Biomedical subjects

D Gagnon

Publications and source records attributed to D Gagnon.

At least 19 recordsLinked to original sources

PubMed1999

The influence of trunk modelling in 3D biomechanical analysis of simple and complex lifting tasks.

OBJECTIVE: The purpose of this study was to evaluate different methods of estimating the body segment parameters and different methods of partitioning the trunk in order to reduce errors in the inverse dynamic analysis of lifting tasks. DESIGN: The same data set was used to evaluate moment errors associated to five linked models differing by the way the trunk was modelled. BACKGROUND: The inverse dynamic analysis of complex lifting tasks involving significant lower limb displacements requires the use of upper body linked models. However, the estimation of the body segment parameters of trunk segments and the flexible properties of the trunk can lead to errors when using this modelling approach. METHODS: Twenty-one male subjects performed four lifting tasks. Five cameras, two force platforms and a dynamometric box provided inputs to five tridimensional (3D) dynamic linked models. Three modelling parameters of the trunk were tested in these models: (1) the use of a geometric or a proportional anthropometric model to estimate the body segment parameters of the trunk, (2) the location of the antero-posterior position of the centre of mass of the trunk segments (at a percentage of the trunk depth vs on a line between hips and shoulders), and (3) the partitioning of the trunk in two or three segments. The behavior of these linked models was assessed with three different error analyses. RESULTS: The results revealed that all three modelling parameters of the trunk can reduce moment errors, especially when applied to subjects characterized by a larger abdomen. CONCLUSIONS: The inverse dynamic analysis of lifting tasks using an upper body modelling approach should take into consideration the interindividual variability inherent to the trunk morphology and non-rigidity. RELEVANCE: The trunk geometry and flexibility shows considerable variability among individuals. The use of upper body linked models requires adequate modelling of this segment to minimize errors in 3D inverse dynamic analysis of lifting tasks.

Adult↗

PubMed1998

Pichia ohmeri fungemia.

A patient with a history of diabetes, coronary artery disease, stroke, previous renal transplantation, and multiple hospital admissions for recurrent pancreatitis was transferred to the hospital from a chronic care facility because of fever and severe epigastric discomfort. At the time of admission, she was receiving hyperalimentation through a central venous TPN catheter. Multiple blood cultures obtained on the first and second hospital days yielded pure cultures of the yeast, Pichia ohmeri. The patient developed acute renal failure, and despite high-dose amphotericin B therapy, ultimately expired.

Female↗

PubMed1998

The relationship between seizure frequency, seizure type and quality of life: findings from three European countries.

Understanding the relationship between seizure frequency, seizure type and scores obtained from quality of life (QOL) measures is important if the incorporation of QOL measures into epilepsy clinical trials is to become standard practice. There is also a need to consider cross-cultural differences obtained from QOL measures, particularly in the context of multicentre international trials. In this study, 300 patients recruited from UK, Germany and France completed the Functional Status Questionnaire (FSQ); information about patients' clinical and demographic status was also collected. Results from the study highlighted that seizure type and seizure frequency, as well as country of origin, were significant predictors of scores on the FSQ. It is important to measure the effect of seizure type, not just seizure frequency, on QOL when testing for differences between antiepileptic therapies in the context of clinical trials.

Cross-Cultural Comparison↗

PubMed1998

A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns.

Idiopathic generalized epilepsies account for about 40% of epilepsy up to age 40 and commonly have a genetic basis. One type is benign familial neonatal convulsions (BFNC), a dominantly inherited disorder of newborns. We have identified a sub-microscopic deletion of chromosome 20q13.3 that co-segregates with seizures in a BFNC family. Characterization of cDNAs spanning the deleted region identified one encoding a novel voltage-gated potassium channel, KCNQ2, which belongs to a new KQT-like class of potassium channels. Five other BFNC probands were shown to have KCNQ2 mutations, including two transmembrane missense mutations, two frameshifts and one splice-site mutation. This finding in BFNC provides additional evidence that defects in potassium channels are involved in the mammalian epilepsy phenotype.

