Search PubMed⌕ Search

Biomedical subjects

W F Whitmore

Publications and source records attributed to W F Whitmore.

At least 181 records · Page 10Linked to original sources

Antigrowth effect of some inhibitors of polyamine synthesis on transplantable prostate cancer.

Inhibitors of polyamine synthesis were tested for therapeutic effectiveness on transplantable prostate cancer. Inhibition of either ornithine decarboxylase or S-adenosyl-L-methionine decarboxylase (AMDC) by alpha-difluormethylornithine (DFMO) or methylglyoxal-bis[guanylhydrazone] (MGBG), respectively, was associated with significant antitumor effect. The combination of DFMO with MGBG was not only more effective but no more toxic than MGBG alone. Combination of MGBG with 9-B-D-arabinofuranosyladenine, an indirect effector of SAMDC, failed to increase therapeutic effectiveness of MGBG.

Animals↗

Experimental chemotherapy in a transplantable renal adenocarcinoma. I: Effects of some inhibitors of polyamine synthesis.

Difluoromethylornithine (DFMO) and methylglyoxal bis (guanylhydrazone) (MGBG), inhibitors of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AMDC), respectively, were tested for antitumor activity in the BALB/C mouse renal adenocarcinoma model, wherein ODC and AMDC activity are elevated compared to the normal kidney. Additionally, an indirect effector of AMDC synthesis, arabinofuranosyladenine and an inhibitor of AMDC synthesis, cycloleucin (CL), were tested in this model. Simultaneous administration of both DFMO and MGBG affected the growth of renal adenocarcinoma less than did administration of DFMO or MGBG alone. Combinations of inhibitors of polyamine synthesis demonstrated a high toxicity with low therapeutic activity. The most effective tumor suppression was observed with CL alone but associated toxicity was severe. Suramin, an ODC stimulator, may have enhanced tumor growth.

Adenocarcinoma↗

Panniculectomy in conjunction with radical cystectomy in the obese patient.

Obesity in the abdominal area causes difficulty not only with the placement of an ileal conduit stoma and conduit length but also with surgical exposure during radical surgery to the pelvis. Such problems may be ameliorated by using a horizontal abdominal dermolipectomy in conjunction with a midline fascial and peritoneal incision and the Turnbull ileal stoma in selected obese patients. The advantages of this technique far outweigh the limited complications which may be encountered.

Abdomen↗

Multivariate analysis of prognostic variables in patients with metastatic testicular cancer.

A majority of patients with metastatic testicular cancer achieve a complete remission as a result of current treatment programs. However, patients who fail to achieve a complete remission have a very poor prognosis, and nearly all die of their disease. A multivariate logistic regression analysis of several clinical variables associated with prognosis was performed using data from 171 patients treated for metastatic testicular cancer at Memorial Hospital between September 1975 and February 1981. A mathematical model was identified which correctly predicted 94% of complete remissions and 83% of all outcomes. The variables achieving statistical significance were the logarithm of the serum values of lactate dehydrogenase (p less than 0.001) and human chorionic gonadotropin (p less than 0.001) and the total number of sites of metastasis (p less than 0.001). The model was tested against 49 patients with metastatic testicular cancer treated at the University of Minnesota Hospitals, and it correctly predicted 86% of complete remissions and 84% of all outcomes. In a highly curable disease such as testicular cancer, mathematical modeling may enable the clinical investigator to anticipate those patients who are least likely to do well. Alternate treatment strategies would be appropriate for such patients.

Antineoplastic Agents↗

Intravenous cisplatin for superficial bladder tumors.

Cisplatin, 1.25 mg/kg IV QM, was administered to 15 patients with recurrent flat carcinoma in situ and/or bladder tumors confined to the mucosa and lamina propria. All patients had a history of multiple transurethral resection and 4 had received prior irradiation and two prior intravesical thiophosphoramide. Response was evaluated by urinary cytologic findings, cystoscopy and biopsy. Of 14 adequately treated cases, four (28%) had disappearance of all visible lesions, cystoscopically, for a median of eight months (range, 8-18), and six exhibited transiently a greater than 50% decrease in the number of tumors. However, no patient demonstrated a complete remission--all had persistently positive urinary cytologies. Nausea and vomiting, even at this dose level, was significant and at times, severe. Cisplatin, in the dose and schedule used, was found to be ineffective in controlling low-stage bladder tumors.

