Search PubMed⌕ Search

Biomedical subjects

A Gass

Publications and source records attributed to A Gass.

At least 37 records · Page 2Linked to original sources
PubMed2001

A phase 1/2 clinical trial of enzyme replacement in fabry disease: pharmacokinetic, substrate clearance, and safety studies.

Fabry disease results from deficient alpha-galactosidase A (alpha-Gal A) activity and the pathologic accumulation of the globotriaosylceramide (GL-3) and related glycosphingolipids, primarily in vascular endothelial lysosomes. Treatment is currently palliative, and affected patients generally die in their 40s or 50s. Preclinical studies of recombinant human alpha-Gal A (r-halphaGalA) infusions in knockout mice demonstrated reduction of GL-3 in tissues and plasma, providing rationale for a phase 1/2 clinical trial. Here, we report a single-center, open-label, dose-ranging study of r-halphaGalA treatment in 15 patients, each of whom received five infusions at one of five dose regimens. Intravenously administered r-halphaGalA was cleared from the circulation in a dose-dependent manner, via both saturable and non-saturable pathways. Rapid and marked reductions in plasma and tissue GL-3 were observed biochemically, histologically, and/or ultrastructurally. Clearance of plasma GL-3 was dose-dependent. In patients with pre- and posttreatment biopsies, mean GL-3 content decreased 84% in liver (n=13), was markedly reduced in kidney in four of five patients, and after five doses was modestly lowered in the endomyocardium of four of seven patients. GL-3 deposits were cleared to near normal or were markedly reduced in the vascular endothelium of liver, skin, heart, and kidney, on the basis of light- and electron-microscopic evaluation. In addition, patients reported less pain, increased ability to sweat, and improved quality-of-life measures. Infusions were well tolerated; four patients experienced mild-to-moderate reactions, suggestive of hypersensitivity, that were managed conservatively. Of 15 patients, 8 (53%) developed IgG antibodies to r-halphaGalA; however, the antibodies were not neutralizing, as indicated by unchanged pharmacokinetic values for infusions 1 and 5. This study provides the basis for a phase 3 trial of enzyme-replacement therapy for Fabry disease.

Adolescent↗
PubMed2001

[Diffusion tensor imaging (DTI) and functional magnetic resonance tomography (fMRI) expand methodological spectrum in psychiatric research].

In psychiatric research, there is a growing interest in the microstructural and functional characteristics of brain networks, which often form the basis of current etiological concepts. As a result of novel magnetic resonance imaging techniques, the pathogenic characteristics of neuronal activity and connectivity can be examined in a noninvasive, safe, and repeatable manner. Functional magnetic resonance imaging (fMRI) uses blood oxygenation level-dependent (BOLD) measures for identifying the gray matter contribution to cognition. Diffusion tensor imaging (DTI) reveals the course and structural integrity of white matter projections. Because DTI does not require special motivation and performance, group differences in psychiatry are more easily interpreted in terms of underlying pathology. To date few studies have tried to investigate both, i.e. dynamic and microstructural data in the sense of a modern multi-dimensional investigation approach. The combination of both techniques, however, seems to offer a promising vehicle to further extent our current understanding of mental disorders and to identify populations at risk. In addition to addressing findings in psychiatric research, the present article presents a technical overview of DTI and examines the limitations and potential applications of both techniques.

