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Biomedical subjects

M R Robinson

Publications and source records attributed to M R Robinson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Discontinuation of anticytomegalovirus therapy in patients with HIV infection and cytomegalovirus retinitis.

CONTEXT: Persons with cytomegalovirus (CMV) retinitis and acquired immunodeficiency syndrome (AIDS) have required lifelong anti-CMV therapy to prevent the progression of retinal disease and subsequent loss of vision. OBJECTIVE: To determine whether patients who were taking highly active antiretroviral therapy (HAART) and who had stable CMV retinitis could safely discontinue anti-CMV therapy without reactivation of their retinitis or increase in human immunodeficiency virus (HIV) viral load. DESIGN: Prospective nonrandomized interventional trial performed from July 1997 to August 1999. SETTING: Clinical Center of the National Institutes of Health, Bethesda, Md. PATIENTS: Fourteen patients with stable CMV retinitis and HIV infection and CD4+ cell counts higher than 0.1 5 x 10(9)/L and being treated with systemic anti-CMV medications and HAART. INTERVENTIONS: Discontinuation of specific anti-CMV therapy. MAIN OUTCOME MEASURES: Reactivation of CMV retinitis, development of extraocular CMV infection, detection of CMV in blood and urine, HIV burden, immunologic function, quality of life, morbidity, and mortality. RESULTS: Twelve (89.7%) of 14 patients had evidence of immune recovery uveitis before anti-CMV drugs were discontinued. No patient had reactivation of CMV retinitis or development of extraocular CMV disease during mean follow-up of 16.4 months (range, 8.3-22.0 months) without anti-CMV therapy. Human immunodeficiency viral load remained stable following cessation of anti-CMV medications. Blood and urine assays for CMV were briefly positive in 9 patients but did not predict reactivation of CMV disease. Worsening immune recovery uveitis was associated with a substantial (>3 lines) vision loss in 3 patients. CONCLUSIONS: Maintenance anti-CMV medications were safely stopped in those patients who had stable CMV retinitis and elevated CD4+ cell counts and who were taking HAART. The study demonstrates that immune recovery following potent antiretroviral therapy is effective in controlling a major opportunistic infection, even in patients with a history of severe immunosuppression.

AIDS-Related Opportunistic Infections↗
PubMed1999

Incorporation of a GnRH agonist, leuprolide acetate, into regimens with exogenous gonadotropins to produce ovarian stimulation and ovulation in the nonpregnant squirrel monkey.

This study was designed to measure the effects of variations in the length of pretreatment with a GnRH agonist, leuprolide acetate (LA), on subsequent follicular development and ovulation. The hypothesis was that the duration of LA suppression of pituitary function does not adversely affect ovarian response to standardized ovulation induction protocols in squirrel monkeys. The first phase determined the dose and duration of LA needed to achieve a hypogonadal state. One of two groups received daily subcutaneous injections of 50 microg of LA. The other received a single injection of 175 microg of a depot suspension of LA. Sera were assayed for estradiol (E2) and progesterone (P). E2 and P levels increased 2- to 5-fold with peak levels on days 4 and 7, respectively. Suppression of steroid levels took 10 to 15 days in the LA-treated group. Depot-LA did not effectively suppress steroid production. After suppression, females receiving daily LA received five daily injections of hMG to stimulate follicular development. E2 and P increased in these animals. These results suggest that cycling squirrel monkeys have P-secreting capacity throughout the cycle. This may explain how the squirrel monkey is able to accommodate both a short (4-5 day) luteal phase of their 9 day cycle and implantation from 5 to 7 days after ovulation. A second study compared exogenous follicle stimulating hormone (FSH) to endogenous gonadotropins released as a response to LA in ovulation induction. Steroid production and hCG-induced ovulation were assessed. LA treatment was compared to a standard ovulation induction protocol by using a randomized cross-over measures design. There were no differences in E2 and P levels in response to dosages of either LA or hMG. The ovulatory response following LA treatment was not significantly greater than that using FSH. The number of animals with unovulated, large follicles was greater on the FSH protocol (12/18) compared to the LA protocol (3/18). Thus, a single injection of a depot preparation of LA is sufficient to stimulate follicular development and ovulation when followed by an hCG injection. Based on this observation and the data on unovulated large follicles, it is suggested that the ovary responds more readily to endogenous gonadotropins released by LA than to exogenous FSH.

Animals↗
PubMed1999

Orchiectomy and orchiectomy plus mitomycin C for metastatic prostate cancer in patients with poor prognosis: the final results of a European Organization for Research in Cancer Therapy Genitourinary Group Trial.

