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Biomedical subjects

R deVere White

Publications and source records attributed to R deVere White.

27 records · Page 2Linked to original sources

Sensitivity of computed tomography in evaluation of pelvic lymph node metastases from carcinoma of bladder and prostate.

Pelvic lymph node evaluation by computed tomography was correlated with histologic diagnosis in patients with prostate and bladder carcinoma. Based on computed tomography alone, the stage of the carcinomas would have been underestimated in 38 per cent of cases and overestimated in 6 per cent. Over-all, the sensitivity of pelvic CT scanning in detecting lymph node involvement was only 14 per cent with specificity of 89 per cent. Although this series is relatively small and both second and fourth generation scanners were used, the limitations of computed tomography in recognizing minimal nodal disease or microscopic invasion of adjacent organs is reemphasized.

Evaluation Studies as Topic↗

The effect of delta 1-testolactone on serum testosterone and estradiol in the adult male rat.

delta 1-Testolactone, an androgen derivative without intrinsic hormonal action, is known to block the aromatization of androgens to estrogens. This study was designed to assess its effect upon serum testosterone (T) and estradiol (E2) in the adult male rat. By itself, testolactone (TL) did not affect T/E2 levels in the dosages utilized. Daily injections of human chorionic gonadotropin (hCG) for 15 days caused a tenfold rise in serum T, although there was no increase in serum E2. When given along with hCG, TL did not alter the Leydig cell response. However, pretreatment of animals with TL increased the testicular response to hCG over that of saline-treated animals. Studies were also carried out to delineate the sources of estrogen in the adult male rat. These experiments demonstrate that (1) the majority of E2 is not testicular in origin but is derived from the adrenal; (2) the conversion of androgen precursors to E2 in the rat is not affected by TL; and (3) in spite of no demonstrable inhibition of E2 production, TL causes an increased Leydig cell responsiveness to hCG.

Animals↗

Limitations of DNA histogram analysis by flow cytometry as a method of predicting chemosensitivity in a rat renal cancer model.

Analysis of DNA histograms obtained from rat renal cancer cells stained with propidium iodide and submitted to flow cytometry revealed a tumor cell population with prominent 2C and 4C peaks and with usually less than 10% each of S-phase or hyper-4C cells. The presence of an increased proportion of 4C cells was found to depend on the age and size of the tumor nodule. Sampling replicate portions of the same tumor or different tumors of the same size and age frequently revealed highly variable 4C:2C ratios. Treatment of animals bearing this tumor with a single i.p. injection of cyclophosphamide (CY), under conditions known to reduce the tumor burden by 80% within 1 week, or with 5-fluorouracil (FUra), which is ineffective against this tumor, in many cases did not yield changes in DNA histograms that permitted one to distinguish the effective drug. Either no marked difference in histogram shape occurred after therapy, or FUra induced more striking differences in cell cycle position than did CY. In tumor generations with greater than 15% S-phase cells, treatment with CY resulted in multiple effects on DNA histograms. These included detecting increased numbers of moribund cells (hypo-2C), a decrease in 4C cells, and an increase in hyper-4C cells. These changes did not occur with the ineffective agent FUra. The tumors grown in vitro show no evidence of replication of 4C cells. The DNA histograms of late-log-phase cultures have a major 2C peak and a minor S plus G2 hump. Since neither the untreated tumor in vivo nor that grown in vitro has a major hyper-4C cell population, it is probable that the tumor stem cells are chiefly 2C (diploid-hyperdiploid). Treatment in vitro of late-log-phase cultures with CY or FUra produces DNA histograms which permit identification of the effective agent. After CY, a major part of the cell population was hypo-2C (moribund) cells.

Animals↗

Maytansine as a cause of acute proliferative disorder of bladder urothelium in the rat.

Male Wistar Lewis rats were injected with maytansine at a total dose of 0.425 to 0.6 mg/kg over a 3-week period. Biopsies taken at 5 weeks showed that 23% of the bladders had hyperplasia or other abnormalities. Of the bladder biopsies done for the first time at 8 weeks, 80% demonstrated papillary hyperplasia. A small number of biopsies at 13 and 19 weeks still showed hyperplasia and minimal inflammatory reaction. These results were seen regardless of prior biopsy, the presence of bladder calculi, and/or the dose level used. It is not clear from the data whether the observed changes are reversible or precarcinogenic. However, these changes closely resembled the histologic features described in the evolution of bladder cancer in rats fed N-C4-(5-nitro-2-furyl)-2-thiazolyl formamide.

Animals↗

Adjunctive therapy with interstitial irradiation for prostate cancer.

Thirty patients with clinically localized adenocarcinoma of the prostate underwent simultaneous staging pelvic lymphadenectomy and interstitial irradiation. Patients were followed for eighteen to forty-five months with regard to progression of disease and development of long-term complications. Upstaging to Stage D1 by virtue of discovering pelvic node involvement was noted in 16 patients (53.3 per cent). Subsequent disease progression (defined as development of bone or soft tissue metastasis) was seen in 9 of 16 upstaged patients with an average time to progression of 12.2 months. Three Stage D1 patients have died with an average time to death of 19.6 months. Only 1 patient whose lymphadenectomy was negative has experienced disease progression, and none has died. Adjuvant chemotherapy (cyclophosphamide and doxorubicin hydrochloride) was given to 9 upstaged patients, in only 3 did disease progress. In contrast, in 6 of 7 upstaged patients not receiving chemotherapy metastatic disease developed, with an average time to progression of 10.3 months. In an attempt to improve local tumor control achieved by interstitial irradiation alone, 18 patients received additional external beam radiation therapy to the prostate, in doses ranging from 2,000 to 4,000 rad. There were sixteen long-term complications in the 30 patients, 75 per cent of which were seen in patients receiving added external beam irradiation.

Adenocarcinoma↗

A stable propidium iodide staining procedure for flow cytometry.

A propidium iodide (PI) staining procedure is described in which 50 micrograms/ml PI in 10(-2) M Tris, pH 7.0, with 5 mM MgCl2 is used to stain murine erythroleukemia cells (MELC) grown in suspension culture as well as single cell suspensions derived from rat kidney adenocarcinoma and human prostatic carcinoma. Specificity of staining of nuclear DNA is achieved by enzymatic removal of RNA using RNAse in the staining solution. Virtually identical histograms, with the same G1 peak height and closely similar coefficients of variation (CVs), are obtained using a wide range of RNAse concentrations on replicate samples of MELC if the incubation times are sufficiently prolonged when employing the lower enzyme concentrations. For 1 mg/ml RNAse on logarithmically growing MELC, 30 min incubation at 37 degrees C is needed to obtain a maximum G1 peak height and optimal CV and there is no significant change in the histogram if the incubation is prolonged to 4 hr. For every 4-fold decrease in RNAse concentration, the incubation time at 37 degrees C must be doubled to obtain the same maximal G1 peak height and optimal CV. Unfixed cell preparations, whether derived from suspension or monolayer cultures or from solid tumors, are stable for 2 or more weeks if stored at 4 degrees C between flow cytometric analyses and histograms are usually only minimally altered if the stained cell samples are stored for 1-2 months at 4 degrees C. Sample decay is associated with bacterial contamination. If sterile preparative techniques are used initially, subsequent contamination of the stained preparations may be minimized by adding sodium azide to the stained samples at 0.1% without influencing fluorescence intensity. Glycerine may be added to 10% and the samples slowly frozen for storage without altering DNA histogram shapes. The simplicity of sample preparation and the stability of the resulting stained cell samples makes this procedure suitable for repetitive comparative sampling of tissue and cell populations over prolonged time spans.

Animals↗