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Biomedical subjects

W Wood

Publications and source records attributed to W Wood.

At least 19 recordsLinked to original sources

Changes in integrity and association of eukaryotic protein synthesis initiation factors during apoptosis.

Induction of apoptosis results in inhibition of the rate of overall protein synthesis in a variety of cell types. We have shown previously that polypeptide chain initiation factor eIF4GI is rapidly cleaved by caspase-3, whereas other components of the eIF4F complex are much more stable during apoptosis in BJAB and Jurkat cells. We have now extended our analysis to other factors involved in the initiation of protein synthesis and we report here that eIF4B, the p35 subunit of eIF3, and minor proportions of the alpha subunit of eIF2 and the eIF4E-binding protein 4E-BP1 are also cleaved to give rise to discrete fragments. These cleavages occur with delayed kinetics relative to that seen for eIF4GI, and eIF2beta and eIF2gamma levels also decrease at a relatively late stage of apoptosis. In contrast, the second form of eIF4G described recently, eIF4GII, is cleaved as rapidly as eIF4GI under the same conditions. Purified recombinant caspase-3 is able to degrade eIF4B and eIF3(p35) in vitro, producing fragments of the same sizes as those seen in intact cells. Induction of apoptosis also results in a biphasic change in the association of 4E-BP1 with eIF4E. Thus the progress of apoptosis is characterized by a complex programme of changes in several initiation factors, including the specific fragmentation or complete degradation of some and alterations in the association status of others. These events are likely to contribute to the inhibition of protein synthesis seen under these conditions.

Adaptor Proteins, Signal Transducing

The anatomy of the extrathoracic intercostobrachial nerve.

BACKGROUND: In the past decade surgeons have become increasingly aware of the morbidity caused by the division of the intercostobrachial nerve (ICBN) during axillary dissection. To prevent this problem and also to explain its variable occurrence, a detailed knowledge of the anatomy of the nerve is required. METHODS: Twenty-eight axillary dissections were performed demonstrating the anatomy of the ICBN. RESULTS: In all dissections the nerve originated from the second intercostal space, with contributions from the first and third intercostal nerve each on one occasion. The posterior axillary branch was constant but may branch early, simulating a second nerve. The ICBN had a variable relationship to the lateral thoracic vein: anterior, posterior or wrapping around it. In 36% there was a connection to the medial cord of the brachial plexus in the axilla. In the upper arm the nerve lies in the subcutaneous fat; in the majority it supplied at least the proximal half of the arm, and in one-third it reached the level of the elbow joint. In 18% there was a connection to the medial cutaneous nerve of the arm. CONCLUSION: The ICBN and its main branch (the posterior axillary nerve) were constant in all dissections. But its origin, size, connection to the brachial plexus and medial cutaneous nerve of the arm were variable, as was its ultimate destination in the arm.

Arm

Accurate and cost-effective evaluation of breast masses in males.

BACKGROUND: Because the majority of breast masses in males are benign and need not be excised if asymptomatic, we studied the combination of physical examination (PE) and fine needle aspiration (FNA), with or without mammography, as a diagnostic alternative to routine surgical biopsy of these lesions. METHODS: A diagnostic test study and cost-effectiveness analysis was performed in three participating multidisciplinary breast clinics, involving a consecutive sample of 51 males with unilateral breast masses. Each lesion was tested with both PE and FNA; 13 were also studied with mammography, and each test was scored as benign or suspicious. Lesions for which all tests were benign were followed up clinically (mean 19 months). Lesions for which any test was suspicious were excised. RESULTS: All tests were benign in 38 cases. No cancers developed at the index sites during follow-up of these lesions, including 8 excisional biopsies done for symptoms (negative predictive value and specificity 100%). Open biopsy confirmed malignancy in all 6 cases for which all tests were suspicious (positive predictive value and sensitivity 100%). In all 7 cases where the tests were not in agreement, open biopsy was benign. In these cases FNA (2 false positives) proved more accurate than PE (5 false positives). Mammography added no additional diagnostic information to the combination of PE and FNA. Compared with routine open biopsy, the combination of PE and FNA avoided surgical biopsy in 30 of the 51 lesions, and was associated with an average decrease in charges of up to $510 per case. CONCLUSIONS: The combination of PE and FNA for the evaluation of breast masses in males is diagnostically accurate and results in a reduction in patient charges compared with routine open biopsy.

