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Biomedical subjects

J Lacroix

Publications and source records attributed to J Lacroix.

At least 37 records · Page 2Linked to original sources

Expression of cytokeratin 20 in thyroid carcinomas and peripheral blood detected by reverse transcription polymerase chain reaction.

We investigated a nested reverse transcriptase polymerase chain reaction (RT-PCR) system to detect CK20 mRNA in thyroid carcinomas, benign thyroid diseases and peripheral blood to improve diagnosis of thyroid carcinoma and to detect disseminated tumour cells. Frozen tissue samples of 46 thyroid carcinomas and 30 benign thyroid diseases (14 multinodular goiters, 14 follicular adenomas, two Hashimoto's thyroiditis) were obtained intraoperatively. Preoperative blood samples were drawn from 31 patients with thyroid cancer, nine patients with benign thyroid disorders and 20 healthy volunteers. Nine out of nine medullary, 9/12 follicular, 7/19 papillary and 2/6 anaplastic carcinomas expressed CK20 transcripts. CK20 mRNA was undetectable in 30 tissue sections of benign thyroid diseases. Circulating tumour cells were found in the blood of 3/8 patients with medullary carcinoma, 2/8 patients with follicular carcinoma, 2/11 patients with papillary carcinoma and 1/4 patients with an anaplastic carcinoma. Nine blood samples of patients with benign thyroid diseases and 20 healthy volunteers tested negative. For the first time CK20 mRNA could be detected in tissue sections of thyroid carcinomas and peripheral blood samples of patients with thyroid cancer. It was not detectable in benign thyroid diseases. Our results therefore strongly suggest that CK20 RT-PCR assays may improve the diagnosis of thyroid carcinoma and is able to detect circulating tumour cells in peripheral blood of thyroid carcinoma patients.

Adenocarcinoma, Follicular↗

Reactive hemophagocytic syndrome presenting as a component of multiple organ dysfunction syndrome.

OBJECTIVE: To report two cases of severe reactive hemophagocytic syndrome (RHS), to discuss their impact, and to present evidence that RHS may be a constitutive part of multiple organ dysfunction syndrome (MODS). DESIGN: Case-report. SETTING: Pediatric intensive care unit (PICU). PATIENTS: Two patients with RHS and MODS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Case #1: A 3 yr-old boy with Mucha-Haberman syndrome (pityriasis lichenoides) was admitted to the PICU for septic shock, acute respiratory distress syndrome, capillary leak, acute renal failure, liver dysfunction, and RHS (pancytopenia and hemophagocytosis on bone marrow aspirate). The pancytopenia was severe (white blood cell count, 0.9 x 10(9)/L; hemoglobin, 59 g/L; platelets, 36 x 10(9)/L), required many transfusions, and resolved 2 months later. The patient needed mechanical ventilation for 6 wks. Length of stay in PICU was 2 months. Case #2: A previously healthy 4 yr-old girl was admitted to the PICU for respiratory failure. She developed acute respiratory distress syndrome, cardiomyopathy with complete atrioventricular block, shock, capillary leak, liver dysfunction, and RHS (pancytopenia and hemophagocytosis on bone marrow aspirate). The pancytopenia was severe (white blood cell count, 1.92 x 10(9)/L; hemoglobin, 65 g/L; platelets, 58 x 10(9)/L) and necessitated transfusional support. Serology for respiratory syncytial virus was positive. RHS duration was 20 days; the patient recovered completely. Length of mechanical ventilation was 16 days and length of stay in PICU was 3 wks. CONCLUSIONS: These cases show that RHS may be a significant cause of pancytopenia in the PICU. It needs to be recognized as a clinical entity because it can be reversible and nonneoplastic. RHS and MODS share some pathophysiologic elements and could be related to each other.

Biopsy↗

Detection of hematogenous micrometastasis in patients with transitional cell carcinoma.

