前列腺增生症证型与体内性激素水平的临床研究

目的:研究前列腺增生症中医证型与体内性激素水平的相关性.方法:选择500例患者,中医辨证分为血瘀下焦、膀胱湿热、肾阴亏虚、肾阳不足、肺热气闭,均在就诊次日上午抽空腹血4 mL,进行血清性激素测定.结果:T值以血瘀下焦、肾阴亏虚证较高,肾阳不足证明显偏低,两者比较差别有显著性(P＜0.01);膀胱湿热证和肺热气闭证居中,与血瘀下焦、肾阴亏虚证比较差别也具有显著性(P＜0.05).E2值以肾阳不足证明显偏高,血瘀下焦和膀胱湿热证次之,肾阴亏虚和肺热气闭证较低.各组间比较差别具有显著性(P＜0.01).结论:前列腺增生症各证型与血清性激素水平变化有一定规律可循,同时也为证型客观化、微观化提供了相应证据.     

颅脑损伤患者上消化道出血的预防和治疗(附625例报告)

目的探讨颅脑损伤后上消化道出血的预防措施及其治疗方法。方法回顾性分析625例颅脑损伤后上消化道出血的病例,在治疗原发伤病基础上,采用止血、制酸、保护胃黏膜等对症处理,同时应用阿托品治疗22例;胃镜下治疗8例;胃次全切除术5例。结果本组病例中,治愈572例,缓解36例,无效5例,死亡12例,其中阿托品治愈20例;胃镜下治愈6例;胃次全切除术治愈4例。结论预防和治疗的重点是消除颅脑损伤病灶和保护胃黏膜,常规处理方案效果满意,简单、经济且安全有效,但必要时应及时使用特殊治疗手段,以迅速控制出血病情。     

谷氨酰胺和生长激素对短肠综合征患者肠道代偿作用

目的探讨谷氨酰胺和生长激素对短肠综合征(SBS)患者的肠道代偿作用。方法26例短肠综合征患者残余小肠长度为0～100(中位数42.5)cm,手术后接受肠外营养(PN)支持3-52个月,联合应用生长激素(GH)(0.10±0.06)mg·kg-1·d-1和谷氨酰胺(GLN)(0.30±0.17)g·kg-1·d-1进行肠道促代偿治疗。结果26例接受GH加GLN治疗的SBS患者,其中9例(34.6%)治疗后近期内完全摆脱PN;8例(30.8%)经治疗后明显减少了PN用量,从每周需要PN(6.0±1.0)d下降至(4.2±1.0)d,每周PN需要量从(13.6±5.2)L降至(8.2±3.3)L;9例(34.6%)在治疗后仍依赖PN维持。结论经过合适的营养支持和肠道促代偿治疗,大多数短肠综合征患者残留肠道能充分代偿,完全摆脱PN或减少PN用量,长期健康生存。     

Thyrotrophin-Releasing Hormone Raises Cytosolic Free Calcium Concentration in Human Adenomatous Somatotrophs and Corticotrophs; Comparison with in vivo Responsiveness to Thyrotrophin-Releasing Hormone in Patients with Acromegaly or Cushing's Disease

