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Biomedical subjects

J M Tellado

Publications and source records attributed to J M Tellado.

6 recordsLinked to original sources

Altered neutrophil function following reperfusion of an ischemic myocutaneous flap.

The neutrophil has been implicated as a source of oxygen free radicals provoking the reperfusion injury in various ischemic organs. This provided the motivation to explore the pathophysiologic role of the neutrophil in a swine model of postischemic latissimus dorsi myocutaneous flaps. Neutrophil function, neutrophil sequestration, and the anatomic distribution of muscle injury were estimated following a 6- to 8-hour global ischemic insult. Neutrophil function as measured by phorbol myristate acetate-stimulated superoxide production was found to be enhanced on reperfusion of ischemic flaps (n = 17). Neutrophil sequestration estimated from the arterial-venous difference of flap blood (n = 12) demonstrated that postischemic flaps more avidly sequester neutrophils than nonischemic flaps. The anatomic distribution of muscle injury (n = 7) was predominantly localized to the proximal portion of the ischemic flap. The enhanced functional response exhibited by neutrophils reperfusing an ischemic myocutaneous flap supports an active neutrophil role in the mediation of reperfusion injury.

Analysis of Variance

Critically ill anergic patients demonstrate polymorphonuclear neutrophil activation in the intravascular compartment with decreased cell delivery to inflammatory focci.

Skin test anergy, the failure to produce a delayed type hypersensitivity (DTH) response, is associated with an increase in infection-related complications and death usually due to multiple organ failure (MOF). Refractory intravascular activation of polymorphonuclear neutrophils (PMNs) has been implicated in the development of MOF. We studied 20 critically ill surgical patients with life threatening infections to determine if PMN intravascular activation was present and how this affected essential PMN functions such as exudation. The 11 anergic patients had a more intense inflammatory response to their infection. Plasma lactoferrin was 6.1 +/- 0.3 microgram/ml in anergic patients compared to 3.9 +/- 1.5 in reactive P less than 0.05, accompanied by reduced total primary (3.3 +/- 1.9 vs 4.7 +/- 2.1 micrograms/10(6) PMN P less than 0.01) and secondary (2.8 +/- 0.4 vs 5.0 +/- 0.9 microgram/10(6) PMN P less than 0.01) granule content, respectively. In vitro superoxide production following 100 ng/ml PMA stimulation was 0.44 +/- 0.1 in anergics vs 0.36 +/- 0.1 nmol/microgram PMN protein in reactivities, P less than 0.05. PMN chemotaxis was 8.2 +/- 0.6 PMNs/HPF in anergics compared to 10.2 +/- 1.6 PMNs/HPF in reactives P less than 0.05, accompanied by decreased PMN delivery to skin blister windows (3.2 +/- 1.4 vs 4.5 +/- 1.9 x 10(7) PMN/ml, respectively, P less than 0.05). We conclude that critically ill anergic surgical patients have increased intravascular PMN activation, which may contribute to oxygen-derived tissue damage in the vascular space, as well as a deficient delivery of effector cells in areas of bacterial invasion. This may lead to inability to clear the inflammatory signals which set up the vicious circle of MOF leading to death.

Cell Adhesion

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

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

In vitro polymorphonuclear neutrophil function in surgical patients does not correlate with anergy but with "activating" processes such as sepsis or trauma.

We studied 199 preoperative patients admitted for esophagogastric, gastric, colonic, or rectal resections, 132 patients with severe blunt trauma, 180 surgical intensive care unit patients with major sepsis, and 95 laboratory controls in order to clarify the role of polymorphonuclear neutrophil (PMN) adherence and chemotaxis to outcome. Patients were also stratified by the delayed-type hypersensitivity response to five ubiquitous antigens. PMN adherence and PMN chemotaxis were not different in preoperative reactive or anergic patients and were equal to the control values, whereas both reactive patients and anergic patients showed altered PMN function after trauma or sepsis. There was no difference in PMN adherence or chemotaxis between patients who died and those who lived. Multiple logistic regression analysis showed that patient age, delayed-type hypersensitivity, and admission serum albumin level, not PMN adherence or chemotaxis, were significantly related to septic mortality. We concluded that altered circulating PMN adherence and chemotaxis is seen in all patients after an "activation" event such as trauma or sepsis. This is a nonspecific immune alteration not related to specific immune events such as delayed-type hypersensitivity; it does not correlate with patient outcome and should not be used as a predictive variable.

Adult

The anergic state as a predictor of pancreatic sepsis.

From 1984 to 1987, 187 patients with acute pancreatitis (AP) were studied. All patients were stratified according to Ranson's criteria upon admission and were followed up by performing a CT scan weekly. One hundred and thirty-eight patients had 3 or less Ranson's criteria (non-severe acute pancreatitis = NSAP) and 49 presented 4 or more (severe acute pancreatitis = SAP). Ninety-six percent of the patients with (p less than 0.0001). Of the 49 patients with SAP, 39 developed pancreatic or peripancreatic NSAP were reactive to skin tests on the third week, while 4% remained anergic necrosis and were operated. Twenty-two of these patients had positive cultures demonstrating the presence of bacteria in the tissue samples. One hundred percent of the infected patients remained anergic until surgery, while only 40% of those with negative cultures remained anergic (p less than 0.05). Mortality rate correlated well with skin test responses, being 31% in anergic patients while only 5% in reactive subjects. Sustained anergic state (AS), sequentially checked, is associated with a high incidence of pancreatic sepsis.

Acute Disease