Why is academic medicine run by former C-students?

The present paper hypothesizes that the top positions in academic medicine are generally occupied by less talented and skilled physicians who find more time to spare for administrative activities as compared to physicians who are successful in their research projects or enjoy their skills as practicing clinicians. A physician's utility in advancing a medical career can be modeled as the product of two preferences, administration and biomedical work, weighted by time and talent, respectively. It corresponds with a characteristic Cobb-Douglass utility function of economics, which physicians will try to maximize in pursuing their preferences. The utility function becomes maximized if the split between administration and research mirrors the split between free time and talent, respectively. Physicians with few talents and lots of time to spare will accumulate in administration and politics, whereas those with talents and little time will remain committed to biomedical research or clinical practice.     

Hospital discharges resulting from esophagitis among medicare beneficiaries

Despite the frequent occurrence of gastroesophageal reflux disease, until now only very few studies have dealt with the epidemiology of this common disorder. The Health Care Fionancing Administration compiles annually 10 million records of all hospital discharges among Medicare beneficiaries distributed throughout the United States. The purpose of the present study was to take advantage of this large data set and analyze the demographic characteristics of patients discharged with esophagitis, esophageal ulcer, or esophageal stricture. The hospital discharge rates of all three diagnoses showed an age-related rise, the rise being most pronounced for esophageal stricture and, less significant, esophageal ulcer. The marked age dependency of esophageal stricture and ulcer may reflect the time necessary for complications to develop. While simple esophagitis affected women more frequently than men, significantly more men contracted its severe forms involving ulcers and strictures. All forms were more common in whites than blacks, and living in the southern parts of the United States was associated with an increased risk for esophagitis and strictures. The data suggest that besides varying exposure to environmental risk factors, differences in the pathophysiology among demographically stratified groups contribute to the occurrence of esophagitis.     

Genotype-by-smoking interaction for leptin levels in the Metabolic Risk Complications of Obesity Genes project

RATIONALE: Recently, we identified a genotype-by-smoking status interaction with serum leptin levels in a sample of Mexican Americans. However, it is unknown whether this phenomenon occurs in other populations as well. OBJECTIVE: The goal of this study was to examine the genetic architecture of the response to smoking in leptin levels using data from Midwestern Caucasian subjects participating in the Metabolic Risk Complications of Obesity Genes project. METHODS: We employed a variance decomposition analysis using maximum likelihood methods to model genotype-by-smoking interactions for leptin levels and examined the impact of the exclusion of smokers in a subsequent linkage analysis. RESULTS: We found significant evidence (p-value=0.027) for a genotype-by-smoking status interaction for serum leptin levels. In the subsequent linkage analysis with smokers excluded, we obtained a maximum LOD score of 3.4 (P=0.00004) near D8S1128. CONCLUSIONS: These results suggest that a QTL on chromosome 8 may have a differential effect on the expression of leptin in smokers vs nonsmokers, as first identified in Mexican Americans.     

Effect of pretreatment with anticonvulsants on theophylline-induced seizures in the rat

Seizures, often with fatal outcome, are a manifestation of pronounced theophylline toxicity. Prodromal symptoms are not always apparent, and the seizures are reported to be, in certain cases, refractory to treatment with anticonvulsant drugs. The purpose of this investigation was to examine, by an established animal model, which of the commonly used anticonvulsants can reduce the central nervous system sensitivity to theophylline neurotoxicity and what should be the preferred treatment in cases in which theophylline toxicity is anticipated. The anticonvulsant agents in doses that are found to be effective in other types of experimentally induced seizures in rats, clonazepam 5 mg/ kg, diazepam 5 mg/kg, phenytoin 8 mg/kg, phenobarbital 100 mg/kg, valproic acid 150 mg/kg, and magnesium sulphate 300 mg/kg, or the vehicle (controls) were administered intravenously to Lewis female rats. Thirty minutes later, theophylline was infused at a constant rate of 1.3 mg/min until onset of maximal seizures. Theophylline concentrations in the cerebrospinal fluid, brain, and serum were assayed by a high-performance liquid chromatography method. It was found that pretreatment with either clonazepam, diazepam, phenobarbital, or valproic acid increased the central nervous system thresholds to the theophylline-induced seizures, whereas phenytoin and magnesium sulphate did not attenuate the sensitivity of the brain to the stimulatory action of this widely used bronchodilator. Therefore, whenever theophylline toxicity is suspected, treatment with either diazepam, clonazepam, phenobarbital, or valproic acid can reduce the hazard associated with theophylline-induced seizures.     

Cost-effectiveness of endoscopy in irritable bowel syndrome

BACKGROUND: It is unknown to what extent at what expense flexible sigmoidoscopy and colonoscopy add to the diagnosis of irritable bowel syndrome (IBS). The aim of the study was to assess the incremental cost-effectiveness of endoscopic procedures in the workup for IBS. METHODS: Using the Bayes formula, we calculated the increase in diagnostic certainty for a consecutive number of tests. We also calculated the incremental cost-effectiveness ratio, which corresponds to the test costs divided by the increment in diagnostic certainty. RESULTS: The diagnosis of IBS can be established with a relatively high probability of more than 80% relying on relatively inexpensive and noninvasive tests only. Flexible sigmoidoscopy or colonoscopy constitute the most costly portion of any workup for IBS, which amounts to 50% to 75% of the overall costs. Because of their high incremental cost-effectiveness ratio, endoscopic procedures should not be used at the beginning of the diagnostic workup. This outcome of the analysis remains largely unaffected within reasonable ranges of the sensitivity and specificity of various tests. CONCLUSIONS: In the diagnosis of IBS, inexpensive, noninvasive tests should be used first to rule out other diagnoses. Despite their high incremental cost-effectiveness ratio, flexible sigmoidoscopy and colonoscopy are indicated when a serious organic disease is reasonably likely and needs to be ruled out.     

