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Biomedical subjects

G Offenstadt

Publications and source records attributed to G Offenstadt.

At least 55 records · Page 3Linked to original sources

[Gastroduodenal stress hemorrhage during intensive care].

Stress gastric erosions are in fact the gastroduodenal expression of a most disseminated injury involving whole organism. Ischemia represents the main factor leading to the decrease of gastric mucosa protective mechanisms. The most important complication of stress ulceration is acute bleeding. Gastrointestinal hemorrhages of clinical relevance are now so scarce that widespread systematic prophylaxis against stress ulcers can be safely withheld. Supportive therapy of associated acute organ failure remains the most accurate prophylaxis. Patients who are the most likely to benefit from specific prophylaxis are still unknown.

Critical Care↗

Incidence, risk factors, and outcome of severe sepsis and septic shock in adults. A multicenter prospective study in intensive care units. French ICU Group for Severe Sepsis.

OBJECTIVE: To examine the incidence, risk factors, and outcome of severe sepsis in intensive care unit (ICU) patients. DESIGN AND SETTING: Inception cohort study from a 2-month prospective survey of 11,828 consecutive admissions to 170 adult ICUs of public hospitals in France. PATIENTS: Patients meeting clinical criteria for severe sepsis were included and classified as having documented infection (ie, documented severe sepsis, n = 742), or a clinical diagnosis of infection without microbiological documentation (ie, culture-negative severe sepsis, n = 310). MAIN OUTCOME MEASURES: Hospital and 28-day mortality after severe sepsis. RESULTS: Clinically suspected sepsis and confirmed severe sepsis occurred in 9.0 (95% confidence interval [CI], 8.5 to 9.5) and 6.3 (95% CI, 5.8 to 6.7) of 100 ICU admissions, respectively. The 28-day mortality was 56% (95% CI, 52% to 60%) in patients with severe sepsis, and 60% (95% CI, 55% to 66%) in those with culture-negative severe sepsis. Major determinants of both early (< 3 days) and secondary deaths in the whole cohort were the Simplified Acute Physiology Score (SAPS) II and the number of acute organ system failures. Other risk factors for early death included a low arterial blood pH (< 7.33) (P < .001) and shock (P = .03), whereas secondary deaths were associated with the admission category (P < .001), a rapidly or ultimately fatal underlying disease (P < .001), a preexisting liver (P = .01) or cardiovascular (P = .002) insufficiency, hypothermia (P = .02), thrombocytopenia (P = .01), and multiple sources of infection (P = .02). In patients with documented sepsis, bacteremia was associated with early mortality (P = .03). CONCLUSIONS: Only three of four patients presenting with clinically suspected severe sepsis have documented infection. However, patients with clinically suspected sepsis but without microbiological documentation and patients with documented infection share common risk factors and are at similarly high risk of death. In addition to the severity of illness score, acute organ failures and the characteristics of underlying diseases should be accounted for in stratification of patients and outcome analyses.

Adult↗

Plasma antiproteinase screen and neutrophil-mediated platelet activation. A major role played by alpha 1 antitrypsin.

Upon activation, human polymorphonuclear neutrophils (PMN) release two serine proteinases, cathepsin G (Cat.G) and elastase (HLE), which in turn synergize to activate nearby platelets. We looked for the inhibitory effect of plasma and the involvement of alpha 1 antichymotrypsin (alpha 1 ACT) and alpha 1 antitrypsin (alpha 1 AT), on this cell-to-cell cooperation. It was observed that inhibition by plasma of PMN-mediated platelet activation was rather correlated with an effect on HLE (r = 0.95) than on Cat.G (r = 0.65) enzymatic activity. Purified alpha 1 AT suppressed in a concentration-dependent manner HLE activity present in the supernatant of activated PMN. When HLE was fully blocked, alpha 1 AT started to inhibit Cat.G activity. By contrast and as expected, purified alpha 1 ACT inhibited only Cat.G activity. Using specific blocking polyclonal antibodies against alpha 1 AT and alpha 1 ACT, it was demonstrated that the inhibitory effect of plasma vs. HLE was entirely mediated by alpha 1 AT. By contrast, blockade of Cat.G activity was only partly due to plasma alpha 1 ACT and around 50% was attributable to alpha 1 AT. When plasma from patients with an acute inflammatory state was used in place of plasma from normal subjects, the inhibitory effect was more pronounced, while plasma depleted in alpha 1 AT and alpha 1 ACT was less effective. These data indicate a predominant role of alpha 1 AT in the inhibition by plasma of the PMN-mediated platelet activation.

