The clinical varicocele in infertility

Of 238 infertile males seen over a 47-month period, 47 (20%) had a varicocele. Of these 51% had an abnormal sperm count (21% were azoospermic and 30% oligozoospermic) and 60% had less than a third of sperms motile; 23 patients were subjected to gonadotrophin assays. Serum follicle stimulating hormone and leutinising hormone levels were elevated in 48% and 70% of patients respectively. Serum prolactin assayed in 19 patients was raised in 10% and serum testosterone estimated in 16 patients was low in 6%. Twenty-five patients (53%) were advised to undergo surgery but only 10 agreed. Of these, 1 showed a dramatic improvement in his spermiogram and a pregnancy ensued. The sperm count and motility of 2 others improved after treatment with prostaglandin synthetase inhibitors, and 1 after testosterone. Medical treatment improved the count and motility in 7 of 8 patients in whom surgery was not suggested as primary treatment because of abnormal hormonal results. This study has shown that infertile patients with varicocele are a heterogeneous group and that improvement in spermiograms can best be achieved by selective treatment; this may be surgery, surgery followed by medical treatment, or medical treatment alone.     

Nephrotoxicity of sirolimus: experimental and clinical data

Sirolimus (SRL, rapamycin) is a potent immunosuppressive drug that binds to and inhibits mammalian Target Of Rapamycine (mTOR) kinase activity, a central controller of cell growth. In response to amino acids, hormones and growth factors, mTOR activates the translational machinery. By inhibiting mTOR, SRL reduces the translational process and T-cell proliferation in the mid-to-late G1 phase of the cell cycle. The antiproliferative effects of SRL are not limited to activated T cells. SRL has also been shown to block the cell cycle in various cell types such as epithelial renal cells, and many types of tumor cell lines. Since the approval by the US Food and Drug Administration and by the European agency, SRL has provoked great interest, as evidenced by the exponential increase in clinical studies. However, whereas preclinical studies failed to show any nephrotoxic effect on animal models, many clinical trials raised the possibility that SRL might be associated with renal adverse events. The evidence for SRL-associated early graft nephrotoxicity emerged from these results, and subsequent experimental data gave some explanations about the involved mechanisms. The aim of this review is to summarize the various renal adverse events reported in clinical studies and to present the experimental evidence for putative mechanisms of action for this SRL-induced nephrotoxicity.     

The blast path: theoretical basis, experimental data and clinical application

Use of the "blast path" may be helpful in patients where positioning for ESWL treatments is difficult. Good pressures are maintained along the blast path and an alternate fracture mechanism may be in effect. The rate of fragmentation, assessed using model material, decreases with distance beyond F2.     

Non-obstructive azoospermia and clinical varicocele: therapeutic options

Ten to fifteen percent of infertile men are azoospermic, and sixty percent of these men have been classified as having non-obstructive azoospermia (NOA). NOA results from testicular failure, and one of the causes of this is the presence of varicocele. Varicocele is observed in 5–10 % of men with NOA. This review discusses the impact of varicocele repair on semen quality and pregnancy rate among men with NOA. Based on the best available evidence, varicocele repair of men with NOA is associated with an improvement in semen quality and pregnancy rate. Thus, it appears to be an effective therapeutic option for this group of men, particularly for those with a female partner who is younger than 35 years of age, before an assisted reproductive technique (ART) is initiated. Semen cryopreservation is recommended once the patient has spermatozoa in the ejaculate. In addition, varicocele repair seems to improve the rate of spermatozoa recovery in testicular sperm extraction for those who requested ART.     

The transverse coloplasty pouch. Review of experimental data and clinical application

The transverse coloplasty pouch. Review of experimental data and clinical application. The transverse coloplasty pouch is a novel technique for sphincter preserving colonic reconstruction after total mesorectal excision. The method was developed in an animal model and resulted in favorable early functional results. Our results in patients with rectal cancer demonstrate that the technique is technically easy and safe. The transverse coloplasty pouch provides a neorectal reservoir of adequate volume and a favorable early functional outcome. It leads to a reduction in stool frequency compared with a straight anastomosis and the outcome is comparable to other colon reservoirs.     

