Platelet activation in the presence of neutral protamine Hagedorn insulin: a new feature of antibodies against protamine/heparin complexes.

Essentials Protamine (PRT) is used to stabilize insulin in neutral protamine Hagedorn (NPH) insulin. The interaction between NPH-insulin, anti-PRT/heparin antibodies and platelets was investigated. Anti-PRT/heparin antibodies activate platelets in presence of NPH-insulin dependent on heparin. Cross-reactivity seems to have no major effect on the clinical outcome of medical patients. SUMMARY: Background Protamine (PRT) is used to stabilize insulin in neutral protamine Hagedorn (NPH) insulin, a commonly used therapeutic agent for diabetes mellitus. Immunization against PRT/heparin complexes is common in diabetic patients. Objectives To investigate the impact of NPH-insulin on the interaction between anti-PRT/heparin antibodies and platelets. Methods The interaction between NPH-insulin and anti-PRT/heparin antibodies was tested using in-house enzyme immunoassays. The ability of anti-PRT/heparin antibodies to activate platelets in the presence of NPH-insulin (and heparin) was investigated using flow cytometry. Results Twenty-one out of 80 sera containing anti-PRT/heparin IgG showed binding to NPH-insulin. Anti-PRT/heparin IgG from immunized patients bound to platelets in the presence of NPH-insulin, but not in the presence of native insulin. Anti-PRT/heparin antibodies induced P-selectin expression in the presence of NPH-insulin in a heparin-dependent way (median mean fluorescence intensity in the presence of NPH-insulin: 55, 95% confidence interval [CI] 18.7-100.5 vs. NPH-insulin and heparin: 204, 95% CI 106.5-372.8). The clinical relevance of platelet-activating anti-PRT/heparin antibodies was assessed by investigating a multicenter study cohort of 332 acutely ill medical patients who received heparin. None of the 21 patients with anti-PRT/heparin IgG developed thrombocytopenia or thromboembolic complications. Conclusions Anti-PRT/heparin antibodies activate platelets in the presence of NPH-insulin in a heparin-dependent way. However, results from our preliminary study indicate no major impact of these antibodies on the clinical outcome in medical patients receiving heparin, particularly on thromboembolic complications.

Perfiles de personalidad de estudiantes de psicología de universidad privada comparados em similitud y congruencia / Personality profiles of psychology students from a privateuniversity compared by similarity and congruence

En continuidad con los estudios del área de Perfiles de la Cátedra de Psicología Experimental I y II, se llevó a cabo un análisis comparativo de Perfiles de Personalidad en estudiantes de psicología. La muestra fue intencional y autoseleccionada, quedó conformada por 153 estudiantes de Psicología. Se ha utilizado un diseño Descriptivo y Comparado. El instrumento utilizado fue el Inventario Multifásico de la Personalidad Minnesota-2 (MMPI-2). Los resultados reportan que existe un patrón de personalidad con similitudes muy acentuadas en los estudiantes de la carrera de psicología, independiente del curso al que pertenecen, y en comparación a los perfiles de años anteriores (n = 152, muestra 2001: n=168, muestra 2007: y n= 101 muestra 2008).

In continuity with the studies of the area of Profiles of the Professorship of Experimental Psychology I and II, a comparative analysis of Profiles of Personality in students of psychology was carried out. The sample was intentional and autoseleccionada, remained conformed by 153 (166) students of Psychology. A Descriptive design has been utilized and Compared. The instrument utilized was the Polyphase Inventory of the Personality Minnesota-2 (MMPI-2). The results report that a boss of personality with similarities exists very accentuated in the students of the career of psychology, independent of the course to which they belong, and in comparison to the profiles of previous years (n = 152 sample 2001; n = 168, sample 2007 and n = 101 sample 2008).

School feeding for improving the physical and psychosocial health of disadvantaged elementary school children.

