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.

Divergent roles of nitrergic and prostanoid pathways in chronic joint inflammation.

BACKGROUND: Nitrergic and prostanoid pathways have both been implicated in inflammatory processes. OBJECTIVE: To investigate their respective contributions in a rat model of chronic arthritis. METHODS: Male Wistar rats (n = 4-6/group) received either an intra-articular injection of 2% carrageenan/4% kaolin (C/K) or intra- and periarticular injections of Freund's complete adjuvant (FCA; 10 mg/ml M tuberculosis). Joint diameter, urinary nitric oxide metabolites (NO(x)), and prostaglandin E(2) (PGE(2)) levels were measured as indices of the inflammatory process. A prophylactic and therapeutic (day 5) dose ranging study of an inducible nitric oxide synthase inhibitor, L-N-(1-iminoethyl)-lysine (L-NIL), and a cyclo-oxygenase-2 (COX-2) inhibitor, SC-236, was performed with the drugs given subcutaneously. Submaximal doses were identified and used for combination studies. Appropriate vehicle controls were included. RESULTS: L-NIL and SC-236 dose dependently inhibited C/K induced acute joint swelling, the magnitude being greatest when they were given in combination. Both prophylactic and therapeutic administration of SC-236 in the FCA induced model of chronic arthritis produced a dose dependent reduction in all the measures assessed. However, although L-NIL demonstrated similar dose dependent inhibition of urinary NO(x) and PGE(2) levels, joint swelling was significantly exacerbated in this model. Co-administration of the inhibitors nullified the benefits of SC-236. CONCLUSION: Whereas COX-2 derived prostaglandins are proinflammatory in both acute and chronic joint inflammation, NO seems to have divergent roles, being anti-inflammatory in chronic and proinflammatory in acute joint inflammation.

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.

Long-term causes of death after traumatic brain injury.

OBJECTIVE: To determine which causes of death are more frequent in persons with traumatic brain injury (TBI), and by how much, compared with the general population. Our focus was the period beginning 1 yr after injury. DESIGN: Subjects were 2320 Californians with long-term mental disability after a TBI at age 10 yr or more, followed up between 1988 and 1997. The units of study were person-years, each linked to the subject's age, gender, level of ambulation, time since injury, and cause of death (if any) for the specific year. Observed numbers of cause-specific deaths were compared with numbers expected according to general population mortality rates. RESULTS: Mortality was higher between 1.0 and 5.0 yr postinjury than after 5.0 yr and was strongly related to reduced mobility. Death rates were elevated for circulatory diseases, respiratory diseases, choking/suffocation, and seizures, with seizure deaths being relatively frequent, even among the most ambulatory. CONCLUSIONS: Death rates for several causes are elevated in persons with long-term sequelae of TBI. The increased risk of choking/suffocation should be of interest to caregivers. Life expectancy seems to be reduced, even for patients who are fully ambulatory.

Reversal of the detrimental effects of chronic protein malnutrition on long bone fracture healing.

OBJECTIVE: To determine whether dietary intervention in the immediate postfracture period will reverse the detrimental influence of protein deprivation on fracture healing in the rat. DESIGN: Adult Sprague-Dawley rats were maintained on a diet containing either a normal or reduced protein concentration. After five weeks, both femora of each rat were pinned with an intramedullary 0.625-millimeter K-wire. A closed fracture of the right femur was created one week later, by use of a handheld device. Groups of rats were killed and the femora harvested at 14 days for histologic study and at twenty-eight and fifty-six days for mechanical testing. INTERVENTION: Control rats (Group I) were maintained on a 20 percent protein diet. Malnourished (Group II) animals were maintained on a 6 percent protein diet during the six-week prefracture period and throughout the fifty-six-day postfracture period. Malnutrition was confirmed by measurement of serum concentrations of transferrin, immunoglobulin, and albumin. Renourished (Group III) animals were started on the 6 percent protein diet but were fed a 20 percent protein diet in the fifty-six-day postfracture period. RESULTS: When compared with control, well-nourished rats, malnourished animals had callus composed primarily of fibrous-type tissue and had decreased periosteal and external callus as well as callus strength. The callus from renourished animals histologically resembled that from well-nourished animals with large amounts of periosteal and external callus. Based on mechanical testing results, callus from malnourished animals showed reduced strength and stiffness as compared with control renourished animals. In renourished animals, the cross-sectional area of the fracture callus, as well as callus stiffness and strength, were greater than those in malnourished and well-nourished animals. CONCLUSION: Protein deprivation has a profound detrimental effect on fracture healing. The identification of a protein-reduced state and its reversal could result in improved fracture healing and presumably a better clinical outcome in malnourished patients.

Life expectancy of children in vegetative and minimally conscious states.

We determined estimates of survival in children, 3-15 years of age, in the vegetative state (VS) (n = 564), immobile minimally conscious state (MCS) (n = 705), and mobile MCS (n = 3,806). Data were extracted from the annual Client Development Evaluation Reports of the California Department of Developmental Services between 1988 and 1997 using the operational definitions for these three states on the basis of 15 descriptive behavioral categories. Patients were also categorized according to the following four etiologies: acquired (traumatic and nontraumatic) brain injury; perinatal/genetic; degenerative; and unknown/undetermined. The percentage of patients surviving 8 years was 63%, 65%, and 81%, for the VS, immobile MCS, and mobile MCS, respectively. Children in the VS and MCSs with acquired brain injury had lower mortality rates and those with degenerative diseases the highest mortality rates. We observed little difference in survival between patients in the VS and immobile MCS, suggesting that the presence of consciousness is not a critical variable in determining life expectancy. Furthermore, survival was much greater for patients in the mobile MCS than for those in the immobile MCS, suggesting that mobility is more important in predicting survival than the level of consciousness.

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).

Transesophageal echocardiographic diagnosis of right atrial thrombi associated with the antiphospholipid syndrome.

Thromboembolic disorders are a hallmark of the antiphospholipid antibody syndrome. We describe a patient with IgM antiphospholipid antibodies associated with pulmonary emboli and in situ thrombosis within an otherwise normal right atrium. Echocardiography, particularly the transesophageal study, proved invaluable in providing a diagnosis and guiding our patient's evaluation and treatment.

Somatostatin in the human heart and comparison with guinea pig and rat heart.

Somatostatin has been shown to have negative inotropic and chronotopic effects and to restore sinus rhythm in some cases of cardiac arrhythmia. Using acid extracts, regions of human heart were examined by radioimmunoassay to determine their somatostatin content. Mean (SD) concentrations of 4.1 (0.8) pmol/g and 2.9 (0.8) pmol/g were found in atrioventricular node and right atria respectively and were significantly higher than in other heart regions. Using fresh heart tissue from guinea pigs, somatostatin was localised to cardiac nerves by immunocytochemistry. Nerves containing somatostatin were most abundant in the atria, where the concentrations measured by radioimmunoassay were 7.6 (1.0) and 2.6 (0.4) pmol/g for right and left atria respectively. Somatostatin contained in cardiac nerves may have a physiological role in the cardiac conduction system.