Management of ascites in cirrhosis

Ascites is one of the earliest and most common complications of patients with cirrhosis. A typical circulatory dysfunction characterized by arterial vasodilation, high cardiac output and stimulation of vasoactive systems is commonly present in these patients and is associated with a poor prognosis. The treatment of ascites has been based on the combination of a low-sodium diet and the administration of diuretics. The reintroduction of paracentesis and the recent introduction of the transjugular intrahepatic portosystemic shunt (TIPS) are the most relevant innovations in the treatment of ascites during the past two decades, although controlled trials in large series of patients are needed to delineate whether TIPS is a safe and useful treatment for these patients.     

Sexual sequelae of antihypertensive drugs: Treatment effects on self-report and physiological measures in middle-aged male hypertensives

Antihypertensive drugs are commonly associated with adverse side effects in both clinical and laboratory studies. We investigated the sexual sequelae of several major classes of antihypertensive drugs (e.g., beta blockers, central alpha agonists, diuretics) in normal males and in hypertensive patients. We compared the effects of four widely used agents (methyldopa, propranolol, atenolol, hydrochlorothiazide-triamterene) and placebo, in a selected sample of 21 sexually dysfunctional male hypertensives, 13 of whom completed all five phases of the study. Each study drug was administered for a 1-month treatment period, followed by a 2-week, single-blind washout phase, according to a randomized, Latin square crossover design. Dependent variables for the study included a broad range of hormonal, NPT, and self-report measures of sexual response. Results indicated a lack of consistent drug effects on measures of sexual response, although more frequent sexual and nonsexual side effects were observed with methyldopa and propranolol. As in our previous studies, age was negatively correlated with both hormonal and NPT measures, whereas changes in blood pressure were not significantly related to sexual function scores. Results do not support the hypothesis that sexually dysfunctional males are at greater risk for adverse sexual sequelae when treated with centrally active agents or diuretics.     

Hepatic-pericardio-phrenic collateral (natural shunt) in a patient with Budd-Chiari syndrome

Hepatic venous outflow tract obstruction, Budd-Chiari syndrome (BCS), leads to portal hypertension and to the development of collaterals that bypass the obstruction. Described here is a BCS patient with an unusually large transdiaphragmatic collateral between the left hepatic and left innominate veins, which decompressed the oesophageal varices. This has not been reported earlier in the literature.     

Patterns of sexual arousal of accused child molesters involved in custody disputes

Penile plethysmography was used to examine sexual preferences of individuals accused of child molestation in the course of custody conflicts. Information regarding the alleged offenders, victims, and sex offense was gathered. In comparison to accused offenders who are not engaged in custody disputes, the subjects were more often accused of sexually abusing a younger child who was a biological relative. The source of accusations was usually the mother. Additionally, the custody-dispute subjects were less likely to have a prior criminal history. Penile tumescence data suggested that the subjects involved in custody disputes were less sexually aroused by children than those subjects who were not involved in custody conflicts. However, the results revealed that in both groups a substantial number of subjects responded equally or more to the child stimuli. In sum, the alleged offenders involved in custody disputes appeared less deviant on several measures.     

Are chronic wheezing and asthma-like attacks related to FEV1 decline? The Cracow study

Analysis is presented of the relationship between decline in ventilatory function and possible symptoms of bronchial hypereactivity. Data comes from three consecutive surveys within a 13-year follow-up study of a population sample of 1747 persons (718 males and 1029 females) who completed spirometric testing and interviews. Chest symptoms recorded in the two initial surveys were used as baselines for the prognostic study on FEV₁ change. To evaluate changes in lung function the FEV₁ decline index, expressed as percentage of FEV₁ loss during the study period, was calculated. Chronic wheezing and asthma-like attacks were very strongly related to FEV₁ baseline level. Multiple linear regression analysis for each separate symptom including age and smoking habits as confounders and showed that the FEV₁ decline index was higher and more significant when wheezing and asthma-like attacks or chronic cough were present. When the combination of symptoms were introduced into the regression model, the effect of wheezing became insignificant. Only attacks of shortness of breath in both sexes and chronic cough in women were significantly associated with more rapid FEV₁ decline. However, the effect of persistent wheezing in men had a rather substantial impact on FEV₁ change. Comparing the effect of the number of cigarettes smoked with the effect of symptoms, one can see that FEV₁ decline due to attacks of shortness of breath is comparable to that seen with heavy smoking. There was no strong evidence that the symptoms under study precede the more rapid FEV₁ decline.     