PURPOSE: Cytokeratin 20 (CK 20) is selectively expressed in urothelium, gastric intestinal epithelium, in Merkel cells and in a variety of malignant neoplasms. CK 20 RT-PCR assay has been extensively used to detect isolated cancer cells in peripheral blood, lymph nodes and bone marrow samples of patients with colorectal carcinoma. Since CK-20 is also actively expressed in transitional cell carcinoma (TCC), we analyzed, whether CK 20 Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) is suitable to detect residual tumor cells in patients with transitional cell carcinoma of the bladder and the upper urinary tract. MATERIALS AND METHODS: Nested Reverse Transcriptase Polymerase Chain Reaction assay was used to analyze CK 20 transcripts in peripheral venous blood samples and tumor biopsies of 49 patients with transitional cell carcinoma. Blood samples of 22 healthy volunteers served as negative controls. RESULTS: CK 20 mRNA was detectable in blood samples of 12 of 49 patients with TCC. All blood samples of the control group tested negative. The detection rate for CK 20 mRNA significantly correlated (p = 0.0019, Cochran-Armitage Trend Test) to the stage of disease and increased from 0% in stage pTa to 63% in stage pT4. CONCLUSIONS: These results suggest that CK 20 is a suitable marker for the detection of disseminated TCC cells in peripheral venous blood samples and may be helpful in the molecular staging of TCC patients. The prognostic relevance has to be evaluated in further followup.

Aged↗

Decision making and end-of-life care in critically ill children.

OBJECTIVES: 1) To comment on the medical literature on decision making regarding end-of-life therapy, 2) to analyze the data on disagreement about such therapy, including palliative care, and withholding and withdrawal practices for critically ill children in the pediatric intensive care unit (PICU), and 3) to make some general recommendations. DATA SOURCES AND STUDY SELECTION: All papers published in peer-reviewed journals, and all chapters on end-of-life therapy, or on conflict between parents and caregivers about end-of-life decisions in the PICU were retrieved. RESULTS: We found three case series, three systematic descriptive studies, two qualitative studies, four surveys, and many legal opinions, editorials, reviews, guidelines, and book chapters. The main determinants of end-of-life decisions are the child's age, premorbid cognitive condition and functional status, pain or discomfort, probability of survival, and quality of life. Risk factors in persistent conflict between parents and caregivers about end-of-life care include a grave underlying condition or an unexpected and severe event. CONCLUSION: Making decisions about end-of-life care is a frequent event in the PICU. Children may need both intensive care and palliative care concurrently at different stages of their illness. Disagreements are more likely to be resolved if the root cause of the conflict is better understood.

Child↗

[Is mammography useful in Paget's disease of the breast?].

PURPOSE: Interest of the mammogram in Paget's disease of the breast, especially for a therapeutic decision in otherwise asymptomatic women with Paget's disease, who would be candidates for conservative treatment. MATERIALS AND METHODS: 61 women with histological Paget's disease of the nipple, treated by mastectomy, were retrospectively analyzed with clinical, radiological and pathological correlations. RESULTS: An underlying carcinoma was found in 60 cases (98.4%), atypical epithelial hyperplasia in one. In the 24 women without breast palpable mass, 17 (71%) had a normal mammogram, 12 (50%) had carcinoma with an invasive component, 14 (58%) had a cancer at a distance from the nipple, 17 (71%) had a multifocal carcinoma. All 37 women with a palpable mass had a pathological mammogram, 36 of them had carcinoma with an invasive component, 35 (95%) a cancer at a distance from the nipple, 31 (84%) a multifocal carcinoma. CONCLUSION: Mammogram is of limited value in management of Paget's disease of the breast for women without breast palpable mass; it can not predict the site of malignancy, nor the invasive component.

Adult↗

Establishing research priorities in etiologic epidemiology.

