Biomedical subjects
Publications and source records attributed to P Goodwin.
The present consensus manuscript defines evidence-based recommendations for state-of-the-art treatment of metastatic breast cancer depending on disease-associated and biologic variables.
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The separation of plant and fungal sequences in EST pools by bioinformatic methods is difficult because of sequence similarities between plants and fungi, lack of enough sequence information, and the short length of the isolated fragments. An algorithm and software that utilize the differences in codon usage bias to discriminate between plant and fungal sequences are described. The software (PF-IND) includes five pairs of fungi and their host plants that can be used to analyze a large number of related species. Analysis of a sequence provides an arbitrary value that defines the likelihood that a sequence will be a fungal or a plant gene. The software can distinguish between homologous fungal and plant genes and it helps identify the correct reading frame of unknown expressed sequence tags (ESTs) for which BLAST analyses do not provide clear information. Short sequences of 100-150 bp can be analyzed with high confidence. PF-IND analysis of 100 sequences derived from fungal infected plants identified the origin of 94 sequences. Only 66 sequences were identified by a BLASTX analysis of the same 100 ESTs. Overall, PF-IND is a novel bioinformatic tool aimed at assisting the research of fungus-plant interactions.
A novel actin-related protein (arp) was found in the plant pathogenic fungus, Colletotrichum gloeosporioides f. sp. malvae (Cgm), which causes anthracnose disease of round-leaved mallow (Malva pusilla). Sequence comparisons showed that this gene, arpA, belongs to the highly divergent 'other arps' category in the current arp classification system. ArpA is most similar to the arp11 gene of Mus musculus but has a unique structure with deletions at the C-terminus similar to that of the arp10 gene of Saccharomyces cerevisiae. A portion of another putative arp gene, arpB, was found immediately downstream of arpA. Expression of arpA was compared to the constitutively expressed Cgm actin gene, actA. In culture, the relative expression of arpA increased when growth conditions favored sporulation. During infection, arpA expression was greatest at the late necrotrophic phase, when sporulation occurred. Arps have been shown to be important in nuclear migration in fungal hyphae, and the expression pattern of arpA indicates that it may have a particular role during sporulation.
The aim of this study was to evaluate the effect of different functional appliances on the soft tissues as assessed by cephalometry and optical surface scanning. Forty-two patients were randomly allocated to Bass, Twin Block (TB), and Twin Block + Headgear (TB + Hg) groups. Lateral cephalograms and optical surface scans were recorded before and after the 10-month study period. ANOVA was used to test the cephalometric variables for differences at the 5 per cent level. The optical surface scanning and cephalometric results were consistent in the sagittal dimension. In the vertical dimension, however, the optical surface scans consistently recorded a greater increase compared with cephalometric values. No differences were detected with regard to cephalometric values at the 5 per cent level. However, the Bass appliance produced greater forward positioning of soft tissue pogonion as assessed by optical surface scanning.
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BACKGROUND: Chronic low-back pain is a significant public health problem for which few therapies are supported by predictable outcomes. In this report, practice activities and 1-month outcomes data are presented for 93 chiropractic patients and 45 medical patients with chronic, recurrent low-back pain. DESIGN: A prospective, observational, community-based feasibility study involving chiropractors and family medicine physicians. SETTING: Forty private chiropractic clinics, the outpatient clinic of the Department of Family Medicine at Oregon Health Sciences University, and 5 other Portland area family medicine clinics. OUTCOMES MEASURES: The main outcome measures were pain severity, functional disability, sensory and affective pain quality at 1 month, and patient satisfaction assessed at 7 to 10 days and at 1 month. RESULTS: Although differences were noted in age, sex, education, and employment, the patients were closely matched at baseline with respect to frequency, severity, and type of low-back pain and the psychosocial dimensions of general health. The treatment of choice for chiropractors was spinal manipulation and physical therapy modalities; for medical physicians antiinflammatory agents were most frequently used. Chiropractic patients averaged 4 visits, and medical patients averaged 1 visit. On average, chiropractic patients showed improvement across all outcomes: 31% change in pain severity, 29% in functional disability, 36% in sensory pain quality, and 57% in affective pain quality. Medical patients showed minimal improvement in pain severity (6%) and functional disability (1%) and showed deterioration in the sensory (29%) and affective (26%) dimensions of pain quality. Satisfaction scores were higher for chiropractic patients. Outcomes for medical patients were heavily dependent on psychosocial status at baseline. CONCLUSION: Patients with chronic low-back pain treated by chiropractors show greater improvement and satisfaction at 1 month than patients treated by family physicians. Nonclinical factors may play an important role in patient progress. Findings from the Health Resources and Services Administration-funded project will include a report on the influence of practice activities, including more frequent visits by chiropractic patients, on the clinical course of low-back pain and patient outcomes. (J Manipulative Physiol Ther 2000;23:239-45).
