Re-evaluation of the effect of non-steroidal anti-inflammatory agents on u.v.-induced cutaneous inflammation

The effect of non-steroidal anti-inflammatory agents on u.v. radiation-induced cutaneous inflammation has been re-evaluated using a model which permits simultaneous and quantitative measurement of vasodilatation, vascular permeability and oedema formation throughout the entire time course of the inflammatory reaction. Indomethacin and phenylbutazone produced a substantial reduction in u.v. erythema during the initial stages but subsequently were far less effective, although small, significant reductions were obtained. Attempts to reverse an established inflammatory response to u.v. injury also yielded small, significant reductions in erythema but vascular permeability remained unaffected. In addition, it was found that arachidonic acid and prostaglandin E₂ selectively produced vasodilatation: the vasodilator response to arachidonic acid, but not prostaglandin E₂, was greatly reduced by indomethacin.It is suggested that cyclo-oxygenase derived arachidonic acid metabolites play an important role in mediating u.v. erythema only during the initial period.     

Aberrant deltaPKC activation in the spinal cord of Wobbler mouse: a model of motor neuron disease

Protein kinase C (PKC) was suggested to play a role in the pathology of amyotrophic lateral sclerosis (ALS) patients. Activation of PKC delta (deltaPKC) modulates mitochondrially induced apoptosis. The goal of the present study was to define whether deltaPKC activation occurs in Wobbler mouse spinal cord (a model of motor neuron disease). The level of deltaPKC in the soluble fraction was significantly decreased in the spinal cord of Wobbler mice, which was associated with a significant increase in deltaPKC cleavage. Since caspase-3 is known to cleave deltaPKC, we determined caspase-3 activation in the Wobbler mice spinal cord, immunohistochemically. The results demonstrated intense immunoreactivity for activated caspase-3 in corticospinal tract motor neurons of Wobbler mice spinal cord. We hypothesize from these results that caspase-3 activation cleaves deltaPKC, which in turn promotes an aberrant signal transduction pathway in the Wobbler spinal cord.     

Real-Time Magnetic Resonance Imaging to Guide Pediatric Endovascular Procedures

Although x-ray fluoroscopy (XRF) has guided diagnostic and therapeutic transcatheter procedures for decades, certain limitations still exist. XRF still visualizes tissue poorly and relies on projection of shadows that do not convey depth information. Adjunctive echocardiography overcomes some of these limitations but still suffers suboptimal or unreliable imaging windows. Furthermore, ionizing radiation exposure in children imparts a cancer risk. An interventional platform using real-time magnetic resonance imaging (MRI) may offer superior image guidance without radiation. Although there are many remaining challenges, but real-time MRI has the potential to revolutionize transcatheter therapeutics.     

Ischemic preconditioning ameliorates excitotoxicity by shifting glutamate/gamma-aminobutyric acid release and biosynthesis

Excitotoxicity is recognized to play a major role in cerebral ischemia-induced cell death. The main goal of the present study was to define whether our model of ischemic preconditioning (IPC) promotes a shift from excitatory to inhibitory neurotransmission during the test ischemia to diminish metabolic demand during the reperfusion phase. We also determined whether gamma-aminobutyric acid (GABA) played a role in IPC-induced neuroprotection. Ten minutes of cerebral ischemia was produced by tightening the carotid ligatures bilaterally following hypotension. Samples of microdialysis perfusate, representing extracellular fluid, were analyzed for amino acid content by HPLC. IPC promoted a robust release of GABA after lethal ischemia compared with control rats. We also observed that the activity of glutamate decarboxylase (the predominant pathway of GABA synthesis in the brain) was higher in the IPC group compared with control and ischemic groups. Because GABAA receptor up-regulation has been shown to occur following IPC, and GABAA receptor activation has been implicated in neuroprotection against ischemic insults, we tested the hypothesis that GABAA or GABAB receptor activation was neuroprotective during ischemia or early reperfusion by using an in vitro model (organotypic hippocampal slice culture). Administration of the GABAB agonist baclofen during test ischemia and for 1 hr of reperfusion provided significant neuroprotection. We concluded that increased GABA release in preconditioned animals after ischemia might be one of the factors responsible for IPC neuroprotection. Specific activation of GABAB receptor contributes significantly to neuroprotection against ischemia in organotypic hippocampal slices.     

Case of the missing penny: thoracoscopic removal of a mediastinal coin

Complications of coin ingestion in children, although rare, include esophageal perforation, tracheoesophageal fistula, esophago-aortic fistula, and death. The authors describe thoracoscopic removal of a mediastinal coin that migrated extraluminally from the esophagus in a 23-month-old girl. Right-sided thoracoscopic exploration using a 3-trocar technique in a modified prone position was used. Coin location was assisted by manipulation of a transorally placed Foley catheter and intraoperative fluoroscopy. The coin was retrieved successfully with no intraoperative or postoperative complications and minimal postoperative pain. This is the first report of successful thoracoscopic removal of a mediastinal coin. Thoracoscopy may be a valuable approach for mediastinal foreign body removal in children.     

