Possibility of selection against mtDNA mutations in tumors

Several studies of tumors have revealed substantial numbers of clonally expanded somatic mutations in mitochondrial DNA (mtDNA), not observed in adjacent intact tissues. These findings were interpreted as indicating the involvement of mtDNA mutations in tumorigenesis. Such comparisons, however, ignore an important confounding factor: the monoclonal origin of tumors as opposed to the highly polyclonal nature of normal tissues. Analysis of recently published data on the incidence of somatic mutations in nontumor monoclonal cells suggests that, contrary to the prevailing view, the process of tumorigenesis may be accompanied by active selection against detrimental mtDNA mutations.     

Clinicopathological review of 18 cases of liver allografts lost due to bile duct necrosis

Clinical, radiographic, and pathological features of 18 patients with biliary necrosis in their explanted liver allografts were reviewed. Twelve patients were men and ages ranged from 27 to 72 years. Indications for initial liver transplant (LT) were viral hepatitis (n = 7), steatohepatitic cirrhosis (n = 3), cryptogenic cirrhosis (n = 3), secondary sclerosing cholangitis (n = 2), primary sclerosing cholangitis (n = 1), biliary atresia (n = 1), and nodular regenerative hyperplasia (n = 1). Donor age ranged from 16 to 75 years. Duct-to-duct biliary anastomoses were fashioned in 13 cases; warm and cold ischemia times were not significantly different from general LT population. Seventeen allograft biopsies after recirculation had no significant findings. Post-LT, clinical and radiographic evaluation indicated biliary strictures (n = 7), bile leak (n = 7), intrahepatic abscess (n = 1), and duodenal perforation (n = 1). Radiographic vascular studies suggested hepatic arterial thrombosis or stenosis in 11 cases. Biopsies prior to retransplantation were performed on 17 patients and showed acute rejection (n = 10), biliary outflow impairment (n = 4), normal histology (n = 2), and centrilobular necrosis (n = 1). Retransplantation was performed 14 to 334 days after initial LT. Pathological examination of explants revealed perihilar duct necrosis in all cases, with bacterial colonies (n = 10) and fungal organisms (n = 2). Arterial thrombi were seen in 10 cases, and two had prominent arteriosclerosis. Infarction and centrilobular necrosis were seen in 9 and 13 cases, respectively. Four explants showed features of biliary outflow impairment. Twelve patients were alive 6 to 18 months following retransplantation. We conclude that post-LT biliary necrosis is associated with ischemia, and such a complication is rarely evident in allograft biopsies. Biliary and vascular imaging studies are essential in evaluating patients for this complication.     

The Papillon-Lefèvre syndrome: neutrophil dysfunction with severe periodontal disease

Two cases of Papillon-LeF evre are described. Both siblings demonstrated neutrophil dysfunction and severe precocious periodontal disease. The neutrophil locomotion defect was characterized by a decreased migration toward a chemotactic factor and decreased random migration. Binding of the chemotactic factor, FMLP, to the neutrophil surface was unchanged. Both patients harbored Actinobacillus actinomycetemcomitans and showed elevated serum IgG levels. Both patients also demonstrated salivary and serum antibody to A. actinomycetemcomitans. The Papillon-LeF evre syndrome is compared with the more common localized juvenile periodontitis.     

Role of a minimally invasive approach in the management of laparoscopic adjustable gastric banding postoperative complications

HYPOTHESIS: Complications after laparoscopic adjustable gastric banding as treatment for morbid obesity may require a major reintervention. A minimally invasive approach represents an attractive management alternative for such complications. DESIGN: Prospective case series. SETTING: Major academic medical and surgical center. PATIENTS: From January 1996 to July 2003, 47 patients who had undergone laparoscopic adjustable gastric banding were operated on again. Considering the causes for reoperation, the patients were divided into 4 groups: group A had major complications (n = 26); group B, minor complications (n= 11); group C, psychological problems (n=6); and group D, insufficient weight loss (n=4). INTERVENTIONS: Forty-three procedures, 38 using general anesthesia (groups A, C, and D) and 5 using local anesthesia (group B), were performed. MAIN OUTCOME MEASURES: Feasibility, safety, and effectiveness of a minimally invasive approach in the treatment of laparoscopic adjustable gastric banding complications. RESULTS: In group A, 9 of 10 patients with irreversible gastric pouch dilatation and 15 of 16 with intragastric band migrations were treated laparoscopically. In group B, 5 ports were substituted and 2 reconnections of the catheter-port system were performed. In group C, 6 laparoscopic band removals were carried out. In group D, 4 laparoscopic revision procedures for insufficient weight loss were performed. The operative mortality was nil. The most frequent cause of reoperation was intragastric migration (37.2%). A minimally invasive approach was adopted in 94.7% of cases. CONCLUSION: Laparoscopy is safe and effective, even as a second operative procedure.     

