Predictive value of local and core laboratory echocardiographic assessment of cardiac function in patients with chronic stable angina: The ACTION study.

AIMS: To evaluate the relationship between echocardiographic cardiac function and outcome in patients with stable symptomatic angina. METHODS: Baseline echo left ventricular ejection fraction and volume data measured in a central laboratory was available for 7016 patients (92% of the total) participating in the ACTION trial (A Coronary disease Trial Investigating Outcome with Nifedipine GITS). Ejection fraction was also measured by investigators. Evaluation of the different echocardiographic variables was based on adjusted hazard ratios comparing the unfavourable limit of the 90% range of the variable concerned to the favourable limit. RESULTS: The centrally measured ejection fraction was the most powerful predictor of all-cause death (adjusted hazard ratio=2.5), myocardial infarction, any stroke or transient ischaemic attack and overt heart failure (adjusted hazard ratio=4.5). The addition of either end systolic volume or end diastolic volume to ejection fraction did not materially affect the power of prediction. Compared to the central ejection fraction measurement, the investigator-measured ejection fraction was a less powerful predictor for all outcomes considered. CONCLUSION: Routine echocardiography carefully analysed by standardised methods provides useful prognostic information in patients with stable angina, including for total mortality.     

REPERFUSION FOLLOWING MYOCARDIAL ISCHAEMIA ENHANCES INOSITOL PHOSPHATE RELEASE IN THE ISOLATED PERFUSED RAT HEART

1. Global myocariial ischaemia (MI) for periods greater tan 5 min caused an inhibition of phosphatidylinositol specific phospholipase C (PtdIns-PLC) activity. 2. Two min reperfusion following a 20 min MI period, a time point associated with reperfusion-induced arrhythmias, resulted in an activation of PtdIns-PLC activity, dependent on endogenous noradrenaline and mediated via al-adrenoceptors. 3. This 2 min reperfusion response, in contrast to healthy myocardium, resulted in: (i) enhanced PtdIns-PLC activity; (ii) increased sensitivity to endogenous noradrenaline; (iii) rapid increases in inositol(1,4,5)trisphosphate (Ins(1,4,5)P3); and (iv) PLC hydrolysis primarily of PtdIns(4,5)P₂, such that the majority of InsP isomers derive from Ins(1,4,5)P₃. 4. Together, these data suggest a functional role for Ins(1,4,5)P3 under postischaemic reperfusion conditions, and provide a possible link between al-adrenoceptor stimulation of the PtdIns turnover pathway and reperfusion injury.     

Repair of large midline incisional hernias with polypropylene mesh: Comparison of three operative techniques

Polypropylene mesh is widely used for the reconstruction of incisional hernias that cannot be closed primarily. Several techniques have been advocated to implant the mesh. The objective of this study was to evaluate, retrospectively, early and late results of three different techniques, onlay, inlay, and underlay. The records of 53 consecutive patients with a large midline incisional hernia — 25 women and 28 men, mean age 60.4 (range 28–94) — were reviewed. Polypropylene mesh was implanted using the onlay technique in 13 patients, inlay in 23 patients, and underlay in 17 patients. Either the greater omentum or a polyglactin mesh was interponated between the mesh and the viscera. The records of these 53 patients were reviewed with respect to: size and cause of the hernia, pre- and postoperative mortality and morbidity, with special attention to wound complications. Patients were invited to attend the outpatient clinic at least 12 months after implantation of the mesh for physical examination of the abdominal wall. Postoperative complications occurred in 14 (26.4%) patients. The onlay technique had significantly more complications, as compared to both other techniques. Reherniation occurred in 15 (28.3%) patients. The reherniation rate of the inlay technique was significantly higher than after the underlay technique (44% vs 12%, P=0.03) and tended to be higher than the onlay technique (44% vs 23%, P=0.22). Repair of large midline incisional hernias with the use of a polypropylene mesh carries a high risk of complications and has a high reherniation rate. The underlay technique seems to be the better technique.     

T wave amplitude as a quantitative index of regional myocardial sympathetic responsiveness

Alterations in T wave morphology have been quantitated in seven open chest anesthetized dogs by simultaneous recording of electrograms from 10 epicardial sites across the anterior left ventricular wall under basal conditions, following left sympathetic stimulation (LSS) at 2, 4, 8, 12, and 16 Hz and during noradrenaline infusions (NAI) of 0.125, 0.25, 0.50, and 1.0 micrograms/kg/min. Overdrive atrial pacing at 175 beats/min was employed and rate of rise of left ventricular pressure (dP/dt) monitored. Linear log dose-response relationships were found between both peak T amplitude and left ventricular dP/dt for NAI between 0.125 and 0.50 micrograms/kg/min (peak T wave amplitude 4.0 +/- 0.9 to 1.4 +/- 0.7 mV). Following LSS, T wave amplitude responses were highly variable both between animals and between electrode sites in individual studies. A linear log dose-response relationship was found at stimulation frequencies between 8 and 16 Hz (T amplitude 3.9 +/- 1.4 to 1.8 +/- 1.2 mV). Changes in QT interval were minor and inconsistent. It is concluded that changes in peak T wave amplitude may provide a useful index of regional myocardial sympathetic responsiveness following NAI, but are more variable following LSS.     

