Search PubMed⌕ Search

Biomedical subjects

P Allard

Publications and source records attributed to P Allard.

At least 37 records · Page 2Linked to original sources
PubMed2000

A brief pain diary for ambulatory patients with advanced cancer: acceptability and validity.

BACKGROUND: Undertreatment of pain is common among ambulatory patients with advanced cancer. Available pain assessment tools are complex and not easy to use in ambulatory care settings. METHODS: The authors developed and assessed the acceptability and psychometric properties of a simple, brief 4-week pain diary for ambulatory care assessing 3 indicators: current pain intensity on rising and retiring, number of daily rescue doses, and weekly impact of pain on quality of life. Selected European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire subscales were administered once concurrently for validation purposes. Subjects were 98 adult French-speaking ambulatory patients with advanced cancers who were on opioids, free of apparent cognitive impairment, and recruited through 2 oncology clinics in Quebec City, Quebec, Canada. RESULTS: In the first 3 weeks, > or =80% of patients completed all requested diary data. Internal consistencies of the 5-item scale assessing pain impact on quality of life were 0.87-0.92 over the study period. Pain intensity predicted both increased use of rescue doses and negative pain impact on quality of life. This latter scale was also responsive to decreases in pain intensity over 1-week intervals. As hypothesized, pain intensity, rescue doses, and pain impact on quality of life correlated with EORTC scale scores. Pain intensity correlated most strongly with the EORTC pain and global quality of life scales (r = 0.65 and -0.55, respectively). CONCLUSIONS: This diary is simple, very brief, acceptable to patients, and appears to be valid. It can thus likely be used to monitor pain management for advanced cancer patients.

Adolescent↗
PubMed2000

The solution structure of ribosomal protein L36 from Thermus thermophilus reveals a zinc-ribbon-like fold.

We have determined the solution NMR structure of the ribosomal protein L36 from Thermus thermophilus. L36 is the smallest protein in the large subunit of the prokaryotic ribosome. The sequence contains three completely conserved cysteine residues and one conserved histidine residue in a C-X(2)-C-X(12)-C-X(4)-H motif. Extended X-ray absorption fine structure spectroscopy was used to confirm that a purified L36 sample contains an equimolar amount of zinc. The structure of L36 was determined using simulated annealing based on NOE distance restraints, dihedral angle restraints and hydrogen bond distance restraints derived from NMR spectra of (15)N-labeled and non-labeled L36 samples at pH 7 and 12 degrees C, and by imposing tetrahedral zinc ion coordination geometry. The L36 fold is characterized by a triple-stranded antiparallel beta-sheet with the zinc-binding site at one end. The structure of the zinc site is well-determined and shows that the three cysteine sulphur atoms are supported by hydrogen bonds to backbone amide protons. The conserved histidine residue is located in a short 3(10)-helix and coordinates zinc by the N(delta1) atom. The electrostatic surface potential and location of conserved Arg, Lys and His side-chains suggest a large continuous L36-rRNA interaction interface. The folding topology as well as position and conformation of many conserved side-chains in L36 are very similar to those of zinc-ribbon domains found in the archaeal transcription factor TFIIB N terminus and the eukaryal transcription elongation factor hTFIIS C terminus. Given the relative antiquity of the ribosome it is possible that L36 reflects the parent of transcription-related zinc ribbons.

Amino Acid Motifs↗
PubMed2000

Links between Fer tyrosine kinase expression levels and prostate cell proliferation.

In our cloning strategy to identify tyrosine kinases implicated in the regulation of prostate growth, the dog fer cDNA was obtained and shown to be highly homologous to known fer cDNAs. Using a polyclonal Fer antibody directed against a C-terminal peptide, we studied its associations with cortactin, beta-catenin and p120Cas in human prostate carcinoma PC-3 cells. In contrast to previous reports, no interactions were observed. To assess its functional role, fer cDNA constructs were transfected in PC-3 cells. Antisense clones exhibiting a marked diminution of Fer expression had a reduced growth rate (doubling time of 29 vs. 42 h) and were unable to form colonies in soft agar. In agreement with these results, Fer protein expression was linked to human prostatic proliferative diseases, with enhanced levels in extracts from cancer tissues as compared to those from normal and hyperplastic ones, and was also expressed in the human prostate carcinoma cell lines DU145 and LNCaP. In the dog model, Fer expression was up-regulated in dividing versus resting prostate epithelial cells in vitro, and also in vivo when basal cell hyperplasia and metaplasia was induced by estrogen after castration. Minimal effects were observed when renewing the luminal epithelium with androgens. Taken together, these results show that Fer expression is associated with prostate cell proliferation and enhanced in prostate cancer.

