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PubMed2006

Maximum oxygen uptake at peak exercise in elderly patients with coronary artery disease and preserved left ventricular function: the role of inflammation on top of tissue Doppler-derived systolic and diastolic function.

BACKGROUND: Several studies have shown that longitudinal systolic function and left ventricular filling pressures, as assessed with tissue Doppler imaging, predict exercise capacity. AIM: The aim of this study was to evaluate whether natriuretic peptides and inflammatory parameters can independently predict maximum oxygen uptake at peak exercise (VO2max) on top of tissue Doppler imaging-derived markers. METHODS: We evaluated 142 patients (age 70 +/- 6 years, 77% men) with known or suspected coronary artery disease and a preserved left ventricular ejection fraction (> or = 50%). All patients underwent bicycle spiroergometry, and N-terminal pro-B-type natriuretic peptide levels were determined. Cytokines (IL-6 and soluble tumor necrosis factor receptors 1 and 2) and high-sensitivity C-reactive protein were measured as inflammatory markers. Tissue Doppler imaging was applied to evaluate peak long axis systolic velocities (Sm) and early mitral annulus velocities (E'). Ratio of early transmitral flow (E) to E' was assessed as marker of left ventricular filling. Analysis of variance, comparing VO2max quartiles, was used to determine univariate predictors and linear regression to determine multivariate VO2max predictors. RESULTS: Average VO2max was 18.5 +/- 5.7 mL/kg per minute (range 6-36.6). Compared with the highest quartile, patients with low VO2max were more frequently women (P < .0001). N-terminal pro-B-type natriuretic peptide and cytokine levels were significantly higher in the lower VO2max categories. Longitudinal myocardial velocities increased, and E/E' decreased along with increasing VO2max. In multivariate linear regression analysis, VO2max was independently predicted by sex, glucose, Sm, E/E', and cytokine levels. CONCLUSION: Maximum oxygen uptake at peak exercise in patients with known or suspected coronary artery disease and preserved systolic function was independently predicted by inflammatory makers on top of tissue Doppler-derived systolic and diastolic function.

Aged↗

PubMed1999

Pulmonary function, cardiac function, and exercise capacity in a follow-up of patients with congestive heart failure treated with carvedilol.

BACKGROUND: Chronic heart failure causes disturbances in ventilation and pulmonary gas transfer that participate in limiting peak exercise oxygen uptake (VO(2p )). The beta-adrenergic receptor blocker carvedilol improves left ventricular (LV) function and not VO(2p). This study was aimed at investigating the pulmonary response to changes in LV performance produced by carvedilol in patients with chronic heart failure. METHODS: Twenty-one patients with New York Heart Association class II to III heart failure were randomly assigned (2 to 1) to carvedilol (25 mg twice daily, n = 14) or placebo (n = 7) for 6 months. Rest forced expiratory volume (FEV(1)), vital capacity, total lung capacity, carbon monoxide diffusing capacity, its alveolar-capillary membrane component, pulmonary venous and transmitral flows (for monitoring changes in LV end-diastolic pressure), LV diastolic and systolic dimensions, stroke volume, ejection fraction, and fiber shortening velocity were measured at baseline and at 3 and 6 months. VO(2p), peak ratio of dead space to tidal volume (VD/VT(p)), ventilatory equivalent for carbon dioxide production (VE/VCO(2)), and VO(2) at anaerobic threshold (VO(2at)) were also determined. RESULTS: FEV(1), vital capacity, total lung capacity, carbon monoxide diffusing capacity, and the alveolar-capillary membrane component were impaired in chronic heart failure compared with 14 volunteers and did not vary with treatment. Carvedilol reduced end-diastolic pressure, end-diastolic diameter, and end-systolic diameter and increased ejection fraction, stroke volume, and fiber shortening velocity without affecting VO(2p), VO(2at), VD/VT(p), or VE/VCO(2) at 3 and 6 months. Placebo did not produce significant changes. CONCLUSIONS: In chronic heart failure carvedilol ameliorates LV function at rest and does not significantly affect ventilation and pulmonary gas transfer or functional capacity. These results suggest that improvement in cardiac hemodynamics with carvedilol does not reverse pulmonary dysfunction. Persistent lung impairment might have some role in the failure of carvedilol to improve exercise performance.

