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Biomedical subjects

A Forster

Publications and source records attributed to A Forster.

At least 37 records · Page 2Linked to original sources

A test-retest reliability study of the Barthel Index, the Rivermead Mobility Index, the Nottingham Extended Activities of Daily Living Scale and the Frenchay Activities Index in stroke patients.

PURPOSE: To assess the test-retest reliability of a range of outcome measures in stroke patients. METHOD: Twenty-two patients > 1 year post-stroke were tested twice at an interval of 1 week using the Barthel Index (BI); the Rivermead Mobility Index (RMI); the Nottingham Extended Activities of Daily Living Scale (NEADL); and the Frenchay Activities Index (FAI). The mean difference (bias) and reliability coefficient (random error) were calculated for the total scores. Percentage agreement and the kappa coefficient were used to analyse individual items. RESULTS: The mean differences and reliability coefficients were BI 0.4 +/- 2.0, RMI 0.3 +/- 2.2, the NEADL 0.6 +/- 5.6, FAI -0.6 +/- 7.1. There was little bias between assessments. The performance of the BI and RMI were better with lower random error. The NEADL and FAI did not perform as well having larger random error components. Percentage agreements were generally high especially for the BI (>75%) and RMI (>85%), but there was considerable variation in the kappa coefficients. CONCLUSION: Measurement of basic activities of daily living and mobility as measured by the BI and RMI is reliable post-stroke. Measurements used to assess extended activities of daily living were less reliable in this study.

Activities of Daily Living↗

Selection of excipients for melt extrusion with two poorly water-soluble drugs by solubility parameter calculation and thermal analysis.

The aim of this study was to determine the miscibility of drug and excipient to predict if glass solutions are likely to form when drug and excipient are melt extruded. Two poorly water-soluble drugs, indomethacin and lacidipine, were selected along with 11 excipients (polymeric and non-polymeric). Estimation of drug/excipient miscibility was performed using a combination of the Hoy and Hoftzyer/Van Krevelen methods for Hansen solubility parameter calculation. Miscibility was experimentally investigated with differential scanning calorimetry (DSC) and hot stage microscopy (HSM). Studies were performed at drug/excipient ratios, 1:4, 1:1 and 4:1. Analysis of the glass transition temperature (T(g)) was performed by quench cooling drug/excipient melts in the DSC. Differences in the drug/excipient solubility parameters of <7.0 MPa(1/2) were predicted to indicate significant miscibility and, therefore, glass solution formation on melt extrusion. In comparison, differences of >10 MPa(1/2) were expected to indicate a lack of miscibility and not form glass solutions when melt extruded. Experimentally, miscibility was shown by changes in drug/excipient melting endotherms and confirmed by HSM investigations. Experimental results were in agreement with solubility parameter predictions. In addition, drug/excipient combinations predicted to be largely immiscible often exhibited more than one T(g) upon reheating in the DSC. Melt extrusion of miscible components resulted in amorphous solid solution formation, whereas extrusion of an "immiscible" component led to amorphous drug dispersed in crystalline excipient. In conclusion, combining calculation of Hansen solubility parameters with thermal analysis of drug/excipient miscibility can be successfully applied to predict formation of glass solutions with melt extrusion.

Calorimetry, Differential Scanning↗

Electric manipulation of bioparticles and macromolecules on microfabricated electrodes.

Bioparticle separation, bioparticle enrichment, and electric field-mediated immune detection were carried out on microfabricated semiconductor chips utilizing ac and dc electric fields. Microscale separation on a chip surface having an active area of approximately 16 mm2 was demonstrated for a mixture of Bacillus globigii spores and Escherichia coli bacteria. Dielectrophoretic enrichment was performed by collecting target bioparticles from a flow stream in flow cells of 47.5 microL, achieving a 20-fold increase in the concentration of E. coli bacteria from a diluted sample, a 28-fold enrichment for peripheral blood mononuclear cells from red blood cells, and a 30-fold increase in white blood cells from diluted whole blood. The ability to manipulate and collect bioparticles and macromolecules at microfabricated electrodes with ac and dc fields was further illustrated in electric field-mediated immunoassays for analyzing the biological identities of E. coli bacteria and B. globigii spores. According to these results, the electric methods for manipulating bioparticles present themselves as viable techniques for novel biomedical applications in sample preparations and biochemical assays on microelectrode arrays.

