Protection against bronchial asthma by CFTR delta F508 mutation: a heterozygote advantage in cystic fibrosis.

Cystic fibrosis (CF) is a multisystem autosomal recessive disorder caused by mutations of the cystic fibrosis transmembrane regulator (CFTR), a protein that regulates cyclic-AMP-mediated chloride conductance at the apical membrane of secretory epithelia. Mutations in the CFTR gene are common in many populations. In North America, 4-5% of the general population are heterozygous for a CFTR mutation. Although there are over 400 known CFTR mutations, a single mutation, a deletion of the phenylalanine at position 508 (delta F508) in exon 10, accounts for about 70% of all CF chromosomes worldwide. The reasons for the high frequency of the delta F508 CFTR allele--the selective advantage associated with CF heterozygosity--are unknown. Many physiological abnormalities have been observed in CF heterozygotes, although the clinical significance of these observations is unknown. Preliminary unpublished data and anecdotal information from CF families suggested that, remarkably, the delta F508 allele might protect heterozygotes against bronchial asthma prompted us to further investigate this possibility. Here we present evidence that the delta F508 CF allele protects against asthma in childhood and early adult life.

Tobacco sales in pharmacies: time to quit.

OBJECTIVE: To assess the pharmacy profession's perceptions of tobacco sales in US pharmacies and explore whether a policy prohibiting sales of tobacco in pharmacies would alter adult consumer shopping behaviour. SUBJECTS AND DESIGN: In California, surveys were administered to 1168 licensed pharmacists and 1518 pharmacy students, and telephone interviews were conducted with 988 adult consumers. RESULTS: Most (58.1%) licensed pharmacists were strongly against sales of tobacco in pharmacies, 23.6% were against it, 16.7% were neutral, 1.2% were in favour of it, and 0.4% were strongly in favour of it. Pharmacists who were current tobacco users were more likely to be in favour of tobacco sales in pharmacies than were pharmacists who were current non-users (p < 0.005). Similar statistics were observed for pharmacy students. Most consumers (72.3%) disagreed with the statement, "I am in favour of tobacco products being sold in drugstores"; 82.6% stated that if the drugstore where they most commonly shopped were to stop selling tobacco products, they would shop there just as often, 14.2% would shop there more often, and 3.2% would shop there less often. CONCLUSION: Little professional or public support exists for tobacco sales in pharmacies.

Frequency of ethical dilemmas in a medical inpatient service.

We studied the frequency of ethical problems in a general medical ward at a university hospital, using a quasi-experimental prospective design. In the baseline period, ethical problems were determined by self-report of residents. In the intervention period, one of us (B.L.) was a participant-observer during attending rounds. Ethical problems were determined by consensus among the attending physician, resident, and participant observer. No significant differences between baseline and intervention periods were found in patient variations, admissions per resident, or rating of each resident's sensitivity to ethical issues. In the baseline period, seven (3.9%) of 179 cases involved ethical problems. In the intervention period, 16 (17%) of 92 cases involved ethical problems. This difference was significant. The data imply that residents underidentify ethical problems but that sensitization, sympathetic listening, information, and advice increase physician recognition of ethical problems.

Frequency and morbidity of invasive procedures: report of a pilot study from two teaching hospitals.

The medical services of two teaching hospitals were assessed for the frequency of and complications from invasive procedures. There were 231 procedures performed on 303 patients. The frequency of procedures was significantly higher at one hospital (62% vs 39%, P less than .01). Twenty-nine complications occurred in 20 cases: 14% of patients who underwent procedures had at least one complication. Left-sided cardiac catheterization was the most common procedure. Procedures with more than one complication included the following: left-sided cardiac catherization (18% probability of complication); arteriovenous shunt (60% probability); thoracentesis (19%); bronchoscopy (25%); and percutaneous liver biopsy (8%). While no permanent damage or deaths were observed, over three fourths of the complications either required specific therapy or prolonged hospitalization or both. This study suggests invasive procedures are common and carry appreciable risks of serious complications. Appropriate clinical decision making and medical-legal protection require accurate estimates of those risks.