Adrenergic beta-Antagonists↗

PubMed2003

Robust localization and lateralization of human language function: an optimized clinical functional magnetic resonance imaging protocol.

An optimized clinical functional magnetic resonance imaging (fMRI) protocol with a total scanning time of 8 min is presented that localizes Broca's and Wernicke's areas robustly and determines hemispheric dominance. Language function was visualized using two different sentence generation (SG) and word generation (WG) tasks. Block designed blood oxygenation level dependent (BOLD) fMRI was applied in 14 right-handed volunteers at 1.5 T during visual stimulation. BOLD-clusters were assessed individually for anatomical localization. Reference data are provided for the maximum correlation of the measured BOLD-signal time course to the applied reference function (r(max)), for the maximum relative signal change (dS%), cluster size and Euklidian coordinates of Broca and Wernicke activation and of the anatomical homologues in the right hemispheres. Statistical means and a lateralization index (LI) were calculated. Broca activation focussed on the inferior frontal gyrus, and Wernicke activation on the superior temporal, supramarginal or middle temporal gyri. Mean BOLD-signals for Broca ranged from 1.53% (SG) to 2.56% (WG), and for Wernicke from 1.47% (SG) to 1.80% (WG). LI indicated left language dominance. The data provided further evidence for the high anatomical variability of language areas, which underlined the relevance of an individual language localization and lateralization prior to brain surgery.

Adult↗

PubMed2000

Specifications for equipment used for infant pulmonary function testing. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/ American Thoracic Society.

The aim of this position paper is to define minimal performance criteria for the separate items comprising equipment used to measure respiratory function in infants together with overall performance criteria for the assembled pieces of such equipment. These guidelines cover numerous aspects including: 1) safety, 2) documentation and maintenance of equipment, 3) physical characteristics of mechanical parts and signal transducers, and 4) data acquisition. Further, validation procedures for individual components as well as for the integrated equipment are recommended. Adherence to these guidelines should ensure that infant lung function measurements can be performed with an acceptable degree of safety, precision and reproducibility. They will also facilitate multicentre collection of data and performance of clinical investigations. Manufacturers of infant respiratory function equipment should make every effort to comply with these guidelines, which represent the current standards of paediatric health professionals in this field.

Data Collection↗

PubMed2002

The functional impact of the Freehand System on tetraplegic hand function. Clinical Results.

STUDY DESIGN: A B design with subjects acting as their own control when the device is turned off. OBJECTIVE: Evaluation of the efficacy of the NeuroControl Freehand System. SETTING: A supra regional spinal unit in the UK. METHODS: The Freehand system is an implanted Functional Electrical Stimulation (FES) device for restoration of lateral and palmar grasps following C5 or C6 tetraplegia. Its use was assessed using the Grasp Relies Test (GRT), Activities of Daily Living (ADL), Grip strength and two-point discrimination. RESULTS: Seven out of nine subjects are currently daily users of the device. There were statistically significant increases in the number of types of task achieved and the number of repetitions of those tasks in the Grasp Release Test. The system produced a functionally strong grasp where no grip strength at all was possible prior to implantation. Three of the four subjects who had sensory ability prior to implant showed improvements in two-point discrimination. Most of the selected tasks were achieved in the ADL assessment indicating a significant improvement in independence. CONCLUSION: The Freehand system can significantly improve the functional ability of C5 and C6 lesion tetraplegics. SPONSORSHIP: This study was funded by the charity INSPIRE.

Activities of Daily Living↗

PubMed2000

A novel CD18 genomic deletion in a patient with severe leucocyte adhesion deficiency: a possible CD2/lymphocyte function-associated antigen-1 functional association in humans.

