The defective glucose sensitivity of the B cell in non insulin dependent diabetes. Improvement after twenty hours of normoglycaemia

In non insulin dependent diabetics (N.I.D.D.) of normal body weight, the acute insulin response to glucose is defective while that to pharmacologic agents such as tolbutamide is less impaired. This specific B-cell insensitivity to glucose results from unknown and perhaps multiple mechanisms. Hyperglycemia may by itself aggravate this phenomenon. To test this hypothesis acute insulin release (Δl: sum of increment at 2, 5, 10 min) after intravenous glucose and tolbutamide injection was studied in 5 N.I.D.D. with fasting blood glucose averaging 12.1 mM/l (range 10.7–13.7) before and after 20 hours of glycemic normalization by an artificial pancreas. Intravenous injection of .3 g/k glucose did not elicit an acute insulin or C-peptide response, but following Tolbutamide (20 mg/kg) Δl was 44 ± 21 μU/ml and ΔC-peptide 0.84 ± 0.37 nM/l. After 20 hr of normoglycemia a response to glucose was apparent (Δl 60 ± 24 and ΔCP 0.86 ± 26) that to Tolbutamide was unchanged (Δl 58 ± 26 and ΔCP 0.97 ± 0.27). These results suggest that 20 hr of normoglycemia improve significantly the “glucoreceptor” function of the B-cell in N.I.D.D.     

The quest to expand the coverage of public health insurance in the occupied Palestinian territory: an assessment of feasibility and sustainability using a simulation modelling framework

Background

In their quest for universal health coverage (UHC), many developing countries explore alternative financing strategies to address the potential budgetary impact of health coverage expansion (for example, deferred debt versus current finance through taxation or premiums). Given the limited fiscal space, these policies may have different implications for fiscal sustainability and may worsen intergenerational inequality.

Severe acute kidney injury following major liver resection without portal clamping: incidence,risk factors,and impact on short-term outcomes

Background

Acute kidney injury (AKI) following major hepatectomy (MH) remains inadequately investigated. This retrospective study aimed to assess the risk factors and prognostic value of AKI on short-term outcomes following MH without portal pedicle clamping.

Short-term outcomes after major hepatic resection in patients with cirrhosis: a 75-case unicentric western experience

Background

The benefit of performing major hepatic resection (MHR) for hepatocellular carcinoma (HCC) in patients with cirrhosis remains controversial because of its high risk of posthepatectomy liver failure (PHLF). This study was conducted to assess the risk of MHR for HCC in patients with cirrhosis.

Thromboxane B2, 6-keto-PGF1 alpha, PGE2, PGF2 alpha, and PGA1 plasma levels in arteriosclerosis obliterans: relationship to clinical manifestations, risk factors, and arterial pathoanatomy

Current concepts of atherogenesis based on animal and human investigations indicate prostaglandins as a key factor in atherosclerotic lesions. The plasma profiles of thromboxane B2 (TXB2), 6-keto-PGF1 alpha, PGE2, PGF2 alpha, and PGA1 were investigated by means of a sensitive radioimmunoassay technique in 40 patients with arteriosclerosis obliterans and in 30 healthy control subjects. Abnormally high levels of TXB2 and PGE2 (222.97 +/- 320.86 pg/ml, mean +/- SD, vs 20 +/- 2.1 and 352.66 +/- 235.54 vs 24.4 +/- 3, p less than 0.01) were detected in arteriosclerosis obliterans patients. The ratio between TXB2 and 6-keto-PGF1 alpha was increased from 1.2 in control subjects to 6.0 in patients. In arteriosclerosis obliterans TXB2 increased in relation to clinical manifestations and to the extension of the vascular damage. In addition, TXB2 was positively related to serum triglyceride content (r = 0.562, p less than 0.05) and inversely related to platelet count (r = 0.727, p less than 0.001). The marked imbalance between the stable metabolites of thromboxane and prostacyclin in arteriosclerosis obliterans patients provides biologic evidence which fits well with the thrombogenic theory of atherosclerosis. These results further support the theory that prostaglandins may be heavily involved in atherosclerosis.     

