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Biomedical subjects

R Gosselin

Publications and source records attributed to R Gosselin.

At least 19 recordsLinked to original sources
PubMed2001

Systemic coagulation and fibrinolysis after laparoscopic and open gastric bypass.

HYPOTHESIS: Laparoscopic gastric bypass (GBP) induces a postoperative hypercoagulable state that is similar or reduced compared with open GBP. SETTING: University hospital. PATIENTS: Between May 1999 and June 2000, 70 patients were randomly assigned to laparoscopic (n = 36) or open (n = 34) GBP. Deep venous thrombosis (DVT) prophylaxis consisted of antiembolism stockings and sequential pneumatic compression devices. MAIN OUTCOME MEASURES: Plasminogen, thrombin-antithrombin complex (TAT), prothrombin fragment 1.2 (F1.2), fibrinogen, D-dimer, antithrombin III (AT), and protein C levels were measured at baseline and at 1, 24, 48, and 72 hours postoperatively. A venous duplex examination of both lower extremities was performed preoperatively and between the third and fifth day postoperatively. RESULTS: The 2 groups were similar in age, weight, and body mass index. Plasminogen levels decreased, and TAT, F1.2, and fibrinogen levels increased after laparoscopic and open GBP. There was no significant difference in these levels between groups. D-dimer levels increased in both groups, but the levels were significantly higher after open GBP than after laparoscopic GBP (P<.01). Antithrombin III and protein C levels decreased in both groups. The reduction of AT (at 1 hour) and protein C (at 72 hours) was significantly less after laparoscopic GBP than after open GBP (P<.05). Postoperative venous duplex examination revealed DVT in 1 (2.9%) of 34 patients after open GBP but in none of 36 patients after laparoscopic GBP. One patient developed pulmonary embolism after open GBP. CONCLUSIONS: Laparoscopic GBP induces a hypercoagulable state similar to that of open GBP. Our findings suggest that DVT prophylaxis should be used during laparoscopic GBP as in open GBP.

Adult↗
PubMed2001

Biochemical basis for the hypercoagulable state seen in Cushing syndrome; discussion 1006-7.

HYPOTHESIS: Cushing syndrome (CS) is associated with a hypercoagulable state that results in a 4-fold increase in the incidence of pulmonary embolism, deep venous thrombosis, and a 4-fold mortality rate compared with the general population. The incidence of CS in humans is approximately 2 to 5 per million per year, whereas in dogs it is much higher. The clinical complications of CS in humans are also manifested in dogs. We used a dog model of CS to better define the biochemical basis for the hypercoagulable state seen in the disease. DESIGN: A consecutive sample of dogs with CS and a cohort of healthy control dogs identified at a "well-dog check" were enrolled. All dogs underwent blood assays to identify the levels of procoagulant factors, natural antithrombotics, and the degree of ongoing activation of the coagulation cascade. SETTING: University veterinary medical teaching hospital. RESULTS: A total of 86 dogs were enrolled, 56 with CS and 30 control dogs. Levels of procoagulation factors II, V, VII, IX, X, XII, and fibrinogen were significantly increased in dogs with CS (P<.05). The natural antithrombotic antithrombin was significantly decreased in dogs with CS (P<.02). Thrombin-antithrombin complexes, a marker of subclinical thrombosis, were significantly increased in dogs with CS (P<.05). CONCLUSIONS: The hypercoagulable state of CS is demonstrated by an increase in thrombin-antithrombin complexes. This hypercoagulable state may be caused in part by (1) an elevation of procoagulant factors, and (2) a decrease in antithrombin. Because of the similar clinical and biochemical changes between dogs with CS and humans, this canine model may be a useful tool for the future study of the hypercoagulable state in CS.

Animals↗
PubMed2001

Diverse prevalence of large deletions within the OA1 gene in ocular albinism type 1 patients from Europe and North America.

