Biomedical subjects
Publications and source records attributed to J Lacroix.
Numerous drugs have been identified as presenting adverse effects towards the driving of vehicles. A large set of these drugs was compiled and classified into ten categories. Nonlinear neural mapping (N2M) was used to derive a typology of these molecules and also to link their adverse effects to therapeutic categories and structural information.
OBJECTIVES: To evaluate the effectiveness of naloxone in human shock; and to estimate the methodologic quality of the clinical trials. DATA SOURCES: Computerized bibliographic search on MEDLINE covering the period from January 1979 to July 1996, review of references of all papers found on the subject, and contact with primary investigators of eligible studies. STUDY SELECTION: To be included in this study, a paper should be a randomized, clinical trial published in a peer-reviewed journal evaluating naloxone in human shock, regardless of the patient's age (adult, child, neonate). Three independent readers reviewed 61 human publications and selected five clinical trials. Overall agreement on study selection was perfect (concordance: 100%). We excluded a posteriori two studies whose authors were unable to provide us with the raw data to complete contingency tables. This meta-analysis deals with three studies including 61 patients with septic shock. DATA EXTRACTION: Three independent reviewers extracted data on study design, intervention, outcome, and methodologic quality. The intraclass correlation coefficient was 0.7. The quality score of each study was 48, 60, and 61, on a scale of 104. DATA SYNTHESIS: Naloxone therapy was associated with statistically significant hemodynamic improvement (typical odds ratio: 0.241; 95% confidence interval: 0.08 to 0.68). The overall effect size was 0.89. However, a publication bias was possible. The case fatality rate was not decreased by naloxone (typical odds ratio: 0.60; 95% confidence interval: 0.21 to 1.67); a chi-square analysis detected significant heterogeneity for the latter outcome (p < .05). CONCLUSIONS: Naloxone improves blood pressure. However, the clinical usefulness of naloxone to treat shock remains to be determined and additional randomized clinical trials are needed to assess its usefulness.
OBJECTIVES: To determine the incidence, risk factors, and complications associated with or attributable to clinically significant upper gastrointestinal (GI) bleeding acquired in a pediatric intensive care unit (ICU). METHODS: Prospective, descriptive epidemiologic study in a multidisciplinary pediatric ICU of a tertiary-care university hospital. Upper GI bleeding was considered to be present if hematemesis occurred or blood was present in the gastric tube. An upper GI bleed was qualified as clinically significant if two or three reviewers independently assessed that at least one of the six complications considered for analysis was attributable to the upper GI bleed. RESULTS: A cohort of 1114 consecutive admissions was enrolled; 108 (9.7%) were excluded mostly (37.0%) because they already had an upper GI bleed at entry to the pediatric ICU. The final sample included 1006 admissions (881 patients); 103 upper GI bleeds (10.2%) were diagnosed, including 16 clinically significant upper GI bleeds (1. 6%). Complications attributed to an upper GI bleed included: decreased hemoglobin concentration (10 cases), transfusion (10), hypotension (3), and surgery (1). Three independent risk factors for clinically significant upper GI bleeding were retained by multivariate analysis: respiratory failure, coagulopathy, and pediatric risk of mortality score >/=10. Nine of the 16 cases (56. 3%) with clinically significant upper GI bleeding had three risk factors, 14 (87.5%) had two, and 1 (6.3%) had none. CONCLUSIONS: Clinically significant upper GI bleeds are rare in critically ill children. Prophylaxis to prevent them may be limited to patients who present with at least two risk factors.
The majority of patients with colorectal cancer present at a stage when the primary cancer can be resected with curative intent. However, despite the high resectability rate, about 30-50% of these patients subsequently develop metastatic disease. In these patients, neoplastic cells were disseminated either before or during surgery of the primary cancer. Due to the lack of appropriate detection systems, the extent of pre- and intraoperative hematogenic tumor cell dissemination has not yet been determined. Using a reverse transcription-PCR assay to amplify cytokeratin 20 transcripts, we were able to detect 10 colorectal cancer cells in 10 ml of blood. Blood samples were taken from 65 patients undergoing resection of primary colorectal cancer or liver metastasis of colorectal cancer pre-, intra-, and postoperatively. Circulating tumor cells were detected in 24 of 58 patients with colorectal resections in correlation to the tumor stage and in 6 of 7 patients who underwent hemihepatectomy for liver metastasis. In 8 of 58 patients with colorectal resection and in 5 of 7 patients with hemihepatectomy, tumor cells could only be detected during or during and after surgery. These results demonstrate that hematogenic tumor cell dissemination is a frequent and early event in colorectal cancer. Surgery enhances the release of tumor cells into the circulation. The long-term follow-up of our patient cohort will provide data on the prognostic relevance of circulating tumor cells and might lead to new therapeutic concepts for perioperative prophylaxis of tumor cell implantation or postoperative adjuvant therapy regimens.
