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Detailed interstitial temperature mapping during treatment with a novel transurethral microwave thermoablation system in patients with benign prostatic hyperplasia.

PURPOSE: To delineate in detail the temperature changes in the prostate gland and adjacent structures during treatment with a newly designed microwave thermoablation system in patients with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Microwave thermoablation treatment was administered to 22 BPH patients at two centers in the U.S. and Argentina using the Urologix Targis targeted transurethral thermoablation system. Continuous temperature measurements were made with widely spatially dispersed fiber optic thermosensors at 11 to 24 prostatic sites in each patient using a recently described accurate stereotactic method. Urethral and rectal temperatures were also measured. RESULTS: Treatment using the microwave thermoablation system resulted in marked elevation of intraprostatic temperatures to as high as 80C in some patients with little or no elevation of urethral or rectal temperatures. Average temperature increased with radial distance from the urethra to a peak at 5 to 7 mm. and declined exponentially at greater distances. Higher maximum intraprostatic temperatures in individual patients were associated with a larger zone, up to 24.0 mm. in radius, of prostatic tissue exposed to thermoablative temperatures of 45C and higher. Along the longitudinal axis of the microwave treatment catheter, thermoablative temperatures were confined to a zone of 11.5 mm. from the microwave antenna midpoint apically and 11.3 mm. basally, that is, a range shorter than the length of the treatment catheter's microwave antenna (2.8 to 3.5 cm.). The mean temperature in the posterior sector of the prostate gland during treatment (43.6C; 95% CI, 41.1 to 46.1C) was significantly lower (p < 0.05) by 6.7C than that in the anterolateral prostate (50.3C; 95% CI, 48.3 to 52.3C), as a consequence of the preferential heating design of the treatment catheter. Intraprostatic mean temperature during treatment, as measured at all thermosensor sites without respect to spatial location, was 47.1C (95% CI, 44.2 to 50.0C), a value significantly higher (p < 0.05) than that measured in the urethra (39.6C; 95% CI, 36.6 to 42.6C) or rectum (37.7C; 95% CI, 36.7 to 38.7C). There was a strong correlation between the temporal pattern of fluctuation in urethral temperature and that of prostate temperature (r = 0.83; p < 0.001) during treatment. CONCLUSIONS: Treatment with the microwave thermoablation system fulfilled the requirements for an effective and safe microwave-based BPH treatment modality by exposing obstructive tissue to high temperatures without endangering vulnerable adjacent tissues.

Aged↗

Weight-reducing diets, the thermic effect of feeding and energy balance in young women.

Six healthy women participated in a longitudinal study. In session one baseline data collection was made: (1) a record of customary food intake by the weighed inventory method; (2) the measurement of resting metabolic rate (RMR) and the thermic effect of feeding (TEF) a meal (2.09 MJ Ensure) together with the collection of blood samples; (3) the measurement of weight, height and assessment of body composition. On three subsequent occasions similar data were collected following periods of energy intake restriction, or free diet. Group mean (range) energy intake for session one (7 days) was 8.97 MJ (6.93-12.24); for session two (14 days) was 4.06 MJ (3.61-4.66); for session three (4 days) 1.75 MJ (1.15-2.20). No record was made for session four (free diet for 21 days). Subjects were 98-118 percent of ideal body weight at the study onset. All lost weight in sessions two and three, mean (range) 2.4 kg (1.0-3.7) and 1.4 kg (0.7-2.6) respectively. A mean of 2.2 kg (1.3-2.7) was gained in session four. Mean RMR was 122 kJ per 30 min in session one and fell by 12 percent of the mean baseline value in session two. Thereafter values returned to basal levels. TEF in session one increased mean (range) 30 percent (13-45) over RMR. There were no changes in session two. In session three TEF was 17 percent (10-28) and similar results were recorded in session four. The study suggests that TEF can be sensitive to alterations in energy intake and that this adaptive mechanism is highly variable among individuals. This has implications for the prediction of changes in body weight in response to varying levels of food intake.

Adult↗

Effects of two estradiol/norgestrel combinations on the ovulatory pattern and on sex hormone binding globulin capacity in women around forty years of age.

