Increased insulin sensitivity and hypoinsulinemia in APS knockout mice

A tyrosine kinase adaptor protein containing pleckstrin homology and SH2 domains (APS) is rapidly and strongly tyrosine phosphorylated by insulin receptor kinase upon insulin stimulation. The function of APS in insulin signaling has heretofore remained unknown. APS-deficient (APS(-/-)) mice were used to investigate its function in vivo. The blood glucose-lowering effect of insulin, as assessed by the intraperitoneal insulin tolerance test, was increased in APS(-/-) mice. Plasma insulin levels during fasting and in the intraperitoneal glucose tolerance test were lower in APS(-/-) mice. APS(-/-) mice showed an increase in the whole-body glucose infusion rate as assessed by the hyperinsulinemic-euglycemic clamp test. These findings indicated that APS(-/-) mice exhibited increased sensitivity to insulin. However, overexpression of wild-type or dominant-negative APS in 3T3L1 adipocytes did not affect insulin receptor numbers, phosphorylations of insulin receptor, insulin receptor substrate-1, or Akt and mitogen-activated protein kinase. The glucose uptake and GLUT4 translocation were not affected by insulin stimulation in these cells. Nevertheless, the insulin-stimulated glucose transport in isolated adipocytes of APS(-/-) mice was increased over that of APS(+/+) mice. APS(-/-) mice also showed increased serum levels of leptin and adiponectin, which might explain the increased insulin sensitivity of adipocytes.     

Vertebral derotation in adolescent idiopathic scoliosis causes hypokyphosis of the thoracic spine

The underlying purpose of this commentary and position paper is to achieve evidence-based recommendations on prevention of work-related musculoskeletal disorders (MSDs). Such prevention can take different forms (primary, secondary and tertiary), occur at different levels (i.e. in a clinical setting, at the workplace, at national level) and involve several types of activities. Members of the Scientific Committee (SC) on MSDs of the International Commission on Occupational Health (ICOH) and other interested scientists and members of the public recently discussed the scientific and clinical future of prevention of (work-related) MSDs during five round-table sessions at two ICOH conferences (in Cape Town, South Africa, in 2009, and in Angers, France, in 2010). Approximately 50 researchers participated in each of the sessions. More specifically, the sessions aimed to discuss new developments since 1996 in measures and classification systems used both in research and in practice, and agree on future needs in the field. The discussion focused on three questions: At what degree of severity does musculoskeletal ill health, and do health problems related to MSDs, in an individual worker or in a group of workers justify preventive action in occupational health? What reliable and valid instruments do we have in research to distinguish ??normal musculoskeletal symptoms?? from ??serious musculoskeletal symptoms?? in workers? What measures or classification system of musculoskeletal health will we need in the near future to address musculoskeletal health and related work ability? Four new, agreed-upon statements were extrapolated from the discussions: 1. Musculoskeletal discomfort that is at risk of worsening with work activities, and that affects work ability or quality of life, needs to be identified. 2. We need to know our options of actions before identifying workers at risk (providing evidence-based medicine and applying the principle of best practice). 3. Classification systems and measures must include aspects such as the severity, frequency, and intensity of pain, as well as measures of impairment of functioning, which can help in prevention, treatment and prognosis. 4. We need to be aware of economic and/or socio-cultural consequences of classification systems and measures.     

Long-term results of elective hepatectomy for the treatment of ruptured hepatocellular carcinoma

Background/Purpose According to the General rules for the clinical and pathological study of primary liver cancer, compiled by the Liver Cancer Study Group of Japan, ruptured hepatocellular carcinoma (HCC) is classified as stage 4, even if the tumor is small and solitary. We examined the long-term results of elective hepatectomy for the treatment of ruptured HCC. Methods A first hepatectomy was performed without operative death in 193 patients with HCC. Ten patients had ruptured HCC (ruptured group) and 183 patients had nonruptured HCC (nonruptured group). The extension of HCC was macroscopically classified as stage 1 in 23 patients, stage 2 in 71, stage 3 in 53, and stage 4 in 46. Results Cumulative survival rates in the ruptured group at 1, 5, and 10 years were 90.0%, 67.5%, and 20.3%, respectively. The cumulative survival rate was lower in patients with stage 4 disease in the nonruptured group than that in patients in the ruptured group (P < 0.05). Cumulative survival rates did not differ significantly between patients in the ruptured group and those with stage 2 or stage 3 disease. Conclusions Survival rates after elective hepatectomy in patients with ruptured HCC are good, even if the disease is classified as stage 4.     

Mumps Hoshino and Torii vaccine strains were distinguished from circulating wild strains

Aseptic meningitis and acute parotitis have been observed after mumps vaccination. Mumps outbreaks have been reported in Japan because of low vaccine coverage, and molecular differentiation is required to determine whether these cases are vaccine associated. RT-nested PCR was performed in the small hydrophobic gene region, and viruses were differentiated by restriction fragment length polymorphism assay. A total of 584 nucleotides were amplified. The PCR product of the Hoshino strain was cut into two fragments (313 and 271 nucleotides) by MfeI; that of the Torii strain was digested with EcoT22I, resulting in 332- and 252-nucleotide fragments. Both strains were genotype B and had an XbaI site, resulting in two fragments: 299 and 285 nucleotides. Current circulating wild types were cut only by XbaI or MfeI. However, the MfeI site of the wild types was different from that of the Hoshino strain, resulting in 451- and 133-nucleotide fragments. Using three restriction enzymes, two mumps vaccine strains were distinguished from wild types, and this separation was applied to the identification of vaccine-related adverse events.     

