PubMed Health⌕ Search

Biomedical subjects

T B Hargreave

Publications and source records attributed to T B Hargreave.

At least 19 recordsLinked to original sources
PubMed1992

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

For 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.

Chromosome Deletion↗
PubMed1992

Intravesical Evans strain BCG therapy: quantitative immunohistochemical analysis of the immune response within the bladder wall.

Previous studies have demonstrated that is is the local immune response which is of importance for the anti-tumour activity of BCG therapy. We have investigated this by quantitative immunohistochemical analysis of serial bladder mucosal biopsies taken before, during and after an eight week course of intravesical Evans strain BCG therapy and three monthly thereafter in 16 patients (15 extensive CIS and one extensive G2pTa papillary tumour). This particular group of patients had a 67% complete response rate at six months post-treatment. The main findings on immunohistochemical analysis were the universal induction of MHC Class II antigens by urothelial cells which was statistically significant up to 6 months after completion of therapy, coupled with a T cell dominated cystitis. Increases in CD3+ T cell infiltration of the lamina propria and that of the CD4+ "Helper" subset which predominated were significant up to 3 months post-therapy and these cells showed evidence of increased immunological activation as shown by increased interleukin-2 receptor and MHC Class II antigen expression. There were also significant increases in CD68+ macrophage and the incidence of CD22+ B cell aggregates but CD57+ NK cells were sparse both before and after therapy. The degree of mononuclear cell infiltration for all markers examined (except CD57) was significantly greater in those biopsies in which the urothelial cells expressed MHC Class II antigens than in those that did not. Also the degree of T cell infiltration (CD3, CD4 and CD8) was significantly greater in the eight patients deemed to have had a complete response compared to those seven with a partial response or treatment failure. These results are discussed in terms of possible mechanisms of action for BCG therapy and in particular the role of enhanced antigen presentation by tumour cells.

Administration, Intravesical↗
PubMed1992

Towards the molecular localisation of the AZF locus: mapping of microdeletions in azoospermic men within 14 subintervals of interval 6 of the human Y chromosome.

We have used a series of 30 DNA probes previously mapped to the long arm of the human Y chromosome, to screen a panel of 21 patients with structural abnormalities in Yq, by genomic blot hybridisation. The results have allowed us to construct a detailed map of interval 6 of the Y chromosome, in which 28 of the probes could be assigned to 14 sub-intervals within interval 6. Some probes detect two or more loci within this region, each of which has been localised. The same set of probes has been used to screen a panel of 19 chromosomally normal azoospermic men, two of whom have been found to carry microdeletions within this region. With the completion of this map we have been able accurately to localise these microdeletions within interval 6 and show that they do not overlap. We believe these microdeletions may disrupt the azoospermia factor (AZF) involved in spermatogenesis, and which is known to lie in this region. These results are an important step towards the localisation of the AZF locus.

Blotting, Southern↗
PubMed1992

Radical radiotherapy with salvage surgery for invasive bladder cancer: results following a reduction in radiation dose.

The management of invasive bladder cancer in Edinburgh, as in many other centres in the UK, has been by radical radiotherapy, with cystectomy reserved for local treatment failure or relapse. A review of the results of this policy in 1987 highlighted what was felt to be an unacceptably severe morbidity rate of 15%. The dose of radiation was therefore reduced from 55 Gy in 20 daily fractions to 52.5 Gy. Forty of 80 patients (50%) treated in this way have achieved a complete response at 6 months which is a similar response rate to that in previous reports. In addition, ten of 23 frail or elderly patients (43%) achieved a complete response with a lower dose of 50 Gy given as a split course over 7 weeks. Eighteen patients have had a salvage cystectomy, and 12 of 18 (67%) are alive and disease-free. Although follow-up is short, to date toxicity has been reduced, and our results support our decision to reduce the radiation dose.

Adult↗
PubMed1991

Immunosuppression by seminal plasma from fertile and infertile men: inhibition of natural killer cell function correlates with seminal PG concentration.

Human seminal plasma has uniquely high concentrations of PGE and 19-hydroxy PGE but the function of these PGs has not been elucidated. PGs of the E series have been shown to be paracrine and autocrine regulators of the function of immune cells and high levels of PGE have been shown consistently to suppress function in such cells. Human seminal plasma has a potent immunosuppressive effect and evidence is accumulating that this is largely due to PG components. In this study the effects of human seminal plasma on the killing activity of natural killer (NK) cells as judged by 51Cr release from K562 cells have been studied in groups of fertile and infertile men. Although there was no significant difference in the PGE, 19-hydroxy PGE or the NK cell inhibitory activity in the two groups, the inhibition of NK cell activity was closely correlated with the PGE and the 19-OH PGE content of the seminal plasma in the fertile group. This finding is further evidence that the major contribution to the immunosuppressive properties of human semen is provide by the high concentration of PGs of the E series in this fluid.

Alprostadil↗
PubMed1991

Study of bilateral histology and meiotic analysis in men undergoing varicocele ligation.

Fifty men underwent testicular biopsy at the time of varicocele ligation. The biopsies were scored and also a portion from each biopsy was subjected to meiotic analysis. All men were followed up (mean follow-up 19.3 months). There were no consistent histologic or meiotic abnormalities, and there was no evidence that the varicocele side was more defective than the contralateral side. Thirteen pregnancies were recorded, and these occurred only when the mean Johnsen score from one or other testis was greater than 6.0.

Adult↗
PubMed1991

Sperm retrieval by electro-ejaculation. Preliminary experience in patients with secondary anejaculation.

