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Biomedical subjects

H W Herr

Publications and source records attributed to H W Herr.

At least 217 records · Page 12Linked to original sources

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↗

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↗

Effect of estrogen on the mixed lymphocyte reaction in normal individuals and prostatic cancer patients.

Lack of initial response or relapse to hormones in advanced prostatic cancer may be due to an adverse effect of estrogen on host immune function. This study investigated the effect of diethylstilbestrol diphosphate (DES-P) on the normal mixed lymphocyte reaction (MLR) and on the MLR in prostatic cancer patients before and during treatment with DES-P. These data showed that the normal MLR was suppressed by high concentrations of estrogen in vitro, but physiologic levels of DES-P were not suppressive. Therapeutic doses of DES-P did not suppress the spontaneous MLR of prostatic cancer patients compared with previous treatment. Estrogens did not significantly impair the immunologic responsiveness of normal individuals or prostatic cancer patients.

Adult↗

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↗

Significance of prostatic biopsies after radiation therapy for carcinoma of the prostate.

The significance of a prostatic biopsy after radiation therapy for prostatic cancer is at present uncertain. Criteria for interpreting residual tumor cells as viable and, more important, determining whether such cells are biologically capable of local growth and/or subsequent dissemination, by histological evaluation, require further clinical correlation and studies designed to better characterize biological behavior and growth potential of neoplastic cells in general and how this may or may not be altered by irradiation. A positive biopsy after radiation therapy must be regarded, however, as ominous simply because its potential significance is yet to be determined. Prostatic biopsies may predict treatment failure in general, but their significance relative to an individual patient requires correlation with 1) tumor stage, grade, size, and site of the original tumor; 2) technique of biopsy, number of cores obtained, and the location relative to the original tumor; 3) time interval of biopsy after treatment and whether biopsy is performed on one or more occasions; 4) circumstances (clinical progression or clinical regression) at the time of biopsy; and 5) treatment artifacts regarding dose delivered and distribution, which is especially important with regard to interstitial irradiation.

Acid Phosphatase↗

Flow cytometry followup of patients with low stage bladder tumors.

A total of 98 urologic outpatients with a history of conservatively treated low stage bladder tumors underwent 325 examinations during a 2-year interval, each comprising conventional cytology, cystoscopy and automated flow cytometry. The flow cytometry results agreed with cystoscopic findings and conventional cytology in 80 per cent of the examinations, while cystoscopy and cytology agreed in 75 per cent. Assuming cystoscopic findings were entirely accurate, the false negative rate for flow cytometry was 8.3 per cent and the false positive rate was 5.8 per cent. On occasion, flow cytometry diagnosis of bladder tumors antedated the development of visible tumor by up to 12 months. Flow cytometry provided an objective and quantitative assay of epithelial abnormalities and, in the absence of skilled, conventional cytology, it appears to be a valuable new tool for the urologist in the diagnosis, management and followup of patients with bladder tumors or a history of bladder tumor.

Carcinoma, Transitional Cell↗

Cyclophosphamide, methotrexate and 5-fluorouracil combination chemotherapy versus chloroethyl-cyclohexy-nitrosourea in the treatment of metastatic prostatic cancer.

