Serial transverse enteroplasty enhances intestinal function in a model of short bowel syndrome

OBJECTIVE/SUMMARY BACKGROUND DATA: Serial transverse enteroplasty (STEP) is a new intestinal lengthening procedure that has been shown to clinically increase bowel length. This study examined the impact of the STEP procedure upon intestinal function in a model of short bowel syndrome. METHODS: Young pigs (n=10) had a reversed segment of bowel interposed to induce bowel dilatation. Five pigs underwent a 90% bowel resection with a STEP procedure on the remaining dilated bowel while 5 served as controls and had a 90% bowel resection without a STEP procedure. Determinations of nutritional status, absorptive capacity, and bacterial overgrowth were conducted 6 weeks after resection. Statistical comparisons were made by 2-sample t test (significance at P<0.05). RESULTS: The STEP procedure lengthened the bowel from 105.2+/-7.7 cm to 152.2+/-8.3 cm (P<0.01). The STEP animals showed improved weight retention compared with controls (mean, -0.5%+/-1.8% body weight versus -17.6%+/-1.5%, P<0.001). Intestinal carbohydrate absorption, as measured by d-Xylose absorption and fat absorptive capacity as measured by serum vitamin D and triglyceride levels, were increased in the STEP group versus controls. Serum citrulline, a marker of intestinal mucosal mass, was significantly elevated in the STEP pigs compared with controls. None of the STEP animals but 4 of 5 control animals were noted to have gram-negative bacterial overgrowth in the proximal bowel. CONCLUSIONS: STEP improves weight retention, nutritional status, intestinal absorptive capacity, and serum citrulline levels in a porcine short bowel model. A salutary effect upon bacterial overgrowth was also noted. These data support the use of this operation in short bowel syndrome.     

Comparison of methods for determining renal function decline in early autosomal dominant polycystic kidney disease: the consortium of radiologic imaging studies of polycystic kidney disease cohort

A decline in renal function suggests progression of chronic kidney disease. This can be determined by measured GFR (e.g., iothalamate clearance), serum creatinine (SCr)-based GFR estimates, or creatinine clearance. A cohort of 234 patients with autosomal dominant polycystic kidney disease and baseline creatinine clearance>70 ml/min were followed annually for four visits. Iothalamate clearance, SCr, and creatinine clearance were obtained at each visit. Estimated GFR (eGFR) was determined with the Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault equations. Renal function slopes had a mean residual SD of 10.7% by iothalamate clearance, 8.2% by MDRD equation, 7.7% by Cockcroft-Gault equation, and 14.8% by creatinine clearance. By each method, a decline in renal function (lowest quintile slope) was compared among baseline predictors. Hypertension was associated with a decline in iothalamate clearance (odds ratio [OR] 5.8; 95% confidence interval [CI] 2.3 to 14), eGFR (OR [MDRD] 2.0 [95% CI 1.0 to 4.2] or OR [Cockcroft-Gault] 1.9 [95% CI 0.9 to 3.9]), and creatinine clearance (OR 2.0; 95% CI 1.0 to 4.2). Each doubling of kidney volume at baseline was associated with a decline in iothalamate clearance (OR 2.4; 95% CI 1.5 to 3.7), eGFR (OR 1.7 [95% CI 1.1 to 2.6] or 2.1 [95% CI 1.4 to 3.3]), and creatinine clearance (OR 1.7; 95% CI 1.1 to 2.5). Predictor associations were strongest with measured GFR. Misclassification from changes in non-GFR factors (e.g., creatinine production, tubular secretion) conservatively biased associations with eGFR. Misclassification from method imprecision attenuated associations with creatinine clearance.     

