Association between cerebral oxygen metabolic rate and the incidence of nosocomial pneumonia in head injury patients

The development of nosocomial pneumonia was monitored in 96 head-trauma patients requiring mechanical ventilation for up to 10 days. Pneumonia occurred in 28 patients (29.2%) or 53.9 cases per 1,000 admission days. The incidence of nosocomial pneumonia was negatively correlated with cerebral oxygen metabolic rate (CMRO$\sb2$) measured during the first five days. The relative risk of nosocomial pneumonia for patients with CMRO$\sb2$ less than 0.6 umol/gm/min is 2.08 (1.09$-$3.98) times those patients with CMRO$\sb2$ greater than 0.6 umol/gm/min. The association between cerebral oxygen metabolic rate and nosocomial pneumonia was not affected by adjustment of potential confounding factors including age, cimetidine and other infections. These findings provide evidences underlying the CNS-immune system interaction. ^

Characterization of the interaction between local cerebral metabolic rate for glucose and acid -base index in ischemic rat brain employing a double-isotope methodology

The association between increases in cerebral glucose metabolism and the development of acidosis is largely inferential, based on reports linking hyperglycemia with poor neurological outcome, lactate accumulation, and the severity of acidosis. We measured local cerebral metabolic rate for glucose (lCMRglc) and an index of brain pH--the acid-base index (ABI)--concurrently and characterized their interaction in a model of focal cerebral ischemia in rats in a double-label autoradiographic study, using ($\sp{14}$C) 2-deoxyglucose and ($\sp{14}$C) dimethyloxazolidinedione. Computer-assisted digitization and analysis permitted the simultaneous quantification of the two variables on a pixel-by-pixel basis in the same brain slices. Hemispheres ipsilateral to tamponade-induced middle cerebral occlusion showed areas of normal, depressed and elevated glucose metabolic rate (as defined by an interhemispheric asymmetry index) after two hours of ischemia. Regions of normal glucose metabolic rate showed normal ABI (pH $\pm$ SD = 6.97 $\pm$ 0.09), regions of depressed lCMRglc showed severe acidosis (6.69 $\pm$ 0.14), and regions of elevated lCMRglc showed moderate acidosis (6.88 $\pm$ 0.10), all significantly different at the.00125 level as shown by analysis of variance. Moderate acidosis in regions of increased lCMRglc suggests that anaerobic glycolysis causes excess protons to be generated by the uncoupling of ATP synthesis and hydrolysis. ^

A study of the relationship between physical activity and cardiovascular fitness and coronary heart disease risk factors in female adolescents

The association of measures of physical activity with coronary heart disease (CHD) risk factors in children, especially those for atherosclerosis, is unknown. The purpose of this study was to determine the association of physical activity and cardiovascular fitness with blood lipids and lipoproteins in pre-adolescent and adolescent girls.^ The study population was comprised of 131 girls aged 9 to 16 years who participated in the Children's Nutrition Research Center's Adolescent Study. The dependent variables, blood lipids and lipoproteins, were measured by standard techniques. The independent variables were physical activity measured as the difference between total energy expenditure (TEE) and basal metabolic rate (BMR), and cardiovascular fitness, VO$\rm\sb{2max}$(ml/min/kg). TEE was measured by the doubly-labeled water (DLW) method, and BMR by whole-room calorimetry. Cardiovascular fitness, VO$\rm\sb{2max}$(ml/min/kg), was measured on a motorized treadmill. The potential confounding variables were sexual maturation (Tanner breast stage), ethnic group, body fat percent, and dietary variables. A systematic strategy for data analysis was used to isolate the effects of physical activity and cardiovascular fitness on blood lipids, beginning with assessment of confounding and interaction. Next, from regression models predicting each blood lipid and controlling for covariables, hypotheses were evaluated by the direction and value of the coefficients for physical activity and cardiovascular fitness.^ The main result was that cardiovascular fitness appeared to be more strongly associated with blood lipids than physical activity. An interaction between cardiovascular fitness and sexual maturation indicated that the effect of cardiovascular fitness on most blood lipids was dependent on the stage of sexual maturation.^ A difference of 760 kcal/d physical activity (which represents the difference between the 25th and 75th percentile of physical activity) was associated with negligible differences in blood lipids. In contrast, a difference in 10 ml/min/kg of VO$\rm\sb{2max}$ or cardiovascular fitness (which represents the difference between the 25th and 75th percentile in cardiovascular fitness) in the early stages of sexual maturation was associated with an average positive difference of 15 mg/100 ml ApoA-1 and 10 mg/100 ml HDL-C. ^

