Neonatal murine macrophages show enhanced chemotactic capacity upon toll-like receptor stimulation.

BACKGROUND: The neonatal surgical patient is threatened by exuberant inflammatory reactions. Neonatal macrophages are key players in this process. We investigated the ability of neonatal macrophages to initiate a local inflammatory reaction upon exposure to different bacterial or viral ligands to toll-like receptors (TLRs). METHODS: Peritoneal wash outs from neonatal (<24 h) and adult (42 days) C57BL/6J mice were gained by peritoneal lavages. In a first set of experiments, macrophages were purified and stimulated for 6 h by four different TLR ligands. mRNA was extracted for transcriptome analysis. In a second set of experiments, lipopolysaccharide was applied into peritoneal cavities. After 6 h of incubation, the cellular composition of the inflamed cavities was evaluated by cytological staining as well as chipcytometry. RESULTS: Neonatal murine peritoneal macrophages differed significantly in the expression of pro- and anti-chemotactic genes. Functional assignment of these genes revealed enhanced chemotactic potential of neonatal macrophages and was confirmed by a higher influx of pro-inflammatory cells into neonatal peritoneal cavities. CONCLUSION: Neonatal peritoneal macrophages demonstrated an enhanced chemotactic potential upon stimulation with four TLR ligands. This was associated with an increased influx of inflammatory cells to the peritoneal cavity. This might contribute to the strong inflammatory responses of neonates and preterms.

Prognostic value of thrombolysis, coronary artery patency, signal-averaged electrocardiography, left ventricular ejection fraction, and Holter electrocardiographic monitoring for life-threatening ventricular arrhythmias after a first acute myocardial infarction.

Prognostic studies after acute myocardial infarction (AMI) have mainly been performed in the prethrombolytic era. Despite the fact that modern management of AMI has reduced mortality rates, the occurrence of malignant ventricular arrhythmias in the late phase of AMI remains an important issue. We prospectively studied 244 consecutive patients (97 treated with thrombolytics) who survived a first AMI. All patients underwent time domain signal-averaged electrocardiography (vector magnitude: measurements of total QRS duration, terminal low [<40 microV] amplitude signal duration, and root-mean-square voltage of the last 40 ms of the QRS complex), Holter electrocardiographic monitoring, and cardiac catheterization. Late life-threatening ventricular arrhythmias were recorded. Eighteen arrhythmic events occurred during a mean follow-up period of 57 +/- 18 months. Three independent factors were associated with a higher risk of arrhythmic events: (1) left ventricular ejection fraction (odds ratio 1.9/0.10 decrease), (2) terminal low-amplitude signal duration (odds ratio 1.5/5 ms increase), and (3) absence of thrombolytic therapy (odds ratio 3.9). Low-amplitude signal duration sensitivity for sudden cardiac death was low (30%). Left ventricular ejection fraction had the highest positive predictive value for sudden cardiac death (10%). Thus, thrombolysis decreases both the incidence of ventricular tachycardia and sudden cardiac death with a higher reopening rate of the infarct-related vessel. Signal averaging predicts the occurrence of ventricular tachycardia and an impaired left ventricular ejection fraction predicts the occurrence of sudden cardiac death.

Influence of cigarette smoking on rate of reopening of the infarct-related coronary artery after myocardial infarction: a multivariate analysis.

