Heterogeneity of anti-beta2-glycoprotein I antibodies. A factor of variability in test results

The aim of this study was to evaluate the heterogeneity of IgGanti-beta2-glycoprotein I antibodies (IgG-abeta2GPI) as regarding their reactivity pattern against different sources of human beta2 GPI, their avidity and their association with clinical events of antiphospholipid syndrome (APS). Three thousand six hundred and eighty-four consecutive patient sera were routinely tested for IgGabeta2 GPI over 1 year using an in-house ELISA with 2 different commercial preparations of human purified beta2GPI. Of the 340 sera found positive, all those clinically documented were included in this study; 61 were positive with only one preparation (S1) and 59 with both (S2). The results of ELISA were confirmed by Western blot. Heterogeneity was stressed by testing sera with a human recombinant protein and 3 beta2GPI-related peptides. No contribution of glycosylation in the binding to beta2GPI was found. The avidity indices for each protein were significantly higher in S1 than in S2 (p=0.0021). S2 were more associated with antiphospholipid antibodies than S1 (75% versus 21% ; p<0.0001). A similar frequency of the main clinical features of APS was found in S1 and S2 sera (69% and 71%, respectively). In conclusion, our data show a heterogeneity in the antigenic reactivity pattern of IgG- abeta2 GPI and a relationship between a binding profile and antibody avidity. This heterogeneity could represent a crucial factor of variability in test results and underlines the difficulty of getting standardisation.     

Risperidone and haloperidol in first-episode psychosis: a long-term randomized trial

OBJECTIVE: The first episode of psychotic illness is a key intervention point. The initial experience with medication can affect willingness to accept treatment. Further, relapse prevention is a treatment cornerstone during the first years of illness because active psychotic illness may affect lifetime outcomes. Thus, initial treatment of active symptoms and subsequent relapse prevention are central goals of pharmacotherapy. This study compared long-term effectiveness of risperidone versus haloperidol in first-episode psychosis patients. METHOD: First-episode psychosis patients (N=555, mean age=25.4 years) participated in a double-blind, randomized, controlled flexible-dose trial that compared risperidone (mean modal dose=3.3 mg) and haloperidol (mean modal dose=2.9 mg). The median treatment length was 206 days (maximum=1,514). RESULTS: Positive and Negative Syndrome Scale scores and Clinical Global Impression ratings improved significantly relative to baseline, with no significant differences between groups. Three-quarters of the patients achieved initial clinical improvement, defined as >20% reduction in total Positive and Negative Syndrome Scale score. However, among those who achieved clinical improvement, 42% of the risperidone group experienced a relapse compared with 55% of the haloperidol group. The median time to relapse was 466 days for risperidone-treated subjects and 205 days for those given haloperidol. These differences were statistically significant based on Kaplan-Meier survival analysis. Adverse effects distinguished the treatments: there were significantly more extrapyramidal signs and symptoms and adjunctive medication use in the haloperidol group and greater prolactin elevation in the risperidone group. There was less weight gain with haloperidol initially but no significant differences between groups at endpoint. CONCLUSIONS: Relatively low doses of antipsychotic drugs lead to significant symptom amelioration in the majority of first-episode psychosis patients. In the long term, risperidone prevents relapse in more patients and for a longer time and also induces less abnormal movements than haloperidol.     

Cellular and molecular tunnels surrounding the forebrain commissures of human fetuses

