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.     

Lack of seasonal variation in the endoscopic diagnoses of Crohn's disease and ulcerative colitis

BACKGROUND: Conflicting data have been reported about the seasonal variation of inflammatory bowel diseases (IBD). The purpose of the present analysis was to assess the occurrence of seasonal variations in the endoscopic diagnosis of Crohn's disease (CD) and ulcerative colitis (UC). METHODS: The Clinical Outcomes Research Initiative (CORI) uses a computerized endoscopic report generator to collect endoscopic data from 73 diverse practice sites throughout the United States. We utilized the CORI database to analyze the date-specific occurrence of colonoscopy, as well as the colonoscopic diagnoses of CD and UC. Time trends were analyzed by autocorrelation, linear, and nonlinear regression. RESULTS: Between January 2000 and December 2003, the number of colonoscopies increased 4.1-fold. The proportion of colonoscopies with a CD diagnosis fell by 28%, and the proportion of colonoscopies with a UC diagnosis fell by 50%. The occurrence of neither CD nor UC was shaped by any clear-cut seasonal periodicity. However, the trends of the two diseases revealed strikingly similar patterns with four resembling peaks superimposed on their monthly fluctuations. CONCLUSIONS: Endoscopic diagnosis of IBD is unaffected by any seasonal variation. The decline in the diagnostic rate of colonic IBD may reflect a relative increase in the utilization of colonoscopy for colon cancer screening. The similarity in the monthly fluctuations of both IBD suggests that their incidence or flare-ups may be influenced by identical exogenous risk factors.     

From the Cover: Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2

In the Ashkenazi Jewish (AJ) population of Israel, 11% of breast cancer and 40% of ovarian cancer are due to three inherited founder mutations in the cancer predisposition genes BRCA1 and BRCA2. For carriers of these mutations, risk-reducing salpingo-oophorectomy significantly reduces morbidity and mortality. Population screening for these mutations among AJ women may be justifiable if accurate estimates of cancer risk for mutation carriers can be obtained. We therefore undertook to determine risks of breast and ovarian cancer for BRCA1 and BRCA2 mutation carriers ascertained irrespective of personal or family history of cancer. Families harboring mutations in BRCA1 or BRCA2 were ascertained by identifying mutation carriers among healthy AJ males recruited from health screening centers and outpatient clinics. Female relatives of the carriers were then enrolled and genotyped. Among the female relatives with BRCA1 or BRCA2 mutations, cumulative risk of developing either breast or ovarian cancer by age 60 and 80, respectively, were 0.60 (± 0.07) and 0.83 (± 0.07) for BRCA1 carriers and 0.33 (± 0.09) and 0.76 (± 0.13) for BRCA2 carriers. Risks were higher in recent vs. earlier birth cohorts (P = 0.006). High cancer risks in BRCA1 or BRCA2 mutation carriers identified through healthy males provide an evidence base for initiating a general screening program in the AJ population. General screening would identify many carriers who are not evaluated by genetic testing based on family history criteria. Such a program could serve as a model to investigate implementation and outcomes of population screening for genetic predisposition to cancer in other populations.Inherited mutations in BRCA1 and BRCA2 predispose to high risks of breast and ovarian cancer. Among female mutation carriers, presymptomatic surgical measures significantly reduce morbidity and mortality (1, 2). In particular, risk-reducing salpingo-oophorectomy (i.e., the removal of ovaries and fallopian tubes from a woman without ovarian cancer) reduces risk both of breast cancer and of ovarian cancer, as well as overall mortality (1). However, for many mutation carriers identified following their first cancer diagnosis, genetic testing was not previously indicated because family history did not suggest inherited cancer predisposition (3–5, 6). From a prevention perspective, it is a missed opportunity to identify a woman as a BRCA1 or BRCA2 mutation carrier only after she develops cancer.Among Ashkenazi (European) Jews (AJ), three mutations, BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT, account for the great majority of inherited cancer risk due to BRCA1 and BRCA2 (7). In the AJ population, 2.5% of persons carry one of these three mutations (8), and the mutations account for 11% of breast cancer (3) and 40% of ovarian cancer (9, 10). These observations suggest that genetic testing in the AJ population for these mutations fulfills WHO criteria for population screening (11, 12): The disease is an important public health burden to the target population; prevalence and attributable risk of disease due to the mutations are known; and effective interventions exist. However, one necessary piece of information remains unknown: What is the disease risk to mutation carriers ascertained from the general population, rather than carriers identified based on family history (13)?Previous studies assessing cancer risks due to mutations in BRCA1 and BRCA2 ascertained carriers through high-incidence families (14), through a single index case with breast or ovarian cancer (3, 15) or through both affected and unaffected carriers (16). In a 1997 study of AJ volunteers, most index cases had no previous cancer diagnosis, but the percentage of index cases with a family history of breast cancer was approximately double that of unselected AJs (17). In principle, these strategies could have yielded risk estimates different from those of carriers ascertained from the local host population, if cancer risk in BRCA1 or BRCA2 carriers were influenced by familial factors other than the BRCA1 or BRCA2 mutation, such as modifier genes or shared environment (18). In addition, in almost all of these studies, risk estimates were based on imputing carrier status, rather than on direct genetic testing of BRCA1 and BRCA2. This year, the Recommendation Statement on BRCA Testing from the US Preventive Services Task Force recommended against population screening for BRCA1 and BRCA2 mutations, because cancer risk to mutation carriers in the general population was not yet known (19). To address this gap, in this study we assessed breast and ovarian cancer risks in confirmed carriers of BRCA1 and BRCA2 mutations ascertained from the general population. The study was undertaken in the AJ population, because screening for only three founder mutations is sufficient to capture nearly all inherited cancer risk in this population due to BRCA1 and BRCA2 (7).     

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.     

Deoxyribonucleic acid-damaged sperm in cryopreserved-thawed specimens from cancer patients and healthy men

A similarity was found between the percentage of thawed, DNA-damaged spermatozoa in cancer patients and that in candidates to become sperm bank donors who had low sperm cryofreezability. Both groups were significantly different from the sperm bank donor group. It is suggested that the higher rate of DNA fragmentation in sperm from cancer patients compared with sperm bank donors is apparently a result of selecting donors by the level of sperm cryofreezability (i.e., high), rather than a direct effect of an existing malignancy.