Biomedical subjects

C Berman

Publications and source records attributed to C Berman.

At least 19 recordsLinked to original sources

PubMed1992

Lymphoscintigraphy in vulvar cancer: a pilot study.

This pilot study was undertaken to correlate the patterns of lymphatic drainage demonstrated by vulvar lymphoscintigraphy with the clinical and pathologic findings of the inguino-femoral lymph nodes in patients with vulvar cancer. Ten patients were studied with the radionuclide Technetium-antimony trisulfide colloid (Tc 99m ASC) using a perilesional technique. Images were obtained at 2-4 hr postinjection. Four of the six patients with central lesions or lesions that crossed the midline had bilateral groin uptake, and two had unilateral uptake to the side on which the lesion was predominantly located. Three of these patients, each with suspicious groin nodes bilaterally, had metastatic nodal disease, two unilateral and one bilateral, in whom the uptake was bilateral and unilateral, respectively. Three of the four patients with unilateral lesions had ipsilateral groin drainage only and one had no drainage. Three underwent a bilateral lymphadenectomy and none had metastasis. The pattern of Tc 99m ASC uptake was not predictive of metastatic nodal disease. In two of the three patients with unilateral groin recurrence the side of recurrence was the same as that demonstrated on lymphoscintigraphy, and in the third case there was bilateral drainage. Further data are needed to determine the role of lymphoscintigraphy in the management of vulvar cancer.

Aged↗

PubMed1992

The effectiveness of skin cancer screening and continuing medical education programs toward increasing the survival of patients with malignant melanoma.

The 5-year survival rate for malignant melanoma has increased 40% over the last 50 years. During this same time period, the treatment for the disease has not changed significantly, and consists of wide excision of the primary tumour and perhaps regional node dissection. The purpose of this study was to investigate the possible impact of screening/education programs on melanoma survival. In 1987, a multimodality University-based Melanoma Treatment Center was established and programs were instituted for skin cancer screening and Continuing Medical Education (CME) of health care providers. During the last 5 years, 594 patients with newly diagnosed melanoma have been registered at the clinic. The number of patients with localized (stage 1 or 2, negative regional nodes) disease was 516 (85%). For all stages of disease, the 3-year actuarial survival for this screened population was 85%. From the National Cancer Database of 9879 patients registered with melanoma for 1988, 75% had localized disease and the 3-year survival was 76%. There were significant differences noted between the screened Florida population and the nationwide database using an odds ratio statistic. This involved a higher frequency of patients diagnosed with localized disease (odds ratio = 1.89 (1.49-2.40)) and a better survival (odds ratio = 1.79 (1.41-2.27)) in the screened population served by CME-educated community physicians.

Actuarial Analysis↗

PubMed1991

Magnetic resonance imaging of the efficacy of specific inhibition of 5 alpha-reductase in canine spontaneous benign prostatic hyperplasia.

A leading role for prostatic levels of dihydrotestosterone (DHT) in the pathogenesis of benign prostatic hyperplasia is well established, if incompletely understood. The present study provides initial confirmation that 5 alpha-reductase inhibition alone is sufficient to prevent prostatic accumulation of DHT and to produce epithelial regression in the canine prostate. In dogs treated with the specific 5 alpha-reductase inhibitor finasteride, prostatic volume decreased to one-third of the baseline volume, while the prostatic concentration of DHT fell fivefold: both were constant in placebo control dogs. Demonstration that MR imaging can serve as accurate modality to assess prostatic volume was provided by serial measurements of the canine prostate and by correlation of the last imaging measurement with the weight of the excised prostate. Significant intensity changes were observed in T2-weighted images measured post-treatment; these changes correlated with the histopathology of the prostate. These results suggest that beyond quantifying regression, multiecho T2 measurements can be useful in probing accompanying changes occurring on the cellular level.

5-alpha Reductase Inhibitors↗

PubMed1991

Effect of castration, DES, flutamide, and the 5 alpha-reductase inhibitor, MK-906, on the growth of the Dunning rat prostatic carcinoma, R-3327.

