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Biomedical subjects

A Combes

Publications and source records attributed to A Combes.

At least 19 recordsLinked to original sources
PubMed2002

Pseudomonas aeruginosa ventilator-associated pneumonia: comparison of episodes due to piperacillin-resistant versus piperacillin-susceptible organisms.

We sought to determine the epidemiological characteristics of patients in an intensive care unit (ICU) who developed ventilator-associated pneumonia (VAP) caused by piperacillin-resistant Pseudomonas aeruginosa (PRPA; n=34) or piperacillin-susceptible P. aeruginosa (PSPA; n=101). According to univariate analysis, the factors associated with the development of PRPA VAP were presence of an underlying fatal medical condition, immunocompromised status, longer previous hospital stay, less-severe illness at the time of ICU admission, duration of mechanical ventilation before onset of VAP, number of classes of antibiotic received, and previous exposure to imipenem or fluoroquinolone. Multivariate logistic regression analysis identified the following significant independent factors: presence of an underlying fatal medical condition (odds ratio [OR], 5.6), previous fluoroquinolone use (OR, 4.6), and initial disease severity (OR, 0.8). We concluded that the clinical characteristics of patients who develop PRPA VAP differ from those of patients who develop PSPA VAP. Restricted fluoroquinolone use is the sole independent risk factor for PRPA VAP that is open to medical intervention.

Aged↗
PubMed2002

PTPN11 mutations in Noonan syndrome type I: detection of recurrent mutations in exons 3 and 13.

We surveyed 16 subjects with the clinical diagnosis of Noonan Syndrome (NS1) from 12 families and their relevant family members for mutations in PTPN11/SHP2 using direct DNA sequencing. We found three different mutations among five families. Two unrelated subjects shared the same de novo missense substitution in exon 13 (S502T); an additional two unrelated families had a mutation in exon 3 (Y63C); and one subject had the amino acid substitution Y62D, also in exon 3. None of the three mutations were present in ethnically matched controls. In the mature protein model, the exon 3 mutants and the exon 13 mutant amino acids cluster at the interface between the N' SH2 domain and the phosphatase catalytic domain. Six of eight subjects with PTPN11/SHP2 mutations had pulmonary valve stenosis while no mutations were identified in those subjects (N = 4) with hypertrophic cardiomyopathy. An additional four subjects with possible Noonan syndrome were evaluated, but no mutations in PTPN11/SHP2 were identified. These results confirm that mutations in PTPN11/SHP2 underlie a common form of Noonan syndrome, and that the disease exhibits both allelic and locus heterogeneity. The observation of recurrent mutations supports the hypothesis that a special class of gain-of-function mutations in SHP2 give rise to Noonan syndrome.

Catalytic Domain↗
PubMed2002

[Fulminating myocarditis: myocardial recovery after circulatory assistance].

The clinical expression of acute myocarditis is variable from paucisymptomatic to fulminating forms which are usually lethal within days. The latter presentation takes the form of very acute cardiac failure. During this phase, the severity of myocardial dysfunction may be such that death ensues. However, if the patient survives, paradoxically, these forms have a better long-term prognosis with complete recovery of myocardial function being possible after the acute phase. The authors report a typical case of fulminating myocarditis with electromechanical dissociation, which recovered completely after a period of circulatory assistance. This case illustrates the rapidity of deterioration of the haemodynamic status and the importance of organ dysfunction despite early management. In a review of the literature, the authors found about 150 reported cases of acute myocarditis treated with circulatory assistance. In the best series, about half the patients were weaned off the circulatory assistance without having to undergo cardiac transplantation. However, the potential recovery of myocardial function is difficult to predict.

Adult↗
PubMed2001

Is it possible to cure mediastinitis in patients with major postcardiac surgery complications?

