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Objectives: To determine whether substance P (SP, also known as neurokinin 1, NK1) receptors are differentially expressed in bladder biopsies from patients with interstitial cystitis (IC) compared with matched controls., Materials and Methods: Cold-cup biopsies were taken during routine diagnostic cystoscopy. NK1-receptor expression was assessed using a quantitative analysis of NK1-receptor-encoding mRNA in bladder biopsies from patients and controls using in situ hybridization histochemistry (ISHH) combined with autoradiographic image analysis., Results: Autoradiographic signal indicating the presence of NK1-encoding mRNA was localized to detrusor muscle, urothelium and vascular structures. In the bladder vasculature, the signal was predominantly associated with endothelial cells. NK1 receptor-encoding mRNA within the vascular endothelium was increased in the biopsies obtained from patients with IC., Conclusion: Increased levels of NK1 receptor-encoding mRNA within the bladder vascular endothelium suggests the up-regulation of NK1 receptor as a putative factor in the pathogenesis of pain related to IC. Increased responsiveness to SP released from the perivascular sensory terminals may result in a local cascade of neurogenic inflammatory responses which trigger the pathophysiological changes, including pain, characteristic of IC.

Two patients treated with chronic dialysis and renal transplantation developed acute hemorrhage from a native kidney. Bilateral native nephrectomy demonstrated acquired cystic disease and adenocarcinoma in each of the four kidneys. The etiology of acquired cystic kidney disease (ACKD) is unclear and its incidence increases with the duration of dialysis. ACKD patients have a propensity to develop adenomas and adenocarcinomas. The increased incidence of renal neoplasms in ACKD patients warrants careful radiologic monitoring of native end-stage kidneys in selected patients.

A patient with chronic urticaria and angioedema developed endoscopically confirmed interstitial cystitis. Bladder biopsy revealed bladder mastocytosis with > 60 mast cells/mm2 (normal < 10) in the detrusor and submucosa. Most of the mast cells were activated and degranulated. The occurrence of IC in a patient with urticaria and angioedema, diseases both associated with mast cell pathophysiology, supports the role of mast cells in interstitial cystitis.

Interstitial cystitis is a urologic disorder with protean pelvic manifestations (urologic, gynecologic, gastroenterologic) and variable prevalence. Although current research indicates a non-bacteriologic etiology, interstitial cystitis has features suggestive of autoimmunity, a deficient bladder wall lining, activated bladder sensory neuropeptides and bladder mastocytosis. Pentosan polysulfate sodium is a recently approved oral treatment for interstitial cystitis. Further research into the gynecologic and pain aspects of interstitial cystitis is clearly needed.

Objectives: To provide a brief overview of intravesical dimethly sulfoxide (DMSO) therapy for interstitial cystitis and offer a practical approach to patient treatment., Methods: A review of the literature and a summation of the experience with treatment of > 300 patients with DMSO at the Interstitial Cystitis Clinic, New England Medical Center., Results: DMSO is helpful in a significant number of patients and it has acceptable morbidity and an excellent safety profile., Conclusions: Intravesical DMSO (singly or in combination) is one of the mainstays in the pharmacologic treatment of interstitial cystitis.

Objectives: To determine the usefulness of oral hydroxyzine for the treatment of symptomatic interstitial cystitis., Methods: This study was an open-label, nonconsecutive case series of patients treated by their local physicians, in consultation with the authors. A case-report form using visual analog scales was used to assess outcomes., Results: Out of 140 patients, 90 (65%) returned the case-report forms. A 40% reduction in symptom scores was reported. This rose to 55% in patients with a history of allergies., Conclusions: Hydroxyzine is a useful drug for the symptomatic treatment of IC, especially in patients with documented allergies and/or evidence of bladder mast cell activation.

Objectives: To develop 2 brief self-administered indices for measuring lower urinary tract symptoms and their impact in patients with interstitial cystitis (IC)., Methods: An initial set of questions was developed and evaluated in focus groups. The index was revised, shortened, and validated with patients diagnosed in 3 large urologic practices with experience in interstitial cystitis (N = 45). Controls were recruited from a group of healthy volunteers in a gynecology clinic (N = 67). Internal consistency, construct validity, and test-retest reliability were evaluated., Results: The IC symptom index and the IC problem index measure urinary and pain symptoms and assesses how problematic symptoms are for patients with interstitial cystitis. Psychometric performance of both instruments is good, with the symptom index demonstrating excellent ability to discriminate characteristics between patients and controls., Conclusion: Both indices should be useful in the evaluation and management of patients with IC and should be particularly useful in clinical trials of new therapies for this condition, where reliable, validated, and reproducible outcome measures are critically important.

