Biomedical subjects

L Beck

Publications and source records attributed to L Beck.

At least 37 records · Page 2Linked to original sources

PubMed2000

Optimal outcome measures, research priorities, and international cooperation.

The participants in the Eriksholm Workshop on "Measuring Outcomes in Audiological Rehabilitation Using Hearing Aids" debated three issues that are reported in this article. First, it was agreed that the characteristics of an optimal outcome measure vary as a function of the purpose of the measurement. Potential characteristics of outcome self-report tools for four common goals of outcome measurement are briefly presented to illustrate this point. Second, 10 important research priorities in outcome measurement were identified and ranked. They are presented with brief discussion of the top five. Third, the concept of generating a brief universally applicable outcome measure was endorsed. This brief data set is intended to supplement existing outcome measures and to promote data combination and comparison across different social, cultural, and health-care delivery systems. A set of seven core items is proposed for further study.

Correction of Hearing Impairment↗

PubMed2000

Cellular and in vivo electrophysiological effects of dronedarone in normal and postmyocardial infarcted rats.

We studied the effects of dronedarone (SR 33589) on the action potentials, membrane ionic currents, and arrhythmic activity in control rats and in rats after myocardial infarction, a model known to develop anomalous electrical activity. Dronedarone increased action potential duration in normal hearts. It had little effect on the action potentials that were already prolonged in the postmyocardial infarcted (PMI) rats. Particularly, dronedarone reduced the late sustained K(+) current, I(K) (or Isus) by 69%. Dronedarone induced only a tonic block of I(K). Similar relative inhibitions of I(K) by dronedarone were obtained in young, sham, and PMI rats, even if I(K) was less in sham than in young and further reduced in PMI rats. The EC(50) values were 0.78 and 0.85 microM in sham and PMI rats. Dronedarone induced a weak increase in the fast transient outward current, I(to). Time-to-peak and inactivation time constant of I(to) were decreased by dronedarone that also induced a marked slowing of I(to) recovery from inactivation. Similar effects were observed on the reduced I(to) recorded in PMI rats. Holter monitoring study in control, unthetered animals showed that dronedarone had no proarrhythmic effect. On rats, which after myocardial infarction exhibited ventricular premature beats, dronedarone significantly decreased beat occurrence during the 7-day treatment; this effect was sustained for two more weeks. Thus, dronedarone exerts antiarrhythmic effects on PMI rat heart. Its effects are attributable for the most part to the inhibition of outward K(+) currents and the increase in effective refractory period.

Action Potentials↗

PubMed2000

[Electrophysiologic and anatomic atrial remodeling: an atrial rhythmic cardiomyopathy].

In 1995, Wijffels and Alessie, using a curious goat model of atrial fibrillation, introduced the concept of atrial remodelling. The classical atrial substrate (anatomopathological-dilatation and hypokinesis-, and electrophysiological-short refractory periods and decreased conduction-), appeared not only to be one of the causes of atrial fibrillation but also the consequence of atrial fibrillation itself, the mechanism being a vicious circle. In addition to ventricular rhythmic cardiomyopathy, responsible for cardiac failure, the concept of atrial rhythmic cardiomyopathy with the same mechanical and electrophysiological consequences, has developed. These changes, characterised mainly by calcium overload associated with cellular hibernation and differentiation, have not been totally elucidated but have already renewed the physiopathology of atrial fibrillation.

Anti-Arrhythmia Agents↗

PubMed2000

Regulation and distribution of body fluid during a 6-day head-down tilt study in a randomized cross-over design.

Head down tilt (-6 degrees HDT) examinations are commonly used simulation models for various microgravity induced changes in body functions. Body fluid distribution (by means of dye dilution and two independent multifrequency impedance techniques), water- and sodium-handling, and the plasma/serum concentrations of fluid balance related hormones have been determined in a randomized, controlled, cross-over study in 8 healthy test subjects. The comparison of responses to HDT and an upright control position with respective experiences from space shows some similarities but also various discrepancies between the terrestrial simulation and real microgravity.

Bed Rest↗

PubMed1999

Identification of a mammalian brain sulfate transporter.