BACKGROUND: The prognosis for mediastinitis after cardiac operation has improved during the last two decades, but most series do not include patients who already have a major postoperative complication when the infection developed. METHODS: Our 9-year prospective study of 371 consecutive patients with mediastinitis compared the characteristics of patients admitted to the intensive care unit primarily for mediastinitis with those who developed mediastinitis after intensive care unit admission for severe postoperative organ failure. RESULTS: We identified 323 (87%) primary and 48 (13%) secondary mediastinitis patients. The incubation time for mediastinitis was longer for secondary mediastinitis patients, despite similar initial operations. Staphylococcus aureus was responsible for approximately 60% of the episodes in both groups; however, the incidence of methicillin resistance was 2.5 times higher in secondary mediastinitis patients (p < 0.0001). The mediastinitis cure rate was similar for both groups. However, intensive care unit mortality (63% versus 21%), duration of mechanical ventilation (40 versus 9 days), and length of intensive care unit stay (53 versus 28 days) were significantly higher for secondary mediastinitis patients (p < 0.0001). CONCLUSIONS: The presence of a prior major postoperative complication does not alter the cure rate of mediastinal infections, but does greatly reduce the survival rate.

Cardiac Surgical Procedures↗
PubMed2001

UV light synergistically enhances the cardiotoxic effects of interleukin 1beta through peroxynitrite formation.

BACKGROUND: Proinflammatory cytokines play an important role in chronic cardiac diseases. METHODS AND RESULTS: Neonatal rat cardiomyocytes were exposed to interleukin (IL)-1beta (2 ng/mL) for 4 days. We assessed contractility through videomicroscopy and calcium transients with the Ca(2+)-sensitive dye fura-2. In IL-1beta-treated cells, the UV excitation (380 nm) necessary to induce dye fluorescence effected a rapid cessation of Ca(2+) transients and contraction, accompanied by calcium overload originating from an intracellular compartment. This occurred in the absence of fura-2 but required UV illumination. Incubation with 10 mmol/L N-acetylcysteine prevented this response, suggesting a free radical-mediated event. However, exposure to IL-1beta either increased or did not change the activity of the free radical scavengers superoxide dismutase, catalase, and glutathione peroxidase. In contrast, lipid peroxidation increased by 600% (P < or =.0001) in the IL-1beta plus UV-treated cells, an effect eliminated by L-NMMA. L-NMMA also completely abolished the UV-mediated cytotoxicity. We used immunohistochemistry to localize nitrotyrosine accumulation in the myocytes cotreated with IL-1beta and UV, an effect that was also blocked by L-NMMA. CONCLUSIONS: We hypothesize that the toxic radical peroxynitrite, arising from nitric oxide and superoxide anion, may be responsible for tetany and acute cardiomyocyte death. These results demonstrate the potential role of peroxynitrite in cardiotoxicity, which may be important in cardiac diseases associated with proinflammatory cytokines.

Animals↗
PubMed2000

The role of tumor necrosis factor in the pathophysiology of heart failure.

Recent studies have focused their attention on the role of the proinflammatory cytokine tumor necrosis factor (TNF) in the development of heart failure. First recognized as an endotoxin-induced serum factor that caused necrosis of tumors and cachexia, it is now recognized that TNF participates in the pathophysiology of a group of inflammatory diseases including rheumatoid arthritis and Crohn's disease. The normal heart does not express TNF; however, the failing heart produces robust quantities. Furthermore, there is a direct relationship between the level of TNF expression and the severity of disease. In addition, both in vivo and in vitro studies demonstrate that TNF effects cellular and biochemical changes that mirror those seen in patients with congestive heart failure. Furthermore, in animal models, the development of the heart failure phenotype can be abrogated at least in part by anticytokine therapy. Based on information from experimental studies, investigators are now evaluating the clinical efficacy of novel anticytokine and anti-TNF strategies in patients with heart failure; one such strategy is the use of a recombinantly produced chimeric TNF alpha soluble receptor. Thus, in view of the emerging importance of proinflammatory cytokines in the pathogenesis of heart disease, we review the biology of TNF, its role in inflammatory diseases, the effects of TNF on the physiology of the heart and the development of clinical strategies that target the cytokine pathways.

