Normothemic Continuous Blood Cardioplegia Improves Electrophysiologic Recovery after Open Heart Surgery

Background: Myocardial protection during open heart surgery is based on administration of oxygenated blood cardioplegia, the preferred temperature of which is still under debate. The current randomized study was designed to prospectively evaluate the quality of myocardial protection and the functional recovery of the heart with either normothermic (group N) or hypothermic (group H) oxygenated blood cardioplegia.

Methods: Under continuous electrocardiographic Holter monitoring, 42 patients were randomly scheduled to receive either normothermic (33.5 degrees C) or hypothermic (10 degrees C) cardioplegia solutions during coronary bypass grafting surgery. Blood samples for creatinine phosphokinase, creatinine phosphokinase-MB, lactate, epinephrine, and norepinephrine were withdrawn during cardiopulmonary bypass via a coronary sinus cannula.

Results: Active cooling in group H on initiation of cardio-pulmonary bypass was characterized by transition through ventricular fibrillation in 75% of patients, whereas in group N atrial fibrillation occurred in 65% of patients. On myocardial reperfusion, sinus rhythm spontaneously resumed in 95% of group N patients compared to 25% in group H (P = 0.0003). In the latter, 75% of patients developed ventricular fibrillation often followed by complete atrioventricular block, which necessitated temporary pacing for a mean duration of 168+/-32 min. Both groups showed a similar incidence of intraventricular block and ST segment changes. However, the incidence of ventricular premature beats in the first 16 h after cardiopulmonary bypass was significantly greater in group H (P < 0.05), 20 +/-26/h, compared to 3+/-5/h in group N. Blood concentrations of lactate, creatinine phosphokinase, epinephrine, and norepinephrine increased gradually during the operation, but the differences between the groups were not significant.     

Ambulatory Mental Health Treatment under Universal Coverage: Policy Insights from Israel

Untested assumptions concerning ambulatory treatment have shaped mental health policies for decades. Three opinions prevail: (1) all use is alike; (2) any use leads to high use; and (3) all high use is discretionary and therefore excessive. These assumptions were tested, using data from a nationwide survey of ambulatory utilizers in Israel, a country that has universal coverage. The findings, based on detailed clinical and treatment records, challenge all three assumptions. Moreover, they document a diversity of clinical needs while also verifying substantial variations in the type, frequency, and duration of treatment provided to meet those needs. In brief, Israeli data do not confirm continuing concerns by policy makers about uncontrollable use of services with expanded mental health coverage. Special policy limitations on mental health treatment should be reconsidered in light of empirical evidence from a system without the restrictions that exist in the United States.     

A novel point mutation (I137T) in the conserved 5-phosphoribosyl-1-pyrophosphate binding motif of hypoxanthine-guanine phosphoribosyltransferase (HPRTJerusalem) in a variant of Lesch-Nyhan syndrome

We identified a novel point mutation (I137T) in the hypoxanthine-guanine phosphoribosyltransferase (HPRT; EC 2.4.2.8) encoding gene, in a patient with partial deficiency of the enzyme (variant of Lesch-Nyhan syndrome). The mutation, ATT to ACT, resulting in substitution of isoleucine to threonine, occurred at codon 137 (exon 6), which is within the region encoding the binding site for 5-phosphoribosyl-1-pyrophosphate (PRPP). We suggest the mechanism by which the mutation-induced structural alteration of HPRT reduced the affinity of the enzyme for PRPP.     

Gastric capacity, test meal intake, and appetitive hormones in binge eating disorder

Binge eating disorder (BED), characterized by ingestion of very large meals without purging afterwards, is found in a subset of obese individuals. We showed previously that stomach capacity is greater in obese than in lean subjects, and in this study, we investigated capacity in obese individuals with BED. We also determined ad-libitum intake of a test meal until extremely full. Furthermore, we measured various appetitive hormones (insulin, leptin, glucagon, CCK, ghrelin) and glucose before a fixed meal and for 120 min afterwards. An acetaminophen tracer was used to assess gastric emptying rate. We compared three groups of overweight women: 11 BED, 13 BE (subthreshold BED), and 13 non-binge-eating normals. The BED individuals had the largest stomach capacity as assessed by either maximum volume tolerated (P=.05) or by gastric compliance to pressure (P=.02) using an intragastric balloon. Although test meal intake did not differ between groups, it correlated (P=.03) with gastric capacity. The BED group showed a tendency (P=.06) to have greater area under the curve (AUC) and had higher values at 5 and 60 min (P<.05) for insulin compared to normals. Moreover, the BED subjects had lower ghrelin baselines premeal, and lower AUC for ghrelin, which then declined less postmeal than for the normals (P<.05). None of the other blood values differed, including glucose, leptin glucagon, and CCK, as well as acetaminophen, reflecting gastric emptying. The lower ghrelin in BED, although contrary to what was expected, is consistent with lower ghrelin in obesity, and suggests down-regulation of ghrelin by overeating. The lack of differences in CCK is consistent with the lack of differences in gastric emptying rate, given that CCK is released when nutrients reach the intestine. The results show that BED subjects have a large gastric capacity as well as abnormalities in meal-related ghrelin and insulin patterns that may be factors in binge eating.     

