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Biomedical subjects

J Trachtenberg

Publications and source records attributed to J Trachtenberg.

At least 55 records · Page 3Linked to original sources
PubMed1997

Staging pelvic lymphadenectomy for localized carcinoma of the prostate: a comparison of 3 surgical techniques.

PURPOSE: Pelvic lymph node dissection continues to be the most effective method of staging extracapsular adenocarcinoma of the prostate. Three principal methods of pelvic lymph node dissection are currently available: intraperitoneal laparoscopic, minilaparotomy and the standard open modified pelvic lymph node dissection. In the hope of determining some of the relative advantages and disadvantages associated with each technique a comparison of these approaches was made. MATERIALS AND METHODS: Of 68 patients with histologically proved clinical stage T3N0M0 adenocarcinoma of the prostate who underwent staging pelvic lymph node dissection 38 underwent modified open, 19 laparoscopic and 11 minilaparotomy procedures. The efficacy of node sampling, resource expenditure and complication rates were compared among the 3 groups. RESULTS: No statistically significant difference was observed in terms of the number of nodes harvested with each technique. Resource expenditure analysis revealed significantly increased operative and procedural time requirements for laparoscopic pelvic lymph node dissection compared to modified open and minilaparotomy procedures. Total hospital stay was significantly longer for the modified open pelvic lymph node dissection (mean plus or minus standard deviation 6.5 +/- 0.9 days) compared to the laparoscopic (mean 2.7 +/- 1.1 days) and minilaparotomy (mean 3.3 +/- 0.2 days) groups. Multiple complications, such as ileus, lymphocele and urinary retention, were observed in the modified open pelvic lymph node dissection group. No complications were noted in the other 2 groups. CONCLUSIONS: Comparison of laparoscopic and minilaparotomy procedures to modified open pelvic lymph node dissection revealed similar staging efficacy, and decreased total hospital stay and complications. Laparoscopic pelvic lymph node dissection required increased operative time. Minilaparotomy should become the open surgical procedure of choice for pelvic lymph node dissection, particularly at institutions where the laparoscopy learning curve, equipment expense and time disadvantages cannot be overcome.

Adenocarcinoma↗
PubMed1997

Innovative approaches to the hormonal treatment of advanced prostate cancer.

Androgen ablation therapy is the treatment of choice for the palliation of patients with advanced prostate cancer. In addition to palliation, maximal androgen ablation (MAA), with a combination of medical or surgical castration and an antiandrogen, has been shown to increase the survival of patients with metastatic prostate cancer in at least three large well-conducted trials. A subgroup analysis of these trials has suggested that patients, particularly those with low volumes of metastatic disease, fared much better when treated with MAA than with castration alone. This observation has prompted many clinicians to begin androgen ablation earlier in men with advanced but not necessarily metastatic prostate cancer, thus exposing them to prolonged periods of androgen ablation and its side effects. These include impotence, loss of libido, loss of muscle mass, malaise, and psychological disturbances. In order to offer the putative advantages of early hormone therapy but to mitigate its side effects a number of innovative methods of androgen ablation are under investigation. These include 'sequential androgen blockade' and 'intermittent androgen suppression'. Sequential androgen blockade uses a 5 alpha-reductase inhibitor to reduce the conversion of testosterone to dihydrotestosterone in conjunction with an antiandrogen or androgen-receptor blocker to prevent residual androgen from reaching the androgen receptor. Circulating testosterone levels are not reduced thus minimizing side effects. Intermittent androgen suppression uses combined therapy to rapidly reduce serum testosterone and induce tumor regression. From time to time treatment is stopped and androgen concentrations rise. This method reduces the total time of exposure to castrate levels of androgen and, although prostate-specific antigen levels rise during the second phase of therapy suggesting tumor growth, proponents of this cycling method suggest that this should prolong the time to androgen independence of the tumor. Early results with both methods suggest that the time to progression is long and side effects are minimized as compared to MAA. Large scale trials will be needed to determine the exact risks and benefits of these novel methods of androgen ablation.

