Search PubMed⌕ Search

Biomedical subjects

P Allard

Publications and source records attributed to P Allard.

At least 73 records · Page 4Linked to original sources
PubMed1997

Anesthetic and surgical complications in 219 cases of myotonic dystrophy.

The objective of this study was to assess the frequency, type, and severity of perioperative complications after a first surgery under general anesthesia in patients with myotonic dystrophy (DM) and to measure the association with suspected risk factors. Numerous cases of perioperative complications in DM patients have been reported. Hazards have been associated with the use of thiopentone, suxamethonium, neostigmine, and halothane. A retrospective study of perioperative complications was conducted for 219 DM patients who had their first surgery under general anesthesia at the Chicoutimi Hospital. The overall frequency of complications was 8.2% (18 of 219). Most complications (16 of 18) were pulmonary, including five patients with acute ventilatory failure necessitating ventilatory support, four patients with atelectasis, and three patients with pneumonia. Using multivariate analysis, we found that the risk of perioperative pulmonary complications (PPC) was significantly higher after an upper abdominal surgery (odds ratio (OR), 24.4; 95% CI, 4.0 to 149.3) and for patients with a severe muscular disability, as assessed by the presence of proximal limb weakness (OR, 14.1; 95% CI, 1.5 to 134.4). The likelihood of PPC was not related to any specific anesthetic drug. Because of the increased risk of PPC, careful monitoring during the early postoperative period, protection of upper airways, chest physiotherapy, and incentive spirometry are mandatory in all symptomatic DM patients, particularly those with a severe muscular disability or those who have undergone an upper abdominal surgery.

Adolescent↗
PubMed1997

[Sensitivity and specificity of thyreostimuline (TSH) determination on filter paper for the diagnosis of hypothyroidism in the elderly].

The aim of this study was to measure the prevalence of hypothyroidism in 239 elderly patients and to determine the validity of TSH assay on blood dried on filter paper (spot-test) for the diagnosis of hypothyroidism. The sensitivity and specificity of the spot-test were evaluated in a subgroup of 177 subjects. The prevalence of hypothyroidism was 14.2% (34/239). The spot-test did not give satisfactory results for the diagnosis of hypothyroidism in elderly subjects. Due to the lack of specificity, most of the positive results were false positives and the clinician had to rely on laboratory determination of plasma TSH level to confirm hypothyroidism in half of the patients. We do not recommend the spot-test for the diagnosis of hypothyroidism in the elderly. Laboratory assay of plasma TSH is required for confirming hypothyroidism in the elderly.

Aged↗
PubMed1996

Reduction in number of dopamine uptake sites but unchanged number of piperazine-acceptor/CYP450IID6 binding sites in the human caudate nucleus in aging.

A substantial decrease in number of striatal dopamine uptake sites is a characteristic finding in aging. This decrease resembles the dopaminergic nigro-striatal degeneration in Parkinson's disease (PD). A dysfunction of cytochrome P450IID6 (debrisoquine-4-hydroxylase) is suggested to be involved in the pathogenesis of PD. In this study, binding sites associated with the neuronal form of P450IID6 were studied in the caudate nucleus from individuals in the age range 20-81 years using [3H]GBR 12935 as a radioligand. No significant changes in binding parameters were obtained, while in the same region a significant decrease in number of dopamine uptake sites occurred. Thus, in aging, P450IID6 and dopaminergic degeneration seem not to be functionally related in this region. Whether such a relation exists in PD is still to be examined.

Adult↗
PubMed1996

[3H]WIN 35,428 binding in the human brain.

The binding of [3H]WIN 35,428 was studied in post-mortem human brain, including extrastriatal regions. In the putamen, dopamine almost completely inhibited the [3H]WIN 35,428 binding. Paroxetine inhibited the binding with similar affinity as cocaine, in the range 200-300 nM. In the frontal cortex, [3H]WIN 35,428 labelled cocaine- and alaproclate sensitive binding sites, of which a major fraction was of protein nature. The elucidation of the cocaine sensitive sites in the frontal cortex should be the subject of further research.

