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Fat is a major energy source for skeletal muscle, and disruption of normal trafficking of fatty acids in muscle is linked to insulin resistance. We quantified muscle triglyceride (TG) and phospholipid (PL) synthesis in lean and obese rabbits by means of l-[U-(13)C(16)]palmitate infusion. Intramyocellular palmitoyl-coenzyme A was used as the precursor for rates of TG and PL synthesis, which were compared with the rates calculated using plasma nonesterified palmitate as the precursor. The muscle of obese rabbits had a greater (P < .05) combined pool of fatty acyl-coenzyme A plus fatty acyl-carnitine than lean rabbits (40.9 +/- 3.7 vs 28.6 +/- 5.3 nmol/g). Although the fractional synthetic rates of muscle TG were almost identical (0.095%/h +/- 0.016%/h vs 0.092%/h +/- 0.019%/h), the absolute synthetic rates were greater (P < .01) in the obese than in lean rabbits (39.7 +/- 9.5 vs 10.1 +/- 2.5 nmol g(-1) h(-1)) because of greater TG content in the muscle of obese rabbits. Plasma nonesterified fatty acids and TG accounted for 51% to 55% of the true precursor pool for muscle lipid synthesis in both groups, and the rest was derived from fatty acids recycled within the muscle. In contrast, the fractional and absolute synthetic rates of muscle PL as well as PL contents were comparable in the 2 groups. In conclusion, the content and synthetic rate of muscle TG rather than PL were increased in obese rabbits, which might be linked to insulin resistance. Plasma lipids and muscle lipolysis were the 2 predominate contributors to the intramyocellular fatty acyl-coenzyme A pool for lipid synthesis.

Background. We propose a continuous kidney donor risk index (KDRI) for deceased donor kidneys, combining donor and transplant variables to quantify graft failure risk. Methods. By using national data from 1995 to 2005, we analyzed 69,440 first-time, kidney-only, deceased donor adult transplants. Cox regression was used to model the risk of death or graft loss, based on donor and transplant factors, adjusting for recipient factors. The proposed KDRI includes 14 donor and transplant factors, each found to be independently associated with graft failure or death: donor age, race, history of hypertension, history of diabetes, serum creatinine, cerebrovascular cause of death, height, weight, donation after cardiac death, hepatitis C virus status, human leukocyte antigen-B and DR mismatch, cold ischemia time, and double or en bloc transplant. The KDRI reflects the rate of graft failure relative to that of a healthy 40-year-old donor. Results. Transplants of kidneys in the highest KDRI quintile (>1.45) had an adjusted 5-year graft survival of 63%, compared with 82% and 79% in the two lowest KDRI quintiles (

This study assessed the effects of resistance training (RT) on energy restriction-induced changes in body composition, protein metabolism, and the fractional synthesis rate of mixed muscle proteins (FSRm) in postmenopausal, overweight women. Sixteen women (age 68 +/- 1 years, BMI 29 +/- 1 kg/m(2), mean +/- s.e.m.) completed a 16-week controlled diet study. Each woman consumed 1.0 g protein/kg/day. At baseline (weeks B1-B3) and poststudy (weeks RT12-RT13), energy intake matched each subject's need and during weeks RT1-RT11 was hypoenergetic by 2,092 kJ/day (500 kcal/day). From weeks RT1 to RT13, eight women performed RT 3 day/week (RT group) and eight women remained sedentary (SED group). RT did not influence the energy restriction-induced decrease in body mass (SED -5.8 +/- 0.6 kg; RT -5.0 +/- 0.2 kg) and fat mass (SED -4.1 +/- 0.9 kg; RT -4.7 +/- 0.5 kg). Fat free mass (FFM) and total body water decreased in SED (-1.6 +/- 0.4 and -2.1 +/- 0.5 kg) and were unchanged in RT (-0.3 +/- 0.4 and -0.4 +/- 0.7 kg) (group-by-time, P < or = 0.05 and P = 0.07, respectively). Protein-mineral mass did not change in either group (SED 0.4 +/- 0.2 kg; RT 0.1 +/- 0.4 kg). Nitrogen balance, positive at baseline (2.2 +/- 0.3 g N/day), was unchanged poststudy. After body mass loss, postabsorptive (PA) and postprandial (PP) leucine turnover, synthesis, and breakdown decreased. Leucine oxidation and balance were not changed. PA and total (PA + PP) FSRm in the vastus lateralis were higher after weight loss. RT did not influence these protein metabolism responses. In summary, RT helps older women preserve FFM during body mass loss. The comparable whole-body nitrogen retentions, leucine kinetics, and FSRm between groups are consistent with the lack of differential protein-mineral mass change.

Few health policy issues in the U.S. are scrutinized as intensely as the distribution of organs for transplantation, with much effort currently underway to examine the efficacy of existing organ allocation algorithms. The design of efficient organ allocation policies depends strongly upon accurate estimates of the survival benefit of transplantation. Many organ allocation policies order patients on the wait-list based on time-dependent health status measures (internal time-dependent covariates), such that priority is given to candidates at the greatest risk for wait-list mortality. It is of great interest to measure the transplant benefit by levels of such health status measures to identify the status levels that represent either futile or unnecessary transplants. In the presence of observational data, the survival benefit of transplantation has, to date, been quantified through the parameter corresponding to a binary time-dependent transplant indicator variable. Parameters from a standard time-dependent ...

Launched in December 1999 as the Earth Observing System's flagship observatory, the Terra Mission (formerly EOS AM-1) carries a suite of five instruments that collect comprehensive global measurements of earth's atmosphere, cryosphere, lands, and oceans. One of the mission's science goals is the collection of data that will enable a better quantitative understanding of earth's carbon cycle through direct observation of atmospheric constituents and the provision of spatially explicit information about biophysical surface properties useful for modeling. In this article, highlights of the mission's use of five main instruments (ASTER, CERES, MISR, MODIS, and MOPITT) to address various aspects of the carbon cycle are reviewed, using examples of earth's photosynthetic production on land, vegetation structure and ecosystem response, and the extent and frequency of fires and their contribution of aerosols and carbon emissions to the atmosphere.

TIMESAT software is used to produce a temporally and spatially Gap-Filled and Smoothed (GFS) version of the MODIS (Moderate Resolution Imaging Spectro-radiometer) ƒPAR (fraction of absorbed photosynthetically active radiation) product (MOD15). We apply this new ƒPAR product within two commonly used carbon and vegetation productivity models, CASA (Carnegie-Ames-Stanford Approach) and the MODIS GPP (Gross Primary Production) algorithm (MOD17). The GFS product removes noise present within the original MOD15 ƒPAR dataset, yet is comparable to the linearly interpolated UMT (University of Montana) ƒPAR used in the MOD17 algorithm. However, the GSF data provides a realistic ƒPAR time-series in relation to magnitude and seasonality associated with radiation in regions where persistent cloud cover is an issue. It is available for North America and the northern part of South America covering the Amazon basin for the MODIS acquisition period (2000-2005).

