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.

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.

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.

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.

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.

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.

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.

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.

Homocyst(e)ine and risk of cerebral infarction in a biracial population : the stroke prevention in young women study.

BACKGROUND AND PURPOSE: Genetic enzyme variation and vitamin intake are important determinants of blood homocyst(e)ine levels. The prevalence of common genetic polymorphisms influencing homocyst(e)ine levels varies by race, and vitamin intake varies by socioeconomic status. Therefore, we examined the effect of vitamin intake, race, and socioeconomic status on the association of homocyst(e)ine with stroke risk. METHODS: All 59 hospitals in the greater Baltimore-Washington area participated in a population-based case-control study of stroke in young women. One hundred sixty-seven cases of first ischemic stroke among women aged 15 to 44 years were compared with 328 controls identified by random-digit dialing from the same region. Risk factor data were collected by standardized interview and nonfasting phlebotomy. Plasma homocyst(e)ine was measured by high-performance liquid chromatography and electrochemical detection. RESULTS: Blacks and whites did not differ in median homocyst(e)ine levels, nor did race modify the association between homocyst(e)ine and stroke. After adjustment for cigarettes per day, poverty status, and regular vitamin use, a plasma homocyst(e)ine level of >/=7.3 micromol/L was associated with an odds ratio for stroke of 1.6 (95% CI, 1.1 to 2.5). CONCLUSIONS: The association between elevated homocyst(e)ine and stroke was independent not only of traditional vascular risk factors but also of vitamin use and poverty status. The degree of homocyst(e)ine elevation associated with an increased stroke risk in young women is lower than that previously reported for middle-aged men and the elderly and was highly prevalent, being present in one third of the control group.

A randomized trial of surgical antimicrobial prophylaxis with and without vancomycin in organ transplant patients.

BACKGROUND: Gram-positive organisms, including vancomycin-resistant enterococci (VRE), have emerged as major pathogens on the organ transplant service at our institution. We hypothesized that our use of vancomycin as part of routine surgical prophylaxis increased the risk of VRE colonization and infection; conversely, there was concern that failure to use vancomycin prophylaxis would increase peri-operative morbidity due to gram-positive organisms. METHODS: Renal transplant recipients (n = 88) were randomized to receive either a) vancomycin/ceftriaxone or b) cefazolin; and pancreas transplants (n = 24) to receive either a) vancomycin/gentamicin or b) cefazolin/gentamicin. Stool samples or rectal swabs were obtained for culture for enterococci within 24 h of transplantation and weekly while hospitalized. RESULTS: Enterococci were isolated on stool culture from 38 (34%) of 102 patients at the time of transplantation; 4 (11%) of the isolates were VRE. The percentage of patients who subsequently acquired VRE was low (1-7% per wk) but remained constant during hospitalization. There was no association between new VRE detection and vancomycin use for either prophylactic or therapeutic purposes. Forty-four patients (39%) had a post-operative infection with 46% of these infections due to gram-positive organisms; rates were unaffected by prophylactic vancomycin use. Pancreas transplant patients who did not receive vancomycin prophylaxis had a significantly longer initial hospitalization (p = 0.03); however, differences were not statistically significant when total length of stay (LOS) within the first 90 d of transplantation was compared. CONCLUSIONS: Vancomycin surgical prophylaxis does not appear to have an effect on VRE colonization or infection, or on rates of infection with gram-positive bacteria. Elimination of vancomycin prophylaxis in renal transplant patients may be a reasonable part of an overall program to limit vancomycin usage, although as a single measure, its impact may be minimal. Vancomycin surgical prophylaxis may be of greater importance in pancreas transplants.

Additive effect of voluntary exercise and growth hormone treatment on bone strength assessed at four different skeletal sites in an aged rat model.

