T. B. Hargreave

Microdeletions in interval 6 of the Y chromosome of males with idiopathic sterility point to disruption of AZF, a human spermatogenesis gene

SummaryFor males with idiopathic sterility, a molecular screen specific for small lesions (microdeletions) in interval 6 of the Y chromosome was set up using 29 Y-DNA probes. A “de novo” microdeletion in Y interval 6 was detected in 2 out of 19 “chromosomally normal” sterile males. The first microdeletion includes the Y-DNA probes pY6HP35 and 12f3; the second microdeletion includes the Y-DNA probes pY6HP52, 49f, FR15-II and the subinterval “C” of probe 50f2. A probe of the pY6H sequence family is present in both deletions. Sequences of this family cross-hybridize to dhMiF1, a DNA sequence of a fertility gene structure on the Y chromosome of Drosophila hydei. It was possible to map the position of the Y-deletion of one patient to the distal part of Yq11.22 or the proximal part of Yq11.23, and the deletion of the second patient to the distal part of Yq11.23. These microdeletions probably do not overlap. Since AZF, a human spermatogenesis gene, has been mapped to Y interval 6, we postulate that the microdeletions detected in this chromosome region affect the functional DNA structure of the AZF gene. If this holds true, it is possible that the AZF locus, cytogenetically mapped to distal Yq11, contains two spermatogenesis genes (AZFa and AZFb) or a large gene structure comparable to the Y fertility genes of Drosophila.

Radio-Immunoassay Detection of Interferon-Gamma in Urine after Intravesical Evans BCG Therapy

Our previous studies suggested that interferon-gamma (IFN gamma) was produced in the local immune response to intravesical BCG. To confirm this we modified a commercially available radio-immunoassay for detection of this lymphokine in urine. The urinary levels of IFN gamma were compared in serial urine samples taken from six patients undergoing treatment with Evans strain BCG and seven patients receiving intravesical mitomycin C/epirubicin. IFN gamma was detected consistently in response to BCG with levels reaching a peak (mean 67.1 U/ml., range 7.9 to 155.9 U/ml.) four to six hours post-instillation whereas after other intravesical agents no IFN gamma was detectable after seven of 13 instillations. After the remaining six instillations lower levels were detected (mean 7.4 U/ml., range 0.6 to 22.4 U/ml.). The difference in peak levels between the two groups was statistically significant (p less than 0.001 Mann Whitney U test). These results are further evidence of specific cellular immune activity in response to intravesical BCG therapy and suggest anti-tumour mechanisms similar to allograft rejection and autoimmunity.

Immunocompetent cells in human testis in health and disease

The authors have investigated lymphocyte subpopulations and macrophages in normal human testes and the testes of patients under investigation and treatment for subfertility. Specific monoclonal antibodies were used in an indirect immunoperoxidase technique. In normal tissues, T lymphocytes (Leu 4-positive cells) were present in the rete testis with a preponderance of cells of the suppressor/cytotoxic phenotype. In contrast, no lymphocytes were detected within the peripheral portions of the testis. Cells reacting with the anti-Leu M3 monoclonal antibody, which defines monocytes/macrophages, were detected in appreciable numbers in peripheral testis with a specific location around the seminiferous tubules. HLA-DR-positive cells (human leukocyte antigens--class II [DR] determinants of the major histocompatibility complex) also were identified and showed a similar pattern of distribution to that of the Leu-M3 positive cells. While no lymphocytes were seen in the normal peripheral testis, T lymphocytes were detected in testicular biopsies from subfertile patients. Suppressor/cytotoxic T cells (Leu 2a-positive) predominated in patients with oligozoospermia and obstructive azoospermia while T cells of the helper/inducer phenotype predominated in patients with unilateral testicular obstruction and in postvasectomy patients. Sperm antibody measurements correlated with these findings.

