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Biomedical subjects

J Trachtenberg

Publications and source records attributed to J Trachtenberg.

At least 73 records · Page 4Linked to original sources
PubMed1993

Workshop summary: screening policies and procedures.

The question of screening for prostate cancer has, since the advent of prostate-specific antigen testing, become a major source of contention. Important issues include: (1) should such screening become part of routine health checks for men; (2) if routine screening is implemented, at what age should it be started, and (3) can the early detection of prostate cancer facilitated by such screening actually benefit the patient in the long run? These were some of the topics put to the audience and debated by the panel of experts in the discussion forum on screening.

Aged↗
PubMed1993

Treatment of advanced prostate cancer with the combination of finasteride plus flutamide: early results.

In an attempt to maximize the quality of life of advanced prostate cancer patients on prolonged total androgen ablation and to minimize side effects, we have devised a strategy of 'sequential androgen blockade'. Animal studies have demonstrated that the combination of the 5 alpha-reductase inhibitor finasteride and the antiandrogen flutamide was as effective as a luteinizing hormone-releasing hormone analog and flutamide in inhibiting the growth of the prostate. In a pilot trial, 10 potent patients with clinical stage C and D1 prostate cancer were given the combination of finasteride (5 mg b.i.d.) and flutamide (125-250 mg t.i.d.). Eight of ten men remained potent. At 3 months the mean prostate-specific antigen level of all patients was 3.8 ng/ml (34 ng/ml prior to therapy). In all patients serum testosterone increased and those with the highest increase demonstrated gynecomastia. The combination was easily tolerable and side effects were few. This treatment regime appears to offer the benefits of total androgen blockade, is less expensive and has fewer side effects. Further trials are warranted.

Aged↗
PubMed1993

The value of prostate-specific antigen levels in pelvic lymph nodes for diagnosing metastatic spread of prostate cancer.

Curative radical therapy for prostate cancer depends on accurate diagnosis of metastatic spread to pelvic lymph nodes. The authors measured prostate-specific antigen (PSA) levels in homogenized pelvic lymph nodes to determine the antigen's diagnostic value and its correlation with histologic findings. No PSA was detectable in the lymph nodes of either women or of men without prostate cancer. A dilution of prostate cancer tissue with nodal tissue showed that PSA is detectable in this assay to a concentration of 1:100,000. In 38 patients who underwent pelvic lymph node dissection for staging stage B prostate cancer the histologic findings were correlated with PSA content. All nine patients with histologic evidence of metastatic disease had measurable PSA in their nodes. Of the 29 patients with no histologic evidence of metastatic disease, 23 had no detectable PSA in their nodes. The six patients with negative histologic findings and positive findings for PSA had no progression of disease at 18-month follow-up. The authors conclude that the measurement of PSA in pelvic lymph nodes can add substantial information to that obtained by standard histologic examination.

Adult↗
PubMed1992

The synergistic effect of hypercholesterolemia and mechanical injury on intimal hyperplasia.

In an attempt to clarify data obtained from animal models of intimal hyperplasia, we used New Zealand white rabbits, a standardized balloon catheter injury model, and a 0.25% cholesterol supplemented diet. The effects of mechanical injury and hypercholesterolemia separately and combined were determined at the carotid and iliac positions at 12 weeks. En-face planimetry of lesioned intima and measurement of transverse intima-to-media thickness were taken as indices of intimal hyperplasia. No animals received antiplatelet agents or postoperative anticoagulation and all vessels remained patent. Neither procedure alone resulted in statistically significant lesion increase. However, combinations of injury and cholesterol resulted in statistically significant and synergistic lesion enhancement. The quantitative data, coupled with distinctive features noted on scanning electron microscopy and transmission electron microscopy, showed separate and synergistic effects of mechanical injury and cholesterol diet on intimal lesions in this model. Additionally, these effects must be considered in evaluation of animal models of intimal hyperplasia and atherosclerosis. Furthermore, this may help dissect mechanisms of failed revascularizations.

