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Biomedical subjects

R Gagnon

Publications and source records attributed to R Gagnon.

At least 55 records · Page 3Linked to original sources

Alterations in fetal and placental deoxyribonucleic acid synthesis rates after chronic fetal placental embolization.

OBJECTIVE: Fetal growth and development are closely related to normal placental growth and function. We performed a study to determine the effect of a 10-day period of fetal hypoxemia induced by umbilical-placental hypoperfusion on tissue deoxyribonucleic acid synthesis rates in the 0.84 to 0.91 of gestation ovine fetus and placenta. STUDY DESIGN: Daily fetal placental embolization was performed in four chronically catheterized sheep fetuses until fetal arterial oxygen content decreased by approximately 30% compared with preembolization values. Five control fetuses received vehicle only. On experimental day 10, the deoxyribonucleic acid synthesis rate was determined by injecting tritiated thymidine (1 mCi/kg) intravenously approximately 8 hours before the end of the study. RESULTS: Fetal arterial oxygen decreased from 3.2 +/- 0.1 (SEM) mmol/L preembolization to 2.2 +/- 0.2 mmol/L on day 10 (p < 0.001) and remained unchanged in controls. On day 10 deoxyribonucleic acid synthesis rates were significantly reduced in embolized fetuses compared with controls, by 38% in cotyledons (83.0 +/- 15.1 vs 133.7 +/- 9.9 disintegrations/min/micrograms deoxyribonucleic acid, p < 0.05), 28% in the left ventricular wall (36.8 +/- 3.7 vs 51.0 +/- 4.7 disintegrations/min/micrograms deoxyribonucleic acid, p < 0.05), and 45% in the quadriceps muscle (15.4 +/- 4.0 vs 28.1 +/- 3.0 disintegrations/min/micrograms deoxyribonucleic acid, p < 0.05). Tritiated thymidine autoradiography demonstrated that cotyledonary deoxyribonucleic acid synthesis occurred exclusively in the fetal trophoblasts cells. CONCLUSION: We concluded that a reduction in cotyledonary, quadriceps muscle, and left ventricular myocardium deoxyribonucleic acid synthesis rates are the earliest adaptive mechanisms of fetal growth associated with development of umbilical-placental insufficiency. We speculate that alteration in the myocardial deoxyribonucleic acid synthesis rate could be a major contributing factor in the deterioration of fetal myocardial function associated with increased placental vascular resistance.

Analysis of Variance↗

Lol p I-specific IgE and IgG synthesis by peripheral blood mononuclear cells from atopic subjects in SCID mice.

BACKGROUND: The development of an animal model representative of the in vivo situation of human atopic diseases is always of interest for a better understanding of IgE production and regulation. Along these lines, mice with severe combined immunodeficiency (SCID mice) engrafted with lymphocytes from atopic subjects might be a suitable model for such studies. OBJECTIVE: This study aims to analyze the production of Lol p I-specific IgE and IgG antibodies in SCID mice after transplantation of human peripheral blood mononuclear cells from atopic patients sensitive to grass pollens and from nonatopic donors. METHODS: Peripheral blood mononuclear cells were transplanted into SCID mice, which were then challenged with Lol p I, and antibody responses (IgG and IgE) were analyzed over a 6-week period. RESULTS: Total IgG antibody was measured in each mouse serum after transplantation. Also, most mice (regardless of whether donors were atopic) that were challenged with Lol p I produced specific IgG antibody. Total IgE antibody production was observed only in mice grafted with cells from atopic patients. Lol p I-specific IgE antibodies were also produced after immunization with Lol p I. Although IgG antibody/response tended to plateau, the IgE antibody response increased until it peaked and declined thereafter. Interferon-gamma was detected in sera from mice producing IgE antibody, which supports a possible role of interferon-gamma in the decrease of IgE response. CONCLUSION: This study suggests that the SCID mouse model could represent an interesting approach to studying specific, total IgG and IgE antibody production, and ultimately their regulation.

Allergens↗

Cardioprotection and thrombolysis by anistreplase in anesthetized dogs.

