Permeation of mouse skin and silicone rubber membranes by phenols: relationship to in vitro partitioning

A discrepancy has been noted in the relationship between the relative skin permeabilities of phenols and their lipophilicities as expressed in commonly used octanol:water partition coefficients (PCoctanol:water). The lack of correlation between partitioning and permeability is seen with the nitrophenols, particularly 4-nitrophenol. In the present study, the permeability coefficients-of 4-nitrophenol and several other phenols through skin and a model lipophilic membrane made of silicone rubber were found to be independent of concentration, ruling out concentration-dependent molecular aggregation as the cause of the partitioning-permeability incongruity. An unexpectedly low permeation rate was observed for the diffusion of 4-nitrophenol through the synthetic, silicone rubber membrane, confirming the anomalous position of this phenol in permeability relative to the octanol:water partitioning scale. However, when oil:water (o/w) partition coefficients for the phenolic compounds based on either n-hexane, CH2Cl2, CHCl3, or silicone rubber as the water immiscible phase are used, permeability coefficients for the skin and the synthetic membrane followed expected permeation-partitioning dependencies. On this basis, it appears that PCoctanol:water does not properly reflect the lipophilicity of the phenols with respect to partitioning into skin and silicone rubber during mass transfer.     

Efficacy and tolerability of pantoprazole 40 mg versus 80 mg in patients with reflux oesophagitis.

BACKGROUND: Pantoprazole is a substituted benzimidazole which is a potent inhibitor of gastric acid secretion by its action upon H+, K+- ATPase. METHODS: Pantoprazole 40 mg and 80 mg were compared in a randomized double-blind study in 192 out-patients with stage II or III (Savary-Miller classification) reflux oesophagitis. Patients received either pantoprazole 40 mg (n = 97) or pantoprazole 80 mg (n = 95), once daily before breakfast for 4 weeks. Treatment was extended for a further 4 weeks if the oesophagitis had not healed. RESULTS: After 4 weeks complete healing of the reflux oesophagitis was seen in 78% of protocol-correct patients given pantoprazole 40 mg daily (n = 86), and in 72% in the 80 mg (n = 87) group. The cumulative healing rates after 8 weeks were 95 and 94%, respectively (P > 0.05, Cochran-Mantel- Haenszel), and time until healing of oesophagitis comparable in both groups. Differences between doses were also not significant in an intention-to-treat analysis. Both dosing schedules were well tolerated and the patients experienced remarkable symptom relief. No adverse event or changes in laboratory values of clinical significance could definitely be ascribed to the trial medication. CONCLUSION: The 40 mg pantoprazole dosage is comparable to 80 mg in reflux oesophagitis, both in efficacy and tolerability.     

Greater trochanteric overgrowth: development and surgical correction

Greater trochanteric advancement (GTA) is an orthopedic procedure designed to correct the biomechanical consequences of overgrowth of the greater trochanter by moving the greater trochanter and its attached muscles laterally and distally. Thirty-one children with trochanteric overgrowth who had secondary pelvic instability (Trendelenburg sign) were studied and underwent a total of 33 GTA procedures. The clinical and radiologic prerequisites for successful surgery are presented. In addition, the radiographic methods of measuring the lateral position of the trochanter, the articulotrochanteric distance, and the amount of trochanteric overgrowth are discussed. Measurements made on preoperative and postoperative radiographs revealed that surgery achieved a mean displacement laterally of 12.1 mm and distally 21 mm. Clinically, there were few complications (two children with mild myositis, one with broken hardware, one with delayed union of trochanter). Pelvic instability had disappeared in the 25 of the 30 patients who could be evaluated.