Amino Acid Sequence↗

PubMed1998

Analysis of the dynamic mutation in the SCA7 gene shows marked parental effects on CAG repeat transmission.

The gene for spinocerebellar ataxia 7 (SCA7) includes a transcribed, translated CAG tract that is expanded in SCA7 patients. We have determined expansions in 73 individuals from 17 SCA7 kindreds and compared them with repeat lengths of 180 unaffected individuals. Subjects with abnormal expansions comprise 59 clinically affected individuals and 14 at-risk currently unaffected individuals predicted to carry the mutation by haplotype analysis. For expanded alleles, CAG repeat length correlates with disease progression and severity and correlates inversely with age of onset. Increased repeat lengths are seen in generational transmission of the disease allele, consistent with the pattern of clinical anticipation seen in these kindreds. Repeat lengths in expanded alleles show somatic mosaicism in leukocyte DNA, suggesting that these alleles are unstable within individuals as well as between generations. Although dynamic repeat expansions from paternal transmissions are greater than those from maternal transmissions, maternal transmission of disease is more common, suggesting germline or embryonic effects of the repeat expansion.

Adolescent↗

PubMed1998

Laminin alpha2 muscular dystrophy: genotype/phenotype studies of 22 patients.

OBJECTIVE: To determine the number of primary laminin alpha2 gene mutations and to conduct genotype/phenotype correlation in a cohort of laminin alpha2-deficient congenital muscular dystrophy patients. BACKGROUND: Congenital muscular dystrophies (CMD) are a heterogeneous group of muscle disorders characterized by early onset muscular dystrophy and a variable involvement of the CNS. Laminin alpha2 deficiency has been reported in about 40 to 50% of cases of the occidental, classic type of CMD. Laminin alpha2 is a muscle specific isoform of laminin localized to the basal lamina of muscle fibers, where it is thought to interact with myofiber membrane receptor, such as integrins, and possibly dystrophin-associated glycoproteins. METHODS: Seventy-five CMD patients were tested for laminin alpha2 expression by immunofluorescence and immunoblot. The entire 10 kb laminin alpha2 coding sequence of 22 completely laminin alpha2-deficient patients was screened for causative mutations by reverse transcription (RT)-PCR/single strand conformational polymorphisms (SSCP) analysis and protein truncation test (PTT) analysis followed by automatic sequencing of patient cDNA. Clinical data from the laminin alpha2-deficient patients were collected. RESULTS: Thirty laminin alpha2-negative patients were identified (40% of CMD patients tested) and 22 of them were screened for laminin alpha2 mutations. Clinical features of laminin alpha2-deficient patients were similar, with severe floppiness at birth, delay in achievement of motor milestones, and MRI findings of white matter changes with normal intelligence. Loss-of-function mutations were identified in 95% (21/22) of the patients studied. SSCP analysis detected laminin alpha2 gene mutations in about 50% of the mutant chromosomes; PTT successfully identified 75% of the mutations. A two base pair deletion mutation at position 2,096-2,097 bp was present in 23% of the patients analyzed. CONCLUSIONS: Our data suggest that the large majority of laminin alpha2-deficient patients show laminin alpha2 gene mutations.

Base Sequence↗

PubMed1997

Margarine intake and subsequent coronary heart disease in men.

Margarine is a major source of trans fatty acids, the intake of which has risen since the early 20th century. Some data indicate that consumption of trans fatty acids increases the risk of coronary heart disease (CHD). In 1966-1969, 832 men from the Framingham Study, age 45-64 years and free of CHD, were administered a single 24-hour dietary recall, from which we estimated total daily margarine intake. We calculated CHD cumulative incidence rates and, using proportional hazards regression, CHD incidence rate ratios over 21 years of follow-up. Mean energy intake was 2,619 kcal; mean margarine intake was 1.8 (range 0-12) tsp per day. There were 267 incident cases of CHD. Age-adjusted CHD cumulative incidence rose over categories of margarine intake, but the increased risk was apparent only in the second half of the follow-up period. Adjusted for age and energy intake, the risk ratio for CHD for each increment of 1 teaspoon per day of margarine was 0.98 [95% confidence interval (CI) = 0.91-1.05] for the first 10 years of follow-up and 1.10 (95% CI = 1.04-1.17) for follow-up years 11-21. Adjustment for total fat intake and for cigarette smoking, glucose intolerance, left ventricular hypertrophy, body mass index, blood pressure, physical activity, and alcohol intake did not materially change the results. Butter intake did not predict CHD incidence. These data offer modest support to the hypothesis that margarine intake increases the risk of coronary heart disease.

