Etanercept decreases tumor necrosis factor-α activity in chronic wound fluid

High levels of tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, are present in the wound fluid of chronic nonhealing wounds. This leads to increased inflammation, cytokine expression, and ultimately results in impaired wound healing and tissue destruction. Etanercept is a recombinant fusion protein that consists of the soluble TNF receptor (p75) linked to the Fc portion of human IgG1. It is an effective inhibitor of TNF-alpha and has been shown to provide rapid and sustained improvement in rheumatoid arthritis by acting as a soluble receptor binding TNF-alpha and preventing its proinflammatory activities. Therefore, the aim of this study was to determine whether Etanercept could inhibit TNF-alpha activity in chronic wound fluid. Wound fluid was collected from the venous leg ulcers of 16 different patients. The effect of Etanercept on TNF-alpha activity was evaluated using both a TNF-alpha bioassay and an enzyme-linked immunoassay. Etanercept was found to reduce the cytotoxic effect of chronic wound fluid on L929 fibroblasts by approximately 30% and neutralized TNF-alpha binding in the enzyme-linked immunoassay by up to 80%. Direct application of Etanercept to chronic wounds may therefore reduce the inflammatory activity of TNF-alpha, which could reduce the chronicity of venous leg ulcers and thus aid in the healing of these wounds.     

Medical and financial implications of discontinuing a statewide free insulin program involving 3,720 people

In 1981 a statewide program supplying free insulin to 3,720 patients of state health clinics was discontinued. We attempted to assess whether this action had an adverse effect medically and financially on those concerned. A computer randomized sample of 351 patients (9%) was studied by personal interview and questionnaire. Information obtained focused on certain events that occurred 18 months before and after the program ceased. Measurements used to determine medical impact were number of hospitalizations, emergency room and physician visits, changes in weight and glucose levels, and episodes of ketoacidosis. Financial impact was measured by cost of hospitalization and physician visits. Our results revealed no significant changes in any of the medical parameters studied except for fasting serum glucose levels above 300 mg/dl, which occurred less frequently after the free insulin program was discontinued. There were fewer hospitalizations, more visits to physicians, and no change in number of emergency room visits after discontinuance of the free program. The overall cost saving was estimated to be +883,558 for the 18-month study period, in addition to the +550,000 the plan had been costing the state.     

Antidepressant and other centrally acting drugs regulate glucocorticoid receptor messenger RNA levels in rat brain

The effect of imipramine, desipramine, ketanserin and lithium on Type II glucocorticoid receptor (GR) mRNA levels was studied in rat brain regions involved in the control of the hypothalamo-pituitary-adrenal (HPA) axis, the dysregulation of which has been implicated in the pathophysiology of major depression. Northern blot analysis of Type II GR mRNA showed that treatment of male rats with either desipramine or imipramine increased hypothalamic and hippocampal GR mRNA levels. Upregulation of GR mRNA following administration of imipramine was found in brain regions of female rats, while desipramine had no effect. Ketanserin increased levels of GR mRNA in hippocampus of male, but not female, rats. Lithium also was able to induce important increases rat brain GR mRNA; this effect was particularly marked in females.

We conclude that desipramine, imipramine, ketanserin and lithium can modulate GR mRNA in regions of rat brain involved in the control of the HPA axis and may have a common mechanism of action at the level of the GR gene. Sexual dimorphism for drug regulation of brain GR mRNA content was shown and may be related to sex differences in the prevalence of certain affective disorders.     

A comparison of placement methods using a two-in-one dentin pin

Experiments were performed to determine the effect of pin channel preparation with standard and reduction speed handpieces, and pin seating by hand and with motor drive. The greatest retention was achieved by preparation with a standard handpiece at 6000 rpm, and manual pin placement with a hand driver. The most consistent retention values were achieved using the reduction handpiece. All preparation and placement combinations examined produced a clinically acceptable result.     

Human gammaherpesvirus cytokines and chemokine receptors.