Androgen Antagonists↗
PubMed1996

A multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of terazosin in the treatment of benign prostatic hyperplasia.

OBJECTIVES: This study was designed to evaluate the safety and efficacy of the selective alpha 1-adrenoceptor blocker terazosin in the treatment of benign prostatic hyperplasia (BPH). METHODS: Two hundred twenty-four patients aged 50 to 80 years, who had a diagnosis of BPH based on medical history, physical examination, and digital palpation, were recruited from 11 different sites between January 1992 and January 1994. The study consisted of a screening phase, a placebo phase, a double-blind dose-titration phase, and a double-blind maintenance phase. RESULTS: Of the patients recruited, 164 entered the double-blind phase and of these 134 were evaluable. Only 11 patients withdrew because of an adverse event, 7 in the terazosin and 4 in the placebo group. Compared to placebo, terazosin significantly increased peak and mean urine flow rates without significantly affecting voided volume or postvoid residual volume. It significantly improved both the obstructive and irritative symptoms associated with BPH. Fifty-one patients from the terazosin group reported a total of 120 adverse events compared with 83 reported by 42 patients in the placebo group. The majority of these events were mild to moderate. Seventeen terazosin-treated patients reported hypotension-related adverse events and 4 withdrew from the study. However, concurrent treatment with antihypertensive agents did not affect the blood pressure response of the terazosin group. CONCLUSIONS: Overall, this study showed terazosin to be safe and effective in relieving the signs and symptoms of BPH and should be considered as a treatment alternative.

Adrenergic alpha-Antagonists↗
PubMed1996

A dose-response study of the effect of flutamide on benign prostatic hyperplasia: results of a multicenter study.

OBJECTIVES: The objective of this study was to evaluate efficacy, safety, and dose-response profiles of four dosing schemes of flutamide over 24 weeks. METHODS: Patients were randomized to receive one of the following five treatment regimens for a period of 24 weeks: placebo capsule, flutamide capsules 125 mg twice daily, 250 mg once daily, 250 mg twice daily, and 250 mg three times daily. Patients were then evaluated at baseline (0 weeks) and at 4, 6, 12, 18, and 24 weeks after the start of treatment, and 8 weeks after the end of treatment (32 weeks). Evaluation of efficacy was performed by noting changes in urine flow rate, residual urine volume, symptom score, prostate volume, and prostate-specific antigen level. A total of 372 patients were enrolled into the study at 32 centers (14 centers in the United States and 18 international centers). RESULTS: Baseline peak urinary flow rate and percent change from baseline in maximum flow rate showed a dose-related increase at 4 and 6 weeks; this increase was significant in the 250 mg three times daily group. At later time points, no significant differences between the flutamide and placebo groups were observed, largely because of the decreasing number of evaluable patients. At 4 and 6 weeks, 25% of patients in the 250 mg three times daily group had more than 3 cc/s increase in uroflow compared to about 10% of placebo patients (P < 0.05). All flutamide-treated groups had a significant decrease in prostate volume from baseline to the last treatment visit compared to placebo and this reduction was dose related (in comparison to placebo: P < 0.05 for 125 mg twice daily and P < 0.001 for all other treatment arms). Median decrease for the flutamide-treated groups ranged from 6% to 23% at 12 weeks and from 14% to 29% at 24 weeks. All treatment groups showed a subsequent increase in prostate volume after treatment was stopped. Furthermore, there was a significant reduction in residual urine volume at 24 weeks only in the 250 mg three times daily group. It increased following cessation of therapy. Urinary symptoms at 6, 12, 18, and 24 weeks did not show any significant difference between placebo and any flutamide dose group. The most common adverse events were nipple and breast tenderness (42% to 52%), diarrhea (29% to 34%), and gynecomastia (14% to 19%). Each of these adverse events had a significantly higher incidence in all flutamide dose groups compared with placebo, but none appeared to occur in a dose-related fashion. Sixteen percent of patients in the placebo group and 25% to 39% of patients in flutamide groups were discontinued due to diarrhea (12% to 17%) or nipple and breast tenderness (4% to 8%). A total of 1% to 3% of patients in various treatment arms discontinued due to deranged liver enzymes (1% for placebo); and 1% to 4% due to impotence (1% for placebo). CONCLUSIONS: Flutamide reduced the prostate volume in a dose-related fashion and resulted in an increase in peak flow rate at 4 weeks (3% for 250 mg three times daily, P value < 0.05), but the early positive effects did not maintain statistical significance due to an increasing number of dropouts due to adverse events. Effect on postvoid residual volume was observed only at the highest dose and at 24 weeks (median reduction, 23 mL, P < 0.05). Despite volume reduction and early improvement in peak flow rate, there were no significant differences in urinary symptoms among the placebo and flutamide groups. Higher incidences of diarrhea, breast tenderness, and gynecomastia, however, were the main limiting factors in this study and until these problems are overcome, the role of flutamide in the management of benign prostatic hyperplasia remains investigational.

