Renal function and outcome after heart transplantation

Objectives

To investigate whether measured glomerular filtration rate (mGFR) is a risk factor for death and/or end-stage renal disease (ESRD) after heart transplantation (HTx).

APC and p53 mutations in de novo colorectal adenocarcinomas

To investigate genetic features in small and flat colorectal carcinomas that arise de novo, we searched for genetic alterations in six sporadic tumors by examining their APC, K-ras, and p53 genes. Two of the six tumors carried detectable mutations within the mutation cluster region (MCR) of the APC gene; both mutations were predicted to cause truncation of the gene product. Four tumors carried mutations of the p53 gene; three were missense mutations in exon 5, and the other was a 3-bp deletion in exon 6. However, neither codon 12 nor codon 13 of K-ras contained detectable mutation in any tumors. Hence, as “adenoma-carcinoma sequence” model of development of colorectal carcinoma, inactivation of the APC and p53 genes appear to be Involved in development of the de novo type of colorectal carcinoma even though the adenoma stage is not observed. © 1994 Wiley-Liss, Inc.     

Routine surveillance endoscopy before and after sleeve gastrectomy?

There is no consensus when it comes to the necessity of an oeso-gastroduodenal fibroscopy(OGDF) before and after bariatric surgery. Many reports expressed the preoccupations about a gastroesophagal reflux disease(an acute risk of Barrett's esophagus) and its consequences after a sleeve gastrectomy(SG) and the risk of leaving a premalignant lesion in an excluded stomach after a Roux-en-Y gastric bypass. The International Federation for the Surgery of Obesity and Metabolic Disorders recommends a surveillance endoscopy, routinely after a SG. After review of the literature, we set out the arguments in favor of performing a systematic preoperative and post-operative OGDF.     

De novo gastric adenocarcinoma 1 year after sleeve gastrectomy in a transplant patient

IntroductionIt has been reported in the literature that upper gastrointestinal malignancies after bariatric surgery are mostly gastro-esophageal, although it is not clear whether bariatric surgery represents a risk factor for the development of esophageal and/or gastric cancer. We report a case of a de novo gastric adenocarcinoma occurring in a transplant patient 1 year after a laparoscopic sleeve gastrectomy.Presentation of caseA 44 year-old woman with a BMI of 38 kg/m², hypertension, type 1 diabetes mellitus, multiple malignancies and a pancreas transplant underwent laparoscopic sleeve gastrectomy. The patient presented with intense dysphagias during the follow up. Studies were performed and the diagnoses of grade 2/3 adenocarcinoma were made. The patient underwent a robotic assisted total gastrectomy with a roux-en-y intracorporeal esophagojejunostomy. The procedure resulted in multiple metastasic lymph nodes, focal and transmural invasions to multiple organs with a tumor free margin resection. The patient presented with a postoperative pleural effusion, with no further complications.DiscussionThe diagnosis of gastroesophageal cancer after bariatric surgery is usually late since these patients have common upper gastrointestinal symptoms related to the procedure that could delay the diagnosis. De novo gastric cancer after sleeve gastrectomy has only been reported in one instance, in contrast with other bariatric surgery procedures.ConclusionsNo direct relation has been established between sleeve gastrectomy and the development of gastric cancer. Robotic procedures allow for complex multiorgan resections, while preserving the benefits of minimally invasive surgery.     

CREBBP 基因突变所致Rubinstein-Taybi 综合征1例

Rubinstein-Taybi 综合征(Rubinstein-Taybi syndrome,RSTS) 又称宽拇指巨趾综合征(broad thumb-great toe syndrome)、巨指(趾)综合征(broad digits syndrome),是一类罕见的常染色体显性遗传病。患者的主要特征为颅面畸 形、骨骼畸形、生长延迟和精神及运动发育迟缓。本例患儿具有典型的RSTS特殊面容及生长迟滞,合并不典型的腹 股沟斜疝。二代测序技术基因结果显示：患儿的16 号染色体CREBBP基因外显子上存在1 个杂合突变位点c.4492C> T(p. Arg1498Ter),且为无义突变,使得肽链合成提前终止。受检者父母未发现上述变异,该变异可能为新生突 变。本病目前尚无特异性治疗方法。     

