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At least 451 records · Page 25Linked to original sources

Amrinone therapy in patients with heart failure. Lack of improvement in functional capacity and left ventricular function at rest and during exercise.

Short-term amrinone therapy has been shown to exert beneficial hemodynamic effects in patients with heart failure. To determine whether this improvement persists longer, the effects of maximally tolerated doses of amrinone on exercise duration, oxygen consumption, and left ventricular function and volumes were examined during maintenance therapy. After four weeks of amrinone therapy, 75 to 150 mg three times a day (mean 292 +/- 70 mg daily), treadmill exercise duration, maximal oxygen consumption, and functional class were unchanged from control values. Radionuclide-derived ejection fraction and end-diastolic and end-systolic volumes were not altered at rest or during maximal supine exercise. Similarly, significant changes in echocardiographic end-systolic and end-diastolic dimensions did not occur. This lack of clinical benefit on functional capacity and left ventricular function, together with frequent adverse reactions, will limit the application of amrinone in the treatment of heart failure. These findings are relevant to the investigation of amrinone-like derivations presently being studied for the treatment of heart failure. Before their release, these agents will require careful evaluation and demonstration of a therapeutic action during maintenance therapy, together with a low incidence of adverse reactions.

Administration, Oral↗

Long-term deficits of goal-directed vestibulo-ocular function following total unilateral loss of peripheral vestibular function.

Brief whole-body movements (+/- 5 to 170 degrees/s peak velocity; approximately equal to 0.5 s duration), applied during 1.44-s intervals of total darkness while subjects "looked" at a just-viewed target, were used to examine vestibulo-ocular function in 3 patients who had compensated to total unilateral loss of peripheral vestibular function. We found that the combined effects of slow-phase and saccadic eye movements both tended to keep the eyes stabilized on the unseen target. Compensatory slow-phases elicited during rapid head movements ipsilateral to (i.e., towards) the lesion were only about 60% as effective as those elicited during rapid contralateral movements. Compensatory gaze-correcting saccades tended to supplement deficient slow-phase movements, especially during rapid ipsilateral head movement. However, the gaze-correcting effect of saccades was only about half of the required for perfect stabilization. Thus, two functional vestibular deficits were observed during rapid ipsilateral head movements: (1) reduced slow-phase stabilization, and (2) reduced saccadic ability to adequately supplement the deficient slow phases. However, overall vestibular functional capability, as assessed by observation of the net effect of both slow phases and saccades, was much better than would be indicated by conventional observation of slow-phase movements alone.

Adult↗

The relation between motor function development and vestibular function tests in four children with inner ear anomaly.

It is well known that the development of motor function is frequently retarded in children with congenital deafness, particularly in cases of inner ear anomaly. The relation between the results of vestibular function tests and the development of motor function in 4 children with inner ear anomaly is studied. CT scan obtained from these cases revealed the absence of lateral semicircular canals in both ears. There were no responses to caloric stimulation using 40 ml ice-water. However, damped rotation test elicited per-rotatory nystagmus in all cases. In contrast to this result, the same nystagmus was provoked only in 2 cases in Barany rotation test. Early development of motor functions, especially that of first walk, was more retarded in the 2 cases showing no per-rotatory nystagmus in Barany rotation test than in the other 2 positive cases.

Child↗

[Controversial opinions regarding the role of Bcml vitamin D receptor gene polymorphism on parathyroid function, calcium absorption and bone mineral density in persons with normal renal function and patients with chronic renal failure].

This paper summarizes current, but controversial opinions of different authors evaluating the effect of Bsml polymorphism of the vitamin D receptor gene on the parathyroid function, calcium absorption from the digestive tract and bone mineral density (BMD) in persons with normal renal function and in patients with chronic renal failure. On the basis of these data, the recapitulation of the prevailing opinions was undertaken. Contemporary it is admitted, that the persons with bb genotype and normal renal function are at risk for the development of the parathyroid adenomas while in the patients with chronic renal failure the bb genotype may favour parathyroids hyperplasia. It is also believed that bb genotype in the persons with normal renal function facilitates calcium absorption and is associated with greater BMD. Few investigations performed in the patients with chronic renal failure suggest that the BB genotype may partially influence lower BMD in the subgroup of younger patients treated with hemodialysis for a relatively short period. Existing controversies need however further clarification.