The recommended dietary allowance (RDA) for protein, as promulgated by the Food and Nutrition Board of the United States National Academy of Science, is 0.8 g protein/kg body weight/day for adults, regardless of age. This value represents the minimum amount of protein required to avoid progressive loss of lean body mass in most individuals. There is an evidence that the RDA for elderly may be greater than 0.8 g/kg/day. Evidence indicates that protein intake greater than the RDA can improve muscle mass, strength and function in elderly. In addition, other factors, including immune status, wound healing, blood pressure and bone health may be improved by increasing protein intake above the RDA. Furthermore, the RDA does not address the recommended intake of protein in the context of a balanced diet. Concerns about potential detrimental effects of increased protein intake on bone health, renal function, neurological function and cardiovascular function are generally unfounded. In fact, many of these factors are improved in elderly ingesting elevated quantities of protein. It appears that an intake of 1.5 g protein/kg/day, or about 15-20% of total caloric intake, is a reasonable target for elderly individuals wishing to optimize protein intake in terms of health and function.

Background. Many older individuals decline functionally during hospitalization, and the deleterious consequences of bed rest may be one cause. This study reports on the effect of 10 days of bed rest on multiple functional parameters in healthy older adults. Methods. Healthy older men and women (n ¼ 11, 67 6 5 years old) remained on bed rest for 10 days continuously, and consumed a eucaloric diet providing the Recommended Dietary Allowance for protein. Measures of lower extremity strength and power, aerobic capacity and physical performance, as well as physical activity were performed before and after bed rest. Results. All measures of lower extremity strength were significantly lower after bed rest including isotonic knee extensor strength (� 13.2 6 4.1%, p ¼ .004) and stair-climbing power (� 14 6 4.1%, p ¼ .01). Maximal aerobic capacity was 12% lower after bed rest (p ¼ .04), whereas measures of physical performance (Short Physical Performance Battery, and a five-item physical performance test) were not significantly different. Voluntary physical activity decreased after bed rest, and the percentage of time spent inactive increased (7.6 6 1.8%, p ¼ .004). There were no medical complications. Conclusions. In healthy older adults, 10 days of bed rest results in a substantial loss of lower extremity strength, power, and aerobic capacity, and a reduction in physical activity, but has no effect on physical performance. Identification of interventions to maintain muscle function during hospitalization or periods of bed rest in older adults should be a high priority.

We have previously reported that local injection of small doses of long-acting insulin-zinc suspension maintained sufficiently high insulin concentration in the wound fluid and accelerated the healing. The present experiment was to measure the rates of cell proliferation (reflected by DNA synthesis) and protein metabolism in the wound. These are the underlying metabolic processes responsible for the healing. Partial thickness skin donor wound was created on the back and indwelling catheters were placed in the carotid artery and jugular vein in adult rabbits under general anesthesia. The wound was covered with Aquaphor gauze, OpSite membrane, and surgical gauze. On day 7 after wounding, the wound was either injected with 0.2 units of insulin-Zn, Zn alone, or no injection; stable isotopes were infused into the jugular vein catheter in conscious rabbits for measurement of DNA synthesis, protein synthesis and breakdown in the wound. The local insulin-Zn injection raised wound insulin concentration to 168 ± 39 μU/ml. In contrast, in the control and Zn groups wound insulin concentrations were below the detectable level. The local injection of insulin-Zn suspension increased (p = 0.03) DNA synthesis in the wound with minor changes in blood glucose concentration which did not require exogenous glucose replacement. In the Zn group, whereas the rate of DNA synthesis tended to increase (p = 0.051 vs. control), the protein net balance (synthesis – breakdown) was lower (p

Forest disturbance and recovery are critical ecosystem processes, but the spatial pattern of disturbance has never been mapped across North America. The LEDAPS (Landsat Ecosystem Disturbance Adaptive Processing System) project has assembled a wall-to-wall record of stand-clearing disturbance (clearcut harvest, fire) for the United States and Canada for the period 1990–2000 using the Landsat satellite archive. Landsat TM and ETM+ data were first converted to surface reflectance using the MODIS/6S atmospheric correction approach. Disturbance and early recovery were mapped using the temporal change in a Tasseled-Cap “Disturbance Index” calculated from the early (~ 1990) and later (~ 2000) images. Validation of the continental mapping has been carried out using a sample of biennial Landsat time series from 23 locations across the United States. Although a significant amount of disturbance (30–60%) cannot be mapped due to the long interval between image acquisition dates, the biennial analyses allow a first-order correction of the decadal mapping. Our results indicate disturbance rates of up to 2–3% per year are common across the US and Canada due primarily to harvest and forest fire. Rates are highest in the southeastern US, the Pacific Northwest, Maine, and Quebec. The mean disturbance rate for the conterminous United States (the “lower 48” states and District of Columbia) is calculated as 0.9 +/− 0.2% per year, corresponding to a turnover period of 110 years.

Sarcopenia is a complex, multifactorial process facilitated by a combination of factors including the adoption of a more sedentary lifestyle and a less than optimal diet. Increasing evidence points to a blunted anabolic response after a mixed nutrient meal as a likely explanation for chronic age-related muscle loss. There is currently insufficient longer-term research with defined health outcomes to specify an optimal value for protein ingestion in elderly individuals. However, there is general agreement that moderately increasing daily protein intake beyond 0.8 g x kg(-1) x d(-1) may enhance muscle protein anabolism and provide a means of reducing the progressive loss of muscle mass with age. The beneficial effects of resistance exercise in aging populations are unequivocal. However, research has not identified a synergistic effect of protein supplementation and resistance exercise in aging populations. There is little evidence that links high protein intakes to increased risk for impaired kidney function in healthy individuals. However, renal function decreases with age, and high protein intake is contraindicated in individuals with renal disease. Assessment of renal function is recommended for older individuals before they adopt a higher-protein diet.

Obesity, with its comorbidities such as metabolic syndrome and cardiovascular diseases, is a major public health concern. To address this problem, it is imperative to identify treatment interventions that target a variety of short- and long-term mechanisms. Although any dietary or lifestyle change must be personalized, controlled energy intake in association with a moderately elevated protein intake may represent an effective and practical weight-loss strategy. Potential beneficial outcomes associated with protein ingestion include the following: 1) increased satiety--protein generally increases satiety to a greater extent than carbohydrate or fat and may facilitate a reduction in energy consumption under ad libitum dietary conditions; 2) increased thermogenesis--higher-protein diets are associated with increased thermogenesis, which also influences satiety and augments energy expenditure (in the longer term, increased thermogenesis contributes to the relatively low-energy efficiency of protein); and 3) maintenance or accretion of fat-free mass--in some individuals, a moderately higher protein diet may provide a stimulatory effect on muscle protein anabolism, favoring the retention of lean muscle mass while improving metabolic profile. Nevertheless, any potential benefits associated with a moderately elevated protein intake must be evaluated in the light of customary dietary practices and individual variability.

