Efficacy of subcutaneous sumatriptan in the acute treatment of early-morning migraine: a placebo-controlled trial

Abstract. Objectives. To evaluate the efficacy of self-administered subcutaneous sumatriptan in the acute treatment of early-morning migraine attacks. Design. A double-blind, randomized, placebo-controlled, cross-over study. Setting. Thirteen neurology centres in France. Subjects. Patients of either sex, 18–65 years old, with two to six attacks of migraine (according to the International Headache Society (IHS) criteria, with or without aura) per month, of which at least two had to be early-morning migraine attacks. One-hundred-and-one patients were included, 96 being evaluable for the first attack and 81 for the cross-over design. Interventions. Two migraine attacks (grade 2/3) were treated with sumatriptan (6 mg) or placebo, with an optional second injection 1–24 h later. Main outcome measures. The primary end-point was headache relief: reduction in headache severity from grade 2/3 (moderate/severe) to grade 1/0 (mild/none) 2 h after treatment. Results. Sumatriptan was superior to placebo for headache relief (32 [78%] vs. 11 [28%] at the first attack; 29 [73%] vs. 8 [20%] at the second; P < 0.001). Because of a significant carry-over effect for some of the secondary end-points, a parallel-group analysis of the first attack was performed, which confirmed a significantly higher efficacy of sumatriptan for all end-points: pain-free rate (22 [46%] vs. 7 [15%]; P = 0.001) and use of a second injection (26 [53%] vs. 38 [81%]; P = 0.004). Sumatriptan was preferred by 74% of patients vs. 17% for placebo, and 9% expressed no preference (P < 0.0001). After complete relief, headache reappeared in 8/23 (35%) patients with sumatriptan and 3/7 (43%) with placebo. Adverse events were significantly more frequent with sumatriptan but they were minor and transient. Conclusion. Subcutaneous sumatriptan auto-injection is an effective and well-tolerated acute treatment of early-morning migraine attacks allowing earlier return to normal activity.     

ONO—802阴道给药抗早孕50例临床效果观察

本文报告了停经56天以内的早孕妇女应用ONO-802阴道栓剂抗早孕的临床观察及效果。50例早孕妇女住院观察24小时,阴道投药1枚(1mg/枚),5枚为一疗程。用药后1周、2周、4～6周门诊随访,复查尿HCG、血红蛋白。在第二周随访时判断用药效果。临床结果:总有效率82%,其中完全流产76%,不全流产6%,失败率18%。ONO-802使用方便,副反应轻,是深受广大妇女欢迎的一种非手术终止妊娠的方法。本项试验结果通过与国内PG 联合用药的结果和研究资料对比,ONO-802如果能与丙睾、R2323、天花粉等联合应用,将会提高其抗早孕的有效率。     

Efficacy of intranasal administration of neostigmine in myasthenic patients

Summary The efficacy of intranasally administered neostigmine was tested in 22 patients with generalized myasthenia gravis (MG). Topical therapy to the highly vascularized oropharynx proved to be quickly effective in 5–15 min both clinically and electrophysiologically. Twenty-eight MG patients were then recruited from different centres and their morning doses of oral pyridostigmine were substituted with intranasal neostigmine over a period of 2 or 3 weeks. Intranasal neostigmine proved to be equally efficacious in this regimen. No side-effect was noted even in 4 patients treated in this way for 1 year. Intranasal administration of anti-acetylcholinesterase may be very beneficial: (1) for patients with irregular absorption of oral doses; (2) early in the morning and every time a fast and temporary effect is needed; (3) in bulbar impairment and emergencies, in which a handy atomizer may be life-saving.Presented in part at the XIV World Congress of Neurology, New Delhi, 22–27 October 1989     

Is captopril effective in controlling blood pressure when administered once daily? An assessment using 24-h ambulatory blood pressure monitoring

Summary Twelve patients with essential hypertension receiving captopril monotherapy or captopril in conjunction with a diuretic had their 24-h blood pressure profiles monitored using an automatic, non-invasive ambulatory method. The study examined the efficacy of once a day versus twice a day administration of the ACE inhibitor in controlling blood pressure.Six untreated subjects with borderline hypertension were also studied using the same monitoring equipment and with the same frequency, to act as controls because of the possibility of repeated use of the device causing a familiarisation effect.The results obtained indicated that if anything, the once daily dosing produced marginally better blood pressure values. The amplitude of the diurnal blood pressure variation was reduced on a second-wearing of the monitoring equipment suggesting some degree of familiarisation with the apparatus.     

