Nitroglycerin-induced headache is not dependent on histamine release: support for a direct nociceptive action of nitric oxide

The molecular mechanisms of migraine pain have not yet been clarified. Monoamine and the peptide neurotransmitters involved in neurogenic inflammation do not cause significant head pain. Our previous studies of glyceryl trinitrate (GTN) and histamine-induced headaches have suggested that nitric oxide (NO) is the causative molecule in migraine pain. We furthermore suggest that substances capable of inducing experimental vascular headache do so via a common mediator which is NO. Finally, it is suggested that drugs exert their antimigraine activity by inhibiting NO or subsequent steps in the cascade of intracellular reactions triggered by NO. These novel observations change current views on vascular headache mechanisms and the importance of NO as an initiator of the migraine attacks dictates new approaches to the pharmacological treatment of migraine and other vascular headaches.     

Noninvasive Detection of Coronary Artery Stenosis Using 16-slice Spiral CT：a Comparison with Selective X-ray Coronary Angiography

Multislice spiral CT(MSCT)has recently e-volved as a modalityfor non-invasive coronaryi ma-ging.16-slice MSCT allows excellent distal coro-nary coverage with higer temporal and spatial reso-lution.It can be usedto detect stenosis of coronaryartery with a diameter≥1.5cm[1,2].We investi-gated a group of coronary MSCT angiography(MSCTA)results,with those of selective X-raycoronary angiography(SCA)serving as the refer-ence standard.1MATERIALS AND METHODS1.1PatientsBetween July20…     

空气喷磨对预防性树脂充填微渗漏的影响

目的 :体外评价空气喷磨、酸蚀和两者结合对预防性树脂充填微渗漏的影响。方法 :对照组 (I,n =12 )对人离体磨牙常规预防性树脂充填。其余组分别用 5 0 μ(Ⅱ,Ⅲ)和 27μ(Ⅳ ,Ⅴ)氧化铝喷磨 ,其中两组 (Ⅳ ,Ⅴ)酸蚀 30s。每组一半牙齿进行热循环处理 (5～ 5 5℃ ,2500周 )后 ,用亚甲基蓝溶液着色。结果 :不论结合酸蚀与否 ,用 5 0 μ氧化铝喷磨 ,均与对照组不存在显著性差异 (p >0.05)。但喷磨后酸蚀比单纯喷磨能显著地减少微渗漏 (p<0.05)。 5 0 μ较 27μ氧化铝微粒显著地减少微渗漏(p <0.05)。结论 :空气喷磨结合酸蚀能显著地减少预防性树脂充填的微渗漏。     

Headache induced by a nitric oxide donor (nitroglycerin) responds to sumatriptan. A human model for development of migraine drugs

Experimental "vascular" headache in humans may be used in characterizing new migraine drugs. The effects of sumatriptan on nitroglycerin-(NTG)-induced headache and arterial responses were therefore studied. Following a double-blind randomized crossover design, 10 healthy volunteers received sumatriptan 6 mg s.c. or placebo succeeded by 20 min NTG (0.12 mg/kg/min) infusion. Headache was rated on a 10 points scale. Temporal and radial artery diameters and velocity in the middle cerebral artery (MCA) were measured with ultrasound. Sumatriptan reduced the NTG-induced headache, median score 1.5 versus 4 after placebo ( p <0.01) and decreased temporal and radial artery diameters 75±3 and 86±3% of baseline respectively ( p <0.05), Blood velocity in the MCA was unaffected. The NTG model may prove to be a valuable tool in the development of future migraine drugs. The results suggest that NTG headache in non-migraineurs may share mechanisms with migraine headache.     

A sudden increase in factor VIII inhibitor development in multitransfused hemophilia A patients in The Netherlands. Dutch Hemophilia Study Group

The development of antibodies to factor VIII (inhibitors) in response to clotting-factor concentrates administration in hemophilia is common during the first few years of treatment but rare in multitransfused patients. We have investigated the possible association of a recently introduced factor VIII concentrate (Factor VIII CPS-P) in The Netherlands with the occurrence of inhibitors. To this effect, we conducted two studies. First, we performed a national multicenter study in which clinical information and inhibitor test results were obtained for 447 hemophilia A patients over the period 1988 through 1991. Secondly, for a baseline comparison we estimated the frequency of inhibitor development in a closely followed cohort of 144 patients, from 1984 through 1989. Before the introduction of Factor VIII CPS-P, the incidence of new inhibitors was 4.4/1,000 patient-years in the national study from March 1988 through May 1990, and 3.9/1,000 patient- years in the cohort followed from 1984 through 1989. These figures are similar to the incidence of new inhibitors that was found in a large cohort of patients in the United States followed in the 1970s. In the period that the new concentrate Factor VIII CPS-P was on the market, from June 1990 through November 1991, 11 clinically relevant inhibitors were detected, which yielded an incidence over this interval of 20.1/1,000 patient-years, a 4.5-fold increase compared with the previous interval (C195: 1.4 to 14.3). Nine of these 11 patients had in their lifetime received over 250 infusions with factor VIII preparations. whereas all of the inhibitors detected in the previous time interval, and all of the 24 inhibitor patients described in the US study, had received less than 250 infusions in their lifetime. All patients who developed inhibitors after June 1990 had been exposed to Factor VIII CPS-P, whereas only 75% of the patients who did not develop an inhibitor had been exposed to this product. In a prospective extension of the study, with a second inhibitor measurement after 3 months, we found that one additional inhibitor had developed during 52.5 patient-years of Factor VIII CPS-P use. In conclusion, there has been a sudden increase in the frequency of inhibitor patients, for a large part among multitransfused patients. It seems more than likely that this increase is associated with the introduction of a new factor VIII concentrate in The Netherlands.(ABSTRACT TRUNCATED AT 400 WORDS)