Purpose: To investigate whether acute psychological stress may activate bladder mast cells which appear to play a significant role in the pathophysiology of interstitial cystitis, a syndrome that occurs primarily in females and is characterized by urinary urgency, frequency and suprapubic pain, all of which often worsen with stress., Materials and Methods: Non-traumatic immobilization stress was used as a model of acute emotional stress by placing a rat in a plexiglass immobilizer, after first bringing each rat in the laboratory daily for 4 days to reduce the stress of handling. The rat was then anesthetized, decapitated and the bladder removed and fixed for light and electron microscopy., Results: This type of stress resulted in activation of over 70% of bladder mast cells within 30 minutes, as evidenced by light and electron microscopy. Pretreatment of the animals with intraperitoneal administration of polyclonal antiserum to corticotropin releasing hormone had no effect on bladder mast cell activation and no nerve fibers positive for this hormone were identified in the bladder. Stress-induced bladder mast cell activation was, however, substantially reduced in animals treated neonatally with capsaicin suggesting that sensory neuropeptides, such as substance P, of which increased positive nerve fibers have been localized close to bladder mast cells, are involved in this response., Conclusions: This is the first time that psychological stress is shown to activate bladder mast cells, apparently via the action of at least some sensory neuropeptides. These findings have implications for the pathophysiology and possible therapy of interstitial cystitis.

Objective: To evaluate changes in histology and semen variables after using an elastomeric-hydrogel matrix plug as a reversible vasectomy device in dogs, and to determine the potential applications for improving fertility after vasectomy reversal., Materials and Methods: Semen samples from six adult male dogs were obtained after left vasal ligation, placement of the plug in the right vas deferens, and subsequent removal of the plug. The vasa, epididymides and testes were evaluated histologically in four of the dogs after removal of the implant., Results: No sperm were present in the ejaculate after the plug was removed. Histological sections showed intraluminal spermatids in areas where the plug had been placed. The lumen was occluded, secondary to foreign-body giant-cell reaction, at the vasotomy suture site, but other areas of the was previously containing the implant remained patent after it was removed., Conclusions: There were no sperm in the ejaculate after the plug was removed because the vasal lumen was occluded as a result of an inflammatory reaction to the suture material. In contrast, areas that had contained the implant but without a vasotomy suture were not inflamed. We suggest that further trials comparing various suture materials are carried out to determine if patency rates can be improved during vasotomy closure or vasovasotomy.

A 65-year-old man presented with a 3.5 cm scrotal mass. Ultrasound showed a solid mass of indeterminate aetiology within the skin. Excisional biopsy revealed a benign chondroid syringoma. This is the first report of chondroid syringoma involving the scrotum.

Objectives: Interstitial cystitis (IC) is a painful, sterile bladder disorder that occurs primarily in women, many of whom also experience allergies with symptoms that worsen perimenstrually. Increased numbers of activated bladder mast cells have recently been implicated in the pathophysiology of IC. These mast cells express high-affinity estrogen receptors and are located close to increased bladder nerves, many of which contain the neuropeptide substance P (SP). We therefore investigated whether the neurotransmitter acetylcholine (ACh) and SP could activate bladder mast cells and whether estradiol could influence this effect., Methods: Bladder pieces from male Sprague-Dawley rats were perfused with carbachol (the stable analogue of ACh), SP, or the mast cell secretagogue compound 48/80 (C48/80) with or without preincubation with beta-estradiol. The effect of carbachol was also investigated after pretreatment with the muscarinic antagonist atropine. Mast cell activation was assessed by release of 3H-serotonin and morphologic evidence of secretion by light and electron microscopy., Results: Carbachol triggered rat bladder mast cell serotonin release in a dose-dependent manner, an effect increased by tissue pretreatment with estradiol and blocked by atropine. The effect of carbachol was accompanied by ultrastructural evidence of mast cell activation and was stronger than that obtained by either C48/ 80 or SP., Conclusions: Bladder mast cell activation is neurogenically mediated and augmented by estradiol, findings that could possibly explain the painful symptoms of IC and its prevalence in women, as well as the worsening of symptoms perimenstrually.

Many patients with interstitial cystitis (IC) also have irritable bowel syndrome (IBS), both of which occur overwhelmingly in women, are characterized by pain, and worsen under stress. Bladder and colon biopsies of a female patient with both IC and IBS were evaluated immunohistochemically. There were 40 +/- 10 mast cells (MC)/mm2 (normal, less than 10) in the bladder, which were degranulated. The colon contained 148 +/- 11 MC/mm2 (normal, less than 50), mostly close to numerous substance P (SP)-positive nerves. Histamine, methylhistamine, and the unique MC enzyme tryptase were evaluated in 24-hour urine during two flare-ups. These results may help explain the concurrent presentation and the painful nature of these syndromes.