Bacillus↗

Information provision for stroke patients and their caregivers.

BACKGROUND: The provision of information has been recommended as a key component of service provision after stroke. However, research suggests that patients' understanding of stroke and associated issues remains poor. We determined to undertake a systematic review of information provision strategies for patients and their carers after stroke. OBJECTIVES: To examine the effectiveness of an information and/or education strategy to improve the outcome of stroke patients and/or their identified caregivers. SEARCH STRATEGY: Relevant trials were identified in the Cochrane Stroke Group Specialised Trials Register (last searched: June 2000). Additional intervention-based search strategies were developed for: The Cochrane Controlled Trials Register (CENTRAL/CCTR) Medline; Embase; CINAHL; ISI citation index; Science and Social Science Citation Indexes; ISI Web of Science Service; Aslib Index to UK theses; Dissertation Abstracts International, ASSIA and Psychlit/PsycINFO. We also searched the Journal of Advanced Nursing, bibliographies of retrieved papers, relevant articles and books. SELECTION CRITERIA: Two or three investigators independently assessed trials and abstracts identified for eligibility, methodological quality and other participant characteristics. DATA COLLECTION AND ANALYSIS: Data were extracted independently using piloted data extraction forms. The primary outcomes were knowledge about stroke and stroke services, and impact on health, specifically mood. MAIN RESULTS: We identified 152 abstracts, of which 36 studies were potentially relevant to this review. The current analysis includes nine completed trials, a further eight studies are ongoing. Of the nine trials, three evaluated a programme of lectures and the remaining trials evaluated the provision of information. There is some evidence that information combined with educational sessions improved knowledge and was more effective than providing information only. Information provision only had no effect on mood, perceived health status or quality of life for patients or carers. Two trials used an objective measure of satisfaction and no significant differences were found between groups. One trial reported that information and education sessions for carers improved 'family functioning'. REVIEWER'S CONCLUSIONS: The results of the review are limited by the variable quality of the trials and the wide range of outcome measures used. The general effectiveness of information provision has not been conclusively demonstrated. Future work should address the expressed needs of patients and carers and seek to identify appropriate teaching strategies which can be successfully implemented within clinical practice.

Caregivers↗

Cost-effective and uniform (13)C- and (15)N-labeling of the 24-kDa N-terminal domain of the Escherichia coli gyrase B by overexpression in the photoautotrophic cyanobacterium Anabaena sp. PCC 7120.

Structural studies of biomolecules using nuclear magnetic resonance (NMR) rely on the availability of samples enriched in (13)C and (15)N isotopes. While (13)C/(15)N-labeled proteins are generally obtained by overexpression in transformed Escherichia coli cells cultured in the presence of an expensive mixture of labeled precursors, those of the photoautotrophic cyanobacterium Anabaena sp. PCC 7120 can be uniformly labeled by growing them in medium containing Na(15)NO(3) and NaH(13)CO(3) as the sole nitrogen and carbon sources. We report here a novel vector-host system suitable for the efficient preparation of uniformly (13)C/(15)N-labeled proteins in Anabaena sp. PCC 7120. The 24-kDa N-terminal domain of the E. coli gyrase B subunit, used as a test protein, was cloned into the pRL25C shuttle vector under the control of the tac promoter. The transformed Anabaena cells were grown in the presence of the labeled mineral salts and culture conditions were optimized to obtain over 90% of (13)C and (15)N enrichment in the constitutively expressed 24-kDa polypeptide. The yield of purified 24-kDa protein after dual isotope labeling under anaerobic conditions was similar to that obtained with E. coli cells bearing a comparable expression vector and cultured in parallel in a commercially available labeling medium. Furthermore, as probed by NMR spectroscopy and mass spectrometry, the 24-kDa N-terminal domain expressed in Anabaena was identical to the E. coli sample, demonstrating that it was of sufficient quality for 3D-structure determination. Because the Anabaena system was far more advantageous taking into consideration the expense for the labels that were necessary, these results indicate that Anabaena sp. PCC 7120 is an economic alternative for the (13)C/(15)N-labeling of soluble recombinant proteins destined for structural studies.