PURPOSE: The outcome of patients with symptomatic metastatic prostate cancer is poor and improved treatment regimens are urgently needed. Theoretically, the combination of orchiectomy and chemotherapy could reduce androgen sensitive and insensitive cells in the prostate. This European Organization for Research in Cancer Therapy Genitourinary Group randomized, multicenter phase III trial demonstrates the outcome of orchiectomy alone versus orchiectomy followed by intravenous mitomycin C. MATERIALS AND METHODS: A total of 189 patients with metastatic prostate cancer and poor prognostic factors were randomized in this trial by 42 institutions. Of these patients 184 (97%) were eligible for study, including 90 treated with orchiectomy alone (orchiectomy only arm) and 94 treated with orchiectomy followed by 15 mg./m.2 mitomycin C in 1 week (combined treatment arm). Mitomycin C was administered every 6 weeks and treatment was continued as long as tolerance and patient compliance allowed, and no progression was observed. Objective and subjective criteria for progression were clearly defined in the protocol. RESULTS: Patient and tumor characteristics were well balanced between the 2 treatment arms. At a median followup of 4.2 years 144 patients had died, including 112 of prostate cancer. No significant differences for time to overall (p = 0.17), subjective (p = 0.25) and objective (p = 0.08) progression were found between the 2 treatment groups. For progression-free survival no difference was noted (p = 0.67) between the 2 treatment groups but a trend in favor of orchiectomy alone was observed for overall survival (p = 0.04). Mitomycin C induced considerable hematological, gastrointestinal, renal and pulmonary toxicity leading to discontinuation in 31% of patients with pulmonary toxicity and 7% with renal deterioration. In addition, the quality of life evaluation revealed significant reduction in the combined treatment arm. CONCLUSIONS: Based on the results of this randomized phase III study orchiectomy plus mitomycin C for metastatic prostate cancer in patients with poor prognostic factors cannot be recommended due to failure of improvement in survival and reduced quality of life parameters.

Antibiotics, Antineoplastic↗
PubMed1999

Ocular manifestations of HIV infection.

Ophthalmic abnormalities are common in HIV-infected patients. Serious ophthalmic diseases often result from opportunistic infections and can cause blindness in the absence of prompt diagnosis and therapy. We review recent advances in the diagnosis and management of HIV-associated ocular disease, including cytomegalovirus retinitis, the leading cause of vision loss in HIV-infected patients. The widespread use of highly active antiretroviral therapy (HAART) over the past 3 years has reduced the morbidity and mortality associated with HIV infection. HAART has dramatically altered the incidence and natural history of many opportunistic infections, and we discuss the impact of HAART on ophthalmic disease.

AIDS-Related Opportunistic Infections↗
PubMed1999

Anterior uveitis associated with intravenous cidofovir use in patients with cytomegalovirus retinitis.

AIM: Intravenous cidofovir is used to treat cytomegalovirus (CMV) retinitis, and has been reported to cause anterior uveitis. Relations were sought between this complication and patient characteristics that might help predict its occurrence. METHODS: 17 patients with AIDS and CMV retinitis who were treated with intravenous cidofovir were identified, and the following data collected in a retrospective chart review: demographic characteristics, duration of CMV retinitis, retinal lesion characteristics, dose and duration of cidofovir therapy, tests of renal function, CD4+ T lymphocyte counts, visual acuity, intraocular pressure, iris colour, history of diabetes mellitus, and use of concomitant medications. Case-control analyses were performed to determine risk factors for developing cidofovir associated uveitis. RESULTS: Anterior uveitis characterised by pain, ciliary injection, and decreased visual acuity occurred in 10 patients (59%). Median interval to development of uveitis was 11 doses of cidofovir. Symptoms developed 4.4 (SD 2.5) days (median 3.5) after an infusion of cidofovir. Patients who developed uveitis had a significantly greater rise in CD4+ T lymphocyte count while receiving cidofovir (68.4 (75.7) x10(6)/l versus 5.0 (0.6) x10(6)/l, (p = 0.04)). By stepwise linear regression, this factor accounted for 33% (p = 0.03) of the effect of developing uveitis. Mean follow up time, intraocular pressure decline during cidofovir therapy, serum creatinine and urine protein concentrations, and rates of protease inhibitor use were not significantly different between patients who developed uveitis and those who did not. Uveitis responded to topical corticosteroids and cycloplegia. CONCLUSION: Anterior uveitis in patients receiving intravenous cidofovir therapy may be related to improving immune function. The uveitis responds to treatment and may not preclude continuation of cidofovir.

