Epidemiological risk factors for non-traumatic osteonecrosis

Certain fractures and/or dislocations of the femoral head are known to cause arterial injury and result in post-traumatic osteonecrosis. However, the more complex etiology of non-traumatic osteonecrosis is multifactorial and includes chemotherapy, radiotherapy, thermal injuries, and especially coagulopathies, which are now commonly observed in these patients. Intravascular coagulation with fibrin thrombosis begins in the capillaries and sinusoids of the intraosseous microcirculation, and residual venous thrombosis is more likely to occur if there is coexistent hypofibrinolysis. Coagulopathies are intermediary events, which are always activated by some underlying etiologic risk factor(s). Conditions capable of triggering intravascular coagulation include familial thrombophilia (resistance to activated protein C, decreased protein C, protein S, or antithrombin III, and hyperhomocystinemia), hyperlipemia and embolic lipid (alcoholism and hypercortisonism), hypersensitivity reactions (allograft organ rejection, immune complexes, and antiphospholipid antibodies), bacterial endotoxic (Shwartzman) reactions and various viral infections, proteolytic enzymes (pancreatitis), tissue factor release (inflammatory bowel disease, malignancies, neurotrauma, and pregnancy), and other thrombophilic and hypofibrinolytic disorders. Currently known risk factors for non-traumatic osteonecrosis of the femoral head are described briefly in this review article.     

Reliability and validity of a psycho-social problem inventory for childhood epilepsy

In response to the need for formal psychosocial assessment in childhood epilepsy, a 25-question inventory was constructed from raw items based on multidisciplinary inputs and tested for practicality, and psychometric attributes. Weighted inter-rater and test-retest reliability estimates were 61.8% and 63.9% respectively. A measure of concurrent validity was satisfactory though a modest discrepancy was observed between two raters (P = 0.019 and 0.0064). Discriminant validity was very satisfactory (average P 0.001) based on compared means of ratings from two groups of subjects with disparate prognosis. The inventory should be useful in the assessment of similar chronic childhood disabilities but interpretations of data should be in a wider clinical context including inputs of informant and school authorities as indicated.     

Gastrointestinal handling of [1-13C]palmitic acid in healthy controls and patients with cystic fibrosis

Accepted 2 January 1997
AIM—To examine the gastrointestinal handling of [1-¹³C]palmitic acid given as the free acid by measuring the excretion of ¹³C label in stool in 16 healthy children and 11 patients with cystic fibrosis on their habitual enzyme replacement treatment.
METHODS—After an overnight fast, each child ingested 10 mg/kg body weight [1-¹³C]palmitic acid with a standardised test meal of low natural ¹³C abundance. A stool sample was collected before the test and all stools were collected thereafter for a period of up to five days. The total enrichment of ¹³C in stool and the species bearing the ¹³C label was measured using isotope ratio mass spectrometry.
RESULTS—The proportion of administered ¹³C label excreted in stool was 24.0% (range 10.7-64.9%) in healthy children and only 4.4% (range 1.2-11.6%) in cystic fibrosis patients. The enrichment of ¹³C in stool was primarily restricted to the species consumed by the subjects (that is as palmitic acid).
CONCLUSION—There does not appear to be a specific defect in the absorption of [1-¹³C]palmitic acid in patients with cystic fibrosis. The reasons why cystic fibrosis patients appear to absorb more of this saturated fatty acid than healthy children is not clear and requires further investigation.

     

Trends in US medical school faculty salaries, 1988-1989 to 1998-1999

Erich Studer-Ellis, PhD, MBA; Jennifer S. Gold, MA; Robert F. Jones, PhD

JAMA. 2000;284:1130-1135.

Expansion of managed care, intensified price competition, and the introduction of the Medicare Fee Schedule have all affected physician compensation during the past decade. We examine trends in the salaries of medical school faculty, particularly MD clinical faculty, based on a more extensive salary database than has been used previously. Data collected through the Association of American Medical Colleges' Faculty Salary Survey for the academic years 1988-1989, 1993-1994, and 1998-1999 were analyzed, and inflation-adjusted salary growth rates for clinical and basic science faculty during two 5-year periods, 1988-1993 and 1993-1998, compared across faculty ranks, departments, and various school characteristics.