A human 9;20 reciprocal translocation associated with male infertility analyzed at prophase and metaphase I of meiosis

Details are given of a meiotic prophase analysis, carried out by spreading, of a human 9;20 reciprocal translocation ascertained in a subfertile, oligospermic male. Air-dried meiotic preparations revealed the presence of translocation quadrivalents at metaphase I. Germ-cell degeneration was evident from the early prophase of meiosis onward. Associations between the translocation quadrivalent and XY bivalent at pachytene were seen in only 20% of the cells and seemed not to be the prime cause of germ-cell failure. Pairing disruption around the breakpoints of the translocation at pachytene and/or pairing failure in one arm of the pachytene cross was observed in a total of 87% of all cells analyzed. This could have contributed significantly to germ-cell atresia.

Nesbit procedure for disabling Peyronie’s curvature: a median follow-up of 84 months

OBJECTIVES To assess patient satisfaction with cosmetic and functional results after surgical correction for symptomatic penile curvature with the Nesbit procedure using postal questionnaire follow-up. METHODS From 1991, 57 patients underwent surgery for a penile bend of greater than 30 degrees that was interfering with sexual function. Fifteen patients had mild to moderate erectile dysfunction on the preoperative assessment. In all patients, correction of curvature was performed by the Nesbit procedure after adequate preoperative counseling and informed consent. All patients were sent a questionnaire, and 42 men (76.4%) responded. The confidentiality of records was maintained at all times. RESULTS Our study shows that 38 patients (90.5%) had either a straighter penis (n = 26) or minor degrees of curvature of less than 30 degrees (n = 12); only 4 patients had severe curvature. Seven patients complained of some bumpy and narrowed areas, and nine noticed reduced sensory changes. Twenty-one patients complained of penile shortening but 16 reported that this did not affect their sexual performance. Overall, 32 patients were fairly satisfied with the operation-10 (23.8%) of 42 men reported dissatisfaction because of multiple factors. Of these, 6 patients had responded that they would not have undergone the procedure if they were able to turn the clock back. CONCLUSIONS Our long-term results after the Nesbit procedure are longer than that reported in any other series. Our results compare favorably with the short-term results of the modified Nesbit procedure, but simple/modified plication surgery results have not been so encouraging.

Postvoid residual urine in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: pooled analysis of eleven controlled studies with alfuzosin

OBJECTIVES A pooled analysis was conducted in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia to examine the relationship between the postvoid residual urine (PVR) volume and various clinical characteristics and to assess the effect of alfuzosin, a clinically uroselective alpha(1)-blocker, on PVR volume and any other associated outcome. METHODS Nine hundred fifty-three patients, 42 to 89 years old, with a baseline PVR volume between 50 and 350 mL (mean 106 mL) were enrolled in 11 double-blind controlled studies and received either alfuzosin (n = 607) or placebo (n = 346) for 1 to 6 months. The relationships between the baseline PVR volume measured by transabdominal ultrasound and age, symptoms, maximum flow rate (Qmax), estimated bladder capacity, and prostate-specific antigen level were assessed. The changes in the PVR volume with treatment were evaluated in all available patients at three endpoints (1, 3, and 6 months). RESULTS At baseline, a PVR volume of 100 mL or greater was observed in 60%, 47%, and 39% of patients with a Qmax less than 8, 8 to 11, and greater than 11 mL/s, respectively (P = 0.001). The bladder capacity was also significantly related to the Qmax (P = 0.0001). No relationship was found between PVR volume and age, symptoms, or prostate-specific antigen level. The changes in the PVR volume with treatment were related to the baseline PVR volume. However, at all endpoints and whatever the baseline PVR volume, the decreases in the PVR volume were significantly (P <0.01) greater with alfuzosin than with placebo. Acute urinary retention occurred in 7 patients (2 [0.3%] of 607 patients taking alfuzosin and 5 [1.4%] of 346 patients taking placebo); 6 of these 7 patients had a baseline PVR volume greater than 100 mL. CONCLUSIONS In this population of men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia, the PVR olume and bladder capacity were related to the baseline Qmax. Alfuzosin significantly reduced the PVR volume compared with placebo, and this effect was more marked in patients with a high PVR volume at baseline. Acute urinary retention occurred mainly in patients with a PVR volume greater than 100 mL and was less frequent in patients taking alfuzosin than in those taking placebo.