Aged↗
PubMed1996

The changing scene of social work in hospitals: a report of a national study by the Society for Social Work Administrators in Health Care and NASW.

The Society for Social Work Administrators in Health Care and NASW collaborated on a national study of the changes affecting social work services in a sample of 340 hospitals drawn from the member list of the American Hospital Association. The findings suggest that the changes affecting social work need to be viewed within the context of the dramatic changes occurring in the hospital and health care field. Although social work departments are experiencing decreases, these decreases often are not occurring at the same rate as those within the hospital overall. Growth is occurring in the types and scope of services. Social work is not being singled out for change, but it is critical that these trends continue to be monitored and proactive strategies used to enhance social work viability within a changing hospital environment.

Administrative Personnel↗
PubMed1996

Healthcare resources should be targeted to chemoprevention: the argument against.

Chemoprevention of prostate cancer is an attractive idea that appeals to many struggling with the treatment of this disease. Many details inherent in any preventive strategy must be considered before embarking on this course, no matter how seductive it may appear. Critical issues of effectiveness, cost, difficulties in implementation, side effects, duration of the preventive cycle, and public acceptance may thwart prevention of prostate cancer from being implemented in the near future.

Anticarcinogenic Agents↗
PubMed1996

Appraisal of current therapies for prostate cancer.

All aspects of the treatment of prostate cancer remain controversial. Even the simplest question--is early detection of prostate cancer beneficial?--remains the subject of heated debate. While it would appear intuitive that early detection should increase the survival of patients with prostate cancer, no high quality evidence actually supports this assumption. Indeed decision-analysis models have suggested that early detection and treatment may impair quality-adjusted survival. More practical issues such as the effectiveness and side effects of traditional treatments for prostate cancer, such as radical therapy for localised disease and androgen ablation therapy, are now under great scrutiny. There are proponents and opponents of all treatments brandishing widely divergent analyses designed to support their views. In an era of cost containment these various treatments are all being subjected to outcome analyses which will determine their true benefit. Nonetheless, the judicious selection of patients most likely to benefit from each individual therapy will assure the best possible outcome.

Androgen Antagonists↗
PubMed1995

Immunocytochemical detection of androgen receptor in human temporal cortex characterization and application of polyclonal androgen receptor antibodies in frozen and paraffin-embedded tissues.

