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PubMed1988

Hemodynamic effects of nitrendipine on systolic ventricular function, diastolic ventricular function, and peripheral circulation in essential hypertension.

Twenty patients (aged 33-60 years) with mild to moderate essential hypertension were studied to assess systolic ventricular function, diastolic ventricular function, and peripheral hemodynamic changes induced by nitrendipine during rest and effort, comparing the acute and chronic treatment phases. We used a randomized, placebo-controlled, double-blind, crossover protocol in the acute phase and a paired, placebo group controlled study, with 20 mg single oral daily dose for a 3-week treatment period (chronic phase). The cardiac and peripheral hemodynamic parameters were quantified by noninvasive radionuclides techniques. During acute treatment, peripheral hemodynamics showed a predominantly arteriolar vasodilatory effect with a significant fall in the previously elevated forearm vascular resistance values (-38%, p less than 0.01) and an important increase in forearm blood flow (+49%, p less than 0.01) without any changes in venous capacity. Simultaneously, nitrendipine produced a significant drop in total peripheral resistance (-36%, p less than 0.01), systolic blood pressure (-13%, p less than 0.01), and diastolic blood pressured (-17%, p less than 0.01). The sudden reduction in left ventricular (LV) afterload caused a reflex increase in heart rate (HR) (+12%, p less than 0.01), cardiac index (+37%, p less than 0.01), LV ejection fraction (+17%, p less than 0.01), and peak ejection rate, with an important decrease in LV end systolic volume (-30%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2004

Functional evaluation of emphysema using diffusion-weighted 3Helium-magnetic resonance imaging, high-resolution computed tomography, and lung function tests.

PURPOSE: To assess the emphysematous enlargement of distal airspaces and concomitant large and small airway disease using diffusion-weighted Helium-magnetic resonance imaging (MRI), high-resolution computed tomography (HRCT), and lung function tests (LFT). METHODS: Seven patients were examined after single lung transplantation (LTx) and 1 before double LTx for various forms of emphysema. Five patients after double LTx served as controls. Patients were assessed by Helium-MRI (apparent diffusion coefficient [ADC]), HRCT (mean lung density [MLD], emphysema index [EI]), and LFT. RESULTS: Transplanted lungs: mean ADC = 0.17 cm/s, MLD = -848 H, EI = 22%. Emphysematous lungs: mean ADC = 0.33 cm/s, MLD = -922 H; EI = 54%. Good correlations were found between ADC and MLD (r = 0.6), EI (r = 0.8), intrathoracic gas volume (r = 0.7), forced expiratory volume in 1 second (r = 0.7), and forced expiratory flows (r = 0.7). In contrast, HRCT only provided moderate correlations with LFT (EI: r = 0.5; MLD: r [le] 0.4). CONCLUSION: In this initial study, He-MRI yield good correlations with HRCT and agrees better than HRCT with the functional characterization of emphysema regarding hyperinflation, large and small airway disease as provided by LFT.

Female↗

PubMed1985

Effects of nadolol and propranolol on renal function in hypertensive patients with moderately impaired renal function.

Effects of oral administration of equipotent antihypertensive doses of propranolol and nadolol on renal function were examined in 20 hypertensive patients with moderately impaired renal function. Creatinine clearance increased, and serum beta 2-microglobulin concentrations decreased, when patients were switched from propranolol to nadolol therapy (creatinine clearance = 46.7 +/- 4.9 ml min-1 on propranolol and 52.7 +/- 5.9 on nadolol; beta 2-microglobulin = 6.14 +/- 0.66 mg l-1 on propranolol and 5.62 +/- 0.62 on nadolol). When patients were put back on propranolol, their creatinine clearances (45.9 +/- 5.0 ml min-1) and serum beta 2-microglobulin concentrations (6.51 +/- 0.67 mg l-1) returned to values comparable to those obtained before the change to nadolol was made. Serum beta 2-microglobulin concentrations correlated significantly with creatinine clearance (r = -0.819, P less than 0.001).

Adult↗

PubMed1991

Functional epitope analysis of the human CD11a/CD18 molecule (LFA-1, lymphocyte function-associated antigen 1) involved in HIV-1-induced syncytium formation.