Anistreplase is a thrombolytic agent comprising a complex of streptokinase, lys-plasminogen, and a p-anisoyl group, which temporarily protects the catalytic center of the enzyme complex. Streptokinase was previously shown to reduce infarct size (IS) in dogs with a fibrin-rich clot in the left anterior descending coronary artery (LAD) without necessarily producing reperfusion. Therefore, we hypothesized that IS in this model would be reduced by anistreplase. In addition, we studied the effect of tissue-type plasminogen activator (t-PA) on IS, testing our hypothesis in anesthetized dogs in which thrombin (100 U) and calcium (50 microliters, 0.05 M) were sequentially injected into the LAD to form a thrombus, anistreplase [0.01, 0.05, or 0.10 U/kg intravenous (i.v.) bolus], t-PA (0.1, 0.5, 2, or 8 micrograms/kg/min infusion for 60 min) or vehicle (VEH) was administered 55 min later. Anistreplase (0.05 or 0.10 U/kg) significantly (p < 0.05) reduced clot weight (VEH 22 +/- 3 mg; anistreplase 0.05 U/kg, 13 +/- 4 mg; anistreplase 0.10 U/kg, 0.7 +/- 0.6 mg), increased incidence of reperfusion (VEH 0%; anistreplase 0.05 U/kg, 42%; anistreplase 0.10 U/kg, 100%) and reduced IS (VEH 23 +/- 3%; anistreplase, 0.05 U/kg, 14 +/- 2%; anistreplase 0.10 U/kg, 15 +/- 2%). t-PA reduced thrombin weight (VEH 26 +/- 3 mg; 2 micrograms/kg/min t-PA 12 +/- 4; 8 micrograms/kg/min t-PA 2 +/- 2 mg) and increased incidence of reperfusion (VEH 0%; 2 micrograms/kg/min 75%; 8 micrograms/kg/min 100%), but IS was not altered (VEH 19 +/- 3%; 0.1 microgram/kg/min 18 +/- 3%; 0.5 microgram/kg/min 23 +/- 2%; 2 micrograms/kg/min 16 +/- 5%; 8 micrograms/kg/min: 19 +/- 3%).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

[Risk of pregnancy complications associated with residency].

OBJECTIVE: To determine, through a review of published articles, whether a higher prevalence of pregnancy complications is associated with residency in medicine. DATA SOURCES: Articles published between January 1980 and December 1992 found through a MEDLINE search using the MeSH terms "pregnancy complications" and "internship and residency" and through a review of the bibliographies of articles found. STUDY SELECTION: Of the 17 articles found, 6 contained data on the prevalence of pregnancy complications in residents. DATA EXTRACTION: The methodologic quality of the studies was evaluated systematically with the use of a grid. Data on the prevalence of the six most common pregnancy complications were retained. DATA SYNTHESIS: Four of the six articles had methodologic weaknesses (missing or inappropriate control groups, poorly controlled historical bias). The best study showed a higher prevalence of premature labour, pre-eclampsia and voluntary abortion in the residents than in the control subjects. CONCLUSIONS: It is difficult to draw definitive conclusions from a single study that met the criteria for methodologic quality. More and better-controlled studies involving larger numbers of subjects are needed.

Confounding Factors, Epidemiologic↗

A flat decelerative fetal heart rate tracing with normal fetal heart rate variability.

We report two cases for which computer interpretation of nonstress test indicated a flat decelerative trace in spite of normal fetal heart rate variability. Fetal behavioral state in the first case and signal loss in the second case were possibly responsible for this computerized interpretation of the tracings in the absence of fetal distress.

Adult↗

Fetal endocrine responses to chronic placental embolization in the late-gestation ovine fetus.