BACKGROUND: Early malnutrition and/or micronutrient deficiencies can adversely affect physical, mental, and social aspects of child health. School feeding programs are designed to improve attendance, achievement, growth, and other health outcomes. OBJECTIVES: The main objective was to determine the effectiveness of school feeding programs in improving physical and psychosocial health for disadvantaged school children. SEARCH STRATEGY: We searched a number of databases including CENTRAL (2006 Issue 2), MEDLINE (1966 to May 2006), EMBASE (1980 to May 2006), PsycINFO (1980 to May 2006) and CINAHL (1982 to May 2006). Grey literature sources were also searched. Reference lists of included studies and key journals were handsearched and we also contacted selected experts in the field. SELECTION CRITERIA: Data from randomized controlled trials (RCTs), non-randomised controlled clinical trials (CCTs), controlled before and after studies (CBAs), and interrupted time series studies (ITSs) were included. Feeding had to be done in school; the majority of participants had to be socio-economically disadvantaged. DATA COLLECTION AND ANALYSIS: Two reviewers assessed all searches and retrieved studies. Data extraction was done by one of four reviewers and reviewed by a second. Two reviewers independently rated quality. If sufficient data were available, they were synthesized using random effects meta-analysis, adjusting for clustering if needed. Analyses were performed separately for RCTs and CBAs and for higher and lower income countries. MAIN RESULTS: We included 18 studies. For weight, in the RCTs and CBAs from Lower Income Countries, experimental group children gained an average of 0.39 kg (95% C.I: 0.11 to 0.67) over an average of 19 months and 0.71 kg (95% C.I.: 0.48 to 0.95) over 11.3 months respectively. Results for weight were mixed in higher income countries. For height, results were mixed; height gain was greater for younger children. Attendance in lower income countries was higher in experimental groups than in controls; our results show an average increase of 4 to 6 days a year. Math gains were consistently higher for experimental groups in lower income countries; in CBAs, the Standardized Mean Difference was 0.66 (95% C.I. = 0.13 to 1.18). In short-term studies, small improvements in some cognitive tasks were found. AUTHORS' CONCLUSIONS: School meals may have some small benefits for disadvantaged children. We recommend further well-designed studies on the effectiveness of school meals be undertaken, that results should be reported according to socio-economic status, and that researchers gather robust data on both processes and carefully chosen outcomes.

Bioactivity of 25-hydroxy-, 26-hydroxy, 25,26-dihydroxy- and 25,26-epoxybrassinolide.

The bioactivity of 25-hydroxybrassinolide, (25S)- and (25R)-26-hydroxybrassinolide, (25S)- and (25R)-25,26-dihydroxybrassinolide, and of (25R)-25,26-epoxybrassinolide was tested in the rice leaf lamina inclination assay. The 25- and (25S)-26-hydroxy derivatives are known metabolites of the naturally-occurring phytohormone brassinolide, whereas the other compounds are novel, but closely related, congeners. When tested alone, all showed either no activity or only weak activity at relatively high doses. When coapplied with indole-3-acetic acid (IAA), an auxin that synergizes the effects of brassinosteroids, enhanced bioactivity was observed for each compound. However, even when applied together with IAA, none of the compounds proved more bioactive than brassinolide with or without IAA. We conclude from these results that enzymatic hydroxylation of endogenous brassinolide at C-25 and/or C-26 does not enhance brassinosteroid activity, and so does not comprise an activation pathway in brassinolide biosynthesis. Instead, these hydroxylations result in modest to appreciable metabolic deactivation.

Design, synthesis, and bioactivity of the first nonsteroidal mimetics of brassinolide.

Ten novel compounds, each consisting of two subunits and a linker, were designed with the aid of molecular modeling to resemble the natural steroidal phytohormone brassinolide. The mimetics were synthesized and subjected to the rice leaf lamina inclination bioassay to test for brassinosteroid activity. Most of the mimetics displayed very weak or no bioactivity, but two were strongly active when coapplied with the auxin indole-3-acetic acid (IAA), which synergizes the activity of brassinosteroids. Thus, 1-(4,6 alpha,7 alpha-trihydroxy-5,6,7,8-tetrahydronaphthyl)-2-(6 alpha',7 alpha'-dihydroxy-5',6',7',8'-tetrahydronaphthyl)ethyne (4) and (E)-1,2-bis[trans-(4a alpha,8a beta)-4-oxo-6 alpha,7 alpha-dihydroxy-4a,5,6,7,8,8a-hexahydro-(3H)-naphthyl]ethylene (11) showed exceptional activity at doses as low as 0.01 ng and 0.001 ng/plant, respectively. These compounds are the first biologically active nonsteroidal brassinolide mimetics.

Synthesis and bioactivity of 6alpha- and 6beta-hydroxy analogues of castasterone.