Spontaneous pneumothorax in children with AIDS.

The incidence of pneumothorax in HIV-infected children has not been reported. In adults with AIDS, pneumothorax has been described exclusively in association with Pneumocystis carinii pneumonia (PCP). We report the cases of three children with AIDS, one with lymphoid interstitial pneumonitis (LIP) without evidence of PCP and two with PCP, all of whom developed spontaneous pneumothorax (SP). On presentation, none of the children had any risk factors for the development of pneumothorax, but all had radiographic evidence of subpleural cystic lesions and bilateral pleural adhesions. None of the patients responded to conservative medical management, which included chest tube thoracostomy and chemical pleurodesis. Two patients underwent pleurectomy that resulted in resolution of the pneumothorax. Both patients with PCP who developed pneumothorax died, but the patient with LIP and SP has had no recurrences of any serious respiratory problems 3 years after pleurectomy and excision of the intrathoracic cysts.

Cellular interstitial pneumonitis in infants. A clinicopathologic study.

Five infants had interstitial pneumonitis with constant histologic findings, which was different from that previously described in children. All the infants presented with tachypnea at birth and persistent disease, both clinically and radiographically, despite treatment. Open-lung biopsy in each case showed a diffuse interstitial thickening due to pale oval and spindle-shaped histiocytes without scarring. This neonatal cellular interstitial pneumonitis differs both clinically and histologically from the usual interstitial pneumonitis, lymphocytic interstitial pneumonitis and desquamative interstitial pneumonitis observed in adults and children. The etiology of this cellular interstitial pneumonitis in neonates is unknown.

Cost containment in U.S. health care.

The author explains why supply factors, particularly the overdevelopment of the nation's medical capacity, are more important than demand factors in explaining the high use and cost of U.S. health care. Yet such costly care often does not translate into better health for Americans. While market forces, especially the efficiencies fostered by managed care, may clear some of the excess acute-care capacity and foster the use of less-costly generalist physicians, such forces favor the strong over the weak. This makes vulnerable those persons without health insurance or on Medicaid only, inner-city and rural hospitals, and academic medical centers. And when health care is treated as a market product, the relationship between doctors and patients is endangered. The author urges that the effects of managed care be watched, particularly for possible neglect of the underserved and for diminished employment opportunities for all health professionals, especially nurses and certain specialists. He thinks it is likely that much of the savings that market forces will create will not stay in the health care sector (where they could be used to expand services for the uninsured, for example) but will go into the business side of health care (e.g., to pay shareholders' dividends). And he stresses that issues of adverse selection, risk adjustment, and outcomes measurement will have increasing importance to persons with chronic illnesses, who may be neglected.(ABSTRACT TRUNCATED AT 250 WORDS)

Training an appropriate mix of physicians to meet the nation's needs.

Although the lack of a national policy on medical manpower has served U.S. medicine well in some ways, it also has created problems, the most important of which is the maldistribution of physicians in the various specialties, with too many specialists and not nearly enough generalists. The author explains why this imbalance is a problem and why it is receiving so much attention, describes three types of forces--economic, practice-related, and scientific--that favor the practice of specialty medicine, and demonstrates that the medical school experience itself may be a critical influence on students' career decisions. He then outlines possible ways to correct the imbalance, both outside and inside academic medicine; for the latter sphere, he proposes five detailed alternative scenarios of how corrective change might come about, which range from doing nothing to making a number of fundamental changes within academic medicine's institutions to having external financial pressures for change brought to bear by the states and the federal government. In conclusion, the author notes that some combination of these scenarios will occur, because spending for medical care in the United States is out of control and cannot be reduced unless the distribution of physicians by specialty is rebalanced to have a much greater percentage of generalists. His hope is that academic medicine will accept this challenge and bring about the best mix of physicians to meet the nation's needs.

Understanding health behavior and speaking out on the uninsured: two leadership opportunities.

