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C Delclaux

Publications and source records attributed to C Delclaux.

At least 19 recordsLinked to original sources
PubMed2003

Induction of type-IIA secretory phospholipase A2 in animal models of acute lung injury.

The aim of this study was to evaluate the presence of type-II secretory phospholipase A2 (sPLA2-IIA) in alveolar space and its possible role in the destruction of surfactant in three rat models of acute lung injury. Alveolar instillation of either lipopolysaccaride or live Pseudomonas aeruginosa resulted in a significant increase in lung oedema and in a decrease in static compliance of the respiratory system together with alveolar-neutrophil influx as compared with healthy control rats. The upregulation of messenger ribonucleic acid and sPLA2-IIA by the lung was evident. This was associated with surfactant degradation and a decrease in large:small ratio of surfactant aggregates in bacteria-instilled rats. A negative correlation between compliance and sPLA2-IIA activity in bronchoalveolar lavage fluid was shown. By contrast, during alpha naphthylthiourea-induced injury, neither alveolar-neutrophil influx nor increase in sPLA2-IIA activity was observed. Additional experiments in rats treated with a specific inhibitor of type-II secretory phospholipase A2 activity (3 acetamine-1-benzyl-2 ethylindolyl-5 oxy; propane phosphonic acid (LY311727)) demonstrated no improvement in physiological parameters despite a biochemical effect, suggesting that its activity is only one of the multiple factors involved in the pathophysiology of lung injury.

Animals↗
PubMed2003

Inflammatory response to infectious pulmonary injury.

This review describing the inflammatory response to infectious pulmonary injury is focused on the innate immunity of the distal lung to bacterial pneumonia. The fact that the inflammatory response varies to some extent with the bacterial strain responsible for the infection is emphasised. The key cellular components present in the distal lung are described. The major role of alveolar macrophage is described, inasmuch as it responds to the usual daily challenges of bacteria entering the terminal airways and is capable of initiating an inflammatory reaction if the microbial challenge is either too large or too virulent. Under these conditions, the alveolar macrophages initiate an inflammatory response that recruits large numbers of neutrophils into the alveolar spaces. The strategy of the innate immune response may not be to recognise every possible antigen, but rather to focus on a few, highly conserved structures present in large groups of microorganisms. These structures are referred to as pathogen-associated molecular patterns and the receptors of the innate immune system that evolved to recognise them are called pattern-recognition receptors. The soluble factors in innate defence, such as cytokines, are described, and a last paragraph discusses whether a specific inflammatory response could characterise nosocomial pneumonia.

Cytokines↗
PubMed2002

[Hemolytic-uremic syndrome complicating a long-term treatment with gemcitabine. Report of a case and review of the literature].

INTRODUCTION: Gemcitabine is a nucleoside analog used in solid tumors since 1987. The main side effect is myelosuppression. Acute renal failure with thrombotic microangiopathy has also been reported. We report a new case and suggest to screen for this complication. EXEGESIS: A 71-year-old man with metastatic adenocarcinoma of the pancreas was treated with gemcitabine. He developed episodes of recurred haemolysis followed by haemolytic uremic syndrome. One single haemodialysis session was performed. No other known causes for haemolytic and uremic syndrome were found. Gemcitabine appears to be a new cause of thrombotic microangiopathy. It results from cumulative effects, arises preferentially when there is a renal dysfunction and diagnosis is often delayed. Treatment must be stopped. CONCLUSION: We suggest that reticulocyte count, haptoglobin level and urinalysis could help the clinician to maintain high vigilance and to have a rapid diagnosis for this rare disorder.

Aged↗
PubMed2001

Long-term (> or =20 yr) status of 14 cadaveric kidney-transplant recipients.

The aim of this study was to analyze the status of patients with a successful long-term (> or =20 yr) kidney graft. Nineteen (8.1%) of the 234 recipients who received a cadaveric kidney transplant between 1968 and 1978 in our center are still alive 21.7+/-1.6 yr (mean+/-standard error of the mean) later with a functioning allograft. Function, including measurement of the renal functional reserve (RFR), histological status, and morbidity were evaluated. Fourteen patients agreed to participate in this study. Their current immunosuppressive regimens combined prednisone (P)+azathioprine (AZA) (n=9), P+AZA+cyclosporine (CsA) (n=3) or P+CsA (n=2). Although they described their quality of life as good, 10 patients had mild hypertension, 5 developed 10 malignancies (9 cutaneous), 5 had replicative hepatitis, 8 had osteopenia, and 6 had cataracts, but none had diabetes mellitus. Proteinuria was detected in 6 patients, but was always less than 1 g/d. Mean serum creatinine was 1.28+/-0.28 mg/dL and glomerular filtration rate was 54.5+/-5.3 mL/min/1.73 m2. RFR was present for 4 patients with a mean value of +14.8+/-1.9 mL/min. Their functional status was not correlated with the histological lesions observed in concomitant transplant biopsies. Kidney grafts are able to function well even more than 20 yr post-transplantation, with some having a RFR whose significance remains unknown. Morbidity is of minor clinical severity, but could be further reduced with optimized management. Moreover, transplantation is much less costly than hemodialysis.

