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Biomedical subjects

P R Malone

Publications and source records attributed to P R Malone.

18 recordsLinked to original sources
PubMed1999

Pharmacodynamics of a long acting depot preparation of avorelin in patients with prostate cancer. Avorelin Study Group.

PURPOSE: We evaluate the pharmacodynamics, pharmacokinetics and tolerability of a sustained release depot formulation of avorelin, a new potent super agonist of luteinizing hormone-releasing hormone receptors, in patients with prostate cancer. MATERIALS AND METHODS: A total of 60 patients were randomized to receive a 10 mg. (31) or 15 mg. (29) avorelin subcutaneous depot. Serum testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and plasma avorelin were measured regularly until depot exhaustion. RESULTS: Of the 10 mg. group patients 3 withdrew from the study after 31 to 35 weeks due to disease progression. Of the 15 mg. group patients 1 did not complete the study for logistical reasons. After the expected flare in serum testosterone, LH and FSH during week 1, medical castration (testosterone concentration less than 1.735 nmol./l.) was achieved within 4 weeks of depot injection. Median duration of testosterone suppression was 40 weeks in the 10 mg. (95% confidence interval 35 to 42) and 39 in the 15 mg. (37 to 43) group. The reduction in serum LH was similar to that of testosterone, while that of FSH was less pronounced. Plasma avorelin was proportional to the dose and correlated with serum testosterone. Normalization of serum prostate specific (4 ng./ml. or less) at 6 months was achieved in 80 and 88% of the 10 and 15 mg. groups, respectively. During the (7 to 20-month) observation period 94 and 86% of the 10 and 15 mg. groups, respectively, complained of adverse events mainly related to androgen suppression (hot flushes, decreased libido and impotence) or the nature of the disease (skeletal pain). In each group 3 patients had serious adverse events requiring hospitalization for reasons unrelated to avorelin treatment. The depot was well tolerated locally. CONCLUSIONS: Subcutaneous depot formulations of avorelin were well tolerated and had protracted inhibitory effects on pituitary gonadotropin secretion in patients with prostate cancer. Testosterone suppression was maintained for more than 6 months in all patients. Avorelin depots could be the first luteinizing hormone-releasing hormone agonist formulation to be administered at 6-month intervals.

Adult↗
PubMed1999

The role of urine cytology in the assessment of lower urinary tract symptoms.

OBJECTIVE: To evaluate the role of urine cytology in the investigation of men with lower urinary tract symptoms (LUTS) in the absence of haematuria. PATIENTS AND METHODS: The study comprised 336 men attending a LUTS assessment clinic, who had neither macroscopic nor microscopic haematuria. One sample of urine was collected for cytology. Those with suspicious urine cytology were investigated with intravenous urography and cystoscopy. RESULTS: Five men had abnormal urine cytology results; on further investigation one of them was found to have carcinoma in situ (CIS) and one to have a transitional cell carcinoma. Three had false-positive urine cytology results. CONCLUSION: A bladder tumour or CIS was detected in 0.6% of the population tested. The cost per cancer diagnosed was GB pound 2020. Urine cytology is a simple noninvasive way of assisting accurate diagnosis of men who have LUTS in the absence of haematuria.

Carcinoma in Situ↗
PubMed1994

Peptides related to thyrotrophin-releasing hormone (TRH) in human prostate and semen.

