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Biomedical subjects

V Kvetan

Publications and source records attributed to V Kvetan.

At least 19 recordsLinked to original sources

Differential effect of selective block of alpha 2-adrenoreceptors on plasma levels of tumour necrosis factor-alpha, interleukin-6 and corticosterone induced by bacterial lipopolysaccharide in mice.

The effect of selective block of alpha 2-adrenoreceptors on plasma levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and corticosterone induced by bacterial lipopolysaccharide (LPS) was investigated in mice using ELISA and RIA. It was found that the LPS-induced TNF-alpha response was significantly blunted in mice pretreated with CH-38083, a novel and highly selective alpha 2-adrenoreceptor antagonist (the alpha 2/alpha 1 ratio is > 2000). In contrast, LPS-induced increases in both corticosterone and IL-6 plasma levels were further increased by CH-38083. Since it has recently been shown that the selective block of alpha 2-adrenoreceptors located on noradrenergic axon terminals resulted in an increase in the release of noradrenaline (NA), both in the central and peripheral nervous systems, and, in our experiments, that propranolol prevented the effect of alpha 2-adrenoreceptor blockade on TNF-alpha plasma levels induced by LPS, it seems likely that the excessive stimulation by NA of beta-adrenoreceptors located on cytokine-secreting immune cells is responsible for this action. Since it is generally accepted that increased production of TNF-alpha is involved in the pathogenesis of inflammation and endotoxin shock on the one hand, and corticosterone and even IL-6 are known to possess anti-inflammatory properties on the other hand, it is suggested that the selective block of alpha 2-adrenoreceptors might be beneficial in the treatment of inflammation and/or endotoxin shock.

Adrenergic alpha-Antagonists

Glycerol metabolism in humans: validation of 2H- and 13C-labelled tracers.

For a tracer to be valid it must follow the metabolism of the tracee without distortion. Especially when the tracer contains several deuterium substitutions, the tracer can be altered or degraded differently from the metabolite it is to trace or be subject to distorting isotope effects. To determine whether 2H5-glycerol is a valid tracer for following glycerol kinetics, 2H5-glycerol and [2-13C]glycerol tracers were infused simultaneously in six healthy postabsorptive adult subjects. After 90 min of tracer infusion, epinephrine was also infused for 60 min to stimulate lipolysis and increase glycerol flux. Glycerol flux increased from 2.2 +/- 0.3 to 6.7 +/- 0.4 mumol/kg per minute (with the 13C tracer) and from 2.2 +/- 0.3 to 6.7 +/- 0.3 mumol/kg per minute (with the 2H tracer) when epinephrine was infused. There was no significant difference in glycerol flux measured with the 2H tracer compared to the 13C tracer either under basal or a stimulated flux condition. These results indicate that 2H5-glycerol is a valid tracer for measuring glycerol metabolism in humans.

Adult

Nutritional and metabolic support.

The problem of hunger accompanies any mass casualty situation that results in large numbers of patients with traumatic and burn injuries complicated by sepsis and end organ failure. This is caused by the inability of many of these patients to eat. Such patients require artificial nutrition. A rescue operation that does not provide adequate artificial nutrition, no matter how well organized with respect to field stabilization, surgical intervention, and intensive care, will find many of its patients dying of multiorgan disorders due to nutritional failure. This article is concerned with how to provide such artificial nutrition.

Carbohydrate Metabolism

Clinical algorithm for initial fluid resuscitation in disasters.

This article reviews past experience with branch-chain decision trees for fluid resuscitation of various emergency conditions and analyzes the effects of compliance with the algorithm on mortality and shock-related complications. On the basis of this analysis, the authors propose a new algorithm for fluid resuscitation of mass casualties when only palpable systolic blood pressure is available and when blood pressure, hematocrit, central venous pressure, urine output, and arterial blood gases are available.

Algorithms

Field management and critical care in mass disasters.

