The open peritoneal cavity: etiology correlates with the likelihood of fascial closure

The use of laparostomy in damage control surgery and uncontrolled intra-abdominal infection has been well described. We examined 71 patients who required laparostomy to see if trends in management and outcome could be identified based on the underlying disease state. The underlying etiology included gastrointestinal sepsis (n = 25), pancreatitis (n = 21), or trauma (n = 25). Pancreatitis patients required more operations per patient (P < 0.05). The likelihood and type of closure (fascial, mesh, or none) was related to the underlying etiology: trauma patients were more likely to have fascial closure (P < 0.02), patients with GI sepsis were more likely to require mesh closure, and pancreatitis patients were more likely to have no formal closure (P < 0.02). Only 29 per cent of patients achieved definitive fascial closure. Mortality in trauma patients was 20 per cent, 36 per cent for GI sepsis, and 43 per cent in patients with pancreatitis. Complications of laparostomy included enterocutaneous fistula (16.9%) and abscess formation (7%). Though the use of laparostomy has become more prevalent, it is still associated with significant hospital stay, morbidity, and mortality. In our study, the number of operations and likelihood of abdominal closure appears to correlate with the etiology of the underlying disease requiring use of laparostomy.     

Predictors of survival after liver transplantation for hepatocellular carcinoma associated with Hepatitis C.

The efficacy of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) is not well defined. This study examines the variables that may determine the outcome of OLT for HCC in HCV patients. From 1990 to 1999, 463 OLTs were performed for HCV cirrhosis. Of these patients, 67 with concurrent HCC were included in the study. Univariate and multivariate analyses considered the following variables: gender, pTNM stage, tumor size, number of nodules, vascular invasion, incidental tumors, adjuvant chemotherapy, preoperative chemoembolization, alpha-fetoprotein (AFP) tumor marker, lobar distribution, and histological grade. Overall OLT survival of HCV patients diagnosed with concomitant HCC was significantly lower when compared to patients who underwent OLT for HCV alone at 1, 3, and 5 years (75%, 71%, and 55% versus 84%, 76%, and 75%, respectively; P < 0.01). Overall survival of patients with stage I HCC was significantly better than patients with stage II, III, or IV (P < .05). Eleven of 67 patients developed tumor recurrence. Sites of recurrence included transplanted liver (5), lung (5), and bone (1). Twenty-four of 67 patients (36%) died during the follow-up time. Causes of deaths included recurrent HCC in 8 of 24 patients (12%) and recurrent HCV in 3 of 24 patients (4.5%), whereas 13 (19.5%) patients died from causes that were unrelated to HCV or HCC. Both univariate and multivariate analysis demonstrated that pTNM status (I versus II, III, and IV; P < .05) was a reliable prognostic indicator for patient survival. Presence of vascular invasion (P = .0001) and advanced pTNM staging (P = .038) increased risk of recurrence. Multivariate analysis showed that pretransplant chemoembolization and adjuvant chemotherapy reduced risk of death after OLT in HCC recipients. In conclusion, this study demonstrates the effectiveness of OLT for patients with HCC in a large cohort of chronic HCV patients. Advanced tumor stage, and particularly vascular invasion, are poor prognostic indicators for tumor recurrence. Early pTNM stage, adjuvant chemotherapy, and preoperative chemoembolization were associated with positive outcomes for patients who underwent OLT for concomitant HCV and HCC.     

Osteopontin is a negative regulator of proliferation and differentiation in MC3T3-E1 pre-osteoblastic cells

Osteopontin (OPN) is an important mediator of bone remodeling. However, the role of OPN in the process of bone formation is not fully understood. In previous studies, we have shown that MC3T3-E1 pre-osteoblastic cells at higher passage number exhibited weakened osteogenic capacity and elevated OPN mRNA expression. In this work, we investigated the role of OPN on proliferation and differentiation of low-passage MC3T3-E1 cells by studying stable cell lines overexpressing either OPN mRNA or its antisense RNA. Overexpression was verified by both Northern and Western blot analyses. Overexpression of OPN markedly inhibited proliferation as determined by daily cell counts, while overexpression of antisense RNA stimulated cellular proliferation. We also examined the effect of OPN level on BMP-2-induced alkaline phosphatase activity. Overexpression of OPN inhibited BMP-2 responsiveness while overexpression of antisense RNA enhanced the effect of BMP-2 on alkaline phosphatase activity. Increased OPN expression also caused decreases in expression of osteocalcin and bone sialoproteins while a reduction of OPN level caused the opposite. Furthermore, endogenous OPN expression in response to BMP-2 exhibited a biphasic pattern, that is, it was initially inhibited and then enhanced by the treatment of BMP-2, indicating that OPN might function as a negative feedback regulator for osteoblastic differentiation. Finally, overexpression of OPN inhibited mineral deposition. In contrast, overexpression of antisense RNA enhanced mineral deposition. These results indicate that OPN is a negative regulator of proliferation and differentiation in MC3T3-E1 cells.     

