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Biomedical subjects

B W Brown

Publications and source records attributed to B W Brown.

At least 91 records · Page 5Linked to original sources
PubMed1988

Association of levels of circulating C1q binding macromolecules with induction chemotherapy response in head and neck cancer patients.

Ninety-five untreated patients with squamous cell carcinoma of the upper aerodigestive tract expressed significantly higher levels of C1q-binding macromolecules as compared to 45 noncancer-bearing controls. No relationship between C1q-binding macromolecules and levels of circulating IgG-immune complexes as determined by the solid-phase C1q-binding assay or the C3d-solid-phase assay could be defined suggesting that C1q-binding macromolecules were distinct from IgG-circulating immune complexes. An elevated level of C1q-binding macromolecules within these patients was predictive of subsequent response to induction chemotherapy; those with elevated levels characteristically showed no response. Using multivariate logistic regression analysis including the covariates of American Joint Committee staging parameters as well as C1q assay results, levels of the isolated macromolecules added significant prognostic information as to the probability of chemotherapeutic response. The quantitation of C1q macromolecules has clinical implication as to choice of therapeutic regimens against head and neck cancer. The nature of these substances remains to be defined.

Adult↗
PubMed1988

Ovarian capillary blood flow in seasonally anoestrous ewes induced to ovulate by treatment with GnRH.

The microsphere technique was used to obtain estimates of ovarian capillary blood flow near ovulation, in 8 seasonally anoestrous ewes, which were induced to ovulate by GnRH therapy. Plasma progesterone concentrations were monitored in jugular blood sampled between Days 4 and 7 after the onset of the preovulatory LH surge. The ewes were then slaughtered. Three of the ewes were treated with a single injection of 20 mg progesterone before GnRH therapy. In these ewes and 1 other, plasma progesterone values increased after ovulation and reached 1.0 ng/ml on Day 7 following the preovulatory LH surge (normal, functional CL), whilst in the other 4 ewes progesterone concentrations increased initially then declined to 0.5 ng/ml by Day 7 (abnormal CL). In the ewes exhibiting normal luteal function, the mean ovarian capillary blood flow was significantly greater (P less than 0.01) than that for ewes having abnormal luteal function. Irrespective of the type of CL produced, capillary blood flow was significantly greater (P less than 0.05) in ovulatory ovaries than in non-ovulatory ovaries. These findings indicate that the rate of capillary blood flow in ovaries near ovulation may be a critical factor in normal development and maturation of preovulatory follicles and function of subsequently formed CL.

Anestrus↗
PubMed1987

Evidence for the role of natural immunity in the control of metastatic spread of head and neck cancer.

Deficient natural killer (NK) cell activity may contribute to the development of distant metastases in the head and neck cancer patient. A total of 246 previously untreated patients expressed deficient NK activity against K562 target cells when compared to 110 age-matched healthy controls (70 +/- 48 lytic units (LU) versus 95 +/- 52 LU) (P less than 0.001). Some 164 consecutive patients have undergone definitive therapy subsequent to NK cell assessment and have been followed for a minimum of 12 months (median = 16 months), and 23 have developed recurrent disease in distant sites. The risk of subsequently (1) developing distant metastases, (2) developing regional metastases, and (3) dying of progressive cancer was inversely related to pretreatment NK LU values (P less than 0.02, less than 0.02, less than 0.005, respectively, by the Cox proportional hazards model). NK cell function within the peripheral blood of the patient with head and neck cancer could be related to the percentage of Leu 11+ NK cell subsets (P less than 0.01 by linear regression analysis) as determined by both single-parameter and multiparameter flow cytometric assessment. Contrastingly, no relationship could be identified between NK function with the percentage of circulating Leu 7+ cell subsets. In vitro measured NK cell function identifies a population at increased risk for developing distant metastases, thus supporting the role of natural immunity as defense mechanism against blood-borne disease.

