Physicians' weight loss counseling in two public hospital primary care clinics.

PURPOSE: Primary care physicians are an important source of information on weight management. Nevertheless, weight loss counseling by these physicians remains inadequate. This study sought to determine physicians' barriers to providing weight loss counseling in a public hospital, patients' recall of physicians' weight loss recommendations, and the influence of physicians' counseling on patients' understanding, motivation, and behavior regarding weight loss. METHOD: In 2001, four focus groups of faculty and residents were held at two primary care clinics affiliated with the Louisiana State University Health Sciences Center-Shreveport to determine the barriers to providing weight loss counseling. Scripted probes were used to uncover consensus norms. In 2001-02, structured exit interviews were conducted with 210 overweight or obese patients recruited from the clinics to determine patients' recall of physicians' weight loss recommendations, and patients' understanding of the relationship between weight and health, and their stages of readiness for weight loss. RESULTS: Physicians identified major barriers to providing weight loss counseling, including insufficient confidence, knowledge, and skills. Obesity was underdocumented as a distinct clinical diagnosis. Only 5% of the patients recalled being given the combined weight loss strategy of diet and exercise. However, patients who recalled being counseled to lose weight were more likely to understand the risks of obesity, the benefits of weight loss, and were at a higher stage of readiness for weight loss. CONCLUSIONS: Physicians' weight loss counseling had a significant effect on patients' understanding of and motivation for weight loss. However, physicians provided insufficient guidance on weight management strategies, possibly because of inadequate counseling skills and confidence.     

Autoimmunity and glomerulonephritis in mice with targeted deletion of the serum amyloid P component gene: SAP deficiency or strain combination?

Human serum amyloid P component (SAP) binds avidly to DNA, chromatin and apoptotic cells in vitro and in vivo. 129/Sv x C57BL/6 mice with targeted deletion of the SAP gene spontaneously develop antinuclear autoantibodies and immune complex glomerulonephritis. SAP-deficient animals, created by backcrossing the 129/Sv SAP gene deletion into pure line C57BL/6 mice and studied here for the first time, also spontaneously developed broad spectrum antinuclear autoimmunity and proliferative immune complex glomerulonephritis but without proteinuria, renal failure, or increased morbidity or mortality. Mice hemizygous for the SAP gene deletion had an intermediate autoimmune phenotype. Injected apoptotic cells and isolated chromatin were more immunogenic in SAP(-/-) mice than in wild-type mice. In contrast, SAP-deficient pure line 129/Sv mice did not produce significant autoantibodies either spontaneously or when immunized with extrinsic chromatin or apoptotic cells, indicating that loss of tolerance is markedly strain dependent. However, SAP deficiency in C57BL/6 mice only marginally affected plasma clearance of exogenous chromatin and had no effect on distribution of exogenous nucleosomes between the liver and kidneys, which were the only tissue sites of catabolism. Furthermore, transgenic expression of human SAP in the C57BL/6 SAP knockout mice did not abrogate the autoimmune phenotype. This may reflect the different binding affinities of mouse and human SAP for nuclear autoantigens and/or the heterologous nature of transgenic human SAP in the mouse. Alternatively, the autoimmunity may be independent of SAP deficiency and caused by expression of 129/Sv chromosome 1 genes in the C57BL/6 background.     

The prion protein in human neuromuscular diseases

The basis of human prion diseases affecting the nervous system is accumulation of a disease-associated conformer (PrPSc) of the normal cellular prion protein (PrPC). Earlier studies demonstrated increased expression of PrPC in inclusion body myositis (IBM), dermato-, and polymyositis, as well as neurogenic muscle atrophy. To define the spectrum and reliability of PrPC immunoreactivity, its expression was examined systematically in a series of pathologically characterized muscular disorders by means of immunohistochemistry, confocal laser microscopy, and immunogold electron microscopy. Anti-PrPC immunolabelling of rimmed vacuoles was observed in IBM, inclusions of myofibrillary myopathy, targets, regenerating, and atrophic fibres, mononuclear cells, in addition to ragged red fibres in mitochondrial myopathies, and focal sarcolemmal immunostaining in non-diseased controls. Quantitative analysis demonstrated that, in neurogenic muscle lesions, anti-PrPC staining detects a significantly broader spectrum of fibres than anti-vimentin or anti-NCAM. In dystrophic muscle, PrPC expression was mainly restricted to regenerating fibres. In IBM, PrPC expression was not confined to rimmed vacuoles or vacuolated fibres and only a small percentage (7.1%) of rimmed vacuoles were PrPC positive. Ultrastructurally, PrPC was observed in the cytoplasm of lymphocytes, in the myofibrillar network of targets, and in rimmed vacuoles. Knowledge of disease circumstances with altered expression of PrPC is important in the setting of a potentially increased chance for extraneural PrPC-PrPSc conversion. In addition, our observations suggest that PrPC may have a general stress-response effect in various neuromuscular disorders.     

The pathogenesis of molybdenum cofactor deficiency, its delay by maternal clearance, and its expression pattern in microarray analysis

Molybdenum cofactor (Moco)-deficiency is a lethal autosomal recessive disease, for which until now no effective therapy is available. The biochemical hallmark of this disorder is the inactivity of the Moco-dependent sulfite oxidase, which results in elevated sulfite and diminished sulfate levels throughout the organism. In humans, Moco-deficiency results in neurological damage, which is apparent in untreatable seizures and various brain dysmorphisms. We have recently described a murine model for Moco-deficiency, which reflects all enzyme and metabolite changes observed in the patients, and an efficient therapy using a biosynthetic precursor of Moco has been established in this animal model. We now analyzed these mice in detail and excluded morphological brain damage, while expression analysis with microarrays indicates a massive cell death program. This neuronal damage appears to be triggered by elevated sulfite levels and is ameliorated in affected embryos by maternal clearance.     