As previously discussed, the majority of injury cases do not necessarily involve dramatic life-saving actions, but rather very rudimentary, promptly applied precautions. For most victims of trauma, therefore, we offer reassurance and simple compassion in their time of need. One of the more important lessons to be learned here is that, beyond prehospital injury "management" or "treatment," we should always remember to provide the best possible prehospital injury care. By responding as soon as possible and by delivering reassurance and compassion to those who are injured and frightened, we are providing one of the most sacred aspects of the Hippocratic mission. Despite wonderful technologic advances and the need for aggressiveness in disaster management, these humanistic values must always be maintained by those to whom care is entrusted. Successful transport of disaster victims, whether in the prehospital phase or during interhospital transfer, requires careful attention to treatment priorities, such as simple measures for airway control and ventilation, and care to prevent further injuries by appropriate immobilization techniques. The use of fully equipped teams of multidisciplinary critical care specialists in mass disaster situations is in its infancy. It is clear that with properly adapted hardware and personnel trained to function in adverse environments while effectively delivering intensive care to a large number of patients with a variety of clinical syndromes, survival can be significantly increased for the most acutely ill.

Burns

Respiratory and sleep patterns during nocturnal infusions of branched chain amino acids.

In the awake, normal subject, infusions of branched chain amino acids (BCAA) alter the ventilatory response to CO2. If this effect extends to the sleep state, it could contribute to our understanding of the neurophysiology of the sleep state as well as having clinical utility in ameliorating or preventing apnea syndromes. This study examined the effect of nocturnal BCAA infusion on sleep patterns (as measured by EEG, chest wall motion, Sao2 and end-tidal CO2) in five normal male subjects. Subjects were monitored with a polysomnograph from 21.00 to 7.00. Each subject was studied double-blind in random order on three occasions: a) baseline, no infusion (B); b) control, with normal saline infusion (S); and c) treatment, infusion of BCAA (BCAA). Sleep pattern analysis did not demonstrate any measurable effect of the BCAA infusion. End-tidal CO2 levels during BCAA infusion were lower than during baseline or control nights (mean +/- s.d.; BCAA: 5.8 +/- 0.7 kPa vs. B: 6.9 +/- 0.1 kPa, P less than 0.01 and S: 6.7 +/- 0.4 kPa, P less than 0.05). This study demonstrates that nocturnal BCAA infusions have effects on respiratory control during sleep; further clinical studies are required to determine whether these data have implications for disease states.

Adult

Growth hormone and pulmonary disease. Metabolic effects in patients receiving parenteral nutrition.

Six severely malnourished patients with chronic obstructive pulmonary disease were maintained for 3 days with infusions of 5% dextrose in water followed by 12 days of eucaloric total parenteral nutrition. On days 8 through 11, they received 30 micrograms/d of growth hormone and twice this amount on days 11 through 15. Growth hormone had no significant effects on the plasma concentration of glucose, cortisol, or glucagon but caused a 50% increase in insulin and a 250% increase in somatomedin C concentrations. A positive nitrogen balance of 2 g/d due to growth hormone was probably mediated by insulin. Growth hormone-induced increases in energy expenditure and fat oxidation and decrease in glucose oxidation cannot be accounted for by insulin. The ability of growth hormone to improve nitrogen balance may be particularly important for malnourished patients with chronic obstructive pulmonary disease who, because of their pulmonary insufficiency, are intolerant of excess nutrients.

Aged

Reassessing intensive care for patients with the acquired immunodeficiency syndrome.

The number of patients with the acquired immunodeficiency syndrome (AIDS) admitted to hospitals is increasing dramatically. Treatments such as zidovudine, aerosolized pentamidine, and nutritional support are being administered to subacutely ill patients with increasing effectiveness. The number of patients with AIDS treated in intensive care units, on the other hand, has been decreasing progressively, perhaps as a result of a mortality rate close to 90%. However, because recent data demonstrate (1) a lower mortality rate in patients with AIDS who receive mechanical ventilation and (2) the ability to reverse the wasting syndrome in selected groups, we propose a reassessment of the criteria for intensive care unit admission of patients with AIDS.

AIDS-Related Complex

Submaximal exercise in emphysema and malnutrition at two levels of carbohydrate and fat intake.

