Linkage between obesity and a marker near the tumor necrosis factor-alpha locus in Pima Indians.

Because tumor necrosis factor-alpha (TNF-alpha) expression is increased in adipose tissue of both rodent models of obesity and obese humans, it has been considered as a candidate gene for obesity. Pima Indians were scored for genotypes at three polymorphic dinucleotide repeat loci (markers) near the gene TNF-alpha at 6p21.3. In a sib-pair linkage analysis, percent body fat, as measured by hydrostatic weighing, was linked (304 sib-pairs, P = 0.002) to the marker closest (10 kb) to TNF-alpha. The same marker was associated (P = 0.01) by analysis of variance with BMI. To search for possible DNA variants in TNF-alpha that contribute to obesity, single stranded conformational polymorphism analysis was performed from 20 obese and 20 lean subjects. Primer pairs were designed for the entire TNF-alpha protein coding region and part of the promoter. Only a single polymorphism located in the promoter region was detected. No association could be demonstrated between alleles at this polymorphism and percent body fat. We conclude that the linkage of TNF-alpha to obesity might be due to a sequence variant undetected in TNF-alpha or due to a variant in some other closely linked gene.     

Food intake measured by an automated food-selection system: relationship to energy expenditure.

Measuring food intake in a laboratory usually involves limited food choices. An automated food-selection system with two vending machines containing a large variety of foods was used to measure food intake in 10 male volunteers (31 +/- 6 y, 69.2 +/- 7.1 kg, 18 +/- 7% fat, mean +/- SD) on a metabolic ward. The effect of carbohydrate, fat, and protein intakes on 24-h energy expenditure (24EE) and substrate oxidations was measured in a respiratory chamber during day 4 of weight maintenance and day 7 of ad libitum intake. Ad libitum intake resulted in a 7-d overfeeding of 6468 +/- 3824 kJ/d above weight-maintenance requirements, leading to a 2.3 +/- 1.2-kg gain. The 10,975 +/- 3774 kJ excess energy intake on day 7 of ad libitum intake caused a 1205 +/- 920 kJ/d increase in 24EE (delta 24EE = 0.17 x delta intake - 695; r = 0.71, P less than 0.02). Of the excess carbohydrate intake, 74% was oxidized (r = 0.86, P less than 0.001), whereas excess fat intake was not. Carbohydrate and protein stores are regulated whereas excess fat intake is channeled to fat stores.     

Obesity in Pima Indians. Distribution characteristics and possible thresholds for genetic studies.

We examined distribution characteristics of the body mass index (BMI; weight/height; kg/m2) in a sample of 1128 male and 1372 female Pima Indians aged 15-65 years. We found that women had a higher mean and variance of BMI than men. From commingling analyses, we determined that the distribution of BMI could be accounted for either by a single skewed distribution or by a mixture of multiple normal components. These component distributions may be used to define provisional thresholds in selecting families for genetic studies. To ensure genetic segregation of obesity predisposing genes in Pima families will require that some members have BMIs > or = 40 kg/m2.     

Two-week stimulation or blockade of the sympathetic nervous system in man: influence on body weight, body composition, and twenty four-hour energy expenditure

Seven lean healthy young men were studied for 6 weeks during exposure to pharmacologic inhibition or stimulation of the sympathetic nervous system. For a period of 2 weeks their beta-adrenergic receptors were either blocked with propranolol hydrochloride (160 mg/d) or stimulated with terbutaline sulphate (15 mg/d). After a further 2 weeks of placebo administration (500 mg lactose/d), the subjects crossed over to the drug they had not been taking at the beginning of the experiment for another 14 days. During the last five days of each 2-week period, the subjects consumed a weight-maintaining diet, composed of 12% protein, 48% carbohydrate, and 40% fat. They consumed exactly the same menus on the same days during the subsequent study periods. Body weight and physical activity were measured every day for 6 weeks. Daily heart rate and nitrogen excretion were measured continuously for days at the end of each 2-week period, the last two days of which were spent in a respiration chamber where energy expenditure and a variety of metabolic parameters were measured. In the respiration chamber on the propranolol, placebo, and terbutaline treatments, respectively, significant differences were observed in mean daily heart rate (65 +/- 3, 75 +/- 4, and 84 +/- 4 beats/min), mean sleeping heart rate (51 +/- 2, 56 +/- 3, and 62 +/- 3 beats/min), nitrogen excretion (13.6 +/- 0.7, 12.6 +/- 0.6, and 11.9 +/- 0.6 g/d), fat oxidation (+1,045 +/- 95, +1,243 +/- 148, and +1,278 +/- 84 kcal/d) and thyroid hormones (12.0 +/- 0.7, 15.7 +/- 0.9, and 17.2 +/- 1.0 T3/T4 ratio).(ABSTRACT TRUNCATED AT 250 WORDS)     

