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At least 19 recordsLinked to original sources

Mendelian randomization analysis reveals higher whole body water mass may increase risk of bacterial infections.

BACKGROUND AND PURPOSE: The association of water loading with several infections remains unclear. Observational studies are hard to investigate definitively due to potential confounders. In this study, we employed Mendelian randomization (MR) analysis to assess the association between genetically predicted whole body water mass (BWM) and several infections. METHODS: BWM levels were predicted among 331,315 Europeans in UK Biobank using 418 SNPs associated with BWM. For outcomes, we used genome-wide association data from the UK Biobank and FinnGen consortium, including sepsis, pneumonia, intestinal infections, urinary tract infections (UTIs) and skin and soft tissue infections (SSTIs). Inverse-variance weighted MR analyses as well as a series of sensitivity analyses were conducted. RESULTS: Genetic prediction of BWM is associated with an increased risk of sepsis (OR 1.34; 95% CI 1.19 to 1.51; P = 1.57 × 10- 6), pneumonia (OR: 1.17; 95% CI 1.08 to 1.29; P = 3.53 × 10- 4), UTIs (OR: 1.26; 95% CI 1.16 to 1.37; P = 6.29 × 10- 8), and SSTIs (OR: 1.57; 95% CI 1.25 to 1.96; P = 7.35 × 10- 5). In the sepsis and pneumonia subgroup analyses, the relationship between BWM and infection was observed in bacterial but not in viral infections. Suggestive evidence suggests that BWM has an effect on viral intestinal infections (OR: 0.86; 95% CI 0.75 to 0.99; P = 0.03). There is limited evidence of an association between BWM levels and bacteria intestinal infections, and genitourinary tract infection (GUI) in pregnancy. In addition, MR analyses supported the risk of BWM for several edematous diseases. However, multivariable MR analysis shows that the associations of BWM with sepsis, pneumonia, UTIs and SSTIs remains unaffected when accounting for these traits. CONCLUSIONS: In this study, the causal relationship between BWM and infectious diseases was systematically investigated. Further prospective studies are necessary to validate these findings.

Humans

Changes in fat, fat-free mass and body water in human normal pregnancy.

Measurements of body weight, total body water and total body potassium (40K) were made serially on three occasions during pregnancy and once post partum in 27 normal pregnant women. Skinfold thickness and fat cell diameter were also measured. A model of body composition was formulated to permit the estimation of changes in fat, lean tissue and water content of the maternal body. Total maternal body fat increased during pregnancy, reaching a peak towards the end of the second trimester before diminishing. Serial measurements of fat cell diameter showed poor correlation, whilst total body fat calculated from skinfold thickness correlated well with our estimated values for total body fat in pregnancy.

Adipose Tissue

Total body water and lean body mass estimated by ethanol dilution.

Total body water (TBW) was determined on 35 subjects with a tritium (HTO) and an ethanol (ETH) dilution method, the latter using breath analyses for blood ethanol content. Lean body mass (LBM) was estimated by hydrostatic weighing. Mean values for water fraction (TBW/wt) were 0.618 +/- 0.05 with HTO and 0.603 +/- 0.06 with ETH. The difference was not significant. The correlation between the two methods was highly significant (r = 0.90, SEE = 3.5 liters, P less than 0.0001). High correlations were also found between TBW and LBM with either method for TBW (r = 0.94 with HTO, r = 0.91 with ETH). Mean values for TBW/LBM were 0.735 with HTO and 0.717 with ETH. The ETH method compares favorably with the HTO, it has the advantage that it is nonradioactive and can be repeated daily if necessary.

Body Composition

A review of body composition studies with emphasis on total body water and fat.

Tritiated water meausres a volume 4 to 15% body weight larger than that by desiccation, and, at present, only 0.5 to 2.0% of the overestimation can be explained by the exchange of hydrogen of tritiated water with those of the proteins and carbohydrates of the body. The remainder of the error is unexplained. Water in the lumen of the gut is an appreciable percentage of total body water (TBW) in many mammalian species, with the pig and the human as possible exceptions, and it should be considered an integral part of TBW. Consequently, the exclusion or inclusion of this transcellular water as part of TBW significantly affects the final TBW volume. As tritiated water exchanges with water in the gut, a comparison of the data from the indirect method with the data from the direct method can only be made when water in the gut is included in the desiccation method. Conceptually, the amount of water in lean body mass is a reflection of the actively metabolizing cell mass of the body. However, water in the gut is outside this cell mass, and if included, it significantly overestimates the water associated with the lean body mass compartment. The percentage of water in fat-free wet weight for most mature animals is estimated at 73.2%, although the mean values in the literature range from 63% for the beagle to 80% for the mouse, with the mean for the majority of species between 70 and 76%. If the percentage of water in fat-free wet weight lies between 70 and 76% for most species, then the error in calculating fat using the figure 73.2% in the equation (% fat = 100 - % TBW/0.732) is significant. In the application of this equation, the largest potential error lies in the estimation of TBW with tritiated water.

