Spermatic and peripheral oestradiol levels in patients affected by azoospermia due to seminiferous tubular damage

Plasma levels of testosterone, androstenedione and oestradiol were determined in the spermatic venous blood of both testes of 17 patient affected by azoospermia due to tubular damage (Group I). The results were compared with those found in 5 patients affected by azoospermia of obstructive origin and 5 patients with an inguinal hernia (Group II). Mean spermatic levels of testosterone and androstenedione were not significantly different in the two groups, while the mean (± SE) oestradiol spermatic level was significantly higher in patients of Group I (5.02 ± 0.75 nM/1 vs 2.20 ± 0 36 nM/1; P < 0.05). Moreover, while the testosterone/androstenedione and the androstenedione oestradiol ratios were not significantly different in the two groups, the mean (± SE) testosterone/oestradiol ratio was significantly lower in patients of Group I (552.71 ± 80.94 vs. 939.86 ± 129.45; P < 0.025). Peripheral testosterone and androstenedione mean levels were not significantly different between the two groups while the mean peripheral oestradiol level (± SE) was significantly higher in Group I (0.107 ± 0.021 nM/1 vs. 0.038 ± 0.05 nM/1; P < 0.025). Peripheral oestradiol was not significantly related to peripheral FSH, nor to spermatic oestradiol in both groups. These results suggest the possibility that oestradiol may be involved in the pathogenesis of some cases of male infertility.     

Testosterone and Dihydrotestosterone Concentrations in Spermatic Venous Blood of Azoospermic Subjects

Testosterone and dihydrotestosterone were measured in spermatic venous blood of 37 azoospermic subjects. On the basis of testicular biopsy and vesiculodeferentography the patients were divided into three groups, i.e. subjects affected by azoospermia of obstructive origin with normal testicular histology, subjects with germinal cell arrest and those with Sertoli cell only syndrome (n = 6, n = 25 and n = 6 respectively).
The mean values (± SE) of hormone concentrations in spermatic venous blood in the three groups were respectively 2312 ± 517 nM/l. 2292 ± 320 nM/l and 2006 ± 342 nM/l for testosterone and 28.8 ± 7.7 nM/l, 39.0 ± 5.9 nM/l and 41.9 ± 17.7 nM/l for dihydrotestosterone. The differences were not statistically significant.     

Low testosterone levels are associated with coronary artery disease in male patients with angina

Historically, high androgen levels have been linked with an increased risk for coronary artery disease (CAD). However, more recent data suggest that low androgen levels are associated with adverse cardiovascular risk factors, including an atherogenic lipid profile, obesity and insulin resistance. The aim of the present study was to evaluate the relationship between plasma sex hormone levels and presence and degree of CAD in patients undergoing coronary angiography and in matched controls. We evaluated 129 consecutive male patients (mean age 58+/-4 years, range 43-72 years) referred for diagnostic coronary angiography because of symptoms suggestive of CAD, but without acute coronary syndromes or prior diagnosis of hypogonadism. Patients were matched with healthy volunteers. Out of 129 patients, 119 had proven CAD; in particular, 32 of them had one, 63 had two and 24 had three vessel disease, respectively. Patients had significantly lower levels of testosterone than controls (9.8+/-6.5 and 13.5+/-5.4 nmol/l, P<0.01) and higher levels of gonadotrophin (12.0+/-1.5 vs 6.6+/-1.9 IU/l and 7.9+/-2.1 vs 4.4+/-1.4, P<0.01 for follicle-stimulating hormone and luteinizing hormone, respectively). Also, both bioavailable testosterone and plasma oestradiol levels were lower in patients as compared to controls (0.84+/-0.45 vs 1.19+/-0.74 nmol/l, P<0.01 and 10.7+/-1.4 vs 13.3+/-3.5 pg/ml, P<0.05). Hormone levels were compared in cases with one, two or three vessel disease showing significant differences associated with increasing severity of coronary disease. An inverse relationship between the degree of CAD and plasma testosterone levels was found (r=-0.52, P<0.01). In conclusion, patients with CAD have lower testosterone and oestradiol levels than healthy controls. These changes are inversely correlated to the degree of CAD, suggesting that low plasma testosterone may be involved with the increased risk of CAD in men.     