The paralysis associated with myelomeningocele: clinical and experimental data implicating a preventable spinal cord injury

Paralysis seen in children with myelomeningocele has been attributed to congenital myelodysplasia. We suspected that paralysis may be due in part to a spinal cord injury caused by exposure of the neural tube to the amniotic fluid. This hypothesis was tested using a fetal rat model of surgically created dysraphism. Each pup from the experimental group of rats in which the spinal cord was intentionally exposed to the amniotic fluid was born with severe deformity and weakness of the hind limbs and tail. Control fetal rats, subjected to the same procedure without directly exposing the spinal cord to the intrauterine environment, were normal at birth. Histological studies of the exposed spinal cord revealed extensive erosion and necrosis, findings similar to those described in children with myelomeningocele. We therefore propose a "two-hit" hypothesis to explain the paralysis seen in children with myelomeningocele: congenital myelodysplasia complicated by an intrauterine spinal cord injury. Intrauterine protection of the exposed spinal cord might prevent some or all of the paralysis. The possible implications of these findings for the future treatment of myelomeningocele are discussed.     

The adolescent varicocele: treatment and outcome

At present, it is reasonable to counsel all patients, as well as family members of patients, who have a palpable varicocele about the long-term risks for impaired fertility. Currently, no one can predict with absolute certainty if any adolescent with a varicocele will be at risk for future infertility. Based on existing data, however, it is not reasonable simply to ignore the potential for such a problem until infertility becomes an issue because by that time the chance for reversibility may be lost. It is important to present a balanced discussion because the majority of men with a varicocele will be fertile, and no one is suggesting that all men with a varicocele undergo surgical treatment. Current recommendations for repair are based on the findings of impaired testicular growth and/or spermatogenesis. With early evaluation and selective treatment, however, we should be able to reduce the potential for future fertility problems significantly in adolescents with a varicocele.     

The significance of clinical practice guidelines on adult varicocele detection and management

Varicoceles are the most common correctable etiology of male factor infertility. However, the detection and management of varicoceles have not been standardized. This has led to decades of debate regarding the effect of varicocele on male infertility and subsequently whether repair leads to an improved fertility status. The current body of evidence investigating the role of varicocele and varicocelectomy is weak and conflicting. The stance taken by the AUA and ASRM suggests that there is insufficient outcomes data to support evidenced-based guidelines, citing evidence used to provide current recommendations are generally of a low quality level. On the other hand, the EAU Guidelines give a level 1a of evidence for management of varicoceles that are clinically palpable, associated with subnormal semen analyses and having otherwise unexplained fertility. Besides aiding with clinical varicocele detection and management, clinical practice opinion statements and guidelines aim to direct and strengthen the infrastructure of future studies. We review the current status of opinion statements and guidelines in varicocele and management detection with focus on their application in practice.     

实验性精索静脉曲张大鼠生精状态评价

目的 通过对大鼠实验性精索静脉曲张(varicocele,VC)模型睾丸生精小管生精上皮结构、性激素水平的分析,探讨精索静脉曲张致不育的机制.方法 40只雄性青春期Wistar大鼠随机分为VC8周组(n=12)、VC12周组(13=12)和相应对照组(分别n=8);左肾静脉部分结扎建立实验性大鼠VC模型.术后8周或12周,分别测量各组大鼠:(1)左侧精索静脉直径、睾丸温度及体质量、睾丸生精小管生精上皮;(2)外周血中促卵泡刺激素(FSH)、黄体生成素(LH)和睾酮(T)的水平.结果 VC8周和VC12周组大鼠左侧精索静脉明显扩张,与对照相比血管直径差异有统计学意义(P<0.01);VC8和VC12周组大鼠左侧睾丸体质量均低于自体右侧睾丸和对照组睾丸,差异有统计学意义(P<0.05);光镜下,VC组大鼠双侧睾丸生精小管生精上皮精子发生阻滞、细胞脱落和细胞层数减少等,VC12周组损伤程度较VC8周组明显加重,左侧较右侧显著;与对照组相比,VC组大鼠外周血FSH、LH升高,T降低,差异均有统计学意义(P<0.01).结论 本研究提示:VC对大鼠双侧睾丸生精小管生精上皮产生明显的损害作用,并导致大鼠血中T水平降低和FSH、LH水平升高.     

