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Biomedical subjects

W Wood

Publications and source records attributed to W Wood.

At least 55 records · Page 3Linked to original sources

Phase II study of echinomycin in patients with advanced breast cancer: a report of Cancer and Leukemia Group B protocol 8641.

Twenty-five women with advanced histologically documented stage IV recurrent or inoperable breast cancer were enrolled on a phase II study of echinomycin administered at a dose of 1.2 mg/m2 intravenously over 30 minutes weekly for 4 weeks followed by a two week rest period. Seventy-six percent of patients had visceral dominant disease at study entry and all patients had previously received chemotherapy. One of 21 eligible patients had a partial response lasting 147 days. The median survival for this group of patients was 5.9 months and the median time to treatment failure was 1.7 months. Nausea and vomiting was the primary toxic effect and was severe or life-threatening in 43% of patients. Transient elevation of liver enzymes occurred in 30% of patients. Bone marrow suppression was not significant. Echinomycin as employed in this study did not demonstrate significant antitumor activity in previously treated patients with advanced breast cancer.

Adenocarcinoma↗

Effects of media violence on viewers' aggression in unconstrained social interaction.

This article provides a meta-analytic review of the experimental effects of media violence on viewers' aggression in unstructured social interaction. In the reviewed experiments, children or adolescents were exposed to violent or control presentations and their postexposure behavior was coded for aggression during spontaneous social interaction. Exposure to media violence significantly enhanced viewers' aggressive behavior when the findings were aggregated across studies, but the effect was not uniform across investigations. Only suggestive evidence was obtained concerning moderators of the effect: Marginally stronger relations were obtained in those studies using a cross-section of the normal population of children (vs. emotionally disturbed children) and in those studies conducted in laboratory settings (vs. other contexts).

Adolescent↗

Prediction of prognosis in primary breast cancer by detection of a high molecular weight mucin-like antigen using monoclonal antibodies DF3, F36/22, and CU18: a Cancer and Leukemia Group B study.

Three monoclonal antibodies (MAbs) (DF3, F36/22, CU18) were used to monitor expression of distinct epitopes present within a family of mucin-like, breast carcinoma-associated molecules. Primary tumor specimens from more than 190 stage II breast cancer patients were evaluated for expression of the high molecular weight antigens. With a median follow-up of 6 years, patients whose tumors exhibited high immunoperoxidase staining scores (greater than 50% positive cells) with MAb DF3 had a superior disease-free survival ([DFS] 56% +/- 6% v 37% +/- 5% at 6 years; P = .0088) and overall survival ([OS] 72% +/- 5% v 59% +/- 5% at 6 years; P = .025). Staining scores with the other two antibodies did not correlate with improved prognosis. For MAbs DF3 and CU18, patients whose tumors exhibited predominantly apical cellular reactivity patterns had improved DFS, although differences reached conventional levels of statistical significance only with MAb CU18. In multivariate analyses, the prognostic value of MAb DF3 staining was independent of other identified prognostic factors. Furthermore, the concordance between primary and axillary lymph node metastases staining with each MAb was 73%, 80%, and 85% for MAbs DF3, F36/22, and CU18, respectively. These results suggest that staining with MAb DF3 identifies a group of node-positive women with a relatively favorable prognosis. Expression of the DF3 mucin-like glycoprotein is related to better differentiation, and staining with MAb DF3 provides an accurate and objective estimate of clinical outcome independent of histopathologic evaluation.

Adult↗

Toxicity equivalency factors for PCBs?

In December 1990 the U.S. Environmental Protection Agency sponsored a workshop to discuss the applicability of an interim "toxicity equivalency factor" (TEF) approach to assessing risks posed by exposures to complex mixtures of polychlorinated biphenyls (PCBs). The group concluded that application of the TEF approach to PCBs would be less straightforward than it was in the case of chlorinated dibenzo-p-dioxins and dibenzofurans (CDDs/CDFs). It appears that "dioxin"-like properties of some PCB congeners are amenable to a TEF treatment that is compatible with that used for CDDs/CDFs. Such a scheme also seems to have utility in assessing risks to wildlife. Other non-"dioxin"-like toxic endpoints (e.g., neurotoxicity) appear to have a different structure-activity-related mechanism-of-action that requires a separate TEF scheme. The workshop identified data gaps in toxicology and analytical chemistry that hinder adoption of proposed TEF schemes for PCBs at this time.

Benzofurans↗

Esorubicin (4'-deoxydoxorubicin, NSC 267469) in advanced breast cancer. A phase II study of the CALGB.