In a prospective, randomized study the effect of cyclophosphamide, methotrexate and 5-fluorouracil combination chemotherapy was compared to the single agent, chloroethyl-cyclohexy-nitrosourea, in the treatment of hormonally refractive metastatic prostatic carcinoma. All patients could be evaluated and were followed for at least 2 years or until death. Responses were defined by the National Prostatic Cancer Project criteria. Of 20 patients who received cyclophosphamide, methotrexate and 5-fluorouracil 3 (15 per cent) had partial (median duration of 2.5 months), 4 (20 per cent) had stable (median duration of 5 months) and 13 had progression of the disease. Of 20 patients who received chloroethyl-cyclohexy-nitrosourea none had a partial response, 6 (30 per cent) had stability (median duration of 6.2 months) and 13 had progression of the disease. The over-all response rate for patients receiving cyclophosphamide, methotrexate and 5-fluorouracil was 35 per cent (stable plus partial regressions) and it was 30 per cent for those receiving chloroethyl-cyclohexy-nitrosourea (stable only). Subjective improvement was noted in all 7 patients who responded to combination chemotherapy and in 3 of the 6 patients who responded to the single agent. After 2 courses resistant patients were crossed over to the opposite regimen and none had an objective, stable or subjective response. Although the duration of response was short (2 to 6 months) patients with partial regressions or stabilized disease survived longer (p less than 0.05) than patients whose disease progressed (52 versus 24 weeks, respectively). The mean interval from diagnosis to chemotherapy (lead time) was 40 months for patients who responded to chemotherapy compared to 19 months for those with progression, which suggested a slower growing pattern of disease in those who did respond. There was no improvement in cohort survival with either treatment regimen. Over-all response rates to cyclophosphamide, methotrexate and 5-fluorouracil were not superior to reported responses to cyclophosphamide alone, and both treatment regimens appeared to be only marginally effective in the treatment of endocrine-resistant, advanced prostatic cancer.

Aged↗

Flow cytometry of normal and nonneoplastic diseases of the bladder: an estimate of the false positive rate.

From July 1980 through February 1981, 100 patients with normal or nonneoplastic disease of the bladder were studied by flow cytometry. These patients had a variety of medical problems, including carcinoma of the prostate, benign prostatic hypertrophy, acute and chronic cystitis and carcinoma of other sites. The results showed that inflammation and cystitis affected flow cytometry analysis and could lead to false positive diagnoses under some circumstances. With present criteria we estimate that the false positive rate in a urologic population is an acceptable 2 per cent.

False Positive Reactions↗

Characterization of bladder papilloma by two-parameter DNA-RNA flow cytometry.

Two-parameter flow cytometry (FCM) studies of 0.9% NaCl solution bladder irrigation specimens were performed on 48 patients with histologically orderly or atypical papilloma of the urinary bladder in order to assess the value of RNA as a possible second parameter, along with DNA, in the detection of bladder tumors. DNA, RNA, and nuclear diameter measurements were obtained for each of 5000 cells/sample, and analyses were based on the distributions of those values. With the use of DNA content alone, 22 cases (46%) were classified positive by FCM. With RNA content as an additional parameter, 40 cases (83%) were positive. Two cases were suspicious, and 6 cases were normal by both parameters. Of 28 patients with papillomas showing histological atypia, 16 patients had positive DNA histograms, including 3 patients with aneuploid stemlines, but 24 of the 28 patients had positive RNA histograms. Of 20 patients with orderly papillomas, 6 patients had positive DNA histograms, including 3 patients with aneuploid DNA stem cell lines, but 16 of the 20 patients had positive RNA histograms. Thus, the probability of positive DNA histograms is higher in atypical papillomas (57%) than in orderly papillomas (30%), whereas elevated (positive) RNA is more characteristic of all papillomas without distinction between those that are histologically atypical (86% positive) or orderly (80% positive). For patients at risk of developing papillary bladder tumors, two-parameter DNA-RNA FCM appears to offer greater diagnostic sensitivity than does FCM based on DNA content alone.

Cell Nucleus↗

HLA antigens in patients with germ cell cancers of the testis.

The expression of HLA-A, -B, -C, and -DR antigens has been analyzed in 145 unrelated Caucasian patients with germ cell tumors of the testis. Eighteen of these patients had pure seminoma, while the remaining patients had nonseminomatous tumors with embryonal carcinoma, teratocarcinoma, choriocarcinoma, and/or yolk sac components, with or without seminoma. Increases were noted in the frequencies of Aw33, B5, DR5, and DRw6 among the patients with pure seminoma, A3 and B7 among the patients with embryonal carcinoma with or without seminoma, and Aw32 among the patients with yolk sac tumor components. A decrease in the frequency of HLA-DR3 was noted in all patients subgroups, although none of these differences were statistically significant after correction for the number of antigens tested. HLA typing results for three affected brothers of patients indicate that, in each family, the affected sibling pair share at least one HLA haplotype. The etiological and prognostic significance of this finding and of the increases in a few HLA antigen frequencies in particular patient groups and the overall decreases in DR3 remain to be determined.

