Hypothalamic-pituitary-gonadal axis function after successful kidney transplantation in men and women

BACKGROUND: Renal transplantation (RT) is the most common solid organ transplant procedure. Several studies have reported on gonadal function in male and female RT recipients with controversial results. METHODS: Forty consecutive patients (20 male, 20 female) with a fully functioning allograft (serum creatinine 0.8-1.3 mg/dl) for at least 15 months after RT were included in the study. Their ages ranged from 23 to 44 years (median 38) and their post-RT follow-up lasted 15-86 months (median 23). FSH, LH, prolactin, 17-beta-estradiol, testosterone, androstenedione and dehydroepiandrostrone were determined in all patients and compared with a group of 80 healthy subjects. Pelvic ultrasonography was performed in all participants. RESULTS: Testosterone was below the normal range in 70% of male patients and within the lowest third in the remainder; a lack of LH increase indicated an inhibition of the reproductive axis. Male testosterone values were negatively influenced by calcineurine inhibitors treatment (P < 0.005), but positively influenced by a better graft function (P < 0.0001). Testicular and prostate volumes were reduced with respect to controls, with the latter related to circulating testosterone levels. Ten of the women (50%) had menstrual cycle disorders after RT, three being affected by transient, and three by persistent, amenorrhea. Another two patients had had transient polymenorrhea. In four women (20%), a premature ovarian failure was diagnosed. No relationship was found between female reproductive function and age, graft function or duration of the post-transplant period. Prolactin was lower in patients on calcineurin inhibitors (P < 0.01). CONCLUSIONS: Abnormalities of the reproductive system were frequent after successful RT in both genders.     

Hypothalamic-pituitary-gonadal function in two infants with Smith-Lemli-Opitz syndrome.

We report on the hypothalamic-pituitary-gonadal function in 2 male infants with the Smith-Lemli-Opitz (SLO or RSH) syndrome. Both infants had abnormal external genitalia. Basal and LHRH stimulated plasma gonadotropins were normal for age (1 month). Plasma testosterone, androstenedione, and dehydroepiandrosterone sulfate were normal for age and sex. Some forms of congenital adrenal hyperplasia (17,20-desmolase deficiency, 17 alpha-hydroxylase deficiency, and 3 beta-hydroxysteroid dehydrogenase deficiency) were ruled out by hormonal studies. The endocrinological findings indicate a normal hypothalamic-pituitary-gonadal function and a normal adrenal steroid biosynthesis in these 2 patients. A partial androgen receptor defect causing the genital malformations seems possible in one patient. Whether 5 alpha-reductase deficiency is the cause of the male pseudohermaphroditism in SLO syndrome remains the subject of future studies.     

Hypothalamic-pituitary-gonadal function in two infants with Smith-Lemli-Opitz syndrome

We report on the hypothalamic-pituitary-gonadal function in 2 male infants with the Smith-Lemli-Opitz (SLO or RSH) syndrome. Both infants had abnormal external genitalia. Basal and LHRH stimulated plasma gonadotropins were normal for age (1 month). Plasma testosterone, androstenedione, and dehydroepiandrosterone sulfate were normal for age and sex. Some forms of congenital adrenal hyperplasia (17,20-desmolase deficiency, 17α-hydroxylase deficiency, and 3β-hydroxysteroid dehydrogenase deficiency) were ruled out by hormonal studies. The endocrinological findings indicate a normal hypothalamic-pituitary-gonadal function and a normal adrenal steroid biosynthesis in these 2 patients. A partial androgen receptor defect causing the genital malformations seems possible in one patient. Whether 5α-reductase deficiency is the cause of the male pseudohermaphroditism in SLO syndrome remains the subject of future studies. © 1992 Wiley-Liss, Inc.     

Acquired immune dysfunction in homosexual men: immunologic profiles

Homosexual men with Kaposi sarcoma, lymphadenopathy syndrome, opportunistic infection, and nonhomosexual traditional Kaposi sarcoma were evaluated for B cell, T cell, and complement immunity and compared to normal controls and homosexual controls. No significant immunologic abnormalities were found in the traditional Kaposi group. All homosexual groups, including the homosexual controls, had a significant decrease in the helper/suppressor cell ratio. Functional abnormalities of T-cell immunity were observed in the homosexual Kaposi sarcoma, lymphadenopathy syndrome, and opportunistic infection groups. Significant elevations of IgG, IgM, IgA, and IgE were found in the lymphadenopathy group, while only IgG and IgA were elevated in the Kaposi sarcoma group. C3, C4, and immune complexes were normal, while total hemolytic complement activity was increased in the Kaposi sarcoma and lymphadenopathy syndrome groups.     

Myofilament dysfunction in cardiac disease from mice to men

In healthy human myocardium a tight balance exists between receptor-mediated kinases and phosphatases coordinating phosphorylation of regulatory proteins involved in cardiomyocyte contractility. During heart failure, when neurohumoral stimulation increases to compensate for reduced cardiac pump function, this balance is perturbed. The imbalance between kinases and phosphatases upon chronic neurohumoral stimulation is detrimental and initiates cardiac remodelling, and phosphorylation changes of regulatory proteins, which impair cardiomyocyte function. The main signalling pathway involved in enhanced cardiomyocyte contractility during increased cardiac load is the β-adrenergic signalling route, which becomes desensitized upon chronic stimulation. At the myofilament level, activation of protein kinase A (PKA), the down-stream kinase of the β-adrenergic receptors (β-AR), phosphorylates troponin I, myosin binding protein C and titin, which all exert differential effects on myofilament function. As a consequence of β-AR down-regulation and desensitization, phosphorylation of the PKA-target proteins within the cardiomyocyte may be decreased and alter myofilament function. Here we discuss involvement of altered PKA-mediated myofilament protein phosphorylation in different animal and human studies, and discuss the roles of troponin I, myosin binding protein C and titin in regulating myofilament dysfunction in cardiac disease. Data from the different animal and human studies emphasize the importance of careful biopsy procurement, and the need to investigate localization of kinases and phosphatases within the cardiomyocyte, in particular their co-localization with cardiac myofilaments upon receptor stimulation.     