After binding to the CD4 receptor, the human immunodeficiency virus 1 (HIV-1) may enter the T cell and induce the formation of multinucleated giant cells (syncytia). As well as the CD4 molecule, other molecules, such as the lymphocyte function-associated antigen 1 (LFA-1, CD11a/CD18) have been shown to be involved in HIV-1-mediated cell fusion. This study was designed to define regions on the human CD11a/CD18 molecule important for the HIV-1-induced syncytium formation. A CD11a/CD18 MoAb panel discriminating at least five distinct and spatially distant domains on the LFA-1 molecule was used. Comparison of the functional activity of different MoAbs demonstrated that all epitopes of the LFA-1 molecule were not of equal importance in HIV-1-induced syncytium formation between H9.III cells chronically infected with HIV-1 and uninfected CD4+ SupT1 cells. We also demonstrated that CD11a/CD18 MoAbs inhibit syncytia formation only at the level of the uninfected SupT1 cells, suggesting that the LFA-1 molecule expressed on SupT1 cells interacts with ligand(s) expressed on the infected H9.III cells. Two potential LFA-1 receptors on the H9.III cells were tested: the ICAM-1 molecule (intercellular adhesion molecule 1, CD54) and the HIV-1 transmembrane glycoprotein 41 (gp41). A CD54 MoAb (84H10) partially inhibited syncytia formation, thus demonstrating the involvement of the ICAM-1 molecule in the HIV-1-mediated cell fusion. However, the CD11a/CD18 MoAbs do not inhibit binding of the viral envelope glycoprotein gp41 to the cell surface, irrespective of the MoAb concentration used. Although we have not been successful in identifying all candidate fusion receptors for the LFA-1 molecule, these data suggest that some LFA-1 regions are important for syncytium formation and, therefore, in the cell-to-cell transmission of virus and in the spread of infection.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Regulation and functional involvement of distinct determinants of leucocyte function-associated antigen 1 (LFA-1) in T-cell activation in vitro.

The expression of leucocyte function-associated antigen 1 (LFA-1) was studied by immunofluorescence method on human peripheral blood mononuclear cells (PBMC) stimulated by the phytohaemagglutinin lectin (PHA). Monoclonal antibodies (MoAb) Mas 191c, IOT18 (directed against the beta-chain, 95 kDa, CD18) and IOT16, SPVL7, MHM24 (identificating the alpha-chain, 180 kDa, CD11a) were used, defining the 'CD11a/CD18' antibody panel. By means of cross-linking or competitive experiments, we showed that these antibodies recognized at least four distinct and spatially distant domains on the LFA-1 molecule. Immunofluorescence analysis revealed that the up-regulation of LFA-1 expression was a late event, similar to the expression kinetics of the HLA DR and CD38 molecules, and followed the appearance of CD25 and CD71 molecules. Moreover, it was established that the LFA-1 up-regulation required mRNA and protein synthesis. Functional activity comparison of the different anti LFA-1 MoAb showed that the CD11a MoAb significantly inhibited the proliferation of lymphocytes stimulated by the phytohaemagglutinin to various extents, as the LFA-1 alpha determinant identified. By contrast, the CD18 MoAb did not influence strongly this cell process. We observed only a dim inhibitory effect with the CD18 MoAb recognizing an epitope common or very close to an LFA-1 alpha determinant. These results suggested that the LFA-1 antigen was important, at a molecular level, in the regulation of T-cell activation.

Antigens, Differentiation↗

PubMed1994

Evolutionary conservation of a human function-associated molecule on murine natural killer cells: expression and function.

