Simple non-mydriatic retinal photography is feasible and demonstrates retinal microvascular dilation in Chronic Obstructive Pulmonary Disease (COPD).

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is associated with an increased risk of myocardial infarction and stroke but it remains unclear how to identify microvascular changes in this population. OBJECTIVES: We hypothesized that simple non-mydriatic retinal photography is feasible and can be used to assess microvascular damage in COPD. METHODS: Novel Vascular Manifestations of COPD was a prospective study comparing smokers with and without COPD, matched for age. Non-mydriatic, retinal fundus photographs were assessed using semi-automated software. RESULTS: Retinal images from 24 COPD and 22 control participants were compared. Cases were of similar age to controls (65.2 vs. 63.1 years, p = 0.38), had significantly lower Forced Expiratory Volume in one second (FEV1) (53.4 vs 100.1% predicted; p < 0.001) and smoked more than controls (41.7 vs. 29.6 pack years; p = 0.04). COPD participants had wider mean arteriolar (155.6 ±15 uM vs. controls [142.2 ± 12 uM]; p = 0.002) and venular diameters (216.8 ±20.7 uM vs. [201.3± 19.1 uM]; p = 0.012). Differences in retinal vessel caliber were independent of confounders, odds ratios (OR) = 1.08 (95% confidence intervals [CI] = 1.02, 1.13; p = 0.007) and OR = 1.05 (CI = 1.01, 1.09; p = 0.011) per uM increase in arteriolar and venular diameter respectively. FEV1 remained significantly associated with retinal vessel dilatation r = -0.39 (p = 0.02). CONCLUSIONS: Non-mydriatic retinal imaging is easily facilitated. We found significant arteriole and venous dilation in COPD compared to age-matched smokers without COPD associated with lung function independent of standard cardiovascular risk factors. Retinal microvascular changes are known to be strongly associated with future vascular events and retinal photography offers potential to identify this risk. TRIAL REGISTRATION: clinicaltrials.gov NCT02060292.

Delayed cortical development in fetuses with complex congenital heart disease.

Neurologic impairment is a major complication of complex congenital heart disease (CHD). A growing body of evidence suggests that neurologic dysfunction may be present in a significant proportion of this high-risk population in the early newborn period prior to surgical interventions. We recently provided the first evidence that brain growth impairment in fetuses with complex CHD has its origins in utero. Here, we extend these observations by characterizing global and regional brain development in fetuses with hypoplastic left heart syndrome (HLHS), one of the most severe forms of CHD. Using advanced magnetic resonance imaging techniques, we compared in vivo brain growth in 18 fetuses with HLHS and 30 control fetuses from 25.4-37.0 weeks of gestation. Our findings demonstrate a progressive third trimester fall-off in cortical gray and white matter volumes (P < 0.001), and subcortical gray matter (P < 0.05) in fetuses with HLHS. Significant delays in cortical gyrification were also evident in HLHS fetuses (P < 0.001). In the HLHS fetus, local cortical folding delays were detected as early as 25 weeks in the frontal, parietal, calcarine, temporal, and collateral regions and appear to precede volumetric brain growth disturbances, which may be an early marker of elevated risk for third trimester brain growth failure.

1H MRS identifies symptomatic and asymptomatic subjects with partial ornithine transcarbamylase deficiency.