Leucocyte adhesion deficiency (LAD) is an autosomal-recessive genetic disease that is characterized clinically by severe bacterial infections and caused by mutations in the CD18 gene that codes for the beta2 integrin subunit. A patient with a severe LAD phenotype was studied and the molecular basis of the disease was identified as a single homozygous defect in a Herpes virus saimiri (HVS)-transformed T-cell line. The defect identified involves a deletion of 171 bp in the cDNA that encodes part of the proteic extracellular domain. This genetic abnormality was further studied at the genomic DNA level and found to consist of a deletion of 169 bp (from -37 of intron 4 to +132 of exon 5), which abolishes the normal splicing and results in the total skipping of exon 5. The 171-bp shortened 'in-frame' mRNA not only resulted in the absence of CD18 expression on the cell surface but also in its absence in the cytoplasm of HVS T-cell lines. Functionally, the LAD-derived HVS T-cell lines showed a severe, selective T-cell activation impairment in the CD2 (but not in the CD3) pathway. This defect was not reversible when exogenous interleukin-2 (IL-2) was added, suggesting that there is also a functional interaction of the lymphocyte function-associated antigen-1 (LFA-1) protein in the CD2 signal transduction pathway in human T cells, as has been previously reported in mice and in the human Papillon-Lefèvre syndrome. Thus, HVS transformation is not only a suitable model for T-cell immunodeficiency studies and characterization, but is also a good system for investigating the immune system in pathological conditions. It may also be used in the future in cellular models for in vitro gene-therapy trials.

Base Sequence↗

PubMed2001

[Comparison of Hannover Functional Ability Questionnaire (FFbH) and the SF-36 subscale "Physical Functioning"].

Pretesting of a questionnaire for evaluating day-patient rehabilitation, which included comparison of the "Hannover Functional Ability Questionnaire" (FFbH) and the SF-36 subscale "physical functioning" (SF-36 PF), gave rise to more extensive validity testing of the two instruments. In the framework of an expanded pretest, a questionnaire including FFbH and SF-36 PF was sent out to 520 adult former patients who had undergone inpatient orthopaedic rehabilitation following total hip or knee replacement an average 16 months ago. Return rate was 76%. Checks on plausibility showed no complaints about the Hannover Functional Ability Questionnaire while, on the SF-36 subscale, it was found that 16 of 374 patients (4.3%) had confused positive and negative ratings. Moreover, problems were found concerning the wording of several items (understanding, multidimensionality). In contrast to the FFbH, the SF-36 subscale shows weaknesses in the formulation of its items and particularly its ratings.

Adult↗

PubMed1983

[Computerized tomography and lung function scintigraphy in central bronchial cancer. Comparison between morphologic and functional changes].

Functional scintigraphic and computer tomographic findings in 20 patients with central bronchial carcinomas were compared in order to determine to what extent functional changes correlate with morphological appearances. Computer tomography shows alterations in the bronchial system more clearly than changes in large or small pulmonary vessels. Pre-operative and subsequent scintigraphy is essential for exact determination of regional lung function. It was shown that short-lived radio-active gases, such as krypton 81, may indicate a total lack of ventilation where there is only a severe bronchial stenosis; the use of longer half-life nucleids, such as krypton 85 or xenon 133, provides good correlation with computer tomographic findings of a bronchial stenosis.

Bronchi↗

PubMed1982

[Excretory pancreatic function: comparison of indirect function tests with the secretin-cholecystokinin test].

In 72 patients with chronic pancreatitis results of tbe secretin-cholecystokinin test were compared with those of several indirect test of pancreatic function (faecal fat content, chymotrypsin activity in faeces, peptide-PABA test, fluorescein-dilaurate test and weight of faeces). In 46 patients with markedly impaired pancreatic secretion the indirect tests were abnormal in 56-83% of cases. In 26 patients with normal or upper-limit-of-normal excretory function the same tests were abnormal in 15-77%. These results indicate that indirect tests of pancreatic function are of only limited value in the early diagnosis of pancreatic insufficiency.

Adult↗

PubMed1994

Protein tyrosine kinase p56-Lck regulates lymphocyte function-associated 1 adhesion molecule expression, granule exocytosis, and cytolytic effector function in a cloned T cell.

