Energy expenditure in the acute renal failure patient mechanically ventilated

Twenty mechanically ventilated patients with acute renal failure were studied on 31 occasions to determine their energy expenditure (EE) during a 2 h period before a hemodialysis. Oxygen consumption and CO₂ elimination were measured continuously with a mass spectrometer system. EE (1660±48 kcal day^-1) was close to the total caloric intake (1682±83 kcal day-1) and represented 1.19±0.03 times the predicted resting energy expenditure (PREE) with large inter-individual variations (0.7-1.7 PREE). EE/PREE was higher when sepsis was present (1.31±0.03 versus 1.14±0.02; p<0.05). Glucose oxidation rate (4.35 mg kg^-1 min^-1) exceeded glucose intake (2.6 mg kg^-1 min^-1). Respiratory quotient was 1.02±0.01. Nitrogen loss was 17.3±1.7 g day^-1 and nitrogen balance-11.9±1.9 g day^-1. In conclusion, EE values were scattered but never exceeded 1.7 times the PREE. Sepsis increased EE. With a nutritional support covering EE, nitrogen balance remained markedly negative and a preferential utilisation of glucose and lipogenesis occurred.     

Cardiovascular and metabolic response to adrenaline infusion in weight-losing patients with and without cancer

Summary. Fasting is generally accompanied by a decrease in energy metabolism and hormones. On the other hand, indirect evidence has suggested that the response to adrenergic agonists may be maintained or even increased in malnutrition. The present study evaluated whether weight-losing patients with and without cancer have increased plasma concentrations of catecholamines and different responses to intravenously infused adrenaline compared to weight-stable individuals. Eight malnourished cancer and 10 non-cancer patients (11% weight loss) were compared to seven well-nourished and weight-stable patients. Adrenaline was infused i.v. at a rate of 0·005 μg min^-1 kg^-1 body weight during 40 min followed by a 40 min rest period (without infusion) and then a final 40 min period with i.v. adrenaline infusion (0·02 μg min^-1 kg^-1 body weight). Plasma glycerol concentration at fast was higher in weight-losing patients compared to weight-stable individuals. Whole body oxygen uptake, carbon dioxide production, heart rate and plasma concentrations of free fatty acids (FFA) increased while the mean arterial pressure decreased significantly in response to adrenaline infusion at 0·02 μg kg^-1 min^-1 in both weight-losing and weight-stable patients. Adrenaline at 0·005 μg kg^-1 min^-1 increased plasma FFA levels by 19% (P<0·05) in weight-losing patients while no significant alteration was observed in well-nourished patients. Adrenaline infusion at 0·02 μg kg^-1 min^-1 decreased the mean arterial blood pressure and stimulated respiratory gas exchange and heart rate significantly more in weight-losing than in weight-stable patients. The slopes for oxygen uptake, carbon dioxide production, heart rate, plasma FFA and plasma glycerol vs. plasma adrenaline and noradrenaline were all significantly steeper (P<0·05–0·01) in malnourished patients than in well-nourished controls. The present study suggests an increased sensitivity to adrenaline in weight-losing patients compared to matched controls with normal nutritional state and stable weight.     

Glucose-induced thermogenesis in patients with small cell lung carcinoma. Before and after inhibition of tumour growth by chemotherapy

