A study on the association between serum amyloid A and sperm concentration

Our aim was to compare peripheral blood and seminal fluid serum amyloid A (SAA) protein levels in men classified on the basis of sperm concentration and investigate whether SAA protein is an important marker of male infertility. A total of 74 first‐attempt IVF male partners of infertile couples classified as azoospermic (n = 25), oligozoospermic (n = 25) and normozoospermic group (n = 24) were recruited for this cross‐sectional study. There was no difference with respect to age, BMI, infertility period and smoking ratio. No difference in haematologic parameters including white blood cell count, neutrophil ratio, lymphocyte ratio, neutrophil‐to‐lymphocyte ratio and blood SAA level was found between the groups. Seminal fluid SAA level was 17.85 ± 2.21 ng ml^?1 in azoospermics, 16.13 ± 3.58 ng ml^?1 in oligozoospermics and 15.67 ± 4.77 ng ml^?1 in normozoospermics, showing no significant difference. Seminal SAA level was found to be not correlated with blood SAA levels. Therefore, we could not find any associations between these parameters at all. However, further studies with more participants are needed to address the exact action of SAA on spermatogenesis.     

Combined effects of chronic hyperglycaemia and oral aluminium intoxication on testicular tissue and some male reproductive parameters in Wistar rats

Exposure to either environmental toxicants or chronic hyperglycaemia could impair male reproductive function. However, the extent to which exposure to such toxicants, in the presence of pre‐existing metabolic dysfunction, could affect male reproduction is unclear. Streptozotocin‐induced diabetic Wistar rats (12 weeks old) were exposed to oral aluminium chloride at 250 ppm for 30 days; followed by evaluation of caudal epididymal sperm count and motility, assay for serum follicle stimulating hormone (FSH), testosterone (T) and oestradiol; and assessment of testicular histology. Moreover, blood glucose was evaluated by the glucose oxidase method. In rats treated with streptozotocin (STZ) or aluminium (Al) alone, erosion of testicular parenchyma and stroma was observed. This effect was most severe in diabetic rats simultaneously exposed to Al; coupled with reduced caudal epididymal sperm count that was least in this (STZ+Al) group (18.75 × 10⁶ ml^?1) compared with controls (61.25 × 10⁶ ml^?1; P < 0.05), STZ group or Al group. Moreover, these reproductive perturbations (in the STZ+Al group) were associated with reduced sperm motility and significantly reduced serum FSH (P < 0.05); but elevated serum T and oestradiol (P < 0.05), compared with control. These suggest that diabetes‐induced testicular lesion is exacerbated by simultaneous oral Al toxicity in Wistar rats.     

醋酸棉酚对男子垂体－性腺轴功能的影响

报道２２例长期停服棉酚男子性激素的水平及其对ＬＨＲＨ和ｈＣＧ刺激的反应。２２例中，１１例生精功能未恢复者（无精子症组）的ＦＳＨ和ＬＨ基础值及其对ＬＨＲＨ刺激反应均显著高于正常对照组（１１例），而睾酮（Ｔ）基础值和Ｔ／ＬＨ比值及Ｔ对ｈＣＧ刺激反应显著低于正常对照组。生精功能恢复组（１１例）的ＦＳＨ基础值及其对ＬＨＲＨ刺激在应均显著高于正常对照组。但是，ＬＨ和Ｔ基础值及其对ＬＨＲＨ和ｈＣＧ刺激反应，二者差异不显著。这些结果说明，不适当的棉酚治疗所引起的永久无精子症者，全睾丸细胞受到严重损害，垂体－睾丸轴系功能调节发生紊乱；而适量的棉酚所引起的暂时无精子症，生精功能恢复以后，睾丸内分泌一般均正常     