Testosterone in a Cyclodextrin-Containing Formulation: Behavioral and Physiological Effects of Episode-like Pulses in Rats

Testosterone, administered in the form of an inclusion complex with 2-hydroxypropyl--cyclodextrin by subcutaneous injection, enters the circulation in a manner markedly similar to the natural episodic release by the testes. The effects of a regimen of once-a-day administration of complexed testosterone to adult (castrated or intact) rats and to senescent (intact) rats were investigated. Although this procedure left the castrated animals with concentrations of circulatory hormone far below physiological levels for much of the day, a significant improvement in androgen-sensitive behavior and physiology was obtained. Furthermore, the testosterone effects were more pronounced when high doses were used periodically rather than when the same total amount of testosterone was equally divided among doses. The same supplementation to intact rats intensified androgen-sensitive behavior and physiology over normal levels. In senescent rats uniform pulses of the testosterone complex also improved behavior and physiology. Specifically, spermatogenesis was stimulated and, notably, the treatment increased muscle weight without substantial enlargement of the prostate. Since the testosterone–cyclodextrin complex also can be effectively administered as a sublingual tablet, the data suggest that similar regimens may be recommended for elderly men suffering from decreases in muscle mass.     

Attitudes toward male fertility control: results of a multinational survey on four continents

BACKGROUND: Following extensive research activity to develop an effective agent to control male fertility, such a product may be available for use within approximately 5 years. However, little is known concerning contraceptive knowledge, desires and attitudes of men in different countries, and their acceptance of male fertility control (MFC). METHODS: A survey of >9000 males aged 18-50 years was performed in nine countries on four continents in 2002. The objective was to compare, on a cross-cultural basis, the knowledge, attitudes and acceptability of MFC among men and assess their willingness to use such a method. RESULTS: Between 50 and 83% of the male respondents currently use contraceptive methods, and 55-81.5% reported that both partners participate in selecting the method of contraception employed. Overall acceptance of hormonal MFC was high (>55%), with 28.5-71.4% of survey participants of various nationalities expressing the willingness to use such a method. CONCLUSION: While MFC appears to be well accepted overall, the willingness to use this type of contraception varies widely between differing population groups. The specific characteristics and profile of any MFC product will have to be carefully evaluated to accurately assess its acceptance, both by men and their female partners.     

Feeding NOD mice with pig splenocytes induces transferable mechanisms that modulate cellular and humoral xenogeneic reactions against pig spleen or islet cells

We have reported previously that oral administration of pig cells to NOD mice modified xenogeneic cellular response against pig islet cells (PICs), and hypothesized that it may have induced active suppression. This preliminary report evaluated only the effect of feeding pig cells by 'primary' proliferation, i.e. when splenocytes from fed mice are confronted with pig cells in vitro. The present study also considered 'secondary' proliferation and cytokine production after feeding and subsequent in vivo graft of pig cells. Additionally, serum IgM and IgG isotypes were quantified by ELISA using pig target cells. Induction of active mechanism by feeding was hypothetical, which led us here to transfer splenocytes from mice fed pig spleen cells (PSC) and evaluate 'primary' (after transfer) and 'secondary' (after transfer and subsequent graft of pig cells) proliferations and cytokine secretions in recipient mice. We also determined whether the effects of feeding pig cells persisted after depression of suppressor mechanisms by cyclophosphamide. Mice fed with PSC displayed increased 'primary' splenocyte proliferation to PSC or PIC (P < 0.0001), while 'secondary' responses were decreased (P < 0.03) in those fed PSC and subsequently grafted with PSC. The increased 'primary' and decreased 'secondary' proliferations were reduced (P < 0.04) by pretreatment with cyclophosphamide. The IL-10/ and IL-4/IFNgamma ratios produced in response to PSC increased (P < 0.04) in mice fed and grafted with PSC compared to those grafted only with PSC. IgM and IgG levels against pig cells were, respectively, increased (P < 0.04) and decreased (P < 0.04) in mice fed and grafted with PSC. IgG2a and IgG2b, but not IgG1, levels were lower (P < 0.01). These effects of feeding PSC on 'secondary' proliferation, cytokine and antibody productions, were not detected when mice were fed PSC only after graft with PSC. Transfer with splenocytes from mice fed PSC increased 'primary' proliferation of splenocytes from recipient mice in response to PSC (P < 0.02) or PIC (P < 0.05). After transfer with splenocytes from PSC-fed mice and graft with PSC, 'secondary' proliferation to pig cells were reduced (P < 0.04), and the IL-10/IFNgamma ratio produced in response to PSC was increased fourfold. Thus, oral administration of PSC induces active transferable mechanisms, characterized by a biphasic pattern with early increased 'primary' xenogeneic cellular reactions to both PSC and PIC, followed by decreased 'secondary' responsiveness and a concomitant shift of the Th1/Th2 balance towards greater Th2 influence. Decreased responsiveness may be due to active suppression, even though induction of anergy or deletion cannot be excluded.     