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BACKGROUND: Approximately 2.0%-2.5% of Ashkenazi Jewish women carry one of three founding mutations in the BRCA1 and BRCA2 genes, and each mutation is associated with a high lifetime risk of invasive breast cancer. We investigated the extent to which these three mutations contribute to breast cancer incidence in the Ashkenazi Jewish population. METHODS: We ascertained 457 Jewish women with prevalent cases of breast cancer who were unselected for age or family history of the disease; 412 of these women were tested for the three founder mutations (case patients). Control subjects consisted of 360 non-Jewish women with breast cancer (control patients) and 380 healthy Jewish women with no history of cancer (control subjects). RESULTS: Mutations were found in 48 (11.7%) of 412 Jewish case patients. Forty-six of 48 mutations occurred in women with early-onset breast cancer (<50 years) or a history of ovarian or early-onset breast cancer in a first-, second-, or third-degree relative. The estimated penetrance to age 70 years for breast cancer was 59.9% for the BRCA1 gene mutations and 28.3% for the BRCA2 gene mutation. Compared with Jewish control subjects, the relative risk (RR) of breast cancer for first-degree relatives of mutation carriers was 5.16 (95% confidence interval [CI] = 3.14-8. 48), but risk was also increased for relatives of noncarriers (RR = 1.66; 95% CI = 1.18-2.33). The RR of prostate cancer for first-degree relatives of Jewish case patients was 3.36 (95% CI = 1. 49-7.56). CONCLUSIONS: Approximately 12% of breast cancers in the Ashkenazi Jewish population are attributable to mutations in the BRCA1 or BRCA2 gene. Genetic testing may be useful when Jewish women with breast cancer are diagnosed before age 50 years or have a close relative with ovarian or early-onset breast cancer. An association between breast and prostate cancers was observed in our study population.
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OBJECTIVE: It has been proposed that cesarean section improves the long-term neurologic outcome of children with meningomyelocele. On the basis of this belief, a trial of labor is not offered in many centers. We hypothesized that there is no difference in immediate or long-term outcome by route of delivery for the fetus with meningomyelocele delivered in a tertiary care center. STUDY DESIGN: All fetuses (n = 60) with meningomyelocele delivered at the University of Iowa Hospitals and Clinics between 1971 and 1995 were analyzed. Thirty-six cases were available for long-term follow-up. Motor, sensory, and anatomic levels were converted to a numeric scale. Variables were compared by one-way analysis of variance, chi2 analysis, and Fisher's exact test with significance at P < .05. RESULTS: There were no significant differences by route of delivery for gestational age of delivery, birth weight, meningomyelocele size, or neonatal mortality (vaginal: 1/22 = 4.5%, cesarean section: 2/17 = 11.8%, P = .82). An antenatal diagnosis was made with similar frequency in the two groups (vaginal: 15/21 = 71.4%, cesarean section: 13/15 = 86.7%). In addition, the length of long-term follow-up was similar (vaginal: 54.7 +/- 11.1 months, cesarean section: 33.7 +/- 8.6 months). There was no difference in long-term neurologic outcome as determined by the change in motor level, the change in sensory level, or when comparing the final motor level with the anatomic level. CONCLUSIONS: This study was unable to detect differences between either immediate or long-term outcome for the infant with isolated meningomyelocele when stratified by route of delivery. A multicenter randomized trial should be required before the acceptance of cesarean section as the optimal route of delivery for the fetus with meningomyelocele.
