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Biomedical subjects

M Lemieux

Publications and source records attributed to M Lemieux.

At least 19 recordsLinked to original sources

Mycoplasmosis in evening and pine grosbeaks with conjunctivitis in Quebec.

An outbreak of conjunctivitis affected evening grosbeaks (Coccothraustes vespertinus) and pine grosbeaks (Pinicola enucleator) in Quebec (Canada) during the winter 1998-99. One to 30% of the individuals from these two species were sick at 13 feeding stations. Sick birds were thin and had unilateral or bilateral catarrhal and lymphoplasmacytic conjunctivitis and rhinitis, and mucopurulent infra-orbital sinusitis. Mycoplasmal organisms were isolated in cultures in an affected evening grosbeak and identified as Mycoplasma gallisepticum by direct immunofluorescence. Random amplified polymorphic DNA (RAPD) fingerprinting of this isolate resulted in a banding pattern that was identical to patterns of M. gallisepticum isolates made from similar lesions in house finches (Carpodacus mexicanus) and American gold finches (Carduelis tristis) throughout eastern North America. Mycoplasma gallisepticum was identified by polymerase chain reaction in another evening grosbeak and a pine grosbeak. These observations suggest that the same strain of M. gallisepticum is the likely etiology for the observed disease in evening and pine grosbeaks in Canada and represent an extension of the host-species range for the ongoing epidemic of M. gallisepticum conjunctivitis in eastern North America.

Animals↗

A single center experience with the freestyle bioprosthesis: midterm results at the Québec Heart Institute.

Stentless bioprostheses show excellent early hemodynamic performance. However, longevity still remains unknown. This study reports midterm follow-up in 419 patients in which a Freestyle bioprosthesis (Medtronic Heart Valves, Minneapolis, MN) was inserted between January 1993 and January 2000 at the Quebec Heart Institute (Ste-Foy, Québec, Canada). Mean age at implantation was 68.0 +/- 8.2 years. Implantation was subcoronary in 81.9% of the patients, as a root replacement in 16.5%, and as a root inclusion in 1.7%. Mortality at 30 days was 6.2% for the whole cohort (2.8% for isolated subcoronary aortic valve replacement). Female gender, root implantation, valve sizes 19 to 21 mm, previous surgery, a history of stroke and diabetes were identified as predictors of 30-day mortality. Actuarial freedom from all death causes was 81.5% at 7 years; freedom from valve-related deaths 97.0%, and freedom from cardiac deaths 92.7%. Freedom from thromboembolic events was 86.1% at 7 years (55.1% of events were < 30 days). Freedom from endocarditis and hemorrhagic complications were respectively 98.5% and 95.6% at 7 years. Six patients required reoperations for valve explantation: 2 for endocarditis, 2 for structural dysfunction, and 2 for nonstructural dysfunction. Incidence of moderate or severe valve insufficiency at annual echocardiographic follow-up was: discharge: 0.6%; year 1: 0.7%; year 2: 1.3%; year 3: 3.3%; year 4: 3.7%; year 5: 2.6%; year 6: 0%. At 6 years after implantation, mean transvalvular gradient and effective valve orifice area were comparable to the year 1 values. This single center experience with the Medtronic Freestyle prosthesis shows preserved hemodynamic performance and low valve-related complications at midterm.

Actuarial Analysis↗

Usefulness of the indexed effective orifice area at rest in predicting an increase in gradient during maximum exercise in patients with a bioprosthesis in the aortic valve position.