The effect of derotational humeral osteotomy on global shoulder function in brachial plexus birth palsy

BACKGROUND: Derotational humeral osteotomies have been used in older children with brachial plexus birth palsy and glenohumeral joint deformity to place the upper extremity in a more functional position. The purpose of this study was to determine the effects of these procedures on shoulder function and joint morphology. METHODS: Forty-three patients underwent a derotational humeral osteotomy for functional impairment in the setting of internal rotation contracture and/or glenohumeral joint deformity at our institution from 1996 to 2004. Osteotomies were performed proximal to the deltoid insertion and were stabilized with plate-and-screw fixation. The average age of the patients at the time of surgery was 7.6 years (range, 2.3 to 17.0 years). Shoulder function was graded according to the modified Mallet classification system. Glenohumeral deformity was graded according to the classification scheme of Waters et al. The results for twenty-seven patients who were followed for a minimum of two years (average, 3.7 years) are reported. RESULTS: The average amount of external rotation achieved with osteotomy was 64 degrees (range, 35 degrees to 90 degrees). The mean aggregate Mallet classification score improved from 13 to 18 points (p < 0.01). The mean Mallet classification scores for the individual elements similarly demonstrated improvement following osteotomy, with the greatest gains in hand-to-mouth, hand-to-neck, and external rotation motions. The mean classification of the glenohumeral deformity was type IV preoperatively and postoperatively, signifying the persistence of glenohumeral dysplasia. There were no nonunions. One patient required a revision osteotomy for inadequate initial correction. One patient sustained a humeral fracture distal to the plate fixation because of sports-related trauma. CONCLUSIONS: Derotational humeral osteotomy improves shoulder function in patients with brachial plexus birth palsy, internal rotation contracture, and/or advanced glenohumeral joint deformity. This osteotomy provides an attractive treatment option for patients with brachial plexus birth palsy who have advanced glenohumeral dysplasia precluding soft-tissue releases and tendon transfers.     

Effect of curcumin (<Emphasis Type="Italic">Curcuma longa</Emphasis> extract) on LPS-induced acute lung injury is mediated by the activation of AMPK

Purpose

Curcumin, a biphenolic compound extracted from turmeric (Curcuma longa), possesses potent anti-inflammatory activity. The present study investigated whether curcumin could increase 5′ adenosine monophosphate-activated protein kinase (AMPK) activity in macrophages and modulate the severity of lipopolysaccharide (LPS)-induced acute lung injury.

Methods

Macrophages were treated with curcumin and then exposed (or not) to LPS. Acute lung injury was induced by intratracheal administration of LPS in BALB/c mice.

Results

Curcumin increased phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), a downstream target of AMPK, in a time- and concentration-dependent manner. Curcumin did not increase phosphorylation of liver kinase B1, a primary kinase upstream of AMPK. STO-609, an inhibitor of calcium²⁺/calmodulin-dependent protein kinase kinase, diminished curcumin-induced AMPK phosphorylation, but transforming growth factor-beta-activated kinase 1 inhibitor did not. Curcumin also diminished the LPS-induced increase in phosphorylation of inhibitory κB-alpha and the production of tumor necrosis factor alpha (TNF-α), macrophage inflammatory protein (MIP)-2, and interleukin (IL)-6 by macrophages. Systemic administration of curcumin significantly decreased the production of TNF-α, MIP-2, and IL-6 as well as neutrophil accumulation in bronchoalveolar lavage fluid, and also decreased pulmonary myeloperoxidase levels and the wet/dry weight ratio in mice subjected to LPS treatment.

Conclusion

These results suggest that the protective effect of curcumin on LPS-induced acute lung injury is associated with AMPK activation.

     

Proteomic analysis to identify biomarker proteins in pancreatic ductal adenocarcinoma