Immunocytochemical and biochemical studies have demonstrated the presence of androgen receptor protein in various regions of the rodent and non-human primate cortex. Localization of androgen receptor in the human brain has, however, not been studied as extensively, because of difficulties in obtaining suitable tissue samples. In the present study, we have localized androgen receptors in both frozen and paraffin-embedded temporal cortex from epileptic patients undergoing resection. Polyclonal antibodies were raised against fusion proteins containing fragments of the human androgen receptor protein. The antibodies were affinity-purified against the corresponding fusion protein. Immunoprecipitation and Western blotting using extracts from human cell lines demonstrated the specificity of the antibodies for the human androgen receptor and lack of cross-reactivity with other steroid hormone receptors. Immunocytochemistry was performed on frozen and paraffin sections of human temporal cortex and in paraffin-embedded benign hyperplastic prostates (BPH), as well as prostate and breast carcinomas, by the streptavidin-biotin-peroxidase method. Antigen-retrieval was performed in paraffin-embedded sections using microwave irradiation. Specific nuclear and cytoplasmic immunoreactivity for androgen receptor was detected in neurons, astrocytes, oligodendrocytes, and microglia cells of the temporal cortex. In contrast, only nuclear staining was observed in BPH, prostate and breast carcinomas. Immunoprecipitation of human temporal cortex lysate and subsequent Western blot analysis demonstrated the expression of a 98 kDa immunoreactive protein, slightly smaller than the reported molecular weight of the wild-type androgen receptor. These results provide further evidence for the expression of androgen receptor in the human temporal cortex. The use of these immunocytochemical techniques should enable the retrospective determination of possible changes in androgen receptor expression in a variety of archival paraffin-embedded tissues, including samples of the human central nervous system.

Adolescent↗
PubMed1995

Phase I-II study of vinblastine and oral cyclosporin A in metastatic renal cell carcinoma.

A phase I-II clinical trial was conducted to determine the maximum-tolerated dose (MTD) of oral cyclosporine (CsA) and vinblastine in patients with metastatic renal cell cancer (RCC) as well as to estimate the response rate. Sixteen patients received a 5 mg/kg oral loading dose of CsA followed by 3 days of CsA in 4 divided daily doses escalating from 10 mg/kg per day up to 17 mg/kg per day. Vinblastine (Vbl) was administered as an intravenous bolus on the morning of the 3rd day with dose escalation from 6 to 10 mg/m2. Cycles were repeated every 4 weeks until tumor progression. Forty-nine cycles of CsA with vinblastine were administered. The maximum tolerated dose of Vbl was 10 mg/m2, with neutropenia as the dose-limiting toxicity resulting in one death. CsA could not be escalated above 17 mg/kg per day because of nausea and vomiting. Other toxicities included constipation (100%), malaise (100%), temporary increase in pain (36%), and one seizure that may have been drug-related. There were no clinically significant changes in renal function or serum bilirubin. Mean peak whole-blood CsA level at the highest CsA dose level was 919 ng/ml (range: 414-1,827) with a trough prior to Vbl injection of 451 ng/ml (range: 128-1,229). There were no tumor responses. The combination of oral CsA and Vbl is not nephrotoxic but is poorly tolerated. In most patients optimal blood levels of CsA for reversal of MDR cannot be reliably achieved, and vinblastine dose intensity must be compromised because of the significant toxicity of this regimen.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Microwave therapy of benign prostatic hyperplasia.

Thermotherapy of the prostate proves to be a safe and effective treatment for patients with symptomatic prostatism secondary to BPH. Present treatment regimens yield results and side effects intermediate between drug therapy and prostatectomy. Future enhancements of the thermotherapy technique are likely to improve its results to the level of surgery.

Aged↗
PubMed1995

Combination finasteride and flutamide in advanced carcinoma of the prostate: effective therapy with minimal side effects.

PURPOSE: The efficacy of the combination of finasteride and flutamide in select patients with advanced prostatic cancer is determined. MATERIALS AND METHODS: A total of 22 sexually active patients with stages C and D1 carcinoma of the prostate was treated with finasteride plus flutamide. Mean followup was 22 months. RESULTS: Initial mean prostate specific antigen level was 42.9 ng./ml. At 3 and 6 months, the mean prostate specific antigen level was 3.6 ng./ml. and 2.9 ng./ml., respectively. The results appear durable at 24 months. Side effects were minimal, with 86% of the men maintaining sexual function. CONCLUSIONS: Finasteride plus flutamide should be considered in sexually active patients with minimal volume advanced prostate cancer.

