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.     

Influences of obese (ob/ob) and diabetes (db/db) genotype mutations on lumber vertebral radiological and morphometric indices: Skeletal deformation associated with dysregulated systemic glucometabolism

Background  

Both diabetes and obesity syndromes are recognized to promote lumbar vertebral instability, premature osteodegeneration, exacerbate progressive osteoporosis and increase the propensity towards vertebral degeneration, instability and deformation in humans.     

Third, fourth, and sixth cranial nerve palsies following closed head injury.

BACKGROUND: The relationship between the circumstances and severity of closed head injury (CHI) and the clinical and imaging features of cranial nerve 3, 4, and 6 palsies has not been rigorously addressed in a large study. METHODS: Retrospective chart review of 210 consecutive patients with CHI examined at a single tertiary care center from 1987 to 2002. Patients were located by searching the ophthalmology inpatient consultation and neuro-ophthalmology outpatient databases and hospital emergency room billing codes for a diagnosis of traumatic 3, 4, or 6 cranial nerve palsy (Cranial Nerve Injury Group) and a diagnosis of CHI without traumatic 3, 4, or 6 nerve palsy (Control Group). The Cranial Nerve Injury Group was then subdivided into two groups: those with injuries to an individual cranial nerve and those with multiple (including bilateral) cranial nerve injuries. Comparisons between groups were based on age, gender, type of accident, Glasgow Coma Scale (GCS), documented loss of consciousness (LOC), type of ocular injury, presence of systemic injury, need for rehabilitation, physical therapy and cognitive scores, and imaging features. RESULTS: The Cranial Nerve Injury Group had a significantly higher severity of head injury, more CT abnormalities, and worse short-term neurologic outcomes as compared with the Control Group. These trends were also found when each cranial nerve injury subgroup was compared with the Control Group. Those with cranial nerve 3 palsy had the most severe head injury; those with cranial nerve 4 palsy had an intermediate level of head injury; and those with cranial nerve 6 palsy had the lowest level of head injury. There were no consistent associations between the location of the imaging abnormalities and which cranial nerve was damaged. CONCLUSIONS: CHI with palsy of an ocular motor nerve was more severe than CHI without ocular motor nerve palsy, as measured by the GCS, intracranial and skull imaging abnormalities, and a greater frequency of inpatient rehabilitation. Palsy of cranial nerve 3 was associated with relatively more severe CHI than was palsy of cranial nerves 4 or 6. The location of the imaging abnormalities did not correlate with a particular cranial nerve injury.     

Intrathecal Ziconotide in the Treatment of Chronic Nonmalignant Pain: A Randomized,Double‐Blind,Placebo‐Controlled Clinical Trial

Objective. The safety and efficacy of intrathecal (IT) ziconotide was studied in a randomized, double‐blind, placebo‐controlled trial. Materials and Methods. Patients (169 ziconotide, 86 placebo) with severe chronic nonmalignant pain unresponsive to conventional therapy and a visual analog scale of pain intensity (VASPI score) ≥ 50 mm were treated over a 6‐day period in an inpatient hospital setting. Initial starting dose was 0.4 µg/hour and was titrated to analgesia or intolerance (maximum dose 7.0 µg/hour). The starting and maximum doses were reduced to 0.1 µg/hour and 2.4 µg/hour, respectively, due to adverse events (AEs). Results. The mean percent reduction in VASPI score from baseline was 31.2% and 6.0% for ziconotide‐ and placebo‐treated patients, respectively (p ≤ 0.001). During the initial titration phase, a significantly greater percentage of patients in the ziconotide group compared to the placebo group reported AEs, including abnormal gait, amblyopia, dizziness, nausea, nystagmus, pain, urinary retention, and vomiting. Conclusion. Ziconotide provided significant analgesia in patients for whom conventional therapy failed. However, there was a considerable incidence of ziconotide‐associated AEs due to the rapid titration and high doses administered.     

Dentistry, neurology and nephrology--what is the connection?

Case report A 28-year-old female patient was admitted because of painlessmacroscopic haematuria. Past history included severe mentalretardation and nystagmus. At age 17, a computed tomography(CT) scan of the brain showed an absent cerebellar vermis andcerebellar hypoplasia. There was no     

Mycophenolate Mofetil Use Is Associated with Decreased Risk of Late Acute Rejection in Adult Liver Transplant Recipients

Mycophenolate mofetil (MMF) used in a triple-drug regimen has been shown to decrease acute rejection rates, compared to a double-drug regimen. The impact of MMF on late acute rejection (LAR) episodes has not been well described. To investigate the risk of LAR (rejection > or = 6 months post-transplantation) data from the Scientific Registry of Transplant Recipients (SRTR) were used. We studied adult primary liver transplant recipients transplanted between June 1, 1995, and April 30, 2004, with hepatitis C virus (HCV) (n = 3356), hepatitis B virus (HBV) (n = 550) or a nonviral (n = 5740) primary cause of liver disease who were recorded as receiving continuous 3-(MMF + Tacro + steroids) versus 2-drug (Tacro + steroids) therapy for at least 6 months immediately post transplantation. Kaplan-Meier analysis showed significantly lower LAR rates 4 years post-transplant in 3- versus 2-drug HCV, HBV and nonviral disease patients. Multivariate regression confirmed 3- versus 2-drug therapy to be associated with a decreased risk of LAR. Late graft survival was significantly lower at 4 years post-transplant for patients with LAR 6-12 months post-transplantation versus patients with early rejection (78.0% vs. 87.0%, p < 0.001) and no rejection (88.1%, p < 0.001). Three-drug versus 2-drug therapy for a minimum of 6 months may offer a better treatment strategy to avoid the consequences and expense of LAR episodes.     

The influence of different error estimates in the detection of post-operative cognitive dysfunction using reliable change indices with correction for practice effects.

The reliable change index (RCI) expresses change relative to its associated error, and is useful in the identification of post-operative cognitive dysfunction (POCD). This paper examines four common RCIs that each account for error in different ways. Three rules incorporate a constant correction for practice effects and are contrasted with the standard RCI that had no correction for practice. These rules are applied to 160 patients undergoing coronary artery bypass graft (CABG) surgery who completed neuropsychological assessments preoperatively and 1 week post-operatively using error and reliability data from a comparable healthy non-surgical control group. The rules all identify POCD in a similar proportion of patients, but the use of the within subject standard deviation, expressing the effects of random error, as an error estimate is a theoretically appropriate denominator when a constant error correction, removing the effects of systematic error, is deducted from the numerator in a RCI.