Bone Density↗

[Relationship between exercise capacity and left ventricular function at rest in patients with heart insufficiency: radionuclide continuous monitoring of left ventricular function].

PURPOSE: To evaluate the relationship of systolic and diastolic function at rest to exercise capacity. MATERIAL AND METHODS: Seventeen patients with ischemic heart failure were included in the study. Ambulatory left ventricular monitoring at rest and during upright exercise with combined analysis of pulmonary gas exchange was performed. Ejection fraction, end-diastolic volume, end-systolic volume, stroke volume, cardiac output, and peak filling rate were measured. RESULTS: Significant positive correlations were found between rest ejection fraction and peak oxygen consumption (r = .60, p < .01), peak cardiac output (r = .77, p < .0001), peak stroke volume (r = .67, p < .005), and peak ejection fraction (r = .69, p < .005). On the other hand, peak filling rate at rest showed a significant inverse correlation with peak end-diastolic (r = -.48, p < .05) and end-systolic (r = -.66, p < .005) volumes. The patients were then subgrouped into two groups according to their rest ejection fraction (lower or higher than 40%). In the group with ejection fraction less than 40% a significant correlation was observed between rest ejection fraction and both peak stroke volume (r = .66, p < .05) and peak ejection fraction (r = .69, p < .05). In the same group of patients an inverse correlation was found between peak filling rate and both end-diastolic (r = -0.65, p < .05) and end-systolic (r = -.82, p < .005) volumes. CONCLUSIONS: The results of the present study suggest that exercise capacity is related to left ventricular function at rest and that rest diastolic function might be a determinant of left ventricular function during exercise in patients with heart failure.

Exercise Tolerance↗

Functional electrical stimulation in tetraplegic patients to restore hand function.

The purpose of this collective review is to describe a new form of functional electrical stimulation called neuroprosthesis. This unique technology has been devised to produce lateral pinch and palmar grasp in persons with C5 and C6 motor level spinal cord injuries. This neuroprosthesis includes external as well as implanted components. First, a receiver is surgically implanted into the patient's chest above a pectoralis major muscle. The receiver stimulator is then connected to 8 surgically implanted epimysial or intramuscular electrodes. Restoration of upper extremity function can greatly improve the lives of people affected with tetraplegia. When contralateral shoulder movements trigger an external transmitting coil, it sends a radio wave impulse to the stimulator inducing contraction of the muscles. Many tetraplegics are regaining hand function using implanted functional electrical stimulation. One major limitation is that the key muscles to be stimulated may have lower motor neuron damage, but this obstacle has been successfully overcome using surgical modifications of the biomechanics of the hand.

Activities of Daily Living↗

Regional time-based functional imaging of hepatocyte function.

Hepatocyte function was analyzed following the injection of 5 mCi of Tc-99m disofenin by the computer generation of three kinds of functional images designed to portray regional rates of hepatic uptake. Nineteen patients were analyzed, of whom eight had no overt liver disease, five had active hepatitis, five had cirrhosis, and one had acute cholecystitis. Functional images were graded according to lack of regional homogeneity of accumulation. Uptake kinetics were found to be significantly more homogeneous in normal subjects, becoming increasingly heterogeneous in hepatitis and cirrhosis patients, respectively. Thus functional imaging may provide a tool for the quantitative analysis of parenchymal disruption in liver disease.

Adult↗

[Respiratory function in extrinsic allergic alveolitis caused by pigeons. Clinical, pathological and functional correlation].

Lung function tests (LFT) were performed in 71 patients with proven extrinsic allergic alveolitis due to pigeons (EAA-P), and they were correlated with lung biopsy (LB) findings. Lung function studies were analyzed to evaluate the clinical course of these patients treated with corticosteroids. Restrictive pulmonary function impairment was found in all cases (vital capacity 38 +/- 4%), residual volume was increased in 9 out of 14 patients (64%) (RV = 0.51 +/- 0.06 L.) and bronchial obstruction was a feature in 11/14 patients (78%) (MMEF = 53 +/- 4%). In all cases a low Pa02 was observed (44 +/- 2 mmHg) and in six an increase in PaC02 was detected. The vital capacity did not correlate with the degree of inflammation or fibrosis observed by LB. A significant negative correlation was found between Pa02 and the degree of inflammation (r = 0.68, p X 0.05) as well as with fibrosis + inflammation degrees (r = -0.63, p less than 0.05). In general, initial LFT and clinical improvement occur simultaneously. Lung function tests support the diagnosis of EAA-P, but are not capable of separating inflammation from lung fibrosis.