Adipose Tissue

Body composition in hypopituitary dwarfs before and during human growth hormone therapy.

The clinical characteristics and body composition of eight hypopituitary dwarfs (10.2-21.6 yr) were analyzed before and after 6 and 12 mo of growth hormone therapy. 2 IU 3 times/wk. Before treatment, growth rate was 1.8 +/- 0.7 cm/yr, height age was 2.0-12.8 yr less, and bone age 2.0-11.1 yr less than chronologic age. Total body water (TBW), lean body mass (LBM), extracellular water (ECW), and intracellular water (ICW) were below normal for chronologic age, but normal for height. Muscle mass (MM) was below normal for age and height. During HGH therapy, growth rate was 7.1 +/- 1.6 cm/yr in the first 6 mo and 7.8 +/- 1.4 cm/yr during the next 6 mo; the ratio of change in height age to change in chronologic age was greater than or equal to 1.0 in all patients and the ratio of change in bone age to change in height age was 1.2 in one patient and less than or equal to 1.0 in the others. TBW, LBM, ECW, and ICW increased according to height increments; however, MM increased at a faster rate than expected from the height gains. Also, a relative or absolute loss of total body fat was recorded during the first 6 mo of therapy. It is suggested (1) that among the body composition parameters studied, muscle mass is the tissue most closely reflecting the lack of HGH and also its therapeutic benefits and (2) evaluation of body composition in hypopituitary dwarfs in response to HGH therapy shows striking changes not reflected by the determination of stature or weight alone.

Adolescent

Assessment of protein reserves (cellular mass) in Aboriginal children.

The body protein reserves, assessed indirectly by the measurement of intracellular water, was determined in free-living Aboriginal children and adolescents located in Central and Northwestern Australia. Fifty one individuals were studied--31 males and 20 females. Significant reductions were observed in intracellular water or cell mass relative to the cube of body length for Aboriginal females when compared to a control female group. Only marginal or borderline differences for the same parameters were observed when Aboriginal males were compared with controls. Comparison of Aboriginal females with Aboriginal males demonstrated significant reductions in cell mass (intracellular water) relative to body length cubed in the female. This finding in the Aboriginal female is of concern because many become pregnant in the early teenage years. Evidence was found during the course of this study that plasma zinc concentrations were frequently low. This led to a concomitant study on serum and plasma trace metals in two Aboriginal settlements (364 individuals) to be published in a subsequent paper.

Adolescent

Body water compartments with human aging using fat-free mass as the reference standard.

Forty-five healthy men and women aged 16-39 and 59-89 yr were studied for total body water (TBW) and extracellular water (ECW); intracellular water (ICW) was calculated as the difference (ICW = TBW - ECW). An independent measurement of total body fat by inert gas uptake provided a value (+/- 2%) for fat-free mass (FFB is wt minus body fat). Results agreed with observations by others that TBW and ICW are lower in the aged and lower in women, whether expressed as absolute volumes or per unit of weight, surface area, or height. However, with FFB as the reference standard very different aging trends appeared. TBW/FFB remained constant to our oldest measured subjects (704 +/- 7 ml/kg). ICW/FFB was slightly lower at advanced age, but the 4-5% decrease for each sex was within statistical variability. With age ECW increased slightly and its proportion within the fat-free body (ECW/FFB) was significantly higher. Based upon FFB, the distribution, proportions, and aging trends of body water compartments were similar for men, women, and male rats. Although its potential limitations must be appreciated, the FFB appears widely useful as a reference standard. The stability of ICW volume and of fat-free mass in aging man does not support the hypothesis that cellular mass is lost by healthy mammals with age.

Adipose Tissue

Simplified body-composition analysis using deuterium dilution and deuteron photodisintegration.

A number of approaches to estimating human body composition (water, lean mass, and fat) are available, and each approach has its own limitations. Deuterium dilution is a comparatively safe and valid procedure for assessing body composition; however, its use has been restricted by the relative complexity of measuring deuterium at low concentrations. A simplified scheme for quantifying low levels of deuterium in body fluid samples promises to expand the use of D2O in body composition studies. The deuterons are quantified by measuring the neutron emission induced by gamma-ray irradiation from 228Th(2.61 MeV). The in vitro aspects of the procedure exhibit coefficients of variation of under 1% throughout the range of assay and near 100% recovery of added D2O. In vivo comparison studies with a reference tritium dilution procedure indicate close agreement in a group of 38 subjects. The chief advantages of the procedure are a small oral dose of D2O and the use of either serum or urine samples. The physical condition of the sample does not affect the measurement so distillation is not required. Thus, small medical facilities can enjoy the advantages of low cost, minimum patient inconvenience, and technical simplicity by submitting subject samples to larger agencies for analysis.

