Search PubMed⌕ Search

Biomedical subjects

A Becker

Publications and source records attributed to A Becker.

At least 109 records · Page 6Linked to original sources

Long-term anticonvulsant therapy leads to low bone mineral density--evidence for direct drug effects of phenytoin and carbamazepine on human osteoblast-like cells.

Anticonvulsant therapy causes changes in calcium and bone metabolism and may lead to decreased bone mass with the risk of osteoporotic fractures. The two widely used antiepileptic drugs phenytoin and carbamazepine are recognized to have direct effects on bone cells. The aim of our study was to measure the influence of long-term treatment with antiepileptic drugs on bone mineral density (BMD) and to look on direct effects of carbamazepine and phenytoin on human osteoblast-like cells. BMD was measured by dual-energy X-ray absorptiometry. Markers of bone formation and bone resorption were determined in serum and urine. Data of 59 patients were compared to 55 age and sex matched controls. Direct effects of phenytoin and carbamazepine on human osteoblast-like cells were investigated in experimental studies. BMD in the lumbar spine region (L2 through L4) was significantly lower in the patient group as compared to controls (p < 0.0004). At femoral sites BMD was lower in patients, but this difference did not reach statistical significance. The decrease in BMD at both sites was dependent on the duration of therapy. Excretion of pyridinoline crosslinks was markedly increased in the patients. 25-hydroxy-vitamin D3 and 1,25-dihydroxy-vitamin D3 were significantly decreased in patients. Proliferation rate of human osteoblast-like cells was increased by phenytoin in low doses. Both, phenytoin and carbamazepine inhibited cell growth at concentrations equivalent to therapeutic doses for the treatment of epileptic diseases. Our clinical and experimental data indicate that long-term treatment with anticonvulsant drugs leads to a lower BMD. The experimentally observed decrease in bone cell proliferation might be clinically associated with impaired new bone formation. Beside alterations in calcium and vitamin D homeostasis leading to osteomalazia, direct effects of anticonvulsant drugs on bone cells may contribute to the damaging effects on the skeletal system.

Absorptiometry, Photon↗

Analysis of lateral tooth movement during forced orthodontic eruption.

STATEMENT OF PROBLEM: Forced eruption is a prosthodontic procedure that enables the treatment of otherwise problematic restorative conditions. During the vertical orthodontic movement, the root may be moved laterally, affecting the position of a tooth in the arch. PURPOSE: This study quantified the degree of lateral movement possible during the eruptive procedure and addressed the significance of this movement from a theoretical and clinical standpoint. MATERIAL AND METHODS: A patient treatment, which demonstrated the movement in a single direction on the buccolingual axis, was isolated. On the basis of this theoretical model, a clinically relevant model was developed: A "worst-case" situation for each posterior tooth was calculated, from which clinical conclusions may be derived. RESULTS: . In a given extrusion angle of 30 degrees, a lateral movement/shift of 0.58 mm resulted per 1 mm of eruption distance. The lateral movement for every millimeter of eruption and the maximum extrusion angle for each of the maxillary and mandibular posterior teeth were calculated. CONCLUSION: The lateral movement that accompanies the forced eruption procedure may compromise or be used to esthetically enhance prosthodontic treatment.

Bicuspid↗

Behaviour management needs for the orthodontic treatment of children with disabilities.

A displeasing dental appearance may have a significant emotional impact on an individual's well being. Although malocclusions occur more often in physically and/or mentally handicapped children than in normal children, the most severely handicapped patients are those least likely to receive orthodontic treatment. This investigation studied the modes of behaviour management used in the orthodontic treatment of disabled children, and the preferred criteria. The files of 49 disabled children were retrospectively evaluated. Two classification systems, the Frankl Behaviour Rating Scale (FBRS), and that of Owen and Graber were found to be unsuitable for determining the appropriate treatment modality. Five specific factors, frequently seen in disabled children, gag reflex, drooling, uncontrollable movements, inability to remain still, and the need for additional procedures, were graded and a scoring system was devised to include these factors within the assessment. This scoring system may be used to evaluate new patients and to assist in the choice of the appropriate behavioural management mode.