Adult↗

An evaluation of automated flow cytometry (FCM) in detection of carcinoma in situ of the urinary bladder.

Among a series of more than 500 urologic patients studied by automated flow cytometry (FCM), there were 123 who proved to have carcinoma in situ of the urinary bladder. Eighty had flat carcinoma in situ and 43 had papilloma with foci of carcinoma in situ or diffuse noninvasive papillary carcinoma. Of those with papillary carcinomas and papilloma with carcinoma in situ, 88% were positive by FCM, as were 98% of the cases of flat carcinoma in situ. The overall false negative rate was 6%. A statistically significant (P less than 0.02) difference in the proportion of cases with aneuploidy was found in papillary CIS (42%) compared with flat CIS (86%). The presence of aneuploidy (cell populations with DNA content other than normal diploid (2c) or tetraploid amount (3.9c-4.1c) as opposed to tetraploidy is thought to imply a more aggressive, less well differentiated tumor.

Aneuploidy↗

Intravesical cisplatin for superficial bladder tumors.

Cisplatin, 50-150 mg in a maximum concentration of 1 mg/ml, was administered intravesically each week to 24 patients with multiple, recurrent carcinoma in situ and/or bladder tumors confined to the mucosa and lamina propria. All patients had a history of multiple transurethral resections and four had received prior chemotherapy. Response was evaluated by urinary cytology, cystoscopy, and biopsy. In a total of 237 weekly doses, toxicities included mild dysuria, pruritus, rash and in one patient, acute anaphylaxis. Only three (13%) patients were classified as achieving complete remission. Cisplatin, in the dose and schedule employed, is ineffective in controlling superficial bladder cancer.

Adult↗

Autopsy findings in 154 patients with germ cell tumors of the testis.

Autopsy findings are reviewed in 154 patients treated for germ cell tumors of the testis. Of the patients with apparently pure seminoma, 44% had autopsy evidence of nonseminomatous metastases. For all tumor types, the most common sites of distant metastasis were lung (89%), liver (73%), brain (31%), and bone (30%). There was a high incidence of brain metastases in choriocarcinoma and of bone metastases in seminoma. Brain, liver, and bone metastases were late occurrences in the course of the disease and were almost always associated with involvement of other sites. Recurrences in the retroperitoneal area after lymph node dissection occurred mainly in those who had had retroperitoneal lymph node metastases. No difference in site or frequency of metastases was apparent in autopsied patients treated before or after introduction of platinum containing regimens. Respiratory failure, secondary to lung metastases, was the most common cause of death. Of the autopsied patients, 6% died of iatrogenic causes.

Autopsy↗

Considerations for the use of testosterone with systemic chemotherapy in prostatic cancer.

Among 52 patients with metastatic adenocarcinoma of the prostate who were treated with exogenous testosterone, 45 (87%) experienced unfavorable subjective and/or objective responses. These unfavorable responses were elicited more frequently and after shorter treatment periods in patients in symptomatic relapse following endocrine therapy than in untreated patients or patients in remission following endocrine therapy. Serious morbidity or mortality, seemingly due to the testosterone administration, occurred in eight cases (15%). It is not known if the action of chemotherapeutic agents will be enhanced by concurrent testosterone therapy but any such investigation should be undertaken with extreme caution.

Acid Phosphatase↗

Testicular cancer in cryptorchids.

