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Biomedical subjects

J S Varma

Publications and source records attributed to J S Varma.

At least 19 recordsLinked to original sources

Long-term outcome of laparoscopic mesh rectopexy for solitary rectal ulcer syndrome.

OBJECTIVE: To determine the long-term outcome of laparoscopic mesh rectopexy for solitary rectal ulcer syndrome (SRUS). PATIENTS AND METHODS: A retrospective review of 11 patients who underwent laparoscopic mesh rectopexy for refractory SRUS between 1993 and 1996. All patients were followed up initially with rigid sigmoidoscopy and seven were involved in long-term evaluation (follow-up at 71-106 months, median 89 months) involving a sickness impact profile questionnaire. RESULTS: Complete endoscopic healing of the ulcer was demonstrated in all 11 patients up to one year postoperatively but one suffered recurrence later. Of seven assessed long-term, none experienced endoscopic recurrence. Six continued to enjoy a significant reduction in symptoms and an improved quality of life. One had persistent problems and demonstrated little symptomatic improvement. CONCLUSION: Laparoscopic mesh rectopexy offers a minimally invasive option for selected patients who remain severely symptomatic despite maximal conservative therapy for SRUS, with demonstrable ulcer healing and long-term improvement in symptoms and quality of life. Larger studies are required to fully evaluate its efficacy compared to 'conventional' surgical options.

Adolescent↗

Homeostatic regulation of zinc transporters in the human small intestine by dietary zinc supplementation.

BACKGROUND: The role of intestinal transporter regulation in optimising nutrient absorption has been studied extensively in rodent and cell line models but not in human subjects. AIMS: The aim of the present study was to investigate the response in vivo of zinc transporters in the human enterocyte to dietary zinc supplementation. SUBJECTS: Eighteen patients who had previously undergone ileostomy, all free of any symptoms of inflammatory bowel disease. METHODS: Subjects took a daily zinc supplement of 25 mg for 14 days in a double blind, placebo controlled, crossover trial. The effect of the supplement on expression in ileal biopsies of the zinc transporters SLC30A1, SLC30A4, SLC30A5, SLC39A1, SLC39A4, and metallothionein was measured by reverse transcription-polymerase chain reaction RT-PCR. Expression of SLC30A1, SLC30A5, and SLC39A4 was also examined by immunoblotting. RESULTS: The zinc supplement reduced SLC30A1 mRNA (1.4-fold) together with SLC30A1, SLC30A5, and SLC39A4 protein (1.8-fold, 3.7-fold, and to undetectable levels, respectively) in ileal mucosa and increased metallothionein mRNA (1.7-fold). The supplement had no effect on expression of SLC30A4 or SLC39A1 mRNA. Localisation of SLC30A5 at the apical human enterocyte/colonocyte membrane and also at the apical membrane of Caco-2 cells was demonstrated by immunohistochemistry. Commensurate with these observations in zinc supplemented human subjects, SLC30A1, SLC30A5, and SLC39A4 mRNA and protein were reduced in Caco-2 cells cultured at 200 muM compared with 100 muM zinc. CONCLUSIONS: These observations indicate that, in response to variations in dietary zinc intakes, regulated expression of plasma membrane zinc transporters in the human intestine contributes to maintenance of zinc status.

Adult↗

Outcome after transperineal mesh repair of rectocele: a case series.