Elevated levels of p56-Lck kinase activity were achieved in an interleukin 2 (IL-2)-dependent cloned cytolytic T cell CTLL-2 through gene transfer approaches. CTLL-2-Lck cells remained dependent on IL-2 for growth and survival in culture but exhibited markedly elevated, IL-2-independent cytolytic activity against a variety of tumor targets. This immune cell effector function was similar to the non-major histocompatibility complex-restricted cytolytic activity previously described for lymphokine activated killer (LAK) cells, and involved a cytolytic mechanism that was independent of protein synthesis in either the T cells or the tumor targets. Characterization of CTLL-2-Lck cells revealed markedly elevated levels of both the alpha (CD11a) and beta (CD18) chains of the cell adhesion molecule lymphocyte function-associated 1 (LFA-1) and increased binding of these T cells to a recombinant protein representing the extracellular domain of the LFA-ligand, intercellular adhesion molecule 1 (ICAM-1). Antibodies to CD11a partially abrogated cytolytic killing of tumor target cells by CTLL-2-Lck cells, suggesting that the upregulation in LFA protein levels potentially accounts at least in part for the phenotype of these T cells. Gene transfer-mediated elevations in p56-Lck kinase activity in an IL-3-dependent myeloid cell clone 32D.3 also resulted in increased LFA-1 expression, demonstrating that the findings are not unique to CTLL-2 cells. In addition to upregulation of LFA-1 expression, CTLL-Lck cells also exhibited more efficient exocytosis of cytotoxic granules upon activation with Ca(2+)-ionophore and phorbol ester, relative to control transfected and untransfected CTLL-2 cells. The findings functionally link the Lck kinase to a T cell effector pathway involved in cell-mediated cytotoxicity.

Cell Adhesion↗

PubMed1996

Critical amino acids in the lymphocyte function-associated antigen-1 I domain mediate intercellular adhesion molecule 3 binding and immune function.

We have identified amino acid residues within the evolutionarily conserved I domain of the alpha-chain (CD11a) of the leukocyte integrin leukocyte function-associated antigen (LFA) 1 that are critical for intercellular adhesion molecule (ICAM) 3 (CD50) binding. ICAM-3, a ligand of LFA-1, is thought to mediate intercellular adhesion essential for the initiation of immune responses. Using a panel of human/murine I domain chimeras and point mutants, we observed that the Ile-Lys-Gly-Asn motif, located in the NH2-terminal part of the CD11a I domain, is required for ICAM-3 but not ICAM-1 binding. These findings demonstrate that the I domain of CD11a contains distinct functional subdomains for ligand specific binding. An aspartic acid located at position 137, which is essential to ICAM-1/LFA-1 interactions (Edwards, C.P., M. Champe, T. Gonzalez, M.E. Wessinger, S.A. Spencer, L.G. Presta, P.W. Berman, and S.C. Bodary. 1995. J. Biol. Chem. 270:12635-12640), was also critical for ICAM-3 binding, whereas Ser at position 139 did not effect ICAM-1 or ICAM-3 binding. A synthetic peptide containing the Ile-Lys-Gly-Asn motif inhibited ICAM-3-dependent adhesion and proliferation of T cells at micromolar concentrations, suggesting that this peptide interferes with immune recognition. These observations underscore the importance of ICAM-3 in leukocyte function, and may lead to development of a new category of immunosuppressive agents.

Amino Acid Sequence↗

PubMed2006

Methylmalonic acid and cognitive function in the Medical Research Council Cognitive Function and Ageing Study.

BACKGROUND: An elevated blood concentration of homocysteine is an established risk factor for cognitive impairment and dementia, but associations between cognition and methylmalonic acid (MMA), a related metabolic marker of vitamin B-12 deficiency, are less clear. OBJECTIVE: The aim was to determine the utility of serum MMA and holotranscobalamin as markers of vitamin B-12 status in relation to cognitive function and to investigate their association with discrete cognitive domains. DESIGN: This was a cross-sectional survey of 84 nondemented elderly participants (aged >69 y) from the Welsh cohort of the Medical Research Council's Cognitive Function and Ageing Study. Cognitive status was determined by Mini-Mental State Examination (MMSE) and the Cognitive Section of the Cambridge Mental Disorders of the Elderly Examination (CAMCOG). RESULTS: Nearly one-half (43%) of the persons selected had likely metabolically significant vitamin B-12 deficiency. Higher MMA concentrations were associated with lower MMSE scores independent of age and education (P = 0.007). MMA concentration correlated inversely with CAMCOG scores of ideational praxis (P < 0.05) and language comprehension (P < 0.05) and expression (P < 0.01). Serum folate correlated weakly but significantly with language (P < 0.05), remote memory (P < 0.05), and constructional and ideational praxis scores (P < 0.05 and P < 0.01, respectively). CONCLUSION: The high prevalence of likely metabolically significant vitamin B-12 deficiency in the elderly is associated with lower cognitive function scores and particularly with lower scores of language comprehension and expression.