Inhibitory effect of oral administration of Lactobacillus casei on 3-methylcholanthrene-induced carcinogenesis in mice

The present study was designed to determine whether tumor induction by 3-methylcholanthrene (MC), a carcinogenic hydrocarbon, can be inhibited by oral administration of Lactobacillus casei strain Shirota (LC). C3H/HeN mice were divided into four groups and assigned to the following treatments: treated with MC and given control or LC-containing diet; treated with vehicle only and given control or LC-containing diet. MC (1 mg) was injected intradermally at 7 weeks of age and the tumor incidence was monitored; LC was mixed into a diet at a concentration of 0.05% (w/w) and the diet was fed from the day of MC injection throughout the study. Spleen cells were analyzed for the immune parameters at 12 and 16 weeks after the MC injection. Oral feeding of mice with LC reduced tumor incidence (P < 0.05). MC treatment lowered the in vitro response to concanavalin A (Con A) of spleen cells, the secretion of interleukin-2 in spleen cell culture after stimulation of the cells with Con A and the proportions of CD3⁺, CD4⁺ and CD8⁺ splenic cells. However, the analysis of the spleen cells obtained from the mice treated with MC and given the LC-containing diet revealed that these disrupted host immune parameters were maintained at the level of normal controls. These results suggest that oral feeding of mice with LC inhibits MC-induced tumorigenesis by modulating the disrupted host immune responses during MC carcinogenesis. Received: 14 April 1999     

Acute effects of vitamin B6 and fixed combinations of vitamin B1, B6, B12 on nociceptive activity evoked in the rat thalamus: Dose-response relationship and combinations with morphine and paracetamol

Summary Nociceptive activity was elicited in neurones of the thalamus by supramaximal electrical stimulation of afferent C fibres in the sural nerve of rats under urethane anesthesia. The fixed combination of vitamin B₁, B₆, B₁₂ (Neurobion^®) as well as of vitamin B₆ administered by i.p. injection dose-dependently reduced the evoked nociceptive activity. The ED₅₀ of Neurobion^® is 4.6 ml/kg (at 100 min after injection) and that of vitamin B₆ is 189mg/kg (at 90 min after injection). The minimum effective doses of Neurobion^® and vitamin B₆ are 0.5 ml/kg and 40 mg/kg, respectively. When Neurobion^® or vitamin B₆ were given at their minimum effective doses, and the minimum effective doses of morphine (0.025 mg/kg) or paracetamol (5 mg/kg) were injected i.v. 80 min later, i.e., when the maximum effect of higher doses of Neurobion^® or vitamin B₆was about to develop, no supraadditive effect developed. It is concluded that the antinociceptive effect caused by a single injection of Neurobion^® is largely due to vitamin B₆. Vitamin B₁₂ may contribute to this effect, whereas vitamin B₁ alone exhibited only a slight effect on nociception. Moreover, it appears that Neurobion^® produces its antinociceptive effect after a single injection and after repeated administration during several days by different mechanisms so that the effect of analgesic agents is not enhanced following a single injection of Neurobion^® but may be enhanced after repeated administration of the compound.