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Biomedical subjects

A Lux

Publications and source records attributed to A Lux.

At least 19 recordsLinked to original sources
PubMed2006

Peritoneal cancer treatment with CYP2B1 transfected, microencapsulated cells and ifosfamide.

The prognosis of peritoneal spread from gastrointestinal cancer and subsequent malignant ascites is poor, and current medical treatments available are mostly ineffective. Targeted chemotherapy with intraperitoneal prodrug activation may be a beneficial new approach. L293 cells were genetically modified to express the cytochrome P450 enzyme 2B1 under the control of a cytomegalovirus immediate early promoter. This CYP2B1 enzyme converts ifosfamide to its active cytotoxic compounds. The cells are encapsulated in a cellulose sulfate formulation (Capcell). Adult Balb/c mice were inoculated intraperitoneally with 1 x 10(6) colon 26 cancer cells, previously transfected with GFP to emit a stable green fluorescence, by injection into the left lower abdominal quadrant. Two or five day's later animals were randomly subjected to either i.p. treatment with ifosfamide alone or ifosfamide combined with microencapsulated CYP2B1-expressing cells. Peritoneal tumor volume and tumor viability were assessed 10 days after tumor inoculation by means of fluorescence microscopy, spectroscopy and histology. Early i.p. treatment with ifosfamide and CYP2B1 cells resulted in a complete response. Treatment starting on day 5 and single-drug treatment with ifosfamide resulted in a partial response. These results suggest that targeted i.p. chemotherapy using a combination of a prodrug and its converting enzyme may be a successful treatment strategy for peritoneal spread from colorectal cancer.

Animals↗
PubMed2006

[On uniform social medical evaluation of performance capacity in orthopedic rehabilitation].

The need for standardized and unified performance capacity assessment in orthopedic rehabilitation has led to the attempt to use an existing standardized procedure. Graduated disease features have been defined which are relevant for work and their effects on performance capacity been formulated as rules. In this way so-called disease-conditioned performance capacities are obtained which help to identify problems in carrying out various activities. These activities can be directly assessed using tests. Appropriate tests are listed in a table.

Disability Evaluation↗
PubMed2005

[Economic aspects of health telematics].

The economic aspects of the health telematics must be considered from two points of view. The administrative applications are suitable as start-applications, because their data structures and processes are well known, and the calculation of the individual monetary effects have a solid empirical basis. However, only the medical applications will exhaust the real potential of health telematics and only these applications will justify the political and financial effort involved.

Computer Communication Networks↗
PubMed2005

[Three conventional eye drops versus a single lyophilisate. A comparative bioavailability study].

PURPOSE: The ocular bioavailability of a single application of a triple dose of sodium fluorescein to the human anterior segment of the eye was studied as a novel drug delivery device. METHODS: The lyophilisate contained a fluorescein dose of 204 microg corresponding to three conventional, preservative-free eye drops of 40 microl Fluorescein SE Thilo 0.17% (68microg each) (Alcon). A single lyophilisate was applied to one eye of 22 healthy volunteers (+1 min) and three conventional eye drops (+1, 16, 31 min) were applied to their fellow eye. In this randomized, open label study, fluorophotometry was performed (Fluorotron Master IItrade mark, Ocumetrics, Mountain View, California, USA) before and +15, 30, 45, 60, 120, 180, 240, 300, 360, 420 min after application. The fluorescein concentrations of the corneal stroma (C), mid-anterior chamber (AC) were analyzed by paired t-test. RESULTS: Cornea and AC mean values (ng/ml) were significantly higher (p < 0.018, paired t-test) in the lyophilisate group up to 7 h after application, with the exception of +45 min. The mean fluorescein bioavailability from the lyophilisate was up to 11 times higher in the C and up to 8.7 times higher in the AC compared with the three preservative-free eye drops. DISCUSSION: For the first time a triple dose was delivered to the human eye with a single lyophilisate application. Significantly better bioavailability was achieved in the C and AC for up to 7 h using this new device. The treatment of glaucoma, bacterial, viral, and fungal infections, as well as dry eye syndrome, for example, will be improved using lyophilisate.

