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Biomedical subjects

H M Shizgal

Publications and source records attributed to H M Shizgal.

At least 19 recordsLinked to original sources

The delayed hypersensitivity response and host resistance in surgical patients. 20 years later.

OBJECTIVE: A 20-year follow-up was conducted on research into the implications of a lack of a delayed-type hypersensitivity (DTH) skin test response among surgical patients. SUMMARY BACKGROUND DATA: The authors' original report showed that a failed DTH response was associated with increased hospital mortality, but the role of specific and nonspecific host defense elements, comorbid factors, nutritional supplementation, and the mechanism for anergy in this adverse outcome was unknown. METHODS: A data base of 4292 patients was analyzed and reported on individual studies designed to answer some of the above questions. RESULTS: Prospective studies showed a strong association between the DTH response and mortality: reactive patients, 2.9% (75/2576); anergic patients, 20.9% (239/1142, chi square = 265, p < 0.0000001). Antibody response to protein antigens was reduced in anergic patients. Antibody response to polysaccharide antigens was normal in all patients. The hallmark of anergy is a lack of T cells in the skin, as measured by mRNA signal (CD3) for T cells. The nonspecific component of host defense, as measured by circulating and exudate polymorphonuclear cell function, showed no statistically significant difference between elective reactive and elective anergic patients. Notwithstanding some mild malnutrition in anergic patients, parental nutrition failed to correct the DTH response or many of the cellular immune functions measured. CONCLUSIONS: Over the last 5 years, because of a reduction in overall patient mortality, the contribution of a reduced DTH response to septic related mortality has lost statistical significance in elective surgical patients. A reduced DTH response maintains its strong association to sepsis-related mortality in intensive care/trauma patients, and this is the group on which future research efforts should be concentrated.

Aged

Anabolic steroids and total parenteral nutrition.

Malnutrition develops rapidly with total starvation, especially when a catabolic stress is superimposed. The measurement of body composition provides an accurate and quantitative measurement of both the nutritional state and the response to nutritional therapy. With malnutrition there is a loss of body fat and BCM with a concomitant expansion of the ECM. With the appropriate administration of calories and amino acid as TPN, a malnourished body composition is restored to normal. However the nutritional state is restored relatively slowly, particularly when compared to the rapid rate at which malnutrition may develop, especially in the septic and starving patient. The administration of nandrolone decanoate, a potent anabolic steroid, significantly improves the efficacy of TPN, resulting in a more rapid correction of the malnourished state. However, to demonstrate this effect an accurate and precise measurement of the nutritional state is required. Furthermore it is essential to account for a number of important independent variable which influence this response; specifically the caloric intake, the nutritional state and the age.

Adolescent

The effect of age on the caloric requirement of malnourished individuals.

The effect of age on the response to total parenteral nutrition (TPN) was evaluated in 325 patients by measuring body composition by multiple-isotope dilution at the onset and at 2-wk intervals during the course of TPN. On the basis of their initial body composition, patients were divided into two groups: normally nourished and malnourished. TPN did not alter the body composition of the normally nourished patients. In the malnourished patients, a statistically significant correlation existed between the daily change in the dependent variable body cell mass (BCM) and the independent variables caloric intake, nutritional state, and age. With advancing age, more calories are required to maintain the BCM of malnourished patients. With a similar nutritional intake, a depleted BCM is restored more slowly in older patients. Age is a significant independent variable affecting the response to nutritional support.

Adolescent

Parenteral and enteral nutrition.

Stress and starvation, especially when complicated by sepsis, will give rise to a rapid erosion of the cellular mass, which significantly affects morbidity and mortality. The best clinical evaluation of the nutritional state is obtained from the medical history and the physical examination. In the patient who cannot eat a balanced diet, specialized nutritional support, in the form of either enteral or parenteral nutrition, is required to prevent malnutrition in the normally nourished, or to correct the nutritional state in the malnourished.

Enteral Nutrition

Insulin and the efficacy of total parenteral nutrition.

This study examined the effect of insulin on the efficacy of total parenteral nutrition (TPN). Patients were randomized to receive either crystalline zinc insulin (CZI) in each liter of TPN solution (insulin group) or no additional insulin (control group). The efficacy of TPN was evaluated by measuring body composition at 2-wk intervals. In malnourished patients the body cell mass (BCM) increased significantly with 2 wk of TPN both with and without additional insulin. The rate of change of BCM was correlated to the total caloric intake, serum insulin concentration, age, and nutritional state. The resulting multiple linear regression demonstrated that the restoration of a depleted BCM was directly related to the caloric intake, plasma insulin concentration, and degree of malnutrition and was inversely related to age. The addition of insulin to TPN solutions increases the rate at which a malnourished state is corrected.