In the late 1980s, minimally invasive surgery experienced unprecedented growth. Centers appeared worldwide, providing a variety of training opportunities and laboratory experiences. Because standard surgical training varies greatly from country to country, it became apparent that this variety was even more pronounced in the area of minimally invasive and laparoscopic surgery, posing significant credentialling difficulties for professional standards committees wishing to certify surgical staff who submit unevaluable credentials from all over the world. In January 1993, the Center for Minimally Invasive Surgery at New England Medical Center and Tufts University School of Medicine was asked to plan and execute a program of education, training, and credentialling for a multispecialty surgical staff in the Eastern province of Saudi Arabia. A four-stage program was designed and developed to provide credentialling from the technician level through the instructor surgeon level. A multidisciplinary course was developed and a team placed on site for 1 month to execute the program. This program began with an 8-h didactic/video session in basic laparoscopy, covering areas common to the involved subspecialties: surgery, urology, and gynecology. This session was followed by hands-on training sessions in general surgery and urology and credentialling in gynecology. Physicians who successfully completed the examination in basic laparoscopy were later eligible for credentialling at one of three clinical specialty levels: basic clinical laparoscopy, advanced clinical laparoscopy, or instructor in clinical laparoscopy. Education and credentialling in minimally invasive surgery can be accomplished by executing a program of basic science and clinical training for physicians, technicians, and nurses that accommodates a wide range of experience of participants, from novice to master surgeon. Support from the hospital administrators and department chairs was instrumental in the program's success. Among the goals we accomplished was identification of persons in an institution who could serve as future instructors and certifiers for the hospital's self-sustaining program as well as providing a relationship in which international institutions can serve as a resource for further continuing medical education and clinical and laboratory training. This program may well serve as the model template for international credential standards of the future.

Objective: To investigate the presence of progesterone receptors and the extent and type of degranulation exhibited by the increased numbers of mast cells (MCs) found in interstitial cystitis (IC), a painful bladder disorder which occurs almost exclusively in women, worsens perimenstrually and is characterized by increased numbers of oestradiol receptor (OR)-positive MCs., Patients and Methods: The state of MC degranulation was analysed blindly using electron microscopy of bladder biopsies from 26 patients with IC and six control patients which included five women with incontinence, with none of the established characteristics of IC, and one man with transitional carcinoma of the bladder. Emphasis was placed on preserving the secretory granule ultrastructure. The presence of progesterone receptors (PRs) in five patients with IC and three controls was investigated using commercially available antibodies against PRs., Results: Over 85% of bladder MCs expressed high affinity PRs, but the number of PR-positive MCs in patients with IC did not differ significantly from that of controls despite the overall increase in MCs seen in IC. MCs were activated to various degrees and were often near to neuronal processes. The secretory granule content of MCs from patients with IC was in different stages of dissolution, ranging from heterogeneous loss of electron density to the appearance of crystalline substructure and target forms containing only remnants of the original material. Typical degranulation by compound exocytosis was not observed. MCs from control patients contained secretory granules with mostly intact, electron-dense granules., Conclusion: These findings indicate that the symptoms of IC may depend on an imbalance of the relative number of oestrogen receptors (ORs) to PRs on bladder MCs resulting in a 'progesterone deficient' state. This possibility is strengthened by demonstration that oestradiol augments the secretion of MC histamine in response to the neuropeptide substance P, which is pro-inflammatory, nociceptive and overexpressed in bladders with IC. Intragranular activation of bladder MCs is a characteristic pathological finding in patients with IC. The lack of extensive degranulation, typically seen in anaphylaxis, may indicate a unique mode of stimulation and/or differential release of mediators.

We have produced a continuous cell line using retroviral transduction of simian virus 40 (SV40) large T antigen into epithelial cells grown from a cystoscopic bladder biopsy from a female patient with interstitial cystitis. Immortalized urothelial cells are grown in a hormonally supplemented medium in the presence of lethally irradiated NIH-3T3 fibroblast coculture. They maintain their epithelial appearance and are positive for cytokeratins. SV40 large T antigen is localized to the cell nucleus. When grown on Anocell permeable supports, the cells form a complex epithelium with scalloped luminal membranes, apical junctional complexes containing tight junctions, stratification, transepithelial resistance of 500-1,000 omega.cm2, amiloride-sensitive short-circuit current indicative of active transepithelial Na+ absorption, and functional evidence for basolateral Na-K-adenosinetriphosphatase. This immortalized bladder cell line will facilitate the study of human bladder epithelial function and the response to diverse physiological and pathophysiological stimuli.