Histological and hormonal testicular function in oligo/azoospermic infertile men

We characterised and correlated the histological and hormonal aspects of a cohort of 261 azo/oligozoospermic men, applying a quantitative/qualitative evaluation of testicular tissue and serum and intratesticular hormonal measurements. One hundred and 93 azo?oligozoospermic patients were diagnosed as: complete sertoli cell only syndrome (cSCOS), n = 76; focal SCOS, n = 31; maturation arrest, n = 34; hypospermatogenesis, n = 17; mixed atrophy, n = 25; and severe atrophy, n = 10. Normal spermatogenesis was observed in 68 infertile men (controls). Patients with cSCOS, focal SCOS, mixed and severe atrophy had larger LC/clusters (11.5; 11.0; 10.7; 18.9 LC/cluster) than controls (6 LC/cluster; P < 0.001). cSCOS, focal SCOS, mixed and severe atrophy patients had higher FSH, LH and lower T/LH ratio serum levels than the other groups. Intratesticular testosterone concentrations were higher in tissues with complete or focal SCOS (45.6 ng mg^?1 protein) and mixed atrophy (79.0 ng mg^?1 protein) than normal tissues (20.3 ng mg^?1 protein; P = 0.03 and P = 0.007). Considering all subjects, significant correlations were found between T/LH ratio and Leydig cells/cluster (r = 0.510, P < 0.001), FSH levels (r = ?0.692, P < 0.001) and with intratesticular testosterone (r = ?0.354, P = 0.001); these correlations follow the pattern of severity of spermatogenic damage. By a thorough histological evaluation, we validate the concept that the severity of spermatogenic impairment is associated with major morphological and functional disturbance of the Leydig cell compartment.     

The relationship between morphology, motility and zona pellucida binding potential of human spermatozoa

Summary. Prediction of the fertilizing potential of human gametes under in vitro conditions has been a major field of interest of assisted reproductive programmes. However, sperm morphology has been regarded as a predictor of human in vitro fertilization rate. This paper prospectively evaluates the relationships among normal sperm morphology and (1) motion characteristics viz. curvilinear velocity (VCL), straight line velocity (VSL), and linearity (LIN) (n = 37) and (2) spermzona pellucida binding capacity under HZA conditions (n = 144) of two separate groups of infertile couples. Semen was evaluated for sperm concentration, percentage motility, forward progression, and percentage normal morphology (strict criteria). The motility characteristics were measured using a computerized Sperm Motility Quantifier (SMQ). The zona binding potential of sperm was evaluated using the hemizona assay. Firstly, the VCL significantly differred between the P-pattern and both the G (72.9 ± 7 vs. 86.3±16 μm s^?1; P = 0.04) and N patterns (72.9 ± 7 vs. 91.0 ± 15 μm s^?1; P = 0.002). The VSL differed only between the P and N patterns, being 19.7 ± 7 vs. 32.6±15 μm s^?1 (P = 0.02), respectively. No significant differences in LIN were noted between any of the three patterns. The sperm concentration differed significantly between the P and both the G (37.9±35 vs. 80.8 ± 9 × 10⁶ ml^?1; P = 0.03) and the N patterns (37.9 ± 35 vs. 89.7 ± 72 × 10⁶ ml^?1; P = 0.05). Significant differences were observed in the percentage motility between the P and both the G (38.0 ± 21% vs. 43.7 ±9%; P = 0.03) and the N patterns (38.0 ± 21% vs. 52.1±8%; P = 0.04). In the second study, the hemizona indices (HZI) differed significantly between the P and both the G (29.3 ± 26% vs. 57.6 ± 62%; P = 0.01) and the N patterns (29.3 ± 26% vs. 102.4 ± 80%; P < 0.001). The G and N patterns also differed significantly in their HZI (57.6 ± 62% vs. 102.4 ± 80%; P = 0.005). Sperm concentration differed between the P and both the G (32.8 ± 29 vs. 76.1±54 × 10⁶ ml^?1; P < 0.001) and the N patterns (32.8 ± 29 vs. 95.44 ± 61 × 10⁶ ml^?1; P < 0.001). The percentage motility differs significantly between the P pattern and both the G (41.2± 17% vs. 50.9±11%; P = 0.002) and the N patterns (41.2±17% vs. 53.4±11%; P = 0.001). Sperm morphology seems to be indicative of important functional characteristics of spermatozoa, for example motility and zona pellucida binding.     