Increased demand for amino acids to sustain acute-phase protein synthesis could be the stimulus for the increased muscle protein catabolism during hemodialysis (HD). This could be attenuated by intradialytic amino-acid infusion. To test this, we measured the fractional synthesis rates of albumin, fibrinogen, and muscle protein in eight patients with end-stage renal disease at baseline before dialysis and during HD without or with amino-acid infusion. The percentage change in the fractional synthesis rates of albumin, fibrinogen, and muscle protein from baseline was significantly higher during HD with amino-acid infusion than without amino-acid infusion. Leg muscle proteolysis was significantly increased during unsupplemented HD compared with baseline, but this was not decreased by amino-acid infusion. Arteriovenous balance studies across the leg showed a net efflux of interleukin-6 (IL-6) from the muscle into the vein during HD. The fractional synthesis rate of albumin, fibrinogen, and muscle protein correlated with each other and with the IL-6 efflux from the leg. Leg muscle protein catabolism was positively related to IL-6 release from the leg and not associated with amino-acid availability. Our results show that intradialytic cytokine activation and not amino-acid depletion is the major protein catabolic signal during HD.

This article provides an overview of solid organ transplantation in the United States and is produced as part of the 2007 OPTN/SRTR Annual Report. The Annual Report is prepared by the Scientific Registry of Transplant Recipients (SRTR) in collaboration with the Organ Procurement and Transplantation Network (OPTN) under contract with the Health Resources and Services Administration (HRSA). The report covers many aspects of solid organ transplantation and is a valuable resource for patients, the transplant community, the public and the Federal Government.

With advancing age there is a gradual decline in muscle mass, strength and function. The aim of this study was to determine if regular intake of a nutritional supplement containing essential amino acids (EAA)+arginine could reverse these responses in elderly subjects.Twelve glucose intolerant subjects (67.0+/-5.6 (SD) years, 7 females, 5 males) ingested 11 g of EAA+arginine two times a day, between meals for 16 weeks. Diet and activity were not otherwise modified. Lean body mass (DEXA) was measured every fourth week. Maximal leg strength was tested and functional tests were performed at week 0, 8, 12, and 16.Lean body mass (LBM) increased during the study (p=0.038). At week 12, the average increase in LBM was 1.14+/-0.36 (SE) kg (p0.05 vs baseline), whereas at week 16, the increase was 0.60+/-0.38 kg (NS vs baseline). The lower extremity strength measure score (sum of individual knee flexors and extensors' one repetition maximum, n=10) was 127.5+/-21.8 kg at baseline, and average increase during the study was 22.2+/-6.1% (p0.001). Improvements were also observed in usual gait speed (p=0.002), timed 5-step test (p=0.007), and timed floor-transfer test (p=0.022).Supplementation of the diet with EAA+arginine improves lean body mass, strength and physical function compared to baseline values in glucose intolerant elderly individuals.

Differences in outcomes indeed exist among transplant programs and organ procurement organizations (OPO). A growing set of tools are available from the Scientific Registry of Transplant Recipients (SRTR) to measure and assess these outcomes in the different phases of the transplant process. These tools are not intended to compare two individual programs, rather to help identify programs whose practices may need further scrutiny, to be either avoided, corrected or emulated. To understand which differences in outcomes might be due to underlying differences in populations served and which might be due to differences in treatment, it is important to compare outcomes to 'risk-adjusted' expected values. Further, it is important to recognize and assess the role that random chance may play in these outcomes by considering the p-value or confidence interval of each estimate. We present the reader with a basic explanation of these tools and their interpretation in the context of reading the SRTR Program-Specific Reports. We describe the intended audience of these reports, including patients, monitoring and process improvement bodies, payers and others such as the media. Use of these statistics in a way that reflects a basic understanding of these concepts and their limitations is beneficial for all audiences.

Whereas diet-induced obese rabbits have been used to study various aspects of obesity, alterations of lipid metabolism in this model have not been clarified. This study aimed to compare plasma nonesterified fatty acid (NEFA) and triglyceride (TG) kinetics in obese and lean rabbits by means of U-(13)C16-palmitate infusion. Young female rabbits consumed either a high-fat diet (49% energy from fat) ad libitum to develop obesity (n = 6) or a normal diet (7.9% energy from fat) as lean control (n = 5). After 10 wk of feeding, the body weight of obese rabbits (5.33 +/- 0.05 kg) was greater (P < 0.001) than that of lean rabbits (3.89 +/- 0.07 kg). The obese rabbits had higher concentrations of plasma NEFA and TG and a greater rate of fatty acid (FA) turnover. Whereas the fractional secretion rates of hepatic TG did not differ, 100% of hepatic secretory TG was synthesized from plasma NEFA in the lean rabbits compared to 59% in the obese rabbits (P < 0.001). In the lean rabbits, hepatic lipase-mediated hydrolysis of lipoprotein TG did not contribute to the FA pool for synthesis of secretory TG, consistent with the naturally occurring deficit in hepatic lipase in this species. We conclude that lipid metabolism in diet-induced obese rabbits is similar to that in obese humans. The deficiency in hepatic lipase in rabbits simplifies the quantitation of hepatic lipid kinetics.

Background: In developing “pay-for-performance” and capitation systems that provide incentives for improving the quality and efficiency of care, policymakers need to determine which healthcare providers to evaluate and reward. Objectives: This study demonstrates methods for determining and understanding the relative contributions of facilities and physicians to the quality and cost of care. Specifically, this study distinguishes levels of variation in resource utilization (RU), based on research to support the development of an expanded Medicare dialysis prospective payment system. Research Design: Mixed models were used to estimate the variation in RU across institutional providers, physicians, patients, and months (within patients), after adjusting for case-mix. Subjects: The study includes 10,367 Medicare hemodialysis patients treated in a 4.2% stratified random sample of dialysis facilities in 2003. Measures: Monthly RU was measured by the average Medicare allowable charge per dialysis session for separately billable dialysis-related services (mainly injectable medications and laboratory tests) from Medicare claims. Results: There was financially significant variation in RU across institutional providers and to a lesser degree across physicians, after adjusting for differences in case-mix. The remaining variation in RU reflects unexplained differences across patients that persist over time and transitory fluctuations for individual patients. Conclusions: The greater variation in RU occurring across dialysis facilities than across physicians is consistent with targeting payments to facilities, but alignment of incentives between facilities and physicians remains an important goal. Similar analytic methods may be useful in designing payment policies that reward providers for improving the quality of care.

Hyperglycemia and insulin resistance have long been recognized in severe burn patients. More recently, it has been observed that controlling hyperglycemia, or alleviating insulin resistance, is associated with improved outcomes. This has led to a renewed interest in the etiology of insulin resistance in this population. The postinjury hyperglycemic response appears to be associated with multiple metabolic abnormalities, such as elevated basal energy expenditure, increased protein catabolism, and, notably, significant alterations in fat metabolism. The synergy of all of the responses is not understood, although many studies have been conducted. In this article we will review the present understanding of the relationship between fat metabolism and insulin resistance posttrauma, and discuss some of the recent discoveries and potential therapeutic measures. We propose that the insulin resistance is likely related to the development of “ectopic” fat stores, i.e., triglyceride (TG) storage in sites such as the liver and muscle cells. Deposition of TG in ectopic sites is due to an increase in free fatty acid delivery secondary to catecholamine-induced lipolysis, in conjunction with decreased β-oxidation within muscle and decreased hepatic secretion of fats. The resultant increases in intracellular TG or related lipid products may in turn contribute to alterations in insulin signaling.