Objective: To evaluate laparoscopic varicocelectomy for the treatment of infertility in Saudi males., Methods: Between January 1992 and July 1994, laparoscopic varicocele repair was performed at Saudi Aramco Dhahran Health Center, in 48 patients, 8 for pain and 40 for infertility., Results: The 8 patients with pain improved postoperatively. As for those with infertility, 63% had an improved sperm count and 66% showed increased sperm motility. Thirty percent had no change in motility or count., Conclusion: Laparoscopic varicocelectomy is a simple and safe technique with good results and can be performed as day surgery with early return to normal activity.

Growing interest in the endoscopic treatment of vesicoureteral reflux and urinary incontinence has led to the development of safe reliable techniques that use an injectable bulking agent. A variety of injectable materials has been studied, such as polytetrafluoroethylene, fat and bovine collagen. We evaluated autologous collagen extracted from the dermis of skin for potential use in the urinary tract. Therefore, an animal model was developed to study the biological behavior of autologous collagen within the bladder. Collagen was extracted from the skin of rabbits and radiolabeled with 125iodine. An aliquot of radiolabeled autologous collagen was injected submucosally in the bladder. The animals were monitored weekly under a gamma camera. The decay of the radiolabeled collagen was recorded during 50 days. The animals were then sacrificed and the bladder wall at the site of injection was studied histologically and on electron microscopy. Decay of the injected collagen within the urinary tract was similar to control material, indicative of good stability within the bladder. A mild inflammatory response with fibroblastic and vascular invasion of the collagen implant was observed. These preliminary data suggest that autologous collagen injected endoscopically can provide a safe reliable bulking material that could be used to treat urinary incontinence and lower grades of vesicoureteral reflux in children.

Objective: To investigate the number of tryptase positive bladder mast cells and the level of urine tryptase in interstitial cystitis (IC), a bladder disorder which occurs mostly in women and is characterized by suprapubic pain, frequency and nocturia., Patients and Methods: Bladder biopsies from 37 women with IC and 15 control women with other bladder conditions (age range 18-63 years) were obtained during diagnostic bladder distension and frozen immediately. Mast cells positive for tryptase were identified by immunohistochemistry and evaluated by light microscopy. Tryptase was measured by solid phase radioimmunoassay in urine samples, collected immediately (spot) and during a period of 24 h, obtained from normal women volunteers, controls and patients with IC. To adequately quantify tryptase, the physiologically active tetramer was dissociated to inactive monomers with supersaturated NaCl (6.0 M), and then dialysed., Results: The patients' spot urine sample tryptase levels were indistinguishable from those of controls, which included the normal women volunteers. However, the tryptase levels in 24 h urine samples were greatly elevated only in patients with IC, both before (P < 0.005), and especially after NaCl treatment and dialysis (P < 0.001)., Conclusion: These results indicate that the tryptase levels of 24 h urine samples, combined with methylhistamine levels and the clinical criteria presently used, may possibly help to better identify IC.

Objective: To explore the presence of the neuropeptide substance P (SP) in the bladders of rats and humans and to investigate its relationship to mast cells (MCs) in interstitial cystitis (IC), a bladder disorder which occurs mostly in women and is characterized by frequency of voiding, nocturia and debilitating suprapubic pain., Patients, Materials and Methods: Bladder biopsies from eight women with untreated IC (mean age 36 years, range 29-58) and five control patients with no IC were analysed and compared with each other and with bladder tissue from 12 rats. Immunohistochemistry and image analysis were used to examine the density of SP-positive nerve fibres and their relationship with MCs., Results: SP-containing nerve fibres were present in the bladder of both rats and humans. They were increased only in the submucosa, but not in the detrusor, of IC patients and were frequently seen in juxtaposition to MCs., Conclusion: SP, a neuropeptide secreted from sensory nerve endings, has been implicated in the pathophysiology of pain and has been shown to trigger MC secretion. Moreover, MC secretion by SP is augmented by oestradiol and bladder MCs have been shown to express high affinity oestrogen receptors. A functional relationship between SP and MCs may explain the pathophysiology of the neuro-inflammatory and painful nature of IC.

Interstitial cystitis, a sterile bladder condition, is characterized by urinary frequency, urgency, burning and suprapubic pain. Increasing evidence indicates that interstitial cystitis is a heterogeneous syndrome that reflects an immune response to a variety of triggers. More than 50% of the patients have allergies, 30% have the irritable bowel syndrome and almost 20% suffer from migraine headaches. Increased numbers of mast cells have been reported in interstitial cystitis. Mast cell activation, which is critical if these cells were to be implicated in this syndrome, has been investigated by electron microscopy, which definitively shows mast cell secretion. Recently, methylhistamine, the major metabolite of histamine, and the specific mast cell marker, tryptase, were shown to be significantly elevated in urine of interstitial cystitis patients. Bladder biopsies from 53 patients were analyzed blindly for the number and degree of activation of mast cells using 4 different stains for light microscopy, as well as electron microscopy. Controls included 16 patients with incontinence and chronic bacterial cystitis. Mast cells in controls were less than 10/mm.2 and were all nearly intact. Surprisingly, mast cells from 11 cancer patients averaged 50/mm.2 but almost all were intact. In contrast, mast cells from 26 interstitial cystitis patients averaged 40/mm.2 and more than 90% were activated to various degrees. Therefore, bladder mast cell activation is a characteristic pathological finding in at least a subset of patients with interstitial cystitis.