Adult↗
PubMed1996

Spectral-Density Mapping of 13Calpha-1Halpha Vector Dynamics Using Dipolar Relaxation Rates Measured at Several Magnetic Fields

The spectral-density mapping of a 13Calpha-1Halpha vector of Leu10 in the 22-residue peptide hormone motilin [P. Allard, J. Jarvet, A. Ehrenberg, and A. Graslund, J. Biomol. NMR 5, 133-146 (1995)] is extended in this paper to three polarizing fields 9.4, 11.7, and 14.1 T in order to improve the accuracy of the calculated spectral-density function J(omega) and to extend the sampling range up to 750 MHz. The problem with a usually large relative error in J(omegaH) is eliminated since the generally more precise J(omegaH - omegaC) and J(omegaH + omegaC) determined at other fields appear at nearly the same frequencies. The fitting of dynamic models to the points of spectral density was made with error weighting, and the influence of J(omegaH) was found to be negligible. Therefore, the high-frequency part of the spectral-density function is determined essentially without influence from the two transverse-type relaxation rates. In the case of a carbon-proton vector, the relaxation is mainly determined by dipolar interaction and is only weakly influenced by other relaxation mechanisms, which makes it particularly suitable for the spectral-density mapping technique. The measured relaxation rates in the time domain are transformed into the frequency domain by spectral-density mapping, and the slopes in different frequency regions are important parameters when comparing experimental data with theoretical models of motion. Using an adjustable internuclear distance reff, combined with the model-free approach, it is possible to obtain a reasonable fit to measured spectral-density points at J(0) and around J(omegaC). At the same time, however, the high-frequency slope of the spectral-density function defined by J(omegaH - omegaC) and J(omegaH + omegaC) could not be reproduced.

Journal Article↗
PubMed1996

Phase-Sensitive Two-Dimensional Heteronuclear Zero- and Double-Quantum-Coherence Spectroscopy

New pulse sequences for two-dimensional phase-sensitive detection of heteronuclear zero- and double-quantum coherence are presented for use with and without pulsed field gradients. The magnetization is phase modulated during t1 and then transferred to a proton for detection using a novel approach similar to the sensitivity-enhancement technique [Palmer et al. J. Magn. Reson. 93, 151 (1991)]. These pulse sequences are useful for the measurement of size and relative sign of passive J couplings as well as for the measurement of the relaxation rates of zero- and double-quantum coherence. They can also be used as building blocks in multidimensional pulse sequences. The pulse sequences are tested on the peptide hormone motilin with a selectively 13C-enriched alpha carbon.

Journal Article↗
PubMed1996

Internal work estimation in three-dimensional gait analysis.

Many studies concerning the internal work of human motion have used two-dimensional kinematic models to estimate kinetic energy of the segments. The generalised co-ordinate concept has been applied here to a simultaneous and bilateral gait analysis. A three-dimensional kinematic model based on quaternions has been developed. To estimate the kinetic energy of a multi-body system, only two constants and two variables are needed: the segment body mass, the inertia tensor, the position and the orientation of the local co-ordinate system with respect to the inertial co-ordinate system. The variation of the kinetic energy is used in the calculation of the internal work for an able-bodies subject during the gait cycle. Both the internal work and the instantaneous energy correlation coefficient enable the determination of a conservative phase delimited by the beginning of the single support phase until the flat-foot phase, and a non-conservative phase corresponding to the period from heel-off to contralateral heel-strike including the double support phase.

Adult↗
PubMed1996

Prognostic significance of nuclear DNA content and S-phase fraction by flow cytometry in primary papillary superficial bladder cancer.

This study is aimed at determining the usefulness of nuclear DNA content and S-phase fraction (SPF) to predict tumor recurrence in papillary superficial bladder cancer. Tumor DNA content and SPF were measured by flow cytometry on formalin-fixed, paraffin-embedded tissue from 199 newly diagnosed pTa/pT1 transitional cell carcinomas of patients enrolled into a multicenter prospective study from 1990 to 1992. The follow-up extended up to March 1994, and, at last follow-up, 122 (61.3%) patients have experienced at least one recurrence. After exclusion of 34 cases, whose coefficient of variation exceeded 8%, 131 (79.4%) tumors were diploid, and 34 (20.6%) were aneuploid. There was no association between tumor DNA content and time to first recurrence. Diploid tumors with low SPF (< 11%) tended to have a longer recurrence-free survival (RFS) than those with high SPF, but this difference did not reach statistical significance (P = .2833). SPF in aneuploid tumors did not add any new information. Aneuploidy was associated with higher stage (P < .001), poorer grade (P < .002), multifocality (P = .028), Her-2/neu (P = .021), and p53 (P = .033) expression. High SPF correlated with higher stage (P = .066) and higher grade (P = .025). This study shows that DNA-ploidy and SPF measured on a single superficial bladder cancer specimen are not predictive of tumor recurrence. The frequent multifocality of the disease may explain, in part, these findings.