Adult↗
PubMed2004

[Relevance of a performance capacity model for uniform and standardized performance diagnostics].

To obtain a standardized method for performance capacity assessment in social medicine reference to a generally accepted model of performance capacity is necessary. Further, such a model enables description of the effects of chronic disease on performance capacity. This article describes how the term "performance capacity" can be reduced to operational basal parameters by a hierarchic breakdown, with the domain "physical performance capacity" having the most complex structure. Furthermore the construction of a graduation according to work-load taxonomies for every parameter is shown. The collection of data on the level of basal parameters is essential to assess the concrete performance capacity. To apply the model as a basis for estimating the effects of chronic disease, graduated disease features have to be created. The benefit of the procedure described lies in increased transparency of the decision process. Hence, performance capacity assessment will gain reliability and objectivity.

Chronic Disease↗
PubMed2004

Bioavailability of fluorescein from a new drug delivery system in human eyes.

AIM: To assess the ocular bioavailability of fluorescein from a novel drug delivery system compared with one single preservative free eye drop. METHODS: Part A: In a randomised study 10 volunteers applied the lyophilisate to one eye and a conventional fluorescein eye drop to the fellow eye. Fluorophotometry was performed before and every 2 minutes up to 30 minutes after application in the cornea and anterior chamber. Part B: Another 10 volunteers applied each form of the application. Fluorophotometry was performed before, +2 minutes, and at +8, +10, +12 hours. The dose corresponding to a single fluorescein dose of the lyophilisate was 68 l microg fluorescein SE 0.17%. RESULTS: Part A: During the first 30 minutes after administration of the preservative free eye drop of 40 microg the corneal and anterior chamber concentration means were up to 16 times higher in eyes treated with the lyophilisate. Part B: 8-12 hours after application the mean fluorescein concentration in the cornea of the lyophilisate group was two times higher than at baseline. Eyes treated with eye drops had baseline values at +8, +10 and +12 hours. CONCLUSION: A significantly better bioavailability was achieved in human eyes by using lyophilisate compared with the same dose from a conventional eye drop. Lyophilisates are a favourable alternative to conventional eye drops since they have no preservatives, higher long term stability, no pH adjustment, and easy handling.

Adult↗
PubMed2003

A comparative bioavailability study of three conventional eye drops versus a single lyophilisate.

AIM: To study the ocular bioavailability of a triple dose, single application of sodium fluorescein to the human anterior segment from a novel drug delivery device. METHODS: In a randomised, open label study 22 healthy volunteers applied a single lyophilisate to one eye (+1 minute) and three conventional eye drops (+1, 16, 31 minutes) of fluorescein ophthalmic solution to the fellow eye. The fluorescein dose of the lyophilisate was 204 mg corresponding to three conventional, preservative-free eye drops of 40 ml fluorescein SE Thilo 0.17% (68 micro g each) (Alcon). Fluorophotometry was performed (Fluorotron Master II Ocumetrics, USA) before and +15, 30, 45, 60, 120, 180, 240, 300, 360, 420 minutes after application. The fluorescein concentrations of the corneal stroma and mid-anterior chamber were analysed by paired t test. RESULTS: Cornea and anterior chamber mean values (ng/ml) were significantly higher (p<0.018, paired t test) in the lyophilisate group up to 7 hours after application with the exception of +45 minutes. The mean fluorescein bioavailability from the lyophilisate was up to 11 times higher in the cornea and up to 8.7 times higher in the anterior chamber compared with the three preservative-free eye drops. CONCLUSION: A triple dose was delivered to the human eye with a single lyophilisate application for the first time. A significantly better bioavailability was achieved in the cornea and anterior chamber for up to 7 hours by means of drug application with lyophilisates. The application of medications by means of the lyophilisate will improve the treatment of, for example, glaucoma, bacterial, viral and fungal infections, as well as dry eye syndrome.

