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Biomedical subjects

P R Shah

Publications and source records attributed to P R Shah.

At least 19 recordsLinked to original sources

Embryonic stem cell derived and adult hematopoietic stem cell transplantation for tolerance induction in a renal allograft recipient:--a case report.

UNLABELLED: We generated an human embryonic stem cell (hESC) line to augment chimerism-associated tolerance. A 40-year-old African with chronic glomerulonephritis-chronic renal failure with 100% G6PD enzyme deficiency presented for renal transplantation with a 27-year-old, 6/6 HLA-matched sister as a willing donor. METHOD: We generated an hESC line from the donor's oocytes using long ovarian stimulation protocol simultaneously with tolerance induction protocol. A nuclear transfer (NT)-hESC line was derived by transferring a donor cumulus cell into an enucleated oocyte, subjected to electrical fusion, and cultured for 5 days. ESCs hatched from the blastocyst on day 6 were cocultured with her unmodified bone marrow for 2 days and suspended in Ringer's lactate. Five milliliters of suspension were collected for cell counting, viability, pluripotency, flow cytometry, and karyotyping. The remaining suspension was infused into the periphery of the recipient. Transplantation was performed 1 week later following a negative lymphocytotoxicity cross-match test using no immunosuppression. Peripheral blood chimerism (PBC) was studied using fluorescent in situ hybridization technique. Allograft biopsy was performed on day 7. RESULTS: NT-hESC CD34+ count was 7.6%, viability 100%, karyotyping normal, pluripotency markers: SSEA-1, SSEA-4, OCT-3/4, TRA-1/60:positive; 12% PBC was noted at 1 week after transplantation. Serum creatinine was 1.2 mg%, graft biopsy was unremarkable, and G6PD enzyme deficiency was corrected to 0% at 100 days posttransplant. Liver function tests and hematology profile were unremarkable for graft-versus-host disease. CONCLUSION: This is the first report of tolerance induction using NT-hESC-induced hematopoietic chimerism with synergistic use of adult bone marrow. It was safe and effective.

Adult↗

Splenic rupture following colonoscopy: rare in the UK?

Splenic injury following colonoscopy is rare, with only 28 cases reported so far in the English language literature. Direct trauma during colonoscopy or traction on the spleno-colic ligament is the proposed mechanism of injury. Computed tomography (CT) of the abdomen is usually considered to be the most sensitive and specific modality for diagnosis. We report a case of a 56-year-old female, who was diagnosed having a splenic rupture following a routine colonoscopy for investigation of anaemia. She underwent an emergency laparotomy with splenectomy and made a satisfactory recovery post-operatively. We wish to highlight that there should be a high index of suspicion of splenic rupture in patients presenting with abdominal pain and demonstrating a positive Kehr's sign following colonoscopy. Only two case reports from the United Kingdom have been published, raising the possibility of under-reporting of such cases.

Colonoscopy↗

Laparoscopic colorectal surgery in Great Britain and Ireland--where are we now?

OBJECTIVE: We aimed to gather information from the members of the Association of Coloproctology of Great Britain and Ireland (ACPGBI) to assess trends in the current practice of laparoscopic colorectal surgery. METHODS: A postal questionnaire survey of the members of ACPGBI. RESULTS: The response rate was 37% (200/540). Only 45 surgeons currently perform laparoscopic colorectal work in Great Britain and Ireland mainly right hemicolectomy and laparoscopic stoma formation, of these about one third practiced laparoscopy for benign colorectal conditions only. The majority (68%) of surgeons had enough resources at their place of work, but further training seemed to be a major issue. Nearly 22% of surgeons had not had any formal training. Only 50% of surgeons trained their specialist registrars. The incidence of conversion rate was not different for benign or malignant conditions and also did not appear to be related to the duration of experience. Only four surgeons had noted port a site recurrence during the past 10 years. Seventy-five percent (150/200) felt that laparoscopic colorectal work could be carried out safely in a District General Hospital. CONCLUSION: Laparoscopic colorectal surgery was being performed by a small minority of members of the ACPGBI although more surgeons had started to work in this field in recent years. The main areas of concern appeared to be a wide variation in the range of experience as indicated by the number of operations performed and limited formal training for consultants.

