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Biomedical subjects

D J Ralph

Publications and source records attributed to D J Ralph.

At least 37 records · Page 2Linked to original sources

Y-27632, an inhibitor of Rho-kinase, antagonizes noradrenergic contractions in the rabbit and human penile corpus cavernosum.

We have examined the effect of an inhibitor of Rho-kinase, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632), on the contractions elicited by noradrenergic nerve stimulation and by phenylephrine in the human and rabbit penile corpus cavernosum. In both tissues, after treatment with scopolamine (10 microM) and N(G)-nitro-L-arginine methyl ester (L-NAME; 300 microM), electrical field stimulation (EFS) elicited noradrenergic contractions. These contractions were inhibited by Y-27632 in a concentration-dependent manner. The compound caused concentration-dependent relaxation of phenylephrine-contracted tissues, which were treated with scopolamine (10 microM), guanethidine (10 microM) and L-NAME (300 microM). These results suggest that Rho-kinase is involved in noradrenergic contractile pathway in the cavernosal smooth muscle of the penis.

Amides↗

The Nesbit operation for Peyronie's disease: an analysis of the failures.

OBJECTIVE: To analyse critically the reasons for a poor outcome of the Nesbit operation for Peyronie's disease in 51 patients over a 20-year period. PATIENTS AND METHODS: Fifty-one patients who were classified as having a poor result from the Nesbit operation were reviewed (mean age 53 years, mean follow-up 21 months). The factors responsible for a poor result were analysed and classified into three groups: (i) deformity > 30 degrees; (ii) penile shortening > 2 cm; and (iii) impaired erection. Patients with a recurrent deformity were further classified according to the interval from surgery to the presentation of the recurrence. RESULTS: Thirty-one patients had a deformity of > 30 degrees; this occurred immediately in three patients through surgical error, soon after surgery in eight patients because of suture failure and after 11 months in the remaining 20 patients because their Peyronie's disease progressed. Penile shortening of > 2 cm was present in 19 patients but this only affected coital function in four. Erection was impaired in 10 patients but this was present before surgery in most. CONCLUSION The results of the Nesbit operation for Peyronie's disease can be improved by a preoperative assessment of erectile function and the use of sutures of high tensile strength. Patients should be warned that the disease may progress and that some penile shortening should be expected, although this does not affect coital function.

Adult↗

Sildenafil: efficacy and safety in daily clinical experience.

OBJECTIVES: Sildenafil citrate (Viagra) is a potent selective inhibitor of phosphodiesterase type 5 proposed for the oral treatment of erectile dysfunction (ED). The aim of this study was to evaluate its efficacy and safety when used in daily practice in patients with ED of various aetiology. PATIENTS AND METHODS: From September 1998 to April 1999, 380 patients chose sildenafil as treatment for their ED. One hundred and forty-five (38%) of them suffered from psychogenic ED, 125 (33%) organic and 110 (29%) of mixed aetiology. The grade of erection achieved and the occurrence of satisfactory sexual intercourse assessed the efficacy. Safety and tolerance were evaluated recording any side effect or adverse event. RESULTS: The overall efficacy of Viagra was 77%, with a response of 100% among the group of hormonal patients, 88% for psychogenic, 72% for mixed, 69% for diabetes, 65% for vascular and 60% for neurological symptoms. A few and mild to moderate side effects were recorded. CONCLUSION: These results indicate that the use of sildenafil citrate is an effective and well-tolerated therapy for men with ED of various aetiology with an overall success rate of 77%.

Adult↗

Cavernosal arterial insufficiency is a major component of erectile dysfunction in some recipients of high-dose chemotherapy/chemo-radiotherapy for haematological malignancies.