Catastrophic fracture of a stable metal acetabular component

Various modes of failure of primary and revision total hip arthroplasty have been well documented in the literature over the past 30 years. Concerns over polyethylene wear, osteolysis, and hypersensitivity reactions leading to component loosening and early revision have been evaluated and reported in the literature. Routine follow-up is important to monitor for postoperative issues that might lead to the subsequent need for revision.This article describes a case of a 64-year-old man who initially presented 11 years prior with an intertrochanteric fracture, which failed secondary to varus alignment and femoral head osteonecrosis. The fixation was converted to a total hip replacement using the S-ROM system (DePuy, Warsaw, Indiana). Subsequently, the patient was lost to follow-up after primary total hip arthroplasty and presented with a catastrophic fracture of the metal acetabular cup system. The failure was suggested by clinical presentation and confirmed by imaging studies showing a fractured acetabular shell with femoral head prosthesis resting in the superolateral ileum. The contributing factors that resulted in mechanical failure were polyethylene wear and component fracture. The acetabular component was revised with an in-growth cementless trabecular metal multihole cup (Zimmer, Warsaw, Indiana) with bone grafting of acetabular defects.Routine assessments help educate patients and allow careful monitoring by physicians while establishing a radiographic timeline for the identification, progression, or lack of postoperative complications.     

Quantitative trait loci analysis of structural and material skeletal phenotypes in C57BL/6J and DBA/2 second-generation and recombinant inbred mice.

QTL analyses identified several chromosomal regions influencing skeletal phenotypes of the femur and tibia in BXD F2 and BXD RI populations of mice. QTLs for skeletal traits co-located with each other and with correlated traits such as body weight and length, adipose mass, and serum alkaline phosphatase. INTRODUCTION: Past research has shown substantial genetic influence on bone quality, and the impact of reduced bone mass on our aging population has heightened the interest in skeletal genetic research. MATERIALS AND METHODS: Quantitative trait loci (QTL) analyses were performed on morphologic measures and structural and material properties of the femur and tibia in 200-day-old C57BL/6J x DBA/2 (BXD) F2 (second filial generation; n = 400) and BXD recombinant inbred (RI; n = 23 strains) populations of mice. Body weight, body length, adipose mass, and serum alkaline phosphatase were correlated phenotypes included in the analyses. RESULTS: Skeletal QTLs for morphologic bone measures such as length, width, cortical thickness, and cross-sectional area mapped to nearly every chromosome. QTLs for both structural properties (ultimate load, yield load, or stiffness) and material properties (stress and straincharacteristics and elastic modulus) mapped to chromosomes 4, 6, 9, 12, 13, 15, and 18. QTLs that were specific to structural properties were identified on chromosomes 1, 2, 3, 7, 8, and 17, and QTLs that were specific to skeletal material properties were identified on chromosomes 5, 11, 16, and 19. QTLs for body size (body weight, body length, and adipose mass) often mapped to the same chromosomal regions as those identified for skeletal traits, suggesting that several QTLs identified as influencing bone could be mediated through body size. CONCLUSION: New QTLs, not previously reported in the literature, were identified for structural and material properties and morphological measures of the mouse femur and tibia. Body weight and length, adipose mass, and serum alkaline phosphatase were correlated phenotypes that mapped in close proximity of skeletal chromosomal loci. The more specific measures of bone quality included in this investigation enhance our understanding of the functional significance of previously identified QTLs.     

A rapid precurarization technique using rocuronium

Purpose

To evaluate a rapid and time-saving precurarization technique using rocuronium to prevent succinylcholine-induced myalgia.

Method

In a prospective, double blind randomized study, 42 ASA 1–2 patients were assigned to one of three pretreatment groups: 0.01 ml · kg^?1 normal saline, 0.1 mg · kg^?1 atracurium, and 0.1 mg · kg^?1 rocuronium. Anaesthesia commenced with 1.5 μg · kg^?1 fentanyl and 0.5 mg · kg^?1 lidocaine at time zero. Pretreatment was administered 60 sec later, followed by 2.5 mg · kg^?1 propofol. At 90 sec, 1.5 mg · kg^?1 succinylcholine was injected and 30 sec later, the trachea was intubated and the ease of intubation was graded. The patient was observed for the presence and severity of fasciculations. Myalgias were recorded on postoperative days 1, 2 and 7.