Bepridil for recurrent sustained ventricular tachycardias: assessment using electrophysiologic testing

Bepridil was found to possess electrophysiologic properties common to class I and IV antiarrhythmic agents. Intravenous and oral bepridil were evaluated using serial electrophysiologic studies in a selected group of 9 patients with recurrent sustained ventricular tachycardia (VT) unresponsive to usual therapy, including amiodarone therapy in 15 patients. Intravenous bepridil treatment terminated sustained, well tolerated, pacing-induced VT in 3 of 6 patients and prevented the initiation of VT in 2 of these and in a patient in whom the drug failed to restore sinus rhythm. Oral bepridil was administered at a loading dose of 800 mg on day 1, and 500 to 600 mg the following days, and programmed electrical stimulation was repeated 2 to 6 days after initial study. Oral bepridil therapy prevented VT initiation in 6 patients (66%). The tachycardia cycle length was prolonged (30 to 105 ms) in 2 patients in whom VT remained inducible. In 1 patient the tachycardia cycle length significantly shortened after bepridil and prompt cardioversion was required. Five of the 6 patients with successful results underwent long-term oral treatment with bepridil. VT recurred in 1 patient during the hospitalization period and an adverse effect (paralytic ileus) in another patient required drug discontinuation. Three patients remain symptom-free over a follow-up of 4 to 13 months. These data suggest that bepridil may be useful in patients with recurrent, sustained VT.     

Prolonged electrical systole in acute myocardial infarction

Electrical systole duration has been studied in two groups of 23 patients (39 M and 7 F) admitted in the coronary care units of two different hospitals for documented acute myocardial infarction (AMI). The mean QT interval duration corrected for heart rate (QTc) was obtained from three measurements of non consecutive complexes in five different leads and compared to the ideal electrical systole duration of a normal population with the same cardiac cycle length. During the evolution of AMI, QT interval increased in both groups of patients (11.5% and 14.8% respectively) and was prolonged (17.6% and 21.5% respectively) at the 48th hour.Prolongation of electrical systole can be best measured using the ratio: QTc (according to Bazett)/normal QT (according to Ashman).     

The importance of health for income inequality in the occupied Palestinian territory: a decomposition analysis and cross-sectional study

Background

The contribution of income inequality to health inequality has been widely examined in developed countries. However, little evidence exists on the effect of health on income inequality in resource-constrained settings. Findings from previous studies have indicated several mechanisms through which health affects income inequality, with the labour market being an important channel. Given the different levels of development, there are reasons to believe that health might represent a greater constraint on earnings in low-income settings. The aim of this study was to examine the relation between income and health in the West Bank and Gaza Strip.

Is progression in the future liver remnant a contraindication for second-stage hepatectomy?

BackgroundTwo-stage hepatectomy (TSH) strategy is used to treat patients with bilobar colorectal liver metastasis (CLM). However, many patients do not undergo the second hepatectomy owing to disease progression in the future liver remnant (FLR) after portal vein embolization (PVE). This study aimed to assess the impact of disease progression in the FLRs of patients who completed the first hepatectomy.Methods68 consecutive patients underwent the first hepatectomy followed by PVE. Six patients (9%) dropped out after the PVE (two-stage failed [TSF] group) because of unresectable hepatic or general disease progression. Seventeen patients (25%) completed their second hepatectomy despite disease progression in the FLR (new CLM [nCLM] group) as it was considered resectable, while 45 patients (66%) underwent the second hepatectomy (control group).ResultsThe 5-year overall survival rates in the TSF, nCLM, and control groups were 0%, 7%, and 60%, respectively (P < 0.001). The median overall survival times between the TSF and nCLM groups were 26 months and 42 months (P = 0.005). Patients in the nCLM group whose hepatic disease progression was detected preoperatively versus intraoperatively had comparable survival rates.ConclusionResectable hepatic disease progression in the FLR after PVE should not be considered a contraindication for the second hepatectomy.     

ABNORMAL HEMOGLOBINS: LABORATORY METHODS

Laboratory methods allowing the detection and characterization of hemoglobin variants are reviewed. Protein chemistry techniques such as isoelectrofocusing, electrophoreses under various experimental conditions, cation exchange and reversed phase high performance liquid chromatography, are the most frequently used for the detection of variants. When associated with a few additional data they may lead to a presumptive diagnosis. DNA studies are also developed in many laboratories. Final identi(r)cation of a variant may be achieved either by molecular biology techniques or by protein sequence analysis in which mass spectrometry now occupies a key position.     

