Biomedical subjects

B Kapadia

Publications and source records attributed to B Kapadia.

7 recordsLinked to original sources

PubMed1996

Expression of human neutrophil L-selectin during the systemic inflammatory response syndrome is partly mediated by tumor factor alpha.

BACKGROUND: Rolling of neutrophils on the vascular endothelium is a requisite step to transmigration to areas of infection or inflammation, and this is regulated in part by the neutrophil cell adhesion molecule L-selectin. OBJECTIVES: To compare L-selectin expression in patients with systemic inflammatory response syndrome (SIRS) and healthy age-matched control subjects and to determine whether tumor necrosis factor alpha modulates L-selectin expression on human neutrophils. SETTING: A tertiary care surgical intensive care unit at a university teaching hospital. SUBJECTS: Patients identified with SIRS (American College of Critical Care Physicians and Society of Critical Care Medicine criteria) were compared with healthy age-matched control subjects. Venous blood samples that were obtained from healthy laboratory control subjects were used to examine the time course of L-selectin expression. MAIN OUTCOME MEASURES: Neutrophil L-selectin expression was determined by flow cytometry in patients with SIRS and control subjects. Tumor necrosis factor alpha concentrations were determined in blood and exudative fluid from patients with SIRS. Neutrophil L-selectin expression was measured during a 45-minute time course in the presence of recombinant human tumor necrosis factor alpha and N-formyl-methionyl-leucyl-phenylalanine. RESULTS: Circulating neutrophils from patients with SIRS had significantly less L-selectin expression than did control subjects. Tumor necrosis factor alpha at concentrations similar to those found in exudative fluid caused a dose- and time-dependent decrease in neutrophil L-selectin expression. CONCLUSION: Tumor necrosis factor alpha may act as a paracrine modulator of site-specific neutrophil rolling, adhesion, and exudation via mechanisms that involve the down-regulation of L-selectin.

Age Factors↗

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↗

PubMed1983

Fatty acid supply and organ phospholipid turnover in two canine shock models.

Serum free fatty acid (FFA) flux is decreased in shock. The question arose whether the limited availability of FFA would result in a fuel deficit in organs containing no stored lipid and also in the slower turnover of organ phospholipids. The fasting dog's lung, stomach, heart, and liver contained little or no triglyceride, while skeletal muscle, diaphragm, and occasionally intestine had large lipid stores. The replacement rate of lipid fuels and the turnover rate of the fatty acyl moieties of phospholipids were determined by radioactive tracer methods in several organs of dogs in shock due to controlled cardiac tamponade or hemorrhage and their respective controls. In the normotensive controls one-third of the FFA available was directly oxidized; the rest was temporarily incorporated into phospholipids and triglycerides. This incorporation represents replacement of lipid fuels in the organs. Both shock models caused a similar decrease in the total FFA flux and a similar pattern of redistribution among organs. Organs other than heart, lung, and diaphragm replenished their lipid stores slowly in shock. This could cause a fuel deficit in liver and stomach, neither of which have large triglyceride stores. FFA incorporation into phospholipids was slower than esterification into triglycerides in all organs except diaphragm and skeletal muscle both in shock and in normotension. The rate of phospholipid turnover decreased significantly in shock in liver, intestine, and stomach, but increased in heart and lung. Thus liver and stomach are the organs most likely to be affected by the decreased availability of FFA in shock.

Animals↗

PubMed1983

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↗

PubMed1982

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↗