Identifying leucocytes and leucocyte subpopulations in semen using monoclonal antibody probes

An indirect immunoperoxidase technique employing specific monoclonal antibodies has been used to identify leucocyte subpopulations in cytocentrifuge smears of washed human ejaculate. Cells reacting with the pan antihuman leucocyte monoclonal antibody (HLe-1) were demonstrated in 63/67 specimens from subfertile patients with a mean count of 14.5 +/- 17.1 leucocytes per HPF (X 320). Cells with similar reactivity were observed in all specimens examined from 10 fertile men with a mean count of 41.6 +/- 26.3 leucocytes per HPF (X 320). Leu-T4+ cells (T-lymphocytes) were demonstrated in only 13/63 of the subfertile group with a mean count of 4.46 +/- 3.3 T-lymphocytes per HPF (X 320). Studies with the anti-leu 2a antibody revealed that these leu-4+ cells were mainly of the suppressor/cytotoxic phenotype. In contrast, no leu-4+ cells were detected in the control group. No leu-12+ cells (B-lymphocytes) were detected in any of the 80 specimens examined.

Scoring sperm morphology from fertile and infertile cigarette smokers using the scanning electron microscope and image analysis

Image analysis was applied to photographs of sperm samples obtained using a scanning electron microscope. This technique is too time-consuming for routine use but could, if automated, provide an objective assessment of sperm morphology. In order to test the technique, sperm samples were evaluated from four groups of men: fertile and infertile smokers and fertile and infertile nonsmokers. There was a significant increase in the numbers of abnormalities in samples from infertile men. There was no association between the numbers of abnormal sperm and cigarette smoking.