UNLABELLED: In order to characterize the role of carnitine during metabolic stress, we prospectively determined carnitine profiles in plasma and urine on admission, days 2, 5, 10 and 15, among 28 critically ill children free of any known conditions associated with secondary carnitine deficiency. More than 25% of plasma and 50% of urinary carnitine measurements were abnormal; 96% (27/28) of patients displayed on at least one occasion an abnormal [< -2 SD or > +2 SD] carnitine value in plasma. Three children had extremely low [< 10 micromol/l] free carnitine (FC) levels in plasma. Plasma esterified and FC levels on admission were not related to the risk of mortality [PRISM score], to muscle lysis [CK values], and to the caloric intake. Levels of FC and esterified carnitine in plasma were unrelated to those measured in urine. CONCLUSION: Abnormal plasma and urine carnitine measurements are frequently found in critically ill children; the biological significance of these perturbations remains unclear. Caution must be exercised before concluding that an abnormal carnitine value is indicative of an underlying hereditary metabolic disorder in this population.
We conducted a prospective study in the multidisciplinary pediatric intensive care unit (pediatric ICU) of a tertiary-care university hospital in order to determine the incidence, risk markers, risk factors, and complications related to bacterial nosocomial pneumonia (BNP) and tracheitis (BNT) in children. A cohort of 1,114 consecutive admissions to the pediatric ICU was enrolled over a 56-wk period; 154 cases were excluded mostly (75%) because they already had a respiratory infection at entry. The final sample included 960 admissions (831 patients). Diagnosis of BNP or BNT was based on Centers for Disease Control of Atlanta criteria using a consensus method involving three experts, who also attributed complications to BNP and BNT. A total of 29 BNP and BNT (3.0%; 95% CI: 1.1 to 4.1%) were diagnosed (BNP: 1.2%, 95% CI: 0.7 to 1.9%; BNT: 1.8%, 95% CI: 0.8 to 2.6%). Three factors were retained by multivariate analysis as independent risk factors or markers for BNP (immunodeficiency, immunosuppression, and neuromuscular blockade), and two for BNT (head trauma and respiratory failure). Gram-negative bacteria and Staphylococcus aureus were the microorganisms most frequently found in the tracheal aspirates. Prescription of antibiotics was commonly attributable to BNP (75%) and BNT (59%). Death, as well as multiple organ system failure, resulted from BNP in 8% of cases, but never from BNT. In BNT, the reintubation rate was 24%. Nosocomial bacterial respiratory infections are rare in critically ill children. However, BNP causes significant complications, and more attention should be focused on BNT in the critically ill child.
Expression of alternatively spliced CD44 adhesion molecules has been implicated in metastatic spread of various rodent and human tumors. To determine whether specific CD44 splice variants contribute to metastatic spread of bronchial cancers, we compared the expression of CD44 splice variants in normal bronchial epithelium and bronchial cancers, including tumors which already spread to regional lymph nodes or distant organs. Variant CD44 expression was analysed by immunohistochemistry using variant exon-specific monoclonal antibodies. The precise composition of CD44 transcripts was delineated by exon-specific RT-PCR. The concurring data obtained by both methods revealed that high levels of standard CD44 and variants v5 and v6 as well as low levels of variants v7 and v10 are expressed both in normal bronchial epithelium and squamous cell lung cancers. No CD44 expression was observed in the highly metastatic small cell lung cancers and adenocarcinomas with the exception of bronchioalveolar cancers showing weak expression of standard CD44. These data suggest that expression of alternatively spliced CD44 molecules in the bronchial tract is related to the distinct differentiation of the respiratory epithelium. No correlation between expression of specific CD44 splice variants and metastasis of bronchial cancers was observed.
