Developing a computer algorithm to identify epilepsy cases in managed care organizations.

The goal of this study was to develop an algorithm for detecting epilepsy cases in managed care organizations (MCOs). A data set of potential epilepsy cases was constructed from an MCO's administrative data system for all health plan members continuously enrolled in the MCO for at least 1 year within the study period of July 1, 1996 through June 30, 1998. Epilepsy status was determined using medical record review for a sample of 617 cases. The best algorithm for detecting epilepsy cases was developed by examining combinations of diagnosis, diagnostic procedures, and medication use. The best algorithm derived in the exploratory phase was then applied to a new set of data from the same MCO covering the period of July 1, 1998 through June 30, 2000. A stratified sample based on ethnicity and age was drawn from the preliminary algorithm-identified epilepsy cases and non-cases. Medical record review was completed for 644 cases to determine the accuracy of the algorithm. Data from both phases were combined to permit refinement of logistic regression models and to provide more stable estimates of the parameters. The best model used diagnoses and antiepileptic drugs as predictors and had a positive predictive value of 84% (sensitivity 82%, specificity 94%). The best model correctly classified 90% of the cases. A stable algorithm that can be used to identify epilepsy patients within MCOs was developed. Implications for use of the algorithm in other health care settings are discussed.     

Hyperbaric oxygenation induced tolerance against focal cerebral ischemia in mice is strain dependent

SV129 or C57BL/6 mice were exposed to hyperbaric oxygenation (HBO, 5 days, 1 h every day, 100% O(2) at 3 atm absolute). One day after the 5th HBO session focal cerebral ischemia was induced. In SV129 mice, HBO induced tolerance against permanent focal cerebral ischemia (n=42, mean infarct volume reduction 27%, P=0.001), but not against transient (30 or 60 min) focal cerebral ischemia. In the C57BL/6 strain of mice, HBO did not induce tolerance against focal cerebral ischemia, even when the duration of ischemia or the HBO protocol were modified. For the first time we demonstrate that HBO can induce tolerance to focal cerebral ischemia, but this effect is strain dependent.     

Frataxin point mutations in two patients with Friedreich's ataxia and unusual clinical features

Two patients with a progressive ataxia are presented with clinical features consistent with classic Friedreich's ataxia (FRDA), but also with features unusual for FRDA. Analysis of DNA showed that each patient is heterozygous for the expanded GAA repeat of FRDA, but carries a base change on his other frataxin allele. For one patient a non-conservative arginine to cysteine amino acid change is predicted at amino acid 165 whereas the other mutation is found at the junction of exon one and intron one. Muscle biopsy showed an absence of frataxin immunoreactivity in the patient harbouring the intronic mutation, confirming the pathological nature of the base change. These mutations extend the range of point mutations seen in FRDA, and agree with recent reports suggesting phenotypic variation in patients with FRDA harbouring point mutations in conjunction with an expanded GAA repeat.     

Effects of remifentanil on neutrophil adhesion, transmigration, and intercellular adhesion molecule expression

BACKGROUND: Anaesthetic drugs are used for pain therapy and anaesthesia. Neutrophils play a significant role during the process of inflammation. The aim of the current study was to investigate the effects of remifentanil and fentanyl on neutrophil migration through endothelial cell monolayers, and on adhesion molecule expression. METHODS: After isolation of polymorphonuclear neutrophils (PMNL) we used a currently described migration assay. PMNL and/or endothelial cell monolayers (ECM) were pre-treated with remifentanil using clinically relevant, as well as higher and lower concentrations or relevant concentrations of fentanyl. RESULTS: Concentrations of remifentanil (50 ng/mL) similar to the relevant plasma concentration were able to inhibit PMNL migration through ECM significantly (migration compared to the control 82+/-7% SD; P<0.05), when both cell types were treated with the synthetic narcotic remifentanil. Fentanyl (30 ng/mL) showed a stronger inhibitory effect (migration compared to the control 67+/-9.2%; P<0.05). Endothelial cell adhesion molecule expression was reduced after either remifentanil or fentanyl. CONCLUSION: The results of the present investigation indicate that remifentanil influences interaction of ECM against human neutrophils. Compared to fentanyl, remifentanil seems to exhibit minor inhibitory effects on neutrophil migration.     

Surface EMG-recordings using a miniaturised matrix electrode: a new technique for small animals

A new method for multichannel surface-EMG measurements in small animals is presented. The underlying scientific aim is the characterisation of the spreading and the co-ordination of skeletal muscle activation between different muscles or muscle parts, depending on various motor tasks. The myoelectrical signals were recorded monopolarly by a 16-channel matrix electrode on the muscle surface directly under the skin on the fascia of the investigated muscle, without damaging the muscle. Surface-EMG's were recorded for at least 5 days after surgery without electrical interferences. During defined motor tasks, the projection of the myoelectrical activation of the different parts of the M. triceps brachii of rats (Rattus norvegicus), pikas (Ochotona rufescens) and cuis (Galea musteloides) or the M. anconeus of toads (Bufo marinus) on the muscle surface was mapped. The locomotion of the investigated animals was monitored by a three-dimensional kinematic analysis (video and/or high-speed cineradiography). There was no perceptible influence from application of EMG matrix electrode. The miniaturised matrix electrode seemed practicable in gaining insight into changes in myoelectrical activation patterns (EMG mapping). This allows a characterisation of the intramuscular co-ordination processes corresponding to the actual morphofunctional state of the investigated animals.     

Analysis of concerted expression of angiogenic growth factors in acute myeloid leukemia: expression of angiopoietin-2 represents an independent prognostic factor for overall survival.