Adult

Predicting mortality based on body composition analysis.

The role of the Nae/Ke ratio (the ratio of exchangeable sodium to exchangeable potassium) was examined as a nutritional marker in surgical patients in relation to anthropometrical and biochemical indexes by its ability to identify patients at risk for mortality after hospitalization. In 73 patients with sepsis and malnutrition (Training Group, Madrid) the following were determined: percentage of recent weight loss, triceps skin fold, midarm muscle circumference, serum albumin, serum transferrin, delayed hypersensitivity skin test response, total lymphocytes, and Nae/Ke ratio by multiple isotope dilution. The predictive power of Nae/Ke ratio was so strong (F = 105.1; p less than 0.00001) that it displaced anthropometric, biochemical, and immunologic variables from the linear equation derived from stepwise discriminant analysis using hospital mortality as the dependent variable. A theoretical curve of expected deaths was developed, based on an equation obtained by logistic regression analysis: Pr/death/ = 1/(1 + e[11.8-5.2 Nae/Ke]). Pre- and post-test probabilities on that curve allowed us to determine two cut-off values, Nae/Ke ratios of 1.5 and 2.5, which were markers for nonrisk and mortality, respectively. The model was tested in a heterogeneous data base of surgical patients (n = 417) in another hospital (Validation Group, Montreal). For patients exhibiting an abnormal Nae/Ke ratio (greater than 1.2) and a greater than 10% of probability of death, 54 deaths were expected and 53 observed (X2 = 1.8 NS). Two tests confirmed the basic agreement between the model and its performance, a G statistic of -0.704 and the area beneath the "receiver-operating-characteristic" (ROC) curve (Az = 0.904 + 0.0516 for the Madrid group vs. Az = 0.915 + 0.0349 for the Montreal group, NS). It was concluded from this analysis that, compared with the usual anthropometric measurements, the Nae/Ke ratio, if available, is the best method for identifying malnourished patients at risk of dying.

Adolescent

Caloric requirement of the critically ill septic patient.

The caloric requirement of the critically ill septic patient was determined by measuring body composition, by multiple isotope dilution, before and at 2-wk intervals while receiving total parenteral nutrition (TPN) in 86 septic and 57 nonseptic malnourished patients. All patients received a TPN solution containing 25% dextrose and 2.75% crystalline amino acids. The body composition of the nonseptic patients, who received 51.9 +/- 1.5 kcal/kg.day, improved significantly, while that of the septic patients, receiving 46.8 +/- 1.1 kcal/kg.day was only maintained. The relationship between caloric intake and the restoration of a malnourished body cell mass (BCM) was determined for each group by correlating, using multiple linear regression, the mean daily change in the BCM with the caloric intake and the nutritional state, as determined by body composition. According to the resultant regressions, an intake of 35.1 and 50.7 kcal/kg.day was required to maintain the BCM of the septic and nonseptic patients, respectively. To restore a depleted BCM, caloric intakes in excess of this amount are required.

Aged

Nutrition after vertical banded gastroplasty.

The authors assessed the nutritional status of 60 morbidly obese patients by determining body composition, using multiple isotope dilution at 13.6 +/- 0.4 months following operation. Body weight was followed for an additional 12.3 +/- 0.8 months. Twenty-four patients lost more than 25% of their preoperative weight and were within 30% of ideal weight (a "good" result). At 1 year they had lost 41.4 +/- 1.8% of preoperative weight and the body mass index (BMI) decreased from 46.7 +/- 1.2 to 27.0 +/- 0.6 kg/m2. Despite rapid weight loss, malnutrition did not develop and their body composition became indistinguishable from that of normally nourished volunteers. Twenty-nine patients had a "satisfactory" result with more than 25% weight loss but were not within 30% of ideal. Their weight decreased by 34.8 +/- 1.0% as their BMI decreased from 55.4 +/- 1.2 to 36.0 +/- 0.8 kg/m2. Seven patients lost less than 25% of their preoperative weight (an "unsatisfactory" result). Malnutrition did not develop in any patient. In the authors' experience, in contrast to other weight reducing operations, vertical banded gastroplasty (VBG) results in rapid weight loss without the concomitant development of malnutrition even in patients who return to normal weight.

Blood Chemical Analysis

Nutritional assessment and skeletal muscle function.