Summary. Seven weight-losing patients with histologically verified small cell lung carcinoma were given an oral glucose load of 75 g before and at least 3 weeks after the end of chemotherapy to examine the effect of glucose on whole body and skeletal muscle thermogenesis before and after reduction of tumour. Whole body energy expenditure was measured by the open circuit ventilated hood system. Forearm blood flow was measured by venous-occlusion strain-gauge plethysmography. The uptake of oxygen in skeletal muscle was calculated as the product of the forearm blood flow and the difference in a-v oxygen concentration. Whole body resting energy expenditure (REE) did not increase, it was 4.4±0.3kJmin^-1(mean±SE) before chemotherapy and 4.4±0.2 kJ min^-1 after chemotherapy. The glucose-induced thermogenesis in the 180 min following the glucose load was 93.6±9.9 kJ 180 min^-1 before chemotherapy. This is significantly increased compared to that found in a healthy control group (74.7±4.8 kJ 180 min^-1, P < 0.02). The glucose-induced thermogenesis was significantly reduced to 47.7±10.2 kJ 180 min^-1 (P < 0.05) after chemotherapy. The oxygen uptake in resting skeletal muscles was 6.9±0.3 μmol 100 g^-1 min^-1 before chemotherapy and 7.0±0.7 μmOI 100 g^-1 min^-1 after chemotherapy. This did not increase during the first 90 min following the glucose load in either investigations. In the period 90–180 min following the glucose load, the oxygen uptake was significantly increased before chemotherapy as compared to after chemotherapy, which suggests that the reduced whole body thermogenesis after chemotherapy in part was due to reduced skeletal muscle thermogenesis.     

Body composition and fuel metabolism after kidney grafting

Abstract. Kidney transplant patients display decreased muscle mass and increased fat mass. Whether this altered body composition is due to glucocorticoid induced altered fuel metabolism is unclear. To answer this question, 16 kidney transplant patients were examined immediately after kidney transplantation (12±4 days, mean ±SEM) and then during months 2, 5, 11 and 16, respectively, by whole body dual energy X-ray absorptiometry (Hologic QDR 1000W) and indirect calorimetry. Results were compared with those of 16 age, sex and body mass index matched healthy volunteers examined only once. All patients received dietary counselling with a step 1 diet of the American Heart Association and were advised to restrict their caloric intake to the resting energy expenditure plus 30%. Immediately after transplantation, lean mass of the trunk was higher by 7±1% (P<0.05) and that of the limbs was lower by more than 10% (P<0.01) in patients than in controls. In contrast, no difference in fat mass and resting energy expenditure could be detected between patients and controls. During the 16 months of observation, total fat mass increased in male (+4.9± 1.5 kg), but not in female patients (0.1 ±0.8 kg). The change in fat mass observed in men was due to an increase in all subregions of the body analysed (trunk, arms + legs as well as head + neck), whereas in women only an increase in head + neck by 9 ±2% (P= 0.05) was detected. Body fat distribution remained unchanged in both sexes over the 16 months of observation. Lean mass of the trunk mainly decreased between days 11 and 42 (P<0.01) and remained stable thereafter. After day 42, lean mass of arms and legs (mostly striated muscle) and head + neck progressively increased over the 14 months of observation by 1.6±0.6 kg (P < 0.05) and 0.4±0.l kg (P < 0.01). respectively. Resting energy expenditure was similar in controls and patients at 42 days (30.0 ±0.7 vs. 31.0±0.9 kcal kg^-1 lean mass) and did not change during the following 15 months of observation. However, composition of fuel used to sustain resting energy expenditure in the fasting state was altered in patients when compared with normal subjects, i.e. glucose oxidation was higher by more than 45% in patients (P<0.01) during the second month after grafting, but gradually declined (P<0.01) over the following 15 months to values similar to those observed in controls. Protein oxidation was elevated in renal transplant patients on prednisone at first measurement, a difference which tended to decline over the study period. In contrast to glucose and protein oxidation, fat oxidation was lower in patients 42 days after grafting (P<0.01), but increased by more than 100% reaching values similar to those observed in controls after 16 months of study. Mean daily dose of prednisone per kg body weight correlated with the three components of fuel oxidation (r>0.93, P<0.01), i.e. protein, glucose and fat oxidation. These results indicate that in prednisone treated renal transplant patients fuel metabolism is regulated in a dose-dependent manner. Moreover, dietary measures, such as caloric and fat intake restriction as well as increase of protein intake, can prevent muscle wasting as well as part of the usually observed fat accumulation. Furthermore, the concept of preferential upper body fat accumulation as consequence of prednisone therapy in renal transplant patients has to be revised.     