PURPOSE: A major goal of epidemiology is to discover the causes of disease in populations. The aim of this study was to develop a method for establishing research priorities within this very broad area of scientific inquiry. METHODS: While the approach is applicable to many diseases, cancer was used here, in part because of its importance to both individuals and governments. Measures of disease were estimated from data in the Ontario Cancer Registry, and combined to yield a single assessment of impact for each cancer site. Measures of exposure prevalence were identified from recent population health surveys. Cross-classification by disease and exposure rankings yielded a matrix of scores of "relative importance" for each cancer-exposure combination. Onto this matrix was overlaid: 1) estimates of statistical power for examining each association; 2) biological plausibility of each association; and 3) strength of the epidemiological evidence supporting each association. RESULTS: The disease-exposure matrix, viewed in light of statistical power, biological plausibility, and current epidemiological evidence, yielded, in the examples shown, some potentially interesting yet understudied associations (e.g., non-Hodgkin lymphoma (NHL) and certain aspects of dietary intake). CONCLUSIONS: The associations identified within the research hierarchy suggest not only new avenues for etiologic research, but also priorities for research focus.

Environmental Exposure↗

Nucleic acid based techniques for the detection of rare cancer cells in clinical samples.

Solid tumors evolve from cells which have lost control functions safeguarding their genomic integrity by mutation within specific genes. Consequently, proliferating cells within a tumor differ slightly from generation to generation. This permits the continuous production of new and subsequent selection of the best adapted cells, which retain this capacity of self-evolution. The threat of neoplastic diseases is due to the clinical experience, that surgical resection of all cells with this potential for autonomous evolution is often not achievable, since they were spread to distant non-resectable sites in the organism before diagnosis and surgical removal of the primary tumor and might later grow out as metastatic lesion. Lack of diagnostic techniques to detect small preneoplastic lesions as well as single spread cancer cells often causes delayed diagnosis when curative therapy is no longer achievable. Recent advances in characterizing the molecular basis of genomic instability, identifying specific gatekeeper mutations and their functional consequences in neoplastic cells now permit the development of new highly sensitive tests to identify preneoplastic lesions as well as spread single cancer cells. These techniques carry a tremendous potential for simple cost effective cancer early detection and screening assays as well as for diagnostic applications to identify spread cancer cells. Thus, they most likely will soon guide indication for surgical and adjuvant therapy protocols for patients with preneoplastic or neoplastic lesions. However, due to the complexity of the assays and the great variety of technical aspects involved almost all diagnostic applications are not yet standardized. This poses significant problems for quality control as well as inter-laboratory comparability of the results and underlines the urgent demand for well controlled collaborative efforts to evaluate indications and diagnostic standards for these assays. Here, the theoretical background, basic principles and some diagnostic applications of these new tests are reviewed.

Animals↗

Protected specimen brush or bronchoalveolar lavage to diagnose bacterial nosocomial pneumonia in ventilated adults: a meta-analysis.

OBJECTIVE: We conducted a meta-analysis by using summary receiver operating characteristic curves to compare the diagnostic value for bacterial nosocomial pneumonia of the following: a) quantitative culture (colony-forming units per milliliter or CFU/mL) of respiratory secretions collected with a bronchoscopic protected specimen brush (PSB); b) quantitative culture of a bronchoscopic bronchoalveolar lavage (BAL); and c) the percentage of infected cells (IC) in BAL. DATA SOURCES: All studies published in the English or the French language, through January 1, 1995, on the evaluation of PSB or BAL for the diagnosis of pneumonia were considered for analysis. The relevant literature was identified through computer and reference searching and by experts in the field. STUDY SELECTION: A study was included if at least two of three independent readers regarded its purpose as the evaluation of CFU-PSB, CFU-BAL, or IC-BAL for the diagnosis in human beings of bacterial nosocomial pneumonia in ventilated adults and if the study was prospective and published in a peer-reviewed journal. DATA EXTRACTION: Three readers reviewed all published articles and decided whether to include each study; consensus was defined as agreement by at least two readers. The authors of each original article included in the meta-analysis were asked to complete a questionnaire in which they were asked to check and to correct the data extracted by one of the independent readers. DATA SYNTHESIS: Summary receiver operating characteristic curves were used to compare the efficacy of three diagnostic tests. Eighteen studies on CFU-PSB (795 patients) were included, as well as 11 studies on CFU-BAL (435 patients) and 11 on IC-BAL (766 patients). The accuracy of these tests was not different. However, it seems that administration of previous antibiotics markedly decreased accuracy of CFU-PSB (p = .0002) but not the accuracy of CFU-BAL and that of IC-BAL. CONCLUSION: Both PSB and BAL are reliable to diagnose bacterial nosocomial pneumonia. Because CFU-BAL and IC-BAL seemed more resistant to the effects of antibiotics, we recommend BAL rather than PSB if the patient is already receiving antibiotics.