Ocular albinism type 1 (OA1) is an X-linked disorder mainly characterized by congenital nystagmus and photodysphoria, moderate to severe reduction of visual acuity, hypopigmentation of the retina, and the presence of macromelanosomes in the skin and eyes. We have previously isolated the gene for OA1 and characterized its protein product as melanosomal membrane glycoprotein displaying structural and functional features of G protein-coupled receptors. We and others have identified mutations of various types within the OA1 gene in patients with this disorder, including deletions and splice site, frameshift, nonsense, and missense mutations. However, different prevalences of large intragenic deletions have been reported, ranging from 10% to 50% in independent studies. To determine whether these differences might be related to the geographic origin of the OA1 families tested, we performed a further extensive mutation analysis study leading to the identification of pathogenic mutations in 30 unrelated OA1 patients mainly from Europe and North America. These results, together with our earlier mutation reports on OA1, allow us to resolve the apparent discrepancies between previous studies and point to a substantial difference in the frequency of large intragenic deletions in European (<10%) compared with North American (>50%) OA1 families. These observations and our overall refinement of point mutation distribution within the OA1 gene have important implications for the molecular diagnosis of OA1 and for the establishment of any mutation detection program for this disorder.

Albinism, Ocular↗
PubMed2000

Clouston hidrotic ectodermal dysplasia (HED): genetic homogeneity, presence of a founder effect in the French Canadian population and fine genetic mapping.

HED is an autosomal dominant skin disorder that is particularly common in the French Canadian population of south-west Quebec. We previously mapped the HED gene to the pericentromeric region of chromosome 13q using linkage analysis in eight French Canadian families. In this study, we extend our genetic analysis to include a multiethnic group of 29 families with 10 polymorphic markers spanning 5.1 cM in the candidate region. Two-point linkage analysis strongly suggests absence of genetic heterogeneity in HED in four families of French, Spanish, African and Malaysian origins. Multipoint linkage analysis in all 29 families generated a peak lod score of 53.5 at D13S1835 with a 1 lod unit support interval spanning 1.8 cM. Recombination mapping placed the HED gene in a 2.4 cM region flanked by D13S1828 proximally and D13S1830 distally. We next show evidence for a strong founder effect in families of French Canadian origin thereby representing the first example of a founder disease in the south-west part of the province of Quebec. Significant association was found between HED in these families and all markers analysed (Fisher's exact test, P < 0.001). Complete allelic association was detected at D13S1828, D13S1827, D13S1835, D13S141 and D13S175 (P(excess) = 1) spanning 1.3 cM. A major haplotype including all 10 associated alleles was present on 65% of affected chromosomes. This haplotype most likely represents the founder haplotype that introduced the HED mutation into the French Canadian population. Luria-Delbrück equations and multipoint likelihood linkage disequilibrium analysis positioned the gene at the D13S1828 locus (likely range estimate: 1.75 cM) and 0.58 cM telomeric to this marker (support interval: 3.27 cM) respectively.

Alleles↗
PubMed2000

Cocoa inhibits platelet activation and function.

BACKGROUND: Epidemiologic studies have shown inverse associations between dietary polyphenols and mortality from coronary heart disease. However, the basis for this protective association is uncertain. Food polyphenols reportedly have antioxidant properties and decrease platelet function in vitro. OBJECTIVE: This study sought to evaluate whether consumption of a polyphenol-rich cocoa beverage modulates human platelet activation and primary hemostasis. DESIGN: Peripheral blood was obtained from 30 healthy subjects before and 2 and 6 h after ingestion of a cocoa beverage (n = 10), a caffeine-containing control beverage (n = 10), or water (n = 10). Platelet activation was measured in terms of expression of activation-dependent platelet antigens and platelet microparticle formation by using fluorescent-labeled monoclonal antibodies and flow cytometry. Primary platelet-related hemostasis was measured with a platelet function analyzer. RESULTS: Ex vivo epinephrine- or ADP-stimulated expression of the fibrinogen-binding conformation of glycoprotein IIb-IIIa was lower 2 and 6 h after consumption of cocoa than before consumption. Cocoa consumption also decreased ADP-stimulated P-selectin expression. In contrast, epinephrine-induced platelet glycoprotein IIb-IIIa expression increased after consumption of the caffeine-containing beverage but not after water consumption. Platelet microparticle formation decreased 2 and 6 h after cocoa consumption but increased after caffeine and water consumption. Primary hemostasis in response to epinephrine in vitro was inhibited 6 h after cocoa consumption. The caffeine-containing beverage inhibited ADP-induced primary hemostasis 2 and 6 h after consumption. CONCLUSIONS: Cocoa consumption suppressed ADP- or epinephrine-stimulated platelet activation and platelet microparticle formation. Cocoa consumption had an aspirin-like effect on primary hemostasis.