AIDS-Related Opportunistic Infections↗
PubMed1997

Intravenous cidofovir for peripheral cytomegalovirus retinitis in patients with AIDS. A randomized, controlled trial.

BACKGROUND: Cytomegalovirus (CMV) retinitis is the most common intraocular infection in patients with the acquired immunodeficiency syndrome (AIDS). If left untreated, it may lead to progressive destruction of retinal tissue and blindness. Cidofovir is a nucleotide analogue of cytosine that has potent, prolonged in vitro and in vivo activity against herpesviruses, including many CMV isolates that are resistant to ganciclovir and foscarnet. OBJECTIVE: To determine whether intravenous cidofovir delays progression of previously untreated CMV retinitis. DESIGN: Randomized, controlled trial comparing immediate with deferred cidofovir treatment. Patients in the deferred treatment group were eligible to receive cidofovir after progression of CMV retinitis was documented by retinal photography. SETTING: Eight academic medical centers and an independent center that read retinal photographs. PATIENTS: 48 patients with AIDS and previously untreated peripheral CMV retinitis who were randomly assigned to immediate (n = 25) or deferred treatment (n = 23). INTERVENTION: Intravenous cidofovir, 5 mg/kg of body weight, once weekly for 2 weeks and then once every other week. To minimize nephrotoxicity, oral probenecid and intravenous hydration with normal saline were administered with each cidofovir infusion. MEASUREMENTS: Progression of CMV retinitis was assessed by bilateral, full-field retinal photographs that were read by an ophthalmologist who was masked to treatment assignment. Incidence of side effects, changes in visual acuity, effect on CMV shedding in urine and blood, and mortality were also assessed. RESULTS: The median time to progression of CMV retinitis was 22 days (95% CI, 10 to 27 days) in the deferred treatment group and 120 days (CI, 40 to 134 days) in the immediate treatment group (P < 0.001). Neutropenia (15%) and proteinuria (12%), both asymptomatic, were the most common serious adverse events considered to be possibly related to cidofovir. Cidofovir treatment was discontinued in 10 of 41 patients (24%) because of protocol-defined treatment-limiting nephrotoxicity. Transient reactions to probenecid, including mild to moderate constitutional symptoms or nausea, occurred in 23 of 41 patients (56%) and were dose limiting in 3 (7%). CONCLUSIONS: Cidofovir was efficacious in delaying progression of previously untreated CMV retinitis. Treatment was associated with manageable side effects; strict adherence to monitoring of renal function before cidofovir was administered and concomitant administration of probenecid and saline hydration appeared to minimize drug-related nephrotoxicity.

AIDS-Related Opportunistic Infections↗
PubMed1996

The quality of life of patients with newly diagnosed M1 prostate cancer: experience with EORTC clinical trial 30853.

This study was undertaken to evaluate the quality of life (QoL) of previously untreated patients with M1 prostate cancer before and during androgen-suppressive treatment. Assessment of QoL was included as an optimal component of EORTC protocol 30853, a phase III trial comparing LH-RH (luteinising hormone-releasing hormone) analogue combined with a non-steroidal anti-androgen versus orchiectomy in patients with M1 prostate cancer. At pretreatment and during the follow-up period, patients were asked to complete a questionnaire assessing their physical and psychosocial functioning, and their symptom levels. Physicians rated the patients' performance status, pain, urological symptoms and erectile function. Due to its optional nature, only a minority of the patients in the trial were recruited for the QoL investigation. 63 patients completed a pretreatment questionnaire, of whom 49 completed a second questionnaire at least once during the initial 15 month follow-up period. While statistically significant correlations were observed between patients' and physicians' ratings of physical functioning and pain, these were of only a moderate magnitude (r = 0.43 and 0.30, respectively). No significant association was observed between physicians' and patients' ratings of micturation problems or of erectile function. Before treatment, fatigue, pain and decreased social role and sexual functioning were the problems most frequently reported by patients. With an average of approximately 1 year follow-up, statistically significant improvements were observed in patients' self-reported urological symptoms and metastatic pain. No significant changes were noted for the other QoL domains assessed. The results of this study confirm earlier findings that physicians' ratings may not reflect accurately the functional health and symptom experience of their patients. Patient-based QoL questionnaires offer the most direct means of evaluating the subjective morbidity associated with prostate cancer and its treatment. To increase participation and compliance rates in future studies, it is recommended that QoL assessment be made mandatory in those clinical trials in which QoL is considered to be an important study endpoint.

Aged↗
PubMed1996

The effect of intravesical mitomycin C on recurrence of newly diagnosed superficial bladder cancer: a further report with 7 years of follow up.