Age Distribution↗

PubMed1997

Relationship between seizure frequency and costs and quality of life of outpatients with partial epilepsy in France, Germany, and the United Kingdom.

PURPOSE: The relationship between seizure frequency and both health care costs and quality of life (QOL) was investigated in a retrospective, cross-sectional, multicenter study in France, Germany, and the United Kingdom. METHODS: Three hundred outpatients with stable partial epilepsy were approximately evenly distributed among five seizure-frequency groups, ranging from seizure-free in the last 3 months (group 1) to daily seizures (group 5). Economic data, obtained through patient interviews and record abstraction, comprised direct medical costs, direct nonmedical costs, and indirect costs for the preceding 3 months. Total societal costs in the three countries were pooled and converted to United States dollar equivalents. QOL was assessed through a self-administered questionnaire, the Functional Status Questionnaire (FSQ). RESULTS: Mean total costs increased from $780 in group 1 to $2,171 in group 5 (p = 0.0001), with significant increases in each cost category as seizure frequency increased. Greater seizure frequency also significantly (p = 0.0270) correlated with lower employment rates, which ranged from 57% in group 1 to 30% in group 5. QOL declined as seizure frequency increased. Particularly affected were basic and intermediate activities of daily living (ADL), mental health, social activity, and feeling about health. CONCLUSIONS: The study results show that higher seizure frequencies are associated with higher direct and indirect costs and with reduced QOL for patients with epilepsy.

Adolescent↗

PubMed1995

Protective effect of fruits and vegetables on development of stroke in men.

OBJECTIVE: To examine the effect of fruit and vegetable intake on risk of stroke among middle-aged men over 20 years of follow-up. DESIGN: Cohort. SETTING: The Framingham Study, a population-based longitudinal study. PARTICIPANTS: All 832 men, aged 45 through 65 years, who were free of cardiovascular disease at baseline (1966 through 1969). MEASUREMENTS AND DATA ANALYSIS: The diet of each subject was assessed at baseline by a single 24-hour recall. The estimated total number of servings per day of fruits and vegetables was the exposure variable for this analysis. Using Kaplan-Meier survival analysis, we examined age-adjusted cumulative incidence of stroke by quintile of servings per day. To adjust for multiple covariates, we used proportional hazards regression to calculate the relative risk (RR) of stroke for each increment of three servings per day. MAIN OUTCOME MEASURE: Incidence of completed strokes and transient ischemic attacks. RESULTS: At baseline, the mean (+/- SD) number of fruit and vegetable servings per day was 5.1 (+/- 2.8). During follow-up there were 97 incident strokes, including 73 completed strokes and 24 transient ischemic attacks. Age-adjusted risk of stroke decreased across increasing quintile of servings per day (log rank P for trend, .01). Age-adjusted RR for all stroke, including transient ischemic attack, was 0.78 (95% confidence interval [Cl], 0.62 to 0.98) for each increase of three servings per day. For completed stroke the RR was 0.74 (95% Cl, 0.57 to 0.96); for completed stroke of ischemic origin the RR was 0.76 (95% Cl, 0.57 to 1.02); and for completed stroke of hemorrhagic origin, 0.49 (95% Cl, 0.25 to 0.95). Adjustment for body mass index, cigarette smoking, glucose intolerance, physical activity, blood pressure, serum cholesterol, and intake of energy, ethanol, and fat did not materially change the results. CONCLUSION: Intake of fruits and vegetables may protect against development of stroke in men.

Cerebrovascular Disorders↗

PubMed1995

Structure-function studies of motilin analogues.

