Core temperature: a forgotten variable in energy expenditure and obesity?

A substantial proportion of energy expenditure is utilized for maintenance of the 'warm-blooded' or homoeothermic state. In normally active humans, this compartment of energy output approximates 40% of total energy expenditure. Many mammalian species utilize regulated decreases in temperature, such as hibernation or shallow torpor, as a means of energy conservation. Inherited forms of rodent obesity (ob/ob mouse, fa/fa rat) have lower core temperatures and withstand cold poorly. Obese humans, however, have normal core temperatures. This review addresses the role of core temperature in the metabolic economy of the obese state and raises the possibility that (i) lower temperatures may contribute to the increase in metabolic efficiency that accompanies weight loss in the obese; and (ii) that lower core temperatures may have initiated weight gain in the pre-obese state and that the normal temperatures in the obese may represent metabolic compensation to restore energy balance and limit further weight gain.

New measurement of the K+-->pi+ nunu branching ratio.

Three events for the decay K+-->pi+ nunu have been observed in the pion momentum region below the K+-->pi+pi0 peak, 140 < Ppi < 199 MeV/c, with an estimated background of 0.93+/-0.17(stat.) -0.24+0.32(syst.) events. Combining this observation with previously reported results yields a branching ratio of B(K+-->pi+ nunu) = (1.73(-1.05)+1.15) x 10(-10) consistent with the standard model prediction.

Improved measurement of the K+-->pi+nunu; branching ratio.

An additional event near the upper kinematic limit for K+-->pi(+)nunu; has been observed by experiment E949 at Brookhaven National Laboratory. Combining previously reported and new data, the branching ratio is B(K+-->pi(+)nunu;)=(1.47(+1.30)(-0.89))x10(-10) based on three events observed in the pion momentum region 211

Observation of a narrow charm-strange meson D(+)(sJ)(2632)-->D(+)(s)eta and D(0)K(+).

We report the first observation of a charm-strange meson D(+)(sJ)(2632) at a mass of 2632.5+/-1.7 MeV/c(2) in data from SELEX, the charm hadro-production experiment E781 at Fermilab. This state is seen in two decay modes, D(+)(s)eta and D0K+. In the D(+)(s)eta decay mode we observe a peak with 101 events over a combinatoric background of 54.9 events at a mass of 2635.4+/-3.3 MeV/c(2). There is a corresponding peak of 21 events over a background of 6.9 at 2631.5+/-2.0 MeV/c(2) in the decay mode D0K+. The decay width of this state is <17 MeV/c(2) at 90% confidence level. The relative branching ratio Gamma(D0K+)/Gamma(D(+)(s)eta) is 0.14+/-0.06. The mechanism that keeps this state narrow is unclear. Its decay pattern is also unusual, being dominated by the D(+)(s)eta decay mode.

First observation of the doubly charmed baryon Xi(+)(cc).

We observe a signal for the doubly charmed baryon Xi(+)(cc) in the charged decay mode Xi(+)(cc)-->Lambda(+)(c)K-pi(+) in data from SELEX, the charm hadroproduction experiment at Fermilab. We observe an excess of 15.9 events over an expected background of 6.1+/-0.5 events, a statistical significance of 6.3sigma. The observed mass of this state is 3519+/-1 MeV/c(2). The Gaussian mass width of this state is 3 MeV/c(2), consistent with resolution; its lifetime is less than 33 fs at 90% confidence.

Precision measurements of the lambda(+)(c) and D0 lifetimes.

We report new precision measurements of the lifetimes of the Lambda(+)(c) and D0 from SELEX, the charm hadroproduction experiment at Fermilab. Based upon 1630 Lambda(+)(c) and 10 210 D0 decays we observe lifetimes of tau[Lambda(+)(c)] = 198.1+/-7.0+/-5.6 fs and tau[D0] = 407.9+/-6.0+/-4.3 fs.

Insulin-mediated sympathetic stimulation: role in the pathogenesis of obesity-related hypertension (or, how insulin affects blood pressure, and why).