OBJECTIVE: To evaluate brain metabolism in subjects with partial ornithine transcarbamylase deficiency (OTCD) utilizing (1)H MRS. METHODS: Single-voxel (1)H MRS was performed on 25 medically-stable adults with partial OTCD, and 22 similarly aged controls. Metabolite concentrations from frontal and parietal white matter (FWM, PWM), frontal gray matter (FGM), posterior cingulate gray matter (PCGM), and thalamus (tha) were compared with controls and IQ, plasma ammonia, glutamine, and disease severity. RESULTS: Cases ranged from 19 to 59 years; average 34 years; controls ranged from 18 to 59 years; average 33 years. IQ scores were lower in cases (full scale 111 vs. 126; performance IQ 106 vs. 117). Decreased myoinositol (mI) in FWM (p=0.005), PWM (p<0.001), PCGM (p=0.003), and tha (p=0.004), identified subjects with OTCD, including asymptomatic heterozygotes. Glutamine (gln) was increased in FWM (p<0.001), PWM (p<0.001), FGM (p=0.002), and PCGM (p=0.001). Disease severity was inversely correlated with [mI] in PWM (r=-0.403; p=0.046) and directly correlated with [gln] in PCGM (r=0.548; p=0.005). N-Acetylaspartate (NAA) was elevated in PWM (p=0.002); choline was decreased in FWM (p=0.001) and tha (p=0.002). There was an inverse relationship between [mI] and [gln] in cases only. Total buffering capacity (measured by [mI/mI+gln] ratio, a measure of total osmolar capacity) was inversely correlated with disease severity in FWM (r=-0.479; p=0.018), PWM (r=-0.458; p=0.021), PCGM (r=-0.567; p=0.003), and tha (r=-0.345; p=0.037). CONCLUSION: Brain metabolism is impaired in partial OTCD. Depletion of mI and total buffering capacity are inversely correlated with disease severity, and serve as biomarkers.

PTA testing, the Westmead post traumatic amnesia scale and opiate analgesia: a cautionary note.

OBJECTIVE: To assess the validity of the Westmead PTA scale in patients treated with opiate analgesia. METHOD: Seventeen non-head injured, non-traumatic, electively hospitalized orthopaedic patients treated with opiate analgesia were tested on the Westmead PTA scale for a minimum of 2 consecutive days (n=17) to a maximum of 4 consecutive days (n=10). RESULTS: Only 20% of participants tested over 4 days reached criteria of three consecutive 12/12 scores on the Westmead PTA scale. Daily failure rates on the 12 item scale ranged from 36-70%. All failures were on the 'new learning' items, orientation items were never failed. CONCLUSIONS: The low pass rate of non-head injured patients treated with opiate analgesics indicates that the Westmead PTA scale is non-specific to traumatic brain injury and is probably an invalid measure of post-traumatic amnesia in patients actively treated with opiates. Implications for the measurement and accurate classification of traumatic brain injury patients are discussed.

Alterations in neuroblastoma ganglioside synthesis by induction of GD1b synthase by retinoic acid.

Recent findings link increased expression of the structurally complex 'b' pathway gangliosides GD1b, GT1b, GQ1b (CbG) to a favourable clinical and biological behaviour in human neuroblastoma (NB). Seeking a model to probe these observations, we evaluated four human NB cell lines. Very low CbG content (4-10%) in three of the four cell lines (LAN-5, LAN-1, SMS-KCNR) reflected the ganglioside pattern observed in the most aggressive NB tumours. Pharmacological alterations of complex ganglioside synthesis in vitro by a 5-7 day exposure to 5-10 microM retinoic acid, which is employed in maintenance therapy of disseminated NB, included markedly increased (i) relative expression of CbG (6.6+/-2.0-fold increase, P=0.037), (ii) relative expression of the analogous 'a' pathway gangliosides, termed CaG (6.4+/-1.4-fold increase in GM1a and GD1a; P=0.010), and (iii) total cellular ganglioside content (2.0-6.3-fold), which in turn amplified the accumulation of structurally complex gangliosides. Substantial increases (2.7-2.9-fold) in the activity of GD1b/GM1a synthase (beta-1,3-galactosyltransferase), which initiates the synthesis of CbG and CaG, accompanied the all-trans retinoic acid (ATRA)-induced ganglioside changes. Thus, increased CbG synthesis in NB cell lines is attributable to a specific effect of ATRA, namely induction of GD1b/GM1a synthase activity. Since the shift towards higher expression of CbG and CaG during retinoic acid-induced cellular differentiation reflects a ganglioside pattern found in clinically less-aggressive tumours, our studies suggest that complex gangliosides may play a role in the biological and clinical behaviour of NB.

Improvement in cognitive function after right temporal arteriovenous malformation excision.