The validity of skeletal muscle function as a functional measure of nutritional state was determined by stimulating the ulnar nerve at the wrist and measuring the force of isometric contractions of the adductor pollicis muscle. Nutritional state was evaluated by measuring body composition, by multiple-isotope dilution, in 21 malnourished and 44 normally nourished patients. No significant correlation between body composition and muscle function was found. In eight normally nourished volunteers, muscle function was determined before, after 24 and 48 h of complete starvation, and 6, 24, and 48 h following resumption of normal diet. Muscle function became abnormal after 24 h of starvation and deteriorated further after 48 h. Six hours following a single normal meal, muscle function returned to normal. Experimental data indicate that the response of the adductor pollicis muscle to ulnar nerve stimulation is not an accurate measure of nutritional state.

Adult

The effect of interleukin-1 and interleukin-2 on the adrenergic control of hormone-sensitive lipase in the human adipocyte.

The effect of interleukin-1 and interleukin-2 on lipolysis and the adrenergic control of lipolysis was studied. Biopsy specimens of human adipose tissue were incubated in media containing 3H-palmitate and 14C-glucose, and the ratio of these isotopes was used to determine adipocyte lipolysis. Isoproterenol, clonidine, and theophylline were used in the media to stimulate the beta 1- and alpha 2-receptors and the subreceptor mechanism, respectively. Interleukin-1 had no effect on basal lipolysis, and at maximal receptor stimulation, it had no effect on the adrenergic receptor control of lipolysis. Interleukin-2 had no effect on basal lipolysis or on the beta-adrenergic receptor. Interleukin-2 significantly (p less than 0.02) decreased the alpha 2-inhibition of lipolysis by 68%. The effect of interleukin-2 on the alpha-receptor was demonstrated to be a significant 45% decrease (p less than 0.03) in the receptor responsiveness (a measure of the postreceptor mechanism) with no alteration in receptor sensitivity (a measure of receptor number). This data suggest that interleukin-2 stimulates lipolysis by decreasing the alpha 2-adrenergic inhibition of hormone-sensitive lipase.

Adipose Tissue

Body composition of patients with malnutrition and cancer. Summary of methods of assessment.

Body composition is determined, by multiple isotope dilution, to obtain an accurate and precise measure of the nutritional state and to evaluate the response to specialized nutritional therapy. Malnutrition results in a loss of body cell mass (BCM) accompanied by an expansion of the extracellular mass (ECM). Thus, in 75 malnourished patients the BCM was 40.5% less and the ECM was 24.6% greater than that of 25 normal volunteers, resulting in a body weight difference of only 16.3%. In 19 normally nourished patients undergoing major elective surgery, by the fifth postoperative day the BCM decreased by 13.9% and the ECM increased by 9.6%, resulting in a 3.9% loss of body weight. During an 18-month period, body composition was determined in 43 patients with cancer. Eighteen patients were nutritionally normal, whereas 25 were malnourished. In 17 of the malnourished patients, body composition was determined at 2-week intervals while they were receiving total parenteral nutrition (TPN). Body composition remained unchanged in nine but improved in eight, with a BCM increase from 14.6 +/- 1.1 to 18.4 +/- 1.2 kg. These data demonstrated that an improvement in the nutritional state can be achieved in patients with cancer.

Adipose Tissue

Reliability of the total lymphocyte count as a parameter of nutrition.

To evaluate the total lymphocyte count as a means of nutritional assessment, body composition studies (a proven method of nutritional assessment) and total lymphocyte determinations were performed simultaneously in 153 patients. The total lymphocyte count correlated poorly with both the body cell mass and the nutritional state measured by the Nae to Ke ratio. For diagnosing malnutrition, the total lymphocyte count had a false-positive rate of 34% and a false-negative rate of 50%. In a group of 78 patients who received total parenteral nutrition for 2 weeks, the total lymphocyte count did not accurately reflect the nutritional changes. Due to its poor sensitivity and specificity, the total lymphocyte count is of no value as a measure of the nutritional state.

Body Composition

The Harris Benedict equation reevaluated: resting energy requirements and the body cell mass.

