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R Persad

Publications and source records attributed to R Persad.

At least 37 records · Page 2Linked to original sources
PubMed2002

Leuprorelin acetate in prostate cancer: a European update.

This review provides an update on leuprorelin acetate, the world's most widely prescribed depot luteinising hormone-releasing hormone analogue. Leuprorelin acetate has been in clinical use in the palliative treatment of prostate cancer for more than 20 years, but advances continue to be made in terms of convenience and flexibility of administration, and in the incorporation of leuprorelin acetate into novel treatment regimens. The drug is administered in the form of a depot injection containing leuprorelin acetate microspheres, and is at least as effective in suppressing testosterone secretion as orchiectomy. In patients with prostate cancer, serum testosterone levels are reduced to castrate levels (< or = 50 ng/dl) within 2-3 weeks of the first one-month depot injection of 3.75 mg or three-month depot injection of 11.25 mg. Both the one-month and three-month formulations are effective in delaying tumour progression and alleviating symptoms of locally advanced and metastatic prostate cancer. Tolerability is generally good, with side-effects reflecting effective testosterone suppression. Recent studies have investigated the place of leuprorelin acetate as part of continuous or intermittent maximal androgen blockade (MAB) and in neoadjuvant therapy (i.e. to reduce the size of the prostate and downsize the tumour before radiotherapy). Additional formulations and presentations are in development, including a six-month injection, with the aim of adding to the clinical flexibility and patient acceptability of this important palliative treatment for prostate cancer.

Antineoplastic Agents, Hormonal↗
PubMed2000

Patient self-injection: a new approach to administering luteinizing hormone-releasing hormone analogues.

OBJECTIVE: To investigate the feasibility and advantages of self-injection of a depot dose of luteinizing hormone-releasing hormone (LHRH) analogue in patients with prostate cancer. PATIENTS AND METHODS: Twenty patients (mean age 70.9 years, range 53-85) with locally advanced or metastatic prostate cancer were recruited from urology clinics and, using a defined protocol, were taught to perform self-injection of a depot LHRH analogue (Prostap SR or Prostap 3, leuprorelin acetate, Wyeth Laboratories, Berks, UK). Patients were then followed for 1 year. RESULTS: Of the 20 patients, 11 successfully learned to use self-injection and administered injections for the duration of the study. Ten of the patients chose self-injection and continued to self-inject after the end of this study. CONCLUSIONS: This pilot study of 20 patients showed that it is feasible for a selected group of patients to be taught self-injection of an LHRH analogue, and that some patients prefer this mode of drug administration.

Aged↗
PubMed2000

Radical cystectomy and bladder substitution.

The incidence of bladder cancer is rising. The main treatment for superficial bladder cancer is local resection and judicious use of intravesical agents. Radical cystectomy can cure organ-confined, invasive disease. The ileal conduit remains the gold standard following cystectomy. Newer methods of bladder substitution and nerve-sparing techniques have resulted in better tolerance of this treatment.

Carcinoma, Transitional Cell↗
PubMed1999

Internal iliac artery embolisation for intractable bladder haemorrhage in the peri-operative phase.

Intractable haemorrhage from the bladder wall during transurethral resection of bladder tumour is uncommon but potentially catastrophic. Internal iliac artery embolisation is a minimally invasive technique, which is now widely practised to stop bleeding from branches of these arteries is situations including pelvic malignancy, obstetric and gynaecological emergencies and trauma. We report its successful use peri-operatively, in an unfit, elderly patient with uncontrolled bleeding.

Aged↗
PubMed1996

Long-term follow-up results with the Stamey operation for stress incontinence of urine.

OBJECTIVE: To assess the results of the Stamey operation for genuine stress incontinence in those patients with over 10 years of follow-up. PATIENTS AND METHODS: Of 46 patients who had undergone a Stamey procedure and had a follow-up of over 10 years, 30 were willing to attend for a clinical review and pad testing. RESULTS: Of the 30 patients assessed, 20 were initially cured, a further eight were significantly improved and two were no better. At 10 years, the number totally dry had fallen to 10, but a further 15 were still symptomatically improved. Only three that had shown some initial benefit were subjectively no better than before the operation. CONCLUSION: There appears to be a continuous decline in the cure rate with time from the Stamey procedure. However, most patients maintain some lasting benefit.

Female↗
PubMed1996

Urinary concentration of human chorionic gonadotrophin and its fragments as a prognostic marker in bladder cancer.