Using a novel anti-natural killer (NK) cell monoclonal antibody (MoAb), we have recently identified an evolutionary conserved function-associated molecule (FAM) present on fish, rat and human NK cells. This molecule is involved in NK cell function as anti-FAM MoAbs inhibit cytotoxicity, stimulate lymphokine secretion and inhibit conjugate formation between effector cells and target cells. We now have examined murine NK cells for the presence of this structure. It was observed by two-colour flow cytometric analysis that the anti-FAM MoAb 5C6 specifically bound to a subpopulation of nylon wool non-adherent splenic lymphocytes (19-20%). The expression of the FAM molecule was restricted to NK cells that expressed the NK1.1 antigen. Neither T cells, B cells, nor macrophages reacted with the anti-FAM MoAb. Analysis of FAM expression in various lymphoid tissues revealed that splenocytes expressed the greatest numbers of MoAb(+) cells. Generation of lymphokine-activated killer (LAK) cells and adherent lymphokine-activated killer (ALAK) cells resulted in higher levels of FAM expression. The anti-FAM MoAb 5C6 also detected the presence of FAM on fresh SCID NK cells. It was demonstrated that the anti-FAM MoAb 5C6 inhibited the lysis of target cells by endogenous NK cells, activated NK cells, 5d LAK cells, ALAK cells and SCID NK cells. Moreover, conjugate assays demonstrated involvement of this molecule in recognition between NK cells and target cells.

Animals↗

PubMedDate not supplied

Failure of platelet parameters and biomarkers to correlate platelet function to severity and etiology of heart failure in patients enrolled in the EPCOT trial. With special reference to the Hemodyne hemostatic analyzer. Whole Blood Impedance Aggregometry for the Assessment of Platelet Function in Patients with Congestive Heart Failure.

Data from small studies have suggested the presence of platelet abnormalities in patients with congestive heart failure (CHF). We sought to characterize the diagnostic utility of different platelet parameters and platelet-endothelial biomarkers in a random outpatient CHF population investigated in the EPCOT ('Whole Blood Impedance Aggregometry for the Assessment of Platelet Function in Patients with Congestive Heart Failure') Trial. Blood samples were obtained for measurement of platelet contractile force (PCF), whole blood aggregation, shear-induced closure time, expression of glycoprotein (GP) IIb/IIIa, and P-selectin in 100 consecutive patients with CHF. Substantial interindividual variability of platelet characteristics exists in patients with CHF. There were no statistically significant differences when patients were grouped according to incidence of vascular events, emergency revascularization needs, survival, or etiology of heart failure. Aspirin use did not affect instrument readings either. PCF correlates very poorly with whole blood aggregometry (r(2) = 0.023), closure time (r(2) = 0.028), platelet GP IIb/IIIa (r(2) = 0.0028), and P-selectin (r(2) = 0.002) expression. Furthermore, there was no correlation with brain natriuretic peptide concentrations, a marker of severity and prognosis in heart failure reflecting the neurohumoral status. Patients with heart failure enrolled in the EPCOT Trial exhibited a marginal, sometimes oppositely directed change in platelet function, challenging the diagnostic utility of these platelet parameters and biomarkers to serve as useful tools for the identification of platelet abnormalities, for predicting clinical outcomes, or for monitoring antiplatelet strategies in this population. The usefulness of these measurements for assessing platelets in the different clinical settings remains to be explored. Taken together, opposite to our expectations, major clinical characteristics of heart failure did not correlate well with the platelet characteristics investigated in this study.

Aged↗

PubMedDate not supplied

Functional recovery of subepicardial myocardial tissue in transmural myocardial infarction after successful reperfusion: an important contribution to the improvement of regional and global left ventricular function.

BACKGROUND: The transmural extent of myocardial necrosis after an acute coronary artery occlusion can vary considerably. The contribution of residual subepicardial viable myocardium to global left ventricular function is largely unknown. METHODS AND RESULTS: We studied 12 patients with single-vessel disease 1 week after successful reperfusion of a first transmural anterior myocardial infarction (MI). With PET, myocardial blood flow (MBF) and glucose metabolism were measured regionally, and the viability was graded as normal, mismatch, or match with severely (<50% of normal) or intermediately (50% to 80% of normal) impaired MBF. Magnetic resonance tagging was used to regionally quantify fiber strains, wall thickening, and ejection fraction in patients 1 week and 3 months after the MI and in age-matched healthy volunteers. From 1 week to 3 months, subepicardial fiber shortening improved significantly in the match region (MBF <50%, -5.1+/-7.0% to -9.9+/-8. 7%; MBF of 50% to 80%, -7.1+/-7.6% to -14.9+/-7.9%). This was associated with an improvement in regional ejection fraction in the infarcted myocardium (29.6+/-21.8% to 43.5+/-15.5%, P<0.0001) and in normal regions (54.3+/-15.1% to 56.5+/-13.1%, P=0.013), contributing to an increase in global ejection fraction from 44.2+/-22.2% to 49. 3+/-17.9% (P<0.0001). CONCLUSIONS: Functional recovery of viable subepicardial regions is a mechanism of late improvement in regional and global ejection fraction after a so-called transmural MI.