Thus, the evidence summarized here supports an important role for insulin and the sympathetic nervous system in the pathogenesis of obesity-related hypertension. Is it possible that insulin-mediated sympathetic stimulation contributes a pro-hypertensive effect in non-obese as well? It seems possible in young borderline hypertensives where sympathetically mediated thermogenic mechanisms are potent enough to compensate for the increased caloric intake, thereby enabling these young hypertensives to avoid obesity. This is consistent with an observation made in the original Framingham cohort that not only did obesity predict the eventual development of hypertension, but hypertension, as well, predicted the eventual development of obesity. A reasonable interpretation of these data suggests that as subjects age and the effectiveness of thermogenic mechanisms wanes, obesity might develop as a consequence of increased caloric intake no longer effectively buffered by the increased SNS activity. It is important to note that the mechanisms described here exert a pro-hypertensive effect and cannot properly be considered to 'cause' hypertension. Hypertension is rarely the consequence of a single mechanism. It is also true, as pointed out convincingly by Julius and his colleagues, that enhanced sympathetic activity, as a primary factor, can be associated with both hypertension, insulin resistance and, possibly, obesity [39]. And, finally, it should be noted that the mechanism described here is not the only mechanism linking obesity and hypertension. A rapidly emerging body of evidence indicates that leptin, the polypeptide product of the ob/ob gene secreted from adipose tissue, exerts potent central neural effects on both appetite and sympathetic activity. Leptin levels, elevated in obese humans, have the potential to increase both sympathetic activity and blood pressure [40-43]. A more comprehensive summary of the relationships between hypertension and obesity may, therefore, involve insulin and leptin, as well as the SNS, as represented in the schema presented in Figure 7. Both leptin and insulin may, therefore, be considered as compensatory mechanisms recruited to restore energy balance, with the SNS as one of the effector arms. Viewed in this way, obesity-related hypertension is inextricably linked to the metabolic economy of the obese.

Inability of an "energy transfer diagnostician" to distinguish between fertile and infertile women.

CONTEXT: Various forms of "energy healing" have become popular in the United States. OBJECTIVE: To test the assertion that an energy healer can, without physical contact, distinguish the presence or absence of internal organ pathology in individuals who lack overt physical findings. DESIGN: Observational randomized study, in which we tested the assertion by a well-recognized alternative healer that he had particular skill in using energy transfer to detect the presence or absence of fertility disorders in women. PATIENTS: Convenience sample of 37 women, 28 of whom had documented pathology resulting in infertility, and 9 of whom were fertile. OUTCOMES: The healer was provided with no medical history and performed diagnostic evaluations without physical contact with the blindfolded, clothed, and silent subjects. We compared to random chance the ability of the healer to establish a diagnosis of fertility or fertility disorder. SETTING: Teaching hospital. MAIN RESULTS: The healer was unable to distinguish the presence or absence of fertility disorders in the study subjects. CONCLUSION: This study points to further need for fair yet rigorous assessment of claims that energy transfer can lead to accurate clinical diagnoses.

Hostility and the metabolic syndrome in older males: the normative aging study.

OBJECTIVE: Several studies have shown that hostility, as measured by the Minnesota Multiphasic Personality Inventory-derived Cook-Medley Hostility Scale (Ho), is positively associated with several cardiovascular risk factors, possibly accounting for the relationship between Ho scores and cardiovascular mortality. This study was undertaken to examine associations between hostility and cardiovascular risk factors representing the metabolic syndrome in 1,081 older men who participated in the Normative Aging Study. METHODS: Subjects included men who completed the Minnesota Multiphasic Personality Inventory in 1986 and who participated in a subsequent laboratory examination within 1 to 4 years. Total and subscale Ho scores were computed, and associations with anthropometric data, cigarette smoking, dietary information, serum lipids, blood pressure, and fasting glucose and insulin levels were examined. RESULTS: The total Ho score was positively associated with waist/hip ratio, body mass index, total caloric intake, fasting insulin level, and serum triglycerides. The Ho score was inversely related to education and high-density lipoprotein cholesterol concentration. Path analysis also suggested that the effects of hostility on insulin, triglycerides, and high-density lipoprotein cholesterol were mediated by its effects on body mass index and waist/hip ratio, which, in turn, exerted their effects on lipids and blood pressure through insulin. CONCLUSIONS: The results are consistent with those of prior research and also suggest that, in older men, hostility may be associated with a pattern of obesity, central adiposity, and insulin resistance, which can exert effects on blood pressure and serum lipids. Furthermore, effects of hostility on the metabolic syndrome appear to be mediated by body mass index and waist/hip ratio.