Adult↗
PubMed1987

Projection from previous studies: a Bayesian and frequentist compromise.

We present methods that use the results of a previous study to predict the outcome of a specified comparative trial in which each subject's outcome is categorized dichotomously (e.g., response or no response). The methods can be generalized to other two-sample cases for which power can be calculated (e.g., exponential survival), and to one-sample cases such as demonstrating a minimal response rate or demonstrating superiority to a historic control. Bayesian methods are used on the results of the preliminary study to obtain a posterior distribution representing the state of knowledge of the parameters of interest. This distribution provides the probability that the experimental regimen is superior to the standard by any particular amount. The probability that a future study will demonstrate the superiority of the experimental treatment is obtained by using the posterior distribution to average the power of the test over the parameter space.

Bayes Theorem↗
PubMed1987

Designing clinical trials with arbitrary specification of survival functions and for the log rank or generalized Wilcoxon test.

This article describes a computer program that allows interactive determination of the length of accrual period and follow-up period sufficient to assure desired level of significance and power. The program allows for arbitrary specification of the hypothesized survival curves and the alternative survival curve. It allows use of either the generalized Wilcoxon test or the log rank test. The program can be run on an IBM personal computer.

Clinical Trials as Topic↗
PubMed1987

Validation of the clinical predictive values of the in vitro phase II clonogenic assay in cancer of the breast and ovary.

The in vitro evaluation of new antineoplastic agents has been advocated as a method of selecting drugs for Phase I-II trials in patients. This paper is an attempt to validate, in an unbiased manner, the so-called in vitro Phase II clonogenic assay with regard to its predictive power in the clinic. Breast and ovarian cancer were chosen because of the relatively large number of drugs clinically evaluated for these diseases; 298 patients were studied. For metastatic breast cancer 12 drugs, six clinically active and six inactive, were tested. It was found that in patients without prior chemotherapy, there is an association between results in vitro and in vivo. In metastatic ovarian cancer, 11 drugs, four of which are known to be clinically inactive, were studied. The same positive association was seen for patients without prior chemotherapy. The implications of these findings are discussed.

Breast Neoplasms↗
PubMed1987

Lack of concordance of growth rates of primary and recurrent breast cancer.

The degree of concordance of growth rates of primary tumors with corresponding recurrences was investigated by using data from 184 patients with breast cancer with measurable recurrences. For conduction of this examination, the detection processes of both the primary tumor and the recurrence were explored. The probability of detection of a recurrence per unit time was found to be nearly proportional to the tumor's diameter. Approximately 60,000 cells initiated the recurrence, and the distribution of doubling times of the recurrences was exponential, with a mean of 2.1 months. The probability of detection of the primary tumor per unit time was approximately proportional to its volume. The distribution of doubling times of primary tumors was nearly exponential; from other evidence, we inferred that the mean doubling time was also close to 2.1 months. Several techniques to measure growth rate agreement between the primary and recurrent tumors within individuals were developed, and all of them yielded the result that the growth rates are nearly unrelated.

Breast Neoplasms↗
PubMed1986

Effect of injectate volume and temperature on thermodilution cardiac output determination.

Six combinations of injectate volume (10, 5, and 3 ml) and temperature (0 degree C and room temperature [RT]) are recommended by the manufacturers of thermodilution cardiac output catheters and computers. We prospectively studied the accuracy and variability associated with these six combinations in critically ill patients requiring intermittent mandatory ventilation. The six methods were similar in their average estimation of cardiac output but differed markedly in their reproducibility. The 10 ml 0 degree C and 10 ml RT combinations produced the least variability. The 5 ml 0 degree C and 5 ml RT combinations produced more variability. Variability was much greater with the remaining two combinations. The 3 ml RT combination resulted in an average range of 1.71 1/min within each set of three repeat measurements and an average absolute difference of 1.51 1/min from the values obtained with 10 ml 0 degree C (each the mean of three injections). We recommend the use of 10 ml 0 degree C or 10 ml RT for cardiac output determinations in critically ill patients. If it is important to minimize volume administration, the use of 5 ml injectate is acceptable for an estimation of cardiac output. The use of 3 ml injectate volumes is rarely, if ever, justified because the small reduction in volume administration results in a large increase in variability.