Objective: To investigate the role of oestrogens in the pathophysiology of interstitial cystitis (IC), specifically with respect to activated bladder mast cells (MC), as well as urine concentrations of MC-derived histamine and methylhistamine, all of which are increased in patients with IC. This goal appeared important because IC is a bladder disorder which occurs almost exclusively in women, and is characterized by polyuria, nocturia and pelvic pain, which worsen perimenstrually., Patients and Methods: Biopsies from six patients with IC and four control patients were analysed blindly for the presence of oestrogen receptors (OR) using both custom-made and commercially available antibodies against OR., Results: Bladder MC alone were shown to express high-affinity OR and there was a higher number of such cells present in patients with IC compared with controls. The identity of MC in the bladder was documented with immunohistochemistry for tryptase. OR were also identified in human MC (HMC-1), a MC line kept in culture. These steps were necessary because of the unique finding that only MC express OR, in spite of the inflammatory infiltrate present., Conclusion: These findings may help to explain why IC occurs primarily in women, why IC and other associated symptoms tend to be worst at the midcycle, and may also suggest that prognostic usefulness of staining bladder biopsies for OR. These results are particularly interesting because oestradiol has been shown to augment MC histamine secretion in response to the neuropeptide, substance P, which may be released in certain neuroinflammatory disorders which have a high prevalence in women, such as IC and irritable bowel syndrome.

Minilaparotomy with placement of a trocar under direct vision has been felt to be a safe approach for establishing access to the intra-abdominal contents during laparoscopy. However, there is potential for hollow viscus injury. We report a case of a 23-year-old man whose small bowel was injured during placement of a Hasson trocar at the time of laparoscopic varix ligation. The literature on laparoscopic complications is reviewed, and recommendations for avoiding difficulties are outlined.

Interstitial cystitis is a painful bladder disorder occurring mostly in women, and is presently diagnosed by clinical presentation, as well as the presence of mucosal glomerulations and inflammation on bladder distention. An increased number of bladder mast cells have been implicated in the pathophysiology of interstitial cystitis but previous reports of spot urine histamine have not confirmed bladder mast cell activation. The availability of easily measurable objective criteria could make the diagnosis easier. Histamine and its major metabolite, methylhistamine, were measured in spot and 24-hour urine specimens from a number of normal female volunteers, control patients and interstitial cystitis patients. In interstitial cystitis patients the histamine levels were only slightly increased in the spot (p < 0.01) and 24-hour urine (p < 0.03) collections. Methylhistamine, on the other hand, was greatly elevated in spot (p < 10(-10)) and 24-hour (p < 0.0008) urine samples. These results indicate that methylhistamine levels could serve as useful diagnostic end points for interstitial cystitis.

The bladder mast cell contains many granules, each of which can secrete many vasoactive and nociceptive molecules. A number of conditions, such as extreme cold, drugs, neuropeptides, stress, trauma, and toxins, can trigger the mast cell to secrete some of its contents; they, in turn, can sensitize sensory neurons, which can further activate mast cells by releasing neurotransmitters or neuropeptides. Additionally, the mast cell can directly cause vasodilation and bladder mucosa damage while also attracting inflammatory cells, thus causing many of the problems seen in interstitial cystitis. The mast cell appears to be involved in the pathogenesis of interstitial cystitis. Although it is not pathognomonic of the disease, mastocytosis does occur in a significant subset of interstitial cystitis patients. Because interstitial cystitis is now regarded as a syndrome caused by multiple factors, it is conceivable that one cause of interstitial cystitis is associated with bladder mastocytosis and mast cell activation. The fact that mast cells are also increased in patients with transitional cell carcinoma of the bladder does not diminish the importance of mastocytosis in interstitial cystitis, because the mast cells are not activated in carcinoma but are activated in interstitial cystitis. Perhaps the common strand between these two bladder diseases is the putative allergens/carcinogens in bladder urine that breach the protective lining of the bladder and then elicit an immune response in the bladder wall. Furthermore, the majority of patients with a history of bladder tumors receive multiple courses of intravesical chemotherapy (such as thiotepa) or immunotherapy (bacille Calmette-Guerin), and it is possible that these agents damage the bladder lining or provoke an inflammation in the bladder wall. The theory of a defective/deficient bladder glycosaminoglycan layer in interstitial cystitis is also consonant with this putative chain of events in the pathogenesis of interstitial cystitis. Thus these two theories interstitial cystitis causation--a glycosaminoglycan deficiency and bladder mastocytosis--may well operate in concert to cause bladder inflammation and the symptoms of interstitial cystitis. Clinicians may be at a distinct disadvantage because they are faced with a multitude of potential mast cell triggers and numerous mediators secreted. It may, therefore, be advisable to block or inhibit the mast cell from responding to many of these various stimuli. Specific mast cell mediators should be assayed as possible diagnostic tools, and potential mast cell inhibitors should be tried under controlled conditions to determine the extent of therapeutic benefit.