The treatment of neurogenic orthostatic hypotension with 3,4-DL-threo-dihydroxyphenylserine: a randomized, placebo-controlled, crossover trial.

OBJECTIVE: To study the therapeutic effect and mechanism of action of 3,4-DL-threodihydroxyphenylserine (DL-DOPS) in neurogenic orthostatic hypotension. METHODS: The blood pressure (BP) response to an orthostatic challenge on DL-DOPS was compared with that of placebo in a randomized, double-blind, placebo-controlled, crossover trial in 10 patients. The mechanism of action of DOPS was studied by measuring forearm vascular resistance and changes in supine and upright plasma DL-DOPS and norepinephrine levels. The effect of DL-DOPS on the quality of life was determined by questionnaire. RESULTS: DL-DOPS increased the supine (p<0.001) and upright (p<0.05) systolic blood pressure (SBP) and diastolic blood pressure (DBP) (both p<0.01). The peak SBP on DL-DOPS in the supine position occurred 300 minutes after ingestion of the medication. The increase in BP was accompanied by an increase in plasma levels of norepinephrine and DL-DOPS in both the supine and upright positions after DL-DOPS ingestion (p<0.0001). There was a trend toward improvement in symptoms of orthostatic intolerance. CONCLUSION: DL-DOPS improved features of neurogenic orthostatic hypotension in patients with central and peripheral autonomic nervous system disease. There was an increase in plasma norepinephrine. No major side effects occurred.

Weight reduction and obesity.

Obesity and hypertension are intimately linked. Weight loss lowers blood pressure and improves the blood pressure response to sodium restriction and antihypertensive medications. In addition to the effects of energy restriction, diets rich in fruits and vegetables (and hence potassium) and rich in low fat dairy products (and hence rich in calcium and magnesium), high in fiber, and low in saturated fat also lower blood pressure independent of sodium and energy content. These dietary modifications, along with weight loss are beneficial in patients only mildly overweight and, because of beneficial effects on other cardiac risk factors should be part of the therapeutic regimen in all obese hypertensive patients.

Insulin resistance and hypertension.

Insulin resistance, a common accompaniment of essential hypertension, increases cardiovascular risk both directly, and via its adverse effect on other cardiovascular risk factors. Decreasing insulin resistance by lifestyle modification including diet, weight loss, and physical exercise is an important component of therapy in all patients. With the exception of thiazide diuretics as monotherapy, the currently utilized classes of agent appear equally effective in lowering blood pressure in insulin resistant patients. Currently utilized agents do, however, differ substantially in their effect on insulin resistance and associated risk factors. Agents that diminish insulin resistance may have a rationale in treating insulin resistant patients with hypertension although a decisive recommendation about class of agent in this group of patients must await several prospective large scale trials currently underway. Lower intervention thresholds and lower therapeutic goals would appear to apply to hypertensive patients with insulin resistance especially in the presence of impaired glucose tolerance or overt diabetes mellitus.

Role of the sympathetic adrenal system in the pathogenesis of the insulin resistance syndrome.