OBJECTIVE: To examine the prognostic significance of elevated urinary beta human chorionic gonadotrophin (beta-hCG) in patients with bladder cancer. PATIENTS AND METHODS: Total beta-hCG was measured in the urine of 142 patients referred for cystoscopic examination. Patients were followed for a minimum of 17 months and grouped according to stage of disease. Because the water output by individual patients varied, urinary creatinine levels were measured as an indicator of the concentration of the urine sample. Patient outcomes were correlated with urinary total beta-hCG levels both corrected and uncorrected for creatinine concentration. After correcting for urinary creatinine levels, 40 patients were excluded because the sample was too dilute (undetectable beta-hCG and a creatinine level of < 4 mmol/L). A further four patients were excluded as they had concurrent malignancies not in the bladder and one patient was lost to follow up. RESULTS: None of the 52 patients with benign conditions, nine of the 27 with Ta-T1, and nine of the 25 with T2-T4 bladder disease had urinary total beta-hCG levels > 3.74 IU/mmol/L creatinine. There was no significant association between urinary total beta-hCG concentrations and the rates of recurrence or progression for Ta-T1 disease at 17 months of follow-up. For patients with T2-T4 disease there was a significant association with widespread metastasis (P < 0.01) and mortality (P < 0.01) at 17 months of follow-up. These associations persisted when urinary total beta-hCG levels were not corrected for urinary creatinine concentration (metastasis, P < 0.01; mortality, P = 0.07; Kaplan-Meier survival time analysis, uncorrected for creatinine P = 0.027, corrected for creatinine P < 0.001). This association could not be accounted for by differences in age, histopathology or treatment. CONCLUSION: Although sample concentration was a serious confounding factor, after correcting for dilution using the creatinine content, the elevated urinary levels of total beta-hCG indicated those T2-T4 lesions which were likely to metastasize and those patients likely to die early. If this test is to be used clinically, concentrated samples, i.e. early-morning urine, and a more sensitive beta-hCG assay are required. Nevertheless, for T2-T4 bladder tumours, an elevated pre-treatment level of urinary beta-hCG is a marker of poor prognosis and may prove useful in deciding appropriate therapy.

Aged↗
PubMed1996

Association of low CYP3A activity with p53 mutation and CYP2D6 activity with Rb mutation in human bladder cancer.

p53 and Rb gene mutations are intermediate biomarkers useful for the prediction of neoplastic progression in bladder cancers. Previously, we have shown that low CYP3A activity, measured by dapsone N-hydroxylation, and high CYP2D6 activity, assessed by debrisoquine 4-hydroxylation, were significant susceptibility risk factors in developing aggressive bladder cancer. However, no information is available about the relationship between drug/xenobiotic metabolizing enzyme activities and p53/Rb mutations that may suggest mechanisms of bladder carcinogenesis. We evaluated in vivo CYP3A activity by the dapsone recovery ratio (DPRR), CYP2D6 activity by the debrisoquine recovery ratio (DBRR), CYP2C19 activity by the mephenytoin R/S ratio (RSR), N-acetyltransferase activity by the monoacetyl dapsone to dapsone ratio and glutathione-S-transferase M1 (GSTM1) genotype by PCR. In immunohistochemical studies of bladder tumor tissue, over expression of p53 protein was detected with antibody pAb1801 and loss of Rb protein expression was evaluated with antibody PMG3-245 in patients with transitional cell carcinoma of the bladder. Low CYP3A activity was significantly associated with over expression of or mutated p53 protein (P < 0.05). High CYP2D6 activity (within the extensive metabolizer group) was significantly associated with loss of expression of or mutated Rb protein (P < 0.05). Positive p53 staining also predicted aggressive bladder cancer histopathology (P < 0.05, odds ratio 2.9), and the lowest tertile of DPRR predicted p53 positivity (P < 0.01, odds ratio 3.9 comparing means of lower tertile versus upper tertile of DPRR). These selective associations are consistent with the hypothesis that an environmental pro-carcinogen fails to be detoxified by CYP3A which may preferentially induce p53 mutations, whereas, an alternative pro-carcinogen that may be activated by CYP2D6, may selectively induce Rb mutations.

Aged↗
PubMed1996

Uretric obstruction in Gardener's syndrome.

Desmoid tumours in Gardener's syndrome are a rare cause of ureteric obstruction. We report two cases of ureteric obstruction caused by desmoids, in a mother and daughter.

Adult↗
PubMed1996

Pancreatitis post-bone marrow transplantation.

Pancreatitis has been reported as a rare complication after bone marrow transplantation (BMT). This paper reports a series of three cases of pancreatitis post-BMT and reviews the literature. Pancreatitis occurred in three of 68 (4.4%) of BMT cases in our transplant program. The etiology of such cases is multifactorial and includes drugs, graft-versus-host disease, infection, cholecystitis, and the lipid in total parenteral nutrition. Pancreatitis should be included in the differential diagnosis of abdominal pain post-BMT. The development of a pancreatic pseudocyst in an immunocompromised host may require surgical drainage since infected pseudocysts are not drained adequately by radiologically guided techniques.

