 2005 issue of the Journal of Urology. All men were treated with comET, which consists of 500mg tetracycline orally, nanobacOTC supplement (a proprietary blend of Vitamin C, selenium, EDTA, coenzyme Q10, bromelain, grapeseed extract, hawthorn berry, quercetin, L-arginine, vitamins B3, B6 and B9, L-lysine, L-ornithine, trypsin and papain), and a rectal suppository containing 1,500 mg EDTA. The nanobact OTC purportedly allows the antibiotic to penetrate the stone and the EDTA allows for stone dissolution. Therapy duration was 3 to 4 months.

A closer look at the study population revealed that the mean age of the patients was 44.6 years, and mean symptom duration was 6.3 years. Using a definition of expressed prostatic secretion inflammation of at least 10 white blood cells per high power field, 7 men had category IIIa (inflammatory) and 8 had category IIIb disease. The initial mean NIH-Chronic Prostatitis Score Index (CPSI) was 25.7 at baseline. Nine men (60%) had nanobacterial antigen or antibody detected in the blood, 6 (40%) had nanobacterial antigen in the urine.

Results revealed that the mean NIH-CPSI total score improved from 25.7 to 13.7 while the pain index decreased from 11.3 to 4.9. A total of 12 patients (80%) had at least a 25% improvement on NIH-CPSI and 8 (53%) had at least a 50% improvement. In 10 patients who underwent transrectal ultrasound after therapy, prostatic stones were decreased in size or resolved in 50%. Seven patients who were examined at least 3 months after completing therapy had no recurrence or worsening of symptoms.

In conclusion, therapy designed to eliminate nanobacteria resulted in significant improvement in the symptoms of recalcitrant CPPS in the majority of men, whether due to the treatment of stones producing nanobacteria or through some other mechanism. As with urinary tract calculi, the key factor in symptoms may be obstruction. Calcification within ducts draining prostatic glands could cause obstruction, secondary inflammation and increased intraprostatic pressures. This comET therapy warrants prospective placebo controlled trails due the paucity of alternative treatments for this chronic condition.

From Uro Today.

The Combination Of Myofascial Trigger Point Release And Paradoxical Relaxation Training Shows Promise In The Treatment Of Chronic Pelvic Pain In Men

Chronic nonbacterial prostatitis/chronic pelvic pain syndrome (CPPS) in men continues to perplex and challenge the urologist in practice. Some estimate the prevalence to be between 5% and 16% of men. Most therapies to this point have focused in the empirical use of antibiotics although 95% of chronic prostatitis syndromes in men are nonbacterial and idiopathic and represent a nonspecific pain disorder. A neurobehavioral perspective to this chronic pain syndrome is starting to emerge.

The authors of a recent study believe that pelvic pain manifests as a myofascial pain syndrome, in which abnormal muscular tension could explain much of the discomfort and abnormal urinary dysfunction seen in men with CPPS. In the July, 2005 issue of the Journal of Urology, R. U. Anderson and colleagues from Stanford University report their experience using a team of a urologist, a physiotherapist and a psychologist to provide urological evaluation, physiotherapy with myofascial trigger point (TrP) release and autonomic and pelvic floor training (PRT) for CPPS.

In the study 138 men referred for chronic pelvic pain with a variety of manifestations were evaluated and treated with myofascial trigger assessment and release therapy with PRT (MRRT/PRT). The mean patient age was 40.5 years and mean symptom duration was 31 months. Treatment consisted of a traditional prostate massage and expressed secretions culture followed by assessment of myofascial trigger points. Tender points were noted and a physiotherapist focused on these spots during sessions of myofascial pressure and release and patient release/hold-relax/contract relax/reciprocal inhibition. Sessions occurred weekly for 4 weeks then bi-weekly for an additional 8 weeks. Patients also received 1 hour of individual verbal instructions and a supervised practice session at weekly intervals for 8 weeks by a psychologist which focused on specific breathing techniques to quiet anxiety and relaxation training sessions focused on directing patients to focus attention on the effortless acceptance of tension in specific areas of the body.

