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Biomedical subjects

B W Brown

Publications and source records attributed to B W Brown.

At least 19 recordsLinked to original sources
PubMed1992

Impact of cyclophosphamide on long-term reduction in sperm count in men treated with combination chemotherapy for Ewing and soft tissue sarcomas.

BACKGROUND: Treatment of cancer with multiple-drug chemotherapy regimens or radiation therapy can cause either temporary azoospermia of various durations or permanent azoospermia in young men. METHODS: To identify which drugs in which doses contribute to long-term or permanent azoospermia, semen analyses were done on patients with Ewing and soft tissue sarcomas before, during, and after treatment with either CYADIC (cyclophosphamide, doxorubicin, and dacarbazine), or CYVADIC (vincristine added to CYADIC). Some patients also received other drugs or radiation therapy. RESULTS: From pretreatment levels that were similar to those of control subjects, sperm production declined to azoospermia within 4 months of treatment. Sperm production returned in some patients after treatment; 40% of men recovered to normospermic levels by 5 years after treatment. Few patients showed continued recovery of sperm production after that time. The cumulative dose of cyclophosphamide was the most significant determinant of recovery to normospermic levels; approximately 70% of those who had received doses less than 7.5 g/m2 (median, 4.1 g/m2) recovered, but only 10% recovered when doses exceeded 7.5 g/m2. CONCLUSIONS: Thus, a risk of permanent sterility is associated with the use of the CYADIC and CYVADIC regimens in young men, especially when the cumulative dose of cyclophosphamide is greater than 7.5 mg/m2.

Adult↗
PubMed1992

Evidence for a programmed life span in a colonial protochordate.

The variety of theories that have attempted to define the mechanisms of aging and life span can be broadly divided into two alternative but nonexclusive viewpoints. The first stipulates that random changes of cellular and molecular structures lead to death following progressive "wear and tear." The second argues that life span is, at least in part, genetically programmed, and therefore aging may also result from time-dependent intrinsic processes. Here we demonstrate that ramets (clonal replicates) experimentally separated from colonies of the acidian protochordate Botryllus schlosseri died months after their separation, almost simultaneously with their parent colony and sibling ramets. In addition, in experimentally joined chimeras between ramets of senescent and nonsenescent colonies, elements from different parent colonies displayed parent-colony-specific timing of mortality. Thus, the senescent phenotype was simultaneously expressed both in chimeras and in unfused ramets of the parent colony that was undergoing senescence, whereas control ramets from the other partner survived. These findings provide experimental evidence for a heritable basis underlying mortality in protochordates, unlinked to reproductive effort and other life history traits of this species.

Aging↗
PubMed1992

Widespread cerebral gray matter volume deficits in schizophrenia.

Magnetic resonance imaging was used to investigate whether the structural brain differences commonly observed in patients with schizophrenia as compared with normal control subjects are specific to gray or white matter, and furthermore whether such abnormalities are localizable to circumscribed cortical regions. Accordingly, 22 patients meeting DSM-III-R criteria for schizophrenia and 20 healthy community volunteers, all 23 to 45 years old, received magnetic resonance imaging scans. Seven axial magnetic resonance imaging sections of 5-mm thickness were segmented into cerebrospinal fluid, gray matter, and white matter compartments and used for volumetric quantification. For the healthy control subjects, age correlated significantly with the percentage of all magnetic resonance imaging sections taken up by gray matter but not white matter. After correcting for the normal effect of age, the schizophrenic group was found to have significantly less gray matter than the control group but no difference in white matter; ventricular volume was 34% greater in the schizophrenic group. The schizophrenic group had less gray matter in all six cortical subregions analyzed; these differences attained statistical significance for all but the parietal measure. These findings have implications for studies of localized gray matter abnormalities and suggest that regional brain volume measurements need to be expressed in the context of possible widespread gray matter volume deficits in schizophrenia.

Adult↗
PubMed1992

Effects of size and growth time of a murine sarcoma on its metastatic spread.

