Differential inhibition of cyclooxygenase-1 (COX-1) and-2 (COX-2) by NSAIDS: Consequences on anti-inflammatory activity versus gastric and renal safety

The discovery of an inducible isoform of cyclooxygenase (COX-2) requires a refinement of the theory that inhibition of cyclooxygenase activity is responsible for both therapeutic and side-effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Pharmacological results with developmental compounds suggest that COX-2 is the relevant target for the therapeutic (i.e. anti-inflammatory) effects of NSAIDs, whereas gastric and renal side-effects are related to inhibition of constitutive COX-1. However a role of COX-1 in inflammation cannot be excluded. Furthermore, more research effort is needed to investigate the functional relevance of COX-2 in normal tissue.     

The use of anencephalic organs: historical and ethical dimensions

The condition of newborn infants with anencephaly, a neural tube defect, is incurable and uniformly fatal. Although physicians reached a consensus two decades ago on the appropriateness of using these infants' organs, ethical and legal questioning has since challenged the grounds on which medical authorities justified transplantation. Advocates have proposed three conceptual strategies to warrant procuring anencephalics' organs: redefining death, excluding the infants from possessing personhood, and intubating and ventilating them while keeping a vigil for brain death. Each of these conceptual schemes has arguable shortcomings in its construction, however; as such, the case for using anencephalic infants as sources of organs has yet to be conclusively demonstrated.     

Ethics and Economics in Search of a Common Language

Book reviewed in this article: The Needs of Strangers . By Michael Ignatieff. The Health Economy . By Victor Fuchs. Just Health Care . By Norman Daniels     

Radiologic diagnosis of an intra-abdominal abscess. Do multiple tests help?

A review was made of the charts of 94 patients who underwent ultrasonography (US), computed tomography (CT), and gallium citrate Ga 67 (Gall) scan to rule out intra-abdominal abscesses. Of all the clinical and laboratory data, only the presence of pain and tenderness differentiated patients with and without abscesses. A review of radiologic data showed that CT was superior to US, and that US was superior to Gall scan with regard to sensitivity, specificity, accuracy, and positive and negative predictive values. When multiple radiologic tests were performed, results agreed in 72% of cases; therefore, the additional tests were essentially redundant. When radiologic test results disagreed, accuracy rates were CT, 0.86; US, 0.00; and Gall scan, 0.44. These findings suggest that, except to rule out pelvic abscesses in the presence of pelvic inflammatory disease, CT is usually the only special radiologic test that should be performed to localize a suspected intra-abdominal abscess.     

Colorimetric and thin-layer chromatographic methods for field assay of chloroquine and its metabolites in urine

Three field-adapted methods for the quantification of the antimalarial drug chloroquine are described. Two of the methods are modifications of the Haskins test and are based on ion-pair formation between chloroquine and methyl orange in either dichloromethane or chloroform. Absorbance values measured at 420 nm with a hand-held, battery-operated filter photometer were linearly related to chloroquine concentrations in urine up to 100 μmol/l (32 μg/ml) for both methods. The contribution of the desethylchloroquine metabolite to the measured absorbance for both methods is less than that of chloroquine; the relative sensitivity for this metabolite is about 50% of that of chloroquine for both methods. The detection limit for modification I is 1 μmol/l (0.3 μg/ml), while that for modification II is 3 μmol/l (1 μg/ml). A single dose of chloroquine diphosphate (300 mg as base) administered to each of three volunteers yielded detectable levels by modification I of chloroquine in the urine for 28 days after dosing. Results for the colorimetric methods correlated well with the liquid chromatographic reference method used. The related thin-layer chromatographic method confirmed the presence of chloroquine and desethylchloroquine in the urine and permitted independent estimation of the concentration of these two compounds if desired. The two colorimetric methods may be used in remote locations where no electricity is available.     

A double-blind combination study of clonazepam with sertraline in obsessive-compulsive disorder.

This double blind, randomized, parallel, placebo-controlled study investigates whether clonazepam accelerates and/ or increases the overall response in patients with obsessive compulsive disorder (OCD) who are treated with sertraline. Thirty-seven patients were randomized with 20 in the sertraline and clonazepam group and 17 in the sertraline and placebo groups. Male and female outpatients, age 18-65 years, met criteria for a primary diagnosis of obsessive compulsive disorder according to DSM-IV, as determined by the structured clinical MINI interview. Appropriate safety and efficacy parameters were measured throughout the study. The determination of efficacy was based primarily on changes from baseline to the last observation taken through week 12. Analysis revealed no significant difference between groups at endpoint on the main scale.