Thirteen women aged 36-46 years (mean 43) who were seeking contraceptive advice, were monitored for 3 months with basal body temperature (BBT) and were then treated for 3 months with CyclabilR (11 tablets of 2 mg estradiol valerate (E2) followed by 10 tablets of 2 mg E2 + 0.5 mg norgestrel). This treatment was immediately followed by another 3 months with CyclabilR + 2 mg E2. BBT revealed a spontaneous ovulatory rate of 89%. Cyclabil reduced the ovulatory rate, as measured with repeated serum progesterone analyses, to 37%, and Cyclabil + 2 mg E2 resulted in a marked reduction in the number of ovulations (3%). Both types of hormonal combination resulted in relatively small changes in Sex Hormone Binding Globulin Capacity. It is concluded that the addition of 2 mg E2 to CyclabilR causes a decrease in ovulation rate to such an extent that women using this combination run a relatively small risk of conceiving. One advantage over contraceptive steroids may be that the present combination contains a natural estrogen at a relatively low concentration.

Adult↗

Energy expenditure in lean and obese diabetic patients using the doubly labelled water method.

Obesity is a common problem among Type 2 diabetic patients. To investigate the role of energy expenditure in the maintenance of obesity in diabetic subjects, total energy output was measured during weight stability in 23 diabetic patients: 8 lean, 5 overweight, and 10 obese. Free living total energy expenditure was measured over 14 days using doubly labelled water method, resting metabolic rate by indirect calorimetry, and urinary energy losses were assessed. Total energy output was higher in the obese (13.66 +/- SD 3.18 MJ 24 h-1) than normal weight patients (10.84 +/- 2.02 MJ 24 h-1; p < 0.05); 11.96 +/- 2.51 MJ 24 h-1 in the overweight. None of the lean but four of the obese had total energy output > 16 MJ 24 h-1. Urinary energy losses accounted for only 0.6% of total energy output in lean, 2.8% in overweight, and 3.1% in obese. Resting metabolic rate was significantly higher in obese (7.47 +/- 1.69 MJ 24 h-1) compared to lean (5.87 +/- 1.07; p < 0.05) and resting metabolic rate correlated with lean body mass (r = 0.8, p < 0.001). Thermogenesis plus physical activity was substantial and not lower in the obese (5.77 versus lean 4.97 MJ 24 h-1). The mean ratio of total energy expenditure to resting metabolic rate was in the moderate exercise category and similar in lean (1.87) and obese (1.80). Resting metabolic rate, total energy expenditure, and thermogenesis and physical activity were similar in all three groups when corrected for differences in lean body mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Galanin is a potent in vivo modulator of mesencephalic serotonergic neurotransmission.

Neurochemical, molecular, immunohistochemical and behavioral methods were used to examine the in vivo effects of the neuropeptide galanin on central 5-HT neurotransmission and on 5-HT(1A) receptor-mediated responses. Intraventricularly infused galanin caused a long-lasting and dose-dependent reduction of basal extracellular 5-HT levels in the ventral hippocampus of awake rats as measured by microdialysis. Infusion of galanin into the dorsal raphe nucleus (DRN), but not intra-hippocampally, reduced 5-HT release. The effect of i.c.v. galanin on 5-HT release was blocked by the galanin receptor antagonist M35, acting most likely via galanin receptors at the level of the DRN. Galanin also reduced the levels of tryptophanhydroxylase mRNA in the DRN. Therefore, the effects of galanin on 5-HT(1A) receptor-mediated responses were further investigated. Surprisingly, galanin significantly attenuated the reduction of hippocampal 5-HT release induced by systemic injection of the 5-HT(1A) receptor agonist 8-OH-DPAT. Galanin also attenuated 8-OH-DPAT-induced hypothermia and locomotor activity in rats. These results indicate that galanin has important inhibitory actions on central 5-HT neurotransmission and on 5-HT(1A) receptor-mediated events.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Daily energy metabolism in patients with type 1 diabetes mellitus.

