Biomedical subjects

N V Christou

Publications and source records attributed to N V Christou.

At least 19 recordsLinked to original sources

PubMed1992

Abnormal in vitro immunoglobulin synthesis in surgical patients.

Blood mononuclear cells from surgical patients produce large amounts of IgG in vitro. This synthesis is not increased by stimulation with pokeweed mitogen. To determine if this abnormal pattern of IgG synthesis extended to other immunoglobulin classes, surgical patients were stratified according to delayed-type hypersensitivity responses as reactive or anergic. Healthy personnel were studied as controls. Mononuclear cells were cultured without or with pokeweed mitogen, and IgG, IgM, and IgA were measured in supernatants. Unstimulated IgG and IgA synthesis was increased in surgical patients, especially in those with reduced delayed-type hypersensitivity responses. Synthesis of IgM was normal or low. With mitogen stimulation, IgG synthesis was increased in control and reactive subjects, but not in anergic subjects. For IgM, mitogen stimulation increased synthesis to a less than normal level in all patients. For IgA, synthesis was increased in all groups.

Adult↗

PubMed1992

[Anomalies of immunoglobulin synthesis in vitro in surgical patients].

It is known that blood mononuclear cells from surgical patients produce large amounts of IgG in vitro, and that this synthesis is not increased by pokeweed mitogen stimulation. The objective of the present study was to determine if this abnormal pattern of IgG synthesis extended to other immunoglobulin classes. Patients were stratified according to delayed type hypersensitivity as reactive (induration > 5 mm to > one skin test antigen), or anergic (no response). Healthy laboratory personnel were studied as controls. Mononuclear cells were cultured for 10 days, without or with pokeweed mitogen. IgG, IgM, and IgA in supernatant was measured using a competitive solid phase radioimmunoassay. Unstimulated IgG and IgA synthesis was increased in surgical patients, especially in those with reduced delayed type hypersensitivity responses. IgM synthesis was normal or low. With mitogen stimulation, normal increases in IgG synthesis were seen in control and reactive subjects. In anergic patients, IgG was not increased by pokeweed mitogen. For IgM, mitogen stimulation increased synthesis but to a lesser degree in patients than in controls. For IgA, synthesis was increased by mitogen stimulation in all groups. In conclusion, surgical patients show abnormalities in the pattern of spontaneous and mitogen stimulated immunoglobulin synthesis. The pattern varies for each isotype. B cell activation is present in surgical patients, especially those with reduced delayed type hypersensitivity. This suggests either recent antigenic stimulation, or non-antigen specific dysregulation of the B cell system in surgical patients.

Cells, Cultured↗

PubMed1991

Humoral immunity in surgical patients with and without trauma.

We measured antitetanus toxoid antibody responses after blunt (n = 24) and penetrating (n = 7) trauma and compared them with responses in patients without trauma (n = 55). Patients were defined as anergic or reactive on the basis of delayed type hypersensitivity response. The response to tetanus toxoid vaccination on admission of patients surviving trauma for over 2 weeks was defined as the ratio of day 14 to day 0 serum IgG antitetanus toxoid levels. Antitetanus toxoid responses were normal after both blunt and penetrating trauma. When stratified according to delayed type hypersensitivity responses, patients with trauma showed better antibody responses than patients without trauma. Major infection rates were similar between trauma groups (three of 24 with blunt trauma vs two of seven with penetrating trauma) and independent of delayed type hypersensitivity (two of 20 reactive patients vs three of 11 anergic patients), in contrast to patients without trauma (one of 19 reactive patients vs 15 of 36 anergic patients). We conclude that decreased delayed type hypersensitivity after moderate trauma is temporary, and that this transient immunodeficiency is not as strongly associated with reduced antibody responses and increased risk of infection as anergy in surgical patients without trauma.

Adolescent↗

PubMed1991

Tumor necrosis factor alone does not explain the lethal effect of lipopolysaccharide.

Lethality and tumor necrosis factor production induced by different types of lipopolysaccharide were studied in naive (non-primed) rats during the late phase of endotoxin tolerance. The correlation with antilipopolysaccharide antibodies was also analyzed. No correlation was found between tumor necrosis factor levels and lipopolysaccharide-induced mortality in naive animals. Low-toxicity lipopolysaccharide preparations induced levels of tumor necrosis factor similar to those induced with more toxic types of lipopolysaccharide. Late tolerance was associated with progressively lower levels of lipopolysaccharide-induced tumor necrosis factor and increasing titers of antilipopolysaccharide antibodies after repeated injections of homologous lipopolysaccharide. During late endotonxin tolerance, a direct correlation between the lipopolysaccharide dose and peak tumor necrosis factor serum levels was found. We conclude that since tumor necrosis factor serum levels do not correlate with mortality, tumor necrosis factor alone cannot explain the lethal effect of lipopolysaccharide.

Animals↗

PubMed1991

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↗

PubMed1991

Clinical outcome of seriously ill surgical patients with intra-abdominal infection depends on both physiologic (APACHE II score) and immunologic (DTH score) alterations.

