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Biomedical subjects

L Chartrand

Publications and source records attributed to L Chartrand.

17 recordsLinked to original sources
PubMed1994

Exudative neutrophils. Modulation of microbicidal function in the inflammatory microenvironment.

OBJECTIVE: To determine whether the inflammatory microenvironment primes neutrophils for increased microbicidal activity. DESIGN: In vitro studies of host defense were performed on surgical patients. SETTING: A tertiary care, university hospital. PATIENTS: A volunteer sample of hospitalized preoperative, noninfected surgical patients. INTERVENTION: Exudative neutrophils were collected from skin-blister chambers and functionally compared with circulating neutrophils. METHODS: Flow cytometry was used to evaluate directly neutrophil microbicidal activity (using fluoresceinated Candida albicans), formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide production (using 123 dihydrorhodamine), and surface expression of CD11b, CD16, and the fMLP receptor. In vitro tumor necrosis factor alpha was used to determine the possibility and extent of further priming in both circulating and exudative neutrophils. RESULTS: Exudative polymorphonuclear neutrophils have enhanced microbicidal activity, superoxide production, and expression of CD11b, CD16, and the fMLP receptor. Exogenous tumor necrosis factor was able to prime circulating neutrophils but did not further augment superoxide production in exudative neutrophils. CONCLUSION: The microbicidal activity of neutrophils is enhanced after exudation and is associated with neutrophil priming. The inability of exogenous tumor necrosis factor to further augment superoxide production after exudation suggests that this priming has been maximized.

Candida albicans↗
PubMed1990

Anergic patients before elective surgery have enhanced nonspecific host-defense capacity.

Albeit anergy in patients before surgery is associated with an increase in septic-related complications and mortality, it is not clear whether this is due to a downregulated nonspecific host defense or a specific cellular immune defect. We studied polymorphonuclear leukocyte neutrophil (PMN) function in 14 patients who were admitted for elective surgery and compared them with 5 healthy controls. At admission, patients were classified according to their delayed-type hypersensitivity skin test response into reactive or anergic groups. In vivo PMN delivery to skin windows, the plasma lactoferrin level, serum and skin window fluid chemoattractant activity, and in vitro superoxide production were measured. Compared with reactive patients, anergic patients showed an increased cell delivery (8.7 x 10(6) PMNs per well vs 1.6 x 10(6) PMNs per well), an increased plasma lactoferrin level (4.4 +/- 1.5 mg/L vs 3.1 +/- 0.8 mg/L), an increased chemoattractant capacity of serum and skin window fluid (38 +/- 21 cells per high-power field vs 16.8 +/- 7.2 cells per high-power field), and an increased superoxide production. We concluded that nonspecific host defense, as reflected by PMNs, is enhanced in anergic patients before surgery and may not explain the increased susceptibility to infection.

Adult↗
PubMed1989

Estimating mortality risk in preoperative patients using immunologic, nutritional, and acute-phase response variables.

We measured the delayed type hypersensitivity (DTH) skin test response, along with additional variables of host immunocompetence in 245 preoperative patients to determine which variables are associated with septic-related deaths following operation. Of the 14 deaths (5.7%), 12 were related to sepsis and in 2 sepsis was contributory. The DTH response (p less than 0.00001), age (p less than 0.0002), serum albumin (p less than 0.003), hemoglobin (p less than 0.02), and total hemolytic complement (p less than 0.03), were significantly different between those who died and those who lived. By logistic regression analysis, only the DTH skin test response (log likelihood = 41.7, improvement X2 = 6.24, p less than 0.012) and the serum albumin (log likelihood = 44.8, improvement X2 = 17.7, p less than 0.001) were significantly and independently associated with the deaths. The resultant probability of mortality calculation equation was tested in a separate validation group of 519 patients (mortality = 5%) and yielded a good predictive capability as assessed by (1) X2 = 0.08 between observed and expected deaths, NS; (2) Goodman-Kruskall G statistic = 0.673) Receiver-Operating-Characteristic (ROC) curve analysis with an area under the ROC curve, Az = 0.79 +/- 0.05. We conclude that a reduced immune response (DTH skin test anergy) plus a nutritional deficit and/or acute-phase response change are both associated with increased septic-related deaths in elective surgical patients.