Adolescent↗

Orthodontic treatment for disabled children: motivation, expectation, and satisfaction.

This study was designed to measure motivation for and expectations of proposed orthodontic treatment for disabled children, and to examine the level of satisfaction with the results of this treatment, in the eyes of the parents. A two-part questionnaire was sent to the parents of consecutively treated disabled children. The first part was sent to the parents of all the patients treated, while the second was only sent to those whose child had completed treatment. The response rate was over 90 per cent. The parents expected improvement in the child's appearance with a concomitant improvement in his/her social acceptance. These expectations from the treatment were found to be exaggerated, with only a minority of the parents claiming a marked improvement in their child's everyday functioning (four out of 27), or a significant social improvement (six out of 27). Nevertheless, most of the parents (26 out of 27) were satisfied with the treatment, and reported that 17 of the children themselves, who were aware of a change, considered it an improvement. A majority of the children understood the reasons for treatment, in the most general of terms. Close friends regarded treatment results as positive (20 out of 27). With only one exception, the parents stated that they would repeat the procedure, given the same set of circumstances, and all of them would recommend it for other disabled children. It may be concluded that even though orthodontic treatment in this groups of patients does not yield the desired social influence, the individual benefits from the treatment are worthwhile.

Adolescent↗

Safe orthodontic bonding for children with disabilities during general anaesthesia.

General anaesthesia (GA) may be employed to overcome management difficulties in the orthodontic treatment of disabled children. This report introduces the application of a rubber dam as a useful aid for a high quality bonding and as an effective safeguard in bonding of brackets in general anaesthesia, in the handicapped in particular. GA was used in 12 patients, of a cohort of 49 disabled patients, to facilitate the placing of the fixed appliance. The first seven were bonded solely with the use of an oropharyngeal pack and a high velocity suction to prevent aspiration, and the last five additionally underwent placement of a rubber dam. The use of a rubber dam to facilitate the safe and reliable bonding of orthodontic brackets in handicapped children under general anaesthesia is highly recommended.

Adolescent↗

MADS-Box gene diversity in seed plants 300 million years ago.

MADS-box genes encode a family of transcription factors which control diverse developmental processes in flowering plants ranging from root development to flower and fruit development. Through phylogeny reconstructions, most of these genes can be subdivided into defined monophyletic gene clades whose members share similar expression patterns and functions. Therefore, the establishment of the diversity of gene clades was probably an important event in land plant evolution. In order to determine when these clades originated, we isolated cDNAs of 19 different MADS-box genes from Gnetum gnemon, a gymnosperm model species and thus a representative of the sister group of the angiosperms. Phylogeny reconstructions involving all published MADS-box genes were then used to identify gene clades containing putative orthologs from both angiosperm and gymnosperm lineages. Thus, the minimal number of MADS-box genes that were already present in the last common ancestor of extant gymnosperms and angiosperms was determined. Comparative expression studies involving pairs of putatively orthologous genes revealed a diversity of patterns that has been largely conserved since the time when the angiosperm and gymnosperm lineages separated. Taken together, our data suggest that there were already at least seven different MADS-box genes present at the base of extant seed plants about 300 MYA. These genes were probably already quite diverse in terms of both sequence and function. In addition, our data demonstrate that the MADS-box gene families of extant gymnosperms and angiosperms are of similar complexities.

Amino Acid Sequence↗

Transforming growth factor-beta and hepatocyte growth factor plasma levels in patients with inflammatory bowel disease.