Male rats bearing implants of the Dunning rat prostatic carcinoma, R-3327, were used in a 42-day study to determine the effect of castration or orally administered flutamide (FL), DES (diethylstilbestrol) or the 5 alpha-reductase inhibitor, MK-906, on the growth of this androgen-responsive cancer. The rate of growth and final weights of the tumor and the ventral prostate (VP) were all reduced (P less than 0.05) by castration. Flutamide (25 mg/kg/day) significantly decreased tumor and VP weights in intact rats and castrates given 100 micrograms/day (SC) of testosterone propionate (TP) or dihydrotestosterone propionate (DHTP). It also significantly retarded tumor growth rate in TP- or DHTP-treated castrates and was marginally effective in intact animals. DES (100 micrograms/kg/day) reduced (P less than 0.05) tumor and VP weights of intact rats but did not significantly affect tumor growth rate or weight in castrates given TP or DHTP. These results indicated that the effect of DES on tumor growth is caused by its inhibition of the secretion or release of the gonadotropins necessary for testicular androgen production. MK-906 (25 mg/kg/day) affected neither the gross nor the histomorphology of the tumor in intact rats or castrates given TP or DHTP. Further, it caused no histological changes in the testes of intact rats. It did, however, significantly reduce VP weight in intact animals and TP-treated castrates but not in those given DHTP. This illustrates that the anti-androgenicity of MK-906 stems from its inhibition of DHT formation. The failure of MK-906 to influence tumor growth in the TP-treated castrates strongly suggests that the R-3327 tumor can respond to testosterone directly. If that is true, then its growth is unlikely to be affected by a pure 5 alpha-reductase inhibitor such as MK-906. In ancillary experiments, tumors from MK-906-treated animals were found to have reduced levels of DHT and, when assayed in vitro, to have a reduced capacity to convert [3H]-T to [3H]-DHT.

5-alpha Reductase Inhibitors↗

PubMed1991

Redefinition of cutaneous lymphatic drainage with the use of lymphoscintigraphy for malignant melanoma.

Lymphoscintigraphy was performed on 82 patients with melanoma registered at the University Melanoma Clinic. From these data, precise lymphatic drainage basins could be drawn for the head, neck, shoulder, and trunk. These drawings differed significantly from the classic anatomic studies, providing a functional look at the cutaneous lymphatic drainage. This new method correlates much better with clinical experiences and demonstrates much larger areas of ambiguous drainage than previously reported. Data from the lymphoscintigrams also emphasize the individuality of cutaneous lymphatic flow. The implications of these data in planning elective node dissections for intermediate thickness melanomas are obvious, since it is estimated that up to 59% of the dissections for trunk and head and neck primary melanomas may be misdirected if based on classic anatomic studies. The data indicate that all patients with head, neck, and shoulder lesions should undergo lymphoscintigraphy to define possible drainage basins at risk for metastatic disease. Similarly, truncal lesions require scintigrams except when they are within four well-defined areas with an extremely low probability of ambiguous drainage. Lesions in these areas show very reliable and predictable drainage to a single nodal group.

Antimony↗

PubMed1991

Topical anti-androgenicity of a new 4-azasteroid in the hamster.

The topical anti-androgenic activity of L-651,580 (methyl 3-oxo-4-methyl-4-aza-5 alpha-androst-1-ene-17 beta-carboxylate) was established in a series of for experiments using castrated male hamsters. During each 21-day experiment, the animals received a daily subcutaneous injection of 40 micrograms testosterone propionate or 20 micrograms dihydrotestosterone propionate. Test compound in 25 microliters of gel was applied daily to the left flank organ. Compounds assayed included L-651,580, WIN 17,665 (17 alpha-propyltestosterone), and SH-434 (17 beta-hydroxy-1 alpha-methyl-17 alpha-propyl-5 alpha-androstan-3-one). Endpoints were flank organ area, sebaceous gland area, and prostate weight. Very similar results were obtained with L-651,580 and WIN 17,665. Daily doses of 0.25 mg or more of either compound usually produced a significant reduction in the areas of treated flank organs and sebaceous glands underlying treated flank organs. Neither compound caused significant changes in the area of the contralateral flank organs and sebaceous glands, which indicated they possess little or no systemic activity at topically effective treatment levels. In direct comparisons, SH-434 was less anti-androgenic than L-651,580 or WIN 17,665, although in one experiment, 0.5 mg/d of SH-434 significantly reduced the area of treated flank organs and sebaceous glands. Neither WIN 17,665 nor SH-434 caused a change in prostate weight; however, in one of four tests, a significant decrease was induced by the 0.5 mg/d level of L-651,580. The results of these experiments show that the topical anti-androgenicity of L-651,580 compares very favorably with that of WIN 17,665 and SH-434. They also indicate that the topical administration of effective dosage levels of L-651,580 causes few, if any, systemic effects.