A patient is presented in whom right temporal AVM excision led to improved cognitive function. Neuropsychological assessment showed a significant postoperative improvement in Performance IQ (p = < 0.05), Full Scale IQ (p = < 0.05), and clinically in visual memory (p = < 0.10). Reversal of vascular steal may lead to increases in cognitive function. We recommend that patients undergoing AVM excision have a complete neuropsychological evaluation.

MRI directed bilateral stimulation of the subthalamic nucleus in patients with Parkinson's disease.

OBJECTIVE: Bilateral chronic high frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) has emerged as an appropriate therapy for patients with advanced Parkinson's disease refractory to medical therapy. Advances in neuroimaging and neurophysiology have led to the development of varied targeting methods for the delivery of this treatment. Intraoperative neurophysiological and clinical monitoring is regarded by many to be mandatory for accurate STN localisation. We have examined efficacy of bilateral STN stimulation using a predominantly magnetic resonance imaging (MRI)-directed technique. METHODS: DBS leads were stereotactically implanted into the STN using an MRI directed method, with intraoperative macrostimulation used purely for adjustment. The effects of DBS were evaluated in 16 patients followed up to 12 months, and compared with baseline assessments. Assessments were performed in both off and on medication states, and were based on the Unified Parkinson's Disease Rating Scale (UPDRS) and timed motor tests. Functional status outcomes were examined using the PDQ-39 quality of life questionnaire. A battery of psychometric tests was used to assess cognition. RESULTS: After 12 months, stimulation in the off medication state resulted in significant improvements in Activities of Daily Living and Motor scores (UPDRS parts II and III) by 62% and 61% respectively. Timed motor tests were significantly improved in the off medication state. Motor scores (UPDRS part III) were significantly improved by 40% in the on medication state. Dyskinesias and off duration were significantly reduced and the mean dose of L-dopa equivalents was reduced by half. Psychometric test scores were mostly unchanged or improved. Adverse events were few. CONCLUSIONS: An MRI directed targeting method for implantation of DBS leads into the STN can be used safely and effectively, and results are comparable with studies using intraoperative microelectrode neurophysiological targeting. In addition, our method was associated with an efficient use of operating time, and without the necessary costs of microelectrode recording.

Inhibitory effects of voluntary wheel exercise on apoptosis in splenic lymphocyte subsets of C57BL/6 mice.

Two-month-old mice were placed in cages with (Ex) or without exercise running wheels with free access to the wheel 24 h/day for 10 mo. An equal amount of food for both groups was provided daily. Ex mice ran an average of 33.67 km/wk initially, and exercise decreased gradually with age. Ex mice had gained an average of 43.5% less body weight at the end of the experiment. Although serum lipid peroxides were not altered by exercise, superoxide dismutase and glutathione peroxidase activities in serum were significantly increased. Flow cytometric analysis of spleen cells revealed an increased percentage of CD8+ T cells and a decreased percentage of CD19+ B cells in Ex mice (P < 0.05). Exercise decreased apoptosis in total splenocytes and CD4+ cells incubated with medium alone or with H(2)O(2), dexamethasone, tumor necrosis factor-alpha (TNF-alpha), or anti-CD3 monoclonal antibody (P < 0.05) and CD8+ cells with medium alone or with TNF-alpha (P < 0.05). Even though exercise did not alter the intracellular cytokines (TNF-alpha and interleukin-2) or Fas ligand, it did significantly lower interferon-gamma in CD4+ and CD8+ cells (P < 0.05). In summary, voluntary wheel exercise appears to decrease H(2)O(2)-induced apoptosis in immune cells as well as decrease interferon-gamma production.

Cohort studies of health effects among people exposed to estuarine waters: North Carolina, Virginia, and Maryland.