OBJECTIVE: An increased mucosal expression of transforming growth factor-beta (TGF-beta) and hepatocyte growth factor (HGF) has been reported in patients with active inflammatory bowel diseases (IBD) and in proximity to injured gastric and intestinal mucosal surfaces. The aim of this study was to measure systemic concentrations of TGF-beta and HGF and to assess their potential value to predict disease activity or severity of inflammation in patients with inflammatory bowel diseases. DESIGN AND METHODS: Plasma HGF and TGF-beta1 peptide levels were determined in 29 patients with ulcerative colitis, 45 patients with Crohn's disease and 28 healthy controls using commercial ELISA assays. Peptide levels were correlated with disease activity indices and various laboratory parameters. RESULTS: HGF and TGF-beta1 plasma levels were detected in all control and IBD subjects. Although a tendency towards increased HGF and TGF-beta1 peptide levels in IBD patients was observed, differences between groups were not significant In ulcerative colitis patients HGF plasma levels positively correlated with white blood cell counts and negatively correlated with serum albumin concentrations and haematocrit. In Crohn's disease patients, a positive correlation between TGF-beta and platelet count was observed. CONCLUSIONS: HGF and TGF-beta1 plasma concentrations are not significantly different in IBD and healthy control subjects. Stratification of IBD patients according to disease activity did not reveal any substantial differences, suggesting that HGF and TGF-beta plasma levels have no value in the assessment of disease activity or severity of inflammation in patients with IBD.

Adult↗

beta-2 adrenergic receptor gene variations, blood pressure, and heart size in normal twins.

Genetic variability, which influences cardiovascular phenotypes in normal persons, is likely to be relevant to cardiovascular disease. We studied normal monozygotic and dizygotic twins and found strong genetic influences on blood pressure and heart size. We then relied on the dizygotic twins and their parents to apply molecular genetic techniques. We performed a linkage analysis with markers close to the beta-2 adrenergic receptor (AR) gene locus in the dizygotic twins and their parents and found strong evidence for linkage to the quantitative traits of blood pressure and heart size. We then used allele-specific polymerase chain reaction to genotype the subjects further. We performed an association analysis and found that 4 functionally relevant polymorphisms in the beta-2 AR gene, namely Arg16/Gly, Gln27/Glu, Thr164/Ile, and a variant in the promoter region (-47C/T), were variably associated with blood pressure and heart size differences but were in linkage dysequilibrium with each other. A subsequent conditional analysis suggested that the Arg16/Gly polymorphism exerted the predominant effect. These findings underscore the importance of the beta-2 AR gene to blood pressure regulation, heart size, and probably to the development of hypertension. We suggest that a combined linkage and association approach will elucidate the genetic variability influencing blood pressure and other cardiovascular phenotypes.

Adolescent↗

Macromolecular contrast agents for optical imaging of tumors: comparison of indotricarbocyanine-labeled human serum albumin and transferrin.

Macromolecules accumulate in solid tumors and can thus be used as carriers for the delivery of attached contrast agents to tumors. We report the synthesis and use of serum protein-dye conjugates consisting of transferrin (Tf) or human serum albumin (HSA) and an indotricarbocyanine (ITCC) derivative as contrast agents for the optical imaging of tumors. The compounds were characterized with respect to their photophysical properties and tested in vitro for their ability to bind to tumor cells and in vivo for their potential to delineate experimental tumors. In contrast to HAS-ITTC, Tf-ITCC showed receptor-mediated uptake by HT29 human colon cancer cells in vitro. After intravenous injection into HT29 tumor-bearing nude mice both compounds induced increased fluorescence contrast of tumors in vivo. After 24 h the contrast between tumor and normal tissue was significantly higher for Tf-ITCC than for HAS-ITCC. Dye-induced fluorescence was found to be predominantly located in perinecrotic areas of the tumor. Furthermore, Tf-ITCC produced fluorescence of viable tumor cells, whereas HAS-ITCC fluorescence was recorded along connective tissue. We conclude that ITCC-labeled Tf and HSA can serve as macromolecular contrast agents for the optical imaging of tumors, with Tf-ITCC showing higher efficiency.

