[A prospective comparison of octylcyanoacrylate tissue adhesive and conventional wound closure].
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Cyanoacrylates↗
Biomedical subjects
P Allard
Publications and source records attributed to P Allard.
How effective are supplementary doses of opioids for dyspnea in terminally ill cancer patients? A randomized continuous sequential clinical trial.
Supplementary doses of opioids are recommended to relieve dyspnea in terminally ill cancer patients. We conducted a randomized continuous sequential clinical trial to evaluate their efficacy. We recruited 33 terminally ill cancer patients from three palliative care centers, all of whom had persistent dyspnea after rest and treatment with oxygen. Patients formed 15 successive pairs matched on route of administration. Within each pair, the order of allocation was randomly assigned, one patient receiving 25%, the other 50% of his 4-hourly opioid dose. Five measurements of dyspnea intensity and respiratory frequency were made during 4 hours of follow-up. For each pair, a preference was attributed to the more effective regimen. The two regimens received an almost equal number of paired preferences (8 vs. 7). Overall, both mean dyspnea intensity and respiratory frequency decreased significantly relative to baseline. Dyspnea reduction was relatively greater in patients with initially low and moderate dyspnea intensity. In terminally ill cancer patients with persistent dyspnea, 25% of the equivalent 4-hourly dose of opioid may be sufficient to reduce both dyspnea intensity and tachypnea for 4 hours.
Analgesics, Opioid↗
Binding of [(3)H]lysergic acid diethylamide to serotonin 5-HT(2A) receptors and of [(3)H]paroxetine to serotonin uptake sites in platelets from healthy children, adolescents and adults.
Possible age effects on binding of [(3)H]lysergic acid diethylamide ([(3)H]LSD) to serotonin 5-HT(2A) receptors and of [(3)H]paroxetine to serotonin uptake sites were studied in platelets from healthy children (11-12 years of age), adolescents (16-17 years of age) and adults. Significant overall age effects were found both for the number of binding sites (B(max)) for [(3)H]LSD binding (p < 0.001), the affinity constant (K(d)) for [(3)H]LSD binding (p < 0.001), B(max) for [(3)H]paroxetine binding (p < 0.001) and K(d) for [(3)H] paroxetine binding (p = 0.006). In general, there was a decrease in B(max) with increasing age, which predominantly occurred between the ages 11-12 years and 16-17 years for the 5-HT(2A) receptor, and after 16-17 years of age for the serotonin uptake site. These developmental changes might have an impact on the effect of treatment with serotonergic drugs in children and adolescents. When the platelet serotonin variables investigated are employed in studies in children or adolescents, age matching or, alternatively, introduction of age control in the statistical analysis should be performed.
Adolescent↗
Predictive value of cell cycle markers p53, MDM2, p21, and Ki-67 in superficial bladder tumor recurrence.
The aim of the study was to determine whether the expression of the cell cycle markers p53, MDM2, p21, and Ki-67 was predictive of superficial bladder cancer recurrence and to compare the relative predictive power for tumor recurrence of a cell cycle index based on the number of abnormally expressed cell cycle markers with a clinicopathological index based on primary clinical tumor characteristics. The expression of p53, MDM2, and p21 proteins and the value of the Ki-67 index were analyzed for 244 patients. One hundred ninety-four lesions were determined to be superficial papillary tumors (pTa), whereas 50 tumors invaded the lamina propria (pT1). Tumor grade was noted low (grade 1) in 83 cases and high (grades 2-3) in 161 cases. An avidin-biotin peroxidase method was performed using monoclonal antibodies against p53, MDM2, p21, and Ki-67 antigens after antigen retrieval treatment of formalin-fixed specimens. The cell cycle marker index was created using the number of abnormally expressed cell cycle markers according to the following cutoff points: p53 (>5%), MDM2 (>20%), p21 (<5%), and Ki-67 (>10%). The clinicopathological index was created using the following adverse tumor characteristics: grades G2-G3, stage pT1, multifocality, and diameter of tumors > 3 cm. Cox regression models were used to calculate the relative risks and their 95% confidence intervals associated with disease recurrence for the clinicopathological index and the cell cycle marker index. The chi2 test was performed to describe the correlation between the Ki-67 index and p53, MDM2, and p21 protein expression. Kaplan-Meier survival curves were generated to demonstrate the disease-free survival according to these two prognostic indexes. The clinicopathological index was a strong, independent predictor of disease recurrence where tumors with three or four adverse tumor characteristics at initial resection had over four times the risk of recurrence than tumors with no risk factors (P for trend = 0.0001). A strong correlation was observed between the Ki-67 index >10% and both MDM2 and p21 proteins. MDM2 was overexpressed in 106 tumors (43%), and p53 was overexpressed in 47 (19%); Ki-67 was >10% in 171 cases (70%). Thirty-nine tumors (16%) were p21 negative. The risk of recurrence increased slightly with the number of abnormally expressed cell cycle markers, but when the clinicopathological index was taken into account in multivariate analysis, the cell cycle marker index was not predictive of disease recurrence (P for trend = 0.72). The cell cycle markers studied provided no added prognostic information on disease recurrence after initial resection of papillary superficial tumors when the clinicopathological parameters were taken into account.