Testosterone, FSH and LH in Human Spermatic and Cubital Venous Plasma in Post-Inflammatory Azoospermia

The testosterone, FSH and LH plasma levels were determined simultaneously in spermatic and cubital veins in 15 patients with post-inflammatory azoospermia. The testosterone levels in spermatic vein was 13,1 +/- 2,9 times higher than in cubital vein. FSH spermatic plasma level was slightly higher than in cubital vein, whereas LH spermatic plasma level did not differ from that found in the cubital vein.     

Aluminium interference in the treatment of haemodialysis patients with recombinant human erythropoietin

In nine chronic haemodialysis patients a desferrioxamine (DFO) load test (40 mg/kg body-weight) was performed 1 year after the beginning of treatment with recombinant human erythropoietin (rHuEpo). The patients were then divided into two groups. Group A comprised five patients with a greater mean aluminium (204 +/- 28 micrograms/l) than the four patients in group B. Group A was given a mean dose of 25.8 g (range 14-39 g) of DFO over 6 months. Group B (aluminium values 112 +/- 36 micrograms/l) was never treated with DFO. During the period of observation, plasma iron, serum ferritin and transferrin, as well as iron supplementation, did not differ between the groups. After DFO treatment a second DFO load test was performed. The mean predialysis aluminium value was significantly reduced in group A (204 +/- 28 vs 111 +/- 72 micrograms/l; P less than 0.05), while remaining unchanged in group B (112 +/- 36 vs 140 +/- 39 micrograms/l; P = ns). In both groups, the doses of rHuEpo necessary to maintain the same haemoglobin values decreased with time, but reduced significantly only in group A (298 +/- 105 vs 110 +/- 61 mu/kg per week; delta -63%; P less than 0.01). Thus, aluminium interferes with the response to rHuEpo in haemodialysis patients, and the correction of aluminium overload with DFO can allow a considerable sparing of rHuEpo.     

Induction of spermatogenesis in men with azoospermia or severe oligoteratoasthenospermia after antegrade internal spermatic vein sclerotherapy for the treatment of varicocele

Aim:To evaluate the treatment outcome of antegrade internal spermatic vein sclerotherapy in men with non-obstruc-tive azoospermia or severe oligoteratoasthenospermia(OTA)as a result of varicocele.Methods:Between September1995 and January 2004,47 patients(mean age 33.8±6.3 years)underwent antegrade internal spermatic vein sclero-therapy for the treatment of varicocele with azoospermia(14 patients)or severe OTA(33 patients).Testicular corebiopsy was also performed in complete azoospermic patients who provided informed consent.The outcome wasassessed in terms of improvement in semen parameters and conception rate.Results:Forty-two(89.4%)of 47patients had bilateral varicocele,Serum follicle stimulating hormone(FSH)did not differ between patients withazoospermia and severe OTA.After the follow-up of 24.8±9.2 months,significant improvement was noted in meansperm concentration,motility and morphology in 35 patients(74.5%).Comparison between groups during thefollow-up revealed significantly higher values of sperm concentration,motility and normal morphology in the severeOTA group.Pregnancy was achieved in 14 cases(29.8%).Testicular histopathology of the azoospermic patientswith postoperative induction of spermatogenesis revealed maturation arrest at spermatid stage,Sertoli-cell-only(SCO)with focal spermatogenesis or hypospermatogenesis.None of the patients with pure SCO pattern or maturation arrestat spermatocyte stage achieved spermatogenesis after the treatment.Preoperative serum FSH levels didn't relate totreatment outcome.Conclusion:Antegrade internal spermatic vein sclerotherapy is an easy and effective treatmentfor symptomatic varicocele.It can significantly reverse testicular dysfunction and improve spermatogenesis in menwith severe OTA,as well as induce sperm production in men with azoospermia,improving pregnancy rates insubfertile couples.(Asian J Androl 2006 Sep;8:613-619)     

Urinary amylase monitoring for early diagnosis of pancreas allograft rejection in dogs

