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Extra protein loss not caused by surgical bleeding in patients with ovarian cancer.

BACKGROUND: [corrected] Clinical experience in patients with ovarian cancer has shown special difficulties in maintaining cardiovascular stability during surgery. METHODS: To evaluate the causes for this observation, 15 patients with benign ovarian tumours (group I) and 13 patients with ovarian cancer (group II) were investigated perioperatively. Plasma volume (indocyanine green-dilution technique), haematocrit, plasma protein concentration, mean arterial pressure, heart rate, and central venous pressure were measured immediately before and after cytoreductive surgery. RESULTS: Normal values of blood-, plasma-, and red cell volume were determined preoperatively in both groups, and in relation to body surface area there were no intergroup differences of these parameters. In group I, the significant decrease in red cell volume of 313 ml postoperatively was compensated for by an increase in plasma volume of 371 ml (median values). In contrast to group I, the decrease in red cell volume of 328 ml in group II was not related to a significant increase in plasma volume, so that blood volume postoperatively was 483 ml lower than preoperatively, although the same standardized infusion regimen as in group I was applied. Patients of group II had a significantly higher loss of intravascular protein (49 g vs 13 g in group I), which left the intravascular space by another way than by surgical bleeding. This extra protein loss is termed Intraoperative Protein Shift (IPS). CONCLUSION: IPS could be an important quantity in perioperative fluid balance. We assume that different surgical procedures predispose to occurrence of differing amounts of IPS.

Adult↗

High tidal volume and positive fluid balance are associated with worse outcome in acute lung injury.

STUDY OBJECTIVES: Recent data have suggested that ventilatory strategy could influence outcomes from acute lung injury (ALI) and ARDS. We tested the hypothesis that infection/sepsis and use of higher tidal volumes than those applied in the ARDS Network (ARDSnet) study (> 7.4 mL/kg of predicted body weight) would worsen outcome in patients with ALI/ARDS. DESIGN: International cohort, observational study. SETTING: One hundred ninety-eight European ICUs participating in the Sepsis Occurrence in Acutely Ill Patients study. PATIENTS OR PARTICIPANTS: All 3,147 adult patients admitted to one of the participating ICUs between May 1, 2002, and May 15, 2002. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Patients were followed up until death, hospital discharge, or for 60 days. Of the 3,147 patients, 393 patients (12.5%) had ALI/ARDS. ICU and hospital mortality was higher in patients with ALI/ARDS than those without ALI/ARDS (38.9% vs 15.6% and 45.5% vs 21.0%, respectively; p < 0.001). A multivariable logistic regression analysis with ICU outcome as the dependent factor showed that the independent risks for mortality were as follows: presence of cancer, use of tidal volumes higher than those used by the ARDSnet study, degree of multiorgan dysfunction, and higher mean fluid balance. Sepsis, septic shock, and oxygenation at the onset of ALI/ARDS were not independently associated with higher mortality rates. CONCLUSIONS: In addition to comorbidities and organ dysfunction, high tidal volumes and positive fluid balance are associated with a worse outcome from ALI/ARDS.

Aged↗

The pathophysiological role of water-sodium balance and renal dopaminergic activity in overweight patients with essential hypertension.

Studies were conducted to evaluate the role of water-sodium balance and renal dopaminergic activity in the hypertensive mechanisms of overweight patients with essential hypertension (EHT). The body mass index (BMI) was correlated positively with mean arterial pressure, plasma volume, extracellular fluid volume, or total exchangeable sodium and negatively with plasma noradrenaline concentration or plasma renin activity in patients with EHT. Fractional excretion of sodium (FENa) was significantly lower in overweight patients than in normal weight patients with EHT. Hypotensive effect of sodium restriction or the natriuretic response to infused dopamine was more remarkable in overweight patients with EHT than in normal weight patients with EHT. Urinary excretion of free dopamine (UDA) was correlated positively with simultaneously measured urinary excretion of sodium or FENa and negatively with the natriuretic response to dopamine infusion. In addition, UDA was positively correlated with the BMI in normal weight patients with EHT, whereas the relation between the UDA and the BMI was significantly negative in overweight patients with EHT. These findings suggest that the expansion of body fluid volume and sodium might result from the blunted natriuretic ability due to an attenuation of the renal dopaminergic activity in overweight patients with EHT. The expansion of body fluid volume and sodium may play an important role in the hypertensive mechanisms of overweight patients with EHT.

Adult↗

Nutritional efficacy of a spermidine supplemented diet.