Biopsy, Needle

The self-esteem motive in social influence: agreement with valued majorities and disagreement with derogated minorities.

This research provides evidence for the role of self-esteem in social influence; it demonstrates that the positions taken by self-relevant social groups can threaten people's self-esteem. Participants who wished to align themselves with a majority group and who learned that the group held a counterattitudinal position suffered a reduction in self-esteem. Similarly, participants who wished to differentiate themselves from a derogated minority group and who learned that the group held attitudes similar to theirs experienced reduced self-esteem. Group attitudes, however, did not affect the self-esteem of participants who were indifferent to the group. In addition, this study demonstrates that self-relevant motivations direct the way people process influence appeals. Participants adopted interpretations of the issues that allowed them to align themselves with valued majorities and differentiate themselves from derogated minorities.

Adult

Correlation of defense gene induction defects with powdery mildew susceptibility in Arabidopsis enhanced disease susceptibility mutants.

We investigated the relative importance of specific Arabidopsis thaliana genes in conferring resistance to bacterial versus fungal pathogens. We first developed a pathosystem involving the infection of Arabidopsis accession Columbia with a virulent isolate of the obligate biotrophic fungal pathogen Erysiphe orontii. E. orontii elicited the accumulation of mRNAs corresponding to the defense-related genes PR1, BGL2 (PR2), PR5 and GST1, but did not elicit production of the phytoalexin camalexin or the accumulation of defensin (PDF1.2) or thionin (THI2.1) mRNAs. We tested a set of 15 previously isolated Arabidopsis phytoalexin deficient (pad), non-expresser of PR (npr) and enhanced disease susceptibility (eds) mutants that are more susceptible to Pseudomonas syringae for their susceptibility to E. orontii. Four of these mutants (pad4-1, npr1-1, eds5-1 and a double npr1-1 eds5-1 mutant) as well as Arabidopsis lines carrying a nahG transgene exhibited enhanced susceptibility to E. orontii and reduced levels of PR gene expression. Comparison of the PR gene induction patterns in response to E. orontii in the various mutants and in the nahG transgenics suggests the existence of NPR1-independent salicylate-dependent and NPR1-independent salicylate-independent defense gene activation pathways. Eleven other eds and pad mutants did not show measurable enhanced susceptibility to E. orontii, suggesting that these mutants are defective in factors that are not important for the limitation of E. orontii growth.

Anti-Bacterial Agents

Evaluation of a room for tuberculosis patient isolation using theatrical fog.

OBJECTIVE: To develop a method to evaluate directional airflow patterns, air dilution, and air mixing in facilities where tuberculosis patients are seen. DESIGN: A tuberculosis patient isolation room was evaluated by analyzing pressure differential between the room and the corridor and by using theatrical fog to visualize room air movement and impact of dilution and exchange, as well as air capture and displacement. Tracer gas was compared to fog results and used to calculate air exchange rates. SETTING: A small research hospital. RESULTS: By adding theatrical fog to the patient room at several locations, we quickly learned that most of the air entering the room through the transom and around the door to the corridor was exhausted through the three exhaust vents. Little air appeared to move toward the exhaust fan. For comparison and to confirm the room air exchange rate, tracer gas was distributed and sampled. The kinetics of decay were very similar whether the tracer gas and room air were mixed during sampling or not. CONCLUSIONS: The fog procedure allowed good visual confirmation of air mixing and airflow patterns and provided quantitative data for evaluating the efficacy of air capture and displacement or dilution and exchange.

Aerosols

Implementation of the i.v. push method of antibiotic administration using the FOCUS/PDCA approach.

Home health agencies constantly seek ways to improve patient care as part of their performance improvement program. This includes revising and updating agency policies and procedures. Changing care processes, such as administering intravenous medications, requires input from pharmacy and nursing staff as well as administration. The authors describe how one agency used this process while adopting the i.v. push method of administering certain antibiotics to home care patients.

Anti-Bacterial Agents

Comparison of the E test with broth microdilution for antifungal susceptibility testing of yeasts.