PURPOSE: This study was designed to establish the safety and efficacy of transperineal mesh repair in patients with obstructed defecation caused by rectocele. METHODS: Between 1998 and 2002, 24 consecutive females with symptomatic rectocele were retrospectively reviewed after mesh repair of rectocele. Two patients had inadvertent rectal perforation during operation and had no mesh implantation. Of the remaining 22 patients, 14 had a prolene mesh implanted, and 8 had a Vipro II mesh implanted. Median age at the time of presentation was 55 (range, 28-66) years. Patients were selected for operation based on clinical and evacuation proctogram findings. All patients complained of incomplete rectal evacuation, and the majority complained of excessive straining, constipation, and the need for vaginal/perineal digital pressure to aid defecation. Patients were followed up in clinic at six weeks, and a telephone questionnaire was performed at a median time of 12.5 (range, 3-47) months. Functional/objective outcomes were assessed for the following five symptoms preoperatively and postoperatively: excessive straining, incomplete evacuation, perineal/vaginal digital pressure, vaginal bulging, and constipation (always, usually, occasionally, never). Subjective outcomes were assessed as excellent, good, moderate, or poor. In addition, patients were asked about preexisting and postoperative dyspareunia. RESULTS: Objective outcomes based on symptoms showed an improvement in two or more symptoms in 20 patients (91 percent). For all symptoms, there was a significant reduction in mean values after repair. Subjective outcomes showed that 17 patients (77 percent) had a moderate/good/excellent result. Patients with abnormal preoperative colonic transit marker studies did as well as those who had no transit studies performed or those who had normal studies. Patients who did not vaginally digitate did as well as those who did not digitate. Only one patient complained of new onset dyspareunia. Two patients with sphincter defects on endoanal ultrasound had a sphincteroplasty performed (1 prerectocele repair and 1 at the same time). There were two superficial wound infections and one deep infection. All infections responded to antibiotic therapy. No mesh has been removed. Semiabsorbable mesh repair was superior to nonabsorbable mesh repair. CONCLUSIONS: Transperineal mesh repair of symptomatic rectocele is a safe technique that avoids the anal dilation and sphincter injury associated with endorectal repair. Objective and subjective results are good in the majority of patients, although a longer follow-up is required to confirm no deterioration.

Adult↗

Sacral nerve stimulation for faecal incontinence in the UK.

BACKGROUND: Sacral nerve stimulation (SNS) is an effective therapy for faecal incontinence. Published studies derive largely from single centres and there is a need to determine the broader applicability of this procedure. METHODS: Prospective data were collected for all patients undergoing SNS in the UK. Records were reviewed to determine the outcome of treatment. RESULTS: In three UK centres 59 patients underwent peripheral nerve evaluation, with 46 (78 per cent) proceeding to permanent implantation. Of these 46 patients (40 women) all but two had improved continence at a median of 12 (range 1-72) months. Faecal incontinence improved from a median (range) of 7.5 (1-78) to 1 (0-39) episodes per week (P < 0.001). Urgency improved in all but five of 39 patients in whom ability to defer defaecation was determined, improving from a median of 1 (range 0-5) to 10 (range from 1 to more than 15) min (P < 0.001). Maximum anal squeeze pressure and sensory function to rectal distension changed significantly. Significant improvement occurred in general health (P = 0.024), mental health (P = 0.008), emotional role (P = 0.034), social function (P = 0.013) and vitality (P = 0.009) subscales of the Short Form 36 health survey questionnaire. There were no major complications. One implant was removed. CONCLUSION: SNS is a safe and effective treatment, in the medium to long term, for faecal incontinence when conservative treatment has failed.

Adult↗

Prospective audit of quality of colonoscopy in a surgical coloproctology unit.

OBJECTIVE: The aim of this study was to prospectively audit the quality of colonoscopy and patient acceptance in a Surgical Coloproctology Unit over a one-year period. PATIENTS AND METHODS: 202 consecutive colonoscopies were evaluated over a 12-month period performed by a Consultant, Specialist Registrars and Research fellows. Data where recorded for adequacy of bowel preparation, completion rate, adequacy of sedation, patient tolerance and duration of the procedure. Adequacy of bowel preparation was monitored by scoring bowel content and the percentage of bowel wall visualised. Patients completed a questionnaire to express their sedation satisfaction, discomfort during the procedure and overall satisfaction. RESULTS: The success rate of bowel preparation was 94%. Completion rate was 90% in intended full colonoscopies by the Consultant and Registrars and 74% by more junior grade endoscopists (overall 86%). The mean dose of midazolam and pethidine was higher in patients with unsatisfactory sedation than those with satisfactory sedation. The pain score was higher when trainees performed the procedure than when performed by the Consultant. Fourteen patients refused to undergo the procedure again due to procedure discomfort (n = 7), inadequate sedation (n = 2) and bowel preparation discomfort (n = 5). CONCLUSION: A high completion rate was achieved, compared with published results. However, further improvements are possible especially by improving the performance of junior endoscopists and by ensuring optimal bowel preparation. Patients' tolerance of colonoscopy was highly acceptable but may also be improved by the same methods.

Adolescent↗

Porcine dermal collagen graft in abdominal-wall reconstruction.

We describe the use of a porcine dermal collagen graft in the reconstruction of a large abdominal-wall defect in a woman. The graft was not rejected and, after 1 year, was not associated with incisional hernia. This graft may become an alternative to synthetic-mesh and flap reconstructions because, despite being of a similar tensile strength, it promotes less adhesion, is incorporated into the host tissue and is less prone to infection.

