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Biomedical subjects

L D MacLean

Publications and source records attributed to L D MacLean.

At least 55 records · Page 3Linked to original sources

Metabolism of prolonged shock.

Dogs in shock due to controlled cardiac tamponade for 4 or 12 h were studied to determine which of the metabolic changes characteristic of early shock persisted if the shock state was prolonged. Moderate hyperglycemia and severe lactacidemia were present in the first few hours but the levels returned to near normal values by the end of 12 h. The entry rate of lactic acid into the circulation as well as the rate of glycogenolysis was high in the first 4 h but decreased thereafter even though skeletal muscle glycogen stores were not exhausted. In early but not in late shock glycogen accumulated in the heart. Glucose entry and exit rates were significantly elevated in early shock only. Increased protein utilization and decreased fatty acid mobilization persisted throughout the experimental period. Both in early and late shock the incorporation of labeled free fatty acid into tissue lipids was decreased in most organs. In the diaphragm free fatty acid incorporation only decreased in late shock. In the heart and lung, incorporation was higher than normal in the early stages but was at control levels after 12 h of shock.

Ammonia↗

Lymphocyte function in anergic patients.

The lymphocyte function of anergic surgical patients who are at increased risk for sepsis and mortality was studied. In vitro lymphocyte responses appear to be normal in most instances, in that over 80% of patients showed a normal response in a standardized mixed leucocyte culture reaction. Similarly, 56% of the lymphocytes from anergic patients showed a positive in vitro proliferative response with PPD. The ability of in vitro-activated lymphocytes to elicit a skin reaction was determined by culturing the cells of anergic patients with PPD and then reinjecting the lymphocytes or their supernatants intradermally into the original donor. When there was a positive proliferative response to PPD in vitro, the reinjected cells or supernatant elicited a positive skin reaction in 79% of the anergic patients. In contrast, a skin reaction was obtained in less than 20% of the instances when there was no in vitro proliferation to PPD or when the cells were cultured without antigen. These results suggest that one of the acquired immune defects in these anergic patients is an in vivo block of lymphocyte activation.

Cells, Cultured↗

Exogenous amino acids as fuel in shock.

It has been suggested that in shock branched-chain amino acids are preferentially oxidized resulting in continued proteolysis and stimulated gluconeogenesis. To determine if exogenous amino acids could be used as fuel in shock, dogs rendered hypotensive by controlled cardiac tamponade and normotensive controls were infused with amino acid mixtures and individual amino acids. When Nephramine, a mixture rich in branched-chain amino acids, was infused, plasma alpha-amino nitrogen levels rose but urea output did not increase in either the control state or in shock, suggesting that these amino acids were not rapidly deaminated to serve as fuels. Travasol, which in addition contained large amounts of alanine and glycine, tripled urea output in the controls and doubled it in shock. The limit of urea production was reached in both groups at 35 mumoles urea/minute/kg. In the Travasol-infused animals plasma alpha-amino nitrogen levels were maintained in normotension but rose sharply in shock. When glycine alone was infused into five dogs in shock urea production rate was 30.6 + 2.1 mumoles/minute/kg; with alanine the same value was 22.5 + 2.2 mumoles/minute/kg. In both cases plasma alpha-amino nitrogen levels were high, suggesting that transport of these amino acids into the cell was slow in shock. In four dogs in shock glycine-14C was added to the glycine infusate as a tracer. At radioactive equilibrium 28% of the label infused appeared in CO2; another 22% appeared in glucose. It is concluded that of all the amino acids tested only glycine and alanine are deaminated rapidly enough to serve as exogenous fuels in shock.

Alanine↗

Reliability of skin testing as a measure of nutritional state.

