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Biomedical subjects

B Henry

Publications and source records attributed to B Henry.

At least 19 recordsLinked to original sources

Effect of repeated L-DOPA, bromocriptine, or lisuride administration on preproenkephalin-A and preproenkephalin-B mRNA levels in the striatum of the 6-hydroxydopamine-lesioned rat.

Abnormal involuntary movements, or dyskinesias, plague current symptomatic approaches to the treatment of Parkinson's disease. The neural mechanisms underlying the generation of dyskinesia following repeated l-3,4-dihydroxyphenylalanine (L-DOPA) or dopamine agonist administration in Parkinson's disease remain unknown. However, de novo administration of bromocriptine or lisuride to either l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned primates or patients can alleviate parkinsonian symptoms without the development of dyskinesia. In this study, we have investigated behavioral responses and alterations in the expression of opioid neuropeptide precursors preproenkephalin-A (PPE-A, encoding methionine- and leucine-enkephalin) and preproenkephalin-B (PPE-B), the precursor encoding dynorphins (dynorphin A1-17 and B1-13, leucine-enkephalin, and alpha-neoendorphin) in striatal output pathways of the 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease. Expression was assessed following repeated L-DOPA, bromocriptine, or lisuride administration. Given the functional organization of basal ganglia circuitry into anatomically discrete parallel circuits, we investigated alterations in peptide expression with reference to the detailed topography of the striatum. Following repeated L-DOPA administration (6.5 mg/kg, b.d., 21 days) in the 6-OHDA-lesioned rat a rotational response was observed. This became markedly enhanced with repeated treatment. We have previously characterized the pharmacology of this enhanced response and have suggested that it is a useful model for the elucidation of the cellular and molecular mechanisms underlying L-DOPA- and dopamine agonist-induced dyskinesia. In contrast to l-DOPA, de novo administration of bromocriptine (1 or 5 mg/kg, b.d., 21 days) or lisuride (0.01 or 0.1 mg/kg, b.d., 21 days) did not lead to an enhanced behavioral response. In vehicle-treated, 6-OHDA-lesioned animals, PPE-A expression was elevated rostrally and dorsally, while PPE-B expression was reduced in the striatum at all rostrocaudal levels. Repeated l-DOPA administration was accompanied by elevations in striatal PPE-B mRNA levels and a further elevation, above lesion-induced levels, in PPE-A expression. This further elevation was restricted to the dorsolateral striatum. However, following repeated bromocriptine or lisuride administration no increase in PPE-B expression was observed and the lesion-induced increase in PPE-A expression was normalized to prelesion levels. Increased PPE-A and PPE-B levels may, through decreasing GABA and glutamate release, respectively, in output nuclei of the basal ganglia, play a role in the development of L-DOPA- and dopamine-agonist induced dyskinesia in Parkinson's disease. These studies suggest that anti-parkinsonian treatments which are not associated with an elevation in PPE-B and/or normalize elevated PPE-A precursor expression, such as NMDA-receptor antagonists or long-acting dopamine D2 receptor agonists, e.g., cabergoline or ropinirole, may reduce dyskinesia in Parkinson's disease.

Animals

Practice and education of nurse anaesthetists.

A survey was conducted of the anaesthesia services provided by nurses and the education available to them in this field in 107 countries. Among the procedures carried out were general anaesthesia, spinal blocks and tracheal intubation. The implications of the findings for health planning and policy-making are discussed with particular reference to workforce structure and women's involvement in it.

Curriculum

Induction of forward mutations at the thymidine kinase locus of mouse lymphoma cells: evidence for electrophilic and non-electrophilic mechanisms.

A database of 209 chemicals tested for induction of forward mutations at the heterozygous thymidine kinase (TK +/-) locus in L5178Y mouse lymphoma cells was analyzed for structure-activity relationships using the MultiCASE expert system. Consistent with evidence of several contributing biological mechanisms, these studies suggest that such mutations may occur by more than one mechanism. As might be expected, there was evidence for a component involving direct electrophilic attack on the cellular DNA, in a manner previously established as causative in the induction of mutations in Salmonella. In addition, however, there was also strong evidence for another mechanism or mechanisms involving chromosome missegregation, cellular toxicity or an alternate site of action, such as the microtubules.