Amino Acid Sequence↗

Biochemical assessment of nutritional status in patients with chronic obstructive pulmonary disease and acute respiratory failure on admission to an intensive care unit.

Although chronic obstructive pulmonary disease (COPD) is associated with weight loss and malnutrition, there is a paucity of relevant data on COPD patients with acute respiratory failure (ARF). We studied 30 consecutive patients on the day of admission to our intensive care unit for ARF. In addition to a clinical work-up, the following biochemical parameters were determined: markers of nutritional status (albumin - ALB, transferrin - TRF, transthyretin - TTR, retinol binding protein - RBP, fibronectin), inflammation (C-reactive protein - CRP, alpha(1) glycoprotein acid - alpha(1)GPA) and catabolism (plasma phenylalanine - PHE, urinary 3-methylhistidine - 3-MH). Values were expressed as mean +/- SD and compared to those of 10 healthy subjects matched for age. COPD-ARF patients had a poor protein status (ALB = 30 +/- 5 vs 42 +/- 3 g.l(-1); TTR = 118 +/- 75 vs 251 +/- 43 mg.l(-1); RBP = 23 +/- 12 vs 46 +/- 8 mg.l(-1); p < 0.001), were hypercatabolic (3-MH Cr = 31 +/- 12 vs 22 +/- 7 mumol.mmol Cr (-1); PHE = 62 +/- 27 vs 46 +/- 10 mumol.l(-1); p < 0.001) and inflamed (CRP = 68 +/- 50 vs 12 +/- 5 mg.l(-1); alpha(1)GPA = 1.2 +/- 0.4 vs 0.5 +/- 0.1 g.l(-1); p < 0.001). Severity of the disease correlated with short half-life proteins and protein catabolism markers but not with inflammation markers. Considering ALB, TTR, RBP, the 3- MH Cr ratio and PHE values, the 30 COPD patients fell into 3 groups: chronic malnutrition (n = 7), acute malnutrition (n = 2), and acute + chronic malnutrition (n = 18). 3 patients had normal nutritional status. We conclude that an assessment of nutritional status at admission to intensive care units could contribute towards a rapid formulation of specific nutritional therapy.

Journal Article↗

Endotoxemia and bacteremia in patients with sepsis syndrome in the intensive care unit.

STUDY OBJECTIVES: To study circulatory endotoxin (ET) in patients with sepsis syndrome (SS) in order to answer three questions: (a) How often and at which concentration is ET present in the plasma of patients with SS and is the presence of ET a prognostic marker in this situation? (b) Is detection of ET helpful in predicting Gram-negative bacterial infections with or without bacteremia? (c) What are the kinetics of clearance of ET concentrations in plasma? DESIGN: Prospective study of consecutive patients fulfilling Bone's criteria for SS. SETTING: Medical ICU in a teaching hospital. PATIENTS: The study included 93 patients. The simplified acute physiologic score was 19 +/- 6, 49 percent were in shock, and 54 percent were mechanically ventilated. The mortality at day 28 was 53 percent. MEASUREMENTS: Endotoxin determinations and blood cultures were performed simultaneously at the onset (day 1) of SS. Samples were collected on several days from 48 patients. Endotoxin concentration was determined using an end point chromogenic Limulus assay. For the first ET determination, the mean circulatory level (mean +/- SEM) was calculated among patients with detectable ET, thus excluding patients with a null value for ET. RESULTS: On day 1, ET was detected in 44 patients (47 percent; 60.2 +/- 16.5 pg/ml) and was statistically more frequent in patients with shock, elevated plasma lactate, and organ failure. There was no statistical difference for age, gender, ratio of PaO2 to fraction of inspired oxygen. Among patients with proven Gram-negative bacterial infection (n = 46), ET was detected in 67 percent as compared with 28 percent without Gram-negative bacterial infection (p = 0.0001). On day 1, among 19 patients who had positive blood cultures with Gram-negative bacteria (GNB), 15 had detectable ET (79 percent, 61 +/- 22 pg/ml). In 14 other patients whose blood cultures were positive for GNB but became negative on day 1, 9 had detectable ET (64 percent; 36 +/- 6.5 pg/ml). Endotoxin declined linearly between days 1 and 4. CONCLUSION: In our study, the plasma ET concentration predicts neither Gram-negative infection, with or without bacteremia, nor the outcome. However, when ET is present in the plasma of patients with SS it remains detectable for a long period of time as compared to its rapid disappearance from plasma of animals or healthy human volunteers receiving ET intravenously. This slow clearance of ET suggests either a continuous release or a defect in its clearance.