Animals↗

Hydrophilic cyanine dyes as contrast agents for near-infrared tumor imaging: synthesis, photophysical properties and spectroscopic in vivo characterization.

We have synthesized a group of glucamine and gluosamine-substituted cyanine dyes structurally related to indocyanine green (ICG) and have characterized these compounds with regard to their potential as contrast agents for biomedical optical imaging. The compounds reported herein exhibit increased hydrophilicity and less plasma protein binding (< 50%), and are thus expected to have different pharmacokinetic properties compared with ICG. Furthermore, we measured enhanced fluorescence quantum yields (7-15%) in a physiological environment with respect to ICG. For the derivative with the highest hydrophilicity (5a) the efflux from tumor and normal tissue was monitored by intensity-modulated diffuse optical spectroscopy after intravenous injection into tumor-bearing rats. In comparison with ICG, 5a exhibited a considerably enhanced tissue-efflux half-life (73 min versus less than 10 min for ICG in tumor tissue), a two-fold higher initial tissue absorption coefficient compared to ICG, and finally, it generated an elevated tumor-to-tissue concentration gradient up to 1 h after injection. In conclusion, compounds such as 5a are promising contrast agents for optical imaging, and could facilitate highly sensitive and specific detection of breast cancer or other malignancies by utilizing mechanisms similar to contrast-enhanced magnetic resonance imaging or computerized tomography.

Animals↗

Clinical evidence with montelukast in the management of chronic childhood asthma.

OBJECTIVE: The aim of this article is to review data on the efficacy and safety of montelukast in the treatment of children with asthma. METHODOLOGY: Available published literature, including published abstracts, is reviewed. RESULTS: In patients aged 6 to 14 years with asthma (n = 27), montelukast 5mg demonstrated a significant decrease in exercise-induced bronchoconstriction 20 to 24 hours postdose after 2 days of treatment. For children with chronic asthma, only one study of the regular use of a leukotriene receptor antagonist has been published. The efficacy and safety of montelukast in children aged 6 to 14 years with asthma (n = 336) were studied during an 8-week, double-blind, placebocontrolled trial. There was a significantly greater improvement in forced expiratory volume in 1 second (FEV1) from baseline for the montelukast group (8.23%) compared with the placebo group (3.58%). There was a significant decrease in the use of a 3-agonist for symptom relief, as well as in the percentage of days and percentage of patients with asthma exacerbations. An asthma specific quality-of-life (QOL) questionnaire revealed a significant overall improvement in QOL and a significant improvement in the QOL domains for symptoms, activity and emotions in montelukast recipients. There was no significant difference between montelukast and placebo recipients in the frequency of adverse events, with the exception of allergic rhinitis, which was more prevalent in the placebo group. An open label follow-up of patients from the above study was undertaken. The effect of montelukast on FEV1 was consistent for up to 1.4 years, with the increase in FEV1 being not significantly different from that in a small control group treated with inhaled beclomethasone dipropionate. QOL remained significantly improved during the open treatment period. CONCLUSIONS: Montelukast appears effective and safe for the treatment of children with asthma.

Acetates↗

Helical and single-slice conventional CT versus electron beam CT for the quantification of coronary artery calcification.

OBJECTIVE: We compared electron beam CT with conventional CT to determine the best method for the assessment of the coronary calcium score. We used conventional CT to examine symptomatic and asymptomatic patients suspected of having coronary artery disease. SUBJECTS AND METHODS: One hundred sixty male patients underwent electron beam CT and helical CT with a pitch of 1 (n = 30) and 2 (n = 30) and using a single-slice mode with (n = 50) and without (n = 50) prospective ECG triggering. In another 50 patients, we determined reproducibility for repeated scanning using electron beam CT. For all images, we derived the calcium score according to the Agatston method. We performed regression analysis and determined mean variability. Mean variability was calculated as the ratio of the absolute difference to the mean of the corresponding calcium scores. RESULTS: The correlation coefficients for electron beam CT and all conventional CT modes were very high (range, 0.93-0.98). The mean variability was highest in the helical mode with a pitch of 2 (61.4%) and lowest for the single-slice mode with prospective ECG triggering (25.4%). For repeated electron beam CT, the correlation coefficient and mean variability were 0.99 and 22.1%, respectively. CONCLUSION: ECG-triggered single-slice conventional CT had the best agreement with electron beam CT calcium scores.