Small-airways dysfunction in never smoking asbestos exposed Danish plumbers

Summary Among 701 Copenhagen plumbers we examined the lung function of 23 never smokers, who had removed asbestos insulation and intermittently been exposed to high levels of asbestos for about 25 years without being exposed to welding fume. The plumbers had significantly lower TLC, MEF₂₅, MEF₅₀, closing volume and closing capacity in comparison to 23 never smoking electricians without asbestos exposure. There was no reduction in TL_CO. Pulmonary clearance of aerosolized ^99mTc-DTPA was normal indicating that the asbestos had not induced increases in pulmonary epithelial permeability. However, in 11 of the 23 plumbers the ^99m-Tc-DTPA ventilation scintigrams had a slightly irregular and spotty appearance, which together with the results of the lung function tests are suggestive of small airways' dysfunction. None of the subjects had symptoms or clinical signs of lung disease.     

Neuroprotection with felbamate: a 7- and 28-day study in transient forebrain ischemia in gerbils

The use of glutamate antagonists and GABA agonists may protect neurons from the effects of transient ischemia. Felbamate is a new antiepileptic drug with glutamate antagonist and GABA agonist properties, We tested the efficacy of felbamate in a gerbil model of transient forebrain ischemia. Damage assessment was done with silver staining at 7 and 28 days after 5 min of bilateral carotid occlusion, Cerebral cortex, hippocampus (CA1 and CA4), thalamus and striatum were evaluated on a 4-point scoring system, The animals sacrificed at 28 days were also tested in a water-maze task to assess recovery of function, The initial dose of felbamate (300 mg/kg) was given 30 min before the ischemic insult in one set of animals and 30 min after the insult in another set of animals. There were 8 animals tested per group (total: 48 animals). There was significant neuronal protection with the use of felbamate, both before and after ischemia in all regions of the brain. Protection was seen in animals sacrificed at 7 and 28 days, Protection was moderate when felbamate was used before ischemia. It was highly significant when felbamate was given 30 min after the insult. Behavioral studies however did not show any difference in the felbamate treated animals versus the saline treated controls. The structural protection with felbamate was very significant when used in the post-ischemic period. This window for protection merits further evaluation in relation to the clinical setting of stroke.     

Disposition Characteristics of Macromolecules in Tumor-Bearing Mice

As part of the strategy for the design of macromolecular carriers for drug targeting, the disposition characteristics of macromolecules were studied in mice bearing tumors that served as target tissues. Eight kinds of macromolecules including four polysaccharides and four proteins with different molecular weights and electric charges were used; tissue distribution and tumor localization after intravenous injection were studied. Pharmacokinetic analysis revealed that the tissue radioactivity uptake rate index calculated in terms of clearance was different among the tested compounds; especially, the urinary radioactivity excretion clearances and the total hepatic radioactivity uptake clearances varied widely. Compounds with low molecular weights (approximately 10 kD) or positive charges showed lower tumor radioactivity accumulation; radioactivity was rapidly eliminated from the plasma via rapid urinary excretion or extensive hepatic uptake, respectively. On the other hand, large and negatively charged compounds, carboxymethyl dextran, bovine serum albumin, and mouse immunoglobulin G, showed higher radioactivity accumulation in the tumor (calculated total amounts were 15.6, 10.8, and 20.8% of the dose, respectively) and prolonged retention in the circulation. These results demonstrated that the total systemic exposure rather than the uptake rate index was correlated with total tumor uptake. Molecular weight and electric charge of the macromolecules significantly affected their disposition characteristics and, consequently, determined radioactivity accumulation in the tumor. It was concluded that a drug–carrier complex designed for systemic tumor targeting should be polyanionic in nature and larger than 70,000 in molecular weight.