Reduction of the acute bioavailability of metformin by the α-glucosidase inhibitor acarbose in normal man

In a double-blind cross-over study, we investigated a possible influence of the α-glucosidase inhibitor acarbose on the bioavailability of the biguanide compound metformin. Each of the six healthy young male volunteers was randomly allocated during two consecutive 7 day periods to either acarbose (days 1–3: 3 times 50mg day^?1; days 4–7: 3 times 100 mg day^?1) or placebo. At day 7 and 14 of the study, the overnight-fasted subjects ingested 1000mg metformin with the first bite of a standardized breakfast (500kcal; 60 g carbohydrates) and together with either placebo or 100 mg acarbose. Acarbose significantly (P < 0·05) reduced the meal-induced increase in blood glucose and plasma insulin levels. Acarbose induced a significant (P < 0·05) reduction in early (90, 120, 180min) serum levels, peak concentrations (Cmax: 1·22 ± 0·14 vs. 1·87 ± 0·60 mgl^?1) and area under the curve of metformin (AUC 0–540min: 423±55 vs. 652±55 mg minl^?1), but did not diminish its 24 h urinary excretion. In conclusion, acarbose significantly reduces the acute bioavailability of metformin in normal subjects.     

Normal levels of energy expenditure in patients with reported ‘low metabolism’

The present study examined the hypothesis that patients with apparent diet-resistant obesity have subnormal energy expenditure. Ten biochemically euthyroid patients (eight women and two men), aged 21–76 years, with either excessive gynoid fat distribution or obesity (BMI 23.8–41.0), were referred to the department thought to be suffering from a low metabolic rate syndrome since dietary records showed very low energy intake (<5 MJ day^?1) in combination with failure to lose weight on low-energy diets. Twenty-four-hour energy expenditure (24-h EE), basal energy expenditure (BEE) and sleeping energy expenditure (SEE) were measured in a respiration chamber on a fixed activity programme. The patients consumed a diet containing 37 energy-per cent (E%) fat, 47 E% carbohydrate and 16 E% protein. The individual energy intake was estimated from a previously established algorithm between 24-h EE and fat-free mass (FFM) estimated by bioimpedance. Results were compared with equivalent values in a reference population of 76 subjects ranging from normal weight to obese. No evidence of low metabolism was found in terms of adjusted 24-h EE in the patients with diet resistance when compared with the control group (9263±819 kJ vs. 9211±558 kJ). No differences were found when comparing adjusted BEE and SEE in the two groups (7655±727 vs. 7411±770 kJ 24 h^?1 and 7048±672 vs. 6911±408 kJ 24 h^?1). The physical activity index (PAI) during the chamber stay was likewise within normal values (1.32±0.07 vs. 1.34±0–04; NS).     

Dietary saturated fatty acids increase cholesterol synthesis and fecal steroid excretion in healthy men and women

Abstract. In a strictly controlled 6-week trial with 47 healthy volunteers we have determined the effect of replacement of polyunsaturated by saturated fatty acids on the fecal steroid excretion and on the rate of whole body cholesterol synthesis, as measured both by the sterol balance method and by the concentration of the cholesterol precursor lathosterol in serum. Subjects were fed mixed natural diets, of which the total fat content was kept constant at 45% energy. Consumption of polyunsaturated fatty acids, mainly linoleic acid, was 21 % energy for the first 3-week period (P: S ratio 1.9), and 5% of energy (P: S ratio 0.2) for the next 3-week period, or vice versa. Cholesterol intake as determined by analysis of duplicate diets was 41 mg MJ^-1 (about 500 mg day^-1) during both periods. Feces were collected for 5 days at the end of both periods. The steroid composition of the feces was not affected by the change of diets. The fecal excretion of neutral steroids was significantly higher on the low P: S high-saturated-fat (2.25 ± 0.68 mmol day-¹) than on the high P:S high-linoleic-acid diet (2.00 ± 0.69 mmol day-¹; P < 0.01). The excretion of bile acids was similar (0.77 ± 0.40 and 0.79 ± 0.41 mmol day^-1, respectively). The cholesterol balance and the rate of cholesterol synthesis were higher during the low P:S (1.86 ± 0.83 mmol day^-1) than during the high P:S period (1.55 ± 0.85 mmol day^-1; P < 0.01). The ratio of lathosterol to cholesterol in serum was 0.86 ± 0.33 μmol mmol^-1 on the high-and 1.07 ± 0.39 μmol mmol^-1 on the low P: S diet (P < 0.01). Thus, both the balance and the cholesterol precursor method suggested that saturated fatty acids stimulate whole-body cholesterol synthesis.     