OBJECTIVE: We evaluated the daily energy balance and main substrate utilization in Type 1 insulin dependent diabetic patients and healthy volunteers. METHODS: Ten patients with Type 1 diabetes mellitus and eight healthy volunteers were studied. Diabetic patients were well controlled under intensive insulin treatment (0.6 UI/kg body weight, HbA1c = 5.5 +/- 0.7%). During the 30 hours each subject spent in the respiration chamber VO2, VCO2, respiratory quotient, daily energy intake, 24-hour, day-time, night-time and basal energy expenditure as well as energy expenditure during exercise (at 40% maximal exercise capacity), main substrate oxidation (carbohydrates, lipids and proteins) and overall diet-induced thermogenesis, were measured. The results were corrected for 24-hour urinary nitrogen loss. RESULTS: Diet-induced thermogenesis, expressed as percent of energy intake, was found to be significantly lower in diabetic patients than in control subjects (6.69 +/- 1.29% vs 11.8 +/- 4.71% of energy intake, p < 0.05). A negative correlation was found between diet-induced thermogenesis and daily average glycemia for diabetic patients (r = -0.65, p < 0.01). Energy expenditure during exercise, calculated in terms of net work efficiency, was not different between the two groups. CONCLUSIONS: In conclusion, since diet-induced thermogenesis is highly correlated with the theoretical cost of glucose storage and since no difference was found in carbohydrate oxidation, glucose storage in diabetic patients is probably reduced when hyperglycemia occurs. Diabetic patients in good metabolic control are able to perform mild exercise with a work efficiency very similar to that of control subjects.

Adult↗

[Pretreatment with aspirin for protection against heat stroke in rats].

OBJECTIVE: To observe the changes in blood pressure and interleukin-1beta (IL-1beta) level after heat stroke in rats and to observe the protective effect of pretreatment with aspirin against heat stroke. METHODS: Rat models of heat stroke were established and randomly assigned into control (n=10) and aspirin groups (n=10). Arterial blood pressure, colonic temperature (T(co)), and electrocardiograph (ECG) were monitored and blood samples taken at 0 and 60 min after heat exposure for determining the plasma IL-1beta levels in the two groups. RESULTS: From 0 to 50 min after heat exposure, the mean arterial blood pressure MAP was not significantly different between the two groups, but at about 55-60 min, the MAP significantly decreased in the control group in comparison with the aspirin group (P<0.01). The K value and the height of the dicrotic notch (h(D)/H) were gradually decreased, especially at 40 min after heat exposure, and the control group showed greater reduction in the K value. T(co) of both groups were increased after heat exposure, without significant difference between groups. The time of the onset of heat stroke was similar in the two groups, but rats in the aspirin group had significantly longer survival time (P<0.05). ECG showed that the heart rate and QT intervals of both groups were increased, while PR intervals were decreased after heat exposure. Plasma IL-1beta levels in the two groups were significantly elevated at 60 min in comparison with the basal level (P<0.05), which was more obvious in the control group (P<0.05). CONCLUSION: Pretreatment with anti-inflammatory dose of aspirin can provide protection against heat stroke in rats, which may be associated with the inhibition of elevation of plasma IL-1beta levels by aspirin.

Animals↗

Evaporative water loss in the new-born baby.

1. Measurements of total evaporative water loss (EWL) were made on sixty-three premature and full-term babies 0-65 days after birth within a closed Perspex chamber under varied environmental conditions by measuring the flow and absolute humidity of air entering and leaving the chamber. Control experiments suggested that the method underestimated loss by about 5%. Measurements of O(2) consumption were made concurrently by recording the volume change of the closed gas circuit.2. The total basal EWL averaged 10.8 g H(2)O/m(2).hr in infants 2-10 days old when ambient water vapour pressure (P(H2O)) was 18 mm Hg; basal EWL was correlated with basal metabolic rate at all ages studied and evaporative heat loss accounted for approximately 23% of basal heat production.3. Respiratory water loss was measured by detecting the water added to air at 33 degrees C passed across the face of eight infants in a trunk plethysmograph. Respiratory water loss was inversely related to the water vapour content of the inspired air; gas appeared to leave the nose approximately 95% sat. at 35.6 degrees C.4. Measurements of total EWL were obtained when humidity was varied and skin loss was calculated by subtracting estimated respiratory loss from total loss; changing P(H2O) from 7 to 25 mm Hg appeared to decrease basal skin water loss by only 1.5 g/m(2).hr.5. No consistent changes in EWL were obtained when environmental temperature (T(E)) was varied between 28 and 34 degrees C. Active sweating occurred in infants 0-10 days old born within 3 weeks of term when T(E) exceeded 34-35 degrees C and rectal temperature (T(R)) rose above 37.2 degrees C. The threshold rectal temperature at which sweating was detected fell significantly in the first 10 days of life; EWL increased two to fourfold when T(R) rose to between 37.5 and 37.8 degrees C.6. In infants of less than 215 days post-conceptual age (term approximately 268 days) EWL increased less than 50% at T(R) 37.7-37.8 degrees C; it is concluded that the sweating mechanism is defective in these infants.