The pathophysiology of the various manifestations of Syndrome X has been poorly understood. A possible mechanism involves stimulation of the sympathetic nervous system (SNS). Insulin plays an important role in the relationship between dietary intake and SNS activity. Because insulin-mediated glucose uptake in central hypothalamic neurons regulates SNS activity in response to dietary intake, a hypothesis was developed that links the hyperinsulinemia of obesity to sympathetic stimulation, the latter exerting a prohypertensive effect mediated by the kidney, the heart, and the vasculature. Evidence in support of this hypothesis has been obtained from the Normative Aging Study (NAS) in which a relationship between insulin (and glucose) and the SNS, and between insulin and SNS activity and blood pressure was demonstrated. The characteristic dyslipidemia in NAS subjects, moreover, was related to insulin and epinephrine. As reported in other studies, insulin level was directly associated with low HDL and high triglyceride levels. An independent inverse association was also noted between urinary epinephrine excretion and lipid levels: high epinephrine excretion rates were associated with high HDL and low triglyceride levels and, conversely, low epinephrine excretion was associated with low HDL and high triglycerides. In the NAS, therefore, increased SNS activity contributes to hypertension while diminished adrenal medullary activity contributes to the low HDL and high triglyceride levels commonly seen in association with hypertension.

On the mechanism of the effects of potassium restriction on blood pressure and renal sodium retention.

Dietary potassium restriction increases sodium and chloride retention, whereas potassium administration promotes both diuresis and natriuresis. In epidemiologic and clinical studies, potassium intake is inversely related to blood pressure and is lower in blacks than in whites. The present studies examined the mechanism by which potassium restriction fosters sodium conservation and the impact of race on this response. Twenty-one healthy black and white men and women ingested an isocaloric, potassium-restricted diet (20 mmol/d) containing 180 mmol/d of sodium with and without a potassium supplement (80 mmol/d) for 9 days on two occasions. Additionally, eight of these subjects ingested the same diets for 3 days followed by a water load to determine free water clearance before and during the early phase of dietary potassium restriction. During potassium restriction, mean arterial pressure (MAP) derived from 24-hour blood pressure measurements was higher (85.7 +/- 1.6 mm Hg v 82.0 +/- 1.3 mm Hg; P < 0.001), cumulative sodium excretion lower (984 +/- 59 mmol/d v 1,256 +/- 58 mmol/d; P < 0.001), and weight greater (71.1 +/- 2.1 kg v 69.3 +/- 2.2 kg; P < 0.001). Blacks displayed no greater increase in MAP, although they excreted less sodium overall and less potassium on the potassium-supplemented diet. After a water load, minimum urine osmolality (Uosm) was lower (53.0 +/- 3.0 mOsm/L v 65.6 +/- 3.5 mOsm/L; P = 0.01) and free water clearance greater (4.44 +/- 0.59 mL/min v3.72 +/- 0.58 mL/min; P = 0.009) during potassium restriction. In conclusion, in healthy, normotensive subjects, potassium restriction was associated with an increase in blood pressure and volume expansion effected by increased renal sodium and chloride retention. Potassium restriction was also associated with increased free water clearance and enhanced diluting capacity consistent with augmentation of Na+, K+:2Cl- cotransporter activity in the thick ascending limb of Henle. This mechanism may play an important role in the renal adaptation required for potassium conservation, but at the expense of sodium chloride retention and an elevation in blood pressure.

Identification of peripheral vascular disease in elderly subjects using optical spectroscopy.