Adult↗
PubMed2001

Evaluation of basement membrane degradation during TNF-alpha-induced increase in epithelial permeability.

We evaluated whether tumor necrosis factor (TNF)-alpha induces an increase in permeability of an alveolar epithelial monolayer via gelatinase secretion and basement membrane degradation. Gelatinase secretion and epithelial permeability to radiolabeled albumin under unstimulated and TNF-alpha-stimulated conditions of an A549 human epithelial cell line were evaluated in vitro. TNF-alpha induced both upregulation of a 92-kDa gelatinolytic activity (pro form in cell supernatant and activated form in extracellular matrix) and an increase in the epithelial permeability coefficient compared with the unstimulated condition (control: 1.34 +/- 0.04 x 10(-6) cm/s; 1 microg/ml TNF-alpha: 1.47 +/- 0.05 x 10(-6) cm/s, P < 0.05). The permeability increase in the TNF-alpha-stimulated condition involved both paracellular permeability, with gap formation visualized by actin cytoskeleton staining, and basement membrane permeability, with an increase in the basement membrane permeability coefficient (determined after cell removal; control: 2.58 +/- 0.07 x 10(-6) cm/s; 1 microg/ml TNF-alpha: 2.82 +/- 0.02.10(-6) x cm/s, P < 0.05). Because addition of gelatinase inhibitors [tissue inhibitor of metalloproteinase (TIMP)-1 or BB-3103] to cell supernatants failed to inhibit the permeability increase, the gelatinase-inhibitor balance in the cellular microenvironment was further evaluated by cell culture on a radiolabeled collagen matrix. In the unstimulated condition, spontaneous collagenolytic activity inhibited by addition to the matrix of 1 microg/ml TIMP-1 or 10(-6) M BB-3103 was found. TNF-alpha failed to increase this collagenolytic activity because it was associated with dose-dependent upregulation of TIMP-1 secretion by alveolar epithelial cells. In conclusion, induction by TNF-alpha of upregulation of both the 92-kDa gelatinase and its inhibitor TIMP-1 results in maintenance of the gelatinase-inhibitor balance, indicating that basement membrane degradation does not mediate the TNF-alpha-induced increase in alveolar epithelial monolayer permeability.

Basement Membrane↗
PubMed2001

Vascular endothelial growth factor synthesis in the acute phase of experimental and clinical lung injury.

Vascular endothelial growth factor (VEGF) is a potent angiogenic and endothelial survival factor, which is abundantly expressed in the normal lung. Conceivably, VEGF may be released by numerous cell types found around the airspaces, including alveolar type 2 cells, alveolar macrophages, and polymorphonuclear neutrophils. Using a bacteria-induced lung injury model in rats, VEGF expression in lung was investigated. Both VEGF protein and VEGF messenger ribonucleic acid (mRNA), 4 and 24 h after bacterial challenge (Pseudomonas aeruginosa), were decreased compared with sham rats. VEGF protein was also investigated in bronchoalveolar lavage (BAL) from patients studied within 7 days of acute respiratory distress syndrome (ARDS) onset and in patients without ARDS. VEGF protein levels in BAL were decreased in patients with ARDS versus those without (14.3 +/- 11.1 pg x mL(-1) versus 76.8 +/- 51.1 pg x mL(-1), p = 0.03). In aggregate, these findings show that the initial phase of acute lung injury is associated with a decrease in vascular endothelial growth factor in the lung. This downregulation may represent a protective mechanism aimed at limiting endothelial permeability, and may participate in the decrease in capillary number that is observed during early acute respiratory distress syndrome.

Animals↗
PubMed2001

Abdominal muscle activity in sleep apnea during continuous positive airway pressure titration.