Animals↗
PubMed1992

Sequential androgen blockade: a biological study in the inhibition of prostatic growth.

We attempted to determine the effects of the combination of a 5-alpha reductase inhibitor and an antiandrogen on rat ventral prostate and seminal vesicle weight. We also attempted to determine whether the prostatic cell death gene TRPM-2 would be expressed using this combination of drugs. Adult male Sprague-Dawley rats were randomly assigned to 7 groups of 15 animals. Four groups served as controls: an intact group sacrificed at the initiation of the trial (group 1), a castrate control group (group 2), an intact control group (group 3), and a group treated with the combination of an LHRH agonist plus antiandrogen (group 7). Three other groups were treated with daily subcutaneous injections of 5 alpha reductase inhibitor (group 5), a nonsteroidal pure antiandrogen (group 4) or both (group 6). After 5 days of treatment 5 animals in each group were sacrificed and prostatic tissue was assayed for the androgen repressed prostatic cell death gene TRPM-2. At 30 days (35 days for group 7) the remaining animals were sacrificed and their ventral prostates, seminal vesicles, and testes (except group 3) were weighed. The combination group (group 6) had a significantly lower prostate weight than either of the monotherapy groups (4, 5), or intact control groups, was equivalent to group 7 but was significantly heavier than the castrate group 2. The seminal vesicle weights of the combination group 6 were significantly lower than the monotherapy groups (4, 5), intact control group, castrate group (3) and was equivalent to group 7. Only castration was able to induce expression of the cell death gene TRPM-2. In this model, the combination of 5 alpha reductase inhibitor and an antiandrogen is as effective a mode of androgen ablation as combination therapy of LHRH agonist plus antiandrogen. Clinically, this combination may translate into adequate androgen blockade without impotence or other side effects of testosterone deprivation. Clinical trials appear warranted to assess this hypothesis.

5-alpha Reductase Inhibitors↗
PubMed1991

Total androgen ablation: Canadian experience.

A multicenter randomized, double-blind trial comparing total androgen blockade obtained by the use of castration with a pure anti-androgen (nilutamide) with simple castration was begun. One hundred and five patients received the combined treatment and 103 the orchiectomy plus placebo. Several features were used to evaluate the efficacy. Bone pain responded better to combined treatment at 6 months (P = 0.042). The number of favorable responses, as evaluated by the NPCP criteria, was 61% with simple castration and 78% with the combined treatment (P = 0.013). There was no statistically significant difference between the two groups in time to progression (logrank test P = 0.462) or survival (logrank test P = 0.137) despite an increase in median survival of 5.4 months. All other measures showed no difference between the two treatments. With total androgen blockade, 50% of the patients had disease progression at 1 year, and 45% were dead at 2 years. A review of the results of similar reported studies suggests no improvement or very modest improvement with total androgen blockade over testicular androgen ablation alone.

Adult↗
PubMed1990

A controlled trial of castration with and without nilutamide in metastatic prostatic carcinoma.

A randomized double-blind trial in patients with disseminated, previously untreated prostate cancer (Stage D2) was conducted in eight Canadian centers. All 203 patients enrolled in this study underwent bilateral orchiectomy and were randomized to receive either the nonsteroidal anti-androgen nilutamide or a placebo. Patient responses were graded according to the criteria of the National Prostatic Cancer Project (NPCP). Patients treated with nilutamide had a significantly greater number of positive objective responses (partial and complete regression) than did the patients treated with castration alone (46% versus 20%, P = 0.001). Progression-free survival was improved initially in the nilutamide group, but the median time to progression was 12 months for both groups. Despite an increase in the median length of survival from 18.9 to 24.3 months with the nilutamide, the survival time was not significantly longer in the nilutamide group (log = rank test, P = 0.048). Although minor side effects were frequent, adverse effects related to the medication and leading to discontinuation of treatment were observed in 9% of cases. These results suggest some benefit of the combined treatment (orchiectomy + nilutamide) over orchiectomy alone in the treatment of metastatic prostatic carcinoma.