Adult↗

Ribavirin in ventilated respiratory syncytial virus bronchiolitis. A randomized, placebo-controlled trial.

We undertook a prospective, double-blind, placebo-controlled trial to resolve the question of the clinical effectiveness of ribavirin in previously well infants who require ventilation for respiratory distress secondary to respiratory syncytial virus (RSV) bronchiolitis. Aerosol ribavirin or NaCl 0.9% was administered within 24 h of initiation of ventilation, 18 h/d, for a maximum of 7 d or until extubation. From March 1994 to March 1997, 42 children were randomized and 41 patients were retained for analysis. Baseline characteristics of each group-ribavirin and placebo (20:21)-were not significantly different with respect to age (62.5 +/- 35.9 versus 62.7 +/- 30.9 d), sex, weight, and length of ventilation pre-aerosol. "Intent to treat" outcome analysis found no significant differences in the length of the following: ventilation (102.16 +/- 65.26 versus 126.28 +/- 78.72 h; p = 0.29), aerosol therapy, stay in the intensive care unit, total oxygen therapy, and hospitalization. The aerosols were well tolerated and no deaths occurred. This trial demonstrates the lack of effectiveness of aerosolized ribavirin in reducing the length of ventilation and course of illness in infants with no underlying illness ventilated for respiratory distress secondary to RSV bronchiolitis.

Administration, Inhalation↗

Stroke-like episodes in autosomal recessive cytochrome oxidase deficiency.

Stroke-like episodes, defined as periods of acute localized neurological dysfunction during which brain imagery suggests cerebral ischemia but vascular anatomy is normal, occurred in 3 patients with autosomal recessive Saguenay-Lac St-Jean (SLSJ) cytochrome oxidase (COX) deficiency. The patients developed focal neurological deterioration and frontal hypodensities on cerebral computerized tomography (CT). Arteriography, performed in 1 patient during an acute episode, showed normal vascular anatomy. Nevertheless, capillary shunting was evident both in regions that appeared abnormal on the initial cerebral CT study and in regions that appeared normal but subsequently developed Leigh disease. Stroke-like episodes did not exacerbate systemic acidosis, and acidotic decompensations occurred independently of stroke-like episodes. In conclusion, stroke-like episodes occur in autosomal recessively inherited congenital lactic acidoses as well as in those caused by mitochondrial DNA mutations. In some cases, acute localized neurovascular changes occur in regions that subsequently develop Leigh disease.

Brain↗

Detection of disseminated colorectal cancer cells in lymph nodes, blood and bone marrow.

Tumor progression after curative resection of colorectal cancer is caused by tumor cell dissemination, currently undetected by standard clinical staging techniques. The detection of disseminated tumor cells could help to identify a patient subgroup at risk for disease relapse who could benefit from adjuvant therapy. In addition, the significance of lymphogenic compared with hematogenic colorectal cancer cell dissemination is unknown. However, this knowledge would strongly influence the development of future therapeutic regimes. The purpose of this study was to determine the extent of colorectal cancer cell dissemination in lymph nodes compared with blood and bone marrow. Using a CK 20-reverse transcription (RT)-PCR assay, we examined 279 lymph nodes, blood, and bone marrow samples from 20 patients with colorectal cancer. Of 16 patients (11 patients stage I, 5 patients stage II) with histopathologically tumor-free lymph nodes: 14 patients (10 patients stage I, 4 patients stage II) were found to have tumor cells in paracolonic lymph nodes; 12 patients (8 patients stage I, 4 patients stage II) were found to have tumor cells in the lymph nodes along the mesentery vessels; and, remarkably, 6 patients (4 patients stage I, 2 patients stage II) were found to have tumor cells in the apical lymph nodes. In contrast, tumor cells were detected in only two blood and three bone marrow samples of these patients. Thus, lymphogenic tumor cell dissemination is a very common and early event in colorectal cancer, preceding hematogenic tumor cell dissemination. In addition, our data strongly suggest that the detection of tumor cells in the apical lymph node by CK 20-RT-PCR has prognostic relevance. Our results underline the therapeutic importance of meticulous lymph node dissection and demonstrate that the detection of lymphogenic or hematogenic tumor cell dissemination by CK 20-RT-PCR will significantly improve current tumor staging protocols.