The reliability of skin testing to assess the nutritional state was evaluated in 257 patients who received total parenteral nutrition (TPN). The nutritional state was assessed by determining body composition, by multiple-isotope dilution. Immunocompetence was simultaneously evaluated by skin testing with five recall antigens. These measurements were carried out before and at two-week intervals during TPN. A statistically significant relationship existed between the response to skin testing and the nutritional state. A body composition consistent with malnutrition was present in the anergic patients, while body composition was normal in the patients who reacted normally to skin testing. However, a considerable overlap existed as 43% of the reactive patients were malnourished, and 21% of the anergic patients were normally nourished. Thirty-seven (43%) of the 86 anergic patients converted and became reactive during TPN, and their body composition improved significantly. The remaining 49 anergic patients (57%) did not convert, and their body composition did not change despite similar nutritional support. The principal difference between the two groups of anergic patients was the nature of the therapy administered. In the anergic patients who converted, therapy was aggressive and appropriate, and clinical improvement occurred in 23 (62.2%) of the patients, with a mortality of 5.4%. In the 49 patients who remained anergic, therapy was often inappropriate or unsuccessful, with clinical improvement in only three (6.1%) of the patients and a mortality of 42.8%. The data demonstrated a significant relationship between the response to skin testing and the nutritional state. However, because of the wide overlap, skin testing does not accurately assess a person's nutritional state. The persistence of the anergic state is indicative of a lack of response to therapy.

Female↗

The predictive role of delayed hypersensitivity in preoperative patients.

Seven hundred and twenty-seven surgical patients who were skin tested with recall antigens prior to operation were analyzed. The analysis included preoperative diagnosis, operative intervention, postoperative septic complications and death. The normal skin test responders were of similar age and had equal degrees of surgical procedures performed compared with patients who were anergic. Preoperatively, polymorphonuclear neutrophil chemotaxis was abnormal in the majority of anergic patients, as was the serum albumin concentration. Postoperatively, sepsis, mortality and death due to sepsis were significantly higher in the anergic population, reconfirming the hypothesis that skin test anergy in patients preoperatively is a signal of increased risk for septic complications and death in such patients.

Adolescent↗

Oxygen consumption during spontaneous ventilation with continuous positive airway pressure: assessment in normal volunteers and patients with acute respiratory failure.

Continuous positive airway pressures (CPAP) of 0.49 kPa and 0.98 kPa were applied to ten healthy volunteers and nine critically ill patients with acute respiratory failure. A modified Godart-Statham NV 16003 spirometer was used to measure respiratory frequency (f), tidal volume (VT), oxygen consumption (VO2), and changes in functional residual capacity (delta FRC). During CPAP of 0.49 kPa, volunteers had a decrease in f, and increased VT and minute volume (MV). At 0.98 kPa CPAP, f did not change but VT and MV significantly increased. VO2 did not change at either pressure. The volume of delta FRC increased with an increased level of CPAP. The entire volunteer group was comfortable throughout the whole study. When CPAP was applied to acutely ill patients, f decreased. VT and MV increased at both CPAP pressures. delta FRC was similar to the volunteers. VO2 in the patient group rose significantly at 0.49 and 0.98 kPa CPAP. Some of the patients were uncomfortable with 0.49 kPa pressure, while all the patients were distressed at 0.98 kPa CPAP. The effects of increased oxygen consumption and patients discomfort should be considered in critically ill patients receiving CPAP therapy.

Adult↗

Intestinal bypass for morbid obesity: a consecutive personal series.

Forty-five patients who underwent end-to-side jejunoileal bypass, with 51 cm in circuit, were followed up from 8 months to 8 years (average 3.4 years). There was no early or late mortality but morbidity was considerable; it included inadequate weight loss or late gain in 22%, malnutrition and liver failure in 11%, severe diarrhea and electrolyte imbalance in 11%. Cholelithiasis and wound complications also occurred. Reanastomosis was necessary in 13% (six patients). The result of the bypass was good in only 20%, satisfactory in 44% and unsatisfactory in 36%. This type of bypass is not adequate treatment for morbid obesity because the proportion of unsatisfactory results (36%) is too high and the number of good results too low and because the outcome is unpredictable. The complication of malnutrition characterized by a decline in body cell mass, an expansion of the extracellular mass and an increase in the ratio of total exchangeable sodium to total exchangeable potassium is quickly and effectively treated by intravenous administration of amino acids or protein hydrolysates. Long-term management of protein malnutrition requires a high protein diet (100 g/d) or reanastomosis.

Adult↗

Therapeutic approaches to anergy in surgical patients. Surgery and levamisole.