Aged↗

Rectal retroflexion: an essential part of lower gastrointestinal endoscopic examination.

PURPOSE: Retroflexion of the endoscope during rectal examination may increase diagnostic yield but is not routinely performed because of concerns about safety and a lack of appreciation of its importance. The purpose of this study was to examine the yield, safety, and tolerance of endoscopic rectal retroflexion. METHODS: Prospective cohorts of subjects undergoing unsedated screening flexible sigmoidoscopy were examined with and without routine retroflexion. Pain scores were recorded. RESULTS: A total of 526 subjects (mean age 60 (range, 55-66) years) underwent flexible sigmoidoscopy in the first period when the endoscope was not routinely retroflexed. Of these, 480 (mean age 60 (range, 55-66) years) were subsequently examined with routine retroflexion. Retroflexion was impossible in 17 subjects (3.5 percent) because of discomfort. In the second group, 12 subjects (2.5 percent) had polyps in the lower rectum seen only on retroflexion. Of these, eight had metaplastic and four had adenomatous polyps (3 tubular <5 mm, 1 tubulovillous 15 mm). There was no difference in mean pain scores between the groups (no retroflexion = 2.13, retroflexion = 2.18). CONCLUSION: With an adenoma pick-up rate of 8 to 12 percent for screening flexible sigmoidoscopy, retroflexion increases adenoma detection by approximately 1 percent without adverse effects and should be an integral part of flexible sigmoidoscopy.

Adenoma↗

Per anal excision of large rectal adenomas using an endoscopic stapler.

Large rectal adenomas can be approached per-anally by open excision or by transanal endoscopic microsurgery (TEMS). We describe the adaptation of an endoscopic linear stapler-cutter for per anal excision of rectal polyps. It can be used for difficult polyps with minimal risk of complications and is easier and more accessible than TEMS.

Adenoma↗

Increased plasma nitrite level in cardiac failure.

Increased Plasma Nitrite Level in Cardiac Failure. Nitric oxide is implicated in the pathogenesis of cardiac failure. Plasma nitrite level (an end product of nitric oxide metabolism) is studied in 15 patients of chronic rheumatic valvular heart disease with myocardial contractile dysfunction and cardiac failure (Group I), 15 patients of chronic rheumatic valvular heart disease with similar valvular lesions, normal myocardial contractile function and without cardiac failure (Group II) and 15 healthy controls (Group III). Patients in Group I had higher nitrite level (242.2+/-31.7 n m) compared to Group II (142.6+/-24.4 n m) and Group III (102.7+/-15.9 n m). Among the patients with rheumatic heart disease, increasing nitrite level correlated significantly with worsening of contractile function [Nitrite v End systolic volume/Body surface area (T(xy.z)=0.23), Nitrite v End systolic dimension/Body surface area (T(xy.z)=0.32), Nitrite v left ventricular ejection fraction (T(xy.z)=-0.24), Nitrite v tricuspid annular plane systolic excursion (T(xy.z)=-0. 29)] and worsening New York Heart Association (NYHA) functional class (r(s)=0.5). We conclude that plasma nitrite, a stable end product of nitric oxide metabolism is increased in patients of rheumatic valvular heart disease with cardiac failure, suggesting increased nitric oxide production. Increased level of nitric oxide might be playing a significant role in myocardial contractile dysfunction and alteration of vascular response in cardiac failure.

Female↗

Cyclin D3 expression, cell proliferation and pathological stage of human primary colorectal cancer.

Cyclin D3 promotes cell cycle progression but its expression and prognostic significance in human colorectal cancer is unknown. This study assayed cyclin D3 expression against cell cycle phase fraction and Duke's stage in 35 fresh human primary colorectal cancers. DNA content, cell cycle phase fraction and cyclin D3 expression were assessed by flow cytometry in disaggregated tumors. Cyclin D3 expression and S-phase fraction were independently related to Duke's stage. In Duke's stage C tumors, a higher proportion of cells expressed cyclin D3 (14.4 vs. 8.8%, mean; p < 0.05 by Mann-Whitney U test) and were in DNA synthesis (S) phase (21.1 vs. 9.7%, mean; p < 0.05 by Mann-Whitney U test). Neoplastic deregulation of cyclin D3 expression may provide a selective growth advantage which is related to stage in human colorectal cancer.

