Search PubMed⌕ Search

Biomedical subjects

T B Hargreave

Publications and source records attributed to T B Hargreave.

At least 19 recordsLinked to original sources
PubMed2001

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.

Adrenergic alpha-Antagonists↗
PubMed2000

Changes of serum prostate-specific antigen following high energy thick loop prostatectomy.

We evaluated the effect of the high electrocuting energy used with the thick loop, in transurethral vaporization resection of the prostate (TUVRP), on serum prostate-specific antigen (PSA). Forty-eight patients with benign protatic hyperplasia (BPH) were included in this prospective single arm sequential study. All patients had TUVRP using the 'Wing' thick resection electrode (Richard Wolf, Germany). Serum PSA was measured before, 1 day and 6 weeks in the morning post TUVRP. PSA values were correlated to preoperative prostate size and to prostatic resection weight. Serum PSA values (mean +/- SD) were 6.29+/-4.4 ng/ml, 14.9+/-11.1 and 2.3+/-1.9 before, 1 day and 6 weeks post TUVRP respectively. The mean increase in the PSA at 1 day over baseline value was 2.72, this was statistically significant (p < or = 0.0001). The PSA level returned to less than pre TUVRP value in all but 3 patients by 6 weeks. The PSA value 1 day post TUVRP correlated well with the pre PSA level, prostate size and prostatic resection weight (r = 0.58, r = 0.38 and r = 0.44 respectively) however, the PSA level at 6 weeks correlated only to pre TUVRP values (r = 0.53). We conclude that that serum PSA is not reliable within 6 weeks of TUVRP. The reversible increase in serum PSA value is similar to other forms of prostatectomy which, suggests that the increased level of electrosurgical energy that is used in TUVRP does not have an added adverse effect on the PSA levels.

Aged↗
PubMed2000

Day-case local anaesthetic radiofrequency thermal ablation of benign prostatic hyperplasia: a four-year follow-up.

OBJECTIVE: This study reports long-term (median 4 years) clinical effectiveness, safety and patient acceptance of transurethral ablation prostatectomy (TURAPY) for symptomatic benign prostatic enlargement (BPE) using a radiofrequency technique. MATERIAL AND METHODS: 25 men were treated as day-case procedures under local anaesthesia for 1 h. The age range was 55-88 years (mean age 65.5 years) and all were suffering from symptomatic BPE with urinary flow rates of 12 ml/s or less. The treatment was carried out with a computer-based device using a special heating element mounted on a Foley-like catheter for prostatic ablation and the temperatures were monitored continuously in the prostatic region, sphincteric area and rectum for safety purposes. RESULTS: TURAPY was carried out in all patients with temperatures ranging from 70 to 82 degrees C depending on the tolerance of the patient. The post-treatment mortality was nil and only 19 patients complained of mild dysuria, passing of some debris and/or minor bleeding on voiding which settled spontaneously in 2-3 weeks, except in two patients who had proven urinary infection requiring antibiotic therapy. At 4 years the International Prostate Symptom Score (I-PSS) improved from a mean value of 16.0 to 7.2 (p < 0.01) with quality-of-life score falling from 4 to 1.9 (p < 0.05); mean flow rate increased from 8.5 to 11.7 ml/s and mean residual volume decreased from 185.04 to 52.8 ml (p < 0.05). Post-treatment pressure flow studies in 14 patients showed normal pressure voiding in one, with four being in an equivocal range, but the rest were obstructed. Prostate ultrasound scanning before and after treatment in 15 patients showed a mean reduction of volume of 16.7 ml suggesting cavitation of prostate following TURAPY. CONCLUSIONS: TURAPY provides lasting subjective but modest objective benefits in symptomatic BPE patients. It is worthy of consideration in elderly patients, or in those who are unfit for surgery or who do not wish to undergo surgery. It is a safe procedure with little transient morbidity but no mortality.

Aged↗
PubMed2000

Genetics and male infertility.

This article reviews chromosomal and genetic disorders in the context of male fertility. Particular emphasis is on those disorders, which are encountered, in clinical practice including Klinefelter's syndrome, Kallman's syndrome, Androgen insensitivity, Y microdeletions, Y fertility gene deletions, and cystic fibrosis gene mutations. These disorders are discussed in relation to the aetiology of male fertility and also risks to children who are born of fathers with these disorders. A list of fathers' categories is proposed for outcome studies for children born after IVF-ICSI. Finally a question is proposed to catalyse debate about germ line therapy.