The diagnosis of pancreas allograft rejection is usually made on the basis of blood glucose concentration, a late indicator of rejection. We performed segmental pancreas transplants in totally pancreatectomized dogs with the exocrine secretions drained into the bladder (ductocystostomy). We directly measured exocrine pancreatic secretions (urinary amylase), in an attempt to find a sensitive indicator for early rejection. Five groups were studied: (I) autografts; (II) autografts immunosuppressed with cyclosporine (CsA), azathioprine and prednisone; (III) allografts without immunosuppression; (IV) allografts immunosuppressed with CsA alone; (V) allografts immunosuppressed with CsA, azathioprine, and prednisone. The control groups (I, II) maintained high urine amylase concentrations indefinitely (mean +/- SE of 125,544 +/- 36,931 u/liter). Rejection, as diagnosed by rise of serum glucose to greater than 150 mg/dl, occurred at a mean (+/- SE) of 9.0 +/- 0.2 days in nonimmunosuppressed recipients of Group III, at 9.3 +/- 0.7 days in cyclosporine-treated dogs of Group IV, and at 28.0 +/- 8.3 days after transplantation in dogs immunosuppressed with triple therapy of Group V. In all allograft recipients, urine amylase declined precipitously (less than 1000 u/liter) before the onset of hyperglycemia, by 1.3 +/- 0.2 days in Group III, 3.3 +/- 1.0 days in Group IV, and 9.4 +/- 2.8 days in Group V. In a further experiment, nine dogs with pancreas allografts received cyclosporine for prophylactic immunosuppression; further antirejection therapy with azathioprine and antilymphocyte globulin was given for 5 days beginning the first day that rejection was diagnosed. In five dogs (Group A) rejection was diagnosed when serum glucose rose to greater than 150 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)     

Male hypogonadism due to nontumorous hyperestrogenism

Male hypogonadism due to the nontumorous production of estrogen was studied in a patient with gynecomastia and bilateral small testicles. Both the gynecomastia and the decrease in testicular size developed in the 5-year period before presentation. Peripheral serum concentrations of testosterone were in the low to low-normal range, while those of 17 beta-estradiol (E2) were significantly elevated, as were the urinary concentrations of total estrogen. Steroid hormone concentrations were measured in the left and right spermatic veins and the left and right adrenal veins in the basal state, and after stimulation with GnRH and ACTH. Spermatic vein concentrations of E2 were 3 to 20 times higher than concentrations previously reported in normal males. Spermatic vein concentrations of testosterone were normal. The spermatic vein concentrations of androstenedione were approximately three times higher than the mean concentration of androstenedione previously reported in the spermatic vein of normal males. The concentrations of E2 and androstenedione in the adrenal veins were also significantly elevated when compared to the concentrations previously reported in normal subjects. The authors postulate that the hyperestrogenism in this patient was due to increased aromatization of the precursor substrates, testosterone in the testes, and androstenedione in the adrenals to E2 and E1 in the testes and adrenals, respectively. Alternatively, an increased abundance or activity of the 17 beta-hydroxysteroid dehydrogenase isoenzyme which converts estrone (E1) to E2 or a relative deficiency of the 17 beta-hydroxysteroid dehydrogenase isoenzyme, which converts androstenedione to testosterone, could theoretically account for the reported abnormalities.     

Induced hypoprolactinemia and testicular steroidogenesis in man

The effects of short-term hypoprolactinemia on the pituitary-gonadal axis were evaluated in a group of patients with untreated prostatic carcinoma. Each patient was studied prior to and during 7-day oral administrations of bromocriptine (2.5 mg q.i.d.). Serum LH, prolactin (PRL), androst-4-ene-3,17 dione (androstenedione), testosterone, and 5 alpha-androstane-3 alpha, 17 beta-diol (5 alpha-Diol) levels, as well as intra-testicular testosterone, dihydrotestosterone (DHT), 5 alpha-Diol and zinc (Zn) concentrations, were determined. Daily administration of bromocriptine caused a marked suppression of serum PRL (mean +/- SEM, 23.8 +/- 2.5 vs. 6.4 +/- 1.0 ng/ml) without concomitant changes in serum LH levels (mean +/- SEM, 8.3 +/- 1.6 vs. 8.9 +/- 2.1 ng/ml). Hypoprolactinemia induced a significant decrease (P less than 0.05) in the mean peripheral testosterone levels; but 5 alpha-Diol and androstenedione remained unchanged. However, in testicular tissues, bromocriptine treatment resulted in significant increases in mean concentrations of total androgens (P less than 0.001), testosterone (P less than 0.001) and DHT (P less than 0.02). Testicular levels of 5 alpha-Diol were not significantly altered. There was no change in Zn levels in basal conditions and during bromocriptine administration. These results indicate that short-term suppression of serum PRL levels in man affects basal testicular function without altering serum LH. However, a direct action of bromocriptine on the human gonad cannot be excluded.     