Adult↗
PubMed2003

Hereditary haemorrhagic telangiectasia: a questionnaire based study to delineate the different phenotypes caused by endoglin and ALK1 mutations.

BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia characterised by mucocutaneous telangiectasis, epistaxis, gastrointestinal haemorrhage, and arteriovenous malformations in the lung and brain. Causative mutations for HHT have been identified in two genes, endoglin and ALK1, which encode proteins involved in serine-threonine kinase signalling in the endothelial cell. METHODS: A number of people affected with HHT had completed a postal questionnaire as part of an international study to delineate the HHT phenotype. We identified questionnaires completed by subjects in whom we had identified a mutation in endoglin or ALK1. Further questionnaires were sent to families with known mutations. Data were only included from questionnaires returned by people known to carry disease causing mutations. RESULTS: Questionnaires were completed by 83 subjects with known mutations. Of these, 49 had endoglin mutations (HHT1) and 34 had ALK1 mutations (HHT2). Subjects with HHT1 reported an earlier onset of epistaxis (p=0.01) and telangiectasis (p=0.0001) than those with HHT2. Pulmonary arteriovenous malformations were only reported in the endoglin mutation group in our study (p<0.001). CONCLUSIONS: Our questionnaire based study provides evidence that the HHT phenotype caused by mutations in endoglin (HHT1) is distinct from, and more severe than, HHT caused by mutations in ALK1 (HHT2). This has significant implications for diagnosis, screening, and treatment in the two different forms of HHT, as well as for understanding the pathogenesis of the disease.

Activin Receptors, Type I↗
PubMed2002

[Peer review of routine clinical case reports - an instrument of quality management? Results of a pilot investigation].

A scoring system for quality assessment of neurological routine case reports was developed in cooperation with the Quality Management Commission of the German Neurological Society (DGN). Five clinical departments of neurology submitted eight anonymized reports for each of seven tracer diagnoses (CNS hemorrhage, ischemic infarction in the anterior circulation, epilepsy, Parkinsonism, bacterial CNS infection, multiple sclerosis (initial diagnosis), polyneuropathy) which were reviewed by two neurologists from different departments. The reports reflect differences between departments concerning certain procedures, especially technical investigations and the use of standardized scores. Interrater reliability was low. However, there were significant and meaningful differences between departments, which can be used for quality improvement. The approach can be recommended for use in peer audits between hospitals.

Benchmarking↗
PubMed2002

Chlamydia pneumoniae DNA in peripheral venous blood samples from patients with carotid artery stenosis.

In the study presented here, peripheral blood specimens obtained from patients with atherosclerosis were examined for the presence of Chlamydia pneumoniae to determine whether these specimens can be used for routine testing. Chlamydia pneumoniae DNA was detected in 7 of 56 patients with carotid stenosis and in three of four patients with other atherosclerotic diseases, but it was not detected in any of 50 healthy controls or in any of 59 age- and gender-matched patients suffering from other nonatherosclerotic diseases. IgG antibodies indicative of an active Chlamydia pneumoniae infection were detected by microimmunofluorescence in two of nine PCR-positive patients but in none of 41 PCR-negative patients. Four of nine serum samples obtained from PCR-positive patients contained IgA antibodies compared to 5 of 41 samples obtained from PCR-negative patients.

Adult↗
PubMed2001

Towards an international consensus on definitions and standardised outcome measures for therapeutic trials (and epidemiological studies) in West syndrome.

This paper argues for a standardized use of definitions and outcome measures in publications on West syndrome. Specific recommendations include the need for a validated definition of hypsarrhythmia, the use of the term non-symptomatic and abandoning the terms cryptogenic and idiopathic, talking about underlying disease association and not aetiology or cause and defining a clinical response to mean that no clinical evidence of a spasm has been seen for a specified time - 48 h was suggested. Patients should be followed up to report development - perhaps at 12-15 months and again at 2 and 5 years. Disease free survival should be reported. Side effects need to be seen as adverse events producing risk modification. Outcomes should be blind whenever possible. A consensus group will take these and other suggestions forward--please contact mail to: mpsjpo@bath.ac.uk if you are interested in taking part.