Carbon Isotopes↗

[Clinical experience with TNF-blockers].

Recently, biologic agents have become available for the treatment of rheumatoid arthritis. Such agents, the so-called TNF blockers, selectively inhibit TNF alpha, a dominant proinflammatory cytokine. They allow good suppression of the disease activity in many patients. Even in nonresponders to conventional disease modifying antirheumatic drugs (DMARDs) a good response may be achieved. The anti-erosive effect appears to be excellent. Major advantages are the fast response and good overall safety. Constitutional symptoms often disappear rapidly, which may contribute substantially to the gain in quality of life. Efficacy and safety are maintained even in long-term use. Because of certain risks and high costs TNF-blocking agents should be reserved for patients who respond poorly to conventional DMARDs or do not tolerate them.

Antibodies, Monoclonal↗

[Clinical quality management in rheumatoid arthritis].

Clinical quality management in rheumatoid arthritis (RA) aims at reducing inflammatory activity and pain in the short term and damage and disability in the long term. In the "Swiss Clinical Quality Management in rheumatoid arthritis" (SCQM) project, which started in 1997, a measurement-improvement system with feedback reports allows the rheumatologists to follow their RA patients with the aim of improving the quality of outcome. Inflammatory activity is measured with the Disease Activity Score (DAS28) and the Rheumatoid Arthritis Disease Activity Index questionnaire (RADAI), damage with an X-ray score and disability with the Stanford Health Assessment Questionnaire (HAQ). The feedback is used by the individual rheumatologist to optimize the therapy of his/her RA patients. Beside the aim of improving the quality of treatment, the SCQM projects wants to build a Swiss cohort of RA patients, to improve the collaboration of rheumatologists in the clinic and in practice and to establish standards of treatment in RA. In this paper we describe the SCQM project in detail, we show two cases illustrating the usefulness of the SCQM in the management of individual RA patients, and we present the cross sectional analysis of the first 1223 RA patients included in the project.

Antirheumatic Agents↗

The potential of small-scale fusion experiments and the Gordon-Taylor equation to predict the suitability of drug/polymer blends for melt extrusion.

The aim of this study was to investigate the use of small-scale fusion experiments and the Gordon-Taylor (GT) equation to predict whether melt extrusion of a drug with an amorphous polymer produces a stable amorphous dispersion with increased drug dissolution. Indomethacin, lacidipine, nifedipine, piroxicam, and tolbutamide were used as poorly soluble drugs. Drug/polyvinylpyrrolidone (PVP) blends were prepared at a 1:1 mass ratio. Small-scale fusion experiments were performed in a differential scanning calorimeter (DSC) and in stainless steel beakers. Extrusion was performed in a Brabender Plasti-corder. The glass transition temperatures Tg were determined by DSC. Taking an average Tg from the DSC melt, beaker melt, and GT equation accurately predicted the extrudate Tg. Physical stability of beaker melt and extrudate samples was tested by X-ray powder diffraction (XRPD) and DSC after storage at 30 degrees C (beaker melt) or 25 degrees C (extrudate) and less than 10%, 60%, and 75% relative humidity, (RH). Beaker melts were amorphous, apart from some residual crystallinity. Extrudates were amorphous after preparation. Except for indomethacin/PVP, which remained amorphous, the crystallinity of beaker melts and extrudates increased only at 75% RH. Recrystallization occurred even when the Tg of the sample was well above the storage temperature. Chemical stability of the beaker melts and extrudates was tested by capillary electrophoresis and high-performance liquid chromatography (HPLC). Stability was slightly improved in the extrudate compared to the beaker melt. In general, the order for rate of dissolution was crystalline drug was less than the physical mixture, which was less than the drug/PVP beaker melt, which was approximately equal to the extrudate. The use of beaker melts allows a conservative estimate of the potential to melt extrude a drug. To predict physical stability, analysis of the Tg must be combined with physical stability experiments.

Algorithms↗

Determinants of social outcome measured by the Frenchay Activities Index at one year after stroke onset.