Bacteremia↗

Generalized air cysts complicated by fatal bilateral pneumothoraces in a patient with AIDS-related Pneumocystis carinii pneumonia.

We describe a case of air cyst lesions in an AIDS patient suffering from Pneumocystis carinii pneumonia. This case is unique because these lesions were generalized to both lungs and initially well tolerated. Pathologic examination revealed extensive tissue invasion by P carinii. The prognosis was complicated by bilateral pneumothoraces. Surgical right pleurodesis allowed lung re-expansion but did not prevent recurrence of fatal contralateral pneumothorax.

AIDS-Related Opportunistic Infections↗

[Enteral nutrition in patients with chronic obstructive bronchopathy treated by artificial ventilation. Effect of conventional feeding on anthropometric and biochemical parameters].

The influence of conventional gastric tube feeding on anthropometric and biochemical parameters was studied prospectively during 12 months in 14 patients with chronic obstructive lung disease put on mechanical ventilation for respiratory failure. The anthropometric parameters were: body weight, tricipital skin fold, brachial and brachial muscle circumferences. The biochemical parameters included albumin, transferrin, retinol binding protein, transthyretin, acid alpha-1-glycoprotein, C-reactive protein, fibronectin and amino acids in blood, and 3-methylhistidine in urine. Measurements were performed on inclusion, then every 3 days until D15. After 15 days of a nutrition bringing 28.8 +/- 8.9 calories/kg/day and 13.9 +/- 2.2 grams of nitrogen per day, no improvement in anthropometric parameters was observed. On D0, comparisons with healthy controls showed that visceral serum proteins levels were significantly lower and inflammatory proteins levels significantly higher (P < 0.05); the levels of protein metabolism markers were higher, but not significantly, and those of the principal glucose-forming amino acids were significantly lower (P < 0.01). On D15, comparisons with the initial values showed that the values of retinol binding protein and transthyretin were increased (P < 0.05 and 0.01 respectively), whereas the values of the other visceral proteins were little modified; yet their concentrations remained significantly lower than those found in controls, except for the retinol binding protein. Inflammatory proteins levels were high, with a significant (P = 0.05) difference for the acid alpha-1-glycoprotein, and the patients remained in slight catabolism while their nitrogen balance was positive. These results should encourage to carry out studies on the qualitative composition of artificial nutrition in order to optimize its effectiveness in the treatment of these patients.

Aged↗

[Interleukins and TNF in septic shock].

Tumor necrosis factor alpha (TNF alpha) and interleukins (IL) are the principal cytokines involved in the clinical and biological manifestations of septic shock. Their secretion are triggered mainly by endotoxin, but products of Gram positive cocci as well as of virus or of parasites are equally effective. Cytokines represent a normal protective defense against infection, but an excessive production have toxic effects. In experimental models of endotoxinemia, TNF alpha is the first cytokine produced, then IL-1 and IL-6. Other inflammatory mediators are secreted later. Thus it seems logical to try to modulate cytokine production or actions. However, several questions remains since experimental data are sometimes not applicable too human diseases, cytokines are organised in a network with several interaction. It is too early to propose routine anti-cytokines drugs in septic shock.

Animals↗

[Therapeutic perspectives of severe infectious states].

Mortality from sepsis is still unacceptably high which justifies a new therapeutic approach complementary of antibiotics and symptomatic treatment. Recent advances in the understanding of sepsis and septic shock opened new fields of therapeutic intervention. Nevertheless, there are so many potential targets that is hard to make a choice for evaluation of these new agents: anti-endotoxin (monoclonal antibodies, lipid A analogs, BPI), anticytokines (monoclonal antibodies, soluble receptors, IL-1 receptor antagonist), anti-inflammatory agents (non-steroidal anti-inflammatory agents, anti-PAF, reactive oxygen radicals scavengers...), extracorporeal removal of toxic molecules, inhibition of the adhesion of polymorphonuclear leucocytes on endothelial surface, optimisation of general and regional circulation. The use of these new and often costly drugs must rely on multicenter randomized clinical trials since extrapolation to the human of experimental data gathered in animal studies are hazardous.