OBJECTIVES: This study sought to determine whether the reopening of the infarct-related vessel is related to clinical characteristics or cardiovascular risk factors, or both. BACKGROUND: In acute myocardial infarction, thrombolytic therapy reduces mortality by restoring the patency of the infarct-related vessel. However, despite the use of thrombolytic agents, the infarct-related vessel remains occluded in up to 40% of patients. METHODS: We studied 295 consecutive patients with an acute myocardial infarction who underwent coronary angiography within 15 days (mean [+/- SD] 6.7 +/- 3.2 days) of the onset of symptoms. Infarct-related artery patency was defined by Thrombolysis in Myocardial Infarction trial flow grade > or = 2. Four cardiovascular risk factors--smoking, hypertension, hypercholesterolemia and diabetes mellitus--and eight different variables-age, gender, in-hospital death, history of previous myocardial infarction, location of current myocardial infarction, use of thrombolytic agents, time interval between onset of symptoms, thrombolytic therapy and coronary angiography--were recorded in all patients. RESULTS: Thrombolysis in current smokers and anterior infard location on admission were the three independent factors highly correlated with the patency of the infarct-related vessel (odds ratios 3.2, 3.0 and 1.9, respectively). In smokers, thrombolytic therapy was associated with a higher reopening rate of the infard vessel, from 35% to 77% (p < 0.001). Nonsmokers did not benefit from thrombolytic therapy, regardless of infarct location. CONCLUSIONS: These observational data, if replicated, suggest that in patients with acute myocardial infarction, thrombolytic therapy may be most effective in current smokers, whereas nonsmokers and ex-smokers may require other management strategies, such as emergency percutaneous transluminal coronary angioplasty.

[Predictive value of intracellular accumulation of daunorubicin and P-glycoprotein expression simultaneously determined by flow cytometry in adult acute myeloid leukemias]. / Intérêt prédictif de l'accumulation intracellulaire de daunorubicine et de l'expression de la glycoprotéine P déterminées simultanément par cytométrie en flux dans les leucémies aiguës myéloïdes de l'adulte.

Multidrug resistance (MDR) phenotype expression was evaluated retrospectively in 87 patients with acute myeloid leukemia (AML), 69 with de novo AML, ten with relapsed AML and eight with AML secondary to myelodysplastic syndrome (MDS). MDR phenotype, characterized by P-glycoprotein expression (MRK16 monoclonal antibody) and decrease in intracellular daunorubicin (DNR) accumulation was determined using flow cytometry. All patients received chemotherapy including cytosine-arabinoside and anthracycline (daunorubicin, zorubicin, idarubicin) or mitoxantrone, and quinine in ten cases. The predictive value of the MDR phenotype for clinical responsiveness was studied using uni- and multivariate analyses. Univariate analysis showed that DNR accumulation (p < 10(-4)), P-glycoprotein expression (p = 10(-4)) and disease status (de novo versus recurrent AML and acute MDS) (p = 10(-4)) were predictive of clinical responsiveness. The significance of these three parameters was maintained in multivariate analysis. When de novo AML was considered, only DNR accumulation was of predictive value (p < 10(-4)) for complete response to chemotherapy.

[Is percutaneous transluminal coronary angioplasty in chronic total coronary occlusion justified? Long term results in a series of 201 patients]. / L'angioplastie transluminale percutanée des occlusions coronaires totales chroniques est-elle justifiée? Résultats à long terme d'une série de 201 patients.

Percutaneous transluminal coronary angioplasty of chronic total coronary occlusions has a low primary success rate and is associated with a high percentage of restenosis. The aim of this retrospective study was to assess the long-term benefits of these procedures. In a series of 201 patients with 203 chronic total occlusions, the technical success rate was 51%, the clinical success rate was 46% with 3% of major complications. The only factor associated with a favourable outcome was the presumed duration of the occlusion. The clinical follow-up period was established at 6 years. The result of the initial procedure was used to establish two groups of patients: group I, clinical success, and group II, clinical failure. Patients in group I had a probability of survival greater than that of those in group II (97 vs 92%; p < 0.05); survival without coronary bypass surgery was also significantly better (89 vs 74%; p < 0.003). On the other hand, the probability without angioplasty was less in group I (70 vs 77%; p < 0.01), the result of a high restenosis rate (48%). A Cox analysis identified clinical success of angioplasty as a good prognostic factor for survival. Moreover, the clinical status at long-term was significantly better in patients in group I. These results indicate that in patients with chronic total coronary occlusions, the success of angioplasty has a favourable effect on long-term outcome both in terms of survival and in quality of life. They must be interpreted in the light of the limitations inherent in a retrospective study and should be confirmed by prospective trials.