Administration, Topical↗

PubMed1989

Anti-uterotrophic and folliculostatic activities of anordiol (2 alpha,17 alpha-diethynyl-A-nor-5 alpha-androstane-2 beta,17 beta-diol).

The estrogenicity and antiestrogenicity of the biologically active metabolite of the contraceptive anordrin was investigated for its actions on both the uterus and ovary. Anordiol (30 micrograms), administered s.c. to ovariectomized mice did not significantly increase wet weight, soluble protein content, or DNA content of uteri 72 hours after a single dose. By comparison, 3 micrograms of estradiol-17 beta under the same conditions significantly increased all three parameters of uterine growth. The increments in uterine wet weight, soluble protein content, and DNA content that were induced by estradiol-17 beta were reduced by 50, 71, and 81%, respectively, when 30 micrograms of anordiol was administered with estradiol-17 beta. A 60 micrograms dose of anordiol did not decrease further any of the three parameters. In further evaluation of the uterine response to anordiol an increase in uterine wet weight and soluble protein was observed with both 30 and 90 micrograms doses of anordiol at 12, 24, 36, and 48 hours, but not at 6 or 72 hr after a single s.c. injection. No significant increase in uterine DNA content was observed with either dose at any time. We conclude that anordiol in this assay is an antiestrogen with weak estrogenic activity. Anordiol was further tested to determine its effect on the estrous cycle of the rat. When given on the afternoon of the first day of diestrus in a dose of 0.8 mg/kg body weight in rats with 5-day estrous cycles, it caused an average lengthening of the cycle to 9.1 +/- 2.1 (S.D.) days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

The clinical utility of the Tc-99m SC intraperitoneal scan in CAPD patients.

The intraperitoneal instillation of dialysate increases intra-abdominal pressure and consequently predisposes to subcutaneous infiltration, leaks, and herniations through defects in the abdominal wall. In this setting, the incidence of abdominal hernias ranges between 9% and 24%. Life-threatening complications (incarceration/strangulation) occur in up to 13.2% of hernias. Therefore, the authors evaluated the efficacy of the Tc-99m sulfur colloid (SC) intraperitoneal scan in the detection of abdominal leaks and hernias in 11 continuous ambulatory peritoneal dialysis (CAPD) patients over a 2-year period at the Hospital of the University of Pennsylvania. Eleven patients (7M, 4F) ranging in age from 24 to 72 (mean = 50.8), on CAPD, were evaluated for clinically suspected abdominal hernias or dialysate leaks with intraperitoneally administered Tc-99m SC. After the injection of 3-5 mCi of Tc-99m into a standard 2 liter dialysate bag, multiple sequential anterior images of the abdomen were obtained in the supine position over the course of one hour. Delayed images were obtained after ambulation and post-drainage two or more hours postinjection in multiple projections and positions in order to demonstrate any abnormal focal accumulations of fluid to the best advantage. Any detected abnormalities were marked and correlated with the physical examination and the patient's symptoms. Two patients had normal scans. Of the nine abnormal scans, five hernias were identified in four patients and six leaks were detected in the other five patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Bone response to plasma-cleaned titanium implants.

Glow-discharged titanium implants, with a presumed high surface energy, and conventionally prepared and sterilized titanium implants were inserted in the rabbit tibia and femur. The removal torque and histology were compared after 6 weeks in situ. No qualitative or quantitative differences were detected for implants with different preoperative preparation. The results indicate that the conventional implant treatment described is sufficient to give a surface condition with similar early healing responses as those observed with glow-discharge-treated implants.

Animals↗

PubMed1988

Panic disorder and depression in female alcoholics.

Eight (32%) of 25 alcoholic women on an inpatient detoxification unit met modified DSM-III criteria for panic disorder, 2 (8%) of 25 met criteria for depressive illness, and 7 (28%) of 25 met criteria for both disorders. These findings replicate the findings of other recent studies and lend preliminary support to the self-medication model of alcoholism.

Alcohol Drinking↗

PubMed1986

Prostatic effects induced in dogs by chronic or acute oral administration of 5 alpha-reductase inhibitors.