Aged↗

PubMed1993

Quantification of function regulator therapy using elliptical Fourier functions.

The application of various functional appliances to correct antero-posterior skeletal discrepancies in the treatment of Class III malocclusion has received increased attention. In this context, elliptical Fourier functions (EFF) are particularly useful for eliciting boundary-outline information. This longitudinal study was undertaken to visually and numerically describe the shape alterations arising as a response to treatment with the FR-3 appliance of Fränkel. The subjects chosen were Caucasians (n = 14) from the Glasgow Dental Hospital and School who presented with Class III incisor relationships. Lateral cephalometric head-films were available prior to the initiation of treatment, at the end of active treatment, and at least one year out of retention. Maxillary and mandibular boundary outlines were carefully traced. A set of points, 42 on the maxilla, and 78 on the mandible, were precisely located. These points were then digitized and used to compute EFF's with 20 harmonics. These equations were then standardized for size. Subsequently, 102 maxillary and 150 mandibular closely spaced points on the outline were calculated from the EFF's. After superimposition on the centroid, expected vectors were then computed to these points from the centroid. Statistically significant dento-alveolar shape changes could be discerned with treatment. These involved a localized anterior repositioning of the maxillary incisal aspect with a concomitant posterior displacement of the mandibular incisal aspect. There was no evidence of shape changes in the basal areas of either the maxilla or mandible. This method of fitting Fourier descriptors, specifically EFF's, provides a precise numerical and visual description of the changes arising from functional regulator therapy.

Adolescent↗

PubMed1985

Indoor air pollution and its effect on pulmonary function of adult non-smoking women: III. Passive smoking and pulmonary function.

The association between pulmonary function and exposure to tobacco smoke in the home was investigated in a sample of adult, non-smoking women living in a rural area. The women were all participants in a large longitudinal survey on the natural history and determinants of chronic non-specific lung disease. On cross-sectional analysis, several pulmonary function parameters were found to be significantly associated with exposure to tobacco smoke in the home. There was no association between exposure and pulmonary function decline.

Adult↗

PubMed1999

Intercellular adhesion molecule-1/leukocyte function associated antigen-1 blockade inhibits alloantigen specific human T cell effector functions without inducing anergy.

BACKGROUND: Intercellular adhesion molecule (ICAM-1) is important in leukocyte adhesion-dependent events and some data suggest that ICAM-1 provides T cell costimulation. We anlayzed the role of the ICAM-1 and leukocyte function associated antigen-1 (LFA-1) interaction in human T cell alloreactivity in vitro. METHODS: Allo-antigen-induced T cell proliferation and cytotoxic T lymphocyte lytic activity were assessed by mixed lymphocyte reaction assay and 51 Chromium release assay, respectively. Immunostaining and flow cytometry were used to assess the expression of receptors on activated T cells. RESULTS: Alloantigen-induced T cell proliferation and cytotoxic T lymphocyte activity were markedly inhibited by antibodies to ICAM-1 and LFA-1. These antibodies had to be present at the time of initial T cell receptor/antigen engagement to inhibit proliferation. Neither IL-2 nor IL-4 were involved in the observed inhibition by antibodies. Inhibition was not associated with altered cell surface expression of receptors such as CD3, CD4, ICAM-1, LFA-1, CD25, and HLA-DR however, these antibodies did impede the ability of generation of functionally active T cells. Interestingly, these antibodies inhibited soluble, but not immobilized OKT3-induced proliferation of peripheral blood leukocytes. Antibody-mediated inhibition of proliferation failed to impair the ability of T cells to subsequently proliferate in response to stimulation by the original or third party alloantigen or mobilize [Ca++]i in response to CD3 or LFA-1 receptor ligation. CONCLUSIONS: These data demonstrate that blockade of ICAM-1/LFA-1 binding at the time of allorecognition potently blocks initial T cell effector functions that could be due to lack of effective T cell/APC engagement.

