Long QT syndrome

The hereditary long QT syndrome (LQTS) is a genetic channelopathy with variable penetrance that is associated with increased propensity to syncope, polymorphous ventricular tachycardia (torsades de pointes), and sudden arrhythmic death. This inherited cardiac disorder constitutes an important cause of malignant ventricular arrhythmias and sudden cardiac death in young individuals with normal cardiac morphology. Risk assessment in affected LQTS patients relies upon a constellation of electrocardiographic, clinical, and genetic factors. Administration of beta-blockers is the mainstay therapy in affected patients, and primary prevention with an implantable cardioverter defibrillator or left cervicothoracic sympathetic denervation are therapeutic options in patients who remain symptomatic despite beta-blocker therapy. Accumulating data from the International LQTS Registry have recently facilitated a comprehensive analysis of risk factors for aborted cardiac arrest or sudden cardiac death in pre-specified age groups, including the childhood, adolescence, adulthood, and post-40 periods. These analyses have consistently indicated that the phenotypic expression of LQTS is time dependent and age specific, warranting continuous risk assessment in affected patients. Furthermore, the biophysical function, type, and location of the ion-channel mutation are currently emerging as important determinants of outcome in genotyped patients. These new data may be used to improve risk stratification and for the development of gene-specific therapies that may reduce the risk of life-threatening cardiac events in patients with this inherited cardiac disorder.     

Hyperamylasemia in inflammatory bowel disease

We determined the prevalance and significance of hyperamylasemia in 180 patients with idiopathic inflammatory bowel disease (IBD) (83 with ulcerative colitis, and 97 with Crohn's disease). Serum total amylase and pancreatic and salivary isoamylase activity were measured in all patients. In all patients with hyperamylasemia, we measured isoamylase activity by cellulose acetate electrophoresis and lipase activity, assayed for the presence of macroamylase, and carried out pancreatic ultrasound examination and barium studies of the upper gastrointestinal tract. Eight of 97 patients with Crohn's disease (8%) had hyperamylasemia; 4 of them had an elevated pancreatic isoamylase and 2 a raised lipase activity. All patients with hyperamylasemia had normal ultrasonographic scans of the pancreas and no evidence of duodenal involvement on barium meal. None had macroamylasemia. We found no relationship of hyperamylasemia to disease site, activity, and duration or therapy and no patient developed clinical evidence of pancreatitis. We conclude that a small but important number of patients with Crohn's disease have hyperamylasemia not associated with overt pancreatitis. In the absence of appropriate indications, it requires no investigation.     

Hospital Costs, Resource Characteristics, and the Dynamics of Death for Hospitalized Gastroenterology Patients

The federal Medicare diagnosis-related group (DRG) hospital payment system has been on-line for 5 yr with no major adverse effects on either access or quality of care. The hospital industry contends that DRGs are underpaying for hospital care, especially for certain types of patients. Analysis of 2,500 gastroenterology patients by outcome (i.e., survivors vs mortalities) demonstrated that the 122 mortalities had a much greater intensity of hospital resource utilization, and generated substantial financial risk under DRG pricing schemes, compared with the 2,378 survivors. Only mortalities that occurred within 1 wk of admission to the hospital were profitable under DRGs. A long hospital length of stay (LOS) for mortalities was very unprofitable (mortalities with more than a 60-day LOS generated $20,210 loss per patient). Emergency gastroenterology admissions who died had greater financial risk under DRGs, compared to nonemergency mortalities. Those mortalities referred to gastroenterology from other clinical services tended to have greater resource utilization and financial risk under DRGs, compared with nonreferred mortalities. These data suggest significant inequities in the current DRG prospective payment system vis-a-vis gastrotenterology mortalities. Predictive variables of greater hospital resource utilization for gastroenterology mortalities include longer hospital lengths of stay, emergency admission, and referral from another clinical service. If equity of DRG payment is not improved by the federal government, certain groups of patients likely to be mortalities may suffer a decline in access and/or the quality of medical care in the future.     

A balanced 5:1 carbohydrate:protein diet: a new method for supplementing protein to patients with chronic liver disease

BACKGROUND AND AIMS: Protein malnutrition in patients with chronic liver disease contributes to bone and muscle weakness and compromises immune function and survival. In contrast, high-protein diets may induce or exacerbate hepatic encephalopathy. The aim of the present study was to test whether increased amounts of protein, balanced by dietary carbohydrate in a 1:5 ratio, may be given to chronic liver disease patients in order to minimize postprandial increases in plasma amino acid (AA) concentrations. METHODS: Eight patients with chronic liver disease were studied. Each received, in a randomized order, three different diets of 2510 kJ of either high protein (37:50:28, carbohydrate:protein:fat), high carbohydrate (126:10:6) or a balanced 5:1 carbohydrate:protein diet (105:21:11). All patients were followed for plasma AA, glucose and insulin levels, as well as for cognitive and behavioral changes. RESULTS: Following the high protein diet, AA concentrations were significantly increased. In contrast, after the balanced diet, AA levels were practically constant enabled. All diets was well tolerated and no cognitive or behavioral changes appeared. CONCLUSION: The administration of a balanced 5:1 carbohydrate:protein diet may enable patients with chronic liver disease to tolerate increased amounts of dietary protein, without altering plasma amino acid concentrations.     