A series of 4-azasteroidal 5 alpha-reductase inhibitors was tested in dogs to determine the effect of chronic (35-44 day) oral administration on prostate size and histology and acute oral administration on prostatic concentrations of testosterone (T) and dihydrotestosterone (DHT). The extent to which the results of the two tests were correlated was also studied in order to see whether the acute test could be used to predict activity in the chronic test. Six delta 1 analogs of the potent 5 alpha-reductase inhibitor, 4-MA (17 beta-N,N-diethylcarbamoyl-4-aza-4-methyl-5 alpha-androstan-3-one) were uniformly active at low dosage levels (less than or equal to 3 mg/kg) in both types of assay whereas several C1-C2 saturated analogs exhibited little activity in the chronic test. The nature of the side chain and whether there was a methyl or a proton at 4-N did not dramatically influence the activity of delta 1 compounds. There was a broad general agreement between the results of the two kinds of test in that if a compound acutely decreased the prostatic concentration of DHT it was likely to reduce prostate size and alter prostatic histology when given on a chronic basis.

5-alpha Reductase Inhibitors↗

PubMed1986

5 Alpha-reductase inhibitory and anti-androgenic activities of some 4-azasteroids in the rat.

Inhibition of 5 alpha-reductase and anti-androgenicity were studied in rats treated with various 4-azasteroids. The known inhibitor, N,N-diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane-17 beta-carboxamide (4-MA) served as a reference compound, and analogs of this basic molecule were assayed. Enhancement of enzyme inhibitory potency was usually seen with delta 1 analogs, whereas reduction in activity was noted with substitutuents such as delta 5, a spirotetrahydrofuran ring at C-17 or 4-deaza groups. Many of the 4-azasteroids had a much greater oral anti-androgenic effect against testosterone propionate (TP) than dihydrotestosterone propionate (DHTP). This difference in activity versus the two androgens is believed to reflect the necessity for TP to undergo reduction to DHT before becoming capable of stimulating prostatic growth. Inhibition of 5 alpha-reductase by active compounds prevented the conversion, thereby producing an anti-androgenic effect. In this regard, certain delta 1 analogs of 4-MA, particularly those bearing a 17 beta-(N-tert butylcarbamoyl) group, proved very effective against TP but were relatively inactive versus DHTP.

Androgen Antagonists↗

PubMed1986

Azasteroids: structure-activity relationships for inhibition of 5 alpha-reductase and of androgen receptor binding.

A series of steroids, primarily 4-azasteroids, were prepared and tested in vitro as inhibitors of human and rat prostatic 5 alpha-reductase and of binding of dihydrotestosterone to the rat androgen receptor. The primary structural modifications were changes of the A ring and of moieties attached at the C-17 position of the steroid nucleus. New A-ring modifications included the 4-cyano-3-oxo-delta 4 system in the carbocyclic series and 1 alpha-CN, 1 alpha-CH3, 1 alpha,2 alpha-CH2, 2 beta-F, 2-aza, 2-oxa, and A-homo changes in the 3-oxo-4-aza series. In addition, 4-azasteroids with a D-homo ring or methyl substitution at C-7 (alpha and beta) or C-16 (alpha and beta) were prepared. The majority of the C-17 substituents were prepared from reactive intermediates derived from the 17 beta-COOH. Enhanced 5 alpha-reductase inhibition in both the human and rat enzyme assays is seen with 4-CN substitution on 3-oxo-delta 4 steroids and with a C-17 side chain incorporating a lipophilically substituted semipolar group on the 4-aza-3-oxo-5 alpha-androstane nucleus. Fewer highly active compounds were found in the human enzyme assay than in the rat assay. Structural requirements for inhibition of the rat androgen receptor are much different from those for inhibition of the enzyme. The 17 beta-OH moiety enhances potency more than any other feature while introduction of double bonds at C-1 or C-5 in the azasteroid gives a small improvement. Azasteroids unsubstituted at the 4-position show greatly diminished receptor activity.

5-alpha Reductase Inhibitors↗

PubMed1986

Chlorhexidine. An adjunct to periodontal therapy.

Chlorhexidine is an effective antimicrobial agent. Its application can enhance periodontal therapy. The pharmacology of chlorhexidine and suggestions for its use are outlined. In addition, its potential for inducing cancer and bacterial resistance are discussed.

Absorption↗

PubMed1985