The effects of experimental varicocele on testicular histology and fertility in monorchic adult rats

OBJECTIVE: To determine the effects of a left-sided experimental varicocele on testicular morphology and fertility in right hemicastrated adult rats. MATERIALS AND METHODS: A double-controlled experimental study was carried out using mature Sprague-Dawley rats, with 12 rats in each treated group and five corresponding controls. Group 1 underwent right orchidectomy, group 2 right orchidectomy and a left varicocele, and group 3 only a left varicocele; each control group underwent a corresponding sham operation. Two months after surgery each rat was placed with two mature female rats for one month to assess fertility. All the rats were then killed and their testes weighed; the mean testicular weight was calculated for each group and the mean seminiferous tubule diameter (STD) measured. Johnsen scores and histological abnormalities were evaluated for each testis using light microscopy. RESULTS: The mean (SEM) testicular weight and STD in group 2 were significantly lower, at 1311 (100) mg and 225 (11) microm, respectively, than in group 1, at 1771 (28) mg and 255 (4) microm (P<0.05). The mean weights of both testes in rats in group 3 were significantly lower than those in group 1 (P<0.05) and although both mean STDs were less than in group 1, the differences were not significant (P>0.05). There were no differences between the Johnsen scores in groups 2 and 3. There were severe histological abnormalities in the left testes in three of nine and two of eight animals in group 2 and 3, respectively; in group 3, changes in the right testis were detected in one rat. Six of nine and seven of eight rats were fertile in group 2 and 3, respectively. CONCLUSION: Experimental left varicocele decreased the left testicular weight and STD in both hemicastrated and intact adult rats. However, the presence of the right testis is important for preserving fertility.     

The effect of varicocele repair on experimental varicocele-induced testicular germ cell apoptosis

The purpose of this study was to evaluate the variance of apoptosis in rats in which experimental varicocele was induced and then treated by varicocelectomy. Forty adult male Wistar albino rats were used in this experimental study. Experimental varicocele was created in 30 rats. A total of 5 rats underwent a sham operation, and the remaining 5 rats were the control group. A total of 5 rats from the varicocele group were sacrificed on the 14th postoperative day, and 5 more were sacrificed on the 28th postoperative day to document the level of apoptosis due to varicocele. Varicocelectomy was performed on 20 rats with varicocele on the 14th postoperative day. These 20 rats were divided into 4 groups to evaluate the level of apoptosis in their testis after varicocelectomy. They were sacrificed on days 7, 14, 21, and 28 after varicocelectomy. The testes were fixated by perfusion with 10% formaldehyde and then placed in paraffin blocks. From each testis, 2 samples were stained with hematoxylin and eosin, and 2 samples were stained using the TUNEL method. In each specimen, apoptotic germ cells stained by TUNEL were counted in the cross section of 100 seminiferous tubules. The apoptotic index was defined by calculating the number of apoptotic cells per seminiferous tubule. Apoptotic index = total apoptotic germ cell count/100. In the adult rats on which experimental varicocele was performed, both in the second and fourth week, apoptosis in both left and right testes were significantly higher compared with the control group (with varicocele day 14: 0.25-0.26, with varicocele day 28: 0.28-0.32, control: 0.11-0.13). After varicocelectomy on the 7th and 14th days, the slight increase in the level of apoptosis continued (day 7 left testis: 0.30, day 7 right testis: 0.28; day 14 left testis: 0.25, day 14 right testis: 0.31). After varicocelectomy, apoptosis decreased significantly on day 21 (left testis: 0.16, right testis: 0,22), and on day 28 it was almost equal to the level of the control group (left testis: 0.14, right testis: 0.16). After the creation of unilateral varicocele, the level of apoptosis increased in both the left and right testes. Apoptosis in both testes decreased after surgical treatment.     