Polyamines (PA) are ubiquitous cell components essential for growth. Dietary PAs are directed preferentially to tissues and organs that have been stimulated to grow by metabolic signals. Nutritional efficacy and growth potential of an oral PA supplement, spermidine (SD), was examined in growing rats. A group of 24-male Sprague-Dawley rats (200-220 g) was adapted to our vivarium conditions for 3 d, then fed ad libitum continuously for 14 d. During feeding they received either a basal diet (n = 8) or a test diet containing the basal diet with 0.05% SD (test diet 1, n = 8) or 0.10% SD (test diet 2, n = 8). This dose of SD corresponds to an intake of 54 and 108 mumol of SD per rat per day. At the end of 14 d of feeding, the animals were sacrificed and plasma, cerebral spinal fluid (CSF) and tissues (muscle, brain, and liver) were harvested for amino acid analysis. Voluntary food intake, body weight gain, and nitrogen excretion and balance were significantly decreased in test diet 2 fed rats compared to test diet 1. The opposing trends in the accumulation/depletion of free amino acids (AA) in muscle and plasma suggests that the exogenous supply of SD blocks the transport of amino acids, as well as PAs from the cells, since AA and PA share the same transport systems. A trend toward decreased weight gain and feeding efficiency was observed when high concentrations of SD were fed. It was concluded that feeding of SD at moderate intake is not toxic and does not retard growth. Oral administration of a smaller dose (<0.05%) of SD may promote further growth. The optimal level of SD dietary supplementation has thus yet to be established.

Amino Acids↗

Surfactant in the gas mantle of the snail Helix aspersa.

Surfactant occurs in cyclically inflating and deflating, gas-holding structures of vertebrates to reduce the surface tension of the inner fluid lining, thereby preventing collapse and decreasing the work of inflation. Here we determined the presence of surfactant in material lavaged from the airspace in the gas mantle of the pulmonate snail Helix aspersa. Surfactant is characterized by the presence of disaturated phospholipid (DSP), especially disaturated phosphatidylcholine (PC), lavaged from the airspace, by the presence of lamellated osmiophilic bodies (LBs) in the airspaces and epithelial tissue, and by the ability of the lavage to reduce surface tension of fluid in a surface balance. Lavage had a DSP/phospholipid (PL) ratio of 0.085, compared to 0.011 in membranes, with the major PL being PC (45.3%). Cholesterol, the primary fluidizer for pulmonary surfactant, was similar in lavage and in lipids extracted from cell homogenates (cholesterol/PL: 0.04 and 0. 03, respectively). LBs were found in the tissues and airspaces. The surface activity of the lavage material is defined as the ability to reduce surface tension under compression to values much lower than that of water. In addition, surface-active lipids will vary surface tension, increasing it upon inspiration as the surface area expands. By these criteria, the surface activity of lavaged material was poor and most similar to that shown by pulmonary lavage of fish and toads. Snail surfactant displays structures, a biochemical PL profile, and biophysical properties similar to surfactant obtained from primitive fish, teleost swim bladders, the lung of the Dipnoan Neoceratodus forsteri, and the amphibian Bufo marinus. However, the cholesterol/PL and cholesterol/DSP ratios are more similar to the amphibian B. marinus than to the fish, and this similarity may indicate a crucial physicochemical relationship for these lipids.

Adaptation, Physiological↗

Protein and energy depletion in chronic hemodialysis patients: clinical applicability of diagnostic tools.

Protein and energy depletion states are common and associated with increased morbidity and mortality in chronic hemodialysis (CHD) patients. Therefore, proper use of diagnostic tools to assess depleted states in CHD patients is critical. Assessment of protein and energy status can be done by an array of methodologies that include simple estimates of the visceral and somatic pools of protein to more refined techniques to measure protein and energy balance. The nutritional and metabolic derangements in the CHD population are highly complex and can be confounded by multiple comorbidities and fluid shifts between body compartments. Therefore, assessment of protein and energy status in CHD patients requires a wide range of methodologies that not only identify depleted states but also monitor nutrition therapy and predict clinical outcome. Most important, these methods require cautious and individualized interpretation in order to minimize the interference of comorbid conditions frequently observed in the CHD population. Currently, there is not a single method that can be considered the gold standard for assessment of protein and energy status in CHD patients. Therefore, a combination of methods is recommended. In this review, we describe available methods to assess protein and energy status, with special considerations pertaining to CHD patients.

Biomarkers↗

The role of peritoneal dialysis in renal replacement therapy: an update on medical aspects.

In this brief review, we discuss various medical factors that are of importance for the role of peritoneal dialysis (PD) in renal replacement therapy (RRT), whereas the complex role of non medical factors will only be mentioned briefly. The aim of any RRT, including hemodialysis, PD and renal transplantation, is to normalize the volume and composition of the body fluids, to remove uremic toxins, and to improve clinical outcome. In the following, we will focus on adequacy, preservation of residual renal function, fluid balance, infections, nutrition, cardiovascular disease and systemic inflammation in PD as these factors are strong predictors of clinical outcome in end stage renal disease patients.

Humans↗

A physiologic approach to fluid therapy in severely burned children.