Ecological and climate models require high-quality consistent biophysical parameters as inputs and validation sources. NASA's moderate resolution imaging spectroradiometer (MODIS) biophysical products provide such data and have been used to improve our understanding of climate and ecosystem changes. However, the MODIS time series contains occasional lower quality data, gaps from persistent clouds, cloud contamination, and other gaps. Many modeling efforts, such as those used in the North American Carbon Program, that use MODIS data as inputs require gap-free data. This letter presents the algorithm used within the MODIS production facility to produce temporally smoothed and spatially continuous biophysical data for such modeling applications. We demonstrate the algorithm with an example from the MODIS-leaf-area-index (LAI) product. Results show that the smoothed LAI agrees with high-quality MODIS LAI very well. Higher R-squares and better linear relationships have been observed when high-quality retrieval in each individual tile reaches 40% or more. These smoothed products show similar data quality to MODIS high-quality data and, therefore, can be substituted for low-quality retrievals or data gaps.

Summary Background & aims Cancer and oncological therapy are associated with a progressive physical deterioration, malnutrition, and enhanced inflammatory burden. Our considerable data showing the strong anabolic potential of amino acids (AA) led us to test whether AA can acutely stimulate muscle protein synthesis in cancer patients (CA) undergoing intense chemotherapy. Methods Mixed muscle fractional synthesis rate (FSR), rates of phenylalanine appearance and disappearance (Ra and Rd), and net phenylalanine balance (NB) were measured during a primed constant infusion of l -[ring- 2 H 5 ]phenylalanine. Blood and muscle tissue samples were collected in the basal state and following ingestion of 40 g of AA given in 30 mL boluses every 10 min for 3 h. Serum and tissue cytokines and NF-κB expression in skeletal muscle were measured and compared to normative, healthy older controls (OC). Results Skeletal muscle TNF-α, IL-6, and NF-κB were elevated in CA. FSR and model-derived protein synthesis (Rd) increased significantly from basal to AA (FSR: 0.052±0.009 vs. 0.120±0.008% h −1 , P −1 100 mL leg −1 , P ⩽0.05). Model-derived protein breakdown (Ra) remained unchanged from basal to AA. Phenylalanine NB improved from a negative basal value (−16±2) to zero (0.8±6 nmol min −1 100 ml leg −1 , P ⩽0.05) following AA. Conclusion Despite advanced cancer, ongoing therapy, and an enhanced inflammatory burden, AA were capable of acutely stimulating muscle protein synthesis in these patients.

and also met with several Minntech executives. During this period, the authors ex- plained their analytical methods and results to Minntech, provided statistical output to Minntech, and considered Minntech’s disagreements with the research. As part of a prepublication review pro- cess, a draft version of the study manuscript

Background Systemically administered insulin has been shown to accelerate wound healing. To minimize the hypoglycemic and hypokalemic effects of insulin, we investigated a new route of insulin administration by local injection into skin wounds. Materials and methods Partial thickness skin donor site wounds were created on the backs of adult rabbits with a dermatome set at 0.015 inch. The wounds were covered by Aquaphor gauze (Smith and Nephew, Largo, FL), and OpSite membrane (Smith and Nephew, Hull, United Kingdom) and protected by rabbit jackets. Long-acting insulin-zinc suspension was selected for local injection. In study 1, insulin was injected into the wound at different doses, and the concentrations of blood glucose and wound insulin were measured to determine the proper dose and injection frequency. In study 2, wound healing days were compared between two groups ( n = 7 each) receiving local injection of either insulin-zinc or zinc alone as control. Based on the results from study 1, a dose of 0.25 units of long-acting insulin-zinc suspension was injected into the wound every other day in the insulin group. Results After injection, 0.25 units of insulin decreased blood glucose concentration (minimum 60 mg/dL) during the first 3 h, which then returned to the preinjection level (80 mg/dL). One injection maintained wound insulin concentration above 50 μU/mL for more than 24 h. With local injection of 0.25 units insulin-zinc every other day, the wound healing time was 11.2 ± 2.3 d, which was faster ( P = 0.02) than 15.1 ± 4.1 d in the control group. Conclusion Local injection of long-acting insulin-zinc suspension accelerated skin wound healing without major systemic side effects, demonstrating its potential usefulness in burn treatment.

This review focuses on the effects of restoring hormonal levels and/or influence on muscle protein metabolism in the stressed state. We have highlighted our clinical experience in the administration of anabolic and anticatabolic agents in stressed clinical populations, primarily adult and pediatric burn injury, as well as patients undergoing elective hip arthroplasty. Our previous experience entails the administration of anabolic hormones, such as testosterone and its derivatives, growth hormone, insulin-like growth factor-1 combined with its binding protein 3, and insulin. Current efforts focus on the administration of anticatabolic agents to reduce the effects of hypercortisolemia. Muscle protein metabolism was determined by stable isotope methodology. Our results indicate that normalization of anabolic hormone concentrations or amelioration of hormonal resistance restores the effects of feeding on skeletal muscle protein metabolism. Anabolic hormone administration results in a more favorable muscle protein balance in severely burned patients. Amelioration of hypercortisolemia in the stressed state leads to an improvement in protein kinetics. To summarize, alterations in hormonal influence that accompany stress states favor the loss of muscle protein. Restoration or normalization of hormonal influence improves muscle protein kinetics and ameliorates the loss of muscle nitrogen. To restore hormonal influence, clinicians should consider reestablishing anabolic stimuli and reducing catabolic stimuli.

Prolonged inactivity associated with bed rest in a clinical setting or spaceflight is frequently associated with hypercortisolemia and inadequate caloric intake. Here, we determined the effect of 28 days of bed rest (BR); bed rest plus hypercortisolemia (BRHC); and bed rest plus essential amino acid (AA) and carbohydrate (CHO) supplement (BRAA) on the size and function of single slow- and fast-twitch muscle fibers. Supplementing meals, the BRAA group consumed 16.5 g essential amino acids and 30 g sucrose at 1100, 1600, and 2100 h, and the BRHC subjects received 5 daily doses of 10–15 mg of oral hydrocortisone sodium succinate throughout bed rest. Bed rest induced atrophy and loss of force (mN) and power (μN·FL·s−1) in single fibers was exacerbated by hypercortisolemia where soleus peak force declined by 23% in the type I fiber from a prevalue of 0.78 ± 0.02 to 0.60 ± 0.02 mN post bed rest (compared to a 7% decline with bed rest alone) and 27% in the type II fiber (1.10 ± 0.08 vs. 0.81 ± 0.05 mN). In the BRHC group, peak power dropped by 19, 15, and 11% in the soleus type I, and vastus lateralis (VL) type I and II fibers, respectively. The AA/CHO supplement protected against the bed rest-induced loss of peak force in the type I soleus and peak power in the VL type II fibers. These results provide evidence that an AA/CHO supplement might serve as a successful countermeasure to help preserve muscle function during periods of relative inactivity.