Galectin-1 is overexpressed in nasal polyps under budesonide and inhibits eosinophil migration

Because of the importance of galectins for various cellular activities, the influence of the glucocorticoid budesonide on the level of expression of galectins-1 and -3 was investigated in human nasal polyposis. Ten nasal polyps obtained from surgical resection were maintained for 24 hours in the presence of various concentrations of budesonide. As quantitatively demonstrated by means of computer-assisted microscopy, 250 ng/ml (the highest dose tested) induced a pronounced increase of galectin-1 expression. This feature was observed in nasal polyps from allergic patients but not in those from nonallergic patients. Since eosinophils represent the main inflammatory cell population in nasal polyps, we investigated the effect of galectin-1 on their migration levels by means of quantitative phase-contrast computer-assisted videomicroscopy. Our results show that galectin-1 (coated on plastic supports) markedly reduced the migration levels of eosinophils in comparison to P-selectin. On the cellular level, marked modifications in the polymerization/depolymerization dynamics of the actin cytoskeleton (as revealed by means of computer-assisted fluorescence microscopy) and, to a much lesser extent, an increase in the adhesiveness of eosinophils to tested substrata were detectable. The present study therefore reveals a new galectin-1-mediated mechanism of action for glucocorticoid-mediated anti-inflammatory effects.     

Detecting depressive disorders in drug abusers : A comparison of screening instruments

Previous investigators have reported a high prevalence of depressive symptoms in drug-dependent patients. Given the responsiveness of depressive disorders to both psychological and pharmacological treatments, it is desirable to find an economical, efficient screening instrument to detect depressive disorders in this population. In this study, 6 depression symptom screening scales (Beck Depression Inventory, Hamilton Depression Scale, Raskin Depression Scale, Degree of Illness Rating, Symptom Checklist 90 Overall, and Depression Subscale) based on either clinician interview or patient self report, were compared according to their utility in detecting cases of depression among 64 applicants for treatment at a substance abuse treatment unit of a community mental health center. The criteria for a case of depression were the Research Diagnostic Criteria (RDC) which are specified and operationalized. Cases identified using previously described cutoff scores on the screening scales were compared to rates based on the RDC and sensitivity and specificity were determined. The results showed that: (1) although the sensitivity of the symptom scales was applicable, ranging from 65--94%, the specificity was less impressive, ranging from 39--61%, and (2) the Beck Depression Inventory, a 13-item patient self report was the most sensitive and specific and is recommended for screening drug-dependent populations for depression.     

Sensitivity to hymenoptera in adult males

The authors studied the sera of 86 selected adult male office workers for IgE antibodies to yellow jacket and honey bee venoms and to environmental inhalants and foods. Structured histories provide information about the experiences of these men with the Hymenoptera and other immunological information. Three men (3%) gave a history of a local or general reaction to the Hymenoptera but no antibodies were detected. Ten men (12%) had IgE antibodies to yellow jacket or honey bee venoms but none gave a history of a reaction. Nine of these men were atopic. The authors speculate that IgE antibodies to the Hymenoptera in atopic adult males may be more common than is currently recognized.     

Classical and alternative pathway complement activation are not required for reactive systemic AA amyloid deposition in mice

During induction of reactive systemic amyloid A protein (AA) amyloidosis in mice, either by chronic inflammation or by severe acute inflammation following injection of amyloid enhancing factor, the earliest deposits form in a perifollicular distribution in the spleen. Because the splenic follicular localization of immune complexes and of the scrapie agent are both complement dependent in mice, we investigated the possible complement dependence of AA amyloid deposition. In preliminary experiments, substantial depletion of circulating C3 by cobra venom factor had little effect on experimental amyloid deposition. More importantly, mice with targeted deletion of the genes for C1q or for both factor B and C2, and therefore unable to sustain activation, respectively, of either the classical complement pathway or both the classical and alternative pathways, showed amyloid deposition similar to wild type controls. Complement activation by either the classical or alternative pathways is thus not apparently necessary for the experimental induction of systemic AA amyloid in mice.     

Evidence that an L-fucose-containing component in the beta-cell plasma membrane is involved in the regulation of glucose-induced insulin release

The effect of the L-fucose-selective lectin Ulex Europeus I (UEA I), a blocker of the Na+, K+, Cl- co-transport system in the kidney, was tested on insulin secretion from isolated beta-cell-rich pancreatic islets. UEA I at doses from 50 to 100 micrograms ml-1 significantly reduced the glucose-induced (20 mmol l-1) insulin release whereas the basal (3 mmol l-1) release was unaffected. The inhibitory effect of 100 micrograms ml l-1 UEA I was completely abolished by 10 mmol l-1 L-fucose. The data suggest that an L-fucose-containing structure in the beta-cell plasma membrane participates in the regulation of glucose-induced insulin release. This structure may be similar to the L-fucose-containing glycoprotein in the kidney tubules that is believed to be the Na+, K+, Cl- cotransporter.