Adenosine Diphosphate↗
PubMed2000

Cocoa and wine polyphenols modulate platelet activation and function.

There is speculation that dietary polyphenols can provide cardioprotective effects due to direct antioxidant or antithrombotic mechanisms. We report in vitro and postingestion ex vivo effects of cocoa procyanidins, a procyanidin-rich cocoa beverage and dealcoholized red wine (DRW) on human platelet activation. In a series of in vitro studies, cocoa procyanidin trimers, pentamers or DRW (3 and 10 micromol/L) were incubated with citrated peripheral whole blood in the presence and absence of platelet agonists. Platelet activation was detected using fluorescent-labeled monoclonal antibodies recognizing the fibrinogen binding conformation of GPIIb-IIIa (referred to herein as PAC-1 binding) and the activation-dependent platelet epitope CD62P (P-selectin). The percentage of CD42a-positive platelets coexpressing PAC-1 binding and/or CD62P was determined by multiparameter flow cytometry. Procyanidin trimers, pentamers and DRW added to whole blood in vitro increased PAC-1 binding and P-selectin expression. In contrast, procyanidin trimers, pentamers and DRW inhibited the platelet activation in response to epinephrine. The effects on platelet activation of cocoa beverage and DRW consumption were also studied in healthy subjects. Citrated blood was obtained before and 2 and 6 h after the ingestion of a cocoa beverage, a caffeine-containing beverage, DRW or water. Platelet activation was measured by flow cytometry. The consumption of DRW did not affect the expression of activation-dependent platelet antigens, either unstimulated or after ex vivo activation with epinephrine. However, the consumption of DRW increased PAC-1 binding in response to 100 micromol/L ADP ex vivo. Cocoa consumption reduced platelet response to agonists ex vivo. The ingestion of water had no effect on platelet activation, whereas a caffeine-containing beverage augmented the response of platelets to epinephrine. In summary, select cocoa procyanidins and DRW added to whole blood in vitro increased expression of platelet activation markers in unstimulated platelets but suppressed the platelet activation response to epinephrine. In contrast, cocoa consumption suppressed unstimulated and stimulated platelet activation in whole blood. This suppressive effect observed on platelet reactivity may explain in part the reported cardioprotective effects of dietary polyphenols.

Adult↗
PubMed2000

A comparison of point-of-care instruments designed for monitoring oral anticoagulation with standard laboratory methods.

Our study compared point-of-care (POC) device monitoring with traditional clinical laboratory methods device of patients on oral anticoagulant therapy. The POC devices used in the study were Coumatrak, CoaguChek, CoaguChek Plus, Thrombolytic Assessment System (TAS) PT-One, TAS PTNC, TAS PT, Hemachron Jr. Signature, ProTime Microcoagulation System, and Medtronics ACT II. The clinical laboratory method used thromboplastins with different ISI values: Innovin and Thromboplastin C Plus (TPC). All POC INRs showed strong correlation with both laboratory methods, with correlation coefficients of >0.900. All POC methods demonstrated a significant (p <0.05) difference in INR values, except the TAS PTNC and ACT II INRs (p: 0.12 and 0.71 respectively) when compared with Innovin INRs. All POC INRs were significantly different from TPC generated INRs (p <0.05). Comparisons of the POC INRs to the group mean of the POC methods, show higher correlation (R>0.93), but there were still significant (p<0.05) differences noted between the POC group INR mean and CoaguChek Plus, ACT II, TAS PT-One, TAS PTNC, and Hemachron Jr Signature INRs. These data indicate that POC INR biases exist between laboratory methods and POC devices. Until a suitable whole blood INR standardization method is available, we conclude that clinicians using point-of-care anticoagulation monitoring should be aware of differences between POC and parent laboratory values.