The effect of thyrotrophin-releasing hormone (TRH) on intracellular free Ca²⁺ concentration, [Ca²⁺)i, was investigated with the fluorescent dye fura-2 in cell suspensions obtained from 13 human growth hormone-secreting adenomas and 6 adrenocorticotrophin-secreting adenomas. Preoperatively, 9 out of 13 acromegalic patients showed a positive growth hormone response to TRH administration while none of the 6 patients with Cushing's disease had a plasma adrenocorticotrophin increase after TRH injection. In all the growth hormone-secreting adenomas the addition of TRH (100 nM) caused a significant rise in [Ca²⁺]i (from a resting level of 133±40 (±SD) to a value of 284±119 nM at 100 nM TRH, n = 42; P<0.001). The transient induced by TRH was found to have a dual origin, one due to Ca²⁺ mobilization from intracellular stores which was maintained in presence of EGTA (3mM) and verapamil (10 μM) and a plateau phase due to Ca²⁺ influx from the extracellular media. Somatostatin (0.1 μM) lowered both resting [Ca²⁺]i and TRH-induced transients. The effect of gonadotrophin-releasing hormone on [Ca²⁺]i was evaluated on cell suspensions obtained from 6 growth hormone-secreting adenomas. Gonadotrophin-releasing hormone (100 nM) caused a marked rise in [Ca²⁺]i (from 179±25 to 283±15nM) on the cell suspension obtained from the only in vivo responsive adenoma while it was ineffective in the remaining 5. Although TRH was ineffective in modifying plasma adrenocorticotrophin levels in all patients with Cushing's disease, in 5 out of 6 tumors the addition of 100 nM TRH caused a significant rise in [Ca²⁺]i (from 102.5 ± 36 to 163±66 nM, n = 22; P < 0.005). However, the effect of TRH on [Ca²⁺]i was significantly lower than that caused by arginine vasopressin, a physiological stimulator of adrenocorticotrophin release ([Ca²⁺]i values; 145±78 nM at 100 nM TRH versus 300±140 at 10 nM arginine vasopressin, n = 15; P<0.05). Moreover, the effect of arginine vasopressin on [Ca²⁺]i was detectable at concentrations as low as 0.1 nM while TRH was effective at concentrations higher than 1 nM. By contrast, gonadotrophin-releasing hormone was ineffective in increasing [Ca²]i in all the adrenocorticotrophin-secreting adenomas studied. Collectively, these data indicate that sensitivity to TRH is present in almost all the growth hormone- and adrenocorticotrophin-secreting adenomas independently of the responsiveness of the individual patients to the peptide.     

Regulation of Basal and Nursing-Induced Secretion of Growth Hormone in the Neonatal Rat: The Involvement of Serotonergic, Muscarinic Cholinergic, Alpha2-Adrenergic, Somatostatin and Growth Hormone-Releasing Hormone Systems

Various neural factors are involved in the suckling-induced increase in serum growth hormone (GH) levels in neonatal rats, and, in the present study the serotonergic, cholinergic, somatostatin and GH-releasing hormone (GHRH) systems were investigated. The serotonin (5-HT) precursor 5-hydroxy-L-tryptophan (5-HTP) and the 5-HT receptor agonist quipazine maleate stimulated serum GH levels in 2-day-old rat pups separated from their mothers for 6 h. The increase in serum GH during suckling was further elevated by 5-HTP. The 5-HT antagonist cyproheptadine decreased serum GH levels in separated 2-day-old pups, and although it reduced the amplitude of the suckling-induced increase in serum GH concentration, it did not alter the increase in serum GH on a percentage basis. The effect of the cholinergic muscarinic antagonist atropine sulfate (ATR) was similar to that of cyproheptadine. Moreover, in separated pups, ATR prevented the increase in serum GH induced by 5-HTP. In contrast with 2-day-old pups, ATR completely eliminated the suckling-induced release of GH in 10-day-old rats. However, ATR failed to prevent GH release induced by the α₂-adrenergic agonist clonidine HCI in 10-day-old male pups. While thyrotropin-releasing hormone increased serum GH levels, rat GHRH failed to alter serum GH levels either in separated or in suckled 2-day-old rat pups. Immunoneutralization for rat GHRH eliminated the increase in serum GH induced by clonidine HCI in 10-day-old pups, but (on a percentage basis) failed to prevent the GH-increasing effect of suckling in 2-day-old pups. While somatostatin failed to significantly decrease serum GH in separated 2-day-old pups, it effectively decreased serum GH levels in 2-day-old pups which were suckled. Cysteamine, which depletes hypothalamic somatostatin, increased serum GH in separated 2-day-old pups, and further increased the suckling-induced levels of serum GH. Cysteamine partially prevented the GH-decreasing effect of ATR. The present findings suggest that 1) the serotonergic and cholinergic systems are involved in the regulation of GH secretion as early as day 2 postpartum; 2) the serotonergic and cholinergic systems modulate the basal, and do not modulate the suckling-induced levels of serum GH; 3) the serotonergic system may exert its stimulatory influence on GH secretion only in the presence of a functional muscarinic cholinergic system; 4) the cholinergic system, at least in part, stimulates GH secretion via a cysteamine-sensitive system (probably by inhibiting somatostatin); 5) the cholinergic system is not functionally coupled with the α₂-adrenergic system, which stimulates GH secretion via rat GHRH; 6) since in 10-day-old pups clonidine HCI was effective only in males, while suckling was effective in both sexes, the α₂-adrenergic system is not involved in the suckling-induced increase of serum GH; and finally 7) neither somatostatin nor rat GHRH seem to be involved in the suckling-induced changes in serum GH. The findings are consistent with the hypothesis that the high circulating GH levels in the neonatal rat are due to alternative GH-releasing factors, perhaps thyrotropin-releasing hormone or γ-aminobutyric acid. The neurohumoral mediator of the suckling-induced GH release in neonatal rats remains to be identified.     