Amino Acid Sequence↗
PubMed2000

Gait pattern classification of healthy elderly men based on biomechanical data.

OBJECTIVES: To distinguish the gait patterns of young subjects from those of elderly men using three-dimensional (3D) gait data, to determine if elderly subjects displayed other than a typical gait pattern, and to identify which parameters best describe them. DESIGN: Nonrandomized study in which video and force plate data were collected at the subject's own free walking speed and used in a 3D inverse dynamic model. Cluster analysis was chosen to identify the gait families, and analyses of variance were performed to determine which parameters were different. SETTING: A gait laboratory. PARTICIPANTS: The sample of convenience involved a single but mixed group consisting of 16 able-bodied elderly subjects (mean age, 62yrs) and 16 able-bodied young subjects aged between 20 and 35 years. MAIN OUTCOME MEASURES: Phasic and temporal gait parameters, as well as the 3D muscle powers developed in the joints of the right lower limb during the gait cycle. RESULTS: The walking patterns in elderly subjects were found to be different from those of the young adults. Three elderly gait families or groups forming a specific gait pattern were identified, and differences were found in the phasic and temporal parameters as well as in 6 peak muscle powers. Four of the peak powers occurred in the sagittal plane, and half of them were related to the hip. CONCLUSIONS: Biomechanical parameters can be used to classify the gait patterns of young and elderly men using cluster analysis rather than age alone. The muscle powers in elderly subjects are perturbed throughout the gait cycle and not only at push-off. It appears that the plane in which the peak powers occurred was related to their occurrence in the gait cycle. Variability in the gait patterns of elderly subjects could reflect natural adaptations or compensations. These should not be indicative of a deficient gait or be misconstrued as some age-related pathology.

Adult↗
PubMed2000

Delirium in terminal cancer: a prospective study using daily screening, early diagnosis, and continuous monitoring.

A pilot prospective cohort study was conducted to determine delirium frequency and outcome in cancer patients consecutively hospitalized for terminal care (median stay: 12 days). Screening for delirium symptoms was performed daily, using the Confusion Rating Scale. Patients positive on screening had a diagnostic assessment within 24 hours using the Confusion Assessment Method. Monitoring of symptoms was continued until death. Eighteen (20%) of the 89 study patients were positive on screening at admission. Among the 71 patients free of delirium at admission, the incidence of confirmed delirium was 32. 8% (95% CI, 21.3-44.3%). Patients positive on screening received a higher mean equivalent parenteral daily dose of morphine than other patients (72 mg vs. 41 mg, p = 0.08). Significant symptom improvement occurred in 16 (50%) of the 32 delirious cases. Delirium is a serious and frequent complication in terminal cancer whose outcome may not be as poor as previously considered.

Aged↗
PubMed2000

Symmetry and limb dominance in able-bodied gait: a review.

As one of the most universal of all human activities, gait in the able-bodied has received considerable attention, but many aspects still need to be clarified. Symmetry or asymmetry in the actions of the lower extremities during walking and the possible effect of laterality on gait are two prevalent and controversial issues. The purpose of this study was to review the work done over the last few decades in demonstrating: (a) whether or not the lower limbs behave symmetrically during able-bodied gait; and (b) how limb dominance affects the symmetrical or asymmetrical behavior of the lower extremities. The literature reviewed shows that gait symmetry has often been assumed, to simplify data collection and analysis. In contrast, asymmetrical behavior of the lower limbs during able-bodied ambulation was addressed in numerous investigations and was found to reflect natural functional differences between the lower extremities. These functional differences were probably related to the contribution of each limb in carrying out the tasks of propulsion and control during able-bodied walking. In current debates on gait symmetry in able-bodied subjects, laterality has been cited as an explanation for the existence of functional differences between the lower extremities, although a number of studies do not support the hypothesis of a relationship between gait symmetry and laterality. Further investigation is needed to demonstrate functional gait asymmetry and its relationship to laterality, taking into consideration the biomechanical aspects of gait.