Hydroxymethylglutaryl-CoA reductase inhibitors (statins) for the treatment of sepsis in adults – A systematic review and meta-analysis

Objectives

The pleiotropic effect of hydroxymethylglutaryl-CoA reductase inhibitors (statins) might have a beneficial effect in sepsis through several mechanisms. The aim was to assess the efficacy and safety of statins, compared with placebo, for the treatment of sepsis in adults.

Systemic inflammatory mediators and cystic fibrosis genotype

Abstract. Morbidity and mortality in cystic fibrosis patients is mainly attributed to pulmonary infection and inflammation. Chemokines play a pivotal role in the inflammatory process. Although genotype-phenotype correlation in cystic fibrosis patients has been defined, a clear relationship between the defect in the cystic fibrosis transmembrane regulator (CFTR) gene and pulmonary inflammation has not been established. The aim of this study was to assess whether serum chemokines levels in cystic fibrosis patients correlate with genotype and pulmonary function tests, as well as with other clinical characteristics. Serum levels of interleukin-8, RANTES, and monocyte chemoattractant protein-1 were measured in 36 cystic fibrosis patients grouped according to their genotype. Group A included 25 patients who carried two mutations associated with a pathological sweat test and pancreatic insufficiency (F508, W1282X, G542X, N1303K, S549R). Group B included 11 compound heterozygote patients who carried one mutation known to cause mild disease with borderline or normal sweat test and pancreatic sufficiency (3849+10kb C to T, 5T). Associations between chemokine levels, genotype, pulmonary function, Pseudomonas aeruginosa colonization, age, sweat chloride level, and pancreatic and nutritional status were examined. Mean interleukin-8 and monocyte chemoattractant protein-1 levels were significantly higher in group A than group B (11.4±2.1 pg/ml vs. 5±0.9 pg/ml and 157±16 pg/ml vs. 88.8±16.4 pg/ml, respectively) (P<0.01). No difference in RANTES levels were found between groups. interleukin-8 levels were inversely related to forced expiratory volume in 1 s (r=-0.37, P<0.02), while there was no association between the latter and RANTES and monocyte chemoattractant protein-1 levels. The Pseudomonas colonization rate was higher among group A patients than group B (88% vs. 40%, P<0.01). No relationship was found between measured chemokines and age, sweat chloride levels, and pancreatic and nutritional status. Our study demonstrates an association between interleukin- 8, forced expiratory volume, and cystic fibrosis genotype. Hence, elevated interleukin-8 serum levels could serve as an indicator of an early inflammatory process and encourage the initiation of anti-inflammatory treatment.     

The Israeli Sexual Behavior Inventory (ISBI): Scale Construction and Preliminary Validation

This study describes the construction and preliminary validation of the Israeli Sexual Behavior Inventory (ISBI). The ISBI was primarily designed to assess the impact of sexual problems, chronic illness and disability on sexual functioning and experience. Scales were designed to measure three areas of healthy sexual functioning and three areas of sexual dysfunction for both males and females. To provide normative data to which clinical samples can be compared, a large randomly selected sample from an adult male and female population was used for scale construction and preliminary validation. Scale reliabilities, intercorrelations between the ISBI scales, comparisons between the above sample and a clinical sample provide evidence of the ISBI's reliability and validity.     

Pharmacokinetic Analysis and Antiepileptic Activity of Tetra-Methylcyclopropane Analogues of Valpromide

Purpose. The described structure pharmacokinetic pharmacodynamic relationships (SPPR) study explored the utilization of tetramethylcyclopropane analogues of valpromide (VPD), or tetra-methylcyclopropane carboxamide derivatives of valproic acid (VPA) as new antiepileptics. Methods. The study was carried out by investigating the pharmacokinetics in dogs and pharmacodynamics (anticonvulsant activity and neurotoxicity) of the following three cyclopropane analogues of VPD: 2,2,3,3-tetramethylcyclopropane carboxamide (TMCD), N-methyl TMCD (M-TMCD) and N-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-glycinamide (TMC-GLD). Results. The three investigated compounds showed a good anticonvulsant profile in mice and rats due to the fact that they were metabolically stable VPD analogues which were not biotransformed to their non-active acid, 2,2,3,3-tetramethylcyclopropane carboxylic acid (TMCA). M-TMCD was metabolized to TMCD and TMC-GLD underwent partial biotransformation to its glycine analogue N-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-glycine (TMC-GLN). Unlike TMC-GLN, the above mentioned amides had low clearance and a relatively long half life. Conclusions. In contrast to VPD which is biotransformed to VPA, the aforementioned cyclopropane derivatives were found to be stable to amide-acid biotransformation. TMCD and M-TMCD show that cyclic analogues of VPD, like its aliphatic isomers, must have either two substitutions at the position to the carbonyl, such as in the case of TMCD, or a substitution in the and in the positions like in the VPD isomer, valnoctamide (VCD). This paper discusses the antiepileptic potential of tetramethylcyclopropane analogues of VPD which are in animal models more potent than VPA and may be non-teratogenic and non-hepatotoxic.