PURPOSE: Bone marrow neoangiogenesis plays an important pathogenetic and possible prognostic role in acute myeloid leukemia (AML). Members of the vascular endothelial growth factor (VEGF) and angiopoietin family represent the most specific inducers of angiogenesis secreted by AML blasts. We therefore correlated expression of angiogenic factors with clinical variables. PATIENTS AND METHODS: We investigated the expression of VEGF-A, VEGF-C, angiopoietin-1 (Ang1), angiopoietin-2 (Ang2), and the receptor Tie2 by quantitative polymerase chain reaction in a cohort of 90 patients younger than 61 years with de novo AML entered into the German AML Süddeutsche H?moblastose Gruppe Hannover 95 trial. Uni- and multivariate analyses were performed using clinical and gene expression variables. RESULTS: Univariate analysis of overall survival indicated the following variables as prognostic factors: good response on a day-15 bone marrow examination after initiation of induction chemotherapy, karyotype, and high Ang2 expression. In multivariate analysis, only bad response and log Ang2 expression remained of statistical significance, with a hazard ratio of 3.51 (95% CI, 1.91 to 6.47) and 0.75 (95% CI, 0.61 to 0.91), respectively. Subgroup analysis suggested that the prognostic impact of Ang2 expression was especially evident in cohorts with low VEGF-C and Ang1 mRNA levels. CONCLUSION: These results show that expression of Ang2 represents an independent prognostic factor in AML. Additional research into interactions of angiogenic cytokines in the pathogenesis of bone marrow angiogenesis in AML is warranted.     

Correction: Phase I clinical study of the recombinant antibody-toxin scFv(FRP5)-ETA specific for the ErbB2/HER2 receptor in patients with advanced solid malignomas

Overcoming dendritic cell (DC) dysfunction is a prerequisite for successful active immunotherapy against breast cancer. CD40 ligand (CD40L), a key molecule in the interface between T-lymphocytes and DCs, seems to be instrumental in achieving that goal. Commenting on our data that CD40L protects circulating DCs from apoptosis induced by breast tumor products, Lenahan and Avigan highlighted the potential of CD40L for immunotherapy. We expand on that argument by pointing to additional findings that CD40L not only rescues genuine DCs but also functionally improves populations of immature antigen-presenting cells that fill the DC compartment in patients with breast cancer.     

Diagnostic specificity of the African swine fever virus antibody detection enzyme‐linked immunosorbent assay in feral and domestic pigs in the United States

African swine fever (ASF) is a highly contagious haemorrhagic disease of pigs that has the potential to cause mortality nearing 100% in naïve animals. While an outbreak of ASF in the United States’ pig population (domestic and feral) has never been reported, an introduction of the disease has the potential to cause devastation to the pork industry and food security. During the recovery phase of an outbreak, an antibody detection diagnostic assay would be required to prove freedom of disease within the previously infected zone and eventually nationwide. Animals surviving an ASF infection would be considered carriers and could be identified through the persistence of ASF viral antibodies. These antibodies would demonstrate exposure to the disease and not vaccination, as there is no ASF vaccine available. A well‐established commercial enzyme‐linked immunosorbent assay (ELISA) detects antibodies against ASF virus (ASFV), but the diagnostic specificity of the assay had not been determined using serum samples from the pig population of the United States. This study describes an evaluation of the World Organization for Animal Health (OIE)‐recommended Ingezim PPA COMPAC ELISA using a comprehensive cohort (n = 1791) of samples collected in the United States. The diagnostic specificity of the assay was determined to be 99.4% (95% confidence interval (CI): [98.9, 99.7]). The result of this study fills a gap in understanding the performance of the Ingezim PPA COMPAC ELISA in the ASF naïve pig population of the United States.     

αCaMKII controls the establishment of cocaine's reinforcing effects in mice and humans

Although addiction develops in a considerable number of regular cocaine users, molecular risk factors for cocaine dependence are still unknown. It was proposed that establishing drug use and memory formation might share molecular and anatomical pathways. Alpha-Ca²⁺/calmodulin-dependent protein kinase-II (αCaMKII) is a key mediator of learning and memory also involved in drug-related plasticity. The autophosphorylation of αCaMKII was shown to accelerate learning. Thus, we investigated the role of αCaMKII autophosphorylation in the time course of establishing cocaine use-related behavior in mice. We found that αCaMKII autophosphorylation-deficient αCaMKII^T286A mice show delayed establishment of conditioned place preference, but no changes in acute behavioral activation, sensitization or conditioned hyperlocomotion to cocaine (20 mg kg⁻¹, intraperitoneal). In vivo microdialysis revealed that αCaMKII^T286A mice have blunted dopamine (DA) and blocked serotonin (5-HT) responses in the nucleus accumbens (NAcc) and prefrontal cortex after acute cocaine administration (20 mg kg⁻¹, intraperitoneal), whereas noradrenaline responses were preserved. Under cocaine, the attenuated DA and 5-HT activation in αCaMKII^T286A mice was followed by impaired c-Fos activation in the NAcc. To translate the rodent findings to human conditions, several CAMK2A gene polymorphisms were tested regarding their risk for a fast establishment of cocaine dependence in two independent samples of regular cocaine users from Brazil (n=688) and Switzerland (n=141). A meta-analysis across both samples confirmed that CAMK2A rs3776823 TT-allele carriers display a faster transition to severe cocaine use than C-allele carriers. Together, these data suggest that αCaMKII controls the speed for the establishment of cocaine''s reinforcing effects.