Postoperative morbidity survey, mortality and length of stay following emergency laparotomy.

Thirty-day mortality following emergency laparotomy is high, and greater amongst elderly patients. Studies systematically describing peri-operative complications are sparse, and heterogeneous. We used the postoperative morbidity survey to describe the type and frequency of complications, and their relationship with outcomes for 144 patients: 114 < 80 years old, and 30 ≥ 80 years old. Cumulative postoperative morbidity survey scores and patterns of morbidity were similar (p = 0.454); however, 28-day mortality was higher in the elderly (10/30 (33.3%) vs. 11/114 (9.6%), p = 0.008), and hospital stay was longer (median (IQR [range]) 17 (13-35 [6-62]) days vs. 11 (7-21 [2-159]) days, p = 0.006). Regression analysis indicated that cardiovascular, haematological, renal and wound complications were associated with longer hospital stay, and that cardiovascular complications predicted mortality. The postoperative morbidity survey system enabled structured mapping of the number and type of complications, and their relationship with outcome, following emergency laparotomy. These results indicate that rather than a greater propensity to complications following surgery, it was the failure to tolerate these that increased mortality in the elderly.

Vascular endothelial growth factor as a survival factor for human islets: effect of immunosuppressive drugs.

AIMS/HYPOTHESIS: Rapamycin, part of the immunosuppressive regimen of the Edmonton protocol, has been shown to inhibit vascular endothelial growth factor (VEGF) production and VEGF-mediated survival signalling in tumour cell lines. This study investigates the survival-promoting activities of VEGF in human islets and the effects of rapamycin on islet viability. MATERIALS AND METHODS: Levels of VEGF and its receptors in isolated human islets and whole pancreas was determined by western blotting and immunostaining. Islet viability following VEGF or immunosuppressive drug treatment was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Islet VEGF release was measured by ELISA. Mouse islets infected with an adenovirus expressing the gene for VEGF were transplanted syngeneically into streptozotocin-induced diabetic mice, with blood glucose levels measured three times per week. RESULTS: Isolated human islets produced multiple isoforms of VEGF and VEGF receptors 1, 2 and 3 and the coreceptor neuropilin 1. Exogenous VEGF (10 ng/ml) prevented human islet death induced by serum starvation, which suggests that VEGF can act as a survival factor for human islets. Transplantation of mouse islets infected with a VEGF-expressing adenovirus in a syngeneic model, improved glycaemic control at day 1 post-transplantation (p < 0.05). Rapamycin at 10 and 100 ng/ml significantly reduced islet VEGF release (by 37 +/- 4% and 43 +/- 6%, respectively; p < 0.05) and at 100 ng/ml reduced islet viability (by 36 +/- 9%) and insulin release (by 47 +/- 7%, all vs vehicle-treated controls; p < 0.05). Tacrolimus had no effect on islet VEGF release or viability. CONCLUSIONS/INTERPRETATION: Our data suggest that rapamycin may have deleterious effects on islet survival post-transplantation, both through a direct effect on islet viability and indirectly through blockade of VEGF-mediated revascularisation.

Over-expression of AMP-activated protein kinase impairs pancreatic {beta}-cell function in vivo.

Treatment of type 1 diabetes by islet transplantation is currently limited by loss of functional beta-cell mass after transplantation. We investigated here whether adenovirus-mediated changes in AMP-activated protein kinase (AMPK) activity, previously shown to affect insulin secretion in vitro, might affect islet graft function in vivo. In isolated mouse and rat islets, insulin secretion stimulated by 17 (vs 3) mmol/l glucose was inhibited by 36.5% (P<0.01) and 43% (P<0.02) respectively after over-expression of constitutively-active AMPK- (AMPK CA) versus null (eGFP-expressing) viruses, and glucose oxidation was decreased by 38% (P<0.05) and 26.6% (P<0.05) respectively. Increases in apoptotic index (terminal deoxynucleotide transferase-mediated deoxyuridine trisphosphate biotin nick end-labelling) (TUNEL)) were also observed in AMPK CA- (22.8 +/- 3.6% TUNEL-positive cells, P<0.001), but not AMPK DN- (2.72 +/- 3.9%, positive cells, P=0.05) infected islets, versus null adenovirus-treated islets (0.68 +/- 0.36% positive cells). Correspondingly, transplantation of islets expressing AMPK CA into streptozotocin-diabetic C57 BL/6 mice improved glycaemic control less effectively than transplantation with either null (P<0.02) or AMPK-DN-infected (P<0.01) islets. We conclude that activation of AMPK inhibits beta-cell function in vivo and may represent a target for therapeutic intervention during islet transplantation.

Porcine dermal collagen graft in pediatric renal transplantation.

Successful closure of the anterior abdominal wall in infants following renal transplantation of adult organs may present a challenging dilemma to the transplant surgeon. Restricted volume of the recipient abdominal cavity and size discrepancy of donor adult kidney may lead to graft compromise. Pressure on the graft may be exacerbated further in the postoperative period by oedema that may lead to abdominal compartment syndrome. Donor/recipient size disparity remains the major obstacle in infant renal transplantation. We describe the use of a porcine collagen graft to facilitate closure of the abdominal wall following intra-peritoneal transplantation of an adult cadaveric kidney.