Acute-Phase Proteins↗
PubMed1988

Quantitative and qualitative study of the restoration by cytokines of mononuclear cell delivery to skin test sites in anergic surgical patients.

We tested the hypothesis that anergy is associated with reduced delivery of mononuclear cells (MNCs) to delayed-type hypersensitivity sites and that cytokine (CK)-rich supernatants from mixed lymphocyte cultures overcome the defect. Significantly fewer MNCs were delivered to skin window chambers placed over purified protein derivative (PPD) injection sites of previously sensitized anergic patients compared with hospitalized PPD-reactive patients; coinjection of CK with PPD restored the MNC delivery in anergic patients to normal levels. The T cells cloned from a PPD + CK site of an anergic patient consisted of CD4+ and CD8+ cells whose capacities included cytotoxicity and lymphokine production. The frequency of PPD-reactive cells was 15 times greater than in the blood. Thus, the restoration by CK of the delivery of antigen-specific cells capable of participating in cell-mediated immunity in anergic patients may be feasible.

Adult↗
PubMed1988

Lack of cytokine-induced skin reaction correlates with acute physiology score and mortality in patients receiving intensive care.

Because the majority of patients receiving intensive care are anergic to ubiquitous skin test antigens, prediction of clinical outcome cannot be based on their delayed-type hypersensitivity score, which is 0, but which is also a strong indicator of sepsis-related mortality in the preoperative patient. However, a cytokine-rich supernatant generated in the mixed lymphocyte culture reaction is able to induce an early skin reaction that peaks at 12 hours and wanes by 24 hours in some, but not all, anergic patients. Assessment of the clinical course of these patients demonstrated that only three of 25 patients who had a skin reaction larger than 5 mm died, compared with ten of 16 patients who failed to display this early reaction. Further analysis showed that both the cytokine-induced reaction and the acute physiology score significantly and independently contributed to the probability of death in anergic patients. These data suggest that the ability to generate a local inflammatory response to cytokines in anergic patients identifies a subpopulation of patients who have maintained some host-defense responsiveness and this response can be utilized to predict outcome.

Acute Disease↗
PubMed1983

Effect of diversion of pancreatic secretions on biliary lipids and bile salt kinetics in the rat.

The hypothesis that the absence of pancreatic secretions from the lumen of the intestinal tract could alter the secretion rate of biliary lipids and the kinetics of bile salts was tested in rats with a pancreatic fistula fed intragastrically either a high or a low fat liquid diet over a 4-day period. In animals with external derivation of all pancreatic secretions who were given the high fat diet, stools were pale and bulky, the basal synthesis rate of bile acids was almost twice that of controls, and there was an increase in the secretion rate of cholesterol and phospholipids calculated from the first 2 h of bile collection. On the low fat diet, there was no change in basal bile salt synthesis, but the pool was larger and the secretion rate of bile acids and phospholipids was increased. A study of the quantitative relationship between the excretion rate of phospholipids and of cholesterol to that of bile acids following complete biliary diversion revealed a disproportionately large output of cholesterol at low bile acid flow rates under both diets in rats with a pancreatic fistula. These data suggest that experimental pancreatic insufficiency leads to alterations of the secretion rate of biliary lipids and to uncoupling of the close relationship between bile acids and cholesterol.

Animals↗
PubMed1980

Gastric emptying and lingual lipase activity in cystic fibrosis.

To identify gastric factors likely to contribute to fat maldigestion and malabsorption in cystic fibrosis (CF), gastric emptying time, secretion rate, and preduodenal lipolytic activity were studied. Gastric emptying of a liquid test meal and gastric acid secretion were determined in five CF teenagers with pancreatic insufficiency and in five healthy controls. During the first hr, the rate of gastric emptying exhibited a linear pattern in both CF patients and controls. Neither the emptying time nor the gastric secretion rate was different. Lingual lipase activity was measured in eight other CF patients with pancreatic insufficiency and in eight controls. Lipase activity was higher (P less than 0.05) in CF patients than in controls with values (mean +/- S.E.) of 34.48 +/- 11.59 and 12.65 +/- 5.60 mumole butyric acid min-1 ml-1, respectively. No correlation with age or body surface was observed. Intragastric lipolysis of a butterfat triglyceride test meal was fast in both groups, but more extensive (P less than 0.05) in CF patients than in controls. The data show that in CF with pancreatic insufficiency, gastric factors contributing to the first step of fat digestion are preserved. In fact, lingual lipase activity was found to be increased, and a more complete intragastric lipolysis was documented.