A 24‐week randomised controlled trial comparing usual care and metabolic‐based diet plans in obese adults

Background: Usual care (UC) practice for weight management often includes providing standardised, ad libitum, low‐calorie nutrition plans. However, weight loss using such plans appears comparable with metabolic‐based diet (MD) plans that are closer to resting energy expenditure (REE) level. In addition, MD plans are approximately 250–750 kcal/day higher in caloric values compared with UC plans. Therefore, the purpose of this study was to compare weight loss and eating behaviour differences between UC and MD plans. Methods: Seventy‐four obese (30.0–51.7 kg/m²) adults (21–67 years) voluntarily participated in a 24‐week randomised study. UC men and women received a fixed, ad libitum, 1600 and 1200 kcal/day nutrient plan, respectively. MD participants received an individualised treatment plan based from measured REE. Bodyweight and eating behaviours (i.e. intake, restraint and uncontrolled eating) were assessed over time. Results: Intent‐to‐treat analysis indicated no significant difference in weight loss (UC: ?5.7 ± 6.3% vs. MD: ?5.3 ± 7.1% p = 0.67) between groups over time. There was no difference in daily energy intake (UC: 2490 ± 576 kcal/day vs. MD: 2525 ± 475 kcal/day) at 24 weeks between groups. Both groups experienced a significant improvement (p < 0.05) in eating dietary restraint and uncontrolled eating yet there was no difference between groups. Conclusion: From this study, UC calorie plans do not generate more weight loss or improve eating behaviours in comparison with MD calorie plans. As treatment effects are comparable, clinicians can select UC or MD plan options based on clinician and patient preference.     

Daily variation in circulating cytokines and acute-phase proteins correlates with clinical and laboratory indices in community-acquired pneumonia

Our objective was to investigate the initial levels of circulating proinflammatory cytokines, such as interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumour necrosis factor alpha (TNF-α), of certain acute-phase proteins, such as C-reactive protein (CRP), fibrinogen (FBN) and albumin, and of the glycoprotein fibronectin at presentation and their daily variation during the clinical course of community-acquired pneumonia (CAP) in relation to clinical and laboratory indices of infection. Thirty otherwise healthy hospitalized patients aged 48 ± 3 years (mean ± SEM) and with bacteriologically confirmed CAP were studied prospectively. IL-1β and IL-6 were found to be 15-fold higher on admission (122 ± 9 pg mL^?1 and 60 ± 4 pg mL^?1 respectively), whereas TNF-α was three-fold higher (102 ± 5 pg mL^?1) than those of controls, all of them showing a decline towards normal. Initial CRP levels were increased 90-fold (416 ± 1 mg L^?1), whereas fibronectin levels were reduced (242 ± 9 mg dL^?1). The presence of parapneumonic effusion was associated with a higher TNF-α serum level (127 ± 7 vs. 86 ± 4 pg mL^?1, P = 0.0002), a more rapid daily decline in TNF-α (–7.2 ± 0.7 vs. ?3.8 ± 0.5 pg mL^?1 day^?1, P = 0.0005), a slower rate of decline in CRP (?42.8 ± 3.0 vs. ?54.6 ± 3.0 mg L^?1 day^?1, P = 0.02) and a slower rate of increase in FBN (5.9 ± 1.0 vs. 11.7 ± 1.0 mg dL^?1 day^?1), P = 0.001]. Furthermore, daily progression of serum levels of cytokines and acute-phase proteins correlated strongly with pyrexia, erythrocyte sedimentation rate (ESR), neutrophil count, alveolar–arterial oxygen difference and radiographic resolution, clinically manifested by improvement in the patients' condition.     

