Progressive systemic sclerosis and the lung

Pulmonary manifestations of systemic sclerosis (scleroderma) are many. The mean survival in these patients is 78 +/- 17 months. Improved diagnostic techniques and better therapeutic options are essential to stem the tide of overwhelming mortality in patients with scleroderma lung disease.     

The TNF-863A allele strongly associates with anticentromere antibody positivity in scleroderma

OBJECTIVE: Scleroderma is characterized by the presence of 3 predominant, yet almost mutually exclusive, antibodies: anticentromere antibody (ACA), antitopoisomerase antibody, and anti-RNA polymerase antibody. The purpose of this study was to investigate tumor necrosis factor (TNF) polymorphisms in scleroderma, with the specific aim of determining whether TNF polymorphisms would prove to be stronger markers for ACA than class II major histocompatibility complex (MHC). METHODS: We studied 214 UK white scleroderma patients and 354 healthy controls. All subjects were investigated for 5 TNF promoter region polymorphisms by sequence-specific polymerase chain reaction. RESULTS: We showed that an NF-kappaB binding site polymorphism (known to be functionally relevant) in the TNF promoter region was present in 51.8% of patients with ACA and 16.3% of patients without ACA (chi(2) = 25.1, P = 0.000004 [corrected P = 0.00002]). Using haplotype mapping, we showed that this was a primary TNF association that could explain the previous weak links between ACA production and class II MHC alleles. In marked contrast to our ACA results, HLA class II (especially DRB1*11) appeared to be primary in that it could explain the weaker TNF association with antitopoisomerase production. Further, we observed a separate TNF haplotype to be associated with scleroderma per se, although the level of significance was much lower (chi(2) = 8.7, P = 0.003 [corrected P = 0.02]). CONCLUSION: We believe these findings may have importance both for the directional pathogenesis of scleroderma progression and for the treatment of scleroderma with anti-TNF agents.     

The management of distal hypospadias with meatal-based, vascularized flaps

In 63 children distal hypospadias was repaired using a meatal-based, vascularized flap. An acceptable glandular meatus was achieved in 62 children. Complications requiring further operation occurred in 5 children (8 per cent) and all were repaired successfully with only 1 other procedure. The technique has proved successful and rewarding in managing these distal lesions.     

Evaluation of some methods of concentration and purification of influenza virus

A number of techniques have been developed in the past 15 years for the concentration and purification of influenza virus, but there has been no comparative evaluation of their efficacy. In this paper the authors report on such an assessment, carried out with particular reference to the suitability of the various techniques for large-scale production of influenza vaccine, the aim being to recover a relatively pure antigen by simple means and without undue loss in the haemagglutinin and virus contents.     

Effect of pentoxifylline on the pharmacokinetics of rosiglitazone in Wistar rats

The aim of this study was to investigate the effect of pentoxifylline (PTX), an antiplatelet agent, on the pharmacokinetics of rosiglitazone (RSG) in rats. Pharmacokinetic parameters of RSG were determined in rats after oral administration (3 mg/kg/day) in the presence and absence of PTX (10 mg/kg) 3 times daily. Compared to control animals, rats pretreated with PTX for 7 days had a decrease in RSG peak plasma concentration (Cmax) of 19% with no change in the values of the area under the concentration-time curve (AUC). Alternatively, rats coadministered single-dose PTX did not show any differences from control with regard to RSG Cmax and AUC parameters. The time to peak concentration (tmax) of RSG was significantly increased in rats pretreated with PTX under both single- and multiple-dose conditions, whereas the elimination half-life (t1/2) of RSG was increased only with multiple-dose PTX pretreatment. In conclusion, the presence of PTX was found to cause a slight decrease in the oral exposure of RSG in rats. Concurrent use of PTX with RSG therefore needs to be appropriately evaluated for proper dose adjustments in humans.