OBJECTIVE: The purpose of this study was to examine the effect of chronic fetal placental embolization on the fetal corticotropin, cortisol, and catecholamines concentrations and on myometrial contractility pattern. STUDY DESIGN: Fourteen fetal sheep were studied (seven embolized, seven controls) for 10 days between 0.84 and 0.91 of gestation. Daily injections of nonradioactive microspheres were performed to decrease fetal arterial oxygen content by 30% to 35% of the preembolization value. Umbilical artery Doppler flow velocity waveforms were measured daily. RESULTS: Chronic fetal placental embolization produced progressive fetal hypoxemia (p < 0.001) with changes in umbilical artery Doppler flow velocity waveforms indicative of a 25% increase in placental vascular resistance (p < 0.01). In response to chronic fetal hypoxemia there was a progressive increase in baseline fetal plasma norepinephrine concentration (p < 0.001). There was a transient fourfold to fivefold increase in baseline fetal plasma cortisol levels concomitant with a significant decrease in baseline immunoreactive corticotropin between days 7 and 9 of embolization (both p < 0.05), with a return to control values by day 10. There was a 57% increase in myometrial contracture frequency in the embolized group when compared with controls (p = 0.001). CONCLUSIONS: During repetitive chronic placental damage that led to fetal hypoxemia, the fetal endocrine environment changed with time in a direction that would prevent the onset of premature activation of the hypothalamic-pituitary-adrenal axis and premature delivery.

Adrenocorticotropic Hormone↗

[Variations of body composition by bioelectric impedancemetry after major surgery].

Body water variations are traditionally measured postoperatively by fluid balance and body weight. Bioelectrical impedance assessment permits the evaluation of body composition, i.e., lean body mass, body fat and total body water. We compared the traditional method (body weight and fluid balance) with bioelectrical impedance assessment while estimating body water. Body weight, fluid balance, resistance, reactance, lean body mass, body fat, total body water, triceps skinfold and total protein blood level were measured prospectively (preop, and on days 1, 3 and 5 postop) in 30 patients admitted for major surgery (thoracic, abdominal or vascular). The results suggest that body composition changed significantly with time (p < .05); in all 3 surgical groups. There was a low correlation between total body water measured by bioelectrical Impedance and fluid balance. Bioelectrical impedance assessment is sensitive to body water changes but appears to overestimate these variations compared to the traditional method.

Blood Proteins↗

[How effective is the teaching of critical analysis of scientific publications? Review of studies and their methodological quality].

OBJECTIVE: To evaluate studies assessing the effectiveness of teaching critical appraisal of the literature to medical students. DATA SOURCES: French and English articles published between 1980 and 1990 indexed on MEDLINE or FAMLI as well as articles identified from the bibliographies. STUDY SELECTION: Studies were evaluated if the subjects were undergraduate or postgraduate medical students and if the teaching intervention was aimed at improving one or more of the following areas: knowledge in clinical epidemiology and biostatistics, reading habits and ability to critically appraise a scientific article. DATA EXTRACTION: The methodologic quality of the articles was assessed by three evaluators, who used a modified version of Poynard's checklist to assign a score. Articles with a score of 60% or more were considered satisfactory. The reliability of the checklist was evaluated by means of the kappa (kappa) coefficient and a coefficient of intraclass correlation. DATA SYNTHESIS: For the three evaluators the mean kappa coefficient was 0.33 and the coefficient of intraclass correlation 0.70. Five of the 10 studies had an overall score of 60% or higher. The quality of the individual sections of the articles varied: purpose of the study 85%, description of the population 58%, methods 44%, analysis of results 50%, and conclusions 90%. CONCLUSIONS: The effectiveness of teaching critical appraisal of the literature remains uncertain. More rigorous methods are needed in research in this area.

Biometry↗

Adjuvant arthritic (AA) rats exhibit enhanced endotoxin-induced plasma TNF (EIPT) levels.

Adjuvant arthritis (AA) was induced in male Lewis rats by a single FCA (M. butyricum) injection into the tail. At various time periods post FCA injection, AA and control rats were anesthetized and administered E. coli endotoxin (30 mg/kg, i.v.). Plasma samples were obtained at 30, 60, 90, 120 and 150 min following endotoxin administration and assayed for TNF alpha levels by ELISA. Compared to control rats, AA rats exhibited enhanced EIPT levels (706% of control, p < 0.05) which was associated with the onset of inflammatory lesions on days 12-14 post FCA, and remained significantly elevated (> 300% of control, p > 0.05) for at least 30 days post FCA. There were no significant correlations between EIPT levels and hindpaw volumes or body weights. The results of this study support previous observations that AA is associated with macrophage activation and suggest that EIPT levels in AA rats may be a useful parameter for the evaluation of novel antiarthritic agents.