Diet-induced thermogenesis in patients with gastrointestinal cancer cachexia

1. Indirect calorimetry has been used to measure resting energy expenditure (REE) and the thermogenic response to a test meal (diet-induced thermogenesis) in groups of weight-stable and weight-losing patients with gastrointestinal adenocarcinoma. Average daily intakes of energy and protein were computed from dietary assessment for the week before hospitalization. Results were compared with a control group of patients with benign gastrointestinal disease. 2. Weight-losing cancer patients had a significantly reduced mean total energy and protein intake. 3. There was no significant difference in REE between the groups when results were normalized in terms of metabolic body size (kJ/kg 0.75) and lean body mass (kJ/kg). 4. Diet-induced thermogenesis was reduced in weight-losing cancer patients. 5. It is suggested that the reduction of diet-induced thermogenesis in weight-losing cancer patients is another element of starvation adaptation, subsequent to their weight loss, and that altered thermogenesis does not contribute to the weight loss seen in cancer cachexia.     

Energy Metabolism in Japanese Patients with Crohn’s Disease

We investigated energy expenditure in hospitalized patients with Crohn’s disease (CD), and determined optimal energy requirements for nutritional therapy. Sixteen patients (5 women and 11 men, mean age 36 year old, mean BMI 18.7 kg/m²) and 8 healthy volunteers were enrolled in this study. Measured resting energy expenditure (mREE) levels were determined by indirect calorimetry. The mREEs in CD patients were significantly higher than those of healthy controls (24.4 ± 2.4 kcal/kg/day vs 21.3 ± 1.7 kcal/kg/day). However, mREEs in CD patients were significantly lower than predicted REEs (pREEs) calculated by the Harris-Benedict equation (26.4 ± 2.5 kcal/kg/day). Furthermore, mREE/pREE values were lower in undernourished patients than in well-nourished patients. CD patients had hyper-metabolic statuses evaluated by mREE/body weight, but increased energy expenditure did not contribute to weight loss in these patients. In conclusion, nutritional therapy with 25–30 kcal/ideal body weight/day (calculated by mREE × active factor) may be optimal for active CD patients, while higher energy intake values pose the risk of overfeeding.     

Main nitrogen balance determinants in malnourished patients

Factors influencing nitrogen balance during total parenteral nutrition have been investigated in 38 malnourished patients studied for a cumulative period of 280 days. According to multiple regression analysis, nitrogen intake (0.213±0.004 g kg^-1 day^-1, mean ±SD) proved to be the major determinant of a positive nitrogen balance (0.018±0.004 g kg^-1 day^-1), followed by non-protein energy intake (43.3±0.5 kcal kg^-1 day^-1). Total calorie intake to predicted basal energy expenditure and non protein calorie to nitrogen ratios appeared to have little significance on nitrogen balance, when corrected for the two former variables.     

Resting energy expenditure in patients undergoing pylorus preserving pancreatoduodenectomies for bile duct cancer or pancreatic tumors

