HCV and diabetes mellitus: evidence for a negative association

OBJECTIVE: Uncontrolled, retrospective clinical studies have recently claimed that HCV infection could trigger the onset of diabetes mellitus (DM). We sought to verify the association between DM and liver diseases of different etiology, stage, and severity in a prospective study including gender- and age-matched controls. METHODS: Two hundred forty-seven patients with liver cirrhosis (184 men, 116 with an associated hepatocellular carcinoma, 34% in Child-Pugh's class A) were evaluated (group 1). One hundred fifty-seven (63.5) of them were HCV positive, 38 (15.5%) HBV positive, 49 (19.8%) alcohol abusers, and three (1.2%) cryptogenic. Two control groups were also included. The first control group consisted of 138 patients with chronic hepatitis due to HCV infection (73.9%), HBV infection (15.9%), or alcohol abuse (10.2%) (group 2). The second control group included 494 patients with an acute osteoarticular trauma, age- and gender-matched with patients in group 1 (group 3). RESULTS: Diabetes mellitus was present in 32.3%, 3.6%, and 9.7% of patients in groups 1, 2, and 3, respectively. When compared with controls (group 3), DM was significantly less frequent in group 2 (p < 0.004) and significantly more frequent in group 1 (p < 0.0001). The prevalence of DM was not different among patients with HCV, HBV infection, or alcohol abuse. In group 3, the prevalence of DM appeared to increase steadily with age. On the contrary, in patients with liver cirrhosis (group 1) DM was detected in about 20-30% of cases in all decades of age. In group 2, diabetics were found only in the 7th and 8th decades of life. At multivariate analysis cirrhosis and age were the only two factors independently associated with DM; odds ratios were 12.5 (95% confidence interval [C.I.], 6.74-20.4) for cirrhosis, and 1.47 for age (95% C.I. 0.39-2.55). CONCLUSIONS: Our findings disprove HCV infection as a trigger factor for DM, which should not be listed among the various extrahepatic manifestations of this viral infection.     

A signal-detection theory based perspective on design of warning

The effects of warnings are analyzed using a distributed signal-detection theory model. It is established that selectivity always increases effectiveness. The implications to optimal warning design for intermittent versus continuous hazards are discussed. The changes in the behavior of the 6 human subjects in response to changes in the warning levels are consistent with the predictions of the model.     

The phosphorylation of eukaryotic initiation factor eIF4E in response to phorbol esters, cell stresses, and cytokines is mediated by distinct MAP kinase pathways

Initiation factor eIF4E binds to the 5'-cap of eukaryotic mRNAs and plays a key role in the mechanism and regulation of translation. It may be regulated through its own phosphorylation and through inhibitory binding proteins (4E-BPs), which modulate its availability for initiation complex assembly. eIF4E phosphorylation is enhanced by phorbol esters. We show, using specific inhibitors, that this involves both the p38 mitogen-activated protein (MAP) kinase and Erk signaling pathways. Cell stresses such as arsenite and anisomycin and the cytokines tumor necrosis factor-alpha and interleukin-1beta also cause increased phosphorylation of eIF4E, which is abolished by the specific p38 MAP kinase inhibitor, SB203580. These changes in eIF4E phosphorylation parallel the activity of the eIF4E kinase, Mnk1. However other stresses such as heat shock, sorbitol, and H2O2, which also stimulate p38 MAP kinase and increase Mnk1 activity, do not increase phosphorylation of eIF4E. The latter stresses increase the binding of eIF4E to 4E-BP1, and we show that this blocks the phosphorylation of eIF4E by Mnk1 in vitro, which may explain the absence of an increase in eIF4E phosphorylation under these conditions.     

Inhibition of ingestive behavior following fourth ventricle bombesin injection in chronic decerebrate rats.

Tested the hypothesis that the effects of 4th ventricle bombesin (BN) injection on feeding require interaction with forebrain neural systems by measuring intraoral sucrose (0.1 M) in tube-fed control and tube-fed supracollicular decerebrate rats after 4th ventricle injections of 1, 5, 10, 20, and 50 ng BN. Fourth ventricle injections of all doses of BN reliably suppressed sucrose intake in both control and chronic decerebrate rats. These results indicate that caudal brain-stem afferent signals produced by 4th ventricle BN injections are integrated by the local neural circuitry of the caudal brain stem, independent of the forebrain systems, to modulate ingestive behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Metastatic carcinoma of the prostate mimicking primary carcinoid tumor of the lung and mediastinum