Significant alterations of serum hormone levels in the spermatic vein plexus of patients with varicoceles

The objective of this study was to evaluate the level of hormone variation between the peripheral blood and spermatic vein plexus in patients with varicoceles. A total of 23 patients diagnosed with varicoceles were enrolled in the study. All patients underwent a testicular artery‐sparing microsurgical varicocelectomy. During the operation, a blood sample from the ipsilateral spermatic vein plexus and a peripheral blood sample were collected. A radioimmunoassay was performed to determine the total testosterone, free testosterone, dihydrotestosterone and oestradiol levels. An enzyme‐linked immunosorbent assay was performed to determine the albumin level. The mean age of the patients was 32.3 ± 9.3 years. Compared with the hormone level in the peripheral blood, the total testosterone, free testosterone, dihydrotestosterone, and oestrogen levels were significantly increased in the left or right spermatic vein plexus (P < 0.05). There were no differences in the albumin levels in the peripheral blood and spermatic vein plexus (P > 0.05). The mean total testosterone, free testosterone, dihydrotestosterone, and oestradiol levels in the left spermatic vein plexus were 10.8‐fold, 29.0‐fold, 2.0‐fold, and 26.6‐fold those of the peripheral blood. The hormone concentration in the spermatic vein plexus was significantly higher than that in the peripheral blood in patients with varicoceles.     

Continuous autotransfusion during liver transplantation

The advantages and disadvantages of continuous autotransfusion during liver transplantation are investigated in our study compared with blood saving and traditional cell saving techniques. Patients were divided into three groups in this retrospective study; Group 1 (n = 14): continuous autotransfusion was applied; in Group 2 (n = 14): no blood saving technique used; in Group 3 (n = 14): Haemonetics cell saver was used. In Group 1 the number of Child B patients was significantly higher than Child C patients (p < 0.05). The initial values of haemoglobin were significantly lower in Groups 1 and 3 (89 +/- 19 vs. 103 +/- 17 vs. 90 +/- 16.8 g/l; p < 0.03). During hepatectomy in Group 1 lower haemoglobin values were detected than in the other two groups (96 +/- 7 vs. 104 +/- 16 vs. 106 +/- 16.6 g/l; p < 0.05). The quantity of total blood utilisation (donor + autotransfusion) was significantly higher in Group 3 than Group 2 and in Group 1 than Group 2 (21.06 +/- 11.2 vs. 11.07 +/- 3.8 vs. 30.71 +/- 18 U; p < 0.001). Comparing the values of ACT in each group during operation periods no significant difference was found. Treatment time on the ICU of the patients in Group 3 was significantly longer than in the other two groups (11.08 +/- 7.8 vs. 9.17 +/- 3.5 vs. 26.62 +/- 14.6 days; p < 0.03). We found that applying CATS is advantageous during liver transplantation, as the device reduces donor blood requirement. No significant complication was observed.     

Characterization and localization of alpha 1-adrenoceptors in human prostate--with special reference to the zonal difference in receptor distribution]

Radioligand binding assay and receptor autoradiography were undertaken to characterize alpha 1-adrenoceptors and to clarify their localization in human prostate. Eleven open prostatectomy specimens obtained from patients with benign prostatic hypertrophy were used for radioligand binding assay. The binding of [3H]-prazosin to prostatic crude membrane fraction was a saturable process of high affinity. Scatchard analysis of the specific [3H]-prazosin binding indicated the existence of a single population of receptor sites with an equilibrium dissociation constant of 1.00 +/- 0.19 nM (mean +/- SE) and a maximum binding capacity of 20.8 +/- 3.56 fmol/mg protein (mean +/- SE). alpha-Adrenergic antagonists competed for [3H]-prazosin binding in an order of potency: prazosin greater than or equal to bunazosin greater than phentolamine greater than yohimbine, suggesting that the binding sites for [3H]-prazosin have characteristics of alpha 1-adrenoceptors. To study the distribution of alpha 1-adrenoceptors in prostatic tissues obtained from total cystoprostatectomy specimens of six male bladder tumor patients, we used for autoradiography (+/-)-beta-[( 125I]Iodo-4-hydroxyphenyl)-ethyl-aminomethyl-tetralone [( 125I]-HEAT). Peripheral zone (PZ), central zone (CZ) and preprostatic region were dissected from the tissues and incubated with [125I]-HEAT, followed by an autoradiographic procedure. Distribution of alpha 1-adrenoceptors was quantitated by grain counting using a light microscope equipped with a micrometer. The specific binding sites for [125I]-HEAT were demonstrated predominantly in the fibromuscular stroma of CZ, that of PZ, preprostatic sphincter and subordinately in the glandular epithelium of CZ, but not in the glandular epithelium of PZ and periurethral glands.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of chronic mechanical circulatory support on neuroendocrine activation in patients with end-stage heart failure.

