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Biomedical subjects

J M Kinney

Publications and source records attributed to J M Kinney.

At least 55 records · Page 3Linked to original sources

Effect of carbohydrate intake on de novo lipogenesis in human adipose tissue.

Rates of synthesis, from [14C]glucose, of fatty acids (de novo lipogenesis) and glycerol (triglyceride synthesis) were measured in biopsies of adipose tissue from nutritionally depleted patients given low- or high-carbohydrate intravenous nutrition. Simultaneously, energy expenditure and whole-body lipogenesis were measured by indirect calorimetry. Rates of whole-body lipogenesis were zero on the low-carbohydrate diet and averaged 1.6 g.kg-1.day-1 on the high-carbohydrate diet. In vitro rates of triglyceride synthesis increased 3-fold going from the low to the high intake; rates of fatty acid synthesis increased approximately 80-fold. In vitro, lipogenesis accounted for less than 0.1% of triglyceride synthesis on the low intake and 4% on the high intake. On the high-carbohydrate intake, in vitro rates of triglyceride synthesis accounted for 61% of the rates of unidirectional triglyceride synthesis measured by indirect calorimetry. In vitro rates of lipogenesis accounted for 7% of whole-body lipogenesis. Discrepancies between in vitro rates of fatty acid synthesis from glucose, compared with acetate and citrate, as reported by others, suggest that in depleted patients on hypercaloric high-carbohydrate diets, adipose tissue may account for up to 40% of whole-body lipogenesis.

Adipose Tissue↗

Energy expenditure in patients with chronic obstructive pulmonary disease.

Energy expenditure was studied in ten patients with chronic obstructive pulmonary disease (COPD) and weight loss, and in five malnourished patients without clinical evidence of COPD (control group) prior to and after a two-week refeeding regimen. Patients received 5 percent dextrose solution (plus electrolytes) for 36 hours to establish standard baseline conditions and were then randomly assigned to either a carbohydrate-based (CB; 53 percent of calories) or fat-based (FB; 55 percent of calories) diet for the first week. The alternate diet was given the following week. Total calorie intake was set at 70 percent above the energy expenditure measured prior to institution of nutritional support. During energy repletion, energy expenditure was greater than predicted (116 percent) in patients with COPD and less than predicted (90 percent) in the control patients. Thermic effect of nutrients during administration of either regimen was significantly greater (p less than .05) in patients with COPD than in those without COPD during both diets. The difference between the two groups was enhanced during the CB regimen. These observations suggest that malnourished patients with COPD have an elevated resting energy expenditure, and an enhanced thermic response to nutrients as compared to malnourished patients without COPD. Increased diet-induced thermogenesis may contribute to weight loss in patients with COPD, in addition to factors previously described such as decreased caloric intake and increased resting energy expenditure.

Aged↗

Metabolic and respiratory changes during weaning from mechanical ventilation.

Weaning from mechanical ventilation is a procedure performed daily in intensive care units. This study sought to determine whether among postoperative patients there were any differences in the changes in oxygen consumption (VO2) and carbon dioxide production (VCO2) between those patients in whom mechanical ventilation was successfully discontinued and those in whom it was continued or reinstituted. A stepwise reduction in mandatory breaths (from 10 to 12 to 4 to 6), followed by a period of continuous positive airway pressure (CPAP), was the weaning method. In the group of patients (N = 18) who were successfully weaned, VO2 and VCO2 increased 10 +/- 8 (SD) percent and 10 +/- 9 percent, respectively, while VE decreased 9 +/- 8 percent and PaCO2 was unchanged when values at an IMV of 10 to 12 were compared with those on CPAP. In the group (N = 17) who were not successfully weaned, VO2 and VCO2 increased 8 +/- 10 percent and 6 +/- 9 percent, respectively, while PaCO2 rose (37.9 +/- 4 to 42.5 +/- 2.9) significantly (p less than 0.02). There was a significantly greater decrease (15 +/- 3 percent) in VE than in the other group. Changes in VO2 or VCO2 did not aid in predicting which patients would be successfully weaned.

Adult↗

Effects of increasing glucose intake on nitrogen balance and energy expenditure in malnourished adult patients receiving parenteral nutrition.