This article focuses on geographic variability in patient access to kidney transplantation in the United States. It examines geographic differences and trends in access rates to kidney transplantation, in the component rates of wait-listing, and of living and deceased donor transplantation. Using data from Centers for Medicare and Medicaid Services and the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients, we studied 700,000+ patients under 75, who began chronic dialysis treatment, received their first living donor kidney transplant, or were placed on the waiting list pre-emptively. Relative rates of wait-listing and transplantation by State were calculated using Cox regression models, adjusted for patient demographics. There were geographic differences in access to the kidney waiting list and to a kidney transplant. Adjusted wait-list rates ranged from 37% lower to 64% higher than the national average. The living donor rate ranged from 57% lower to 166% higher, while the deceased donor transplant rate ranged from 60% lower to 150% higher than the national average. In general, States with higher wait-listing rates tended to have lower transplantation rates and States with lower wait-listing rates had higher transplant rates. Six States demonstrated both high wait-listing and deceased donor transplantation rates while six others, plus D.C. and Puerto Rico, were below the national average for both parameters.

This brief overview of solid organ transplantation in the United States is produced as part of the 2006 OPTN/SRTR Annual Report. The Annual Report is prepared by the Scientific Registry of Transplant Recipients (SRTR) in collaboration with the Organ Procurement and Transplantation Network (OPTN) under contract with the Health Resources and Services Administration (HRSA). The report gathers a large amount of information on many aspects of solid organ transplantation in one publication, making it a valuable resource for patients, the transplant community, the public and the Federal Government.

Acute exercise can reverse muscle insulin resistance, but the mechanism(s) of action are unknown. With the use of a hindlimb perfusion model, we have found that acute contraction restores insulin-stimulated glucose uptake in muscle of obese Zucker rats to levels witnessed in lean controls. Previous reports have suggested that obesity-related insulin resistance stems from lipid oversupply and tissue accumulation of toxic lipid intermediates that impair insulin signaling. We reasoned that contraction might activate hydrolysis and oxidation of intramuscular lipids, thus alleviating “lipotoxicity” and priming the muscle for enhanced insulin action. Indeed, analysis of mitochondrial-derived acyl-carnitine esters suggested that contraction caused robust increases in β-oxidative flux and mitochondrial oxidation. As predicted, contraction decreased intramuscular triacylglycerol content; however, diacylglycerol and long chain acyl-CoAs, lipid intermediates presumed to trigger insulin resistance, were either unchanged or increased. In muscles from obese animals, insulin-stimulated tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 remained impaired after contraction, whereas phosphorylation of the downstream signaling protein, AS160, was partially restored. These results suggest that acute exercise enables diabetic muscle to circumvent upstream defects in insulin signal transduction via mechanisms that are more tightly coupled to increased mitochondrial energy metabolism than the lowering of diacylglycerol and long chain acyl-CoA.

Borsheim E, Bui Q-UT, Wolfe RR. Plasma amino acid concentrations during late rehabilitation in patients with traumatic brain injury. Objectives To investigate whether the basal plasma amino acid concentrations in patients with traumatic brain injury (TBI) have returned to levels found in healthy controls at about 17 months postinjury and to determine the effect of intake of a mixture of essential amino acids (EAA) on plasma amino acid concentrations in TBI versus healthy controls. Design Peripheral venous amino acid concentrations in subjects with TBI were compared with concentrations in healthy controls both at rest and for 1 hour after intake of 7g of EAA. Setting Postacute brain injury rehabilitation center. Participants Six men with TBI (age ± standard deviation, 27±6y; months postinjury, 17±4) and 6 healthy men (age, 43±7y). Intervention Intake of a drink consisting of 7g of EAA. Main Outcome Measures Individual and total plasma amino acid concentrations. Results Total amino acid concentration was about 12% lower in TBI versus controls ( P =.022). Valine was reduced by 33% in the TBI group versus controls ( P =.003), whereas the other EAA did not differ between groups. After intake of the EAA drink, plasma non-EAA increased to a significantly higher level in controls versus TBI subjects ( P =.017). Conclusions Plasma total amino acid concentration is still reduced 17 months postinjury in patients with TBI versus healthy controls, mainly because of a lower valine level. This may be of importance for both brain and muscle metabolic functions, and warrant further study. Further, ingested EAA are apparently not as readily converted to non-EAA in TBI patients as in healthy controls, suggesting that in recovery from TBI, certain non-EAA may become provisionally essential.

The purpose of this study was to assess a novel technique for quantifying in vivo muscle protein metabolism and phenylalanine transport in septic patients and normal volunteers and thereby assess the influence of sepsis on muscle protein kinetics. In patients resuscitated from sepsis, blood flow and edema may influence the extent of muscle loss. Six adult patients septic from pneumonia underwent a study protocol consisting of infusion of isotopic phenylalanine, indocyanine green dye, and sodium bromide; biopsies of skeletal muscle; and sampling from the femoral artery, vein, and interstitial fluid. Study results demonstrate a substantial net catabolism of muscle, an accelerated flux of phenylalanine, and an increased leg blood flow for septic patients compared with normal volunteers. For septic patients and normal volunteers, the rate of phenylalanine transport through the interstitium was rate limiting for the movement of phenylalanine between vasculature and muscle. Measurements demonstrate a concentration gradient of phenylalanine favoring the net efflux of amino acids from the leg in the septic patients. Despite whole body edema, the extracellular fluid volume within muscle of septic patients was similar to normal. These findings demonstrate that the extent of muscle loss in critically ill patients results from the net increase in the rate of muscle protein breakdown, which subsequently drives amino acids through the interstitial compartment down their concentration gradient. Therefore, any effective therapy to correct illness-induced muscle catabolism should be directed at altering the rates of breakdown and synthesis of muscle protein and are not likely related to tissue edema.

We have determined whole body protein kinetics, i.e., protein synthesis (PS), breakdown (PB), and net balance (NB) in human subjects in the fasted state and following ingestion of ∼40 g [moderate protein (MP)], which has been reported to maximize the protein synthetic response or ∼70 g [higher protein (HP)] protein, more representative of the amount of protein in the dinner of an average American diet. Twenty-three healthy young adults who had performed prior resistance exercise (X-MP or X-HP) or time-matched resting (R-MP or R-HP) were studied during a primed continuous infusion of l-[2H5]phenylalanine and l-[2H2]tyrosine. Subjects were randomly assigned into an exercise (X, n = 12) or resting (R, n = 11) group, and each group was studied at the two levels of dietary protein intake in random order. PS, PB, and NB were expressed as increases above the basal, fasting values (mg·kg lean body mass−1·min−1). Exercise did not significantly affect protein kinetics and blood chemistry. Feeding resulted in positive NB at both levels of protein intake: NB was greater in response to the meal containing HP vs. MP ( P < 0.00001). The greater NB with HP was achieved primarily through a greater reduction in PB and to a lesser extent stimulation of protein synthesis (for all, P < 0.0001). HP resulted in greater plasma essential amino acid responses ( P < 0.01) vs. MP, with no differences in insulin and glucose responses. In conclusion, whole body net protein balance improves with greater protein intake above that previously suggested to maximally stimulating muscle protein synthesis because of a simultaneous reduction in protein breakdown.

