Clinical and biochemical effects of stanozolol therapy for hereditary angioedema

Stanozolol, an inexpensive anabolic steroid with a 30:1 anabolic:androgenic ratio, was administered to 12 male and 15 female patients with biochemically proven hereditary angioedema over a 2-yr period to obtain a systematic assessment of the relationship between drug dosage and clinical response, incidence of side effects, and amelioration of complement abnormalities. All 27 patients attained the minimal effective dose, ranging from 0.5 to 2 mg daily, which controlled the frequency and intensity of symptoms with minimal side effects. At daily maintenance doses of 2, 1, and 0.5 mg the frequencies of attacks per weeks of therapy were 1/14.6, 1/7.2, and 1/8.2 wk, respectively. Side effects with maintenance therapy included menstrual abnormalities and virilization in four females and elevation of serum creatinine phosphokinase (CPK) in five males. In six patients on maintenance doses of stanozolol, serum levels of testosterone, free thyroxin (T4), and thyroxin binding globulin (TBG) (four males), and of estradiol, progesterone, T4, and TBG (two females) were normal. Slightly low serum levels of progesterone and TBG were found in two females who had normal menstrual cycles. Statistically significant elevations above pretherapy levels of serum inhibitor to the activated first component of complement function and C4 protein and function occurred when patients were on maintenance therapy, but these measurements remained below the lower limit of normal range. Higher doses of stanozolol (4 mg/day), which caused greater immunochemical responses, were unnecessary for control of clinical disease and were unjustified for chronic therapy because of more frequent side effects.     

Neuroendocrine changes in acute schizophrenia as a function of clinical state and neuroleptic medication.

Changes in levels of prolactin, growth hormone, luteinizing hormone, and follicle stimulating hormone in serum, and testosterone in plasma, have been studied in 38 patients with acute schizophrenic illnesses in a 4-week double-blind comparison of the 2 isomers of flupenthixol and placebo. Only prolactin showed changes which could be related either to changes in clinical state or to the effects of medication. Prolactin levels increased during treatment with the therapeutically active alpha-isomer of flupenthixol but were unchanged with the inactive beta-isomer and placebo. Although there was a significant relationship between prolactin level and antipsychotic effect in patients on alpha-flupenthixol, in the individual case prolactin level was not a strong predictor of therapeutic response; and in patients on inactive medication changes in prolactin level could not be related to sympton change. There was a time lag of at least 2 weeks between the increase in prolactin secretion in patients on alpha-flupenthixol and the therapeutic effect attributable to medication. This delay suggests that if the antipsychotic effect is dependent upon dopamine receptor blockade it is not a direct consequence of this action. Perhaps dopamine receptor blockade permits other, and slower, changes to take place and it is these changes, rather than dopamine receptor blockade itself, which are reflected in clinical improvement.     

Prolactin, AVP, angiotensin II, corticosterone and aldosterone in the rat during weaning

In the rat significant changes in the control of body water and electrolyte homeostasis take place during the weaning period (16-24th day of life). This study was performed to analyse how the serum levels of hormones that are known to modulate body water homeostasis change during that period. The serum levels of aldosterone, corticosterone and prolactin increased significantly from 10 to 20 days, whereas those of arginine vasopressin were the same between 10 days and 20 days but increased significantly from 10 to 40 days. Serum levels of angiotensin II increased significantly from 10 to 20 days but decreased from 20 to 40 days, at which time they were significantly lower than in 10-day-old rats. In prolonged-suckling rats, that is, rats which suckled until the 20th day of life, the serum levels of corticosterone, aldosterone and prolactin were somewhat lower than in control rats and those of prolactin were not detectable at 16-20 days. It is concluded that important changes in the serum levels of hormones that regulate body water and electrolyte homeostasis take place during weaning. The postnatal increase in the serum levels of corticosterone and aldosterone is independent of weaning to solid food. The prolactin serum levels seem to be influenced by the length of the nursing period.     

Immunological effects of high dose administration of anti-CD4 antibody in rheumatoid arthritis patients.