We measured the energy expenditure weekly in patients undergoing a pylorus preserving pancreatoduodenectomy for bile duct cancer or pancreatic tumors. Twelve patients (5 women and 7 men; mean age 70.1 years) were enrolled in this study, and their resting energy expenditure levels were determined by indirect calorimetry. In these patients, a significant correlation was observed between the measured resting energy expenditures and the predicted resting energy expenditures calculated by the Harris-Benedict equation. The resting energy expenditures measured before surgery were almost the same as the predicted resting energy expenditures (measured resting energy expenditure: 22.4 ± 3.9 kcal/kg/day vs predicted resting energy expenditure: 21.7 ± 2.0 kcal/kg/day). The measured resting energy expenditure/predicted resting energy expenditure ratio, which reflects the stress factor, was 1.02 ± 0.10. After the pylorus preserving pancreatoduodenectomy, a significant increase in energy expenditure was observed, and the measured resting energy expenditure was 25.7 ± 3.5 kcal/kg/day on postoperative day 7 and 25.4 ± 4.9 kcal/kg/day on postoperative day 14. The measured resting energy expenditure/predicted resting energy expenditure ratio was 1.16 ± 0.14 on postoperative day 7, and 1.16 ± 0.18 on postoperative day 14 respectively. In conclusion, patients undergoing a pylorus preserving pancreatoduodenectomy showed a hyper-metabolic status as evaluated by their measured resting energy expenditure/predicted resting energy expenditure ratio. From our observations, we recommend that nutritional management based on 30 kcal/body weight/day (calculated by the measured resting energy expenditure×activity factor 1.2–1.3) may be optimal for patients undergoing a pylorus preserving pancreatoduodenectomy.     

Acute lymphoblastic leukemia and obesity: increased energy intake or decreased physical activity?

Background  Obesity is a well-known problem in children with acute lymphoblastic leukemia (ALL), and it might be the result of an excess in energy intake, reduced energy expenditure, or both. The aim of this study is to describe energy intake and physical activity during treatment for ALL with intermittent dexamethasone (DEXA). Methods  Body mass index (BMI), energy intake, and physical activity were measured in 16 ALL patients on maintenance treatment and in 17 healthy controls. ALL patients were measured during (“on DEXA”) and in between (“off DEXA”) DEXA treatments. Results  In patients, the mean increase in BMI z-score was 1.4 ± 1.1. Energy intake on DEXA was higher (2,125.9 ± 476.0 vs 1,775.1 ± 426.1 kcal/24 h, p < 0.05) and energy intake off DEXA was lower (1,305.0 ± 249.4 vs 1,775.1 ± 426.1 kcal/24 h, p < 0.05), compared to healthy controls. Physical activity on DEXA was lower compared to healthy controls (30.0 ± 3.9 vs 40.0 ± 6.0 kcal kg⁻¹ 24 h⁻¹, p < 0.001 and 7,303.1 ± 4,622.9 vs 13,927.2 ± 3,822.7 steps, p < 0.05). Physical activity off DEXA was not different compared to healthy controls. Conclusion  Weight gain in patients on ALL treatment might be owing to increased energy intake and decreased physical activity during treatment with DEXA.     

Resting energy expenditure and nutritional status in patients undergoing transthoracic esophagectomy for esophageal cancer

This study was to assess the resting energy expenditure of patients with esophageal cancer using indirect calorimetry. Eight male patients with esophageal cancer and eight male healthy controls were enrolled in this study. All patients underwent transthoracic esophagectomy with lymph nodes dissections. The resting energy expenditure was measured preoperatively, and on postoperative day 7 and 14 using indirect calorimetry. Preoperatively, the measured resting energy expenditure/body weight in these patients was significantly higher than that of the controls (23.3 ± 2.1 kcal/kg/day vs 20.4 ± 1.6 kcal/kg/day), whereas the measured/predicted energy expenditure from the Harris-Benedict equation ratio was 1.01 ± 0.09, which did not differ significantly from the control values. The measured resting energy expenditure/body weight was 27.3 ± 3.5 kcal/kg/day on postoperative day 7, and 23.7 ± 5.07 kcal/kg/day on postoperative day 14. Significant increases in the measured resting energy expenditure were observed on postoperative day 7, and the measured/predicted energy expenditure ratio was 1.17 ± 0.15. In conclusion, patients with operable esophageal cancers were almost normometabolic before surgery. On the other hand, the patients showed a hyper-metabolic status after esophagectomy. We recommended that nutritional management based on 33 kcal/body weight/day (calculated by the measured resting energy expenditure × active factor 1.2–1.3) may be optimal for patients undergoing esophagectomy.     