Aged↗
PubMed1994

Screening for prostate cancer. A decision analytic view.

OBJECTIVE: To determine the clinical and economic effects of screening for prostate cancer with prostate-specific antigen (PSA), transrectal ultrasound (TRUS), and digital rectal examination (DRE). DESIGN: Decision analytic cost-utility analysis comparing four screening strategies with a strategy of not screening. We assumed that the cancer detection rate and stage distribution were predicted by each combination of tests and that localized cancer was treated with radical prostatectomy. For each strategy, we calculated life expectancy, quality-adjusted life expectancy (QALE), and cost-utility ratios for unselected and high-prevalence populations. DATA: Probabilities and rates for clinical events were gathered from published data. We assessed utilities by the time-trade-off method using urologists, radiation oncologists, and internists as subjects. The Clinical Cost Manager at the New England Medical Center provided cost data. RESULTS: In unselected men between the ages of 50 and 70 years, screening with PSA or TRUS prolonged unadjusted life expectancy but diminished QALE. Screening with DRE alone yielded no reduction in mortality at any age. All programs increased costs. Results were sensitive only to assumptions about the efficacy of treatment. In high-prevalence populations, screening produced a similar pattern: gains in unadjusted life expectancy, losses in QALE, and increased costs. CONCLUSIONS: Our analysis does not support using PSA, TRUS, or DRE to screen asymptomatic men for prostatic cancer. Screening may result in poorer health outcomes and will increase costs dramatically. Assessment of comorbidity, risk attitude, and valuation of sexual function may identify individuals who will benefit from screening, but selecting high-prevalence populations will not improve the benefit of screening.

Aged↗
PubMed1994

Inhibition of neointimal hyperplasia by blocking alpha V beta 3 integrin with a small peptide antagonist GpenGRGDSPCA.

PURPOSE: Neointimal hyperplasia is a leading cause of restenosis after vascular procedures. Recent findings showed that smooth muscle cell (SMC) migration from the media into the neointima is a critical step in the development of the hemodynamically compromising neointimal lesion. Moreover, integrins are believed to play a role in SMC motility. Therefore we studied the role of one ubiquitous integrin, alpha V beta 3, in SMC migration. METHODS: Transwell assay was used to study in vitro migration of human and rabbit SMCs after stimulation with platelet-derived growth factor (PDGF). A neutralizing monoclonal antibody to alpha V beta 3, LM609, and a specific arginine-glycine-aspartic acid (RGD) antagonist, GpenGRGDSPCA, were used in the migration assay to inhibit alpha V beta 3-mediated SMC migration. In addition, GpenGRGDSPCA was administered locally to rabbit carotid artery after balloon angioplasty to determine the effect of blocking alpha V beta 3 on neointimal hyperplasia. RESULTS: We showed that PDGF-induced human SMC migration is mediated by the alpha V beta 3 integrin by use of LM609 to inhibit migration and that SMC migration is RGD dependent by use of GpenGRGDSPCA to inhibit migration. We have also inhibited rabbit SMC migration with GpenGRGDSPCA to demonstrate the cross-species preservation of the RGD peptide sequence in SMC mortality. Finally, when we administered GpenGRGDSPCA locally to rabbit carotid artery after balloon angioplasty, there was a statistically significant reduction in neointimal lesion formation compared with arteries administered an inactive peptide or saline solution. CONCLUSIONS: We have demonstrated the important role of the alpha V beta 3 integrin in SMC migration in vitro and in neointimal hyperplasia in vivo.

Amino Acid Sequence↗
PubMed1994

High temperature microwave thermotherapy of the prostate.