STUDY OBJECTIVES: The aim of this study was to investigate whether presence of expiratory abdominal muscle activity (EAMA) in obstructive sleep apnea syndrome (OSAS) patients during nasal continuous positive airway pressure (nCPAP) is due to either nCPAP overprescription or nCPAP underprescription. DESIGN: Airflow, esophageal pressure (Pes), and gastric pressure (Pga) were routinely measured during polysomnography aimed at determining the optimal nCPAP level, and the magnitude of EAMA was evaluated in relation to the nCPAP level and to the conventional indexes of upper-airway obstruction used during nCPAP titration. PATIENTS: The study was performed 12 patients with OSAS. RESULTS: Six patients displayed sustained EAMA, ie, EAMA lasting > 3 min, and characterized by a decrease in abdominal diameter and a paradoxical rise in Pga during expiration. In all six patients, EAMA decreased gradually as nCPAP neared optimal levels, and then disappeared when the optimal nCPAP level was achieved. The decrease in EAMA as nCPAP increased was associated with an increase in minute ventilation, decreases in both inspiratory and expiratory resistance, a decrease in Pes swing, and the normalization of the inspiratory flow contour. CONCLUSIONS: We conclude that the EAMA observed in some OSAS patients might be an indirect marker of upper-airway obstruction, and that the presence of EAMA during nCPAP titration might indicate a suboptimal nCPAP level rather than a deleterious effect of nCPAP.

Abdominal Muscles↗
PubMed2001

Use of glass capillaries avoids the time changes in high blood PO(2) observed with plastic syringes.

STUDY OBJECTIVES: In adults, arterial blood samples are usually drawn using plastic syringes. In contrast to glass syringes, plastic syringes let oxygen diffuse through their wall. This results in PO(2) changes during storage, especially when PO(2) is high. An alternative to glass syringes is the Microsampler (Roche Diagnostics; Schaffhausen, Switzerland), a commercially available device consisting of a heparinized glass capillary fitted with a 26-gauge needle and used to collect arterial blood in the same way as a plastic syringe fitted with a needle. DESIGN: We evaluated the performance of the Roche Microsampler for storing arterial blood in view of PO(2) measurement, comparatively with glass and plastic syringes. Five approximate initial PO(2) levels (650, 400, 200, 130, and 80 mm Hg) and two storage temperatures (ambient temperature and 4 degrees C) were studied. SETTINGS: Bench study. RESULTS: Plastic syringes allowed reliable measurement of PO(2) values when initial PO(2) was too low to ensure complete hemoglobin oxygen saturation, but were associated with time-dependent underestimation of PO(2) at higher initial PO(2) values. No such underestimation occurred with the Roche Microsampler stored at 4 degrees C for up to 1 h for all PO(2) levels studied. CONCLUSION: The Roche Microsamplers appeared to be reliable devices in preventing oxygen diffusion.

Blood Specimen Collection↗
PubMed2000

Treatment of acute hypoxemic nonhypercapnic respiratory insufficiency with continuous positive airway pressure delivered by a face mask: A randomized controlled trial.

CONTEXT: Continuous positive airway pressure (CPAP) is widely used in the belief that it may reduce the need for intubation and mechanical ventilation in patients with acute hypoxemic respiratory insufficiency. OBJECTIVE: To compare the physiologic effects and the clinical efficacy of CPAP vs standard oxygen therapy in patients with acute hypoxemic, nonhypercapnic respiratory insufficiency. DESIGN, SETTING, AND PATIENTS: Randomized, concealed, and unblinded trial of 123 consecutive adult patients who were admitted to 6 intensive care units between September 1997 and January 1999 with a PaO(2)/FIO(2) ratio of 300 mm Hg or less due to bilateral pulmonary edema (n = 102 with acute lung injury and n = 21 with cardiac disease). INTERVENTIONS: Patients were randomly assigned to receive oxygen therapy alone (n = 61) or oxygen therapy plus CPAP (n = 62). MAIN OUTCOME MEASURES: Improvement in PaO(2)/FIO(2) ratio, rate of endotracheal intubation at any time during the study, adverse events, length of hospital stay, mortality, and duration of ventilatory assistance, compared between the CPAP and standard treatment groups. RESULTS: Among the CPAP vs standard therapy groups, respectively, causes of respiratory failure (pneumonia, 54% and 55%), presence of cardiac disease (33% and 35%), severity at admission, and hypoxemia (median [5th-95th percentile] PaO(2)/FIO(2) ratio, 140 [59-288] mm Hg vs 148 [62-283] mm Hg; P =.43) were similarly distributed. After 1 hour of treatment, subjective responses to treatment (P<.001) and median (5th-95th percentile) PaO(2)/FIO(2) ratios were greater with CPAP (203 [45-431] mm Hg vs 151 [73-482] mm Hg; P =.02). No further difference in respiratory indices was observed between the groups. Treatment with CPAP failed to reduce the endotracheal intubation rate (21 [34%] vs 24 [39%] in the standard therapy group; P =.53), hospital mortality (19 [31%] vs 18 [30%]; P =.89), or median (5th-95th percentile) intensive care unit length of stay (6.5 [1-57] days vs 6.0 [1-36] days; P =.43). A higher number of adverse events occurred with CPAP treatment (18 vs 6; P =.01). CONCLUSION: In this study, despite early physiologic improvement, CPAP neither reduced the need for intubation nor improved outcomes in patients with acute hypoxemic, nonhypercapnic respiratory insufficiency primarily due to acute lung injury. JAMA. 2000;284:2352-2360.