Symptoms were then assessed with a pelvic pain symptom survey (PPSS) and the National Institutes of Health-CP Symptom Index. Patients also reported perceptions of overall effects of therapy using a global response assessment questionnaire. Analysis of results showed that global response estimates of moderately improved or markedly improved, considered clinical successes, were reported by 72% of patients. More than half of the patients treated with the MFRT/PRT protocol had a 25% or greater decrease in pain and urinary symptom scores as assessed by the PPSS. In those at the 50% or greater improvement level (38% of all patients), median scores decreased 69% and 80% for pain and urinary symptom scores, respectively.

This case study analysis indicates that the MFRT/PRT protocol was successful in producing improvement in the majority of men with CPPS and it may be an effective treatment approach in these patients to provide both pain and urinary symptom relief. The treatment described in based on the new understanding that certain chronic pelvic pain reflects a self-feeding state of tension in the pelvic floor, perpetuated by cycles of tension, anxiety and pain. The treatment in this study aims to rehabilitate the pelvic floor, while simultaneously modifying the habit of focusing tension under stress.

From Uro Today.

New Chronic Prostatitis Drugs in Development

Nanobac Pharmaceuticals, Inc. announced last year a sharpened focus in three areas: 1) developing safe and effective drug therapies for diseases where soft tissue calcification, or "calcium deposits," is a dominant feature, 2) validating the Company's antibody and antigen derived diagnostics to determine levels of calcification, and 3) scientific studies to determine the infectious nature of the calcifying nano particles (CNPs).

The sharpened focus on drug therapies led to a Pre-IND (Investigational New Drug) meeting with the FDA on January 19, 2007. With positive results from this meeting, the Company is moving forward with the IND application for Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) also referred to as category III prostatitis. In the United States, more than 2 million men per year visit their physician for prostatitis. Nanobac's strategic partner at the Cleveland Clinic will be the principal investigator for the clinical trial portion of this IND.

The sharpened focus on determining if there is an infectious nature to CNPs is through collaborative efforts with the Mayo Clinic and investigators at China's Coal Medical College. These studies are scheduled to conclude in June. If successful, they will establish that CNPs are a causative agent in the formation of calcific diseases, and in the specific case of the China study, Gall Stones. It also suggests that CNPs might play a similar role in the formation of kidney stones, prostatic stones and could be the agent involved with the calcification stage of atherosclerosis.

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Prostatitis Papers

The International Prostatitis Research Foundation provides research papers as a public service. Some of these prostatitis documents are LARGE and may take a long time to download. Due to heavy traffic, this prostatitis site is sometimes suspended. Try again in a few days if downloads are not allowed. All documents are in Adobe Acrobat format unless otherwise noted. If you don't have Acrobat Reader, download it here.

Prostatitis Papers >>

Chronic prostatitis/chronic pelvic pain syndrome: The biomedical model has failed! So what's next?

Prostatitis, particularly the chronic condition not associated with a bacterial etiology, is a common urologic condition. This "disease" is the most common diagnosis seen in urology outpatient practice in men under 50 years of age and is the third most common in men over age 50, representing between 3% and 12% of male urology visits. Between 2% and 9% of men have recently experienced prostatitis-like symptoms, and up to 16% have received a diagnosis of prostatitis.

Until several years ago, urologists only had clinical trial data that provided reliable evidence to treat bacterial prostatitis. The vast majority of patients previously diagnosed with nonbacterial prostatitis and/or prostatodynia, now referred to as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), were managed with strategies that evolved from dogma, tradition, anecdotal experience, and results from a few small uncontrolled clinical series. The recent consensus-derived definition and classification of the prostatitis syndromes and the development of a validated outcome measure—the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), which has been proven to be useful in clinical research trials and clinical practice—have led to a literal tsunami of peer-reviewed published evidence that provides the potential for better management of patients with CP/ CPPS.

Despite this recent rising tide of research, the traditional biomedical model that has driven our understanding of the etiology, diagnosis, and management of CP/CPPS has not yielded the hoped-for breakthrough in treating this condition. This article outlines the most up-to-date information from recently published clinical trials and documents that our traditional treatment modalities, at best, lead to only modest symptom improvement in some patients. The article further describes:

• where our traditional etiologic model may not be correct,
• how our new understanding of the pathogenesis of CP/CPPS may eventually lead to more effective treatment strategies, and
• what the research community is currently doing with this new understanding.

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