Animals

Topographical organization of opioid peptide precursor gene expression following repeated apomorphine treatment in the 6-hydroxydopamine-lesioned rat.

Many studies have previously described changes in preproenkephalin-A (PPE-A) and preproenkephalin-B (PPE-B) gene expression in the striatum of the 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (both with or without dopamine replacement treatment). To date, these studies have either taken the striatum as a whole or have focused on a single subregion of the striatum. However, the striatum is organized into anatomically discrete parallel circuits serving different functions (motor, associative, and limbic). We have therefore employed in situ hybridization to examine the detailed topography of changes in opioid precursor expression following dopamine depletion and subsequent treatment with apomorphine (5 mg/kg twice daily for 10 days). In the untreated 6-OHDA-lesioned striatum PPE-A expression was elevated only in the dorsal (sensorimotor) caudate-putamen. Following apomorphine treatment PPE-A mRNA levels were further raised in the sensorimotor striatum (</=77%) and approximately doubled and tripled in the ventral caudate-putamen (associative) and nucleus accumbens (limbic), respectively. These subsequent elevations were mostly restricted to rostral portions of the striatum. Although unchanged following vehicle treatment, PPE-B gene expression in the lesioned caudate-putamen (sensorimotor and associative) was elevated some 30-fold by apomorphine treatment. A smaller rise (fivefold) was seen in rostral regions of the lesioned nucleus accumbens. Thus, differential regulation of opioid peptide transmission exists in motor, limbic, and associative regions of the striatum and may contribute to the generation of motor and cognitive disturbances following long-term treatment of the dopamine-depleted striatum.

Animals

Characterization of enhanced behavioral responses to L-DOPA following repeated administration in the 6-hydroxydopamine-lesioned rat model of Parkinson's disease.

Long-term treatment of Parkinson's disease with dopamine-replacing agents such as L-3,4-dihydroxyphenylalanine (L-DOPA) is compromised by many side-effects, most notably involuntary movements, L-DOPA-induced dyskinesia. Acute challenge with dopamine-replacing drugs elicits a rotational response in the 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease. This rotation is contraversive to the lesion and is considered to represent an antiparkinsonian effect. More recently, it has become clear that the rotational response shows plasticity and that repeated L-DOPA or apomorphine therapy is accompanied by a marked enhancement in this response. In this study, we demonstrate that the enhanced behavioral response to repeated dopamine-replacement therapy seen in the 6-OHDA-lesioned rat has pharmacological characteristics similar to L-DOPA-induced dyskinesia seen in MPTP-lesioned primates and man. Thus, the magnitude and rate of development of the enhanced response to L-DOPA treatment is related to both the number of doses and the size of the dose of L-DOPA administered. In contrast, de novo administration of dopaminergic drugs that are associated with a lower incidence of dyskinesia, e.g., bromocriptine or lisuride, does not lead to an enhanced behavioral response following repeated treatment. However, following a single "priming" administration of apomorphine, the rotational response elicited by subsequent bromocriptine administrations is enhanced with repeated treatment. Once established, the enhanced behavioral response to repeated L-DOPA-administration (6.5 mg/kg, twice daily) can, like L-DOPA-induced dyskinesia in man and MPTP-treated monkeys, be selectively reduced by coadministration of L-DOPA with the alpha2-adrenergic receptor antagonist yohimbine (10 mg/kg, -95%), the 5-HT uptake inhibitor 5-MDOT (2 mg/kg, -90%), or the beta-adrenergic receptor antagonist propranalol (10 mg/kg, -35%). While these rats do not exhibit symptoms of dyskinesia per se, this rodent model does exhibit behaviors, the underlying mechanism of which is likely to be similar to that underlying L-DOPA-induced dyskinesia and may prove useful in studying the molecular and cellular mechanisms of L-DOPA-induced dyskinesia in Parkinson's disease.