We report an investigation to identify patient factors which influence social outcome measured by the Frenchay Activities Index at 12 months after a disabling stroke. Using data from a previous randomised trial a logistic regression model identified gait speed, prestroke Frenchay Activities Index, the Abbreviated Mental Test score, sensory neglect, chronic obstructive airways disease and left hemiplegia as significantly associated with 12-month social outcome scores. The model correctly predicted the social outcome for 78% of the study population and, when tested on a second data set, correctly predicted 76% of cases. These patient factors provide insight into social activity recovery after stroke and could be considered as stratification factors in future community stroke randomised trials.

Activities of Daily Living↗

Characterization of glass solutions of poorly water-soluble drugs produced by melt extrusion with hydrophilic amorphous polymers.

Indomethacin, lacidipine, nifedipine and tolbutamide are poorly soluble in water and may show dissolution-related low oral bioavailability. This study describes the formulation and characterization of these drugs as glass solutions with the amorphous polymers polyvinylpyrrolidone (PVP) and polyvinylpyrrolidone-co-vinyl acetate by melt extrusion. The extrudates were compared with physical mixtures of drug and polymer. X-ray powder diffraction, thermal analysis, infrared spectroscopy, scanning electron microscopy, HPLC, moisture analysis and dissolution were used to examine the physicochemical properties and chemical stability of the glass solutions prepared by melt extrusion at a 1:1 drug/polymer ratio. Depending on the temperature used, melt extrusion produced amorphous glass solutions, with markedly improved dissolution rates compared with crystalline drug. A significant physico-chemical interaction between drug and polymer was found for all extrudates. This interaction was caused by hydrogen bonding (H-bonding) between the carbonyl group of the pyrrole ring of the polymer and a H-donor group of the drug. Indomethacin also showed evidence of H-bonding when physical mixtures of amorphous drug and PVP were prepared. After storage of the extrudates for 4-8 weeks at 25 degrees C/75% relative humidity (RH) only indomethacin/polymer (1:1) extrudate remained totally amorphous. All extrudates remained amorphous when stored at 25 degrees C/< 10% RH. Differences in the physical stability of drug/polymer extrudates may be due to differences in H-bonding between the components.

Chemical Phenomena↗

Tissue plasminogen activator for the treatment of deep venous thrombosis of the lower extremity: a systematic review.

OBJECTIVE: To assess, by systematic review, the efficacy and safety of recombinant tissue plasminogen activator (rt-PA) in the treatment of lower extremity deep venous thrombosis (DVT). A secondary objective is to assess the optimal dose and route of administration of rt-PA. METHODS: Included studies were randomized, controlled trials comparing rt-PA plus unfractionated heparin (UFH) to UFH alone, rt-PA at different doses, or rt-PA by different routes of administration in the treatment of DVT. Outcomes had to be described in terms of percent change in venographic patency for efficacy (>50% lysis) and in sufficient detail for complications (major and minor hemorrhages and other). The search strategy included searching electronic databases and contacting pharmaceutical agencies and content experts. Study quality was assessed using the Jadad scale. A threshold quality score was used to exclude trials. RESULTS: Five studies met the following inclusion criteria: three comparing rt-PA plus UFH vs UFH alone (180 patients); one comparing high-dose vs low-dose rt-PA (32 patients); and one comparing systemic vs local administration of rt-PA (151 patients). In studies comparing rt-PA vs placebo, patients assigned to rt-PA were more likely to have > 50% lysis and complications (summary odds ratios [OR], 11.7; 95% confidence interval [CI], 2.61 to 52.5; and OR, 9.95; 95% CI, 2.21 to 44.7, respectively). Major and intracerebral hemorrhages were not significantly increased. One study comparing different doses demonstrated that high-dose and low-dose rt-PA were equally efficacious (OR, 0.88; 95% CI, 0.05 to 14.78). Local rt-PA was neither more efficacious nor riskier than systemic rt-PA. CONCLUSION: This systematic review does not support routine use of rt-PA for DVT.

Anticoagulants↗

Tumorigenesis in mice with a fusion of the leukaemia oncogene Mll and the bacterial lacZ gene.