Can testosterone level be a good predictor of late‐onset hypogonadism?

Androgens are essential for the development and growth of the genitalia. They regulate the erectile physiology by multiple mechanisms. Several studies have examined associations among sex hormones' serum levels, erectile function and sex drive. We sought to identify a protocol for using testosterone in men with erectile dysfunction and late‐onset hypogonadism (LOH). During a 16‐month period, men with erectile dysfunction who presented to the andrology clinic were selected. They underwent a complete physical examination and filled out the International Index of Erectile Function‐5 questionnaire. Serum luteinising hormone (LH) and testosterone levels were evaluated. Patients received a single intramuscular injection of 250 mg testosterone. Thereafter, serum levels of LH and testosterone were measured 3 weeks later. The mean age was 53 years old. After treating patients with testosterone, 45 (94%) showed improvement in LOH symptoms including libido, loss of energy, irritability and quality of life. The mean International Index of Erectile Function was 9 and 13.1, prior to and after treatment respectively. Mean serum testosterone levels before and after treatment were 4.2 and 4.1 ng ml^?1 respectively (P = 0.849). Mean serum LH revealed a significant decrease after the study (P = 0.004) (6.12 and 5.1 ng ml^?1, before and after the study respectively). Our findings suggested that testosterone replacement therapy improves libido and LOH symptoms in individuals with almost normal or lower limit normal value of serum testosterone levels.     

Circulating mitochondrial DNA in serum: A universal diagnostic biomarker for patients with urological malignancies

ObjectiveCell-free circulating mitochondrial DNA (mtDNA) has been proposed as universal diagnostic and prognostic biomarker in cancer patients.Patients and methodsCell-free DNA was isolated from 1 ml serum from patients with bladder cancer (BCA, n = 84), renal cell carcinoma (RCC, n = 33), and prostate cancer (CaP, n = 23), and compared with healthy individuals (n = 79). Quantitative real-time PCR was used to analyze the levels of a 79 bp (mtDNA-79), and 220 bp (mtDNA-220) fragment of the mitochondrial specific 16S-RNA. The mitochondrial DNA integrity (mtDNA-integrity) was defined as ratio of mtDNA-220 to mtDNA-79 fragments.ResultsIn healthy controls, mtDNA-79 levels were increased in male volunteers; mtDNA-230 levels and mtDNA-integrity were correlated with age. Neither mtDNA levels nor mtDNA-integrity were correlated with age or gender in cancer patients. Circulating mtDNA-79 (median 8.75 × 10⁶ vs. 0.43 × 10⁶ copies/ml) and mtDNA-230 (8.11 × 10⁶ vs. 0.27 × 10⁶ copies/ml) levels were significantly increased in cancer patients and allowed sensitive (84%) and specific (97%) discrimination from healthy controls. mtDNA levels were unequally distributed among the different cancer entities (mtDNA-79: BCA 9.54 × 10⁶ vs. RCC 6.69 × 10⁶ vs. CaP 4.48 × 10⁶ copies/ml; mtDNA-230: BCA 9.78 × 10⁶ vs. RCC 6.74 × 10⁶ vs. CaP 1.94 × 10⁶ copies/ml). The mtDNA-integrity was increased in RCC and BCA patients compared to control subjects and CaP patients. Serum mtDNA-integrity was correlated with pathological stage in RCC and with tumor grade in BCA patients.ConclusionCirculating mtDNA levels are associated with gender and age in healthy individuals, but not in cancer patients. Quantification of circulating mtDNA may help identify patients with urologic malignancies.     