Adolescent↗
PubMed1979

The role of gastric lipolysis on fat absorption and bile acid metabolism in the rat.

In vivo studies were carried out in young Sprague-Dawley rats to examine the role of gastric lipolysis on fat absorption and bile acid metabolism. When fed by gastric perfusion 5 times (corn oil, 4 g/day) their usual dietary intake of fat, rats deprived of lingual lipase by the creation of an esophageal fistula had a significant degree of fat and bile acid malabsorption as well as a shortened bile acid half-life when compared to animals with a gastrostomy. The % fat absorption, bile acid loss and bile acid pool were normal in 2 groups of esophageal fistula rats fed the same quantity of corn oil or twice (8 g/day) that amount as a fine emulsion. In view of a negligible gastric lipase activity in animals with an esophageal fistula and of decreased hydrolysis of a triglyceride test meal, these data suggest that gastric lipolysis is of physiological importance in situations where lipolytic mechanisms are stressed by a large fat intkae. Its principal role is to potentiate intestinal lipolysis by facilitating the emulsification of dietary lipids through its formed products and, therefore, the contact of pancreatic lipase with its substrates.

Animals↗
PubMed1976

Relationship between bile acid malabsorption and pancreatic insufficiency in cystic fibrosis.

Bile acid loss (mg/m2 24h) in the stools of 43 cystic fibrosis (CF) children with pancreatic insufficiency was 751-1 +/- 48-3, while that of six without clinical evidence of pancreatic disease (133-4 +/- 15-9) did not differ from values in 25 controls (109-8 +/- 9-8). There was a good correlation between the degree of bile acid (BA) and fat sequestration. Concomitant changes in bile acid and fat loss were observed in the one group of six patients studied on and off pancreatic enzymes as well as in a second group of seven children treated with pancreatic supplements and maintained on a normal diet followed by a low fat diet supplemented with medium chain triglycerides. Administration of NA bicarbonate led to a significant decrease in fat loss (15-8 +/- 2-7 leads to 10-3 +/- 1-9) without any simultaneous change in bile acid excretion (533-1 +/- 58-3 leads to 500-4 +/- 58-6). Qualitative bile acid patterns in controls, in infants after an ileal resection, and in patients with CF or with coeliac disease showed that the percentage of primary BA followed closely the total amount excreted except in situations where antibiotics were administered. The exact mechanism for the increased loss of BA in CF is unknown. It is found in all age groups and is related to the presence and degree of pancreatic insufficiency. The possibility that unhydrolysed triglycerides may interfere with the intestinal absorption of bile acid needs further confirmation.

Adolescent↗
PubMed1975

Correction of the malabsorption of the preterm infant with a medium-chain triglyceride formula.

After receiving milk-based formula for one week, 16 preterm infants, weighing 1,300 to 1,800 gm, were fed two isocaloric formulas containing either medium-chain or long-chain triglycerides for 15 days; the alternate formula was given for a second period of identical duration. While receiving MCT, the infants had greater (P smaller than 0.01) percent fat absorption (83.4 leads to 97.1%) and weight gain (7.5 leads to 11.5 gm/kg/100 calories). Because metabolic acidosis occurred with the LCT formula, the chloride content was adjusted to that of the MCT were confirmed and, in addition, there was a higher (P smaller than .01) percent retention of nitrogen (67.3 leads to 82.1).

Body Weight↗
PubMed1975

The effect of bile and of sodium taurocholate on the epithelial cell dynamics of the rat small intestine.

The absence of bile from the intestinal lumen of rats for a period of 48 hr led to: a decreased proliferative cell pool, reduced cell shedding, and a 50% decrease of the labeling index in the ileum. The constant duodenal perfusion of Na taurocholate for periods of 48, 60, 72, and 96 hr in animals with a biliary diversion was associated with: deepening of crypts and decreased crypt/villus ratios as well as with acceleration of the epithelial cell migration rate on the crypt-villus units. The data suggest that bile and bile acids constitute important regulatory factors influencing enterocyte proliferation, migration and loss.

Animals↗