The TRH-related peptide, pGlu-Glu-ProNH2, which was first identified in rabbit prostate has recently been named fertilization-promoting peptide (FPP) because of its ability to enhance the in vitro fertilizing potential of mouse epididymal spermatozoa. This study set out to examine the nature of the TRH-related peptides in human prostate and semen but, first, the optimal conditions for collection of semen samples were investigated. FPP was degraded slowly (t1/2 = 163 min, S.E. +/- 51.3, n = 6) in seminal plasma which has allowed us to measure accurately the concentrations of FPP, after extraction of the peptide in acidified acetone precisely 5 min after ejaculation. In this way, high levels of FPP (mean: 49.5 nmol/l) were detected in normal human semen, from young men, although other TRH-related peptides did not appear to be present. We have also examined the TRH-related peptides present in prostate samples from clinical patients both with and without evidence of benign prostatic hyperplasia (BPH), by ion-exchange chromatography followed by radioimmunoassay. Substantial concentrations of FPP were observed in normal (4.10 pmol/g tissue, S.E. +/- 1.46) and BPH prostate (6.27 pmol/g tissue, S.E. +/- 1.65). In addition, a second, neutral TRH-immunoreactive peptide was always detected in BPH tissue (7.40 pmol/g tissue, S.E. +/- 1.98) with only low levels generally present in normal prostate. The possibility that the presence of high levels of the neutral peptide in prostate may be used as an indicator of the onset of BPH deserves further scrutiny.

Adult↗
PubMed1992

Actinomycosis associated with pilonidal sinus of the penis.

We report a case of actinomycosis associated with a penile pilonidal sinus. This association does not appear to have been described previously. We recommend the submission of biopsies of unusual lumps in the genital region (fresh biopsies for bacteriological examination and fixed biopsies for histomorphological assessment).

Actinomycosis↗
PubMed1990

Aromatase inhibition in advanced prostatic cancer: preliminary communication.

We report the results of the first use of a steroidal aromatase inhibitor, 4-hydroxyandrostenedione (4-OHA, CGP 32349), in the palliation of patients with advanced, hormone resistant, prostatic cancer. Twelve of 19 patients (63%), who had relapsed following castration and other therapies, gained significant pain relief following weekly intramuscular injections of 4-OHA. Five patients (31%) experienced a transient 'tumour flare', represented by an increase in bone pain soon after commencing treatment. The mechanism of action of 4-OHA in palliating patients with advanced prostatic cancer is obscure at present, but may represent an important new treatment modality which may lead to greater insight into prostatic biology.

Aged↗
PubMed1989

The Mitrofanoff principle for continent urinary diversion.

A continent urinary diversion was formed for 16 patients using the Mitrofanoff principle for continence. As originally described, this system used the appendix tunnelled into the bladder to form a continent catheterisable vesicostomy. We have expanded the technique and have used all available narrow tubes as continent conduits (ureter 10 cases, appendix 5, Fallopian tube 1). The urine container was made of large and small intestine and bladder in several combinations. The system has been very satisfactory: 14 patients were continent and able to catheterise; 1 required a revision to achieve continence and 1 awaits revision; 3 patients required revision procedures for stricture.

Adolescent↗
PubMed1989

Transabdominal ultrasound surveillance for bladder cancer.

Transabdominal ultrasound may have a limited but useful role in the surveillance of bladder cancer. Its advantages over other diagnostic methods are that it is easy to use and that it can be repeated as many times as necessary without harm or discomfort to the patient. As such, it is an extension of the physical examination by the clinician, who should, if politics allow, take up its use more frequently. Only by using it routinely and understanding its limitations can urologists hope to use ultrasound as a safe and helpful aid to diagnosis.

Humans↗
PubMed1988

Prostatectomy: patients' perception and long-term follow-up.

We have reviewed 500 consecutive prostatectomies with a follow-up period of between 5 and 8 years; 184 surviving patients were sent a questionnaire and patients with residual urinary symptoms were interviewed, examined and a flow rate was performed. The operative mortality rate was 0.5%. Patients who presented with retention of urine had a high mortality rate in the first 3 years after the operation. Thirty-six per cent of surviving patients with chronic retention and 24% of those who underwent elective prostatectomy had residual urinary symptoms at the time of the study. Of patients who were sexually active pre-operatively, 34% felt that the operation was responsible for a deterioration in their sex lives. The incidence of retrograde ejaculation was 93%. It was concluded that prostatectomy is a safe operation with good patient acceptability. Patients with symptoms of prostatism require careful evaluation before prostatectomy and sexually active patients should be warned of the risks of impotence and decreased satisfaction due to retrograde ejaculation.

