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Biomedical subjects

G R Sant

Publications and source records attributed to G R Sant.

At least 37 records · Page 2Linked to original sources
PubMed1997

Intravesical dimethyl sulfoxide (DMSO) for interstitial cystitis--a practical approach.

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.

Administration, Intravesical↗
PubMed1997

Hydroxyzine therapy for 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.

Cystitis, Interstitial↗
PubMed1997

The interstitial cystitis symptom index and problem index.

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.

Cystitis, Interstitial↗
PubMed1997

Histological evidence of an inflammatory reaction to suture material in the dog vas deferens.

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.

Animals↗
PubMed1997

Interstitial cystitis and bladder mastocytosis in a woman with chronic urticaria.

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.

Adult↗
PubMed1997

Stress-induced bladder mast cell activation: implications for interstitial cystitis.

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.

Animals↗
PubMed1997

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.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

Carbachol-induced bladder mast cell activation: augmentation by estradiol and implications for interstitial cystitis.

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.

Acetylcholine↗
PubMed1996

Mast cell and substance P-positive nerve involvement in a patient with both irritable bowel syndrome and interstitial cystitis.

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.

Chymases↗
PubMed1996

Intragranular activation of bladder mast cells and their association with nerve processes in interstitial cystitis.

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.

Adult↗
PubMed1996

Immortalized human bladder cell line exhibits amiloride-sensitive sodium absorption.

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.

Absorption↗
PubMed1996

Laparoscopic varicocelectomy for infertility. An initial report from Saudi Arabia.

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.

Adult↗
PubMed1996

Planning, development, and execution of an international training program in laparoscopic surgery.

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.

Education, Medical, Continuing↗
PubMed1995

Activation of bladder mast cells in interstitial cystitis: a light and electron microscopic study.

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.

Adult↗
PubMed1995

The biological behavior of autologous collagen injected into the rabbit bladder.

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.

Animals↗