Basal Metabolism↗

Autoclave sterilization produces acrylamide in rodent diets: implications for toxicity testing.

Acrylamide (AA) is a neurotoxic and carcinogenic contaminant that is formed during the cooking of starchy foods. Assessment of human risks from toxicants is routinely performed using laboratory rodents, and such testing requires careful control of unintended exposures, particularly through the diet. This study describes an analytical method based on liquid chromatography with electrospray tandem mass spectrometry that was used to measure endogenous AA in rodent diets and to survey a number of commercial products for contamination. Method sensitivity permitted accurate quantification of endogenous levels of AA in raw diets below 20 ppb. Autoclaving a standard rodent diet (NIH-31) increased the AA content 14-fold, from 17 to 240 ppb. A nutritionally equivalent diet that was sterilized by irradiation was found to contain approximately 10 ppb of AA (NIH-31IR). A toxicokinetic study of AA and its epoxide metabolite, glycidamide, was performed by switching mice from NIH-31IR to the autoclaved diet for a 30 min feeding period (average AA dose administered was 4.5 microg/kg of body weight). The concentrations of AA and glycidamide were measured in serum collected at various times. The elimination half-lives and the areas under the respective concentration-time curves were similar for AA and glycidamide. Mice maintained on autoclaved NIH-31 diet, but otherwise untreated, showed elevated steady state levels of a glycidamide-derived DNA adduct in liver relative to mice maintained on the irradiated diet. This study demonstrates that a heat sterilization procedure used in laboratory animal husbandry (i.e., autoclaving) can lead to the formation of significant levels of AA in basal diets used for toxicity testing. AA in rodent diets is bioavailable, is distributed to tissues, and is metabolically activated to a genotoxic metabolite, which produces quantifiable cumulative DNA damage. Although the contribution of endogenous AA to the incidence of tumors in multiple organs of rodents otherwise untreated in chronic carcinogenicity bioassays (i.e., control groups) is not known, the reduction of endogenous AA through the use of a suitable irradiated diet was deemed to be critical for ongoing studies of AA carcinogenicity and neurotoxicity.

Acrylamide↗

Basal metabolic temperature vs. laboratory assessment in "posttraumatic hypothyroidism".

OBJECTIVES: To compare standard laboratory analytical methods with measurement of basal metabolic temperature in cases of hypothyroidism arising posttraumatically. SETTING: Private medical office. SUBJECTS: One hundred and one consecutive status post-whiplash trauma patients. DESIGN: All subjects were evaluated with standard laboratory tests (T3RU, T4, FT4I, TSH) for thyroid function. Ninety-four were also evaluated with the newer fluorescence-activated microsphere assay test (FAMA) and basal metabolic temperature (BMT) was measured in all. Correlations were investigated between BMT, age, gender, standard laboratory values and the FAMA test. The differences between low and high BMT vs. normal and abnormal standard laboratory values and the differences between normal and abnormal standard laboratory values vs. normal and elevated FAMA test results were also investigated. RESULTS: In 86.4%, the BMTs were below normal. Of this subgroup, 30% had abnormal standard laboratory values. Of the 13% whose BMT was within the normal range, 33% had abnormal standard laboratory values and 66% had increased FAMA titers. Statistically significant correlation was found between BMT and T3RU (p = .05), whereas the correlation between BMT and T4 was somewhat weaker (p = .07). Correlations between BMT and all other laboratory indices failed to reach significance. The laboratory abnormalities observed in this group of subjects were atypical for common types of hypothyroidism. A significant portion of our posttraumatic hypothyroid group (30%) were not identified with either standard laboratory tests or the FAMA test-a group we referred to as lab-normal. CONCLUSIONS: Measurement of BMT seems to be a sensitive screening test, in combination with laboratory analysis, for the hypothyroidism seen after whiplash trauma. Whiplash seems to result in a form of hypothyroidism suggesting direct injury to central tissues.

Adolescent↗

Rosiglitazone up-regulates lipoprotein lipase, hormone-sensitive lipase and uncoupling protein-1, and down-regulates insulin-induced fatty acid synthase gene expression in brown adipocytes of Wistar rats.