Aged↗

PubMed1999

Hemodynamic function at rest, during acute stress, and in the field: predictors of cardiac structure and function 2 years later in youth.

Left ventricular hypertrophy is an independent predictor of cardiovascular morbidity and mortality. However, predictors of cardiac structure and function in youth are not completely understood. On 2 occasions (2.3 years apart), we examined 146 youth aged initially 10 to 19 years (mean age, 14.2+/-1.8 years). On the initial visit, hemodynamic function was assessed at rest, during laboratory stress (ie, orthostasis, car-driving simulation, video game, and forehead cold), and in the field (ie, ambulatory blood pressure). Quantitative M-mode echocardiograms were obtained on both visits. On both visits, black compared with white youth had higher resting laboratory systolic blood pressure (P<0.02), greater relative wall thickness (P<0.003), greater left ventricular mass indexed by either body surface area or height(2.7) (P<0.01 for both), and lower midwall fractional shortening ratio (P<0.05). Hierarchical stepwise regression analysis indicated that significant independent predictors of follow-up left ventricular mass/height(2. 7) were the initial evaluation of left ventricular mass/height(2.7), body mass index, gender (males more than females), and supine resting total peripheral resistance (final model R(2)=0.53). Left ventricular mass/body surface area was predicted by initial left ventricular mass/body surface area, weight, gender, mean supine resting total peripheral resistance, and systolic pressure response to car-driving simulation (final model R(2)=0.48). Midwall fractional shortening was predicted by initial midwall fractional shortening, race (white more than black), and lower mean supine total peripheral resistance (final model R(2)=0.13). The clinical significance of these findings and their implications for improved prevention of cardiovascular diseases are yet to be determined.

Adolescent↗

PubMed2004

The functional neuroanatomy of episodic and semantic autobiographical remembering: a prospective functional MRI study.

Autobiographical memory comprises episodic and semantic components mediated by dissociable states of consciousness, one promoting the experience of the self at a specific moment in the past, and the other involving self-knowledge that does not require ''mental time travel.'' These components can be difficult to dissociate using retrospective autobiographical stimuli collection. In this study, we manipulated the episodic/semantic distinction within prospectively collected autobiographical stimuli. Over several months, participants made recordings documenting specific episodes, repeated episodes, and world knowledge. These recordings were later played back to participants during scanning with functional MRI. The results indicated overlapping but distinct patterns of brain activity corresponding to episodic and semantic autobiographical memory. Both episodic and semantic autobiographical memory engaged the left anteromedial prefrontal cortex associated with self-reference, but the episodic condition did so to a greater degree. The episodic condition uniquely engaged the medial temporal, posterior cingulate, and diencephalic regions associated with remote memory recovery. Whereas the episodic condition engaged the right temporo-parietal cortex involved in reconstruction of spatial context and attentional orienting, the semantic condition engaged the left temporo-parietal and parieto-frontal systems involved in egocentric spatial processing and top-down attentional control. Episodic recollection was also associated with suppression of emotional paralimbic regions. These findings support a functional neuroanatomical dissociation between episodic and semantic autobiographical memory, providing concordance to amnesic syndromes with disproportionate impairment in one of these two forms of autobiographical memory.

Adult↗

PubMed1977

Lung function in infants and young children: functional residual capacity, tidal volume, and respiratory rats.

Functional residual capacity was measured by the closed-circuit, helium-equilibration method in 121 normal children 3 months to 6 years of age. Prediction equations for functional residual capacity for normal children of this age range are presented for the first time. This study demonstrates that some aspects of lung functiok can be studied relatively conveniently in young children.

Body Height↗

PubMed2001

Functional magnetic resonance imaging evidence for disrupted basal ganglia function in schizophrenia.

