Non-alcoholic fatty liver syndrome: a hepatic consequence of common metabolic diseases

BACKGROUND AND AIMS: The association of liver steatosis with a number of common metabolic conditions has been suggested. The aim of the present study was to evaluate the clinical features of subjects with different severities of steatosis. METHODS: The present study was performed in 282 consecutive patients with 'bright liver' at ultrasonography and in 58 subjects without steatosis. They had no history of alcohol abuse and negative tests for the presence of hepatitis B and C virus. Patients underwent clinical examination, anthropometry, laboratory tests and routine liver ultrasonography. Steatosis was graded as absent, mild, moderate and severe. RESULTS: A progressive increase in the prevalence of obesity (P < 0.001), type 2 diabetes (P < 0.001), alanine aminotransferase (ALT) elevation (P < 0.001) and hypertriglyceridemia (P < 0.001), and a decrease of hypercholesterolemia (P < 0.05) was observed from the control group to the groups with mild, moderate and severe steatosis. More than half the subjects with liver steatosis had insulin resistance metabolic syndrome. Obesity, diabetes and hypertriglyceridemia were more common by 5.3-fold, 4.0-fold, and 6.7-fold, respectively, in subjects with severe steatosis, as compared to controls. Prevalence of obesity, diabetes and hyperlipidemia was significantly higher in subjects with fatty liver and ALT elevation. CONCLUSION: Fatty liver can be considered as the hepatic consequence of common metabolic diseases.     

A new variant of Bernard-Soulier syndrome characterized by dysfunctional glycoprotein (GP) Ib and severely reduced amounts of GPIX and GPV

We describe a new variant of Bernard-Soulier syndrome characterized by almost normal amounts of GPIb and severely reduced GPIX and GPV. Despite surface expression, GPIbα failed to support ristocetin-induced platelet agglutination and to bind two conformation-dependent monoclonal antibodies, suggesting a qualitative defect. Sequence analysis of the gene coding for GPIX revealed a T-to-C substitution at base 1811, leading to a Leu40Pro conversion, whereas no defects were found in the coding region of the GPIbα gene. Allele-specific restriction enzyme analysis showed that the propositus and one of his sisters, both with severe bleeding diathesis, were homozygous for the GPIX mutation; the members of the family with mild bleeding diathesis and/or giant platelets in the peripheral blood were heterozygous, whereas the healthy ones were homozygous for the normal allele.
Infusion of 1-desamino-8- d -arginine vasopressin normalized bleeding time in the two severely affected patients, although it did not modify ristocetin-induced platelet agglutination or membrane expression of GPIbα, GPIX, GPIIb–IIIa and GMP-140. Moreover, in one patient, normalization of bleeding time and rise of von Willebrand factor plasma concentration did not seem to be directly related.     

HIV-1 matrix protein p17 enhances the proliferative activity of natural killer cells and increases their ability to secrete proinflammatory cytokines

We investigated the effects of human immunodeficiency type-1 virus (HIV-1) matrix protein p17 on freshly isolated and purified human natural killer (NK) cells. HIV-1 p17 increased the cytokines interleukin (IL) 2, IL-12 and IL-15, and induced natural killer cell proliferation, but not cytotoxicity. This effect was specific because it was abrogated by anti-p17 monoclonal antibody. Moreover, HIV-1 p17 enhanced the cytokine-induced production of tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma by NK cells. IL-4 downregulated IFN-gamma and TNF-alpha secretion in IL-2- and IL-15-treated NK cells. HIV-1 p17 restored the ability of NK cells to produce both cytokines when added to the cultures simultaneously with IL-4. The property of p17 to increase the production of TNF-alpha and IFN-gamma might be a mechanism used by HIV-1 to modulate the immune system to support its replication and spreading.     

Abrupt changes in fibrillatory wave characteristics at the termination of paroxysmal atrial fibrillation in humans

Aims We investigated the process of spontaneous terminationof atrial fibrillation (AF) to determine its time course fromthe surface ECG. Methods and results We studied fibrillatory waves in Holterrecordings of paroxysmal and sustained AF. Following QRS-T cancellationdominant frequencies (DFs) were computed and the relationshipof DF to termination was scrutinized. For 57 episodes of paroxysmalAF (PAF) in 24 patients, DF ranged from 4.4 to 6.5 Hz (5.2 ±0.4 Hz) compared to 5.8 to 7.4 Hz (6.6 ± 0.6 Hz) forsustained AF recordings. Comparison of the atrial frequencyof the ultimate to the penultimate second demonstrated a dropin frequency in 51 of 57 episodes, P < 0.00001. No comparablechange was seen at longer time periods. Moments of comparablylow frequency without termination were only occasionally seenin patients with PAF but not in patients with sustained AF. Conclusion Low frequency fibrillation was found to be much morelikely to terminate. Frequency changes preceding spontaneoustermination were abrupt, in contrast to the gradual frequencydrop reported with drug-induced termination. The analysis offibrillatory wave characteristics and their change over timemight be used to target specific moments for pacing therapyin patients with AF.     

How general practitioners perceive and grade the cardiovascular risk of their patients.