Cytokines (IL-6, IL-8, TNF): early and reliable predictors of severe acute pancreatitis

BACKGROUND: Severe acute pancreatitis is associated with a high mortality, especially when compared with mild acute pancreatitis. Early intervention in patients with severe acute pancreatitis has been shown to improve mortality. The value of cytokines (interleukin [IL]-6, IL-8 and tumor necrosis factor [TNF]-alpha) in diagnosing severe acute pancreatitis at an early stage was studied. STUDY: Thirty-six patients with acute pancreatitis were prospectively evaluated. Age-matched controls were obtained from healthy volunteers. Levels of IL-6, IL-8, and TNF-alpha were obtained within 24 hours of admission. Ranson's prognostic signs and Bank's clinical criteria were used to differentiate patients into mild and severe pancreatitis. RESULTS: There was significant difference in IL-6 levels between controls and mild pancreatitis, controls and severe pancreatitis, and mild and severe pancreatitis. IL-8 levels were significantly different between controls and severe pancreatitis and mild and severe pancreatitis. There was no significant difference between controls and mild pancreatitis. The results for TNF-alpha were similar to the findings for IL-8. CONCLUSION: IL-6, IL-8, and TNF can be used independently in differentiating mild acute pancreatitis from early severe acute pancreatitis.     

P amylase is always greater than S in spot urine of normal subjects. Diagnostic implications.

Single random samples of urine were collected from 50 control subjects; 27 patients with chronic pancreatitis; 19 with acute pancreatitis; 6 with acute on chronic pancreatitis; five in the recovery phase of acute attack; four patients with pseudocysts. Salivary (S) and pancreatic (P) amylase values were measured by cellulose acetate electrophoresis. The P amylase values always exceeded those of S amylase in the control specimens. In acute pancreatitis, both the lower and upper levels of total and P amylase were considerably higher than in the controls, and these high values tended to return to normal during the recovery phase of acute pancreatitis. The S amylase values were often very low or undetectable during the acute phase. Values for P amylase exceeded control values in patients with pseudocysts even in the presence of chronic pancreatitis. In chronic calcific pancreatitis, S amylase was higher than P amylase. We conclude that P amylase is always greater than S amylase in normal urine specimens, and a change in this pattern may be helpful in diagnosing various forms of pancreatitis.     

Time dependence of defibrillator benefit after coronary revascularization in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II.

OBJECTIVES: The study was designed to assess the effect of elapsed time from coronary revascularization (CR) on the benefit of the implantable cardioverter-defibrillator (ICD) and the risk of sudden cardiac death (SCD) in patients with ischemic left ventricular dysfunction. BACKGROUND: The ICD improves survival in appropriately selected high-risk cardiac patients by 30% to 54%. However, in the Coronary Artery Bypass Graft (CABG)-Patch trial no evidence of improved survival was shown among a similar population of patients in whom an ICD was implanted prophylactically at the time of elective CABG. METHODS: The outcome by time from CR was analyzed in 951 patients in whom a revascularization procedure was performed before enrollment in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II. RESULTS: The adjusted hazard ratio (HR) of ICD versus conventional therapy was 0.64 (p = 0.01) among patients enrolled more than six months after CR, whereas no survival benefit with ICD therapy was shown among patients enrolled six months or earlier after CR (HR = 1.19; p = 0.76). In the conventional therapy group, the risk of cardiac death increased significantly with increasing time from CR (p for trend = 0.009), corresponding mainly to a six-fold increase in the risk of SCD among patients enrolled more than six months after CR. CONCLUSIONS: In patients with ischemic left ventricular dysfunction, the efficacy of ICD therapy after CR is time dependent, with a significant life-saving benefit in patients receiving device implantation more than six months after CR. The lack of ICD benefit when implanted early after CR may be related to a relatively low risk of SCD during this time period.     

Endocannabinoids and liver disease--review.

AIMS: Endocannabinoids are endogenous compounds that bind to the same receptors as tetrahydrocannabinol, the active component in marijuana and hashish. They have been found to have many physiological and patho-physiological functions, including mood alteration, control of feeding and appetite, motor and co-ordination activities, analgesia, immune modulation and gut motility. In this review we aim to elucidate current knowledge as to their role in liver physiology and disease. METHODS: The major findings published to date concerning endocannabinoids and liver disease are described, and their implications with regard to understanding disease mechanisms, and the development of new treatments is considered. RESULTS: Recently, endocannabinoids have been implicated in the hemodynamic alterations occurring in cirrhosis. These changes appear to be mediated via specific cannabinoid receptors (CB1) on splanchnic and hepatic vascular endothelium. Plasma levels of endocannabinoids also seem to be elevated in hepatitis, and are involved in apoptosis of hepatocytes by a membrane mechanism not related to a specific receptor. Other studies suggest a beneficial role for cannabinoids in reducing the inflammation of experimental hepatitis. In an animal model of acute hepatic failure, both endocannabinoids and the antagonist to the CB1 receptor have been found to have a beneficial effect on neurological and cognitive function. CONCLUSIONS: Endocannabinoids appear to be involved in several aspects of acute and chronic liver disease, including vascular changes, modulation of inflammatory process and neurological function, Further research may provide new insights into the pathophysiology of liver disease, as well as a basis for novel treatment modalities.