Temporal ranges of central nervous processing: clinical evidence

 The organization of the time frames for perceiving, generating, and updating information in the CNS has as of yet received little attention despite its elementary character for human behavior. We investigated temporal epochs in perceiving, acting, and updating in patients with anterior and posterior lesions of the left and right hemisphere, in patients with lesions in the left hemisphere without aphasia, and in healthy controls. Three temporal ranges, 30, 300, and 3000 ms, were assessed with different psychophysical paradigms. Prolongation of the temporal perception of order (30 ms) was most pronounced with left posterior lesions, of repetitive action (300 ms) with left anterior lesions, and updating (3000 ms) with left and right anterior lesions. Temporal deficits are group as well as parameter specific. Our results support the notion of coordinated coexistence of different temporal mechanisms.     

In vivo efficacy of azithromycin in treatment of systemic infection and septic arthritis induced by type IV group B Streptococcus strains in mice: comparative study with erythromycin and penicillin G.

We compared the activities of azithromycin, erythromycin, and penicillin G in a mouse model of systemic infection and septic arthritis induced by type IV group B streptococci (GBS). The in vitro and in vivo efficacy data for these drugs were analyzed relative to the pharmacokinetics of the drugs in sera, joints, and kidneys. Adult CD-1 mice were infected intravenously with 10(7) CFU of type IV GBS. Intraperitoneal drug administration was initiated with different dose regimens at different times after infection. A single dose of azithromycin (100 mg/kg) strongly reduced the incidence of articular lesions with respect to that with erythromycin or penicillin G. Treatment with azithromycin (three intraperitoneal administrations of 50 mg/kg at 12-h intervals) resulted in the complete prevention of arthritis. In contrast, erythromycin was poorly effective and penicillin G was effective only if inoculated 30 min after infection and at high doses (400,000 or 600,000 IU/kg). Furthermore, azithromycin was able to cure about 70% of the mice when administered 7, 8, and 9 days after GBS infection. Azithromycin was much more active than erythromycin and penicillin G with respect to bacterial killing in the joints and kidneys. In fact, cultures from these tissues were always negative no matter what treatment schedule was employed. The pharmacokinetics of azithromycin account for its superior in vivo efficacy against type IV GBS. A longer half-life and higher levels of this drug in serum and tissues with respect to those for erythromycin or penicillin G were achieved. The high affinity of azithromycin for the joints strongly supports its potential value for therapy of septic arthritis, which is a severe and frequent clinical manifestation of GBS infection.     

Holographic interferometry forIn Vitro investigation of bioprosthetic valves

Dysfunction of heart valve prostheses—mechanical as well as biological—is a common problem in cardiac surgery. The reasons for the valve failures are still not well understood. Biological valves especially have an unsatisfactory durability; degeneration and calcification very often lead to the failure of the valves. In our opinion, hidden defects present in the valve material prior to implantation of the valves is a plausible explanation for the dysfunction. Hitherto there has been no technique to detect these defects without destructing the specimen. Holographic interferometry proved to be applicable forin vitro evaluation of mechanical heart valve prostheses. In the present paper we describe application of this method to biological valves. Nine porcine bioprostheses and four fresh porcine aortic valves were investigated by means of holographic interferometry. In eight of nine bioprostheses, the results showed irregularities of the leaflet structure which depend on anomalies of the connective tissue of the leaflets of the valves. To make sure that these findings are not due to normal variations of the morphology, the investigations were carried out with fresh and unfixated porcine aortic valves. In the latter, no such anomalies of the structure were detected. The results obtained confirm the above hypothesis on the origin of the later valve dysfunction. Thus, holographic interferometry tests of bioprostheses prior to their implantation prevent the use of potentially dysfunctional valves.Presented at the 35th World Congress, International College of Angiology, Copenhagen, Denmark, July 1993     

Systemic and peritoneal host defense in peritonitis

Most of the work of host defense has been carried out in mixed patient populations. It is now clear that elective preoperative surgical patients have totally different host defense capabilities as compared to posttrauma patients or those suffering from peritonitis. Specific cell-mediated immune studies need to be repeated in these 2 patient groups as well. What will contribute clinical relevance to these studies will be the means to correct the defects. If these defects or—more correctly termed—abnormalities of host defense are, indeed, important and contribute to an increased sepsis rate and mortality from sepsis in affected patients, then correcting them should reduce these complications. This hypothesis can only be tested when such means become available. The issues of most interest in the next few years will be the significance of serum albumin in host outcome, the role of immunomodulators, the involvement of cytokines in the overall process of host defense, and the use of specific nutritional support regimens targeted to the immune system.