OBJECTIVE: To evaluate if the improvement of patients supported with a Novacor was associated with a normalization in neuroendocrine activity. METHODS: Six patients had a Novacor implanted for end-stage heart failure. Four patients were transplanted after a mean of 4.5 months (range 3-6). One patient was weaned after 5 months and one died of a cerebral haemorrhage 5 weeks after implantation. Analysis of neuroendocrine activity was made prior to implantation and after 14, 30, 60 and 90 days. Levels of aldosterone, renin, cortisol, testosterone and T3 were measured using radio-immunoassays. Twenty-four hour urinary collections were made for assessment of adrenaline and noradrenaline excretion. RESULTS: Renin activity fell to normal after 14 days (16 +/- 3.0 ng/ml per h to 4.28 +/- 2.1 ng/ml per h, P < 0.05) and was maintained at 90 days. A similar picture was seen with aldosterone (1.5 +/- 0.4 nM to 0.12 +/- 0.07 nM, P < 0.05). Norepinephrine (67.46 +/- 14.1 microg/24 h) and epinephrine 12.9 +/- 2.5 microg/24 h) fell to normal physiological levels during the same time period. Cortisol levels were above normal pre-implantation but fell by day 30 (665.25 +/- 80.0 nM to 461.8 +/- 43.0 nM, P < 0.01). T3 and testosterone were lower than normal pre-implantation (T3 50 +/- 9.5 ng/dl vs. 90-200 ng/dl, testosterone 6.83 +/- 1.7 nM vs. 13-35 nM). T3 normalized after 90 days (81 +/- 11.7 ng/dl) and testosterone after 60 days (16.3 +/- 1.7 nM). CONCLUSION: Neuroendocrine function is abnormal in patients with cardiac failure who require circulatory support. The Novacor improved this, but metabolic recovery was delayed. The positive effect on the neuroendocrine axis, in the absence of activation of other endocrine systems, suggests that prolonged support may be well tolerated.     

Testosterone concentrations in spermatic venous blood plasma of prepubertal boys

Testosterone concentration has been measured in spermatic and peripheral venous plasma obtained during surgery from a total of 25 prepubertal boys affected either by inguinal hernia (Group I; N = 6; age range 2–8 years) or unilateral undescended testis (Group II; N = 19; age range 5–11 years). Median spermatic venous testosterone level was 58.7 ng/dl) (range 14.0–120.8 ng/dl) in Group I and 43.2 ng/dl (range 12.2–267.5 ng/dl) in Group II: median peripheral testosterone level was 4.9 ng/dl (range 2.3–15.4 ng/dl) and 5.6 ng/dl (range 1.1–89.3 ng/dl) in Group I and II, respectively. The difference between the spermatic and peripheral level was statistically significant in both groups ( P < 0.01 in Group I and P < 0.001 in Group II). These results indicate that the prepubertal human testis secretes testosterone, even if in a very low amount. It is also suggested that this secretion can be responsible for LH inhibition in prepubertal boys.     