Many different chromosomal translocations occur in man at chromosome 11q23 in acute leukaemias. Molecular analyses revealed that the MLL gene (also called ALL-1, HRX or HTRX) is broken by the translocations, causing fusion with genes from other chromosomes. The diversity of MLL fusion partners poses a dilemma about the function of the fusion proteins in tumour development. The consequence of MLL truncation and fusion has been analysed by joining exon 8 of Mll with the bacterial lacZ gene using homologous recombination in mouse embryonic stem cells. We show that this fusion is sufficient to cause embryonic stem cell-derived acute leukaemias in chimeric mice, and these tumours occur with long latency compared with those found in MLL-Af9 chimeric mice. These findings indicate that an MLL fusion protein can contribute to tumorigenesis, even if the fusion partner has no known pathogenic role. Thus, truncation and fusion of MLL can be sufficient for tumorigenesis, regardless of the fusion partner.

Amino Acid Sequence↗

The oncogenic LIM-only transcription factor Lmo2 regulates angiogenesis but not vasculogenesis in mice.

The LMO2 gene is activated by chromosomal translocations in human T cell acute leukemias, but in mouse embryogenesis, Lmo2 is essential for initiation of yolk sac and definitive hematopoiesis. The LMO2 protein comprises two LIM-zinc-finger-like protein interaction modules and functions by interaction with specific partners in DNA-binding transcription complexes. We have now investigated the role of Lmo2-associated transcription complexes in the formation of the vascular system by following the fate of Lmo2-null embryonic stem (ES) cells in mouse chimeras. Lmo2 is expressed in vascular endothelium, and Lmo2-null ES cells contributed to the capillary network normally until around embryonic day 9. However, after this time, marked disorganization of the vascular system was observed in those chimeric mice that have a high contribution of Lmo2-null ES cells. Moreover, Lmo2-null ES cells do not contribute to endothelial cells of large vessel walls of surviving chimeric mice after embryonic day 10. These results show that Lmo2 is not needed for de novo capillary formation from mesoderm but is necessary for angiogenic remodeling of the existing capillary network into mature vasculature. Thus, Lmo2-mediated transcription complexes not only regulate distinct phases of hematopoiesis but also angiogenesis, presumably by Lmo2 interacting with distinct partners in the different settings.

Adaptor Proteins, Signal Transducing↗

Medical day hospital care for the elderly versus alternative forms of care.

BACKGROUND: Geriatric day hospitals provide multi-disciplinary rehabilitation in an outpatient setting. Concern has been expressed that evidence for effectiveness is equivocal and that day hospital care is expensive. OBJECTIVES: To assess the effects of medical day hospitals for elderly people. SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, Sigle, Bids, and Cinahl up to January 1997, and reference lists of articles. We also searched Index Medicus and International Dissertation Abstracts up to January 1997. We contacted authors of previous studies of day hospital care. SELECTION CRITERIA: Randomised trials comparing geriatric medical day hospitals with alternative forms of care. The participants were elderly medical patients. The outcomes were death, place of residence, dependency, global 'poor' outcome (death, institutionalisation or dependency), activities of daily (ADL) score, subjective health status, patient satisfaction, and resource use. DATA COLLECTION AND ANALYSIS: Three reviewers independently extracted data and assessed study quality. MAIN RESULTS: Twelve studies were included involving 22 day hospitals and 2867 patients. Five studies compared day hospital with comprehensive elderly care, four compared day hospital with domiciliary care and three compared day hospital with no comprehensive elderly care. There were no significant differences between day hospital attendance and comparison treatments for the outcomes of death, death or requiring institutional care, death or deterioration in ADL. When death or a 'poor' outcome at follow up was examined there was a significant difference in favour of day hospital attendance when compared to no comprehensive elderly care (odds ratio 0.73; 95% confidence interval 0.53-1.00; P < 0.05). Dependency was measured in 11 studies using a variety of ADL measures; two described short-term improvement for the day hospital group, one reported improved outcome for the comparison group, while in the remainder there was no statistically significant difference. Using the outcome of deterioration in ADL among survivors, day hospital patients showed reduced odds of deterioration compared with those receiving no comprehensive elderly care (0.60; 0.38-0.97; P <0.05). When resource use was examined the day hospital group showed trends towards reductions in hospital bed use and placement of survivors in institutional care. Nine studies comparing treatment costs indicated that day hospital attendance was a more expensive option, although only two analyses took into account long-term care costs. REVIEWER'S CONCLUSIONS: Medical day hospital care for the elderly appears to be more effective than no intervention but may have no clear advantage over other forms of comprehensive elderly medical services.