Chromosome Aberrations↗
PubMed2000

Genetic basis of male fertility.

We are in the age of genetic discovery. Now the human genome has been completely sequenced1, there will be increasing understanding and ability to manipulate biochemical pathways downstream of genes. At the same time, further development of in vitro fertilization (IVF) and intracytoplasmic sperm injection(ICSI) will enable procreation in situations that were formerly impossible and when there may be an increased possibility of genetic abnormality. Furthermore, preimplantation diagnosis will enable defects to be diagnosed and will give the opportunity for the couple to decide whether to continue with treatment towards a pregnancy or not. Thus, there is a need for clinicians to have a good knowledge of the gentics and hereditary aspects of male (and indeed female) infertility and for couples to have access to correct information and expert counselling. Also, there are ethical implications of these scientific and clinical advances for the future child, the individual, the couple and society. There is increasing public unease about this new science of reproduction and, in the UK, there is regulation by law; thus, there is a need for clinicians and scientists to give accurate information in everday language to the public.

Chromosome Aberrations↗
PubMed2000

Efficacy of PSA in the detection of carcinoma of the prostate in patients presenting with acute urinary retention.

OBJECTIVES: A temporary elevation in serum-prostate specific antigen (PSA) levels has been reported in association with acute urinary retention. In spite of this, it is not uncommon for clinicians to assay PSA at the time a patient presents with acute urinary retention. We sought to evaluate whether this practice can be justified. PATIENTS AND METHOD: Fifty-four patients, aged between 55 and 89 years, who presented to a single institution with acute urinary retention were studied. A PSA assay was performed on admission and a record made of the prostatic size as assessed by digital rectal examination. All patients underwent a trial without catheter, those that failed to void underwent prostatic surgery whilst all others were followed up as outpatients. RESULTS: Five patients were found to have prostatic carcinoma, three following transurethral resection of the prostate (TURP) and two following needle biopsy, performed because of persistent elevation of the PSA. A significant elevation in the PSA was associated with acute urinary retention, with only 15 (28%) patients having a PSA of 4.0 ng/ml or less. This elevation reduced the sensitivity of PSA in detecting carcinoma of the prostate; even with a cut-off of 20 ng/ml, the positive predictive value of the test was only 21%. CONCLUSIONS: A PSA assay should not be performed at the time of presentation with acute urinary retention as it may lead to unnecessary investigations and anxiety for the patient. For those in whom a PSA assay is desirable a delay of 2 weeks should be allowed prior to sampling, as the half-life of PSA is known to be 2-3 days.

Aged↗
PubMed1999

Sustained-release alfuzosin and trial without catheter after acute urinary retention: a prospective, placebo-controlled.

OBJECTIVE: To establish whether the administration of sustained-release (SR) alfuzosin improves the outcome of a trial without catheter (TWOC) after an episode of acute urinary retention. PATIENTS AND METHODS: In a prospective, randomized, placebo-controlled trial, 81 patients with acute urinary retention related to benign prostatic obstruction received either SR alfuzosin (n=40), an alpha1-selective blocker, given at a dose of 5 mg twice daily, or placebo (n=41) for 48 h. The catheter was removed after 24 h of treatment. The main outcome measurement was success or failure of the TWOC. At the end of this double-blind phase the patients were followed up on an open basis. RESULTS: After removal of the catheter, 42% of patients voided successfully, 22 of 40 (55%) with SR alfuzosin and 12 of 41 (29%) with placebo (P=0.03). The mean age of patients voiding successfully, regardless of treatment group, was 68. 4 years, whilst the mean age of those who were not successful was 72. 9 years (P=0.015). In an intention-to-treat analysis of outcome adjusted for this age difference, the benefit in favour of those receiving SR alfuzosin was not significant, but at P=0.052 there was a strong suggestion of a positive treatment effect. The observed benefit remained significant in a per-protocol analysis adjusted for age. Taken together, these results indicate that treatment with SR alfuzosin was effective and that the observed benefit was not simply the effect of age difference between the groups. Of the 34 patients who voided successfully 23 (68%) required no further intervention within a mean follow-up of 7 months. CONCLUSIONS: Treatment with SR alfuzosin is effective in improving the success rate of a TWOC after an episode of acute urinary retention, although older patients are less likely to void successfully. By reducing the numbers of men sent home with urinary catheters, such treatment may result in a reduction in the associated perioperative morbidity in those undergoing prostatic surgery, and is clearly desirable for the patients' comfort and convenience.