Cytokines↗

Prospective evaluation of self-extubations in a medical intensive care unit.

OBJECTIVE: To evaluate the incidence, associated factors and gravity of self-extubations. DESIGN: Prospective study about all patients intubated over an 8 month period. SETTING: A medical intensive care unit of a University Hospital. PATIENTS: Patients were divided into two groups: self-extubated and those that did not. The self-extubations were separated into deliberate acts by the patients and accidental. RESULTS: 24 of the 197 patients included presented a total of 27 extubations (12%). There were 21 deliberate incidents and 6 accidental. The only differences between the cases and the rest of the population were a higher mean age (67 vs 59 years) and a larger proportion of chronic respiratory failure (66% versus 35%). Reintubation was necessary in 20 cases (74%) within 30 min in 16 cases. The main indication for reintubation was acute respiratory distress (90%). Reintubation was associated with one death. CONCLUSION: Self-extubation is a frequent and serious complication of mechanical ventilation. Deliberate self-extubation, the most frequent type of incident could possibly be reduced by better sedation of agitated patients and accidental self-extubation by better training of the nursing staff.

Adult↗

Four markers of collagen metabolism as possible indicators of disease in the adult respiratory distress syndrome.

During the adult respiratory distress syndrome (ARDS), an irreversible fibrotic process can occur extremely rapidly. To establish indices of ARDS in pneumonia as well as the severity of the lung fibrosis, we have undertaken for the first time a study of four markers of collagen metabolism obtained from both bronchoalveolar lavage fluid (BALF) and serum: Type I (CI), Type III (CIII), N-terminal peptide of Type III procollagen (PIIINP), and galactosylhydroxylysylglucosyltransferase activity (GGT). We studied 61 patients (13 coma controls, 29 with pneumonia, and 19 with ARDS). In BALF, the average values of CI, CIII, PIIINP, and GGT were significantly higher in ARDS than in the control patients. The values for patients with pneumonia, although increased, were significantly lower than those in ARDS for CI, CIII, and PIIINP. In serum, the mean CI and PIIINP were significantly increased in pneumonia and ARDS, but the mean CIII was significantly increased only in ARDS compared with the control group. Significant positive linear correlations were observed for ARDS between CI and CIII or PIIINP and CIII in BALF and serum. Such correlations were observed for pneumonia only in serum. Molecular mass determinations demonstrated that CI- and CIII-related antigens in BALF were essentially intact triple helices of collagens or procollagens. Among patients with histologically defined interstitial fibrosis, the level of PIIINP in BALF was significantly higher for those with an additional intraalveolar fibrosis. In conclusion, measurements of these collagen markers may be useful for assessing disease activity and reflecting the flux of collagen molecules in the lung.

Adult↗

Mechanical ventilation for Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. Is the prognosis really improved?

The mortality rate among patients with human immunodeficiency virus (HIV) requiring mechanical ventilation (MV) for acute respiratory failure (ARF) secondary to Pneumocystis carinii pneumonia (PCP) is still a matter of discussion. For some authors, it is in the 50 percent range, while for others the prognosis is grim, with virtually no survivors. The aim of this retrospective study conducted between January 1987 and January 1992 was to analyze the outcome of such patients. We studied 33 patients, 29 men and 4 women (38.6 +/- 9.9 years, 21 homosexuals, 8 intravenous drug users, 3 transfusion related, 1 heterosexual) infected by HIV for at least 19.7 +/- 21.6 months. It was the first PCP episode in all but 2 patients and the diagnosis was made by bronchoalveolar lavage (n = 32) or lung biopsy specimen (n = 1). Only three patients were receiving primary prophylaxis for PCP (trimethoprim-sulfamethoxazole [TMP-SMZ], n = 2; pentamidine, n = 1). Pneumocystis carinii pneumonia was the first manifestation of AIDS in nine patients. The duration of symptoms prior to treatment was 19.6 +/- 11.3 days. At the time of hospital admission, laboratory findings were as follows: PaO2 = 40.7 +/- 7.8 mm Hg on room air; serum LDH = 1,172 +/- 792 IU/L; T4 cell count = 60.2 +/- 67/mm3. Mechanical ventilation was always required for ARF, which was never induced by bronchoscopy. The interval between treatment and MV was 8.1 +/- 6.5 days and the duration of MV was 11.4 +/- 9.9 days. The patients were classified into 3 groups on the basis of the duration and type of treatment before MV, as follows: group 1, n = 10: TMP-SMZ (20-100 mg/kg) IV and methylprednisolone (MP) < 5 days before MV; group 2, n = 4: TMP-SMZ > or = 5 days and MP < 5 days; group 3, n = 19: TMP-SMZ and MP > or = 5 days before MV. (The MP dose was as follows: 240 mg/d once a day from day 1 to day 3; 120 mg/d from day 4 to day 6; and 60 mg/d from day 7 to day 9.) Despite MV, TMP-SMZ, and MP, death secondary to PCP-related ARF occurred in 81.9 percent of patients, 20 +/- 4.8 days after the beginning of treatment and 11.4 +/- 9.9 days after the beginning of MV. Six patients survived, five in group 1 and one in group 3.(ABSTRACT TRUNCATED AT 400 WORDS)