Effects of sibutramine on thermogenesis in obese patients assessed via immersion calorimetry

Glucose utilization studies show that sibutramine-induced thermogenesis is mediated via selective sympathetic activation of brown adipose tissue. The goal of the present study was to use a new calorimetry method in which resting metabolic rate is enhanced to evaluate the effects of sibutramine treatment on thermogenesis. Sixty obese women were included in the study. Subjects were divided into 2 equal groups-the placebo and sibutramine treatment groups. The sibutramine group was given sibutramine 10 mg daily for 12 wk. At baseline and at the end of the 12-wk treatment period, thermogenic measurements were taken with the use of water immersion calorimetry. Subjects were examined at weeks 4, 8, and 12 of treatment to identify adverse effects. Body mass index, measured at 31.5±2.05 kg/m² in the placebo group, decreased to 30.4±2.94 kg/m² after 12 wk (P=.07). In the sibutramine group, it decreased from 33.5±4.1 kg/m² to 30.9±4.8 kg/m² (P < .05). In the sibutramine group, mean thermogenic response changed from a baseline value of 1.27±0.29 kcal/kg/h to 1.44±0.13 kcal/kg/h after 12 wk of treatment. In the placebo group, the baseline value was 1.56±0.27 kcal/kg/h; it changed to 1.33±0.36 kcal/kg/h at the end of 12 wk. The findings of this study suggest that sibutramine treatment promotes thermogenesis, thus facilitating weight loss. Calorimetry enhances resting metabolism through more efficient heat transfer from the body.     

Apixaban, an oral, direct and highly selective factor Xa inhibitor: in vitro, antithrombotic and antihemostatic studies

Summary. Background: Apixaban is an oral, direct and highly selective factor Xa (FXa) inhibitor in late‐stage clinical development for the prevention and treatment of thromboembolic diseases. Objective: We evaluated the in vitro properties of apixaban and its in vivo activities in rabbit models of thrombosis and hemostasis. Methods: Studies were conducted in arteriovenous‐shunt thrombosis (AVST), venous thrombosis (VT), electrically mediated carotid arterial thrombosis (ECAT) and cuticle bleeding time (BT) models. Results: In vitro, apixaban is potent and selective, with a K_i of 0.08 nm for human FXa. It exhibited species difference in FXa inhibition [FXa K_i (nm ): 0.16, rabbit; 1.3, rat; 1.7, dog] and anticoagulation [EC_2× (μm , concentration required to double the prothrombin time): 3.6, human; 2.3, rabbit; 7.9, rat; 6.7, dog]. Apixaban at 10 μm did not alter human and rabbit platelet aggregation to ADP, γ‐thrombin, and collagen. In vivo, the values for antithrombotic ED₅₀ (dose that reduced thrombus weight or increased blood flow by 50% of the control) in AVST, VT and ECAT and the values for BT ED_3× (dose that increased BT by 3‐fold) were 0.27 ± 0.03, 0.11 ± 0.03, 0.07 ± 0.02 and > 3 mg kg^?1 h^?1 i.v. for apixaban, 0.05 ± 0.01, 0.05 ± 0.01, 0.27 ± 0.08 and > 3 mg kg^?1 h^?1 i.v. for the indirect FXa inhibitor fondaparinux, and 0.53 ± 0.04, 0.27 ± 0.01, 0.08 ± 0.01 and 0.70 ± 0.07 mg kg^?1 day^?1 p.o. for the oral anticoagulant warfarin, respectively. Conclusions: In summary, apixaban was effective in the prevention of experimental thrombosis at doses that preserve hemostasis in rabbits.     