Fluid balance data in 30 severely burned children hydrated according to a fluid resuscitation program were reviewed. The formula to estimate fluid requirements is based upon body surface area and surface area burned rather than weight. It uses two independent figures to estimate maintenance fluid needs and fluid requirements as a result of the burn. A standard isotonic solution containing 12.5 grams of human serum albumin is used for hydration. The state of hydration is monitored using several clinical and laboratory guides. The use of hourly urine volume for this purpose has been de-emphasized. Although no complications directly related to fluid therapy were encountered, five of the 30 children died as a result of septicemia five, ten, 12, 23 and 37 days postburn, respectively. A maximal weight increase following resuscitation averaged 4 kilograms per square meter of body surface burned. The volumes of urine that can be expected from patients similarly resuscitated have been defined. This program is safe, accurate and effective for a wide range of burn sizes and age groups.

Adolescent↗

A spermine-coupled cholesterol metabolite from the shark with potent appetite suppressant and antidiabetic properties.

OBJECTIVE: We describe the pharmacological properties of a novel spermine-cholesterol adduct, MSI 1436 (3beta-N-1(spermine)-7alpha, 24R-dihydroxy-5alpha-cholestane 24-sulfate), which causes reversible suppression of food and fluid intake in mammals resulting in profound weight loss, not associated with other signs or symptoms of illness, and which exhibits antidiabetic properties in genetically obese mice. METHODS: Wild-type rodents and strains with genetic obesity were studied. Effects on food and fluid intake, body weight and composition were examined along with pharmacological and toxicological parameters. RESULTS: MSI-1436 induces profound inhibition of food and fluid intake in rats and mice, resulting in significant weight loss. MSI-1436 is active when introduced directly into the third ventricle of the rat, suggesting the compound acts on central targets. Pair-feeding studies suggest that MSI-1436 causes weight loss by suppressing food intake. Fluid intake is also profoundly reduced but animals remain normally hydrated and defend both water and electrolyte balance from parenteral administration. MSI-1436 is active in ob/ob, db/db, agouti and MC4 receptor knockout mice. MSI-1436 has been administered to ob/ob mice over a 4 month period via a regimen that safely controls body weight, glucose homeostasis and serum cholesterol levels. Following MSI-1436 treatment, db/db mice preferentially mobilize adipose tissue and hyperglycemia is corrected. CONCLUSION: A naturally occurring spermine metabolite of cholesterol, isolated from the dogfish shark, Squalus acanthias, has been identified that induces profound reduction in food and fluid intake in rodents in a setting where thirst is preserved and fluid and electrolyte homeostasis appears to be functioning normally. MSI-1436 probably acts on a central target involving neural circuits that lie downstream from the leptin and the MC4 receptors. Although long-term administration can be accomplished safely in mice, the utility of this compound as a potential human therapeutic awaits an analysis of its pharmacological properties in man.

Animals↗

Influence of saline infusion on blood-tissue albumin transport.

Anesthetized rats were infused with lactated Ringer solution (LR) at constant rate for 30 or 60 min; delivered volume loads ranged from 0.03 to 0.08 ml/g body wt. Controls were given only a sustaining infusion of saline at 0.002 ml.g-1.h-1. Only 7-14% of the LR remained in the plasma at the end of the infusion; 76-88% entered the interstitial compartment, and 7-17% was excreted. The amount of plasma protein lost from the circulation with the extravasated fluid was studied simultaneously by two methods: 1) material balance in the whole animal and 2) changes in 131I-labeled albumin uptake (VA) and water content (VW) in individual tissues. The extravasation of 0.03-0.06 ml fluid/g body wt (75-160% initial plasma volume) did not significantly increase plasma protein extravasation in the whole rat. Nearly all of the sampled tissues of LR-infused rats had higher VW than controls. Tissue VA tended to increase with VW, but the regression slopes (delta VA/delta VW), a measure of the tracer albumin concentration of capillary filtrate relative to plasma, were low; skin, 0.006; paw, 0.018; skeletal muscles, 0.007; heart, 0.057; jejunum, 0.095; ileum, 0.045; cecum, 0.026; and colon, 0.027. These ratios are consistent with the very small loss of total plasma protein observed and attest to high solvent-drag reflection coefficients (sigma approximately equal to 1 - delta VA/delta VW): greater than 0.98 in capillaries of skeletal muscles, skin, and paw and 0.91-0.97 in heart and intestine.

Animals↗

Comparison of body fluid compartment sizes in Brattleboro homozygous and Long-Evans rats.