Biomechanical Phenomena↗
PubMed2000

Reduction of gait data variability using curve registration.

Timing in peak gait values shifts slightly between gait trials. When averaged, the standard deviation (S.D.) in gait data may increase due to this inter-trial variability unless normalization is carried out beforehand. The objective of this study was to determine how curve registration, an alignment technique, can reduce inter-subject variability in gait data without perturbing the curve characteristics. Twenty young, healthy men participated in this study each providing a single gait trial. Gait was assessed by means of a four-camera high-speed video system synchronized to a force plate. A rigid body three-segment model was used in an inverse dynamic approach to calculate three-dimensional muscle powers at the hip, knee and ankle. Curve registration was applied to each of the 20 gait trials to align the peak powers. The mean registered peak powers increased by an average of 0.10 +/- 0.13 W/kg with the highest increases in the sagittal plane at push-off. After performing curve registration, the RMS values decreased by 13.6% and the greatest reduction occurred at the hip and knee, both in the sagittal plane. No important discontinuities were reported in the first and second derivatives of the unregistered and registered curves. Curve registration did not have much effect on the harmonic content. This would be an appropriate technique for application prior to any statistical analysis using able-bodied gait patterns.

Adult↗
PubMed2000

Simulations of NMR pulse sequences during equilibrium and non-equilibrium chemical exchange.

The McConnell equations combine the differential equations for a simple two-state chemical exchange process with the Bloch differential equations for a classical description of the behavior of nuclear spins in a magnetic field. This equation system provides a useful starting point for the analysis of slow, intermediate and fast chemical exchange studied using a variety of NMR experiments. The McConnell equations are in the mathematical form of an inhomogeneous system of first-order differential equations. Here we rewrite the McConnell equations in a homogeneous form in order to facilitate fast and simple numerical calculation of the solution to the equation system. The McConnell equations can only treat equilibrium chemical exchange. We therefore also present a homogeneous equation system that can handle both equilibrium and non-equilibrium chemical processes correctly, as long as the kinetics is of first-order. Finally, the same method of rewriting the inhomogeneous form of the McConnell equations into a homogeneous form is applied to a quantum mechanical treatment of a spin system in chemical exchange. In order to illustrate the homogeneous McConnell equations, we have simulated pulse sequences useful for measuring exchange rates in slow, intermediate and fast chemical exchange processes. A stopped-flow NMR experiment was simulated using the equations for non-equilibrium chemical exchange. The quantum mechanical treatment was tested by the simulation of a sensitivity enhanced 15N-HSQC with pulsed field gradients during slow chemical exchange and by the simulation of the transfer efficiency of a two-dimensional heteronuclear cross-polarization based experiment as a function of both chemical shift difference and exchange rate constants.

Flow Injection Analysis↗
PubMed2000

Ansig for Windows: an interactive computer program for semiautomatic assignment of protein NMR spectra.

Assignment of NMR spectra is a prerequisite for structure determination of proteins using NMR. The time spent on the assignment is comparatively long compared to that spent on other parts in the protein structure determination process, but it can be shortened by using either interactive or fully automated computer programs. To benefit from the advantages of both types of program we have developed a version of the interactive assignment program ANSIG to include automatized, yet user-supervised, routines. The new program includes tools for (i) semiautomatic sequential assignment, (ii) plotting of distances from PDB structure files directly in NMR spectra and (iii) statistical analysis of distance restraint violations with the possibility to directly zoom to violated NOEs in NOESY spectra.

Databases, Factual↗
PubMed2000

Two systems for phosphate uptake in Yarrowia lipolytica cells grown at acidic conditions.

Inorganic phosphate (Pi) is accumulated by Yarrowia lipolytica cells grown at acidic pH conditions by two kinetically discrete H+/Pi-cotransport systems with apparent K(m) values for Pi of 12-18 microM and 2-3 mM Pi at pH 5.5, respectively. One of these is derepressible and operates at low external Pi concentrations; the other is most likely constitutively expressed and comes into play at high Pi concentrations. The derepression of the high-affinity Pi transport system is under the control of available extracellular Pi as well as the amount of intracellular polyphosphates stores. Characteristics of the Pi transport behavior in Yarrowia lipolytica are discussed.

