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.

Faculty retirement.

I would like to point out several errors of citation at the end of my article ;;Cocaine addiction: Psychology and neuropsychology'' (29 Mar., p. 1580). In the References and Notes, reference 42 was missing. It should have read, ;;42. T. Kosten et al., in preparation.'' Also in the References and Notes, reference 44 should have been numbered 43. In the text, citation 43 should have been numbered 41. In figure 3, the attribution was missing. It should have read, ;;Reprinted with permission from T. Kosten et al. (42).''

Computed tomographic analysis of meteorite inclusions.

The discovery of isotopic anomalies in the calcium- and aluminum-rich inclusions of the Allende meteorite has improved our knowledge of the origin of the solar system. Inability to find more inclusions without destroying the meteorite has hampered further study. By using a fourth-generation computed tomographic scanner with modifications to the software only, the interior of heterogeneous materials such as Allende can be nondestructively probed. The regions of material with high and low atomic numbers are displayed quickly. The object can then be cut to obtain for analysis just the areas of interest.

Eosinophilic granuloma of lung. Clinical aspects of primary histiocytosis in the adult.

One hundred cases of eosinophilic granuloma diagnosed by open lung biopsy were reviewed. There were 60 women and 40 men, ages 18 to over 60 years. Radiographs and clinical histories were contributed by physicians referring the cases for pathological consultation. Clinical follow-up information was obtained in 60 cases. The outcome was generally benign; the 16 asymptomatic patients remained well; 17 others had complete remission of symptoms, 22 had persistent symptoms, though half had partial improvement; 4 patients had progressive disease despite treatment, but only 1 patient died (of bilateral pneumothoraces complicating severe fibrosis). The more severe manifestations were found in young men, who had a higher incidence of pneumothorax, fibrosis and honeycombing, and diabetes insipidus. Many previously reported cases have had a less favorable outcome; milder cases of primary pulmonary histiocytosis have probably been overlooked in the past. In this series the prognostic value of histologic, clinical, or radiologic findings was limited. The diagnosis can often be strongly suggested radiologically, though infectious granulomata must be excluded; it is arguable whether exclusion of sarcoidosis is clinically important. The effectiveness of treatment with adrenal corticosteroids could not be assessed because of lack of controls; some individuals appeared to benefit, but relapse was very unusual in any case. The etiology of EG remains obscure, but in view of the paucity of patients with a history of allergy or asthma, and the lack of eosinophilia in any case, hypersensitivity seems unlikely. Smoking was far more common among these patients (97% altogether; 80% current) than in the general population (about 35%), an unexplained finding.

Treatment of coccidioidomycosis with ketoconazole: an evaluation utilizing a new scoring system.

The evaluation of the response of patients with coccidioidomycosis to any therapeutic modality is a major challenge. A numerical scoring system was devised to quantitate separately the severity of disease on clinical presentation, the findings on chest film, bone scan, gallium scan, serology and skin test with coccidioidin and spherulin. The scoring system was used to evaluate the response to treatment with ketoconazole of seven patients with infiltrate pulmonary coccidioidomycosis; 20 patients with chronic cavitary coccidioidomycosis; and 40 patients with disseminated coccidioidomycosis. Dissemination included the soft tissue in 15, bone in 15, synovium in 11 and skin in 18. In all categories clinical severity scores improved dramatically. Radiographic scores showed similar improvement in cases of infiltrative pulmonary coccidioidomycosis but showed no change in cavitary coccidioidomycosis. Serology scores improved significantly (-2 or more) in one of seven infiltrative pulmonary cases, three of twenty chronic cavitary cases and twenty-three of forty disseminated cases. Among those with adequate mycology followup, cultures converted to negative in two of three infiltrative pulmonary coccidioidomycosis; seven of fourteen chronic cavitary coccidioidomycosis; and sixteen of twenty-two with disseminated disease. Unfortunately, when ketoconazole was discontinued or interrupted, symptoms recurred in four of twenty (20 percent) with chronic cavitary and ten of forty (25 percent) of disseminated cases. The disease in two patients progressed while on ketonconazole. One of those developed meningitis.

Fluconazole in the treatment of persistent coccidioidomycosis.

Fluconazole is one of the new antifungal triazoles undergoing clinical trials. We used fluconazole at a dose of 50 or 100 mg/day in an open trial for the treatment of patients with persistent coccidioidomycosis. Fourteen patients were enrolled and treated for a mean of 13 +/- 7 months. Two failed to respond. Of the 12 who responded, one reactivated while being treated, and one died of myocardial infarction after successful treatment of his fungal infection; six had relapses from nine days to 15 months after treatment was stopped. Only four patients are asymptomatic at a mean of 14 +/- 3 months after cessation of treatment. Fluconazole is well tolerated at this dose. In view of its low toxicity, the partial clinical efficacy observed, and the high recurrence rate of chronic coccidioidal infection, it would be justified to try higher doses.