This study examines the hemodynamic behavior of aortic bioprosthetic valves during maximum exercise. Nineteen patients with a normally functioning stented bioprosthetic valve and preserved left ventricular function were submitted to maximum ramp bicycle exercise. In 14 of the 19 patients, valve effective orifice area and mean gradient were measured at rest and during exercise using Doppler echocardiography. At peak exercise (mean maximal workload 118 +/- 53 W), the cardiac index increased by 122 +/- 34% (+3.18 +/- 0.71 L/min/ m2, p <0.001), whereas mean gradient increased by 94 +/- 49% (+12 +/- 8 mm Hg, p <0.001), and effective orifice area by 9 +/- 13% (+0.15 +/- 0.22 cm2, p = 0.02). A strong correlation was found between the increase in mean gradient during maximum exercise and the valve area at rest indexed for body surface area (r = 0.84, p <0.0001). Due to the increase in valve area, the increase in gradient was less (-9 +/- 7 mm Hg, -41 +/- 33%, p = 0.0006) than theoretically predicted assuming a fixed valve area. These results suggest that the effective orifice area of the bioprostheses has the capacity to increase during exercise; therefore, limiting the increase in gradient. The relation found between the indexed effective orifice area at rest and the increase in gradient during exercise should be useful in predicting the hemodynamic behavior of a stented bioprosthesis during exercise.

Aged↗

Midterm follow-up of unstented biological valves.

We have used the stentless aortic biosprosthesis for aortic valve replacement during the last 10 years. Since 1988, 647 stentless aortic prosthesis were implanted: 384 unstented heterografts, 176 Ross procedures, and 87 homografts. Patients up to age 50 were offered the Ross procedure, those between the ages of 50 and 60 a homograft, and patients 60 years old and older received heterografts. All patients were evaluated at our clinic. An echocardiogram was obtained before discharge from the hospital, at 3 to 6 months postoperatively, and yearly thereafter. Gradients, regurgitation, and effective orifice area were recorded at each visit. The patient was also evaluated clinically. Early mortality rate was 5.4%, 1.7%, and 5.8% for heterograft, autograft, and homograft, respectively. The mean gradient for the unstented porcine valve was 7.6 mm Hg at 3 to 6 month but 5 mm Hg or less for the homografts or autografts. Unstented valves are relatively new but they showed superior hemodynamic performance compared with either mechanical or biological stented valves. Anticoagulation is not mandatory, which should decrease the number of complications. They are the replacement of choice for young and old patients with a small aortic root and are the best alternative to the natural valve.

Adult↗

Transcriptional interferences at the Hoxa4/Hoxa5 locus: importance of correct Hoxa5 expression for the proper specification of the axial skeleton.

We have previously described a Hoxa5 mutant mouse line in which specification of axial identity is perturbed and viability is markedly reduced. In the present study, we assay the Hoxa5 mutation in different genetic backgrounds and carry out a complete analysis of skeletal transformations. Although Hoxa5 is expressed over a large domain during embryogenesis, homeotic transformations of the axial skeleton are confined between cervical vertebra C3 and thoracic vertebra T2, which corresponds to the specific expression domain of the major Hoxa5 transcript. Loss of Hoxa5 function also affects the formation of the acromion in the appendicular skeleton. Disruption of the adjacent Hoxa4 gene leads to similar homeotic transformations of the cervicothoracic vertebrae. To discriminate the respective role of each gene, we generated transheterozygous animals carrying inactivated Hoxa4 and Hoxa5 alleles on different chromosomes. Compound heterozygous mutants exhibit homeotic transformations in the cervicothoracic transition region more reminiscent to those observed in Hoxa5 homozygous mutants. Although the Hoxa5 mutation does not significantly affect Hoxa4 expression, the pattern of Hoxa5 expression is impaired in cis by the Hoxa4 mutation, specifically in the cervicothoracic region of the prevertebral column. The expression of Hoxa5 in this particular domain is also perturbed by the Hoxa5 mutation itself, raising the possibility of regional autoregulation. Altogether, these results demonstrate the crucial role of Hoxa5 in the specification of the cervical and upper thoracic region of the skeleton and establish the importance of its correct expression for the proper patterning of the embryo.

Animals↗

Impact of prosthesis-patient mismatch on hemodynamic and symptomatic status, morbidity and mortality after aortic valve replacement with a bioprosthetic heart valve.

