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Biomedical subjects

J M Kinney

Publications and source records attributed to J M Kinney.

31 records · Page 2Linked to original sources

Whole body protein synthesis and catabolism in septic man.

The protein catabolic response to sepsis has been measured in three patients and in two normal subjects using a pulse injections of L-[15N]alanine. In addition, the urea kinetics were measured using a pulse administration of [15N]urea. Several nitrogen models which simulated the metabolic pathways of nitrogen-labeled compounds were tried. Best curve fits and acceptable confidence limits were obtained with a four-pool model containing two metabolic pools and two urea pools. Using this model, synthesis and catabolism rates were calculated for a fast and slow protein turnover pool. The mean daily total protein synthesis rate in the normal was 3.695 g/kg compared to 4.479 g/kg in sepsis. Because all subjects were in negative nitrogen balance, the mean total protein catabolic rate in the normal was 4.379 g/kg, compared to 5.298 g/kg in sepsis. These data suggest an increase in both protein synthesis and catabolism during sepsis.

Abscess

Nonsuppressability of gluconeogenesis by glucose in septic patients.

The contribution of alanine to the synthesis of glucose and the oxidation of alanine was evaluated in normal and septic patients using (14C)L-alanine. The data indicate that there is a twofold increase in the conversion of alanine into glucose in sepsis and, further, this increase was observed while the patients were receiving a constant glucose infusion (100 mg/min) prior to and during the single injection of (14C)L-alanine. Failure of glucose to decrease this gluconeogenic response in these septic patients clearly indicates that the controlling mechanism for glucose synthesis is modified following injury and undoubtedly plays a role in the abnormal carbohydrate metabolism observed in injury. The contribution of alanine carbon to oxidation was the same in the control and septic group as measured by the per cent of the (14C)L-alanine dose expired in 3 h. Since the control subjects received glucose continuously during the study with and without amino acids, it is clear that nutritional intake and injury has minimal effect on the oxidation of alanine. This suggests that transamination is not affected by sepsis nor is there an inhibition of pyruvate oxidation following sepsis.

Adult

Parenteral nutrition in the septic patient: nitrogen balance, limiting plasma amino acids, and calorie to nitrogen ratios.

A series of eight septic patients was provided varying levels of beef fibrin protein hydrolysate by central vein in the presence of adequate calories for evaluation of nitrogen retention under septic conditions. The mean nitrogen intake to achieve nitrogen equilibrium was 240 mg/kg of body wt per day. This represents a 40% increase over that required to produce nitrogen equilibrium in normal adults. The mean caloric intake of these patients was 43.3 kcal/kg of body wt per day. The calorie to nitrogen ratio based on the above intake was calculated to be 180:1. In order to utilize effectively calorie to nitrogen ratios in the nutritional care of patients, it is suggested that ratios be standardized using daily total coloric expenditures. Correcting the mean measured resting calorie expenditures of these patients for minimal daily activity, a caloric to nitrogen ratio of 138:1 was obtained. The plasma amino acid ratios in these septic patients confirm the finding that valine and phenylalnine are limiting amino acids in a beef fibrin hydrolysate at infusion levels below 240 mg of N/kg of body wt per day. Analysis of the urinary excretion of total nitrogen, urea, and amino acids in two patients suggests that 30 to 50% of the infused peptides of a beef fibrin hydrolysate are lost in the urine in these septic patients.

Abscess

Metabolism of 3-methylhistidine in man.

The metabolism of L-3-methylhistidine was studied in man using intravenously administered ((14)C)3-methylhistidine. Analysis for expired (14)CO2 for periods up to 2 hr following a single intravenous injection revealed no radioactivity, indicating that this compound is not oxidized in man. Analysis of urine samples for total radioactivity showed that 75% of the administered dose was excreted in 24 hr and 95% in 48 hr. Ion-exchange chromatography of urine samples with monitoring of the column eluated by a flow liquid-scintillation technique showed the presence of only two radioactive peaks. The time taken to elute these peaks was compatible with the major excretory component (95.5%) being ((14)C)3-methylhistidine, accompanied by a small amount (4.5%) in the form of N-acetyl-((14)C)3-methylhistidine. The plasma disappearance curves of ((14)C)3-methylhistidine suggested a half-life of approximately 130 min. The inability ot oxidize 3-methylhistidine and its quantitative excretion as the original compound as well as its N-acetyl derivative is similar to its metabolic fate in the rat and therefore suggests that 3-methylhistidine excretion may provide a reliable measure of actin and myosin turnover in the whole animal or in human subjects.

Acetylation

Correlation of blood rheology with vascular resistance in critically ill patients.

Blood rheologic measurements together with peripheral resistance determinations in vivo were made in 27 critically ill patients. Eighteen of these patients (group I) suffered from violent trauma or operative injury and the other 9 (group II) were patients with generalized sepsis. As a result of fluid therapy all patients underwent hemodilution, resulting in a decrease in blood viscosity. This drop in blood viscosity was counteracted to some extent by an increased plasma viscosity due to elevated fibrinogen levels and a decreased red cell deformability associated with massive transfusions of stored blood. The correlation of vivo hemodynamics with blood rheological data made it possible to separate the relative roles of vascular dimensions and blood viscosity in affecting the total peripheral resistance. This approach permitted us to distinguish varying degrees of vasoconstriction in nonseptic patients in low flow states (group I) and varying degrees of vasodilation in septic patients (group II). This type of analysis serves to elucidate the pathophysiology of hemodynamic alterations in disease and provides a rational basis for devising an effective therapeutic program.

Acute Disease

Metabolic rate in acute respiratory failure complicating sepsis.

A simple, reproducible, and noninvasive method was developed for measuring metabolic rate in patients receiving assisted ventilation and increased concentrations of inspired O2. In nonseptic patients requiring assisted ventilation, metabolic rate was within the predicted normal range, but in septic patients it was increased by an average of 60 percent over the predicted normal. This level of resting hypermetabolism is greater than previously reported in septic patients not requiring assisted ventilation. The explanation of this difference is likely to be related to the greater severity of the illness in the present group. The potential clinical significance of these findings is discussed.

Humans

Effects of major abdominal operations on human blood rheology.

Serial blood rheological measurements were systematically carried out in 14 patients undergoing major elective abdominal operations for a period up to 10 days after operation. The measurements included blood viscosity over a wide range of shear rates (0.01 to 208 sec.-minus 1), hematological data, and plasma protein concentrations. Significantly elevated plasma viscosity preoperatively accounted for a normal blood viscosity in the presence of anemia. After an initial drop due to hemodilution lasting for 1 to 3 days after operation, blood viscosity returned to normal by the tenth postoperative day. This was the result of an increased plasma viscosity, primarily due to rise in plasma fibrinogen and alpha2- and beta2-globulin concentrations. The red cell deformability of these patients was normal except for one patient who received seven units of transfused blood. The results of this investigation suggest that abnormal rheological properties of blood and plasma should be considered in therapeutic attempts to improve microcirculatory flow and oxygen delivery to tissues.

Abdomen