To determine if age-associated vascular dysfunction in older adults with heart failure (HF) is due to insufficient synthesis of nitric oxide (NO), we performed two separate studies: 1) a kinetic study with a stable isotope tracer method to determine in vivo kinetics of NO metabolism, and 2) a vascular function study using a plethysmography method to determine reactive hyperemic forearm blood flow (RH-FBF) in older and young adults in the fasted state and in response to citrulline ingestion. In the fasted state, NO synthesis (per kg body wt) was ∼50% lower in older vs. young adults and was related to a decreased rate of appearance of the NO precursor arginine. Citrulline ingestion (3 g) stimulated de novo arginine synthesis in both older [6.88 ± 0.83 to 35.40 ± 4.90 μmol·kg body wt−1·h−1] and to a greater extent in young adults (12.02 ± 1.01 to 66.26 ± 4.79 μmol·kg body wt−1·h−1). NO synthesis rate increased correspondingly in older (0.17 ± 0.01 to 2.12 ± 0.36 μmol·kg body wt−1·h−1) and to a greater extent in young adults (0.36 ± 0.04 to 3.57 ± 0.47 μmol·kg body wt−1·h−1). Consistent with the kinetic data, RH-FBF in the fasted state was ∼40% reduced in older vs. young adults. However, citrulline ingestion (10 g) failed to increase RH-FBF in either older or young adults. In conclusion, citrulline ingestion improved impaired NO synthesis in older HF adults but not RH-FBF, suggesting that factors other than NO synthesis play a role in the impaired RH-FBF in older HF adults, and/or it may require a longer duration of supplementation to be effective in improving RH-FBF.

A tremendous amount of Earth and Climate related data and information are available from the U.S. Federal government. Among the proposed actions of the President's Climate Action Plan are several efforts to foster the use of existing data to encourage development of additional data products and tools that can be used to improve community resilience and prepare for the impacts of climate change. Building on previous efforts to organize the presentation of this material from Federal web pages and data centers, the Climate Data Initiative is working together with other related efforts to link Earth observation systems through to data resulting from them and on to related web pages, case studies, decision making tools, and other relevant content. Often such information is not located in a single web site, data center, or even a single agency, but distributed across the Federal Government. Linking such information across the breadth of interagency holdings can increase understanding of the complexity of those holdings and their inter-relationships and allow a more cohesive presentation of all of the material.

The Global Change Information System was created by the US Global Change Research Program to provide specialists and the general public with accessible and usable global change related information. This system uses a relational and semantic web approach to describe the detailed provenance of global change information, such as “in report x, figure y is derived from dataset z”. The system supported the development of the US Third National Climate Assessment, which was released in May 2014 and improves our understanding of climate change in the US. Over the last year, a partnership has been developed with the Committee on Earth Observing Satellites and now their database of missions, instruments and observations is being used to provide traceability to the specific platforms and instruments that support the assessment's findings and figures.

It has been reported that the maximal protein synthetic response to protein intake is achieved with an intake of 20 - 35 g of protein. However, in these studies account was not taken of possible ch...

Proteins and amino acids are widely considered to be subcomponents in nutritional support. However, proteins and amino acids are fundamental to recovery and survival, not only for their ability to preserve active tissue (protein) mass but also for a variety of other functions. Understanding the optimal amount of protein intake during nutritional support is therefore fundamental to appropriate clinical care. Although the body adapts in some ways to starvation, metabolic stress in patients causes increased protein turnover and loss of lean body mass. In this review, we present the growing scientific evidence showing the importance of protein and amino acid provision in nutritional support and their impact on preservation of muscle mass and patient outcomes. Studies identifying optimal dosing for proteins and amino acids are not currently available. We discuss the challenges physicians face in administering the optimal amount of protein and amino acids. We present protein-related nutrition concepts, including adaptation to starvation and stress, anabolic resistance, and potential adverse effects of amino acid provision. We describe the methods for assessment of protein status, and outcomes related to protein nutritional support for critically ill patients. The identification of a protein target for individual critically ill patients is crucial for outcomes, particularly for specific subpopulations, such as obese and older patients. Additional research is urgently needed to address these issues.

Muscle plays a central role in whole-body protein metabolism by serving as the principal reservoir for amino acids to maintain protein synthesis in vital tissues and organs in the absence of amino acid absorption from the gut and by providing hepatic gluconeogenic precursors. Furthermore, altered muscle metabolism plays a key role in the genesis, and therefore the prevention, of many common pathologic conditions and chronic diseases. Nonetheless, the maintenance of adequate muscle mass, strength, and metabolic function has rarely, if ever, been targeted as a relevant endpoint of recommendations for dietary intake. It is therefore imperative that factors directly related to muscle mass, strength, and metabolic function be included in future studies designed to demonstrate optimal lifestyle behaviors throughout the life span, including physical activity and diet.

This study was designed to evaluate the effects of enriching an essential amino acid (EAA) mixture with leucine on muscle protein metabolism in elderly and young individuals. Four (2 elderly and 2 young) groups were studied before and after ingestion of 6.7 g of EAAs. EAAs were based on the composition of whey protein [26% leucine (26% Leu)] or were enriched in leucine [41% leucine (41% Leu)]. A primed, continuous infusion of l-[ ring-2H5]phenylalanine was used together with vastus lateralis muscle biopsies and leg arteriovenous blood samples for the determinations of fractional synthetic rate (FSR) and balance of muscle protein. FSR increased following amino acid ingestion in both the 26% (basal: 0.048 ± 0.005%/h; post-EAA: 0.063 ± 0.007%/h) and the 41% (basal: 0.036 ± 0.004%/h; post-EAA: 0.051 ± 0.007%/h) Leu young groups ( P < 0.05). In contrast, in the elderly, FSR did not increase following ingestion of 26% Leu EAA (basal: 0.044 ± 0.003%/h; post-EAA: 0.049 ± 0.006%/h; P > 0.05) but did increase following ingestion of 41% Leu EAA (basal: 0.038 ± 0.007%/h; post-EAA: 0.056 ± 0.008%/h; P < 0.05). Similar to the FSR responses, the mean response of muscle phenylalanine net balance, a reflection of muscle protein balance, was improved ( P < 0.05) in all groups, with the exception of the 26% Leu elderly group. We conclude that increasing the proportion of leucine in a mixture of EAA can reverse an attenuated response of muscle protein synthesis in elderly but does not result in further stimulation of muscle protein synthesis in young subjects.