Seminal plasma androgen/oestrogen balance in infertile men

The hypothesis that the balance between oestrogen and androgen in seminal plasma is important for normal fertility was investigated. We determined the concentrations of oestradiol and testosterone in blood and seminal plasma from 62 infertile men and 32 normozoospermic men. Infertile men were classified according to semen analysis (concentration, motility and morphology): asthenozoospermia, oligozoospermia and oligoteratoasthenozoospermia. Serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were determined in all participants. For all subjects, mean testosterone levels were lower and mean oestradiol were higher in seminal plasma than in blood. Seminal plasma testosterone levels were lower in the infertile groups vs. control men ( p < 0.0002). Oligpzoospermic and oligoteratoasthenozoospermic men had significantly higher seminal plasma oestradiol levels compared with controls ( p < 0.03). The three infertile groups had significantly lower seminal plasma testosterone/oestradiol ratio than control men ( p < 0.001). Sperm analysis data (concentration, motility and morphology) significantly correlated with seminal plasma testosterone/oestradiol ratio. The findings of elevated seminal plasma oestradiol, decreased testosterone and testosterone/oestradiol ratio in infertile men, and the significant correlation between hormone levels and sperm analysis data suggest that the local balance between androgen and oestrogen is important for spermatogenesis.     

Hemodynamic changes during hemodialysis: role of nitric oxide and endothelin

BACKGROUND: Etiology of dialysis induced hypotension and hypertension remains speculative. There is mounting evidence that nitric oxide (NO) and endothelin (ET-1) may play a vital role in these hemodynamic changes. We examined the intradialytic dynamic changes in NO and ET-1 levels and their role in the pathogenesis of hypotension and rebound hypertension during hemodialysis (HD). METHODS: The serum nitrate + nitrite (NT), fractional exhaled NO concentration (FENO), L-arginine (L-Arg), NGNG-dimethyl-L-arginine (ADMA) and endothelin (ET-1) profiles were studied in 27 end-stage renal disease (ESRD) patients on HD and 6 matched controls. The ESRD patients were grouped according to their hemodynamic profile; Group I patients had stable BP throughout HD, Group II had dialysis-induced hypotension, and Group III had intradialytic rebound hypertension. RESULTS: Pre-dialysis FENO was significantly lower in the dialysis patients compared to controls (19.3 +/- 6.3 vs. 28.6 +/- 3.4 ppb, P < 0.002). Between the experimental groups, pre-dialysis FENO was significantly higher in Group II (24.1 +/- 6.7 ppb) compared to Group I (17.8 +/- 5.6 ppb) and Group III (16.1 +/- 4.2 ppb; P < 0.05). Post-dialysis, FENO increased significantly from the pre-dialysis values (19.3 +/- 6.3 vs. 22.6 +/- 7.9 ppb; P=0.001). Pre-dialysis NT (34.4 +/- 28.2 micromol/L/L) level was not significantly different from that of controls (30.2 +/- 12.3 micromol/L/L). Serum NT decreased from 34.4 +/- 28.2 micromol/L/L at initiation of dialysis to 10.0 +/- 7.4 micormol/L/L at end of dialysis (P < 0.001). NT concentration was comparable in all the three groups at all time points. Pre-dialysis L-Arg (105.3 +/- 25.2 vs. 93.7 +/- 6.0 micromol/L/L; P < 0.05) and ADMA levels were significantly higher in ESRD patients (4.0 +/- 1.8 vs. 0.9 +/- 0.2 micromol/L/L; P < 0.001) compared to controls. Dialysis resulted in significant reduction in L-Arg (105.3 +/- 25.2 vs. 86.8 +/- 19.8 micromol/L/L; P < 0.005) and ADMA (4.0 +/- 1.8 vs. 1.6 +/- 0.7 micromol/L/L; P < 0.001) concentrations. Pre-dialysis ET-1 levels were significantly higher in ESRD patients compared to the controls (8.0 +/- 1.9 vs. 12.7 +/- 4.1 pg/mL; P < 0.002), but were comparable in the three study groups. Post-dialysis ET-1 levels did not change significantly in Group I compared to pre-dialysis values (14.3 +/- 4.3 vs.15.0 +/- 2.4 pg/mL, P=NS). However, while the ET-1 concentration decreased significantly in Group II (12.0 +/- 4.0 vs. 8.7 +/- 1.8 pg/mL, P < 0.05), it increased in Group III from pre-dialysis levels (12.8 +/- 3.8 vs. 16.7 +/- 4.5 pg/mL, P=0.06). CONCLUSION: Pre-dialysis FENO is elevated in patients with dialysis-induced hypotension and may be a more reliable than NT as a marker for endogenous NO activity in dialysis patients. Altered NO/ET-1 balance may be involved in the pathogenesis of rebound hypertension and hypotension during dialysis.     

