Intracranial hypotension presenting with severe encephalopathy. Case report

A patient with severe and protracted symptoms from intracranial hypotension is described. The patient's presentation was marked by diffuse encephalopathy and profound depression of consciousness. This case report expands the presently known clinical spectrum of this uncommon and generally benign illness. The clinical and laboratory findings typically observed in the syndrome of intracranial hypotension are outlined. The pathophysiological mechanisms of the phenomenon are briefly discussed. Intracranial hypotension is a potentially severe illness with specific treatments that are distinct from the treatment of most neurological diseases. Three cardinal features--postural headache, pachymeningitis, and descent of midline cerebral structures--should prompt the diagnosis.     

Approaches to deductive object-oriented databases

The paper is concerned with the problem of combining deductive and object-oriented features to produce a deductive object-oriented database system which is comparable to those currently available under the relational view of data modelling not only in its functionality but also in the techniques employed in its construction and use. Under this assumption, the kinds of issues that have to be tackled for a similar research strategy to produce comparable results are highlighted. The authors motivate their terms of comparison, characterize three broad approaches to deductive object-oriented databases and introduce the notion of language convergence to help in the characterization of some shortcomings that have been perceived in them. Three proposals that have come to light in the past three years are looked into in some detail, in so far as they exemplify some of the positions in the space of choices defined. The main contribution of the paper is towards a characterization of the language convergence property of deductive database languages which has a key role in addressing critiques of the deductive and object-oriented database research enterprise. A basic familiarity with notions from deductive databases and from object-oriented databases is assumed.     

Excitotoxin lesions in primates as a model for Huntington's disease: histopathologic and neurochemical characterization

Excitotoxin lesions induced by quinolinic acid (QA) were made unilaterally in the caudate nucleus and putamen of 12 rhesus monkeys. Both acute (2-3 weeks) and chronic (4-6 months) effects were evaluated. Excitotoxin striatal lesions were characterized by a central zone of intense astrogliosis and marked neuronal depletion, which was surrounded by a transition zone in which there was partial neuronal sparing throughout the entire lesioned side. Immunocytochemical and enzyme histochemical markers for both large and medium-sized aspiny- and spiny-striatal neurons clearly demonstrated a selective pattern of neuronal vulnerability to the excitotoxic effects of QA within lesioned striata. Medium-sized spiny neurons containing calbindin Dk28, enkephalin, and substance P were disproportionately lost, while aspiny neuronal subpopulations containing NADPH diaphorase (NADPH-d) and choline acetyltransferase activity (ChAT) were relatively spared. Combined labeling by NADPH-d enzyme histochemistry and Nissl staining, as well as NADPH-d histochemistry and calbindin Dk28 immunocytochemistry, demonstrated significant increases in the ratio of aspiny to spiny neurons within the lesioned striata. Neurochemical measurements confirmed a loss of GABA and substance P-like immunoreactivity yet no significant depletion of somatostatin-like immunoreactivity, neuropeptide Y-like immunoreactivity, or ChAT were seen. The striatal patch-matrix pattern persisted, as demonstrated by acetylcholinesterase activity. The pattern was altered, however, in the chronic animals, such that the matrix zone was significantly reduced, while the total area of patches remained within normal limits. Ultrastructural analysis confirmed axon sparing lesions with neuronal loss and astrogliosis. Pretreatment of 3 monkeys with MK-801, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, blocked striatal QA neurotoxicity. The present results provide an experimental primate model which closely resembles the neuropathologic and neurochemical features of Huntington's disease. These findings further strengthen the possibility that an NMDA receptor-mediated excitotoxic process plays a role in the pathogenesis of this disorder.     

The alpha-synuclein Ala53Thr mutation is not a common cause of familial Parkinson''s disease: a study of 230 European cases. European Consortium on Genetic Susceptibility in Parkinson''s Disease

Deoxyguanosine kinase (dGK) is an enzyme responsible for the phosphorylation of purine deoxynucleosides in mitochondria of mammalian cells. Its role in activation of pharmacologically used nucleoside analogs is not well understood, because of the low levels of dGK found in tissue extracts and its inactivation during purification. The cDNA for dGK was recently cloned and expressed in Escherichia coli. Here we present an improved procedure for expression and purification of a highly active form of human recombinant dGK. The enzyme showed a broad substrate specificity toward natural purine and pyrimidine deoxynucleosides as well as toward important nucleoside analogs. The Km and Vmax values for deoxyguanosine, deoxyinosine, deoxyadenosine, and deoxycytidine were 4, 13, 460, 330 microM and 43, 330, 430 and 60 nmol/min/mg of protein, respectively. Antileukemic purine analogs such as arabinosyl guanine, 2-chloro-2'-deoxyadenosine, 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine, and 2-fluoro-arabinosyl-adenine were phosphorylated as efficiently by dGK as the natural nucleoside substrates. This is the first report in which 2-fluoro-arabinosyl-adenine and 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine were shown to be good substrates for dGK. The antiviral analogs dideoxyinosine and arabinosyl adenine also showed significant activity with dGK, as did several pyrimidine analogs (e.g., the cytostatic drugs 5-fluoro-2'-deoxycytidine and difluorodeoxycytidine). The broad specificity of dGK described here may change our understanding of the mechanisms responsible for the efficacy and mitochondrial toxicity of several nucleoside analogs.     

