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Biomedical subjects

P R Schloerb

Publications and source records attributed to P R Schloerb.

At least 19 recordsLinked to original sources

Glutamine in the support of patients following bone marrow transplantation.

Bone marrow transplantation is being utilized with increasing frequency in the treatment of patients with malignancy; it is also being applied to the treatment of patients with genetic diseases and as an adjunct to solid organ transplantation. The high dose cytotoxic chemotherapy, often accompanied by total body irradiation, results in severe catabolism, disruption of the gastrointestinal mucosa and marked immunosuppression. A variety of studies show that the supplementation of the amino acid glutamine, by the enteral or parenteral route, as either the free or dipeptide form, appears safe and efficacious in patients undergoing bone marrow transplantation. Further double-blind controlled clinical trials of glutamine supplementation in patients undergoing bone marrow transplantation and receiving more contemporary treatment, which often includes the administration of novel combinations of cytoreductive agents and hematopoietic growth factors, are warranted.

Administration, Oral↗

Patterns and problems of adult total parenteral nutrition use in US academic medical centers.

OBJECTIVE: To determine the pattern of total parenteral nutrition (TPN) use in US academic medical centers because TPN in adults may be associated with complications related to excessive glucose (dextrose) administration and a respiratory quotient greater than 1.0. DESIGN: Two surveys of the University HealthSystems Consortium (n = 106, 74 members and 32 network partners using TPN) to determine TPN formulas and amounts of TPN nutrients given to 2 hypothetical abdominal trauma patients (1 man and 1 woman), each of whom weighed 70 kg. MAIN OUTCOME MEASURES: Amounts of dextrose, amino acids, and fat and rates of administration of TPN. RESULTS: In the first survey, 80% (59/74) of members and 41% (13/32) of network partners of the University HealthSystems Consortium reported using TPN formulas with more than 20% dextrose; half used 25% dextrose. In the second survey, the mean (+/-SD) TPN dextrose concentrations were 190+/-43 and 170+/-45 g/L (902+/-204 and 807+/-214 mmol/L), with amino acid concentrations at 40 to 50 g/L, in the male and female patients, respectively. The amounts of amino acids and glucose given, when referred to body cell mass in the male and female patients, were equivalent. In 26% (22/86) of the institutions surveyed, the amounts of glucose given in TPN were high enough (>4.48 mg/kg per minute) to produce a respiratory quotient greater than 1.0. A standard TPN formula was derived as 4.25% amino acids, 15% dextrose, and 20% fat emulsion, at a rate to provide required calories. CONCLUSION: Excessive TPN glucose administration, found in at least one fourth of US academic medical centers, suggests use of a TPN formula with no more than 15% dextrose, administered at a rate to provide no more than 4 mg/kg of glucose per minute.

Abdominal Injuries↗

Relative validity of clinical techniques for measuring the body composition of persons with amyotrophic lateral sclerosis.

Tracking body composition is necessary to understand how amyotrophic lateral sclerosis (ALS) is affecting a patient's morphology and to provide a basis for appropriate nutritional advice throughout disease progression. Dual X-ray absorptiometry (DEXA) has been shown to reliably detect body composition changes in persons with ALS. However, this procedure is expensive and available primarily for research. The purpose of this study was to determine the relative validity of two common clinical techniques, anthropometry and bioelectrical impedance analysis (BIA), for measuring the body composition of persons with ALS. Twenty-three persons with ALS volunteered for the study; seven with primarily bulbar symptoms, five with primarily arm weakness, five with primarily leg weakness, and six with significant weakness in all extremities. On a single day subjects underwent body composition analysis by the three techniques, with DEXA serving as the criterion method. Anthropometry and BIA results were converted to lean and fat mass using eight prediction equations commonly cited in the literature. Anthropometry measures were also converted to estimates of muscle mass using two additional equations. Both BIA and anthropometry tended to overestimate lean mass and underestimate fat mass compared to DEXA. However, the BIA prediction equations had smaller mean differences, larger correlations, and smaller standard errors of estimate than the anthropometry equations. The Lukaski et al. BIA equation (Lukaski, H.C., Bolonchuk, W.W., Hall, C.B., Siders, W.A., 1986. Validation of tetrapolar bioelectrical impedance method to assess human body composition. J. Appl. Physiol. 60, 1327-1332) most closely matched the values derived by DEXA and is probably the best method for measuring the lean and fat mass of persons with ALS, as long as they maintain adequate hydration levels. The Heymsfield et al. equation (Heymsfield, S.B., McManus, C., Smith, J., Stevens, V., Nixon, D.W., 1982. Anthropometric measurement of muscle mass: revised equations for calculating bone-free arm muscle area. Am. J. Clin. Nutr. 36, 680-690) for estimating muscle mass may also be a useful clinical tool for this population. Further longitudinal studies are needed to determine whether the equations that correlated best with DEXA at a single point in time are also sensitive enough to detect changes in body composition over a period of time.