Because of their hypothalamic diabetes insipidus (DI), Brattleboro homozygous rats exhibit profound polyuria and polydipsia with elevated plasma osmolalities. This combination of symptoms has led to the tacit assumption that these animals are chronically volume contracted. However, the few direct measurements that have been published indicate otherwise. In the present study, total body water (TBW), total body lipid content, and plasma volume were measured in conscious DI rats and compared with corresponding values in weight-matched conscious Long-Evans (LE) rats. Fat content of DI rats (5.0 +/- 0.4 g/100 g body wt) was significantly lower than that of LE rats (7.6 +/- 0.6, P less than 0.005). TBW was not significantly different between the two strains whether expressed as milliliters per 100 g wet wt (DI 69.2 +/- 0.4 vs. LE 67.7 +/- 0.7) or as milliliters per 100 g fat-free wet wt (DI 73.4 +/- 0.5 vs. LE 73.3 +/- 0.4). Plasma volume of DI rats (4.4 +/- 0.1 ml/100 g body wt) was significantly higher than that of LE rats (3.9 +/- 0.2, P less than 0.025). Extracellular fluid volume was similar in the two strains although, for this measurement, the animals were neither weight- nor age-matched. Accordingly, the data indicate that under the conditions of this study the DI rat is not chronically volume contracted. It would appear that, given an adequate water supply, water balance can be achieved via the thirst mechanism, perhaps abetted by vasopressin-independent mechanisms of urine concentration.

Adipose Tissue↗

Protease and antiprotease concentrations in serum and vaginal fluid of patients with carcinoma of the cervix.

The capacity of malignant cells to invade and disseminate throughout the tissues is partly due to the fact that these cells synthesize and secrete proteases and plasminogen activators. Its growth can be inhibited by antiproteolytic substances in vitro or by natural inhibitors such as alpha-1-antitrypsin (A1AT) and alpha-2-macroglobulin (A2MG). It is a known fact that in cervical cancer, serum A1AT levels are elevated, but so far it has not been determined if serum proteolytic activity is elevated and if both occur simultaneously in vaginal fluid. 32 cases of invasive carcinoma of the cervix, and 25 non-cancerous women were studied. A1AT, A2MG, cathepsin B, trypsin inhibitory capacity (TIC), plasminogen and proteins in plasma and vaginal fluid were studied. In cancer cases, proteolytic activity of serum and vaginal fluid (cathepsin B) is elevated, when compared to controls (p less than 0.001). A1AT and A2MG levels are clearly elevated in plasma, but not in the vaginal fluid; TIC was elevated in serum in cancer cases (1.31 vs. 1.74 p less than 0.005) but was not altered in vaginal fluid. It was found that in cases of carcinoma in situ cathepsin B, plasminogen, A1At and A2MG and CIT were significantly increased (p less than 0.001, p less than 0.001, p less than 0.001 and p less than 0.01 respectively). In vaginal fluid the only statistically significant figure increased was cathepsin B (p less than 0.001). These studies show an altered protease-antiprotease balance in patients with carcinoma of the cervix uteri.

Adult↗

Glutathione-conjugated arsenics in the potential hepato-enteric circulation in rats.

The metabolic pathways for arsenic were precisely studied by determining the metabolic balance and chemical species of arsenic to gain an insight into the mechanisms underlying the animal species difference in the metabolism and preferential accumulation of arsenic in red blood cells (RBCs) in rats. Male Wistar rats were injected intravenously with a single dose of arsenite (iAs(III)) at 2.0 mg of As/kg of body weight, and then the time-dependent changes in the concentrations of arsenic in organs and body fluids were determined. Furthermore, arsenic in the bile was analyzed on anion and cation exchange columns by high-performance liquid chromatography-inductively coupled argon plasma mass spectrometry (HPLC-ICP MS). The metabolic balance and speciation studies revealed that arsenic is potentially transferred to the hepato-enteric circulation through excretion from the liver in a form conjugated with glutathione (GSH). iAs(III) is methylated to mono (MMA)- and dimethylated (DMA) arsenics in the liver during circulation in the conjugated form [iAs(III)(GS)(3)], and a part of MMA is excreted into the bile in the forms of MMA(III) and MMA(V), the former being mostly in the conjugated form [CH(3)As(III)(GS)(2)], and the latter being in the nonconjugated free form. DMA(III) and DMA(V) were not detected in the bile. In the urine, arsenic was detected in the forms of iAs(III), arsenate, MMA(V), and DMA(V), iAs(III) being the major arsenic in the first 6-h-urine, and DMA(V) being increased in the second 6-h-urine. The present metabolic balance and speciation study suggests that iAs(III) is methylated in the liver during its hepato-enteric circulation through the formation of the GSH-cojugated form [iAs(III)(GS)(3)], and MMA(III) and MMA(V) are partly excreted into the bile, the former being in the conjugated form [CH(3)As(III)(GS)(2)]. DMA is not excreted into the bile but into the bloodstream, accumulating in RBCs, and then excreted into the urine mostly in the form of DMA(V) in rats.

Animals↗