Neurological status predicts response to alpha-blockers in men with voiding dysfunction and Parkinson's disease

OBJECTIVES:To evaluate predictors of the response to doxazosin, a selective alpha-adrenoceptor antagonist, when used for the treatment of lower urinary tract symptoms in men with Parkinson''s disease.METHODS:In a prospective study, 33 consecutive men (mean age 59.2±7.0 years) with Parkinson''s disease and lower urinary tract symptoms were evaluated. Neurological dysfunction was assessed with the Unified Parkinson''s Disease Rating Scale. Urological assessment was performed at baseline and after 12 weeks of treatment with 4 mg/day of extended-release doxazosin, including symptom evaluation with the International Continence Society male short-form questionnaire, an assessment of the impact of lower urinary tract symptoms on quality of life and urodynamics. Clinical and urodynamic predictors of response were specifically evaluated.RESULTS:Compared with the score at baseline, the total International Continence Society male short-form score was reduced after doxazosin administration, from 17.4±7.5 to 11.1±6.9 (p<0.001). The impact of lower urinary tract symptoms on quality of life was also significantly reduced, from 1.8±1.1 to 1.0±1.0 (p<0.001) and the maximum urinary flow varied from 9.3±4.4 to 11.2±4.6 ml/s (p = 0.025). The severity of neurological impairment was the only predictor of the clinical response. Additionally, patients with a Unified Parkinson''s Disease Rating Scale score lower than 70 had a significantly higher chance of clinical improvement with doxazosin treatment than those with higher Unified Parkinson''s Disease Rating Scale scores did (RR = 3.10, 95% CI = [1.15 to 5.37], p = 0.011).CONCLUSIONS:Doxazosin resulted in the improvement of lower urinary tract symptoms and the maximum flow rate and was well tolerated in men with Parkinson''s disease. The response to treatment is dependent on the severity of neurological disability.     

Antiprostatic effect of cimetidine in rats

Administration of large doses of cimetidine for 45 days to rats decreases the weight of the prostate and seminal vesicles without affecting the testicles. The decrease in weight is due to a marked regression in the prostate of both epithelial and stromal tissue.Treatment with cimetidine also causes an increase in the plasma testosterone level without modifying the plasma values of LH and prolactin. The mechanism of action of cimetidine is discussed. In presence of high levels of testosterone, cimetidine depresses structures such as the prostate and seminal vesicles, which are sensitive to androgens, but does not depress the weight or change the histology profile of the testicles, which are also rich in androgen receptors. Perhaps cimetidine binds to androgen receptors differently in the prostate and in the testicles because of differences in receptor structure or more probably, cimetidine interacts with zinc metal ion essential to prostate growth and androgen action by lowering zinc prostatic levels and consequently depresses the prostatic weight.     

Immunomodulation of cimetidine in healthy volunteers

Summary The effect of cimetidine, a histamine H2-receptor antagonist, on the immune system in man was investigated in 11 healthy volunteers. Cimetidine was administered orally in daily doses of 800 mg for a period of 7 days. At the end of the administration period the number of peripheral CD8+ (cytotoxic/suppressor) cells had diminished significantly (P<0.05) along with a corresponding increase in the CD4+ (helper/inducer): CD8+ (cytotoxic/suppressor) cell ratio (P<0.01). Compared with pretreatment values, a significant in vitro blastogenic response to mitogen stimulation with concanavalin A (P<0.005), phytohemagglutinin (P<0.01), and pokeweed mitogen (P<0.05) was observed in lymphocytes of volunteers after cimetidine intake. The cell-mediated hypersensitivity as assessed by skin testing of seven recall antigens was also enhanced significantly (P<0.001). Using Spearman's coefficient of correlation to compare mitogen-stimulation tests and skin tests of delayed hypersensitivity to the CD4+:CD8+ ratio, yielded a positive correlation (r=0.89;r=0.85, respectively). These effects were reversible 96 h after the last cimetidine dose. In contrast, leukocytes, total T lymphocytes (CD2+, CD3+), CD4+ (helper/inducer) cells, natural killer cells (Leu7+), immunoglobulins, and total complement, C3, C4 were unaffected by cimetidine administration.Abbreviations Con A concanavalin A - NK natural killer - PHA phytohemagglutinin - PWM pokeweed mitogen This work is dedicated to the memory of Professor Dr. med. E.E. Ohnhaus, a stimulating teacher and a great person, who passed away in 1988     

Regulatory dysfunction in leukotaxis.

The chemotactic factor inactivator (CFI) in human serum appears to have important regulatory function in the inflammatory response. In humans with elevated serum levels of CFI, defective mobilization of leukocytes in vivo has been noted, both in skin windows and in skin testing with various antigens. In experimental immune complex-induced acute inflammatory reactions in rat skin and lung, purified human CFI at very low doses has potent antiinflammatory effects and is able to suppress permeability changes, neutrophil infiltration, and hemorrhage, all of which are dependent initially on the role of leukotactic mediators.