The loss of skeletal muscle with injury or critical illness can be dramatic. This review emphasizes the importance of skeletal muscle as a metabolic reserve. Changes in protein metabolism with bed rest alone and during physiological stress are discussed. Nutritional and hormonal interventions that ameliorate the loss of skeletal muscle are highlighted.The loss of skeletal muscle that occurs with inactivity alone can be prevented by nutritional supplementation with an essential amino acid formula. Bed rest with accompanying hypercortisolemia produces a threefold greater loss of skeletal muscle than bed rest alone. Essential amino acids stimulate muscle anabolism during acute hypercortisolemia; however, their effects during chronic hypercortisolemia must be explored.Skeletal muscle loss with trauma or critical illness is due in great part to the interaction of bed rest (muscular inactivity) and stress (hypercortisolemia). Younger individuals respond to nutritional and pharmacological interventions during bed rest alone. Given a lower relative lean mass in the elderly and the importance of skeletal muscle as a metabolic reserve during stress, it is understandable that clinical outcomes are worse in older patients. Countermeasures to the loss of skeletal muscle, especially in the stressed patient, must be developed.

In response to injury, muscle catabolism can be extensive, and in theory, the wound consumes amino acids to support healing. The purpose of this study is to assess a technique by which in vivo protein kinetics of muscle, wound, and normal skin can be quantified in burn-injured patients.Study protocol consisting of infusion of d5 phenylalanine; biopsies of skeletal muscle, skin, and donor-site wound on the leg; quantification of blood flow to total leg, wound, and skin; and sequential blood sampling from the femoral artery and vein. Five-compartment modeling was used to quantify the rates of protein synthesis, breakdown, and phenylalanine transport between muscle, wound, and skin.The study results demonstrated a net release of phenylalanine from muscle yet a net consumption of phenylalanine by the wound. Compared with skin, the wound had a substantially increased rate of protein synthesis and a reduced rate of protein breakdown (p.01). Transport rates into and out of muscle were significantly higher than those for wound (p.01).This novel methodology enables in vivo quantification of the integrated response of muscle, wound, and skin protein/amino acid metabolism and confirms the long-held theory of a net catabolism of muscle and a net anabolism of wound protein in patients after injury. This methodology can be used to assess the metabolic impact of such measures as nutrition, pharmacologic agents, and surgical procedures.

Measuring and monitoring performance—be it waiting list and posttransplant outcomes by a transplant center, or organ donation success by an organ procurement organization and its partnering hospitals—is an important component of ensuring good care for people with end-stage organ failure. Many parties have an interest in examining these outcomes, from patients and their families to payers such as insurance companies or the Centers for Medicare and Medicaid Services; from primary caregivers providing patient counseling to government agencies charged with protecting patients. The Scientific Registry of Transplant Recipients produces regular, public reports on the performance of transplant centers and organ procurement organizations. This article explains the statistical tools used to prepare these reports, with a focus on graft survival and patient survival rates of transplant centers—especially the methods used to fairly and usefully compare outcomes of centers that serve different populations. The article concludes with a practical application of these statistics—their use in screening transplant center performance to identify centers that may need remedial action by the OPTN/UNOS Membership and Professional Standards Committee.

Background Selective beta adrenergic antagonists are commonly used to reduce myocardial demise in patients at risk for cardiac-related death. The purpose of this study was to examine the hemodynamic and metabolic effects of cardiac selective beta adrenergic blockade in patients. Methods Muscle protein kinetics were quantified using isotopic tracer methodology in 6 moderately septic, mechanically ventilated patients with pneumonia before and then at the conclusion of a 3-hour infusion of esmolol of sufficient dose to reduce heart rate by 20% from baseline. A battery of hemodynamic measurements as facilitated by a thermodilution pulmonary artery catheter and indirect calorimetry were also measured before and after the 3-hour selective beta adrenergic blockade. Results Selective beta adrenergic blockade was associated with the 20% reduction in heart rate and a comparable decrease in cardiac output. Esmolol administration failed to affect systemic or pulmonary vascular resistance, oxygen consumption, hepatic or leg blood flow, energy expenditure, or ATP availability/energy charge within muscle. Esmolol infuse did incite a shift in fuel oxidation toward an increase in palmitate oxidation and with a decrease in the oxidation of glucose. There was no demonstrable influence β 1 adrenergic blockade on muscle protein kinetics. Conclusions Cardiac selective beta adrenergic blockade with esmolol reduces cardiac output in proportion to the percentage decreases in heart rate in moderately severe septic patients without adversely affecting oxygen utilization or hepatic, peripheral blood flow.

Whereas Sulfamylon is effective in treatment of burn wound infection, controversy exists regarding its effect on the healing process.A partial thickness skin donor site wound was created on the back and indwelling catheters were placed in the carotid artery and jugular vein in rabbits under general anesthesia. Sulfamylon cream (8.5%, BERTEK Pharmaceuticals Inc., Morgantown, W Va) was applied on the wound, with either open or occlusive dressing. The control wound was covered with dressings only. On day 7 after injury, stable isotope tracers were infused to determine the fractional synthetic rate (FSR) of DNA, and FSR and fractional breakdown rate (FBR) of protein in the wound.In the Sulfamylon-open dressing group, the DNA FSR was 1.3 +/- 0.6%/day, the protein FSR was 8.0 +/- 3.5%/day, and the net protein deposition (FSR - FBR) was -0.3 +/- 3.7%/day. These values were lower (P.01 to .05) than the corresponding values in the control group (DNA FSR: 2.9 +/- 0.9%/day; protein FSR: 20.5 +/- 8.4%/day; net protein deposition: 7.9 +/- 6.0%/day). Sulfamylon cream selectively inhibited DNA FSR from the de novo base synthesis pathway (2.3 +/- 1.2 vs 0.8 +/- 0.5%/day, P.05 vs control). With the occlusive dressing Sulfamylon cream did not decrease wound DNA FSR due to a stimulation of the base salvage pathway, but still decreased protein FSR (11.5 +/- 5.1%/day, P.05 vs control). Histologic slides indicated that Sulfamylon cream inhibited re-epithelialization, collagen formation, and angiogenesis in the wound.Topical Sulfamylon cream application inhibited DNA and protein synthesis in the wound, which would be expected to retard the healing process.

Previous studies have examined the response of muscle protein to resistance exercise and nutrient ingestion. Net muscle protein synthesis results from the combination of resistance exercise and amino acid intake. No study has examined the response of muscle protein to ingestion of protein in the context of a food. This study was designed to determine the response of net muscle protein balance following resistance exercise to ingestion of nutrients as components of milk.Three groups of volunteers ingested one of three milk drinks each: 237 g of fat-free milk (FM), 237 g of whole milk (WM), and 393 g of fat-free milk isocaloric with the WM (IM). Milk was ingested 1 h following a leg resistance exercise routine. Net muscle protein balance was determined by measuring amino acid balance across the leg.Arterial concentrations of representative amino acids increased in response to milk ingestion. Threonine balance and phenylalanine balance were both0 following milk ingestion. Net amino acid uptake for threonine was 2.8-fold greater (P0.05) for WM than for FM. Mean uptake of phenylalanine was 80 and 85% greater for WM and IM, respectively, than for FM, but not statistically different. Threonine uptake relative to ingested was significantly (P0.05) higher for WM (21 +/- 6%) than FM (11 +/- 5%), but not IM (12 +/- 3%). Mean phenylalanine uptake/ingested also was greatest for WM, but not significantly.Ingestion of milk following resistance exercise results in phenylalanine and threonine uptake, representative of net muscle protein synthesis. These results suggest that whole milk may have increased utilization of available amino acids for protein synthesis.