Forty-six eligible women with advanced metastatic breast cancer were entered on a Phase II trial utilizing esorubicin (4'-deoxydoxorubicin) given in a dosage of 30 mg/m2 intravenously every 3 weeks. No patient had received anthracyclines or cytotoxic therapy for metastatic disease. Twenty-three (50% of patients) had prior adjuvant chemotherapy, 21 (46%) had prior hormonal therapy, and 32 (70%) were postmenopausal. Dominant site of disease was visceral in 26 (57%), bone in 14 (30%), and soft tissue in 6 (13%). There were 3 complete and 13 partial responders observed, for a 35% response rate; 95% confidence interval for response was 21-49%. Median response duration was 4.0 months (range 2-21 months), and one partial responder remains on study at 6.3 months. Thirty-nine of 46 patients have died; median survival was 10.1 months. Toxicity was primarily hematologic, with 2 drug-related septic deaths. In addition, 2 patients developed severe congestive heart failure secondary to esorubicin cardiotoxicity (at 687 and 770 mg/m2, respectively), which resulted in one patient death. Nausea and vomiting were severe in 16% of patients, but total alopecia was only noted in 4 (9%). Esorubicin is an active agent in metastatic breast cancer; its role in treatment remains undefined.

Adult↗

A feasibility study of intensive CAF as outpatient adjuvant therapy for stage II breast cancer in a cooperative group: CALGB 8443.

In preparation for a national Phase III study of dose and dose intensity in the treatment of node-positive, Stage II adenocarcinoma of the female breast, CALGB instituted a pilot study of intensive intravenous outpatient CAF (cyclophosphamide, Adriamycin, 5-fluorouracil) for four months. This study was designed to give full doses of drugs without dose reduction for hematologic toxicity. In order to evaluate the feasibility of physician and patient compliance with a potentially toxic therapy, a multi-institution pilot study was performed. This protocol demonstrated that a cooperative group could deliver toxic drug doses to outpatients with a median of 98% of cyclophosphamide, 97% of Adriamycin (doxorubicin), and 91% of 5-fluorouracil administered on schedule. Major side effects, as expected, were leukopenia, nausea, and vomiting. Disease-free survival is at least equivalent to that observed in previous studies.

Adenocarcinoma↗

The growth hormone receptor gene in the African pygmy.

Multiple studies indicate that the pygmy responds poorly to GH. A GH-binding protein, which is a fragment of the GHR is markedly diminished in pygmy serum, suggesting a defect in the GHR. Full analysis of the molecular nature and function of the GHR gene is incomplete, but with one enzyme BstNI restriction fragment length, polymorphism was noted in pygmies located in an intron. This was an uncommon finding in other non-pygmy populations. The alteration noted may be in linkage disequilibrium with an effective mutation responsible for changes in the GHR of the pygmy. This is most likely in the regulatory regions of either the 3' or 5' extensions.

Africa↗

Helping traumatically brain injured patients return to work with supported employment: three case studies.

Three case studies illustrating the use of supported employment methods to help individuals with severe head injury are presented. Before supported employment intervention, these individuals were unable either to obtain or maintain employment. Neuropsychologic evaluation revealed many intellectual impairments which contributed to diminished employment potential. Through intervention, all three persons were able to obtain and maintain employment. Consecutive number of months employed ranged from 17.5 to 35, and hours worked per week ranged from 30 to 40. Current hourly earnings exceed the minimum wage, ranging from +5.00 to +5.16 per hour. These cases represent a subset within a larger supported employment program, which assists patients with severe traumatic brain injury to reenter the labor force and maintain employment.

Adult↗

Normal murine and porcine embryos recruit NK cells to the uterus.

Decidual NK cells, indistinguishable from those found in lymphoid tissues, are present in cell suspensions prepared from maternal decidua of random-bred mice between Days 6.5 and 10.5 of first gestation. The stringency of the correlation between NK cells and normal embryos during successful pregnancy is unknown. Our previous finding that active NK cells were unable to mediate lysis of fresh embryonic tissues at any stage during gestation suggests that if NK cells play a functional role in normal pregnancy it would be a noncytolytic role. Before studies on the function of uterine NK cells were undertaken, evidence that the association of NK cells with normal embryos is widespread was sought by assessing NK cell activity in cell suspensions from decidua of syngeneically mated mice, from decidua of multiparous, random-bred mice, and from the endometrium of pigs during first pregnancy. Neither parity nor maternal-fetal compatibility changed the pattern of high levels of decidual NK cell activity early in pregnancy followed by decline. Porcine NK cell activity was not detected in uterine cells isolated from cycling pigs but in pregnant animals it gradually increased during the preattachment period and reached levels greater than those in blood, postattachment (Day 28). Some of this activity was hormone dependent but sustained increases in NK cell activity required the presence of an embryo. These studies demonstrate that the association of functional NK cells with normal embryos is widespread during early pregnancy.

Animals↗

Evaluation of intrauterine immune suppression during pregnancy in a species with epitheliochorial placentation.

Cells capable of suppressing the immune response of PBL to the mitogen PHA are associated with the epitheliochorial placenta during normal first pregnancy in the pig. Because placentation in the pig is noninvasive, these suppressor cells are not associated with decidua. Cells with similar activity are also found between the implantation sites and in the uterus of pseudopregnant pigs, suggesting that fetal trophoblast is not essential for recruitment of intrauterine suppressor cells. Cell separation studies demonstrate that two independent populations of suppressor cells are present in the pig uterus on day 28 of gestation, as well as a population of PHA-responsive cells. The inability of unseparated porcine uterine cells to respond to PHA, plus the reconstitution of suppression in remixing experiments, demonstrate directly that a functional, putative T effector cell population is blocked within the uterus during normal mammalian pregnancy.