Adult↗
PubMed1996

Epidemiological study of reptured intracranial aneurysms in the Saguenay-Lac-Saint-Jean region (Quebec, Canada).

BACKGROUND: Using a population-based register of the Saguenay-Lac-Saint-Jean region (Quebec, Canada), the genealogical reconstruction of 533 individuals with intracranial aneurysm (IA) showed a familial aggregation (the presence of aneurysm in two or more first- to third-degree relatives) for 159 (29.8%) of them; this proportion is much higher than reported elsewhere. OBJECTIVE: As part of an ongoing project to assess a genetic predisposition to intracranial aneurysms in the Saguenay-Lac-Saint-Jean population, the objective of the present study was to determine whether age-specific rates of reputed cerebral aneurysms were higher than in other populations. DESIGN: A retrospective study of cases of proven ruptured IAs which were hospitalized during the 1973 to 1992 period was conducted. Age-adjusted rates were computed and compared to those reported in the Helsinki population. RESULTS: We identified 412 cases of ruptured aneurysms. The age-adjusted incidence rate was 7.2/100,000/year (6.2 for men, 8.1 for women), which is similar to the incidence rates reported in other studies. Although the mean age at time of rupture was younger (46.6 years +/- 13.8) than usually reported, no increase in age-specific incidence rates was detected. CONCLUSIONS: The results of this epidemiological study neither support nor reject the hypothesis of a genetic predisposition to intracranial aneurysms in the Saguenay-Lac-Saint-Jean population.

Adolescent↗
PubMed1996

Risk factors for peak dose dyskinesia in 100 levodopa-treated parkinsonian patients.

BACKGROUND: No clinical parameter other than "sufficient" dopamine denervation and exposure to exogenous levodopa has been unquestionably linked to dyskinesia in levodopa-treated Parkinson's disease patients. METHODS: We retrospectively analyzed data on 100 consecutive patients treated with levodopa for 1 to 18 years to identify clinical risk factors for dyskinesia. The cumulative dyskinesia-free survival probability in relation to levodopa therapy was assessed using the Kaplan-Meier method. RESULTS: Overall, 56% of patients developed dyskinesia after a mean of 2.9 years, a figure similar to the average duration of levodopa treatment in the non-dyskinetic group. Dyskinetic patients were significantly younger at disease onset, but their mean latency to dyskinesia induction after levodopa initiation was not different from older dyskinetic individuals and the overall dyskinesia-free survival of younger subjects was not worse either. Dyskinetic patients were on a higher daily levodopa dose than non-dyskinetic subjects when dyskinesia emerged, but the cumulative levodopa dose used prior to dyskinesia did not discriminate dyskinetic from non-dyskinetic patients. A delay in initiating levodopa therapy of more than three years after disease onset and levodopa treatment initiation in Hoehn-Yahr stage II compared to stage I patients did not increase the probability of developing dyskinesia over time. CONCLUSIONS: Since withholding levodopa therapy did not increase the risk for dyskinesia in our patients and can delay the emergence of dyskinesia after onset of parkinsonian symptom, a trial with a dopaminomimetic agonist as initial treatment appears logical.

Adult↗
PubMed1996

Effect of initial posture on biomechanical adjustments associated with a voluntary leg movement in rock climbers.

This study compares the biomechanical adjustments following a leg displacement in vertical and horizontal position on expert rock climbers. The results show a non-diagonal pattern in the vertical condition and a diagonal one in the horizontal condition. A multi-link analysis shows that the non-diagonal pattern displayed by expert climbers in the vertical condition resulted in a new distribution of body weight to preserve the possibility of moving any limb from the three legged stance. Conversely, in the horizontal condition, the diagonal pattern appears to be strongly dominated by mechanical and anthropometric factors.

Adult↗
PubMed1996

Radiation inactivation and in situ renaturation of protein tyrosine kinases reveal a major 50-kDa enzyme as part of a membrane complex present in dividing but not in resting prostatic epithelial cells.

