Varicocele--the most common cause of male factor infertility?

Varicocele is often cited as the most common cause of male factor infertility. Arguments in support of this statement include reports of increased prevalence of varicocele in populations of infertile men compared with fertile or otherwise unselected men, association of varicocele with abnormal semen parameters, and improvements in semen parameters and/or pregnancy rates after varicocele repair. Logically, there would appear to be three possibilities regarding the relationship between varicocele and fertility: (i) varicocele has no association with or effect on male fertility; (ii) varicocele may be associated with, but is not the cause of, male subfertility; and (iii) varicocele is a direct cause of male subfertility. In the following, we review evidence from the literature for and against these three possibilities: at the current time, available evidence appears inadequate to confirm or deny any of these three possibilities. Since the ultimate goal of infertile couples is to conceive, it seem logical that future varicocele research should focus primarily on adequately powered, controlled clinical trials in well-characterized infertile couples, randomized to intervention or appropriate controlled observation, with pregnancy as the primary outcome.     

Increased brain natriuretic peptide and atrial natriuretic peptide plasma concentrations in dialysis-dependent chronic renal failure and in patients with elevated left ventricular filling pressure

Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) plasma concentrations were measured in patients with dialysis-dependent chronic renal failure and in patients with coronary artery disease exhibiting normal or elevated left ventricular end-diastolic pressure (LVEDP) (n = 30 each). Blood samples were obtained from the arterial line of the arteriovenous shunt before, 2 h after the beginning of, and at the end of hemodialysis in patients with chronic renal failure. In patients with coronary artery disease arterial blood samples were collected during cardiac catheterization. BNP and ANP concentrations were determined by radioimmunoassay after Sep Pak C₁₈ extraction. BNP and ANP concentrations decreased significantly (P < 0.001) during hemodialysis (BNP: 192.1 ± 24.9, 178.6 ± 23.0, 167.2 ± 21.8 pg/ml; ANP: 240.2 ± 28.7, 166.7 ± 21.3, 133.0 ± 15.5 pg/ml). The decrease in BNP plasma concentrations, however, was less marked than that in ANP plasma levels (BNP 13.5 ± 1.8%, ANP 40.2 ± 3.5%; P < 0.001). Plasma BNP and ANP concentrations were 10.7 ± 1.0 and 60.3 ± 4. 0 pg/ml in patients with normal LVEDP and 31.7 ± 3.6 and 118.3 ± 9.4 pg/ml in patients with elevated LVEDP. These data demonstrate that BNP and ANP levels are strongly elevated in patients with dialysis-dependent chronic renal failure compared to patients with normal LVEDP (BNP 15.6-fold, ANP 2.2-fold, after hemodialysis; P < 0.001 or elevated LVEDP (BNP 6.1-fold, ANP 2.0-fold, before hemodialysis; P < 0.001), and that the elevation in BNP concentrations was more pronounced than that in ANP plasma concentrations. The present results provide support that other factors than volume overload, for example, decreased renal clearance, are also involved in the elevationin BNP and ANP plasma levels in chronic renal failure. The stronger elevation in BNP concentrations in patients with chronic renal failure and in patients with elevated LVEDP and the less pronounced decrease during hemodialysis suggest a different regulation of BNP and ANP plasma concentrations.[/ p]Abbreviations ANP atrial natriuretic peptide - BNP brain natriuretic peptide - LVEDP left ventricular end-diastolic pressure Correspondence to: C. Haug     