The Harris Benedict equations (HBE) were derived from indirect calorimetric data obtained in 239 normal subjects. Using these data and additional data published by Benedict, which were obtained from subjects spanning a wider age range (n = 98), the present study evaluated the relationship between measured resting energy expenditure and age, sex, and predicted body cell mass (BCM). When the additional subjects from the subsequently published series are included, the regression equations, standard error of the estimate, and 95% confidence limits are similar to the original equations. The HBE estimate resting energy expenditure of a normal subject with a precision of 14%. Resting energy expenditure is directly related to the size of the BCM and is independent of age and sex. The variables of height, weight, age, and sex in the HBE reflect the relationship between body weight and the BCM. Indirect calorimetry and body composition measurements were performed in both normally nourished and malnourished patients (n = 74) to assess the accuracy of the HBE in malnourished patients. Malnutrition is associated with an increase in resting oxygen consumption (VO2) which becomes apparent only when VO2 is expressed as a function of the BCM. There is no difference in resting VO2 between the sexes when expressed as a function of BCM. A regression equation was derived from the Harris Benedict data to predict resting VO2 from age, height, weight, and sex. Predicted VO2 was not significantly different from measured VO2 for the normally nourished patients (n = 33) whereas in the malnourished (n = 41) predicted VO2 underestimated the measured value. The HBE accurately predict resting energy expenditure in normally nourished individuals with a precision of +/- 14%, but are unreliable in the malnourished patient.

Adult

Inspiratory muscle strength and body composition in patients receiving total parenteral nutrition therapy.

We examined the relationship between inspiratory muscle strength and body composition in 59 patients receiving total parenteral nutrition (TPN). Inspiratory muscle strength was assessed by measuring maximal inspiratory pressure (Pm) after a tidal expiration, with the patient supine and the nose occluded. Body composition was determined by multiple isotope dilution. Body cell mass (BCM) and extracellular mass were estimated by measuring total exchangeable potassium (Ke) and total exchangeable sodium (Nae), respectively; Nae/Ke, an index of the nutritional state, was calculated from these values. The effect of changes in muscle mass was evaluated in 29 of the patients by simultaneous determination of Pm and body composition, prior to and at 2-wk intervals during TPN therapy. The Pm was lower (mean +/- 1 SE:33.5 +/- 2.8 cm H2O) in malnourished patients than in those who were in the normal Nae/Ke range (45.3 +/- 4.8 cm H2O, p less than 0.05). Loss of strength was related to reduction in muscle mass because BCM was also reduced in malnourished patients (15.6 +/- 0.8 kg) when compared to those with normal Nae/Ke (19.3 +/- 0.9 kg), (p less than 0.05), and Pm was positively correlated with BCM (r = 0.27, p less than 0.01). Changes in BCM were accompanied by appropriate changes in Pm during the study period (r = 0.44, p less than 0.01); the majority (21 patients) showed improvement in both BCM and Pm.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Composition

Nutrition following gastric operations for morbid obesity.

Nutritional status after 238 gastric operations designed to reduce caloric intake and body weight to within 30% of ideal was assessed by measuring body composition using the multiple isotope dilution technique. Body cell mass (BCM) and body fat were quantitated before and at 24 months after operation. Malnutrition was defined as a total exchangeable sodium (Nae) to total exchangeable potassium (Ke) ratio greater than 1.22. Data were collected on 96 patients. All had lost a mean of 26% of preoperative weight by 24 months. Significant malnutrition occurred in 47 patients whose Nae/Ke ratio ranged from 1.23 to 2.17 (1.45 +/- 0.03). There was a 34% reduction in body fat. The malnourished patients lost 10% more BCM by 24 months than did the normally nourished group. Malnutrition resolved as the stoma enlarged in 19 patients, and dietary counselling helped eight patients. Eighteen patients required reoperation to establish a larger orifice, and endoscopic dilatation was successful in two patients. Administration of a liquid diet via the gastrostomy was required for prolonged periods in some malnourished patients. Seventeen patients who had lost weight rapidly over a short time had low vitamin B12, thiamine, and serum and RBC folate levels. One patient had a markedly decreased serum thiamine level with neuropathy. Symptoms of weakness, easy fatigability, and lassitude were found in the malnourished patients. Low thiamine and serum folate levels were also seen in patients ingesting a liquid diet of 750 kcal with a standard multivitamin supplement. Malnutrition was not seen in these patients. In the 49 patients who remained well nourished, BCM decreased by 19%, but the Nae/Ke remained normal. Weight loss was well tolerated, and no patients required reoperation or supplemental liquid diet to increase caloric or protein intake. The degree of malnutrition in patients after gastric operations is as great as following intestinal bypass but is not associated with liver failure. Malnutrition with vitamin deficiency is a great potential hazard in patients who undergo intake-limiting operations, especially if the goal of the operation is to restore near-normal weight. Current operations are successfully designed to maintain a small orifice size, so that the risks of malnutrition are likely to increase in the future.

Adult

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