STUDIES ON ENERGY METABOLISM IN THE HIPPOCAMPUS AFTER ISCHEMIA

The gerbil model of ischemia was used to determine the effect of carotid occlusion on energy metabolites in cellular layers of discrete regions of the hippocampus and dentate gyrus. Levels of glucose, glycogen, ATP and phosphocreatine (PCr) were unchanged after 1 minute of ischemia. However, 3 minutes of ischemia produced a dramatic decrease in net levels of all metabolites. No additional decrease was observed after 15 minutes of ischemia. Re-establishment of the blood flow for 5 minutes after a 15 minute ischemic episode returned all metabolites to pre-ischemia levels. Concentrations of glucose and glycogen were elevated in sham-operated animals as a function of the pentobarbital anesthetic employed. In other studies, elevated GABA levels (produced by inhibiting GABA-transaminase with (gamma)-vinyl-GABA (GVG)) were found to decrease the rate of utilization of the high-energy phosphate metabolites ATP and PCr in the mouse cortex. In addition, glucose and glycogen levels were increased. Thus, tonic inhibition by GABA produced decreased cellular activity. Additional experiments demonstrated the attenuation of ischemia-induced metabolite depletion in cellular layers of regions of the hippocampus, dentate gyrus and cortex after GVG administration. Under ether, 1 minute of bilateral carotid occlusion produced a dramatic decrease in metabolite levels. After GVG treatment, the decrease was blocked completely for glucose, glycogen and ATP, and partially for PCr. Therefore, GABA-transaminase inhibition produced increased levels of GABA which subsequently decreased cellular activity. The protection against ischemia may have been due to (a)decreased metabolic rate; the available energy stores were utilized at a slower rate, and (b)increased levels of energy substrates; additional supplies available to maintain viability. These data suggest that the functional state of neural tissue can determine the response to metabolic stress. ^

ASSESSMENT OF SKELETAL MUSCLE BLOOD FLOW AND GLUCOSE METABOLISM WITH POSITRON EMITTING RADIONUCLIDES

In order to evaluate factors regulating substrate metabolism in vivo positron emitting radionuclides were used for the assessment of skeletal muscle blood flow and glucose utilization. The potassium analog, Rb-82 was used to measure skeletal muscle blood flow and the glucose analog, 18-F-2-deoxy-2-fluoro-D-glucose (FDG) was used to examine the kinetics of skeletal muscle transport and phosphorylation.^ New Zealand white rabbits' blood flow ranged from 1.0-70 ml/min/100g with the lowest flows occurring under baseline conditions and the highest flows were measured immediately after exercise. Elevated plasma glucose had no effect on increasing blood flow, whereas high physiologic to pharmacologic levels of insulin doubled flow as measured by the radiolabeled microspheres, but a proportionate increase was not detected by Rb-82. The data suggest that skeletal muscle blood flow can be measured using the positron emitting K+ analog Rb-82 under low flow and high flow conditions but not when insulin levels in the plasma are elevated. This may be due to the fact that insulin induces an increase in the Na+/K+-ATPase activity of the cell indirectly through a direct increase in the Na+/H+pump activity. This suggests that the increased cation pump activity counteracts the normal decrease in extraction seen at higher flows resulting in an underestimation of flow as measured by rubidium-82.^ Glucose uptake as measured by FDG employed a three compartment mathematical model describing the rates of transport, countertransport and phosphorylation of hexose. The absolute values for the metabolic rate of FDG were found to be an order of magnitude higher than those reported by other investigators. Changes noted in the rate constant for transport (k1) were found to disagree with the a priori information on the effects of insulin on skeletal muscle hexose transport. Glucose metabolism was however, found to increase above control levels with administration of insulin and electrical stimulation. The data indicate that valid measurements of skeletal muscle glucose transport and phosphorylation using the positron emitting glucose analog FDG requires further model application and biochemical validation. (Abstract shortened with permission of author.) ^