Aged↗
Circannual variations in the binding of [3H]lysergic acid diethylamide to serotonin2A receptors and of [3H]paroxetine to serotonin uptake sites in platelets from healthy volunteers.
BACKGROUND: Circannual variations occur in several serotonergic parameters, including platelet serotonin uptake and platelet [3H]imipramine binding. METHODS: Binding of [3H]lysergic acid diethylamide ([3H]LSD) to platelet serotonin (5-HT)2A receptors and binding of [3H]paroxetine to platelet serotonin uptake sites were studied longitudinally for 1 year in 12 healthy volunteers. RESULTS: For [3H]LSD, the number of binding sites (Bmax) showed no significant seasonal variation (two-way analysis of variance), although Bmax was significantly higher during the months October through February than during the months April through August (32.6 vs. 29.8 fmol/mg protein; p = .015). For [3H]paroxetine, Bmax showed a significant seasonal variation (p = .003) with maximum in August (1322 fmol/mg protein) and minimum in February (1168 fmol/mg protein). The affinity constant (Kd) showed a significant seasonal variation for [3H]LSD binding (p = .046), but not for [3H]paroxetine binding. The seasonal fluctuations in [3H]LSD binding and in paroxetine binding tended to be inversely correlated for Bmax (r = -.70; p = .08) and were significantly negatively correlated for Kd (r = -.88; p = .009). CONCLUSIONS: The present study demonstrates a seasonal effect on platelet serotonin uptake site binding and indicates a possible seasonal effect on 5-HT2A receptor binding. The results imply that circannual fluctuations should be taken into account when these platelet serotonin markers are studied.
Adult↗
Solution structure of the SH3 domain from Bruton's tyrosine kinase.
X-linked agammaglobulinemia (XLA) is a heritable immunodeficiency caused by mutations in the gene coding for Bruton's tyrosine kinase (Btk). Btk belongs to the Tec family of tyrosine kinases. Each member of the family contains five regions and mutations causing XLA have been isolated in all five regions. We have determined the solution structure of the Src homology 3 (SH3) domain of Btk using two- and three-dimensional nuclear magnetic resonance (NMR) spectroscopy on natural abundance and 15N-labeled protein material. The structure determination is complemented by investigation of backbone dynamics based on 15N NMR relaxation. The Btk SH3 forms a well-defined structure and shows the typical SH3 topology of two short antiparallel beta-sheets packed almost perpendicular to each other in a sandwich-like fold. The N- and C-termini are more flexible as are peptide fragments in the RT and n-Src loops. The studied Btk SH3 fragment adopts two slowly interconverting conformations with a relative concentration ratio of 7:1. The overall fold of the minor form is similar to that of the major form, as judged on the basis of observed NOE connectivities and small chemical shift differences. A tryptophan (W251) ring flip is the favored mechanism for interconversion, although other possibilities cannot be excluded. The side chain of Y223, which becomes autophosphorylated upon activation of Btk, is exposed within the potential SH3 ligand binding site. Finally, we compare the present Btk SH3 structure with other SH3 structures.
Agammaglobulinaemia Tyrosine Kinase↗
The complete homogeneous master equation for a heteronuclear two-spin system in the basis of cartesian product operators
The complete homogeneous form of the quantum mechanical master equation for a heteronuclear two-spin system is presented in the basis of Cartesian product operators. The homogeneous master equation is useful since it allows fast, single-step computation of the density operator during pulse sequences, without neglecting relaxation effects. The homogeneous master equation is also a prerequisite for an expansion of the average Hamiltonian theory to include relaxation, thus forming average Liouvillian theory. The coherences of the two-spin system are assumed to be relaxed both by mutual dipole-dipole interaction and by chemical shift anisotropy interaction with the static magnetic field. The cross-correlation between dipole-dipole and chemical shift anisotropy relaxation mechanisms is also considered. To illustrate the applicability of the developed formalism we simulate the overall transfer efficiency of three different inverse detection 1H-15N correlation experiments with parameters corresponding to a large protein. Copyright 1998 Academic Press.