Adrenergic alpha-Antagonists↗
PubMed1998

The impact of HIV on a fertility problems clinic.

This article describes the impact of the human immuno-deficiency virus (HIV) on clinical infertility practice. HIV is responsible for acquired immuno-deficiency syndrome (AIDS) and first became apparent in 1979, but was not fully recognised by clinicians and scientists until 1981. It is a new disease which now infects large numbers of humans, and there is the possibility that the virulence of the virus may change or mutations may render current testing strategies ineffective. For these reasons, it is important to have a cautious and flexible approach to minimise risk to infertile couples and to future children.

Female↗
PubMed1998

Characterisation of the coding sequence and fine mapping of the human DFFRY gene and comparative expression analysis and mapping to the Sxrb interval of the mouse Y chromosome of the Dffry gene.

DFFRY (the Y-linked homologue of the DFFRX Drosophila fat-facets related X gene) maps to proximal Yq11.2 within the interval defining the AZFa spermatogenic phenotype. The complete coding region of DFFRY has been sequenced and shows 89% identity to the X-linked gene at the nucleotide level. In common with DFFRX , the potential amino acid sequence contains the conserved Cys and His domains characteristic of ubiquitin C-terminal hydrolases. The human DFFRY mRNA is expressed in a wide range of adult and embryonic tissues, including testis, whereas the homologous mouse Dffry gene is expressed specifically in the testis. Analysis of three azoospermic male patients has shown that DFFRY is deleted from the Y chromosome in these individuals. Two patients have a testicular phenotype which resembles Sertoli cell-only syndrome, and the third diminished spermatogenesis. In all three patients, the deletions extend from close to the 3' end into the gene, removing the entire coding sequence of DFFRY. The mouse Dffry gene maps to the Sxrb deletion interval on the short arm of the mouse Y chromosome and its expression in mouse testis can first be detected between 7.5 and 10.5 days after birth when type A and B spermatogonia and pre-leptotene and leptotene spermatocytes are present.

Adult↗
PubMed1998

Dynamic changes in the subnuclear organisation of pre-mRNA splicing proteins and RBM during human germ cell development.

RBM is a germ-cell-specific RNA-binding protein encoded by the Y chromosome in all mammals, implying an important and evolutionarily conserved (but as yet unidentified) function during male germ cell development. In order to address this function, we have developed new antibody reagents to immunolocalise RBM in the different cell types in the human testis. We find that RBM has a different expression profile from its closest homologue hnRNPG. Despite its ubiquitous expression in all transcriptionally active germ cell types, RBM has a complex and dynamic cell biology in human germ cells. The ratio of RBM distributed between punctate nuclear structures and the remainder of the nucleoplasm is dynamically modulated over the course of germ cell development. Moreover, pre-mRNA splicing components are targeted to the same punctate nuclear regions as RBM during the early stages of germ cell development but late in meiosis this spatial association breaks down. After meiosis, pre-mRNA splicing components are differentially targeted to a specific region of the nucleus. While pre-mRNA splicing components undergo profound spatial reorganisations during spermatogenesis, neither heterogeneous ribonucleoproteins nor the transcription factor Sp1 show either developmental spatial reorganisations or any specific co-localisation with RBM. These results suggest dynamic and possibly multiple functions for RBM in germ cell development.

Cyclic AMP Response Element Modulator↗
PubMed1997

Expression of RBM in the nuclei of human germ cells is dependent on a critical region of the Y chromosome long arm.

The association of abnormal spermatogenesis in men with Y chromosome deletions suggests that genes important for spermatogenesis have been removed from these individuals. Recently, genes encoding two putative RNA-binding proteins (RBM and DAZ/SPGY) have been mapped to two different regions of the human Y chromosome. Both of these genes encode proteins that contain a single RNA recognition motif and a (different) internally repeating sequence. Y-linked RBM homologues are found in all mammalian species. We have raised an antiserum to RBM and used it to show that RBM is a nuclear protein expressed in fetal, prepubertal, and adult male germ cells. The distribution of RBM protein in the adult correlates with the pattern of transcriptional activity in spermatogenesis, suggesting that RBM is involved in the nuclear metabolism of newly synthesized RNA. RBM sequences are found on both arms of the Y chromosome making genotype-phenotype correlations difficult for this gene family. To address the location of the functional genes and the consequences of their deletion, we examined a panel of men with Y chromosome deletions and known testicular pathologies using this antiserum. This approach enabled us to map a region of the Y chromosome essential for RBM expression. In the absence of detectable RBM expression we see stages of germ cell development up to early meiosis, but not past this point into the haploid phase of spermatogenesis.