Eight malnourished patients with emphysema (EMPH) and eight malnourished patients without evidence of lung disease (MLAN) received an infusion of 5% dextrose plus electrolytes (D5W) for 48 h and were then randomly assigned to a hypercaloric diet with either 53% of the calories as carbohydrate (CB) or with 55% as fat (FB) for the 1st wk, maintaining a constant protein intake. The alternate diet was given the following week. Ventilation and gas exchange were measured during supine cycle ergometry at 0, 12, and 25 W during the D5W, CB, and FB diet periods. At each exercise intensity, the EMPH group demonstrated a 12-15% greater O2 consumption, a lower respiratory quotient, and an O2 debt larger than that of the MALN group. Resting ventilation was higher during the CB than FB regimen in both groups of patients, but during the CB diet the EMPH group had a more exaggerated ventilatory response than the MALN group. The results demonstrate that EMPH patients have an unusual metabolic pattern during hypercaloric feeding and exercise. Furthermore in EMPH patients a FB regimen does not appear to create the additional stress on the respiratory system during exercise that is generated with a CB regimen.

Adult

Intravenous fat emulsions and lung function: a review.

Numerous studies have reported varying degrees of apparent pulmonary dysfunction when iv fat emulsions (IVFE) are given. These changes have generally not been of sufficient magnitude to carry clinical significance. The lung dysfunction observed has been attributed to an associated hyperlipemia. Recent studies, however, suggest that the associated impairment in lung function is due to alterations in pulmonary vascular tone (which results in ventilation/perfusion inequalities) caused by an IVFE-related increase in prostaglandin (PG) production. The polyunsaturated fatty acids in the IVFE serve as precursors to the PGs. Due to the varied effects of PGs on inflammation and pulmonary vasomotor tone, infusion of IVFE could have profound physiologic and pharmacologic actions aside from the provision of lipid calories. In some circumstances, IVFE may, in fact, be beneficial to the lung via alterations in

Animals

Nitrogen and energy relationships in malnourished patients with emphysema.

The purpose of this study was to examine the impact of nutritional support on nitrogen-energy relationships and functional parameters in malnourished patients with emphysema. Malnourished patients without lung disease served as the control group. Ten ambulatory, stable patients with emphysema and six patients without lung disease received an infusion of 5% dextrose (baseline) plus electrolytes (D5W) for two days, which was followed by an enteral or a parenteral infusion of either a carbohydrate-based (CB, 53% carbohydrate) or a fat-based diet (FB, 55% fat) for 1 wk each, in a randomized cross-over design. All patients had greater than 10% weight loss. Caloric intake was set at 1.7 times the resting energy expenditure (REE) as measured during the baseline period. The REE of patients with emphysema was 23 and 27% above that of the control group during baseline and refeeding periods, respectively. The increased REE was met primarily by an increased carbohydrate oxidation. During the infusion of D5W, N balance was lower in patients with emphysema, but during repletion N balance was similar in both groups of patients. Two weeks of nutritional support with either a CB or a FB diet increased body weight, N balance, and arm muscle area and improved maximal inspiratory pressure, skeletal muscle strength, and endurance-strength (using quadriceps, hamstring, and handgrip) to a similar degree in malnourished patients with and without lung disease. In other stress states, such as infection, it has been shown that hypermetabolism, hypercatabolism, and preferential fat oxidation occur concomitantly. Patients with emphysema are unusual because, although they are hypermetabolic, they are not hypercatabolic and do not demonstrate preferential fat oxidation.

Aged

Improved exercise tolerance with long-term parenteral nutrition in cystic fibrosis.

Two cystic fibrosis (CF) patients with severe pulmonary disease and malnutrition were followed during a course of long-term home total parenteral nutrition (TPN), which included iv fat emulsion. They gained 7 and 12 kg in body weight, respectively, and their ability to participate in daily activities increased. Progressive exercise testing before and during TPN showed a marked increase in maximal work load: 100% and 30%, respectively. At any given work load, oxygen uptake was increased while the respiratory quotient remained lower after the course of TPN. We believe that the lower respiratory quotient and greater oxygen consumption during exercise were due to a reduction in anaerobic metabolism after TPN.

Adult