Tuberculous meningitis: a 30-year review

Tuberculous meningitis remains an important illness that can be difficult to diagnose in a timely fashion and carries significant morbidity. We present a retrospective review of the cases of tuberculous meningitis diagnosed and treated at a single institution. Fifty-eight cases were identified and stratified according to stage of disease at presentation. Four patients (7%) died; three (5%) developed severe neurological sequelae. Poor outcomes were largely confined to cases presenting in an advanced stage and at the extremes of age. Corticosteroids were administered to 56 patients and may have contributed to the comparatively good outcome in these cases.     

Protein adsorption onto poly(ether urethane ureas) containing Methacrol 2138F: a surface-active amphiphilic additive

Surface characterization and protein adsorption studies were carried out on a series of additive dispersed and additive coated poly(ether urethane ureas), PEUUs, to characterize early events in the blood compatibility of these materials. A hypothesis that is based on surface hydrophilicity, surface flexibility, and adsorption media has been developed to understand the modulated adsorption of plasma proteins by PEUU additives. Electron spectroscopy for chemical analysis (ESCA) and contact angle analysis were performed on two PEUU formulation as well as on PEUU formulations modified with Methacrol 2138F (co[diisopropylaminoethyl methacrylate (DIPAM)/decyl methacrylate (DM)][3/1]) or acrylate or methacrylate polymer or copolymer analogs of Methacrol 2138F. Methacrol 2138F is a commercially used amphiphilic copolymethacrylate. ESCA showed that the PEUUs loaded with Methacrol 2138F or with its hydrophilic component, homopoly (DIPAM) (h-(DIPAM)), had a higher percentage of nitrogen at their surfaces than did the base PEUUs. Contact angle analysis also showed that the air side of PEUU formulations loaded with Methacrol 2138F were more hydrophobic than was the air side of base PEUUs when films were cast from dimethylacetamide. However, during contact angle testing, the air side of PEUU films loaded with Methacrol 2138F rapidly became more hydrophilic than did the air side of the base PEUU films. A radioimmunoassay and whole or diluted human plasma were also used to characterize the presence of the proteins fibrinogen, immunoglobulin G, factor VIII/von Willebrand factor, Hageman factor (factor XII), and albumin, on the surface of the same PEUUs as analyzed by ESCA and contact angle. The protein adsorption assay showed that PEUU films loaded or coated with Methacrol 2138F, with a copolyacrylate analog of Methacrol 2138F (co(diisopropylaminoethyl acrylate [DIPAA]/decyl acrylate [DA]) [3/1]), or with the hydrophilic polyacrylate or polymethacrylate component analogs of Methacrol 2138F (h-DIPAM or h-DIPAA) adsorbed significantly lower amounts of the proteins than did either the base PEUU formulations or the homopoly(decyl methacrylate) (h-DM) or homopoly(decyl acrylate) (h-DA) coated or loaded PEUUs.     

Parameter estimation and model verification of first order quasistatic error model for three-axis machining centers

Quasistatic error sources, which include thermal, mechanical loading and geometric error sources, are responsible for a very large proportion (typically, 70%) of the volumetric errors of a numerically controlled machine-tool. This paper, the first in a set of three, discusses the development of a very general model for the effects of geometric errors of the components of the kinematic chain (structural members and axes) of a machine on the volumetric errors in the work space. The effects of the other two sources are modeled as changes in the geometric error. The generality of the model arises from the fact that the errors along an axis of the machine can be characterized by any polynomial functions and the model is recursive in the order of these polynomials. This model can be used as the basis of a compensation scheme as well as in budgeting of errors on a machine-tool.     

Dyspnea resulting from phrenic nerve paralysis after interscalene brachial plexus block in an obese male--a case report

While current psychiatric taxonomies recognise a classification of amphetamine dependence, derived from the notion of an alcohol dependence syndrome, little research has validated that such a condition exists for this drug. Current amphetamine users (N = 331), were interviewed using the World Health Organization operationalisation of DSM-III-R substance dependence criteria, and a measure of the psychological components of dependence. Structural analyses indicated that a unidimensional dependence syndrome as assessed by DSM-III-R and DSM-IV criteria exists for amphetamine, and that physiological, psychological and behavioural indicators were all important in accounting for the variance in responses. It was demonstrated that the concept of a dependence syndrome is applicable to amphetamine, and that the inclusion of the amphetamine dependence syndrome in DSM-III-R and DSM-IV is valid.     