Calcinosis↗

Up-regulation of the metabotropic glutamate receptor mGluR4 in hippocampal neurons with reduced seizure vulnerability.

Selective hippocampal cell loss and altered neurotransmitter receptor expression have been proposed as pathogenic mechanisms in the development of chronic mesial temporal lobe epilepsy (TLE). Studies in animal models point to metabotropic glutamate receptors (mGluRs) as modulators of hippocampal epileptogenesis. In addition, mGluRs may constitute specific targets for the development of novel anticonvulsive drugs. As mGluR4 represents an inhibitory class III mGluR associated with the reduction of intracellular cyclic AMP levels and calcium influx, we have analyzed the regional and cellular expression of mGluR4 in surgical hippocampal specimens obtained from patients with TLE by using immunohistochemistry and in situ hybridization. Although the hippocampi of control specimens (n = 11) were almost devoid of mGluR4 immunolabeling, all TLE specimens (n = 35) showed a striking up-regulation of mGluR4 immunoreactivity, in particular within the dentate gyrus. Immunoelectron microscopy localized the receptor protein to the periphery of presynaptic and postsynaptic membranes. In situ hybridization revealed increased transcript levels of mGluR4 in dentate granule cells and residual CA4 neurons of TLE specimens compared with controls. Our results suggest a potential role of mGluR4 in counteracting excitatory hippocampal activity and in modulating seizure-associated vulnerability of hippocampal neurons. These data may also provide a basis for pharmacological studies of mGluR4 agonists as potential novel drugs in the treatment of TLE.

Adult↗

A short history of MADS-box genes in plants.

Evolutionary developmental genetics (evodevotics) is a novel scientific endeavor which assumes that changes in developmental control genes are a major aspect of evolutionary changes in morphology. Understanding the phylogeny of developmental control genes may thus help us to understand the evolution of plant and animal form. The principles of evodevotics are exemplified by outlining the role of MADS-box genes in the evolution of plant reproductive structures. In extant eudicotyledonous flowering plants, MADS-box genes act as homeotic selector genes determining floral organ identity and as floral meristem identity genes. By reviewing current knowledge about MADS-box genes in ferns, gymnosperms and different types of angiosperms, we demonstrate that the phylogeny of MADS-box genes was strongly correlated with the origin and evolution of plant reproductive structures such as ovules and flowers. It seems likely, therefore, that changes in MADS-box gene structure, expression and function have been a major cause for innovations in reproductive development during land plant evolution, such as seed, flower and fruit formation.

Animals↗

Dental age in maxillary canine ectopia.

An etiologic connection between palatally ectopic canines and small and missing teeth is well established in the literature. Additionally, it has been observed that patients with palatally ectopic canines have a delayed dental development. The present study was designed to examine the validity of this latter observation. We radiographically assessed the subjects' dental ages using criteria of tooth calcification, rather than tooth eruption pattern. A similar determination was made in relation to subjects in whom buccally ectopic canines were present. The experimental group consisted of panoramic radiographs of 55 consecutively treated patients with palatally displaced maxillary canines and of 47 consecutively treated patients with buccally displaced canines. They were compared with a control group of 57 consecutively treated patients with normally placed canines. Approximately half the subjects with palatal displacement exhibited a late-developing dentition, whereas the timing of dentition in the remaining subjects appeared to be normal. Buccal displacement was not associated with a retarded dental development, and the ranges of the dental age values were similar to those seen in the control group. The results support the idea that there are different etiologies for the occurrence of buccal versus palatal ectopia in maxillary canines. They also suggest that dentitions with a palatal canine appear to be of 2 distinct varieties, with different dental characteristics and, perhaps, different etiologies.