Animals↗
PubMed1998

Selenium, systemic immune response syndrome, sepsis, and outcome in critically ill patients.

OBJECTIVES: To confirm early, marked decrease in plasma selenium concentrations in patients admitted to a surgical and medical intensive care unit (ICU), and to study this decrease according to the presence or absence of systemic inflammatory response syndrome (SIRS), sepsis, or direct ischemia-reperfusion. DESIGN: Prospective, observational study. SETTINGS: Collaboration between the adult ICU of a 1,100-bed general hospital and a biochemical research laboratory of a university medical center. PATIENTS: One hundred thirty-four consecutive surgical and medical ICU patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In the first 31 patients, plasma and urine selenium concentrations were measured by electrothermal atomic absorption spectrometry on admission and once weekly during their ICU stay. These values were compared first with severity scores, criteria for SIRS, sepsis, and organ system failure taken on admission, and then with nosocomial infection, organ system failure during ICU stay, and hospital mortality. An early, low mean plasma selenium concentration was observed in these patients compared with selenium laboratory reference values. Plasma selenium, measured on ICU admission, inversely correlated with Acute Physiology and Chronic Health Evaluation II or Simplified Acute Physiology II scores. Patients with SIRS had lower selenium concentrations than those without SIRS. Mean urine selenium losses were normal in the first 31 patients. Plasma selenium concentration was low in all patients with severe sepsis and septic shock (range 0.20 to 0.72 micromol/L) and in those patients with ischemia-reperfusion from aortic cross-clamping (range 0.34 to 0.68 micromol/L). Despite recommended specific selenium supplementation, plasma selenium concentrations remained low for >2 wks in patients with SIRS. However, there was a slight increase in plasma selenium concentrations in surviving SIRS patients, whereas plasma selenium concentrations decreased in nonsurviving patients. The frequency of ventilator-associated pneumonia, organ system failure, and mortality was three times higher in patients with low plasma selenium concentration at the time of admission (selenium < or =0.70 micromol/L) than for the other patients. CONCLUSIONS: In severely ill ICU patients with SIRS, we observed an early 40% decrease in plasma selenium concentrations, reaching values observed in deleterious nutritional selenium deficiency. This prolonged decrease in selenium concentrations could explain the three-fold increase in morbidity and mortality rates in these patients compared with other ICU patients. The efficacy of selenium treatment in SIRS patients with a high gravity index score or hypoperfusion needs further investigation.

APACHE↗
PubMed1997

Interleukin-1 beta inhibits phospholamban gene expression in cultured cardiomyocytes.

Phospholamban is a key regulatory protein that defines diastolic function. Proinflammatory cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) can depress contractility and intracellular Ca2+ currents and transients. An alteration in phospholamban expression is a possible pathway by which these cytokines modulate cardiac function. To test this hypothesis, primary cultures of neonatal rat cardiomyocytes were incubated with IL-1 beta, TNF-alpha, or both, and the level of phospholamban transcripts was examined by Northern blot analyses. Phospholamban transcript levels were decreased approximately equal to 50% (P < .0001) in cells exposed to 2 ng/mL IL-1 beta (20 hours), whereas TNF-alpha had no effect. Western blot analyses showed that IL-1 beta also reduced phospholamban protein levels (60% of control, P < .0001). The effects on transcript levels were gene specific; IL-1 beta induced transcripts for inducible NO synthase (iNOS), did not alter GAPDH transcripts, and reduced sarcoplasmic reticulum Ca(2+)-ATPase (65% of control, P < .001) transcripts. Cardiomyocytes treated with IL-1 beta showed no alterations in basal contractile parameters (maximum velocity of contraction and relaxation and maximal amplitude of contraction) but were unresponsive to beta-adrenergic stimulation. Studies performed in the presence of second-messenger inhibitors showed that the effect of IL-1 beta on phospholamban transcript levels was blocked by dexamethasone, was insensitive to inhibitors of iNOS, cyclooxygenase, or tyrosine kinases, but was enhanced by the addition of the protein kinase inhibitor staurosporine. These data demonstrate that IL-1 beta alters the expression of phospholamban, a key regulator of cardiac contractility, at both the transcript and protein levels. The results suggest novel mechanisms by which IL-1 beta may modify cardiac function.