Tuberculin Skin Test Results and the Booster Phenomenon in Two-Step Tuberculin Skin Testing in Hemodialysis Patients

Background. Angiotensin II (ang II) receptor subtype I binding sites has been recently demonstrated on bone cell precursors. Ang II stimulates DNA and collagen synthesis in human adult bone cells. The aim of this study is to evaluate the role of renin angiotensin system in the bone metabolism and to address the genetic influence of angiotensin converting enzyme (ACE) gene polymorphism on bone mass in hemodialysis patients. Methods. Forty‐eight end‐stage renal disease patients (28 male, 20 female mean age 42 ± 13 years,) on maintenance hemodialysis were included in the study. Bone mineral density (BMD) was estimated at lumbar spine and T score worse than ? 1.5 were considered as osteopenia. Serum parathyroid hormone (iPTH) and osteocalcin (OC), bone alkaline phosphatase (bAP) and carboxy terminal propeptide type 1 collagen (PICP) levels were measured as markers of bone metabolism. Plasma renin activity (PRA), serum ACE activity and ACE gene polymorphism (II, ID, DD) were determined. Results. Bone mineral density and T score of the hemodialysis patients were 0.92 ± 0.17 g/cm² and ? 1.36 ± 1.50, respectively. Twenty‐one patients (43,7%) were osteopenic (T score worse than ? 1.5) and mean T score of osteopenic patients was ? 2.72 ± 0.72. T score of nonosteopenic group was ? 0.29 ± 0.99. Serum calcium, serum, phosphorus, serum OC, serum bAP, serum PCIP, serum PTH levels were similar in osteopenics and nonosteopenics. No difference was observed in predialysis PRA and in both pre‐ and postdialysis serum ACE activity of patients in both groups. PRA after hemodialysis in nonosteopenic group was higher than osteopenics (p < 0.05). Percent increment in PRA in hemodialysis patients was correlated with T score (R = 0.48 p < 0.05). Serum ACE activity was positively correlated with serum iPTH (R = 0.29, p = 0.02), serum OC (R = 0.35, p = 0.01), serum bAP (R = 0.34, p = 0.01), serum PCIP (R = 0.36, p = 0.01). T score (? 0.7 ± 1.5, vs ? 1.7 ± 1.3 p < 0.05) was higher in DD group (n = 19) compared to II + ID group (n = 29). Conclusions. Association of biochemical and radiological signs of increased bone formation with activated RAS in hemodialysis patients might be an evidence for the involvement of this system in the regulation of bone metabolism.     

Magnesium carbonate for phosphate control in patients on hemodialysis. A randomized controlled trial

Background Magnesium salts bind dietary phosphorus, but their use in renal patients is limited due to their potential for causing side effects. The aim of this study was to evaluate the efficacy and safety of magnesium carbonate (MgCO₃) as a phosphate-binder in hemodialysis patients. Methods Forty-six stable hemodialysis patients were randomly allocated to receive either MgCO₃ (n = 25) or calcium carbonate (CaCO₃), (n = 21) for 6 months. The concentration of Mg in the dialysate bath was 0.30 mmol/l in the MgCO₃ group and 0.48 mmol/l in the CaCO₃ group. Results Only two of 25 patients (8%) discontinued ingestion of MgCO₃ due to complications: one (4%) because of persistent diarrhea, and the other (4%) because of recurrent hypermagnesemia. In the MgCO₃ and CaCO₃ groups, respectively, time-averaged (months 1–6) serum concentrations were: phosphate (P), 5.47 vs. 5.29 mg/dl, P = ns; Ca, 9.13 vs. 9.60 mg/dl, P < 0.001; Ca × P product, 50.35 vs. 50.70 (mg/dl)², P = ns; Mg, 2.57 vs. 2.41 mg/dl, P = ns; intact parathyroid hormone (iPTH), 285 vs. 235 pg/ml, P < 0.01. At month 6, iPTH levels did not differ between groups: 251 vs. 212 pg/ml, P = ns. At month 6 the percentages of patients with serum levels of phosphate, Ca × P product and iPTH that fell within the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines were similar in both groups, whereas more patients in the MgCO₃ group (17/23; 73.91%) than in the CaCO₃ group (5/20, 25%) had serum Ca levels that fell within these guidelines, with the difference being significant at P < 0.01. Conclusion Our study shows that MgCO₃ administered for a period of 6 months is an effective and inexpensive agent to control serum phosphate levels in hemodialysis patients. The administration of MgCO₃ in combination with a low dialysate Mg concentration avoids the risk of severe hypermagnesemia.     