AIMS: To investigate the current use of thrombolytic therapy in the management of patients with acute myocardial infarction and to determine the potential for an increased use of thrombolysis or percutaneous transluminal coronary angioplasty (PTCA). METHODS AND RESULTS: All hospitalised cases of acute myocardial infarction were identified in three health districts in the UK (population of 960,000) in patients under the age of 76 years during a 2-year period; 2439 patients had acute myocardial infarction, of whom 1264 (52%) received thrombolytic therapy. Failure to administer thrombolytic therapy was a result of the absence of diagnostic electrocardiograms in 712 (29.2%) patients, late presentation in 127 (5.2%), therapeutic error in 112 (4.6%), presence of a bleeding risk in 139 (5.7%) and other miscellaneous reasons in 80 (3.3%) patients. Thirty-eight of the 139 patients in whom bleeding risk was reported as a contra-indication could, in retrospect, have received thrombolytic therapy and a further 76 would have been suitable for primary PTCA. CONCLUSIONS: The potential for increasing the use of thrombolytic therapy seems to be limited and is unlikely to make a major impact on the in-hospital mortality from acute myocardial infarction. However, primary PTCA should be considered in those who are ineligible for thrombolysis because of bleeding risk as a contra-indication.     

T-cell tumour necrosis factor-alpha receptor binding in demented patients

Dementia of Alzheimer type (DAT) is a neurodegenerative disease of the central nervous system (CNS), in which an unbalanced cytokine network may lead to an altered immunoregulation. Tumour necrosis factor (TNF)-alpha is a cytokine with manifold effects on the neuroimmune system. Specific TNF-alpha receptors have been found on human peripheral blood lymphocytes. The aim of the present study has been to assay TNF-alpha binding on T cells from DAT patients and healthy sex- and age-matched controls. We found that T lymphocytes from demented patients bear significantly more p60 and p80 TNF-alpha receptors than those from controls (Bmax: 705, 29 vs 131, 6 (mean, SEM) receptors/cell). Such TNF-alpha binding sites, of the same type in DAT patients and healthy subjects (Kd: 67.6, 5.0 vs 70.7, 5.6 (mean, SEM) pM), are functional, since they are able to mediate in vitro NF-kappa B activation. These results are discussed in terms of DAT pathogenesis. Since it has been reported that activated T cells have more TNF-alpha receptors than resting cells, an increased number of lymphocyte TNF-alpha receptors might indicate a systemic immune activation in DAT patients as compared with healthy controls.     

Rapid inhalation induction in children: 8% sevoflurane compared with 5% halothane

BACKGROUND: Ultrasonography (US) by acknowledged experts enhances the diagnostic performance and reduces the rate of negative laparotomies in patients with suspected acute appendicitis (AA). METHODS: The diagnostic accuracy and clinical impact of routine US performed by surgical residents was prospectively studied in 504 unselected patients admitted for AA. Clinical and US findings were correlated with laparotomy findings and pathological outcome in 135 patients (113 cases with proven AA, prevalence 22.4%) and clinical as well as follow-up data were compared in the remainder. RESULTS: The overall accuracy, sensitivity, and specificity of the clinical diagnosis of AA were 84.9%, 51.3%, and 94.6% and those of US were 93. 6%, 83.1%, and 96.6%. Joint evaluation of the results from clinical evaluation and US further improved diagnostic performance (accuracy 93.4%, sensitivity 84.1%, specificity 96.2) and significantly reduced the rate of diagnostic errors to 3.4% (p < 0.001) and unnecessary laparotomies to 9.6% (p < 0.01) in patients with suspected AA. CONCLUSIONS: Ultrasonographic evaluation of the patient with suspected AA is considered to be of value in surgical practice.     

Complement C6 and C2 biosynthesis in syngeneic PVG/c- and PVG/c+ rat strains

A PVG rat with total deficiency of C6 and partial deficiency of C2 (PVG/c-), and a syngeneic control strain (PVG/c+), were used to study the production of extrahepatically synthesized complement. Livers of complement deficient rats were transplanted in sufficient rats (Tx-L). The C6 and C2 levels in Tx-L rats declined within 2 days to 25% and 30%, respectively, and remained stable for more than 6 weeks. To investigate the contribution of C6 synthesis by the liver, C6 sufficient livers were grafted in deficient rats (Tx + 1). After an initial increase, with maximum C6 levels of 119% at 10 days following transplantation, the C6 levels decreased gradually and C6 was no longer detectable 28 days after transplantation. This decline in C6 levels was dependent on antibody production against C6. No significant change in the C3, C4, factor H and factor B levels was observed. Expression of C6 mRNA in the grafted PVG/c+ sufficient liver was comparable to the expression of C6 mRNA in control PVG/c+ livers while C6 mRNA expression in the transplanted PVG/ c- liver and the control PVG/c- liver was lower. In conclusion, it was demonstrated in vivo that not only C6 but also C2 is synthesized extrahepatically in PVG/c rats.