Restricted pulmonary function in cystic fibrosis.

Some patients with cystic fibrosis have reduced pulmonary volumes, indicating a restrictive pattern of pulmonary disease. We identified ten patients with pulmonary functional evidence of restriction among 158 patients with cystic fibrosis followed at the University of California San Diego Medical Center in 1984 and 1985. We characterized the radiographic, pulmonary functional, and clinical characteristics of these restricted patients compared to matched nonrestricted patients. Pulmonary volumes were measured by three different techniques: plethysmography; nitrogen washout; and radiography. Except for plethysmographic pulmonary volumes, there were no significant differences between the matched restricted and nonrestricted patients. Radiographic pulmonary volume tended to overestimate gas volume measured by the other techniques. Differences among these techniques (thought to represent air-space filling) correlated best with radiographic evidence of air trapping and bronchial markings and not with parenchymal lesions. Serial pulmonary function tests demonstrated changes in pulmonary volume in several patients and a trend toward improvement in pulmonary volume in the restricted patients over time. We conclude that restricted pulmonary function does not necessarily indicate more severe disease in patients with cystic fibrosis and may be reversible in some. The mechanism of restriction may be related more to radiographic evidence of airway disease than to parenchymal abnormalities.

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.

Measuring lung volumes from chest films using equations derived from computed tomography.

Computed tomographic scans show true cross-sectional area of a segment of the chest. Measurement of the cross-sectional area of the lung at several adjacent levels permits calculation of a geometrically defined volume. CT scans from 26 cases were used to derive equations to predict regional volume from measurements which can be obtained from plain PA and lateral chest films. Separate equations were derived for slices above and below the top of the diaphragm. The best correlation between linear dimensions and true volume was obtained with equations that used lung width and antero-posterior (AP) diameter of each scan, maximum AP lung diameter, and relative scan level (apex to base). These equations predicted the volumes of individual slices above the diaphragm with a correlation coefficient (r) of 0.99 on the right, 0.97 on the left. Below top of the diaphragm, r was 0.91 on the right, 0.92 on the left. Total lung volume was predicted with an r of 0.98 (s.e. 4.8%) on the right and 0.97 (s.e. 5.3%) on the left. Using total chest width instead of AP diameter of each slice reduced r to 0.96 for the volume of either lung. This method compares favorably with previous regression or geometric approximation methods for total lung volume and also makes it possible to obtain estimates of portions of lung volume from chest films.

Chest dimensions in young adults with spontaneous pneumothorax.

Chest dimensions measured from standard chest roentgenograms of 46 young adult patients with pneumothorax were compared with measurements from an age- and sex-matched control group. The ratio of men to women was 3:1. On the average, the male patients had longer chests and greater height-to-width ratios than the controls. The only significant difference between female groups was a diminished anteroposterior diameter in the patients with pneumothorax. The study suggests that the physical shape of the chest, probably because of stress distribution in the lungs, can play a major role in the development of spontaneous pneumothorax.

Aging of medical school faculty and the end of mandatory retirement.

In anticipation of the end of mandatory retirement for tenured professors in 1994 (mandatory retirement ended for other academics in 1986), the author analyzed the demographics of medical school faculty, using 25 years of data taken in mid-1989 from the Faculty Roster of the Association of American Medical Colleges. The annual growth rate of the number of full-time faculty dropped from well over 10% before 1972 to about 1.5% after 1982, while the mean age of the faculty increased from under 42 years to over 45 in 1988. Retirement patterns changed little after the minimum mandatory retirement age was raised in 1982 from 65 to 70 (for tenured professors). Only about 2.5% of all faculty separations in 1984-1987 occurred at or after age 70, and only 5.5% did even in the tenure tracks of the 20 largest private medical schools. Since such a small proportion of openings is created each year by mandatory retirement, uncapping will have little effect on the age or turnover of medical faculty.

Modelling the end of mandatory retirement for U.S. medical school faculty.

The author used data taken in mid-1989 from the Faculty Roster of the Association of American Medical Colleges to calculate the age distributions of U.S. medical school faculty active at any time from 1978 to 1988 and their age-specific probabilities of separating from their academic positions (e.g., to take another position, to enter the private sector, or to retire). A simple Markov model was constructed to predict the future faculty age distributions, isolating the factors of growth rate, separation probability, and potential delays in retirement. Age projections proved most sensitive to assumptions about future growth rate, less sensitive to the choice of separation probabilities within the range of those observed in the previous decade, and least sensitive to modelled delays in retirement of as much as five years for half the retiring faculty. The same pattern of sensitivity was true of projected turnover. The conclusion is that the end of mandatory retirement alone will have a negligible effect on medical faculty demographics.

