Hypoxic pulmonary vasoconstriction does not contribute to pulmonary blood flow heterogeneity in normoxia in normal supine humans.

We hypothesized that some of the heterogeneity of pulmonary blood flow present in the normal human lung in normoxia is due to hypoxic pulmonary vasoconstriction (HPV). If so, mild hyperoxia would decrease the heterogeneity of pulmonary perfusion, whereas it would be increased by mild hypoxia. To test this, six healthy nonsmoking subjects underwent magnetic resonance imaging (MRI) during 20 min of breathing different oxygen concentrations through a face mask [normoxia, inspired O(2) fraction (Fi(O(2))) = 0.21; hypoxia, Fi(O(2)) = 0.125; hyperoxia, Fi(O(2)) = 0.30] in balanced order. Data were acquired on a 1.5-T MRI scanner during a breath hold at functional residual capacity from both coronal and sagittal slices in the right lung. Arterial spin labeling was used to quantify the spatial distribution of pulmonary blood flow in milliliters per minute per cubic centimeter and fast low-angle shot to quantify the regional proton density, allowing perfusion to be expressed as density-normalized perfusion in milliliters per minute per gram. Neither mean proton density [hypoxia, 0.46(0.18) g water/cm(3); normoxia, 0.47(0.18) g water/cm(3); hyperoxia, 0.48(0.17) g water/cm(3); P = 0.28] nor mean density-normalized perfusion [hypoxia, 4.89(2.13) ml x min(-1) x g(-1); normoxia, 4.94(1.88) ml x min(-1) x g(-1); hyperoxia, 5.32(1.83) ml x min(-1) x g(-1); P = 0.72] were significantly different between conditions in either imaging plane. Similarly, perfusion heterogeneity as measured by relative dispersion [hypoxia, 0.74(0.16); normoxia, 0.74(0.10); hyperoxia, 0.76(0.18); P = 0.97], fractal dimension [hypoxia, 1.21(0.04); normoxia, 1.19(0.03); hyperoxia, 1.20(0.04); P = 0.07], log normal shape parameter [hypoxia, 0.62(0.11); normoxia, 0.72(0.11); hyperoxia, 0.70(0.13); P = 0.07], and geometric standard deviation [hypoxia, 1.88(0.20); normoxia, 2.07(0.24); hyperoxia, 2.02(0.28); P = 0.11] was also not different. We conclude that HPV does not affect pulmonary perfusion heterogeneity in normoxia in the normal supine human lung.

Severe alveolar proteinosis following chemotherapy for acute myeloid leukemia in a lung allograft recipient.

A 64-year-old man was diagnosed with acute myeloid leukemia (AML) 5 years following single lung transplantation performed for severe pulmonary hypertension from scleroderma. Chemotherapy for treatment of AML with fludarabine, cytosine arabinoside, G-CSF (FLAG) regimen was initiated. Despite intensive antibiotic treatment for a presumptive diagnosis of bacterial pneumonia, the patient developed acute respiratory failure and died before a complete cycle of chemotherapy could be administered. At autopsy, both native and allograft lungs showed widespread alveolar proteinosis that was determined as the main cause of acute respiratory failure. Alveolar proteinosis, a potentially treatable disease, should be considered in the radiologic differential diagnosis of diffuse lung disease in this clinical setting.

Distribution of obstructive intimal lesions and their cellular phenotypes in chronic pulmonary hypertension. A morphometric and immunohistochemical study.

We investigated the distribution of pulmonary arteriopathy in chronic pulmonary hypertension (PH) in a quantitative histopathologic study, using computer-assisted image analysis. We also examined the histologic manifestations and cellular phenotypes of various obstructive intimal lesions in PH with an immunohistochemical method. A total of 53 lungs removed at autopsy or explantation were obtained for the study from 51 documented cases of moderate to severe PH (15 cases of primary pulmonary hypertension [PPH], eight cases of Eisenmenger's syndrome [EISEN], 22 cases of chronic major-vessel thromboembolic disease [CTED], and three cases of PH associated with other known causes), and two unused donor lungs served as normal controls. Intimal thickening in PPH was most prominent in small pulmonary arteries and arterioles less than 200 micrometer in diameter. Plexiform lesions in PPH were associated with significantly smaller arteries than in EISEN. Arteries larger than 400 micrometer showed a significant intimal thickening only in CTED. Obstructive intimal lesions in PH comprised a morphologic spectrum with frequent intermediate forms between plexiform and thrombotic lesions. Most cells within various intimal lesions showed an immunoprofile of myofibroblasts that were positive for vimentin and alpha-smooth muscle actin, but negative for desmin and endothelial markers including Factor VIII, clonal designator (CD)31, and CD34. Endothelial markers were positive only in the single layer of cells lining slitlike lumens, when the latter were present. In conclusion, major types of PH had characteristic distribution patterns of obstructive intimal lesions, showing mainly a myofibroblastic phenotype and variable endothelial/vascular differentiation.

Isokinetic peak torque in women with unilateral cumulative trauma disorders and healthy control subjects.