Aged↗

Clinical, echocardiographic, and angiographic profile of patients with double-chambered right ventricle: experience with 48 cases.

Forty-eight patients with double-chambered right ventricle (DCRV) were prospectively studied over a 3-year period. Clinical, echocardiographic, hemodynamic, and angiographic studies were done in all. Three patients were studied postoperatively also. Fifteen patients underwent surgery confirming the diagnosis. Echocardiography detected anomalous muscle bundles (AMBs) in 39/41 patients in whom this study was carried out. Angiographically AMBs were best demonstrated in anteroposterior views in a systolic frame. Common associated anomalies found with DCRV were ventricular septal defects (69%), pulmonary valve stenosis (38%), and double-outlet right ventricle (10%).

Adolescent↗

Hereditary non-polyposis colorectal cancer.

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant condition in which affected individuals develop colorectal cancer or extracolonic cancers, most commonly endometrial, at an early age. Recent advances in molecular genetics have led to the identification and sequencing of four genes thought to be responsible for the majority of cases of hereditary non-polyposis colorectal cancer. A description of the disease along with details of the underlying genetics and pathological features are presented. Current management and screening policies in these pedigrees are not clearly established. This article discusses some of the controversies in the light of predictive testing.

Colonic Neoplasms↗

Autonomic functions in restrictive cardiomyopathy and constrictive pericarditis: a comparison.

BACKGROUND: This study was undertaken to analyze autonomic functions in restrictive cardiomyopathies. Restrictive cardiomyopathies have clinical and hemodynamic similarity with chronic constrictive pericarditis. Autonomic dysfunction has been described in the latter. METHODS AND RESULTS: Autonomic function analysis has not been reported in restrictive cardiomyopathy. Six consecutive patients with restrictive cardiomyopathy were included in this study (5 men, 1 woman, mean age 35+/-5.4 years). The tests performed were designed to test the sympathetic efferent pathway, that is, by cold hand immersion and loud noise tests, parasympathetic efferent pathway by Valsalva ratio and expiration/inspiration ratio and the baroreceptor function by testing their sensitivity slope. The results were compared with 20 patients with chronic constrictive pericarditis and with 10 healthy age- and sex-matched control subjects previously studied. The rise of systolic blood pressure after cold hand immersion and sudden loud noise was not significantly different compared with control subjects. The expiration/inspiration ratio was 1.1+/-0.01 compared with 1.57+/-0.1 in the control group (p < 0.01). The Valsalva ratio was significantly lower (1.1+/-0.04) compared with control subjects (1.83+/-0.1, p < 0.01). The baroreceptor sensitivity was not reduced compared with that in control subjects. In comparison to constrictive pericarditis, sympathetic efferent pathway is preserved in restrictive cardiomyopathy (p < 0.0001). The parasympathetic efferent pathway is borderline abnormal in restrictive cardiomyopathy but not significantly as compared with constrictive pericarditis (p=not significant). The baroreceptor sensitivity slope is normal in patients with restrictive cardiomyopathy as compared with significant depression seen in constrictive pericarditis (p < 0.05). Autonomic functions are better preserved in patients with restrictive cardiomyopathies compared with chronic constrictive pericarditis. CONCLUSIONS: Autonomic dysfunction is localized to parasympathetic efferent pathway. This is in comparison to constrictive pericarditis, in which severe autonomic dysfunction is a universal feature and includes all segments of autonomic nervous system.

Adolescent↗

Colonic epithelial cell proliferation in hereditary non-polyposis colorectal cancer.

BACKGROUND: Despite the recent discovery of four genes responsible for up to 90% of all cases of hereditary non-polyposis colorectal cancer (HNPCC), there will still be families in whom predictive testing is not possible. A phenotypic biomarker would therefore be useful. An upwards shift of the proliferative compartment in colonic crypts is reported to be one of the earliest changes in premalignant mucosa. AIMS: To assess the role of crypt cell proliferation as a phenotypic biomarker in HNPCC. PATIENTS: Thirty five patients at 50% risk of carrying the HNPCC gene (21 of whom subsequently underwent predictive testing and hence gene carrier status was known) and 18 controls. METHODS: Crypt cell proliferation was measured at five sites in the colon using two different techniques. Labelling index was determined using the monoclonal antibody MIB1 and whole crypt mitotic index was measured using the microdissection and crypt squash technique. The distribution of proliferating cells within the crypts was also assessed. RESULTS: There were no significant differences in the total labelling index or mean number of mitoses per crypt, nor in the distribution of proliferating cells within the crypt, between the study and control groups at any site. When the 21 patients in whom gene carrier status was known were analysed separately there were no significant differences in the measured indices of proliferation between the HNPCC gene carriers and non-gene carriers. CONCLUSION: Crypt cell proliferation is not a discriminative marker of gene carriage in HNPCC.