Age Factors↗
PubMed1986

The use of transabdominal ultrasound in the detection of early bladder tumours.

We have studied the accuracy of transabdominal ultrasound (TAUS) in the diagnosis of early superficial bladder carcinoma. One hundred and twenty-six patients returning for check cystoscopy were scanned pre-operatively with the Technicare Autosector Scanner and the results compared with the endoscopic findings. Forty-four patients (37%) had a tumour recurrence. TAUS demonstrated a lesion in 50% of these with a false positive rate of 11%. The diagnostic accuracy was proportional to the tumour size (82% of patients with tumours above 5 mm were detected compared with 38% below 5 mm), but was not affected by grade, stage or position in the bladder. TAUS may prove a useful adjunct to cytology as a screening test for bladder cancer.

Humans↗
PubMed1986

Metabolic consequences of forced diuresis following prostatectomy.

The efficacy and metabolic consequences of a standardised forced diuresis regime following prostatectomy were studied in three parts. A retrospective review of 372 patients. A detailed prospective study of blood and urine electrolyte changes in 25 patients. A prospective study of urinary oxalate levels in 15 patients. The regime was effective in safely preventing post-operative clot retention. In 54% of patients the plasma sodium fell below 135 mmol/l. Hypokalaemia was mild and transient except in patients on long-term diuretics. There was a significant per-operative fall in serum calcium levels. It was concluded that forced diuresis is a safe and effective method of reducing clot retention following prostatectomy. The high incidence of post-operative hyponatraemia suggests that absorption of glycine solution at transurethral prostatectomy is a common occurrence.

Creatinine↗
PubMed1985

Oncogenes and bladder cancer.

We screened a series of 15 superficial and invasive transitional cell carcinomas of the bladder for transforming activity on the NIH/3T3 transfection assay. In addition, by obtaining tumour DNA and normal lymphocyte DNA from the same patients we looked for evidence of gene amplification or rearrangement of the c-H-ras-1 gene by Southern blot analysis. One patient (with a grade 2T1 tumour) was shown to have an activated oncogene on the NIH/3T3 transfection assay and this was identified as a c-H-ras-1 gene. We could find no evidence of gene amplification or rearrangement of this gene in any tumour. The significance of activation of ras oncogenes in the pathogenesis of human bladder carcinoma is unclear.

Carcinoma, Transitional Cell↗
PubMed1985

Urinary diversion for incontinence--a beneficial procedure?

In the past 8 years at St George's Hospital, 13 women underwent urinary diversion for disabling incontinence. Seven patients had multiple sclerosis, 2 had suffered trauma to the lumbar spine and 4 had failed repeated surgery for urethral sphincter incompetence. One patient died several months postoperatively due to relapse of her multiple sclerosis. The remaining 12 were interviewed to determine the effect of the operation on their quality of life. Preoperatively, 9 patients (75%) were either housebound or only ventured out to do the shopping and none led a full social life. Postoperatively 8 patients (67%) managed a full social life and all were improved. Most managed their stomas proficiently and none regretted having the operation. The most common late complication was pyocystis. We conclude that patients with disabling incontinence can have their quality of life substantially improved by urinary diversion. The incidence of pyocystis is probably high enough to warrant vaginal vesicostomy to be performed routinely at the time of diversion, at least in those women with chronic urinary infection.

Adult↗
PubMed1984

Early prognosis in traumatic tetraplegia.

This is a retrospective study of 18 acute traumatic tetraplegic patients admitted to the Cardiff Royal Infirmary within 12 hours of injury. The nursing charts of pulse rate, blood pressure and respiratory rate were scrutinized and the mean values over a 24-hour period were plotted against outcome with regard to mortality and respiratory complications. A systolic blood pressure below 115 mmHg was found to be associated with a high morbidity and mortality. A hypothesis is advanced that this finding is related to autonomic imbalance.

Accidents↗