The reduction of castasterone with sodium in ethanol produced chiefly the known 6alpha-hydroxy stereoisomer, whereas reduction with sodium orohydride in methanol afforded mainly the novel 6beta-epimer. Both compounds showed variable bioactivity through four separate assays via the rice leaf lamina inclination bioassay. However, when treated with an appropriate statistical program to remove outliers, the averaged results clearly indicated that the two 6-hydroxy epimers possess comparable and significant bioactivity, which is, however, lower than that of castasterone or brassinolide. When applied together with 1000 ng of the auxin, indole-3-acetic acid (IAA), the activity of both the 6alpha and 6beta hydroxy epimers was enhanced by ca. one order of magnitude across a wide range of doses.

Percent body fat and bone mass in healthy Canadian females 10 to 19 years of age.

The primary aim of the investigation was to assess the relationship between whole-body fat expressed as a percentage of body weight with whole-body bone mineral content relative to age and anthropometry. Sixty females between 10 and 19 years of age were recruited to this cross-sectional study, which included measurements of weight and height and whole-body fat and bone mineral content using dual-energy X-ray absorptiometry. To assess bone mineral content, data were expressed as a weight or standard deviation scores using age and bone area. Relationships between outcome variables were determined using multiple correlation analysis followed by multiple linear regression with age, weight, height, and fat as predictor variables for outcomes of bone mineral content and density. Correlation analysis indicated that whole-body fat expressed as a percent was significantly related to weight (p < 0.01), but was not related to age or bone mineral content or density unless bone mineral content was corrected to age or bone area using standard deviation scores. In addition, body fat was associated with bone area for age and height (p < 0.01). However, multiple linear regression yielded opposite results. When included in regression, body fat had a negative impact on bone mineral content (p = 0.003), mineral content corrected to bone area (p = 0.02), and bone density (p = 0.003), while age, weight, and height had positive impacts on these outcome measurements. The data suggest that for younger children, the relative influence of percent body fat will be greater and could be linked with suboptimal attainment of peak bone mass. The females in this study appeared to be within reference limits for percent body fat. However, greater amounts of body fat relative to weight could be a marker for lifestyles that do not support attainment of optimal peak bone mass.

Effect of chain length and ring size of alkyl and cycloalkyl side-chain substituents upon the biological activity of brassinosteroids. Preparation of novel analogues with activity exceeding that of brassinolide.

A series of brassinosteroids with different alkyl or cycloalkyl substituents in place of the isopropyl group at C-24 of brassinolide (1) were prepared by the CuCN-catalyzed addition of Grignard reagents to (threo-2R,3S,5alpha,22R,23R,24S)-23,24-epoxy-6, 6-(ethylenedioxy)-2,3-(isopropylidenedioxy)-26, 27-dinorcholestan-22-ol (9), followed by deketalization and Baeyer-Villiger oxidation. Compound 9 was employed as part of a 70:30 threo/erythro mixture of epoxides 9 and 10, from which the erythro-epoxide 10 was recovered intact after the Grignard additions. Thus, the corresponding n-dodecyl, n-hexyl, n-propyl, tert-butyl, cyclohexyl, cyclopentyl, cyclobutyl, and cyclopropyl analogues of brassinolide were obtained. A rearrangement byproduct was observed during the preparation of the cyclopropyl-substituted brassinosteroid when ether was used as the solvent in the Grignard reaction, but could be avoided by the use of THF. A method for recycling the undesired erythro-epoxide 10 was developed on the basis of deoxygenation with tellurium and lithium triethylborohydride. The rice leaf lamina inclination assay was then used to measure the bioactivity of the products. In general, increasing activity was observed as the length or ring size of the C-24 hydrocarbon substituent decreased. The novel cyclobutyl- and cyclopropyl-substituted analogues of brassinolide (1) were ca. 5-7 times as active as 1 and thus appear to be the most potent brassinosteroids reported to date. Further enhancement of the bioactivity of all of the above brassinosteroids, except that of the inactive n-dodecyl derivative, was observed when the brassinosteroid was applied together with an auxin, indole-3-acetic acid (IAA). The synergy between the brassinosteroids and IAA thus increased the bioactivity of the brassinosteroids, including the cyclopropyl and cyclobutyl derivatives, by ca. 1-2 orders of magnitude.