Primary gonadal failure in men selectively amplifies the mass of follicle stimulating hormone (FSH) secreted per burst and increases the disorderliness of FSH release patterns: reversibility with testosterone replacement

The neuroendocrine mechanisms by which primary gonadal failure in men increases mean serum FSH concentrations (castration-like response) are not known. To investigate the testosterone-dependent mechanisms of the FSH castration response: (i) blood was sampled at 10-min intervals for 24 h for later FSH assay in seven normal middle-aged men and in six patients with primary testicular failure, during testosterone withdrawal and after 6 weeks of parenteral testosterone replacement; (ii) using a specific two-site IRMA, serum FSH concentrations were measured, since this assay correlates well with an in-vitro Sertoli cell bioassay; (iii) multiparameter deconvolution analysis was then applied to estimate the frequency, amplitude, duration, and mass of underlying FSH secretory bursts, and the half-life of endogenous FSH, and (iv) approximate entropy was calculated to quantify the relative orderliness of FSH release over 24 h. Mean (+/- SEM) 24-h serum FSH concentrations were 3.9 +/- 0.8 IU/L in control subjects and 39 +/- 10 IU/L in unreplaced hypogonadal patients (p = 0.034). Deconvolution analysis revealed similar estimated mean FSH half-lives of 346 +/- 40 min (control) and 321 +/- 47 min (untreated patients), and indistinguishable FSH secretory burst frequencies, namely, 20 +/- 0.95 (normal) and 21 +/- 1.3 (patients) pulses per 24 h. In contrast, the daily production rate of FSH was markedly increased in testosterone-withdrawn hypogonadal men at 117 +/- 25 vs. 9.3 +/- 1.8 IU/L/day (control) (p < 0.01). This was due to a 10-fold higher calculated maximal rate (amplitude) of FSH secretion achieved within each FSH release episode (normal 0.078 +/- 0.02 vs. gonadal failure 0.74 +/- 0.087 IU/L/min, p < 0.01), yielding a 10-fold increase in the mass of FSH secreted per burst (control 0.53 +/- 0.06 vs. patients 5.3 +/- 0.81 IU/L, p < 0.01). In contrast, the mean half-duration of FSH secretory bursts was unaltered in unreplaced hypogonadal men at 8.2 +/- 2.2 min (control) vs. 7.0 +/- 1.0 min (patients). Approximate entropy (ApEn), a scale- and model-independent statistic designed to quantify the orderliness or regularity of hormone release, revealed greater irregularity of serum FSH concentrations in the hypoandrogenic state: ApEn = 1.8 +/- 0.025 (testosterone-withdrawn) vs. 1.6 +/- 0.037 (control) (p < 0.05). Parenteral testosterone replacement for 6 weeks significantly decreased mean serum FSH concentrations by reducing the daily FSH secretion rate and FSH secretory burst amplitude and mass, and concomitantly restored the orderliness of FSH release patterns. Testosterone treatment did not change FSH secretory burst half-duration, number, interburst interval, or half-life. It is concluded that primary gonadal failure in men evokes FSH hypersecretion which is marked by more disorderly FSH release patterns and a selectively amplified mass of FSH secreted per burst. These hypergonadotrophic mechanisms are, to a significant extent, testosterone-suppressible.     

Hormonal response to captopril pre-treatment during sodium nitroprusside-induced hypotension in man

To assess the hormonal response to captopril pre-treatment during sodium nitroprusside (SNP) -induced hypotension, 12 patients were studied during a spinal surgical procedure. Haemodynamic data, plasma-renin activity, aldosterone, adrenaline and noradrenaline levels were measured. Patients were randomly allocated to two groups: Group I, control patients; Group II, 3 mg kg-1 captopril pre-treated patients. SNP requirement for the same level (mean arterial pressure (MAP) = 55 mmHg) and duration of hypotension (88.5 +/- 28.7 vs. 95.2 +/- 22.5 min) was significantly lower in Group II than in Group I (16.5 +/- 14.2 mg vs. 39.3 +/- 16.7 mg; P less than 0.05) and a lower SNP infusion rate was required to induce and to maintain hypotension. In Group II patients, MAP remained significantly lower than the control and Group I values for 30 min after SNP withdrawal. Cardiac index (CI) remained stable in both groups. Heart rate was not modified in Group II during hypotension. Plasma-renin activity rose more dramatically in Group II patients than in Group I both during hypotension (13.9 +/- 7.5 vs. 2.8 +/- 0.9 ng ml-1 h-1; P less than 0.05) and after hypotension (23.4 +/- 15.4 vs. 2.2 +/- 0.8 ng ml-1 h-1; P less than 0.05). Plasma catecholamine levels increased in both groups during hypotension and remained raised in captopril patients after SNP withdrawal. It can be concluded that recovery from hypotension may be delayed when using captopril and that sympathoadrenal activity induced by hypotension is not substantially altered by captopril pre-treatment, suggesting that sympathetic blockade might not be the mechanism by which captopril reduces SNP requirement during controlled hypotension for surgical procedure in man.     