Background: Pancreatic ductal adenocarcinoma (PDAC) is the fifth most common cause of death from cancer in Korea. PDAC is difficult to diagnose at an early stage and even more difficult to cure. Thus, there is an urgent need to identify molecular targets for early diagnosis and effective treatment. The objectives of this study were to identify differentially expressed biomarker proteins of PDAC using proteomic analysis, to validate the identified biomarker proteins associated with carcinogenesis using western blot analysis and to evaluate clinical factors influencing expression of candidate biomarker proteins. Methods: In the present study, we carried out proteomic analysis in 10 pairs of PDAC specimens with matching adjacent normal tissues to clarify the different patterns of protein expression. The proteins were separated by high‐resolution 2‐D polyacrylamide gel electrophoresis (2D PAGE) and the differentially expressed proteins were identified by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS). Differential expression of candidate biomarker proteins associated with carcinogenesis was further validated using western blot analysis. Standard statistical analysis was carried out in an attempt to establish a correlation between clinical variables and expression of candidate biomarker proteins. Results: Analysis of PDAC and the adjacent normal tissues showed reproducibly similar proteomic patterns for each group. Approximately 700 spots each were seen by silver‐stained gels from both PDAC and normal tissues. Differentially expressed protein spots were gel digested and identified by MALDI‐TOF MS. Twenty‐five proteins were identified, of which five proteins (galectin‐1, enolase‐2, α‐1‐antitrypsin, N‐myc interactor, peroxiredoxin‐4) were previously reported as being differentially expressed either at the mRNA level or protein level in human cancer. The five proteins were selected for candidate biomarker proteins related to carcinogenesis. These proteins were further validated by western blot analysis. Among the candidate biomarker proteins, galectin‐1 expression was highly correlated to histology (P = 0.019), T stage (P = 0.047), N stage (P = 0.033) and American Joint Committee on Cancer stage (P = 0.011). Conclusion: Differentially expressed 25 proteins in PDAC were identified using proteomic analysis and five proteins related to carcinogenesis were validated by western blot analysis. galectin‐1 expression was highly correlated to tumour histology and stage.     

Performance of Posttransplant Model for End-Stage Liver Disease (MELD) and Delta-MELD Scores on Short-Term Outcome After Living Donor Liver Transplantation

The performance of the Model for End-stage Liver Disease (MELD) and delta-MELD scores in predicting posttransplant survival has been variable and the results are conflicting, suggesting that posttransplantational factors are more important than pre- or peritransplantational factors in outcomes following liver transplantation (OLT). We assessed the value of posttransplant MELD and delta-MELD scores to predict short-term (90-day) posttransplant survival. We evaluated 279 consecutive patients undergoing living donor OLTs. The MELD scores were calculated serially from pretransplantation as well as 3, 7, and 14 days after transplantation. Twenty-seven (9.7%) among 279 patients died within 90 days after transplantation. Pretransplant MELD score was not associated with short-term posttransplant mortality. The area under the receiver operating characteristic (AUROC) curve in predicting 90-day mortality was 0.637 for posttransplant 3-day MELD, 0.746 for posttransplant 7-day MELD, and 0.859 for posttransplant 14-day MELD score (P = .047, <.001, and <.001, respectively); AUROC was 0.582, 0.646, and 0.784 for 3-day, 7-day, and 14-day delta-MELD scores (P = .235, .034, <.001, respectively). Upon multivariate analysis, posttransplant 14-day MELD (≥20 vs <20), and 14-day delta-MELD scores (≥−3 vs <−3) were independent short-term prognostic factors with risk ratios of 18.875 (95% confidential interval [CI]: 4.625-77.028, P < .001) and 13.577 (95% CI: 2.641-69.791, P = .002), respectively. In conclusion, determination of posttransplant 14-day MELD and 14-day delta-MELD scores may afford suitable short-term prognostic predictors for patients following living donor OLT.     

Second-generation cementless total hip arthroplasty in patients with osteonecrosis of the femoral head

The results of cementless total hip arthroplasties in patients with osteonecrosis have been inferior to those in patients with other diagnoses. Fifty-eight primary total hip arthroplasties with insertion of a femoral stem with a circumferentially proximal porous coating and a cementless acetabular component were followed for a mean of 11.1 years. Fifty-seven (98%) of 58 stems were biologically stable, and one stem was loose. There were acetabular revisions in 18 hips (31%) because of polyethylene wear and osteolysis. One hip (1.7%) underwent revision of both acetabular and femoral components. Osteolysis around the acetabular component was seen on radiographs in 22 hips (37.9%). Femoral osteolysis was seen in 9 hips (15.5%), and there was no osteolysis below the lesser trochanter in any hip. Second-generation femoral prostheses provide excellent fixation in patients with osteonecrosis of the femoral head. However, a high rate of polyethylene wear and osteolysis in these high-risk patients remains a challenging problem.     