Administration, Oral↗
PubMed2000

Effects of a hemoglobin-based oxygen carrier (HBOC-201) on coagulation testing.

Polymerized bovine hemoglobin (HBOC-201) is currently under investigation as an alternative to blood banked human red cells. Due to the dark red, hemolyzed appearance of HBOC-201, we sought to describe the effects of HBOC-201 on coagulation analyzers that perform prothrombin times (PT), activated partial thromboplastin times, fibrinogen, and antithrombin. Pooled normal plasma was combined with HBOC-201 to achieve plasma hemoglobin levels of 1.4, 2.6 3.8, 4.8, and 6.2 g/dL. Results for each test from HBOC-201 prepared plasmas were compared to saline matched controls. Two consecutive absolute result differences of > 10% between saline controls and HBOC-201 samples were used for determining interference on test accuracy by the concentration of HBOC-201. Mechanical detection methods (fibrometer, STA, CS-190) and the MDA-180 were less affected by increasing levels of HBOC-201 than optical detection devices for all test parameters.

Blood Coagulation Tests↗
PubMed1999

Increased use of prophylactic vena cava filters in trauma patients failed to decrease overall incidence of pulmonary embolism.

BACKGROUND: Recent studies have reported that placement of vena cava filters (VCFs) early after injury may decrease the incidence of pulmonary embolism (PE) in high-risk trauma patients. STUDY DESIGN: This was a retrospective review of all trauma patients with placement of VCFs admitted to a single level-1 trauma center between 1989 and 1997. Two cohorts corresponding to years of high or low prophylactic VCF use (PVCF) were compared. RESULTS: Records were reviewed for 299 trauma patients identified as having had placement of a VCE Two hundred forty-eight filters were placed before the diagnosis of PE. During years of low PVCF use, the overall PE incidence was 0.31%; during years of high PVCF use, the incidence of PE was higher at 0.48% (p = 0.045, chi-square). CONCLUSIONS: Increased use of PVCFs failed to decrease the overall rate of PE in our trauma patient population.

Adult↗
PubMed1998

PFA-100 system: a new method for assessment of platelet dysfunction.

The PFA-100 system is a platelet function analyzer designed to measure platelet-related primary hemostasis. The instrument uses two disposable cartridges: a collagen/epinephrine (CEPI) and a collagen/ADP (CADP) cartridge. Previous experience has shown that CEPI cartridges detect qualitative platelet defects, including acetylsalicylic acid (ASA)-induced abnormalities, while CADP cartridges detect only thrombocytopathies and not ASA use. In this seven-center trial, 206 healthy subjects and 176 persons with various platelet-related defects, including 127 ASA users, were studied. The platelet function status was determined by a platelet function test panel. Comparisons were made as to how well the defects were identified by the PFA-100 system and by platelet aggregometry. The reference intervals for both cartridges, testing the 206 healthy subjects, were similar to values described in smaller studies in the literature [mean closure time (CT) 132 s for CEPI and 93 s for CADP]. The use of different lot numbers of cartridges or duplicate versus singleton testing revealed no differences. Compared with the platelet function status, the PFA-100 system had a clinical sensitivity of 94.9% and a specificity of 88.8%. For aggregometry, a sensitivity of 94.3% and a specificity of 88.3% were obtained. These values are based on all 382 specimens. A separate analysis of sensitivity by type of platelet defect, ASA use versus congenital thrombocytopathies, revealed for the PFA-100 system a 94.5% sensitivity in identifying ASA users and a 95.9% sensitivity in identifying the other defects. For aggregometry, the values were 100% for ASA users and 79.6% for congenital defects. Analysis of concordance between the PFA-100 system and aggregometry revealed no difference in clinical sensitivity and specificity between the systems (p > 0.9999). The overall agreement was 87.5%, with a Kappa index of 0.751. The two tests are thus equivalent in their ability to identify normal and abnormal platelet defects. Testing 126 subjects who took 325 mg ASA revealed that the PFA-100 system (CEPI) was able to detect 71.7% of ASA-induced defects with a positive predictive value of 97.8%. The overall clinical accuracy of the system, calculated from the area under the ROC curve, was 0.977. The data suggest that the PFA-100 system is highly accurate in discriminating normal from abnormal platelet function. The ease of operation of the instrument makes it a useful tool to use in screening patients for platelet-related hemostasis defects.