Sulfate is an essential anion involved in many biosynthetic and pharmacological reactions. Sulfate is an important constituent of myelin membranes in the brain; however, very little is known as to how sulfate enters brain cells. In this study, our aim was to determine whether the mammalian brain possesses a sulfate transporter. Injection of rat brain poly A(+) RNA into Xenopus oocytes led to an induction of Na(+)-independent sulfate transport, which was inhibited by oxalate, probenecid, phenol red, thiosulfate and DIDS. Hybrid depletion using sat-1 antisense oligodeoxyribonucleotides led to a complete inhibition of brain mRNA-induced sulfate transport in Xenopus oocytes, suggesting the presence of a functional sat-1 transcript in the brain. By RT-PCR, sat-1 mRNA was detected throughout the rat brain and in situ hybridisation showed highest sat-1 expression in the hippocampus and cerebellum. This is the first study to identify and characterise a functional mammalian brain sulfate transporter.

Animals↗

PubMed1999

Photoscreening for refractive errors in children and young adults with severe learning disabilities using the MTI photoscreener.

PURPOSE: To test the potential ability of the MTI photoscreener to facilitate screening for significant refractive errors in children and young adults with severe learning disabilities. METHODS: Thirty-eight patients with severe learning disabilities from a special school were examined with the photoscreener, and underwent cycloplegic refraction, an ophthalmological and an orthoptic examination. The age at examination, the cause of learning disability, the pupil size, the number of photographs required for accurate interpretation, the co-operation of the subject and the presence or absence of strabismus were recorded. An educational psychologist had performed a psychological assessment on all the children. The results of the cycloplegic retinoscopy were compared with the photorefraction results. RESULTS: A photorefraction was possible in 37 patients and cycloplegic refraction in all the patients. The patients had severe learning difficulties with an intelligence quotient of less than 50. All the patients had behavioural problems, 9 patients had associated cerebral palsy, 8 had chronic epilepsy, 1 patient was brain damaged from a non-accidental injury and 1 from a road traffic accident. The mean age of the patients was 10.0 +/- 4.9 years (range 3-18 years), the average pupil diameter during photoscreening was 6.1 +/- 0.9 mm (range 4-8 mm) and the average number of photographs required for each subject was 2.1 +/- 0.9 (range 1-4). The photoscreener detected 10 patients with a manifest strabismus. There was one false positive and one false negative result giving a sensitivity of 92.8% and a specificity of 90%. CONCLUSION: The examination of children with severe learning disabilities for refractive errors can be extremely difficult. The MTI photoscreener is an effective means of screening such children and young adults for refractive errors and strabismus so that the children with these abnormalities may be targeted for a more detailed evaluation.

Adolescent↗

PubMed1999

A "dysautonomic" head-up tilt test pattern in elderly patients with neurocardiogenic syncope.

The characteristics of neurocardiogenic syncope (NCS) in elderly patients remain unclear. We compared the hemodynamic profiles of young and older patients with consecutive and positive head-up tilt tests (HUT). Continuous, noninvasive, and reliable monitoring of arterial pressure (AP) and heart rate (HR) was done throughout 46 consecutive positive HUTs of symptomatic patients. The population (12-82 years old) was divided into two groups: younger patients, Y (n = 25, < or = 65 years), and older patients, O (n = 21). Changes in AP and HR after the first minute of tilting, during the stable orthostatic phase and during syncope were compared. Except for systolic pressure, baseline hemodynamic parameters were similar in Y and O. No difference appeared in the mean time elapsed before syncope (19+/-9 vs 22+/-2 min). Asymptomatic hypotension was observed, only in O, 1 minute after tilting, followed by a progressive fall in the mean AP before syncope (0+/-0.9 vs -1+/-0.7 mmHg/min) without HR increase (0.7+/-1 vs 0+/-0.6 beats/min). This pressure slope was strongly related to age (r = 0.54, P < 0.001). Hemodynamic recording during HUT identifies a dysautonomic pattern in elderly patients with NCS and the abnormal AP/HR responses to orthostasis may be a feature specific to this population. Although the central mechanism of NCS is common to all ages, the age-related characteristics of the trigger event may indicate the need for specific management at different ages.

Adolescent↗

PubMed1999

Immunolocalization of CD34 in nasal polyposis. Effect of topical corticosteroids.