The aim of the study was to assess the effect of growth hormone (GH), voluntary exercise (Ex), and the combination of GH and Ex on bone strength, mass, and dimensions in aged, intact female rats. In addition, the effect of food restriction (FR) was studied. Fourteen-month-old virgin F-344 rats were divided into 6 groups with 13 animals in each: (1) baseline (BSL); (2) control + solvent vehicle (CTRL); (3) GH 2.5 mg/kg/day (GH); (4) exercise, voluntary: 0.6-0.7 km/day (Ex); (5) GH treatment and voluntary exercise (GH + Ex); and (6) FR. Group 1 was killed at the beginning of the study and served as baseline. All the other groups were killed after 18 weeks' treatment. The effects of aging and treatment regimes were measured at four different skeletal sites: lumbar vertebrae, femoral cortical bone, femoral neck, and the distal femoral metaphysis. Aging in itself induced a decline in vertebral body strength and ash density. At the appendicular skeletal sites, bone mass and strength were unchanged or increased. Treatment with GH alone induced a significant increase in the biomechanical parameters at the vertebral body and the femoral diaphysis, but not at the femoral neck or the distal femoral metaphysis. Voluntary exercise on its own increased load values significantly over CTRL at the vertebral body site, but not at any of the appendicular skeletal sites. The combination of GH and voluntary exercise resulted in an additive effect at the vertebral site and at the femoral diaphysis, and a synergistic (potentiating) effect at the two femoral metaphyses. FR, on the other hand, had a negative effect on cortical bone area and strength at the femoral diaphysis, but no significant effect on the other sites tested. We conclude that GH treatment and voluntary exercise both have skeletal anabolic effects; however, these effects are exerted to differing degrees at different sites. Importantly, when dosed together, GH and Ex have either an additive or synergistic anabolic effect on all sites (axial and appendicular).

Elevated tissue plasminogen activator antigen and stroke risk: The Stroke Prevention In Young Women Study.

BACKGROUND AND PURPOSE: Abnormalities in endogenous fibrinolysis are associated with an increased risk for stroke in men and older adults. We tested the hypothesis that elevated plasma tissue plasminogen activator (tPA) antigen, a marker for impaired endogenous fibrinolysis, is an independent risk factor for stroke in young women. METHODS: Subjects were 59 nondiabetic females ages 15 to 44 years with cerebral infarction from the Baltimore-Washington area and 97 control subjects frequency-matched for age who were recruited by random-digit dialing from the same geographic area. A history of cerebrovascular disease risk factors was obtained by face-to-face interview. Plasma tPA antigen was measured by enzyme-linked immunosorbent assay. RESULTS: Mean plasma tPA antigen levels were significantly higher in stroke patients than control subjects (4. 80+/-4.18 versus 3.23+/-3.67 ng/mL; P=0.015). After adjustment for age, hypertension, cigarette smoking, body mass index, and ischemic heart disease, there was a dose-response association between tPA antigen and stroke with a 3.9-fold odds ratio of stroke (95% CI, 1.2 to 12.4; P=0.03) for the upper quartile (>4.9 ng/mL) of tPA antigen compared with the lowest quartile. The dose-response relationship between tPA antigen and stroke was equally present in white and nonwhite women, and further adjustment for total and HDL cholesterol levels only modestly attenuated this association. CONCLUSIONS: This population-based case-control study shows that elevated plasma tPA antigen level is independently associated with an increased risk for ischemic stroke in nondiabetic females 15 to 44 years of age. These findings support the hypothesis that impaired endogenous fibrinolysis is an important risk factor for stroke in young women.

Distribution and correlates of elevated total homocyst(e)ine: the Stroke Prevention in Young Women Study.

PURPOSE: To determine the distribution and correlates of elevated total homocyst(e)ine (tHcy) concentration in a population of premenopausal black and white women. METHODS: Data from the Stroke Prevention in Young Women Study (N = 304), a population-based study of risk factors for stroke in women aged 15-44 years of age, were used to determine the distribution and correlates of elevated tHcy in black (N = 103) and white women (N = 201). RESULTS: The mean tHcy level for the population was 6.58 micromol/L (range 2.89-26.5 micromol/L). Mean tHcy levels increased with age, cholesterol level, alcohol intake, and number of cigarettes smoked (all: p < 0.05). There were no race differences (mean tHcy 6.72 micromol/L among blacks and 6.51 micromol/L among whites; p = 0.4346). Regular use of multivitamins and increasing education was associated with significant reductions in tHcy concentration. Approximately 13% of the sample had elevated tHcy levels, defined as a tHcy concentration > or = 10.0 micromol/L. Multivariate-adjusted correlates of elevated tHcy included education > 12 vs. < or = 12 (odds ratio [OR] = 0.4, 95% confidence interval [CI] = 0.2-0.8); smoking > or = 20 cigarettes/day vs. nonsmokers (OR = 2.8, 95% CI = 1.1-7.3); and the regular use of multivitamins (OR = 0.4, 95% CI = 0.2-0.9). CONCLUSIONS: These results suggest that a substantial proportion of healthy young premenopausal women have tHcy levels that increase their risk for vascular disease. A number of potentially modifiable behavioral and environmental factors appear to be significantly related to elevated tHcy levels in young women.

Single muscle fiber discharge transformations: fibrillation potential to positive sharp wave.