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STUDY OBJECTIVES: To determine the cumulated incidence and the density of incidence of systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, and multiple organ dysfunction syndrome (MODS) in critically ill children; to distinguish patients with primary from those with secondary MODS. DESIGN: Prospective cohort study. SETTING: Pediatric ICU of a university hospital. PATIENTS: One thousand fifty-eight consecutive hospital admissions. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: SIRS occurred in 82% (n=869) of hospital admissions, 23% (n=245) had sepsis, 4% (n=46) had severe sepsis, 2% (n=25) had septic shock; 16% (n=168) had primary MODS and 2% (n=23) had secondary MODS; 6% (n=68) of the study population died. The pediatric risk of mortality (PRISM) scores on the first day of admission to pediatric ICU were as follows: 3.9 +/- 3.6 (no SIRS), 7.0 +/- 7.0 (SIRS), 9.5 +/- 8.3 (sepsis), 8.8 +/- 7.8 (severe sepsis), 21.8 +/- 15.8 (septic shock); differences among groups (p=0.0001), all orthogonal comparisons, were significant (p<0.05), except for patients with severe sepsis. The observed mortality for the whole study population was also different according to the underlying diagnostic category (p=0.0001; p<0.05 for patients with SIRS and those with septic shock, compared with all groups). Among, patients with MODS, the difference in mortality between groups did not reach significance (p=0.057). Children with secondary MODS had a longer duration of organ dysfunction (p<0.0001), a longer stay in pediatric ICU after MODS diagnosis (p<0.0001), and a higher risk of mortality (odds ratio, 6.5 [2.7 to 15.9], p<0.0001) than patients with primary MODS. CONCLUSIONS: SIRS and sepsis occur frequently in critically ill children. The presence of SIRS, sepsis, or septic shock is associated with a distinct risk of mortality among critically ill children admitted to the pediatric ICU; more data are needed concerning children with MODS. Secondary MODS is much less common than primary MODS, but it is associated with an increased morbidity and mortality; we speculate that distinct pathophysiologic mechanisms are involved in these two conditions.
The developed formula of some 200 antiviral molecules were treated by molecular connectivity matrix method. This technic allows the search and the automatically count of structural binary fragments of these molecules. It has been possible to establish a spanning tree (Prim's arborescent squeleton) which gathers the different molecules and permits to put a priori some new structures.
Expression of splice variants of the CD44 adhesion molecule has been implicated in metastatic spread of various human tumor cells, including malignant lymphomas and colon, mammary, and gastric carcinomas, and has been correlated to a poor prognosis for the respective patients. To determine whether variant CD44 molecules might also contribute to the metastatic spread of cervical cancer, we analyzed the CD44 expression pattern in normal cervical epithelium and in low- and high-grade cervical dysplasia and compared it with invasive and metastasizing cervical cancers, including cell lines derived thereof by immunofluorescence and exon-specific PCR amplification of reverse-transcribed CD44 transcripts. We observed that normal cervical epithelium and dysplastic lesions express high levels of standard CD44 in the basal and spinous epithelial layers. CD44 molecules encompassing variant exons v5 and v6 are strongly expressed throughout the epithelium. Low levels of variants encompassing exon v7 are expressed in basal and spinous layers, with particular strength in the suprabasal layer. Low levels of epitopes encoded by v8 and v10 are expressed in the basal and spinous layers. In cervical cancers, including lymph node metastasis, we observed strong expression of v5 and v6, but almost no expression of v7, v8, and v10. Expression of the CD44 standard form appeared to be down-regulated in some cancers when compared to normal cervical epithelium. Thus, expression of variant CD44 molecules is related to distinct differentiation of mucosal squamous epithelia in the female genital tract. No correlation of the expression of variant CD44 isoforms, including the v7-v8 fusion epitope with tumor progression or lymphatic spread, was observed.