Propofol in der Neuroanästhesie

The quality, result, and prognosis of neurosurgery relies heavily on the anaesthetic technique. Many different classes of drugs have been used during neurosurgical anaesthesia. This article reviews the use of intravenous (IV) propofol as an alternative to volatile anaesthetic techniques. Anaesthesia requirements for neurosurgical procedures are elaborated upon in the first part of the article. The priority of neuroanaesthesia is to preserve neuronal function by avoiding complications such as hypoxia, hypercarbia, and cardiovascular instability. Thereafter, the chosen anaesthetic technique should minimally interfere with cerebral autoregulation and CO₂ responsiveness, while brain relaxation is encouraged by decreasing the cerebral metabolic rate for oxygen (CMRO₂) and cerebral blood flow (CBF). In addition, the anaesthetic technique should be associated with rapid and predictable recovery in the operating theatre in order to allow early evaluation of the surgery. The second part of the article describes IV techniques for neurosurgery as an alternative to volatile anaesthetics, all of which increase CBF, cerebral blood volume, and intracranial pressure (ICP) in a dose-related manner and diminish cerebral autoregulation and interfere with cerebrovascular CO₂ reactivity. Nitrous oxide has a stimulant effect on cerebral metabolism and is associated with an increase in CBF. On the other hand, all IV agents except ketamine are associated with decreases in CMRO₂ and are cerebral vasoconstrictors. For this reason, it is rational to use them for the induction and maintenance of anaesthesia for neurosurgery as part of a total IV anaesthetic technique. The third part of the article focuses on propofol as the newest representative of IV anaesthetics. It is a sedative-hypnotic agent that has a pharmacokinetic-dynamic profile ideally suited for continuous infusion. Propofol reduces ICP, CBF, and CMRO₂. Animal models have suggested the possibility of cerebral protection. The responsiveness of the cerebral circulation to alterations in arterial blood pressure is maintained. Evaluating propofol for major neurosurgery demonstrated good quality and depth of anaesthesia, excellent brain relaxation, and minimal surgical bleeding. In conclusion, total IV anaesthesia with propofol has proven to be a valid alternative to conventional thiopentone-isoflurane anaesthesia for intracranial surgery.     

Is proximal airway pressure a good reflection of peripheral airspace pressure in infants and children models under HFJV?

This expriimental study was carried out to determine if an alveolar positive end-expiratory pressure (PEEP) could occur during high frequency jet ventilation (HFJV) in infants, and if tracheal pressure is a good estimation of alveolar pressure.We used physical models simulating a 1.5 kg premature (P), a 3 kg newborn (N) and a 6 kg child (C) with normal compliance and normal resistance. Moreover, in the N model, we used two different resistances and lung compliance heterogeneity was studied in the P model. Pressure was measured simultaneously in the tube simulating trachea (Paw) and in the bottle simulating the lung (Palv). HFJV was performed either via an endotracheal tube (ETT) or via a long catheter as in laryngoscopy. The ratio of injection time upon cycle duration (Ti/Ttot) was 20% or 30%, jet frequency was altered from 150 to 300 min^–1 and the driving pressure was set as in clinical practice (0.5 and 0.6 bar).PEEP occurred mainly in N (1.1 to 3.2 cm H2O) and C models (0 to 3.5 cm H2O). It was inversely related to expiratory time (Te). The end-expiratory pressure drop between Palv and Paw (EEP) was higher in N and increased from 0.5 to 2 cm H2O with the shortening of Te and with airway resistances, i.e. the presence of ETT. In the heterogeneous model, PEEP and EEP were greater in the higher compliance alveolus.This study shows that the end-expiratory Palv is underestimated by end-expiratory Paw. This is particularly important in the presence of an heterogeneity of distribution in lung compliance. In this case the airway PEEP overestimates the PEEP in the lower compliance alveolus and underestimates the PEEP in the higher compliance alveolus.     

Twenty-four-hour energy expenditure in Pima Indians with Type 2 (non-insulin-dependent) diabetes mellitus

Summary To assess the impact of Type 2 (non-insulin-dependent) diabetes mellitus on energy metabolism, 24-h energy expenditure, basal metabolic rate and sleeping metabolic rate were measured in a respiratory chamber in 151 Pima Indians, 102 with normal glucose tolerance (67 male/35 female, (mean ± SD) 28±7 years, 99±24 kg, 32±9% body fat) and in 49 with Type 2 diabetes (22 male/27 female, 35±11 years, 107±33 kg, 39±7% body fat), after at least 3 days on a weight maintaining diet. After adjustment for differences in fat-free mass, fat mass, age and sex, 24-h energy expenditure, basal metabolic rate and sleeping metabolic rate were significantly higher in diabetic patients than in control subjects (72 kcal/day, p<0.05; 99 kcal/day, p<0.005; 99 kcal/day, p<0.001 respectively). Spontaneous physical activity was similar in both groups whereas the thermic effect of food, calculated as the mean energy expenditure corrected for activity throughout the day above sleeping metabolic rate and expressed as a percentage of energy intake, was significantly lower in Type 2 diabetic patients (17.1±7.1 vs 19.8±5.6%, p<0.05). Adjusted values of 24-h energy expenditure, basal metabolic rate and sleeping metabolic rate were correlated with hepatic endogenous glucose production (r=0.22, p<0.05; r=0.22, p<0.05; r=0.31, p<0.01 respectively). Therefore, increased basal and sleeping metabolic rates, resulting in increased 24-h sedentary energy expenditure may play a role in the weight loss so often observed in Type 2 diabetic subjects in addition to the energy loss from glycosuria.     

Meal frequency and timing in health and disease

Although major research efforts have focused on how specific components of foodstuffs affect health, relatively little is known about a more fundamental aspect of diet, the frequency and circadian timing of meals, and potential benefits of intermittent periods with no or very low energy intakes. The most common eating pattern in modern societies, three meals plus snacks every day, is abnormal from an evolutionary perspective. Emerging findings from studies of animal models and human subjects suggest that intermittent energy restriction periods of as little as 16 h can improve health indicators and counteract disease processes. The mechanisms involve a metabolic shift to fat metabolism and ketone production, and stimulation of adaptive cellular stress responses that prevent and repair molecular damage. As data on the optimal frequency and timing of meals crystalizes, it will be critical to develop strategies to incorporate those eating patterns into health care policy and practice, and the lifestyles of the population.