The intracellular concentrations of essential amino acids (EAA) in muscle are maintained relatively constant under a variety of conditions. However, the effect of a decrease in blood amino acid concentrations on intracellular concentrations is not clear. Similarly, the relation between intracellular and interstitial concentrations has not been determined in this circumstance. Thus the aim of this study was to determine the effect of hypoaminoacidemia on intracellular, interstitial, and plasma concentrations of EAA and the mechanisms responsible for the respective changes. Twelve normal pigs were investigated before and during 120 min of hemodialysis by use of stable-isotope tracer methodology, microdialysis technique, and muscle biopsies. During hemodialysis, there was a decrease in the interstitial fluid concentrations of phenylalanine, leucine, alanine, and lysine that corresponded to their decrease in plasma concentration. Nonetheless, the intracellular concentrations of these amino acids were maintained at the basal levels throughout the entire period due principally to a reduction in the rate of incorporation of amino acids into protein that was approximately equivalent to the decrease in uptake from the plasma. In conclusion, intracellular concentrations of amino acids are regulated to maintain relatively constant values, even when plasma and interstitial concentrations fall as a consequence of hemodialysis.

Recent diabetes and obesity research has been focused on the role of intracellular lipids in insulin resistance. Fatty acyl-coenzyme A (CoA) esters play a central role in the trafficking of intracellular lipids, but there has not previously been a method with which to quantify their kinetics using tracer methodology. We have therefore developed a high-performance liquid chromatography (HPLC)-mass spectrometry method to simultaneously measure the (13)C stable isotopic enrichment of palmitoyl-acyl-CoA ester and the concentrations of five individual long-chain fatty acyl-CoA esters extracted from muscle tissue samples. The long-chain fatty acyl-CoA can be effectively extracted from frozen muscle tissue samples and baseline separated by a reverse-phase HPLC with the presence of a volatile reagent-triethylamine. Negative ion electrospray mass spectrometry with selected ion monitoring was used to analyze the fatty acyl-CoAs to achieve reliable quantification of their concentrations and (13)C isotopic enrichment. Applying this protocol to rabbit muscle samples demonstrates that it is a sensitive, accurate, and precise method for the quantification of long-chain fatty acyl-CoA concentrations and enrichment.

In this paper, we propose a model for medical costs recorded at regular time intervals, e.g. every month, as repeated measures in the presence of a terminating event, such as death. Prior models have related monthly medical costs to time since entry, with extra costs at the final observations at the time of death. Our joint model for monthly medical costs and survival time incorporates two important new features. First, medical cost and survival may be correlated because more 'frail' patients tend to accumulate medical costs faster and die earlier. A joint random effects model is proposed to account for the correlation between medical costs and survival by a shared random effect. Second, monthly medical costs usually increase during the time period prior to death because of the intensive care for dying patients. We present a method for estimating the pattern of cost prior to death, which is applicable if the pattern can be characterized as an additive effect that is limited to a fixed time interval, say b units of time before death. This 'turn back time' method for censored observations censors cost data b units of time before the actual censoring time, while keeping the actual censoring time for the survival data. Time-dependent covariates can be included. Maximum likelihood estimation and inference are carried out through a Monte Carlo EM algorithm with a Metropolis-Hastings sampler in the E-step. An analysis of monthly outpatient EPO medical cost data for dialysis patients is presented to illustrate the proposed methods.

The Landsat Ecosystem Disturbance Adaptive Processing System (LEDAPS) at the National Aeronautics and Space Administration (NASA) Goddard Space Flight Center has processed and released 2100 Landsat Thematic Mapper and Enhanced Thematic Mapper Plus surface reflectance scenes, providing 30-m resolution wall-to-wall reflectance coverage for North America for epochs centered on 1990 and 2000. This dataset can support decadal assessments of environmental and land-cover change, production of reflectance-based biophysical products, and applications that merge reflectance data from multiple sensors [e.g., the Advanced Spaceborne Thermal Emission and Reflection Radiometer, Multiangle Imaging Spectroradiometer, Moderate Resolution Imaging Spectroradiometer (MODIS)]. The raw imagery was obtained from the orthorectified Landsat GeoCover dataset, purchased by NASA from the Earth Satellite Corporation. Through the LEDAPS project, these data were calibrated, converted to top-of-atmosphere reflectance, and then atmospherically corrected using the MODIS/6S methodology. Initial comparisons with ground-based optical thickness measurements and simultaneously acquired MODIS imagery indicate comparable uncertainty in Landsat surface reflectance compared to the standard MODIS reflectance product (the greater of 0.5% absolute reflectance or 5% of the recorded reflectance value). The rapid automated nature of the processing stream also paves the way for routine high-level products from future Landsat sensors.

Catecholamine-mediated hypermetabolism,1–3 lipolysis4, and fatty liver5–7 are striking characteristics of the stress response to a major thermal injury. The deposition of fat in the liver is a common pathologic finding, as is liver size, which may vary 2- to 3-fold.6,8–11 Hepatic fat accumulation (fatty liver) may be due to a high rate of peripheral lipolysis coupled with a lack of increased fat oxidation.12,13 The extent to which triglycerides (TGs) are produced and the capacity of the liver to excrete them into the blood via very low density lipoproteins (VLDLs) is important in determining net fat accumulation in the liver. It has previously been shown that plasma free fatty acid (FFA) is the primary precursor for hepatic TG synthesis.14 The increase in basal lipolysis in burn patients is caused by excessive catecholamine production, which can be diminished by beta-adrenergic blockade with propranolol.12,13,15 Acute use of β-blocking agents precipitously decreases the rate of release or appearance of plasma FFAs, indicating the important role that preexisting sympathetic activity plays in the mobilization of FFAs.4 We recently found in an acute study that β-blockade decreased TG accumulation in the liver by decreasing the supply of FFAs to the liver.16 The effect of chronic treatment with β-blockade on hepatic TG accumulation has not been assessed. Cardiac output and heart rate have been shown to be higher in the dynamic phase of a thermal injury than most other hyperdynamic conditions.3 In the hypermetabolic phase of burn recovery, cardiac dysfunction contributes significantly to mortality.7,17 Beta-adrenergic blockade has been used with success in pathologic states produced by excessive quantities of endogenous or exogenous thyroid hormone or catecholamines by decreasing the myocardial workload.18,19 We have previously shown that, after adrenalectomy or catecholamine depletion by chronic reserpine administration, rats given a 50% total body surface area (TBSA) burn had lower metabolic rates and increased mortality.20 Wilmore et al1 have shown that the dose of β-blocking agent required for decreasing heart work in patients with major burns also decreases metabolic rate, core and skin temperatures, and may be beneficial in maintaining the responsiveness of subcellular enzymes to catecholamine control.12 The purpose of this study was to test the hypothesis that propranolol, given to children with severe thermal injuries, could be beneficial by attenuating peripheral lipolysis, portal blood flow, and hepatomegaly.