In-vitro/in-vivo correlation of pulsatile drug release from press-coated tablet formulations: a pharmacoscintigraphic study in the beagle dog.

The aim of the current study was to investigate the in-vitro and in-vivo performance of a press-coated tablet (PCT) intended for time delayed drug release, consisting of a rapidly disintegrating theophylline core tablet, press-coated with barrier granules containing glyceryl behenate (GB) and low-substituted hydroxypropylcellulose (L-HPC). The PCTs showed pulsatile release with a lag time dependent upon the GB and L-HPC composition of the barrier layer. In-vivo gamma-scintigraphic studies were carried out for PCTs containing GB:L-HPC at 65:35 w/w and 75:25 w/w in the barrier layer in four beagle dogs, in either the fed or fasted state. The in-vivo lag time in both the fed and fasted states did not differ significantly (p>0.05) from the in-vitro lag time. Additionally, no significant difference (p<0.05) between in-vivo fed and fasted disintegration times was observed, demonstrating that in-vivo performance of the PCT was not influenced by the presence or absence of food in the gastrointestinal tract. A distinct lag time was obtained prior to the appearance of drug in plasma and correlated (R2=0.98) with disintegration time observed from scintigraphic images. However, following disintegration, no difference in pharmacokinetic parameters (AUC(0-6 dis), K(el), Cmax) was observed. The current study highlighted the potential use of these formulations for chronopharmaceutical drug delivery.     

Electrolyte and humoral responses of renal transplant patients to head-out water immersion

Eighteen renal transplant recipients and sixteen volunteers were subjected to the physiological manoeuvre of head-out water immersion, in order to compare changes in electrolyte and humoral responses known to occur in healthy individuals with those arising as a result of renal denervation in the transplant recipients. Although the tubular sodium response to water immersion was normal, tubular potassium excretion was markedly different in the transplant patients. Plasma values of atrial natriuretic factor increased in both groups and showed a close temporal relationship to urinary excretion of cyclic GMP. The attenuation in transplant recipients of the well-documented suppression of plasma renin activity during water immersion was probably due to a combination of factors, namely lack of renal innervation and an increase in circulating ANF. The small but significant increase in the excretion of enzymically active urinary kallikrein observed only in the transplant recipients during immersion still requires explanation.     

Cutis Marmorata Telangiectatica Congenita Associated with a Double Aortic Arch

Abstract: We report a patient with cutis marmorata telangiectatica with the hitherto unreported anomaly of a double aortic arch. The presence of two major vascular anomalies in this patient may be secondary to a developmental defect of the mesoderm during embryogenesis.     

Detection of undiagnosed coeliac disease with atypical features using antireticulin and antigliadin antibodies.

Eighteen patients with a variety of non-gastrointestinal symptoms were incidentally found to have circulating antireticulin antibody and on subsequent testing were also positive for antigliadin antibody. They prospectively underwent jejunal biopsy to determine whether or not they had coeliac disease. Their age range was 21-79 years (mean 42 years). Enteropathy was present in 13 (72 per cent) and was always associated with circulating IgA antigliadin antibody. Enteropathy was not present in the five cases who had only IgG antibody. Clinical improvement occurred in eight of 11 patients who complied with a gluten-free diet and was paralleled by an improvement in the mucosal histology in seven of eight who were re-biopsied. The most remarkable cases were two patients who presented with severe debility and no apparent haematological or biochemical abnormalities, and who subsequently made a dramatic recovery on a gluten-free diet. It is concluded that antireticulin antibody detected by routine autoantibody screening and confirmed to have IgA antigliadin antibody specificity is a useful indicator of an otherwise undiagnosed enteropathy. This serves to emphasize that the condition can sometimes be associated with atypical features and significant morbidity.     

腕管综合征主要症状体征敏感性与特异性的比较

目的　比较腕管综合征 (carpaltunnelsyndrome ,CTS)主要症状、体征的敏感性与特异性。方法　对 10 1例 ( 162只手 )进行症状严重程度与功能状况的询问 ,感觉、运动功能的检查 ;其中 62只手在术后 6周再次测定。结果　 162只患手中 15 8只具有典型症状 ( 98% )。Phalen征、前臂正中神经加压征、Semmes Weinstein单丝纤维测试阳性率分别为 98%、96%、82 %。 87%的患手出现肌力下降 ,拇短展肌肌力测定 (定量法 )结果显示 ,与徒手法相比 ,不同性别间、术前与术后的差异均具非常显著意义 (P <0 .0 1)。结论　典型症状、Phalen征、前臂正中神经加压征、拇短展肌肌力变化的敏感性与特异性最高 ,拇短展肌肌力定量法测定是判断腕管综合征严重程度、评定疗效的一个良好的客观指标。     

Zinc deficiency and hyperprolactinaemia are not reversible causes of sexual dysfunction in uraemia

We selected a group of male dialysis patients complaining of sexual dysfunction in whom penile vascular insufficiency and drug-induced impotence had been excluded. Monitoring of nocturnal penile tumescence was used to confirm organic disturbance. Patients with normal serum prolactin concentrations (n = 18) had significantly lower serum zinc values than normal controls (P less than 0.001) and were entered in a 6-month double-blind study comparing oral zinc acetate with placebo. Patients with elevated prolactin concentrations (n = 8) were entered in a 3-month double-blind crossover study comparing oral pergolide mesylate with placebo. In the zinc study, serum zinc concentrations increased (P less than 0.05) in the zinc-treated but not the placebo-treated group. One of nine patients receiving zinc reported improved sexual function, as did two of nine patients receiving placebo. There were no significant changes in sperm counts, nocturnal penile tumescence, testosterone, sex hormone binding globulin or gonadotrophin concentrations in either treatment group. In the pergolide study, serum prolactin values decreased (P less than 0.01) in the pergolide but not in the placebo treatment period. One patient reported improved sexual function during the pergolide treatment period and two during the placebo period. There were no significant changes in sperm counts, nocturnal penile tumescence, testosterone, sex hormone binding globulin or gonadotrophin concentrations after pergolide. These studies show no benefit of zinc or pergolide compared with placebo in the treatment of uraemic impotence.