Absorptiometry, Photon↗

Bioelectrical impedance in the clinical evaluation of liver disease.

Liver disease is often characterized by an accumulation of excess body water as ascites, edema, or both. It was our purpose, using bioelectrical impedance analysis (BIA), to measure total body water (TBW) and extracellular water (ECW) in 35 patients with end-stage liver disease, including those undergoing orthotopic liver transplantation and, in 15 of these patients, to compare these values with measurements of TBW by deuterium oxide and of ECW by bromide dilutions. Poor correlation of TBW derived from BIA with TBW by deuterium dilution was found (r = 0.36, P = 0.35). In 19 patients, in whom TBW and ECW were not measured by dilution studies, 158 BIA measurements were taken for determining TBW. In 15 orthotopic liver transplantation patients with various amounts of fluid overload, a modest correlation was found between short-term weight change and BIA (r = 0.38, p = 0.001). In patients with fluid overload not exceeding 25% of ECW, ECW correlated with reactance (r = -0.96, P = 0.0025). TBW and ECW were covariant (r = 0.68, P = 0.01). In three patients with cirrhotic ascites, impedance measurements were taken with source electrodes on the hand and foot and detector electrodes on the abdomen during paracentesis of 8-11 L. Calculated volume of ascites correlated with measured volume (r = 0.99, P = 0.001). Segmental electrode placement and parallel impedance measurements were effective in determining ascites fluid volume.

Adult↗

Optimum doses of deuterium oxide and sodium bromide for the determination of total body water and extracellular fluid.

A practical approach for determining optimum tracer doses is described for measurements of total body water (TBW) and extracellular water (ECW) based on dilution of deuterium oxide and sodium bromide with respective analyses by nuclear magnetic resonance and anion-exchange chromatography. Using these techniques and plasma concentrations corresponding to adult doses up to 1.5 g kg-1 body weight of deuterium oxide and 0.05 g kg-1 of sodium bromide, the variations of analyses of these tracers, at these respective doses, were calculated. TBW determination with an RSD of less than 2% was found to require administration of 0.4 g kg-1 of deuterium oxide. Because basal concentrations of bromide are quantifiable, the accuracy of the extracellular water determination depends upon the magnitude of the increase in plasma bromide concentration; a sodium bromide dose of 0.01 g kg-1 provides a deviation in the determined ECW volume of approximately 1%.

Body Water↗

Glutamine-enriched intravenous feedings attenuate extracellular fluid expansion after a standard stress.