Adult↗
PubMed1997

The incidence of cystic fibrosis gene mutations in patients with congenital bilateral absence of the vas deferens in Scotland.

OBJECTIVE: To examine the incidence of cystic fibrosis transmembrane-conductance regulator (CFTR) gene mutations in Scottish patients with congenital bilateral absence of the vas deferens (CBAVD). PATIENTS AND METHODS: Thirty patients with CBAVD presenting consecutively to the Edinburgh infertility clinic were examined for CFTR gene mutations. All patients were assessed clinically and tested for 15 gene mutations using a single-tube polymerase chain-reaction multiplex system. RESULTS: All patients were in good health and without clinical evidence of cystic fibrosis. CFTR gene mutations were found in 70% of patients with CBAVD. CONCLUSION: CFTR gene-testing and genetic counselling are important in all men with CBAVD.

Cystic Fibrosis↗
PubMed1997

Preliminary investigations on androgen receptor gene mutations in infertile men.

A total of 50 men were selected from all patients attending an infertility clinic on the basis of oligozoospermia or azoospermia with concentrations of luteinizing hormone >6 IU/l and testosterone >30 nmol/l. Six of these men responded to written invitation and DNA was extracted from blood leukocytes. Individual exons of the androgen receptor gene were amplified by polymerase chain reaction and screened for the presence of mutations by denaturing gradient gel electrophoresis. The glutamine rich portion of exon 1 was sequenced directly. All of the coding sequence of the gene was examined except the glycine rich portion of exon 1 in all patients. No mutations or deletions were identified. Androgen receptor gene mutations do not appear to be present in infertile men with biochemical disturbances compatible with androgen resistance. It is therefore unlikely that such mutations are a major factor in the pathogenesis of oligozoospermia/azoospermia and infertility.

Humans↗
PubMed1996

Mortality after transurethral and open prostatectomy in Scotland.

OBJECTIVE: To use the linked medical and death records in Scotland to investigate the possible increased mortality that has been reported after transurethral prostatectomy (TURP) compared with open prostatectomy. PATIENTS AND METHODS: Scotland has maintained linkable hospital, cancer and death records for more than 20 years, representing one of the largest such databases in the world. From these computerized records, data on various cohorts of men aged 55-84 years selected from 81,997 men who underwent prostatectomy in Scotland between 1968 and 1989 were analysed. The risk of late mortality was calculated for each type of operation, whether there was prior comorbidity and for a range of specific causes (cancer, respiratory and circulatory conditions) after prostatectomy. RESULTS: Among the largest cohort, consisting of 65,519 men who underwent prostatectomy between 1968 and June 1989, the relative risk of late mortality after TURP compared with open prostatectomy was 1.13 (95% CI, 1.10-1.16), after controlling for age and the presence of a diagnosis of cancer. A more restricted cohort of 18,732 men who underwent prostatectomy between 1974 and 1979 allowed adjustment for prior hospitalization with, or concurrent diagnosis of, circulatory and respiratory conditions. In this cohort, the relative risk of late mortality after TURP as compared with open prostatectomy was 1.15 (95% CI, 1.11-1.19) after adjusting for prior and comorbidity and age. Finally, a cohort of 'healthy patients' restricted to the 6932 men who underwent prostatectomy from 1974 to 1979 and with no evidence of hospitalization in the previous 5 years or any current diagnosis other than benign hypertrophy of the prostate, showed a relative risk of 1.14 (95% CI, 1.07-1.21). There was no evidence of an increased risk of dying from circulatory disease in general, ischaemic heart disease or acute myocardial infarction after TURP as opposed to open prostatectomy. However, there was an increased risk of dying from respiratory conditions and from cancer, especially of the prostate and bladder. The analysis suggested the possibility that open prostatectomy may have cured some patients with early prostatic cancer, because the late death rate from prostatic cancer was greater in patients who underwent TURP than open prostatectomy. CONCLUSION: The present analysis confirmed the increased risk of late mortality after TURP compared with open prostatectomy, as shown in previous studies based on administrative records. However, limitations in the coding of comorbidities and the absence of coding of more subtle aspects of the condition of the patient which may influence the choice between the forms of prostatectomy mean that the differential mortality after the two procedures could still be a reflection of the pre-operative selection of patients rather than the effects of the surgical procedure.

Aged↗