AIMS/HYPOTHESIS: Although thiazolidinediones are now widely used to treat type 2 diabetes, their mechanism of action remains largely unknown. They are agonists for the transcription factor PPARgamma, and in addition to their insulin-sensitising effects, they can promote adipogenesis and control gene expression in adipose tissues. We have explored the effect of rosiglitazone on insulin-mediated induction of pivotal genes involved in lipid metabolism and thermogenesis in brown fat. The genes studied were: (1) lipoprotein lipase (lpl), which is involved in lipid uptake; (2) hormone-sensitive lipase (hsl), which mobilises fatty acids from stored triglycerides; (3) fatty acid synthase (fas), which regulates de novo lipogenesis; and (4) the uncoupling proteins (ucp) 1 and 3, which control thermogenesis. METHODS: We used fetal rat primary brown adipocytes cultured with insulin, rosiglitazone or both combined. Then, we studied gene expression by northern and western blotting, as well as 'run-on' and gel-shift assays to identify binding of potential transcription factors to the fas promoter. RESULTS: Exposure to rosiglitazone for 24 h induced ucp-1, lpl and hsl gene expression and when rosiglitazone was combined with insulin a synergistic effect on lpl and ucp-3 mRNA expression was produced. These effects were consistent with increased LPL and HSL activities as well as respiration rates, mainly in response to exogenous palmitate. In contrast, treatment with rosiglitazone did not alter FAS mRNA basal levels but prevented the induction elicited by insulin in a time- and dose-dependent manner. Correspondingly diminished FAS protein levels and activity, as well as cellular lipid content, were observed, indicating an antilipogenic action of rosiglitazone in brown adipocytes. Furthermore, rosiglitazone impaired insulin increase in the FAS transcription rate by antagonising insulin-induced binding of upstream stimulatory factors to the E-box consensus sequence in the FAS promoter and insulin-induced binding of activating protein-1. CONCLUSIONS/INTERPRETATION: Rosiglitazone prevents insulin-induced up-regulation of the main lipogenic enzyme but increases the expression of those enzymes involved in lipid uptake and mobilisation, favouring fatty acid utilisation through uncoupled respiration.

Adipocytes↗

Pituitary-adrenal and pituitary-thyroid hormone responses during exercise-cold exposure after 7 days of exhaustive exercise.

BACKGROUND: After several days of exhaustive exercise in mild-warm environments, cutaneous vasoconstrictor responses to cold exposure are less effective in conserving body heat than in the rested condition. Hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axes hormones could mediate this response since they may affect vasoconstriction. The effects of exertional fatigue on pituitary-adrenal hormones and thyroid hormone responses to exercise-cold stress are unknown. HYPOTHESIS: We hypothesized that 7 consecutive days of exercise would decrease adrenocorticotropin (ACTH) and cortisol, while elevating thyroid stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) and that these hormones would be related to a blunted vasoconstrictor response to cold. METHODS: Nine male volunteers walked, completely wetted, for up to 6 h in 5 degrees C air, when rested (day 0, control) and after 7 consecutive days (day 7) of exhaustive exercise (4 h each day of mixed aerobic and anaerobic activities in thermoneutral conditions). Blood was sampled on day 0 and day 7 at baseline (0700 hours), and before and immediately after cold exposure. RESULTS: At 0700 hours, ACTH and cortisol were elevated (p < 0.05) after 7 d of exercise, compared with control conditions. Following exercise-cold exposure, cortisol, T3, and T4 increased (p < 0.05) similarly on both day 0 and day 7. ACTH and TSH did not increase as a result of exercise-cold exposure on either day. CONCLUSIONS: These data indicate that 7 d of exercise elevates basal (0700 hours) pituitary-adrenal stress hormones (ACTH, cortisol). However, 7 d of exercise did not modify adrenal or thyroid hormone responses, relative to the day 0 cold exposure, suggesting that they are not responsible for the blunted vasoconstriction during exercise-cold exposure following 7 consecutive days of exercise.

Adrenocorticotropic Hormone↗

Suppression of colitis-related mouse colon carcinogenesis by a COX-2 inhibitor and PPAR ligands.

