颅内蛛网膜囊肿34例

1　临床资料1.1　一般资料　 1986 / 1997收治颅内蛛网膜囊肿 34(男 2 8,女 6 )例 .年龄 3～ 6 8岁 ,其中 16岁以下 17例 .有头部外伤史者 15例 ,无明显诱因者 19例 .病程 :2 m o～ 14a.头部外伤至发病时间 :7d～ 2 a. 34例中幕上 30例 ,幕下 4例 ,其中侧裂池 15例 .1.2　临床症状　表现头疼、头昏或伴呕吐、视力下降、视乳头水肿等颅内压增高的症状 18例 ,癫痫发作 7例 ,偏瘫 6例 ,行走不稳 2例 ,失语 1例 .1.3　辅助检查　本组 2 8例作 CT检查 ,6例行 MRI检查证实 .头颅 CT扫描特征 :脑实质外有一边界清楚的低密度病灶 ,CT值与脑脊液…     

Conformational preferences in a benzodiazepine series of potent nonpeptide fibrinogen receptor antagonists

Previously, we reported the direct design of highly potent nonpeptide 3-oxo-1,4-benzodiazepine fibrinogen receptor antagonists from a constrained, RGD-containing cyclic semipeptide. The critical features incorporated into the design of these nonpeptides were the exocyclic amide at the 8-position which overlaid the Arg carbonyl, the phenyl ring which maintained an extended Gly conformation, and the diazepine ring which mimicked the gamma-turn at Asp. In this paper, we investigate conformational preferences of the 8-substituted benzodiazepine analogues by examining structural modifications to both the exocyclic amide and the seven-membered diazepine ring and by studying the conformation of the benzodiazepine ring using molecular modeling, X-ray crystallography, and NMR. We found that the directionality of the amide at the 8-position had little effect on activity and the (E)-olefin analogue retained significant potency, indicating that the trans orientation of the amide, and not the carbonyl or NH groups, made the largest contribution to the observed activity. For the diazepine ring, with the exception of the closely analogous 3-oxo-2-benzazepine ring system described previously, all of the modifications led to a significant reduction in activity compared to the potent 3-oxo-1, 4-benzodiazepine parent ring system, implicating this particular type of ring system as a desirable structural feature for high potency. Energy minimizations of a number of the modified analogues revealed that none could adopt the same low-energy conformation as the one shared by the active (S)-isomer of the 3-oxo-1, 4-benzodiazepines and 3-oxo-2-benzazepines. The overall data suggest that the features contributing to the observed high potency in this series are the orientation of the 3-4 amide and the conformational constraint imposed by the seven-membered ring, both of which position the key acidic and basic groups in the proper spatial relationship.     

Efficacy of Zoladex LA (goserelin) in the treatment of girls with central precocious or early puberty

OBJECTIVE: To assess the efficacy of a longer acting preparation of the gonadotrophin releasing hormone (GnRH) analogue goserelin (Zoladex LA, 10.8 mg) in 12 girls with central precocious or early puberty. METHODS: Two girls started treatment de novo; the remainder had been on suppressive treatment for a median duration of 1.5 (range, 0.2-5.6) years. Assessment comprising auxology, pubertal staging, and pelvic ultrasound examination was carried out at weeks 0, 4, 8, 10, and 12 (first cycle) and weeks 8, 10, and 12 (second cycle) to evaluate the required injection frequency. Thereafter, assessment was performed on the day of injection. Zoladex LA was given every 12 weeks unless pubertal progression occurred. RESULTS: Satisfactory control was achieved in eight patients using this regimen, and three patients required more frequent injections. One girl was removed from the study because of clinical progression and extreme mood swings. No serious adverse effects occurred. Mean height velocity during the study period was 4.5 cm/year (range, 3.1-6.6) compared with 6.5 cm/year (range, 3.8-9.6) before treatment in nine patients for whom data were available. CONCLUSIONS: Zoladex LA was effective in controlling precocious puberty in girls when given at intervals of 9-12 weeks and it is recommended that an initial assessment is made eight weeks after beginning treatment.     