Hospital discharges for inflammatory bowel disease

The present study analyzes time trends of inflammatory bowel disease (IBD) in England-Wales and the United States based on nationwide hospitalization statistics. Because these statistics cover the total population of each country, they may give a more representative picture of the true trends than previous analyses concerning only one region or health center. The Hospital In-patient Enquiry was used to evaluate time trends in England-Wales from 1962 to 1985, data from the National Hospital Discharge Survey and the Commission on Professional Activities were used for trends in the United States from 1970 to 1987. A rise of Crohn's disease persisted unabated in the old age groups throughout the observation period. It was less marked in those aged under 35 and reached a plateau during the most recent decade. In ulcerative colitis, discharge rates increased in the older age groups, but remained constant or declined in the middle or younger age groups, respectively. Similar trends were observed in all three surveys. The hospitalization data confirm similar age-specific trends of mortality. The difference between younger and older age groups suggests that generations born 60–80 years ago have become more likely to be affected by IBD leading to hospitalization and mortality. As these high-risk generations grow older, there is a relative rise of hospitalization and mortality from IBD in these subjects.Supported by grant So 172/1-1 from the Deutsche Forschungsgemeinschaft.     

Cys 618 Arg mutation in the RET proto-oncogene associated with familial medullary thyroid carcinoma and maternally transmitted Hirschsprung's disease suggesting a role for imprinting

The multiple endocrine neoplasia type 2 (MEN2) syndromes and Hirschsprung's disease (HSCR) are inherited neurocristopathies characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, parathyroid disease, and gastrointestinal neuromatosis. Mutations in the RET proto-oncogene are the underlying cause of the MEN2 syndromes and some cases of HSCR. In this report, we show that Cys 618 Arg mutation cosegregates with familial MTC and HSCR in two Moroccan Jewish families in which no involvement of pheochromocytoma or parathyroidism was observed. A single haplotype shared by chromosomes bearing the Cys 618 Arg mutation in both families strongly suggests a founder effect for this mutation. We have observed in our and in several other previously reported families, an excess of maternal over paternal mutated RET alleles in offsprings affected by HSCR. We suggest that parental imprinting may play a role in the ethiology of HSCR caused by mutations in the RET protooncogene. Hum Mutat 10:155–159, 1997. © 1997 Wiley-Liss, Inc.     

Stability and change of emotional functioning in late life: modelling of vulnerability profiles

BACKGROUND AND AIMS: The present study investigated stability and change in emotional well-being in a prospective study of a large sample of community-dwelling older adults (> or = 55 years). Emotional functioning was conceptualized according to the tripartite model distinguishing three aspects: general negative affect (NA), depression, and anxiety. The study tested models for the decline of mental health in late life based on the diathesis-stress model. In previous studies, support has been found for the diathesis-stress model (for an overview, see [Goldberg, D.P., Huxley, P., 1992. Common mental disorders: a biosocial model. Routledge, London; Zuckerman, M., 1999. Vulnerability to psychopathology. American Psychological Association, Washington, DC.]). The predictive ability of vulnerability factors (the personality characteristics mastery and neuroticism) and stressful life events and their interaction was tested for an increase in general negative affect, decreased positive affect (PA), and increased anxiety. More specifically, we tested the hypothesis that loss leads to decreased positive affect in subjects with low mastery, whereas threat leads to anxiety in subjects with high neuroticism. METHODS: Data from the Longitudinal Aging Study Amsterdam (LASA) were used. LASA is a longitudinal study in a large representative sample of adults aged 55 to 85 (N=1837). Self-report data on depression, anxiety, and negative affect were collected from adults over a 6-year period in three waves. The data were analyzed using multilevel analysis. RESULTS: The findings revealed an association between low mastery, high neuroticism, and an increase in negative affect, lack of positive affect, and anxiety. Furthermore, high mastery protected against the negative impact of loss events, but neuroticism did not augment the negative impact of threat events on emotional health. CONCLUSION: Partial support was found for a diathesis-stress model of change in emotional functioning in late life. Furthermore, support was found for distinguishing between symptoms of negative affect, depression, and anxiety.     

Use of antibody avidity assays for diagnosis of severe acute respiratory syndrome coronavirus infection

An indirect immunofluorescent assay (Euroimmun AG, Luebeck, Germany) was used to investigate the avidity of immunoglobulin G (IgG), IgM, IgA, and total Ig (IgGAM) antibody responses to severe acute respiratory syndrome coronavirus (SARS CoV) infections. Serial serum samples from eight patients collected during the first, third, and ninth months after the onset of infection were evaluated. It was found that low-avidity IgG antibodies were detected in 15/15 (100%), 1/5 (20%), and 0/8 (0%) serum samples collected during the first, third, and ninth months after the onset of symptoms, respectively. Low-avidity antibodies of IgA and IgM subclasses were detected in 14/14 (100%) and 3/14 (21%) serum samples, respectively, collected in the first month after the onset of infection. However, IgA antibodies remained low in avidity in a proportion of patients even during late convalescence. As a consequence, IgG antibody avidity assays gave better discrimination between acute-phase and late-convalescent-phase serum samples than IgM, IgA, or IgGAM assays. In two of these patients, sequential serum samples were also tested for IgG avidity against human CoV strains OC43 and 229E in parallel. While SARS CoV infections induced an anamnestic IgG antibody response to the 229E and OC43 viruses, these cross-reactive antibodies remained of high avidity from early (the first month) postinfection. The results showed that assays to detect low-avidity antibody may be useful for discriminating early from late antibody responses and also for distinguishing anamnestic cross-reactive antibody responses from primary specific responses. This may be useful in some clinical situations.