Causes of death in remote symptomatic epilepsy.

OBJECTIVE: To determine the causes of death of individuals with developmental disabilities that occur more frequently among those with remote symptomatic epilepsy (i.e., epilepsy occurring in persons with developmental delay or identified brain lesions) than for those without. METHODS: The authors compared causes of mortality in persons with (n = 10,030) and without (n = 96,163) history of epilepsy in a California population of persons with mild developmental disabilities, 1988 to 2002. Subjects had traumatic brain injury, cerebral palsy, Down syndrome, autism, or a developmental disability with other or unknown etiology. There were 721,759 person-years of data, with 2,397 deaths. Underlying causes of death were determined from the State of California's official mortality records. Cause-specific death rates and standardized mortality ratios (SMRs) were computed for those with and without epilepsy relative to subjects in the California general population. Comparisons were then made between SMRs of those with and without epilepsy, and CIs on the ratios of SMRs were determined. RESULTS: Death rates for persons with epilepsy were elevated for several causes. The greatest excess was due to seizures (International Classification of Diseases-9 [ICD-9] 345; SMR 53.1, 95% CI 28.0 to 101.0) and convulsions (ICD-9 780.3; SMR 25.2, 95% CI 11.7 to 54.2). Other causes occurring more frequently in those with epilepsy included brain cancer (SMR 5.2, 95% CI 2.2 to 12.1), respiratory diseases (SMR 1.7, 95% CI 1.2 to 2.5), circulatory diseases (SMR 1.3, 95% CI 1.0 to 1.7), and accidents (SMR 2.7, 95% CI 1.9 to 3.7), especially accidental drowning (SMR 12.8, 95% CI 7.0 to 23.2). CONCLUSIONS: Remote symptomatic epilepsy is associated with an increased risk of death. Seizures, aspiration pneumonia, and accidental drowning are among the leading contributors.

Absence of salting out effects in forensic blood alcohol determination at various concentrations of sodium fluoride using semi-automated headspace gas chromatography.

Blood alcohol measurements determined by headspace gas chromatography have been challenged on the grounds that the presence of the preservative sodium fluoride in blood samples artificially increases headspace alcohol concentrations due to a salting out effect. Blood samples containing varying amounts of ethanol and sodium fluoride were tested using semi-automated headspace gas chromatography with n-propyl alcohol as the internal standard to assess the validity of this challenge. We find, in fact, that under these test conditions the measured alcohol levels are systematically depressed as the amount of sodium fluoride in the blood sample increases. The challenge thus has no basis.

Combined inhibition of nitrergic and prostanoid pathways in J774 macrophages.

OBJECTIVES: Nitric oxide and prostaglandins are both implicated in the pathogenesis of inflammatory conditions such as rheumatoid arthritis (RA). The hypothesis that simultaneous inhibition of nitric oxide synthase (NOS) and cyclooxygenase (COX) was more effective than inhibition of either enzyme alone was tested. METHODS: J774 macrophages were pre-incubated with L-NAME and/or indomethacin, prior to activation with LPS (10 micrograms/ml). RESULTS: LPS significantly increased NO2-; PGE2 and TNF-alpha levels by 24 h. Quantitative real-time PCR demonstrated a dose-dependent reduction in the expression of COX-2 in the presence of increasing doses of L-NAME. NO2- and PGE2 production were inhibited in a dose-dependent manner by either indomethacin or L-NAME. Combined administration of L-NAME and indomethacin produced a significantly greater inhibition of NO2- and PGE2 than either inhibitor alone. CONCLUSION: The data supports the therapeutic potential of combined inhibition of the prostanoid and nitrergic systems as an anti-inflammatory treatment strategy and supports the progression of this work into models of arthritis.

Usefulness of hypotension during dobutamine echocardiography in predicting perioperative cardiac events.

This study was undertaken to determine the prognostic significance of hypotension induced during preoperative dobutamine stress echocardiography (DSE) before vascular and noncardiac thoracic surgery. Wall motion abnormality during DSE predicts perioperative risk. Although hypotension during DSE has not been shown to correlate with the presence or severity of coronary artery disease, its significance in perioperative risk assessment is unknown. We retrospectively studied 300 patients who had DSE within 6 months of noncardiac surgery. Perioperative events including death, myocardial infarction, ischemia, and arrhythmias were recorded. Odds ratios with 95% confidence intervals were used to examine the association between clinical and echocardiographic variables and perioperative events. A hypotensive response during DSE was seen in 85 patients (28%). Forty-eight patients (16%) had 54 perioperative complications including 4 cardiac-related deaths, 10 myocardial infarctions, 12 myocardial ischemic events, and 28 arrhythmias. Hypotension during DSE was predictive of the combined end point of perioperative cardiac mortality, myocardial infarction, and ischemia (odds ratio 4.04, 95% confidence interval 1.72 to 9.51). In a multivariate logistic regression model, hypotension during DSE remained a significant predictor (odds ratio 4.10, p<0.01). DSE-related hypotension was predictive of perioperative cardiac events and therefore may have a role in risk stratification before vascular or noncardiac thoracic surgery.

Multiple P2Y receptor subtypes in the apical membranes of polarized epithelial cells.

Apical ATP, ATP, UTP and UDP evoked transient increases in short circuit current (I(SC), a direct measure of transepithelial ion transport) in confluent Caco-2 cells grown on permeable supports. These responses were mediated by a population of at least three pharmacologically distinct receptors. Experiments using cells grown on glass coverslips showed that ATP and UTP consistently increased intracellular free calcium ([Ca(2+)](i)) whilst sensitivity to UDP was variable. Cross desensitization experiments suggested that the responses to UTP and ATP were mediated by a common receptor population. Messenger RNA transcripts corresponding to the P2Y(2), P2Y(4) and P2Y(6) receptors genes were detected in cells grown on Transwell membranes by the reverse transcriptase - polymerase chain reaction. Identical results were obtained for cells grown on glass. Experiments in which I(SC) and [Ca(2+)](i) were monitored simultaneously in cells on Transwell membranes, confirmed that apical ATP and UTP increased both parameters and showed that the UDP-evoked increase in I(SC) was accompanied by a [Ca(2+)](i)-signal. Ionomycin consistently increased [Ca(2+)](i) in such polarized cells but caused no discernible change in I(SC). However, subsequent application of apical ATP or UTP evoked a small rise in I(SC) but no rise in [Ca(2+)](i). UDP evoked no such response. As well as evoking increases in [Ca(2+)](i), the ATP/UTP-sensitive receptors present in Caco-2 cells thus allow direct control over ion channels in the apical membrane. The UDP-sensitive receptors, however, appear to simply evoke a rise in [Ca(2+)](i).