Journal Article↗
The early clinical course of primary Ta and T1 bladder cancer: a proposed prognostic index.
OBJECTIVE: To develop a simple prognostic index for anticipating more precisely the early clinical course of primary superficial bladder cancer. PATIENTS AND METHODS: The prognostic value of patient and tumour characteristics was examined in 333 patients with primary Ta or T1 bladder cancer who participated in a multicentre prospective study already completed. Primary tumour multiplicity, a diameter of > 3 cm, stage T1, and grade 2 or 3 were independent predictors of earlier recurrence in a multivariate analysis. A simplified prognostic index consisted of the number of adverse tumour characteristics (ATCs) initially present. RESULTS: After a median follow-up of 35.3 months, the 60 patients free of ATCs (19%) had a recurrence-free probability at 12 and 24 months of 86% and 69%, respectively, and none experienced progression. Recurrence outcomes deteriorated consistently as the number of ATCs increased among the other three groups. In patients with 3-4 ATCs, the 12- and 24-month recurrence-free probability was as low as 30% and 19%, and recurrence and tumour rates were about 2.6 times higher than in patients free of ATCs; 7% of these patients experienced progression within 35 months of follow-up. CONCLUSION: A prognostic index based on the number of ATCs (primary tumour multiplicity, diameter > 3 cm, stage T1, and grade 2 or 3) is a strong indicator of the clinical course of superficial bladder cancer within 3 years of the first endoscopic resection. This proposal is suggested for discussion and for validation in future studies but if confirmed, this simple prognostic index may greatly help to identify indicators for adjuvant intravesical therapy and to determine the optimal periodicity of control cystoscopy regimens.
Adult↗
Physiological regulation of the derepressible phosphate transporter in Saccharomyces cerevisiae.
The extracellular phosphate concentration permissive for the expression of different amounts of the active high-affinity Pho84 phosphate transporter in the plasma membrane as well as the PHO84 messenger RNA levels in low-phosphate-grown Saccharomyces cerevisiae cells is very narrow and essential for a tight regulation of the transporter. The Pho84 transporter undergoes a rapid degradation once the supply of phosphate and/or carbon source is exhausted.
Carrier Proteins↗
Is spa therapy cost-effective in rheumatic disorders?
OBJECTIVE: To evaluate the cost-effectiveness of spa therapy for rheumatic diseases and sequelae of bone and joint injuries. PATIENTS AND METHODS: A prospective randomized, case-control design was used with health care cost reimbursements during the year before and after spa therapy as the measure of efficacy. Spa therapy is reimbursed by the national health insurance system in France, subject to prior agreement. The 220 patients who filed applications for spa therapy with the national health insurance payment center for northern France during the first half of 1994 were included in the study. Seventy-two patients met national health insurance system criteria for spa therapy (Group 1), the remaining 148 patients were assigned at random to spa therapy (Group 2, n = 74) or no spa therapy (Group 3, n = 74). This method allowed us to avoid selection bias during recruitment of our control group. RESULTS: Perceived morbidity was evaluated based on health care utilization, expressed as numbers of health care investigations or procedures and as days of medication use in mean recommended dosages. Health care cost reimbursements by the national health insurance system failed to decrease during the year after spa therapy, and increased in those patients who had already received spa therapy on one or more occasions. Only in the first-ever spa patients were decreases in health care utilization in the area of rheumatology seen during the year after spa therapy; the largest decreases were for use of nonsteroidal antiinflammatory drugs (from 49 to 26 days) and muscle relaxants. No differences in health care utilization were found in patients who had received spa therapy on at least one other occasion. Also, when criteria for spa therapy were not met, no differences in health care utilization were found between patients who did and did not receive spa therapy. CONCLUSION: These data suggest that current national health insurance policies regarding the reimbursement of spa therapy need to be reevaluated.
Age Factors↗
[3H]GBR 12935 binding in platelets: a possible association with cytochrome P-450IID6?
The nature of [3H] (1-[2-(diphenylmethoxy)ethyl)-4-(3-phenylpropyl) piperazine dihydrochloride) (GBR 12935) binding to human platelets was investigated. A common property of the inhibitors of this binding was their association with the cytochrome P-450 system. cis-Flupenthixol and (1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-[3-phenylpropyl) piperazine dihydrochloride) (GBR 12909) biphasically inhibited the binding. The fraction of [3H]GBR 12935 binding that was inhibited by low concentrations of cis-flupenthixol was sensitive to protease treatment. [3H]GBR 12935 binding in this fraction was saturable and of high affinity (Kd 4.5 nM). The present results reveal that [3H]GBR 12935 binds to multiple sites in platelets and suggest that part of the binding is associated with cytochrome P-450IID6.