Most herpesviruses of the beta and gamma subfamilies encode homologues of cytokines and chemokine receptor- related G protein-coupled receptors (GPCRs). The roles of these proteins during normal virus replication in the infected host have not been defined in most cases, but the available data and extrapolation from what is known about the properties and functions of their cellular counterparts indicate that they play primary roles in immune evasion or in activating cellular signaling cascades that enhance virus productive replication. Cytokines and chemokine receptors specified by the two human gammaherpesviruses, human herpesvirus 8 (HHV-8) and Epstein-Barr virus (EBV), are the subject of this review. HHV-8 encodes three chemokines, a homologue of interleukin-6, and a CXCR2-related chemokine receptor, while EBV encodes a distinct GPCR and a homologue of interleukin-10. While these viral cytokines and chemokine receptors no doubt contribute to virus biology, their properties indicate that they may also be involved in virus-induced neoplasia. This review discusses the properties, functions, and likely roles of HHV-8 and EBV cytokines and chemokine receptors in relation to both virus biology and virus-associated disease.     

The structure and correlates of perfectionism in African American children.

This study examined the structure and symptom correlates of perfectionism in a sample of 6th-grade, urban, African American children using the Child and Adolescent Perfectionism Scale (CAPS; Flett, Hewitt, Boucher, Davidson, & Munro, 2000). Confirmatory factor analysis showed inadequate fit of the original subscales. Exploratory factor analysis suggested 3 dimensions of perfectionism: A Socially Prescribed and a Self-Oriented-Critical factor were described as maladaptive, whereas a Self-Oriented-Striving factor was proposed as adaptive. Cross-sectional correlations among the perfectionism dimensions and symptoms of psychopathology fit well with the adaptive versus maladaptive model. In addition, Socially Prescribed Perfectionism showed a robust predictive relation to 7th-grade internalizing symptoms, especially depression, in boys. Results are discussed in the context of the cultural and socioeconomic characteristics of this African American sample and suggestions for future research are provided.     

Rapid Immunofluorescence Microscopy for Diagnosis of Melioidosis

An immunofluorescent (IF) method that detects Burkholderia pseudomallei in clinical specimens within 10 min was devised. The results of this rapid method and those of an existing IF method were prospectively compared with the culture results for 776 specimens from patients with suspected melioidosis. The sensitivities of both IF tests were 66%, and the specificities were 99.5 and 99.4%, respectively.     

Die Verwendung eines Nervenstimulators zur sicheren Platzierung von Ilisarov-Drähten

OBJECTIVE: Avoidance of potential iatrogenic nerve injury during insertion of Ilizarov fine wires into areas of high anatomic risk by using a modified nerve stimulation technique. INDICATIONS: Application of the Ilizarov ring fixator to areas of high anatomic hazard, in situations where anatomic topography may be distorted by previous surgery, trauma, or congenital anomalies. CONTRAINDICATIONS: Use of systemic muscle relaxants. Caution in patient with cardiac pacemaker. SURGICAL TECHNIQUE: Preliminary experiments showed that a standard nerve-stimulating device can deliver a negatively charged, monophasic square pulse of current through Ilizarov wires. During the application of an Ilizarov frame to potentially hazardous anatomic regions, providing no systemic muscle relaxants are used, a voltage field sufficient to cause nerves in close proximity to the Ilizarov wire to depolarize is produced. Identification of a distal muscle twitch provoked by the stimulation may indicate a potential for iatrogenic nerve injury. RESULTS: Results show that with the nerve stimulator set at 2.5 mA (pulsed at a frequency of 2 Hz), peripheral nerves are stimulated if they lie within 5 mm of the wires. Should a distal muscle twitch occur, wires should be repositioned so that equivalent stimulation produces no twitch. The technique was used during Ilizarov frame application in ten patients, with only a single occurrence of distal muscle twitches in a lower-leg frame. Following repositioning of the Ilizarov wire in this case, no further twitches were observed, indicating that no Ilizarov wire was inserted close to peripheral nerves. No neurologic impairment was present postoperatively.