Metaanalysis of statins and survival in de novo cardiac transplantation

BACKGROUND: The use of HMG CoA reductase inhibitors (statins) after cardiac transplantation has been suggested to decrease the incidence of severe rejection and improve survival. Individual investigations that have led to this suggestion are randomized (but not placebo-controlled) studies, including small patient numbers that have (and thus underpowered) and enrolling heterogeneous subjects (including retransplant recipients). The purpose of this pooled analysis was to quantify the benefit of statins on survival in de novo cardiac transplant recipients. METHODS: Medline (1966 to 2003) was queried using the keywords statin, HMG CoA reductase inhibitors, cardiac transplantation, transplant, cholesterol, atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin. In addition, we searched the cited literature and previously published systematic reviews. Of 36 articles retrieved, 3 randomized controlled studies met our population inclusion criteria; namely age >18 years, de novo heart transplant recipients, statin therapy within 3 months, and > or = 1-year follow-up. Pooled data were metaanalyzed by Mantel-Haenszel tests using a random effects model that included tests for heterogeneity. RESULTS: The three pooled studies included 246 patients (statin, n = 129; no statin, n = 117) and 27 events (11%). The pooled analysis demonstrated a significant reduction in mortality with statin use (RR 0.31; 95% CI 0.13 to 0.7; P = .006) without significant heterogeneity (P = .7) among the studies. Two of the three studies reported allograft rejection with hemodynamic compromise. The pooled analysis demonstrated a significant benefit on this endpoint (RR 0.22, 95% CI 0.08 to 0.63; P = .004). CONCLUSION: This meta-analysis demonstrates that statin therapy decreases rejection episodes with hemodynamic consequences and improves 1-year heart transplant survival.     

Alterations in plasma lipid profile patterns in head and neck cancer and oral precancerous conditions

BACKGROUND: The changes in lipid profile have long been associated with cancer because lipids play a key role in maintenance of cell integrity. AIMS: The present study evaluated alterations in plasma lipid profile in untreated head and neck cancer patients as well as patients with oral precancerous conditions (OPC) and its association with habit of tobacco consumption. MATERIAL AND METHODS: This hospital-based case control study included 184 head and neck cancer patients, 153 patients with OPC and 52 controls. Plasma lipids including: (i) Total cholesterol, (ii) LDL cholesterol (LDLC), (iii) HDL cholesterol (HDLC) (iv) VLDL cholesterol (VLDLC) and (v) triglycerides were analysed by spectrophotometric kits. STATISTICAL ANALYSIS USED: Student's t-test was performed to compare mean values of the parameters. RESULTS: A significant decrease in plasma total cholesterol and HDLC was observed in cancer patients (P=0.008 and P=0.000 respectively) as well as in patients with OPC (P=0.014 and P=0.000, respectively) as compared to the controls. The plasma VLDL and triglycerides levels were significantly lower in cancer patients as compared to the patients with OPC (P=0.04) and controls (P=0.059). The tobacco habituates showed lower plasma lipid levels than the non-habituates. Our data strengthen the evidence of an inverse relationship between plasma lipid levels and head and neck malignancies as well as OPC. CONCLUSION: The lower levels of plasma cholesterol and other lipid constituents in patients might be due to their increased utilization by neoplastic cells for new membrane biogenesis. The findings strongly warrant an in-depth study of alterations in plasma lipid profile in head neck cancer patients.     

The relative bioavailability of metoprolol following oral and rectal administration to volunteers and patients

The pharmacokinetics, efficacy and safety of metoprolol tartrate 25 mg fatty suppositories were studied in 5 healthy volunteers and in 8 patients suffering from instable angina pectoris. Metoprolol 25 mg capsules were used as a control oral dosage form. Metoprolol showed a considerable rectal bioavailability (AUC, C max) and was absorbed quickly from the rectum (T max). In both groups rectal bioavailability was comparable. However, oral bioavailability was much lower in the volunteer group than in the patient group. Furthermore, ratios of metoprolol/aOHmetoprolol concentrations in plasma and urine gave an indication for a partial avoidance of the first pass effect after rectal administration. Further research is necessary to define an exact rectal dosage of metoprolol. In all patients, a substantial drop in heart rate, systolic and diastolic blood pressure was seen after administration of the first suppository. Metoprolol suppositories appear to be an effective, safe and suitable alternative for patients who are in need for beta blocking medication and who are unable to take oral medication for a certain amount of time.     

Hepatic scintigraphy in management of infants and children with liver disease

Scintiscans of liver and spleen using technetium 99m sulphur colloid in 15 infants with extrahepatic biliary atresia and 11 infants with severe obstructive jaundice (7 with genetic deficiency of alpha 1-antitrypsin) showed similar hepatic size, pattern of isotope uptake, and splenic abnormality with no distinguishing features. In 37 older children with a variety of liver disorders, the scan was invaluable in showing filling defects in five instances. Selenomethionine was taken up not only by the two filling defects due to hepatoblastoma but also in a haemangioendothelioma. In the remaining patiens liver scanning confirmed hepatic abnormality and the necessity for more specific invasive diagnostic investigations.