A phase I/II trial of the anti-CD4 monoclonal antibody (mAb) was undertaken in seven rheumatoid arthritis patients in order, (1) to investigate changes in clinical symptoms and possible side effects, and (2) to study the pharmacokinetics and to determine the dose required to achieve saturation of antibody binding sites on blood leucocytes. BL4mAb is a murine IgG2a which binds to the group 2B epitope of the V1 N terminal domain of the CD4 molecule. It inhibits syncitium formation by human immunodeficiency virus-infected cells. BL4 was administered by one hour-long intravenous infusion each day, for 10 days. Doses were steadily increased from 20 mg/d to 40 mg/d in the first three patients (group I) in an attempt to reach a serum antibody residual level sufficient to saturate CD4+ circulating cells. The three other patients (group II) received a dose of 40 mg/d during 10 consecutive days. One patient who presented chills and mild fever during the first BL4 infusion was not included in the analysis. No clinical side effects were observed in the six other BL4-treated patients. Clinical parameters of disease activity were improved within the first 14 days. Clinical improvement was still significant at day 30 in five patients, but at day 60, only the Ritchie index was still below pretreatment levels. Delayed type hypersensitivity reactions decreased in the three patients who exhibited positive reactions before BL4 administration. A transient drop in peripheral blood CD4+ lymphocyte counts occurred during each infusion in the first days of treatment. Pre-infusion CD4+ lymphocyte counts were moderately decreased within the first 8 days, but rose to pretreatment levels 3 days after the last infusion. BL4 residual levels in serum steadily increased to reach 8.0 micrograms/ml in group I and 9.8 micrograms/ml in group II. Saturation of BL4 binding sites was achieved after 2 days of treatment in all patients of group II but in only one of group I. Four out of six patients produced antibodies against the anti-CD4 mAb. Immunization appeared between days 12 and 50. This study shows that saturation of anti-CD4 mAb binding sites can be achieved by infusions of high doses (40 mg/d) of BL4 without clinical side effects. The results would encourage further placebo-controlled trials, since no definite conclusion can be drawn from the present study as regards clinical efficacy.     

Effect of vitamin E therapy on sexual functions of uremic patients in hemodialysis.

Twenty-four uremic patients on hemodialysis who had never been treated with vitamin E or related drugs and 12 control patients with normal renal function were studied. Hemodialysis patients were randomly divided into two groups; 12 were treated with oral vitamin E (300 mg/day) for eight weeks and 12 uremic patients and 12 controls were given placebo. Serum vitamin E, prolactin, FSH, LH, and free testosterone levels were measured in all patients before and after treatment. After the vitamin E treatment serum prolactin levels were significantly decreased (50.8 vs 15.4 ng/ml, p < 0.01). Vitamin E levels were significantly increased (1.11 vs 1.22 mg/dl, p < 0.05). Serum FSH, LH and free testosterone were not affected. In the other two groups there were no significant changes. These results show that vitamin E treatment lowers prolactin levels in uremic hemodialysis patients. This might be due to inhibition of central prolactin secretion. Vitamin E inhibits pituitary gland hypertrophy in vitamin E-deficient rats.     

阿立哌唑辅助治疗抗精神病药引发的高催乳素血症的对照研究

目的 探讨合并小剂量阿立哌唑对利培酮引起的高催乳素血症的治疗作用.方法 选择长期住院,且服用利培酮治疗导致高催乳素血症的缓解期精神分裂症患者86例,随机分成3组,分别合并阿立哌唑5mg,阿立哌唑10mg,安慰剂(对照组)进行4周对照研究.分别于治疗第0、1、4周末测定血清PRL水平,并采用阳性和阴性症状量表(PANSS...     

Effects of a postnatal exposure to cigarette smoke on hypothalamic catecholamine nerve terminal systems and on neuroendocrine function in the postnatal and adult male rat. Evidence for long-term modulation of anterior pituitary function