Hydrogen-Ion Concentration↗
PubMed2000

P53 point mutations in initial superficial bladder cancer occur only in tumors from current or recent cigarette smokers.

Sequencing of p53 exons 5-8 was carried out on 51 initial superficial bladder tumors selected on the basis of high grade and/or p53 overexpression (immunohistochemistry without antigen retrieval). Fourteen point mutations in 13 tumors and one 21 bp deletion in another tumor were identified. In addition, a germ-line mutation corresponding to a previously described polymorphism was detected in exon 6, in two tumors. Mostly G-->A transitions (10) were found. Only three occurred at CpG sites, suggesting a major role for exogenous carcinogens in bladder tumorigenesis. Immunostaining for p53 and MDM2, using antigen retrieval, was carried out on the same tumors. A correlation was found between the percentage of p53-positive cells and the presence of p53 mutations (P = 0.005). No correlation was found between overexpression of p53 and MDM2 in this selected cohort of mostly high grade tumors. The presence of p53 mutations was also analyzed as a function of the smoking habits of the patients. A significant association was found between the presence of p53 point mutations and the number of years of smoking (P = 0.043). All patients with tumors carrying missense or nonsense p53 mutations had smoked for >/=30 years and if former smokers, had stopped for </=5 years. However, no correlation was found between the presence of p53 point mutations and the number of cigarettes smoked. The deletion mutation was the only one present in a tumor from a non-smoker. The data suggest that duration of exposure to carcinogens is the most critical factor in p53 mutagenesis in bladder cancer.

Genes, p53↗
PubMed1999

[3H]tiagabine binding to GABA uptake sites in human brain.

The binding of [3H]tiagabine ((RS-1-(4,4-(3-methyl-2-thienyl)-3-butenyl)-3-piperidine carboxylic acid) to homogenates of frozen post-mortem human brain has been characterized. Inhibition experiments with gamma-aminobutyric acid (GABA), GABA uptake inhibitors, ligands active at postsynaptic GABA receptors and receptors for other neurotransmitters, suggest that [3H]tiagabine binds with high affinity to GABA uptake sites. Inhibition and kinetic experiments suggests that 70%-80% of the binding is to a high affinity site. Saturation experiments showed that the binding was saturable. Bmax was 3.4 pmol/mg protein and Kd 16 nM in frontal cortex. The dissociation constants (Kd) measured in kinetic and equilibrium experiments were in the same range (16-56 nM). The regional distribution was studied in nine brain regions and the binding was heterogenous, with the highest binding in frontal cortex and parietal cortex and the lowest binding in nucleus caudatus and putamen. This is, to our knowledge, the first study on [3H]tiagabine binding in human tissue. It is concluded that [3H]tiagabine binding can be used as a specific marker for the GABA transporter GAT-1 in homogenates of human brain.

Adult↗
PubMed1999

Solution structure of the ribosomal protein S19 from Thermus thermophilus.

Ribosomal protein S19 is a 10.6 kDa protein in the small subunit of the prokaryotic ribosome. We have determined a high-resolution solution structure of S19 from Thermus thermophilus. Structures were calculated using 1160 distance and dihedral angle restraints derived from (1)H, (15)N and (13)C NMR spectra. The structures show that S19 is a mixed alpha/beta protein with long disordered tails. The folding topology is not homologous to that of any other known protein structure. Potential rRNA and protein binding sites have been identified on the S19 surface.

Binding Sites↗
PubMed1999

A 10-year study of mortality in a cohort of patients with myotonic dystrophy.

