A path analysis of medical school and residency performance. Implications for housestaff selection.

The selection and subsequent performance of 212 internal medicine residents was examined by factor analysis and path analysis. A three-factor solution accounted for most of the variance among the nine selection variables. These three factors, labeled Board Scores, Faculty Evaluations, and Academic Distinction, were then combined with in-training residency performance evaluations and composite scores on the ABIM certifying examination to produce a comprehensive path model of house staff selection and performance. The Academic Distinction factor emerged as the strongest predictor of residency performance,; the Faculty Evaluations factor was also a significant component of the model. Standardized test scores correlated poorly with clinical performance. The data suggest that increased attention to the content of letters of reference could substantially improve their predictive validity. Other means of reporting subjective evaluations may also be needed to increase the stature of non-cognitive attributes in house staff selection decisions.     

Synthesis-secretion coupling of insulin: effect of aging

Synthesis-secretion coupling of insulin was measured in four age groups of perfused pancreases taken from Sprague-Dawley rats ranging in age from 2-12 months. The effect of long term (6 h) near-maximal glucose stimulation (300 mg/dl) on both insulin secretion and net insulinogenesis demonstrated an age-related increase in both parameters. Net insulinogenesis as well as total insulin secretion increased linearly as a function of aging. Compared to that in 2-month-old rats, total net insulin synthesis was more than 3-fold greater in 12-month-old rats, slightly less than 3-fold greater in 8-month-old rats, and twice as much in 4-month-old rats. Compared to that in 2-month-old rats, total glucose-stimulated insulin secretion was 3-fold greater in 12-month-old rats, approximately 2.2-fold greater in 8-month-old rats, and about 1.7-fold greater in 4-month-old rats. A shorter term (90 min) glucose stimulation at 150 mg/dl produced an age-related increase in insulin secretion which was relatively comparable to the higher glucose stimulus. Of equal importance is that fact that pancreases from the older rats exhibited the same degree of secretory responsiveness to changing glucose levels as did pancreases from the younger rats. Regardless of age, first phase insulin secretion was approximately twice as much in response to the higher glucose level as to the lower. Similarly, second phase insulin secretion was almost 3 times greater regardless of age. When normalized and reported in terms of insulin content, total insulin secretion was no different as a function of aging during the first 1 h of glucose stimulation (i.e. the first two phases of secretion), but it was significantly elevated in the third secretory phase (2-6 h) by the older rat groups. Total 6-h net insulinogenesis was also greater in the older rat groups. When normalized and reported in terms of total body weight, both insulin synthesis and total insulin secretion became comparable and showed no specific age-related difference. Thus, there is no indication that aging results in an uncoupling of relatively long term (6-h) insulin synthesis-secretion, since both glucose-induced responses parallel one another as a function of aging. Furthermore, reporting insulin secretion and synthesis on the basis of body weight, rather than age, totally normalizes synthesis-secretion coupling of insulin.     

Differences in preconceptional and prenatal behaviors in women with intended and unintended pregnancies.

OBJECTIVES: This study examined whether pregnancy intention was associated with cigarette smoking, alcohol drinking, use of vitamins, and consumption of caffeinated drinks prior to pregnancy and in early pregnancy. METHODS: Data from a telephone survey of 7174 pregnant women were analyzed. RESULTS: In comparison with women whose pregnancies were intended, women with unintended pregnancies were more likely to report cigarette smoking and less likely to report daily vitamin use. Women with unintended pregnancies were also less likely to decrease consumption of caffeinated beverages or increase daily vitamin use. CONCLUSIONS: Pregnancy intention was associated with health behaviors, prior to pregnancy and in early pregnancy, that may influence pregnancy course and birth outcomes.     

Tumor vascular signals in renal masses: detection with Doppler US

The vascularity of 49 renal masses (26 malignant and 23 benign lesions) was investigated with duplex Doppler ultrasound. Doppler signals obtained at the margins of renal masses were defined as "tumor signals" when the Doppler-shifted frequency of the lesion exceeded the frequency shift in the ipsilateral main renal artery. These exceeded 2.5 kHz with a 3-MHz insonating frequency. Among the 26 renal masses that subsequently proved to be malignant, tumor signals were obtained in 15 of 18 (83%) untreated renal cell carcinomas, in three of four Wilms tumors, and in two patients with metastases to the kidney, but not in the one patient with lymphoma. None of the 23 benign renal masses demonstrated tumor signals. Tumor vascularity in malignant lesions gives rise to abnormal, high-velocity, Doppler-shifted signals that can help in the differential diagnosis of renal masses.     

Inherited chondrodysplasia punctata due to a deletion of the terminal short arm of an X chromosome

We studied two families with an inherited deletion of the short arm of an X chromosome (Xp) in which affected male offspring have epiphyseal stippling in infancy (chondrodysplasia punctata), nasal hypoplasia, ichthyosis, and mental retardation. The presence of ichthyosis and the apparent pattern of X-linked recessive inheritance prompted investigation of the short arm of the X chromosome through studies of genetic markers and focused cytogenetic analysis. Biochemical studies suggested that there was a deletion of three genes previously mapped to the X-chromosome short arm, including the steroid sulfatase locus, the Xg locus, and the M1C2X locus. Prometaphase chromosomes demonstrated a deletion of Xp at p22.32 in the affected boys, in their obligate-carrier mothers, and in 11 of 25 women at risk as potential carriers. The women carrying the Xp deletion had normal gonadal function and fertility but were shorter than the noncarriers in their families (P less than 0.00001). These findings have implications for the genetic organization of this portion of the human X chromosome and demonstrate that small cytogenetic abnormalities may account for disorders with apparent mendelian patterns of inheritance.     