Atrial natriuresis under the condition of a constant renal perfusion pressure

An experimental elevation of left atrial pressure (eLAP ) by means of a reversible mitral stenosis is accompanied with an increase in sodium excretion (UNa—) and arterial blood pressure (by about 20 mm Hg, 2.7 kPa), and by a decrease in plasma renin activity.It is well established that an increase in renal perfusion pressure (Pren) can augment UNa—. Therefore the present study was undertaken to examine whether the eLAP -induced natriuresis was caused by the increased Pren. — Four female beagle dogs were kept under controlled environmental conditions. They received asodium rich diet (14.5 mmol/Na/kg/d). The dogs were chronically instrumented: purse string around the mitral annulus, catheter in the left atrium, carotid loop, pneumatic cuff above the renal arteries, pressure transducer below the renal arteries. Pren was kept constant by means of a digital servofeedback control circuit. The dogs served as their own controls (13 experiments without and 15 experiments with a controlled renal perfusion pressure were performed).After eLAP(+1.0 kPa), UNa— rose from 4.1±2.6 to 10.3±3.9 mol Na/min/kg. If Pren was kept constant, the corresponding values were 4.2±2.8 and 9.3±2.9 mol/min/kg. These data clearly indicate that the atrial natriuresis is not mediated by an augmentation of renal perfusion pressure. Therefore these results support the hypothesis that atrial natriuresis probably is due to an eLAP-induced suppression of the renin-angiotensin-system or other natriuretic mechanisms.Abbreviations ADP 3×20 min After distension period - AN Atrial natriuresis - bw kg Body weight - CP 3×20 min Control period - DP 3×20 min Distension period - eLAP kPa Experimental increase of left atrial pressure (during all DP's about +1.0 kPa) - HR l/min Heart rate - LAP kPa Left atrial pressure - n ₁ Number of dogs used - n ₂ Number of experiments (1 expt/day) - n ₃ Number of collection periods (urine) or number of samples (HR) - Part kPa Mean systemic arterial blood pressure (carotid artery) - Pren kPa Mean renal perfusion pressure (aorta, below the renal arteries) - UCI— mol/min/kg Chloride excretion - UK— mol/min/kg Potassium excretion - UNa— mol/min/kg Sodium excretion - Uosm— osm/min/kg Osmolar excretion - — l/min/kg Urine volume Preliminary parts of this work have been presented in Kiel (Spring meeting of the Deutsche Physiologische Gesellschaft, March 1979) and in Stockholm, Sweden (III. European Colloquium on Renal Physiology, June 1979).     

Importance of luxury flow for critically ill patients receiving a left ventricular assist system

The presence of a significant organ dysfunction does not immediately exclude patients from consideration for treatment with a left ventricular assist system (LVAS). However, in treating morbid circulatory shock patients with multiple organ failure, it is important to know the preoperative and postoperative factor or factors related to the recovery of the damaged organ function. In this study, we retrospectively analyzed patients receiving a LVAS at our institution and tried to determine the important factors related to the survival of patients with multisystem failure. Twenty-seven patients who underwent LVAS placement at Saitama Medical School Hospital between 1993 and 2003 were included in this study. The preoperative risk factors analyzed were renal dysfunction, respiratory dysfunction, hepatic dysfunction, the existence of active infection, and the combination of all four factors. As a postoperative factor, the pump flow index (mean LVAS pump flow during the first 2 weeks after LVAS surgery divided by the body surface area) was analyzed. None of the analyzed preoperative factors could predict survival after LVAS surgery, but a pump flow index of less than 2.5 l/min/m² had a significant relationship with death after LVAS surgery. Further analysis revealed that all the patients with a pump flow index of 3.0 l/min/m² or more could overcome preoperative organ dysfunction. Congestive heart failure patients with multisystem failure need luxury pump flow for successful LVAS surgery; this factor could be especially important in device selection and postoperative management.     

Monitoring effects of α-human atrial natriuretic polypeptide (α-hANP) on left ventricular function in patients with essential hypertension with a cardiac probe

The effects of -hANP on left ventricular function were studied with a cardiac probe in ten patients with essential hypertension. Our data showed that intravenous administration of -hANP significantly elevated left ventricular function. At 5 min, the elevation of EF, RCO, ER, RSV, PFR were 13.23% (P<0.02), 12.7 (P<0.02), 0.618 (P<0.02), 0.133 (P<0.05), 0.283 (P<0.01), respectively. At 10 min, the increase of EF, ER, were 11.07% (P<0.02) and 0.233 (P<0.01), respectively. Atriopeptin significantly reduced systolic and diastolic blood pressure from 2 min to 20 min (P<0.001–0.05).Supported by IAEA Grant No. 4062/RI/RB     

Left ventricular function before and after kidney transplantation. A prospective study in patients with juvenile-onset diabetes mellitus

The aim of the present investigation was to discover whetherdisturbed left ventricular (LV) function limits renal replacementtherapy in patients with juvenile onset diabetes mellitus. Seventeenpatients given functioning kidney grafts were studied non-invasively(M-mode echocardiography, apexcardiography, phonocardiography)before renal transplant and an average of six, 13 and 44 monthsafter transplant. The main pretransplant findings were pronouncedLV hypertrophy with impaired diastolic LV function (prolongedrelaxation time + signs of decreased LV distensibility) anda hyperdynamic circulation. Most of these abnormalities were significantly less severe aftersuccessful kidney transplantation. LV mass decreased by 37%44 months after transplant (p<0.01) and LV diastolic andsystolic volumes decreased with a subsequent increase in ejectionfraction from 0.65 to 0.78 (p<0.01). The LV distensibilityand filling pattern improved significantly while the prolongedrelaxation time was unchanged. These findings imply that pretransplant disturbances in LV functionare related more to factors such as hypertension, volume overloadand uraemia than to diabetes per se because no pronounced improvementin the metabolic disorder resulting from diabetes can be expected,even after the most successful transplant. Disturbed LV functionshould not, therefore, exclude uraemic diabetics from renalreplacement.     