[Comparative outcome of aortic valve endocarditis with or without annular abscess]. / Profil évolutif comparé des endocardites aortiques avec ou sans abcès de l'anneau.

Annular abscess is a not uncommon but serious complication of aortic valve endocarditis. The aim of this retrospective study was to evaluate the prognosis of aortic valve endocarditis with and without annular abscess. Between January 1981 and 1989, 122 consecutive cases of aortic endocarditis fulfilling the diagnostic criteria of Duke University were admitted to hospital. Group I included 40 cases with aortic ring abscess confirmed at surgery, in 35 patients; group II comprised 43 cases of operated aortic valve endocarditis without annular abscess in 41 patients and group III comprised 38 cases of aortic valve endocarditis treated medically without echocardiographic or angiographic signs of annular abscess in 36 patients. The patients in group III were significantly older than those in group I (57 +/- 14 years vs 44 +/- 17 years; p < 0.001). From the clinical point of view, endocarditis of prosthetic valves was slightly more common, but without reaching statistical significance, in group I, but the abscess was associated with more severe cardiac failure. Systemic embolism, atrioventricular block and pericardial effusion were equally common in the three groups. On the other hand, endocarditis with annular abscess was more often the result of infection with streptococci A, B, C or pneumoniae, than forms without abscess (22.5% vs 5% and 3% respectively in the 3 groups; p < 0.05). Of the patients treated surgically, destructive lesions of the valves were more common in cases of abscess (57.5% vs 35%; p < 0.05): the hospital mortality was higher in cases of abscess (17.5% vs 7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Refractory anemia with excess of blasts: a multivariate analysis of prognostic factors in 91 patients and a simplified scoring system for predicting survival.

Prognosis in myelodysplastic syndromes is extremely variable. The prognostic value of the FAB classification has been demonstrated in many studies. However, within the same FAB subtype, some patients may experience prolonged survival, whereas others die in a few weeks. This prognostic heterogeneity makes the therapy decision difficult. In an attempt to identify significant prognostic factors for survival in refractory anemia with excess of blasts (RAEB), clinical and hematological characteristics were analyzed in 91 patients. Multivariate regression analysis showed that bone marrow total blast cells percentages, sex and hemoglobin level were the characteristics significantly associated with survival. A scoring index based upon these three characteristics may be proposed and had a great prognostic value (p < 0.00001). It allows us to separate patients into three groups with low, intermediate and high score with a median survival of 239, 133 and 45 days for each group respectively. This scoring index may be useful in the design of therapy and analysis of future clinical trials. However, its predictive value needs to be confirmed in other series.

Predictive value for treatment outcome in acute myeloid leukemia of cellular daunorubicin accumulation and P-glycoprotein expression simultaneously determined by flow cytometry.

To evaluate the clinical relevance of multidrug resistance (MDR) phenotype, the intracellular daunorubicin accumulation (IDA) and P-glycoprotein (P-gp) expression were investigated in 87 adult patients with acute leukemia: 69 patients with de novo acute myeloid leukemia (AML), 10 with AML at relapse, and eight with secondary leukemia to myelodysplastic syndromes (MDS-AML). IDA and P-gp expression were determined by double-labeling flow cytometry analysis. Of 87 patients, 36 expressed P-gp (41%). P-gp expression was more frequently observed in AML at relapse and MDS-AML as compared with de novo AML (P = .0001). P-gp expression was significantly associated with CD34 expression (P = .0003) and chromosome 7 abnormalities (P = .027). A significantly reduced IDA was observed in P-gp+ as compared with P-gp- patients (P = .0007). Of the 87 patients, 51 achieved complete remission (CR). A reduced IDA was observed in patients in failure as compared with patients in CR (22% +/- 17% v 42% +/- 21%; P = 10(-4). Twelve of 36 P-gp+ patients as compared with 40 of 51 P-gp- patients achieved CR (33% v 78%; P = 10(-4). The prognostic value of IDA and P-gp expression was confirmed in multivariate analysis. These data suggest that the determination of IDA and P-gp expression may be useful in designing therapy for patients with AML.