Attitude of Health Personnel↗

Laparoscopic colorectal surgery: learning curve and training implications.

AIMS: This paper is a review of experience of laparoscopic colorectal surgery at a district general hospital with particular emphasis on the learning curve and training implications. METHODS: All patients undergoing colorectal surgery where laparoscopy was attempted between March 1998 and October 2003 were included in this study. RESULTS: There were 80 patients of which 49 had malignancy. Twenty eight stomas and 52 bowel resections were performed laparoscopically. The conversion rate for bowel resection was 32% (decreasing from 38% to 44% to 22%). This was significant (p = 0.001) when compared with stoma formation (7%). The firm has support from a specialist registrar and staff grade surgeon. In 22% of cases, one of the middle grades was the principal operating surgeon, mainly laparoscopic mobilisation and stoma formation. Only 6% of resections were performed by the middle grades. Conversely, a middle grade was the main operating surgeon in 66% of open resections and 61% of stoma formations during the same period. There were in all two deaths and 14 postoperative complications. All patients who had laparoscopic resections for malignancy had clear resection margins. CONCLUSION: This audit highlights that there is a long learning curve in laparoscopic colorectal surgery with decrease in conversion rates with increasing experience. There is also a reduction in training opportunities in open surgery during the learning phase of the consultant, although this may be counterbalanced by the exposure to laparoscopic techniques. Laparoscopic colonic mobilisation, as a part of stoma formation, is a good starting point for specialist registrar training.

Adult↗

Myocardial effects of repeated electrical defibrillations in the isolated fibrillating rat heart.

OBJECTIVE: Although substantial myocardial cell injury has been reported after high-energy electrical defibrillation, only minimal injury with transient functional defects seems to develop at energy levels not exceeding those required to reverse ventricular fibrillation. Because multiple electrical shocks are often delivered in clinical settings during attempts to reverse ventricular fibrillation, we investigated the effects of repetitive shocks on postresuscitation myocardial dysfunction by using an isolated rat heart model of ventricular fibrillation. DESIGN: Prospective and randomized. SETTING: Cardiopulmonary resuscitation research laboratory. SUBJECTS: Twenty-seven Sprague-Dawley rats. INTERVENTIONS: Hearts were harvested and perfused at a constant flow of 10 mL/min by using a modified Krebs-Henseleit solution equilibrated with 95% oxygen and 5% CO2. Ventricular fibrillation (VF) was induced by a 0.05-mA current delivered to the right ventricular endocardium and the perfusate flow was stopped. After 10 mins, the perfusate flow was resumed at 20% of baseline flow and maintained for 15 additional minutes before returning to baseline flow after 25 mins of VF (VF25 mins). Twenty-seven hearts were randomized to receive from VF22 mins to VF25 mins either 0 epicardial shocks, 6 epicardial shocks, or 12 epicardial shocks. MEASUREMENTS AND MAIN RESULTS: Isovolumic indices of left ventricular function were obtained by using a latex balloon advanced through the mitral valve into the ventricular cavity. After defibrillation, indices of contractile function rapidly returned to baseline without differences among groups. The isovolumic end-diastolic pressure, however, remained elevated throughout the postresuscitation interval. A left shift of the diastolic pressure-volume curves without changes in their slope was observed at 10 mins after resuscitation with partial return to baseline by 30 mins postresuscitation. The shifts were significantly greater in hearts that received 12 shocks. CONCLUSIONS: These findings indicate that repetitive low-energy electrical shocks do not accentuate postischemic systolic dysfunction in the isolated fibrillating rat heart but adversely affect postischemic diastolic dysfunction by reducing the unstressed left ventricular end-diastolic volume.

Animals↗

Effect of renal transplantation (surgical stress) on serum levels of oxidants and reducing system.