Airway inflammation in patients with nasal polyps is characterized by the increased presence of eosinophils, the numbers of which are reduced after treatment with topical corticosteroids. Because eosinophilic responses in the airways are in part due to eosinophil progenitor differentiation, we hypothesized that CD34, a cell surface, sialomucinlike glycoprotein that specifically marks hemopoietic progenitors and endothelium, would be expressed in nasal polyp tissue. We sought to identify CD34(+) leukocytes or endothelial cells in nasal polyps. We also investigated the effect of the topical corticosteroid budesonide on the numbers of CD34(+) cells and vessels in nasal polyps. To accomplish this, we performed immunostaining for CD34 protein in tissue sections of nasal polyps from topical steroid-treated and -untreated groups of patients, as well as from one patient before and after systemic corticosteroid therapy. We also examined myeloid colony formation by isolated polyp mononuclear cells, and performed flow cytometry to detect the presence of CD34(+)/CD45(+) cells within these isolated populations. We also examined the in vitro effects of steroids on human umbilical vein endothelial cell (HUVEC) expression of CD34. We detected CD34-immunoreactive mononuclear cells and blood vessels in the lamina propria of all nasal polyps. CD34(+) mononuclear cells resembled immature hemopoietic cells morphologically. Mononuclear cell fractions from polyps contained myeloid colony-forming cells and cells bearing CD45, a pan-leukocyte marker, as well as CD34, and gated as true hemopoietic blast cells. The numbers of CD34(+) cells and CD34(+) vessels in steroid-treated nasal polyps were significantly higher than in steroid-untreated nasal polyps (15.67 +/- 2.08 cells/10 hpf, versus 5.33 +/- 1.36 cells/10 hpf, P = 0.002; 101.25 +/- 6.24 vessels/0.5 mm2 of lamina propria, versus 57.22 +/- 8.00 vessels/0.5 mm2 of lamina propria, P = 0.0008, respectively). A similar upregulation of CD34 immunostaining, especially for mononuclear cells, was observed in one patient after systemic corticosteroid therapy. Steroid treatment in vitro of HUVECs did not result in enhanced CD34 expression. Both CD34(+)/CD45(+) mononuclear cells and CD34(+) endothelial cells are present within nasal polyps, with higher numbers in patients who have received topical corticosteroid treatment. Because enhancement of CD34 expression was not seen in cultured umbilical vein endothelial cells treated in vitro with corticosteroid, the findings of the study suggest that in nasal polyp tissue, steroids enhance numbers of CD34(+) progenitors and endothelial cells via indirect mechanisms.

Administration, Topical↗

PubMed1998

Targeted inactivation of Npt2 in mice leads to severe renal phosphate wasting, hypercalciuria, and skeletal abnormalities.

Npt2 encodes a renal-specific, brush-border membrane Na+-phosphate (Pi) cotransporter that is expressed in the proximal tubule where the bulk of filtered Pi is reabsorbed. Mice deficient in the Npt2 gene were generated by targeted mutagenesis to define the role of Npt2 in the overall maintenance of Pi homeostasis, determine its impact on skeletal development, and clarify its relationship to autosomal disorders of renal Pi reabsorption in humans. Homozygous mutants (Npt2(-/-)) exhibit increased urinary Pi excretion, hypophosphatemia, an appropriate elevation in the serum concentration of 1,25-dihydroxyvitamin D with attendant hypercalcemia, hypercalciuria and decreased serum parathyroid hormone levels, and increased serum alkaline phosphatase activity. These biochemical features are typical of patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a Mendelian disorder of renal Pi reabsorption. However, unlike HHRH patients, Npt2(-/-) mice do not have rickets or osteomalacia. At weaning, Npt2(-/-) mice have poorly developed trabecular bone and retarded secondary ossification, but, with increasing age, there is a dramatic reversal and eventual overcompensation of the skeletal phenotype. Our findings demonstrate that Npt2 is a major regulator of Pi homeostasis and necessary for normal skeletal development.

Animals↗

PubMed1998

Model based characterization of microgravity induced alterations of CVS-regulation.