Adult↗
PubMed1989

The effect of liposome encapsulated antineoplastic agents on transitional cell carcinoma in tissue culture.

Liposomes are microscopic vesicles composed of one or more phospholipid bilayers separated by an equal number of aqueous interspaces. These "capsules" are formed when dried lipid is combined with excess water, agitated, and warmed above the transition temperature of the lipid (the temperature at which the lipid changes from a gel state to a fluid state). If a chemical in solution is present when the vesicles form, the chemical will be trapped in either the aqueous interspaces (hydrophilic compounds), or the lipid bilayer (hydrophobic compounds). The urinary bladder is an attractive site for the topical application of liposome encapsulated compounds due to its accessibility and since the introduction of various agents, including antineoplastic compounds, into the bladder is a well established treatment option. Utilization of liposome technology may provide the means for a more effective intravesical treatment of transitional cell carcinoma.

Administration, Intravesical↗
PubMed1989

Ketoconazole: a possible direct cytotoxic effect on prostate carcinoma cells.

Ketoconazole has been recently used in the treatment of advanced prostatic cancer and is believed to exert its effect by inhibition of androgen production. In order to determine whether ketoconazole exerts an additional direct cytotoxic effect on prostate cancer cells, we studied its effect on human hormone-independent prostate cancer cell lines (PC-3 and DU-145) in an in vitro clonogenic tumor assay. We showed that clinically achievable doses of ketoconazole caused greater than 90% suppression of tumor colony growth.

Carcinoma↗
PubMed1989

Effects of high-dose ketoconazole on patients who have androgen-independent prostatic cancer.

Forty-four patients who had metastatic cancer of the prostate that had not responded to conventional hormonal manipulation were treated with high-dose ketoconazole (600 to 1200 mg/d). All had castrate serum concentrations of testosterone prior to therapy. All patients had been categorized as having progressive cancer on assessment by the criteria of the National Prostatic Cancer Project. After treatment with ketoconazole, 57% were recategorized as having stable disease. The majority showed marked subjective lessening of pain on this therapy. Objective responses were noted but were not consistent. Side-effects were common but tolerable. The mean survival time was 73.3 weeks. Ketoconazole may be a useful palliative adjunct in the treatment of hormone-refractory prostatic cancer.

Aged↗
PubMed1989

Synergistic effect of ketoconazole and antineoplastic agents on hormone-independent prostatic cancer cells.

Ketoconazole has been recently used in the primary treatment of patients with metastatic cancer of the prostate and is identified as a potent inhibitor of cytochrome P450-dependent adrenal and testicular androgen production. The drug has also shown activity in patients failing conventional hormonal manipulation. We subsequently showed that ketoconazole in vitro has a direct cytotoxic effect on human androgen-independent prostatic cancer cell lines. In order to better define the possible role of ketoconazole on hormone-independent prostatic cancer, we incubated the cells from human androgen-independent prostatic cancer lines in a methylcellulose tumour colony assay with different doses of the drug and increasing doses of conventional cytotoxic agents (etoposide, bleomycin, vinblastine, methotrexate, and teniposide). We demonstrated synergistic suppression of prostate cancer clonogenic cell growth by ketoconazole in the presence of vinblastine or etoposide. This observation may assign a new and important role for ketoconazole as part of combination chemotherapy in the treatment of patients with advanced prostatic cancer.

Antineoplastic Agents↗
PubMed1988

Effects of high-dose ketoconazole in patients with androgen-independent prostatic cancer.

Forty-four patients with metastatic cancer of the prostate that had failed conventional hormonal manipulation were treated with high-dose ketoconazole (600-1,200 mg/day). All patients had castrate serum concentrations of testosterone prior to therapy. All of the patients had been assessed by the criteria of the National Prostatic Cancer Project and been categorized as progressing. Over 50% of the patients were recategorized as having stable disease. The majority of the patients showed marked subjective improvement in pain on this therapy. Objective responses were noted but were not consistently seen. Side effects were common but tolerable. The median time of survival was 73.3 weeks. Ketoconazole may be a useful palliative adjunct in the treatment of hormone refractory prostatic cancer.