Adult weight gain and risk of colon cancer in men

Previous research supports the hypothesis that a "rich" diet (i.e., high in fat and low in fiber) increases the risk of colon cancer. Previous research also supports the hypothesis that physical inactivity increases the risk of colon cancer, perhaps because physical inactivity decreases gut motility, thereby increasing tee time that carcinogens are in contact with the intestinal mucosa. Habitual physical inactivity, combined with rich diet, ordinarily results in chronic energy imbalance and gain in weight, except when energy balance is modified by disease or factors such as cigarette smoking. Cigarette smokers typically stay lean because of effects of smoking on the resting metabolic rate as well as on efficiency of caloric intake and storage. Therefore, if physical inactivity and rich diet do increase the risk of colon cancer, then weight gain during young adulthood should be positively associated with incidence of colon cancer during later life, especially in nonsmokers.^ This hypothesis was investigated in a cohort of 2,059 randomly selected middle-aged men who were employed at the Western Electric Company in Chicago and were free of clinically diagnosed cancer at initial examination in 1958. Body mass index (BMI) in middle age was calculated from measured height and weight at the initial examination. BMI at age 20 was estimated from weight at age 20 as recalled at the initial examination and height as measured at the initial examination. Change in BMI between age 20 and middle age was estimated by subtracting the BMI at 20 from the BMI in middle age. Forty-nine incident cases of colon cancer were detected during 25 years (43,326 person-years) at risk. When stratified by level of change in BMI from age 20 to middle age ($\le$1.9, 2.0-3.9, 4.0-5.9, $\ge$6.0 kg/m$\sp2$), age-adjusted relative hazards of colon cancer in never-smokers were 1.00, 1.22, 2.31, and 5.01, respectively (p for trend = 0.008); corresponding values in ever-smokers were 1.00, 0.95, 0.77, and 0.87, These associations did not change appreciably after further adjustment for BMI at age 20, subscapular-triceps skinfold ratio, cigarette smoking, consumption of alcohol, energy, fat, and calcium.^ We also investigated the hypothesis that the risk of colon cancer was higher in men who were lean at age 20 and became fat by middle age (lean-to-fat) than in men who were fat at age 20 and stayed fat in middle-age (fat-to-fat). "Lean" was defined as BMI $<$24 kg/m$\sp2$ at age 20 and as BMI $<$27.0 kg/m$\sp2$ in middle age. Among never-smokers, in comparison to men who were lean at age 20 and in middle age (lean-to-lean), the age-adjusted relative hazard of colon cancer was 1.43 in the fat-to-fat group (95% confidence interval (CI) 0.37-5.52) and 3.36 in the lean-to-fat group (95% CI 1.21-9.37). This investigation provides new results on the magnitude of risk of colon cancer associated with weight gain during adulthood (from age 20 to middle age). This relation was obscured or underestimated in previous studies due to effect-modification by cigarette smoking. Finally, the result supports the idea that a life-style characterized by chronic energy imbalance during young adulthood increases risk of colon cancer. ^

RESPONSES OF INDICATOR AND PATHOGENIC BACTERIA TO THE PRESENCE OF CARBARYL IN WATER

Biodegradability is a desirable, if not a necessary characteristic of pesticides. Carbaryl, as Sevin, is one of the more widely used insecticides for the control of agricultural pests and has been reported to be readily degraded by microorganisms. Because of its broad application, the concentration of Sevin in surface waters has been reported to reach nearly four parts per million (PPM) in surface waters, where it has been reported to affect the growth and metabolic rates of aquatic bacterial populations. Following these reports, it is of public health importance to determine the effects of this insecticide on the growth and metabolic rates of bacteria used to indicate water pollution, and on pathogenic organisms which are found in polluted water.^ This study was conducted to determine the effect of carbaryl on the growth and metabolic rates of indicator and pathogenic organisms. Escherichia coli and Streptococcus faecalis were used as indicators, while Staphylococcus aureus and Salmonella typhimurium were the pathogens studied. Pure and mixed cultures of these organisms were exposed to two concentrations of carbaryl (Sevin).^ The study demonstrated that the fecal pollution indicator organisms, E. coli and S. faecalis respond differently to the presence of small concentrations of carbaryl in water as do the two pathogens tested, (S. typhimurium and S. aureus). The growth of all test organisms as measured by spread plate counts, was reduced by the presence of either one mg/l or five mg/l carbaryl within a period of eight days. Survival of the organisms in the presence of five mg/l carbaryl varied dependent upon whether the organism was in pure or mixed culture. In the presence of five mg/l carbaryl, both pure and mixed culture of E. coli showed longer survival. S. faecalis survived for more than eight days in pure culture, neither S. typhimurium nor S. aureus survived for eight days in pure culture.^ The metabolic rate of S. faecalis and S. aureus was reduced by both five mg/l and one mg/l Sevin concentrations, contrary to E. coli and S. typhimurium which had reduced metabolic rate with the introduction of five mg/l Sevin but showed an increase in the metabolic rate with one mg/l Sevin. There was no difference between the test and control when mixed populations were exposed to five mg/l Sevin and the metabolic rate tested. A mixture of E. coli and S. typhimurium populations showed a respiration increase over the control when exposed to one mg/l Sevin concentration. If similar effects occur in polluted surface waters, misleading results from bacteriological water quality testing may occur. ^