The susceptibilities of 26 recent invasive clinical isolates to amphotericin B (AMP), 5-flucytosine (5FC), fluconazole (FLU) and itraconazole (ITR) were determined by a broth microdilution modification of the NCCLS M27P method and also by E test. Using breakpoint criteria each result was classified as either sensitive (S), intermediate (I) or resistant (R). Taking the optical density (OD)80 as the standard, the results were further classified into major (M) or minor (m) errors. E test: AMP = 0M 0m, 5FC = 0M 5m, FLU = 1M 12m, ITR = 1M 5m errors. Minimal inhibitory concentrations (MIC): AMP = 0M 2m, 5FC = 0M 0m, FLU = 3M 4m, ITR = 1M 7m errors. The E test was quick and relatively simple to perform. Results using the E test compared favourably with those of the OD80 and it should be suitable for the routine susceptibility testing of yeasts to antifungal agents.

Amphotericin B

The proteolytic cleavage of eukaryotic initiation factor (eIF) 4G is prevented by eIF4E binding protein (PHAS-I; 4E-BP1) in the reticulocyte lysate.

A common feature of viral infection is the subversion of the host cell machinery towards the preferential translation of viral products. In some instances, this is partly mediated by the expression of virally encoded proteases which lead to the cleavage of initiation factor eIF4G. The foot-and-mouth disease virus encodes two forms of a cysteine proteinase (L protease) which bisects the eIF4G polypeptide into an N-terminal fragment containing the eIF4E binding site, and a C-terminal fragment which contains binding sites for eIF4A and eIF3 and which associates with the 40S ribosomal subunit. Previously, we have demonstrated that the cleavage of eIF4G by L protease stimulates the translation of uncapped transcripts encoding cellular proteins and supports internal initiation driven by picornavirus internal ribosome entry segment (IRES) elements. Use of reticulocyte lysates manipulated to deplete them of eIF4E and the N-terminal fragment suggests that the C-terminal fragment of eIF4G is responsible for these effects, and we have now confirmed this by purifying the C-terminal fragment and analysing its effects directly in the absence of L protease. Interestingly, we find that pre-incubation of reticulocyte lysates or ribosomal salt wash fractions with the specific eIF4E binding protein, PHAS-I (eIF4E-BP1), blocks the proteolytic cleavage of eIF4G by L protease. This effect can be reversed by addition of recombinant eIF4E. These data are consistent with a model whereby the L protease cleavage site in eIF4G is inaccessible until a change in conformation is induced by the binding of eIF4E. This may have implications for a role for eIF4E binding in triggering changes that expose other domains in the eIF4G molecule during initiation of translation.

Animals

Conformity to sex-typed norms, affect, and the self-concept.

The self-concept plays an important role in conformity to sex-typed social norms. Normative beliefs that men are powerful, dominant, and self-assertive and that women are caring, intimate with others, and emotionally expressive represent possible standards for whom people ought to be and whom they ideally would like to be. In the present research, to the extent that sex role norms were personally relevant for participants, norm-congruent experiences (i.e., those involving dominance for men and communion for women) yielded positive feelings and brought their actual self-concepts closer to the standards represented by ought and ideal selves.

Affect

Phase II trial of biweekly paclitaxel and cisplatin in advanced breast carcinoma: an Eastern Cooperative Oncology Group study.

PURPOSE: To determine the efficacy of a biweekly paclitaxel and cisplatin regimen in patients with advanced breast carcinoma, which has previously been reported to produce an 85% response rate in such patients. PATIENTS AND METHODS: Sixteen patients with metastatic breast carcinoma who had relapsed after prior doxorubicin-containing adjuvant chemotherapy were treated with paclitaxel (90 mg/m2) by intravenous (i.v.) infusion over 3 hours followed by cisplatin (60 mg/m2) given by i.v. infusion over 1 hour on an outpatient basis. Treatment was repeated every 2 weeks if the absolute neutrophil count was > or = 750/microL and platelet count > or = 75,000/microL. After a maximum of eight cycles of paclitaxel/cisplatin, patients received biweekly paclitaxel alone (90 mg/m2 with dose escalation). Thirteen patients were assessable for response and all for toxicity. Nine of 13 patients assessable for response (69%) had at least three sites of metastases and 10 patients (77%) had visceral-dominant disease. RESULTS: Partial response occurred in three of 13 assessable patients (23%; 90% confidence interval, 7% to 49%). All responders had two or fewer sites of metastases. The median time to progression was 4.3 months and the median survival duration was 11.4 months. Patients received a median of seven cycles of therapy (range, two to 21). Severe and/or life-threatening toxicity occurred in 50% and 38%, respectively, and consisted primarily of granulocytopenia, anemia, and neuropathy. The trial was terminated after the first interim analysis as per its two-stage design, since it was unlikely that the response rate would exceed 70%. CONCLUSION: Biweekly paclitaxel/cisplatin is not likely to produce a response rate greater than 70% in patients with metastatic breast cancer who have relapsed after prior doxorubicin-containing adjuvant chemotherapy and who have multiple sites of metastases and/or visceral-dominant disease.

