The consequences of H2 receptor antagonist — piroxicam coadministration in patients with joint disorders

Summary A randomised crossover study was performed in subjects with rheumatoid arthritis (or other arthropathies) to investigate if any alteration in the steady pharmacokinetics of the NSAID piroxicam (a drug which is extensively metabolised via cytochrome P450) or its major metabolites occurred as a result of coadministering either cimetidine or nizatidine.Twelve females and 2 males with mean age, weight, and albumin concentrations of 58 years, 61 kg, and 40 g·L^–1 respectively, completed the study. Comparisons were made between the following parameters: plasma piroxicam AUCs [AUC_0-24(P)], plasma 5-hydroxypiroxicam AUCs [AUC_0-24(5-OHP)], the ratio of these i.e. AUC_0-24(5-OHP):AUC_0-24(p), the % piroxicam daily dose excreted in urine as 5-hydroxypiroxicam (before and after glucuronidase incubation); and the mean of the steady state trough piroxicam, and 5-hydroxypiroxicam concentrations (obtained during each study phase in addition to the wash-out period).A statistically significant difference as a result of initiating either cimetidine or nizatidine was obtained only for the ratio AUC_0-23(5-OHP):AUC_0-24(P). This was indicative of a weak potential to inhibit piroxicam hydroxylation.No clinically significant alteration in the steady state pharmacokinetics of piroxicam occurred in these subjects as a result of cimetidine or nizatidine coadministration. Consequently it is unlikely that any adverse events would arise from these combinations.     

The interaction of parafluorohexahydrosiladiphenidol at muscarinic receptors in vitro

1. The antagonistic actions of parafluorohexahydrosiladiphenidol (pFHHSiD) at muscarinic receptors has been studied in cardiac muscle, smooth muscle and cell culture preparations. In this paper, the classification scheme of Doods et al. (1987) is employed. This scheme is based upon differential affinities of muscarinic antagonists. pFHHSiD exhibited high pA2 values at M3 receptors mediating contractions of guinea-pig ileum and oesophageal muscularis mucosae (7.8 and 8.2 respectively) whereas low values were determined at M2 receptors mediating negative inotropic responses in guinea-pig atria (6.0). Intermediate pA2 values were determined at M1 receptors mediating contractions of the canine femoral and saphenous veins. 2. The pA2 values of pFHHSiD at receptors mediating endothelial-dependent relaxation of rat aortic rings, rabbit jugular vein and canine femoral artery (7.6-7.9) were similar to those determined on the ileum. However, the pA2 values of pFHHSiD at receptors mediating contractions of the guinea-pig trachea (7.1), which has been previously shown to possess M3 receptors, were different from those determined in the ileum. 3. The similarity in pA2 values of pFHHSiD between the M3 receptors in guinea-pig ileum and the receptors mediating endothelial-dependent relaxations provide further evidence for the role of M3 receptors in this vascular response. Taken together, pA2 values for pFHHSiD range from 7.1 to 8.2, depending upon the M3 preparation used. The selectivity of the compound therefore for the M3 versus the M2 muscarinic receptor ranged from 13 to 163 fold.(ABSTRACT TRUNCATED AT 250 WORDS)     

Safety of GM-CSF in Patients with AIDS: A Review of the Literature

We performed a literature search for all clinical studies reporting outcomes in patients with the acquired immunodeficiency syndrome (AIDS) receiving granulocyte-macrophage colony-stimulating factor (GM-CSF) for any indication. Safety outcomes included human immunodeficiency virus replication, immune status, and frequency of opportunistic infections and neoplasms. Data were synthesized qualitatively. We identified 22 studies (274 patients): 12 addressed AIDS neutropenia, 8 AIDS cancer therapy, and 2 opportunistic infections. Viral burden was assessed by serum p24Ag in 15 studies. Nine reported no change in levels, three net decreases, and three net increases. All studies showing net increases involved patients receiving GM-CSF without a concurrent antiretroviral. The CD4 counts were unchanged in 5 studies, increased in 3, and not reported in 14. The incidence of neoplasms or new opportunistic infections was low. The literature suggests no increased risk of viral replication or clinical deterioration in patients with AIDS who take GM-CSF concurrently with zidovudine.     

Auditory Perception and the Control of Spatially Coordinated Action of Deaf and Hearing Children

From birth onwards, auditory stimulation directs and intensifies visual orientation behaviour. In deaf children, by definition, auditory perception cannot take place and cannot, therefore, make a contribution to visual orientation to objects approaching from outside the initial field of view. In experiment 1, a difference in catching ability is demonstrated between deaf and hearing children (10-13 years of age) when the ball approached from the periphery or from outside the field of view. No differences in catching ability between the two groups occurred when the ball approached from within the field of view. A second experiment was conducted in order to determine if differences in catching ability between deaf and hearing children could be attributed to execution of slow orientating movements and/or slow reaction time as a result of the auditory loss. The deaf children showed slower reaction times. No differences were found in movement times between deaf and hearing children. Overall, the findings suggest that a lack of auditory stimulation during development can lead to deficiencies in the coordination of actions such as catching which are both spatially and temporally constrained.