Anisotropy↗
PubMed2001

Acute stroke patterns in patients with internal carotid artery disease: a diffusion-weighted magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Diffusion-weighted (DW) MRI is a sensitive method that facilitates early stroke pattern identification. There are limited data about the influence of stenosis grade on the development of particular stroke patterns in internal carotid artery (ICA) disease. We therefore investigated the lesion patterns on DW MRI in acute stroke patients with ICA disease. METHODS: DW MRI was analyzed in 102 consecutive acute stroke patients with different degrees of ipsilateral ICA disease. Patients were assigned to 1 of 5 observed lesion patterns: (1) territorial ischemia, (2) subcortical ischemia without or (3) with embolus fragmentation, (4) disseminated lesions in distal cortical regions, and (5) multiple lesions in hemodynamic risk zones. In addition, perfusion-weighted (PW) MRI and MR angiography information was included in the assessment. RESULTS: All patterns were observed in the different stages of ICA disease. Half of the patients with high-grade or subtotal stenosis had lesions in hemodynamic risk zones. Territorial stroke occurred in 47.6% of patients with ICA occlusion. Statistical analysis showed a significant relationship between the degree of stenosis and the observed stroke pattern (P=0.001). In 77.8% of patients exhibiting high-grade ICA stenosis, subtotal stenosis, or occlusion, the perfusion lesion was larger than the diffusion lesion (PW/DW mismatch). CONCLUSIONS: Although in the individual patient any of the infarct patterns may occur, in statistical terms the incidence of a particular stroke pattern is clearly dependent on the degree of stenosis.

Aged↗
PubMed2001

Pulmonary complications in cardiac transplant recipients.

BACKGROUND: The incidence of pulmonary complications in heart transplant recipients has not been extensively studied. We report pulmonary complications in 159 consecutive adult orthotopic heart transplantations (OHTs) performed in 157 patients. MATERIALS AND METHODS: Retrospective review of medical records. RESULTS: Forty-seven of 159 recipients (29.9%) had 81 pulmonary complications. Pneumonia was the most common (n = 27), followed by bronchitis (n = 15), pleural effusion (n = 10), pneumothorax (n = 7), prolonged respiratory failure requiring tracheotomy (n = 7), and obstructive sleep apnea syndrome (n = 6). All patients with late-onset (> 6 months after transplantation) community-acquired bacterial pneumonia presented with fever, cough, and a new lobar consolidation on the chest radiograph, and responded promptly to empiric antibiotics without undergoing an invasive diagnostic procedure. In contrast, early-onset nosocomial bacterial pneumonias carried a 33.3% mortality rate. A positive tuberculin skin test result was associated with a significantly higher rate of pulmonary complications (62.5% vs 26.8%, p = 0.007). Lung cancer and posttransplant lymphoproliferative disorder (PTLD) developed exclusively in 6 of the 61 patients (8.1%) who received induction immunosuppression with murine monoclonal antibody (OKT3). CONCLUSION: Pulmonary complications are common following heart transplantation, occurring in 29.9% of recipients, and are attributed to pneumonia of primarily bacterial origin in one half of cases. Late-onset community-acquired pneumonia carried an excellent prognosis following empiric antibiotic therapy, suggesting that in the appropriate clinical setting invasive diagnostic procedures are unnecessary. Analogous to reports in other solid-organ transplant recipients, induction therapy with OKT3 was associated with an increased incidence of lung cancer and PTLD. Overall, the development of pulmonary complications after OHT has prognostic significance given the higher mortality in this subset of patients.

Bronchitis↗
PubMed2000

The contribution of magnetic resonance imaging in the differential diagnosis of optic nerve damage.

In this paper we review the findings of magnetic resonance imaging (MRI) in optic neuritis and visual dysfunction due to other optic neuropathies. With advances in MRI technology, it has become possible to visualise optic nerve pathology. STIR and RARE sequences, contrast-enhanced sequences, and phased array surface coils are technical developments that provide fine anatomical detail and that are sensitive to pathological changes. MRI can offer information in the differential diagnosis of optic neuropathies, the monitoring of their treatment, and in some instances should provide new insights into the underlying pathophysiological mechanisms.

Diagnosis, Differential↗
PubMed2000

The contribution of MRI in the differential diagnosis of posterior fossa damage.