A mouse model for varicella-zoster virus latency

Following primary infection with varicella-zoster virus (VZV), the virus establishes a latent infection in humans. The molecular pathogenesis of VZV latency is not well understood, mainly due to the lack of an adequate animal model. We report here that we have developed a mouse model for VZV infection that involves corneal inoculation of mice. Although infected animals showed no signs of disease, most of the animals could not eliminate the virus early after infection. By PCR, we demonstrated that at 33 days post-infection (p.i.), viral DNA was still present in more than 60% of the animals (14/21). VZV DNA was most frequently detected in the trigeminal ganglia (7/14) followed by the brain stem (10/21), kidneys (4/21), spleen (3/20), liver (2/21) and brain (1/21). By in situ hybridization, a few cells positive for VZV mRNA were detected in the trigeminal ganglia, brain stem, cerebellum and spleen of a small number of the infected animals as late as 33 days p.i. No viral proteins were detected at the site of inoculation or in any other tissue by immunostaining. Our results suggest that VZV spreads in mice by both viraemia and axonal transport and establishes a non-productive (latent) infection.     

The relationship of effective dose to personnel and monitor reading for simulated fluoroscopic irradiation conditions

The exposure of staff during fluoroscopic procedures was simulated for overcouch x-ray tube/undercouch image intensifier and undercouch x-ray tube/overcouch image intensifier geometries. A Rando phantom with film badge dosimeters attached to the skin surface at seven commonly used monitoring sites and loaded with lithium fluoride thermoluminescent dosimeters was irradiated for an extended period in the vicinity of a patient couch. Scattered radiation generated from the irradiation of an anthropomorphic phantom using primary radiation in the range of 70 kVp-110 kVp was used. The radiation dose to organs which were shielded by a lead apron was estimated from the unattenuated organ dose readings by applying an experimentally determined scattered radiation transmission factor. The ratio of effective dose to film badge reading was obtained for a range of irradiation conditions and lead apron thicknesses. For most irradiation conditions studied, a dosimeter worn above the lead apron will significantly overestimate effective dose by a factor of between 2 and 60, depending on the irradiation conditions. A dosimeter worn under the apron at either waist or chest level, will generally yield a closer (although usually an underestimate of) effective dose, typically within a factor of 7 for the most common lead apron thicknesses and irradiation conditions. No single dosimeter can accurately monitor effective dose for all irradiation conditions in fluoroscopy.     

Novel role of transmembrane SCF for mast cell activation and eotaxin production in mast cell-fibroblast interactions

Mast cell activation can be induced by multiple mechanisms, including IgE-, complement-, and stem cell factor (SCF)-mediated pathways. In addition, the interaction of mast cells with particular cell populations, such as fibroblasts, have also demonstrated increased mast cell reactivity. In these studies, we have investigated the role of fibroblast-mast cell interaction for induction of histamine release and chemokine production and the specific role of SCF during this interaction. Primary pulmonary fibroblast cell lines were grown in culture and used throughout these studies. Mast cells were grown in parallel with fibroblasts by incubation of bone marrow cells with SCF and IL-3. During mast cell-fibroblast coculture, increased histamine release could be attenuated either by separation of the cell populations using a Trans-Well setup, which did not allow cellular contact, or by specific anti-SCF Ab. In addition, a significant increase in eotaxin, a potent eosinophil-specific C-C chemokine, was also observed during fibroblast-mast cell interaction. The production of eotaxin was cell contact dependent and could be inhibited using an anti-SCF Ab or specific antisense therapy. SCF was constitutively produced from fibroblasts in its transmembrane form and could be induced by TNF. SCF-coated plates induced significant mast cell-derived eotaxin production, whereas soluble SCF induced little or no eotaxin, suggesting a necessity for receptor cross-linking for activation. These studies indicate that fibroblast-mast cell contact plays a role in exacerbation of histamine release and eotaxin production.