Adult↗

PubMed2004

Addition of sirolimus to cyclosporine delays the recovery from delayed graft function but does not affect 1-year graft function.

Delayed graft function (DGF) has long been identified as one of the main correlates of poor graft survival in cadaveric renal transplantation, but the factors that affect its onset and duration are not fully elucidated. The impact of two immunosuppressive protocols on the incidence and length of DGF among kidney transplant recipients of a suboptimal organ was evaluated. Patients were randomly treated with corticosteroids (CS); low-dose cyclosporine (CsA) and sirolimus (SRL; group 1; n = 42); or CS, full-dose CsA, and mycophenolate mofetil (group 2; n = 48). All recipients received immunoprophylaxis with basiliximab. After 3 mo, group 1 discontinued CsA and continued with SRL, whereas group 2 continued the same treatment. The incidence of DGF was similar in the two groups (group 1 = 52.4%; group 2 = 58.3%), whereas its duration was significantly higher in the group 1 (19.0 +/- 6.0 versus 10.3 +/- 3.2 d; P = 0.001). Both groups showed 100% actuarial graft and patient survival at 1-yr. Among DGF patients, serum creatinine (sCr) at discharge was significantly worse in group 1 (sCr, 3.0 +/- 1.0 versus 1.5 +/- 0.2 mg/dl; calculated creatinine clearance, 31.2 +/- 9.3 versus 61.1 +/- 10 ml/min; P = 0.001). During the first year, the former group displayed a significant improvement of graft function, such that at 1-yr, no difference could be measured between groups (sCr, 1.8 +/- 0.5 versus 1.7 +/- 0.4 mg/dl; calculated creatinine clearance, 51.5 +/- 10.2 versus 53.3 +/- 9.4 ml/min). In conclusion, in de novo renal transplanted patients, the administration of SRL, in combination with low-dose CsA, is associated with a delayed recovery from DGF but does not worsen 1-yr graft function.

Cyclosporine↗

PubMed2004

Respiratory symptoms and lung function of coke oven workers: a lung function surveillance system from 1990-2000.

This study investigated the association of exposure to coke oven emissions with respiratory symptoms and with lung function. Data for respiratory symptoms and lung function were repeatedly collected from 764 male coke oven workers between 1990 and 2000. The data were analyzed cross-sectionally and longitudinally. Working in "Operation" increased the risk for cough (odds ratio [OR] = 2.37), phlegm (OR = 2.55), and shortness of breath (OR = 1.52). Cross-sectionally, each year of working in Operation was associated with a reduction in FEV1 of approximately 10 mL (P = 0.006) and in FVC of around 21 mL (P = 0.0001). From longitudinal analysis, each year of working in Operation was associated with an extra annual decline in FEV1 of 1.5 mL (P = 0.0012) and in FVC of around 1.8 mL (P = 0.0017). Exposure to coke oven emissions increased the risk for respiratory symptoms and adversely affected lung function.

Adult↗

PubMed2005

Boys with posterior urethral valves: outcome concerning renal function, bladder function and paternity at ages 31 to 44 years.

PURPOSE: The short-term prognosis for boys with posterior urethral valves (PUV) has improved in recent decades, but the long-term prognosis in terms of renal and bladder function and fertility is still a matter of great concern. This study is a followup of boys with PUV and dilated upper urinary tract treated in 1956 to 1970 at the Children's Hospital in Göteborg, Sweden. MATERIALS AND METHODS: The records of 54 boys treated for PUV were reviewed. Of 27 boys with PUV and upper urinary tract dilation, 5 boys (18%) died at an early age and 3 boys were lost to followup during adolescence, leaving 19 to be included in the followup. They all answered a questionnaire about renal and bladder function and paternity. RESULTS: Of the 19 men 32% were uremic, 21% had moderate renal failure and 47% had not been checked since adolescence. There were signs of bladder dysfunction in 40% and all these subjects had bladder symptoms suggesting detrusor weakness as the cause. All the men were continent. The ability to father children was dependent on whether or not the man was uremic. CONCLUSIONS: This long-term followup study emphasizes the importance of checking renal and bladder function throughout life in men born with PUV. Increasing attention to bladder dysfunction and its early treatment could probably improve the long-term prognosis.

Adolescent↗