The Relation of Optical Density of Seminal Plasma with Serum FSH and LH Levels in Azoospermic Patients

The aim was to investigate the relation between optical density of seminal plasma, serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels in azoospermic patients and to establish criteria depending on optical density measurements in order to estimate serum FSH and LH levels. Optical density of seminal plasma and serum FSH and LH levels were measured in 45 azoospermic patients. The semen samples with an optical density (OD) of more than 0.5 showed normal levels of FSH and LH, while those with less than 0.5 were observed to have high levels of FSH and LH. The optical density of seminal plasma can be used in the prediction of serum FSH and LH levels in azoospermic patients.     

无精子症患者睾丸组织病理分型与血清抑制素B关系的研究

目的:探讨无精子症患者睾丸组织病理分型与血清抑制素B(INH B)水平间的关系,了解血清INH B在评估无精子症患者睾丸生精功能状态的敏感性和特异性。方法:对83例无精子症患者进行睾丸活组织病理检查诊断,根据病理形态的不同分为:唯支持细胞综合征组(n=21)、生精功能低下组(n=20)、生精阻滞组(n=24)和生精功能基本正常组(n=18)。患者睾丸活检前分别测定其血清INH B、卵泡刺激素(FSH)、黄体生成素(LH)及睾酮(T)水平。结果:上述4组血清INH B水平分别为(20.85±18.78)、(67.25±40.98)、(73.63±25.54)和(149.48±27.92)ng/m l。INH B水平在生精阻滞组与生精功能低下组之间差异无显著性(P>0.05),其他各组间以及与上述两组血清INH B水平间差异均有极显著性(P<0.001);FSH水平在生精阻滞组与基本正常组间差异无显著性(P>0.05),其他各组间以及与上述两组血清FSH水平间差异均有显著性(P<0.05);4组血清LH及T水平之间无相关性。结论:血清INH B水平在生精小管生精功能受损时明显降低,唯支持细胞综合征者下降最为显著。血清INH B水平可直接反映睾丸生精功能的总体状态,是判断无精子症患者睾丸生精功能更有效的诊断指标。     

Reproductive Hormones and Longitudinal Change in Bone Mineral Density and Incident Fracture Risk in Older Men: The Concord Health and Aging in Men Project

The objectives of this study were to examine relationships between baseline levels of reproductive hormones in older men and (1) change in bone mineral density (BMD) over 5 years and (2) incident fractures over an average of 6 years' follow‐up. A total of 1705 men aged 70 years and older from the Concord Health and Ageing in Men Project (CHAMP) study were assessed at baseline (2005–2007), 2 years follow‐up (2007–2009), and 5 years follow‐up (2010–2013). At baseline, testosterone (T), dihydrotestosterone (DHT), estradiol (E2), and estrone (E1) were measured by liquid chromatography–tandem mass spectrometry (LC‐MS/MS), and sex hormone–binding globulin (SHBG), luteinizing hormone (LH), and follicle‐stimulating hormone (FSH) by immunoassay. Hip BMD was measured by dual X‐ray absorptiometry (DXA) at all three time‐points. Fracture data were collected at 4‐monthly phone calls and verified radiographically. Statistical modeling was by general estimating equations and Cox model regression. Univariate analyses revealed inverse associations for serum SHBG, FSH, and LH and positive association for E1 but not DHT or E2 with BMD loss at the hip across the three time points. Serum levels of SHBG (β = –0.071), FSH (β = –0.085), LH (β = –0.070), and E1 (β = 0.107) remained significantly associated with BMD loss in multivariate‐adjusted models; however, we were unable to identify any thresholds for accelerated BMD loss according to reproductive steroids. Incident fractures (all, n = 171; hip, n = 44; and nonvertebral, n = 139) were all significantly associated with serum SHBG, FSH, and LH levels in univariate models but none remained significantly associated in multivariate‐adjusted model. Serum T, DHT, E2, and E1 levels were not associated with incident fractures in univariate or multivariate‐adjusted analyses. In older men, lower serum SHBG, FSH, and LH and higher E1 levels protected against loss of BMD without increasing fracture rate. This means these reproductive variables may be considered as novel biomarkers of bone health during male aging. © 2015 American Society for Bone and Mineral Research.     