A double-blind, randomized controlled trial was performed to determine the effect of glutamine (GLN)-enriched intravenous feedings on the volume and distribution of body fluids in catabolic patients. Subjects with hematologic malignancies in remission underwent a standard treatment of high-dose chemotherapy and total body irradiation before bone marrow transplantation. After completion of this regimen, they were randomized to receive either standard parenteral nutrition (STD, n = 10) or an isocaloric, isonitrogenous nutrient solution enriched with crystalline L-glutamine (0.57 g/kg/day, GLN, n = 10). Extracellular water (ECW) and total body water (TBW), determined by bromide and heavy water dilution techniques, were measured before the conditioning treatment and after termination of the intravenous feedings that were administered for 27 +/- 1 days. In addition electrical resistance (R, in ohms, omega) and reactance (Xc, omega) of the body to a weak alternating current were measured at these time points. Both study groups were comparable for age, weight, height, sex, and diagnosis. Initial TBW was highly related to electrical resistance (r = -0.93, p less than 0.001). After conditioning therapy, bone marrow infusion, and intravenous feedings, a 20% expansion in ECW was observed in the STD group (ECW: 18.0 +/- 1.1 L vs. 14.9 +/- 1.0, p = 0.012), and this fluid retention was associated with a marked decrease in electrical resistance (R: 514 +/- 28 omega vs. 558 +/- 26, p less than 0.05). In contrast the extracellular fluid compartment in patients receiving GLN-supplementation did not change (ECW: 15.8 +/- 0.9 L vs. 15.4 +/- 0.8, p = 0.49), and the body's resistance was maintained (R: 552 +/- 27 omega vs. 565 +/- 23, p = 0.42). Expansion of ECW could not be related to differences in fluid or sodium intake, or to the use of diuretics or steroids. Patients receiving the STD solution, however, exhibited a greater number of positive microbial cultures (p less than 0.01) and a higher rate of clinical infection compared with the GLN patients (5/10 vs. 0/10, p less than 0.05); the fluid expansion in infected STD patients was greater compared with uninfected individuals (delta ECW: + 5.0 +/- 1.4 vs. 0.7 +/- 0.5, p = 0.007). In this model of catabolic stress, fluid retention and expansion of the extracellular fluid compartment commonly observed after standard total parenteral nutrition can be attenuated by administering glutamine-supplemented intravenous feedings, possibly by protecting the host from microbial invasion and associated infection.

Adult↗

Cardiopulmonary response of the rat to gram-negative bacteremia.

Hemodynamic and respiratory effects of a continuous 5-h intravenous infusion of live Escherichia coli were studied in rats. Control animals were infused with saline. Rats infused with 1.8 +/- 0.4 X 10(10) bacteria/h did not survive a 5-h infusion. These animals developed early hypotension and reduced cardiac output (CO) measured by thermal dilution technique. Rats infused with 8.0 +/- 0.4 X 10(9) bacteria/h survived a 5-h infusion with hypotension and reduced CO occurring later in the course of bacteremia. Heart rate was markedly elevated in both septic groups. Arterial blood gas measurements revealed that partial pressure of O2 was not affected by bacteremia, but partial pressure of CO2 was significantly decreased. Arterial pH remained within the normal range indicating respiratory compensation of a metabolic acidosis. Since hypotension and reduced CO were accompanied by a fall in right atrial pressure (RAP) during bacteremia, a third septic group was studied to evaluate cardiac performance during volume loading. After 3-5 h of bacteremia, a 40% reduction in CO was associated with a significant drop in arterial pressure and RAP. Despite volume loading, ventricular stroke work and arterial pressure were significantly reduced compared with control animals. The results indicate that severe gram-negative bacteremia produces myocardial depression in the rat. This model can be useful for further studies of cardiac dysfunction during sepsis.

Animals↗

Liver adenosine triphosphate (ATP) in hypoxia and hemorrhagic shock.

Reduction of liver ATP in proportion to the severity of shock and hypoxia is well known. We have studied the interrelationships among arterial oxygenation, arterial pH, and liver ATP in experimental hypoxia and in hemorrhagic shock in rats. No significant correlation was found between liver ATP and arterial pH in both hemorrhagic shock and hypoxia and between liver ATP and arterial PO2 in hypoxia. Induction of experimental observations suggest that in this form of hemorrhagic shock, arterial pH may be a sensitive indicator of decreased hepatic perfusion and impaired liver ATP production.

Acidosis, Respiratory↗

Rapid computer prediction of total body water in fluid overload.