Distinguishable patterns of connectivity in serum immunoglobulins from SLE patients and healthy individuals

Given that normal individuals maintain significant levels of serum autoantibodies that share many characteristics with those found in association with autoimmune diseases (AID), it has been proposed that disease could result from defects in supraclonal regulation, namely deviations of normal patterns of immunoglobulin (Ig) connectivity. Using conventional methods, together with a recently developed technique to quantitatively score a variety of V-region-dependent serum IgG interactions, the authors have now compared serum Ig connectivity in a group of patients with systemic lupus erythematosus (SLE) to healthy controls. The results demonstrate the existence of V-region interactions of serum IgG and IgM in SLE patients and healthy donors, with comparable connectivity titres, diversity and average affinities (microM range), but a wider individual variation and a tendency for higher F(ab')2 directed reactivities in the group of SLE patients. Multivariate statistics analysis of the data derived from reactivity patterns on F(ab')2 subsets, however, distinguished the two groups of donors, and demonstrated a larger dispersion and wider time-dependent variations in the patient population, as compared to healthy controls. The authors conclude that SLE is associated with circulating antibody repertoires that deviate from the patterns and levels of V-region connectivity characteristic of healthy individuals. These findings may shed light on the mechanisms of disease maintenance, and on the basis for the therapeutic effects of normal polyclonal Igs at high doses.     

The additivity of substrate fragments in enzyme-ligand binding

BACKGROUND: Enzymes have evolved to recognise their target substrates with exquisite selectivity and specificity. Whether fragments of the substrate--perhaps never available to the evolving enzyme--are bound in the same manner as the parent substrate addresses the fundamental basis of specificity. An understanding of the relative contributions of individual portions of ligand molecules to the enzyme-binding interaction may offer considerable insight into the principles of substrate recognition. RESULTS: We report 12 crystal structures of Escherichia coli thymidylate synthase in complexes with available fragments of the substrate (dUMP), both with and without the presence of a cofactor analogue. The structures display considerable fidelity of binding mode and interactions. These complexes reveal several interesting features: the cofactor analogue enhances the localisation of substrate and substrate fragments near the reactive thiol; the ribose moiety reduces local disorder through additional specific enzyme-ligand interactions; the pyrimidine has multiple roles, ranging from stereospecificity to mechanistic competence; and the glycosidic linkage has an important role in the formation of a covalent attachment between substrate and enzyme. CONCLUSIONS: The requirements of ligand-protein binding can be understood in terms of the binding of separate fragments of the ligand. Fragments which are subsystems of the natural substrate for the enzyme confer specific contributions to the binding affinity, orientation or electrostatics of the enzymatic mechanism. This ligand-binding analysis provides a complementary method to the more prevalent approaches utilising site-directed mutagenesis. In addition, these observations suggest a modular approach for rational drug design utilising chemical fragments.     

Losses of volatile compounds during fermentation

The ability of fermentative CO₂ to blow off the volatile compounds that are synthesized during fermentation has been studied. Model solutions simulating a fermenting must were purged at different CO₂ flow rates and temperatures, and the amount of volatile compounds blown off by the stream of CO₂ was recorded by high-resolution gas chromatography. Data showed that under normal fermenting conditions, fatty acid ethyl esters and some fusel alcohol acetates are blown off the solution at a high rate. The maximum loss rate was observed for ethyl decanoate. The purging speed is doubled when temperature increases from 17 °C to 27 °C. Losses can be interpreted by a linear model and are a function of the compound and the flow rate of CO₂. These models allow us to reconstruct the volatile synthesis vs time functions through graphic calculus and to estimate the proportion of volatile material retained, hydrolysed and purged. Synthesis takes place during the tumultuous period of fermentation together with CO₂ production that blows off the volatile material. Hydrolysis takes place in the last stages of fermentation. In a 10-1 open fermenter, up to 80% of volatile material can be blown off while an average of 10% is retained. Residual esterase activity accounts for about 20% of the total amount of ester synthesized.