Jansson , A., Anderson , K., Bjelke , B., Fuxe , K. & Eneroth , P. 1991. Effects of a postnatal exposure to cigarette smoke on hypothalamic catecholamine nerve terminal systems and on neuroendocrine function in the postnatal and adult male rat. Evidence for long-term modulation of anterior pituitary function. Acta Physiol Scand. 144 , 453–462. Received 10 August 1 991 , accepted 11 August 1991. ISSN 0001–6772. Department of Histology and Neurobiology, Karolinska Instituter, Stockholm, Sweden, Department of Internal Medicine and Unit for Applied Biochemistry, Huddinge Hospital, Huddinge, Sweden. The purpose of this paper was to study the possible long-term effects of postnatal exposure to cigarette smoke. Male Sprague-Dawley rats were exposed to the smoke from 2 cigarettes (Kentucky reference IR-I type) every morning from day 1 after birth for a period of 5 , 10 or 20 days. The rats were decapitated 24 hours ( 5 , 10 and 20 days of exposure), 1 week (20 days of exposure) or 7 months (20 days of exposure) after the last exposure. Using the Falck-Hillarp methodology in combination with quantitative histofluorimetry catecholamine levels and changes in catecholamine utilization (aMT-induced CA fluorescence disappearance) in discrete hypothalamic catecholamine nerve terminal systems were analysed. Serum prolactin, LH, TSH and corticosterone levels were determined by means of radioimmunoassay procedures. In the postnatal period serum LH levels were significantly increased 24 hours after a 10 and 20 day exposure to cigarette smoke. In adult life after a 20–day postnatal exposure to cigarette smoke a highly significant increase was observed in serum prolactin levels, which were unaltered by this exposure when measured in the postnatal period. Twenty-four hours following a 20–day postnatal exposure, catecholamine utilization was increased in the medial palisade zone of the median eminence and substantially reduced in the parvocellular and magnocellular parts of the paraventricular hypothalamic nucleus. One week and 7 months following a 20–day postnatal exposure to cigarette smoke no alterations were observed in catecholamine levels or utilization in various hypothalamic areas including the median eminence. All the above changes were observed in the presence of an unaltered development of body weight. The results indicate that marked but temporary increases in LH secretion occur 24 hours after a postnatal exposure to cigarette smoke, while increase in prolactin secretion only develop in adult life, when the maturational processes of the brain and/or the anterior pituitary gland are completed. Changes in catecholamine levels and utilization are found in discrete hypothalamic nerve terminal networks but do not play a major role in mediating the above changes in anterior pituitary function and are probably the result of a withdrawal phenomenon.     

Low doses of dopamine agonists in the long-term treatment of macroprolactinomas

To evaluate the long-term effects of dopamine agonists in the treatment of macroprolactinoma, we studied prolactin levels and tumor size for 30 to 88 months (57 +/- 14, mean +/- S.D.) in 38 patients treated with bromocriptine or lisuride. Elevated prolactin levels became normal in 30 patients, and the tumor shrank in 29. After two years of treatment, we attempted to reduce the maintenance dose (5 to 20 mg of bromocriptine per day or 0.4 to 0.8 mg of lisuride per day); in 21 patients no changes in prolactin levels or tumor size were observed over 6 to 52 months with 0.625 to 10 mg of bromocriptine per day or 0.05 mg of lisuride per day. However, it was possible to withdraw the drug in only one patient. We conclude that dopamine agonists are usually effective treatments for macroprolactinoma and that after a response has been obtained, it can be maintained in many patients with a greatly reduced dose.     

Clinical and hormonal effects of long-term veralipride treatment in post-menopausal women

The clinical and hormonal effects of long-term, continuous treatment with veralipride, a benzamide derivative, were investigated in 10 post-menopausal women. The efficacy of veralipride in relieving hot flushes was confirmed. No significant change was detected in depressive mood scores. Except for the late appearance of moderate extrapyramidal side effects in one patient, the clinical tolerance of veralipride was good. As regards hormonal effects, veralipride, by virtue of its antidopaminergic action, raised prolactin levels. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels declined significantly, while the serum concentration of dehydroepiandrosterone sulphate (DHEAS) increased. These hormonal changes were presumably secondary to the chronic hyperprolactinaemia.     

Adverse effects of anticholinergic medication on positive schizophrenic symptoms

In a series of 36 patients with acute schizophrenia flupenthixol dosage was blindly adjusted to give a fixed level of sedation. Patients were than randomly allocated to procyclidine or placebo. The patients receiving procyclidine experienced more positive schizophrenic symptoms and less severe extrapyramidal features by comparison with placebo patients. Blood levels of prolactin and flupenthixol estimated by radioimmunoassay were not significantly changed by the addition of procyclidine. Flupenthixol dosage and levels and prolactin levels were significantly related. There was no significant association between clinical and laboratory measures, with the exception that a curvilinear (inverted U) relationship was demonstrated between flupenthixol levels and antipsychotic and extrapyramidal effects. This relationship may be due to the fact that, in a study of this design, patients resistant to the effects of neuroleptic medication are likely to be given the highest doses. The findings support earlier claims that anticholinergic medication has adverse effects on schizophrenic symptoms.     