Characterization of antibody and selection of alternative drug therapy in hydrochlorothiazide-induced immune hemolytic anemia

The authors report the clinical and laboratory findings of a patient who had severe immune hemolytic anemia due to hydrochlorothiazide (HCTZ). In this case, the HCTZ antibody reacted not only with other thiazide and thiazide-like drugs, but also with a chemically unrelated diuretic, ethacrynic acid. These results indicate that HCTZ antibody activity is not restricted solely to the thiazides and imply that therapy with any of the reactive drugs would be contraindicated for this patient. The serologic screening for drug reactivity may be useful for selecting alternative therapy for patients with drug-induced immune hemolytic anemia.     

The effects of paracetamol (acetaminophen) on hepatic tests in patients who chronically abuse alcohol – a randomized study

Aliment Pharmacol Ther 2010; 32: 478–486

Summary

Background Retrospective accounts suggest that therapeutic doses of paracetamol can produce severe hepatic injury in patients with putative high‐risk conditions, including alcoholism and infectious hepatitis. Metabolism of paracetamol to its hepatotoxic metabolite is enhanced in patients who abuse alcohol, who also have compromised liver defences from depressed hepatic glutathione. Aim To determine the effect of paracetamol on serum liver tests of newly abstinent subjects who abuse alcohol, including subjects with hepatitis C infection. Methods A randomized, double‐blind, placebo‐controlled study. Adult alcohol abusers with a current drinking episode longer than 7 days received either placebo or paracetamol 4 g/day for 5 days. Results Of 142 subjects enrolled, 74 received paracetamol and 68 received placebo. Mean ALT activity during treatment increased from 48 to 62 IU/L in the paracetamol group and from 47 to 49 IU/L in the placebo group. Maximum ALT was 238 and 249 IU/L in the paracetamol and control groups respectively. The INR remained unchanged and serum bilirubin decreased in both groups. Subgroup analyses for subjects with alcoholic hepatitis, hepatitis C virus antibody and other subgroups showed no statistical difference between groups. Conclusion Administration of paracetamol 4 g/day appears safe in newly abstinent patients who abuse alcohol.     

Increases in plasma beta-endorphin concentrations during exercise do not contribute to increases in heart rate following autonomic blockade in man.

1. Intrinsic heart rate (IHR: heart rate following autonomic blockade with atropine and propranolol) increases with exercise. The opioid antagonist naloxone has been shown to decrease IHR at rest, raising the possibility that increases in IHR with exercise are beta-endorphin related, since beta-endorphin concentrations have also been shown to rise during exercise. 2. We examined the effects of naloxone (10 mg) on IHR and plasma beta-endorphin levels during aerobic exercise in eight healthy, male subjects in a single blind, crossover study. 3. IHR increased with 25 min bicycling from 97.1 +/- 1.4 to 129.7 +/- 1.2 beats min-1 (mean +/- s.e. mean). This rise was not affected by administration of naloxone. 4. Plasma beta-endorphin concentration rose from 31.1 +/- 3.8 to 94.9 +/- 23.9 pg ml-1 after 25 min exercise. This exercise-induced rise in beta-endorphin concentration was further increased (P less than 0.05) in the presence of naloxone. 5. Our results confirm a rise in IHR and beta-endorphin concentrations with acute exercise but indicate that the changes in IHR are not endorphin-related.     

Sporadic diffuse corneal endotheliitis

We studied two patients with acute diffuse corneal endotheliitis who had no family history of the disease. Endothelial specular photographs taken during and after an attack of endotheliitis demonstrate the deposition of inflammatory material on edematous endothelial cells, with areas of focal endothelial cell loss that resolved with treatment. These cases are distinctly different than the previously described "idiopathic" primary endotheliitis entities, which have included focal or sectoral areas of corneal edema, corneal edema in association with a migrating rejection line, or diffuse edema occurring as a dominantly inherited condition. No definitive causative agents have been established. It is likely that the disease results from an immune response to autoantigens or antigens from an unidentified viral infection. The pathogenesis may be similar to that of corneal homograft rejection.