Formation of prostacyclin during administration of β1-selective and non-selective β-adrenergic antagonists in healthy humans

Summary. Vascular formation of prostacyclin is increased by propranolol in patients with essential hypertension. However the possible effect of β-adrenoceptor blocking drugs in healthy subjects is, however, not known. We studied this issue by analysis of the urinary excretion of the prostacyclin metabolite, 2,3-dinor-6-keto-prostaglandin F_la during intake of a (β₁-selective (metoprolol) or a non-selective (propranolol) (3-adrenoceptor antagonist. After 14 days of metoprolol treatment (100 mg d^-1) the urinary excretion of PGI-M did not differ from control (253 ± 77 vs. 220 ± 33 pg mg^-1 creatinine, respectively). Five days of randomized cross-over treatment with propranolol (80 mg day^-1) or placebo did not affect urinary PGI-M significantly either (177 ± 11 vs. 202 ± 11 pg mg^-1 creatinine, respectively). Furthermore, a daily increasing dose of propranolol (80–480 mg) progressively lowered resting blood pressure and heart rate, but failed to influence urinary excretion of PGI-M. The data demonstrate that metoprolol and propranolol do not affect basal cardiovascular formation of prostacyclin in healthy subjects. Thus, the biosynthesis of prostacyclin does not appear to be regulated by p-adrenoceptor activity under normal conditions.     

Weight-adjusted resting energy expenditure is not constant in critically ill patients

Objective In critically ill patients, energy requirements are frequently calculated as a multiple of total body weight presuming a linear relationship between total body weight and resting energy expenditure (REE); however, it is doubtful if this estimation of energy needs should be applied to all patients, particularly to overweight patients, since adipose tissue has a low contribution to REE. This study was undertaken to test the hypothesis that REE adjusted for total body weight decreases with increasing body mass index in critically ill patients. Additionally, measured REE was compared with three predictive equations. Design and Setting Clinical study in a university hospital intensive care unit. Patients One hundred critically ill patients admitted to the intensive care unit. Measurements and results Patients were included into four groups according to their body mass index (normal weight, pre-obese, obese, and morbidly obese). Measured REE was assessed using indirect calorimetry. Energy needs were calculated using the basal metabolic rate, the Consensus Statement of the American College of Chest Physicians (REEacs), and 25 kcal/kg of ideal body weight (REEibw). Adjusted REE was 24.8 ± 5.5 kcal/kg in normal weight, 22.0 ± 3.7 kcal/kg in pre-obese, 20.4 ± 2.6 kcal/kg in obese, and 16.3 ± 2.3 kcal/kg in morbidly obese patients (p < 0.01). Basal metabolic rate underestimated measured REE in normal weight and pre-obese patients. REEacs and REEibw over- and underestimated measured REE in overweight patients, respectively. Conclusions Predictive equations were not able to estimate measured REE adequately in all the patients. Adjusted REE decreased with increasing body mass index; thus, a body mass index group-specific adaptation for the estimation of energy needs should be applied.     

Changes in energy metabolism after induction therapy in patients with severe or moderate ulcerative colitis

We investigated the changes in energy expenditure during induction therapy in patients with severe or moderate ulcerative colitis. Thirteen patients (10 men, 3 women; mean age, 36.5 years) with ulcerative colitis admitted to the Shiga University Hospital were enrolled in this study. We measured the resting energy expenditure and respiratory quotients of these patients before and after induction therapy with indirect calorimetry. We analyzed the changes of nutritional status and serum inflammatory cytokine levels and also evaluated the relationship between energy metabolism and disease activity by using the Seo index and Lichtiger index. The resting energy expenditure was 26.3 ± 3.8 kcal/kg/day in the active stage and significantly decreased to 23.5 ± 2.4 kcal/kg/day after induction therapy (p<0.01). The resting energy expenditure changed in parallel with the disease activity index and C-reactive protein and inflammatory cytokine levels. The respiratory quotient significantly increased after induction therapy. Thus, moderate to severe ulcerative colitis patients had a hyper-metabolic status, and the energy metabolism of these patients significantly changed after induction therapy. Therefore, we recommend that nutritional management with 30–34 kcal/kg/day (calculated as measured resting energy expenditure × activity factor, 1.3) may be optimal for hospitalized ulcerative colitis patients.