Acid Phosphatase↗
PubMed1988

Total androgen blockade for metastatic cancer of the prostate.

This randomized, double-blind study comparing orchiectomy plus placebo to orchiectomy plus a nonsteroid antiandrogen (Anandron) shows that total androgen blockade for metastatic cancer of the prostate provides a significantly better early objective response when compared to castration alone. This response, however, is less apparent at 18 months. The study also suggests a longer survival for the patients with total androgen blockade.

Androgen Antagonists↗
PubMed1988

Steroid synthesis inhibition by ketoconazole: sites of action.

Ketoconazole is an antifungal agent that, in high doses, inhibits testicular and adrenal steroid synthesis. The ability of ketoconazole to block steroid synthesis has prompted us to use it in the treatment of advanced prostatic carcinoma. This study was designed to determine the site of steroid synthetic blockade that was induced by ketoconazole. Twelve patients with metastatic prostate carcinoma on long term high dose ketoconazole therapy were compared with 12 control volunteers. Values of serum progesterone, 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone sulphate, testosterone, and cortisol were measured in a baseline state and after Cosyntropin and human chorionic gonadotropin stimulation. Baseline data showed that serum levels of testosterone, androstenedione, and dehydroepiandrosterone sulphate were lower and that plasma progesterone, luteinizing hormone, and adrenocorticotropin were higher in the ketoconazole group. With Cosyntropin, plasma cortisol, androstenedione, and dehydroepiandrosterone sulphate increased only in the control group. With human chorionic gonadotropin, testosterone increased only in the control group. Basal 17-hydroxyprogesterone and progesterone rose after Cosyntropin only in the ketoconazole group. Following human chorionic gonadotropin, progesterone rose in the ketoconazole group but not in the control group. These results suggest that ketoconazole is a potent inhibitor of steroid synthesis. The major site of action appears to be in the inhibition of 17-20 desmolase. A moderate blockade of 17-hydroxylase may be present. There is a marked inhibition of 21- and/or 11-hydroxylase. The ability of ketoconazole to inhibit steroid synthesis should have therapeutic potential in the treatment of steroid dependent disease. Frequent high dose ketoconazole therapy can inhibit adrenal steroid synthesis, which can be important for patients undergoing stressful situations.

17-alpha-Hydroxyprogesterone↗
PubMed1988

Erosion of the ureter by ileofemoral arterial prosthesis.

We report a case of erosion of the ureter by a prosthetic vascular graft subsequent to an ileofemoral bypass. The diagnosis, etiology, and management from both vascular and urologic points of view are discussed, and the available literature is reviewed. Therapeutic principles include early intervention, ureteric reconstruction or ureteronephrectomy depending on circumstances, removal of prosthesis and delayed vascular reconstruction if feasible to avoid contamination, or revascularization with extraanatomic bypass if urgent.

Aged↗
PubMed1987

Experimental treatment of prostatic cancer by intermittent hormonal therapy.

In order to determine if intermittent hormonal therapy might prove to be beneficial in the treatment of prostatic cancer, animals bearing the Dunning R3327H prostatic adenocarcinoma were castrated and intermittently subjected to hormonal stimulation by means of indwelling silastic testosterone-filled implants. The growth of these tumors, as measured by increases in volume, was compared to that of a castrate control group, a chronic implant group and an intact control group. By the end of an initial 49 day experimental period there was no significant growth reduction with the intermittent stimulation group as compared to the implanted control or intact groups. The castrate group had a significant lower rate of growth than any other group. The incidence of massive tumor growth or tumor necrosis was significantly lower in the castrate group than the other groups by the end of the 16 week experimental period. Intermittent hormonal therapy is clearly inferior to early castration in preventing tumor growth; furthermore it does not appear to offer any growth-retarding advantages when compared to delayed hormone therapy. The most effective growth-retarding technique for the Dunning R3327H hormone dependent prostatic adenocarcinoma is early castration.

Adenocarcinoma↗