The author reviews the growth of managed care and its transforming effect on academic medical centers. He then maintains that in this time of fundamental changes and stress, academic medical centers should not only attend to the organization and financing of the clinical enterprise and the enhancement of biomedical research capacity, but also ask how academic medicine can live up to the unique opportunities and responsibilities it has been entrusted with to improve the health of the public, particularly in two neglected areas. First, if the nation does not expand the research agenda to include social and behavioral factors involved in preventable causes of morbidity and mortality, it will fail to maximize the dividends from the generous public investment in research and fail to learn how to promote healthy personal behavior. Academic medicine can promote such behavior by increasing the science base of prevention and translating into action what is already known, including how to market that knowledge so the public will respond. Second, the number of the medically uninsured is increasing; the largest percentage are the working poor. It is becoming more difficult for teaching hospitals to continue providing a third of the nation's uncompensated care. The author shares a variety of statistics about the uninsured and their care, and maintains that academic medicine, which has been entrusted with the health of the public, can declare that the high number of the uninsured is not acceptable and is a dangerous side effect of the U.S. health care system that must be treated. Doing so will also set an example to medical students and trainees that medicine's responsibility is to all Americans.

Specialty choices at one medical school: recent trends and analysis of predictive factors.

Recent reports have raised the concern that personal care specialties, especially primary care specialties, are attracting fewer medical school graduates. In the present study, the authors evaluated the proportions of University of California, San Francisco (UCSF), medical school graduates entering personal care specialties and technology-oriented specialties from 1982 through 1988 and found no significant trend away from personal care specialties such as internal medicine, family practice, pediatrics, and psychiatry during these years. For the graduating class of 1988, admissions and questionnaire data were used to evaluate the importance of pre-admission, medical school, and postgraduate factors as determinants of specialty choice. The group entering personal care specialties (66% of all 1988 graduates) was significantly older and included more women and fewer minority students than the group entering technology-oriented specialties. Students rated income and lifestyle factors as being less important determinants of specialty choice than are medical school experiences and intrinsic qualities of the chosen specialties. However, compared with the students who entered personal care specialties, those who chose technology-oriented specialties over an alternate choice in personal care rated as significantly more important the opportunity to do procedures (p less than .001), income (p less than .005), the lesser degree of diagnostic uncertainty (p less than .005), and the rejected specialty's allowing less time for family (p less than .005) and for other interests (p less than .008). Exposure to acquired immunodeficiency syndrome and loan indebtedness were rated the least significant influences on specialty choice.(ABSTRACT TRUNCATED AT 250 WORDS)

Merchandising of cigarettes in San Francisco pharmacies: 27 years later.

OBJECTIVE: To estimate changes since 1976 in the proportion of San Francisco pharmacies that sell cigarettes and to characterise the advertising of cigarettes and the merchandising of non-prescription nicotine replacement therapy (NRT) products in these retail establishments. METHODS AND SETTING: 100 randomly selected San Francisco pharmacies were visited in 2003. Pharmacies were characterised based on the sale of cigarettes, advertising for cigarettes, and the merchandising of non-prescription NRT products. RESULTS: In 2003, 61% of pharmacies sold cigarettes, a significant decrease compared to 89% of pharmacies selling cigarettes in 1976 (p < 0.001); 84% of pharmacies selling cigarettes also displayed cigarette advertising. Non-prescription NRT products were stocked by 78% of pharmacies, and in 55% of pharmacies selling cigarettes, the NRT products were stocked immediately adjacent to the cigarettes. CONCLUSIONS: Since 1976, there has been a decline in the overall proportion of pharmacies in San Francisco that sell cigarettes yet most pharmacies, particularly traditional chain pharmacies, continue to merchandise the primary known risk factor for death in the USA.

The importance of relating medicine and public health.

The historical division between medicine and public health is arbitrary and not in the best interest of the health of the American public. Combating the major causes of death and disability requires integration of medicine and public health by government and academia.

Structure, dynamics, and stability of beta-cyclodextrin inclusion complexes of aspartame and neotame.