Adolescent↗

[Deterioration of liver function following endoscopic injection sclerotherapy of esophageal varices--significance of the new liver function test "intravariceal injection (I.I.) index"].

Changes of liver functions associated with endoscopic injection sclerotherapy (EIS) were investigated in 143 patients with remarkable esophageal varices. The index used for evaluating hepatic reserve was the ratio between the increase of total bilirubin and the increase of LDH after EIS [I.I. index = (delta T.Bil./delta LDH) x 100] in cases treated by intravariceal injection of 5% ethanolamine oleate. I.I. index value caused by hemolysis was stable and always below 0.2, while the elevation of I.I. index above 0.2 was regarded as the reflection of the deterioration of liver function. After the entire sessions of EIS, the changes of liver function tests before and after EIS were estimated in 104 cases using 3 factors as follows; (1) delta T.Bil.; increase of total bilirubin more than 0.5 mg/dl (2) delta PT; decrease of prothrombin time more than 5% (3) delta ICG R15; increase of ICG R15 more than 5%. I.I. index of group I (without any changes of 3 factors mentioned above; n = 66) was 0.22 +/- 0.16, approximately within normal range. However, in group II (with 1 factor; n = 29), group III (with 2 factors; n = 5), group IV (with all factors; n = 4), I.I. index was elevated according to the severity of their liver dysfunction. The cases whose I.I. index value increased gradually during the course of EIS, were apt to deteriorate the liver functions and therefore, should be carefully observed. Also, I.I. index seems to reflect the prognosis of the patients treated by EIS for some extent, since the survival period of the cases treated by EIS were correlative with the value of I.I. index (r = -0.542, p < 0.01), and I.I. index of 32 cases who survived for longer than 5 years after EIS was almost normal (0.22 +/- 0.15).

Adult↗

Kinetics of hepatocellular proliferation as a function of the microvascular structure and functional state of the liver.

An analysis of hepatocellular proliferation in regenerating rat liver reveals a dependence of kinetic parameters on the microvascular structure of the liver. Influx kinetics of hepatocytes into DNA synthesis as well as cell cycle phases vary in different parts of the liver lobule between the afferent and efferent vascular poles. Heterogeneity of the proliferative response and size limitations on cell cycle compartments appear to be intimately related to the actual functional state of the individual liver cell. Modifications of liver cell functions result in variations of the proliferative activity. Phenobarbital-induced hypertrophy of hepatocytes reveals a permissive action on G1- S influx. Selective destruction of the subpopulations, by allyl formate, leads to a new functional determination of the residual liver and to a change in proliferative compartments. Maximum modulation of cell cycle compartments is obtained by hydroxyurea-induced synchronization of hepatocytes after partial liver resection. During hydroxyurea treatment, the regenerating liver shows a pronounced cellular hypertrophy. After release from hydroxyurea block, cells embark on DNA synthesis simultaneously. The DNA synthesizing compartment comprises almost the entire liver cell population. Heptotrophic factors might play a part in regulating or modifying hepatocellular function and proliferative response after cell loss.

Allyl Compounds↗

Longitudinal study of leukocyte functions in homosexual men seroconverted for HIV: rapid and persistent loss of B cell function after HIV infection.

The early effects of infection with human immunodeficiency virus (HIV) were investigated in homosexual men who had seroconverted for anti-HIV antibodies. Leukocyte functional activities were determined in longitudinally collected peripheral blood mononuclear cell samples. During the first 10 months following seroconversion, anti-CD3 monoclonal antibody-induced T cell proliferation, monocyte accessory function and T helper activity on B cell differentiation in a pokeweed mitogen-driven system were not affected. In contrast, from the moment of seroconversion on, B cells of seroconverted men failed to produce immunoglobulin in the pokeweed mitogen-driven system. This defect was not restored by addition of normal CD4+ T cells. Immunoglobulin synthesis induced by Staphylococcus aureus and interleukin 2 decreased gradually, until it was completely lost 10 months after seroconversion. In addition, proliferation in response to anti-IgM or Staphylococcus aureus by B cells from HIV seroconverted men was decreased. The lack of inducible in vitro B cell activity was not accompanied by elevated spontaneous Ig synthesis by B cells of the seroconverted men. In the second group of men studied during the 2nd year following seroconversion, T helper activity on normal B cell differentiation significantly decreased, whereas anti-CD3-induced T cell proliferation and monocyte accessory function were not significantly affected. Our results demonstrate that in almost all HIV-infected individuals B cell functional defects are the first leukocyte abnormalities observed preceding defects in T helper activity.

