In-vivo effects of Glu298Asp endothelial nitric oxide synthase polymorphism.

Endothelial nitric oxide synthase catalyses the formation of the vasodilator nitric oxide, a major regulator of vascular tone. The Asp298 polymorphism of the nitric oxide synthase gene is associated with altered function and expression of the enzyme in vitro and myocardial infarction and coronary artery spasm in vivo. We examined the effect of the Glu298Asp polymorphism on: (1) local vascular responses to phenylephrine, acetylcholine, glyceryl trinitrate and prostaglandin E1 in the dorsal hand vein; (2) changes in forearm blood flow during mental stress, a measure of nitric oxide-mediated effect on resistance vessels; (3) excretion of urinary nitrite/nitrate as a measure of total body nitric oxide production; and (4) F2-isoprostane metabolite, a measure of oxidative stress, in healthy Glu298 (n = 12) and Asp298 (n = 13) homozygotes. There were no significant differences in acetylcholine dose responses (P = 0.29) in Glu298 and Asp298 homozygotes. Responses to glyceryl trinitrate, prostaglandin E1 and the alpha-adrenergic agonist phenylephrine did not differ by genotype. Forearm blood flow was similar at rest and increased significantly (from 7.5 ml/min/100 ml to 12.2 ml/min/100 ml; P = 0.003), but similarly (P = 0.2), during mental stress in both genotypes. Asp298 homozygotes excreted significantly less nitrate/nitrite than Glu298 homozygotes (nitrate + nitrite/creatinine ratio 0.05 +/- 0.01 vs. 0.09 +/- 0.01, respectively; P < 0.005). Urinary F2-isoprostane metabolite excretion did not differ (Glu298, 2.04 +/- 0.25 ng/mg creatinine; Asp298, 1.85 +/- 0.37 ng/mg creatinine; P = 0.7). We conclude that in healthy volunteers the Glu298Asp polymorphism affects endogenous nitric oxide production without affecting nitric oxide-mediated vascular responses. This polymorphism may only have clinical significance in the presence of endothelial dysfunction.

Comparative study of epidurally administered clonidine and buprenorphine on anesthetic requirement and electroencephalographic activity.

The author investigated the effects of epidurally administered buprenorphine (BPN) and clonidine (CLO) on the potentiation of halothane anesthesia in terms of the minimum alveolar concentration (MAC), hemodynamics, and electroencephalographic activity in the patients undergoing lower abdominal surgery. Thirty-four women (ASA-1) were studied after the epidural administration of either 10 ml saline (group A, n = 8), 10 ml saline with 0.4 mg BPN (group B, n = 13), or 10 ml saline with 150 micrograms CLO (group C, n = 13). The MAC of halothane was reduced by 32% in group B (p < 0.05), and by 23% in group C (p < 0.05) compared with group A. The delta activity on the electroencephalogram (EEG) was more dominant in groups B and C 20 and 30 minutes after the administration of BPN and CLO compared with group A. The alpha activity in group A was significantly greater than that in the other groups. The delta activity in groups B and C was increased significantly compared with group A. The blood pressure was significantly lower after the epidural administered of CLO in group C, compared with groups A and B. The study concluded that epidurally administered CLO significantly reduce the MAC of halothane and also resulted in significant acceleration of delta activity on the EEG, as did BPN. The mechanisms by which the central nervous system (CNS) is depressed by epidural BPN and CLO are different, but this may have resulted from their direct action on the CNS via the systemic and spinal absorption of BPN and CLO.

[Effect of intrathecal administration of opioid on minimum alveolar concentration and postoperative pain relief--a comparison of morphine and buprenorphine].

Intrathecal morphine (Mor) exerts potent analgesic effect and decreases anesthetic requirement. However, morphine was reported to have various uncomfortable side effects, and buprenorphine (BPN) is considered as an alternative opioid. The aim of this study was to investigate the effect of intrathecal BPN and Mor on the MAC of halothane and the relief of postoperative pain. The result shows that the MAC of halothane decreases dose dependently both in the BPN and Mor groups. The decrease in halothane MAC with 0.05 mg intrathecal BPN was equipotent with the intrathecal administration of 0.5 mg Mor. Adequate postoperative analgesia and severe pruritus were observed in the 0.5 mg Mor group. The intrathecal administration of 0.05 mg and 0.075 mg BPN has shown mild analgesic effect without any side effects.

Partial trisomy of the distal segment 14q.

The case of a male infant with duplication of the distal segment of chromosome 14q is described. There was an extra chromosomal segment at the distal end of the long arm of chromosome 17. Banding techniques suggested that the extra segment might be the distal segment of chromosome 14q. DNA analysis using probes from distal 14q as well as from other parts of the genome confirmed that the extra segment consisted of the distal part of 14q. Both the proband's parents and his elder sister had normal karyotypes.

Thirty-one autopsy cases of trisomy 18: clinical features and pathological findings.

The clinical features and morphological findings in 31 Japanese infants with trisomy 18 are presented. The majority were small-for-date infants. There was no sex predominance in our series, as opposed to male:female ratios of 1:3 reported in the literature. The average age at death was greater in females than in males. Cardiovascular anomalies were consistently present; ventricular septar defect and patent ductus arteriosus being the most common malformations. Various other internal malformations including the Arnold-Chiari malformation were observed.