1-Aryl 3-(2-chloroethyl) ureas (CEUs), a new class of potent antineoplastic agents, were recently developed in our laboratory. These compounds were designed from the aromatic moiety of chlorambucil and the unnitrosated pharmacophore of carmustine. In the present study we investigated the effect of the potent CEU derivative 4-tert-butyl-[3-(2-chloroethyl)ureido] benzene (tBCEU) on tumor cell lines selected for resistance to a wide range of anticancer drugs. The resistance mechanisms found in these cells included increased expression of P-glycoprotein, increased intracellular concentration of glutathione and/or glutathione-S-transferase activity, alteration of topoisomerase II, and increased DNA repair. Whereas the resistant cell lines were found to be highly resistant to a panel of clinically known anticancer drugs, tBCEU was found to be equally cytotoxic to both resistant and parental cells. The nitrobenzylpyridine assay indicated that tBCEU is a weaker alkylating agent than chlorambucil. This lack of cross-resistance in various resistant tumor cells suggests that tBCEU could be potentially useful in the treatment of cancers resistant to conventional anticancer drugs.
OBJECTIVE: To characterize the etiology, course, and prognosis in children admitted to a pediatric intensive care unit (ICU) for status epilepticus. DESIGN: Retrospective, descriptive study. SETTING: Pediatric ICU in a university hospital. PATIENTS: One hundred forty-seven children admitted with status epilepticus. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Status epilepticus was defined as a prolonged (> 30 mins) or repeated tonic or tonic-clonic seizure with a persistent altered state of consciousness. Over 10 yrs, 147 children 0 to 16 yrs of age (median 1; mean 3.4 +/- 3.9 [SD]) were admitted to a pediatric ICU for, or with, 153 episodes of status epilepticus. Status epilepticus was caused most often by epilepsy (n = 52), atypical febrile convulsions (n = 21), bacterial meningitis (n = 20), encephalitis (n = 20), intoxication (n = 8), or a metabolic disorder (n = 12). Two infants, 1 and 3 months of age, and a patient with intoxication by isoniazid, responded to pyridoxine. Among 114 previously normal children, 34 patients displayed a new neurologic problem on discharge from the ICU, among whom, 68% (23/34) still had some neurologic abnormality 1 yr after the episode of status epilepticus. Nine patients died during their ICU stay, mostly from underlying disease rather than from the status epilepticus itself. A normal neurologic status before status epilepticus and age < 4 yrs seem to be markers of good prognosis, while encephalitis and meningitis appear to be markers for morbidity and mortality. CONCLUSIONS: Most cases of status epilepticus were caused by epilepsy, atypical febrile seizure, encephalitis, meningitis, or metabolic disease. The mortality rate during the ICU stay was 6%. The prognosis was good in most surviving cases, more so if the neurologic development of the child was normal before the status epilepticus.
OBJECTIVES: To describe the timing of onset of organ system failure, multiple organ system failure diagnosis, and the subsequent death in children admitted to a pediatric intensive care unit (ICU). Second, to identify independent risk markers of death in pediatric patients with multiple organ system failure. DESIGN: Review of a database. SETTING: Pediatric ICU within a tertiary care center. PATIENTS: We analyzed the pediatric ICU course of 777 consecutive patients aged < 18 yrs. MEASUREMENTS AND MAIN RESULTS: Eighty-five (10.9%) of 777 children had multiple organ system failure, defined as the simultaneous occurrence of at least two organ system failures. Of 85 children, 37 (43.5%) were postoperative cardiac surgery patients and 48 (56.5%) patients were in the ICU for other reasons. The diagnostic criteria for multiple organ system failure were met on the day of admission by 73 (86%) of 85 patients. The maximum number of organ system failures occurred within 72 hrs in 74 (87%) children. The mortality rate for all patients with multiple organ system failure was 50.6%. Thirty-eight (88.4%) of deaths occurred within 7 days after the diagnosis of multiple organ system failure. Survival analysis was comparable for both postoperative cardiac surgery patients and patients with other diagnoses. Multivariate analysis identified three factors as independent risk markers of death in pediatric patients with multiple organ system failure: maximum number of simultaneous organ system failures during the pediatric ICU stay: odds ratio, 55.9 (95% confidence interval, 7.9 to 396.1); age < or = 12 months: odds ratio, 17.1 (95% confidence interval, 1.8 to 158.7); and the Pediatric Risk of Mortality (PRISM) score on the day of admission: odds ratio, 1.25 (95% confidence interval, 1.1 to 1.5). CONCLUSIONS: The mortality rate associated with multiple organ system failure in pediatric patients is high. The maximum number of simultaneous organ system failures during pediatric ICU stay, age < or = 12 months, and the PRISM score on the day of admission are independent risk markers of death. Diagnosis of multiple organ system failures, development of maximum number of organ system failures, and deaths occur remarkably early after pediatric ICU admission; the rationale for using prophylactic therapy under such circumstances is unclear.