Adrenergic alpha-Agonists

Hot particle detection using uncertainties in activity measurements of soil.

The uncertainty in gamma spectroscopic activity measurements is investigated for soil containing hot particles. A radioactivity inhomogeneity uncertainty needs to be taken into account, which depends on the density of hot particles in the sample geometry, the distribution of their activities, and the specific source-detector geometry. The maximum activity error due to hot particles in our sampled Chernobyl soil with a 137Cs activity of 100 kBq kg(-1) soil was 6% for our source detector geometry. The methodology presented might have a practical application in nuclear power plants to detect hot particles in a large quantity of dust or dirt. The number of hot particles present can be estimated if the activity of all particles is assumed to be similar. With this assumption 100 g of the investigated soil sample would contain about 500 hot particles with an approximate activity of 20 Bq each.

Computer Simulation

Analysis of respiratory chain regulation in roots of soybean seedlings

Changes in the respiratory rate and the contribution of the cytochrome (Cyt) c oxidase and alternative oxidase (COX and AOX, respectively) were investigated in soybean (Glycine max L. cv Stevens) root seedlings using the 18O-discrimination method. In 4-d-old roots respiration proceeded almost entirely via COX, but by d 17 more than 50% of the flux occurred via AOX. During this period the capacity of COX, the theoretical yield of ATP synthesis, and the root relative growth rate all decreased substantially. In extracts from whole roots of different ages, the ubiquinone pool was maintained at 50% to 60% reduction, whereas pyruvate content fluctuated without a consistent trend. In whole-root immunoblots, AOX protein was largely in the reduced, active form at 7 and 17 d but was partially oxidized at 4 d. In isolated mitochondria, Cyt pathway and succinate dehydrogenase capacities and COX I protein abundance decreased with root age, whereas both AOX capacity and protein abundance remained unchanged. The amount of mitochondrial protein on a dry-mass basis did not vary significantly with root age. It is concluded that decreases in whole-root respiration during growth of soybean seedlings can be largely explained by decreases in maximal rates of electron transport via COX. Flux via AOX is increased so that the ubiquinone pool is maintained in a moderately reduced state.

Journal Article

Survey of nurse anesthesia practice, education, and regulation in 96 countries.

In Phase I of this international study, we systematically identified, for the first time, that nurses were providing anesthesia services in more than 100 countries, which is about 60% of all member states of the World Health Organization. The purpose of Phase II reported here, was to describe nurse anesthesia practice, education, and regulation in those countries. Data were collected from 96 countries, in all world regions, and at four levels of development, then were analyzed for commonalties and differences. It was found that the use of nurses to provide anesthesia is not related to a country's level of development; nurses provide anesthesia in two thirds of developed, developing, and least developed countries, working with or without anesthesiologists. They perform all the critical tasks required in the administration of anesthesia. Nurse anesthetists worldwide are making a significant contribution to health. These data can serve as a basis for future decisions about human, fiscal, and government resources required to make anesthesia services available to each country's population. They can also provide opportunity to identify educational requirements to assure the safety and well-being of patients worldwide requiring anesthesia services.

Cross-Sectional Studies

Accuracy and safety of laparoscopic lymphadenectomy: an experimental prospective randomized study.