In multiple sclerosis patients, magnetic resonance imaging (MRI) frequently detects lesions in the brain stem and cerebellum. However various pathologies that have a predelection to occur in posterior fossa parenchyma may share similar features with inflammatory-demyelinating lesions. In this paper, we review the contribution of MRI to the differential diagnosis of posterior fossa pathology. Vascular lesions due to chronic hypoperfusion and arteriolosclerosis or occlusion of the main supplying arteries of the posterior circulation leading to acute infarction frequently produce characteristic pontine or cerebellar lesions. Neoplastic disease, in particular pontine gliomas in younger patients may have similar MRI features and may be difficult to distinguish from inflammatory-demyelinating lesions. Central pontine myelinolysis usually occurs in severely ill patients but the pontine MRI changes have an overlapping profile with inflammatory demyelination. Diffuse axonal injury of the midbrain and brainstem after head trauma and atrophy of posterior fossa structures in degenerative diseases may appear similar on MRI to tissue changes also seen frequently in MS. Analysis of the MRI appearance and clinical information is most often useful to narrow the fairly long list of differential diagnoses of posterior fossa pathology.

Brain Diseases↗
PubMed2000

Failure to demonstrate peri-infarct depolarizations by repetitive MR diffusion imaging in acute human stroke.

BACKGROUND AND PURPOSE: Peri-infarct depolarizations (PIDs) have been demonstrated with diffusion-weighted MRI (DWI) in experimental stroke and are regarded as an important mechanism of ischemic injury. We tested the hypothesis that PIDs are of relevance for the early enlargement of human brain infarcts. METHODS: Ten stroke patients were investigated by repetitive imaging of the apparent diffusion coefficient (ADC) in the acute phase (7 patients) or subacute phase (3 patients) of developing cortical infarction. In each patient, 20 ADC maps were obtained from serially measured echo-planar DWI (interval of 45 seconds). Data analysis focused on the potential spatial and temporal ADC changes, including structured qualitative analysis, calculation of subtraction images, serial analysis of regions of interest positioned in the infarct core and border, and calculation of hemispheric lesion areas, depending on various ADC thresholds ranging between 0 and 800 microm(2)/s. RESULTS: Data analysis was unable to disclose any time-dependent changes in ADC that would resemble PID. In ischemic regions, the ADC reduction significantly progressed from the infarct border (555+/-96 microm(2)/s) to the infarct core (431+/-104 microm(2)/s, P:<0.01). CONCLUSIONS: By using an MRI protocol with high temporal resolution and elaborated postprocessing, we were unable to demonstrate a pattern of diffusion changes that would be indicative of PID in human stroke. Experimental infarction and human stroke may differ in the detectability of PID.

Acute Disease↗
PubMed1999

A multicenter measurement of magnetization transfer ratio in normal white matter.

To assess the importance of intercenter variations when measuring magnetization transfer ratio (MTR) in the brain, six European centers measured MTR in normal white matter. MTR ranged from 9 to 51 percent units (25 sequences). The effective flip angle of the saturating pulse divided by the pulse repetition time (ENRsat degrees/msec) was a good predictor of MTR (MTR = 3.25 ENRsat).

Brain↗
PubMed1999

[Echo-planar diffusion-weighted MRI in the diagnosis of acute ischemic stroke: characterisation of tissue abnormalities and limitations in the interpretation of imaging findings].

INTRODUCTION: An accurate diagnosis is frequently difficult in early stroke. Diffusion-weighted (DW) magnetic resonance imaging (MRI) allows visualization of ischemic parenchyma and quantitative assessment of tissue changes before unequivocal abnormalities appear on T(2)-weighted MRI. METHODS: We analyzed 105 MRI examinations of patients with acute stroke (<24 h) with regard to patterns of abnormalities in T(2)-weighted and DW MRI. Furthermore we assessed the influence of artifacts related to DW echo-planar single-shot MRI on image interpretation. RESULTS: Depending on the time of patient assessment there were three partly overlapping T(2)/DW patterns: (1) in the very early phase (</=1.5 h after symptom onset) there was no T(2) abnormality and no definite abnormality of diffusion; (2) no T(2) abnormality and restricted diffusion (1.5-4 h); (3) T(2) hyperintensity and restricted diffusion (>/=3 h). Typical artifacts (susceptibility distortions, N/2 artifact, chemical shift artifact and eddy currents artifact) had to be considered when interpreting images. CONCLUSIONS: Provided typical artifacts are taken into consideration, echo-planar DW MRI allows a more precise diagnostic assessment in acute stroke.