APACHE↗
PubMed2000

Association of noninvasive ventilation with nosocomial infections and survival in critically ill patients.

CONTEXT: Invasive life-support techniques are a major risk factor for nosocomial infection. Noninvasive ventilation (NIV) can be used to avoid endotracheal intubation and may reduce morbidity among patients in intensive care units (ICUs). OBJECTIVE: To determine whether the use of NIV is associated with decreased risk of nosocomial infections and improved survival in everyday clinical practice among patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) or hypercapnic cardiogenic pulmonary edema (CPE). DESIGN AND SETTING: Matched case-control study conducted in the medical ICU of a French university hospital from January 1996 through March 1998. PATIENTS: Fifty patients with acute exacerbation of COPD or severe CPE who were treated with NIV for at least 2 hours and 50 patients treated with mechanical ventilation between 1993 and 1998 (controls), matched on diagnosis, Simplified Acute Physiology Score II, Logistic Organ Dysfunction score, age, and no contraindication to NIV. MAIN OUTCOME MEASURES: Rates of nosocomial infections, antibiotic use, lengths of ventilatory support and of ICU stay, ICU mortality, compared between cases and controls. RESULTS: Rates of nosocomial infections and of nosocomial pneumonia were significantly lower in patients who received NIV than those treated with mechanical ventilation (18% vs 60% and 8% vs 22%; P<.001 and P =.04, respectively). Similarly, the daily risk of acquiring an infection (19 vs 39 episodes per 1000 patient-days; P =.05), proportion of patients receiving antibiotics for nosocomial infection (8% vs 26%; P =.01), mean (SD) duration of ventilation (6 [6] vs 10 [12] days; P =.01), mean (SD) length of ICU stay (9 [7] vs 15 [14] days; P =.02), and crude mortality (4% vs 26%; P =.002) were all lower among patients who received NIV than those treated with mechanical ventilation. CONCLUSIONS: Use of NIV instead of mechanical ventilation is associated with a lower risk of nosocomial infections, less antibiotic use, shorter length of ICU stay, and lower mortality. JAMA. 2000;284:2361-2367.

APACHE↗
PubMed2000

[Acute renal failure after polyvalent immunoglobulin therapy].

BACKGROUND: Acute renal failure can be induced by intravenous administration of immunoglobulins, especially in patients with a predisposition for nephrotoxicity. The onset and resolution of acute renal failure is typically rapid, but in some cases hemodialysis may be needed. CASE REPORT: We present 2 cases of acute renal failure associated with intravenous immunoglobulin therapy: a 76-year-old man with a history of non-insulin-dependent diabetes mellitus and hypertension and a 77-year-old woman using nonsteroidal antiinflammatory drugs. DISCUSSION: Intravenous immunoglobulins must be used with precaution in patients with risk factors for acute renal failure. In such patients, renal failure may be avoided by using preparations without sucrose.

Acute Kidney Injury↗
PubMed2000

Nasal obstruction as a risk factor for sleep apnoea syndrome.