Pulmonary root translocation for repair of Taussig-Bing anomaly with interrupted arch

Anterior translocation of the pulmonary root was used as a new approach to the staged repair of Taussig-Bing anomaly with an interrupted aortic arch. It was performed to construct the right ventricle outflow tract with intraventricular baffling of the left ventricle to the aorta as the second stage operation after repair of the interrupted arch and pulmonary artery banding. This technique allows minimization of pulmonary regurgitation and has the major theoretical advantage for growth potential, which could diminish the need for reoperation.     

The role of enteral nutrition in the reversal of parenteral nutrition-associated liver dysfunction in infants

Background

Liver dysfunction in children dependent on parenteral nutrition (PN) is well established, and the extent of hyperbilirubinemia has been shown to correlate with morbidity and mortality. The aim of this study was to assess whether increasing provisions of enteral nutrition can improve PN-associated hyperbilirubinemia over time.

Methods

A retrospective review was conducted on infants in our institution's Short Bowel Syndrome Clinic from 1999 to 2004. Inclusion criteria included PN duration more than 1 month, serum direct bilirubin more than 3 mg/dL while on PN, and tolerance of full enteral nutrition with eventual discontinuation of PN. Paired t tests were used for statistical analyses.

Results

Twelve infants were identified with a PN duration of 5 ± 1 months. Five patients underwent liver biopsy while on PN, and histological evidence of cholestasis was found on all specimens. Peak total and direct bilirubin levels were 10.5 ± 1.9 and 7.0 ± 1.6 mg/dL, respectively, and occurred at time of PN discontinuation. Only 2 patients had improvement in serum bilirubin levels before initiation of full enteral nutrition. After initiation of full enteral nutrition and discontinuation of PN, all patients achieved permanent normalization of bilirubin levels by 4 months (P < .05) after a 1-month plateau phase. Alkaline phosphatase levels approached reference range within this time but were not significant.

Conclusion

These data demonstrate for the first time that although PN-dependent infants can achieve normalization of marked hyperbilirubinemia with enteral nutrition, the improvement in liver function usually begins only after full enteral nutrition is tolerated and PN is withdrawn. These findings support the aggressive weaning of PN to enteral nutrition in infants with short bowel syndrome.     

Fontan conversion with arrhythmia surgery.

OBJECTIVE: Hemodynamic abnormalities and refractory atrial arrhythmias in patients late after the Fontan operation result in significant morbidity and mortality. We reviewed our experience with Fontan conversion and concomitant arrhythmia surgery. METHODS: Between January 1996 and February 2004, 16 patients underwent Fontan conversion and arrhythmia surgery. Mean age at the initial Fontan operation was 5.1+/-3.5 (range: 2-15) years and mean age at Fontan conversion was 17.0+/-5.8 (range: 6-30). The initial Fontan operations were atriopulmonary connections in 14 patients, extracardiac lateral tunnel in 1, and intracardiac lateral tunnel in 1. The types of arrhythmia included atrial flutter in 10 patients and atrial fibrillation in 3. Fontan conversion operation was performed with intracardiac lateral tunnel in 5 patients and extracardiac conduit in 11. Arrhythmia surgery included isthmus cryoablation in 10 patients and right-sided maze in 3. RESULTS: There has been no mortality. At Fontan conversion operation, 7 patients required permanent pacemaker. All patients have improved to New York Heart Association class I or II. With a mean follow-up of 26.9+/-30.6 (range:1-87) months, 16 patients had sinus rhythm, 2 patients had transient atrial flutter which was well controlled, and 2 patients required permanent pacemaker during follow-up. CONCLUSIONS: Fontan conversion with concomitant arrhythmia surgery and permanent pacemaker placement is safe, improves New York Heart Association functional class, and has a low incidence of recurrent arrhythmias. In most patients, concomitant permanent pacemakers are needed.