The comparison showed that, between 1988 and 1998, the actual median clinical faculty salary increased from $101,000 to $150,000, and the actual median basic science faculty salary increased from $52,000 to $78,000. Bivariate and multivariate analyses showed that the proportionate change in real mean salary (base year, 1988) in each 5-year period was related to department and faculty rank for clinical faculty (P<.001) and faculty rank for basic science faculty (P<.001). The inflation-adjusted annualized compound growth rate of clinical faculty salaries declined from 1.9% per year (1988-1993) to 0.2% per year (1993-1998), while the growth rate of basic science faculty salaries increased from 0.3% per year (1988-1993) to 1.3% per year (1993-1998). From 1993 to 1998, inflation-adjusted annualized salary growth rates in several clinical departments were negative (anesthesiology, –1.1%; obstetrics and gynecology, –0.5%; radiology, –0.4%; and neurology, –0.1%) but were positive for family practice (+2.7%). Significant differences in salary growth related to school characteristics (eg, geographic region, public vs private, community based vs non–community based, and research intensity) were specific to particular study periods. Overall, while actual average medical school faculty salaries are increasing, the real growth rate of average clinical faculty salaries is declining and that of basic science faculty increasing.

     

Median nerve compression in Proteus syndrome

Proteus syndrome is a multi–organ disorder, a prime feature of which is localized gigantism, usually clinically obvious. Symptoms secondary to hypertrophy of nerves has not been previously recognized as a part of the syndrome. Accepted: 16 May 1997     

p53 Protein expression in tumours from head and neck subsites,larynx and hypopharynx,and differences in relationship to survival

The present study involves an immunohistochemical analysis of p53 protein expression in head and neck tumours located at two separate subsites, the larynx and hypopharynx. It attempts to relate differences in expression to differences in the behaviour of these tumours. Detection of the p53 protein was performed using immunohistochemistry on 32 specimens of hypopharyngeal squamous cell carcinoma and 35 specimens of laryngeal squamous cell carcinoma. p53 overexpression was found in 66% of the hypopharyngeal tumours and in 51% of the laryngeal specimens analysed. Some differences between the two tumour types were noted in the pattern staining. p53 staining in those with hypopharyngeal tumours was associated with a statistically significant increased survival. For laryngeal carcinoma the converse was true but did not reach statistical significance. Differences in the behaviour of different head and neck tumour types may be reflected in differences in expression of the p53 protein. While p53 protein expression does not appear to be a useful prognostic indicator in laryngeal carcinoma it might be a useful prognostic indicator in tumours of the hypopharynx. Moreover, it may help predict those tumours which are radioresistant, thus suggesting other modes of treatment for these tumours. Of particular importance is the molecular basis for the observed differences in survival associated with p53 expression in the two tumour sites. This is under further investigation.     

Vascular endothelial growth factor and nitric oxide synthase expression in human lung cancer and the relation to p53.

Vascular endothelial growth factor (VEGF) expression and mutations of cancer-related genes increase with cancer progression. This correlation suggests the hypothesis that oncogenes and tumour suppressors regulate VEGF, and a significant correlation between p53 alteration and increased VEGF expression in human lung cancer was reported recently. To further examine this hypothesis, we analysed VEGF protein expression and mutations in p53 and K-ras in 27 non-small-cell lung cancers (NSCLC): 16 squamous cell, six adenocarcinomas, one large cell, two carcinoids and two undifferentiated tumours. VEGF was expressed in 50% of the squamous cell carcinomas (SCC) and carcinoids but none of the others. p53 mutations occurred in 14 tumours (52%), and K-ras mutations were found in two adenocarcinomas and one SCC; there was no correlation between the mutations and VEGF expression. As nitric oxide also regulates angiogenesis, we examined NOS expression in NSCLC. The Ca2+-dependent NOS activity, which indicates NOS1 and NOS3 expression, was significantly reduced in lung carcinomas compared with adjacent non-tumour tissue (P < 0.004). Although the Ca2+-independent NOS activity, which indicates NOS2 expression, was low or undetectable in non-tumour tissues and most carcinomas, significant activity occurred in three SCC. In summary, our data do not show a direct regulation of VEGF by p53 in NSCLC. Finally, we did not find the up-regulation of NOS isoforms during NSCLC progression that has been suggested for gynaecological and breast cancers.