The treatment of interstitial cystitis is difficult and at time frustrating--both for the patient and for the physician. Treatment is hampered by the lack of a clear understanding of its pathophysiology, which makes it difficult to objectively assess disease severity and/or progression. Intravesical therapy appears to be the most successful approach to the relief of symptoms. Clearly, there are drawbacks to intravesical therapy, particularly Clorpactin lavage. Responses to intravesical lavage are variable in duration, unpredictable, and unamenable to objective measurement. Multiple treatments are frequently needed, as with DMSO, and multiple anesthetics may be required for Clorpactin therapy. There have been no double-blind, placebo-controlled studies comparing the mainstays--Clorpactin and DMSO--of intravesical treatment. It is hoped that current research into the pathogenesis and causation of interstitial cystitis will lead to an improved understanding of this disease or syndrome. The introduction of newer, more specific intravesical therapies will surely follow such advances.

We report an unusual metastatic renal cell carcinoma in the right cardiac ventricle in a 53-year-old man who presented with increasing dyspnea. Diagnostic evaluation revealed a left renal tumor without contiguous extension into the inferior vena cava and a right ventricular mass. To our knowledge this is only the second reported case of metastatic renal cell carcinoma to the right cardiac ventricle diagnosed ante mortem. We discuss the case and review the literature.

A randomized, prospective, double-blind, placebo-controlled study was conducted at 7 clinical centers on 148 patients. Patients received orally either 100 mg. pentosanpolysulfate (a synthetic polysaccharide) 3 times per day or a placebo. Of the patients on drug therapy 32% showed significant improvement compared to 16% of those on placebo (p = 0.01). This study provides a model to assess this disease quantitatively in a prospective manner using a method whereby the patients globally assess their symptoms as either worse or improved by 0, 25, 50, 75 or 100%. Patients on drug therapy also experienced a significant decrease in pain and urgency (p = 0.04 and 0.01) on analogue scales when compared to placebo and also more drug patients showed an average increase of more than 20 ml. in voided volume than did placebo patients (p = 0.02). All adverse effects were minor, with 7 in the drug group and 10 in the placebo group. The results support the concept that some patients with the interstitial cystitis syndrome may have abnormal bladder surface glycosaminoglycans.

The biocompatibility of a new elastomeric-hydrogel matrix biomaterial for use as an intravasal occlusive device was assessed by inserting it into the vas deferens of dogs. The vas was removed and examined histologically after varying periods of time. The biomaterial resulted in total occlusion of the vas. Epithelial changes were limited to squamous metaplasia in areas adjacent to the implant. Changes in the subepithelium were minimal. This new material is biocompatible with the dog vas, and it has potential as an occlusive device for "reversible" vasectomy in men. Semen analysis studies are needed to assess the completeness and reversibility of the vasal occlusion achieved with this implant.

A bladder disorder of unknown etiology, interstitial cystitis affects mainly women, and its prevalence may be increasing. Little information is available on the demographic, clinical, diagnostic, and treatment aspects of interstitial cystitis in the minority population. This retrospective review of the patient database at the Interstitial Cystitis Center, New England Medical Center, identified 17 minority women among a total of 201 patients who satisfied the criteria of the National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases for diagnosis of interstitial cystitis. Minority women accounted for 8.5% of the patients, with 3% being African American; 3.5%, Hispanic American; and 2.0%, Asian American. The clinical and endoscopic findings as well as responses to treatment were similar in both the minority and nonminority populations. However, the average duration of symptoms prior to diagnosis was 2.9 years in the minority group, compared with an average of 13 months in the nonminority group. Minority women with interstitial cystitis appear to be symptomatic for longer periods before a definitive diagnosis is made. Their response to treatment parallels that of the nonminority population. Further studies are needed to address the natural history, urologic referral patterns, and treatment outcomes in minority women who have interstitial cystitis.

Interstitial cystitis (IC) is a sterile, inflammatory bladder condition characterized by urinary frequency and urgency, as well as burning and suprapubic pain, which occurs more frequently in women who may suffer for years before diagnosis. An increased number of mast cells have been associated with IC, but the published reports are inconclusive and often conflicting. Human bladder biopsies were analysed blindly for the degree of activation of mast cells in control and IC patients. It was found that mast cells from IC patients averaged as high as 34 cells/mm2 as compared to less than 16/mm2 in controls. Electron microscopy revealed that over 90% of mast cells from IC patients were activated to various degrees. It is concluded that mast cell activation is a pathologic characteristic for IC.