OBJECTIVE: To determine the age and causes of death as well as the predictors of survival in patients with myotonic dystrophy (DM). METHODS: In a longitudinal study, a cohort of 367 patients with definite DM was followed for 10 years. RESULTS: During the 10-year period, 75 of the 367 DM patients (20%) died. The mean age at death (53.2 years, range 24 to 81) was similar for men and women. Among these 75 patients, 32 (43%) died of a respiratory problem, 15 (20%) of cardiovascular disease, 8 (11%) of a neoplasia, and 8 (11%) died suddenly. The ratio of observed to expected deaths was significantly increased to 56.6 (95% confidence interval [CI] 38.7 to 78.0) for respiratory diseases, 4.9 (95% CI 2.7 to 7.7) for cardiovascular diseases, and 2.5 (95% CI 1.1 to 4.6) for neoplasms. The mean age at death was 44.7 years for the childhood phenotype of DM, 47.8 years for the early-adult, 55.4 years for the adult, and 63.5 years for the mild phenotype (F = 4.8, p = 0.005). The age-adjusted risk of dying was 3.9 (95% CI 1.3 to 11.0) times greater for a patient with a distal weakness and 5.6 (95% CI 2.2 to 14.4) times greater for a patient with proximal weakness as compared with a person without limb weakness. CONCLUSIONS: Life expectancy is greatly reduced in DM patients, particularly in those with early onset of the disease and proximal muscular involvement. The high mortality reflects an increase in death rates from respiratory diseases, cardiovascular diseases, neoplasms, and sudden deaths presumably from cardiac arrhythmias.

Adolescent↗
PubMed1999

Platelet [3H]paroxetine and [3H]lysergic acid diethylamide binding in seasonal affective disorder and the effect of bright light therapy.

BACKGROUND: Seasonal affective disorder (SAD) has been regarded as a melatonin disorder, but the pathophysiological mechanisms of SAD are to a large extent unclarified. Serotonergic mechanisms have also been studied, but they have shown inconsistent results. METHODS: We have compared [3H]paroxetine and [3H]lysergic acid diethylamide (LSD) binding in platelets from 23 SAD patients and 23 controls. Then SAD patients had 4 weeks of light therapy. On the last treatment day new blood samples were drawn. Symptoms before and after light treatment were measured by SIGH-SAD. RESULTS: Bmax for paroxetine binding before light treatment was higher in SAD patients compared to controls and also higher in responders than in nonresponders. Bmax decreased significantly during light treatment. We also found a negative correlation between the two Bmax values before but not after light treatment. There was a negative correlation between Bmax for paroxetine binding before treatment and clinical status after treatment. Patients with reduced Bmax for LSD binding after treatment had a better clinical treatment response. CONCLUSIONS: The present study indicates that serotonin receptor parameters might be suitable in the prediction of clinical response to light treatment.

Adult↗
PubMed1999

[3H]GBR 12935 binding in platelets from poor and extensive cytochrome P-4502D6 metabolizers.

Previous studies have indicated that part of the binding of [3H] [1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl) piperazine dihydrochloride] ([3H]GBR 12935) to human platelets is to a piperazine acceptor site, which might be associated with cytochrome P-450IID6 (CYP4502D6, debrisoquine-4-hydroxylase). Due to mutant CYP4502D6 alleles, 5-10% of Caucasians are poor metabolizers of CYP4502D6 substrates such as debrisoquine and dextromethorphan. In the present study, possible differences in binding characteristics of [3H]GBR 12935 in platelets from CYP4502D6 poor and extensive metabolizers were investigated. The most prominent finding was a gender difference, with males having significantly higher Kd values than females. There were no differences in Bmax. After correction for gender, there was a tendency towards higher Kd values in poor metabolizers than in extensive metabolizers, although the difference was not statistically significant. Whether this finding corresponds to reduced CYP4502D6 activity is a matter of further investigation.

Adult↗
PubMed1999

[Cyclical intravenous antibiosis as an effective therapy concept in chronic recurrent erysipelas].

The treatment of choice for prevention of recurrent erysipelas is the long-term therapy with intramuscular penicillin. The results are often unsatisfactory. Usually erysipelas recurs when the treatment is stopped. The aim of the present study was to evaluate a new treatment regimen, consisting of intravenous penicillin combined with lymphatic drainage. Fifteen patients who had suffered from three or more episodes of erysipelas within the last two years received 10 Mega I.U. of penicillin per day over ten days every third month over a one year period (patients who were allergic to penicillin received erythromycin). Use of intravenous penicillin was combined with lymphatic drainage performed by a sequential pneumatic compressing device. The treatment results were assessed by clinical examination and laboratory tests as well as by laser Doppler imaging every third month. During the one year treatment period and a further year of follow-up, 14 of 15 patients had no recurrent erysipelas. Only a 65 year old patient suffering from Parkinson heart failure, chronic lymphedema and an extensive stasis ulcers had recurrent erysipelas. The present treatment regimen appears to be an effective therapy for prevention of recurrent erysipelas.

Adult↗