Rare coding variants in ALPL are associated with low serum alkaline phosphatase and low bone mineral density

Alkaline phosphatase (ALP) plays an essential role in the regulation of tissue mineralization, and its activity is highly heritable. Guided by genetic associations discovered in a murine model, we hypothesized a role for rare coding variants in determining serum ALP level and bone mineral density (BMD) in humans. We sequenced the coding regions of the ALP gene (ALPL) in men with low and normal serum ALP activity levels. Single‐nucleotide ALPL variants, including 19 rare nonsynonymous variants (minor allele frequency <1%), were much more frequent among the low ALP group (33.8%) than the normal group (1.4%, p = 1 × 10^?11). Within the low ALP group, men with a rare, nonsynonymous variant had 11.2% lower mean serum ALP (p = 3.9 × 10^?4), 6.7% lower BMD (p = 0.03), and 11.1% higher serum phosphate (p = 0.002) than those without. In contrast, common nonsynonymous variants had no association with serum ALP, phosphate, or BMD. Multiple rare ALPL coding variants are present in the general population, and nonsynonymous coding variants may be responsible for heritable differences in mineralization and thus BMD. © 2012 American Society for Bone and Mineral Research     

Serum levels of dimeric and monomeric inhibins and the degree of seminal alteration in infertile men with varicocele

The aim of the present study was to establish the serum levels of inhibins and their relationship with the degree of seminal alteration in infertile men. Thirty-six patients with varicocele (Va) and seven non-obstructive azoospermic men (Az) were included. The Va group was divided into two subgroups: Va I (sperm concentration: >20 x 106; n = 21) and Va II (sperm concentration: < 20 x 106; n = 15). Twelve fertile men were included as a control group (Co). Semen analysis and serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), inhibin B and Pro-alphaC levels were determined. Serum inhibin B and T levels were significantly lower and FSH and LH significantly higher in group Az when compared with the Co. Inhibin B was unable to differentiate Va I from Va II groups. However, in Va II an increase in FSH levels was observed. An inverse correlation between inhibin B and FSH, a direct correlation between inhibin B and testosterone, sperm concentration, motility and morphology were found. No such correlations were seen when only the Va group was analysed. The lack of correlation between serum levels of inhibin B, gonadotrophins, sperm concentration and seminal parameters observed in Va, adds other factor to the complex pathophysiology of varicocele. Finally, further studies are needed to elucidate if oligozoospermic patients with varicocele have also an impaired negative feed-back mechanism that regulates FSH synthesis and secretion.     

Nitrous oxide can enhance the hypnotic effect, but not the suppression of spinal motor neuron excitability by propofol in humans

Purpose We investigated whether nitrous oxide can enhance the suppressive effect of propofol on spinal motor neuron excitability in humans. Methods Sixteen adult patients were prospectively randomly assigned to be given either propofol alone (group P; n = 8) or a supplement of 66% nitrous oxide with propofol (group PN; n = 8) for intraoperative sedation. Propofol was administered by a target-controlled infusion system to maintain sequentially increasing plasma propofol concentrations (Cpt) of 0.5, 0.8, 1.0, 1.3, 1.5 and 1.8 μg·ml⁻¹ in all patients. Assessment of the patient's level of sedation in both groups was performed with the Wilson Sedation Scale (WSS). F-wave analysis on the left abductor pollicis brevis muscle was carried out for the assessment of spinal motor neuron excitability at each plasma propofol concentration. Results Significant differences in the WSS scores between group P and group PN were observed at 0.8, 1.0, 1.3, and 1.5 μg·ml⁻¹ of Cpt (group P < group PN; P < 0.01). Cpt greater than 1.0 μg·ml⁻¹ significantly reduced F-wave persistence in a concentration-dependent manner, and the ICpt 50 and ICpt 95 values for plasma propofol concentration (plasma propofol concentrations that produced 50% and 95% inhibition of the baseline, respectively) were 1.05 and 1.95 μg·ml⁻¹ in group P, and 1.07 and 2.14 μg·ml⁻¹ in group PN, respectively. Conclusion These results suggest that nitrous oxide can enhance the hypnotic effect, but not the suppression of spinal motoneuron excitability by propofol in humans at clinical levels of Cpt.     