Nasal obstruction has frequently been mentioned as a possible risk factor in obstructive sleep apnoea syndrome (OSAS). Over a 2-yr period, 541 unselected consecutive snorers referred for suspected breathing disorders during sleep were included to undergo posterior rhinomanometry. In addition cephalometric landmarks and body mass index (BMI) were obtained. Polysomnography was used to determine the number of abnormal respiratory events that occurred during sleep. OSAS was defined as 15 episodes, or more, of apnoea or hypopnoea per hour of sleep (AHI). Of the 541 consecutive snorers 528 underwent nasal resistance measurement by posterior rhinomanometry (failure rate: 2.4%). Patients with OSAS (259 patients) had higher nasal resistance than patients without OSAS (2.6+/-1.6 hPa x L x s(-1) versus 2.2+/-1.0 hPa x L x s(-1), respectively, p<0.005). A stepwise multiple regression analysis showed that BMI, male sex, nasal resistance, and cephalometric parameters were contributing factors to the AHI. The r2-value of the multiple regression analysis was 0.183. Nasal resistance contributed 2.3% of the variance (p<0.0001), whereas mandibular plane-hyoid distance, BMI, male sex and age contributed 6.2%, 4.6%, 3% and 1.3% of the variance, respectively. To conclude, daytime nasal obstruction is an independent risk factor for OSAS.

Airway Resistance↗
PubMed2000

No change of hyperleptinemia despite a decrease in insulin concentration in patients with chronic renal failure on a supplemented very low protein diet.

Chronic renal failure (CRF) is often accompanied by hyperleptinemia caused by deficient renal metabolism of leptin and possibly increased leptin production, which in turn may result from the hyperinsulinemia and increased proinflammatory cytokine levels in patients with CRF. The hyperinsulinemia and insulin resistance observed in patients with CRF improve on supplemented very low protein diets (SVLPDs). The goal of our study is to determine whether the correction of hyperinsulinemia and insulin resistance in patients with CRF by SVLPDs is accompanied by improvement in hyperleptinemia. Thirteen patients were studied before and 1 year after following SVLPDs providing 0.3 g/kg/d of protein, supplemented with amino acids and ketoanalogues. After 1 year, patients showed markedly less hyperinsulinemia (7.4 +/- 1.6 versus 13.8 +/- 2 microU/mL at the start of diet; P: = 0.05) and insulin resistance, whereas serum leptin levels remained unchanged (16.1 +/- 4.7 versus 19.1 +/- 7.4 ng/mL at start of the study; P: = not significant). The initial correlation between serum leptin level and percentage of body fat persisted during follow-up. No correlation was found between insulin and leptin levels or between the variation of these two parameters during the study. Our study shows that the correction of hyperinsulinemia and insulin resistance in patients with CRF by SVLPDs is not accompanied by improvement in hyperleptinemia, which consequently does not appear to result from changes in carbohydrate metabolism.

Dietary Proteins↗
PubMed2000

Multicenter prospective study of ventilator-associated pneumonia during acute respiratory distress syndrome. Incidence, prognosis, and risk factors. ARDS Study Group.

We investigated the incidence, risk factors for, and outcome of ventilator-associated pneumonia (VAP) in patients with acute respiratory distress syndrome (ARDS). We compared 134 patients with ARDS with 744 patients without ARDS on mechanical ventilation. Fiberoptic bronchoscopic examination and quantitative bacterial cultures (protected brush or catheter sampling [threshold: 10(3) cfu/ml], or bronchoalveolar lavage [threshold: 10(4) cfu/ml]) were used to diagnose pneumonia. VAP occurred in 49 patients (36.5%). The incidence of pneumonia was 23% (173 of 744 patients) among patients without ARDS (p < 0.002). Nonfermenting gram-negative rods caused significantly more pneumonia in ARDS patients. Mortality rates were identical in ARDS patients with (28 of 49 patients, 57%) and without (50 of 85 patients, 59%) pulmonary infection (p = 0.8). VAP resulted in a considerable increase in attributable time on mechanical ventilation of both the overall population of ARDS patients and of survivors. Both the use of sucralfate (adjusted odds ratio [OR]: 4. 42; 95% confidence interval [CI]: 2.01 to 9.7, p = 0.0002) and the duration of exposure to sucralfate (adjusted OR: 1.206; 95% CI: 1. 095 to 1.328, p = 0.0002) were associated with an increased risk of VAP during ARDS. VAP considerably prolongs the time on mechanical ventilation without affecting survival. Patients given sucralfate may be at greater risk of developing pulmonary infection during ARDS.

Adult↗
PubMed2000

Hemodynamic tolerance of intermittent hemodialysis in critically ill patients: usefulness of practice guidelines.