性腺轴激素分泌的节律性变化及临床意义

目的探讨性腺轴激素的节律性变化规律及其对临床诊断治疗的指导意义.方法采用Beckman-Coulter ACCESS全自动微粒子化学发光免疫分析系统,分别测定了30例健康成年男性上午8点和下午4点的血清催乳素(PRL)、黄体生成素(LH)、卵泡刺激素(FSH)、雌二醇(E2)和睾酮(T)的水平,并将不同时间段的结果分别进行配对t检验分析.结果 PRL 和T的血清水平上午8点均显著高于下午4点(P＜0.01),而E2、LH和FSH血清水平在这两个时间段没有显著性差异(P＞0.05).结论部分性腺轴激素在1天的不同时间段有波动,尤其是PRL和T,建议临床上对性腺轴激素的监测应采集同一时间段的标本进行分析.     

Effect of incremental doses of folate on homocysteine and metabolically related vitamin concentrations in nondiabetic patients on peritoneal dialysis

The role of folate supplementation in reducing hyperhomocystinemia in patients on dialysis has been reported, but the optimal dose of folate is still unknown. The aim of the present study was to investigate whether greater than 5 mg/day folate supplementation provides any additional effect on plasma homocysteine (HCY) levels. The study was prospective, open, and had no control group. Of the 64 eligible nondiabetic patients on peritoneal dialysis with hyperhomocystinemia (>20 micromol/L), 56 were given oral folate (5 mg/day) for 3 months. When Hcy did not fall below 20 micromol/L, folate doses were increased by 5 mg every 3 months to up to 15 mg/day. With 5 mg/day supplementation, serum folate concentrations increased above the upper confidence limit in 23 patients and erythrocyte folate concentrations in 27 patients. Hcy levels decreased to less than 15 micromol/L in 6 cases and by more than 50% in 12 cases. Nineteen of the remaining patients were given 10 mg/day folate. After increasing the dose, serum and erythrocyte folate levels rose above the upper detection limit. In one patient, plasma Hcy concentrations decreased to less than 15 micromol/L. Ten patients were given 15 mg/day oral folate for an additional 3 months with no effect on homocystinemia. This study confirms that oral folate supplementation may improve hyperhomocystinemia even in patients on dialysis with normal serum or erythrocyte folate concentrations. In fact, serum and erythrocyte levels cannot predict the effect of supplementation on plasma Hcy levels. However, 5 mg/day folate supplementation normalized Hcy in 10% of cases and reduced Hcy levels in another 21%. Increasing the folate dose to greater than 5 mg/day had a minimal (10 mg/day) or no (15 mg/day) additional effect on Hcy concentrations. Despite the minimal effect of increasing folate doses, given the low cost, the absence of side effects, and the high cardiovascular risk for patients on peritoneal dialysis, a careful attempt to increase the dose of oral folate up to 10 mg/day might be suggested.     

Effects of blinding,olfactory bulbectomy,and pinealectomy on prolactin and growth hormone cells of the rat,with special reference to ultrastructure

The effects of combined blinding and olfactory bulbectomy alone or with pinealectomy on body growth, and pituitary and serum levels of growth hormone and prolactin were examined in young female rats. The animals were 23–24 days old at the time of the operations, and they were sacrificed 52 days later. Blind, anosmic rats had elevated serum and depressed pituitary stores of prolactin. The blind, anosmic rats which were also pinealectomized showed prolactin levels which were intermediate between those of the blind, anosmic and sham control animals. On the other hand, combined blindness and anosmia decreased serum growth hormone levels and again pinealectomy prevented this effect. The observed changes in the ultrastructure of prolactin and growth hormone cells were well correlated with these alterations in hormone levels.     