Twelve patients with spinal cord injury and 2 diabetics with secondary anejaculation underwent 26 sessions of electro-ejaculation, using a technique which has previously been popular only in veterinary medicine. Ejaculate was obtained on 21 occasions. Semen quality was adequate for cryostorage on 9 occasions (8 patients); on 8 occasions (5 patients) it was used for immediate artificial insemination of the partner. To date, there has been 1 pregnancy resulting in a live birth.

Adult↗
PubMed1991

Surgery following chemotherapy for metastatic testicular teratoma.

Twenty patients with metastatic testicular teratoma underwent surgery for residual disease after chemotherapy. Twelve patients in whom complete excision of all residual masses was possible are alive with no evidence of disease. Four patients have died of malignant teratoma, 2 have active malignant disease and 2 have inoperable residual cystic disease. Patients with malignant teratoma intermediate (MTI) primary testis tumours, and those with bulky abdominal disease at presentation, are more likely to have residual masses requiring excision. Completeness of excision appears to be the most important predictor of disease-free survival.

Adolescent↗
PubMed1991

Neoadjuvant chemotherapy with methotrexate and cisplatin prior to radiotherapy for invasive transitional cell carcinoma of the bladder. Assessment of feasibility and toxicity.

A prospective study has been performed to assess the feasibility and toxicity of administering neoadjuvant chemotherapy with methotrexate (200 mg/m2) and cisplatin (100 mg/m2) prior to radical radiotherapy. Twenty patients with advanced transitional cell carcinoma of the bladder were assessed after each of 3 courses of chemotherapy, after radiotherapy and 6 months following treatment. Of particular concern was whether neoadjuvant chemotherapy compromised the ability to give potentially curative radical radiotherapy, delayed effective palliation of distressing urinary symptoms, or allowed local tumour progression prior to definitive treatment. It was concluded that this chemotherapy regimen was well tolerated, did not compromise the ability to give radical radiotherapy and resulted in the prompt palliation of urinary symptoms. This treatment, however, did not stop the development or progression of metastatic disease in some patients. In only 1 patient was there local progression during chemotherapy.

Adult↗
PubMed1990

Comparison of prednisolone and placebo in subfertile men with antibodies to spermatozoa.

43 subfertile men with circulating antibodies to spermatozoa entered a double-blind crossover trial and received soluble prednisolone (20 mg twice daily on days 1-10 of the female partner's menstrual cycle, followed by 5 mg on days 11 and 12) or matching placebo tablets for 9 months each. 9 pregnancies were produced by men during prednisolone treatment, compared with 2 by men randomised to placebo (although only 1 was actually taking the placebo). No serious complications were produced, although 60% of those receiving prednisolone experienced mild side-effects.

Agglutination Tests↗
PubMed1990

Survey of antibiotic prophylaxis in European renal transplantation practice.

Death and morbidity resulting from infection in the immunosuppressed patient following renal transplantation has been much reduced as immunosuppressive regimens have become less aggressive. Such complications, however, remain a considerable risk to transplant recipients and the use of prophylactic antibiotics has been advocated. This survey documents current practices and attitudes to the use of antibiotic prophylaxis in renal transplantation centres throughout Europe on the basis of response to a postal questionnaire.

Anti-Bacterial Agents↗
PubMed1990

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.

Administration, Intravesical↗
PubMed1990

Granulocyte elastase levels do not correlate with anaerobic and aerobic bacterial growth in seminal plasma from infertile men.

Seminal culture and leucocyte elastase measurements were undertaken on samples from 30 men attending an infertility clinic. Elastase levels over 1000 ng ml-1 were obtained in 14 men and positive bacterial culture in 11 men, but there was no correlation between these two sets of measurements. While granulocyte elastase measurement in semen may reflect inflammation, our study suggests that it cannot be used as a simple marker of infection particularly in a population such as ours where the prevalence of prostatitis and genital infection is low.

Bacteria, Aerobic↗
PubMed1990

Antibiotic compared with antiseptic prophylaxis for prostatic surgery.

Two different regimens of cephalosporin antibiotic prophylaxis were compared with antiseptic lubricating jelly to try to prevent infection and complications in 196 men after prostatic surgery. Pre-operative urine was cultured and prostatic chips (170 cases) were also cultured to define the source of any infection. The use of antibiotics was associated with a reduced risk of postoperative bacteriuria. No serious complications occurred, although 1 patient in the antiseptic treated group developed rigors; 79 of 170 patients (46%) had positive prostatic chip cultures, of whom 74 had sterile pre-operative urine. There was no association between the result of chip culture and the presence of a pre-operative catheter. Culture positive patients had an increased risk of post-operative urine infection, although the same organism was found in the prostate and urine in only 36% of cases of post-operative bacteriuria and in 43 (54%) the organism cultured from the prostate was Staphylococcus albus. This study provides further evidence of the benefit of true prophylactic antibiotic therapy for transurethral prostatic surgery and the prostatic chip data suggest that some of the risk is due to pre-operative contamination of the prostate in the absence of per-operative urinary infection or catheterisation.

Aged↗
PubMed1990

A multi-centre phase two study of intravesical epirubicin in the treatment of superficial bladder tumour.

Epirubicin (4'-epi-adriamycin) was used in the treatment of widespread superficial carcinoma of the bladder. Thirty-seven patients received 50 mg in 50 ml of saline retained for 60 min. There was an overall response rate of 59% but this was of short duration. Thirty percent of patients progressed despite therapy. Therapy was associated with an incidence of side effects which necessitated therapy withdrawal in 12 (32.4%) patients. It is concluded that epirubicin, in the dose used in this study, cannot be recommended for routine intravesical chemotherapy and that further studies, at a reduced dosage, are necessary to evaluate this agent.

Administration, Intravesical↗