Adolescent↗
PubMed1997

Endothelin receptor changes in hypoxia-induced pulmonary hypertension in the newborn piglet.

Endothelin (ET)-1, a potent vasoconstrictor and mitogen, acts through ETA and ETB receptors and may be involved in the pathogenesis of persistent pulmonary hypertension of the newborn. We hypothesized that hypoxia-induced pulmonary hypertension in the newborn is associated with increased ET-1 release and modified ET receptor characteristics leading to vasoconstriction and vascular remodeling. Therefore, we studied 1-day-old piglets exposed for 3 or 14 days to hypoxia (fraction of inspired O2 = 0.10) or normoxia (controls). ET-1 circulating levels in pulmonary artery and vein were measured. Pulmonary vascular reactivity to ET-1 was evaluated using isolated-perfused lungs. ET binding characteristics were examined in microsomes from pulmonary arteries (down to 100 microns). ET-1 circulating levels are low and are not altered by hypoxia. The magnitude of the initial dilator response to ET-1 decreases after 3 days of hypoxia (P < 0.05), whereas the number of ETB receptors is reduced by 40% in the pulmonary arteries (P < 0.05). ETA receptors are predominant (65-90%) in pulmonary arteries. ETA receptors decrease by 50% after 14 days of exposure to hypoxia (P < 0.05), whereas the constrictor response to ET-1 remains unchanged. The fact that the reduction in vasodilator response parallels the decrease in ETB receptors suggests a decrease in receptor expression. We speculate that the maintenance of the vasoconstrictor response to ET-1 despite a reduction in the number of binding sites is likely due to receptor occupancy. In conclusion, in the newborn piglet pulmonary vasculature, ETA and ETB receptors may be affected differently by hypoxia.

Animals↗
PubMed1997

Reduced vasodilator response to ANF in hypoxia-induced pulmonary hypertension in the newborn piglet.

Recent evidence suggests that, in adult animals with hypoxia-induced pulmonary hypertension, atrial natriuretic factor (ANF) may modulate pulmonary vascular tone and may have a protective effect. However, its role in the pathogenesis of pulmonary hypertension of the newborn is unknown. We hypothesized that, in the newborn, hypoxia-induced pulmonary hypertension would result in ANF receptor downregulation, resulting in decreased dilator response, favoring pulmonary vasoconstriction and vascular remodeling. Therefore, we studied, in 1-day-old piglets exposed to hypoxia (fraction of inspired O2 0.10) for 3 or 14 days to induce pulmonary hypertension, 1) ANF release by measuring circulating levels of ANF by radioimmunoassay in pulmonary artery and veins, 2) pulmonary vascular reactivity to ANF using isolated perfused lungs, and 3) binding characteristics by examining the concentration dependence of ANF binding and competitive binding of 125I-labeled ANF with ANF, brain natriuretic peptide, C-type natriuretic peptide, and the specific ligand for ANF clearance receptor on microsomes from pulmonary arteries (down to 100 microns). ANF circulating levels are increased after exposure to hypoxia compared with normoxia, reaching significance at 14 days (P < 0.005). The magnitude of ANF dilator response is diminished after exposure to hypoxia (P < 0.05). Saturation studies reveal that the number of ANF receptors is diminished in hypoxia after 3 days but reaches significance after 14 days (P < 0.01) compared with their respective normoxic control. At either condition, the majority of these receptors are of the functional type, whereas clearance receptors are virtually undectable. These results suggest that hypoxia increases circulating ANF and causes a decreased responsiveness of the pulmonary vasculature to ANF. Receptor down-regulation may explain part of the reduced dilator response, although the involvement of other mechanisms is not excluded.