Adipose Tissue

[Nutritional status in critically ill patients. Relationship with mortality (author's transl)].

Plasma proteins, triglyceridemia, body composition and delayed hypersensitivity were determined in 154 critically ill patients after admission. Plasma proteins levels were significantly increased in patients that were subsequently discharged vs. those that died: albumin: 33 +/- 6 g/l vs 28 +/- 6 g/l (p < 10(-6)); transferrin 2,18 +/- 0,65 g/l vs. 1,54 +/0 0,55 g/l (p < 10(-7)); prealbumin: 14,32 +/- 7,79 mg/100 ml vs. 7,28 +/-5,36 mg/100 ml (p < 10(-7)) and triglyceridemia was decreased: 1,07 +/- 0,38 g/l vs. 1,66 +/- 1,12 g/l (p not equal to 10(-3)). Body weight, fat weight and lead body mass were not correlated to subsequent mortality. Muscle cell mass was decreased (-17%, p < 10(-2)) and extracellular water was increased (+14%, p < 10(-4)), in patients who subsequently died. Total body water and visceral cell mass did not change. Initial anergy (tested with 3 antigens: candidin, tuberculin, varidase) did correlate with mortality: 35/62 died when delayed hypersensitivity was negative vs. 13/71 when it was positive (p < 10(-4)). Mortality was associated with decreased total lymphocyte count: 884 +/- 1025 vs. 1270 +/- 870 (p < 0,02) and serum iron: 51 +/- 40 micrograms/100 ml vs. 74 +/- 45 micrograms/100 ml (p < 10(-2)). Sepsis correlated with mortality (p < 10(-3)) and could produce these changes. These results suggest that critically ill paients have a protein-calorie malnutrition syndrom marktly different from that observed in simple starvation. Nutritional therapy must be, in this group of patients, adapted to this concept.

Adolescent

Behavioral effects of strong 60-Hz electric fields in rats.

Eight individually housed male Long Evans rats were raised, beginning at age 30 days, for six weeks in an electric field exposure apparatus. During five of the six weeks, the animals were exposed to a 25 kV/m, 60-Hz electric field. A similar population of rats housed in an identical environment, except for the absence of the high voltage field, were used as control animals. Differences between the two groups in body mass, food and water intake, and exploratory activity were studied. Statistical analysis shows the high voltage fields to have no significant effects on the above parameters.

Animals

How to minimize side effects of psychotropic drugs.

Aging has a direct effect on drug absorption, distribution, and elimination. With aging, there is an alteration in the neurotransmitters whereby dopaminergic and catecholaminergic systems are relatively depleted of monoamines while acetylcholine is largely unaffected. Pharmacotherapy in the elderly requires an understanding of the physiologic effects of medications. Dosage generally should be lower for the elderly patient on the basis of a milligram per kilogram of body weight, but determining the appropriate dosage required more than allowing for "smaller body mass" or "less body water." Because of lengthened half-life and slowed distribution of medications, it is necessary to start with very low dosages and observe the patient for relatively longer periods of time before giving another dose, increasing the medication, or adding another drug.

Aged

Design and use of an inhalation chamber for air pollution studies in small animals.

Environmental chambers provide a convenient means of studying the toxicology of gases in experimental animals. The specialised equipment needed for these studies is not commercially available. This paper reports on the design, construction and performance of a simple, and inexpensive, inhalation chamber and gas mixing unit for air pollution studies in small laboratory animals. Provision has been made for controlling the mixing of gases, the ventilation rate, the even distribution of gases in the chamber and for the removal of vented gases to prevent the hazard of air pollution in the laboratory animal facility. No significant differences were found between the food and water consumption and body mass gain of a group of rats housed in the chamber for 5 days and a control group housed im similar cages located in a rodent room and managed under conventional laboratory conditions. The chamber fulfills all the requirements for an animal inhalation system.

Air Pollutants

Electrolytes and whole body potassium in acute leukemia.

In a consecutive series of 22 patients with acute leukemia, the total body potassium was studied in 18 patients on 39 occasions during relapse and remission. Total body water was also determined. A control group consisting of 88 age-matched healthy volunteers was also studied. The patients had a significantly lower mean potassium concentration, per kg body weight, per kg lean body mass and per kg water, than the controls (p less than 0.001). Individually, 11 out of the 18 patients had at least one value below the lower 95% confidence limit. Hypokalemia was frequent both in the patients with low (7/11) and normal (3/6) potassium per kg lean body mass. Five of 13 investigated patients showed laboratory indications of secondary hyperaldosteronism, which might be partly responsible for the hypokalemia. Increased serum or urine levels of lysozyme were found in 62% of the patients.