The purpose of this study was to determine the usefulness of near-infrared spectroscopy (NIRS) measurements to identify peripheral vascular disease (PVD). Usefulness was determined by the frequency of a successful test, as well as comparison with standard clinical assessments. Study subjects (N = 117, mean age = 67.8 +/- 8.1 yrs) responded to a free screening for PVD. NIRS was used to measure the relative O2 saturation of hemoglobin in the soleus muscle. The time to 1/2 recovery of O2 saturation (O2T1/2) was measured after 1 minute of repeated plantar flexions using a Cybex Eagle seated calf machine. O2T1/2 was used as many subjects had recovery curves that did not have an exponential line shape. The test was done on both legs and the worst leg was used for analysis. For comparative purposes, a clinical history and physical examination were performed by a physician or nurse practitioner, which included questions on intermittent claudication, examination of peripheral pulses, and questions to identify cardiovascular risk factors. NIRS signals were obtained on 105 of 117 subjects (89% success rate). Subjects with body mass index (BMI) values above 32 appeared to have NIRS O2T1/2 values that were less reliable than subjects with BMI values < or = 32 (77% success rate). The O2T1/2 was longer in subjects with claudication and reduced pulses than in subjects without these conditions. Sensitivity comparing O2T1/2 to claudication and reduced pulse varied from 51-76% and specificity from 65-80%, depending on the cutoff value for O2T1/2 that was used (normal value plus 1 or 2 SD). A longer O2T1/2 was significantly associated with incidence of diabetes, smoking, hypercholesterol, and coronary bypass surgery. In summary, successful NIRS O2T1/2 measurements were made in 77% of the subjects, with failure primarily occurring in obese subjects. NIRS O2T1/2 measurements showed reasonable although not strong agreements with clinical assessment of PVD, and with some risk factors for cardiovascular disease.

Suppression of sympathetic nervous system during fasting.

Two days of fasting in rats significantly reduces the turnover of norepinephrine in the heart. In contrast to the effects of ganglionic blockade in fed controls, similar blockade in fasted animals is without significant effect on [3H]-norepinephrine retention or endogenous norepinephrine in the heart. These data are consistent with suppression of centrally mediated sympathetic activity in the fasted state. The decrease in norepinephrine turnover during fasting is completely reversed by 1 day of refeeding.

The treatment of postprandial hypotension in autonomic failure with 3,4-DL-threo-dihydroxyphenylserine.

Postprandial hypotension occurs commonly in patients with autonomic failure and may be due to attenuation of the normal sympathetic nervous system activation in response to meal ingestion. In a randomized, double-blind, placebo-controlled study, we investigated the therapeutic effect of the norepinephrine precursor 3,4-DL-threo-dihydroxyphenylserine (DL-DOPS) on this condition. We measured blood pressure, heart rate, forearm vascular resistance, and plasma DL-DOPS and norepinephrine in 11 patients with autonomic failure. DL-DOPS attenuated the postprandial fall in blood pressure. This was associated with an increase in plasma norepinephrine and forearm vascular resistance. DL-DOPS therapy did not change the postprandial increase in heart rate. There was a trend toward increased supine hypertension associated with DL-DOPS treatment. This study shows that DL-DOPS is a promising treatment for postprandial hypotension and provides support for the hypothesis that postprandial hypotension is, at least in part, due to decreased activation of the sympathetic nervous system.

Factors predicting assistive device use in the home by older people following rehabilitation.

The purpose of this article is to (a) describe the pattern of assistive device use by older adults the first 3 months home following rehabilitation, (b) examine factors that predict home use, and (c) describe characteristics of users. The study involved 86 patients 55 years of age or older who were hospitalized for a stroke, orthopedic deficit, or lower limb amputation and discharged home with assistive devices. Of the 642 devices provided in the hospital, 50% were used frequently to always, with those using devices in Month 1 continuing over time. A respondent's expectation while hospitalized to use devices was an independent predictor of actual home use. Although there were no differences between users and nonusers among sociodemographic variables, respondents with a lower limb amputation used devices with greater frequency than those with either a stroke or orthopedic deficit.

Obesity and the insulin resistance syndrome.

Obesity is one component of a risk factor constellation that consists of insulin resistance (and/or hyperinsulinemia), hypertension, and a dyslipidemia characterized by a low HDL cholesterol level and high triglyceride levels. This risk factor constellation, which conveys enhanced risk for cardiovascular disease, is sometimes referred to as the "insulin resistance syndrome", "syndrome x", or the "metabolic" syndrome. Although the hyperinsulinemia and insulin resistance associated with the syndrome appear to play a central role, the relationship between insulin and the other manifestations of the syndrome have remained obscure.