Over 100 motilin fragments and analogues, including monosubstituted C-terminal-deleted analogues, conformationally restricted analogues, analogues with peptide bond isoteres (CH2-NH), and N-terminal fragments adjunct to an amphiphilic helix, were synthesized by solid-phase methodology, purified by reverse-phase HPLC, and assayed in vitro in a muscle strip bioassay (rabbit duodenum) and in a radioligand binding assay on crude membrane extracts from smooth muscle (rabbit antrum). The data suggest the existence of three distinct regions involved in the interaction of motilin with its receptor: the N-terminal region (amino acids 1-7) constitutes the minimal basic unit of binding and activity; the transition region (amino acidsa 8-9) links the N-terminal and C-terminal regions; and the C-terminal region (amino acids 10-22) forms an alpha-helix that stabilizes the interaction of the N-terminal residues at the active site.

Amino Acid Sequence↗

PubMed1995

Structural effects of the selective reduction of amide carbonyl groups in motilin 1-12 as determined by nuclear magnetic resonance.

Motilin is a 22-residue peptide stimulating stomach and intestinal motility. The motilin 1-12 fragment displays biological effects similar to the native peptide. Selective reduction of the amide carbonyl groups to form CH2NH analogs leads to a significant reduction in activity for the first two N-terminal positions and to a complete loss of activity for all other positions. The structures of motilin 1-12 and ten reduced analogs were investigated using the temperature dependence of the amide NH chemical shifts. In all the analogs, the structure of the N-terminal region (residues 1-5) was different from the structure of motilin 1-12, which is characterized by hydrogen bonding between Phe1 and Ile4. The structure of the C-terminal region of analogs was similar to the structure of motilin 1-12 for the first two reduction positions only (1-2 and 2-3), indicating that the C-terminal portion of motilin 1-12 is more critical for biological activity. Complete structural characterizations of motilin 1-12, [CH2NH]1-2, and [CH2NH]4-5-motilin 1-12 were performed by two-dimensional NMR spectroscopy and molecular modeling. The structural features observed confirm the differences based on the temperature dependence of the amide NH chemical shifts. These results demonstrate that conservation of the amide bond rigidity is essential for the activity of non-hydrolyzable analogs.

Amides↗

PubMed1994

Motilin synthetic analogues and motilin receptor antagonists.

While studying the structure-activity characteristics of motilin with motilin synthetic analogues, two compounds, motilin 1-12 [CH2 NH]3-4 and motilin 1-12 [CH2 NH]10-11, showed high affinity for the motilin receptor combined to a weak contractile activity. The following data suggest that motilin 1-12 [CH2 NH]10-11 is a potent motilin receptor antagonist. It showed a high affinity for the motilin receptor present on membranes of rabbit antrum (pIC50: 8.24 +/- 0.08 for the analogue vs 8.96 +/- 0.02 for the native peptide). When tested in vitro on strips of rabbit duodenum, the dose-response curve to motilin 1-22 was displaced to the right with motilin 1-12 [CH2 NH]10-11 (pIC50: 8.91 +/- 0.06 in presence of saline versus 7.19 +/- 0.40 with the analogue). However, when injected i.v. in dogs, motilin 1-12 [CH2 NH]10-11 was undetectable in the peripheral blood, suggesting enzymatic degradation precluding its use in vivo.

Animals↗

PubMed1994

Studies on the structure-activity of motilin in vivo. Effect of motilin synthetic analogues in conscious dog.

Synthetic analogues of motilin were tested for their capacity to stimulate the intestinal motor activity of the conscious dog. Physiological doses (75 pmol/kg) of motilin 1-22 and of motilin fragments 1-21, 1-20 and 1-19 induced premature periods of phase III activity in all tested animals. Motilin fragments 1-15, 1-12, 1-11 and 1-10 failed to influence the intestinal myoelectrical activity even when given at doses 10-times superior (750 pmol/kg). Motilin-like-immunoreactivity was measured in plasma during the analogues infusion. During the infusion of the bioactive analogues (1-22, 1-21, 1-20, 1-19), plasma motilin increased by 174 +/- 25 fmol/ml while a small rise (22 +/- 7.6 fmol) was noted with the inactive fragments (P < 0.001). Our data are in agreement with the in vitro findings that the N-terminal portion of the motilin molecule is responsible for its biological activity and suggests that the middle portion of the molecule is important to prevent degradation and maintain biological activity in vivo.