BACKGROUND AND AIMS OF THE STUDY: Previous studies have shown that the effective orifice area of an aortic prosthetic valve may be too small in relation to the patient's body surface area, resulting in abnormally high gradients. The consequences of this condition, termed prosthesis-patient mismatch, have not been fully studied. The study objective was to determine if the condition has a detrimental effect on symptomatic and hemodynamic status, morbidity and mortality of patients undergoing aortic valve replacement. METHODS: A cohort of 392 patients was prospectively followed for up to seven years after implantation of a Medtronic Intact bioprosthesis. Doppler echocardiography was performed annually in 72 patients. Based on previous studies, presence of mismatch was defined as an indexed valve area < or = 0.85 cm2/m2. RESULTS: Mismatch was associated with less postoperative improvement of NYHA functional class (p < 0.009) independently of other predictors, such as age and preoperative functional class, but had no significant impact on patient survival (mismatch: 75 +/- 4%, no mismatch: 79 +/- 3%; p = 0.59) and valve-related morbidity up to seven years. Cardiac index was similar in patients with and without mismatch up to three years after operation but decreased significantly thereafter only in patients with mismatch (-0.54 +/- 0.32 versus -0.17 +/- 0.49 l/min/m2; p = 0.04). Likewise, the mean transprosthetic gradient, which was higher at one year after operation in patients with mismatch (22 +/- 8 versus 15 +/- 7 mmHg), increased significantly (+6 +/- 6 versus +1 +/- 1 mmHg; p = 0.008) only in this group during follow up. CONCLUSIONS: Patients with mismatch have less symptomatic improvement and worse hemodynamics that continue to deteriorate with time. However, medium-term prognosis (up to seven years) is relatively good. Further studies are necessary to determine the longer-term effects of mismatch on morbidity and mortality.

Aged↗

Early postnatal lethality in Hoxa-5 mutant mice is attributable to respiratory tract defects.

To uncover roles for the Hoxa-5 gene during embryogenesis, we have focused on identifying structural and functional defects in organ systems underlying the perinatal lethality in Hoxa-5 homozygous mutants. Analysis of the mutant phenotype shows that Hoxa-5 is essential for normal organogenesis and function of the respiratory tract. In homozygous newborn mutants, improper tracheal and lung morphogenesis can lead to tracheal occlusion, and to respiratory distress associated with a marked decrease in the production of surfactant proteins. Collectively, these defects likely underlie the pronounced mortality of homozygous mutant pups. Furthermore, the loss of Hoxa-5 function results in altered TTF-1, HNF-3 beta, and N-myc gene expression in the pulmonary epithelium. Since expression of Hoxa-5 is confined to the mesenchymal component of the developing trachea and lung, the effects observed in epithelial cells may result from a disruption of normal epithelial-mesenchymal interactions.

Animals↗

Maximizing the benefits of thrombolytic therapy for acute myocardial infarction.

Thrombolytic therapy is a huge advance in the management of acute myocardial infarction (AMI). The results of large clinical trials over the past 9 years have unequivocally demonstrated its benefit: of every 1000 patients treated 30 will be saved, at a cost of two cases of nonfatal cerebral hemorrhage and seven of noncerebral major hemorrhage. The concurrent use of acetylsalicylic acid increases the benefit of thrombolytic therapy. Sales figures for thrombolytic agents indicate that their use in Canada is less than optimal and lags behind that in several European countries. Major educational efforts are needed to promote awareness of the efficacy of thrombolytic therapy and of optimal approaches for maximizing its potential benefit for patients with AMI.

Clinical Trials as Topic↗

[Pulmonary autograft as aortic valve replacement in children].

The aortic stenosis represents 5% of all congenital cardiac pathology. The conventional treatments often do not give very satisfactory results. Since 1990, as alternative to the traditional aortic valve replacement, we used, in our institution, the Ross procedure (pulmonary autograft). This consists in using the pulmonary valve as an autograft in aortic position to replace the diseased valve. Then, the pulmonary outflow is reconstructed with a cryopreserved homograft. This study includes 15 patients, aged between 16 months and 18 years, treated with this technique since 1990. There has been no mortality. All the patients are alive at the follow-up, and all in NYHA functional class I. No reoperation has been necessary for valvular dysfunction. The post-operative doppler study at aortic level demonstrated those gradients: Mean + SD, 3.8 +/- 8.1 (range 0-23). No regurgitation haemodynamically important has been recorded at aortic level nor in the pulmonary position. Post-operative gradients at pulmonary level were: Mean + SD, 14.6 + 10.6 (range 14-32).