It is presently believed that a fibrillation potential (FP) can transform into a positive sharp wave (PSW) by displaying a number of individual transitional potentials with a high degree of morphological variation between different sets of independent transformations. Clinically obtained examples of FP-to-PSW transformations and a myotonic discharge transformation are simulated by a finite fiber computer model. The simulations demonstrate that the two clinical FP-to-PSW examples may well be the result of two independent muscle fibers synchronously firing for a short period of time such that their separate waveforms summate at the electrode to create a false impression of one potential changing into another through a specific series of transitional waveforms. The transition characterized by the myotonic discharge is substantiated through modeling to define the most reasonable transitional series of waveform morphologies for a single muscle fiber. The combination of clinical examples, histological needle electrode muscle penetration studies, and simulations of single muscle fiber discharge transitions support the hypothesis that a needle recording electrode is capable of inducing a variable degree of mechanical compression with a commensurate amount of action potential blockade. The degree of action potential blockade directly contributes to the clinically observed configuration for the single muscle fiber discharge in both innervated and denervated tissues.

Effects of fiber type on ischemia-reperfusion injury in mouse skeletal muscle.

Tourniquets frequently used during surgery involve tissue ischemia followed by postoperative reperfusion. However, little information is available on the functional consequences of this procedure in skeletal muscle. The goal of this study was to use skeletal muscles of C57BL/6 adult male mice to assess functional, structural, and biochemical characteristics after hindlimb vessel occlusion. Experimental manipulation involved application of a tourniquet to the hindlimb for a 3-hour period (n = 65). Muscles were then excised after various periods of reperfusion. Soleus and extensor digitorum longus muscles were chosen as representative of slow oxidative and fast glycolytic muscle fiber types, respectively. The most striking functional change found after ischemia-reperfusion injury was markedly improved endurance of extensor digitorum longus muscles. These fast-twitch glycolytic muscle fibers became much more resistant to fatigue during recovery from ischemia-reperfusion injury. There was a progressive increase in force generation in both muscles during recovery; however, soleus muscles recovered function more quickly after ischemia-reperfusion than extensor digitorum longus muscles. Also, extensor digitorum longus muscles recovered mass more slowly than soleus muscles at 7 and 14 days after ischemia. Structurally, extensor digitorum longus muscles had more severely damaged mitochondria, sarcoplasmic reticulum, and myofibrils. Surprisingly, no differences in oxidative enzyme activity (citrate synthase) and oxidative damage (in protein and lipids) were found after ischemia-reperfusion. The results indicate that muscle fiber type has a significant impact on the nature of ischemia-reperfusion injury in skeletal muscle. Thus, muscle fiber composition would be expected to affect recovery from the clinical use of tourniquets and other ischemic procedures. Furthermore, the results suggest that damage to structures involved in energy transduction and excitation-contraction coupling may play a role in the effects.

Effect of beta-blockade on mortality among high-risk and low-risk patients after myocardial infarction.

BACKGROUND: Long-term administration of beta-adrenergic blockers to patients after myocardial infarction improves survival. However, physicians are reluctant to administer beta-blockers to many patients, such as older patients and those with chronic pulmonary disease, left ventricular dysfunction, or non-Q-wave myocardial infarction. METHODS: The medical records of 201,752 patients with myocardial infarction were abstracted by the Cooperative Cardiovascular Project, which was sponsored by the Health Care Financing Administration. Using a Cox proportional-hazards model that accounted for multiple factors that might influence survival, we compared mortality among patients treated with beta-blockers with mortality among untreated patients during the two years after myocardial infarction. RESULTS: A total of 34 percent of the patients received beta-blockers. The percentage was lower among the very elderly, blacks, and patients with the lowest ejection fractions, heart failure, chronic obstructive pulmonary disease, elevated serum creatinine concentrations, or type 1 diabetes mellitus. Nevertheless, mortality was lower in every subgroup of patients treated with beta-blockade than in untreated patients. In patients with myocardial infarction and no other complications, treatment with beta-blockers was associated with a 40 percent reduction in mortality. Mortality was also reduced by 40 percent in patients with non-Q-wave infarction and those with chronic obstructive pulmonary disease. Blacks, patients 80 years old or older, and those with a left ventricular ejection fraction below 20 percent, serum creatinine concentration greater than 1.4 mg per deciliter (124 micromol per liter), or diabetes mellitus had a lower percentage reduction in mortality. Given, however, the higher mortality rates in these subgroups, the absolute reduction in mortality was similar to or greater than that among patients with no specific risk factors. CONCLUSIONS: After myocardial infarction, patients with conditions that are often considered contraindications to beta-blockade (such as heart failure, pulmonary disease, and older age) and those with nontransmural infarction benefit from beta-blocker therapy.