A variety of human symptoms have been associated with exposure to the dinoflagellate Pfiesteria and have been grouped together into a syndrome termed "possible estuary-associated syndrome." Prospective cohort studies of health effects associated with exposure to estuarine waters that may contain Pfiesteria spp. and related organisms are in progress in North Carolina, Virginia, and Maryland. The three studies recruited cohorts of 118-238 subjects who work or engaged in recreation in estuary waters. Baseline health and neuropsychological evaluations are conducted, and study subjects are followed prospectively for 2-5 years with periodic assessments of health and performance on a battery of neuropsychological tests. Health symptoms and estuary water exposure are recorded by telephone interviews or diaries every 1-2 weeks. Water quality information, including measurements of Pfiesteria spp., is collected in the areas where the subjects are working. Because it is not possible to measure individual exposure to Pfiesteria or a toxin produced by this organism, these studies examine surrogate exposure measures (e.g., time spent in estuary waters, in a fish kill area, or in waters where Pfiesteria DNA was detected by molecular amplification). Preliminary analyses of the first 2 years (1998-2000) of data indicate that none of the three ongoing cohorts have detected adverse health effects. However, there have not been any reported fish kills associated with Pfiesteria since the studies began, so it is possible that none of the study subjects have been exposed to toxin-producing Pfiesteria spp.

Back to basics: validation of the admission systemic inflammatory response syndrome score in predicting outcome in trauma.

BACKGROUND: We have previously documented that the admission systemic inflammatory response syndrome (SIRS) score, calculated with four variables-temperature, heart rate, neutrophil count, and respiratory rate-is a significant predictor of outcome in trauma (n = 4,887). The objective of this current study was to validate our previous findings in a larger trauma patient population, to analyze the predictive accuracy of the four individual components of the SIRS score (temperature, heart rate, neutrophil count, and respiratory rate), and to assess whether the admission SIRS score is an accurate predictor of intensive care unit (ICU) resource use in trauma. METHODS: Prospective data were collected on 9,539 patients admitted to a Level I trauma center over a 30-month period (January 1997-July 1999). Patients were stratified by age, sex, race, and Injury Severity Score (ISS). SIRS score was calculated at admission, and SIRS was defined as a SIRS score > or = 2. RESULTS: SIRS score was validated as a significant independent predictor of outcome in trauma by logistic regression analysis after controlling for age and ISS. Of the four SIRS variables, hypothermia (temperature < 36 degrees C) was the most significant predictor of mortality after controlling for age and ISS. Leukocytosis (neutrophil count > 12,000/mm3) was the most significant predictor of total hospital length of stay. SIRS scores of > or = 2 were increasingly predictive of mortality and ICU admission by logistic regression analysis (p < 0.001). CONCLUSION: These data provide further validation that an admission SIRS score of > or = 2 is a significant independent predictor of outcome and ICU resource use in trauma. Temperature (hypothermia) is the individual component of the SIRS score with the greatest predictive accuracy. SIRS score should be calculated on all trauma admissions.

Systemic inflammatory response syndrome score at admission independently predicts infection in blunt trauma patients.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) score has been demonstrated to be an accurate predictor of outcome in critical surgical illness. To our knowledge, there is a paucity of data using SIRS score as a tool to predict posttraumatic infection. Our goal was to determine whether the severity of SIRS score at admission is an accurate predictor of infection in trauma patients. METHODS: Prospective data were collected on 4,887 blunt trauma patients admitted to a primary adult resource center designated trauma center over an 18-month period. Patients were stratified by age and Injury Severity Score (ISS). SIRS score was calculated at admission. SIRS was defined as an SIRS score > or = 2. Each patient was screened for infection by an infectious disease specialist. Those at high risk for infection were then monitored daily throughout their hospitalization. Centers for Disease Control and Prevention guidelines were used to diagnose infection. RESULTS: Of the 4,887 patients, 1,850 (38%) were admitted > 24 hours and evaluated for subsequent infection (mean ISS, 16 +/- 9; mean age, 43 +/- 19, SD). Thirty-one percent (577) of the patients acquired an infection. The mean hospital length of stay (20.2 days vs. 6.5 days) and mortality (7.8% vs. 2.7%) were significantly greater in the infected group (p < 0.001). Of the four SIRS variables (temperature, heart rate, white blood cell count, and respiratory rate), hypothermia and leukocytosis were the most significant predictors of infection (p < 0.001) when adjusted for age and ISS. SIRS scores of > or = 2 were increasingly predictive of infection when analyzed by multiple logistic regression analysis. CONCLUSION: An admission SIRS score of > or = 2 is a significant independent predictor of infection and outcome in blunt trauma. Daily SIRS scores may be a meaningful method of assessing postinjury risk of infection, and may initiate earlier diagnostic intervention for determination of infection.