INTRODUCTION: The goal of this study was to investigate the accuracy and safety of bilateral pelvic and paraaortic lymphadenectomy performed via transperitoneal laparoscopy (LS) compared to laparotomy (LT) in a porcine model. MATERIALS AND METHODS: Fifteen adult, female hogs underwent LS and 15 underwent LT. A complete pelvic and paraaortic lymphadenectomy was performed in each animal by an experienced surgeon. Lymph nodes were counted by a pathologist in each case. Operative times were reviewed and included all procedures performed. The intraoperative complications were noted. Four weeks after the lymphadenectomy, the animals underwent exploratory laparotomy, and intraperitoneal adhesions were quantified. RESULTS: Thirty animals were evaluable. The average total number of lymph nodes retrieved by LS was 16.9 +/- 3.8, which was not statistically (P = 0.77) different from 16.5 +/- 4.9 nodes in LT. The average operating time in LT was 60 +/- 16 min compared with 128 +/- 24 min in LS. Twenty-eight animals were evaluable for adhesion formation. The average adhesion scores observed in anterior abdominal wall (P = 0.0006), paraaortic (P = 0.0005), right (P = 0.015), and left (P = 0.0324) iliac areas after LS were uniformly lower than after LT. DISCUSSION: This study indicates that laparoscopic pelvic and paraaortic lymphadenectomy is a safe and effective procedure. The node yield is similar for both approaches. The transperitoneal laparoscopy pelvic and paraaortic lymphadenectomy may not induce the degree of adhesion formation associated with laparotomy.

Animals

Construction and validation of a quality of life questionnaire in chronic lower limb venous insufficiency (CIVIQ).

Quality of life may be considerably reduced in patients who are suffering from chronic lower limb venous insufficiency, although existing generic quality of life instruments (NHP, SF-36 or SIP) cannot completely identify their specific complaints. The Chronic Venous Insufficiency Questionnaire (CIVIQ) has been developed by iterative process. First, a pilot group of 20 patients was used to identify a number of important features of quality of life affected by venous insufficiency, other than physical symptoms of discomfort. A second study involving 2,001 subjects was used to reduce the number of items. Subjects were asked to score both the severity of their problems and the importance they attributed to each problem on a 5-point Likert scale. The importance items found in patients with venous insufficiency were subjected to factorial analyses (PCA, PAF). The final version is a 20-item self-administered questionnaire which explores four dimensions: psychological, physical and social functioning and pain. Internal consistency of the questionnaire was validated for each dimension (Cronbach's alpha > 0.820 for three out of four factors). Reproducibility was confirmed in a 60 patient test-retest study. Pearson's correlation coefficients for both the four dimension subscales and for the global score at 2-week intervals were greater than 0.940. Finally, the questionnaire was tested in a randomized clinical trial of 934 patients in order to assess responsiveness and the convergent validity of the instrument, together with the patient's own quality of life. This study demonstrated that convergence was valid: Pearson's correlation coefficients between clinical score differences and quality of life score differences were small (from 0.199-0.564) but were statistically different from 0 (p < 0.001). Standardized response mean (SRM) and effect size (ES) were calculated to assess sensitivity to change. SRM and ES both demonstrated considerable responsiveness to change (> 0.80). Reliability, face, content, construct validity and responsiveness were also determined for this specific quality of life questionnaire relating to venous insufficiency. Results suggest that this questionnaire may be used with confidence to assess quality of life in clinical trials on chronic venous insufficiency.

Factor Analysis, Statistical

Potential of opioid antagonists in the treatment of levodopa-induced dyskinesias in Parkinson's disease.

Current treatments for Parkinson's disease (PD) rely on dopamine-replacing strategies, and centre around dopamine precursors (e.g. levodopa) or directly acting dopamine agonists. With long-term therapy these agents lose much of their clinical utility due to the appearance of adverse effects such as dyskinesias and/or a wearing off of efficacy. Although dyskinesias in Huntington's disease, hemiballism and experimental animals are thought to be associated with reductions in amino acid transmission within the lateral and medial segments of the globus pallidus, the neural mechanisms underlying treatment-related dyskinesias in PD are poorly understood. Recent evidence suggests that, within these regions of the brain, the opioid peptides enkephalin and dynorphin, acting at delta and kappa opioid receptors, respectively, can reduce the release of amino acid transmitters. Furthermore, the synthesis of these peptides appears to be enhanced in neurons projecting to the pallidal complex in animal models of PD following repeated treatment with dopamine-replacing agents that also cause dyskinetic adverse effects (e.g. levodopa and apomorphine). In contrast, dopamine receptor agonists such as bromocriptine and lisuride do not cause dyskinetic adverse effects following long-term treatment, and do not elevate peptide synthesis when given de novo. These data, together with recent data on the behavioural effects of opioid antagonists in a rodent model of levodopa-induced dyskinesia in PD, suggest the possibility that antagonists of opioid receptors may prove useful as adjuncts to levodopa. By limiting the severity of dyskinetic adverse effects, these drugs may help extend the time for which the antiparkinsonian effects of such compounds can be usefully exploited.