OBJECTIVE: This study was an examination of basal ganglia dysfunction in schizophrenia using functional magnetic resonance imaging (fMRI). METHOD: The authors used a motor sequencing task to investigate activation of the caudate, anterior putamen plus globus pallidus, and posterior putamen plus globus pallidus in eight subjects with schizophrenia and 12 group-matched comparison subjects. Differences in activation of the thalamus, the target of direct output from the globus pallidus, were also examined. RESULTS: The schizophrenia subjects showed significant bilateral deficits in the posterior putamen, globus pallidus, and thalamus but not the anterior putamen plus globus pallidus or caudate. Functional connectivity analysis revealed that the deficits in thalamic activation were related to deficits in posterior putamen and globus pallidus activation. CONCLUSIONS: These results provide fMRI evidence for basal ganglia dysfunction in subjects with schizophrenia and suggest that this deficit results in disrupted outflow to the thalamus. These deficits may underlie the behavioral impairments in goal-directed action observed in schizophrenia.

Adult↗

PubMed2000

Specification for signal processing and data handling 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 present paper is to define minimal performance criteria for the separate items comprising signal processing and data handling used to measure respiratory function in infants. These guidelines cover numerous aspects including: signal processing, data handling and subsequent analysis, reporting of results, demographics and handling of reference values. Adherence to these guidelines should ensure that infant lung function measurements can be performed with an acceptable degree of safety, precision, and reproducibility. Furthermore, they will facilitate multicentre collection of data and the performance of clinical investigations.

Electronic Data Processing↗

PubMed1998

Echocardiography, a non-invasive method for the investigation of heart morphology and function in laboratory dogs: 2. Effects of minoxidil and quinidine on the left ventricle function.

We used echocardiography to investigate the changes in the cardiac function of dogs treated with minoxidil (a vasodilator, administered at doses which can produce mild lesions in the myocardium of the left ventricle) and quinidine (an antiarrhythmic at doses up to 8 times the upper limit of the therapeutic range in dogs). Groups of three beagles received a single administration of minoxidil at doses of 0.5 or 2 mg/kg. Two groups of two dogs received a single administration of quinidine at doses of 80 or 160 mg/kg. Two groups of three control dogs were treated concurrently with the vehicle alone. M-mode echocardiography was performed under two-dimensional echocardiography guidance on three occasions the day before treatment, immediately before dosing and 1, 3 and 24 h after dosing. We measured or calculated end diastolic, end systolic, and stroke volumes (EDV, ESV and SV), fractional shortening (FS), ejection fraction (EF), the percentage of thickening of the septum and of the left ventricle posterior wall (PST and PWT), and the mean and maximal velocities of the left ventricle posterior wall (PWVm and PWVM). At the same time as echocardiography recording, heart rate was measured by cardiac auscultation. Minoxidil produced a marked tachycardia. Less marked increases in heart rate occurred after quinidine. Both compounds were associated with a decrease in ESV and with marked increases in FS, EF, PWVm and PWVM which, in comparison with data for controls, are indicative of an increase in the amplitude and velocity of cardiac contraction. Both drugs also produced a decrease in EDV and consequently there was no increase in SV despite the increased amplitude of ventricular contraction. Cardiac output increased in proportion to the increase in heart rate. Overall, the effects were dose-related and are consistent with the pharmacological properties of the compounds. However, to date these effects have been demonstrated only by invasive methods. To conclude, we have shown that echocardiography allows a non-invasive investigation of the cardiac effects of suprapharmacological doses of antiarrhythmics and of the changes in heart function induced by vasodilators known to cause left ventricular lesions in dogs.

Animals↗

PubMed2003

A spirometry-based algorithm to direct lung function testing in the pulmonary function laboratory.