"Early-peak" carbon monoxide production in certain erythropoietic disorders

The "early-labeled" peak (ELP) of 14CO excretion following injection of glycine-2-14C was used to study erythropoiesis in a patient with sideroblastic anemia and in four subjects with myeloproliferative disorders. The ELP was greatly enlarged in all patients, as compared with a normal volunteer. The contour of the peaks from the hematologically abnormal subjects suggested the presence of increased erythroid heme degradation. In the patient with sideroblastic anemia, all hours of the early peak were significantly reduced after transfusion. This was interpreted to mean that even the earliest or "nonerythroid" phase of the peak is influenced by erythropoietic activity, at least under conditions of erythropoietic stress.     

Muscarinic modulation of the vasodilatory effects of vasoactive intestinal peptide at the rat thyroid gland

In the thyroid gland, vasoactive intestinal peptide (VIP) and acetylcholine (ACh) are found in nerve fibers associated with secretory cells and blood vessels. We have, therefore, initiated studies to explore the actions of and interactions between cholinergic agents and VIP in the regulation of thyroid vascular conductance (VC). Thyroid and other organ blood flows were measured using radiolabelled (141Ce) microspheres injected directly into the left cardiac ventricle of anesthetized male rats. The mean systemic arterial pressure was monitored and used in the calculation of organ VC (blood flow/arterial pressure). Plasma TSH, T3, and T4 levels before and after infusions were measured by RIA. The acute administration of ACh (3 x 10(-8) mol/100 g BW) over 4 min increased thyroid VC, whereas nicotine (10(-7) mol/100 g BW) had no such effect. Circulating TSH and thyroid-hormone levels following ACh or nicotine were not different from those in vehicle-treated animals at 20 min or 2 h after infusion. This observation suggested that ACh acts through muscarinic receptors at the thyroid gland to increase VC. In order to extend these observations and to evaluate whether VIP might exert any of its thyroidal effects on VC via muscarinic receptors, we assessed the effects of ACh, methacholine chloride (MCC), and VIP in the presence and absence of the muscarinic receptor blocker atropine. Rats were treated intravenously with saline or atropine (3 mg/kg) 20 min before intravenous infusions of vehicle, ACh (3 x 10(-8) mol/100 g BW), MCC (5 x 10(-9) mol/100 g BW), or VIP (10(-11) mol/100 g BW).(ABSTRACT TRUNCATED AT 250 WORDS)     

Impairment of antipyrine clearance in humans by propranolol

The effect of propranolol on antipyrine clearance in humans was evaluated in six healthy volunteers who received single 1.4 to 1.5 g doses of intravenous antipyrine on two occasions. The first (control) antipyrine trial was without concurrent drug administration; the second trial was done during treatment with therapeutic doses of propranolol (40 mg every 4 to 6 hours). Antipyrine elimination half-life (t1/2), volume of distribution (Vd), and total clearance were determined after each trial. In all subjects isoproterenol sensitivity decreased markedly during propranolol treatment, indicating a high degree of beta blockade produced by the drug. Mean antipyrine t1/2 during the propranolol treatment period was significantly prolonged, and total clearance significantly reduced, over the control values. Twenty-four-hour urinary excretion of 4-hydroxyantipyrine, the major metabolite of antipyrine, likewise was reduced from 23.6% of the dose on the control trial to 14.8% of the dose during propranolol coadministration (0.1 less than P less than 0.2). Vd however, was nearly identical during both trials (0.62 L/kg). Thus propranolol prolongs the half-life and reduces the clearance or biotransformation rate of antipyrine, a drug whose clearance is independent of hepatic blood flow. Propranolol may influence the activity of hepatic microsomal enzymes responsible for drug hydroxylation.