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Biomedical subjects

R Sharifi

Publications and source records attributed to R Sharifi.

At least 19 recordsLinked to original sources

Effects of sex steroids on cell growth and C-myc oncogene expression in LN-CaP and DU-145 prostatic carcinoma cell lines.

The prostate gland is dependent on androgens for the maintenance of its normal growth and functional integrity. Initially, growth of the majority of prostate tumours can be manipulated by endocrine therapy. In the present study, we evaluated the effects of sex steroids on the cell growth and expression of the C-myc oncogene in two human prostatic adenocarcinoma cell lines. We found that dihydrotestosterone increases the proliferation rate of prostatic cells, and amplification of C-myc oncogene is hormone-dependent. We also demonstrated a positive correlation between the number of cells positive for C-myc oncogene and oncoprotein in hormone-treated prostate cell lines.

Adenocarcinoma

A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Casodex Combination Study Group.

OBJECTIVES: To compare the efficacy and safety of bicalutamide and flutamide, each used in combination with luteinizing hormone-releasing analogue (LHRH-A) therapy, in patients with untreated metastatic (Stage D2) prostate cancer. METHODS: Randomized, double-blind (for antiandrogen therapy), multicenter study with a 2 x 2 factorial design. Eight hundred thirteen patients were allocated 1:1 to bicalutamide (50 mg once daily) and flutamide (250 mg three times daily) and 2:1 to goserelin acetate (3.6 mg every 28 days) and leuprolide acetate (7.5 mg every 28 days). RESULTS: With a median duration of follow-up of 49 weeks, time to treatment failure, the primary endpoint, was significantly (P = 0.005) better for the bicalutamide plus LHRH-A group than for the flutamide plus LHRH-A group. Patients in the flutamide plus LHRH-A group were 34% more likely to fail treatment over the given time period, as indicated by the hazard ratio of 0.749 (95% confidence interval, 0.61 to 0.92) for bicalutamide plus LHRH-A to flutamide plus LHRH-A. Results for secondary endpoints (survival, quality of life, and subjective response) were similar between groups. Diarrhea occurred in 24% of patients in the flutamide plus LHRH-A group, compared with 10% of patients in the bicalutamide plus LHRH-A group (P < 0.001). CONCLUSIONS: In patients with metastatic prostate cancer, bicalutamide plus LHRH-A is well tolerated and provides superior efficacy to flutamide plus LHRH-A with respect to time to treatment failure. Assessment of the effects of these regimens on longer term survival requires additional time for follow-up.

Adenocarcinoma

Single-agent therapy with bicalutamide: a comparison with medical or surgical castration in the treatment of advanced prostate carcinoma.

OBJECTIVES: Single-agent therapy with bicalutamide, a nonsteroidal antiandrogen, was compared with castration, either surgical or medical, in patients with untreated Stage D2 prostate cancer. METHODS: In an open, randomized, multicenter trial, patients were randomized to treatment with 50 mg bicalutamide (n = 243) once daily or to castration (n = 243), either orchiectomy or depot injection of goserelin acetate every 28 days. Primary efficacy endpoints were times to treatment failure and objective disease progression and survival. Assessments included review of measurable metastases, prostate dimensions, Eastern Cooperative Oncology Group performance status, pain, analgesic requirements, and quality of life responses. RESULTS: The median duration of therapy was 39 weeks for bicalutamide-treated patients and 42 weeks for castrated patients; treatment failure occurred in 53% and 42% and disease progression in 43% and 33%, respectively. Treatment effects favored castration for both endpoints (P < or = 0.002), with hazard ratios (bicalutamide:castration) of 1.54 (95% confidence interval [CI], 1.18 to 2.00) for time to treatment failure and 1.6 (95% CI, 1.19 to 2.15) for time to disease progression. From the 1-year survival analysis, the hazard ratio for probability of death was 1.29 (95% CI, 0.96 to 1.72). Thus far, with a median follow-up of 86 weeks, median survival has not been reached in either group. Changes from baseline in several quality of life variables were significantly different (P < or = 0.01) between treatment groups periodically from months 1 to 6, and all favored bicalutamide. Overall, the antiandrogen was well tolerated compared with castration; with bicalutamide, hot flushes occurred less often and breast tenderness and gynecomastia more often. CONCLUSIONS: Although a dosage of 50 mg of bicalutamide once daily was not as effective as castration, the favorable quality of life outcomes and the low incidence of nonhormonal adverse events provide reasons to evaluate bicalutamide, as a single therapeutic agent, at higher doses.