The effects of the size of an implanted tumor and of its time of growth on metastasis were examined in the same tumor grown under two different conditions. Tumors were implanted either in the untreated legs of mice or in legs that had been irradiated one day earlier. The radiation slowed the growth of tumors. When the tumors grew to predetermined diameters, the legs were excised and 20 days later the mice were examined for the presence of lung metastases. Equal changes in the time to excision of the tumors grown under the two conditions led to nearly equal changes in the proportions of animals with metastases. Tumor volume effects were not apparent in this consideration of changes in metastasis rates with time. This work reanalyses the data of that study using the variability in growth rates within a tumor growth condition to investigate the effect of tumor size on metastatic intensity. This intensity increased at least linearly with tumor volume for both irradiated and control animals. The finding of equal effect at equal growth times of the implanted tumors under the two growth conditions was confirmed but is due to: (1) metastatic intensity changing five times as rapidly with tumor size in the irradiated group as compared to the control group and (2) non-exponential retarded growth of the tumors in the control treatment group.

Animals↗
PubMed1991

Expression of blood-group antigen A--a favorable prognostic factor in non-small-cell lung cancer.

BACKGROUND: New prognostic factors are needed to guide the treatment of patients with non-small-cell lung cancer. We evaluated the prognostic value of altered expression of ABH blood-group antigens, which has been implicated in the multistep process of carcinogenesis and tumor progression. METHODS: The presence of blood-group antigens was assessed immunohistochemically in paraffin-embedded tumor samples from 164 patients who underwent curative surgery for non-small-cell lung cancer from 1980 through 1982. Monoclonal antibodies were used to detect the A and B antigens, and Ulex europaeus agglutinin I to detect H antigen. RESULTS: Survival of the 28 patients with blood type A or AB who had primary tumors negative for blood-group antigen A was significantly shorter than that of the 43 patients with antigen A-positive tumors (P less than 0.001) and of the 93 patients with blood type B or O (P = 0.002). The respective median survival times were 15, 71, and 39 months. Disease progressed significantly earlier in the 28 patients with tumors negative for blood-group antigen A than in the antigen A-positive patients (P less than 0.001). Expression of blood-group antigen B or H in tumor cells did not correlate with survival. Cox proportional-hazards regression analysis showed that expression of blood-group antigen A in tumor cells added significantly to the prediction of overall survival provided by other known prognostic factors among the patients with blood type A or AB (P = 0.004). CONCLUSIONS: Expression of blood-group antigen A in tumor cells is an important favorable prognostic factor in patients with non-small-cell lung cancer. This variable needs to be considered in the design of future trials of therapy.

ABO Blood-Group System↗
PubMed1991

Direct analyses of in vivo colony survival after single and fractionated doses of radiation.

Several methods are described for analysing the results of in vivo colony assays using the statistical procedure called maximum-likelihood analysis. The methods differ in the way in which they take into account possible sources of variability in the data. The methods described here for analysing microcolony data are direct methods, in that they use the observed colony counts rather than transformed (e.g. Poisson-corrected) data. Each method can be used to estimate the average number of surviving cells per tissue structure (e.g. per jejunal crypt) in a single dose group, together with 95% confidence intervals, or to fit cell-survival models to data from a range of dose groups (e.g. to obtain estimates of D0 or of the linear-quadratic parameters alpha and beta). Experimental microcolony data from murine jejunum, colon, and hair follicles irradiated in anagen (proliferative) or telogen (resting) phase have been analysed. Estimates of D0 have been derived from single-dose data and estimates of alpha, beta, and the initial number of clonogenic cells per structure have been derived from fractionation data. For hair follicles, the half-time of repair of sublethal radiation injury has also been derived from fractionation data.

Animals↗
PubMed1991

Establishing the reliability and developmental validity of a neurobehavioral assessment for preterm infants: a methodological process.

The Neurobehavioral Assessment of the Preterm Infant was developed in 3 phases: a pilot study, an exploratory study, and a validation study. In the exploratory study, clusters characterized by conceptual cohesion and face validity were systematically subjected to statistical analyses to determine whether they also had high test-retest reliability and developmental validity. In the validation study, a shortened version of the test was used with an independent cohort of 290 preterm infants. A step-by-step methodological process was used to test whether the results from the exploratory study would generalize over cohorts, different versions of the test, different hospitals, and changes in examiners. This process yielded 7 highly stable, developmentally valid, and representative preterm neurobehavioral functions that generalized over the exploratory and the validation studies. These were: motor development and vigor, scarf sign, popliteal angle, alertness and orientation, percent asleep ratings, irritability, and vigor of crying.

