A phase II study of recombinant interferon-beta (r-hIFN-beta 1a) in combination with 5-fluorouracil (5-FU) in the treatment of patients with advanced colorectal carcinoma.

The combination of 5-fluorouracil (5-FU) and interferon-alpha (IFN-alpha) has reported activity in the treatment of advanced colorectal carcinoma. Laboratory studies of IFN-beta suggest that this agent may offer theoretical advantages over IFN-alpha in combination with 5-FU. A total of 27 patients with advanced or recurrent colorectal carcinoma were treated in a non-randomized open phase II study with a combination of 5-fluorouracil (750 mg m(-1) daily for 5 days as a continuous intravenous (i.v.) infusion followed, from day 15, by i.v. bolus 750 mg m(-2) every 7 days) and recombinant interferon-beta [r-hIFN-beta-1a; 9 MIU (total dose) by subcutaneous injection from day 1 on every Monday, Wednesday and Friday throughout the treatment period]. Toxicity was less than that seen with this schedule of 5-FU in combination with IFN-alpha. Among 21 evaluable patients, four objective responses were seen. Recombinant human interferon-beta-1a in combination with 5-FU is an acceptable regimen in terms of toxicity. However, the study did not demonstrate a superior response rate when compared with previous reports of treatment with 5-FU alone or in combination with IFN-alpha.     

Treatment of hyperlipidaemia

The primary goal of therapy in the treatment of hyperlipidaemia is to reduce the plasma concentrations of known atherogenic lipoproteins thereby reducing or even reversing the flux of lipids from plasma into the arterial wall. A less common goal is to prevent the adverse sequellae of hyperchylomicronaemia in patients with severe hypertriglyceridaemia. The aetiologic factor(s) responsible for hyperlipidaemia in a given patient need to be clearly established and it is important not to overlook potentially treatable secondary disorders. Diet is the cornerstone of therapy in the treatment of hyperlipidaemia; the decision to begin drug therapy should be individualized and should be made only after an adequate trial of diet has failed to achieve satisfactory concentrations of plasma lipids and lipoproteins. In this review I will discuss the use of diet and drugs in the treatment of patients with hypercholesterolaemia due to increased plasma concentrations of low density lipoproteins, patients with combined hyperlipidaemia in which very low and low density lipoproteins are elevated and patients with severe hypertriglyceridaemia in which chylomicronaemia is present.     

Changes in dimeric inhibin A and B during normal early puberty in boys and girls

OBJECTIVE Although recently developed specific and sensitive assays of bioactive dimeric inhibin A and B have given new insights into the pituitary-gonadal axis in adult men and during the adult female menstrual cycle, there have been no reports on circulating inhibin A and B during normal human puberty. The aim of this study was to assess the relationship of dimeric inhibin A and B to pubertal stage, FSH and testosterone or oestradiol in late prepuberty and in early puberty. STUDY DESIGN AND SUBJECTS Serial samples were collected during a prospective longitudinal trial of GH treatment in short normal children. Seven boys were studied from late prepuberty to genital stage 3, and six pre-menarche girls from late prepuberty to breast stage 4. MEASUREMENTS Dimeric inhibin A (girls only) and inhibin B (boys and girls) were measured by highly specific and sensitive two-site ELISAs, FSH by IRMA, testosterone and oestradiol by RIA. RESULTS In boys, inhibin B increased progressively from pubertal stages 1 to 3 (ANOVA P<0.0001) and correlated strongly with mean testicular volume (r=0.72, P=0.0005). Prepubertal boys showed a positive correlation between inhibin B and FSH (r=0.65, P=0.056), whereas pubertal boys gave a strong negative correlation (r=0.75, P=0.012). In both prepubertal and pubertal boys positive correlations were observed between inhibin B (y) and testosterone (x) (r=0.81, P=0.008 and r=0.62, P=0.054 respectively), but the slope of the regression line between the two was much steeper before than after the onset of clinical puberty. In girls, both inhibin A and B increased through pubertal stages 1–4 (ANOVA P=0.01 and P=0.047 respectively). Both showed strong positive correlations with oestradiol (r=0.80 and 0.79, P=0.001) and with FSH (r=0.83, P=0.0004 and r=0.80, P=0.001). Inhibin A and B were also strongly correlated with each other (r=0.92, P=0.0001). CONCLUSIONS In boys, testicular production of inhibin B increases as puberty progresses. Our results show for the first time that the initiation of puberty is accompanied by a dramatic switch from a positive to a negative relation between inhibin B and FSH as inhibin B begins to exert the expected negative feedback on FSH. The results in girls suggest that, prior to menarche, the ovarian follicles produce inhibin A and B in strict proportion, and in progressively greater amounts as puberty proceeds. Measurement of dimeric inhibin A and B may provide a sensitive new tool for determining gonadal maturity in late prepuberty and early puberty.     

The association of hemifacial spasm and facial pain.

The recognition of an association between trigeminal neuralgia and ipsilateral hemifacial spasm has been delayed by confusion over the nomenclature of the two conditions. Three patients are presented who had facial pain associated with hemifacial spasm. The findings on investigation of these patients, and an analysis of the literature, suggests that the combination is almost inevitably associated with pathological processes in the posterior fossa, particularly anomalous, ectatic or aneurysmal blood vessels.