We studied 24 male patients aged 26-62 years (median 41) prospectively presenting over a 5 year period with clinical features of hypogonadism and erectile dysfunction (ED), who had been treated with autologous or allogeneic bone marrow/stem cell transplant for a variety of haematological malignancies and had received either high-dose chemotherapy or high-dose chemotherapy combined with total body irradiation (TBI). Ten healthy adult controls (aged 35-50 years) were also studied. Erectile dysfunction (ED) was assessed clinically and by colour flow Doppler studies of the cavernosal vessels. Testicular function was assessed by testicular volume including orchidometry, FSH, LH and testosterone measurements. Libido and ejaculatory function were also recorded. Patients had severe hypogonadism as evidenced by low mean testicular volume (7.0 +/- 2.4 ml vs 20 +/- 2.0 ml; P < 0.001), elevated gonadotrophins (FSH = 18.54 +/- 7.61 vs 5 IU/l (P < 0.001); LH = 8.02 +/- 2.89 vs 3. 9 IU/l (P < 0.001)) and low normal mean testosterone levels (16.4 nmol/l +/- 9.1 vs 22.4 nmol/l (P < 0.5)). Cavernosal arterial insufficiency was found in 11/14 of TBI-treated and in 3/10 HDC-treated patients, indicative of vasculogenic damage to corpora cavernosal vessels. Patients were given a therapeutic trial with testosterone replacement therapy (TRT). Those who had diminished libido had a marked improvement in their symptoms but the effect of TRT on ED was equivocal. In conclusion, this is the first report to show vasculogenic insufficiency in patients with haematological malignancies treated by BMT. Although hypogonadism can account for diminished libido, arteriogenic insufficiency is likely to be an important factor accounting for ED in these patients, especially those treated by TBI. We recommend a comprehensive assessment including endocrine profile and colour flow Doppler study in formulating the best management plan in recipients of high-dose therapy presenting after transplant with ED.

Adult↗

The Nesbit operation for congenital curvature of the penis.

OBJECTIVE: To assess the results of the correction of congenital penile curvature using the Nesbit operation. PATIENTS AND METHODS: The records of 106 patients who had a Nesbit operation to correct a congenital penile curvature between 1977 and 1992 were reviewed. RESULTS: An excellent (78.3%) or satisfactory (17.9%) result was achieved representing an overall success rate of 96.2%. The reasons for a poor or satisfactory result were either an impaired erection--7 (6.6%) [all psychogenic] or a residual deformity of 10 degrees--16 (15.1%). There were no major complications although five patients (5.3%) needed a further Nesbit operation. CONCLUSION: The Nesbit operation is a simple and effective technique for the correction of a congenital penile curvature.

Adolescent↗

What's new in Peyronie's disease.

Within the past year further scientific studies have been performed to find the aetiology of Peyronie's disease. Advances in the conservative management of the disease by extracorporeal shockwave therapy have been reported in many centres. The operation of plaque excision and grafting, which has been performed for over 25 years, has now been replaced by the superior operation of plaque incision with venous patch.

Female↗

Clinical aspects associated with Sertoli-cell-only histology.

OBJECTIVE: To assess the clinical features found in infertile men in whom the histological diagnosis of Sertoli-cell-only (SCO) was made on testicular biopsy. PATIENTS AND METHODS: A retrospective review was carried out of the seminal fluid analysis, testis size and follicle-stimulating hormone (FSH) levels of 72 men who had bilateral testicular biopsies due to infertility when one (30) or both (42) of bilateral testicular biopsies showed tubules containing only Sertoli cells. In a subgroup of 15 men, the biopsies were re-examined to correlate the morphological features with the plasma FSH level. RESULTS: When both biopsies showed bilateral SCO the patient had azoospermia (86%) or oligozoospermia (14%); the testicular size was normal in 36% and the FSH level was normal (43%), raised (21%) or grossly elevated (more than twice normal, 36%). When one biopsy showed SCO, the opposite testis showed appearances which varied from grossly impaired spermatogenesis to almost normal spermatogenesis. The clinical findings were also very variable. CONCLUSIONS: The clinical features associated with the histological diagnosis of SCO are extremely variable. Biopsy evidence of bilateral SCO cannot be relied upon to indicate a total absence of spermatogenesis in the testes.

Biopsy↗

The genetic and bacteriological aspects of Peyronie's disease.