BACKGROUND: It is generally assumed that inflammatory bowel disease (IBD)-related carcinogenesis occurs as a result of chronic inflammation. We previously developed a novel colitis-related mouse colon carcinogenesis model initiated with azoxymethane (AOM) and followed by dextran sodium sulfate (DSS). In the present study we investigated whether a cyclooxygenase (COX)-2 inhibitor nimesulide and ligands for peroxisome proliferator-activated receptors (PPARs), troglitazone (a PPARgamma ligand) and bezafibrate (a PPARalpha ligand) inhibit colitis-related colon carcinogenesis using our model to evaluate the efficacy of these drugs in prevention of IBD-related colon carcinogenesis. METHODS: Female CD-1 (ICR) mice were given a single intraperitoneal administration of AOM (10 mg/kg body weight) and followed by one-week oral exposure of 2% (w/v) DSS in drinking water, and then maintained on the basal diets mixed with or without nimesulide (0.04%, w/w), troglitazone (0.05%, w/w), and bezafibrate (0.05%, w/w) for 14 weeks. The inhibitory effects of dietary administration of these compounds were determined by histopathological and immunohistochemical analyses. RESULTS: Feeding with nimesulide and troglitazone significantly inhibited both the incidence and multiplicity of colonic adenocarcinoma induced by AOM/DSS in mice. Bezafibrate feeding significantly reduced the incidence of colonic adenocarcinoma, but did not significantly lower the multiplicity. Feeding with nimesulide and troglitazone decreased the proliferating cell nuclear antigen (PCNA)-labeling index and expression of beta-catenin, COX-2, inducible nitric oxide synthase (iNOS) and nitrotyrosine. The treatments increased the apoptosis index in the colonic adenocarcinoma. Feeding with bezafibrate also affected these parameters except for beta-catenin expression in the colonic malignancy. CONCLUSION: Dietary administration of nimesulide, troglitazone and bezafibrate effectively suppressed the development of colonic epithelial malignancy induced by AOM/DSS in female ICR mice. The results suggest that COX-2 inhibitor and PPAR ligands could serve as an effective agent against colitis-related colon cancer development.

Animals↗

Seasonal changes in energy and water use by verdins, Auriparus flaviceps.

We used the doubly labeled water (DLW) method to measure field metabolic rate (FMR) and water turnover during winter and summer in a very small (6.5 g) insectivorous desert passerine bird, the verdin (Auriparus flaviceps). Concurrently, we monitored weather conditions and used time-activity budget data of free-living birds and laboratory data on resting metabolic rate to construct time-activity laboratory (TAL) estimates of daily energy expenditure (DEE ) and to partition the verdins' energy budget into thermoregulatory, activity and basal components. The FMR of adult verdins was 33.6+/-0.9 kJ day(-)(1) (mean +/- s.e.m.; N=14) in winter and 22.8+/-0.45 kJ day(-)(1) (N=7) in summer. FMR correlated negatively with the mean standard operative environmental temperature (T(es)) prevailing during the measurement period. TAL analysis produced DEE estimates that corresponded on average to within -0.9+/-2.4 % of our DLW-measured FMR values (range of individual values -18.3 % to +14.3 %). Metabolic expeditures for cold defense were 19.5+/-2.1 % of DEE in winter (computed assuming substitution of exercise thermogenesis for thermoregulatory costs in active birds). In the summer, thermoregulatory costs amounted to 9.0+/-0.4 % of DEE for keeping warm and 1.0+/-0.1 % of DEE for keeping cool in the heat. Activity costs were 21.0+/-0.5 % of DEE in winter and 17.5+/-0.1 % of DEE in summer. The water efflux of nonbreeding adult verdins was 3.9+/-0.2 ml day(-)(1) (624+/-22 ml kg(-)(1 )day(-)(1)) in summer (N=5) and 3. 4+/-0.2 ml day(-)(1) (498+/-26 ml kg(-)(1 )day(-)(1)) in winter (N=14). The water economy index (WEI; water efflux per unit FMR) of verdins was higher in summer (0.17+/-0.01 ml kJ(-)(1)) than in winter (0.10+/-0.01 ml kJ(-)(1)) and correlated negatively with mean T(es).

Animals↗

Heart rate and metabolic response to burn injury in humans.