Effects of intraventricular injections of galanin on neuroendocrine functions in the male rat. Possible involvement of hypothalamic catecholamine neuronal systems

Galanin-catecholamine interactions have been analysed within the hypothalamus and the anteromedial frontal cortex of male rats by means of quantitative histofluorimetrical and biochemical measurements of catecholamine fluorescence in discrete catecholamine nerve terminal systems and measurements of serum levels of adenohypophyseal hormones and corticosterone using radio-immunoassay determinations. 125I-galanin binding sites were analysed and related to the distribution of galanin-immunoreactive neuronal structures in the median eminence and paraventricular hypothalamic nucleus. The results show that intraventricular injections of galanin in the awake and unrestrained male rat produce rapid increases of prolactin and growth hormone secretion but no effects on serum luteinizing hormone, thyroid stimulating hormone or on corticosterone levels. These changes in neuroendocrine function were associated with a selective reduction of the catecholamine stores in the medial palisade zone of the median eminence at the 20 min time interval. 125I-galanin binding sites were found throughout the hypothalamus including the median eminence and the magnocellular part of the paraventricular hypothalamic nucleus with a good correspondence with galanin immuno-reactivity. It is suggested that the enhancement of prolactin secretion induced by galanin involves an interaction between galanin and dopamine in the medial palisade zone leading to a reduced synthesis and/or release of dopamine and thus to a reduced prolactin inhibitory activity and to increases in prolactin secretion. A possible involvement of hypothalamic catecholamines in the galanin-induced changes of growth hormone secretion remains to be established.     

The development of subsensitivity to chlorpheniramine

To assess the development of subsensitivity to antihistamines, titrated prick skin test (PSTs) were performed to seven fivefold dilutions of histamine and either morphine or antigen at specific intervals during therapy. Ten subjects received chlorpheniramine, 24 mg per day, and placebo in a double-blind crossover study. Total wheal area was measured at baseline and after 1, 3, 7, 21, and 24 days. The dose of chlorpheniramine (or placebo) was doubled from days 22 to 24 to assess the response to dosage increase. Serum levels of chlorpheniramine were measured at days 3 and 21 in six patients. Maximal skin test suppression was observed on days 3 or 7. On day 21 there was significantly less (p less than 0.01) suppression of all PSTs than on days 3 or 7. Mean serum chlorpheniramine was 48.7 ng/ml on day 3 and 36.1 ng/ml on day 21 (not significant). There was no significant correlation between changes in serum chlorpheniramine levels and changes in PST suppression. Doubling the dose of chlorpheniramine did not achieve the maximal suppression observed at days 3 or 7. We conclude that subsensitivity to antihistamines develops between 7 and 21 days of therapy and cannot be completely overcome by doubling the dose. The decreased effect does not appear to be due to induced metabolism but may be related to increased H1 receptor number.     

Lipid effects, effectiveness and acceptability of tibolone versus transdermic 17 beta-estradiol for hormonal replacement therapy in women with surgical menopause

OBJECTIVE: To compare the effectiveness of tibolone and 17 beta-estradiol on climacteric symptoms, lipid and biochemical parameters in women with surgical menopause. METHODS: In a prospective randomised clinical trial group comparative study, the effects on the aforementioned parameters, as well as treatment compliance and side effects were studied with oral tibolone 2.5 mg per day and with transdermic 17 beta-estradiol at 50 microg per day for a period of 12 months. Statistical analysis was carried out using the Fisher-test, analysis of the variance (ANOVA) for the two factors and the Bouferoni test. RESULTS: Lipid metabolism analysis showed lower levels of HDL and triglycerides in the tibolone group. Other biochemical parameters were not affected. Similar reductions in climacteric symptoms were found in both the groups, but the tibolone group revealed a greater improvement in psychological problems and in sexual behaviour. No differences were observed with respect to compliance and side effects. CONCLUSIONS: Tibolone is as effective or more than 17 beta-estradiol in reducing climacteric symptoms, and shows greater triglyceride and total cholesterol improvements. Tibolone is a good alternative to estrogens in women with surgical menopause.     