Transurethral microwave thermotherapy of the prostate has been touted as a minimally invasive means of treating symptomatic prostatism. High temperatures (>55 degrees C) appear to yield improved results but require general anesthesia. To determine if high temperature thermotherapy of the prostate was feasible in an outpatient, nonanesthetic setting, we subjected men with symptomatic prostatism secondary to benign prostatic hyperplasia to treatment with a newly developed circumferentially cooled transurethral microwave thermotherapy device, the UroWave. Intraprostatic temperatures were measured on-line and treatment was targeted to achieve temperatures ranging from 45 degrees C-65 degrees C. Fifty-five men with benign prostatic hyperplasia underwent transurethral microwave thermotherapy using the UroWave in an outpatient setting without general anesthesia. Baseline mean peak urinary flow rates were 8.0 cc/sec and mean American Urology Association of the prostate displayed three distinct phases: an initial slow heating phase, a plateau phase of variable duration and a rapid secondary heating phase. The final intraprostatic temperature did not correlate with urethral or rectal temperatures or the amount of power applied. At six months, peak flow increased by 50% and symptoms score declined by 52%. Ninety-four percent of patients had a transurethral resection of the prostate-like defect at cystoscopy with a greater proportion at higher temperatures. Side effects were rare and no patients had to be admitted to hospital. Transurethral microwave thermotherapy at high intraprostatic temperatures can be achieved with general anesthesia. Symptom relief was considerable and anatomic changes resembling a transurethral resection of the prostate were noted in the majority of patients. Intraprostatic temperatures are the only means of assessing the thermal damage to the prostate and thus the effectiveness if therapy. Future studies must develop less invasive means of monitoring intraprostatic temperatures and define the role of the bladder neck. Ultimately, randomized controlled trials will define the value of this treatment.

Journal Article↗
PubMed1994

State-of-the-art hormonal management of prostate cancer.

For more than 30 years, maximal androgen blockade has been used in urologic oncology clinical trials practiced with varied degrees of success in the treatment of prostate cancer. While the popularity of maximal androgen blockade has waxed and waned, currently maximal androgen blockade appears to be the optimum treatment for the management of advanced prostate cancer. This opinion paper is intended to review the current approach of maximal androgen blockade and, in particular, address its role in clinical practice. This article reflects the views of 14 urologic experts from Canada, the US and Europe.

Journal Article↗
PubMed1993

Androgen-induced inhibition of cell proliferation in an androgen-insensitive prostate cancer cell line (PC-3) transfected with a human androgen receptor complementary DNA.

A full length human androgen receptor complementary DNA was introduced into androgen receptor-negative PC-3 cells to determine if androgen sensitivity could be established in this cell line and to assess what influence, if any, androgen exposure would have on the growth of these cells. The androgen receptor complementary DNA was inserted into pSG5 in the region controlled by the SV40 promoter. This construct was cotransfected with pSR1neo into PC-3 cells and stably transfected cells were selected and screened for the expression of the androgen receptor. Active expression of the receptor was demonstrated by Western blotting using a rabbit anti-androgen receptor antiserum and by [3H]methyltrienolone binding to cytosol extracts. Saturation ligand-binding analysis revealed the presence of a single class, high affinity (Kd = 0.122 nM) androgen-binding site in cytosol extracts of transfected cells but not in extracts from mock-transfected cells. In cells expressing the transfected androgen receptor, androgen decreased the proliferation rate and cloning efficiency and induced a more differentiated phenotype. These results demonstrate that PC-3 cells have retained the mechanisms required to respond to the activated androgen receptor and that the loss of androgen sensitivity in these cells is due to the lack of functional androgen receptor. This also provides a technique for determining whether androgen-resistant tumor cells contain functional androgen receptors or whether androgen sensitivity is due to abnormalities in downstream signaling pathways. The apparent androgen-induced decreased malignant state of these transfected cells suggests new directions for the treatment of prostate cancer.

Animals↗