OBJECTIVE: To design a spirometry-based algorithm to predict pulmonary restrictive impairment and reduce the number of patients undergoing unnecessary lung volume testing. DESIGN: Two prospective studies of 259 consecutive patients and 265 consecutive patients used to derive and validate the algorithm, respectively. SETTING: A pulmonary function laboratory of a tertiary care hospital. PATIENTS: Consecutive adults referred to the laboratory for lung volume measurements and spirometry. MEASUREMENTS: The sensitivity of the algorithm for predicting pulmonary restriction and the cost savings associated with its use. RESULTS: Total lung capacity correlated strongly with FVC (r = 0.66) and showed an inverse correlation with the FEV(1)/FVC ratio (r = - 0.41). According to the algorithm, only patients with an FVC < 85% of predicted and an FEV(1)/FVC ratio >or= 55% required lung volume measurements following spirometry. The algorithm had a high sensitivity for predicting restriction and a high negative predictive value (NPV) for excluding restriction (sensitivity, 96%; NPV, 98%). The diagnostic properties of the algorithm were reproducible in the validation study. Application of the algorithm would eliminate the need for lung volume testing in 48 to 49% of patients referred to the pulmonary function test (PFT) laboratory, reducing costs by 33%. CONCLUSIONS: A spirometry-based algorithm accurately excludes pulmonary restriction and reduces unnecessary lung volume testing in the PFT laboratory almost in half.

Algorithms↗

PubMed1979

Clinical significance of pulmonary function tests. Alterations in pulmonary function following respiratory viral infection.

Respiratory viral illness is a major cause of morbidity in both adults and children. This report focuses on both the acute and chronic effects on respiratory function of these ubiquitous infections. Infant airways are particularly vulnerable due to the relatively low conductance in immature peripheral airways. Bronchiolitis, caused predominantly by respiratory syncytial virus, is the most important of these viral illnesses and is emerging as a major risk factor for the subsequent development of obstructive airway diseases in adults, possibly by interference with normal alveolar proliferation. The basic pathogenic mechanism involved in adult respiratory viral infection is bronchial hyperreactivity, presumably secondary to epithelial damage and resultant sensitization of rapidly adapting airway receptors. In addition, there may be virus-related alterations in the autonomic and humoral regulation of airway tone. Viral infections may alter the effects of common air pollutants on respiratory function.

Adult↗

PubMed2006

Leukocyte function-associated antigen-1: structure, function and application prospects.

This review focuses on the structure, function and pathological role of leukocyte function-associated antigen-1 (LFA-1) which is a heterodimeric protein consisting of two subunits. LFA-1 plays a most important role in the immune system including adhesion, extravasation, migration, apoptosis, cytotoxicity, cytokine production, and proliferation of lymphocytes. Therefore, T-cell activation can be suppressed by blocking ICAM-1/LFA-1 interaction in autoimmune diseases and organ transplantation. Many different inhibitors (i.e. antibodies, peptides, small molecules) have been demonstrated to block ICAM-1/LFA-1 interaction, and some of them are promising for medical treatment or have reached clinical trials.

Animals↗

PubMed2001

The effect of acute hypoglycemia on brain function and activation: a functional magnetic resonance imaging study.

The authors' aim was to examine the regional anatomy of brain activation by cognitive tasks commonly used in hypoglycemia research and to assess the effect of acute hypoglycemia on these in healthy volunteers. Eight right-handed volunteers performed a set of cognitive tasks-finger tapping (FT), simple reaction time (SRT), and four-choice reaction time (4CRT)-twice during blood oxygen level-dependent (BOLD) functional magnetic resonance imaging of the brain on two occasions. In study 1 (n = 6), plasma glucose was maintained at euglycemia (5 mmol/l) throughout. In study 2 (n = 6), plasma glucose was reduced to 2.5 mmol/l for the second set. Performance of the tasks resulted in specific group brain activation maps. During hypoglycemia, FT slowed (P = 0.026), with decreased BOLD activation in right premotor cortex and supplementary motor area and left hippocampus and with increased BOLD activation in left cerebellum and right frontal pole. Although there was no significant change in SRT, BOLD activation was reduced in right cerebellum and visual cortex. The 4CRT deteriorated (P = 0.020), with reduction in BOLD activation in motor and visual systems but increased BOLD signal in a large area of the left parietal association cortex, a region involved in planning. Hypoglycemia impairs simple brain functions and is associated with task-specific localized reductions in brain activation. For a task with greater cognitive load, the increased BOLD signal in planning areas is compatible with recruitment of brain regions in an attempt to limit dysfunction. Further investigation of these mechanisms may help devise rational treatment strategies to limit cortical dysfunction during acute iatrogenic hypoglycemia.

Adult↗