Andrology for the clinician

Andrology: Definition, Clinical Issues and Prevalence.- Layout and How to Use the Book.- General Considerations.- Evidence-Based Medicine in Reproductive Medicine and Andrology.- Economic Cost and Cost-Effectiveness.- Ethics of Reproductive Research and Treatment.- Human Tissue for Research.- Diagnosing and Solving Clinical Problems.- Gender Dysphoria.- Disorders of Sexual Differentiation.- Problem: Abnormal Pubertal Development.- The Consensus-Based Approach to Standardized Diagnosis and Management of the Infertile Male.- The WHO Recommended Diagnostic Flow Chart.- Implications of Multifactorial Aetiology in the Diagnosis and Management of Male Infertility.- Sexual Dysfunction and Male Fertility.- Reference Values of Semen Variables and Their Interpretation.- Normal Spermatozoa and Isolated Abnormalities of Seminal Plasma.- Immunological Causes.- Iatrogenic Causes of Abnormal Spermatozoa.- Systemic Causes of Male Infertility.- Congenital Disorders and Male Infertility.- Acquired Testicular Damage.- Cause: Varicocele.- Infection/Inflammation of the Accessory Sex Glands.- Endocrine Factors.- Oligo-Astheno-Teratozoo-Spermia with No Demonstrable Cause (Idiopathic O-A-T).- Azoospermia.- Erectile Dysfunction.- Erectile Deformity, Including Peyronies Disease.- Ejaculatory Dysfunction: Premature Ejaculation, Delayed Ejaculation, Anejaculation, Low-Volume Ejaculation, Retrograde Ejaculation and Painful Ejaculation.- Orgasm Dysfunction.- Abnormal Libido.- Sexual Deviation and Paraphilias.- Controversies Regarding Postvasectomy Management.- Vasectomy Reversal.- Male Contraception.- Traditional Methods.- Reproductive Tract Infections/Sexually Transmitted Diseases.- HIV Infection.- Testicular Torsion.- Blunt Testicular Trauma.- Penile Fractures.- Priapism.- Testicular Pain and Related Pain Syndromes.- Scrotal Benign Lesions, Epididymal Cysts, Epididymal Tumours.- Testicular Cancer, CIS, Microcalcifications, TNM Classification.- Penile Inflammations.- Penile Cancer.- Circumcision.- Benign Prostatic Hyperplasia and Prostatic Cancer.- Prostatitis.- Gynaecomastia and Benign Breast Hyperplasia Including Iatrogenic Causes.- Skin Diseases of the Male Nipple.- Male Breast Cancer.- Neuroendocrine Regulation of Testicular Function.- Male Ageing: Wear and Tear.- Organ Failure and Common Disease of the Ageing Male.- Rationale.- Anatomy and Histology of the Male Genital Tract.- Sexual Differentiation and Development.- Physiology of Spermatogenesis.- Physiology of Sexual Function.- Endocrine Regulation.- Immunology of the Testis and Excurrent Ducts.- Male Contributions to the Biology of Conception and Fertilization.- Disorders of Prenatal Sexual Development.- Endocrine Disorders and the Role of Hormone Disrupters.- Infection/Inflammation of the Male Genital Tract as Cause of Abnormal Spermatozoa.- Urethritis, Sexually Transmitted Diseases (STD), Acquired Immunodeficiency Syndrome (AIDS).- Disorders of Blood Flow: Arterial and Venous/Sexual Dysfunction and Varicocele.- Effects of Lifestyle and Toxicants.- Influence of Systemic Diseases and Iatrogenic Factors on Sexual and Reproductive Functions.- Mechanisms of Pathogenesis of Uro-Genital Cancers.- History and Examination for Andrological Problems.- Semen Analysis and Sperm Function Tests.- Cytomorphological Semen Analysis.- Clinical Microbiology.- Hormonal Evaluation in Infertility and Sexual Dysfunction.- Tumour Markers in Andrology.- Technical Investigations Including Imaging Procedures: Doppler, MRI, PET, Echo for Tumours.- Technical Investigations Including Imaging Procedures: Colour Flow Doppler and Thermography for the Detection of Reflux in Varicocele.- Evaluation of Testicular Biopsy Samples from the Clinical Perspective.- Genetics and Male Infertility.- Tumour Genetics (Prostate/Testis/Penis).- to Surgical Section.- Surgical Procedures in Andrology.- Vasectomy Technique.- Vasovasostomy and Vasoepididymostomy.- Nonsurgical Cure of Varicocele by Transcatheter Embolization of the Internal Spermatic Vein(s) with a Tissue Adhesive.- Hormonal Treatment of Infertility.- Hormonal Male Contraception.- Treatment of Gender Dysphoria.- Treatment of Sexual Dysfunction.- Therapeutic Options for Benign Prostate Hyperplasia (BPH) and Prostatic Cancer.- Partial Androgen Deficiency of the Ageing Male (PADAM) and Testosterone Supplementation: Use, Misuse or Abuse?.- Abuse of Androgens.- Exotic Hormones.- Anti-Ageing Nutrition and Food Supplements.- Nutriceuticals and Food Supplements in the Treatment of the Infertile Man.- Assisted Reproductive Techniques.- Cryopreservation of Spermatozoa and Testicular Tissue Including Autotransplantation of Germinal Epithelium.- Current Research and Future Prospects for Gene Therapy in Andrology.- Behavioural Therapy and Counselling.- Donor Insemination, Egg and Embryo Donation.- Aesthetic Andrology: Surgical Interventions.- Aesthetic Andrology: Skin Care for Men - Male Cosmetics and Cosmetic Dermatologic Procedures.

Short arm dicentric Y chromosome with associated statural defects in a sterile man

SummaryA short arm dicentric Y chromosome is described as the predominant cell line in a sterile man. The patient also presents with short stature. Tooth development appears normal. Only Sertoli cells are present in the seminiferous tubules. It is suggested that the function of the gene controlling spermatogenesis in Yq11 in man might be to prevent proliferation or migration of germ cells to the gonad of the early embryo.