Adult↗
PubMed1986

Mathematical model for human myeloma relating growth kinetics and drug resistance.

We present a computer-based mathematical model that can simulate characteristic features of the clinical time course of human myeloma. It asserts that therapy resistance in myeloma cells is an inherited trait associated with the longer inter-mitotic times of some cells and that the strength of this trait affects tumour growth characteristics. These kinetic differences within the malignant cell clone may also influence therapeutic efficacy. In the model, the same total therapy, administered in different time-dose fractions, could be 'curative' or 'minimally effective' depending on kinetic properties. For example, as others have shown, in myeloma pulsed intermittent therapy is often more effective than low dose continuous therapy. According to our model this finding is compatible with a high coefficient of inheritability of resistance from one cell generation to the next. The model also suggests that if there are subclones of varying resistance, a therapy must have some effect on each of them if it is to be employed in a curative fashion. While many aspects of the model are not yet clinically testable, exploration of its concepts might increase knowledge about fundamental neoplastic mechanisms.

Antineoplastic Agents↗
PubMed1986

Mammographic microcalcifications: detection with xerography, screen-film, and digitized film display.

Pulverized bone specks and aluminum oxide specks were measured by hand into sizes ranging from 0.2 mm to 1.0 mm and then arranged in clusters. These clusters were superimposed on a human breast tissue phantom, and xeromammograms and screen-film mammograms of the clusters were made. The screen-film mammograms were digitized using a high-resolution laser scanner and then displayed on cathode ray tube (CRT) monitors. Six radiologists independently counted the microcalcifications on the xeromammograms, the screen-film mammograms, and the digitized-film mammograms. The xeromammograms were examined with a magnifying glass; the screen-film images were examined with a magnifying glass and by hot light; and the digitized-film images were examined by electronic magnification and image processing. The bone speck size that corresponded to a mean 50% detectability level for each technique was as follows: xeromammography, 0.550 mm; digitized film, 0.573 mm; and screen-film, 0.661 mm. We postulate that electronic magnification and image processing with edge enhancement can improve the capability of screen-film mammography to enhance the detection of microcalcifications.

Breast Diseases↗
PubMed1986

Tumor volume, nodal status, and metastasis in breast cancer in women.

The relationship between primary tumor volume at detection, number of positive nodes, and probability of and time until first distant metastasis was examined for a group of 2,663 women with breast cancer. Time until metastasis was shown to decrease and probability of metastasis to increase as tumor volume and number of nodes increased. Either factor remained significant after correction for the other. Simple proportional hazards models were shown to be inadequate to describe the data. Graphic techniques were used to obtain nonparametric estimates of the forms of the relationships between tumor volume, nodal status, and the time course of the occurrence of metastasis. A simple calculation demonstrated that the average contribution per cell to the probability of metastasis decreased with increasing volume.

Breast Neoplasms↗
PubMed1986

Cardiotoxicity of epirubicin and doxorubicin: assessment by endomyocardial biopsy.

Forty-two evaluable endomyocardial biopsies were obtained from 29 patients treated with epirubicin, the 4'-epimer of doxorubicin in cumulative doses ranging from 147 mg/m2 to 888 mg/m2. In this study of the Northern California Oncology Group, myofibrillar loss and sarcoplasmic vacuolization were identified and shown to be identical to those previously described for doxorubicin. However, when these biopsies were compared to 119 biopsies obtained from 98 patients treated with doxorubicin, milligram for milligram, epirubicin caused less endomyocardial injury than doxorubicin (P = 0.0013). Age, sex, type of primary malignancy, prior cardiac disease, and hypertension did not influence the degree of histologically demonstrated anthracycline injury induced by epirubicin.