Antibody Formation↗

Nuclear factor NF-kappa B can interact functionally with its cognate binding site to provide lymphoid-specific promoter function.

Enhancers and promoters, cis-acting regulators of mammalian gene expression, are modular units containing multiple short binding sites for specific trans-acting transcription factors. To investigate if factors binding to enhancer sequences are functionally different from promoter-binding factors, we asked if a short DNA sequence element in the immunoglobulin kappa (kappa) light chain enhancer that binds to the nuclear factor NF-kappa B could also serve as a functional promoter element. A synthetic oligonucleotide containing this binding site was placed in either orientation upstream of the beta-globin TATA-element. In myeloma cells, the NF-kappa B binding site efficiently directed transcription. The promoter activity was directly correlated with the presence of the nuclear factor NF-kappa B: there was no transcription in fibroblasts or in unstimulated pre-B cells where the factor was absent. Transcription could be stimulated in pre-B cells by treatments known to activate NF-kappa B. Thus, the same nuclear factor can act as a positive activator of both enhancer and promoter function, suggesting that the two functions involve similar events in the transcription process.

Animals↗

Performance of time-dependent density functional and Green functions methods for calculations of excitation energies in radicals and for Rydberg electronic states.

Time-dependent density functional (TD-DFT) and perturbation theory-based outer valence Green functions (OVGF) methods have been tested for calculations of excitation energies for a set of radicals, molecules, and model clusters simulating points defects in silica. The results show that the TD-DFT approach may give unreliable results not only for diffuse Rydberg states, but also for electronic states involving transitions between MOs localized in two remote from each other spatial regions, for example, for charge-transfer excitations. For the. O-SiX(3) clusters, where X is a single-valence group, TD-DFT predicts reasonable excitation energies but incorrect sequence of electronic transitions. For a number of cases where TD-DFT is shown to be unreliable, the OVGF approach can provide better estimates of excitation energies, but this method also is not expected to perform universally well. The OVGF performance is demonstrated to be satisfactory for excitations with predominantly single-determinant wave functions where the deviations of the calculated energies from experiment should not exceed 0.1-0.3 eV. However, for more complicated transitions involving multiple bonds or for excited states with multireference wave functions the OVGF approach is less reliable and error in the computed energies can reach 0.5-1 eV.

Journal Article↗

Technical considerations in two-stage functioning free muscle transplantation reconstruction of both flexor and extensor functions of the forearm.

We report on two patients with severe injuries of the forearm who were reconstructed using functioning free muscle transplantation (FFMT) for individual replacement of flexor and extensor function. In both cases a two-stage procedure was performed: The extensor reconstruction preceded the flexor reconstruction by 4-6 months. The extensor digitorum communis and flexor digitorum profundus were successfully reconstructed in both cases using bilateral gracilis FFMT. In one case the flexor pollicis longus and extensor pollicis longus were also reconstructed using the adductor longus in addition to the gracilis. Clinical follow-up was a minimum of 2 years. Both patients achieved wrist control, excellent finger flexion, and metacarpophalangeal joint extension. One patient also had good interphalangeal finger extension, but the other developed a persistent claw deformity due to the lack of recovery of ulnar nerve function. Performing the extensor reconstruction prior to the flexor reconstruction theoretically allows a more rapid return of function and a shorter rehabilitation period than using the converse sequence.

Adult↗

The functional scout image: immediate mapping of cortical function at 4 Tesla using receiver phase cycling.

A rapid method of generating functional scout images to map cortical activity is presented. Maps were produced immediately "on-line" on the scanner's console using fast low-angle shot gradient-recalled echo and echo-planar imaging sequences without special hardware. To demonstrate the technique, raw data collected during photic stimulation and dark control periods were subtracted through phase alternation of the receiver with constant transmitted radio frequency phase. A blood oxygen level-dependent signal difference map was produced by magnitude reconstruction of the resulting complex-difference data. Maps improved in contrast with an increasing number of stimulation-control cycles and showed similar areas of activation to traditional fMRI processing methods. Such a functional scout procedure allows rapid localization of brain function within the anatomical region of interest. From these functional scout images, slices or voxels may be planned by using the scanner manufacturers prescription tools for further specialized studies.

