Effect of danazol on clotting factor levels, bleeding incidence, factor infusion requirements, and immune parameters in hemophilia

Several recent studies have reported conflicting results on the effectiveness of danazol, an attenuated androgen, in raising plasma levels of clotting factors VIII and IX in patients with hemophilia. We undertook a randomized, double-blind cross-over trial using 8 weeks' administration of danazol (D), 600 mg/d, and 8 weeks' administration of placebo (P) separated by 2 weeks of rest in 12 patients with hemophilia A and four patients with hemophilia B. Plasma factor VIII and IX levels, frequency and type of bleeding episodes, amount of factor concentrate infused, fibrinogen, fibrinolysis assays, antithrombin III, liver function, and immune parameters were followed. During the danazol phase a minimal increase was noted in the average clotting factor levels, an increase that, although statistically significant, was of hemostatically marginal magnitude. Significant increases in protein C and plasminogen levels, however, were observed during the danazol period, suggestive of danazol-mediated enhanced fibrinolysis. Clinically, bleeding frequency was significantly increased, and more clotting factor was consumed during the danazol period. Furthermore, eight episodes of hematuria and oral mucosal bleeding was reported during the danazol phase in contrast to only one episode of hematuria during the placebo phase, consistent with an enhancement of fibrinolytic activity with danazol. We conclude that danazol does not have a hemostatically significant effect on plasma levels of factor VIII and IX but may be associated with enhancement of fibrinolytic activity, resulting in increased bleeding frequency and requiring more clotting factor infusions. Therefore, danazol is not a viable alternative in the treatment of hemophilia.     

Return of autologous blood donors as homologous blood donors

Autologous blood donors (ABDs) have been reported to have favorable attitudes toward returning as homologous blood donors (HBDs), but the frequency of return has not been well documented. ABDs eligible by history to be HBDs were followed at one blood center: 255 donating for elective surgery and 234 donating during pregnancy were followed for an average of 18 months and 20 months, respectively, from time of eligibility after surgery or postpartum. Male ABDs had a higher rate of return as HBDs, as 34 percent (21/62) returned to donate an average of 3 units, whereas 13 percent (56/427) of female ABDs returned as HBDs to donate an average of 2 units. Although a history of donation was associated with a higher rate of return (30%, 34/113), 11 percent (43/376) of ABDs with no history as HBDs returned to donate homologous units, despite having been recruited less frequently than prior HBDs. Overall, all male ABDs and female ABDs with an HBD history returned most frequently. The extra effort required for an autologous donor program may result in the recruitment of new donors into the HBD pool.     

Efficacy and safety of a new single-dose terbinafine 1% formulation in patients with tinea pedis (athlete''s foot): a randomized, double-blind, placebo-controlled study

BACKGROUND: Tinea pedis is a common dermatophyte infection with frequent recurrences. Terbinafine (presently used as a 1-week topical treatment of tinea pedis) is now available in a novel topical solution (film-forming solution--FFS), developed to allow single application. OBJECTIVES: To demonstrate the efficacy and safety of terbinafine 1% FFS in a randomized, double-blind, placebo-controlled, phase III trial, and to determine relapse or re-infection rate of tinea pedis at 12 weeks. PATIENTS/METHODS: Fifty-four centres (27 in France; 27 in Germany) enrolled 273 evaluable patients (2 : 1 randomization). Patients applied terbinafine 1% FFS or placebo only once between, under and over the toes, soles and sides of both feet. Efficacy assessments included direct microscopy, mycological culture, and clinical signs and symptoms at baseline, and at weeks 1, 6 and 12 after the single drug application. RESULTS: Effective treatment (negative mycology plus absent/minimal symptoms) at week 6 in the terbinafine 1% FFS group was 63%; vehicle was 17% (P相似文献   

Inhibition of monocyte esterase activity by organophosphate insecticides

Organophosphate insecticides, such as Vapona, Naled, and Rabon, are highly potent inhibitors of an enzyme found in human monocytes. The enzyme, a specific monocyte esterase, could be inhibited by Vapona in blood samples via airborne contamination at levels easily achieved from commercial slow-release insecticide strips. Fifty percent inhibition (I50)--as measured on the Hemalog D (Technicon Corp.)--occurred at solution concentrations of 0.22, 1.5, and 2.6 X 10(-6) g/liter for Vapona, Rabon, and Naled, respectively. Parathion (a thiophosphate) and Baygon (a carbamate) were less potent, with I50 values of 3.7 X 10(-5) and 1.5 X 10(-4) g/liter, respectively. Dursban (another thiophosphate) and Carbaryl (a carbamate) showed only marginal inhibition. Eserine, malathion, nicotine and pyrethrum had no inhibitory effect up to 0.5 g/liter. The occurrence of this effect in vivo has not yet been shown, nor is it clear what the implications of such an effect would be. The inhibition of this enzyme by airborne contaminants, however, may interfere with the proper functioning of the Hemalog D.     

Dual suppression with oral contraceptives and gonadotrophin releasing- hormone agonists improves in-vitro fertilization outcome in high responder patients

Certain patients have a tendency for high response to gonadotrophin therapy which is often not ameliorated with prior gonadotrophin- releasing hormone agonist (GnRHa) suppression. As a result, these patients are frequently cancelled and often experience ovarian hyperstimulation syndrome (OHSS) episodes during in-vitro fertilization (IVF)-embryo transfer cycles. Patients with polycystic ovarian syndrome (PCOS) have been noted to be particularly sensitive to exogenous gonadotrophin therapy. We have developed a protocol which is effective in improving IVF outcome in high responder patients, including those with PCOS. Oral contraceptive pills (OCP) are taken for 25 days followed by s.c. leuprolide acetate, 1 mg/day, which is overlapped with the final 5 days of oral contraceptive administration. Low-dose gonadotrophin stimulation is then initiated on the third day of withdrawal bleeding in the form of either human menopausal gonadotrophins or purified urinary follicle-stimulating hormone at a dosage of 150 IU/day. Over a 5 year period, we reviewed our experience utilizing this dual method of suppression in 99 cycles obtained in 73 high responder patients. There were only 13 cancellations prior to embryo transfer (13.1%). The clinical and ongoing pregnancy rates per initiated cycle were 46.5 and 40.4% respectively. Only eight patients experienced mild-moderate OHSS following treatment. For those patients who had undergone previous IVF-embryo transfer cycles at our centre, significant improvements were noted in oocyte fertilization rates, embryo implantation rates and clinical/ongoing pregnancy rates with this protocol. Hormonal analyses revealed that the chief mechanism may be through an improved luteinizing hormone/follicle-stimulating hormone ratio following dual suppression. An additional feature of this dual method of suppression is significantly lower serum androgen concentrations, particularly dehydroepiandrosterone sulphate.      

Octreotide dependency and headache: a case report

We report on headache induced by a somatostatin octapeptide analog (octreotide) used for the treatment of acromegaly, This "rebound" headache has severe tension-type characteristics and occurs every 6–8 h. It resolves dramatically within minutes with octreotide administration. This is the first report of headache developing under treatment with octreotide.