The pharmacokinetics of isoxicam in elderly patients with rheumatoid arthritis

Nineteen patients, aged 60 years and over, with rheumatoid arthritis participated in a clinical trial to investigate the pharmacokinetics of isoxicam (a new non-steroidal anti-inflammatory drug) in this age group. The purpose of the study was to determine if the pharmacokinetics are different compared to a younger healthy population. The half-lives were independent of dosage, indicating linearity of pharmacokinetics. Furthermore, the half-lives after repeated dosing were not different from those found after single doses of 400 mg. This shows that there is neither undue accumulation of the drug nor induction of its own metabolism. These results are similar to the results obtained in other centres when isoxicam was administered to healthy subjects between 18 and 32 years.     

Chronic exposure to cold stress alters electrophysiological properties of locus coeruleus neurons recorded in vitro.

Chronic stress exposure can alter central noradrenergic function. Previously, we reported that in chronically cold-exposed rats the release of norepinephrine and electrophysiological activation of locus coeruleus (LC) neurons is enhanced in response to multiple excitatory stimuli without alterations in basal activity. In the present studies, we used in vitro intracellular recording techniques to explore the effect of chronic cold exposure on the basal and evoked electrophysiological properties of LC neurons in horizontal slices of the rat brainstem. Consistent with our findings from in vivo experiments, chronic cold exposure did not affect basal firing rate. Furthermore, gross morphology of LC neurons and spike waveform characteristics were similar in slices from control and previously cold-exposed rats. However, excitability in response to intracellular current injection and input resistance were larger in slices from previously cold-exposed rats. In addition, the accommodation of spike firing in response to sustained current injection was smaller and the period of postactivation inhibition appeared to be less in LC neurons from cold-exposed rats. These data demonstrate that the stress-evoked sensitization of LC neurons observed in vivo is at least in part maintained in the slice preparation and suggest that alterations in electrophysiological properties of LC neurons contribute to the chronic stress-induced sensitization of central noradrenergic function observed in vivo. Furthermore, the present data suggest that an alteration in autoinhibitory control of LC activity is involved in the chronic stress-induced alterations. The enhanced functional capacity of LC neurons following cold exposure of rats may represent a unique model to study the mechanisms underlying the alterations in central noradrenergic function observed in humans afflicted with mood and anxiety disorders.     

Sluggish glucose tolerance in tuberculosis patients.

OBJECTIVE: To examine glucose tolerance in sputum-positive non-treated pulmonary tuberculosis (TB) patients as part of a general metabolic profile. Subjects. Sixty-three sputum-positive non-treated patients (male and female) attending the pulmonary clinic at Mthatha General Hospital in the Eastern Cape and 89 apparently healthy sex and age-matched volunteers. METHODS: Sixty-three untreated TB patients who came to the Mthatha General Hospital's pulmonary clinic with classic symptoms of TB, confirmed by sputum analysis, were recruited for the study. Eighty-nine apparently healthy sex and age-matched volunteers served as the control group. Anthropometric measurements were taken using an electronic scale. Standard oral glucose tolerance tests (OGTTs) were performed in both groups in the morning after an overnight fast. Anticoagulant-treated blood was analysed for glucose and insulin using Peridochrome Glucose (Boehringer Mannheim, Mannheim, Germany) and radioimmunoassay (RIA) (Diagnostic Products Corporation, Los Angeles, USA) respectively. RESULTS: There was sluggish response to glucose and insulin in the TB patient group compared with the control group. Glucose and insulin levels were significantly higher in patients at 0, 30, 60, 120, and 180 minutes. Analysis of variance gave the following p-values, viz. p = 0.0000, 0.0004, 0.0000, 0.0000 and 0.0000 for glucose, and p = 0.0317, 0.0071, 0.0000, 0.0005 and 0.0000 for insulin respectively. CONCLUSIONS: The results of this study suggest an altered glucose/insulin metabolism in TB patients. This might play an important role in the clinical course of the disease.     