Metabolic adaptations in skeletal muscle overexpressing GLUT4: effects on muscle and physical activity.

To understand the long-term metabolic and functional consequences of increased GLUT4 content, intracellular substrate utilization was investigated in isolated muscles of transgenic mice overexpressing GLUT4 selectively in fast-twitch skeletal muscles. Rates of glycolysis, glycogen synthesis, glucose oxidation, and free fatty acid (FFA) oxidation as well as glycogen content were assessed in isolated EDL (fast-twitch) and soleus (slow-twitch) muscles from female and male MLC-GLUT4 transgenic and control mice. In male MLC-GLUT4 EDL, increased glucose influx predominantly led to increased glycolysis. In contrast, in female MLC-GLUT4 EDL increased glycogen synthesis was observed. In both sexes, GLUT4 overexpression resulted in decreased exogenous FFA oxidation rates. The decreased rate of FFA oxidation in male MLC-GLUT4 EDL was associated with increased lipid content in liver, but not in muscle or at the whole body level. To determine how changes in substrate metabolism and insulin action may influence energy balance in an environment that encouraged physical activity, we measured voluntary training activity, body weight, and food consumption of MLC-GLUT4 and control mice in cages equipped with training wheels. We observed a small decrease in body weight of MLC-GLUT4 mice that was paradoxically accompanied by a 45% increase in food consumption. The results were explained by a marked fourfold increase in voluntary wheel exercise. The changes in substrate metabolism and physical activity in MLC-GLUT4 mice were not associated with dramatic changes in skeletal muscle morphology. Collectively, results of this study demonstrate the feasibility of altering muscle substrate utilization by overexpression of GLUT4. The results also suggest that as a potential treatment for type II diabetes mellitus, increased skeletal muscle GLUT4 expression may provide benefits in addition to improvement of insulin action.

Comparative effects of three beta blockers (atenolol, metoprolol, and propranolol) on survival after acute myocardial infarction.

The beneficial impact of beta blockade after an acute myocardial infarction (AMI) is clear, but beta-adrenergic blockers differ in multiple characteristics, including lipophilicity and selectivity. The impact of these factors on the effects of beta blockade is unknown. We therefore compared the effects of different beta blockers on mortality after AMI. Charts of 201,752 patients with AMI were abstracted by the Cooperative Cardiovascular Project, a quality assurance program sponsored by the Health Care Financing Administration. Of the 69,338 patients prescribed beta blockers, we compared mortality of patients receiving different beta-adrenergic blockers using the Cox proportional-hazards model accounting for multiple factors that might influence survival. The mortality rates of the 2 selective agents, metoprolol and atenolol, were virtually identical (13.5% and 13.4% 2-year mortality, respectively). Compared with metoprolol, patients discharged on propranolol had a slightly increased mortality (15.9% 2-year mortality), which may be related to undetected differences at baseline. Survival with all of the drugs was superior to the 23.9% 2-year mortality seen in patients not receiving beta blockers. Beta blockade overall was associated with a 40% improvement in survival. Although the use of beta blockade after AMI has major prognostic importance, the present study suggests that the specific beta blocker chosen will have little influence on mortality.

Age, fatigue, and excitation-contraction coupling in masseter muscles of rats.