Animals↗

Lol p I-induced IL-4 and IFN-gamma production by peripheral blood mononuclear cells of atopic and nonatopic subjects during and out of the pollen season.

The reciprocal effects of IL-4 and IFN-gamma on IgE synthesis have been well established. It has also been shown that these two lymphokines are secreted by different subsets of CD4+ T cells (TH1 and TH2), and that TH2 helper T lymphocytes could be involved in the pathophysiology of allergic diseases. But little is known about the effects of an allergen on the profile of lymphokine synthesis by human peripheral blood mononuclear cells (PBMCs) of allergic and nonallergic subjects. We studied the production of IL-4 and IFN-gamma by PBMCs of atopic and nonatopic donors after in vitro stimulation by the group 1 allergen from Lolium perenne pollen (Lol p I), during and out of the grass pollen season. On natural exposure to pollen, Lol p I-induced IL-4 production was observed only with atopic donors (6 of 8), whereas the synthesis of IFN-gamma was observed for all nonatopic donors (7 of 7) and most allergic patients (5 of 7). At the time of the study, higher amounts of IFN-gamma were produced by PBMCs of nonatopic donors than by PBMCs of atopic patients. Out of the pollen season the production of IL-4 was not observed either by atopic (n = 11) or by nonatopic subjects (n = 5). On the other hand, IFN-gamma was produced by PBMCs of most subjects (atopic, 10 of 11; nonatopic, 5 of 5), but at the time of the study no difference was observed between the two groups. These results show that Lol p I induces different profiles of IL-4 and IFN-gamma production by PBMCs of atopic and nonatopic subjects. In atopic subjects this profile of lymphokine synthesis is influenced by the natural exposure to pollen, which is in keeping with the seasonal rise of IgE antibodies.

Adult↗

A comparison between visual and computer analysis of antepartum fetal heart rate tracings.

OBJECTIVE: This study was designed to determine the intraobserver and interobserver variability in the visual assessment of fetal heart rate tracings and to evaluate the accuracy of the visual detection of accelerations and decelerations when compared with computerized fetal heart rate analysis. STUDY DESIGN: One hundred antepartum fetal heart rate tracings, of good quality and of 30 minutes' duration, were visually assessed by five expert observers on three occasions during a 12-month period. There were a total of seven questions related to either judgment or accuracy of each recording. Visual detection of fetal heart rate acceleration, deceleration, and estimated baseline was compared with computerized analysis. Statistical significance was determined by kappa coefficient and contingency table chi 2 analysis. RESULTS: Analysis with kappa coefficient reflecting intraobserver and interobserver agreement of judgment-related questions indicated poor agreement between observers when assessing short-term fetal heart rate variability (kappa 0.18), when making a decision to stop or continue recording (kappa 0.39), and when judging whether there is concern regarding fetal heart rate tracing (kappa 0.26). When compared with computerized analysis, clinicians had a tendency to recognize tracings as normal. In particular, they failed to identify 35% of tracings with 0 or 1 acceleration and failed to detect 92% of fetal heart rate decelerations. Variable decelerations associated with fetal movements were the major source of disagreement between observers and the computer. Only the estimation of baseline fetal heart rate had a high level of accuracy. CONCLUSION: We concluded that the poor level of accuracy in several components of the nonstress test was responsible for the low interobserver agreement seen in simple judgment-related questions such as decision to continue or stop fetal heart rate recordings.

Computers↗

Seasonal enhancement of IL-4 induced IgE synthesis by peripheral blood mononuclear cells of atopic patients.