Animals↗

PubMed1994

Occupational allergy after exposure to caddis flies at a hydroelectric power plant.

A cross sectional survey was conducted in a hydroelectric power plant in which the workforce was exposed to large numbers of caddis flies. 28 of 57 employees participated. About 50% of the participants reported work related eye, nose, and sinus symptoms and wheezing. Working in locations with greater exposure to caddis flies was significantly associated with work related symptoms. 17 workers (61%) were skin prick positive to a laboratory prepared caddis fly antigen (LCFA) made from the remains of caddis flies present in the plant and 11 (39%) had positive reactions to a commercial caddis fly antigen (CCFA). Workers stationed in heavily exposed areas were 3.7 times as likely to have a positive response to the LCFA (p = 0.009) and 5.3 times as likely to have a positive response to the CCFA (p = 0.036). 13 (46%) of survey respondents reported three or more work related symptoms. 10 (91%) CCFA positive workers reported three or more work related symptoms. Pulmonary function studies revealed slight, but not significantly decreased forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and FEV1/FVC ratios in workers who were skin test positive to either caddis fly preparation when compared with those who were negative. One worker who was skin test positive to both antigens had a cross shift fall in FEV1 of 20% predicted. Occupational allergy to caddis flies proved to be a significant health problem at this work site.

Adult↗

PubMed1994

Conformational and biological studies of neuropeptide Y analogs containing structural alterations.

We evaluated the alpha-helix content, the biological activities and the affinities of a series of neuropeptide Y (NPY) analogs containing structural alterations, mainly in the central portion of the molecule for which a putative alpha-helix arrangement has been proposed. First, we investigated the conformational and pharmacological characteristics of derivatives containing the N-terminal tetrapeptide linked to C-terminal peptide-amide segments of various lengths. In some of these, the missing portion was replaced with epsilon-aminocaproic acid, a flexible arm-linker. Data revealed that (1-4)-Aca-(18-36)NPY is a discontinuous analog almost as potent as the native peptide in a pharmacological preparation enriched in Y2 receptors (rat vas deferens), whereas it is about 5 times less potent in a Y1 bioassay (rabbit saphenous vein). This analog showed a similar profile in [125I]PYY binding assays performed in rat frontoparietal cortex (Y1) and hippocampus (Y2) membrane preparations. In a series of truncated derivatives obtained with the successive removal of the 5-13 to 5-17 segments of the NPY molecule, no apparent correlation was observed between the affinity or potency in bioassays and the alpha-helix content, as measured by circular dichroism spectroscopy. Other truncated analogs, obtained by linking the C-terminal 31-36 fragment to various N-terminal tetrapeptides were also investigated. None showed any affinity in brain membrane preparations (frontoparietal cortex and hippocampus) or activity in the rat vas deferens bioassay. However, a weak short-lasting contraction was measured with some of these analogs in the rabbit saphenous vein, thus suggesting that the 1-4 and 31-36 segments of the molecule contains pharmacophores recognized by the Y1 receptor subtype. The contribution of the arginine residues also was evaluated in relation with the alpha-helix. Their successive substitution with lysine, an excellent helix-promoter, showed that the replacement of Arg-19 or Arg-25, two residues found in the putative alpha-helix, gave active analogs. Furthermore, the substitution of Arg-19 with lysine increased the activity in the rat vas deferens as well as the affinity in the brain membrane binding assays. On the other hand, the substitution of Arg-33 produced a weak agonist, whereas the replacement of Arg-35 generated an inactive analog in the Y2-pharmacological preparation and a very weak competitor in the CNS binding assays. Interestingly, this latter analog was still active in the rabbit saphenous vein, thus identifying the position 35 as an additional potential target for the development of Y1 versus Y2 specific molecules.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

PubMed1993

Healthy People 2000. The rationale and potential efficacy of preventive nutrition in heart disease: the Framingham Offspring-Spouse Study.