The effects of increasing glucose intake on nitrogen balance, energy expenditure and fuel utilization were measured in malnourished adult patients receiving parenteral nutrition with constant nitrogen intake and high or low glucose intakes for 8 day periods. Energy balance, nitrogen balance, weight and temperature were determined daily. Blood samples taken at admission and at the end of days 7 and 8 of each diet were analysed for glucose, fatty acids, urea, insulin, glucagon and thyroid hormones. The effect of increasing glucose intake was to increase nitrogen balance by 0.28 +/- 0.08 (SEM) mg/kJ. A scheme is proposed, based on present and previous findings, of the separate effects of nitrogen and energy intake on nitrogen balance, permitting calculation of rates of repletion of fat and lean body mass from estimates of nitrogen intake and energy balance. Malnourished patients are shown to attain markedly positive nitrogen balances at zero or negative energy balances. Large errors in estimation of energy requirements have little effect on nitrogen balance. Changes in nitrogen balance were entirely due to changes in urea excretion. Creatinine excretion increased 12% with high glucose intake, attributed mainly to increased muscle mass (7%) and body temperature (4%). A 12% increase in resting energy expenditure was only partly due to costs of glycogen storage and lipogenesis; the remainder, about one-half, is probably due to glucose and insulin mediated increases in sympathetic activity. There were marked increases in 3,5,3'-triiodothyronine (T3) concentrations with time, but no difference between the high and low glucose diets. The T3/thyroxine ratio, an index of free T3 concentration, increased much more rapidly on the high than on the low glucose diet. Changes in T3 could not account for the effect of glucose, under these conditions, to increase resting energy expenditure.

Adult↗

Nutrition in the intensive care patient.

The experiences of the past decades have shown that critically ill patients regularly suffer marked tissue depletion. Recently, it has come to light that malnutrition may cause this depletion. The need, thus, arises for a comprehensive study of nutrition in the intensive care unit, a study relating present knowledge concerning the metabolic and catabolic states of the critically ill to possible applications in parenteral nutritional support.

Critical Care↗

Influence of injury and nutrition on muscle water and electrolytes: effect of severe injury, burns and sepsis.

The changes in water and electrolyte metabolism associated with severe injury and sepsis are well recognized but changes in tissue content have seldom been available. This report combines the experience obtained from muscle biopsies of such patients performed in two centers; one located in Sweden and one in the U.S. Normal values for muscle water and electrolytes in each center are in close agreement. Needle biopsies of muscle were performed in 45 Swedish patients and 17 U.S. patients at intervals after injury or infection from the second to the thirtieth day. The patients' nutrition varied from brief periods of hypocaloric intake to prolonged high calorie parenteral nutrition with and without amino acids, as well as with and without fat. Prominent changes appeared during the first week and persisted up to 30 days regardless of the associated nutritional intake. These changes included an increased total muscle water, extracellular water, sodium and chloride and a decrease in muscle potassium and magnesium. This study demonstrates a simultaneous expansion of extracellular volume and a loss of intracellular components. This is in contrast to the experiences reported with less severe injury such as elective operation, where a more modest expansion of extracellular volume is seen and which is not associated with any loss of potassium or magnesium. The magnitude and persistence of these changes in muscle tissue deserve further study, both as to mechanism and implications for therapy.

Adult↗

Automated microanalysis of adenosine phosphates, phosphocreatine, creatine, and lactate in muscle.

An automated enzymatic procedure suitable for determination of ATP, ADP, AMP, phosphocreatine, creatine, and lactate in needle biopsies of human skeletal muscle (ca. 30 mg dry wt) using a fast centrifugal analyzer (Multistat III, Instrumentation Laboratory Inc.) is presented. Coefficients of variation ranged from 0.7 to 4.2% for multiple determinations of ATP, ADP, phosphocreatine, and creatine; from 6 to 24% for lactate; and from 9 to 20% for AMP. The procedure should be usable, with appropriate modification, with other tissues and with other fast centrifugal analyzers. Muscle samples are collected into liquid freon, lyophilized, and extracted with 600 microliter of 0.65 M perchloric acid. Neutralized supernatants can be stored for up to 3 years at -80 degrees C with no significant deterioration. The procedure takes much less time than similar manual procedures and gives better reproducibility, particularly for ADP and AMP.