PURPOSE: We determined the role, if any, of 1 and 5 instillations of intravesical mitomycin C in the treatment of newly diagnosed superficial bladder cancer. MATERIALS AND METHODS: A multicenter randomized clinical trial was done involving 502 patients with newly diagnosed superficial bladder cancer. After complete transurethral resection patients with newly diagnosed superficial bladder cancer. After complete resection patients were randomized into 1 of 3 treatment arms: no further treatment, 1 instillation of mitomycin C at resection and 1 instillation at resection and at 3-month intervals for 1 year (total 5 instillations). The dose of mitomycin C used was 40 mg./40 ml. water. End points were interval to first superficial recurrence, recurrence rate (defined as the number of positive cystoscopies per year) and progression-free interval rate (progression defined as the development of muscle invasive or metastatic disease, or death from bladder cancer). RESULTS: After median followup of 7 years 1 and 5 instillations of mitomycin C resulted in decreased recurrence rates and increased recurrence-free interval. The benefit of mitomycin C was observed in patients at low, medium and high risk for subsequent recurrence. There was suggestive but not conclusive evidence that 5 instillations of mitomycin C offered a slight advantage over 1 instillation. CONCLUSIONS: Our analysis confirms the positive benefit of mitomycin C to decrease the number of subsequent recurrences and increase the recurrence-free interval.

Administration, Intravesical↗
PubMed1995

Replacing ganciclovir implants.

PURPOSE: The authors report their surgical experience replacing empty ganciclovir implants in patients with acquired immune deficiency syndrome (AIDS)-related cytomegalovirus (CMV) retinitis. METHODS: A chart review of all patients receiving two or more ganciclovir implants was performed. RESULTS: Nine eyes in eight patients received two or more implants. The average time before a second implant was needed was 6 months. Cytomegalovirus retinitis was controlled in all patients except one. Three patients required intermittent intravenous exogenous anti-CMV therapy, one for persistent CMV retinitis and two for systemic CMV. Visual acuity of 20/40 or better was maintained in five of eight patients, despite a longstanding history of CMV retinitis. CONCLUSION: In this small series, most patients retained good vision after ganciclovir implant replacement.

AIDS-Related Opportunistic Infections↗
PubMed1995

Tryptophan metabolites, pyridoxine (vitamin B6) and their influence on the recurrence rate of superficial bladder cancer. Results of a prospective, randomised phase III study performed by the EORTC GU Group. EORTC Genito-Urinary Tract Cancer Cooperative Group.

This double-blind randomised phase III trial was designed to assess the effect of pyridoxine administration on the recurrence of Ta and T1 transitional cell tumours of the bladder. The trial accrued 291 patients and showed no significant difference between the pyridoxine and placebo treatment groups with respect to the time to first recurrence or the recurrence rate. Adjustment for the main prognostic factors, namely the recurrence rate prior to entry, the number of tumours at entry, the G grade and the levels of the tryptophan metabolites kynurenine plus acetyl kynurenine at entry do not change the overall conclusions.

Administration, Oral↗
PubMed1995

[Renaissance of estrogen therapy in advanced prostate carcinoma?].

Oestrogen therapy or orchidectomy reigned supreme for the treatment of metastatic prostatic cancer for almost 40 years. In the last 15 years many alternative agents have been tested alone and more recently in combination. This contribution evaluates the results of some of these newer therapies considering relief of symptoms, toxicity, quality of life, survival, and benefit to the community. The results are compared with those of oestrogen therapy and with the way in which such treatment might be amended in light of more modern knowledge.

Antineoplastic Agents, Hormonal↗
PubMed1995

The final analysis of the EORTC Genito-Urinary Tract Cancer Co-Operative Group phase III clinical trial (protocol 30805) comparing orchidectomy, orchidectomy plus cyproterone acetate and low dose stilboestrol in the management of metastatic carcinoma of the prostate.

This report is the final analysis of an EORTC Genito-Urinary Group Phase III trial (Protocol 30805) comparing orchidectomy, orchidectomy plus cyproterone acetate 50 mg 3 times a day and stilboestrol 1 mg daily in the management of metastatic carcinoma of the prostate. Three hundred and twenty-eight eligible patients admitted into the study have been followed up for a median period of 4 years. There was no difference in time to metastatic progression and overall survival between the treatment arms. The cardiovascular toxicity of stilboestrol 1 mg daily has resulted in more cardiovascular deaths as compared with the orchidectomy treatment arm. The outcome for individual patients has been determined by on-study prognostic factors, especially the performance status, rather than the treatment given.

Adenocarcinoma↗