BACKGROUND: To examine the rationale for preventive nutrition intervention and the potential efficacy of nutrition-related risk factor modification on heart disease incidence, the cardiovascular disease risk and dietary profiles of Framingham (Mass) men and women, 30 to 79 years old (n = 1798 and 1845, respectively), were compared with the Healthy People 2000: National Health Promotion and Disease Prevention Objectives for the Nation and used to project the 10-year incidence of coronary heart disease with and without lowering serum cholesterol levels. METHODS: Data for this report are derived from the 1984 to 1988 cycle III examinations of the Framingham offspring-spouse cohort. Estimates of the reduction in coronary heart disease risk associated with modifications in serum cholesterol levels and other cardiovascular disease risk factors are projected using Framingham models. RESULTS: About 40% met guidelines for desirable total cholesterol levels (< 5.17 mmol/L [< 200 mg/dL]); 20% were hypertensive; one quarter smoked; and 10% of women and 20% of men were obese. Twenty-four-hour dietary data, adjusted for estimates of usual intake, indicated that about 50% to 80% met dietary cholesterol (< 300 mg) and 55% to 94% met sodium (< 3 g/d) objectives. In contrast, mean total fat intakes were high (38% of total energy), and only 6% to 9% of subjects met total fat, 9% to 14% met saturated fat, and fewer than 3% met dietary fiber guidelines. Ten-year cumulative incidence for coronary heart disease was projected to be up to 25% lower with reduction in serum cholesterol level. CONCLUSION: Risk factor lowering, emphasizing preventive nutrition measures, is an important element of health care reform, particularly strategies to reduce cardiovascular disease rates and to promote population health.

Adult↗

PubMed1992

N-terminal portion of motilin determines its biological activity.

This study aimed to identify the portion of the 22 amino acid sequence of motilin responsible for the biological activity of the peptide. The contraction of rabbit duodenal muscle in vitro was measured when exposed to synthetic fragments of motilin corresponding to various sequences of the C- or N-terminal portions of the molecule. Fragments 2-22 or 3-22 (where the initial amino acids of the N-terminal ending were removed) were more than 1000 times less potent than the native molecule 1-22. Fragment 1-9 (where the last 13 amino acids located at the C-terminal side of motilin were removed) was devoid of any contractile capacity, while synthetic fragments whose C-terminal structure extended beyond the 1-9 motilin sequence maintained almost complete biological activity. N-terminal amino acid sequence 1-9 is therefore an essential determinant of the contractile activity of motilin.

Animals↗

PubMed1992

The influence of dynamic factors on triaxial net muscular moments at the L5/S1 joint during asymmetrical lifting and lowering.

Asymmetrical lifting and lowering are predominant activities in the workplace. Mechanical causes are suggested for many back injuries and the dynamic conditions within which spine loading occurs are related to spine loading increase. More data on tridimensional biomechanical lumbar spine loading during asymmetrical lifting and lowering are needed. A tridimensional dynamic multisegment model was developed to compute spinal loading for asymmetrical box-handling situations. The tridimensional positions of the anatomical markers were generated by a direct linear transformation algorithm adapted for the processing of data from two real and two virtual views (mirrors). Two force platforms measured the external forces. Five male subjects performed three variations (slow, fast and accelerated) of asymmetric lifting and two variations (slow and fast) of asymmetric lowering. The torsional, extension/flexion and lateral bending net muscular moments at the L5/S1 joint were computed and peak values selected for statistical analysis. For the lifting task, the fast and accelerated conditions showed significant increases over the slow condition for torsion, extension/flexion and lateral-bending moments. The accelerated condition also showed significant increases over the fast condition for extension. A comparison between lifting and lowering tasks showed equivalent loadings for torsion and extension. The moments were compared to average maximal values measured on equivalent male subject populations by isokinetic dynamometry. This showed torsional and extension values of 30 and 83% of the maximal possible subject capacity, respectively. These results demonstrated that dynamic factors do influence the load on the spine and highlighted the influence of both lifting and lowering on the loading of the spine. This suggested that for a more complete analysis of asymmetrical handling, the maximal velocity and acceleration produced during lifting should be included.

Adult↗