Adenine Nucleotides↗

Protein synthesis and degradation in biopsies of rat skeletal muscle.

The use of 20- to 40-mg biopsies of rat skeletal muscle to measure protein synthesis and degradation rates in vitro was investigated and compared to that of the intact extensor digitorum longus (EDL) and soleus muscles. During incubations in oxygenated Krebs-Ringer bicarbonate buffer with glucose, insulin, 23 amino acids at 10 times rat plasma levels, and [14C]tyrosine, the specific activity of intracellular tyrosine approximated that of the incubation medium and was constant in the biopsy, the EDL, and the soleus. The rate of incorporation of tyrosine into the protein of the biopsy was constant for 3 hr and was 39 and 32% of the rates of the EDL and soleus, respectively. The rate of release of tyrosine from protein in the biopsy during incubations in buffer with glucose and cycloheximide was constant for 3 hr and was intermediate between the rates of the EDL and soleus. The effects of starvation on the in vitro protein metabolism of the biopsy were the same as on the intact muscles. The 42% decrease in synthesis and the 53% increase in degradation in the biopsy were intermediate between the changes measured in the EDL and soleus muscles. The ability of this technique to identify proportional changes in the in vitro protein synthesis and degradation rates makes this a valid technique suitable for the measurement of changes of in vitro protein metabolism using serial biopsies from larger animals, including man.

Animals↗

The effects of posture on the metabolic and ventilatory response to low level steady state exercise.

Low level exercise is frequently used to assess cardiac and pulmonary function. This study examines the differences in both metabolic and respiratory patterns between the sitting and supine position. Six normal male subjects were studied in both positions during four levels of exercise (12.5, 25, 37.5 and 50 W). Oxygen consumption (VO2), carbon dioxide production (VCO2) and minute ventilation (VE) were greater when sitting as were the ventilatory equivalents to O2 (VE/VO2) and CO2 (VE/VCO2). Respiration was compared at equivalent workloads; the greater minute ventilation observed during sitting was due to greater tidal volumes (VT) and mean inspiratory flows (VT/TI). Expiratory time (TE) was longer and inspiratory duration shorter under most conditions when sitting. When breathing patterns were compared at similar degrees of minute ventilation, VT, TE and VT/TI were greater when sitting, while respiratory frequency (fR) was slower.

Carbon Dioxide↗

Response to tubular airway resistance in normal subjects and postoperative patients.

Critically ill patients must often breathe spontaneously through an endotracheal tube that acts as a fixed inspiratory and expiratory tubular airway resistor. Although this practice is common, its effect on the pattern of breathing is not known. The mean breathing patterns of seven normal, healthy male subjects and eight male patients who had undergone upper abdominal surgery 2-4 days previously were studied breathing through a mouthpiece fitted in random order with a 5, 6, 7, 8, or 15 mm diameter (17 mm long) resistor. These diameters were selected because they simulate the pressure-flow relationships of adult endotracheal tubes. With the 15 mm aperture, the patients had a greater breathing frequency (f) than did the normal subjects (21 +/- 5 [SD] vs. 14 +/- 4 breaths/min, P less than 0.01) as well as a smaller mean tidal volume (VT). In both groups, minute ventilation (VE) and f progressively decreased as resistance was increased by decreasing the aperture size from 15 to 16 mm. In the normal subjects but not the patients, VT also progressively decreased. When the diameter was decreased from 6 mm to 5 mm, there were increases in VT and decreases in f that were more marked in the normal subjects. In both groups, the changes in VE were accompanied by decreases in mean and peak inspiratory and expiratory flow rates. Throughout the study, oxygen consumption (VO2) and carbon dioxide production (VCO2) did not change. This, coupled with the decreases in VE resulted in decreases in the ventilatory equivalents to CO2 and O2 (VE/VCO2, VE/VO2).(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

Resting metabolic rate of the critically ill patient: measured versus predicted.