The purpose of this study was to determine if masseter muscle endurance changes with increasing age and, if so, to examine mechanisms of fatigue. Characteristics of fatigue were measured under isometric conditions using high-frequency stimulation of anterior deep masseter (ADM) muscles of male Fischer 344 rats, 5 to 24 months old, and fed a hard (HD) or a soft (SD) diet. Potentiating effects of caffeine on ADM muscle performance in vitro were also examined. Fatigability increased by 48% with age in muscles of HD rats. Muscles of SD rats were highly fatigable at all ages. Increased HD fatigability was associated with significantly decreased concentrations of Na+/K+-adenosine triphosphatase (22%) and decreased responsiveness to caffeine postfatigue (29%). The pH levels decreased similarly in fatigued muscles of all groups. We conclude that the age-related increase in fatigability is associated with alterations in excitation-contraction coupling mechanisms. However, differences between SD and HD on ADM muscles represent possible fiber-type transitions.

Constancy of masseter muscle structure and function with age in F344 rats.

Senile muscle atrophy is a characteristic feature of advancing age. Despite the growing body of knowledge about weight-bearing muscles in rodents and man, there is relatively little such information on the muscles of mastication. Therefore, the primary goal here was to develop a masseter muscle preparation from male Fischer 344 rats suitable for studying contractile characteristics in vitro. And, secondarily, the goal was to examine this preparation for evidence of age-related changes in muscle composition and function in rats aged 4--24 months. Histochemical analysis of the composition of the four anatomical regions (branches) of the masseter revealed a mixture of rapidly contracting, fatiguable and fatigue-resistant muscle fibres with no significant differences between branches. Fibre type and size were determined with myosin ATPase, NADH-TR and toluidine blue staining of quick- frozen muscle sections. No significant changes in fibre type or fibre area were found with increasing age. One branch of the masseter, the anterior deep masseter, is sufficiently thin (less than 0.8 mm thickness) for adequate diffusion of oxygen and nutrients in studies of isometric contractile properties in vitro. Contraction time, half-relaxation time, dry weight:wet weight ratio and maximum force per unit area were found to be similar in muscles of young and old rats. Our results demonstrate that the anterior deep masseter of the rat is a suitable preparation for investigating masseter function in vitro. The surprising absence of age-related changes in composition and function is consistent with some, but not all, data on ageing rodent limb muscles. The results suggest that masticatory muscle performance is preserved with age in rats.

Prophylactic chlorhexidine oral rinse decreases ventilator-associated pneumonia in surgical ICU patients.

BACKGROUND: Pneumonia is one of the most common nosocomial infections in hospitalized patients. The risk of nosocomial pneumonia increases with age, severity of acute illness and preexisting co-morbid conditions. Ventilator-associated pneumonia (VAP) significantly increases morbidity, length of stay, resource utilization and mortality. The purpose of this study was to determine whether adherence to a ventilator weaning protocol (WP) and the use of chlorhexidine gluconate (CH) oral rinse for oral hygiene would decrease the incidence of VAP in surgical ICU patients. METHODS: A prospective study was conducted over a period of 10 months (October 1998-July 1999) in surgical ICU patients requiring mechanical ventilation (n = 95). During the first 5 months, a WP was applied to all patients requiring mechanical ventilation. During the following 5 months, a CH 0.12% oral rinse administered twice daily was added to the protocol, initiated on ICU admission in all intubated patients. The data collection included age, gender, race, risk factors, co-morbid conditions, severity of the acute illness (APACHE II) at admission, duration of ventilation, ICU and total-hospital length of stay, and incidence of VAP and in-hospital mortality rates. Both WP and WP+CH groups were compared using the National Nosocomial Infection Surveillance (NNIS) and hospital databases as historic controls. RESULTS: The institution of the WP alone led only to a slight decrease in the incidence of VAP but a significant reduction in the median duration of mechanical ventilation by 40% (4.5 days, p < 0.008). The addition of CH to the WP led to a significant reduction and delay in the occurrence of VAP (37% overall, 75% for late VAP, p < 0.05). The median duration of mechanical ventilation in this group was similar to that of the WP group. There was no significant difference in the overall hospital or ICU length of stay between the groups. CONCLUSIONS: Improved oral hygiene via topical CH application in conjunction with the use of a WP is effective in reducing the incidence of VAP and the duration of mechanical ventilation in surgical ICU patients.