Adolescent↗

Surgical treatment of left main coronary aneurysm.

Aneurysms of the coronary arteries occur in 0.3% to 4.9% of angiograms. Only 13 cases of left main artery (LMA) aneurysms have been reported. Of these, three were treated by ligation of the aneurysm and coronary revascularization; the others by revascularisation alone. We report the case of a 56 years old man presenting with unstable angina and previous history of myocardial infarction. Coronary angiography confirmed three vessels disease and the presence of an aneurysm of the LMA extending to the proximal part of the left anterior descending artery (LAD). The patient was treated with ligation of the aneurysm and total myocardial revascularization. The clinical and radiological features are reviewed, and the surgical options considered.

Angina, Unstable↗

Specification of axial identity in the mouse: role of the Hoxa-5 (Hox1.3) gene.

Numerous lines of study have suggested that the Hox genes, encoding putative transcription factors, are key genes in the establishment of the body plan of the mammalian embryo. To examine the role of Hoxa-5 (Hox1.3) gene during development, we have used targeted mutagenesis in embryonic stem cells to produce a strain of mice carrying a disrupted Hoxa-5 allele. The viability of homozygous mutant mice is markedly reduced, with 50% of the mutant animals dying at birth or shortly thereafter. Analysis of the skeleton of Hoxa-5 mutants reveals a number of homeotic transformations restricted to the cervical and thoracic regions. Of these, one of the most frequent morphological abnormalities is the posterior transformation of the seventh cervical vertebra into the likeness of a thoracic vertebra complete with a pair of ribs. These results demonstrate that the Hoxa-5 gene has an important role in the establishment of the skeleton during development and contributes to the process whereby the axial structures are determined.

Animals↗

Haemodynamic and abdominal motor reflexes elicited by neurotensin in anaesthetized guinea-pigs.

1. Single intraperitoneal (i.p.) injections of neurotensin (NT) (0.14- 140 nmol kg-1) in anaesthetized guinea-pigs were found to trigger transient abdominal wall contractions (TAWC) accompanied by relatively sustained increases of systemic blood pressure (BP) and heart rate (HR). The modification of the latter NT effects by various drugs and surgical manipulations was examined to obtain some insight into the nature of, and possible relationship between, these responses. 2. The abdominal motor response (i.e. TAWC) to i.p. NT (14 nmol kg-1) was inhibited by prior i.v. injection of the guinea-pigs with pancuronium (0.27 mumol kg-1), morphine (1.5 and 15 mumol kg-1), clonidine (0.34 mumol kg-1), by concomitant i.p. injection of procaine 2% w/v, or by acute spinalization. It was potentiated by naloxone (2.8 and 28 mumol kg-1), but not affected by i.v. injection of autonomic drugs (i.e. pentolinium, prazosin, yohimbine and atropine), by capsaicin desensitization, or by acute bilateral cervical vagotomy. In spinalized animals a sustained abdominal wall contraction (SAWC) was unmasked, which was resistant to i.v. morphine, clonidine or baclofen but suppressed by i.v. pancuronium or i.p. lignocaine 2% w/v. 3. Haemodynamic responses to i.p. NT were not affected by i.v. pancuronium, morphine, naloxone, atropine, or by vagotomy. They were inhibited by i.v. pentolinium or clonidine (BP, HR), i.v. prazosin (BP), i.p. procaine 2% w/v (BP, HR), capsaicin desensitization or acute spinalization (BP, HR). Yohimbine (i.v.) potentiated BP and HR increases caused by i.p. NT.4. These results suggest that: (1) the haemodynamic and TAWC responses to i.p. NT in this animal model, are two independent, neurally-mediated reflexes which are likely to originate from the abdominal cavity and require a functionally intact spinal cord for their full expression; (2) the neural pathways subserving both types of responses appear to be different from each other. The nature and time-response characteristics of the reflexes caused by i.p. NT, raise the possibility that i.p. NT is a noxious stimulus, at least in guinea-pigs.