Results

The incidence of fasciculations in the rocuronium group (21.4%) was lower (P < 0.001) than atracurium (78.5%) or placebo (92.8%) groups. On postoperative day 1, the incidence of postoperative myalgia in the rocuronium group (14.2%) was less than the placebo group (78.2%;P < 0.002) and atracurium group (85.7%;P < 0.001). The incidence of myalgia in the rocuronium group (7.1%) was lower than in the placebo group (78.5%;P < 0.001) but not different from the atracurium group (42.8%;P = 0.077) on postoperative day 2. On postoperative day 7, there was no difference among the three groups. Fasciculations were related to post-operative myalgia. There was no difference in intubating conditions among the three groups.

Conclusion

Rocuronium pretreatment given just before induction of anaesthesia with propofol reduces fasciculations and succinylcholine-induced myalgia.     

Inducible nitric oxide synthase has divergent effects on vascular and metabolic function in obesity

Previous studies have suggested an involvement of inducible nitric oxide synthase (iNOS) in obesity, but the relation, if any, between this and mechanisms underlying endothelial dysfunction in obesity is unknown. We studied mice fed an obesogenic high-fat or standard diet for up to 8 weeks. Obesity was associated with elevated blood pressure; resistance to the glucoregulatory actions of insulin; resistance to the vascular actions of insulin, assessed as the reduction in phenylephrine constrictor response of aortic rings after insulin preincubation (lean -21.7 +/- 11.5 vs. obese 18.2 +/- 15.5%; P < 0.05); and evidence of reactive oxygen species (ROS)-dependent vasodilatation in response to acetylcholine in aortic rings (change in maximal relaxation to acetylcholine after exposure to catalase: lean -2.1 +/- 6.0 vs. obese -15.0 +/- 3.8%; P = 0.04). Obese mice had increased expression of iNOS in aorta, with evidence of increased vascular NO production, assessed as the increase in maximal constriction to phenylephrine after iNOS inhibition with 1400W (lean -3.5 +/- 9.1 vs. obese 42.1 +/- 11.2%; P < 0.001). To further address the role of iNOS in obesity-induced vascular and metabolic dysfunction, we studied the effect of a high-fat diet in iNOS knockout mice (iNOS KO). Obese iNOS KO mice were protected against the development of resistance to insulin's glucoregulatory and vascular effects (insulin-dependent reduction in maximal phenylephrine response: obese wild-type 11.2 +/- 15.0 vs. obese iNOS KO -20.0 +/- 7.7%; P = 0.02). However, obese iNOS KO mice remained hypertensive (124.0 +/- 0.7 vs. 114.9 +/- 0.5 mmHg; P < 0.01) and had evidence of increased vascular ROS production. Although these data support iNOS as a target to protect against the adverse effects of obesity on glucoregulation and vascular insulin resistance, iNOS inhibition does not prevent the development of raised blood pressure or oxidative stress.     

Calcineurin Inhibitor Withdrawal from Sirolimus-Based Therapy in Kidney Transplantation: A Systematic Review of Randomized Trials

Calcineurin inhibitor (CNI) withdrawal has been used as a strategy to improve renal allograft function, however, it also carries risk of acute rejection. We conducted a systematic review of randomized trials that involved CNI withdrawal from a sirolimus-based immunosuppressive regimen. The search strategy yielded six trials (n = 1047 patients) reported in eight publications. CNI withdrawal from sirolimus-based therapy, was associated with an increased risk of acute rejection (risk difference, 6%; 95% CI 2-10%, p = 0.002) but a higher creatinine clearance (mean difference, 7.49 mL/min; 95% CI 5.08-9.89 mL/min, p < 0.00001) at 1 year compared to continued CNI and sirolimus therapy. Graft loss (relative risk, 0.87; 95% CI 0.46-1.64, p = 0.66) and death (relative risk, 0.88; CI 0.40-1.96, p = 0.76) were similar in both groups at 1 year. Hypertension was significantly reduced in the CNI withdrawal group (relative risk, 0.56; 95% CI 0.40-0.78, p = 0.0006). CNI withdrawal from sirolimus-based therapy is associated with an increased risk of acute rejection in the short term with a significant improvement in renal function and a reduction in hypertension. Longer follow-up is needed to determine if these changes will result in a significant improvement in patient and graft survival.