Skin tests (ST) in 1332 patients are associated with increased morbidity from sepsis. Patients with normal skin tests had a 7% major sepsis rate and 2% mortality rate. Thirty-six per cent of anergic (A) patients and 21% of relatively anergic (RA) patients died; 52% of A patients and 34% of RA patients had sepsis. These data include all patients studied and represent their worst skin test. Two studies were done. The first was a retrospective evaluation of effect of surgery upon 49 anergic patients with biliary tract disease, colon cancer, bowel obstruction, hypovolemia and visceral abscesses. The patients did not receive total parenteral nutrition (TPN). The data show that surgery without TPN can reverse the anergic state and did so in 84% of patients reported. The second study was a prospective, double-blind, randomized trial of the effect of levamisole on skin tests, neutrophil chemotaxis (CTX), sepsis and mortality iin 39 preoperative anergic patients. Major sepsis was significantly increased in placebo group (p less than 0.05). Mortality, minor sepsis, restoration of skin tests and chemotaxis were somewhat better in levamisole patients but not statistically so. These studies show that in addition to TPN, surgery and immunorestorative drugs are viable approaches to the management of selected anergic patients.

Adult↗

Protein malnutrition following intestinal bypass for morbid obesity.

Intestinal bypass surgery, performed for weight reduction in the morbidly obese patient, is frequently complicated by the development and hepatic complications. In 44 morbidly obese individuals, 55 inches of proximal jejunum were anastomosed, end to side, to 5 inches of distal ileum. All the patients were followed with body composition measurements, performed by multiple isotope dilution, prior to and at regular time intervals following bypass surgery. In 33 patients a decrease in body fat accounted for the entire postbypass weight loss, while the lean body mass remained normal in both size and composition. In these patients, at 1 year, body weights had decreased by 24.4 +/- 2.1%, while the body cell masses had decreased by 2.1 +/- 7.1%. In the remaining 11 patients, the postbypass weight loss resulted from a loss of both body fat and body cell mass. Their body weights at 1 year had decreased by 27.0 +/- 3.0%, while the body fat and body cell mass. Their body weights at 1 year had decreased by 27.0 +/- 3.0%, while the body cell masses decreased by 22.0 +/- 6.1%. Furthermore, their body compositions were characteristic of protein malnutrition with a contracted body cell mass and an expanded extracellular mass. Six of these 11 patients have required admission to hospital on 10 occasions because of malaise, anorexia, debilitating weakness, hypokalemia, and abnormal liver function. They were treated for 14.5 +/- 1.9 days with an intravenous infusion of amino acids without additional nonprotein calories. The body composition, initially characteristic of malnutrition, became normal. Their symptoms disappeared and hepatic function returned to normal. Subsequently a high-protein diet was required to prevent a recurrence of symptoms and to maintain a normal body composition. The data indicate that protein malnutrition developed in 11 of 44 patients undergoing jejunoileal bypass for weight reduction.

Adult↗

The role of stress hormones in the catabolic metabolism of shock.

The role of catecholamines in shock metabolism in dogs was studied by comparing the metabolism of shock due to cardiac tamponade, shock with catecholamine depletion from prior reserpine adminstration and metabolism in the normal dog with continuous epinephrine infusion. It was concluded that the high serum concentrations of catecholamines in shock probably cause the increased blood lactate, initial hyperglycemia and, possibly, the poor free fatty acid oxidation seen in shock, but do not cause the increased protein catabolism of shock. With the simultaneous infusion of glucagon, cortisol and epinephrine in physiologic dosages, catabolic metabolism similar to that observed in shock was established in the normal dog. Lactacidemia, hyperglycemia, poor ability to oxidize free fatty acid and massive protein breakdown were observed. The decreased metabolic rate and diminished fatty acid mobilization of shock were not duplicated in those in the normal group and are probably a function of hypoperfusion. The importance of these observations is that impaired use of fat and increased protein breakdown, as seen in shock and trauma, are mediated by hormonal changes. It follows that there may be the opportunity to reverse or modify this catabolism by hormonal manipulation in the surgical patient.

Animals↗