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Biomedical subjects

J M Kinney

Publications and source records attributed to J M Kinney.

At least 19 recordsLinked to original sources

Kinetics of intravenously administered 15N-L-alanine in the evaluation of protein turnover.

After a pulse injection of 15N-L-alanine to a healthy male subject, the distribution of 15N in the various components of blood and urine were determined as function of time. The rapid appearance of the isotope both in the urinary urea and ammonia and in the plasma amide and urea suggests that transamination (and not deamination) may be the key step in the interaction. After 30 to 60 min postinjection, the tracer dynamics represents the overall metabolic pool characteristics and does not reflect the metabolism of alanine only. The nitrogen of alanine is used effectively in the synthesis of body protein.

Adult

Changes in nitrogen balance of depleted patients with increasing infusions of glucose.

Depleted patients were maintained on intravenous infusions of amino acids and glucose with constant N intake (173 mg/kg body weight), and three different levels of energy intake (15.4, 37.6, and 58.5 kcal/kg) given sequentially for 4 days each. Changes in N balance were abrupt and maximal in 1 to 2 days. Maximal changes in N balance preceded, and were not dependent on maximal changes in fat and glucose metabolism. N retention increased 1.7 mg/kcal of increased energy balance, during both hypocaloric and hypercaloric intakes, a value similar to that observed in normal adults. No increase in resting energy expenditure occurred with increasing energy intake during negative energy balance. During positive energy balance resting energy expenditure increased by 1 kcal for each 5 of intake. It seems likely that increasing energy restores mainly that portion of lean body mass associated with fat deposition; and rapid restoration of lean body mass requires high N intakes. At zero energy balance, N balance in these depleted patients was only slightly positive at an intake of 173 mg N per kilogram. This is about twice the intake of N required to maintain zero N balance in normal adults.

Adult

Influence of increasing carbohydrate intake on glucose kinetics in injured patients.

The metabolic and hormonal effect of glucose loads, ranging from 125 to 504 g/70 kg/day, were studied in severely injured patients. There was little or no correlation of glucose intake with nitrogen balance, plasma glucose, fatty acid concentrations, or epinephrine excretion. Increased norepinephrine excretion correlated with and may have resulted from increased glucose intake. Serum glucagon concentrations averaged 320 pg/ml and were not depressed by glucose intake. Insulin concentrations rose with glucose intake but were low for the level of plasma glucose. Glucose oxidation and non-oxidative metabolism, including glycogen deposition, correlated well with glucose intake. Gluconeogenesis from alanine was much higher than normal but was completely suppressed at very high intakes. The data imply that cycling of glucose, with glycerol, glycogen, or both, increased with increasing glucose intake.

Adult

Patterns of ventilation in postoperative and acutely ill patients.

Acutely ill patients commonly increase minute ventilation (V) to varying degrees. The pattern of breathing utilized to increase V was analyzed in normal subjects and acutely ill surgical patients. V = tidal volume (VT) x frequency (f), or V = inspiratory flow x (TI/TTOT, inspiratory time/total cycle time). CO2 inhalation and exercise were used to induce supine hyperventilation in normal subjects. This was compared to hyperventilation in acutely ill surgical patients. Measurements were made of O2 consumption, CO2 production, V, VT, f, inspiratory flow, TI, and TTOT. With small increases in V (up to twice control), normal subjects increased inspiratory flow and TI/TTOT with both CO2 and exercise. CO2 inhalation increased VT with no change in f, while exercise increased both VT and f. When V increased beyond twice control, TI/TTOT remained constant and increases in inspiratory flow accounted for the entire increase in V. In acutely ill patients with increased V, average f was elevated and VT decreased, but there was no constant relationship of f and VT with increasing V. However, TI/TTOT was relatively constant at 0.40- 0.46; therefore, in order to increase V, inspiratory flow had to increase! Patients also showed a tendency to breathe at a relatively fixed VT while normal subjects did not show this phenomenon, even with increases of up to 3 times control V. Continuous, rapid analysis of gas exchange and breathing patterns holds promise for early detection of patients with V inappropriate to metabolic demands, and serves as a sensitive indicator of abnormal patterns used by acutely ill patients to increase V.

Acute Disease

Changes in metabolism and muscle composition associated with total hip replacement.

Metabolic changes in 10 patients undergoing total hip replacement were studied. Metabolic expenditure postoperatively remained within 5--10% of preoperative values. Net nitrogen loss for the postoperative period was less than 35 gm for the first 4 postoperative days, well below changes seen in major nonsurgical trauma. Fluid balance was positive in all patients for the first 4 postoperative days. Patients not in negative fluid balance by the fourth postoperative day should be closely monitored for complications. Recognition of delayed fluid excretion is essential in order to avoid the complications of further fluid loading in the postoperative period. Muscle composition reveals predictable changes in extracellular water, sodium, and chloride composition following surgery. Our data showed that metabolic changes following total hip replacement are in the order of major general surgical procedures and well below that observed with major trauma.

Adult

Effects of hypercaloric glucose infusion on lipid metabolism in injury and sepsis.

UNLABELLED: Lipolysis was studied by measuring glycerol turnover (GTO) in injured and infected patients. GTO was elevated two to three times the normal values in five injured and four infected patients during D5W infusion. No correlation was found between GTO and plasma glycerol concentration in the two patient groups. GTO showed similar levels when measured during TPN in five injured and three infected patients. During TPN, plasma FFA levels remained unchanged in injured but decreased by 48% in septic patients. B-OH butyrate concentrations were high during D5W and dropped in both groups during TPN. Norepinephrine urinary output was high in both groups during D5W and TPN. CONCLUSIONS: 1) GTO was elevated two to three times the normal range in injury and infection; plasma glycerol concentration was not related to GTO. 2) In face of high catecholamine output, the insulin response to TPN did not inhibit TG breakdown but did decrease plasma ketone body concentrations.

Adult

Influence of exercise and CO2 on breathing pattern of normal man.

Ventilatory patterns during rest, CO2 inhalation (2, 3, and 4%) and three levels of exercise were analyzed in supine men using a canopy system for noninvasive measurements. Changes in tidal volume (VT) and breathing frequency (f) with equal increases in minute ventilation (VE) differed significantly during exercise and CO2 inhalation. Increases in VE during exercise was accompanied by increases in VT and f. During CO2 inhalation, the change in frequency was less than during exercise. However, when analyzed in terms of inspiratory flow (VT/TI) and inspiratory duty cycle (TI/Ttot), the response to both stimuli was similar. With increases to twice control VE both TI/Ttot and VT/VI increased. Thereafter only VTTI increased with increasing VE. At rest, inspiratory time on a breath by breath basis increased minimally with VT, while changes in inspiratory flow accounted for the variability in VT. These two respiratory stimulants appear to increase ventilation through different mechanisms when analyzed in terms of VT and f. However, changes in inspiratory flow and duty cycle are similar in both.

Adult

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