Critically ill patients requiring mechanical ventilation are particularly susceptible to malnutrition. A knowledge of the energy requirements of these patients is essential in designing nutritional regimens. This study examines 45 resting energy-expenditure measurements performed in a group (n = 40) of postoperative, critically ill patients who were hemodynamically stable, noncomatose, and receiving mechanical ventilation. It examines in particular to what degree the resting energy expenditure of such patients can be predicted using the Harris-Benedict and Aub-Dubois formulae. Resting energy expenditure was measured using indirect calorimetry. There was only a moderate correlation between measured resting energy expenditure and that predicted using the Harris-Benedict (r = 0.57) and Aub-Dubois (r = 0.59) formulae. There was little correlation between the ratio of the measured to the predicted (Harris-Benedict) resting energy expenditure and age, or the ratio of actual to ideal body weight and body weight. The measured resting energy expenditure differed widely (70-140%) from predicted, reflecting the many complex factors that influence these patients' metabolic rate. The role of standard predictive formulae in such patients is as an arbitrary reference point to be used to define hypermetabolism (measured greater than predicted) and hypometabolism (predicted greater than measured).

Adolescent↗

Effect of immediate postoperative nutritional support on length of hospitalization.

This study is a retrospective review of the effect of nutritional support on duration of hospitalization in patients undergoing radical cystectomy. Thirty-five patients were randomly assigned to receive either 5% dextrose (D5W) solution plus electrolytes or total parenteral nutrition (TPN) following operation. The assigned nutritional regimen was continued for 1 week after operation until oral intake resumed. If the patients receiving D5W remained incapable of oral intake after 1 week, TPN was instituted. The group receiving immediate postoperative TPN had a median duration of hospitalization of 17 days, while the median duration for the group receiving 5% dextrose solution was 24 days. All other patient characteristics, such as age, sex, stage/grade of tumor, and extent of preoperative radiotherapy, were similar in the two groups. These results demonstrate that immediate postoperative institution of nutritional support reduced hospitalization time following radical cystectomy. This indicates that the routine use of 5% dextrose as postoperative nutrition should be reevaluated.

Aged↗

The metabolic and ventilatory response to the infusion of stress hormones.

Sepsis and trauma result in increases in epinephrine, glucagon, and cortisol secretion as well as alterations in respiratory pattern that is characterized by increased minute ventilation, decreased tidal volume, and increased frequency. Six male subjects were infused for 5.5 hours with cortisol, epinephrine, and glucagon in amounts designed to simulate plasma levels seen in patients following trauma. During the initial 20 minutes of the hormone infusion, minute ventilation (VE), oxygen consumption (VO2), and carbon dioxide production (VCO2) increased above preinfusion values. VCO2 increased more than VO2 resulting in an increase in respiratory quotient (RQ) from 0.93 to 1.14. The increase in VE was due to increased tidal volume and not frequency (f). After 4.5 hours, the VE, VO2, and VCO2 were still above preinfusion levels but the RQ had decreased to 0.98 because of a decrease in VCO2. Frequency had increased from 19 +/- 4.8 breaths/min preinfusion to 22 +/- 4.7 after 4.5 hours. After 4.5 hours, VT was still above preinfusion levels while pH and PaCO2 had decreased below them. The latter was associated with an increase in serum lactate. At no time was a decrease in tidal volume observed. Therefore, the infusion of these hormones does not simulate all the alterations observed during trauma and sepsis.

Adult↗

Ventilatory effects of the stress hormones in normal man.

The ventilatory responses to catecholamine infusions have been well studied. Increases in plasma levels of cortisol and glucagon during stress may exert a synergistic effect with epinephrine. We examined the effect of epinephrine and a combined hormone infusion in four normal postabsorptive subjects. On three separate occasions each subject was assigned randomly to receive a 5.5-h infusion of saline (control), epinephrine (1.2 micrograms/m2 . min), or epinephrine plus cortisol (5 mg/m2 . min) plus glucagon (3 mg/kg . min). Oxygen consumption (VO2), CO2 production, minute ventilation (VE), tidal volume (VT), frequency (f), inspiratory flow, and inspiratory time during room-air breathing and inhalation of 2% and 4% CO2 were measured before infusion and during the last 2 h of infusion, using a noninvasive canopy system. VO2 increased significantly (p less than .05) from the control condition during both combined and epinephrine infusions (23% and 11%, respectively). The increase in VE was related linearly to the increase in VO2, and was primarily due to an increase in VT; however, there was a small rise in f. The VE-PaCO2 regression during CO2 inhalation was shifted leftward to an equal degree during both infusions. These data indicate that cortisol and glucagon augment the calorigenic action of epinephrine; ventilatory effects are augmented in relation to the changes in VO2.