Laparoscopic adjustable silicone gastric banding: prospective evaluation of intragastric migration of the lap-band

Intragastric prosthesis (Lap-Band, BioEnterics Co., Carpinteria, CA, U.S.A.) migration is one of the major long-term complications of laparoscopic adjustable silicone gastric banding. The causes, clinical signs, timing, and overall incidence of band entrapment have not been prospectively investigated in a large series. The purpose of this study was to assess prospectively the incidence of Lap-Band intragastric migration and to establish the safety and effectiveness of minimally invasive band removal. Between January 1996 and June 2000, 148 consecutive patients enrolled in a multidisciplinary bariatric program underwent laparoscopic adjustable silicone gastric banding. In the follow-up treatment, gastrointestinal endoscopy was performed routinely. One hundred twenty-three patients with a minimum follow-up period of 12 months were entered into the study group. Eleven (9.2%) patients had long-term major complications. Intragastric band migration was observed in nine (7.5%) patients. The diagnosis was established by routine endoscopy between 10 and 41 months after surgery. Five erosions occurred in the first 30 cases (learning curve period). In six patients, the band was removed by an intragastric endoscopic-assisted approach avoiding laparotomy. The remaining three patients are under endoscopic surveillance. The results of this study show that routine upper gastrointestinal endoscopy can discover asymptomatic band migrations early. Band erosion did not require emergency treatment and can be removed safely by a minimally invasive approach.     

RENAL FUNCTION IN CHRONICALLY CATHETERIZED CONSCIOUS DIABETIC RATS USING CONSTANT AND SERVO-CONTROLLED INFUSION

1. Infusion experiments were performed on chronically catheterized conscious rats to assess kidney function before and after the induction of diabetes mellitus with streptozotocin. 2. Two infusion regimens were used, a conventional constant-infusion protocol and a novel computer-driven, servo-controlled fluid replacement technique. The latter enables body fluid status to be maintained throughout a study occasion by servo-controlled replacement of spontaneous urinary fluid losses. 3. The chronically catheterized conscious rat infused using a servo-controlled system appears to be the optimum model for a study of diabetic renal function. The conscious preparation circumvents problems associated with anaesthesia and acute surgery. The servo-controlled infusion protocol maintains the altered fluid status of the diabetic condition. Both hyperfiltration and polyuria, characteristics of human diabetes often absent in anaesthetized and/or constantly infused diabetic rats, were seen in all conscious servo-controlled diabetic animals. 4. The new regimen enables a more accurate assessment of renal function in experimental diabetes than with previous protocols. It should prove useful in future studies, particularly those assessing the role of anti-diabetic drugs on the kidney.     

Unexplained diarrhoea and failure to thrive in 2 siblings with unusual facies and abnormal scalp hair shafts: a new syndrome

A family is described in which 2 siblings born to healthy parents presented with abnormal facies, persistent diarrhoea, and early death. Exhaustive pathological and biochemical investigations failed to find a cause. The scalp hair of both babies had an abnormal amino-acid composition, and presented an appearance that was unique on scanning electron microscopical examination; this fact and the clinical picture probably represents a new syndrome.     

Modulation of implantation-associated integrin expression but not uteroglobin by steroid hormones in an endometrial cell line

In order to test the hypothesis that integrin and uteroglobin (UG) expression in cultured endometrial cells are affected by hormone treatment, Ishikawa-CH endometrial cancer cells were cultured and exposed to oestradiol or oestradiol and progesterone regimens and assayed using immunohistochemistry. We evaluated the intensity of immunohistochemical staining for the integrin monomers alpha(v) and beta1, the dimers alpha(v)beta3 and alpha(v)beta6, and for the secretory protein uteroglobin under various experimental conditions. Cells grown in control media stained positively for the integrin monomers alpha(v) and beta1, the dimer alpha(v)beta3, and for UG. Oestradiol and sequential oestradiol/progesterone reversibly suppressed staining for the dimer alpha(v)beta3. Hormone treatment had no effect on the staining of the beta1 and alpha(v) monomers or UG. The alpha(v)beta6 dimer antibody did not stain under any experimental treatment conditions. These data indicate that expression of the integrin complex alpha(v)beta3 is reversibly suppressed by oestradiol in Ishikawa cells and that these cells may be a good model for studying hormone-driven molecular changes in endometrium.