The lack of memory B cells including T cell independent IgM+ IgD+ memory B cells in chronic graft‐versus host disease is associated with susceptibility to infection

The chronic graft‐versus host disease (cGVHD) is associated with a perturbed B cell homeostasis and an increased infection rate. Aiming to determine the impact of lymphocyte subsets on cGVHD, blood samples from 98 patients at least 100 days following allogeneic haematopoietic stem cell transplantation (median 1066 days) were analyzed, serum levels of immunoglobulins measured and the incidence of severe infections retrospectively documented. Absolute CD19⁺ B cell counts, including counts of immature (CD10⁺ CD38⁺⁺ CD20⁺ IgM⁺⁺) and transitional (CD10^? CD38⁺⁺ CD20⁺ IgM⁺⁺) as well as class switched memory (CD19⁺ CD27⁺ IgM^? IgD^?) B cells in patients with active cGVHD (n = 52) were significantly decreased as compared to those with inactive (n = 18) or without cGVHD (n = 28). In addition, nonclass switched IgM⁺ memory B cells (CD19⁺ CD27⁺ IgM⁺ IgD⁺) were absent in patients with cGVHD, but not in patients with inactive (0.4 × 10⁶/l) or without (1.7 × 10⁶/l) cGVHD (both P < 0.001). In line with these results we found significantly decreased lgG levels in patients with cGVHD, which was associated with a significantly higher rate of severe infections in cGVHD patients. Our data underline the close association of diminished B cell counts with cGVHD and the onset of severe infections. The lack of IgM⁺ memory B cells in patients with cGVHD may indicate functional asplenia.     

Molecular analysis of CAG repeat length of the androgen receptor gene and Y chromosome microdeletions among Jordanian azoospermic infertile males

Assisted reproductive technology is a common procedure which helps millions of couples who suffer fertility problems worldwide every year. Screening for genetic abnormalities prior to such procedure is very important to prevent the transmission of harmful genetic mutations to future generations. Microdeletions within the azoospermia factor (AZF) region of the Y chromosome and the expansion of the CAG trinucleotides in the androgen receptor (AR) gene are among the susceptible causes of male infertility in different ethnic groups. Such association has never been studied in Jordan. In this study, we compared CAG repeat length between azoospermic infertile and normospermic fertile Jordanian males and we also screened the frequency of Y chromosome microdeletions in the same cohort. The study included 142 nonobstructive azoospermic cases and 145 normospermic controls. Results have shown that the median CAG repeat length in the azoospermic group is 19 ± 2 compared to 19 ± 1.5 (p = .6262) in the control group. Deletions within the Y chromosome AZF region were detected in 7 of 142 cases (4.93%) and no deletions were seen in the control group. The results of this study confirm the importance of the AZF region in normal spermatogenesis, whereas it shows no link between the length of CAG repeats in the AR gene and male azoospermia in Jordanian group examined.     

Changes in serum prolactin, sex hormones and thyroid function with alternate nightly nocturnal home haemodialysis