OBJECTIVES: To compare isokinetic peak torque in the symptomatic and asymptomatic limbs of women with lateral epicondyle or forearm pain due to cumulative trauma disorders (CTDs), and to compare peak torque in women with CTDs to peak torque in healthy women. DESIGN: Case control comparison. SETTING: Private occupational rehabilitation clinic and a sports science tertiary education center. SUBJECTS: Women with CTDs involving one arm (n=17) and a convenience sample of healthy women (n=7) INTERVENTION: Subjects performed isokinetic strength testing for wrist extension and flexion, wrist supination and pronation, and knee extension and flexion. MAIN OUTCOME MEASURES: Peak torque at 120 degrees/sec on a Biodex isokinetic dynamometer. RESULTS: Control subjects had significantly higher peak torque in wrist extension, flexion, supination, and pronation than CTD subjects on the symptomatic side. Control subjects also had significantly higher peak torque of wrist flexion, pronation, and supination than CTD subjects on the asymptomatic side; wrist extension was greater, but this did not reach significance. In addition, control subjects had significantly higher peak torque in knee extension and flexion than CTD subjects. CTD subjects had significantly greater left-right asymmetry in wrist extension torque than did control subjects. CONCLUSIONS: Isokinetic peak torque is diffusely reduced in women with unilateral CTDs compared with healthy control subjects, these differences occurring in symptomatic and asymptomatic limbs.

Predictors of work disability in work-related upper-extremity disorders.

The aim of this study was to compare symptoms, signs, grip strength, passive wrist flexion angle, and self-rated disability in work-related upper extremity disorders (WRUEDs) to determine predictors of work disability in 106 consecutive patients. Age, gender, and duration of symptoms were unrelated to current work status. The best predictors of current work hours were, in descending order, the Fibromyalgia Impact Questionnaire (FIQ), Modified Stanford Health Assessment Questionnaire (SHAQ), weeks of work absence, passive wrist flexion angle of the affected arm, neck pain or stiffness on movement, and grip in affected arm. FIQ and SHAQ scores were significantly correlated with objective measures of upper-extremity function. FIQ and SHAQ scores are valid measures of work disability in WRUEDs, which are more closely related to current work hours than to time off work, symptoms, or physical signs.

Poststroke depression: prevalence, course, and associated factors.

Despite the considerable amount of research that has been undertaken on poststroke depression, a review of the literature demonstrates that there are many inconclusive findings in the area. In particular, the causes and course of the disorder remain to be firmly established. While studies of prevalence differ with respect to the nature and timing of their assessment procedures, most conclude that poststroke depression has a negative impact on the rehabilitation of the stroke patient. Very little research is available on te relationship between poststroke depression and care-giver burden. However, recent studies have adopted more rigorous methodological procedures, allowing some insights into the complex mixture of factors which determine the occurrence of poststroke depression.

Advice to individuals involved in misconduct accusations.

The author offers advice to faculty, students, and staff who become involved in issues of research misconduct, whether as the accuser or as the accused. After reviewing the different definitions of research misconduct used by various authorities and discussing other kinds and degrees of misconduct, he provides information to those who suspect research misconduct, to help them identify their responsibilities and the risks involved: he makes it clear that an accusation of research fraud or other misconduct has serious consequences for all parties. The author then discusses how to pursue concerns about improper research practices, emphasizing a nonconfrontational approach and the use of proper channels for reporting. He explains the process of a formal review, including characteristic institutional responses; the role of the Office of Research Integrity; and when to seek the advice of an attorney. He argues that education is clearly preferable to denunciation as a way to improve scientists' ethics and practices. The author then gives similarly detailed advice to the accused, including a caution not to take criticism of methods or results as an accusation of fraud. He discusses the significances of the two stages of review of an allegation of misconduct, with practical advice for cooperative participation in any review; use of legal counsel; the importance of avoiding retaliation; information about due process and material evidence; the impact of a formal investigation; peer standards for evaluating misconduct; and the unavoidable discomfort that the accused will experience during the lengthy process. He advises that practicing good science is the first step in avoiding this unpleasant experience.

Intravascular bronchioloalveolar tumor of the lung presenting as pulmonary thromboembolic disease and pulmonary hypertension.

Intravascular bronchioloalveolar tumor, the pulmonary counterpart of epithelioid hemangioendothelioma, typically presents as bilateral pulmonary nodules in young women. We report a case of intravascular bronchioloalveolar tumor that clinically mimicked acute pulmonary thromboembolic disease initially and was subsequently proven to have pulmonary hypertension with right ventricular dysfunction by angiography. The diagnosis of intravascular bronchioloalveolar tumor was confirmed by immunohistochemical and ultrastructural studies after it was suspected on routine histologic examination. In addition, the tumor cells expressed glycoprotein cell adhesion molecule CD44, which has been implicated in increased tumor invasiveness and metastasis in various carcinomas and several aggressive non-Hodgkin's lymphomas.

Stroke outcome in elderly people living alone.