Apgar Score↗
PubMed1990

Late pulmonary sequelae of bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia is a chronic lung disease that often develops after mechanical ventilation in prematurely born infants with respiratory failure. It has become the most common form of chronic lung disease in infants in the United States. The long-term outcome for infants with bronchopulmonary dysplasia has not been determined. METHODS: We studied the pulmonary function of 26 adolescents and young adults, born between 1964 and 1973, who had bronchopulmonary dysplasia in infancy. We compared the results with those in two control groups: 26 age-matched adolescents and young adults of similar birth weight and gestational age who had not undergone mechanical ventilation, and 53 age-matched normal subjects. RESULTS: Sixty-eight percent of the subjects with bronchopulmonary dysplasia in infancy (17 of the 25 tested) had airway obstruction, including decreases in forced expiratory volume in one second, forced expiratory flow between 25 and 75 percent of vital capacity, and maximal expiratory flow velocity at 50 percent of vital capacity, as compared with both control groups (P less than 0.0001 for all comparisons). Twenty-four percent of the subjects with bronchopulmonary dysplasia in infancy had fixed airway obstruction, and 52 percent had reactive airway disease, as indicated by their responses to the administration of methacholine or a bronchodilator. Hyperinflation (an increased ratio of residual volume to total lung capacity) was more frequent in the subjects with a history of bronchopulmonary dysplasia than in either the matched cohort (P less than 0.0006) or the normal controls (P less than 0.0004). Six of the subjects who had bronchopulmonary dysplasia in infancy had severe pulmonary dysfunction or current symptoms of respiratory difficulty. CONCLUSIONS: Most adolescents and young adults who had bronchopulmonary dysplasia in infancy have some degree of pulmonary dysfunction, consisting of airway obstruction, airway hyperreactivity, and hyperinflation. The clinical consequences of this dysfunction are not known.

Adolescent↗
PubMed1990

Significance of C1q-binding macromolecules within the head and neck cancer patient.

Elevated levels of macromolecules, within the peripheral blood of head and neck cancer patients, capable of binding the first component of complement (C1qBM) in vitro have prognostic implication. Namely, elevated levels of C1qBM have been associated with nonresponse to induction chemotherapy. In this investigation, a series of in vitro studies regarding the biological properties of C1qBM were combined with a longitudinal analysis of 112 previously untreated head and neck cancer patients. Our purpose was to shed light on the biological significance of this circulating macromolecule, a substance composed, in part, of IgG and IgM. A potential confounding influence of C1qBM with induction chemotherapy, which could contribute to observed prognostic findings, was negated by two in vitro observations: the macromolecule failed both to bind the chemotherapeutic agents cisplatin, bleomycin, and 5-fluorouracil and to impede the cytotoxic effect of these same drugs on a cultured human head and neck cancer cell line. The clinical relevance of C1qBM was reinforced by the observation that elevated levels predicted a high probability of death with disease (P = 0.005 by Cox's proportional hazards model). The prognostic implication was independent of the use of induction chemotherapy, i.e., patients with high C1qBM levels treated with multimodality therapy not composed of anticancer drugs did equally poorly. Thus, the prognostic significance of C1qBM in patients undergoing induction chemotherapy appears independent of drug effect and appears reflective of tumors that are more rapidly progressive and potentially less responsive to therapeutic intervention, including combinations of surgery, radiation, and/or chemotherapy.

Antigen-Antibody Complex↗
PubMed1990

Concomitant boost radiotherapy schedules in the treatment of carcinoma of the oropharynx and nasopharynx.