Aim: Uraemia is associated with hyperprolactinaemia, low total (TT) and free (FT) serum testosterone, high luteinizing hormone (LH) and follicle‐stimulating hormone (FSH) and, in women, anovulatory cycles and premature menopause. We hypothesize that extended hours haemodialysis may improve these derangements. Methods: This is an observational cohort study of 30 men (age 54 ± 13 years, body mass index (BMI) 28.1 ± 5.8 kg/m²) and seven women (age 41 ± 11 years, BMI 32.2 ± 11.2 kg/m²) established on chronic home haemodialysis (3–5 h, 3.5–5 sessions weekly) who were converted to nocturnal home haemodialysis (6–9 h, 3.5–5 sessions weekly). Serum was collected at baseline and 6 months for measurement of TT, sex hormone binding globulin (SHBG), LH, FSH, prolactin, thyroid‐stimulating hormone and thyroxine. Results: In the male patients (n = 25), serum prolactin significantly fell (281 (209.5–520) vs 243 (187–359) mU/L, P = 0.001) and TT (12.6 ± 5.8 vs 15.2 ± 8.1 nmol/L, P = 0.06) and FT (281 ± 118 vs 359 ± 221 pmol/L, P = 0.01) increased. SHBG, LH and FSH were unchanged. At 6 months, two of the three women under 40 years of age had return of regular menses after being amenorrhoeic or having prolonged and irregular menses at baseline. There were insufficient women in this study to further analyse changes in sex hormone levels. Thyroid function tests remained stable. Conclusion: Alternate nightly nocturnal haemodialysis significantly improves hyperprolactinaemia and hypotestosteronaemia in men. Menstrual cycling may be re‐established in young women. The effect of these changes on fertility has not been established. Patients should be counselled about the possibility of increased fertility before conversion to extended hours haemodialysis regimens.     

Association between serum folic acid level and erectile dysfunction

This study measured the serum folic acid (FA) level in patients with erectile dysfunction (ED) and evaluated the possible association between the serum FA level and erectile function. The study divided 120 patients with ED into 3 groups of 40 patients each: those with severe, moderate and mild ED. Forty healthy men served as controls. Fasting serum samples were obtained, and the total testosterone, cholesterol and FA levels were measured using chemiluminescent immunoassays. There were no significant differences in the mean age, mean body mass index or mean serum total testosterone and cholesterol levels among the three ED groups and controls (P > 0.05). The mean serum FA concentrations were 7.2 ± 3.7, 7.1 ± 3.2, 10.2 ± 4.6 and 10.7 ± 4.6 ng ml^?1 in the severe, moderate and mild ED and control groups respectively. The mean serum FA concentration was significantly higher in the control group than in the severe and moderate ED groups (both P < 0.001), but not the mild ED group (P = 0.95). Considering the significant differences in the serum FA levels between the control and ED groups, serum FA deficiency might reflect the severity of ED.     

Late-onset hypogonadism: beyond testosterone

Late-onset hypogonadism is defined as a combination of low testosterone (T) levels and typical symptoms and signs. A major area of uncertainty is whether T concentrations are always really sufficient to fully reflect Leydig cell (dys)function. Mild testicular alteration could be diagnosed only by additional biochemical markers, such as luteinizing hormone (LH) and 25-hydroxyvitamin D levels. These markers help in identifying the so-called “subclinical” hypogonadism (normal T, high LH levels). Patients with hypogonadism have frequently low levels of 25-hydroxyvitamin D due to impairment of the hydroxylating enzyme CYP2R1 in the testis. However, no data have been published dealing with the best treatment option (cholecalciferol – the Vitamin D precursor, or calcidiol - 25-hydroxylated form of Vitamin D) in these patients. We studied 66 patients with classic hypogonadism (total T [TT] <12 nmol l⁻¹, LH ≥ 8 IU l⁻¹) (n = 26) and subclinical hypogonadism (TT ≥ 12 nmol l⁻¹, LH ≥ 8 IU l⁻¹) (n = 40) and low 25-hydroxyvitamin D (<50 nmol l⁻¹). Subjects received cholecalciferol (5000 IU per week) (n = 20) or calcidiol (4000 IU per week) (n = 46), and 25-hydroxyvitamin D and parathyroid hormone (PTH) were evaluated after 3 months of therapy. Supplementation with calcidiol significantly increased 25-hydroxyvitamin D and significantly decreased PTH levels in both groups of men with hypogonadism (primary, n = 16 and subclinical, n = 30), whereas supplementation with cholecalciferol did not modify their levels. This study shows for the first time that the administration of the 25-hydroxylated form of Vitamin D (calcidiol), and not the administration of the precursor cholecalciferol, restores 25-hydroxyvitamin D levels in subjects with hypogonadism.