Review of the management of recurrent inguinal hernia.

BACKGROUND: There is little available evidence on the optimal management of recurrent inguinal hernia, particularly if the original procedure involved the use of mesh. This study was a review of recurrent hernia repair in a district hospital, involving both laparoscopic and open procedures. METHODS: The case notes of all patients who had a repair of a recurrent hernia between 1991 and 2000, inclusive, were examined; 171 procedures were included. Where known, the original repair was a nylon darn in 31%, mesh repair in 18%, and laparoscopic repair in 8%. RESULTS: The recurrent hernia was repaired using a Lichtenstein open mesh technique in 63% and by the totally extraperitoneal (TEP) method in 22%. Complication rates were highest after emergency surgery (all had open surgery), where 71% had complications and one patient died. For elective repairs, complication rates were similar after open (13%) and TEP (8%) repairs. The duration of hospital stay was also similar (1.2 vs 1.3 days, respectively), and a single recurrence was seen in each group. Patients with recurrence after primary mesh repair were also managed by both techniques with similar results. Open re-operation for mesh failure was technically straightforward. CONCLUSIONS: Most recurrent hernias are still repaired by open techniques. There was no convincing evidence of different outcomes for open and TEP repairs in this review. Even when the original hernia repair involved the use of mesh, further open repair by an experienced surgeon is justified.

Management of primary and recurrent inguinal hernia by surgeons from the South West of England.

BACKGROUND: The National Institute of Clinical Excellence (NICE) has advocated open mesh repair for primary hernia but suggested laparoscopic repair may be considered for recurrent hernias. AIM: To establish current surgical practice by surgeons from the South West of England. METHODS: A postal survey was distributed to 121 consultant surgeons and a response rate of 75% was achieved. RESULTS: The majority (86%) of the surgeons surveyed performed hernia repairs, and most (95%) of these used open mesh repair as standard for primary inguinal hernia. Only 8% used laparoscopic repair routinely for primary hernias. Few consultants (only 28%) were able to quote formally audited hernia recurrence rates. A total of 90% of respondents still employed open mesh repair routinely for recurrent hernias; however, if mesh had been used for the primary repair, this figure fell to 55%. Some 7% of respondents recommended laparoscopic repair for recurrent hernia, but this increased to 17% if the primary repair was done with mesh. All laparoscopic surgeons in the South West employed the totally extraperitoneal approach (TEP). There was a range of opinion on the technical demands of repair of a recurrent hernia previously mended with mesh; the commonest cause of mesh failure was thought to be a medial direct recurrence (insufficient mesh medially). CONCLUSIONS: Current surgical practice for primary hernias in the South West England reflects NICE guidelines although many surgeons continue to manage recurrent hernias by further open repair. In this survey, there was anecdotal evidence to suggest that hernia recurrence can be managed effectively by open repair.

MSH6 and MSH3 are rarely involved in genetic predisposition to nonpolypotic colon cancer.

A set of 90 nonpolypotic colon cancer families in which germ-line mutations of MSH2 and MLH1 had been excluded were screened for mutations in two additional DNA mismatch repair genes, MSH6 and MSH3. Kindreds fulfilling and not fulfilling the Amsterdam I criteria, showing early and late onset colorectal (and other) cancers, and having microsatellite stable and unstable tumors were included. Two partly parallel approaches were used: genetic linkage analysis (19 large families) and the protein truncation test (85, mostly smaller, families). Whereas MSH3 was not involved in any family, a large Amsterdam-positive, late-onset family showed a novel germ-line mutation in MSH6 (deletion of CT at nucleotide 3052 in exon 4). The mutation was identified through genetic linkage (multipoint lod score 2.4) and subsequent sequencing of MSH6. Furthermore, the entire MSH6 gene was sequenced exon by exon in families with frameshift mutations in the (C)8 tract in tumors, previously suggested as a predictor of MSH6 germ-line mutations; no mutations were found. We conclude that germ-line involvement of MSH6 and MSH3 is rare and that other genes are likely to account for a majority of MSH2-, MLH1-mutation negative families with nonpolypotic colon cancer.

Profile patterns, consistency, and change in the Millon Clinical Multiaxial Inventory-II in cocaine abusers.

This study examined the MCMI-II in samples of cocaine-dependent subjects who were receiving treatment in three separate residential facilities. Profile characteristics, patterns of scale stability, and change are reported. MCMI-II elevations are found in all three samples on the Antisocial, Aggressive/Sadistic, Narcissistic, Passive-Aggressive, Borderline, Drug Dependence, and Alcohol Dependence scales at both intake into treatment and discharge. Moderate stability coefficients are found on Basic Personality, Pathological Personality, and Symptom scales. Although some statistically significant mean scale changes between intake and discharge are noted in each sample, few involve change from clinically elevated to below clinical levels.