We prospectively followed 178 elderly people living alone prior to stroke who survived at least 30 days. At the time of hospital discharge and at months 2, 6 and 12 post-stroke one-third of survivors were living alone and half were living at home, either alone or with another person. Seventy-five per cent of survivors discharged to live alone were still living alone 6 months after stroke. Subjects discharged to live alone did not differ from other subjects with respect to age, gender or pre-stroke Barthel ADL score. The group discharged to live alone had less severe stroke deficits and higher ADL scores 1 week after stroke. This difference in ADL scores was maintained at hospital discharge and maximal recovery. Eleven variables were significant univariate predictors of discharge home to live alone. In multivariate models the strongest predictors of discharge home to live alone were high Barthel ADL score at day 7, high Mini-Mental State Score, high leg power and absence of homonymous hemianopia.

Comparison of patients with central sleep apnea. With and without Cheyne-Stokes respiration.

This study was designed to determine the impact of central sleep apnea with or without Cheyne-Stokes respiration (CSR) on morbidity and mortality. Central sleep apnea was found in 77 male general medical ward in-patients. Cheyne-Stokes respiration was found in 49 of the 77 men; in 15 men, CSR was severe, ie, > or = 25 percent of the night spent in CSR, in 34 men CSR was mild (1 to 25 percent CSR). Twenty-eight men had central sleep apnea but no CSR. An additional 31 patients had no sleep apnea and no CSR. The patients with severe CSR had more central apneas, more, but shorter desaturations, more awakenings and more wake time during the night, but spent more time in bed than those with no CSR or no apnea. Radiographic evidence was consistent with an association of CSR and heart failure. In addition, patients with severe CSR were at almost twice the risk of dying compared with those with no apnea and had a shorter survival time. Nevertheless, we could not confirm that CSR was an independent predictor of elevated mortality risk, implying that some other factors specific to severe CSR predispose these patients to shorter survival time.

Integrity in the education of researchers.

Great efforts are being made to provide training in appropriate research practices, but less is said about how trainees should be treated and how this treatment will affect the ethics they will absorb from the research environment rather than from the ethics training. Research laboratories by definition create tension between the productivity needed on a project that is essentially the intellectual property of the faculty investigator and the goals and needs of the trainee for education. After examining issues involved in how trainees are recruited to laboratories, the authors discuss some of the ethical problems that routinely arise in the laboratory setting. The faculty preceptor has clear obligations to trainees, such as assistance in the development of the trainee's research work, ongoing supervision, feedback, and interaction, training in oral and written presentations, and mentoring in complex issues of contemporary science. Increasing commercialization of research presents additional difficulties for both preceptor and trainee. Finally, both are concerned with issues of completion and separation, about the end of the training relationship and the beginning of the trainee's professional career. The authors conclude that it is not enough to rely on the traditional approach of transmitting ethical and technically valid research practices "by example"--being a preceptor now carries with it an obligation to inculcate these standards consciously and systematically.

Semi-quantitative SPECT scanning in acute ischaemic stroke.

We performed semi-quantitative SPECT scans using 99mTcm-HMPAO on 34 elderly subjects 10-15 days after ischaemic stroke. Each cerebral hemisphere was divided into five regions of interest. Asymmetry scores were determined for ten slices in each region using activity ratios to the other hemisphere and to the ipsilateral cerebellum. Outcome was assessed by maximal Barthel ADL score during the first two months after stroke. Asymmetry scores in the hemisphere involved by the stroke event were much higher than those in the opposite hemisphere. Subjects with poor outcome (maximal Barthel 0-12) had significantly higher asymmetry scores than those with good outcome (Barthel 13-20). The total asymmetry score (both hemispheres) and the score of the involved hemisphere predicted Barthel ADL score in a general linear model. Total asymmetry score remained a significant predictor of maximal Barthel score in multivariate models. Thus semi-quantitative SPECT scanning is of value in predicting functional recovery after stroke.

Three views on faculty tenure in medical schools.

Three distinguished academicians share their thoughts on tenure and its future in academic medicine. Paul J. Friedman, from the University of California, San Diego, School of Medicine, explains and defends tenure as practiced in medical schools. He examines the question of giving tenure to clinical faculty, explains posttenure academic review, reports that the impending end of mandatory retirement will not have a significant effect on faculty turnover, and suggests that medical schools make the status of emeritus faculty more attractive. Next, Gail H. Cassell, from the University of Alabama School of Medicine, examines various beliefs about tenure and tenured faculty in the light of available studies, and concludes that many of the negative "myths" about the effect of tenure (e.g., promoting mediocrity and discouraging productivity) are not borne out by research findings. While she supports tenure, she maintains that better criteria are needed for awarding it; that the evaluation of faculty members' teaching needs much improvement; and that more research on tenure is needed. Finally, Richard A. Cooper, from the Medical College of Wisconsin, states that tenure should not continue, because the purposes of tenure (e.g., ensuring freedom of expression; providing long-term financial security and stability) should be and can be accomplished in other ways for all faculty, not just tenured faculty. A different system is needed, one that respects the value of all faculty, that responds to their diverse objectives, is fiscally responsible, and fosters the continuing culture and vitality of medical schools.(ABSTRACT TRUNCATED AT 250 WORDS)