Aged↗

Anesthetic assessment in an outpatient consultation clinic reduces preoperative anxiety.

PURPOSE: Preoperative anxiety in relation to anesthesia remains for many patients a major subject of concern. The aim of the present study was to compare the level of preoperative anxiety in patients assessed in an outpatient consultation clinic with the anxiety level of those having been assessed by the anesthesiologist after entering the hospital. METHOD: We studied two groups of 20 patients who underwent elective transurethral prostate or bladder resection: group A having the anesthetic assessment between one-two weeks before hospitalisation, group B having this assessment the evening before surgery, after entering the hospital. Two different methods to assess anxiety were used: the Multiple-Affect-Adjective-Check-List (MAACL) and the visual analogue scale of anxiety (VAS). RESULTS: Both anxiety provided scores, assessed by two different methods, were lower in group A, than in group B(P<0.01). CONCLUSION: The results of this study confirm that an anesthetic assessment in an outpatient consultation clinic reduces preoperative anxiety, when compared with an assessment on the evening before surgery.

Adult↗

Treatment efficacy is not an index of pain intensity.

PURPOSE: To determine if the efficacy of pain treatment assessed by the patient is a valid indicator to evaluate pain management. METHODS: Three hundred and ninety one adult patients were investigated on the day of surgery and on the two following days after intraperitoneal or orthopedic surgery. Pain scores and efficacy of pain treatment were evaluated using ungraduated visual analog scales (VAS). According to the evolution of pain between two consecutive days, patients were classified as having "worse pain", "same pain" or "lower pain". RESULTS: During the first time interval, pain treatment was considered effective by 42% of patients with worse pain, compared with 55% with less pain (OR= 1.9, 95% CI=1.1-3.7) and to 58% of patients with the same pain (OR =2.0, 95%CI=1.2-3.0). During the second time interval, these proportions were: 46% (worse pain), 63% (lower pain vs worse: OR= 1.8, 95%CI= 1.0-3.2) and 66% (same pain vs worse: OR=2.1, 95%CI=1.1-4.1). Using pain evolution as a"gold standard", patient assessment of pain treatment efficacy had sensitivity of 0.55 and specificity 0.5 during the first time interval, and of 0.63 and 0.43 during the second time interval. CONCLUSION: Patient evaluation of the efficacy of pain treatment can mislead the clinician about the severity of pain. Patients tend to be satisfied with pain treatment, even when pain is not relieved. The relation of intensity of pain to patient perception of treatment efficacy is weak.

Adolescent↗

Pain intensity and pain relief after surgery. A comparison between patients' reported assessments and nurses' and physicians' observations.

BACKGROUND: Postoperative pain remains a problem for many patients. One of the reasons could lie in the insufficient evaluation of pain and analgesia. This study was designed to obtain more insight in the performance of nurses and physicians in evaluating patients' postoperative pain and pain relief. METHODS: Forty patients hospitalised in one surgical unit and the 8 nurses and the 2 surgical residents in charge of this unit were investigated. Patients were asked to assess on a visual analogue scale the intensity of their pain and their pain relief at rest, on coughing and globally since the operation, on the first and second postoperative days and the day before hospital discharge. Separately, the nurses and the physicians were asked to evaluate the pain intensity and the pain relief for each patient involved. A MANOVA and a multiple comparisons test with Bonferroni adjustment were used. RESULTS: At rest, only nurses underestimated pain intensity on the day before hospital discharge. On coughing, physicians underestimated pain intensity in all 3 assessments, whereas nurses only in the 3rd assessment (on the day before hospital discharge). Globally, physicians underestimated pain intensity in all 3 assessments, nurses in the 2nd and the 3rd assessment. Only physicians overestimated pain relief on coughing on the day before hospital discharge and globally in all 3 assessments. Surprisingly, the pain scores rated by the patients before hospital discharge were high. CONCLUSION: The results of this survey suggest that assessment of pain and pain relief is inadequately done by both physicians and nurses. This emphasises the importance of a better training, and a systematic assessment of pain intensity and pain relief.

Female↗