Serum androgen bioactivity during 5alpha-dihydrotestosterone treatment in elderly men

The androgens used in the treatment of age-related androgen decline have different bioactivities that cannot be evaluated with conventional detection methods for serum steroids. We have recently developed a recombinant cell bioassay for the determination of androgen bioactivity in human serum that is based on androgen-specific interaction between the ligand-binding domain (LBD) and the N-terminal region of the androgen receptor (AR). In this work, we examined the effect of topically applied 5alpha-dihydrotestosterone (DHT; 7.5-10 g of 2.5% DHT gel daily for 6 months) on circulating androgen bioactivity in 14 men (age range, 51-63 years) with symptoms of andropause and pretreatment serum testosterone less than 15 nM, or serum sex hormone-binding globulin concentration greater than 30 nM, or both. The mean (+/-SEM) pretreatment androgen bioactivity was 3.3 +/- 0.3 nM testosterone equivalents, and the levels correlated with serum testosterone concentration (r =.55, P <.05). DHT gel treatment induced a sixfold increase (from 1.5 +/- 0.1 nM to 9.0 +/- 0.7 nM) in mean serum DHT level, whereas endogenous testosterone and estradiol levels measured with radioimmunoassays were suppressed by approximately 70% and approximately 50%, respectively (P <.0001). Concomitantly, serum androgen bioactivity increased by sevenfold (from 3.3 +/- 0.3 to 23.6 +/- 2.8 nM testosterone equivalents; P <.0001). We conclude that DHT gel therapy in elderly men significantly increases their circulating androgen bioactivity as measured with a mammalian cell bioassay. An androgen-specific bioassay such as ours may enable investigation of other androgens with different bioactivities, such as selective AR modulators.     

The clinical value of correction of acidosis by acetate-free biofiltration in patients on regular dialysis treatment

Effects of metabolic acidosis were compared between bicarbonate dialysis (BCD) and acetate-free biofiltration (AFB). Three stable dialysis patients (1M, 2F, mean age 30 yrs) were selected for the study because their bicarbonate (BC) pre-dialysis plasma concentration were always under 16 mmol/l while they were on 33 mmol/l-BCD thrice weekly for 12 months. They were switched to a 6 months period of AFB. Pre- and post-dialysis BC plasma concentration, other blood chemical parameters and mass removal (total collection of used dialysate) of urea (U), creatinine (Cr), uric acid (UA), and phosphate (P) were measured during the last week of each period, including 3 dialysis sessions. Mean calorie and protein intake were 29.4 KCal/kg.d and 1.5 g/Kg.d (BCD period) and 38.2 Kcal/Kg.d and 1.5 g/Kg.d (AFB period) respectively. BC plasma concentration (Mean +/- SE, mmol/l) at the pre and post-dialysis in AFB were significantly higher than those in BCD (16.6 +/- 0.7 vs 20.8 +/- 0.6; p less than 0.001, 22.7 +/- 0.8 vs 25.8 +/- 0.8; P less than 0.02). Pre- and post-dialysis U plasma concentration (Mean +/- SE, mmol/l) in AFB were significantly lower than those in BCD (34.3 +/- 2.51 vs 20.8 +/- 0.59, 10.5 +/- 1.32 vs 7.5 +/- 0.92; P less than 0.001). Pre-dialysis P plasma concentration (Mean +/- SE, mmol/l) in AFB was significantly lower than that in BCD (1.85 +/- 0.09 vs 1.50 +/- 0.15; P less than 0.01). Cr, UA and P mass removal in BCD and AFB were not significantly different. However, U mass removal in AFB was significantly lower than that in BCD.(ABSTRACT TRUNCATED AT 250 WORDS)