The delayed-type hypersensitivity (DTH) response and the APACHE II score in 118 patients with surgical infections were measured prospectively and related to outcome. Logistic regression analysis generated the equation: [formula: see text]. The risk assessment as calculated by this model was compared to that using the APACHE II system alone in a separate group of 354 patients. There was an improvement in the predictive capacity of the APACHE II + DTH equation compared to APACHE II alone, as shown by a better fit of expected and observed deaths, an improved Goodman-Kruskal G statistic, and a larger area under the receiver operating characteristic curve. It is concluded that the DTH response (a broad marker of immunocompetence) is an independent prognostic factor in surgical patients and can be used in combination with the APACHE II score (a measure of acute physiology) to estimate better the outcome of surgical patients.

Abdomen↗

PubMed1991

Species differences in the infectability of vascular grafts.

The susceptibility of different species to bacteremia may influence the results of studies on vascular graft infection. The present study compares prosthetic graft infection in canine and porcine models. Thirty-four mongrel dogs and 38 Yorkshire pigs underwent replacement of the infrarenal aorta with a 3-cm segment of a woven Dacron prosthesis. At the time of closure, each animal received an intravenous inoculum of 10(2) to 10(8) Staphylococcus aureus (S. aureus). Graft cultures at 1 week produced a predictable infection rate in dogs, while pigs developed only random infections (dogs: 23/34; pigs: 7/38; p = .0001). The median infective dose (ID50) in dogs was 10(2.9) but pigs did not develop enough infections to determine this value. Electron microscopy revealed a smooth fibrin surface in grafts explanted from pigs, while grafts from dogs demonstrated bacteria enmeshed in an irregular fibrinous lining. Prosthetic vascular grafts in dogs are more susceptible to hematogenous infection than those in pigs. Because hematogenous infection in humans is a rare event, the swine model may be a more appropriate representation of the clinical situation.

Animals↗

PubMed1991

Species differences in the clearance of Staphylococcus aureus bacteremia.

Studies on vascular graft infections may be influenced by species differences in bacteria clearance. The present study compares the bloodstream elimination of Staphylococcus aureus (S. aureus) in dogs and pigs. Four mongrel dogs and four Yorkshire pigs received a 20-min infusion of 10(6) S. aureus labeled with indium-131. Through a catheter placed in the infrarenal aorta, blood samples were removed at intervals for 5 h after infusion. The liver, spleen, and lungs were biopsied at 5 h. Blood and tissue samples were then counted in a gamma counter. The calculated phagocytotic index, k, for dogs was 8.6 X 10(-4), while for pigs it was 1.5 X 10(-3), indicating significantly faster bacterial clearance in pigs (p = .009). After 2 1/2 h, significantly fewer counts were present in pigs at most time points (p less than .05). Organ counts indicated higher counts in the dog liver and spleen and in the lungs of pigs (p less than .0001). This study indicates that S. aureus bacteremia is cleared faster by pigs, primarily by the lungs, compared to dogs, in which liver-spleen clearance predominated. These differences should be considered when the results of graft infection studies are compared.

Animals↗

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↗

PubMed1990

Pathogenicity of the enterococcus in surgical infections.

The enterococcus has been relegated to a position of unimportance in the pathogenesis of surgical infections. However the increasing prevalence and virulence of these bacteria prompt reconsideration of this view, particularly because the surgical patient has become increasingly vulnerable to infectious morbidity due to debility, immunosuppression, and therapy with increasingly potent antibiotics. The enterococcus is a versatile opportunistic nosocomial pathogen, causing such diverse infections as wound, intra-abdominal, and urinary tract infections; catheter-associated infection; suppurative thrombophlebitis; endocarditis; and pneumonia. Although surgical drainage remains the cornerstone of therapy for enterococcal infections involving a discrete focus, in the circumstances typified by the compromised surgical patient, specific antibacterial therapy directed against the enterococcus is warranted. Recent evidence indicates that parenteral antibiotic therapy for enterococcal bacteremia is mandatory and that appropriate therapy clearly reduces the number of deaths.

Cross Infection↗

PubMed1990

Results of a multicenter trial comparing imipenem/cilastatin to tobramycin/clindamycin for intra-abdominal infections.

We designed a multicenter study to compare tobramycin/clindamycin to imipenem/cilastatin for intra-abdominal infections. We included the Acute Physiology and Chronic Health Evaluation (APACHE II) index of severity and excluded patients without established infection. Two hundred ninety patients were enrolled, of whom 162 were evaluable. Using logistic regression to analyze both outcome at the abdominal site of infection and outcome as mortality, we found a significant correlation for both with APACHE II score (p less than 0.0001 for both). Next we analyzed the residual effect of treatment assignment and found a significant improvement in outcome for imipenem/cilastatin-treated patients (p = 0.043). The differences in outcome were explained by a higher failure rate for patients with gram-negative organisms for tobramycin/clindamycin-treated patients (p = 0.018). This was reflected in a significantly higher incidence of fasciitis requiring reoperation and prosthetic fascial replacement. Maximum peak tobramycin levels were analyzed for 63 tobramycin/clindamycin patients harboring gram-negative organisms. For failures the maximum peak was 6.4 +/- 1.9 micrograms/mL, and time to maximum peak was 4.6 +/- 5.2 days. For successes the maximum peak was 6.1 +/- 1.7 micrograms/mL, occurring at 3.8 +/- 2.6 days. This study supports inclusion of severity scoring in statistical analyses of outcome results and supports the notion that imipenem/cilastatin therapy improves outcome at the intra-abdominal site of infection as compared to a conventionally prescribed amino-glycoside-based regimen.