Adolescent↗

Rectal hypersensitivity in the irritable bowel syndrome.

Studies of rectal sensory thresholds and compliance in patients with the irritable bowel syndrome have produced conflicting results though there is persistent evidence of rectal hypersensitivity particularly in those with diarrhoea-predominant symptoms. This study examined rectal sensation and compliance in 31 patients with constipation-predominant irritable bowel syndrome (mean age 41 years, 27 female) and 17 healthy volunteers (mean age 45 years, 17 female). A rectal balloon was inflated with fluid at a constant rate and the volume and intrarectal pressure at sensory threshold was recorded. The volumes at first (129 +/- 8 vs 229 +/- 24 ml, P < 0.001 Mann-Whitney-U test), constant (159 +/- 12 vs 286 +/- 21, P < 0.001) and maximum tolerated sensation (290 +/- 13 vs 509 +/- 19, P < 0.001) were all significantly less in the irritable bowel group. There was no significant difference in intrarectal pressures at any of these volumes (29.0 +/- 2.2 cmH2O vs 29.0 +/- 2.5, 35.0 +/- 2.5 vs 34.0 +/- 2.8, 71 +/- 2.5 vs 65.0 +/- 3.0 respectively). Rectal compliance was significantly less in the irritable bowel group (3.6 +/- 0.2 ml/cmH2O vs 8.7 +/- 0.4, P < 0.001). Twenty two patients complained of abdominal pain on balloon inflation, mimicking that experienced as part of their symptoms. Patients with constipation-predominant irritable bowel syndrome have rectal hypersensitivity and reduced compliance.

Adult↗

Abnormalities in the contractile properties of colonic smooth muscle in idiopathic slow transit constipation.

BACKGROUND: The underlying pathophysiology of idiopathic slow transit constipation (ISTC) remains unclear. At present, there is little evidence to implicate a smooth muscle myopathy in the aetiology of this condition. This study compared the effect of cisapride on the cholinergic response of colonic muscle strips from patients with this condition with that of control tissue. METHODS: Isometric tension production was recorded from circular smooth muscle strips taken from five patients undergoing colectomy for ISTC in response to cumulative concentrations of carbachol (100 nmol/1-100 mumol/l) alone and in the presence of cisapride 400 nmol/l. Similar dose-response activity was obtained for a control group consisting of six patients undergoing resection for colorectal carcinoma. RESULTS: In the absence of cisapride, smooth muscle from patients with carcinoma exhibited a significantly lower sensitivity to cholinergic stimulation (agonist concentration required to produce half-maximal activation (EC50) 4.83 mumol/l) than that from patients with ISTC (EC50 1.63 mumol/l, P = 0.036), and also a greater maximal frequency of the oscillatory activity associated with the increase in isometric tension (0.070 versus 0.049 Hz, P = 0.035). Cisapride had no effect on the sensitivity to carbachol of the carcinoma tissue but brought about a significant reduction in the sensitivity of smooth muscle from patients with ISTC (EC50 3.24 mumol/l, P = 0.043). CONCLUSION: These findings indicate that colonic smooth muscle from patients with ISTC is hypersensitive to cholinergic stimulation and suggest the existence of a smooth muscle myopathy in this condition.

Adolescent↗

Clinical impact of colonoscopic screening in first-degree relatives of patients with hereditary non-polyposis colorectal cancer.

Sixty-one asymptomatic individuals with an affected first-degree relative from five large hereditary non-polyposis colorectal cancer (HNPCC) kindreds were screened by colonoscopy. Neoplasms were found in nine (15 per cent) of 61 individuals on the first screen. Five subjects had a single adenoma while two had two adenomas each. There were two patients (3 per cent) with malignant neoplasms: one with a Dukes B adenocarcinoma and one with synchronous Dukes C adenocarcinomas in the caecum and ascending colon. These findings support the hypothesis that adenomas do not occur in large numbers in HNPCC families but, because of the high malignant conversion rate, biennial colonoscopy with removal of polyps seen is recommended.

Adenocarcinoma↗