BACKGROUND: Although frequently done, estimating the energy requirements of individual burn patients without measuring their resting metabolic rate is a less than satisfactory method of evaluation. METHODS: We tested whether heart rate, which relates to the energy expenditure during physical activity, is also associated with postburn hypermetabolism (calculated as percentage increase of resting metabolic rate above the predicted normal fasting resting metabolic rate). Twenty-three patients [12 men and 11 women, aged 38 +/- 13 years (mean +/- SD); weight, 71.6 +/- 14.8 kg; body mass index, 25.4 +/- 3.6; total burn surface area, 35.3 +/- 17.8% (percentage of body surface)] were studied weekly for 3 weeks after an overnight fast. RESULTS: Measured resting metabolic rates and heart rates were 2016 +/- 497 kcal/d, 101 +/- 13 bpm (n = 19); 2231 +/- 485 kcal/d, 107 +/- 13 bpm (n = 18); and 1903 +/- 598 kcal/d, 99 +/- 14 bpm (n = 11) for weeks 1, 2, and 3, respectively. Postburn hypermetabolism was +36% +/- 19%, +55% +/- 27%, and +36% +/- 35% in the first, second, and third week, respectively. In each week postburn hypermetabolism correlated with heart rate (r = 0.65, p = .003; r = 0.69, p = .001; and r = 0.80, p = .002, respectively). Only in the second week did postburn hypermetabolism correlate with total burn surface area (r = 0.52, p = .02); there was no correlation with body temperature. In a multiple regression analysis, predicted resting metabolic rate, heart rate, and total burn surface area together explained 77% of all of the variance observed in the 48 fasting resting metabolic rates that were measured in the study (r2 = 0.77, p < .0001), and each of these variables also had a significant partial correlation with fasting resting metabolic rates (r2 = 0.45, p < .0001; r2 = 0.29, p < .0001; and r2 = 0.03, p < .03, respectively). CONCLUSIONS: In burn patients, variability in heart rate is associated with a significant part of postburn hypermetabolism variability. Therefore, heart rate may be considered a useful variable to be used for the evaluation of the energy requirements of severely burned patients.

Adolescent↗

Body temperature and heat production in suckling rat endotoxaemia: beneficial effects of glutamine.

BACKGROUND/PURPOSE: Sepsis is an important cause of neonatal mortality. The aim of the study was to investigate the metabolism of endotoxic neonatal rats and the potential beneficial effect of glutamine. METHODS: Suckling rats received intraperitoneal saline (control; C), endotoxin (300 microg/g LPS; E), saline+glutamine (2 mmol/g; CG), endotoxin+glutamine (EG), saline+leucine (2 mmol/g; CL) or endotoxin+leucine (EL). Sepsis score (0-8) and rectal temperature were monitored. Hypothermia was defined as rectal temperature less than 32 degrees C. Oxygen consumption (VO2, mL/kg/h), a determinant of heat production, was measured by indirect calorimetry. Data (mean +/- SEM) were compared by analysis of variance (ANOVA), paired t test or Fisher's Exact test. RESULTS: Endotoxic (E) rats had significantly lower VO2 than C rats from 90 minutes postinjection to the end of the experiment, 210 minutes (VO2 from 150 to 210 minutes: C 671 +/- 45; E 429 +/- 36, P <.0004; n = 8; paired t test). VO2 of CL or CG rats was elevated between 90 and 210 minutes compared with control, but significantly (P <.01) only in the L group (C 706 +/- 31; CG 871 +/- 63; CL 984 +/- 31; n = 7-9, ANOVA). VO2 was significantly higher (P <.05) in EG rats than E rats (E 460 +/- 29; EG 654 +/- 68; n = 9-10). In the EL group, VO2 was raised but was not significantly different from E (E 460 +/- 29; EL 637 +/- 52; n = 8-10). EG rats were significantly less hypothermic between 90 and 210 minutes (58 of 132 measurements) compared with E (95 of 147; P =.0007, Fisher's Exact test), whereas the EL group were similarly hypothermic (74 of 120) to E (P =.7). Sepsis score was significantly lower in the EG group than both E and EL groups (E 4.9 +/- 0.3; EG 3.6 +/- 0.3; EL 5.0 +/- 0.3; n = 40; P <.01; ANOVA). CONCLUSIONS: Neonatal endotoxaemia lowers VO2, heat production, and body temperature. Glutamine and leucine both cause nutrient-induced thermogenesis in control animals and restore VO2 of endotoxic animals. Glutamine additionally increases rectal temperature, reduces incidence of hypothermia, and improves clinical signs of endotoxic rats. This suggests that glutamine may be beneficial for nutrition in neonatal sepsis.