Spectrum of dolichospondylic dysplasia: two new patients with distinctive findings

Dolichospondylic dysplasia (DD) is a rare skeletal dysplasia primarily characterized by tall vertebral bodies and disproportionate short stature. Radiographic manifestations include tall vertebral bodies and gracile bones of the hands. Patients usually have eye and ear findings in addition to borderline mental retardation; however, tall vertebral bodies and slender tubular bones are also seen in the 3-M syndrome. Patients with the 3-M syndrome have a characteristic face with a triangular shape, frontal bossing, a flattened malar region, full eyebrows, a short nose with a bulbous tip, upturned nares, and full lips. We present two unrelated patients who share a distinct phenotype and have tall vertebral bodies, overtubulation of long bones, and short tubular bones of the hands and feet. We discuss the overlapping and distinguishing features between DD and the 3-M syndrome. Patient 1 was a 13-year-old female, and patient 2 was an unrelated adult female. These patients had normocephaly and short stature. They shared a common phenotype consisting of mild malar hypoplasia, a narrowed nasal body with a fleshy tip, full lips, and normal intelligence. In addition, they showed mild hand and foot abnormalities. These two patients lack many of the typical clinical features of both DD and the 3-M syndrome. They share a common phenotype and likely represent a distinct disorder. The spectrum of disorders with tall vertebral bodies as a key feature may include different entities that may be further defined with the characterization of the molecular defect(s).     

Detection of reactive oxygen species (ROS) and apoptosis in human fragmented embryos

In human in-vitro fertilization (IVF)-embryo transfer, the in-vitro culture environment differs from in-vivo conditions in that the oxygen concentration is higher, and in such conditions the mouse embryos show a higher concentration of reactive oxygen species (ROS) in simple culture media. ROS are believed to cause damage to cell membranes and DNA fragmentation in somatic cells. This study was conducted to ascertain the level of H2O2 concentration within embryos and the morphological features of cell damage induced by H2O2. A total of 62 human oocytes and embryos (31 fragmented, 15 non-fragmented embryos, 16 unfertilized oocytes) was obtained from the IVF-embryo transfer programme. The relative intensity of H2O2 concentrations within embryos was measured using 2',7'-dichlorodihydrofluorescein diacetate by Quanti cell 500 fluorescence imaging and DNA fragmentation was observed with transmission electron microscopy and an in-situ apoptosis detection kit. The H2O2 concentrations were significantly higher in fragmented embryos (72.21 +/- 9.62, mean +/- SEM) compared to non-fragmented embryos (31.30 +/- 3.50, P < 0.05) and unfertilized oocytes (30.75 +/- 2.67, P < 0.05). Apoptosis was observed only in fragmented embryos, and was absent in non-fragmented embryos. Electron microscopic findings confirmed apoptotic bodies and cytoplasmic condensation in the fragmented blastomeres. We conclude that there is a direct relationship between increased H2O2 concentration and apoptosis, and that further studies should be undertaken to confirm these findings.      

Neonatal phenotype in Kabuki syndrome

The Kabuki syndrome is a well-established pattern of human malformation with readily recognizable features, however the diagnosis is rarely made in the newborn period. The purpose of this study was to determine if there exists a neonatal phenotype for this disorder. We ascertained 16 infants evaluated in the first 28 days of life by a dysmorphologist who subsequently received the diagnosis of Kabuki syndrome. The average age of initial evaluation was 8 days and the average age of diagnosis was 2 years 6 months. Based on these findings, it is suggested that the distinctive clinical phenotype seen in older patients is also evident in the newborn period.     

Human amniotic fluid lacks interleukin-2 and interleukin-15 but can interact with the beta-chain of the interleukin-2 receptor

The present study investigated whether an explanation for the conflicting reports on the interleukin-2 (IL-2) status of amniotic fluid is due to the presence of IL-15 which shares biological activities with IL-2 and utilizes the IL-2 receptor beta-chain. Amniotic fluids from 45 normally progressing pregnancies between 14 and 16 weeks after the last menstrual period were assayed for IL-2 and IL-15 by bioassay and enzyme-linked immunosorbent assay (ELISA). The ability of amniotic fluids to induce cytotoxic T lymphoblastoid line-2 (CTLL-2) cell proliferation was demonstrated to be dependent upon bioassay culture conditions. In serum-free medium each amniotic fluid stimulated CTLL-2 proliferation with a mean level of IL-2-like bioactivity of 14.7 +/- 2.3 ng/ml but amniotic fluids failed to induce CTLL-2 proliferation in serum-supplemented medium. Treatment with neutralizing anti-IL-2 or anti-IL-15 antibodies failed to inhibit amniotic fluid-induced CTLL cell proliferation in serum-free medium, indicating a lack of IL-2 and IL-15 bioactivity. In contrast, treatment with anti-IL-2 receptor beta-chain antibody significantly reduced amniotic fluid-induced proliferation. The lack of IL-2 and IL-15 activity in amniotic fluids was confirmed using ELISA. Although high levels of IL-15 immunoactivity were detected in all samples, specificity controls showed a lack of specific IL-15 immunoactivity in amniotic fluid. Pretreatment of amniotic fluids with 100-500 ng/ml mouse immunoglobulin G abrogated IL-15 immunoactivity, indicating that amniotic fluid contains molecules binding to Fc regions of immunoglobulins and responsible for false ELISA positivity. These studies unequivocally show that amniotic fluid lacks IL-2 and IL-15 but can stimulate CTLL-2 cell proliferation via the IL-2 receptor beta-chain. The absence of IL-2 and IL-15 in normal mid-trimester amniotic fluid suggests that the cytokine profile of human pregnancy appears to be associated with a bias against type 1 cytokines within the feto-placental unit.