Abscess↗

PubMed1990

Double-blind study of endotracheal tobramycin in the treatment of gram-negative bacterial pneumonia. The Endotracheal Tobramycin Study Group.

A prospective, double-blind, placebo-controlled study was conducted to determine the safety and efficacy of endotracheal tobramycin (ETT) for treatment of gram-negative bacterial pneumonia. Patients were randomized to either 40 mg of tobramycin or a placebo instilled endotracheally every 8 h. Patients also received intravenous tobramycin plus either cefazolin or piperacillin. Of 85 patients enrolled, 41 were assessable. Most microbiologic diagnoses were made by endotracheal aspiration with strict grading criteria. The clinical-radiographic responses of patients and standard demographic data were recorded. Pseudomonas aeruginosa, "multiple pathogens," and Klebsiella-Enterobacter-Serratia-Citrobacter species were isolated in 41, 32, and 15% of the instances, respectively. Causative pathogens were eradicated from sputum significantly more frequently by patients who received ETT (P less than 0.05). However, no significant differences were noted in the clinical outcomes of the two study groups. No local adverse reactions attributable to the administration of this agent were observed, but four patients had supraventricular tachycardia, compared with none who received the placebo (P = 0.053). ETT may be considered as adjunctive therapy for seriously ill individuals.

Adult↗

PubMed1990

Imipenem versus tobramycin--antianaerobe antibiotic therapy in intra-abdominal infections.

The authors compared broad-spectrum monotherapy with imipenem to an aminoglycoside-based antibiotic regimen for the management of intra-abdominal infections. One hundred and four patients who had intra-abdominal infection were randomly allocated to receive imipenem (52) or tobramycin plus clindamycin or metronidazole (52). Patients treated with imipenem had fewer febrile episodes and occurrences of breakthrough bacteremia, less antibiotic resistance and need for drug change; their hospital stay was shorter. The death rate from sepsis was 4% in patients who received imipenem and 13% in those who received the combined regimen (p = 0.08). Treatment was successful in 79% of patients on imipenem versus 67% of those receiving an aminoglycoside. Patient stratification by the APACHE II system and probability of death calculation using delayed-type hypersensitivity scores predicted a similar death rate for the two treatment groups. Imipenem appears to be a safe and efficacious alternative broad-spectrum antibiotic for treating patients who are seriously ill with intra-abdominal infection.

Abdomen↗

PubMed1990

Induction of an immune response to keyhole-limpet hemocyanin in surgical patients with anergy.

Groups of surgical patients, classified as reactive or anergic on the basis of delayed type hypersensitivity skin testing with five recall antigens, were immunized with keyhole-limpet hemocyanin (KLH) alone or KLH together with mediators derived from leukocytes of a KLH immune donor cultured with antigen. Patients with anergy injected with KLH alone did not generate an immune response as judged by a T cell proliferative reaction performed 14 days after immunization. In contrast, leukocytes of patients with anergy immunized with KLH together with the mediators reacted to KLH in vitro in similar numbers and with a magnitude comparable to that given by reactive, hospitalized patients without anergy immunized with KLH alone. These results confirm and extend our previous observations showing that anergy defined as a lack of cell-mediated immunity to recall antigens such as purified protein derivative extends to the generation of a systemic immune response to a neoantigen such as KLH and mediators that could restore a state of delayed hypersensitivity to purified protein derivative could also be instrumental in inducing cell-mediated immunity de novo when injected together with the antigen.

Antibody Formation↗

PubMed1989

Endotoxin tolerance is associated with reduced secretion of tumor necrosis factor.

Bacterial endotoxin effects are partially mediated by tumor necrosis factor (TNF). It is known that sublethal doses of endotoxin induce transient refractoriness (tolerance) to some of its effects. We studied the role of TNF in endotoxin tolerance in rats. Weight loss, lethality, and TNF production were measured after an initial dose of endotoxin and after subsequent doses. Weight loss reached its peak 72 hours after the initial endotoxin challenge, followed by recovery even under continued administration of endotoxin. While tolerant, rats could survive a dose of endotoxin that was lethal for 100% of naive rats. The high serum levels of TNF, observed 90 minutes after the first dose of endotoxin, markedly diminished when rechallenged during tolerance. Recovery of responsiveness to these effects followed the refractory phase by 3 weeks. We concluded that endotoxin tolerance is associated with a reduced secretion of TNF.

Animals↗

PubMed1989

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↗

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↗

PubMed1989

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↗