Animals↗
PubMed1997

Acquired antithrombin deficiency following severe traumatic injury: rationale for study of antithrombin supplementation.

Hemorrhage, head injury, and multiple organ dysfunction are the most frequent causes of mortality in patients who experience severe injury. Acceleration of the coagulation cascade is known to result in hemorrhage secondary to disseminated intravascular coagulation (DIC) and end-organ dysfunction, as manifest by pulmonary and renal failure. Few studies have been conducted to evaluate the effects of injury on the endogenous anticoagulants that inhibit excessive coagulation activation. We evaluated a group of patients following severe injury and found that procoagulant markers (prothrombin fragment 1.2, thrombin antithrombin complexes, and D dimers) were significantly elevated for the population as a whole. Levels of circulating endogenous anticoagulants [antithrombin (AT) and protein C] were relatively unchanged for the total population. However, patients with adverse outcomes [DIC and adult respiratory distress syndrome (ARDS)] had significant reductions in AT and protein C activities. Decreased levels of AT and protein C 8 hours after admission served as independent predictors of both DIC and ARDS. Prospective, randomized studies should be conducted to evaluate the effect of supplementation of these factors after severe injury has occurred.

Adolescent↗
PubMed1996

Effect of critical injury on plasma antithrombin activity: low antithrombin levels are associated with thromboembolic complications.

OBJECTIVE: Determine whether severe injury results in decreased plasma antithrombin (AT) activity and whether this decreased AT activity is associated with thromboembolic complications. DESIGN: Prospective observational. SUBJECTS: A total of 157 critically injured trauma patients. METHODS: Each patient underwent laboratory analysis on arrival to the emergency room at hours 8, 16, 24, and 48, and days 3, 4, 5, and 6. Laboratory analyses included AT, tissue factor pathway inhibitor, protein C, prothrombin fragment 1.2, thrombin-antithrombin complex, and D-dimer. Patients were followed for thromboembolic complications including: deep venous thrombosis (DVT), pulmonary embolus, disseminated intravascular coagulation (DIC) and adult respiratory distress syndrome (ARDS). RESULTS: Mean Injury Severity Score was 23 (+/-11). AT activity fell below normal in 95 (61%) patients; AT activity rose to greater than normal in 51 (32%) patients. Nine (6%) patients developed DVT, two (1%) pulmonary embolus, 13 (8%) DIC and 26 (17%) ARDS. Using logistic regression analysis, low AT levels were a significant predictor of DVT, DIC, and ARDS (p < 0.05). Supranormal At levels were associated with closed head injury (p < 0.05). D-dimer levels were inversely correlated with AT (p < 0.05). CONCLUSIONS: AT activity was depressed in critically injured patients. Patients with head injury developed supranormal AT activity. The risk factors for AT deficiency mimicked those for thromboembolism. Patients with decreased AT activity were at increased risk for thromboembolic complications. Given heparin's dependence on AT, these data call into question the use of unmonitored heparin thromboembolism prophylaxis.

Adult↗
PubMed1985

The Quebec health care system in the Canadian context: impact on medical practice.

Despite their close kinship, the United States and Canada have evolved very different health care systems. Apart from the fundamental difference of voluntary versus compulsory insurance, the contrasts are most pronounced in the case of Quebec, whose approach to health care reform is the most radical of the Canadian provinces. Key features of the Quebec health care system include mechanisms for the planning and coordination of services and institutions, for the evaluation of health programs, and for regulation of the health professions, especially medicine. Freedom to choose a specialty and practice location is relatively tempered and constrained. Compensation is negotiated via physicians' unions. Physicians mostly practice on a fee-for-service basis and make claims to a single government authority which, in the process, acquires many data about physician practice.

Canada↗
PubMed1984

Decentralization/regionalization in health care: the Quebec experience.

The decentralization policy in Canada was initially aimed at decentralizing the management of services by creating regional bodies within which interested parties would participate in establishing priorities, elaborating programs, allocating resources and assessing program efficiency and effectiveness. A look at the Quebec experience provides insight into the difficulties and implications of decentralization.

Catchment Area, Health↗