Antipsychotic Agents↗
Estradiol activates p60src, p53/56lyn and renatured p50/55 protein tyrosine kinases in the dog prostate.
Protein tyrosine kinases (PTKs) are key enzymes implicated in signal transduction pathways regulated by growth factors (GFs). We have previously shown by immunohistochemistry that the level of phosphotyrosine (pY) proteins is increased in prostatic basal epithelial cells following estrogen treatment in castrated dogs. In this study, we investigated if this treatment increases the level and distribution of prostatic PTK activity, and more specifically, if it alters the expression and/or activity of the Src family members p60src and p53/56lyn. Prostates from normal and hyperplastic dog prostates, as well as those from castrated dogs treated with androgens, were also examined. Only the glands obtained from estrogen-treated dogs had a significantly increased total and specific PTK activity, observed uniquely in the particulate extract, as compared to the other types of prostates studied. In addition, this increased activity was correlated upon gel filtration chromatography with the presence of an additional peak of activity with an apparent molecular weight of 130 kDa, which was absent in other prostate fractions presenting only 50 kDa peaks. Using antibodies, we demonstrate that active p60src and pp53/56lyn kinases accounted for 81% of the activity in this 130 kDa peak. On the other hand, in situ renaturation also revealed the presence of still uncharacterized 50/55 kDa PTKs in the 130 kDa peak. Altogether, these findings raise the possibility that these PTKs contribute to the transmission of mitogenic signals originating directly or indirectly from estrogen stimulation of the basal cell layer of the prostate.
Animals↗
NMR Relaxation Mechanisms for Backbone Carbonyl Carbons in a 13 C, 15 N-Labeled Protein
The predominant relaxation mechanisms for backbone carbonyl carbon (13 C') relaxation in a 13 C, 15 N-doubly enriched sample of the thermostable Sso7d protein have been investigated. Pulse sequences for measurements of longitudinal and transverse 13 C' relaxation rates were implemented, and these rates were measured at magnetic fields of 11.7 and 14.1 T. The field dependence in measured rates is small and consistent with a predominant contribution from chemical-shift anisotropy (CSA) to 13 C' relaxation. A pulse sequence for measurement of {1 H}-13 C' cross-relaxation rates (steady-state NOEs) was also developed. This experiment reveals a significant NOE between protons and all 13 C', indicating that dipolar interactions between these nuclei contribute to 13 C' relaxation. Experiments designed to suppress cross correlation between CSA relaxation and dipole-dipole (DD) relaxation due to neighboring 13 Calpha indicate that this effect is negligible. A more quantitative treatment is also presented, in which backbone dynamics parameters are fitted to average 13 C' relaxation rates using Lipari-Szabo expressions for the spectral density. This fit, which reproduces well expected backbone dynamics parameters for a folded protein, is used to estimate the relative contributions of various mechanisms to 13 C' relaxation. It is found that both longitudinal and transverse relaxation rates are dominated by CSA relaxation and contain significant contributions due to DD relaxation induced by nearby protons. Contributions from DD relaxation due to covalently bound 13 Calpha and 15 N are comparably small. The predominant effects of CSA and 1 H-13 C' DD interactions, for which physical and geometrical parameters are uncertain, complicate the use of 13 C' relaxation as a sequence-specific probe for protein backbone dynamics.
Journal Article↗
A method for simulation of NOESY, ROESY, and off-resonance ROESY spectra
A formalism is proposed for simulation of NOESY, ROESY, and, more specifically, off-resonance ROESY nuclear magnetic resonance spectra. The off-resonance ROESY experiment has several advantages compared to standard NOESY and ROESY experiments. A simplified formalism which allows rapid computer simulation of the development of magnetization, including relaxation, in the presence of an RF field is of general use, in particular in the implementation and interpretation of off-resonance ROESY experiments. The relevant matrix equations can be derived either from the classical Bloch and Solomon equations or from the quantum mechanical homogeneous master equation in the basis of the Cartesian product operators. Examples of simulated spectra and behavior of magnetization during pulse sequences are shown. In addition, we present the full quantum mechanical theory for a two-spin system derived from the homogeneous master equation. The proposed formalism, here applied to off-resonance ROESY, has many potential applications, e.g., in the development and analysis of ROESY and TOCSY mixing sequences, selective pulses, and decoupling in which the complete spin dynamics, including relaxation, is taken into account. Copyright 1997 Academic Press. Copyright 1997Academic Press
Journal Article↗
Unchanged density of caudate nucleus dopamine uptake sites in depressed suicide victims.