Because protein tyrosine kinases play a crucial role in the regulation of cell division and carcinogenesis, we have herein measured such enzyme activities (specific activity and subcellular distribution) and compared their characteristics with respect to hydrodynamic properties and radiation inactivation sizes as well as renaturation after electrophoresis in denaturing conditions in canine prostatic epithelial cells either in a resting (freshly isolated) or in a dividing (cultured cells) state. In quiescent cells, most protein tyrosine kinase activity was expressed by soluble proteins with a Stokes' radius (Rs) of 3.05 nm, a sedimentation coefficient (S20,w) of 4.0 S, and a molecular mass of 50 kDa. By contrast, in dividing cells (three days in primary culture), the specific activity was higher and the enzyme was mainly membrane bound. The use of a detergent (Triton X-100) allowed the extraction of most of that enzyme; its partial specific volume, S20,w and Rs were then 0.883 cm3/g, 4.0 S, and 5.6 nm, respectively, hence yielding a molecular mass of 215 kDa, which decreased to 125-145 kDa when corrected for detergent binding. Probing these chromatography-peak fractions, 50 kDa from cytosol of resting cells and 215 kDa from membrane extracts of dividing cells, with a phosphotyrosine antibody following their incubation with ATP and electrophoresis in denaturing conditions revealed the presence of a common 50-kDa phosphotyrosylated protein along with three other bands (130, 75, and 40 kDa) in the high-Mr peak of enzyme. However, the radiation inactivation size for protein tyrosine kinases expressed in both resting and dividing cells were similar, 47.2 +/- 8.7 and 44.5 +/- 6.1 kDa, respectively. Furthermore, by renaturation after electrophoresis in denaturing conditions, major protein tyrosine kinase polypeptides of 50 kDa were identified in both cell populations. Taken together, these results indicate that, in dividing prostatic epithelial cells, membrane-bound protein tyrosine kinases of low molecular weight with properties similar to those of monomeric soluble forms present in quiescent cells are part of high-molecular weight complexes. This activation process may be critical for hormone-independent proliferation of prostatic epithelial cells.

Animals↗
PubMed1996

Regulation and activation of focal adhesion kinase and paxillin during the adhesion, proliferation, and differentiation of prostatic epithelial cells in vitro and in vivo.

Focal adhesion kinase (pp125FAK) is a nonreceptor protein tyrosine kinase transducing signals initiated through integrin activation triggered by cell/extracellular matrix (ECM) interactions. To examine its role in epithelial cell adhesion, proliferation, and differentiation, we have studied pp125FAK expression, activity, and association with paxillin in two canine prostate models in which these functions can be selectively regulated: in vitro by vitronectin (VN) and serum factors, and in vivo by sex steroids. Kinetic studies revealed that the adhesion and spreading of prostatic epithelial cells in primary culture was regulated by serum VN and a natural ECM containing VN produced by prostate cells. While barely detectable in freshly isolated prostate cells, proliferating cells, after 72 h in culture, expressed higher levels of FAK mRNA (8-fold), pp125FAK (50-fold), and paxillin (50-fold). In prostate cells with a reduced growth rate after 2 weeks in culture, we observed a decrease in pp125FAK (4-fold) and its transcript (3-fold), but no change in paxillin. In vivo, both proteins were undetectable in normal and hyperplastic glands composed of a well differentiated epithelium, and in prostates restored by androgen supplementation. In contrast, pp125FAK and paxillin were up-regulated by androgen deprivation (castration) and further increased by estrogen treatment, which yielded metaplastic prostates mostly composed of proliferating basal epithelial cells. Moreover, both proteins were constitutively phosphorylated on tyrosine in the metaplastic prostate, as well as in proliferating cultured cells. Together, these results demonstrate that pp125FAK expression is regulated at the protein and mRNA levels and forms active signaling complexes with paxillin when epithelial cells in contact with ECM proteins are induced to proliferate in vivo and in vitro.

Amino Acid Sequence↗
PubMed1996

Prevalence and clinical significance of HER/2neu, p53 and Rb expression in primary superficial bladder cancer.

PURPOSE: The usefulness of the expression of HER2/neu oncoprotein and of p53 and Rb suppressor gene product as predictors of tumor recurrence was evaluated by using a bank of prospectively collected primary papillary bladder tumors treated initially only by transurethral resection. MATERIALS AND METHODS: The expression of HER-2/neu oncoprotein and p53 and Rb suppressor genes was evaluated by immunohistochemistry in 256, 265 and 74 specimens of primary Ta/T1 superficial bladder tumors obtained from patients enrolled in a prospective study from 1990 to 1992. Survival analysis was used to evaluate the association between time to first recurrence and expression of each marker, the follow-up period extending to March 1994. Immunostaining for p53 and HER-2/neu was performed on paraffin-embedded tissue and, for Rb, on frozen tissue only. RESULTS: Her-2/neu was expressed in 21 (8.2%) cases and p53 in 39 cases (14.7%); Rb expression was altered in 12 (16.2%). In this study, p53 expression was only related to earlier recurrence in a univariate analysis. Multivariate analysis, however, failed to recognize p53 expression as an independent predictor of recurrence. CONCLUSIONS: Our study demonstrates the low prevalence of HER2/neu, p53 and altered Rb expression in superficial TCC at initial resection. Only p53 expression was significantly associated with an earlier first tumor recurrence, but this association was not independent of other prognostic factors.