Bilateral carotid stenting for bilateral carotid artery stenosis improved vascular dementia

We report a case of bilateral internal carotid artery (ICA) stenosis treated with stenting. A 78-year-old man suffered from vascular dementia and left hemiparesis, and, by magnetic resonance angiogram (MRA), was diagnosed as having bilateral ICA stenosis. Cerebral angiogram showed severe, bilateral ICA stenosis (right; 88%, left; 93%) and xenon single photon emission tomography (SPECT) showed severely decreased cerebral blood flow (CBF) and cerebrovascular reactivity (CVR). We performed bilateral carotid angioplasty with self-expanding stents. Both CBF and CVR were improved bilaterally after the operation. The patient was discharged without neurological deficits. Carotid stenting may be an alternative treatment for severe ischemia caused by severe, bilateral ICA stenosis.     

Application of Polyethylene Glycolic Acid Felt with Fibrin Sealant to Prevent Postoperative Pancreatic Fistula in Pancreatic Surgery

Objective

The purpose of this nonrandomized retrospective study was to report our new procedures using polyethylene glycolic acid (PGA) felt with fibrin sealant to prevent severe pancreatic fistula in patients undergoing pancreatic surgery.

Methods

From 2000 to 2008, 54 and 63 patients underwent pancreaticoduodenectomy (PD) and distal pancreatectomy (DP), respectively. Of those patients, we applied PGA felt with fibrin sealant to 18 PD patients and 26 DP patients. In PD patients, the PGA felt was wrapped around the pancreatic suture site, while in DP patients, the PGA felt was wrapped around the predictive division site. The pancreaticojejunostomy site in PD patients and the cut stump in DP patients were coated with fibrin sealant. We compared the occurrence rates for severe postoperative pancreatic fistula (POPF) that occurred after PD or DP both with and without our new procedures.

Results

Before introduction of our procedures, severe POPF developed in 14 of 36 PD patients (39%) and 10 of 37 DP patients (27%). In contrast, after introduction of our procedures, the incidence of POPF was only one in both of 18 PD (6%; P?=?0.016) and 26 DP (4%; P?=?0.017) patients.

Conclusion

In summary, our procedure using PGA felt with fibrin sealant may reduce the risk of severe POPF.     

Solitary fibrous tumor of the inguinal region

Solitary fibrous tumors (SFT) have recently been established to be of mesenchymal origin. Although there are numerous reports of SFTs arising from the pleura, reports of the tumor arising from extrapleural sites are comparatively rare [Fletcher CDM, Unni K, Mertens F (eds) World Health Organization classification of tumors, pathology & genetics, tumors of soft tissue and bone. IARC Press, Lyon, pp 86–901, 2002]. We report a case of SFT arising in the inguinal region.     

Specific Antibiotic Prophylaxis Based on Bile Cultures Is Required to Prevent Postoperative Infectious Complications in Pancreatoduodenectomy Patients Who Have Undergone Preoperative Biliary Drainage

Background Preoperative biliary drainage (PBD) is associated with bacterial contamination of bile, but the effects of PBD on morbidity after pancreatoduodenectomy remain controversial. The aim of this study was to characterize bile contamination to develop successful specific antibiotic prophylactic strategies for pancreatoduodenectomy. Methods Ninety-one consecutive patients who underwent pancreatoduodenectomy for periampullary tumor were prospectively evaluated. Prophylactic antibiotics were selected based on preoperative bile cultures. Bile cultures and postoperative complications were compared in 46 patients who underwent PBD (drainage group) versus 45 patients who did not (nondrainage group). Results The incidence of positive bile cultures was higher in the drainage group (78%) than in the nondrainage group (36%) (P < 0.001). In the drainage group, positive bile cultures were frequently polymicrobial (61%) and demonstrated resistance to several antibiotics, including cefazolin (83%), cefmetazole (72%), and cefpirome (64%). Overall morbidity (30% and 22%) and infectious morbidity (13% and 11%) did not differ significantly between the drainage and nondrainage groups, respectively. Conclusions PBD had a notable influence on bile microbial contamination, including a higher rate of antibiotic resistance. Therefore, specific antibiotic prophylaxis based on bile culture is required for preventing infectious complications in pancreatoduodenectomy patients who undergo PBD.     

Altered glycosylation of alpha-dystroglycan in neurons of Fukuyama congenital muscular dystrophy brains

To test the hypothesis that the disruption of fukutin protein produces the brain pathology through hypoglycosylation of alpha-dystroglycan (alpha-DG), we immunostained Fukuyama congenital muscular dystrophy (FCMD) brains with an antibody that recognizes the polysaccharide epitope of alpha-DG. Immunoreactivity of the glia-limitans along the cortical surface, as well as that of the glial endfeet around vessel walls, was preserved in the FCMD cerebrum. However, fragmentation of the immunostained glia-limitans was noted in association with parenchymal protrusion and gyral fusion. In the FCMD cerebellum, this fragmentation of alpha-DG labeling was limited to the area of micropolygyria, and immunostaining at the glia-limitans and vessel walls was comparable to that of the control brains, in structurally normal areas. In the hippocampus, neurons of the dentate gyrus and corpus ammonis were immunopositive for alpha-DG in control subjects, but this staining was markedly decreased in FCMD brains. In contrast, immunolabeling of blood vessels and the glia-limitans was preserved in this region. Fukutin antisera clearly labeled hippocampal neurons in control brains, while this labeling was decreased in FCMD brains. Thus, hypoglycosylation of alpha-DG was evident in neurons, but not in the glial cell population of FCMD brains. This suggests that the mechanism of alpha-DG glycosylation may differ between neurons and glial cells, and that a fukutin gene defect may result in functional disruption through hypoglycosylation of both neuronal and glial alpha-DG.