An overview of levodopa in the management of restless legs syndrome in a dialysis population: pharmacokinetics, clinical trials, and complications of therapy.

OBJECTIVE: To review published literature investigating the efficacy and safety of levodopa in the management of restless legs syndrome (RLS), with emphasis on the hemodialysis population. DATA SOURCES: An English-language literature search using MEDLINE was conducted from 1966 to 1997 (key terms: restless legs syndrome, levodopa, hemodialysis). The bibliographies of all identified published articles were reviewed and cross-referenced to ensure that all possible references were identified. STUDY SELECTION AND DATA EXTRACTION: All identified human studies investigating the use of levodopa for the management of RLS in uremic and nonuremic patients were analyzed. RESULTS: The prevalence of RLS is 20-40% in patients with endstage renal disease (ESRD) and approximately 5% in the general population. Although the benefits of levodopa/(carbidopa/benserazide) in reducing the signs and symptoms of RLS are documented in nonuremic patients, evidence in patients with ESRD is less readily available. Three small (< 30 subjects) clinical trials in uremic patients provide preliminary evidence for the usefulness of levodopa/(carbidopa/benserazide) in this population. CONCLUSIONS: In general, the small amount of published literature supports the empirical use of levodopa/carbidopa as a safe and effective therapy to manage the distressing symptoms of RLS in a hemodialysis population. We also report personal observations over a 4-year period in our hemodialysis unit that support levodopa as an effective first-line therapy. We have averted suicidal ideation in two patients and frequently modified symptoms of severe sleep deprivation. The dose of levodopa/carbidopa must be individually titrated to each patient's symptomatology, and morning rebound and afternoon augmentation should be monitored.

Intramedullary chondroid tumors of bone: correlation of abnormal peritumoral marrow and soft-tissue MRI signal with tumor type.

OBJECTIVE: To determine whether enchondromas and chondrosarcomas can be differentiated on the basis of peritumoral MR signal abnormality. DESIGN: STIR and T2-weighted MRI images were retrospectively assessed for the presence and extent of abnormal peritumoral marrow and soft-tissue signal. The cause of the peritumoral signal abnormality was determined by histologic correlation with resection specimens. The presence or absence of bone destruction was noted. PATIENTS: Twenty-three patients were studied: ten with enchondromas (three men, seven women; ages 33-73 years) and 13 with chondrosarcomas (seven men, six women; ages 25-88 years). RESULTS: Abnormal peritumoral marrow signal was present on STIR images around none of 10 enchondromas and all of 13 chondrosarcomas (P < 0.0001). The marrow signal abnormality corresponded histologically to fine marrow fibrosis in all cases. Adjacent abnormal soft-tissue signal was present on STIR images around none of ten enchondromas and eight (62%) of 13 chondrosarcomas (P = 0.0026). Abnormal soft-tissue signal was more common around high-grade than low-grade chondrosarcomas (100% vs 38%, P = 0.028), and was more extensive (mean extent 28 mm vs 8 mm; P > 0.04). In the subset of tumors without bone destruction, peritumoral marrow signal abnormality was present around none of ten enchondromas and all of five chondrosarcomas (P = 0.0003); abnormal soft-tissue signal was present around none of ten enchondromas and two of five chondrosarcomas (P > 0.05). CONCLUSION: Abnormal marrow or soft-tissue signal around a chondroid tumor is suggestive of chondrosarcoma, even in the absence of bone destruction. STIR images are necessary for adequate detection of peritumoral signal abnormalities.

Vaccine-induced hepatitis B surface antigen positivity in adult hemodialysis patients: incidental and surveillance data.

This report describes hepatitis B vaccinations that resulted in transient hepatitis B surface antigen positivity in six adult hemodialysis patients. Initially, three patients were incidentally discovered to be hepatitis B surface antigen-positive temporally related to hepatitis B vaccination. Two other patients who displayed transient positivity were among 15 hemodialysis patients under prospective surveillance after receiving a dose of hepatitis B vaccine. The sixth patient was negative for hepatitis B surface antigen when monitored in the prospective surveillance group but was incidentally found to be positive after a nonsurveillance dose of the vaccine. All positive cases cleared hepatitis B surface antigen within 20 days of vaccination. In our search of the literature, this is the first report of hepatitis B vaccine inducing hepatitis B surface antigen positivity in adult hemodialysis patients. Because this study proposes that this transient surface antigen positivity is vaccine-induced and not a true hepatitis B infection, we recommend that renal dialysis patients not be screened for hepatitis B surface antigen for at least 21 to 28 days after hepatitis B vaccination. As well, blood donors should not donate blood in this early postvaccination period. These guidelines would incorporate a measure of safety to prevent individuals in the early postinoculation period from being erroneously labeled as having hepatitis B viral infections.