Diseases in Twins↗

Combined chemotherapy and surgery in treatment of advanced germ-cell tumors.

Forty-eight selected patients with GCT who were suspected of having residual disease after two or three chemotherapy inductions underwent an attempt at resection of this residual tumor. In 37 patients all gross disease was resected: 11 had malignant tissue, eight adult teratoma, and 18 no residual neoplasm, and 9, 7 and 17, respectively, remain free of disease. Patients in whom complete resection was not possible generally did poorly. Elevated serum tumor markers following the completion of preoperative chemotherapy indicated residual malignant disease and poor probability for complete resection. Twenty-nine percent of patients with negative preoperative markers had malignancy at the time of surgery, but disease was resectable in most of these patients. The key for success is, first, the response to chemotherapy and, second, complete resection of residual disease. It is recommended that patients with initially bulky metastases (diameter greater than 5 cm) be first managed by chemotherapy, employing successive close inductions, and subsequently explored with intent to resect residual disease. When the resected specimen shows malignant elements, the patients should receive additional inductions, otherwise, maintenance chemotherapy is employed.

Antineoplastic Agents↗

Androgen stimulated chemotherapy in the Dunning R-3327 prostatic adenocarcinoma.

This study was undertaken to determine whether hormonal stimulation followed by chemotherapy with a cell-cycle specific agent would improve the effectiveness of the chemotherapy in a prostatic adenocarcinoma model. One hundred Copenhagen rats were randomised into 5 equal groups and injected subcutaneously with 2 x 10(7) cells of Dunning G strain prostatic adenocarcinoma. The groups were treated in the following fashion: 1. sham operated controls, 2. castration, 3. castration and methotrexate, 4. castration, testosterone and methotrexate and 5. castration and testosterone. When the tumours became palpable, all animals received the surgery to which they were randomised. Subsequent hormonal and chemotherapy was started 1 week thereafter. Therapy was given for 5 consecutive days followed by a 16-day recovery period and then continued in a cyclical fashion. Serial measurements of animal weights and tumour size were obtained. Analysis of tumour growth was restricted to the first 29 days of therapy because of a rapid decline in animal survival beyond that point. The group treated with castration, testosterone, and methotrexate inhibited tumour growth more than any other group and was the only group that was significantly different from control (P less than 0.05).

Adenocarcinoma↗

Automated flow cytometry to monitor intravesical BCG therapy of superficial bladder cancer.

The automated flow cytometry system (FCM) at Memorial Sloan-Kettering Cancer Center has been used to monitor the effect of intravesical BCG in the therapy of superficial bladder cancer. Analysis of saline bladder washings prior to therapy, weekly during the six weeks of therapy, and at follow-up examination in 2 patients, 1 responder and 1 nonresponder, provides the basis for some projections regarding the potential value of this technique.

Adult↗

Adherent suppressor cells in the blood of patients with bladder cancer.

Patients with advanced bladder cancer frequently show a low mixed lymphocyte reaction. Depressed mixed lymphocyte reactions may be augmented by removing adherent cells, which appear to be monocytes. Since cancer patients often have a larger proportion of monocytes than normal individuals they may have suppression simply because of an increase in the number of these cells. This possibility was tested by adding increasing numbers of autologous irradiated monocytes or lymphocytes to mixed lymphocyte reactions depleted of adherent cells. The results showed that 1) monocytes from normal individuals increased the mixed lymphocyte reaction at optimal concentrations 3 to 4-fold and suppressed it at higher than optimal concentrations, 2) lymphocytes at equivalent concentrations were not suppressive and 3) monocytes from the cancer patients whose mixed lymphocyte reaction was low did not increase the mixed lymphocyte reaction at any concentration and suppressed it at lower concentrations than monocytes from the normal controls. These results suggest that suppression of the mixed lymphocyte reaction by patient monocytes was not owing to an over-all increase in their number but appeared to reflect a fundamental change in their suppressive function.

Humans↗