UPTAKE, METABOLISM, AND METABOLIC EFFECTS OF THE ANTITUMOR TRICYCLIC NUCLEOSIDE, 3-AMINO-1, 5-DIHYDRO-5-METHYL-1-BETA-D-RIBOFURANOSYL-1, 4, 5, 6, 8 PENTAAZAACENAPHTHYLENE

The uptake, metabolism, and metabolic effects of the antitumor tricyclic nucleoside (TCN, NSC-154020) were studied in vitro. Uptake of TCN by human erythrocytes was concentrative, resulting mainly from the rapid intracellular phosphorylation of TCN. At high TCN doses, however, unchanged TCN was also concentrated within the erythrocytes. The initial linear rate of TCN uptake was saturable and obeyed Michaelis-Menten kinetics. TCN was metabolized chiefly to its 5'-monophosphate not only by human erythrocytes but also by wild-type Chinese hamster ovary (CHO) cells. In addition, three other metabolites were detected by means of high-performance liquid chromatography. The structures of these metabolites were elucidated by ultraviolet spectroscopy, infrared spectroscopy, mass spectrometry, and further confirmed by incubations with catabolic enzymes and intact wild-type or variant CHO cells. All were novel types of oxidative degradation products of TCN. Two are proposed to be (alpha) and (beta) anomers of a D-ribofuranosyl nucleoside with a pyrimido{4,5-c}pyridazine-4-one base structure. The third metabolite is most likely the 5'-monophosphate of the (beta) anomer. A CHO cell line deficient in adenosine kinase activity failed to phosphorylate either TCN or the (beta) anomer. No further phosphorylation of the 5'-monophosphates by normal cells occurred. Although the pathways leading to the formation of these TCN metabolites have not been proven, a mechanism is proposed to account for the above observations. The same adenosine kinase-deficient CHO cells were resistant to 500 (mu)M TCN, while wild-type cells could not clone in the presence of 20 (mu)M TCN. Simultaneous addition of purines, pyrimidines, and purine precursors failed to reverse this toxicity. TCN-treatment strongly inhibited formate or glycine incorporation into ATP and GTP of wild-type CHO cells. Hypoxanthine incorporation inhibited to a lesser degree, with the inhibition of incorporation into GTP being more pronounced. Although precursor incorporation into GTP was inhibited, GTP concentrations were elevated rather than reduced after 4-hr incubations with 20 (mu)M or 50 (mu)M TCN. These results suggested an impairment of GTP utilization. TCN (50 (mu)M) inhibited leucine and thymidine incorporation into HClO(,4)-insoluble material to 30-35% of control throughout 5-hr incubations. Incorporation of five other amino acids was inhibited to the same extent as leucine. Pulse-labeling assays (45 min) with uridine, leucine, and thymidine failed to reveal selective inhibition of DNA or protein synthesis by 0.05-50 (mu)M TCN; however, the patterns of inhibition were similar to those of known protein synthesis inhibitors. TCN 5'-monophosphate inhibited leucine incorporation by rabbit reticulocyte lysates; the inhibition was 2000 times less potent than that of cycloheximide. The 5'-monophosphate failed to inhibit a crude nuclear DNA-synthesizing system. Although TCN 5'-monophosphate apparently inhibits purine synthesis de novo, its cytotoxicity is not reversed by exogenous purines. Consequently, another mechanism such as direct inhibition of protein synthesis is probably a primary mechanism of toxicity. ^

Systematic review of worksite-based behavior change programs that target metabolic syndrome risk factors