BACKGROUND: This study attempts to understand the correlation (if any) between surgical stress of renal transplantation and serum levels of pro-oxidant/antioxidants. METHODS: Twenty-four ESRD patients having undergone transplant surgery followed from day-1 to day-10 postsurgery were investigated for serum levels of MDA, SOD, Vit. C and E. The drug regimen received was immunosuppressant, H2 blockers and antihypertensives as per the situation. RESULTS: The typical observations indicated elevated serum levels of MDA from preoperative stage reaching peak value 24 hrs after surgery followed by a steady fall and achieving minima on the 10th day. As regards antioxidants enzyme SOD, Vit. C, Vit. E were low from pretransplant day reaching minima 24 hours postoperatively and returning to normal from 7th day. CONCLUSIONS: The present investigation has amply shown a typical imbalance between pro-oxidant/antioxidants from pretransplant day up to 24 hrs and there after returning to normal level from 7th day suggestive to desired recovery and surgical stress not a limiting factor in way of health progress renal transplant. Dietary intake of Vit. C and E in mega doses can be a good therapeutic measure.

Adult↗

Interactions between oxytocin, glucagon and glucose in normal and streptozotocin-induced diabetic rats.

Oxytocin has been suggested to have glucoregulatory functions in rats, man and other mammals. The hyperglycemic actions of oxytocin are believed to be mediated indirectly through changes in pancreatic function. The present study examined the interaction between glucose and oxytocin in normal and streptozotocin (STZ)-induced diabetic rats, under basal conditions and after injections of oxytocin. Plasma glucose and endogenous oxytocin levels were significantly correlated in cannulated lactating rats (r = 0.44, P less than 0.01). To test the hypothesis that oxytocin was acting to elevate plasma glucose, adult male rats were injected with 10 micrograms/kg oxytocin and killed 60 min later. Oxytocin increased plasma glucose from 6.1 +/- 0.1 to 6.8 +/- 0.2 mM (P less than 0.05), and glucagon from 179 +/- 12 to 259 +/- 32 pg/ml (P less than 0.01, n = 18). There was no significant effect of oxytocin on plasma insulin, although the levels were increased by 30%. A lower dose (1 microgram/kg) of oxytocin had no significant effect on plasma glucose or glucagon. To eliminate putative local inhibitory effects of insulin on glucagon secretion, male rats were made diabetic by i.p. injection of 100 mg/kg STZ, which increased glucose to greater than 18 mM and glucagon to 249 +/- 25 pg/ml (P less than 0.05). In these rats, 10 micrograms/kg oxytocin failed to further increase plasma glucose, but caused a much greater increase in glucagon (to 828 +/- 248 pg/ml) and also increased plasma ACTH. A specific oxytocin analog, Thr4,Gly7-oxytocin, mimicked the effect of oxytocin on glucagon secretion in diabetic rats. The lower dose of oxytocin also increased glucagon levels (to 1300 +/- 250 pg/ml), but the effect was not significant. A 3 h i.v. infusion of 1 nmol/kg per h oxytocin in conscious male rats significantly increased glucagon levels by 30 min in normal and STZ-rats; levels returned to baseline by 30 min after stopping the infusion. Plasma glucose increased in the normal, but not STZ-rats. The relative magnitude of the increase in glucagon was identical for normal and diabetic rats, but the absolute levels of glucagon during the infusion were twice as high in the diabetics. To test whether hypoglycemia could elevate plasma levels of oxytocin, male rats were injected i.p. with insulin and killed from 15-180 min later. Plasma glucose levels dropped to less than 2.5 mM by 15 min. Oxytocin levels increased by 150-200% at 30 min; however, the effect was not statistically significant.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗

Hydrazones of isoniazid for colorimetric analysis.

Two sensitive color reactions of isoniazid are described. They are based on the formation of hydrazone Schiff bases when isoniazid is reacted with 4-nitrobenzaldehyde or pyridoxal. Linear curves were obtained with both reagents when absorbance values were plotted against concentrations.

Benzaldehydes↗