Brain Mapping↗

Mapping the functional surface of insulin by design: structure and function of a novel A-chain analogue.

Functional surfaces of a protein are often mapped by combination of X-ray crystallography and mutagenesis. Such studies of insulin have yielded paradoxical results, suggesting that the native state is inactive and reorganizes on receptor binding. Of particular interest is the N-terminal alpha-helix of the A-chain. Does this segment function as an alpha-helix or reorganize as recently proposed in a prohormone-convertase complex? To correlate structure and function, we describe a mapping strategy based on protein design. The solution structure of an engineered monomer ([AspB10, LysB28, ProB29]-human insulin) is determined at neutral pH as a template for synthesis of a novel A-chain analogue. Designed by analogy to a protein-folding intermediate, the analogue lacks the A6-A11 disulphide bridge; the cysteine residues are replaced by serine. Its solution structure is remarkable for segmental unfolding of the N-terminal A-chain alpha-helix (A1 to A8) in an otherwise native subdomain. The structure demonstrates that the overall orientation of the A and B chains is consistent with reorganization of the A-chain's N-terminal segment. Nevertheless, the analogue's low biological activity suggests that this segment, a site of clinical mutation causing diabetes mellitus, functions as a preformed recognition alpha-helix.

Amino Acid Sequence↗

An algorithm for rapid calculation of a probabilistic functional atlas of subcortical structures from electrophysiological data collected during functional neurosurgery procedures.

The paper introduces an optimal algorithm for rapid calculation of a probabilistic functional atlas (PFA) of subcortical structures from data collected during functional neurosurgery procedures. The PFA is calculated based on combined intraoperative electrophysiology, pre- and intraoperative neuroimaging, and postoperative neurological verification. The algorithm converts the coordinates of the neurologically most effective contacts into probabilistic functional maps taking into account the geometry of a stimulating electrode. The PFA calculation comprises the reconstruction of the contact coordinates from two orthogonal projections, normalizing (warping) the contacts modeled as cylinders, voxelizing the contact models, calculating the atlas, and computing probability. In addition, an analytical representation of the PFA is formulated based on Gaussian modeling. The initial PFA has been calculated from the data collected during the treatment of 274 Parkinson's disease patients, most of them operated bilaterally (487 operated hemispheres). It contains the most popular stereotactic targets, the subthalamic nucleus, globus pallidus internus, and ventral intermedius nucleus. The key application of the algorithm is targeting in stereotactic and functional neurosurgery, and it also can be employed in human and animal brain research.

Algorithms↗

Modulation of endothelial function by hypoxia: perturbation of barrier and anticoagulant function, and induction of a novel factor X activator.

Exposure of the vessel wall to hypoxemia is a central feature of ischemic cardiovascular disease. This led us to examine the perturbation of endothelial cell properties under hypoxia. An atmosphere of pO2 of 12 mmHg is not lethal to the endothelial cells for up to five days, but barrier function was impaired. Increased passage of macromolecule tracers were observed in time- and dose-dependent manner and electron microscopy demonstrated small gaps (0.5-1.0 micron) between cells. Expression of the anticoagulant cofactor thrombomodulin was also perturbed: thrombomodulin activity and antigen decreased in parallel. Northern blots showed almost complete suppression of thrombomodulin in hypoxic culture. Furthermore, synthesis of other proteins, such as fibronectin, was slightly enhanced under hypoxia. In addition to the suppression of these anticoagulant cofactor, hypoxic endothelial cell displayed a noval procoagulant activity distinct from tissue factor. Further study revealed that hypoxic endothelial cultures directly activated Factor X, as assessed by functional assays and SDS-PAGE. In addition to this no activation of Factor IX or prothrombin was observed. The hypoxia-induced Factor X activator was membrane-associated, required calcium to form Factor Xa, was inhibited by HgCl2 but not by PMSF, and had Km approximately 25 micrograms/ml. Co-incubation of hypoxic cultures with cycloheximide prevented the expression of this activity, suggesting that protein synthesis is required for its expression. These functional perturbations of endothelial cells were reversible following reoxygenation. These data indicate that hypoxia imposes a selective perturbation on endothelial cell function, suggesting the possible contribution of hypoxemia to vascular dysfunction in ischemia.

Animals↗