One-hundred thirty-seven patients with a history or clinical evidence of cryptorchidism and testicular germinal tumor were treated at our hospital from 1934 to 1976. Cryptorchidism was corrected ipsilaterally or contralaterally in 93 patients with intrascrotal testis cancer when they were from 2 to 42 years old, either spontaneously (24 patients), by orchiopexy (58 patients), or by hormonal therapy (11 patients). Forty-four cryptorchid patients (uncorrected cases) had either ipsilateral inguinal (24 patients), or abdominal (14 patients), or contralateral intrascrotal tumors (six patients). Tumor histologic types on orchiectomy were pure seminoma in 56 patients, embryonal carcinoma in 41, teratocarcinoma in 37, and pure choriocarcinoma in 3. The five-year survival rates were similar in the corrected (61%) and uncorrected (63%) cases, and they were higher in patients with pure seminoma (79%) than in patients with germinal carcinomas (50%). The majority (64 of 80) of five-year survivors received regional lymphatic irradiation in 41 patients with pure seminoma and/or systemic chemotherapy in 23 patients with other germinomas. Since the testicular tumors that developed despite correction of the cryptorchid state were predominantly (72%) germinal carcinomas, unilateral cryptorchidism, which usually is associated with testicular atrophy, should be treated by orchiectomy instead of orchiopexy to prevent ipsilateral carcinogenesis. Cryptorchid patients with testicles that descended late should be observed periodically, especially after the 20-year latent period, for early detection of cancer.

Adolescent↗

Preoperative irradiation and cystectomy for bladder cancer.

Between 1971 and 1974, 101 patients at Memorial Sloan-Kettering Cancer Center underwent planned integrated treatment for bladder cancer with 2000 rads by megavoltage delivered to the whole pelvis over five consecutive days followed by radical cystectomy within a week. The overall five-year survival rate was 39%; the hospital mortality rate was 2%. In the pelvis alone tumor recurred in 9% of the patients. These results support other studies demonstrating the efficacy of this and other regimens of preoperative irradiation and cystectomy.

Adult↗

Correlation of histochemical and biochemical analyses of androgen binding in prostatic cancer: relation to therapeutic response.

A histochemical technique for the detection of androgen binding in prostatic cancer was performed on specimens from 108 patients and compared with a biochemical method in a double blind study of 77. Statistical analyses showed a significant agreement between the two assay systems for the qualitative and quantitative presence or absence of specific androgen binding, as well as for the subcellular localization of binding in nucleus and/or cytoplasm. Although the number of cases studied was too small for statistical analysis, there appeared to be good correlation between histochemical androgen binding results and clinical response, or lack of response to hormonal manipulation in 20 patients with State C and Stage D carcinoma. No correlation was evident between androgen binding and tumor grade or clinicopathologic stage of disease of either histochemistry or biochemistry.

Adenocarcinoma↗

Flow cytometry of low stage bladder tumors: correlation with cytologic and cystoscopic diagnosis.

Flow cytometry examinations (FCM) were carried out on 110 bladder irrigation specimens from 84 urologic outpatients who had had prior conservative treatment for low stage bladder tumors. The specimens were easily obtained, and adequately cellular in all cases. Of 60 examinations on patients with no cytoscopic abnormalities, FCM and conventional cytology were both negative in 30 and both positive in 12 instances; there were 18 with positive FCM and negative cytology. Of 15 instances with cystoscopically benign appearing papillary lesions, FCM and cytology were both negative in three and both positive in three cases; FCM was positive and cytology negative in nine. Of 35 instances with suspicious cystoscopic findings, FCM and cytology were both positive in 19 and both negative in four; FCM was positive and cytology negative in 12. There were no examples of positive conventional cytology and negative FCM. These findings indicate that, after conservative treatment of low stage tumors, FCM of bladder irrigation specimens may be a more sensitive measure of cytologic abnormalities than is conventional cytology. Specimen collection is feasible as part of the routine urologic examination in an outpatient clinic.

Carcinoma in Situ↗

Effects of estrogen administration on serum testosterone in Copenhagen rats.

In order to develop a standard experimental method of exogenous therapy in the Copenhagen rat, several treatment regimens were evaluated to determine their effect on the serum testosterone. Diethylstilbestrol diphosphate (DES-P) was administered either continuously in the drinking water or as a single intraperitoneal injection. Oral low-dose estrogen (0.4-1.6 microgram/ml) yielded reliable suppression of serum testosterone to castrate levels. A single intraperitoneal injection of 0.5 mg DES-P caused prompt suppression of serum testosterone with return to normal levels two weeks later.

Administration, Oral↗