Acute Disease↗
PubMed1999

Antithrombotic effect of FK506 vs cyclosporine in cardiac transplant recipients: potential implications in transplant arteriopathy.

BACKGROUND: An activated coagulation system has been implicated as a potential initiating or inciting factor in the development and progression of cardiac allograft vasculopathy (CAV). METHODS: By performing ex vivo perfusion studies of blood thrombogenicity under constant rheologic conditions and with a constant substrate, we sought to determine the relative effects on the coagulation system of FK506 vs cyclosporine in patients who have undergone cardiac transplantation. RESULTS-CONCLUSIONS: Compared with cyclosporine, FK506 significantly decreased the propensity to form thrombus; this suggests that FK506 may have a favorable impact on the development of CAV.

Blood Coagulation↗
PubMed1999

[MRI follow-up in multiple sclerosis. A guideline for quality assurance].

Magnetic resonance imaging (MRI) is highly sensitive to pathological tissue changes in multiple sclerosis (MS) patients. It demonstrates the frequently subclinical disease activity and follow-up examinations regularly show the accumulation of new lesions and the development of atrophy. The increasing importance of follow-up examinations in MS patients makes it necessary to provide comparable MRI data even over long observation periods. This review article focusses on critical variables in this regard and technical issues; practical guidelines for MRI protocols in MS patients are presented. The influence of field strength, MR systems from different manufacturers, and new software releases is described. Guidelines concerning the graphic planning of the examination, sequence protocols, documentation and reporting of cranial MR studies in MS patients are presented.

Atrophy↗
PubMed1999

Lack of evidence of acute ischemic tissue change in transient global amnesia on single-shot echo-planar diffusion-weighted MRI.

BACKGROUND AND PURPOSE: There is uncertainty concerning the etiology of transient global amnesia (TGA). Previous CT and MRI studies have indicated that permanent structural abnormality is rare in TGA. Diffusion-weighted (DW) MRI is very sensitive to early ischemic parenchymal changes and has recently demonstrated embolic infarction in the posterior cerebral artery territory in 2 TGA patients. We report the findings of DW MRI in 8 patients in acute stages of TGA. METHODS: Conventional and echo-planar DW MRI was performed in 2 patients in the active phase and 6 patients in the recovery phase (1 to 8 hours after cessation of anterograde memory dysfunction) of spontaneously occurring TGA. RESULTS: None of the patients showed signs of hyperintensity on DW images or hypointensity on quantitative apparent diffusion coefficient (ADC) maps to suggest regional decreases of water mobility or acute T2 changes on transverse or coronal slices. CONCLUSIONS: We were unable to detect ADC or acute T2 changes with echo-planar DW MRI in patients with TGA, which suggests that mechanisms other than ischemic infarction may cause TGA. We did not identify spreading depression-associated changes of the ADC. Further refinement of MRI sequences may be necessary to detect subtle or transient signal change in brain parenchyma.

Aged↗
PubMed1998

Assessment of T2- and T1-weighted MRI brain lesion load in patients with subcortical vascular encephalopathy.

Previous cross-sectional studies in patients with subcortical vascular encephalopathy (SVE) have shown little or no correlation between brain lesion load and clinical disability, which could be due to the low specificity of T2-weighted MRI. Recent studies have indicated that T1-weighted MRI may be more specific than T2-weighted MRI for severe tissue destruction. We studied 37 patients with a diagnosis of SVE and 11 normal controls with standardised T1- and T2-weighted MRI. All patients underwent detailed clinical assessment including a neuropsychological test battery and computerised gait analysis. Both the T2- and T1-weighted total MRI lesion loads different between patients and controls different, particularly T1. The ratio of T2-/T1-weighted lesion load was lower in controls than in patients. There was no overall correlation of T1- or T2-weighted lesion load with clinical disability, but group comparison of patients with severe and mild clinical deficits showed different lesion loads. We suggest that T1- and T2-weighted MRI lesion loads demonstrate relevant structural abnormality in patients with SVE.

Aged↗