Aged↗
PubMed1995

Activation of a serine/threonine kinase signaling pathway by transforming growth factor type beta.

Transforming growth factor type beta (TGF-beta) is a multifunctional factor that regulates proliferation and differentiation of many cell types. TGF-beta mediates its effects by binding to and activating cell surface receptors that possess serine/threonine kinase activity. However, the intracellular signaling pathways through which TGF-beta receptors act remain largely unknown. Here we show that TGF-beta activates a 78-kDa protein (p78) serine/threonine kinase as evidenced by an in-gel kinase assay. Ligand-induced activation of the kinase was near-maximal 5 min after TGF-beta addition to the cells and occurred exclusively on serine and threonine residues. This kinase is distinct from TGF-beta receptor type II, as well as several cytoplasmic serine/threonine kinases of similar size, including protein kinase C, Raf, mitogen-activated protein kinase kinase kinase, and ribosomal S6 kinase. Indeed, these kinases can be separated almost completely from p78 kinase by immunoprecipitation with specific antibodies. Furthermore, using different cell lines, we demonstrate that p78 kinase is activated only in cells for which TGF-beta can act as a growth inhibitory factor. These data raise the interesting possibility that protein serine/threonine kinases contribute to the intracellular relay of biological signals originating from receptor serine/threonine kinases such as the TGF-beta receptors.

3T3 Cells↗
PubMed1995

NMR studies of binding of 5-FdUDP and dCDP to ribonucleoside-diphosphate reductase from Escherichia coli.

5-Fluoro-2'-deoxyuridine-5'-diphosphate (5-FdUDP) has been synthesised using an original route, previously applied to the synthesis of natural nucleoside diphosphates. The interaction between 5-FdUDP and the enzyme ribonucleoside-diphosphate reductase (EC 1.17.4.1) has been studied with 19F-NMR. The product analogue is shown to be in fast exchange with substrate binding sites on protein subunit 1 (R1) of ribonucleoside-diphosphate (NDP) reductase. The number of binding sites is reduced to half when the complete holoenzyme R1R2 is formed. The temperature dependence of the line broadening of 5-FdUDP was studied using 19F-NMR, and of dCDP and dUDP using 1H-NMR. The temperature dependences are complex and a molecular model in which R1 is in a temperature dependent equilibrium between at least two conformations is suggested in order to explain the observed behaviour. Binding of a ligand to the substrate binding sites affects the conformational equilibrium in a ligand specific way. Formation of the holoenzyme R1R2 also affects the equilibrium.

Binding Sites↗
PubMed1995

Mapping of the spectral density function of a C alpha-H alpha bond vector from NMR relaxation rates of a 13C-labelled alpha-carbon in motilin.

The peptide hormone motilin was synthesised with a 13C-enriched alpha-carbon in the leucine at position 10. In aqueous solution, six different relaxation rates were measured for the 13C alpha-H alpha fragment as a function of temperature and with and without the addition of 30% (v/v) of the cosolvent d2-1,1,1,3,3,3-hexafluoro-2-propanol (HFP). The relaxation rates were analysed employing the spectral density mapping technique introduced by Peng and Wagner [(1992) J. Magn. Reson., 98, 308-332] and using the model-free approach by Lipari and Szabo [(1982) J. Am. Chem. Soc., 104, 4546-4570]. The fit to various models of dynamics was also considered. Different procedures to evaluate the overall rotational correlation time were compared. A single exponential time correlation function was found to give a good fit to the measured spectral densities only for motilin in 30% (v/v) HFP at low temperatures, whereas at high temperatures in this solvent, and in D2O at all temperatures, none of the considered models gave an acceptable fit. A new empirical spectral density function was tested and found to accurately fit the experimental spectral density mapping points. The application of spectral density mapping based on NMR relaxation data for a specific 13C-1H vector is shown to be a highly useful method to study biomolecular dynamics. Advantages are high sensitivity, high precision and uniform sampling of the spectral density function over the frequency range.

Amino Acid Sequence↗