Long-term follow-up after coronary angioplasty in patients younger than 40 years of age.

Over an 11-year period, the initial and late outcomes of percutaneous transluminal coronary angioplasty (PTCA) were studied in 140 consecutive patients younger than 40 years of age (mean, 34 +/- 3 years; range, 23 to 39 years; 132 men). Before the procedure, 28% of the patients had unstable angina, and 44% had a history of prior myocardial infarction. Mean left ventricular ejection fraction was 64% +/- 10%, and 75% of the patients had one-vessel disease. Primary success was 86% (77% for the first 70 patients vs 93% for the last 70, p < 0.02). Complications were nine periprocedural myocardial infarctions, eight emergency coronary surgical procedures, and no deaths. During follow-up (mean, 6 +/- 3 years; range, 1 to 12 years), 39 (28%) of the 104 patients who had repeat coronary angiography had angiographic restenosis (all < 6 months after PTCA). Late events were 13 elective coronary surgical procedures (11 for restenosis, one for failed PTCA, and one for progression of coronary artery disease), 13 PTCAs on a new site, five deaths, and four nonfatal myocardial infarctions. Ten-year survival was 96% +/- 1%, and 10-year event-free survival (without myocardial infarction, elective coronary surgery, or repeat PTCA) was 58% +/- 6%. Among survivors, 88% were free of angina, and 93% had returned to work. In patients younger than 40 years of age, PTCA yields excellent long-term survival, provided that the eventuality of repeat procedures during the first months is accepted. In addition, PTCA for progression on a new site is not unusual after several years.

[Estimation with bacteriology of the evolution of nosocomial infections between 1989 and 1991 in an university hospital]. / Estimation à partir de la bactériologie de l'évolution des infections nosocomiales entre 1989 et 1991 dans un hôpital universitaire.

The bacteriological laboratory data base was studied with an original software (Bacterio) and an appropriate method ("doubles" and early samples are not taken in account) to estimate the nosocomial infections. The incidence rates for 100 hospitalizations at the University hospital of Nancy are 9.2, 8.2 et 8.2 for respectively 1989, 90 et 91. These values are corrected while taking into account a method's sensibility of 65%. The 1000 days of hospitalization's rates allow a better comparison between the medical departments. For the whole hospital, the results are respectively of 7.9, 7.2 and 7.5%. Even if the many bias described cannot always been checked, the method gives some evolutivity indicators which are very useful for the hygienists.

[Immediate and long-term results of coronary transluminal angioplasty in patients under 35 years of age]. / Résultats immédiats et à long terme de l'angioplastie transluminale coronaire avant 35 ans.

Over an eleven year period, 57 patients under 35 years of age underwent percutaneous transluminal coronary angioplasty (PTCA). The features of the study population were: 55 men and 2 women, average age 32 +/- 3 years; unstable angina in 30%, previous myocardial infarction in 53%, average left ventricular ejection fraction 59 +/- 12%, single vessel disease in 84%. A total of 63 vessels were dilated. The primary success rate was 81% (72% in the first 29 patients compared with 89% in the latter 28 patients, p = 0.1). The following complications were observed: peri-procedural infarction (4 cases), emergency coronary bypass surgery (4 cases), no fatalities. During follow-up (average 6 +/- 3 years), of the 43 patients who underwent control coronary angiography in the last 6 months, 14 (33%) had angiographic restenosis. The long-term outcome was marked by 5 coronary bypass operations (3 for restenosis, 1 after failure of PTCA and 1 for progression of the coronary disease), 8 PTCAs for a new lesion due to progression of the coronary disease, 2 deaths and 2 non-lethal infarctions. The 10 year survival was 96 +/- 3% and the survival rate without cardiac events (infarction, surgical revascularisation or repeat PTCA) was 62 +/- 10% at 10 years. Of the 54 survivors, 50 (92%) have no angina, and 44 (81%) continue to take antiischaemic drug therapy. Of the 50 patients who were in full employment, 37 (74%) have gone back to full-time working and 8 (16%) have taken part-time jobs. (ABSTRACT TRUNCATED AT 250 WORDS)

Results of percutaneous transluminal coronary angioplasty of either the left anterior descending or left circumflex coronary artery in patients with chronic total occlusion of the right coronary artery.