A concept called model individualization is presented. It is used to modify computer based models to reproduce observed individual behavior. During D2-, MIR97- and Neurolab-missions tilt-table and LBNP-experiments were carried out. Physiological data describing the cardiovascular reactions of the astronauts were recorded. The appropriateness of the rheoretical principles is demonstrated with MIR97 tilt-table experiments. Finally the resulting individualized model is investigated to propose hypotheses on probable alterations in the cardiovascular system induced by microgravity.

Aerospace Medicine↗

PubMed1998

Spatial analysis of lymphatic filariasis distribution in the Nile Delta in relation to some environmental variables using geographic information system technology.

Geographic information system (GIS) was used to analyze the spatial distribution of filariasis in the Nile Delta. The study involved 201 villages belonging to Giza, Qalubiya, Monoufiya, Gharbiya, and Dakahliya governorates. Villages with similar microfilarial (mf) prevalence rates were observed to cluster within 1-2 km distance, then, clustering started to decrease significantly with distance up to 5 km (Pearson correlation coefficient = -0.98). the likelihood of negative and high prevalence villages being contiguous was very low (approximately 1.8%, n = 612 village-pairs) indicating homogeneity in disease processes within the defined spatial scales. Of the villages located within 2 km from the main Nile branches (n = 46), 95% exhibited low prevalence. In addition, the spatial pattern of mf prevalence was shown to be negatively associated with annual rainfall and relative humidity, while it was positively associated with annual daily temperature. Average mf prevalence in warmer, relatively drier areas receiving 25 mm of rain was significantly higher (3.9%) than that in less warmer but more humid areas receiving 50 mm of rain (1.6%) (P < 0.0001). Based on the results of the present study, GIS was used to generate a "filariasis risk map" that could be used by health authorities to efficiently direct surveillance and control efforts. This investigation identified some of the factors underlying filariasis spatial pattern, quantified clustering and demonstrated the potential of GIS application in vector-borne disease epidemiology.

Animals↗

PubMed1998

[Vasovagal syndromes].

Most cases of dizziness or syncope referred to the emergency department or to services of internal medicine are caused by vasovagal syndromes. They comprise relative bradycardia with vasoplegia, the cardiovascular response to a neurological stimulus. It is possible to distinguish vagal or vasovagal syncope which is very common, the very stereotype reflex syncopes, carotid sinus hypersensitivity sometimes associated with sinus node dysfunction and borderline forms such as orthostatic sinus tachycardia and cerebrovascular syncope. The differential diagnosis is vast, from simple hysteria to severe cardiac disease. Tilt testing should be indicated for diagnosis of most cases of syncope with apparently normal hearts. Therapeutic abstention is the rule, providing certain preventive measures are taken, but, should treatment be necessary, cardiac pacing remains an exceptional modality in vasovagal syncope. Strict clinical and physiopathological studies are still required to determine the long-term prognosis and the underlying mechanisms of these syndromes.

Cardiac Pacing, Artificial↗

PubMed1998

[Role and significance of cytokines in the development of cardiac insufficiency].

The hypothesis of immune and inflammatory activation occurring during chronic cardiac failure, capable of maintaining the disease, is supported by many experimental and clinical trials. Plasma cytokines levels, particularly the tumour necrosis factor alpha (TNF alpha), are raised at advanced stages of the disease, especially in cachectic patients. The correlations with other, more traditional markers, especially neurohumoral, are not very close, probably suggesting different mechanisms. Cytokines are a group of very different molecules with multiple, non-specific, and even beneficial effects. However, the lack of regulation in severe cardiac failure may lead to deleterious effects on the heart. The experimental effects of TNF alpha (mini-pumps, transgenic animals) include features of myocarditis, chamber dilatation and contractile dysfunction. Large scale therapeutic trials of long acting TNF alpha antagonists could confirm the "inflammation hypothesis" of mutual interaction between cardiac failure and the production of cytokines.

Cardiac Output, Low↗

PubMed1997

Pex/PEX tissue distribution and evidence for a deletion in the 3' region of the Pex gene in X-linked hypophosphatemic mice.