Aged

Ethanolamine sclerotherapy of a renal cyst.

We report the effective use of 5% ethanolamine oleate to sclerose a large simple renal cyst. The comparative advantages of ethanolamine versus other sclerosants are discussed in terms of adverse effects, availability and convenience. Guidelines to optimize sclerotherapy with ethanolamine are provided.

Aged

Randomized prospective study comparing radical prostatectomy alone versus radical prostatectomy preceded by androgen blockade in clinical stage B2 (T2bNxM0) prostate cancer. The Lupron Depot Neoadjuvant Prostate Cancer Study Group.

PURPOSE: Nonrandomized clinical trials have suggested that preoperative androgen deprivation can decrease the likelihood of positive surgical margins in patients with clinically localized prostate cancer. A multicenter prospective randomized trial compared radical prostatectomy alone to radical prostatectomy after 3 months of leuprolide acetate depot and flutamide in patients with stage cT2bNxM0 prostate cancer and a serum prostate specific antigen level less than 50 ng./ml. MATERIALS AND METHODS: We randomized 149 patients to undergo androgen deprivation and 138 to undergo lymphadenectomy with (137) or without (1) prostatectomy. Of the 154 patients randomized to the surgery alone group 144 underwent pelvic node dissection with (138) or without (6) prostatectomy. RESULTS: There was no statistically significant difference between the 2 groups in operating time, blood loss, need for transfusion, postoperative morbidity or length of hospital stay. There were 4 rectal and 2 ureteral injuries in the surgery alone group and none in the pretreatment group (p < 0.05). Patients who received androgen deprivation preoperatively had a significantly lower rate of capsule penetration (47% versus 78%, p < 0.001), positive surgical margins (18% versus 48%, p < 0.001) and tumor at the urethral margin (6% versus 17%, p < 0.01). CONCLUSIONS: Long-term followup data will be needed to determine whether there will be a lower incidence of biochemical relapse as determined by prostate specific antigen, local recurrence or metastasis, with an improvement in patient survival.

Aged

Chart for preparation of dilutions of alpha-adrenergic agonists for intracavernous use in treatment of priapism.

Treatment of priapism with intracavernous alpha-adrenergic agonist vasoconstrictor agents is well accepted, particularly for patients with priapism secondary to intracavernous injections of papaverine, phentolamine and/or prostaglandin E1. Although many alpha-adrenergic agonists are commercially available, phenylephrine is preferred because it has potent and selective alpha 1-adrenergic stimulatory properties, which can decrease arteriolar flow to the cavernous sinusoids, and no beta 1-stimulatory effect, which could cause arrhythmias and angina in susceptible patients. Before intracavernous injection or irrigation an alpha-adrenergic agonist must be diluted. However, no readily available reference source lists this information. Therefore, we prepared a chart for extemporaneous preparation of dilutions of alpha-adrenergic agonists for intermittent injection or irrigation.

Adrenergic alpha-Agonists

Bone scan as a stratification variable in advanced prostate cancer.

The serial technetium 99 (99Tc) bone scans of 76 patients with Stage D-2 prostate cancers were reviewed. Sites of metastases in skeletal areas in decreasing order were vertebrae, ribs, pelvis, long bones, and skull. Patients with one or two involved skeletal areas had a significantly longer progression-free interval and survival time than patients with three or more bony areas of uptake. Bone scans might be used as a stratification variable in future prospective clinical trials of Stage D-2 prostate cancer.

Aged

Phase I-II evaluation of intravesical novantrone (mitoxantrone) in superficial bladder cancer.