伽玛刀治疗垂体腺瘤126例的临床分析

目的 评价伽玛刀治疗垂体腺瘤的疗效和并发症.方法 对2000年8月至2005年12月间伽玛刀治疗垂体腺瘤并有完整临床资料.病人年龄15～76岁,肿瘤最大径<10mm 68例、10～20mm 56例、>20mm 2例,伽玛刀治疗剂处方量为15～30Gy、50%～65%等剂量曲线.结果 随访1～6年,肿瘤消失75例,肿瘤缩小28例,肿瘤无变化15例,肿瘤继续增大8例.肿瘤生长控制率93.6%(118/126);激素水平恢复正常率63%(49/78),垂体功能低下发生率为15%,因肿瘤复发或激素水平未恢复再行肿瘤切除术5例.结论 伽玛刀治疗垂体腺瘤,能控制垂体腺瘤肿瘤生长,可恢复垂体内分泌功能异常改变.     

Safety, tolerability and pharmacokinetic study of recombinant human parathyroid hormone in healthy male Chinese subjects

AIM： To determine the safety, tolerability and pharmacokinetic parameters of a new drug recombinant human parathyroid hormone [ rhPTH （1-84）] in healthy male Chinese subjects. METHODS： domly divided Thirty-six healthy male volunteers were rangroups received into 3 groups. The volunteers in these single subcutaneous injection of rhPTH （ 1-84） in a dosage of 1, 2 and 4 μg/kg respectively. Blood samples were obtained before and after administration within 24 hours. The rhPTH concentrations in sennn were determined by enzyme linked immunosorbent assay （ELISA）. The pharmacokinetic parameters determined with use of standard noncompartmental analysis were the maximum serum concentration （ Cmax ）, the time to attain that concentration （ tmax ）, and the area under the serum concentration-time curve up to 24 hours（ AUC0-24 ） and up to infinity （AUC0-∞）. Dose proportionality of pharmacokinetic parameters （AUC, Cmax of every volunteer of each dosage and A UC was computed from log transformed data） and was examined by mean of analysis of variance （ANOVA） using SPSS software package. In the study, subjects＇ symptoms, objective signs, and vital signs, including blood pressure, heart rate, respiratory rate and body temperature, were checked and 12-lead electrocardiography was recorded before and after drug administration within 24 hours. Routine laboratory tests, including hematology, blood biochemistry, serum electrolyte, and urinalysis, were performed before and after drug administration within at 24 hours.[第一段]     