Animals

A cost-utility analysis of second-line chemotherapy in metastatic breast cancer. Docetaxel versus paclitaxel versus vinorelbine.

The aim of this study was to determine the incremental effectiveness, the incremental health-related quality of life (differences in quality-adjusted progression-free survival between treatments), the incremental cost and the incremental cost-effectiveness and cost-utility ratios, for docetaxel, paclitaxel and vinorelbine, when these drugs were used as second-line treatment in patients with metastatic breast cancer. In the absence of comparative direct evidence of the relative efficacy of docetaxel, paclitaxel and vinorelbine in this setting, a model was designed to determine the effects of the 3 interventions on health outcome and cost. A Markov process model, based on 53 disease states, was thus constructed to evaluate the socioeconomics of the 3 treatment regimens. The model allows assessments from the start of second-line chemotherapy until death. Costs were evaluated from the combined view of the healthcare system and the patient. Direct nonmedical and indirect costs were excluded. Consumption per episode of care was estimated by retrospective analysis of 153 medical reports from 5 different hospitals. Hospital costs were allocated values from the national accounting costs by diagnosis-related group (DRG). The content of the health states was based on the multiattribute health states classification system (MASH). Preference values were assigned by application of a standard reference lottery using 20 oncological nurses as proxies for the patients. The health-related quality-of-life score was used as a quality adjustment weighting factor to calculate quality-adjusted progression-free survival associated with the 3 different regimens. Docetaxel reduces the time spent in progression, decreases the number of complications due to progressive disease and thereby provides better quality of life. It provides a benefit of 57 disease- and discomfort-free days compared with vinorelbine and 22 days compared with paclitaxel. Docetaxel may be thought of as self-financing as a result of savings in hospital admissions, providing net savings of 6800 French francs (FF; 1993 values) compared with expenditure associated with vinorelbine treatment and FF700 compared with the equivalent figures for paclitaxel.

Antineoplastic Agents

Countries where anesthesia is administered by nurses.

Nurse anesthetists make significant contributions to healthcare worldwide. A little known fact is that, in many countries of the world, nearly all anesthesia is provided by nurses. This international survey, in five languages, was done to provide information about nurse anesthesia care delivered in countries in the regions of the world designated by the World Health Organization. Phase I, reported here, of a three-phase project, determined that nurses administer anesthesia in at least 107 of the world's nearly 200 countries. They administer anesthesia in developed, developing, and least developed countries, as well as in all regions of the world. A goal of disseminating data in this article is to further validate these 1992-1994 study findings. Readers are encouraged to contact the authors with follow-up information. Support for the study was provided by the American Association of Nurse Anesthetists, Council on Recertification of Nurse Anesthetists, and the International Federation of Nurse Anesthetists.

Anesthesiology

Temperamental origins of child and adolescent behavior problems: from age three to age fifteen.

We assessed relations between early temperament and behavior problems across 12 years in an unselected sample of over 800 children. Temperament measures were drawn from behavior ratings made by examiners who observed children at ages 3, 5, 7, and 9. Factor analyses revealed 3 dimensions at each age: Lack of Control, Approach, and Sluggishness. Temperament dimensions at ages 3 and 5 were correlated in theoretically coherent ways with behavior problems that were independently evaluated by parents and teachers at ages 9 and 11, and by parents at ages 13 and 15. Lack of Control was more strongly associated with later externalizing behavior problems than with internalizing problems; Approach was associated with fewer internalizing problems among boys; and Sluggishness was weakly associated with both anxiety and inattention, especially among girls. Lack of Control and Sluggishness were also associated with fewer adolescent competencies. These results suggest that early temperament may have predictive specificity for the development of later psychopathology.

Adolescent