Female medical leadership: cross sectional study

OBJECTIVE: To assess the relation between male and female medical leadership. DESIGN: Cross sectional study on predictive factors for female medical leadership with data on sex, age, specialty, and occupational status of Norwegian physicians. SETTING: Oslo, Norway. SUBJECTS: 13 844 non-retired Norwegian physicians. MAIN OUTCOME MEASURE: Medical leaders, defined as physicians holding a leading position in hospital medicine, public health, academic medicine, or private health care. RESULTS: 14.6% (95% confidence interval 14.0% to 15.4%) of the men were leaders compared with 5.1% (4.4% to 5.9%) of the women. Adjusted for age men had a higher estimated probability of leadership in all categories of age and job, the highest being in academic medicine with 0.57 (0.42 to 0.72) for men aged over 54 years compared with 0.39 (0.21 to 0.63) for women in the same category. Among female hospital physicians there was a positive relation between the proportion of women in their specialty and the probability of leadership. CONCLUSION: Women do not reach senior positions as easily as men. Medical specialties with high proportions of women have more female leaders.     

Self-reported assessment of visual function in a population-based study: the SEE project. Salisbury Eye Evaluation

PURPOSE: To report on the usefulness of the Activities of Daily Vision Scale (ADVS) questionnaire for assessing visual functioning, a population-based sample of elderly Americans. METHODS: The ADVS questionnaire was administered to a population-based sample of 2520 community-dwelling individuals 65 to 84 years of age in Salisbury, MD. Items and subscales were evaluated for internal consistency, item discrimination, and content validity. Published subscale groupings and item associations in our population were compared for coherence using correlation, factor, and cluster analyses. Whole-sample and race- and gender-specific analyses were conducted. External validity was explored by regressing ADVS scores on standard psychophysical vision measures. RESULTS: ADVS scores were skewed to high visual functioning levels; approximately 60% of the population had function scores of 95 or better (of a possible 100). The overall, night driving, and near vision scales were internally consistent and had strong item-subscale associations; the day driving and glare subscales were not acceptable regarding these properties. The far vision subscale was acceptably scalable but only weakly differentiated from the other subscales. Overall, night driving, near vision, and far vision scores were all statistically and independently associated with multiple psychophysical vision measures. Findings were consistent across race and gender subgroups. CONCLUSIONS: As assessed by the ADVS, reported visual functioning is high in our representative older population. The overall scale and selected subscales effectively distinguish persons along a spectrum of ability. They correlate with measures of visual impairment in a reasonable way and thus hold promise for risk factor investigations. The published day driving and glare subscales should be examined for relevance and consistency before being applied in population-based settings. Methods specific to population-based settings should be investigated for their ability to better elicit additional visual function dimensions and early visual disability.     

Cells capable of bone production engraft from whole bone marrow transplants in nonablated mice

Allogeneic and autologous marrow transplants are routinely used to correct a wide variety of diseases. In addition, autologous marrow transplants potentially provide opportune means of delivering genes in transfected, engrafting stem cells. However, relatively little is known about the mechanisms of engraftment in transplant recipients, especially in the nonablated setting and with regard to cells not of hemopoietic origin. In particular, this includes stromal cells and progenitors of the osteoblastic lineage. We have demonstrated for the first time that a whole bone marrow transplant contains cells that engraft and become competent osteoblasts capable of producing bone matrix. This was done at the individual cell level in situ, with significant numbers of donor cells being detected by fluorescence in situ hybridization in whole femoral sections. Engrafted cells were functionally active as osteoblasts producing bone before being encapsulated within the bone lacunae and terminally differentiating into osteocytes. Transplanted cells were also detected as flattened bone lining cells on the periosteal bone surface.     

Dobutamine stress echocardiography for assessing coronary artery disease after transplantation in children

OBJECTIVES: The purpose of this study was to determine the feasibility, safety and diagnostic accuracy of dobutamine stress echocardiography (DSE) for evaluating posttransplant coronary artery disease (TxCAD) in children, and to determine the frequency of selected cardiac events after normal or abnormal DSE. BACKGROUND: Posttransplant coronary artery disease is the most common cause of graft loss (late death or retransplantation) after cardiac transplantation (CTx) in children. Coronary angiography, routinely performed to screen for TxCAD, is an invasive procedure with limited sensitivity. The efficacy of DSE for detecting atherosclerotic coronary artery disease is established, but is unknown in children after CTx. METHODS: Of the 78 children (median age 5.7 years, range 3 to 18) entered into the study, 72 (92%) underwent diagnostic DSE by means of a standard protocol, 4.6 +/- 1.9 years after CTx. The results of coronary angiography performed in 70 patients were compared with DSE findings. After DSE, subjects were monitored for TxCAD-related cardiac events, including death, retransplantation and new angiographic diagnosis of TxCAD. RESULTS: No major complications occurred. Minor complications, most often hypertension, occurred in 11% of the 72 subjects. The sensitivity and specificity of DSE were 72% and 80%, respectively, when compared with coronary angiography. At follow-up (21 +/- 8 months), TxCAD-related cardiac events occurred in 2 of 50 children (4%) with negative DSE, versus 6 of 22 children (27%) with positive DSE (p < 0.01). CONCLUSIONS: DSE is a feasible, safe and accurate screening method for TxCAD in children. Positive DSE identifies patients at increased risk of TxCAD-related cardiac events. Negative DSE predicts short-term freedom from such events.     