Animals↗

Moderate hypothermia for uncontrolled intracranial hypertension in acute liver failure.

BACKGROUND: Increased intracranial pressure as a complication of acute liver failure has a mortality of about 90% in patients who do not respond to treatment with mannitol and ultrafiltration. We investigated the safety and efficacy of moderate hypothermia for uncontrolled increase in intracranial pressure in patients with acute liver failure. METHODS: We studied seven consecutive patients aged 16-46 years (five women, four candidates for orthotopic liver transplantation [OLT]) with acute liver failure who fulfilled criteria for poor-prognosis liver failure and had increased intracranial pressure that was unresponsive to two treatments with mannitol and ultrafiltration. We used cooling blankets to lower the patients' core temperature to 32-33 degrees C. Patients who were not suitable candidates for OLT (patients 1-3) were cooled for 8 h and then gradually rewarmed over 1 h to a baseline temperature of 37 degrees C. Patients who were suitable candidates for OLT (patients 4-7) were cooled before and during the OLT procedure. We measured cerebral blood flow and metabolic indices before and after cooling. FINDINGS: The four patients who were candidates for OLT were successfully maintained until transplantation with 13 (range 10-14) h of hypothermia. The three patients who were unsuitable candidates for OLT died after rewarming. Intracranial pressure before cooling was 45 (25-49) mm Hg and was reduced in all patients to 16 (13-17) mm Hg (p<0.05). Cerebral blood flow decreased from 103 (25-134) mL 100 g(-1) min(-1) before cooling to 44 (24-75) mL 100 g(-1) min(-1) after cooling (p<0.05). The corresponding changes for cerebral perfusion pressure was an increase from 45 (37-56) mm Hg to 70 (60-78) mm Hg (p<0.05) and for cardiac index a decrease from 9.8 (7-13) to 5.1 (4.3-6.1) L per min per m2 of body surface area. During hypothermia there was no significant relapse of increased intracranial pressure. Arterial ammonia and cerebral uptake of ammonia were significantly reduced with cooling. No adverse effects of hypothermia were observed. INTERPRETATION: Moderate hypothermia is useful in the treatment of uncontrolled increase in intracranial pressure in patients with acute liver failure and may serve as a bridge to OLT.

Acute Disease↗

External bioenergy increases intracellular free calcium concentration and reduces cellular response to heat stress.

BACKGROUND: External bioenergy (energy emitted from the body) can influence a variety of biological activities. It has been shown to enhance immunity, promote normal cell proliferation, increase tumor cell death, and accelerate bone fracture recovery. In this study, we investigated whether external bioenergy could alter intracellular calcium concentration ([Ca2+]i, an important factor in signal transduction) and regulate the cellular response to heat stress in cultured human lymphoid Jurkat T cells. METHODS: A practitioner emitted bioenergy toward tubes of cultured Jurkat cells for one 15-minute period. [Ca2+]i was measured spectrofluorometrically using the fluorescent probe indo-1. The heat shock protein 72 kd was detected using 35S-methionine prepulse and Western blot analysis. RESULTS: The resting [Ca2+]i in Jurkat T cells was 90+/-3 nM in the presence of external calcium. The removal of external calcium decreased the resting [Ca2+]i to 54+/-2 nM, indicating that Ca2+ entry from the external source is important for maintaining the basal level of [Ca2+]i. In the presence of external Ca2+, treatment of Jurkat T cells with external bioenergy for 15 minutes increased [Ca2+]i by 22+/-3%. [Ca2+]i remained elevated in these cells for 2 hours. Surprisingly, we also observed that [Ca2+]i increased by 11+/-1% if cells were simply placed in the area where external bioenergy had been used. This lingering effect of external bioenergy dissipated within 24 hours. Treatment with external bioenergy reduced cellular responses to heat stress and did not induce the production of heat shock protein 72 kd, which is known to provide cytoprotection. CONCLUSIONS: These results suggest that externally applied bioenergy can upregulate [Ca2+]i and downregulate the cellular response to stress. The association between the external bioenergy and increases in [Ca2+]i may be a good index for detecting presence of bioenergy.

Bioelectric Energy Sources↗