Concomitant boost schedules are characterized by delivering the boost (10-12 fractions) as second daily treatments during rather than following the basic wide field irradiations. This results in shortening the overall time to administer 69-72 Gy from 7 1/2-8 weeks to 6 weeks, which we hoped would improve the tumor control rate by reducing the opportunity for tumor clonogens to regenerate during treatment. From August 1985 to August 1988, 79 patients with T2-4 carcinomas of the oropharynx (72 patients) or nasopharynx (7 patients) were treated according to 1 of the 3 variants of the concomitant boost technique. The median age of patients was 60 years (range: 19-84 years) and the male-to-female ratio was 2.6. The overall 2-year actuarial primary and nodal control rates by radiotherapy alone were 74% and 76%, respectively. The ultimate 2-year control rates after surgical salvage were 82% and 84%, respectively. If the boost given during the last 2-2 1/2 weeks of basic treatment, a slightly better primary control rate (p = 0.11) resulted than if the boost was delivered during the first 2-2 1/2 weeks or twice a week throughout the basic treatment. The 2-year actuarial primary control rate of the 13 patients receiving induction chemotherapy prior to radiotherapy was significantly lower than that of patients treated with radiation only (81% vs 34%, p = 0.01), but this could be partly attributed to a more advanced stage in the chemotherapy group. The acute mucosal reactions were, as expected, more severe than those observed with conventional fractionation. Fifty patients developed confluent mucositis covering more than half of the boost area. Such reactions lasted for more than 6 weeks in seven patients. Late complications, however, so far observed, have been few. Three patients experienced chronic mucosal tenderness, 1 chronic mucosal ulceration, 2 transient bone exposure, and 1 carotid rupture following salvage surgery. The results so far appear to be better than the outcome of conventional radiotherapy. Its real value will be determined in a prospective randomized study.

Adult↗
PubMed1990

Prompt orchiectomy reduces morbidity and mortality from testicular carcinoma.

The records of 154 patients with non-seminomatous germ cell testicular tumours were reviewed to determine the potential effect of prompt diagnosis and orchiectomy on morbidity and mortality from this disease. Orchiectomy was performed 30 days or less after the onset of testicular symptoms on 65 patients (Group 1) and more than 30 days after the onset of symptoms on 89 patients (Group 2). The initial clinical stages of Group 1 patients were: I, 40 (62%); II, 14 (22%); III, 5 (8%); marker only, 6 (9%). The initial clinical stages for Group 2 patients were: I, 25 (28%); II, 15 (17%); III, 35 (39%); marker only, 14 (16%). The difference between the percentages of Group 1 and Group 2 patients with stage I disease was statistically significant, as was the difference between the percentages of Group 1 and Group 2 patients with stage III disease. One of the Group 1 patients died, whereas 11 of the Group 2 patients died. In 5 of the Group 2 patients who died, orchiectomy had been performed more than 120 days after the onset of testicular symptoms. This study suggests that orchiectomy performed promptly after the onset of testicular symptoms not only helps to reduce mortality from testicular cancer but also has a major effect on its morbidity by reducing the need for systemic chemotherapy or major surgery.

Humans↗
PubMed1990

Sleep enhanced and irritability reduced in preterm infants: differential efficacy of three types of waterbeds.

The purpose of this study was to determine whether waterbeds enhance preterm infants' sleep and reduce irritability, and whether plain, continuously, or intermittently oscillating waterbeds are differentially effective in producing these effects. The baseline states and motility of 52 stable preterm infants were assessed on two consecutive days for 100 minutes each. The infants then were randomly assigned to four groups: a control group who remained on the incubator mattress, or to one of the three experimental groups, each using a different waterbed. On days 3 and 4 in the assigned test condition, the infants' states and motility were again assessed for 100 minutes each day. The results indicate that, compared with infants in the control group, infants assigned to any of the waterbed groups slept significantly more and better, had significantly fewer unsmooth movements, state changes, and transitional states, and were significantly less irritable. Differential treatment effects were found, with infants on continuously oscillating waterbeds showing the most marked reductions in irritability, restlessness, state changes, and unsmooth movements. Thus, to enhance restful sleep and to reduce irritability and/or restlessness, it would be clinically advantageous to use waterbeds in the care of preterm infants. Since even the simple, nonoscillating waterbed improved sleep and reduced restlessness, the use of these beds would be the least costly to achieve these effects.

Arousal↗
PubMed1989

A two-period crossover design for the comparison of two active treatments and placebo.