Adult↗
PubMed1995

The procarcinogen hypothesis for bladder cancer: activities of individual drug metabolizing enzymes as risk factors.

Bladder cancer provides the most definitive example for an association between environmental agents and cancer. However, in the absence of industrial occupational exposure, the primary carcinogen is rarely identified, and the mechanisms involved in cancer formation are poorly understood. The environmental procarcinogen hypothesis of tumour pathogenesis proposes that many carcinogens require metabolic activation by drug metabolizing enzymes to form the proximate carcinogen. A balance of exposure to the carcinogen, the activity of the enzymes involved in either formation of proximate carcinogen, or production of non-toxic metabolites, will determine tumour risk. We have used mephenytoin, debrisoquine and dapsone as selective probes for the phenotypic measures of activity of CYP2C19, CYP2D6, and CYP3A4, respectively. Within subject reproducibility of phenotypic measures, and the lack of cross-inhibition when the three drugs are given in a concurrent cocktail, have been confirmed. We have applied the cocktail drug approach in two, non-overlapping series of cases with bladder cancer and matched controls. In both series, patients with aggressive bladder cancer (GIII histopathology) had a history of excess alcohol intake, an under-representation of poor metabolizers of debrisoquine, a significant mean reduction in dapsone recovery ratio, but no difference in mephenytoin phenotype. Collectively, these observations involving multiple routes of drug metabolism support the procarcinogen environmental hypothesis for bladder cancer and suggest that measurement of activity of selected individual drug metabolizing enzymes involved in the pathogenesis of this tumour can be used to identify subjects at high risk of developing bladder cancer.

Aryl Hydrocarbon Hydroxylases↗
PubMed1995

Clinical presentation and pathophysiology of meatal stenosis following circumcision.

OBJECTIVE: To describe the clinical presentation and pathophysiology of meatal stenosis occurring after circumcision. PATIENTS AND METHODS: The clinical presentation and operative findings are reported in 12 children who presented with meatal stenosis over a period of 3 years. RESULTS: The cardinal symptoms of meatal stenosis were penile pain at the initiation of micturition (12 of 12), narrow, high velocity stream (8 of 12) and the need to sit or stand back from the toilet bowl to urinate (6 of 12). Following surgical correction with meatotomy there was no recurrence of stenosis after a mean follow-up of 13 months. Traumatic meatitis of the unprotected post-circumcision urethral meatus and/or meatal ischaemia following damage to the frenular artery at circumcision are suggested as possible causes of meatal stenosis. CONCLUSION: Preservation of the frenular artery at circumcision, or the use of an alternative procedure (preputial plasty), may be advisable when foreskin surgery is required, to avoid meatal stenosis after circumcision.

Child↗
PubMed1994

Correlation of polymorphic expression of CYP2D6 mRNA in bladder mucosa and tumor tissue to in vivo debrisoquine hydroxylase activity.

Debrisoquine hydroxylase activity has been attributed to CYP2D6 and poor metabolizers of debrisoquine have a reduced relative risk of developing aggressive bladder cancer. Production of a proximate carcinogen could occur in liver or bladder mucosa. However, it is not known if CYP2D6 is expressed in human bladder mucosa. In vivo whole body debrisoquine hydroxylase activity was measured as the debrisoquine recovery ratio (DBRR) following single dose oral administration of debrisoquine (10 mg) in 10 normal subjects and 20 patients with bladder cancer prior to diagnostic cystoscopy. Semi-quantitative PCR was used to measure mRNA for CYP2D6 in bladder tissue obtained at cystoscopy. Of the 30 subjects, three were phenotypically and genotypically poor metabolizers. Among the extensive metabolizers, there were extensive intersubject variations in DBRR. A 10-fold variation in CYP2D6 mRNA levels was observed in bladder tissue. There was a highly significant association between DBRR and CYP2D6 mRNA expression (r2 = 0.702, P < 0.001). These results demonstrate the presence of CYP2D6 mRNA in bladder mucosa. Furthermore, they are consistent with debrisoquine hydroxylation being mediated by CYP2D6 and suggest that differences in mRNA concentration are rate limiting for enzyme activity and that bladder mucosal regulation reflects total body regulation for this enzyme. The expression of CYP2D6 in bladder mucosa suggests that this enzyme could be involved in the local production of a proximate carcinogen in this tissue and contribute to the pathogenesis of bladder cancer in man.

Base Sequence↗