Chest tubes are placed to empty the pleural space of air or fluid which prohibits full lung expansion. The function of these tubes is dependent on adequate placement, effective drainage and frequent re-evaluation of the patient and the chest drainage system. Knowledge of the principles of chest tube drainage is important to evaluate adequately the function of a tube thoracostomy.
The marked decrease in neuropsychiatric morbidity (NPM) following coronary artery bypass (CAB) over a period of four years led us to carry out a retrospective study in order to identify the cause. Two hundred fifty-eight consecutive CAB procedures were performed between 1983 and 1986. For 133 patients (group A), the CAB procedure was performed with left ventricular vent (LVV) and for 125 patients (group B) without LVV. In group A, 93 patients (group A1) had cardiopulmonary bypass (CPB) with a bubble oxygenator and 40 patients (group A2) had CPB with a membrane oxygenator. In group B, 30 patients (group B1) had CPB with a membrane oxygenator without filter in the arterial line and 95 patients (group B2) had CPB with a membrane oxygenator and filter in the arterial line. The reduction in NPM arose from the removal of the LVV, as the incidence of NMP was in group A 24.6% versus 12.3% in group B (p < 0.05). The substitution of the bubble oxygenator by a membrane oxygenator does not alter the incidence of NPM: 23.3% in group A1 versus 27.5% in group A2 (p > 0.05) nor did incorporation of a filter in the arterial line: 10% in group B1 versus 13.1% in group B2 (p > 0.05). Introduction of air in the left ventricle via an LVV catheter opening and coronary arteriotomy therefore causes gazeous microembolic events responsible for NPM following CAB.
OBJECTIVE: To determine if the magnitude of blood pressure (BP) increase could differentiate convulsion caused by a hypertensive crisis from a primary convulsive disorder, which itself increases BP. DESIGN: Retrospective analysis. SETTING: Admission to a pediatric intensive care unit (ICU) within a tertiary care center. PATIENTS: All children with hypertensive crisis admitted to the pediatric ICU from 1976 to 1990 were studied. Thirty-eight episodes occurred in 36 patients. The charts of children admitted for status epilepticus from 1976 to 1986 were also reviewed. One hundred and fifty-three episodes occurred in 145 patients. MEASUREMENTS AND MAIN RESULTS: BP values at entry to the pediatric ICU in patients with hypertensive crisis were compared with the highest BP values obtained within an hour after cessation of convulsion in 120 patients admitted for status epilepticus. The Z scores for BP, adjusted for age and sex, were compared. The BP values for children in hypertensive crisis with or without convulsions were by far greater than the BP values observed in patients in status epilepticus (p < .0001). For a patient in the postictal phase, a BP > or = 4.0 SD above the mean for age and sex predicted with 78% probability the presence of a hypertensive crisis requiring emergency treatment. If the BP was < 4 SD below the mean, the possibility of a hypertensive crisis was excluded (negative-predictive value 100%). CONCLUSIONS: Children with hypertensive crisis, as well as children with status epilepticus, can present with a high BP. In a postictal patient, the magnitude of BP increase is a useful clinical parameter to exclude a hypertensive crisis that requires specific treatment of the BP.
Drugs part in traffic accidents is not well known. We attempted to specify it taking out of pawn the adverse effects which could be liable: drowsiness; consciousness lose; dizziness; eye-sight troubles; hallucinations, hearing troubles; drunken feelings, behaviour modification; propensy to suicide, interference with alcohol. Drugs involving such effects were indexed; their therapeutic indications and their chemical structure were taking into account. Statistical classical count allowed us to quantify relative importance of this ten adverse effects category. Multivariate analysis worked out structuration this undesirable effects into 97 different profiles by the mean of the Minimum Spanning Tree method and established proximity links between the 409 active principles recorded. This results are reported here.