The objective of this study was to determine the safety and efficacy of intravesical novantrone in refractory superficial bladder cancer. The eligibility criteria included proven carcinoma in situ or superficial transitional cell carcinoma of the bladder at stage Ta or T1 that was proven refractory to or in relapse after the use of at least one other standard anti-cancer agent. The patient was to have received no prior radiotherapy or intravesical therapy for at least 4 weeks prior to entry. Patients also did not suffer significant cardiac dysfunction, such as angina, congestive heart failure, or uncompensated cardiomyopathy. All patients were given 4-6 doses of intravesical novantrone at the same dose level at weekly dosing interval. Patients were required to retain the drugs in the bladder for 2 h. Baseline study included history/physical, hematology, blood chemistry, cystoscopy, bladder barbotage, urine cytology, cystometrogram to assess the bladder capacity, and finally, chest X-ray, EKG, and MUGA scan, if indicated. Weekly assessment involved toxicity notation, blood chemistry, hematology and urinalysis. Monthly assessment included physical examination, toxicity notation, hematology, urinalysis and blood chemistry. Within 4 weeks of completion of the last dose, patients underwent repeat cystoscopy to assess disease status. Patients who responded to the 4-6 week induction phase were entered in a monthly dose regimen for up to 5 months. A total of 23 patients were enrolled: 22 males and 1 female. One patient dropped out before receiving medication because of a protocol violation for entry criteria. Twenty-two patients were eligible for assessment of safety and 20 were eligible for assessment of efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Clinical study of leuprolide depot formulation in the treatment of advanced prostate cancer. The Leuprolide Study Group.

In a phase III, open, multicenter study we evaluated the safety and efficacy of the depot formulation of leuprolide (7.5 mg. injected intramuscularly every 4 weeks) in patients with stage D2 prostate cancer who had not previously received systemic treatment. Serum testosterone, luteinizing hormone and plasma leuprolide levels were monitored during the 24-week study period. Median interval to onset of castrate testosterone levels was 21 days and mean testosterone levels decreased to within the castrate range by week 3 of treatment. After onset of castrate levels there were no escapes (defined as 2 consecutive values of greater than 50 ng./dl.) of testosterone levels during the 24 weeks. Suppression of testosterone did not differ significantly from that observed in patients receiving the daily subcutaneous injection of leuprolide acetate in the first 24 weeks of another study. Objective response (no progression) to treatment occurred in 81% of 53 evaluable patients and adverse (related and unrelated) events were reported in 45 of the 56 patients. The response rate and incidence of adverse events in this study did not differ significantly from those occurring with the daily formulation. We conclude that the depot formulation of leuprolide is safe and effective in the treatment of advanced prostatic cancer, and that the safety and efficacy of this formulation do not differ significantly from those of the daily subcutaneous formulation.

Aged

'Acute on chronic' effect of depot leuprolide in patients with stage D2 cancer of prostate.

During a phase III open study of depot leuprolide for stage D2 cancer of the prostate, we studied the effect of depot leuprolide on chronic leuprolide users. To determine whether there was a transient elevation of testosterone or luteinizing hormone (LH) 4-24 h and 3-5 days following the monthly injections, we monitored the changes of testosterone and LH before injection and 24 h post-injection in 10 patients who have been under depot leuprolide Rx for 24-36 weeks, and in 35 patients before injection and 3-5 days post-injection who have received depot leuprolide for 8-24 weeks prior to monitoring. Comparison of the data between pre-injection within 24 h and 3-5 days post-injection showed no significant changes of testosterone and LH values between these levels for either testosterone (P = 0.31) or LH (P = 0.45). We therefore conclude that there was no 'acute on chronic' effect of depot formulation in chronic users of depot leuprolide.

Clinical Trials as Topic

Oxybutynin-induced reflux esophagitis.

Oxybutynin has less anticholinergic activity than propantheline bromide. Therefore, oxybutynin is often preferentially prescribed for patients at risk of morbid complications of atropine-like adverse effects. We report a case of oxybutynin-induced reflux esophagitis. This probably resulted from the anticholinergic action of oxybutynin, which decreased lower esophageal sphincter tone. We outline a management approach for patients who experience this adverse effect due to oxybutynin or other commonly prescribed medications.