Clinical Trials as Topic↗
PubMed2000

Expression analysis of endoglin missense and truncation mutations: insights into protein structure and disease mechanisms.

Hereditary hemorrhagic telangiectasia (HHT) is an inherited autosomal dominant vascular dysplasia caused by mutations in either endoglin (HHT1) or activin-like kinase receptor-1 (ALK-1) (HHT2). The majority of the mutations in endoglin cause frameshifts and premature stop codons. Although initial reports suggested a dominant-negative model for HHT1, more recent reports have suggested that mutations in endoglin lead to haploinsufficiency. In this study, we investigated six different missense mutations and two truncation mutations in the endoglin gene to examine whether mechanisms other than haploinsufficiency might be involved in HHT1. Expression of the missense mutants alone revealed that they are misfolded and that most show no cell surface expression. When co-expressed with wild-type endoglin, the missense mutants are able to dimerize with the normal endoglin protein and are trafficked to the cell surface. We also show that although one truncation mutation acts through haploinsufficiency, the other acts in a dominant-negative way. This implies that either dominant-negative protein interactions or haploinsufficiency can cause HHT1. The biochemical analyses for the different mutations suggest that the endoglin N-terminus is important for correct protein folding and that cysteine residues in the first 350 amino acids are involved in intramolecular disulfide bonds, whereas cysteines located closer to the C-terminus of the extracellular domain are responsible for inter-molecular disulfide bond dimerization.

Antigens, CD↗
PubMed2000

[Considerations for standardization of assessment of performance capacity in rehabilitation medicine].

Specific difficulties in the assessment of reduced performance capacity in patients with gastroenterologic illness led to the development of a standardized and unified assessment method. The following five steps--exemplified for chronic liver-disease--were designed: (1) determination of disease features (and their graduations), leading to reduced performance capacity; (2) construction of a detailed performance capacity model using more concrete factors (e.g. motivation, cognition, cardiovascular-pulmonary system, etc.); (3) deduction of rules between disease features and the concrete factors of performance capacity, describing the expected (unfavourable) limitations; (4) consideration of individual limitations on the level of the concrete factors, and (5) conversion into a computer-aided expert system. The benefit of the method developed lies in prompt and practicable assistance by the expert system and in transparency of the decision processes. Therefore, performance capacity assessment will certainly gain in reliability and objectivity.

Algorithms↗
PubMed1999

High-performance liquid chromatographic determination of peroxisomicine A1 (T-514) in genus Karwinskia.

A chromatographic method was developed for the T-514 determination in Karwinskia leaves, stems and roots. A C18 analytical column and a mobile phase consisting of methanol and McIlvaine buffer (pH 3) were used. T-514 was detected using a diode array detector and the chromatograms were recorded at 269 and 410 nm. A linear dependence of a peak area on the T-514 concentration (r=0.9991) was obtained in the range of 0.126-12.6 microg/ml. Limits of T-514 quantification (signal-to-noise ratio 10) in plant samples were 126 ng/ml at 410 nm and 28 ng/ml at 269 nm. T-514 was extracted from the plant material with ethyl acetate. Optimal extraction conditions were studied: number of extraction steps, volume of extracting agent and extraction time. The extracts were cleaned up using solid-phase extraction (SPE). SPE recoveries of 99.9% and 98.4% were achieved for the T-514 concentrations of 1.4 microg/ml and 0.26 microg/ml, respectively.

Anthracenes↗
PubMed1999

Assignment of transforming growth factor beta1 and beta3 and a third new ligand to the type I receptor ALK-1.

