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Biomedical subjects

W F Whitmore

Publications and source records attributed to W F Whitmore.

At least 271 records · Page 15Linked to original sources
PubMed1979

Identification of polymorphonuclear leukocytes in cytologic samples for flow cytometry.

Inflammatory cells are commonly present in cytologic specimens obtained for flow cytometry, and may interfere with the analysis of epithelial cells. We have found that detergent (Triton X-100) pretreatment in the two-step acridine orange staining procedure disrupts granulocyte cell membranes to yield bare nuclei; bladder epithelial and squamous cells on the other hand are quite resistant to the detergent treatment. Being deprived of their cytoplasmic RNA, the granulocytes lose red fluorescence. Moreover, the shearing forces in the cytometer extend the multisegmented granulocyte nuclei and align them in the direction of flow. Thus, they present as elongated objects in the measuring system, giving a large DNA fluorescence pulsewidth (nuclear size). These two phenomena make it possible to identify granulocytes in the recorded data, where they are discernible from the mononucleated leukocytes and from epithelial cells. By data selection the granulocytes can be excluded, rendering epithelial cell populations more amenable to analysis. This method may make it unnecessary to remove physically leukocytes from the specimen before flow cytometry; it may also provide a way to analyze the morphology of granulocyte nuclei and to assess methods to manipulate their membrane stability. Full protection from membrane disruption is accomplished by alcohol fixation, and partial protection by 20-30% serum.

Cytological Techniques↗
PubMed1979

Effect of flutamide on estradiol metabolism.

The effect of flutamide, a potent nonsteroidal antiandrogen, on the metabolism of iv tracers of [3H]estradiol was studied in five patients with advanced prostate cancer. The drug produced no change in the percentage of the injected radioactivity recovered in urine or in the glucuronide or nonglucuronide conjugate fractions. Of the five individual metabolites that were quantitated, estrone, estradiol, and estriol were unaffected by flutamide, but the drug caused striking decreases in conversion of estradiol to 2-hydroxyestrone (4.0% vs. 7.4%) (P less than 0.005) and 2-methoxyestrone (1.1% vs. 2.6%; P less than 0.05); every one of the patients showed a marked fall in recovery of both of these compounds. This depression of the formation of 2-oxygenated metabolites is reminiscent of the findings in liver disease; the same abnormality occurs regularly in cirrhosis and frequently in extrahepatic biliary obstruction. Taken together with our previous studies of the effects of flutamide on testosterone and cortisol metabolism, this study demonstrates that flutamide produces multiple functional, reversible, cirrhosis-like disturbances of steroid metabolism. Because these disturbances are universal in the patients studied regardless of whether they had clinical responses to flutamide, we doubt that the steroid metabolic changes play a role in the therapeutic effect of the drug.

Anilides↗
PubMed1979

Regional lymph node reactivity in explanted bladder cancer of mice as measured by flow cytometry.

The reactivity of lymphocytes in lymph nodes draining the site of a transplantable experimental bladder tumor (MBT2 in C3H/HeJ mice) has been measured in a multiparameter flow cytometry system. Acridine orange was used as a nucleic acid probe. This dye intercalates in helical DNA, emitting green (530 nm) fluorescence upon exposure to blue light; it stacks to single-stranded RNA, emitting red (640 nm) fluorescence. The relative magnitude of the increase of lymphocyte DNA and RNA has been evaluated simultaneously in tumor-draining nodes, in nondraining nodes of the same animal, and in untreated control animals. Stimulation of the regional node lymphocytes could be observed after 20 days but not after 10 days. It was uniformly high at 35 days. The transcriptive response (increased proportion of lymphocytes with high RNA) was more pronounced than the proliferative (increased proportion of lymphocytes with more than diploid DNA). The histological changes in the stimulated nodes resembled closely those described by others in human tumor-draining nodes. The described method has the advantage of being simple, rapid, and able to measure a representative part of the whole-cell population.

Animals↗
PubMed1979

Lymph node reactivity to experimental bladder tumor in preimmunized animals as measured by two parameter flow cytometry.

Lymph node lymphocyte reaction to an explanted, transplantable mouse bladder tumor (MBT-2) was investigated by flow cytometry in animals previously immunized with irradiated tumor cells. Nodal lymphocytes in representative samples from four different lymph node sites were differentially stained for DNA and RNA with the fluorescent dye acridine orange; cell proliferation and the increase in RNA content were measured. Immunization abrogated tumor growth; one immunization reduced tumor take to 25 per cent of the animals, and two immunizations to 14 per cent. Lymphocyte reactivity to the tumor was reflected both by an increase of DNA synthesizing cells and by diploid cells with high RNA. The latter response was more pronounced and thus the more sensitive parameter for measuring immunologic lymph node reactivity. The juxtatumoral node displayed the most pronounced reactivity, but all node sites showed some degree of reaction.