INTRODUCTION: The Prostate Cancer Specific Quality of Life Instrument (PROSQOLI) was developed to be a pragmatic outcome measure for clinical trials in symptomatic men with advanced hormone-resistant prostate cancer. DESIGN AND SETTING: A comparative assessment of responsiveness was made with longitudinal data from a positive multicenter randomized trial of palliative chemotherapy in 161 symptomatic men with advanced hormone-resistant prostate cancer. INSTRUMENTS: The PROSQOLI, the European Organisation for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30), and a specific quality of life module for advanced prostate cancer [QLM-P14] were administered every 3 weeks while patients received their allocated treatment. FINDINGS: Sixteen of the 19 health-related quality of life (HRQL) scales demonstrated improvements in palliative responders. All three pain scales detected a beneficial effect of palliative chemotherapy. The relative efficiency statistics favored the PROSQOLI for physical symptoms and physical function but the QLQ-C30 for emotional function, social function, and global perceptions. The PROSQOLI linear analog scale was the most responsive measure of pain. Bootstrap confidence intervals for the relative efficiency statistics were wide. CONCLUSIONS: Both the PROSQOLI and the analogous scales from the QLQ-C30 were responsive to improvements in HRQL. Differences between the instruments were generally subtle. The PROSQOLI is a short, simple, responsive measure of HRQL in men receiving systemic treatment for advanced hormone-resistant prostate cancer.
Sixty-one women with newly diagnosed locoregional breast cancer (T1-3, N0-1, M0) having an initial Body Mass Index (BMI) between 20 and 35 kg/m2 who were receiving standard adjuvant treatment (chemotherapy, tamoxifen, and/or radiation) were asked to avoid weight gain (if initial BMI < or = 25 kg/m2) or to lose up to 10 kg (if initial BMI 25-35 kg/m2) over one year. Women participated in twenty group sessions (10 weekly, 10 monthly) which involved a psychological supportive-expressive group intervention supplemented by individual weight goals, and nutrition and exercise programs. Fifty-five non-censored women (5 developed recurrence, 1 died of a subarachnoid hemorrhage) lost a mean of 0.53 +/- 3.72 kg. Weight loss was greatest in initially overweight women (BMI > or = 25 kg/m2) who lost 1.63 +/- 4.11 kg (p = 0.01 compared to normal weight women) and in those not receiving chemotherapy who lost 2.15 +/- 2.83 kg (p = 0.0004 compared to those receiving chemotherapy). 70.9% met predefined criteria for success. Aerobic exercise increased significantly during the intervention (p = 0.00005) and was the strongest predictor of success (OR 1.73 for each additional 30 minutes of exercise weekly, p = 0.003). Changes in caloric intake were not significant, but fat intake decreased and carbohydrate and fibre intake increased significantly during the intervention. Eating behavior and psychological status improved significantly. Thus, this multidisciplinary weight management intervention successfully prevented weight gain in women with newly diagnosed locoregional breast cancer, and helped overweight women lose weight.