Glial cells and extracellular matrix (ECM) molecules surround developing fiber tracts and are implicated in axonal pathfinding. These and other molecules are produced by these strategically located glial cells and have been shown to influence axonal growth across the midline in rodents. We searched for similar cellular and molecular structures surrounding the telencephalic commissures of fetal human brains. Paraffin-embedded brain sections were immunostained for glial fibrillary acidic protein (GFAP) and vimentin (VN) to identify glial cells; for microtubule-associated protein-2 (MAP-2) and neuronal nuclear protein (NeuN) to document neurons; for neurofilament (NF) to identify axons; and for chondroitin sulfate (CS), tenascin (TN), and fibronectin (FN) to show the ECM. As in rodents, three cellular clusters surrounding the corpus callosum were identified by their expression of GFAP and VN (but not MAP-2 or NeuN) from 13 to at least 18 weeks postovulation (wpo): the glial wedge, the glia of the indusium griseum, and the midline sling. CS and TN (but not FN) were expressed pericellularly in these cell groups. The anterior commissure was surrounded by a GFAP+/VN+ glial tunnel from 12 wpo, with TN expression seen between the GFAP+ cell bodies. The fimbria showed GFAP+/VN+ cells at its lateral and medial borders from 12 wpo, with pericellular expression of CS. The fornix showed GFAP+ cells somewhat later (16 wpo). Because these structures are similar to those described for rodents, we concluded that the axon guiding mechanisms postulated for commissural formation in nonhuman mammals may also be operant in the developing human brain.     

What do surgery residents do on their call nights?

BACKGROUND: Surgical resident education is entering a critical era of achieving core competencies despite work hour restrictions. An assessment of on-call activity is needed to maximize educational merit. METHODS: A time-motion study of resident on-call activity was performed at a university medical center and an urban affiliate hospital. Residents were followed by "shadow" residents who concurrently recorded resident activity. RESULTS: Activities of daily living and patient evaluation comprised the majority of on-call activity. Residents slept a median of 200 minutes per night. Cross-coverage activities accounted for 41% of pages and 19% of patient evaluation. Direct patient contact comprised only 7% of call night duties. Communication activity occupied 15% of total minutes, and a mean of 16 pages were received nightly. Significant differences in activities existed between resident levels and hospitals. CONCLUSIONS: Call activity consists primarily of activities of daily living, patient evaluation, and communication. Sleep accounts for nearly one third of all on-call activity. These data may be useful in improving both patient care and resident call experience.     

Efficacy and safety of long-acting risperidone in stable patients with schizoaffective disorder

BACKGROUND: The treatment of schizoaffective disorder is often complicated by the variety of symptoms that contribute to its pathology. Data from a large study (n=725), which included schizoaffective patients to assess the effect of long-acting risperidone, are presented. METHOD: A multicenter, open-label study enrolled non-acute, clinically stable patients with schizoaffective disorder (n=110). Patients on a stable dose of antipsychotic for at least 4 weeks at study entry were switched to long-acting risperidone every 2 weeks for 50 weeks. RESULTS: Mean Positive and Negative Syndrome Scale (PANSS) total scores (+/-S.E.) improved significantly (p<0.001) at each measured time point, including endpoint (-9.0+/-1.6), compared with baseline. Significant reductions were observed on mean PANSS cluster scores for both anxiety/depression (-1.3+/-0.4, p<0.001) and uncontrolled hostility/excitement (-0.7+/-0.3, p<0.05). In addition, scores improved significantly for positive symptoms (-2.2+/-0.5, p<0.001), negative symptoms (-3.1+/-0.5, p<0.001), and disorganized thoughts (-1.7+/-0.4, p<0.001). The overall subjective score of movement disorders was low at baseline (3.6+/-4.1) and had significantly decreased at endpoint (2.75; p<0.05). Patients were previously treated with antipsychotics for 398+/-790 days before being switched to long-acting risperidone. LIMITATIONS: Although this was a 50-week study, which included over 100 patients with schizoaffective disorder, limitations include the open-label design and that it was not designed specifically to assess patients with this disorder. PANSS symptom domains previously defined by factor analytic methods were used for mood symptom measures. No specific mood symptom scales were administered in this study. CONCLUSION: Patients with schizoaffective disorder, considered stable on their antipsychotic medication at study entry, experienced additional significant clinical improvements and minimal side effects with injections of long-acting risperidone over a 50-week study period.     