Faculty renewal: modeling the impact of the end of mandatory retirement in the University of California medical schools.

The Age Discrimination in Employment Act was amended in 1986 to remove age-determined mandatory retirement for nearly all employees. The present study was prompted by the concern that if medical school faculty failed to retire, there would be no positions available for new faculty. The author used 1984-85 data on both tenure-track and non-tenure-track faculty of the five medical schools of the University of California (UC) to make projections, over 20 years, of faculty age distributions and available positions, at several possible growth rates and delays in retirement age. Association of American Medical Colleges data on all U.S. medical school faculty in 1980 were used to show that the UC data were not exceptional. Acknowledging the various assumptions used in manipulating the data and the need to examine longitudinal data on faculty age, growth, turnover, and retirement to make more realistic projections, the author demonstrates that the impact of delaying retirement by several years would be minimal. Because of this conclusion and also the inevitable aging of the faculty resulting from the slowed growth of medical schools, academic institutions should pay more attention to maintaining the vitality and productivity of their individual faculty members, regardless of age.

A last call for self-regulation of biomedical research.

The indecisive response of the academic community to well-publicized cases of research fraud or serious misconduct has been characterized as a failure of self-regulation. The Institute of Medicine (IOM) Report on the Responsible Conduct of Research suggests measures for improving the research environment, by a combination of more explicit definition of standards of acceptable research practices, appointment of individuals to promote research standards and to respond to charges or complaints, improvement of supervision of research trainee, teaching of research ethics as well as technical skills, and reduction of the pressure to publish. The National Institutes of Health was asked to ensure that research institutions take such actions by requiring assurances as a condition of research funding. This essay discusses the recommendations and implications of the IOM report.

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.

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.

A pilot study of biomedical trainees' perceptions concerning research ethics.

The authors surveyed 2,010 biomedical trainees in the fall of 1990 at the University of California, San Diego, regarding their perceptions about unethical practices in research and the extent of their training exposure to the ethics of scientific investigation; 549 responded, representing both clinical and basic science departments and including graduate students and postdoctoral fellows in addition to medical students, residents, and fellows. Of the 549 trainees, 129 (23%) responded that they had received no training in research ethics; 195 (36%), that they had observed some kind of scientific misconduct (although not necessarily in the sense of research fraud defined in federal regulations); and 81 (15%), that they would be willing to select, omit, or fabricate data to win a grant or publish a paper. The trainees planning an academic career were more likely to report having been aware of others' scientific misconduct. Reported exposure to ethics training was not associated with a difference in past or potential unethical behavior. The authors conclude that while the apparent ineffectiveness of past ethics instruction does not preclude the possibility that more systematic training may be useful, it does underscore the need to assess the efficacy of training activities.

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)

Computed tomography in lung cancer.

Computed-assisted tomography produces a cross-sectional image of the body using x-ray absorption measurements. Density differences are much more apparent than on conventional radiographs, although spatial resolution is not so fine. Lung cancer, can be evaluated accurately with regard to size, location, and whether regional or mediastinal lymph nodes are enlarged. Although enlarged granulomatous nodes generally tend to be dense, histologic specificity is not available. Computed tomography is recommended as a screening technique in lung cancer staging for patients whose routine radiographs are normal but whose primary lesions fulfill criteria for mediastinoscopy. If findings on computed tomography are normal, thoracotomy should then be performed; if enlarged nodes are detected, then a biopsy is needed to exclude operability. This strategy presumes that computed tomography has high sensitivity, although it remains to be proven by further experience whether the false-negative rate of computed tomography is an acceptable 10 to 15 percent. Computed tomography has been shown to be of considerable value in optimizing radiation therapy of lung cancer, and in diagnosing pleural complications of the cancer or its treatment.

Severe arm-muscle wasting: sign of lethal malnutrition in sick elderly men.

During a 3-yr period, I detected 29 sick men with severe muscle wasting defined by corrected arm-muscle area less than or equal to 16.9 cm2. Almost invariably, these men had weight and body mass index below the 3rd percentile. All had marked depletion of total-body muscle and protein mass, as evidenced by low urinary creatinine-height ratio and total-body nitrogen from neutron-activation analysis. Median survival was only 1.2 mo. Subjects were divided according to survival at 3 mo. The 8 survivors differed from the 21 who died in that they had higher energy intake and a greater chance of restoring muscle mass (5/8 vs. 0/21, P less than 0.001). Treatment of this lethal wasting state remains unsatisfactory. Hence, the most sensible approach is prevention.