AIDS-Related Opportunistic Infections↗

[Cytokines and severe infections].

In severe infections two factors play a part: the infectious agent and the response of the host. The response of the host involves production of a large number of endogenous mediators including a number of cytokines that are currently the focus of many studies: tumor necrosis factor (TNF alpha), interleukins (IL-1 and IL-6), and interferon gamma (IGN gamma). These cytokines are part of the body's normal defense mechanisms but can have toxic effects when produced in excessive amounts. Although levels of these cytokines are often high in the blood of patients with sepsis, persistence of these elevations is the main indicator of severe infection. Experimentally, injections of TNF alpha and IL-1 reproduce the manifestations of severe sepsis. Mice that are genetically unable to produce TNF alpha are resistant to the injection of endotoxin. Severe sepsis can be prevented by pretreatment of animals with anticytokine agents (polyclonal and monoclonal antibodies and anti-receptor agents ...). Many issues remain unresolved: for instance, the experimental results obtained with an intravenous bolus of endotoxin or bacteria have not been confirmed in some animal models of subacute infection. These models may more closely resemble human infections. The interrelations between these cytokines are extremely complex. Synergistic effects do occur, but the effects of combinations of cytokines can be different from those of each cytokine given alone... It follows that therapeutic use in humans of anti-cytokine molecules is still an approach of uncertain outcome that will perhaps be clarified by ongoing multicenter clinical trials.

Animals↗

Meningoencephalitis due to penicillin-resistant Streptococcus pneumoniae.

The case of a 68-year-old man suffering from pneumococcal meningoencephalitis is reported. Antibacterial susceptibility tests revealed a multiply resistant pneumococcal strain. High doses of cefotaxime were necessary to sterilize the cerebrospinal fluid despite the achievement of a satisfactory level of antibiotic in the cerebrospinal fluid with moderate dosage. In France, as well as in many countries, high doses of third-generation cephalosporins such as cefotaxime or ceftriaxone should be administered for the initial therapy of suspected pneumococcal meningitis.

Aged↗

[Efficacy and tolerance of Elohes in plasma exchanges].

This study aimed to compare two plasma substitution regimens used during plasma exchanges (PE). It was a prospective cross-over randomized trial. Each patient (n = 12) had two PE at a 48 h interval. During one PE, only albumin was administered (PEA), and during the other one, equal volumes of albumin and low molecular weight hydroxyethylstarch (HES) (Elohes) were given (PEA+E). The order in which these different protocols were used was random. Plasma was separated by filtration, and the total volume extracted was one and a half the plasma volume. The parameters recorded every 15 min until 1 h after the end of PE, were heart rate, blood pressure and central venous pressure (CVP). Plasma volume, calculated from the mean body haematocrit and blood volume, was measured before and after PE. The clinical and biological tolerance of the rapid infusion of a large volume of HES was also assessed. PE characteristics were similar in both groups. For PEA and PEA+E, PE lasted 152 +/- 21 min and 154 +/- 25 min; the plasma volume extracted was 3,907 +/- 772 ml and 3,933 +/- 717 ml; the volume of plasma substitute infused was 4,097 +/- 617 ml and 3,933 +/- 717 ml, respectively. As haemodynamic and biochemical values were not significantly different in both groups, they were pooled together irrespective of the order of PE.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