Adenosine as a vasodilator in primary pulmonary hypertension

BACKGROUND. The acute administration of vasodilator drugs to patients with primary pulmonary hypertension has been advocated to identify those with reversible pulmonary vasoconstriction. Unfortunately, the usefulness of the drugs currently available is limited by accompanying systemic hypotension. A vasodilator with effects confined to the pulmonary circulation would therefore be advantageous in such patients. METHODS AND RESULTS. The purine nucleoside adenosine was infused into the pulmonary artery in seven patients with primary pulmonary hypertension (baseline pulmonary vascular resistance [PVR], 442-1,295 dyne/cm/sec-5) to determine its effect on PVR. In all patients, there was a dose-dependent and significant reduction (mean maximal percent decrease from baseline, 38.9%; p less than 0.001) in PVR mediated through a decrease in pulmonary artery pressure and an increase in cardiac output. Systemic vascular resistance (SVR) also decreased, but the ratio of PVR to SVR decreased (maximal mean percent decrease from baseline) by 10.5% (p less than 0.025), indicating that adenosine has a preferential vasodilator effect on the pulmonary circulation when administered in this manner. CONCLUSIONS. Because of its pharmacokinetic and vasodilator properties, adenosine may have a specific role in the investigation of primary pulmonary hypertension.     

Positive Thinking Among Slot Machine Gamblers: A Case of Maladaptive Coping?

Background  Research has demonstrated that optimism and “positive illusions” can be used a coping mechanism among those facing adversity. Gamblers are a little studied group who also experience adversity and uncertainty. They often feel considerable levels of frustration, guilt, anger and a sense of feeling cheated after making significant losses. In order to deal with such feelings it is hypothesized that these individuals will search for positive consequences from their behaviour in order to offset this negative affect. Objectives  To (1) determine whether after gambling, gamblers compensate and reduce negative affect by identifying positive consequences from experiencing a loss, and (2) identify types of strategies which gamblers employ and consider how these should be classified. Materials and Methods  Eighty-seven regular slot machine gamblers were interviewed in a variety of environments housing slot machines. Each participant was asked a series of questions in a semi-structured format, to explore possible styles of positive thinking. Results  Nine types of ‘positive thinking’ experienced by gamblers were identified. These included Comparative thinking, Prophylactic thinking, Biased frequency thinking, Responsibility avoidance, Chasing Validation, Prioritization, Resourcefulness, Thoughtfulness, and Fear Reduction. Gamblers who were positive thinkers experienced significantly less guilt than non-positive thinkers. Conclusions  While reduction of negative affect may be perceived as positive in many other contexts, it is argued that it may counteract efforts to promote responsible gambling. Clinical implications and directions for future research are discussed.     

An alternate origin for the placental isoenzyme of alkaline phosphatase.

By means of an electrofocusing technique, the serum specimens of pregnant women routinely revealed three bands of alkaline phosphatase (ALP) that were released by placental syncytiotrophoblast, germ cell (ovary), and fetal intestine at pl of 4.73, 4.65, and 4.55, respectively. When defining reference ranges for ostensibly healthy persons of all decades of age and investigating patients with elevated total ALP activity, we found the isoenzyme at pl 4.73 to be above the established reference range in some nonpregnant women and in men. Evidence suggests that T lymphocytes from whole blood or in vivo tissue were the origin of this pl 4.73 ALP band; the isoenzyme being released during cell lysis, in cellular turmoil from any cause, or when active cell division occurs. A designation of lymphocyte ALP is proposed for this ALP band that is observed in a broad group of diseases associated with abnormal lymphocyte function.     

External fixation of complex open humeral fractures

Seven cases of complex open humeral fractures treated by external fixation are reported. The external fixation allowed the associated injuries to nerves, arteries and soft tissues to be adequately treated. Four cases developed non-union and of these, three cases treated by bone-grafting and plating united, but the one case treated by intramedullary nail without bone-graft did not unite. Frame construction and pin placement are discussed. The recommended plan for treatment of these fractures is initial external fixation until adequate soft tissue healing is achieved and sepsis controlled. Then early bone-grafting and plating is advocated if there is no progressive fracture healing. The problems and advantages encountered in the use of external fixation are also described.     

Traumatic rupture of extracardiac valved conduit: unusual late complication producing outflow tract obstruction

A 22-year-old woman died suddenly 15 years after successful repair of truncus arteriosus with a valved Dacron conduit. At autopsy there was complete obstruction of the right ventricular outflow tract by a large organizing thrombus between the outer aspect of the conduit and the adherent pericardial tissue. This rare late complication may have resulted from an unrecognized deceleration injury occurring at the time of a serious automobile accident 5 months before death.     

1,2,4-Triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity. 1. Synthesis and biological properties of alkyl alcohol and statine derivatives

A series of 1,2,4-triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity, which incorporate (1S,2S)-2-amino-1,3-dicyclohexyl-1-hydroxypropane, statine (Sta), and (3S,4S)-4-amino-5-cyclohexyl-3-hydroxy-pentanoic acid (ACHPA) transition-state mimetics, have been prepared. Structure-activity relationships for renin inhibitory activity in the series are consistent with the 2-[8-isobutyl-6-phenyl-1,2,4-triazolo[4,3-a]pyrazin-3-yl]-3-(3 pyridyl)propionic acid moiety 10b acting as a non-peptidic replacement for the P4-P2 (Pro-Phe-His) residues of the natural substrate angiotensinogen. Compounds 12m, 12o and 12q were potent inhibitors of partially purified human renin (IC50 values 1.7, 6.8, and 3.7 nM, respectively), and also effectively lowered blood pressure in anesthetized, sodium depleted marmosets following intravenous administration. On oral administration however, no blood pressure lowering activity could be detected, and absorption studies in bile duct cannulated rats indicate that this may be due primarily to poor oral absorption, rather than rapid biliary excretion. The reason for the observed poor oral activity is not clear, but it seems unlikely that poor aqueous solubility or metabolic instability to gut enzymes are rate-determining, and other factors such as high molecular weight may also be very important.