PURPOSE: Peyronie's disease has been associated with HLA tissue types, including HLA-A1, DR3, DQw2 and HLA-B7 cross-reactive group antigens which include HLA-B27. This association was tested as was the process of molecular mimicry where the host HLA surface antigen cross-reacts with a microorganism. MATERIALS AND METHODS: HLA tissue typing was performed on 51 white patients with Peyronie's disease, of whom 15 also had Dupuytren's contracture of the hand. Fecal, urine and urethral samples were taken from patients with Peyronie's disease who had proved penile inflammation on biopsy. The samples were cultured for species of Campylobacter, Shigella, Salmonella, Yersinia, Chlamydia and gonococcus, all known to cross-react with the HLA-B27 surface antigen. Antibodies to Klebsiella species, Proteus species and Escherichia coli were also assessed in the sera of 65 patients with Peyronie's disease. RESULTS: A significant association between Peyronie's disease and HLA-B27 was found (p = 0.02). The remaining antigens of the HLA-B7 group were not significantly associated with the disease individually (HLA-B7 p > 0.2, HLA-B22 p > 0.6, HLA-B40 p > 0.7) or as a group (p = 0.69). The previously found associations did not reach significance in this study (HLA-A1 p > 0.5, HLA-B8 p > 0.2, HLA-Cw7 p = 0.1, HLA-DR3 p > 0.4, HLA-DQ2 p > 0.4). Cultures for all enteric and urethral organisms were negative, and patients with Peyronie's disease did not have elevated serum titers of anti Klebsiella, anti Proteus or anti E. coli antibodies. CONCLUSIONS: Although there is an association between Peyronie's disease and HLA-B27, molecular mimicry does not occur with the organisms tested, and an infectious agent has not been found in this study.

Bacterial Infections↗

The immunological features of Peyronie's disease.

PURPOSE: We investigated the immunological features and possible autoimmune basis of Peyronie's disease. MATERIALS AND METHODS: The sera of 100 patients with Peyronie's disease were tested for circulating autoantibodies, including anti-penis antibodies, by indirect immunofluorescence. Antibody deposition and the immunological activity in Peyronie's plaque tissue from patients with early and long-standing disease were also assessed. RESULTS: Circulating anti-penis antibodies were not found in any patient although antinuclear antibodies were present in 24%. Patients with early Peyronie's disease had IgM antibody deposition, marked T lymphocytic and macrocytic infiltration in the sub-tunical space, increased expression of adhesion molecules by endothelial cells and an increased human lymphocyte antigen class 2 expression by the cellular infiltrate, indicating cellular immune activation. CONCLUSIONS: These results show that some of the features of autoimmunity, in particular the cell mediated response, are present in Peyronie's disease.

Autoantibodies↗

The Nesbit operation for Peyronie's disease: 16-year experience.

PURPOSE: We analyze the long-term outcome of the Nesbit operation for the correction of the penile deformity due to Peyronie's disease. MATERIALS AND METHODS: Between 1977 and 1992, the penile deformity due to Peyronie's disease was corrected in 359 patients using the Nesbit operation. RESULTS: The overall success rate was 82%, which increased to 90% during the last 8 years with better patient selection due to improved preoperative investigation. Complications were minimal and only 6 patients had significant penile shortening that precluded sexual intercourse. CONCLUSIONS: The Nesbit operation remains the procedure of choice to correct the penile curvature of Peyronie's disease.

Adult↗

Laparoscopic varicocele ligation.

A laparoscopic varicocele ligation was performed in 49 men with a clinically proven varicocele. Patients were treated predominantly on a day case or overnight basis with minimal post-operative morbidity. Identification of the testicular artery was aided by a laparoscopic Doppler probe in the majority of patients and preserved in 39 cases. The varicocele persisted in 7 patients, 4 of whom have subsequently had an inguinal exploration confirming a missed testicular vein as the source. In all 7 patients the artery was identified without the use of the Doppler probe, this being suggestive of misidentification of the vessels at laparoscopy. The complications included 4 wound infections, 1 scrotal haematoma and 1 vasal injury which necessitated an open vasovasostomy. Laparoscopic varicocele ligation is a simple and safe technique, causing minimal morbidity and enabling a rapid return to normal activity. The success rate can be improved by accurate identification of the testicular vessels with the use of a laparoscopic Doppler probe.

Adolescent↗