Adult

Resting metabolic rate, weight, surface area and body composition in obese women.

Resting metabolic rate was measured in 22 women with varying degrees of obesity. Body composition was estimated from total body potassium and from total body water, and creatinine excretion in urine was measured over a period of three weeks while the patients were on a creatinine and creatine-free reducing diet. Resting metabolic rate was highly significantly correlated with body weight, surface area, creatinine excretion and lean body mass calculated either from potassium or water measurements (P less than 0.001). Correlation with adipose tissue was less strong, and when multiple regression of both fat and lean on metabolic rate was performed, the relationship was seen to depend mostly on the mass of lean rather than adipose tissue. In obese people the water content of fat-free tissue is greater than that in normal subjects, so it is not valid to assume that fat content can be calculated accurately from a measurement of total body water.

Adipose Tissue

Body water distribution after operation.

The effect of a major surgical procedure on the distribution of body water was investigated in two groups of patients. The first group of four patients did not receive any salt during the first 24 hours following operation, while the second group of five patients received a moderate amount of isotoric saline solution during this period. For seven days prior to operation, the patients were maintained by bed rest and a daily intake of 100 milliequivalents of sodium and 100 milliequivalents of potassium. A multiple isotope dilution technique was used, before and after operation, to measure red cell mass, plasma volume, extracellular water, total body water and total exchangeable sodium. In addition, the aldosterone secretion rate was measured, both before and after operation, to assess the physiologic control of the extracellular water volume. In the patients who did not receive any salt, the mean extracellular water volume decreased following operation from 39.7 to 37.5 per cent of the total body water; a mean decrease of 0.9 liter while the aldosterone secretion rate increased significantly, p less than 0.02, by 101 per cent from 206 to 414 micrograms per day. In the second group of patients who received an average of 1.3 liters of isotonic saline solution during the first 24 postoperative hours, the extracellular water increased from 37.9 to 42.8 per cent of total body water; a mean increase of 1.1 liters p less than 0.02. The mean aldosterone secretion rate in this group of patients increased by only 13 per cent from 167 to 188 micrograms per day. The blood volume did not change in either group as a result of operation. These data support the hypothesis that, following operation, sequestration of extracellular water occurs within the injured tissues, necessitating the postoperative infusion of a moderate amount of a balanced salt solution.

Adult

[Possibilities of calculating the fat-free body mass and its reaction to a carbohydrate-poor, fat-rich diet].

9 healthy medical students got an isocaloric fat-rich carbohydrate-reduced diet during 14 days. Body-weight and lean body mass were registrated. We calculated lean body mass from measurement of skinfold thickness, total body potassium and total body water. Body-weight was reduced highly significantly by 3.4 kg on an average. Body potassium and body water remained unchanged. It can be concluded from these results that weight loss was caused by an exclusive reduction of the fat mass.

Adult

Physiological and behavioral effects of chronic exposure to 2450-MHz microwaves.

Long-Evans male adult rats were exposed for sixteen weeks to 2450-MHz CW microwaves at an average power density of mW/cm2. The resulting dose rate was 1.23 (+/- 0.25SEM) mW/g. The animals were exposed eight hours a day, five days a week, for a total of 640 h in a monopole-above-ground radiation chamber while housed in Plexiglas holding cages. Daily measures of body mass and of food and water intakes indicated no statistically significant effects of microwave irradiation. Biweekly stabilimetric tests immediately after exposure revealed a significant depression of behavioral activity by 15 microwave-exposed rats as compared with 15 sham-exposed animals. Measures of locomotor activity based on revolutions of a running wheel, which were obtained during 12-h periods between each 8-h exposure, showed no significant effect of irradiation. Blood sampled after 2, 6, 10, and 14 weeks of exposure indicated slight alterations of sulfhydryl groups, and of red and white blood-cell counts. Measures of levels of 17-ketosteroids in urine at weeks 1, 5, 9, and 12 of exposure, and mass of adrenals, heart, and liver at the end of the sixteen-week period of exposure, revealed no indications of stress.

Animals

Assessment of obesity in pigtailed monkeys (Macaca nemestrina).

Obesity was studied in a colony of 873 Macaca nemestrina to establish tools for epidemiologic studies, to examine a genetic form of obesity, to document age/sex relationships to obesity, and to compare metabolic profiles of obese and normal monkeys. Age/weight growth curves were analyzed to select the most obese monkeys and age- and sex-matched normal controls. Degree of adiposity was determined using tritiated water for estimation of lean body mass. Body weight, anterior trunk height, and abdominal and triceps skinfolds were measured. Fasting insulin, fasting free fatty acids, and glucose disappearance rate were determined. The results give evidence of similarities between macaque and human obestiy.

Age Factors