Adult↗
PubMed1985

Dissociation of antitumor potency from anthracycline cardiotoxicity in a doxorubicin analog.

The search for new congeners of the leading anticancer drug doxorubicin has led to an analog that is approximately 1000 times more potent, noncardiotoxic at therapeutic dose levels, and non-cross-resistant with doxorubicin. The new anthracycline, 3'-deamino-3'-(3-cyano-4-morpholinyl)doxorubicin (MRA-CN), is produced by incorporation of the 3' amino group of doxorubicin in a new cyanomorpholinyl ring. The marked increase in potency was observed against human ovarian and breast carcinomas in vitro; it was not accompanied by an increase in cardiotoxicity in fetal mouse heart cultures. Doxorubicin and MRA-CN both produced typical cardiac ultrastructural and biochemical changes, but at equimolar concentrations. In addition, MRA-CN was not cross-resistant with doxorubicin in a variant of the human sarcoma cell line MES-SA selected for resistance to doxorubicin. Thus antitumor efficacy was dissociated from both cardiotoxicity and cross-resistance by this modification of anthracycline structure.

Animals↗
PubMed1985

Relationship between lymph nodal status and primary tumor control probability in tumors of the supraglottic larynx.

A retrospective review of 248 patients with squamous cell carcinoma of the supraglottic larynx was undertaken to determine the relationship between the probability of control of the primary lesion, the extent of neck nodal disease at initial presentation, and its ultimate control. All patients were treated at the U.T. M. D. Anderson Hospital between 1960 and 1980, and had a minimum of 3 years follow-up. The primary lesion was staged T1 in 38 patients, T2 in 132, T3 in 50 and T4 in 28. The initial volume of neck nodal disease was scored on a scale of 0 (no palpable nodes) to 9 (bilateral neck nodes greater than 6 cm in diameter). All primary lesions were treated definitively with megavoltage radiation therapy. Treatment to the neck varied according to the extent of lymph node involvement. There was no significant difference in the range of total radiation doses delivered to the primary lesion, stage for stage, in patients who presented with clinically negative or positive nodes, or in those with controlled versus uncontrolled neck disease. Analysis of the probability of primary tumor control was made by life table methods because of the poorer survival expectation in node positive patients. For T1 and T2 primary lesions, any positive node decreased the probability of primary tumor control (p = 0.06). For T3 and T4 lesions, a single node less than 3 cm in diameter did not worsen the chance of primary tumor control, but any greater degree of lymph node involvement did (p = 0.03). For both T stage groupings, the probability of primary tumor control at 5 years decreased progressively with increasing neck nodal disease. Primary tumor control probability was also significantly associated with control of the neck disease, independent of the modality of neck treatment. No correlation could be demonstrated between the histological grade of the primary tumor and initial lymph node status or tumor control probability. Possible interpretations of this manifestation of biological heterogeneity are discussed.

Biopsy↗
PubMed1985

The Stanford Five-City Project: design and methods.

The Stanford Five-City Project is a large experimental field study of community health education for the prevention of cardiovascular disease. It will provide data on fundamental questions in cardiovascular disease epidemiology, communication, health education, behavior change, and community organization, and will also test the ability of a potentially cost-effective program to prevent cardiovascular disease at the community level. This paper describes the purposes, hypotheses, design, and methods of the Five-City Project as a reference for future papers describing results. It is hypothesized that a 20% decrease in cardiovascular disease risk will lead to a significant decline in cardiovascular disease event rates in two treatment communities compared with three reference communities as a result of a six-year intervention program of community-wide health education and organization. Risk factor change will be assessed through four surveys of independent samples and in a repeatedly surveyed cohort. Cardiovascular disease event rates will be assessed through continuous community surveillance of fatal and nonfatal myocardial infarction and stroke.

Adolescent↗