Using computer analysis of the early plasma arterial disappearance curve of tritiated water (HTO), we sought the fewest points and earliest times needed to predict the final volume of dilution, total body water (TBW). In ten anesthetized adult female dogs weighing 19.1 +/- 0.5 kg, with bilateral ureteral ligation, 500 muC HTO were given IV. Arterial blood samples were taken until equilibrium (3 hours), when the approximate equivalent of extracellular fluid (ECF), 4,000 ml of lactated Ringer's solution, was given IV within 1 hour. The next day, in the second phase of the study, 1,000 muC of HTO were given IV and arterial blood samples were taken at intervals up to equilibrium (5 hours). TBW at 3 hours after the first HTO infusion was 63.3 +/- 1.2% body weight. Using a curve-fitting Fortran program (CFIT), the arterial plasma HTO concentrations were fitted to one or two exponentials. Although initial TBW could be predicted from arterial plasma concentrations of HTO during 20 minutes after injection in normally hydrated dogs, values during 60 minutes were required for accurate prediction of TBW after infusion of 4 L of fluid. TBW in normal and fluid-loaded animals was predicted within 2.3 +/- 0.6% of the final HTO equilibrium (r = 0.987).

Animals↗

Intravenous adenosine triphosphate (ATP) in hemorrhagic shock in rats.

The effect of intravenous (iv) infusion of 6.25 mumol of ATP-MgCl2 on survival and tissue ATP levels in hemorrhagic shock was investigated using a rat model. Mortality in ATP-MgCl2-treated shocked rats was 50% compared with 53% in saline-treated controls. Tissue ATP levels in ATP-MgCl2-treated shocked rats did not differ from those in saline-treated shocked rats nor from those in sham-operated controls. After iv infusion of 6.25 mumol of [8-14C]ATP-MgCl2, shocked, sham-operated, and nephrectomized rats had similar tissue distributions of 14C. The 14C in heart, lung, kidney, and liver of shocked and sham-operated rats was present almost entirely as nonphosphorylated [8-14C]ATP catabolites. It is concluded that ATP-MgCl2 iv did not benefit survival or enhance tissue ATP levels in shocked animals and that the administered ATP was rapidly and extensively degraded.

Adenosine Diphosphate↗

Metabolic effects of experimental bacteremia.

Hemodynamic and metabolic effects of a lethal 5-hour infusion of Ps. aeruginosa at a dose 10(8) organisms per ml per min were studied in 39 dogs. Blood glucose, insulin, catecholamines, body temperature, WBC, and hemodynamic parameters were measured before and at 1-hour intervals during controlled bacterial infusions. Induced bacteremia in the upper 10(4) range per ml of blood was accompanied by a decline of mean arterial blood presure from 130+/-6 mm Hg to 84+/-12 mm Hg at 4 hours, hypothermia, leukopenia, and hypoglycemia. Death within 24 hours was associated with hypoinsulinemia and increased blood catecholamines. Survival was characterized by maintenance of arterial blood pressure, only moderate decline in blood glucose levels, and normal plasma insulin concentrations with little change in plasma catecholamines. Mortality could be reduced significantly by glucose administration. This was associated with correction of hypoglycemia, rise in plasma insulin activity and increased energy production.

Animals↗

Cardiac depression in bacteremia.

Hemodynamic and respiratory effects of a 5-hr IV infusion of Ps. aeruginosa at a dose of 10(8) organisms per ml per minute were studied in 6 dogs. Four dogs served as controls. Gramnegative bacteremia, with 70,000 +/- 1,800 organisms per ml of blood, caused a 50% reduction of cardiac output at three hrs. Peripheral vascular resistance increased significantly, but mean heart rate fell below control levels. Decline in mean systemic blood pressure from 150 +/- 5 mm Hg to 88 +/- 6 mm Hg was accompanied by a significant increase in pulmonary arterial wedge pressure with normal right atrial and pulmonary arterial pressures. Pulmonary vascular resistance also remained unchanged. With progression of the low output state and development of hypothermia, arteriovenous oxygen difference (A-V DO(2)) fell significantly. Despite a decline in functional residual capacity, venoarterial admixture diminished in the face of reduced pulmonary capillary perfusion, normal arterial Po(2) values, decline in body temperature and finally very narrow A-V DO(2). Histologically, ventricular myocardium revealed severe interstitial edema. It is concluded that myocardial dysfunction may occur early during gramnegative bacteremia, and formation of myocardial edema appears to be a significant contributing factor in myocardial failure.

Animals↗