rFVIIa– for acute rebleeding of a cerebral cavernous malformation

Recurrent bleeding episodes of cavernomas especially in the brainstem can cause progressive neurological deficits. Therefore brainstem cavernomas are still a therapeutic dilemma and a treatment challenge for the neuro critical care community. We report a 39-year-old woman with spontaneous ataxia diplopia and vomiting, who has been treated for multiple intracerebral cavernomas during the last 10 years. A cerebral computed tomography (cCT) revealed a re-bleeding cavernoma in the left cerebral peduncle with consecutive obstructive hydrocephalus. As a result of the difficult anatomical location, no surgical approach was possible. As an off-label treatment, recombinant activated factor VII (rFVIIa) was administered to prevent possible further bleeding and especially further sequelae. The patient recovered well and no adverse events and especially no further bleeding of the cavernoma were observed. To our knowledge, this is the first report of the safe and successful use of rFVIIa to treat re-bleeding episodes in cavernomas. Further clinical studies are needed to specify the future potential of rFVIIa.     

Protonated form of histidine 238 quenches the fluorescence of tryptophan 241 in subtilisin Novo

The pH dependence of the fluorescence of phenylmethanesulfonyl-subtilisin Novo after excitation at 300nm is studied. pK values of 5.9 and 10.3 were determined from the titration curve. The major source of indole fluorescence is tryptophan 106. Evidence is presented that the protonated form of histidine 238 quenches the fluorescence of tryptophan 241 in this enzyme. The quenching is explained by a charge-transfer complex formation between the excited indole and imidazole rings which are parallel and quite close to each other in the X-ray model.     

The effects of hyperinsulinemia on arterial wall and peripheral muscle metabolism in dogs

Peripheral hyperinsulinemia may be associated with metabolic consequences that could contribute to the high incidence of macrovascular disease in patients with diabetes mellitus. Arterial wall and striated muscle cells were studied in dogs to examine the effect of hyperinsulinemia on the lipid content and on lipogenic and glycolytic enzyme activity. Eight pancreatectomized dogs received segmental pancreatic autografts with venous drainage into the iliac vein. Glucose disappearance rates (K values) were normal four years after transplantation, but both fasting serum insulin levels (48.9 +/- 4.8 v 11.8 +/- 1.9 microU/mL) and the total area under the glucose-insulin response curve (1797 +/- 196 v 1110 +/- 158 microU X min/mL) were significantly greater than in control animals (P less than 0.05). The hyperinsulinemic dogs had a marked triglyceride elevation in arterial smooth muscle (20.6 +/- 8.0 v 0.5 +/- 0.4 mumol/g) and striated muscle (171.4 +/- 46.6 v 41.2 +/- 7.7 mumol/g) (P less than 0.001). Moreover, key enzymes in lipid synthesis (glucose-6-phosphate dehydrogenase, malic enzyme, and 3-hydroxyacyl-CoA DH) were significantly increased (P less than 0.01) in the hyperinsulinemic animals, while the glycolytic enzymes, (phosphofructokinase, hexokinase, pyruvate kinase, and alpha-glycerophosphate DH) were not significantly different. These data demonstrate substantial enhancement of lipid synthesis in arterial wall and striated muscle in hyperinsulinemic dogs. Altered substrate metabolism in arterial walls, in association with hyperinsulinemia, may have important implications with regard to macrovascular disease in diabetes, particularly in insulin-treated patients. In addition, these studies may serve to stimulate longer term assessments of macroangiopathy in the increasing number of patients with functioning pancreatic allografts draining into the systemic circulation.     

Squalene Epoxidase Induces Nonalcoholic Steatohepatitis Via Binding to Carbonic Anhydrase III and is a Therapeutic Target

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