Parathyroid hormone decreases in vivo insulin effect on glucose utilization

Hyperparathyroidism is associated with impaired glucose tolerance, and parathyroidectomy may improve carbohydrate homeostasis. It has been suggested that parathyroid hormone (PTH) suppresses insulin secretion but it is unclear whether it also interferes with the peripheral action of insulin. To evaluate in vivo effects of PTH on insulinmediated glucose utilization, 15 male Sprague Dawley rats were continuously infused with rat PTH (1–34) using an Alzet miniosmotic pump at a rate of 0.03 nm/hour. Controls were infused with the vehicle alone. Following 5 days of PTH infusion, plasma calcium (Ca) levels were higher in the PTH-infused rats (12.3±0.2 versus 9.9±0.1 mg/dl, P<0.01). On the 5th day, glucose (700 mg/kg) and insulin (0.175 U/kg) were given as a bolus infusion through the left femoral vein, blood samples were obtained from the right femoral vein, and plasma glucose and insulin were measured at basal (0 minutes) and at 2, 5, 10, and 20 minutes postinfusion. Basal, nonfasting glucose levels were higher (166±4 versus 155±4 mg/dL, P<0.04) in the PTH-infused rats but their insulin levels were similar to those of controls (6.5±0.6 versus 5.6 ±0.5 ng/ml). Postinfusions and maximal (2 minutes) glucose and insulin levels were similar in both groups. However, although insulin levels were similar in both groups at all measured time points, glucose levels at 20 minutes were higher in the PTH-treated rats (205±13 versus 173±9; P<0.03). Also, calculated glucose disappearance rates (Kg) were decreased in the PTH-infused rats (4.05±0.3 versus 4.63±0.8; P=0.054), suggesting an impaired peripheral effect of insulin on glucose utilization. To gain insight into the potential contribution of the hypercalcemia or the PTH to these abnormalities, correlation evaluations were performed. Only in PTH-infused rats did plasma Ca correlate with plasma glucose at 0 and 20 minutes (r=0.6, P=0.02; r=0.7, P=0.01) and with the area under the glucose curve (r=0.6, P=0.03) during the glucose-insulin infusion. Also only in PTH-infused rats did PTH correlate with 0 (P=0.07) and 20-minute (P=0.02) plasma glucose levels. There was no correlation between either Ca or PTH and basal insulin levels or the area under the insulin curve in either group. Consequently, we suggest that in the rat, PTH infusion associated with hypercalcemia impairs insulin effect on glucose utilization in vivo and this defect may be induced by the Ca, PTH, or both.This study was presented in part at the 76th Annual Meeting of the Endocrine Society, Anaheim, CA, USA, June 1994.     

Effects of tumor necrosis factor alpha on parathyroid hormone-induced increases in osteoblastic cell cyclic AMP

Summary Tumor necrosis factor α (10⁻¹⁰–10⁻⁸M) had no effects on cyclic AMP production by the osteoblastic osteosarcomal cells, Saos-2 and G292, or normal rat calvarial cells. The cytokine did, however, inhibit the parathyroid hormone (PTH)-induced effect on cyclic AMP in the Saos-2 and normal rat osteoblastic cells. This inhibitory effect did not occur on prostaglandin E₂-induced cyclic AMP increases in the osteoblastic cells. Interleukin-1 (10 U/ml −100 U/ml) did not produce any effect on basal levels or PTH-induced cyclic AMP increases in these cells.     

Effects of androgen treatment in impotent men with normal and low levels of free testosterone

The relation between sexual function and serum free testosterone (fT) levels, which represent the active fraction of circulating testosterone, was evaluated. Two groups of impotent male subjects with mild hypogonadism were treated with oral testosterone undecanoate (TU); these men presented with tT/luteinizing hormone (LH) ratio and tT levels at the lower limits of normal. The first group had serum fT below 6.6 ng/ml, considered the lower normal value, according to our laboratory method, whereas the second group had normal fT limits. Administration of TU improved sexual function only in impotent men with low fT levels, but not in subjects with normal fT levels, even though the tT levels and the tT/LH ratio of the two groups were not significantly different. The results of our study suggest the presence of a minimun serum fT threshold, lying near the lower normal range, which determines the male sexual function. Moreover, serum fT levels were a more sensitive index than tT for identifying impotent men who can be successfully treated with androgens.