Poor hemodynamic tolerance of intermittent hemodialysis (IHD) is a common problem for patients in an intensive care unit (ICU). New dialysis strategies have been adapted to chronic hemodialysis patients with cardiovascular insufficiency. To improve hemodynamic tolerance of IHD, specific guidelines were progressively implemented into practice through the year 1996 in our 26-bed medical ICU. To evaluate the efficiency of these guidelines we retrospectively compared all IHD performed during the years before (1995) and after (1997) implementation of these recommendations. Forty-five patients underwent 248 IHD sessions in 1995 and 76 patients underwent 289 IHD sessions in 1997. The two populations were similar for age, sex, chronic hemodialysis (26% versus 17%), and secondary acute renal failure. In 1997, patients were more severely ill with a higher SAPS II (50 +/- 17 versus 59 +/- 24; p = 0.036), and more patients required epinephrine or norepinephrine infusion before dialysis sessions (16% versus 34%; p < 0.0001). The compliance to guidelines was high, inducing a significant change in IHD modalities. As a result, hemodynamic tolerance was significantly better in 1997, with less systolic blood pressure drop at onset (33% versus 21%, p = 0. 002) and during the sessions (68% versus 56%, p = 0.002). IHD with hypotensive episode or need for therapeutic interventions were less frequent in 1997 (71% versus 61%, p = 0.015). The ICU mortality was similar (53.3% in 1995 versus 47.3% in 1997; p = 0.52) but death rate in 1997, but not in 1995, was significantly less than predicted from SAPS II (47.3% versus 65.6%; p = 0.02). Length of ICU stay was also reduced for survivors in 1997 (p = 0.04). Implementation of practice guidelines for intermittent hemodialysis in ICU patients lessens hemodynamic instability and may improve outcome.

Critical Illness↗
PubMed2000

Predictive value of pulmonary function parameters for sleep apnea syndrome.

Nocturnal polysomnography is the standard diagnostic test for sleep apnea syndrome (SAS) but is both expensive and time-consuming. We developed a predictive index for SAS based on pulmonary function data, including respiratory resistance determined by the forced oscillation technique, from 168 obese snorers with suspected SAS. Our model used logistic regression to obtain case-by-case predictions of the probability of SAS, defined as an apnea-hypopnea index (AHI) > or = 15 during overnight polysomnography. We then tested our model in a prospective group of 101 similar patients. Specific respiratory conductance and daytime oxygen saturation contributed significantly to the model. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the index computed from these parameters were 98%, 86%, 90%, and 97%, respectively. In the prospective group, the model proved repeatable, with 100% sensitivity, 84% specificity, 86% PPV, and 100% NPV. The high NPV may help to identify obese snorers with a SAS risk that is so low as to make polysomnography unnecessary. Based on the 50% prevalence of SAS in our study and on the fact that polysomnography is required in all patients with daytime somnolence, we calculated that using our model would have obviated the need for polysomnography in 38% of our patients.

Female↗
PubMed1999

Association of TNF2, a TNF-alpha promoter polymorphism, with septic shock susceptibility and mortality: a multicenter study.

CONTEXT: Tumor necrosis factor alpha (TNF-alpha) is believed to be a cytokine central to pathogenesis of septic shock. TNF2, a polymorphism within the TNF-alpha gene promoter, has been associated with enhanced TNF-alpha production and negative outcome in some severe infections. OBJECTIVES: To investigate the frequency of the TNF2 allele in patients with septic shock and to determine whether the allele is associated with the occurrence and outcome of septic shock. DESIGN: Multicenter case-control study conducted from March 1996 to June 1997. SETTING: Seven medical intensive care units in university hospitals. SUBJECTS: Eighty-nine patients with septic shock and 87 healthy unrelated blood donors. MAIN OUTCOME MEASURES: Frequency of the TNF2 allele among patients with septic shock and among those who died and the level of corresponding TNF-alpha concentrations. RESULTS: Mortality among patients with septic shock was 54%, consistent with the predicted mortality from the Simplified Acute Physiologic Score (SAPS II) value. The polymorphism frequencies of the controls and the patients with septic shock differed only at the TNF2 allele (39% vs 18% in the septic shock and control groups, respectively, P =.002). Among the septic shock patients, TNF2 polymorphism frequency was significantly greater among those who had died (52% vs 24% in the survival group, P =.008). Concentrations of TNF-alpha were higher in 68% and 52% with the TNF2 and TNF1 polymorphisms, respectively, but their median values (48 pg/mL vs 29 pg/mL) were not statistically different (P = .31). After controlling for age and the probability of death, derived by the SAPS II score, multiple logistic regression analysis showed that, for the same rank of SAPS II value, patients with the TNF2 allele had a 3.7-fold risk of death (95% confidence interval, 1.37-10.24). CONCLUSION: The TNF2 allele is strongly associated with susceptibility to septic shock and death due to septic shock.

Alleles↗