Aged↗

Markers of cellular dysoxia during orthotopic liver transplantation in pigs.

OBJECTIVE: To characterize global, regional, and end-organ markers of cellular dysoxia during orthotopic liver transplantation and early reperfusion in pigs. DESIGN: Descriptive study. SETTING: University hospital research laboratory. ANIMALS AND INTERVENTIONS: 7 fasted, anesthetized, and mechanically ventilated Yorkshire pigs underwent orthotopic liver transplantation. Oxygen consumption (VO2) and oxygen delivery (DO2) were both calculated using standard formulae. Gastric interstitial pH and the gastroarterial partial pressure of carbon dioxide (PCO2) gradient were measured with a gastric tonometer. The following were determined from arterial blood samples: serum lactate to pyruvate ratio, serum 3-hydroxybutyrate to acetoacetate ratio, plasma free fatty acids, and plasma free and total carnitine levels. MEASUREMENTS AND RESULTS: Data were collected 1 h after induction of anesthesia (I), at the end of the anhepatic phase (A), and 1 h after reperfusion (R), Median (range) VO2 values obtained at the specified time points were: I 318 (206-1860), A 210 (152-408), R 330 (214-424) ml/kg per min, respectively (NS); DO2 values were: I 1828 (1382-3259), A 1219 (452-2492), R 1741 (1345-12,071) ml/kg per min, respectively (NS). The lactate to pyruvate ratio, reflecting the redox potential of the cytosol, progressively increased: I 22 (9-46), A 29 (16-68), R 43 (23-55), (p < 0.05). Gastric interstitial pH, as well as the gastroarterial PCO2 gradient values at the specified time points did not reach statistical significance. Levels of ketone bodies (3-hydroxybutyrate+acetoacetate) remained lower than 0.120 mmol/l. The ketone body ratio did not significantly vary over time (NS). Plasma esterified and free carnitine concentrations and free fatty acid values remained within normal limits (NS). Among these markers, the ketone body ratio presented the largest area under the receiver operating characteristic curve as a marker of postoperative mortality, with an inflexion point at 0.9. CONCLUSION: In this study, orthotopic liver transplantation was associated with significant variations over time in the redox potential of the cytosol. Postoperative mortality was, however, related to the redox state of the liver mitochondria. Our data suggest the occurrence of abnormal tissue oxygenation during liver transplantation.

3-Hydroxybutyric Acid↗

Incidence and risk factors of catheter-related deep vein thrombosis in a pediatric intensive care unit: a prospective study.

OBJECTIVE: To estimate the incidence and to characterize risk factors for central venous catheter (CVC)-related deep vein thrombosis (DVT) in a pediatric intensive care unit. STUDY DESIGN: Consecutive children admitted to a pediatric intensive care unit who required a CVC for more than 48 hours were examined by Doppler ultrasonography of the catheterized vein at days 2, 4, 6, or 7 after insertion and weekly thereafter until CVC removal. RESULTS: The incidence of CVC-related DVT was 18.3% (17 of 93) (95% confidence interval = 10.2% to 25.8%). Thromboses were diagnosed within the first 4 days of catheter placement for 15 of 17 CVC-related thromboses. Multivariate analysis showed that risk factors most predictive of CVC-related DVT were presence of a cancer (odds ratio = 17.23, 95% confidence interval = 1.5 to 194) and young age (odds ratio for age = 0.72, 95% confidence interval = 0.54 to 0.96). CONCLUSION: The frequency of CVC-related DVT is substantial in pediatric intensive care units. Risk is highest during the 4 days after insertion and decreases thereafter. The clinical impact, optimal prevention, and therapy of these thromboses remain to be determined.

Catheterization, Central Venous↗