The acute and long-term results of percutaneous transluminal coronary angioplasty (PTCA) of the left coronary artery in 106 patients (group 1) with chronic occlusion of the right coronary artery were compared with those of 106 patients matched for sex (92 male) and age (56 +/- 10 years) undergoing left PTCA with a normal right coronary artery (group 2). Before the procedure, group 1 had more unstable angina (42 vs 29%; p < 0.05), more frequent prior myocardial infarction (80 vs 25%; p < 0.001), and a lower left ventricular ejection fraction (56 +/- 10% vs 65 +/- 11%; p < 0.005). Acute results were not different in the 2 groups with respect to primary success (group 1: 93%; and group 2: 89%) and complications (group 1: 2 with emergency coronary surgery, and 4 with periprocedural myocardial infarction and no death; and group 2: 1 with emergency coronary surgery, 1 death, and 3 with periprocedural myocardial infarction). At 6 months, 79 patients in group 1 and 71 patients in group 2 had reangiography; the rate of restenosis was 35% in group 1 and 42% in group 2. In both groups, left ventricular ejection fraction increased significantly in patients without restenosis (58 +/- 12% vs 63 +/- 10%, p < 0.001 [n = 44] in group 1; and 66 +/- 9% vs 70 +/- 10%, p < 0.001 [n = 29] in group 2). In group 1, improvement was significant only for patients without collaterals to the occluded right coronary artery (59 +/- 10% vs 66 +/- 7%; p < 0.003 [n = 24]).(ABSTRACT TRUNCATED AT 250 WORDS)

[Modalities of detection of abnormal blood level of thyroid hormones in hospitalized aged patients]. / Modalités du dépistage des dyshormonémies thyroïdiennes chez le sujet âgé hospitalisé.

In a continuous series of 3836 patients over 60 years old, 24.1% have abnormal tests, 1.28% present hyperthyroidism and 1.98% hypothyroidism. Screening with TSH alone and T4 if abnormality, appears as the most helpful and costless method in order to detect thyroid dysfunction in hospitalised elderly patients.

Percutaneous transluminal coronary angioplasty in patients more than 75 years old: early and long-term results.

Over 4 yr, 102 consecutive patients more than 75 yr old (56 men, 46 women; mean age 78 +/- 3 years, range: 76-89 years) underwent 120 percutaneous transluminal coronary angioplasty procedures. At baseline, 86% had severe anginal symptoms (Canadian class III or IV), 43% had a history of prior myocardial infarction; 61% had multivessel coronary artery disease, and mean left ventricular ejection fraction was 60 +/- 11%. Calcifications were observed on 66% of the dilated arteries. A total of 158 vessels (1.3 vessel per procedure) were attempted: 1 vessel in 89 procedures (74%), 2 vessels in 24 (20%) and 3 vessels in 7 (6%). The primary success rate was 80% per lesion (126/158) and 77% per procedure (92/120). Complications included 3 deaths (3%), 9 Q-wave infarctions (7.5%) and there was no emergency coronary bypass surgery. The primary success rate was significantly related to the absence of coronary calcifications on the dilated segment (88% versus 75%, p < 0.05) and to the initial patency of the dilated artery (subtotal stenosis: 83% versus total occlusion: 53%, p < 0.05). Follow-up data were obtained in the 79 consecutive patients with a duration of follow-up exceeding 8 months. The mean duration of follow-up was 23 +/- 13 months (range 8 to 61 months). No patient was lost to follow-up; 11 patients died (cardiac causes: 7), 2 had a non-fatal infarction, 7 had aortocoronary bypass surgery and 18 had repeat percutaneous transluminal coronary angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

[Transluminal coronary angioplasty in patients over 75 years of age. Immediate and long-term results]. / Angioplastie transluminale coronaire après 75 ans. Résultats immédiats et à long terme.