Adult

Warfarin for atrial fibrillation. The patient's perspective.

OBJECTIVE: To determine the minimal clinically important difference (MCID) of warfarin therapy for the treatment of nonvalvular atrial fibrillation from the perspective of patients using 2 different elicitation methods. DESIGN: All patients completed 2 face-to-face interviews, which were 2 weeks apart. For each interview, they were randomized to receive 1 of 2 elicitation methods: ping-ponging or starting at the known efficacy. SETTING: The practices of 2 university-affiliated family medicine centers (8 physicians each), 14 community-based family physicians, and 2 cardiologists. PATIENTS: Sixty-four patients with nonvalvular atrial fibrillation who were initiated with warfarin therapy at least 3 months before the study. INTERVENTION: During each interview, the patients' MCIDs were determined by using (1) a pictorial flip chart to describe atrial fibrillation; the consequences of a minor stroke, a major stroke, and a major bleeding episode; the chance of stroke if not taking warfarin; the chance of a major bleeding episode if taking warfarin; examples of the inconvenience, minor side effects, and costs of warfarin therapy; and then (2) 1 of the 2 elicitation methods to determine their MCIDs (the smallest reduction in stroke risk at which the patients were willing to take warfarin). Patients' knowledge of their stroke risk, acceptability of the interview process, and factors determining their preferences were also assessed. MAIN RESULTS: Given a baseline risk of having a stroke in the next 2 years, if not taking warfarin, of 10 of 100, the mean MCID was 2.01 of 100 (95% confidence interval, 1.60-2.42). Fifty-two percent of the patients would take warfarin for an absolute decrease in stroke risk of 1% over 2 years. Before eliciting their MCIDs, patients showed poor knowledge of their stroke risk, which improved afterward. The interview process was well accepted by the patients. The MCID using the ping-ponging elicitation method was 1.015 of 100 smaller compared with use of the starting at the known efficacy method (P = .01). CONCLUSIONS: We were able to determine the MCID of warfarin therapy for the prevention of stroke from the perspective of patients with nonvalvular atrial fibrillation. Their MCIDs were much smaller than those that have been implied by some experts and clinicians. The interview process, using the flip chart approach, appeared to improve the patients' knowledge of their disease and its consequences and treatment. The method used to elicit the patients' MCIDs can have a clinically important effect on patient responses. The method used in our study can be generalized to other conditions and, thus, could be helpful in 3 ways: (1) from a clinical decision-making perspective, it could facilitate patient-physician communication; (2) it could clarify the patient perspective when interpreting the results of previously completed trials; and (3) it could be used to derive more clinically relevant sample sizes for randomized treatment trials.

Aged

Psychological symptoms and disease-free and overall survival in women with stage II breast cancer. Cancer and Leukemia Group B.