Animals↗
PubMed1978

Radical cystectomy with or without planned preoperative irradiation in the treatment of bladder cancer.

A retrospective analysis of 342 patients with carcinoma of the bladder treated by radical cystectomy at Memorial Sloan Kettering Cancer Center with or without planned preoperative irradiation revealed that preoperative irradiation significantly improved survival of patients with deeply infiltrating tumours (pathological Stage B2 and C), and reduced the prognostic importance of distinctions between pathological B1 and B2 neoplasms. Preoperative irradiation had no discernible effect on the survival of patients with superficially infiltrating neoplasms.

Humans↗
PubMed1978

Carcinoma of prostate presenting as retroperitoneal mass.

The pattern of dissemination of prostatic carcinoma varies, but skeletal metastasis is the single most common symptomatic mode of presentation. The clinical course and treatment of the 2 cases presenting with symptomatic metastases to the retroperitoneum are described in detail and pertinent literature is reviewed.

Adenocarcinoma↗
PubMed1978

Extended total excision of prostatic adenocarcinoma.

Cases of locally advanced prostatic adenocarcinoma (stages B and C) managed by exenteration or prostatocystectomy were reviewed. Local control and survival rates seem to justify this approach in selected cases, especially when conservative measures, such as hormonal therapy and irradiation, have been exhausted.

Adenocarcinoma↗
PubMed1978

Spermatic cord sarcoma in adults.

The clinical courses are presented for 6 patients with sarcoma of the spermatic cord seen between 1967 and 1976. There were 3 fibrosarcomas, 2 liposarcomas and 1 malignant fibrous histiocytoma, making the total reported cases of spermatic cord sarcoma 212. Management of spermatic cord sarcoma is discussed.

Adult↗
PubMed1978

Experience with anteromedian (12 o'clock) external urethral sphincterotomy in 100 male subjects with neuropathic bladders.

One hundred male spinal cord injured patients have now undergone anteromedian (12 o'clock) external urethral sphincterotomy alone or in combination with transurethral incision or resection of the bladder neck. The functional affect of this procedure has been documented by voiding cystourethrogram and urodynamic studies. The morbidity and clinical results including blood loss and loss of reflex erection are reviewed. The short-term clinical results suggest that this is the best of currently available techniques to lower external urethral sphincter resistance.

Erectile Dysfunction↗
PubMed1978

Effect of flutamide on cortisol metabolism.

The effect of flutamide on cortisol metabolism was studied in eight patients with prostate cancer. Flutamide markedly decreased the formation of 3 alpha, 17,21-trihydroxypregnane-11,20-dione (THF), and the 11-oxy-17-ketosteroid metabolites by 72%, 50%, and 46% respectively; however, 3 alpha, 11 beta, 17,21-tetrahydroxy-5 alpha- pregnan-20-one was increased by 46%. The 24-h mean plasma cortisol concentration was not altered. The cortisol production rate decreased by an average of 53% (from 32.7 to 15.5 mg/24 h). The effect of the drug on plasma cortisol kinetics was studied in three patients. This showed that flutamide increased the t1/2 (from 80 to 108 min) but decreased the distribution volume (from 17.8 to 13.8 liters) and the MCR (from 222 to 130 liters/24 h). The changes in THE and THF formation and in the t1/2 and MCR of [C]cortisol are similar to the effects observed in patients with intrahepatic cholestasis. It is suggested that in the case of flutamide these changes were also due to a cholestasis-producing effect of the drug on the liver. As the clinical response to the drug did not correlate with the cortisol metabolic changes, its therapeutic effect was probably not mediated by its effects on cortisol metabolism.

Aged↗
PubMed1978

Immunocompetence of patients with transitional cell carcinoma as measured by dinitrochlorobenzene skin tests and in vitro lymphocyte function.

Patients with transitional cell carcinoma of the bladder have a highly significant stepwise decrease in responsiveness to challenge with DNCB with advancing stage of disease. Seventy-five percent of those patients with superficial tumors are skin-test positive versus only 35% for those having tumors that are locally advanced and/or metastatic. MLC response and ability to stimulate in this culture as well as PHA and Con A response of blood leukocytes have been studied in relation to stage of disease and therapy. Recent irradiation appears to inhibit significantly MLC responsiveness, and PHA and Con A blastogenesis. Although responsiveness for this group of patients is decreased from normal, a further decrease occurs in responsiveness to Con A with advancing stage of disease. Blood leukocytes from some patients with urinary bladder carcinoma appear to have a decreased ability to function as stimulator cells in one-way MLC. This ability to stimulate returns to normal levels with tumor removal.

Carcinoma, Transitional Cell↗