Adolescent↗

Unfair treatment, neighborhood effects, and mental health in the Detroit metropolitan area.

Why do racial differences in many indicators of mental and emotional well-being show inconsistent patterns? We propose that mental and emotional well-being are influenced by aspects of the social context, including experiences of unfair treatment and the concentration of households with incomes below the poverty level, and that differential exposure to these factors influences racial differences in mental well-being. We analyze the reporting of psychological distress and life satisfaction in a multistage area probability sample of 1,139 African American and white residents of the Detroit metropolitan area aged 18 and older. Both psychological distress and life satisfaction are significantly associated with exposure to unfair treatment and with the proportion of households in the census block group that were below the poverty level. Racial differences in psychological distress and life satisfaction were eliminated or reversed once differentials in the percent of households living below the poverty line and exposure to unfair treatment were accounted for. These findings contribute to a growing body of evidence that "race" effects operate through multiple pathways that include race-based residential segregation and its attendant economic disinvestment at the community level, and interpersonal experiences of unfair treatment.

Adolescent↗

Canadian Asthma Consensus Report, 1999. Canadian Asthma Consensus Group.

OBJECTIVES: To provide physicians with current guidelines for the diagnosis and optimal management of asthma in children and adults, including pregnant women and the elderly, in office, emergency department, hospital and clinic settings. OPTIONS: The consensus group considered the roles of education, avoidance of provocative environmental and other factors, diverse pharmacotherapies, delivery devices and emergency and in-hospital management of asthma. OUTCOMES: Provision of the best control of asthma by confirmation of the diagnosis using objective measures, rapid achievement and maintenance of control and regular follow-up. EVIDENCE: The key diagnostic and therapeutic recommendations are based on the 1995 Canadian guidelines and a critical review of the literature by small groups before a full meeting of the consensus group. Recommendations are graded according to 5 levels of evidence. Differences of opinion were resolved by consensus following discussion. VALUES: Respirologists, immunoallergists, pediatricians and emergency and family physicians gave prime consideration to the achievement and maintenance of optimal control of asthma through avoidance of environmental inciters, education of patients and the lowest effective regime of pharmacotherapy to reduce morbidity and mortality. BENEFITS, HARMS AND COSTS: Adherence to the guidelines should be accompanied by significant reduction in patients' symptoms, reduced morbidity and mortality, fewer emergency and hospital admissions, fewer adverse side-effects from medications, better quality of life for patients and reduced costs. RECOMMENDATIONS: Recommendations are included in each section of the report. In summary, after a diagnosis of asthma is made based on clinical evaluation, including demonstration of variable airflow obstruction, and contributing factors are identified, a treatment plan is established to obtain and maintain optimal asthma control. The main components of treatment are patient education, environmental control, pharmacotherapy tailored to the individual and regular follow-up. VALIDATION: The recommendations were distributed to the members of the Canadian Thoracic Society Asthma and Standards Committees, as well as members of the board of the Canadian Thoracic Society. In addition, collaborating groups representing the Canadian Association of Emergency Physicians, the Canadian College of Family Physicians, the Canadian Paediatric Society and the Canadian Society of Allergy and Immunology were asked to validate the recommendations. The recommendations were discussed at regional meetings throughout Canada. They were also compared with the recommendations of other similar groups in other countries. DISSEMINATION AND IMPLEMENTATION: An implementation committee has established a strategy for disseminating these guidelines to physicians, other health professionals and patients and for developing tools and means that will help integrate the recommendations into current asthma care. The plan is outlined in this report.

Adolescent↗