Substance‐Abusing Schizophrenics: Do They Self‐Medicate?

In spite of having been formulated nearly two decades back, there is as yet no consensus on the validity of the clinically popular self-medication hypothesis (SMH) of substance use disorders in patients with dual diagnosis. SMH broadly proposes that patients use substances in a non-random fashion so that the psychopharmacologic characteristics of particular substances are used to alleviate a variety of psychiatric symptoms and emotional distress. In order to test the SMH empirically, it was broken down to five sub-hypotheses, which were tested in a group of dual-diagnosis schizophrenia (DDS) patients vis-à-vis a group of only-schizophrenia (S) patients (n = 22 each). The DDS group scored lower than the S group regarding general and some specific psychopathology. The DDS patients ascribed reasons for substance use more often for hedonistic pursuit but also for reduction in symptoms and distress. There was a trend for alcohol to be used more for self-medication purposes compared to opioids and cannabis. The perceived effects of these three substances were significantly different on several symptom/distress dimensions. Finally, there was some degree of "match" between symptom-oriented reasons for use of substances and the effect that was perceived. All of this evidence provides a consistent but modest support for the SMH for "some patients, some substances, and some symptoms." The implications are discussed.     

Penetrating injury of ascending aorta with arrow in situ

Penetrating injuries of the aorta are rare and highly lethal; very few patients are able to reach the hospital alive. We report a case of penetrating injury into the ascending aorta with the arrow still in situ, shot by a bow in a tribal region of India. The wound of entry into the aorta was sealed by the arrow itself. The patient came to us walking and supporting the arrow with his left hand. He was operated on, and the arrow was successfully removed from the aorta.     

Purification and partial characterization of a haemorrhagin (VRH-1) from Vipera russelli russelli venom

A haemorrhagic toxin (VRH-1) has been purified to homogeneity from Vipera russelli russelli venom by subjecting it to chromatography twice successively on CM-Sephadex C-50. It is a protein of mol. wt 22,000 and contains one mole of Mg²⁺. Intradermal administration of this haemorrhagin in mice resulted in severe lung haemorrhage but produced little haemorrhage in skin. This apparent organ preference led us to develop a new haemorrhage assay method utilizing dye diffusion from lung in vitro. Proteolytic activity of VRH-1 was demonstrated using dimethylcasein as substrate following quantitation by reaction with trinitrobenzoyl sulfonic acid. Both haemorrhagic and proteolytic activities of VRH-1 were inhibited by serine protease inhibitors like phenylmethyl sulfonyl fluoride and chymostatin, but metal chelators had no effect. Lung haemorrhage is unlikely to be a direct reflection of a high local concentration of VRH-1. The administration of supernatant generated by incubation of chopped liver from untreated mouse and VRH-1 (in subhaemorrhagic dose) results in severe lung haemorrhage. This raises the possibility that VRH-1 leads to the formation of intermediate(s) which causes the haemorrhage.     

Effect of piperine on the steady-state pharmacokinetics of phenytoin in patients with epilepsy

Piperine, the active principle of Piper longum, Piper nigrum and Zingiber officinalis, has been reported to enhance the oral bioavailability of phenytoin in human volunteers. The objective of this study was to explore the effect of a single dose of piperine in patients with uncontrolled epilepsy on the steady-state pharmacokinetics of phenytoin. Two groups of 10 patients each receiving either a 150 mg or 200 mg twice daily dose of phenytoin were selected. Twelve hours after the night dose, venous blood samples were collected at 0, 0.5, 1, 2, 4, 6, 9, 12 h after administration of phenytoin. On the next study day, piperine 20 mg was administered along with phenytoin and samples were collected similarly. The mean plasma drug concentrations at different time points and the pharmacokinetic parameters before and after piperine administration were compared by Student's t-test. Piperine increased significantly the mean plasma concentration of phenytoin at most of the time points in both dose groups. There was a significant increase in AUC((0-12h)) (p < 0.01), C(max) (p < 0.001) and K(a) (p < 0.05) whereas the changes in K(el) and t(max) were not significant. The results showed that piperine enhanced the bioavailability of phenytoin significantly, possibly by increasing the absorption.