The changes in testicular vascular permeability during progression of the experimental varicocele

OBJECTIVES: The vascular permeability of testicular capillaries which play a role in controlling the formation of testicular interstitial fluid was studied during the progressive course of experimental varicocele. MATERIALS AND METHODS: The pathology was developed through partial ligation of left renal vein in four groups of rats. Controls of each group were subjected to sham surgery. After different periods of varicocele creation (1, 3, 6 and 14 weeks), animals' testes per one of the study groups were extirpated and weighed. The volume density percentages of polymorphnuclear leukocytes (PMN) per testicular blood vessels; which are markers of the increase in vascular permeability, were also estimated in both testes. To further verify the obtained findings, another group of animals received human chorionic gonadotrophin (hCG) treatment 6 weeks after varicocele creation and their histopathological sections were examined. RESULTS: Animal testes' of (1 and 3 weeks) groups were found to be significantly heavier (p<0.05) than their controls. PMN showed accumulation in testicular blood vessels and their volume density percentages per these blood vessels in both testes were significantly higher in each study group than in those of its controls. However, these percentages showed gradual significant decline as the duration of varicocele bearing gradually increased. The hCG-treated animals revealed more accumulation of the PMN in their histopathological sections. CONCLUSION: The present results suggest that experimental varicocele may induce an increase in testicular vascular permeability, which then decreases gradually with time. It is supposed that parallel changes in the rate of formation of testicular interstitial fluid may be accompanied. The results have also showed that the vasculature of the testis with experimental varicocele can still respond to hCG.     

Diagnosis of clinical and subclinical varicocele: how has it evolved?

In this review, we examine the evolution and application of various diagnostic modalities for varicoceles starting with venography, scintigraphy, and thermography and their role in the evaluation of a varicocele patient. Some of these methods have been supplanted by less invasive and more easily performed diagnostic modalities, especially ultrasound and Doppler examination of the scrotum. Advances in ultrasound and magnetic resonance imaging hold the potential to expand the role of imaging beyond that of visual confirmation and characterization of varicoceles. The ability to identify the early indicators of testicular dysfunction based on imaging findings may have implications for the management of varicoceles in the future.     

Opioids and protection against ischemia-reperfusion injury: from experimental data to potential clinical applications

Ischemic preconditioning, first demonstrated in animal myocardium, is an intrinsic and ubiquitous mechanism of marked protection against ischemia. Accumulating evidences have established that endogenous opioid peptides and their receptors play an important role in this adaptive phenomenon in the heart and other major organs. Of interest for therapeutic developments, opioid receptor agonists have been administered successfully to improve tolerance against experimental ischemia-reperfusion in various tissues. Recent human studies now raise the possibility to exploit this opioid-induced protection in clinical cardiac ischemia. These remarkable anti-ischemic properties of opioids and their emerging potential for organ protection in perioperative medicine will be reviewed at the light of pertinent results from basic and clinical researches.     

精索静脉曲张患者精子顶体酶活性研究

目的　探讨精索静脉曲张患者在精索静脉高位结扎术前、后的精液常规和精子顶体酶活性 (SAA)的变化 ,以及它们之间的相关性。方法　分别用常规方法和改良的Kennedy’s法测定精液常规和精子顶体酶活性 ,再分析它们之间的相关性。结果　精索静脉高位结扎术后患者的精子密度、形态正常率、存活率、活动力以及精子顶体酶活性都较术前明显增高 (P <0 .0 5 ) ;术前、后精子顶体酶活性的变化与精子密度的变化和与精子形态正常率的变化呈正相关关系 (P <0 .0 5 )。结论　精索静脉高位结扎术后精索静脉曲张患者精液质量如精子密度、形态正常率、存活率、活动力和精子顶体酶活性得到明显的提高 ,而且术后精子顶体酶活性的提高与精子密度和形态正常率的提高具有正相关关系