The bladder mast cell contains many granules, each one of which can secrete many vasoactive and nociceptive molecules. A number of conditions such as extreme cold, drugs, neuropeptides, stress, trauma, toxins, etcetera, can trigger the mast cell to secrete some of its contents. In turn, these chemicals can sensitize sensory neurons, which can further activate mast cells by releasing neurotransmitters or neuropeptides. Additionally, the mast cell can directly cause vasodilation and bladder mucosa damage while attracting inflammatory cells, thus causing many of the problems observed in IC. Clinicians may be at a distinct disadvantage because they are faced with a multitude of potential mast cell triggers and numerous mediators secreted. Therefore, it may be advisable to block or inhibit the mast cell from responding to many of these various stimuli. Specific mast cell mediators should be assayed as possible diagnostic tools, whereas potential inhibitors of mast cell secretion should be tried under controlled conditions to determine the extent of therapeutic benefit.

Surgical ablation of five-sixths renal mass in Munich-Wistar rats fed a high protein diet leads to focal sclerosis in the remnant kidney and progressive renal failure. Experimental data suggest that this injury results from intraglomerular hypertension and/or chronic glomerular hyperfiltration. Data in humans largely are limited to patients with unilateral renal agenesis or uninephrectomy, either for unilateral renal disease or for kidney transplant donation. Isolated case reports have documented focal sclerosis and progressive renal failure in two patients with a remnant kidney. To obtain data in humans with a remnant kidney, we surveyed more than 800 urologists and nephrologists in the United States and abroad. Criteria for inclusion in the study were (1) surgical resection (in one or more operations) resulting in the presence of a remnant kidney; and (2) an adequate period of follow-up, defined as 5 years or greater. A total of 13 patients were identified (from 13 different centers). Twelve patients had renal cancer and one had tuberculosis. Six patients were observed for 10 or more years postoperatively and all have stable serum creatinine levels of less than 270 mumol/L (3.0 mg/dL); two of these six patients are now more than 25 and 30 years postoperation. The other seven patients, observed for 5 to 7 years, have serum creatinine levels less than 270 mumol/L (3 mg/dL), while one has an increasing serum creatinine level. The two longest surviving patients both have undergone successful pregnancy with no overall change in serum creatinine. These observations demonstrate that it is possible for humans to survive more than 30 years with a stable serum creatinine, despite the presence of only a remnant kidney.

A patient with false elevation of serum creatinine level due to 5-fluorocytosine (5-FC) is reported. 5-FC interferes with the enzymatic method used for creatinine determination in the Kodak Ektachem analyzer. Clinicians should be aware of the potential for spurious azotemia in patients receiving 5-FC therapy for fungal urinary tract infections.

Infected urachal cysts present with protean clinical manifestations. Diagnosis is frequently difficult in spite of the use of modern genitourinary radiologic imaging techniques. Patients with intra-abdominal or pelvic symptoms are frequently misdiagnosed. Surgical excision is the treatment of choice for infected urachal cysts.

Pentosan polysulfate sodium (PPS) was compared with placebo for the symptomatic therapy of interstitial cystitis in a double-blind, multicenter study. A total of 110 patients were enrolled and treated for three months. In this study, overall improvement of greater than 25 percent was reported by 28 percent of the PPS-treated patients and by 13 percent of the placebo-treated patients (p = 0.03). The investigators' overall evaluation provided similar results, 26 percent vs 11 percent in favor of PPS (p = 0.04). Improvement in pain and pressure to urinate also favored PPS over placebo and approached statistical significance (p = 0.07 and 0.08). The incidence of adverse reactions was 6 percent in the PPS-treated group and 13 percent in the placebo-treated group. All adverse reactions were minor, and treatment was discontinued by 1 patient in the PPS group and 2 in the placebo group. In this study, PPS was found to be significantly more effective than, and equally as safe as, placebo.

Exclusive reliance on radiographic techniques for the diagnosis of renal angiomyolipoma can lead to misdiagnosis when the histological status is atypical, computerized tomographic findings are equivocal or renal cell carcinoma coexists. We report our experience and those of others in combining fine needle aspiration biopsy and radiological imaging to identify renal angiomyolipoma. Fine needle aspiration biopsy is safe and provides accurate histological diagnosis of renal angiomyolipoma.

