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.     

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.     

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.     

Letter to the editors: comment on “Emerging themes in idiopathic intracranial hypertension”

Journal of Neurology -     

Non-Epstein–Barr virus associated lymphoepithelioma-like carcinoma of the esophagogastric junction with microsatellite instability,K-ras wild type

A 60-year-old male was admitted to our hospital for gastric cancer. Considering his general condition, total gastrectomy and dissection of regional lymph nodes were performed. Macroscopically, a 45 mm × 20 mm × 10 mm-sized, ulcero-infiltrative tumor located in the esophagogastric junction was described. Microscopically, the tumor consisted of a poorly differentiated adenocarcinoma intermingled with dense lymphoid infiltration predominantly composed of T-cell lymphocytes. The tumor cells infiltrated the submucosa, muscularis and subserosal layers of the stomach, respectively the esophageal adventitia. No metastases were noticed in the 58 regional lymph nodes. Based on the histopathological features, the diagnosis was lymphoepithelioma-like carcinoma, pT3N0 stage. In situ hybridization for Epstein–Barr virus showed no nuclear signal in tumor cells. The p53 expression was observed in fewer than 10% of the tumor cells. Real-time PCR analysis showed microsatellite instability without K-ras mutation in codon 12. No recurrences or metastases were reported 6 months after surgical intervention. No adjuvant therapy was performed.     

The nonsense mutation stop+4 model correlates with motor changes in Duchenne muscular dystrophy

The aim was to assess 3-year longitudinal data using 6MWT in 26 ambulant boys affected by DMD carrying nonsense mutations and to compare their results to other small mutations. We also wished to establish, within the nonsense mutations group, patterns of change according to several variables. Patients with nonsense mutations were categorized according to the stop codon type newly created by the mutation and also including the adjacent 5′ (upstream) and 3′ (downstream) nucleotides. No significant difference was found between nonsense mutations and other small mutations (p > 0.05) on the 6MWT. Within the nonsense mutations group, there was no difference in 6MWT when the patients were subdivided according to: Type of stop codon, frame status of exons involved, protein domain affected. In contrast, there was a difference when the stop codon together with the 3′ adjacent nucleotide (“stop+4 model”) was considered (p < 0.05) with patients with stop codon TGA and 3′ adjacent nucleotide G (TGAG) having a more rapid decline. Our finding suggest that the stop+4 model may help in predicting functional changes. This data will be useful at the time of interpreting the long term follow up of patients treated with Ataluren that are becoming increasingly available.