Studies of the high-intensity sweetener aspartame show that its stability is significantly enhanced in the presence of beta-cyclodextrin (beta-CyD). At a 5:1 beta-CyD/aspartame molar ratio, the stability of aspartame is 42% greater in 4 mM phosphate buffer (pH 3.1) compared to solutions prepared without beta-CyD. Solution-state (1)H NMR experiments demonstrate the formation of 1:1 beta-CyD/aspartame complexes, stabilized by the interaction of the phenyl-ring protons of aspartame with the H3 and H5 protons of beta-CyD. Inclusion complex formation clearly accounts for the observed stability enhancement of aspartame in solution. The formation of inclusion complexes in solution is also demonstrated for beta-CyD and neotame, a structural derivative of aspartame containing an N-substituted 3,3-dimethylbutyl group. These complexes are stabilized by the interaction of beta-CyD with both phenyl-ring and dimethylbutyl protons. Solid-state NMR experiments provide additional characterization, clearly demonstrating the formation of inclusion complexes in lyophilized solids prepared from solutions of beta-CyD and either aspartame or neotame.

Managing the U.S. health care workforce: creating policy amidst uncertainty.

Managing the health care workforce will have important implications for costs, quality, and access. Factors influencing supply include the production of new professionals, their relative effort, and rates of retirement. Demand will depend upon the development of new diseases, new drugs, and technologies, as well as the growth of managed care, which uses fewer physicians, fewer specialists, and more midlevel practitioners. There is a general consensus that there are too many physicians, especially specialists. Reducing the number of residency positions would reduce supply, predominantly by slowing importation of international physicians. Obstacles to workforce reform include a distrust of supply projections, skepticism about governmental planning, conservatism of established institutions, and the reality that some hospitals would lose positions and resources.

What's so special about special care?

Special care units are the most advanced, intensive, technological, and costly of hospital services. They also have proliferated rapidly. Yet little is understood about the definition, prevalence, genesis, costs, or benefits of SCUs. This paper defines and examines the many forces that have promoted the growth of special care, including hospital cost containment policies, fee-for-service reimbursement, medical ethics, standards of care, and manpower, and the much less numerous forces that have inhibited its spread. It is concluded that a sound appreciation of the dynamics of SCUs will be crucial to guiding future policy decisions as the nation's population ages and as hospitals continue to improve their capability to care for critically ill patients.

An interview with Steven A. Schroeder.

In 1972, with a ! billion endowment from the immense personal fortune left by the late Robert Wood Johnson, the Robert Wood Johnson Foundation became the world's largest health care philanthropic organization. Now, with a new chairman of the board, Sidney F. Wentz, and president, Steven A. Schroeder, MD, the foundation has revised its overall grant-making prospectus. In this interview, Dr. Schroeder discusses the foundation's grant-making strategies and health manpower projects, forces affecting the U.S. health care system, and his vision for health care over the next decade.

Person of the year. Steven A. Schroeder, MD.

The mission of the Robert Wood Johnson Foundation is to improve the health and health care of all Americans. An ambitious goal, but the Foundation has the financial resources to do just that. The Foundation also has another resource: President and Chief Executive Officer Steven A. Schroeder, MD, who has led the philanthropic organization since 1990. For his work with the Robert Wood Johnson Foundation, Dr. Schroeder is New Jersey Medicine's 1999 Person of the Year.

Medical costs crisis: Part 1. Doctors as culprits, victims--and keys to the solution.

Although the rising cost of US medicine actually reflects the "good news" about the improved quality and availability of health care today, physicians are increasingly being pressed to achieve cost containment. The causes of the problem are identified as supply-and-demand factors that have been obscured during more economically abundant periods, but that now are forcing reevaluation of such accepted practices as fee-for-service payment. Evaluation of these factors leads to suggestions for measures that could help to reduce costs.

Medical costs crisis: Part 2. How to regain control while retaining quality of care.

Physicians often are singled out as major culprits in driving up the cost of health care, principally because of our role in ordering tests and in employing technologically advanced diagnostic procedures. In fact, these activities play a much smaller part in cost increases than has been thought. The forces actually responsible are the fundamental medical decisions we make on hospitalization, major surgery, intensive care, and the like. Tighter control of these decisions, which have so altered the dimensions of medical care costs, call for reexamination of our basic uses of medical manpower as well as better allocation of our technologic and physical resources.