BACKGROUND: The possible link between psychological factors and length of cancer survival has generated a literature of contradictory findings. Associations usually have not been found when general psychological symptoms are assessed. Associations usually have been found for predictors related to expressive versus repressive emotional coping (e.g., depression, "fighting spirit," hostility, and type C personality); however, even these associations have been relatively small, when compared with those for medical factors. Yet few studies have adequately controlled for medical and treatment-related factors. PURPOSE: Within a Cancer and Leukemia Group B (CALGB) national clinical trial of four adjuvant therapy regimens for stage II breast cancer (CALGB 8082), this study prospectively examined the contribution of potential psychological predictors to length of disease-free and overall survival over a 15-year period. METHODS: Subjects were 280 women with stage II breast cancer, out of a total of 899, who were randomly assigned to receive CMFVP (cyclophosphamide-methotrexate-fluorouracil-vincristine-prednisone) for two 6-week cycles or six 4-week cycles, then subsequently randomly assigned to receive or not to receive VATH (vinblastine-doxorubicin-thiotepa-fluoxymesterone). Subjects were recruited during the period between October 1980 and August 1984, inclusive, and followed until January 1996. Prior to chemotherapy, psychological symptoms were assessed using the Symptom Check List-90-Revised (SCL-90-R). SCL-90-R scores were trichotomized into categories representing high, medium, and low distress. Basic base-line sociodemographic data (including age, ethnicity, education, and marital status) and medical data (including lymph node status, estrogen receptor status, menopausal status, and performance status) were collected. Subjects with psychosocial data differed from those without psychosocial data solely in their higher percentage of classification in the mild limitation category of the Zubrod (Eastern Cooperative Oncology Group) performance status rating (subjects with psychosocial data: 14%; subjects without psychosocial data: 8%). RESULTS: In stepwise Cox regression analyses that controlled for sociodemographic and medical variables, there was no significant predictive effect of the level of distress (as measured by the SCL-90-R trichotomized scores) on length of disease-free and overall survival of the study subjects. Risk ratios for low versus high distress were 1.01 (95% confidence interval [CI] = 0.62-1.66) for disease-free survival and 1.03 (95% CI = 0.58-1.82) for overall survival. CONCLUSIONS: This study failed to provide evidence that psychological factors contributed to length of disease-free or overall survival of women who received adjuvant chemotherapy (either CMFVP alone or CMFVP followed by VATH) for treatment of stage II breast cancer. IMPLICATIONS: In the context of far more potent medical factors, the contribution of psychological factors to disease-free and overall survival is likely to be relatively small. Future research should focus on specific theory-driven predictors rather than on general psychological symptoms. Moreover, it should be based on clinical studies using a controlled, prospective design, in which the effects of medical factors may be distinguished and psychological predictors are clear antecedents of survival outcomes.

Adaptation, Psychological

Self-definition, defensive processing, and influence: the normative impact of majority and minority groups.

Past research has found that recipients agree with majority group positions and resist minority group positions on direct measures of influence. The authors suggest that these attitude shifts reflect normative pressures to align with valued majorities and to differentiate from derogated minorities. In support of this idea, participants who considered a majority group relevant to their own self-definitions (but not those who judged it irrelevant), on learning that the group held a counterattitudinal position, shifted their attitudes to agree with the source. In a second study, recipients who judged a minority group (negatively) self-relevant, on learning that the group held a similar attitude to their own, shifted their attitudes to diverge from the source. These shifts in attitudes were based on participants' interpretations of the attitude issues.

Analysis of Variance

Eliminating language barriers for non-English-speaking patients.

OBJECTIVES: More than 31 million persons living in the United States do not speak English, therefore language discordance between the clinician and patient may hinder delivery of cost-effective medical care. A new language service was developed in which interpreters are trained in the skills of simultaneous interpretation commonly used at international conferences. The interpreters are linked from a remote site to headsets worn by the clinician and patient through standard communication wires. The service is called "remote-simultaneous interpretation," to contrast it with a traditional method of an interpreter being physically present at the interview and interpreting consecutively "proximate-consecutive interpretation." The aim of this study is to assess in a randomized protocol the quality of communication, interpretation, and level of patient, interpreter, and physician satisfaction with these two language services. METHODS: The first postpartum visit with each of 49 mothers and their new born babies was assigned randomly to proximate-consecutive interpretation (control) or to remote-simultaneous interpretation (experimental). Main outcome measures included (1) the number of physician and mother utterances in the visit, (2) the quality of the interpretation, and (3) physician, interpreter, and mother preferences between the two services. RESULTS: The remote-simultaneous interpreter service averaged 8.3 (10%) more physician utterances (95% confidence interval [CI] 4.3, 12.4) and 9.1 (28%) more mother utterances (95% CI 6.1, 12.1). On average, there were 2.8 (12%) fewer inaccuracies of physician utterances in experimental visits compared with control visits (95% CI -5.9, 0.4) and 3.0 (13%) fewer inaccuracies of mother utterances in experimental visits compared with control visits (95% CI -5.4, -0.6). Mothers and physicians significantly preferred the remote-simultaneous service to proximate-consecutive interpretation service. Interpreters stated that they thought mothers and physicians better understood each other using the remote-simultaneous service, although the interpreters preferred to work with the proximate-consecutive service. CONCLUSIONS: Using remote-simultaneous interpretation to improve the quality of communication in discordant-language encounters promises to enhance delivery of medical care for the millions of non-English-speaking patients in the United States.

Attitude of Health Personnel