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Resumen La mayor parte del trabajo sobre los mecanismos de defensa del huésped ha sido realizada en poblaciones mixtas de pacientes. Actualmente aparece claro que los pacientes preoperatorios electivos poseen una capacidad de defensa de huésped totalmente diferente que la de los pacientes en estado posttrauma o de aquellos con peritonitis. Aparece necesario realizar estudios específicos de inmunidad celular en estos 2 grupos de pacientes; aquello que aporte pertinencia clínica en tales estudios habrá de representar medios para corregir estos defectos. Si tales defectos, mejor denominados anormalidades en las defensas del huésped, son de verdad importantes y contribuyen a mayores tasas de infección y de mortalidad por sepsis en los pacientes afectados, su corrección debe resultar en reducción de estas complicaciones. Esta hipótesis sólo puede ser puesta a prueba cuando tales medios se hallen disponibles. Los aspectos de mayor interés en los próximos años serán el significado de la albúmina sérica en la evolución final del huésped, el papel de los inmunomoduladores, la participación de las citocinas en el proceso general de defensa del huésped, y el uso de regimenes especificos de soporte nutricional dirigidos hacia el sistema inmune.

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Résumé La plupart des travaux sur les mécanismes de défense ont été faits sur les populations mixtes. Il est à présent certain que les patients opérés électivement ont des mécanismes de défense préopératoire totalement différents de ceux des traumatisés ou des patients ayant une infection péritonéale. Les études immunologiques sur la médiation cellulaire spécifique méritent d'être refaites chez ces deux populations. Ce qui ressortira de ces études donnera les moyens de corriger les défauts ou plutôt les anomalies des mécanismes de défense qui contribuent à augmenter septicité et mortalité en rapport avec l'état septique. Cette hypothèse ne peut être vérifiée qu'avec ces moyens. Les questions les plus intéressantes dans les années à venir sera peut-être de connaître l'influence de l'albumine sérique sur l'évolution, le rôle des immunomodulaterus, celui des cytokinines dans le procédé global des mécanismes de défense, et celui de l'utilisation de l'alimentation spécifique pour améliorer le système immune.

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Supported in part by grants from the Medical Research Council of Canada and the Fonds de recherche de Santé.     

Lines of Murine Oligodendroglial Precursor Cells Immortalized by an Activated neu Tyrosine Kinase Show Distinct Degrees of Interaction with Axons In Vitro and In Vivo

Replication-defective retroviruses expressing the t- neu oncogene, or a hybrid protein with the neu tyrosine kinase linked to the external region of the human epidermal growth factor receptor ( egfr-neu ), were used to establish lines of murine oligodendroglial precursor cells. Differentiation of the t- neu lines into myelin-associated glycoprotein (MAG)-positive oligodendrocytes was induced by dibutyryl cAMP, and the egfr-neu line showed limited differentiation in vitro upon withdrawal of epidermal growth factor. Cerebellar granule cell neurons expressed mitogens for the cell lines. Upon transplantation into demyelinated lesions, t- neu line cells engaged with the demyelinated axons whereas the egfr-neu line cells differentiated further and ensheathed the axons. These cell lines thus interact with neurons in vitro and in vivo and can be used as tools to define the molecules involved in different stages of neuron-glia interaction.     

Increased CSF neopterin levels in subarachnoid hemorrhage

Neopterin concentrations, reflecting T-cell macrophage activation, were analyzed in serum and cerebrospinal fluid (CSF) obtained from 14 patients with subarachnoid hemorrhage (SAH). Neopterin concentrations were elevated in both the serum and CSF. The increase in neopterin concentrations was most marked in the CSF, rising from Days 1 to 3 through Days 6 to 9; levels were highest in patient suffering from delayed cerebral ischemia. The present data were interpreted as signs of an ongoing T cell activation both systemically and in the CSF compartment following SAH.     

Malignant peripheral neuroectodermal tumors in urology

Summary During the past few years, a new tumor type has emerged in the pediatric and adolescent group of cancer patients, which has been designated malignant peripheral neuroectodermal tumor (MPNT). This tumor has some clinical and pathological signs in common with either soft-tissue sarcomas or classic Ewing's sarcoma, but is defined as a distinct entity because of its immunohistological characteristics. The tumor expresses neuronal markers, but the pattern varies: chromogranin, neuron-specific enolase, synaptophysin, protein S-100 and others. MPNT can occur in the urogenital region. The differential diagnosis on clinical grounds must include Ewing's and soft tissue sarcomas, and also Wilms' tumor and its variants. MPNT are often wide spread in the urogenital region when first diagnosed. Response to radiotherapy and combination chemotherapy is limited. Radical surgery is not always possible. The prognosis therefore remains rather poor at this time. A selection of MPNT patients is presented to demonstrate the various problems associated with this diagnosis. MRI and CT of all patients showed large tumors with direct infiltration of the surrounding structures. MRI is the best imaging modality for diagnosis and therapy monitoring in these tumors, because of its high soft-tissue contrast.     

Comparison of three immunoassays for diagnosing sensitization to latex in children with spina bifida

As natural rubber latex (latex) has become more widespread in our environment, physicians have become increasingly aware of the problem of possible allergic reactions. Many fatal and near-fatal incidents have been reported (mainly during surgery) (1—3) and data has been published on groups frequently exposed to latex, such as patients with spina bifida (4—9), healthcare professionals (10—12) and occupationally exposed persons (13). The incidence of latex allergy in children seems to be increasing (14). Tests are therefore needed which can reliably detect sensitization to latex. Our aim was to compare the diagnostic accuracy of three commercial immunoassays for measuring specific IgE in serum to latex.