Gene Delivery to Human B-Precursor Acute Lymphoblastic Leukemia Cells

Autologous leukemia cells engineered to express immune-stimulatingmolecules may be used to elicit antileukemia immune responses. Genedelivery to human B-precursor acute lymphoblastic leukemia (ALL) cellswas investigated using the enhanced green fluorescent protein (EGFP) asa reporter gene, measured by flow cytometry. Transfection of the Nalm-6and Reh B-precursor ALL leukemia cell lines with an expression plasmidwas investigated using lipofection, electroporation, and a polycationiccompound. Only the liposomal compound Cellfectin showed significantgene transfer (3.9% to 12% for Nalm-6 cells and 3.1% to 5% for Rehcells). Transduction with gibbon-ape leukemia virus pseudotyped Moloneymurine leukemia virus (MoMuLV)-based retrovirus vectors wasinvestigated in various settings. Cocultivation of ALL cell lines withpackaging cell lines showed the highest transduction efficiency forretroviral gene transfer (40.1% to 87.5% for Nalm-6 cells and 0.3%to 9% for Reh cells), followed by transduction with viral supernatant on the recombinant fibronectin fragment CH-296 (13% to 35.5% for Nalm-6 cells and 0.4% to 6% Reh cells), transduction on human bonemarrow stroma monolayers (3.2% to 13.3% for Nalm-6 cells and 0% to0.2% Reh cells), and in suspension with protamine sulfate (0.7% to3.1% for Nalm-6 cells and 0% for Reh cells). Transduction of bothNalm-6 and Reh cells with human immunodeficiency virus-type 1 (HIV-1)-based lentiviral vectors pseudotyped with the vesicular stomatitis virus-G envelope produced the best gene transfer efficiency, transducing greater than 90% of both cell lines. Gene delivery intoprimary human B-precursor ALL cells from patients was then investigatedusing MoMuLV-based retrovirus vectors and HIV-1-based lentivirusvectors. Both vectors transduced the primary B-precursor ALL cells withhigh efficiencies. These studies may be applied for investigating genedelivery into primary human B-precursor ALL cells to be used forimmunotherapy.     

Factors influencing the likelihood of successful decisions to treat dentin caries from bitewing radiographs

The purpose of this study was to describe the role played by the ability to estimate caries depth in successfully deciding to treat dentin caries when making use of bitewing radiographs as a diagnostic test. A 10% random sample (n = 444) of Dutch dental practitioners was sent a two-wave questionnaire concerning radiographic caries diagnosis and restorative treatment decision making. The second wave consisted of simulated bitewing radiographs of 105 tooth surfaces with and without dentin caries according to two measuring standards: (a) a micro-radiographic "gold" standard and (b) a norm of expert observers. The dentists were asked to diagnose caries at 4 depths of penetration using a 5-point certainty scoring system to measure diagnostic ability; and to make a treatment decision for each surface. The overall response was 61% (273). A regression analysis was carried out using the chance per dentist of correctly deciding to treat dentin caries as the dependent variable. The degree of agreement with the experts' diagnosis of radiographic caries depth was used to create variables measuring diagnostic ability. Five significant (P less than 0.05) variables explained 60% (R2 = 0.60) of the variation in decision making. The best diagnostic ability variable explained 47% of the variation while the treatment criterion reportedly used explained 3%. We conclude that the ability of practitioners to interpret radiographs plays a major role in treatment decision making and that their reported treatment decision making criteria should not be taken at face value.     

Immune activation and oxidative damage in HIV-positive and HIV-negative adolescents

In a cross-sectional study involving subjects from the Reaching for Excellence in Adolescent Health cohort, we examined the associations between HIV status, disease severity, immune activation, and oxidative damage. Subjects (265 HIV-positive and 127 HIV-negative) were young (range: 14-23 years of age) and primarily female (75%) and black (67%). Many subjects, particularly female subjects, were overweight or obese. Relatively few HIV-positive subjects had advanced HIV disease (13%), and 54% were taking antiretroviral therapy (ART). The 2 markers of oxidative damage used in this study (plasma malondialdehyde and protein carbonyl concentrations) did not correlate with each other, and neither was higher in HIV-positive subjects than in HIV-negative controls. Increased oxidative damage was seen in association with male gender, cigarette smoking, marijuana use, immune activation (as indicated by activated CD8 T-cell counts and plasma C-reactive protein concentration), and use of ART, however. Plasma ceruloplasmin was associated with decreased oxidative damage in HIV-positive subjects, although this association was not seen in those taking ART.     

Prevention of Postinfectious Asthma in Children by Reducing Self-Inoculatory Behavior

Recent studies have shown that the spread of infectious nasalsecretions from hand-to-hand or hand-to-object, followed byself-inoculation is an efficient means of viral transmission.The present study was designed to investigate whether self-inoculationbehavior in asthmatic children could be reduced and, if so,whether this reduction would reduce the frequency of infectionand asthma. Sixteen subjects aged 4 to 8, all diagnosed withpostinfectious asthma, were assigned to a treatment (differentialreinforcement of other behavior and contingent education) orplacebo control condition. Results indicate that self-inoculatorybehavior, infection, and asthma were signjficantly reduced.These findings may indicate an important role for behavioralmedicine inpostinfectious asthma.