The aim of this study was to survey Canadian oncology practitioners' attitudes toward psychosocial concerns and issues in women with breast cancer. Surveys were mailed to 351 medical, radiation and surgical oncologists and 375 oncology nurses. Standard questionnaires assessed attitudes towards psychosocial issues in women with primary and metastatic breast cancer and evaluated the practitioners' willingness to refer women to psychosocial intervention trials in the presence and absence of competing drug trials. Responses were obtained from 74% of those surveyed. Respondents reported being aware of the common occurrence of psychosocial problems in women with metastatic breast cancer, however, physicians were less likely than nurses to offer these women psychosocial support on a prophylactic basis (p < 0.0001) and they expressed greater concern than nurses about scientific validity of (p = 0.0003), and potential psychological damage from (p = 0.005), psychosocial support groups. Nurses were more likely than physicians to favour a study investigating group psychosocial support over competing drug studies (p < or = 0.003) in the metastatic setting. Physicians were less likely than nurses to deal with weight problems prophylactically in women with primary breast cancer (p = 0.0009) and they expressed greater concern over scientific validity of psychosocial interventions addressing weight than nurses (p = 0.0008); nurses were more concerned about excessive expectations of patients regarding potential benefits of such interventions (p < 0.0001). Regardless, nurses were more likely than physicians to favour a psychosocial intervention study focused on weight management over drug studies in pre- (p = 0.0006) and postmenopausal women (p = 0.05) with primary breast cancer. Canadian oncology practitioners are aware of the common occurrence of psychosocial distress in women with breast cancer. Physicians and nurses assigned differing priorities to psychosocial interventions in both clinical and research situations.
To examine the effects of maternal ageing on the meiotic apparatus, we obtained oocytes from naturally cycling women in two age groups, including younger (aged 20-25 years) and older (aged 40-45 years) women. Using high-resolution confocal microscopy we obtained a detailed picture of the meiotic spindle and chromosome placement during various phases of meiosis. Our data revealed that the meiotic spindle in older women is frequently abnormal, both with regard to chromosome alignment and the microtubule matrix that comprise the meiotic spindle. The spindle in 79% of the oocytes from the older group exhibited abnormal tubulin placement and one or more chromosomes were displaced from the metaphase plate during the second meiotic division. In contrast, only 17% of the oocytes from the younger age group exhibited aneuploid conditions. The majority of eggs from this group possessed a well ordered, meiotic spindle containing chromosomes that were fully aligned within a distinct metaphase plate in the spindle. Chromosome management during meiosis is directed by microtubule assembly within the spindle. These data suggest that the regulatory mechanisms responsible for assembly of the meiotic spindle are significantly altered in older women, leading to the high prevalence of aneuploidy.
BACKGROUND: Along with fine needle aspiration (FNA) cytology, core-biopsy has become an integral part of the assessment of mammographically detected breast lesions. METHODS: A series of stereotactic large-core-biopsies of mammographically detected breast lesions was studied to assess the accuracy and limitations of the technique in diagnosing malignancy and in giving specific benign diagnoses, and its use in determining surgical management. RESULTS: Eighty per cent of carcinomas were diagnosed as malignant (absolute sensitivity). In 88.8% of the cancers, the core-biopsy was classified as malignant, suspicious or atypical/indeterminate (complete sensitivity), and in 72% of the invasive carcinomas, invasive tumour was present in the core. The technique was more successful for invasive carcinomas than for ductal carcinoma in situ (DCIS) (absolute sensitivity 86.1 and 55.5, respectively; P = 0.28) and for malignant mass lesions than for a mass with associated microcalcifications or for pure microcalcifications (absolute sensitivity 91, 71 and 66.6%, respectively; P = 0.19). In five of the 45 cancers (11.1%), no tumour tissue was present in the core, but all were excised after mammographic review and no delays in diagnosis have been experienced to date. The benign to malignant ratio for excised lesions was 0.11:1. Of the benign lesions, a specific diagnosis was given in 49% (calcifications in the core in a background of fibrocystic change, or postoperative scarring, or fibro-adenoma); the remainder showed non-specific benign findings. All patients where invasive carcinoma was diagnosed in the core underwent axillary clearance and wide local excision or mastectomy at their first operation. CONCLUSIONS: This technique can markedly reduce the number of benign lesions needing open biopsy, and provide information allowing definitive management of most carcinomas at the first operation. The accuracy of core-biopsy was lower in DCIS/microcalcification lesions; extra core samples or a combination of FNA and core-biopsy may be of value in these cases.
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