PEX, a phosphate-regulating gene with homology to endopeptidases on the X chromosome, was recently identified as the candidate gene for X-linked hypophosphatemia. In the present study, we cloned mouse and human Pex/PEX cDNAs encoding part of the 5' untranslated region, the protein coding region, and the entire 3' untranslated region, determined the tissue distribution of Pex/PEX mRNA, and characterized the Pex mutation in the murine Hyp homologue of the human disease. Using the reverse transcriptase/polymerase chain reaction (RT/PCR) and ribonuclease protection assays, we found that Pex/PEX mRNA is expressed predominantly in human fetal and adult mouse calvaria and long bone. With RNA from Hyp mouse bone, an RT/PCR product was generated with 5' but not 3' Pex primer pairs and a protected Pex mRNA fragment was detected with 5' but not 3' Pex riboprobes by ribonuclease protection assay. Analysis of the RT/PCR product derived from Hyp bone RNA revealed an aberrant Pex transcript with retention of intron sequence downstream from nucleotide 1302 of the Pex cDNA. Pex mRNA was not detected on Northern blots of poly (A)+ RNA from Hyp bone, while a low-abundance Pex transcript of approximately 7 kb was apparent in normal bone. Southern analysis of genomic DNA from Hyp mice revealed the absence of hybridizing bands with cDNA probes from the 3' region of the Pex cDNA. We conclude that Pex/PEX is a low-abundance transcript that is expressed predominantly in bone of mice and humans and that a large deletion in the 3' region of the Pex gene is present in the murine Hyp homologue of X-linked hypophosphatemia.

Amino Acid Sequence↗

PubMed1997

PUVA-induced phototoxicity: incidence and causes.

BACKGROUND: Phototoxicity is the most significant short-term adverse effect of PUVA therapy. OBJECTIVE: We attempted to determine the incidence and possible causes of phototoxicity of sufficient degree to cause interruption of treatment. METHODS: A retrospective study was conducted of 16,506 PUVA treatments given to 414 patients in two treatment centers. RESULTS: Phototoxicity occurred in 10.9% of patients and was an adverse effect in 0.3% of treatments. Problems with the treatment protocol were the main cause. CONCLUSION: Phototoxicity is a common adverse effect, and patients should be warned of this potential occurrence. Awareness of the causes may help to reduce the incidence of this problem.

Clinical Protocols↗

PubMed1997

Chronic left main coronary artery occlusion: a complication of radiofrequency ablation of idiopathic left ventricular tachycardia.

We describe in this report the development of chronic left main coronary artery (LMCA) occlusion in a young patient 2 years after an uncomplicated, successful ablation of idiopathic left ventricular tachycardia. This complication appears to be a late consequence of trauma to the LMCA during the procedure rather than an acute or subacute embolic event.

Adult↗

PubMed1997

Cardiovascular regulation: a modelling approach.

A detailed analysis of autonomic cardiovascular control (ACVC) may provide a key to a better understanding of the mechanisms underlying postflight orthostatic hypotension. The central substrate of human ACVC is not directly accessible to measurements and observation in space research. Modelling--supporting inference and physiological reasoning--is a valuable tool to disclose its involvement We are currently determining the suitability of artificial neural networks (ANN's) as a model of the central substrate of ACVC. Having conducted a number of experiments with simulated tilt test data to clarify the choice of input coding and of architectural biases in network training we will now report on the approximation of data obtained from human subjects during preparation of the German MIR'97 and D-2 missions.

Adaptation, Physiological↗

PubMed1997

Vascular development: cellular and molecular regulation.

The vascular system forms through a combination of vasculogenesis and angiogenesis. In vasculogenesis, vessels form de novo via the assembly of endothelial precursors called angioblasts, whereas in angiogenesis new vessels arise by migration and proliferation of endothelial cells from preexisting vessels. Although the two processes are distinct in some respects, recent evidence suggests that they share a number of regulatory mechanisms. The identification of a number of defined growth factors, observations of genetically manipulated mice, and the recognition of the importance of cell-cell interactions have greatly expanded our understanding of the regulation of vascularization. The paracrine actions of a variety of polypeptide growth factors, including platelet-derived growth factor, vascular endothelial growth factor, transforming growth factor-beta, and the angiopoietins, appear to be orchestrated in a complex sequence of steps that lead to the development of the adult vascular system. Thus, communication between the forming vasculature and the tissue parenchyma, as well as interactions among cells of the vascular wall, all appear to influence vascular development and growth.

Animals↗