The role of IL-4 on IgE synthesis has been well established. IL-4 has been shown to promote IgE production by B cells from atopic and non-atopic donors. In this study, the effects of natural exposure to pollens on IL-4-induced IgE synthesis by peripheral blood mononuclear cells of atopic and non-atopic donors were examined. The results confirm production of IgE in an IL-4 dose-dependent manner by PBMC cultures of these two groups. When cultures were performed out of the pollen season, following stimulation by IL-4, no significant differences was observed between the levels of IgE produced by PBMC of atopic and non-atopic donors. In contrast, upon natural exposure to pollens, significant higher levels of IgE were measured in the atopic group than in the non-atopic one. These results show that the pollen season influences the IL-4-induced IgE synthesis by PBMC of allergic patients and are in keeping with seasonal rise of specific IgE antibodies.

Dose-Response Relationship, Drug↗

Fluid resuscitation improves survival of endotoxemic or septicemic rats: possible contribution of tumor necrosis factor.

The present study was designed to investigate the effects of fluid administration on survival in endotoxemic or septicemic male Sprague-Dawley rats. Endotoxemia was induced by intravenous injection of Escherichia coli lipopolysaccharide (LPS), and septicemia produced by cecal ligation and puncture (CLP). In endotoxemic animals deprived of fluid resuscitation, 7-day survival following injection of LPS at doses of 1, 3, or 10 mg/kg LPS were 70% (n = 10), 30% (n = 10), and 0% (n = 10), respectively. In rats resuscitated with 3.3 ml/kg/h of 0.9% NaCl, the dose-response curve for survival was shifted 5-fold rightward in a parallel manner (p < 0.001, between the fluid-resuscitated and nonfluid resuscitated LPS groups), indicating a reduced sensitivity to the effects of LPS following fluid resuscitation. LPS increased serum tumor necrosis factor (TNF alpha) concentrations in fluid-resuscitated endotoxemic animals from a baseline value of 20 U/ml to 2,350 U/ml at 1 h, which returned to 200 U/ml at 2 h. In endotoxemic animals not receiving fluid resuscitation, serum TNF alpha levels at 1 and 2 h were 5-fold and 27-fold higher, respectively, than in fluid-resuscitated animals. There were no differences in arterial blood pressure or heart rate between the two groups of endotoxemic animals; total peripheral resistance was significantly lower at 1 h, and cardiac index was significantly greater at 3 h in the fluid-resuscitated LPS group; otherwise there were no further differences in hemodynamic parameters between the two groups. The survival rate at 4 days following CLP without fluid resuscitation was 14%, whereas CLP with fluid resuscitation improved survival to 74% (p < 0.01). TNF alpha was undetectable (i.e., < 20 U/ml) in the serum of animals subjected to CLP. The improvement in survival with fluid infusion in the LPS and CLP models cannot be attributed to catheter implantation, or to improved hemodynamic parameters in the LPS model. The improvement in survival in the LPS model with fluid infusion was associated with attenuated increases in TNF alpha levels. Furthermore, these studies illustrate that fluid-resuscitated and nonfluid-resuscitated experimental animal models should not be considered equivalent.

Animals↗

Waldenström hypergammaglobulinemic purpura and pregnancy.

BACKGROUND: Waldenström hypergammaglobulinemic purpura is characterized by hypergammaglobulinemia, recurring purpura, and an elevated erythrocyte sedimentation rate. It is a rare disease and, to our knowledge, there have been no previous reports of its presence during pregnancy. We report a patient with this disease whose pregnancy was complicated by severe fetal growth restriction (FGR) and acute fetal distress. CASE: A 24-year-old primigravid woman with a history of Waldenström hypergammaglobulinemic purpura and renal insufficiency developed FGR at 32 weeks' gestation. Cesarean delivery was performed at 33.5 weeks because of acute fetal distress, and a 1305-g male infant was delivered. Neonatal outcome was successful. No deterioration of the woman's medical condition occurred during or after her pregnancy. CONCLUSION: Successful pregnancy outcome is possible in women with Waldenström hypergammaglobulinemic purpura. In view of the risk of FGR, close monitoring of fetal growth and well-being is recommended in women with this condition.

Adult↗