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Biomedical subjects

J M Kinney

Publications and source records attributed to J M Kinney.

At least 145 records · Page 8Linked to original sources

Protein and energy sparing of glucose added in hypocaloric amounts to peripheral infusions of amino acids.

After abdominal surgery, patients were given peripheral infusions of amino acids alone for 4 days followed by amino acids plus glucose for 4 days, or the same solutions in the reverse order. Although there was a wide variation in the response of individual subjects, the typical effect of glucose under these conditions was to reduce both nitrogen excretion (average of 2.8 g N/day) and resting metabolic expenditure (average of 110 kcal/day).

Adult↗

Metabolism and recycling of urea in man.

The rate of breakdown and reutilization of urea in man has been measured in five normal and two septic patients using 15N and 13C labeled ureas. The labeled molecules of the 15N urea dose were distinguished from the labeled molecules of the recycled urea by analyzing in a mass spectrometer the isotopic nitrogens produced when the recrystalized urine urea was treated with a hypobromite solution. In a normal subject with regular nitrogen intake, it was found that only 4/5 of the produced urea was excreted in urine and the rest was endogenously degraded. Seventy percent of the nitrogen and 63% of the carbon of the degraded urea were returned to the urea pool. On a nitrogen-free diet or after neomycin treatment with regular diet in the normal, the extent of urea splitting is considerably reduced. In the septic patients, breakdown, as well as recycling of urea was almost eliminated. It appears that the reate of endogenous catabolism of urea depends mainly on the activity of the gut flora which may be affected by dietary intake and clinical status of the subject. The method developed here could be applied for the quantitation of urea dynamics under different physiological and pathological conditions.

Adult↗

Muscle and plasma amino acids after injury: the role of inactivity.

The amino acid pattern following total hip replacement is characterized by increases in muscle of the branched chain amino acids (leucine, isoleucine and valine), the aromatics (phenylalanine and tyrosine) as well as methionine. The nonessential amino acids in muscle tend to decline, glutamine having the most marked change. Plasma levels of the essential amino acids increase while the nonessentials tend to decrease. This pattern differs from that observed in other catabolic states (uremia, starvation, untreated diabetes) and is significantly different from the effects of inactivity and starvation combined. This suggests that injury can be characterized by a unique pattern of muscle and plasma amino acids.

Amino Acids↗

Changes in blood viscosity and plasma proteins in carcinoma.

Blood viscosity and plasma protein concentrations were measured in 31 patients with a variety of visceral carcinomas. The mean whole blood viscosity was not elevated over normal controls because of a significantly lowered mean hematocrit. However, when hematocrit was eliminated as a variable by adjusting the hematocrit to 45%, the mean whole blood viscosity was significantly elevated in the group with carcinoma. Both the plasma viscosity and the tendency for red cell aggregation were significantly elevated. Since blood is a non-Newtonian fluid, and its viscosity increases markedly at low shear rates, these rheological abnormalities would be most important at the low shear rates characteristic of the venous circulation. It is suggested that these abnormalities in blood viscosity and red cell aggregation may be contributing to the high incidence of venous thromboembolism seen in patients with neoplastic.

Alpha-Globulins↗

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↗