Systemic inflammatory response syndrome score at admission independently predicts mortality and length of stay in trauma patients.

BACKGROUND: Recent studies have documented that the systemic inflammatory response syndrome (SIRS) score is a useful predictor of outcome in critical surgical illness. The duration and severity of SIRS are associated with posttrauma multiple organ dysfunction and mortality. We sought to determine whether the severity of SIRS at admission is an accurate predictor of mortality and length of stay (LOS) in trauma patients. METHODS: Prospective data of 4,887 trauma admissions to a Level I trauma center over a 18-month period (January 1997 to July 1998) were analyzed. Patients were stratified by age and Injury Severity Score (ISS), and a SIRS severity score (1 to 4) was calculated at admission (1 point for each component present: fever or hypothermia, tachypnea, tachycardia, and leukocytosis). The SIRS score was evaluated as an independent predictor of mortality and LOS by chi2 and multivariate logistic regression. RESULTS: Trauma patients (n = 4,887, 83% blunt injuries, 72% male) had the following characteristics: 73.1% were age 18 to 45 years, 17.5% were age 46 to 65 years, and 9.4% were age > or =66 years; 77.7% had ISS less than 15, 18.8% had ISS 16 to 29, and 3.5% had ISS greater than 29. Analysis of variance adjusting for age and ISS determined that SIRS score of 2 was a significant predictor of LOS. Furthermore, the relative risk of death increased significantly with SIRS score of 2 when age and ISS were held constant. CONCLUSION: Logistic regression analysis confirmed that a SIRS score of 2 was a significant independent predictor of increased mortality and LOS in trauma patients. These data suggest that admission SIRS scoring in trauma patients is a simple tool that may be used as a predictor of outcome and resource utilization.

Cognitive functioning after subthalamic nucleotomy for refractory Parkinson's disease.

OBJECTIVE: To evaluate whether subthalamic nucleotomy produces adverse cognitive effects in patients with Parkinson's disease. METHOD: Twelve patients with Parkinson's disease underwent stereotactic surgery to the subthalamic nucleus. Presurgical and postsurgical neuropsychological assessment of attention, memory, executive function, language, and verbal intellect were undertaken with a battery of tests designed to minimise potential contamination of cognitive effects by motor symptoms. RESULTS: There was no statistically significant difference in the cognitive tests results after operation for the group as a whole. Reliable change indexes were generated for the cognitive tests. Reliable change postoperatively was found on specific tests of verbal memory, attention, and planning. Left sided operations were associated with greater incidence of deterioration postsurgery. CONCLUSIONS: Preliminary data on the first reported cognitive changes after subthalamic nucleotomy suggested few adverse cognitive effects of the surgery although discrete neuropsychological changes were seen in some patients. These effects were consistent with current theories on the cognitive functions of the basal ganglia.

Lipoprotein (a) and the risk of ischemic stroke in young women.

BACKGROUND AND PURPOSE: lipoprotein (a) (lp (a)) is a lipid-containing particle similar to LDL which has been found in atherosclerotic plaque. The role of lp (a) in ischemic stroke remains controversial, but some studies suggest lp (a) is particularly important as a risk factor for stroke in young adults. We investigated the role of lp (a) as a risk factor for stroke in young women enrolled in the Stroke Prevention in Young Women Study. METHODS: subjects were participants in a population-based, case-control study of risk factors for ischemic stroke in young women. Cases were derived from surveillance of 59 regional hospitals in the central Maryland, Washington DC, Pennsylvania and Delaware area. Lp (a) was measured in 110 cases and 216 age-matched controls. Demographics, risk factors, and stroke subtype were determined by interview and review of medical records. RESULTS: lp (a) values were higher in blacks than whites, but within racial groups, the distribution of lp (a) values was similar between cases and controls. After adjustment for age, race, hypertension, diabetes, cigarette smoking, coronary artery disease, total cholesterol and HDL cholesterol, the odds ratio for an association of lp (a) and stroke was 1.36 (95% CI 0.80-2.29). There was no dose-response relationship between lp (a) quintile and stroke risk. Among stroke subtypes, only lacunar stroke patients had significantly elevated lp (a) values compared to controls. CONCLUSIONS: we found no association of lp (a) with stroke in a population of young women with ischemic stroke. Small numbers of patients limit conclusions regarding risk in ischemic stroke subtypes, but we could not confirm previous suggestions of an association of lp (a) with atherosclerotic stroke in young adults.