Germ line mutations in one of two distinct genes, endoglin or ALK-1, cause hereditary hemorrhagic telangiectasia (HHT), an autosomal dominant disorder of localized angiodysplasia. Both genes encode endothelial cell receptors for the transforming growth factor beta (TGF-beta) ligand superfamily. Endoglin has homology to the type III receptor, betaglycan, although its exact role in TGF-beta signaling is unclear. Activin receptor-like kinase 1 (ALK-1) has homology to the type I receptor family, but its ligand and corresponding type II receptor are unknown. In order to identify the ligand and type II receptor for ALK-1 and to investigate the role of endoglin in ALK-1 signaling, we devised a chimeric receptor signaling assay by exchanging the kinase domain of ALK-1 with either the TGF-beta type I receptor or the activin type IB receptor, both of which can activate an inducible PAI-1 promoter. We show that TGF-beta1 and TGF-beta3, as well as a third unknown ligand present in serum, can activate chimeric ALK-1. HHT-associated missense mutations in the ALK-1 extracellular domain abrogate signaling. The ALK-1/ligand interaction is mediated by the type II TGF-beta receptor for TGF-beta and most likely through the activin type II or type IIB receptors for the serum ligand. Endoglin is a bifunctional receptor partner since it can bind to ALK-1 as well as to type I TGF-beta receptor. These data suggest that HHT pathogenesis involves disruption of a complex network of positive and negative angiogenic factors, involving TGF-beta, a new unknown ligand, and their corresponding receptors.

Activin Receptors↗
PubMed1999

Left ventricular mass and microalbuminuria: relation to ambulatory blood pressure. Hypertension Diagnostic Service Investigators.

1. Both microalbuminuria and left ventricular hypertrophy may reflect target organ damage in essential hypertension. Both are related to the prevailing level of blood pressure and both are associated with an increase in morbidity and mortality. 2. The database of the Hypertension Diagnostic Service, a multicentre secondary referral clinic for patients with essential hypertension, was analysed in order to clarify the level of association between microalbuminuria and left ventricular hypertrophy, which might explain the observed increase in morbidity and mortality in patients with microalbuminuria. Microalbuminuria was measured semiquantitatively by urine dip-stix. After the exclusion of patients with potential secondary hypertension, renal disease and diabetes mellitus, patients with complete data for microalbuminuria, left ventricular mass (LVM) and 24 h blood pressure monitoring were selected. 3. Data were complete for 704 patients (47% male, age 51 +/- 12 years) and 42% tested positive for microalbuminuria. Microalbuminuria was positively related to 24 h systolic blood pressure and weight and was negatively related to age. Left ventricular mass was higher in patients with microalbuminuria (men, 265 +/- 69 g; women, 207 +/- 61 g) than in those without (men, 250 +/- 64 g, P < 0.05; women, 185 +/- 50 g, P < 0.001). After correction for the effects of gender, body mass index and 24 h systolic blood pressure, the presence of microalbuminuria was associated with an increase in LVM of 10 g (P < 0.05, 95% confidence interval, 2-19 g).

Adult↗
PubMed1998

Mutation and expression analysis of the endoglin gene in hereditary hemorrhagic telangiectasia reveals null alleles.

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder characterized by multisystemic vascular dysplasia and recurrent hemorrhage from the sites of vascular lesions. Two genes have been identified for HHT. Endoglin, a TGF-beta binding protein which maps to chromosome 9q3, is the gene for HHT1. The type and location of most of the previously described mutations in the endoglin (ENG) gene suggested a dominant-negative model of receptor-complex dysfunction for the molecular basis of this disorder. In this article we describe 11 novel ENG mutations in HHT kindreds, which include missense and splice-site mutations. Two identical missense mutations in unrelated families disrupt the start codon of the gene. In addition, some frameshift and nonsense mutations lead to very low or undetectable levels of transcript from the mutant allele. These combined data suggest that the nature of most ENG mutations is to create a null (nonfunctional) allele, and that there is no requirement for the synthesis of a truncated endoglin protein in the pathogenesis of HHT.

Alleles↗