This paper discusses a two-period crossover design for the comparison of two active treatments (A and B) and placebo (P) for relief of recurrent symptoms of a chronic health disorder. It is based on blocks of ten patients for which the treatment sequences A:B and B:A are each assigned to three patients and the sequences A:P, P:A, B:P, and P:B are each assigned to one patient; thus, treatment periods have a 2:2:1 allocation for A, B, and P. The principal model for analysis of this design involves additive subject effects, period effects, and treatment effects. Analysis of within-patient differences provides an estimate of the comparison between active treatments with variance (2vw/7r) and an estimate of the comparison between an active treatment and placebo with variance (4vw/7r); here vw is the within-patient variance and r is the number of blocks of ten patients. Analyses which address carryover effects and treatment effects adjusted for carryover effects are also described. An example using simulated data on relief of recurrent gastrointestinal pain illustrates the methodology.

Chronic Disease↗
PubMed1989

Treatment of patients with advanced colorectal carcinomas with fluorouracil alone, high-dose leucovorin plus fluorouracil, or sequential methotrexate, fluorouracil, and leucovorin: a randomized trial of the Northern California Oncology Group.

We compared the effectiveness of fluorouracil (5-FU) alone (arm A), high-dose leucovorin plus 5-FU (arm B), and sequential methotrexate, 5-FU, and leucovorin (arm C) for treatment of patients with advanced colorectal carcinomas who had not received prior chemotherapy. Arm A consisted of infusions of 5-FU at 12 mg/kg/d intravenously (IV) for 5 days followed by weekly infusions of 5-FU at 15 mg/kg; arm B consisted of leucovorin infusions at 200 mg/m2/d IV plus infusions of 5-FU at 400 mg/m2/d IV on days 1 through 5 of a 28-day cycle; arm C consisted of methotrexate at 50 mg/m2 orally every 6 hours for five doses followed by infusions of 5-FU, 500 mg/m2 IV, and leucovorin, 10 mg/m2 orally, every 6 hours for five doses every other week. A total of 265 patients were entered into the trial, of whom 249 (94%) were fully evaluable. The objective response rate (complete [CR] plus partial [PR] responses) was 17.3% on arm A, 18.8% on arm B, and 19.8% on arm C (log-rank test, P greater than .4). The median time to failure was 138 days on arm A, 166 days on arm B, and 182 days on arm C (log-rank test, P values of arm A v B = .06; arm A v arm C = .04). Median survival was 345 days on arm A, 324 days on arm B, and 356 days on arm C (log-rank test, P greater than .4). Treatment with 5-FU alone was significantly more dose intensive and more toxic than either of the experimental combinations. The rates of grade 3 or greater nonhematologic toxicity were 42.3% on arm A, 24.3% on arm B, and 14.3% on arm C. Hematologic toxicity was milder but had the same pattern. This study indicates that these regimens of high-dose leucovorin plus 5-FU and sequential methotrexate, 5-FU, and leucovorin are not more effective than is 5-FU alone for treatment of patients with colorectal carcinomas when 5-FU is administered at high-dose intensity.

Adult↗
PubMed1989

Immunologic determinants of head and neck cancer response to induction chemotherapy.

Various measures of immune response were assessed prior to induction chemotherapy (intravenous [IV] cisplatin, fluorouracil [5-FU], and bleomycin) in 43 previously untreated head and neck cancer patients to derive a clinical response prediction model. These were parameters of functional cellular immunity (natural killer [NK] cell activity, lymphocyte blastogenesis response to mitogens), total lymphocyte and lymphocyte subset numbers and percentages, and circulating humoral immunity (total immunoglobulin, immunoglobulin classes, and C1q binding activity [C1q BA]). The C1q BA may reflect levels of circulating immune complexes within peripheral blood. The objective primary tumor response rate was 65% (16 complete responses and 12 partial responses). Univariate logistic regression analysis showed that failure to respond to therapy was significantly related to higher value (vis-à-vis response) of humoral immune parameters total immunoglobulin (Ig), P less than .01; IgG, P less than .01; and C1q BA, P less than .001. No association between cellular immune response measurements and response to chemotherapy was identified. By multivariate logistic regression analysis, only C1q BA levels were predictive of drug therapy responsiveness (P less than .001). Results extend our previous investigations regarding C1q BA measurement in head and neck cancer patients, and show that C1q BA levels add accuracy of prediction of subsequent chemotherapy response to that based solely on standard staging criteria and other parameters of immune status.

Adult↗