Biomedical subjects

G R Sant

Publications and source records attributed to G R Sant.

At least 55 records · Page 3Linked to original sources

PubMed1995

Bladder mast cell expression of high affinity oestrogen receptors in 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.

Cystitis↗

PubMed1995

Increased number of substance P positive nerve fibres in interstitial cystitis.

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.

Adult↗

PubMed1995

Elevated mast cell tryptase in the urine of patients with interstitial cystitis.

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.

Adolescent↗

PubMed1994

Increased urine histamine and methylhistamine in interstitial cystitis.

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.

Adolescent↗

PubMed1994

Metastatic renal cell carcinoma to the right cardiac ventricle without contiguous vena caval involvement.

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.

Carcinoma, Renal Cell↗

PubMed1994

Minilaparotomy for laparoscopy: not a foolproof procedure.

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.

Adult↗

PubMed1994

The role of the mast cell in 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.

Animals↗

PubMed1994

Standard intravesical therapies for interstitial cystitis.

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.

Administration, Intravesical↗

PubMed1993

New matrix material for potential use in "reversible" vasectomy. Preliminary animal biocompatibility studies.

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.

Animals↗

PubMed1993

A quantitatively controlled method to study prospectively interstitial cystitis and demonstrate the efficacy of pentosanpolysulfate.

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.

Aged↗

PubMed1993

Interstitial cystitis in minority women.

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.

Adult↗

PubMed1992

Activation of bladder mast cells in 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.

Cystitis↗

PubMed1991

Prolonged survival with a remnant kidney.

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.

Adult↗

PubMed1991

Bladder mast cell activation in interstitial cystitis.

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.

Animals↗

PubMed1990

Pentosan polysulfate sodium for therapy of interstitial cystitis. A double-blind placebo-controlled clinical study.

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.

Adult↗

PubMed1990

Spurious azotemia associated with 5-fluorocytosine therapy.

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.

Aminohydrolases↗

PubMed1990

Infected urachal cysts.

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.

Adult↗

PubMed1990

Spontaneous rupture of a bladder diverticulum.

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.

Aged↗