Analysis of the effects of growth hormone, voluntary exercise, and food restriction on diaphyseal bone in female F344 rats.

The aim of this study is to examine the effects of growth hormone, exercise, and weight loss due to food restriction on tibial diaphyseal bone and on tibial muscle mass. Thirteen-month-old female F344 rats were divided into six groups: group 1, baseline controls (B); group 2, age-matched controls (C); group 3, GH treated (GH); group 4, voluntary wheel running exercise (EX); group 5, GH + EX; and group 6, food restricted (FR). The dose of GH was 2.5 mg recombinant human (rh) GH/kg body weight/day, 5 days per week, given in two divided doses of 1.25 mg at 9-10 A.M. and 4-5 P.M. Food-restricted rats were fed 60% of the mean food intake of the age-matched controls. All animals except the baseline controls were killed after 4.5 months. The baseline controls were killed at the beginning of the study. Growth hormone increased the body weight and tibial muscle mass of the rats markedly, while EX caused only a slight decrease in body weight and partially inhibited the increase caused by GH in the GH + EX group. Food restriction greatly decreased body weight below that of age-matched controls, but neither FR nor EX had a significant effect on the mass of the muscles around the tibia. Growth hormone and EX independently increased tibial diaphyseal cortical bone area (p < 0.0001, p < 0.0001), cortical thickness (p < 0.0001, p < 0.0001), cortical bone mineral content (p < 0.0001, p < 0.0001), periosteal perimeter (p < 0.0001, p < 0.0001), and bone strength-strain index (SSI) (p < 0.0001, p < 0.0001). The effects of GH were more marked and resulted in a greater increase in the weight of the mid tibial diaphysis (p < 0.0001). The combination of GH and EX produced additive effects on many of the tibial diaphyseal parameters, including bone SSI. GH + EX, but not GH or EX alone, caused a significant increase in endocortical perimeter (p < 0.0001). In the FR rats, cortical bone area and cortical mineral content increased above the baseline level (p < 0.001, p < 0.0001) but were below the levels for age-matched controls (p < 0.0001, p < 0.0001). In addition, marrow area, endocortical perimeter, and endocortical bone formation rate increased significantly in the FR rats (p < 0.01, p < 0.0001, p < 0.0001). Three-point bending test of right tibial diaphysis resulted in maximum force (Fmax) values that reflected the group differences in indices of tibial diaphyseal bone mass, except that GH + EX did not produce additive effect on Fmax. The latter showed good correlation with left tibial diaphyseal SSI (r = 0.857, p < 0.0001), and both indices of bone strength correlated well with tibial muscle mass (r = 0.771, Fmax; r = 0.700, SSI; p < 0.0001). GH increased serum IGF-I (p < 0.0001), and the increase was partially reduced by EX. Serum osteocalcin was increased by GH with or without EX (p < 0.01, p < 0.01), and FR or EX alone did not alter serum IGF-I and osteocalcin levels. The bone anabolic effects of GH with or without EX may relate, in part, to increased load on bone from tibial muscles and body weight, which were increased by the hormone. The osteogenic effect of EX with or without GH may relate, in part, to increased frequency of muscle load on bone as EX decreased body weight (p < 0.05), but had no significant effect on tibial muscle mass. The enhanced loss of endocortical bone by FR may relate, in part, to decreased load on bone due to low body weight (p < 0.0001), as FR did not cause a significant decrease in tibial muscle mass (p = 0.357). The roles of humoral and local factors in the bone changes observed remain to be established.