Taina Methuen

Polymorphisms of the Tnf, Cd14, and Hspa1b Genes in Patients With Acute Alcohol-induced Pancreatitis

Objectives: Genotype assessment has been suggested to be a tool for predicting disease severity in acute pancreatitis (AP). To study this hypothesis, we performed genotype analysis of tumor necrosis factor (TNF) −308 A/G, CD14 −159C/T, and HSPA1B +1267 A/G polymorphisms. Methods: This is a case-control association study of 397 patients with AP (214 of whom had an alcohol-induced AP) and 300 controls. The control group comprised 218 subjects with detailed data of alcohol consumption, 70 of whom were heavy drinkers (daily alcohol intake >40 g), and 92 blood donors. The severity of AP was determined according to the Atlanta classification. Genotyping was performed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry-assisted genotyping method. Results: Major allele frequency in TNF gene was 0.87 for patients with AP and 0.86 for controls. For CD14, the gene major allele frequency was 0.60 for patients and 0.63 for controls. For HSPA1B, the major allele frequencies were 0.52 for patients and 0.49 for controls, respectively. The allele frequencies did not differ significantly between AP patients with organ failure and those with mild disease, patients with alcohol-induced AP, or those with biliary AP. The patients with septic infectious complications (n = 47) had genotype distribution no different from those with mild, uncomplicated disease (n = 245). Conclusions: The TNF, CD14, and HSPA1B polymorphisms studied seem not to play a role in determining the severity of AP or the risk of alcohol-induced AP and thus do not serve as a tool for predicting disease severity.

Disialotransferrin, determined by capillary electrophoresis, is an accurate biomarker for alcoholic cause of acute pancreatitis.

Objectives: Serum disialotransferrin is a specific marker of heavy alcohol consumption. We tested its accuracy and probability in detecting alcoholic cause of acute pancreatitis (AP). Methods: Blood samples from 271 consecutive AP patients, admitted to the Helsinki University Central Hospital emergency unit, were analyzed. Results: The median (range) disialotransferrin value was significantly higher (P = 0.001) in AP patients with alcoholic (n = 172) 1.6% (0.3%-14.4) than with biliary (n = 60) 0.7% (0.3%-1.3%) or other causes (n = 39) 0.8% (0.3%-4.1%). In receiver operating curve analysis, disialotransferrin, as a single analyte, was significantly (P = 0.001-0.0001) more accurate (area under the curve [AUC], 0.88; 95% confidence interval [CI], 0.84-0.92) in detecting alcoholic AP as compared with glutamyl transferase (AUC, 0.51; 95% CI, 0.45-0.57), aspartate aminotransferase (AUC, 0.57; 95% CI, 0.51-0.63), alanine aminotransferase (AUC, 0.63; 95% CI, 0.57-0.69), erythrocyte mean cell volume (AUC, 0.72; 95% CI, 0.67-0.78), amylase (AUC, 0.74; 95% CI, 0.67-0.78), C-reactive protein (AUC, 0.65; 95% CI, 0.59-0.71), and bilirubin (AUC, 0.55; 95% CI, 0.49-0.62). At a disialotransferrin cutoff of 1.2%, giving an 8% false-positive rate, the positive likelihood ratio was 8.47. Thus, a positive disialotransferrin test result, performed within 24 hours of admission, increased the probability of alcoholic AP from pretest 64% to posttest 94%.Abbreviations: AP - acute pancreatitis, DST - disialotransferrin, CDT - carbohydrate-deficient transferrin, CE - capillary electrophoresis, CI - confidence interval, CV - coefficient of variation, ERCP - endoscopic retrograde cholangiopancreaticography, HPLC - high-performance liquid chromatography, LR - likelihood ratio, NPV - negative predictive value, PPV - positive predictive value Conclusions: Disialotransferrin, determined by capillary electrophoresis, is accurate, simple, and a rapid single biomarker of the alcoholic cause of AP.

Hemostatic gene polymorphisms in severe acute pancreatitis.

Objective: Systemic inflammatory reaction in acute pancreatitis (AP) is associated with activation of the coagulation system. The prothrombotic component of the coagulation system, which may promote microvascular thrombosis and vital organ injury, is strengthened by genetic factors such as polymorphism of plasminogen activator inhibitor type 1 (PAI-1) and factor V Leiden (FVL) mutation. This prompted us to study the occurrence of FVL and PAI-1 4G/5G polymorphisms in patients with AP. Methods: This case control association study included 397 patients with AP and 310 controls. Severe AP was determined according to the Atlanta Classification. Genotyping was performed by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry-assisted genotyping method. Results: Factor V Leiden was identified in 5 (3.3%) of 152 cases of severe AP and in 8 (3.3%) of 245 cases of mild AP. The prothrombotic PAI-1 4G allele frequency was 0.49 for patients with severe AP and 0.57 for patients with mild AP (P < 0.05). Patients with septic infectious complications (n = 47) and patients with organ failure (n = 55) had genotype distribution not different from those with mild, uncomplicated disease (n = 245). Conclusions: The results do not support the hypothesis that prothrombotic polymorphisms such as FVL mutation and PAI-1 4G/5G are associated with AP severity.

The impacts of nitrous oxide gas on sleep quality during alcohol withdrawal

BackgroundPoor quality of sleep among alcoholics and persons undergoing alcohol withdrawal has been described as a possible cause of alcohol relapse. It has been suggested earlier that nitrous oxide gas has a significant effect on the signs of alcohol withdrawal syndrome (AWS) and thus might be expected to reduce sleep disturbance during withdrawal. The aim of the present study was to investigate sleep quality during alcohol withdrawal, to evaluate the correlation between sleep quality and the severity of AWS and alcohol craving, and to determine if nitrous oxide treatment does counteract withdrawals effects on the quality of sleep. Voluntary patients (n = 105) admitted to the A-Clinic detoxification center with AWS were included in the study. The AWS patients were randomly assigned to one of the following 45-minute gas treatments: (1) nitrous oxide/oxygen; (2) normal air/O2; and (3) medical (normal) air. The study was single-blind by design. Sleep quality was assessed after these treatments during the inpatient period; sleep time, sleep efficiency and the fragmentation of sleep were recorded by wrist-worn actigraphs. Severity of AWS was evaluated by the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) and that of alcohol dependence and craving by the Obsessive Compulsive Drinking Scale [OCDS] and the Severity of Alcohol Dependence Data (SADD) questionnaire.ResultsThe fragmentation index and the time awake while in bed were both much above the reference values for the Finnish population. These values reflect the restless and disturbed night sleep of the subjects. The only statistically significant effects between the treatment groups were found in the correlations of CIWA-Ar (severity of AWS) scores, OCDS-scores (alcohol craving) and coffee consumption, all of which were positively associated with movement time and negatively with total sleep time and sleep efficiency. The sleep quality of patients treated with nitrous oxide gas did not differ from the sleep quality of those treated with normal air.ConclusionsThe severity of AWS and coffee consumption had the most significant negative impact on sleep quality. According to our results, nitrous oxide gas does not differ from placebo in its effect on sleep quality during alcohol withdrawal.