Animals↗
PubMed1997

[Survival of patients with myasthenia gravis after thymectomy. Analysis of 100 cases].

In order to evaluate the survival of patients with myasthenia gravis (MG) after thymectomy (T), 100 patients with MG in which T had been performed between 1967 and 1995 were studied. Patients were divided into different groups for their analysis: patients with thymoma (TI), 22 cases; and patients without thymoma (NTI), 78 cases. In addition those patients belonging to the latter group were further separated according to the date of their surgery into two other subgroups: patients operated before 1980 (A80), 43 cases; and after 1980 (D80), 35 cases; trying to evaluate the prognostic implications of the therapeutical advances achieved over the last 15 years. The population studied was composed mainly of women (78%) but with a slight predominance of men in TI. The mean age was 29.47 years (range 10-70) for the entire population, with a tendency toward older ages in TI (mean 46 years, range 23-70). The mean follow-up period was 4.3 years (range 0.08-23.2) without significant differences between TI and NTI. The results showed that the overall mortality rate was 16/100 (16%) [Fig. 1], with nine of those deaths corresponding to TI (9/22, 40.91%) and only the remaining seven to NTI (7/78, 8.97%). These differences in mortality rate between TI and NTI were statistically significant in all the specific times of follow-up analyzed up to 10 years after surgery (p < 0.05) [Fig. 2]. Notoriously, all deaths in NTI occurred in the A80 subgroup giving a p value < 0.001 when compared with D80 [Fig. 3]. In terms of morbidity, 55/100 (55%) reached complete clinical remission (CCR) defined by the complete absence of symptoms related to MG: 8/22 (36.36%) in TI and 47/78 (60.25%) in NTI [Fig. 4]. Most interestingly the differences were statistically significant (p < 0.01) when the rates of CCR in A80 and D80 were compared for all the times assessed [Fig. 5-6-7-8]. It can be concluded that the best results in survival in MG after T are obtained in patients without thymoma and also that the benefits of the rational use of modern therapeutic modalities, including surgery and immunosuppression with drugs, can offer those patients high possibilities of leading completely normal lives.

Adolescent↗
PubMed1992

[Recurrence of Guillain-Barré syndrome].

Fifteen of the 238 patients (6.3%) who recovered from an initial episode of Guillain-Barré syndrome had one or several acute relapses. Usually, there was only one relapse. The durations of the plateau and recovery phases of the relapses were longer than those of the initial episodes. The protein level in the cerebrospinal fluid was higher during relapses (1.37 +/- 1.30 milligrams) than during the initial episode (0.87 +/- 0.44 milligrams). The intensity of the symptoms during relapses was comparable to that of the initial episodes, but the occurrence of these relapses aggravated functional sequelae. Comparison of relapsing patients with those who experienced monophasic Guillain-Barré syndromes and were treated in the same unit revealed no element predictive of relapses.

Adolescent↗
PubMed1983

[Extrahypothalamic efferent pathways of the suprachiasmatic nucleus in the rat].

Efferent connections of the suprachiasmatic nucleus (SCN) in the Rat were evidenced using specific silver impregnation techniques designed to explore degenerating nerve fibers and terminals after a unilateral destruction of the suprachiasmatic nucleus. Suprachiasmatic efferences were confirmed and terminal buttons were identified in the septum, habenula and paraventricular nucleus of the thalamus. In addition suprachiasmatic fibers and nerve endings were revealed in the medial, cortical and central nuclei of the amygdala in the hippocampic subiculum, in different areas of the olfactory system and in the area parolfactoria.

Animals↗