Isoform-specific effect of apolipoprotein E on cell survival and beta-amyloid-induced toxicity in rat hippocampal pyramidal neuronal cultures

Dermatosparaxis is a recessive disorder of animals (including man) which is caused by mutations in the gene for the enzyme procollagen N-proteinase and is characterised by extreme skin fragility. Partial loss of enzyme activity results in accumulation of pNcollagen (collagen with N-propeptides) and abnormal collagen fibrils in the fragile skin. How the N-propeptides persist in the tissue and how abnormal fibril morphology results in fragile skin is poorly understood. Using biochemical and quantitative mass mapping electron microscopy we showed that the collagen fibrils in the skin of a dermatosparactic calf contained 57% type I pNcollagen and 43% type I collagen and the fibrils were irregularly arranged in bundles and hieroglyphic in cross-section. Image analysis of the fibril cross-sections suggested that the deviation from circularity of dermatosparactic fibrils was caused by N-propeptides of pNcollagen being located at the fibril surface. Comparison of experimental and theoretical axial mass distributions of the fibrils showed that the N-propeptides were located to the overlap zone of the fibril D-period (where D=67 nm, the characteristic axial periodicity of collagen fibrils). Treatment of the dermatosparactic fibrils with N-proteinase did not remove the N-propeptides from the fibrils, although the N-propeptides were efficiently removed by trypsin and chymotrypsin. However, the N-propeptides were efficiently cleaved by the N-proteinase when the pNcollagen molecules were extracted from the fibrils. These results are consistent with close packing of N-propeptides at the fibril surface which prevented cleavage by the N-proteinase. Long-range axial mass determination along the fibril length showed gross non-uniformity with multiple mass bulges. Of note is the skin fragility in dermatosparaxis, and also the appearance of mass bulges along the fibril long axis symptomatic of the fragile skin of mice which lack decorin. Western blot analysis showed that the dermatosparactic fibrils bound elevated levels of the proteoglycan, compared with normal skin fibrils. The results showed that N-propeptides can distort the morphology of fibrils, that they do not inhibit binding of gap-associated macromolecules (such as decorin) and that the normal mechanical properties of skin are strongly dependent on the close association of near-cylindrical fibrils, thereby enabling maximal fibril-fibril interactions.     

Reduced Purkinje cell size in the cerebellar vermis of elderly patients with schizophrenia

OBJECTIVE: The authors' goal was to compare the size and linear density of Purkinje cells in the cerebellar vermis of subjects with and without schizophrenia. METHOD: Blocks of alcohol-fixed cerebellar vermis were dissected at autopsy from the brains of 14 elderly patients with schizophrenia and 13 elderly subjects with no history of neuropsychiatric illness. The blocks of vermis were sectioned and stained with 1% cresyl violet. The linear density and cross-sectional area of Purkinje cells were measured by using computer-assisted image analysis. The subjects with schizophrenia had been assessed with clinical rating scales within 1 year prior to death. RESULTS: The average cross-sectional areas of Purkinje cells of the patients with schizophrenia were significantly smaller (by 8.3%) than those of the subjects without neuropsychiatric illness. No difference in Purkinje cell linear density was observed between the two groups. Significant correlations were seen between Purkinje cell size and scores on the Mini-Mental State, the Brief Psychiatric Rating Scale, and the antipsychotic drug dose. CONCLUSIONS: These data indicate cerebellar involvement in schizophrenia; they are also consistent with reports of reduced neuronal size in other brain regions of patients with schizophrenia. These findings support a model of wide-spread central nervous system abnormality in schizophrenia.     

An analysis of the biological rhythms of pain sensitivity in mice during thermal stimulation

Circadian oscillations of the 8-hr rhythmic components in nociceptive sensitivity were found in mice. A 12-hr rhythm was close to a sinusoidal one. Circadian waves of the pain threshold were asymmetric and the highest in the middle of the light phase, about 16 hrs. The group rhythms of nociceptive sensitivity appeared to be a result of synchronised separate rhythms.     

Loss of haloperidol induced gene expression and catalepsy in protein kinase A-deficient mice

The antipsychotic drug, haloperidol, elicits the expression of neurotensin and c-fos mRNA in the dorsal lateral region of the striatum and produces an acute cataleptic response in rodents that correlates with the motor side effects of haloperidol in humans. Mice harboring a targeted disruption of the RIIbeta subunit of protein kinase A have a profound deficit in cAMP-stimulated kinase activity in the striatum. When treated with haloperidol, RIIbeta mutant mice fail to induce either c-fos or neurotensin mRNA and the acute cataleptic response is blocked. However, both wild-type and mutant mice become cataleptic when neurotensin peptide is directly injected into the lateral ventricle, demonstrating that the kinase deficiency does not interfere with the action of neurotensin but rather its synthesis and release. These results establish a direct role for protein kinase A as a mediator of haloperidol induced gene induction and cataleptic behavior.