Inter-observer reproducibility of measurements of range of motion in patients with shoulder pain using a digital inclinometer

Background  

Reproducible measurements of the range of motion are an important prerequisite for the interpretation of study results. The digital inclinometer is considered to be a useful instrument because it is inexpensive and easy to use. No previous study assessed inter-observer reproducibility of range of motion measurements with a digital inclinometer by physical therapists in a large sample of patients.     

Dose-volume effects in rat thoracolumbar spinal cord: an evaluation of NTCP models

PURPOSE: To evaluate models for normal-tissue-complication probability (NTCP) on describing the dose-volume effect in rat thoracolumbar spinal cord. METHODS AND MATERIALS: Single-dose irradiation of four field lengths (4, 1.5, 1.0, and 0.5 cm) was evaluated by the endpoints paresis and white-matter necrosis. The resulting dose-response data were used to rank phenomenological and tissue architecture NTCP models. RESULTS: The 0.5-cm field length showed a steep increase in radiation tolerance. Statistical analysis of the model fits, which included evaluation of goodness of fit (GOF) and confidence intervals, resulted in the rejection of all the models considered. Excluding the smallest field length, the Schultheiss (D(50) = 21.5 Gy, k = 26.5), the relative seriality (D(50) = 21.4 Gy, s = 1.6, gamma(50) = 6.3), and the critical element (D(50,FSU) = 26.6 Gy, gamma(50,FSU) = 2.3, n = 1.3) model gave the best fit. CONCLUSION: A thorough statistical analysis resulted in a serial or critical-element behavior for the field lengths of 1.0 cm and greater. Including the 0.5-cm field length, the radiation response markedly diverged from serial properties, but none of the models applied acceptably described this dose-response relationship. This study suggests that the commonly assumed serial behavior of the spinal cord might be valid for daily use in external- beam irradiation.     

Rapid antimanic effect of risperidone monotherapy: a 3-week multicenter, double-blind, placebo-controlled trial

OBJECTIVE: This study evaluated the efficacy and safety of risperidone monotherapy in the treatment of acute bipolar mania. METHOD: Patients with DSM-IV bipolar I disorder experiencing an acute manic episode (baseline Young Mania Rating Scale score >/==" BORDER="0">20) were randomly assigned to 3 weeks of treatment with risperidone (flexible dose: 1-6 mg/day) or placebo. The primary efficacy measure was the mean baseline-to-endpoint change in total score on the Young Mania Rating Scale. Secondary efficacy measures included the Clinical Global Impression (CGI) severity rating and scores on the Montgomery-Asberg Depression Rating Scale, Positive and Negative Syndrome Scale, and Global Assessment Scale (GAS). Safety assessments consisted of monitoring adverse events, vital signs, electrocardiogram and laboratory results, and scores on the Extrapyramidal Symptom Rating Scale. RESULTS: Subjects (N=259) received treatment with either risperidone (N=134) or placebo (N=125). The mean modal dose of risperidone was 4.1 mg/day. Improvement in mean Young Mania Rating Scale total score (adjusted for covariates) was significantly greater in the risperidone than in the placebo group at endpoint (mean change=-10.6 [SD=9.5] versus -4.8 [SD=9.5], respectively), with significant between-group differences seen as early as 3 days after start of treatment (change with risperidone: mean=-6.8 [SD=5.8]; change with placebo: mean=-4.0 [SD=5.8]) and continuing throughout all time points. Improvements in CGI severity ratings and scores on the Montgomery-Asberg Depression Rating Scale, Positive and Negative Syndrome Scale, and GAS were also significantly greater among patients receiving risperidone than those given placebo. The most common adverse event reported among risperidone patients was somnolence. While Extrapyramidal Symptom Rating Scale scores were significantly greater in patients receiving risperidone, mean total and subscale scores were low. CONCLUSIONS: Risperidone monotherapy was significantly more efficacious than placebo in the treatment of acute mania and demonstrated a rapid onset of action. Risperidone was well tolerated by patients in this study.