Animals↗

Sex differences in interaction style as a product of perceived sex differences in competence.

Males' and females' interaction styles were observed while they worked in four-person, mixed-sex groups on a discussion task. In some groups, members were only given information about each others' names and gender. In this circumstance, men were perceived by themselves and other group members to be higher in competence than women. Further, men engaged in a greater amount of active task behavior than women (e.g., giving information, giving opinions), and women exhibited a greater amount of positive social behavior than men (e.g., agreeing, acting friendly). In other groups, members' competency-based status was manipulated by providing false feedback that they were high or low relative to their group in intellectual and moral aptitude. High status members were then perceived to be more competent than low status ones and, further, high status individuals engaged in more active task and less positive social behavior than low status ones. In this condition, no sex differences were obtained on perceived competence or on active task or positive social behavior. Overall, these findings support the idea that the gender differences obtained in interaction when status was not specified were partially a function of group members' belief that the sexes differ in competence. Direct information concerning members' intellectual and moral competence apparently blocked the perceived gender-to-competence link, and status alone affected perceived competence and interaction style.

Achievement↗

Chemotherapy with cyclophosphamide, adriamycin, and 5-fluorouracil compared to chemotherapy plus hormonal therapy with tamoxifen in the treatment of advanced breast cancer: an interim analysis.

Between February 1980 and August 1982, the Cancer and Leukemia Group B (CALGB) performed a randomized study aimed to compare chemotherapy with CAF (Cyclophosphamide, Adriamycin, 5-Fluorouracil) versus the same chemotherapeutic regimen plus tamoxifen (T-CAF) in stage IV breast cancer patients. Patients were stratified on the basis of menopausal status, estrogen receptors (ER) status, dominant site of metastasis and prior adjuvant treatment. Overall 474 patients were entered into the study of whom 433 were assessable for response. 314 patients were postmenopausal, 85 premenopausal and 34 patients were unknown as far menopausal status was concerned. No difference was evident among postmenopausal patients in overall response rate and duration of responses between T-CAF and CAF (52% vs 50% respectively). Similarly no difference was shown among premenopausal patients, response rates being 63% with T-CAF and 60% with CAF. Lack of benefit from adding T to chemotherapy was seen also according to the different strata, including patients with ER positive tumors. The failure for this combination to be synergistic might reflect an effect of T on tumor kinetics interfering with the activity of chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Selection bias in clinical trials.

Of 90 patients with intermediate or high-grade sarcoma eligible for a randomized trial of adjuvant doxorubicin (Adriamycin, Adria Laboratories, Columbus, Ohio), 48 were not entered: 24 (27%) by physician's choice and 24 refused randomization. Sixty-five percent of lower stage patients were randomized compared with 37% of those with higher stage (P = .02). Patients with extremity lesions were more frequently offered participation in the study (P = .07). Patients with lower stage lesions accepted randomization more readily than those with higher stage lesions (P = .01). As predicted by the higher stage and percentage of central lesions, the disease-free survival of nonrandomized patients was inferior to that of randomized patients (P = .15). Thus, patients at high risk appeared to avoid randomization and adjuvant doxorubicin in this trial, resulting in an inferior disease-free survival for the nonrandomized control group. Important questions generally require randomized trials that reliably determine relative treatment differences. If, however, the patients in a clinical trial are not representative of the entire patient population because of patient and physician selection biases, the generalizability of the results to the entire patient population may be compromised. For example, the prognosis of the general population cannot necessarily be inferred from the selected group in the study. In this study, the randomized and nonrandomized series yielded differing conclusions regarding treatment efficacy, even when an adjustment was made for known prognostic facts.

Clinical Trials as Topic↗

The knee in arthrogryposis.

Of 104 patients with arthrogryposis multiplex congenita treated between 1952 and 1982, 74 had significant knee contractures, instability, or recurvatum. The minimum follow-up period was two years. Nonoperative treatment modalities included physical therapy, bracing, and serial casting in 43 patients (78 knees). Thirty-one other patients (46 knees) had 62 operative procedures, including hamstring and posterior capsular release, epiphysiodesis, distal femoral or proximal tibial osteotomy, arthrodesis, and knee disarticulation. Surgery was reserved for the more resistant causes and was recommended only as part of an overall treatment plan including the correction of foot and hip deformities. The average follow-up period for the surgically treated patients was 11 years, with a range of two to 20 years. Recurrence of deformity was frequent, with no one procedure being clearly favored. Physiotherapy alone rarely resulted in clinically significant improvement unless accompanied by prolonged casting and bracing. The most useful surgical procedure in the growing child was posterior capsular release performed in conjunction with hamstring tenotomy. Contractures treated by osteotomies before the completion of growth had a high rate of recurrence.

Arthrodesis↗