CAR-T cells : lymphocytes exprimant un récepteur chimérique à l’antigène

CAR-T cells are genetically modified human lymphocytes and gene therapy medicinal products. They are developed to treat cancers that express a membrane antigen targeted by the CAR. The FDA approved the two first-in-class medicinal products in 2017 and EMA in August 2018; both are autologous CAR-T cells targeting CD19 that is expressed at the surface of normal B-cells throughout their differentiation, and on B-cell lymphoid malignancies. Clinical efficacy was demonstrated for B-cell acute lymphoblastic leukemias, non-Hodgkin's lymphoma and chronic lymphocytic leukemia, although the marketing authorizations are less liberal in terms of indications. Manufacturing of these personalized treatments necessitates that a novel organization and supply chain be set in place, to ensure product preservation, patient safety and compliance with complex regulatory requirements. Side effects are commensurate with clinical efficacy and can be life-threatening: proper management imposes tight coordination between various specialists, particularly between hematologists and intensive care practitioners. High pricing for these treatments is part of a long-term trend for increasing costs of innovations in hematology and oncology; it questions the ability of healthcare systems to sustain their reimbursement.     

Control of intraabdominal hemorrhage and shock: a comparison of fluid resuscitation, MAST, and balloon occlusion

Our study examined the efficacy of four treatment modalities in controlling hemorrhage and achieving hemodynamic stabilization in hemorrhagic shock: intravenous fluid replacement (IV); military antishock trousers used concomitantly with fluids (MAST); balloon occlusion at the level of the diaphragm with concomitant fluid replacement (balloon); and a combination of MAST inflation, balloon occlusion, and fluid resuscitation (MAST and balloon). Twenty-eight mongrel dogs were anesthetized, and the spleen was exposed and completely crushed. The abdomen was closed, and treatment was initiated and continued for four hours or until the dog died. For all conditions the hematocrit dropped during the course of the experiment; balloon occlusion was effective at slowing this drop (P less than .0001), but MAST had no statistically significant effect. Animals with balloons bled more slowly into the abdominal cavity than did animals in the other two groups (P less than .0001). MAST also were effective at slowing the bleeding (P less than .05). Of the balloon and the MAST and balloon dogs, all except one survived the entire four hours; this difference between balloon and nonballoon dogs is significant (P = .002). MAST did not have a statistically significant effect on survival. Perfusion pressure (PP) declined during the course of the experiment, and the balloon was effective at slowing this decline (P less than .0001); none of the other comparisons was statistically significant.     

A Call to Action to Enhance Filovirus Disease Outbreak Preparedness and Response

The frequency and magnitude of recognized and declared filovirus-disease outbreaks have increased in recent years, while pathogenic filoviruses are potentially ubiquitous throughout sub-Saharan Africa. Meanwhile, the efficiency and effectiveness of filovirus-disease outbreak preparedness and response efforts are currently limited by inherent challenges and persistent shortcomings. This paper delineates some of these challenges and shortcomings and provides a proposal for enhancing future filovirus-disease outbreak preparedness and response. The proposal serves as a call for prompt action by the organizations that comprise filovirus-disease outbreak response teams, namely, Ministries of Health of outbreak-prone countries, the World Health Organization, Médecins Sans Frontières, the Centers for Disease Control and Prevention—Atlanta, and others.     

Interplay between interferon-mediated innate immunity and porcine reproductive and respiratory syndrome virus

Innate immunity is the first line of defense against viral infection, and in turn, viruses have evolved to evade host immune surveillance. As a result, viruses may persist in host and develop chronic infections. Type I interferons (IFN-α/β) are among the most potent antiviral cytokines triggered by viral infections. Porcine reproductive and respiratory syndrome (PRRS) is a disease of pigs that is characterized by negligible induction of type I IFNs and viral persistence for an extended period. For IFN production, RIG-I/MDA5 and JAK-STAT pathways are two major signaling pathways, and recent studies indicate that PRRS virus is armed to modulate type I IFN responses during infection. This review describes the viral strategies for modulation of type I IFN responses. At least three non-structural proteins (Nsp1, Nsp2, and Nsp11) and a structural protein (N nucleocapsid protein) have been identified and characterized to play roles in the IFN suppression and NF-κB pathways. Nsp's are early proteins while N is a late protein, suggesting that additional signaling pathways may be involved in addition to the IFN pathway. The understanding of molecular bases for virus-mediated modulation of host innate immune signaling will help us design new generation vaccines and control PRRS.