In depressive states, theories concerning serotonin and norepinephrine have been dominating, but there are several lines of evidence indicating the involvement of the dopamine system as well, especially in suicidal depression. In this post-mortem study, the binding of the ligand [3H]WIN 35,428 to dopamine uptake sites in the caudate nucleus was investigated in 13 depressed suicide victims and 19 controls. There were no differences in Bmax or Kd between the suicide group and controls. Subdividing the suicide group into subgroups regarding the presence of major depression, antidepressant medication and suicide method, respectively, did not yield any differences. Previous findings regarding reduced CSF HVA in suicidal depression and indications of striatal dopaminergic biochemical and receptor changes in depression seem, according to the present study, not to be reflected by alterations in density or affinity of dopamine uptake sites in depressed suicide victims.
Adult↗
Three-dimensional joint moments analysis in a vertical quadrupedal posture associated with a leg release.
This study reports on rock climbers biomechanical adjustments following a leg release from a quadrupedal vertical initial stance. Six climbers of international level have been studied. They were asked to maintain a quadrupedal posture on artificial holds equipped with strain gauges and then to release their right foot. The results show that all the rock climbers adjust differently the vertical forces and the horizontal forces on the holds. They distribute the vertical forces over the three remaining holds and the horizontal forces over the controlateral holds. A quasi-static three-dimensional multi-segment model was used to produce the net reaction forces and joint moments at each joint. Moment results enhance the role of the controlateral limbs, particularly the left leg. The gravity seems to be counteracted at the left knee joint, while body balance seems to be managed at the left hip and ankle joints.
Adult↗
Foot position awareness in younger and older men: the influence of footwear sole properties.
OBJECTIVES: To test the hypotheses that foot position awareness is related positively to stability, positively to shoe sole hardness, and negatively to shoe sole thickness, and that foot position awareness declines with advancing years. SETTING: Older subjects were consecutive volunteers from a medical clinic; younger subjects were volunteers from the community. DESIGN: Randomized-order, cross-over, controlled comparison. PARTICIPANTS: Older subjects were a random sample of 13 healthy men, mean age 72.58 years, SD +/- 4.50. Younger subjects were a random sample of 13 male subjects from the general population, mean age 28.13 years, SD +/- 3.96. Additional selection criteria were absence of disabilities influencing ability to walk and no history of frequent falls. MEASUREMENTS: Balance failure frequency, defined as falls per 100 meters of beam walking; rearfoot angle in degrees, measured via an optical position measurement system; perceived maximum supination when walking, in degrees, estimated by subjects using a ratio scale; foot position error, in degrees, was defined as the rearfoot angle minus perceived maximum supination. RESULTS: Foot position error during walking: (1) increases with advancing years; footwear conditions absolute mean error for older sample of 15.48 degrees, SE +/- 1.56 degrees, and younger sample 5.44 degrees, SE +/- 1.03 degrees (P > .001); (2) is positively related to stability (r = .367, P < .001); (3) is positively related to midsole thickness (F(1,11) = 19.89, P < .001); (4) is negatively related to midsole hardness (F(2,22) = 29.80, P < .001); (5) correlates best with perceived maximum supination (r = .901, P < .001). CONCLUSION: Foot position awareness is related causally to stability; shoes with thin, hard soles provide better stability for men than those with thick, soft midsoles. Foot position awareness declines with advancing years.
Adult↗
GABA uptake sites in frontal cortex from suicide victims and in aging.
The binding of [3H]nipecotic acid to GABA uptake sites was studied in post mortem human frontal cortex from 17 suicide victims and 21 controls without known neurological or psychiatric disorder. The suicide victims were subclassified according to the use of violent or non-violent methods and to the presence or absence of a known history of a depressive disorder. No difference was found between the suicide victims and the controls with regard to [3H]nipecotic acid binding to GABA uptake sites (Bmax) and apparent affinity (Kd). No differences were found either with regard to method of suicide or whether a depressive symptom existed or not. The binding of [3H]nipecotic acid to GABA uptake sites was also studied in post mortem human frontal cortex with regard to aging. The age of the subjects ranged from 16 to 84 years. No significant difference in either Bmax or Kd was found. The present findings suggest that the GABA uptake sites in the human frontal cortex are not subjected to regulation or degenerative changes in conditions investigated.
Aged↗