BACKGROUND: Although risk assessment charts have been proposed to identify patients at high cardiovascular risk, in everyday practice general practitioners (GPs) often use their knowledge of the patients to estimate the risk subjectively. DESIGN: A cross-sectional study aimed to describe how GPs perceive, qualify and grade cardiovascular risk in everyday practice. METHODS: General practitioners had to identify in a random sample of 10% of their contacts the first 20 consecutive patients perceived as being at cardiovascular risk. For each patient essential data were collected on clinical history, physical examination and laboratory tests, for the qualification of risk. At the end of the process GPs subjectively estimated the overall patient's level of risk. General practitioners grading was compared with the risk estimate from a reference chart. RESULTS: Over a mean time of 25 days 3120 patients perceived as being at cardiovascular risk were enrolled. According to the inclusion scheme each GP had contact with more than 200 patients at cardiovascular risk every month. Thirty percent of these patients had atherosclerotic diseases. Up to 72% of patients without any history of atherosclerotic diseases but perceived to be at risk could be classified according to a reference chart as being at moderate to very high risk. Comparing GPs' grading of risk with a chart estimate there was agreement in 42% of the cases. Major determinants of GPs' underestimation of risk were age, sex and smoking habits, while obesity and family history were independently associated with overestimation. CONCLUSIONS: On the basis of their perception GPs properly identify patients at cardiovascular risk in the majority of cases. General practitioners subjective grading of risk level only partially agreed with that given by a chart.     

Treatment of Eating Disorders in Adults Versus Adolescents: Similarities and Differences

FindingsAlthough several individual psychotherapies for adults with eating disorders are empirically supported, with family-based treatment (FBT) being the leading recommended empiric treatment in adolescents, patients with eating disorders are still difficult to treat, and outcomes are often poor. In some countries, the clinical services for adolescents and adults are separate, and it is common for patients to receive treatments that differ in terms of both theory and content when they are switched from adolescent to adult services. Changes in the nature of treatment also often occur when patients move from less intensive types of care to more intensive treatment, and vice versa. These transitions may create a discontinuity in the care pathway and disorient patients and their significant others about the strategies and procedures used for addressing eating problems. However, the observation that younger and older patients essentially share the same eating-disorder psychopathology has led to evidence-based enhanced cognitive–behavioral therapy (CBT-E) being adapted for use in adolescents. Originally an evidence-based treatment for adults with eating disorders, CBT-E has yielded promising results in trials in cohorts of adolescent outpatients and inpatients, and is recommended as an alternative to FBT in adolescent patients.ImplicationsWith a unified treatment such as CBT-E, several issues that plague conventional eating-disorder services could be partially overcome, as patients can move seamlessly from adolescence to adulthood and through different levels of care, with no change in the nature of the treatment itself. Future randomized, controlled trials should compare FBT to CBT-E to better clarify the specific therapeutic needs of subgroups of adolescents and adult patients with eating disorders.     

Phagocytosis of Hemozoin (Native and Synthetic Malaria Pigment), and Plasmodium falciparum Intraerythrocyte-Stage Parasites by Human and Mouse Phagocytes

Hemozoin, the detoxification product of hemoglobin heme, piles up as electron-dense material in the food vacuole (FV) of intraerythrocytic malaria parasites (malaria pigment). In infected individuals, pigment is internalized by both circulating and resident phagocytes, thus modulating their functions. Synthetic beta-hematin, prepared in vitro from hematin (ferriprotoporphyrin IX hydroxide) in acidic condition, is spectroscopically identical to hemozoin. In this electron microscopy study, native and synthetic hemozoin also prove to be morphologically indistinguishable (large polygonal crystals with apparent transverse banding) and to undergo the same process when internalized by phagocytes (primarily a direct uptake of crystals, similar to what is described for asbestos fibers). On the contrary,whole parasites appear to follow a classical endocytic pathway. This suggests that there may be differences between the ingestion of free particles and whole parasites in terms of modulation of phagocytes' functions.     

Pentraxin 3 (PTX3) inhibits plasma cell/stromal cell cross‐talk in the bone marrow of multiple myeloma patients

Pentraxin 3 (PTX3) is a soluble pattern recognition receptor that binds with high affinity and selectivity to fibroblast growth factor‐2 (FGF2), thus inhibiting its pro‐angiogenic activity. Here we investigated the effects of PTX3 on monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) patient‐derived bone marrow (BM) plasma cells (PCs), endothelial cells (ECs), and fibroblasts (FBs), and assessed whether PTX3 can modulate the cross‐talk between PCs and those microenvironment cells. PTX3 and FGF2 expression was evaluated by ELISA. Functional studies, including cell viability, wound healing, chemotaxis, and Matrigel^® assays, were performed on MGUS and MM ECs and FBs upon the PTX3 treatment. Through western blot PTX3‐induced modulation in FGF2/FGF receptor signalling pathways was evaluated in MGUS and MM ECs and FBs through western blot. Co‐cultures between MM ECs/FBs and human PC lines were used to evaluate possible PTX3 indirect effects on MM PCs. Adhesion molecules were studied by flow cytometry. PTX3 provides a direct time‐ and dose‐dependent apoptotic effect on MM ECs and FBs, but not on either MM primary PCs or human PC lines. PTX3 inhibits migration of MM ECs and FBs in a dose‐dependent manner, and impacts in vitro and in vivo FGF2‐mediated MM angiogenesis. Co‐cultures of PCs and ECs/FBs show that PTX3 treatment indirectly impairs PC viability and adhesion. We conclude that PTX3 is an anti‐angiogenic factor in MM and behaves as a cytotoxic molecule on MM cells by inhibiting the cross‐talk between PCs and ECs/FBs. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.