Over a 4-year period, 120 transluminal coronary angioplasties were performed in 102 patients older than 75 years. There were 56 men and 46 women aged from 75 to 89 years (mean: 78 +/- 3 years) presenting with the following characteristics: left ventricular ejection fraction 60 +/- 11 percent; severe angina (class III or IV) 86 percent; history of myocardial infarction 43 percent; one-vessel lesion 39 percent; 66 percent of the arteries dilated were calcified. Altogether, 158 vessels (1.3 per procedure) were dilated: 1 vessel in 74 percent of the patients, 2 in 20 percent and 3 in 6 percent. The primary success rate was 80 percent per lesion (126/158 lesions) and 77 percent per procedure (92/120 procedures). This primary success rate was significantly higher when the stenosis dilated was not calcified (88 versus 75 percent, P < 0.05) and in cases with stenosis rather than complete occlusion (83 versus 53 percent, P < 0.01). Three patients died (3 percent) and 9 (7.5 percent) developed infarction with Q wave, but no emergency bypass was needed. The first 79 patients could be followed up for a mean period of 23 +/- 13 months (range: 8-61 months), and no patient was lost sight of. During that period, 11 patients died (including 7 of cardiac cause), 2 had a non-lethal infarction, 7 underwent distant aortocoronary bypass and 18 had a second angioplasty for restenosis. The long-term survival rate (Kaplan-Meier) was 83 +/- 6 percent at 4 years (90 percent when the angioplasty was successful and 73 percent when it failed; P < 0.02). Among the 65 survivors, 73 percent no longer had angina, 96 percent are in the New York Heart Association class I or II, and 92 percent are still on oral anti-angina therapy. Thus, transluminal coronary angioplasty can be performed in very old patients with good efficacy and an acceptable complication rate. The improvement obtained persists for a long time when the angioplasty is successful.

[Coronary transluminal angioplasty after 70 years of age. Multivariate analysis of parameters influencing immediate results and long-term prognosis]. / L'angioplastie transluminale coronaire après 70 ans. Analyse multivariée des paramètres influençant les résultats immédiats et pronostic à long terme.

Between January 1986 and July 1990, 186 patients over 70 years of age underwent 215 transluminal coronary angioplasties. The patients' characteristics were: 117 men and 69 women; mean age 75.5 +/- 4 years (70-89 years): left ventricular ejection fraction 62 +/- 12%: 40% had previous myocardial infarction; 48% had single vessel disease; 80% had severe angina (19% Class III and 61% Class IV) and 58% of dilated vessels had calcification. In all, 276 vessels (1.3 patient) were dilated: one vessel in 77%, 2 vessels in 18% and 3 or more in 5% of patients. The primary success rate defined as a reduction of the diameter of stenosis below 50% was 81% (174/215 procedures) (85%-215/253 stenosis--in dilatations and 65%-15/23 obstructions--in attempted disobliterations). There were 4 deaths (2.1%), 12 Q wave infarcts (5.5%) and 5 non Q wave infarcts (2.3%), 2 emergency bypass grafts procedures and no cerebrovascular accidents. A multivariate analysis identified two factors which reduced the primary success rate: coronary calcification (p less than 0.02) and a history of previous infarction (p less than 0.02). Three factors were associated with an increased risk of perioperative infarction: the female sex, age greater than 75 years (p less than 0.01) and previous infarction (p less than 0.03). The first 154 patients were followed up for 25 +/- 14 months (8-61 months) without any patients being lost to follow-up. In this period, 16 patients died (11 of cardiac causes), 2 had non-fatal infarction, 13 underwent secondary aortocoronary bypass surgery and 30 patients (20%) developed an angiographic restenosis.(ABSTRACT TRUNCATED AT 250 WORDS)