Approximately one-third of US adults have metabolic syndrome, the clustering of cardiovascular risk factors that include hypertension, abdominal adiposity, elevated fasting glucose, low high-density lipoprotein (HDL)-cholesterol and elevated triglyceride levels. While the definition of metabolic syndrome continues to be much debated among leading health research organizations, the fact is that individuals with metabolic syndrome have an increased risk of developing cardiovascular disease and/or type 2 diabetes. A recent report by the Henry J. Kaiser Family Foundation found that the US spent $2.2 trillion (16.2% of the Gross Domestic Product) on healthcare in 2007 and cited that among other factors, chronic diseases, including type 2 diabetes and cardiovascular disease, are large contributors to this growing national expenditure. Bearing a substantial portion of this cost are employers, the leading providers of health insurance. In lieu of this, many employers have begun implementing health promotion efforts to counteract these rising costs. However, evidence-based practices, uniform guidelines and policy do not exist for this setting in regard to the prevention of metabolic syndrome risk factors as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III). Therefore, the aim of this review was to determine the effects of worksite-based behavior change programs on reducing the risk factors for metabolic syndrome in adults. Using relevant search terms, OVID MEDLINE was used to search the peer-reviewed literature published since 1998, resulting in 23 articles meeting the inclusion criteria for the review. The American Dietetic Association's Evidence Analysis Process was used to abstract data from selected articles, assess the quality of each study, compile the evidence, develop a summarized conclusion, and assign a grade based upon the strength of supporting evidence. The results revealed that participating in a worksite-based behavior change program may be associated in one or more improved metabolic syndrome risk factors. Programs that delivered a higher dose (>22 hours), in a shorter duration (<2 years) using two or more behavior-change strategies were associated with more metabolic risk factors being positively impacted. A Conclusion Grade of III was obtained for the evidence, indicating that studies were of weak design or results were inconclusive due to inadequate sample sizes, bias and lack of generalizability. These results provide some support for the continued use of worksite-based health promotion and further research is needed to determine if multi-strategy, intense behavior change programs targeting multiple risk factors are able to sustain health improvements in the long-term.^

Fasting blood glucose and 8-year mortality in the hypertension detection follow-up program population

This study analyzed the relationship between fasting blood glucose (FBG) and 8-year mortality in the Hypertension Detection Follow-up Program (HDFP) population. Fasting blood glucose (FBG) was examined both as a continuous variable and by specified FBG strata: Normal (FBG 60–100 mg/dL), Impaired (FBG ≥100 and ≤125 mg/dL), and Diabetic (FBG>125 mg/dL or pre-existing diabetes) subgroups. The relationship between type 2 diabetes was examined with all-cause mortality. This thesis described and compared the characteristics of fasting blood glucose strata by recognized glucose cut-points; described the mortality rates in the various fasting blood glucose strata using Kaplan-Meier mortality curves, and compared the mortality risk of various strata using Cox Regression analysis. Overall, mortality was significantly greater among Referred Care (RC) participants compared to Stepped Care (SC) {HR = 1.17; 95% CI (1.052,1.309); p-value = 0.004}, as reported by the HDFP investigators in 1979. Compared with SC participants, the RC mortality rate was significantly higher for the Normal FBG group {HR = 1.18; 95% CI (1.029,1.363); p-value = 0.019} and the Impaired FBG group, {HR = 1.34; 95% CI (1.036,1.734); p-value = 0.026,}. However, for the diabetic group, 8-year mortality did not differ significantly between the RC and SC groups after adjusting for race, gender, age, smoking status among Diabetic individuals {HR = 1.03; 95% CI (0.816,1.303); p-value = 0.798}. This latter finding is possibly due to a lack of a treatment difference of hypertension among Diabetic participants in both RC and SC groups. The largest difference in mortality between RC and SC was in the Impaired subgroup, suggesting that hypertensive patients with FBG between 100 and 125 mg/dL would benefit from aggressive antihypertensive therapy.^

Risk factors for metabolic syndrome among overweight and obese Hispanic children attending a pediatric clinic in New Braunfels, Texas

Childhood obesity is a persistent problem in the U.S., especially among Hispanics. Health complications like hypertension, type II diabetes, and metabolic syndrome (Met-S) are being seen at younger ages, and current screening procedures may be inadequate. This study sought to describe the risk factors for Met-S present in a sample of 106 overweight and obese Hispanic children, aged 5-14 years, participating in Nutrition and Exercise Start Today (NEST), a randomized weight management intervention trial at a rural health clinic in New Braunfels, Texas; and to determine associations between these factors and other clinical and socio-demographic characteristics linked to obesity. Baseline data was analyzed for the prevalence of large waist circumference (WC), elevated blood pressure (BP), high fasting serum glucose and serum triglycerides (TG), and low serum HDL cholesterol, in relationship with selected sample characteristics. Main findings included high baseline prevalence rates of large WC (77%), reduced HDL (57%), and elevated BP (30%). WC was significantly associated with BMI percentile and the serum liver function test alanine aminotransferase (ALT) by Fisher's exact test (p<0.001 and p=0.032, respectively), while there were significant relationships between HDL and both female gender and ALT. BMI percentile and ALT were associated with all sets of Met-S diagnostic criteria examined. BMI percentile also had a strong association (p=0.005) with total number of Met-S risk factors, while ALT had a weaker association (p=0.093). WC is a low-cost, simple measure whose use may improve clinic surveillance for childhood obesity and complications like Met-S. WC, BP, HDL and ALT may be used as part of targeted screening for obesity complications like Met-S, particularly in situations where resources are limited.^