Animals↗

Validation and applications of mitral prosthetic valvular areas calculated by Doppler echocardiography.

Doppler echocardiography is used in the noninvasive evaluation of mitral valve prostheses using parameters heretofore validated primarily for native valves. Accordingly, this study was designed to examine the validity and relative usefulness of valve gradient and area measurements in a group of 26 patients (17 women, 9 men, mean age 62 +/- 8 years), 19 +/- 4 months after implantation of different sizes (25 to 31 mm) of a given type of bioprosthesis. Areas obtained with both the continuity equation, using stroke volume measured in the left ventricular outflow tract, and the pressure half-time method are compared to known prosthetic areas derived from an in vitro hydraulic model. Areas calculated by the continuity equation correlate well with in vitro areas (r = 0.82, standard error of the y estimate = 0.1 cm2, p less than 0.001), and are within the range of predicted in vitro values in 92% of cases. Areas derived by the pressure half-time method do not correlate with in vitro areas (r = 0.15, p greater than 0.3) or continuity equation areas (r = 0.23, p greater than 0.2), and are above the range of predicted values in 69% of cases. Correlations are also found between continuity equation areas and the peak and mean valvular gradients (r = 0.59, p less than 0.005 and r = -0.63, p less than 0.0005, respectively). Taking the effect of cardiac output on gradients into account results in projected relations between indexed prosthetic areas and the pressure gradients at rest and during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

An antigen located in the kinetochore region in metaphase and on polar microtubule ends in the midbody region in anaphase, characterised using a monoclonal antibody.

We describe a new component of the kinetochore region of Chinese hamster ovary cells, which was characterised using a monoclonal antibody (mAb). This antigen was localised on the kinetochore regions of purified metaphase chromosomes, but in anaphase it was instead located on the polar microtubules in the midbody region, where they terminate in the stembody. It was not detectable in prophase or interphase cells by immunofluorescence, but was present in the interphase nucleus as shown by immunoblotting after SDS-polyacrylamide gel electrophoresis. The mAb recognised two polypeptides of Mr 140,000 and 155,000. The localisation of this antigen in metaphase on the kinetochore region, where the plus ends of the kinetochore microtubules are temporarily stabilised when they attach, and later in the stembody and midbody where the plus ends of the polar microtubules are stabilised in anaphase and telophase, suggests that it could play a role in stabilising the plus ends of microtubules and thus in the control of microtubule dynamics during mitosis.

Anaphase↗

Validation and applications of indexed aortic prosthetic valve areas calculated by Doppler echocardiography.

Doppler echocardiographic evaluation of aortic valve prostheses is based on the use of variables heretofore validated mostly for native valves. Accordingly, this study examined the validity and relative usefulness of the Doppler valve gradient and area measurements in 31 patients (mean age 69 +/- 10 years) 20 +/- 4 months after implantation of a given type of aortic bioprosthesis ranging in size from 19 to 29 mm. Valve area data obtained with both the standard and simplified continuity equations were compared with known in vitro prosthetic valve area measurements and an excellent correlation was obtained between the standard and simplified continuity equations (r = 0.98, SEE +/- 0.07 cm2, p less than 0.0005) and between in vivo and known in vitro prosthetic valve areas (r = 0.86, SEE +/- 0.16 cm2, p less than 0.0005). Peak gradient ranged from 10.8 to 75.0 mm Hg (mean 35 +/- 16) and mean gradient from 7.6 to 43.7 mm Hg (mean 20.5 +/- 9.5). The correlations between prosthetic valve gradient and in vivo area were r = -0.53, SEE +/- 14 mm Hg and r = -0.49, SEE +/- 8.63 mm Hg for peak and mean gradient, respectively. These relations were improved by indexing valve area by body surface area. The best correlations were obtained between indexed valve area and a quadratic function of the gradient (r = -0.72, SEE +/- 11.72 mm Hg and r = -0.70, SEE +/- 7.28 mm Hg for peak and mean gradient, respectively), reflecting a curvilinear relation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