Suppression of prolactin and cytotoxic T-lymphocyte activity in PCB-treated mice

Halogenated aromatic hydrocarbons (HAH) are ubiquitous environmental contaminants. Studies in rats have shown that HAH treatment can lead to dysregulation of circulating hormone levels, including prolactin. Reduction of prolactin levels in both rats and mice is inhibitory to immune function. Previous studies have reported suppression of alloantigen-specific cytotoxic T-lymphocyte (CTL) activity in mice treated with 3,3′,4,4′,5,5′-hexachlorobiphenyl (HxCB). Here we report that treatment of mice with HxCB (10 mg/kg body weight) leads to a significant reduction of serum prolactin levels (by 89% to 3.7 ng/ml) on day 10 post alloantigen injection (P815 mastocytoma), the day of peak alloantigen-specific CTL activity. Prolactin levels were not altered on day 3 post alloantigen injection. Treatment with bromocryptine (5 mg/kg/day) reduced serum prolactin levels slightly on day 3 and significantly (94% to 2.1 ng/ml) on day 10 post alloantigen injection. Splenic CTL activity was not altered by treatment with bromocryptine. The data presented here suggest that reduction of prolactine levels alone, to the extent observed in HxCB-treated mice, is not causative for CTL suppression.     

Lipoprotein(a) changes during natural menstrual cycle and ovarian stimulation with recombinant and highly purified urinary FSH

This prospective, randomized, controlled study compared the effects of recombinant human FSH (r-hFSH) and highly purified urinary FSH (u-hFSH HP) on lipoprotein(a) [Lp(a)] concentrations in women undergoing ovarian stimulation. Fifty infertile women were randomly allocated into two equally sized treatment groups (n = 25 per group). Thirty normal ovulation women were recruited as controls. The infertile women received u-hFSH or r-hFSH 150 IU/day starting on cycle day 2. From cycle day 6 the dose was adjusted according to ovarian response. Human chorionic gonadotrophin 10,000 IU was administered once there was at least one follicle > or =18 mm in diameter. The luteal phase was supported with progesterone 50 mg/day for at least 15 days. Repeated measurements of Lp(a) concentrations were performed during both stimulated and natural cycles. A significant increase in luteal phase Lp(a) concentrations was detected in the stimulated cycles, whereas no significant changes in serum Lp(a) concentrations were observed during natural cycles. There were no significant differences between the urinary and recombinant FSH effects on serum Lp(a). The luteal Lp(a) increase was transitory because after 1 month Lp(a) concentrations returned to baseline values if pregnancy failed to occur; in pregnant women persistent increased Lp(a) concentrations were found at the 8th week. The percentage changes in serum Lp(a) were positively correlated with the luteal progesterone increase (r = 0.40, P < 0.05), but not with follicular or luteal oestradiol increase. The women with low baseline Lp(a) (< or =5 mg/dl) had a greater increase of the Lp(a) concentrations at midluteal phase than women with baseline Lp(a) >5 mg/dl. In conclusion, the recombinant or urinary hFSH administration does not directly influence Lp(a) concentrations. The luteal Lp(a) increase in stimulated cycles is not related to gonadotrophin treatment per se, but appears to be related to the high luteal progesterone concentrations, physiologically or pharmacologically determined. Our results also suggest that the sensitivity to the progesterone changes could be related to apolipoprotein(a) phenotype.     

Postmenopausal femur bone loss: effects of a low dose hormone replacement therapy

OBJECTIVES: Previous studies indicate that low-dose hormone replacement therapy (LD-HRT) can relieve vasomotor symptoms and prevent spine bone loss. METHODS: In the present study, we evaluated the effects of a low dose of conjugated equine estrogens (CEE; 0.3 mg) associated with different progestins in continuous combined scheme [2.5 mg of medroxyprogesterone acetate (n=25), 5 mg dydrogesterone (n=27), 2.5 mg nomegestrol (n=11)] as single group, on femur bone mineral density (BMD) and bone metabolism in young postmenopausal women (相似文献   

利培酮、氟哌啶醇对血浆泌乳素影响及其与疗效的关系

目的：研究典型、非典型抗精神病药对精神分裂症患者血浆泌乳素（ＰＲＬ）水平的影响及其与疗效的关系。方法：选择符合ＩＣＤ－１０和ＣＣＭＣ－２－Ｒ诊断标准的精神分裂症患者,按双盲、随机法分为利培酮组和氟哌醇组,治疗１２周。采用阳性和生症状量表（ＰＡＳＳ）在治疗前后分别评定一次;用放射免疫法在治疗前后 浆ＰＲＬ浓度。结果：有、后两组在ＰＡＮＳＳ 发及其因子分上均无显著差异,但部酮组症状改善者明显多于氟哌啶