Adult

Causes, presentation and survival of fifty-seven patients with necrotizing fasciitis of the male genitalia.

This analysis of our experience with 57 men with necrotizing fasciitis of the genitalia was done to identify prognostic variables and to assess the results of a treatment policy of immediate and, if required, repetitive surgical debridements. The mean age of the patients was 55 years. Thirty-eight patients were alcoholics or diabetics, or both. All of the infections were of a genitourinary, anorectal or cutaneous source. Thirty-five per cent of the infections were confined to the genitalia and 65 per cent extended to the abdominal wall or thigh, or both. Forty-seven patients survived. Survival was associated significantly with a younger age, a serum blood urea nitrogen (BUN) level of less than 50 milligrams per deciliter at presentation, the absence of a constellation of abnormalities at presentation consistent with sepsis and a decreased incidence of major complications after initial débridement (p less than 0.05 to 0.01). Survival was not associated with the extent of infection, the duration of symptoms before hospitalization, systemic risk factors, the source of infection, abnormal findings at presentation (excluding a BUN of greater than 50 milligrams per deciliter) and the bacteriologic factors of the infection. Both localized and extensive necrotizing fasciitis of the male genitalia are potentially lethal disorders that require prompt treatment.

Bacterial Infections

Inferior vena cava thrombosis. Unusual presentation of testicular tumor.

We report an unusual case of testicular tumor presenting as thrombosis of the inferior vena cava. However, in contrast to a previous report, thrombosis in this patient was not caused by compression of the vena cava by neoplasm metastases. In our patient, we postulate that tumor invaded the vena cava and that thrombosis was exacerbated by a hypercoagulable state induced by the tumor.

Adult

Humoral hypercalcemia due to squamous cell carcinoma of renal pelvis.

We describe an unusual and rare case of humoral hypercalcemia due to Stage D squamous cell carcinoma of the renal pelvis in a patient with no evidence of bony metastases. The literature on humorally mediated hypercalcemia associated with epithelial tumors of the renal pelvis is reviewed.

Adult

Lipogenic activity and brown fat content of human perirenal adipose tissue.

The incorporation of 3H2O and/or 14C-glycerol into lipids and the specific activities of the enzymes acetyl CoA carboxylase and lipoprotein lipase were measured in the perirenal and subcutaneous adipose tissue of human subjects. The perirenal adipose tissue of younger subjects with higher brown adipocyte content had higher rates of lipogenesis and enzyme activities per gram tissue than the corresponding subcutaneous tissue. However, in individual specimens, the perirenal/subcutaneous ratios of all but one of the above parameters failed to show a correlation with the brown adipocyte content of the perirenal adipose tissue. One parameter, namely 3H2O incorporation into fatty acids per adipocyte, did relate to the brown adipocyte content of the perirenal adipose tissue in four normal-weight patients only.

Adipose Tissue

Comparison of ciprofloxacin and beta-lactam antibiotics in the treatment of urinary tract infections and alteration of fecal flora.

Ciprofloxacin treatment of urinary tract infections in 23 patients (16 with and seven without urorenal abnormalities) was compared with beta-lactam antibiotic therapy given orally to 10 comparable patients. The alteration of aerobic gram-negative fecal flora was monitored. Ciprofloxacin eliminated bacteria from the urine of all patients; beta-lactam antibiotics failed in two of 10 patients. There were no relapses one week following ciprofloxacin treatment; six of nine patients experienced a relapse following beta-lactam treatment (p less than 0.01). By four to six weeks, all patients infected with gram-positive cocci had a relapse. Six of 14 patients with urorenal abnormalities in whom cures had been achieved acquired new infections. Before treatment, the bowel flora of 80 percent of the patients was resistant to amoxicillin, 20 percent was resistant to cefixime, and none was resistant to ciprofloxacin. Penicillin and cefixime increased the incidence of resistant flora to 93 and 36 percent, respectively. Ciprofloxacin suppressed aerobic bowel flora, and no resistant strains persisted after treatment. Ciprofloxacin promises effective short-term oral treatment of complicated urinary tract infections with minimal risk of drug-resistant recurrences.

Adult