Adult↗

Semistarvation and exercise.

Nutritional intake plays an important role in determining metabolic and respiratory demands during both rest and exercise. This study examines the effects in normal subjects of 4 days of semistarvation with 440 kcal/day of intravenously infused dextrose followed by the infusion of 480 kcal/day of amino acids for 48 h on the metabolic and ventilatory response to exercise (1.25, 2.50, and 5.0 kg . m/s.). After 4 days of the dextrose infusion, arterial PCO2 (P less than 0.05), and the ventilatory equivalent for CO2 (VE/VCO2, P less than 0.05) were decreased at rest compared with control measurements made prior to the dextrose infusion. During all three levels of steady-state exercise, arterial PCO2 was significantly lower (P less than 0.05) than observed before the start of the dextrose infusion. The subsequent infusion of amino acids resulted in increases in O2 consumption (V02; P less than 0.05) and minute ventilation (VE; P less than 0.05), a decrease in arterial PCO2 (P less than 0.05), and little change in CO2 production (VCO2) at rest. During low levels of exercise, compared with the values obtained following the 4 days of dextrose infusion, there were larger increases in VE and VO2, whereas VCO2 changed little. Mechanical efficiency (kcal work/kcal energy utilized) during exercise increased after 4 days of dextrose and returned to near control levels with the amino acid infusion. The adaptive response characteristic of semistarvation with dextrose appears to be altered when isocaloric amounts of amino acids are subsequently administered for short periods.

Adult↗

The energy expenditure of the mechanically ventilated critically ill patient. An analysis.

This study characterizes the pattern of caloric expenditure of a group of 19 mechanically ventilated critically ill patients after surgery. Continuous measurements of metabolic rate were used to examine the total energy expended over an eight-hour period (10 AM to 6 PM) on 21 occassions. This allowed for determination of the energy expended during activity, rest, and sleep. The patients were observed to be resting, defined as lying motionless with eyes open and responsive to surrounding events, for 44 +/- 4 percent (SE) of the studied period. Sleeping, a state where the patient was not aroused by surrounding events, was observed for 17 +/- 3 percent of the studied period. Total energy expenditure was 4.8 +/- 1.8 percent greater than resting energy expenditure (REE). The REE was 13.1 +/- 2.3 percent above sleeping energy expenditure (awakeness factor), while activity energy expenditure was 17.1 +/- 2.9 percent above REE (activity factor). The respiratory quotient (RQ) during activity in the 15 patients receiving infusions of physiologic saline solution or 5 percent dextrose solution was significantly less (p less than 0.02) than the RQ during rest. This appears to be due to increased fat oxidation during activity.

Critical Care↗

Forms of malnutrition in stressed and unstressed patients.

PCM can be usefully considered in terms of edematous (kwashiorkor-like) and nonedematous (marasmic) forms, as long as the limitations of the traditional terms are kept in mind. The body composition of subjects with undernutrition, or total starvation, both appear to maintain an extracellular fluid volume at a normal level, which increases as a percentage of the shrinking body weight. This is in contrast to patients with hospital malnutrition, in whom there is often an absolute increase in the extracellular volume while the body cell mass is shrinking. Data from the starvation literature suggest that the adult subject must gain approximately 10% of his or her body weight as extracellular expansion before edema is clinically evident. Preliminary evidence indicates that the hospitalized patient with the edematous form of malnutrition is at greater risk for complications and death when undergoing an operation, or requiring intensive care. The depleted patient who shows a rise in a depressed serum albumin after 7 to 10 days of TPN will have an improved prognosis when undergoing the stress of an elective operation. This improvement appears to be more the result of decreasing the expanded extracellular fluid volume than achieving a major increase in protein stores. The severely catabolic patient, particularly during episodes of major infection, can be expected to benefit by a nutritional intake that is carefully designed to provide calorie and nitrogen equilibrium. Nutritional intake high enough to guarantee positive balances of calories and nitrogen should be delayed until the acute catabolic stimulus has subsided, at which time the nutritional objective is to rebuild lost tissue.

Adaptation, Physiological↗