The Nutraceutical N-Palmitoylethanolamide (PEA) Reveals Widespread Molecular Effects Unmasking New Therapeutic Targets in Murine Varicocele

Varicocele is an age-related disease with no current medical treatments positively impacting infertility. Toll-like receptor 4 (TLR4) expression is present in normal testis with an involvement in the immunological reactions. The role of peroxisome proliferator-activated receptor-α (PPAR-α), a nuclear receptor, in fertility is still unclear. N-Palmitoylethanolamide (PEA), an emerging nutraceutical compound present in plants and animal foods, is an endogenous PPAR-α agonist with well-demonstrated anti-inflammatory and analgesics characteristics. In this model of mice varicocele, PPAR-α and TLR4 receptors’ roles were investigated through the administration of ultra-micronized PEA (PEA-um). Male wild-type (WT), PPAR-α knockout (KO), and TLR4 KO mice were used. A group underwent sham operation and administration of vehicle or PEA-um (10 mg/kg i.p.) for 21 days. Another group (WT, PPAR-α KO, and TLR4 KO) underwent surgical varicocele and was treated with vehicle or PEA-um (10 mg/kg i.p.) for 21 days. At the end of treatments, all animals were euthanized. Both operated and contralateral testes were processed for histological and morphometric assessment, for PPAR-α, TLR4, occludin, and claudin-11 immunohistochemistry and for PPAR-α, TLR4, transforming growth factor-beta3 (TGF-β3), phospho-extracellular signal-Regulated-Kinase (p-ERK) 1/2, and nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) Western blot analysis. Collectively, our data showed that administration of PEA-um revealed a key role of PPAR-α and TLR4 in varicocele pathophysiology, unmasking new nutraceutical therapeutic targets for future varicocele research and supporting surgical management of male infertility.     

高血压及血糖水平对老年冠心病患者左室舒张功能的影响

目的：探讨年龄、高血压及血糖异常对老年冠心病（CHD）患者左室舒张功能的影响。方法：采用二次瓣彩色多普勒频谱测定中午CHD组24例、老年CHD组25例、合并症（CHD合并高血压、高血糖）组20例的左室舒张功能参数及空腹血糖值。结果：各组心脏指数和射血分数均正常。各线间血糖值相比（均为P＜0．05）。老年CHD组舒张早、晚期血清峰值比（E／A）下降（P＜0．01）,舒张早期血流加速度（AC）减低（P＜0．01）,以合并症组尤为明显（P＜0．001）。结论：随年龄增长,高血压及血糖异常可明显加重老年CHD患者左室舒张功能障碍。     

倍他乐克逆转高血压左室肥厚的临床观察

目的　比较 2药对高血压左室肥厚患者的疗效及运动后对心率、血压的影响。方法　采用随机分组法将 80例高血压左室肥厚的病人分成两组 ,倍他乐克组和硝苯地平组 ,治疗前后查超声心动图 ,测定IVST、PWT及LVMI ,心率及血压。结果　① 2药降压效果无明显差异。② 2组患者IVST、PWT、LVMI的下降幅度相同。③中度体力活动后 ,倍他乐克组心率增快 9± 2次 ,收缩压、舒张压上升均小于 3kPa(7 5mmHg) ,硝苯地平组心率增快 2 0± 4次 ,2组相比P <0 0 1,具有显著意义 ;收缩压、舒张压上升幅度均为 3 4± 1 2kPa(2 6±9mmHg) ,明显大于倍他乐克组。④结论　 2药对高血压患者的左心室肥厚有相似的逆转作用 ,但倍他乐克可减少体力活动时血压及心率的上升 ,对心脏更具有保护作用。     

Protein profiling in unlocking the basis of varicocele-associated infertility

Varicocele is one of the major causes of male infertility and has a negative impact on spermatogenesis. The conventional semen analysis does not reveal the underlying subcellular mechanisms associated with defects in spermatozoa. Proteomics and bioinformatics analysis can be used to identify the molecular aetiologies associated with poor semen quality in varicocele patients. Mitochondrial dysfunction has been identified as the main factor affecting normal physiological functions of spermatozoa. This article discusses the proteomic studies of spermatozoa and seminal plasma in varicocele patients. Proteomics can identify potential spermatozoa and seminal plasma biomarkers in varicocele-mediated male infertility. In future, these protein biomarkers can be useful in the development of noninvasive diagnostic and therapeutic strategies for varicocele patients.