Response to methotrexate in a patient with idiopathic eosinophilic fasciitis, morphea, IgM hypergammaglobulinemia, and renal involvement.

A 35-year-old man with idiopathic eosinophilic fasciitis (EF) and morphea developed renal disease characterized by microscopic hematuria, nephrotic range proteinuria, and rapidly progressing hypertension, an association that has not previously been reported in EF. Initial clinical symptoms of EF began in July 1989; peripheral eosinophilia peaked at 30% in August 1990; an abnormal urinalysis was first observed in March 1992 and subsequently a renal biopsy was performed. Renal biopsy demonstrated focal segmental glomerulosclerosis and a subepithelial immune-type deposit. Partial fasciectomy and a course of methotrexate resulted in overall functional improvement of his extremities. Proteinuria and hematuria was reduced during methotrexate therapy.

Neuropsychological evaluation of preschoolers with fetal alcohol syndrome.

Children with Fetal Alcohol Syndrome (FAS) manifest a variety of central nervous system deficits which may include mental retardation, perceptual, linguistic and fine motor deficits, as well as behaviour problems. The neuropsychological performance of to preschool-aged children with FAS was compared to age, sex, and race-matched controls. Profile analysis revealed significant deficits in the FAS group on measures of intelligence and linguistic abilities. Comparison of group profiles revealed that the FAS group displayed impaired visual-motor integration in the presence of average visual-perceptual matching. The FAS children were also reported to exhibit a greater frequency of behaviour problems compared to controls. Although the FAS group were significantly growth delayed, the often reported association between cognitive abilities and skeletal growth was not evident. These results indicate that preschoolers with FAS display a distinct pattern of impairments, and understanding of this unique ability profile is important for the development of support and intervention programs for these patients and their families.

Glycerylphosphocholine phosphocholine phosphodiesterase activity is reduced in multiple sclerosis plaques.

Glycerylphosphorylcholine (GPC) phosphocholine phosphodiesterase activity (EC 3.1.4.38) is significantly reduced in multiple sclerosis plaques compared to adjacent tissue with a P less than 0.01 based upon the Student-Newman-Keuls or Tukey test. This finding is in accord with the proposal that this particular form of the enzyme is myelin-specific. Similar activities for GPC phosphocholine phosphodiesterase were obtained with samples from various regions of the same individual brain.

Financing outpatient mental health care: how much does insurance actually help?

Providers of mental health services in both public and private sectors are becoming increasingly dependent on third-party health insurance to cover the costs of outpatient psychotherapy. The present investigation examines reimbursement rates for the cost of the average course of psychotherapy for a sample of industries in one city. Results suggest that insurance coverage should not be viewed as a panacea by mental health providers.

Comparison of a commercial ELISA assay for indole-3-acetic Acid at several stages of purification and analysis by gas chromatography-selected ion monitoring-mass spectrometry using a c(6)-labeled internal standard.

Quantitative analysis of indole-3-acetic acid (IAA) using selected ion monitoring gas chromatography-mass spectrometry (GC-MS) with (13)C(6)[benzene ring]-IAA as the internal standard was used to compare the quantitative accuracy of commercial enzyme-linked immunoabsorbent assay (ELISA) kits. Plant materials differed in the amount of purification required prior to use of ELISA for reliable estimates to be made. Purification similar to that obtained by at least one high performance liquid chromatographic (HPLC) step was generally necessary prior to ELISA analysis of plant materials. Additional levels of purification appeared to be required for some plant materials prior to HPLC in order to obtain an accurate estimate by ELISA techniques. In no case was it possible to obtain reasonable estimates of IAA from crude extracts or even from acidic fractions of extracts of plant tissues. GC-MS techniques provide a rapid and simple method for checking the validity of ELISA techniques. Quantitative GC-MS, or a similar technique that provides an independent quantitative validation, should, whenever possible, be applied to each new plant material under study if use of the ELISA is planned.