A case of spontaneous rupture of an acquired bladder diverticulum is presented. Diagnosis was made preoperatively and full recovery followed surgical treatment. A review of the literature revealed 9 other cases of spontaneous rupture. Bladder outlet obstruction and urinary tract infection were present in the majority of cases. In the past misdiagnosis and delayed treatment led to significant mortality. However, the prognosis currently is better due to the use of broad-spectrum antibiotics, better radiological imaging studies, and earlier diagnosis and treatment.

A case of global renal infarction resulting from blunt renal trauma is presented. The cortical 'rim sign' on computed tomographic (CT) scanning is suggestive of major renal arterial occlusion. Clinicians who use CT scanning as the initial imaging modality for the evaluation of blunt kidney trauma should be aware of this sign and its implications for management.

We treated successfully 3 patients with upper urinary tract obstruction after an aortoiliac reconstructive vascular operation: 2 with ureterolysis and 1 with transureteroureterostomy. A review of the literature reveals that the incidence of this complication of reconstructive vascular surgery is unknown. Obstruction occurred whether the ureter was anterior or posterior to the graft, and usually presented within 1 year postoperatively in 62 per cent of the patients and was silent in 13 per cent. The obstruction was caused by retroperitoneal fibrosis in 90 per cent of the patients, direct surgical injury in 5 per cent and pseudoaneurysm formation in 5 per cent. Prior pelvic irradiation, and extensive and/or repeat vascular surgical procedures may have been contributory. Ureterolysis, the most common form of treatment, resulted in improvement in 85 per cent of the upper tracts, while renal loss occurred in 10 per cent. The ureter should be placed anterior to the graft during aortoiliac graft procedures. A prospective study is needed to ascertain the true incidence of this complication after reconstructive vascular surgery.

Renacidin (10 per cent hemiacidrin) irrigation has been used in the management of renal struvite calculi in 25 patients. Of these patients 22 were free of stone after irrigation: 16 after dissolution of residual stone fragments postoperatively, 4 after prophylactic postoperative irrigation and 2 after primary, nonsurgical percutaneous dissolution. Recurrent urinary tract infections owing to the original urease-producing bacteria occurred in 14 per cent of these patients and recurrent nephrolithiasis occurred in 9 per cent during an average followup period of 66 months.

Twenty patients with prostatodynia were studied urodynamically with synchronous video-pressure-flow studies and electromyography of the external urethral sphincter. The most striking finding was a significant increase in maximum urethral closure pressure compared to an age and sex-matched control group. Typically, peak and average urinary flow rates were decreased. Another prominent feature was incomplete funneling of the bladder neck during voiding with an accompanying urethral narrowing at the level of the external urethral sphincter. These findings are not consistent with a diagnosis of tension myalgia of the pelvic floor or detrusor-striated sphincter dyssynergia but suggest a primary abnormality involving the pelvic sympathetic nervous system. We believe that more advanced methods than those available currently are needed to elucidate fully the role of the autonomic nervous system, especially its sympathetic component, in the etiology of prostatodynia.

Endometriosis involving the muscular wall of the bladder may cause symptoms similar to those of interstitial cystitis. Vesical endometriosis should be considered in the differential diagnosis of interstitial cystitis, especially in patients with a history of prior gynecologic or pelvic surgery.

Accurate preoperative diagnosis of renal angiomyolipomas is essential if conservative resection or angiographic embolization is to be used. Computed tomographic (CT) scanning failed to diagnose angiomyolipoma preoperatively in 2 patients, and this led to a retrospective review of 6 patients to define the limits of CT scanning in preoperative diagnosis. The CT findings were correlated with the histology of the tumors. Two tumors with positive attenuation coefficients suggestive of renal adenocarcinoma had significant amounts of immature "fetal" fat, and one of these had a virtual absence of mature fat. The relative inability of CT scanning to identify immature "fetal" fat, especially in the presence of abundant vessel and muscle elements, is a limitation to its use in the preoperative diagnosis of angiomyolipoma. A negative attenuation coefficient is highly characteristic of renal angiomyolipoma with mature fat elements. A positive attenuation coefficient, although suggestive of renal cell carcinoma, may be found in angiomyolipomas with paucity of mature fat or high proportions of immature fat.

Rupture of the corpus cavernosum ("fracture" of the penis) is an uncommon injury that occurs in an erect penis. The tunica albuginea is torn during coitus or as a result of external forces, resulting in sudden pain, swelling, and discoloration of the penis. Urethral rupture is associated with the cavernous injury in approximately 10% of cases. Treatment of the injury aims at full functional and cosmetic recovery. Nonoperative treatment results in a 10% incidence of penile deformity and requires a substantial hospital stay. However, surgical repair eliminates resultant deformity and allows for earlier hospital discharge. Three patients had fractured penises, including one penis associated with a torn urethra. Early surgical repair was performed in each patient, and the results were excellent. Prompt surgical repair should be given to all patients with a fractured penis.