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Biomedical subjects

E Tolosa

Publications and source records attributed to E Tolosa.

At least 127 records · Page 7Linked to original sources

Synaptophysin in spinal anterior horn in aging and ALS: an immunohistological study.

Aged-related spinal cord changes such as neuronal loss have been related to the degree of clinical severity of amyotrophic lateral sclerosis (ALS); morphological data on synapses are, however, wanting. Variations in synaptophysin (Sph) expression in aging and ALS were thus studied at the level of lower motor neurons in 40 controls with non-neurological diseases and 11 cases of ALS. Control sections of formalin fixed paraffin embedded cervical (C7/8), thoracic (T10) and lumbar spinal cord (L5) and C6, C7, C8 and L5 of ALS cases were stained with haematoxylin and eosin, luxol fast blue (LFB), and immunostained with a mouse monoclonal antibody against Sph. The neuropil of the anterior horn (AH) in all control cases demonstrated Sph positivity. A dot-like pattern of positivity of presynaptic terminals on soma of motor neurons and fine immunoreactivity along neuronal processes were observed. A significant reduction of Sph immunostaining was observed in the neuropil with increasing age and 3 different somatic patterns were seen: a- well preserved Sph reactivity around the soma and the proximal dendrites of histologically normal neurons; b- few chromatolytic neurons showing large numbers of dot-like presynaptic terminals around the cell body and in a "fused" pattern; c- intense, diffuse, and homogeneous reactivity of some neurons. Attenuation of Sph reactivity in the AH neuropil, to its complete loss, was observed in all ALS cases. In addition to patterns a-c, two additional microscopic findings were noted in ALS: d- chromatolytic neurons showing complete absence of Sph reactivity; e- absence of Sph reactivity around the soma and the proximal dendrites of histologically normal surviving neurons. Our findings demonstrate that there is a decrease in Sph immunostaining with aging, thus suggesting an alteration in dendritic networks of the AH with aging. Changes in the pattern of Sph immunoreactivity in cell bodies may represent synaptic plasticity and/or degeneration. Reinnervation may also be a possible mechanism as a response to neuronal loss in oldest control cases. Sph reactivity results may thus lend support to the presence of superimposed aging components in ALS cases which may give an insight into explaining the increasing severity of the disease which is encountered with advancing age.

Adult↗

Regional cerebral blood flow pattern in normal young and aged volunteers: a 99mTc-HMPAO SPET study.

The aim of this study was to investigate the normal pattern of regional cerebral blood flow (rCBF) distribution in normal young and aged volunteers using technetium-99m hexamethylpropylene amine oxime (99m-Tc-HMPAO) as a tracer. The region brain perfusion of young and aged subjects was compared, especially regarding rCBF differences due to age and gender, and interhemispheric rCBF asymmetries. Sixty-eight right-handed normal volunteers - 40 young (mean age 29. 5+/-6.3 years) and 28 aged (mean age 71.2+/-4.3 years) - were included in the study. rCBF was estimated on the basis of a semiquantitative approach by means of a left/right index and two region/reference ratios, using the cerebellum and the whole brain activity as references. A good correlation between these two region/reference ratios was found (P<0.005 in all cerebral regions). The highest rCBF ratios corresponded to the cerebellum, followed by the occipital lobe. The remaining cortical regions (temporal, parietal, frontal and basal ganglia) showed slightly lower values. The white matter showed rCBF ratios substantially lower than the grey matter. In neither young nor aged subjects were significant rCBF differences between the genders found in any of the two region/reference indices employed. Aged subjects showed significantly lower rCBF ratios than young subjects in the left frontal lobe and in the posterior region of the left temporal lobe. In both young and aged subjects, lower perfusion was found in the left hemisphere, except for the white matter region in both age groups and the frontal lobe in the young subjects. Aged subjects presented a slightly higher interhemispheric asymmetry in the frontal lobe. However, interhemispheric asymmetry was minimal (-1. 01% to 3.14%). Consequently, a symmetrical rCBF distribution can be assumed between homologous regions, independent of age.

Adult↗

Cyclosporine-associated mutism in liver transplant patients.

Four liver transplant recipients treated with cyclosporine developed a reversible neurologic syndrome characterized by a speech disorder leading to mutism. This complication, previously reported in a few liver transplant recipients treated with the immunosuppressive drug FK506, had not been described with cyclosporine. Recognition of this syndrome should prompt withdrawal of the drug and avoidance of unnecessary diagnostic procedures.

Adult↗

Neurologic complications of autologous and allogeneic bone marrow transplantation in patients with leukemia: a comparative study.

We retrospectively evaluated the neurologic complications in 425 patients who underwent bone marrow transplant (BMT) (310 allogeneic, 115 autologous) for leukemia. Forty-six patients (11%) developed 47 central and three peripheral neurologic complications. The most common complications were cerebral hemorrhage (3.8%), metabolic encephalopathy (3%), and CNS infections (2%). All CNS infections occurred with allogeneic BMT. Eleven of 16 hemorrhages were subdural hematomas (69%), which were more frequent in autologous (8%) than in allogeneic (0.6%) BMT (p < 0.0001), and in patients with acute myelogenous leukemia (AML) (5%) than in the remaining leukemia patients (0.8%) (p = 0.013). Eight of 11 subdural hematomas occurred in AML patients receiving autologous BMT. When we compared patient-, disease-, and transplant-related characteristics of these patients with those without subdural hematoma, only platelet refractoriness correlated with an increased risk of subdural hematoma. The actuarial probability of developing subdural hematoma was 44% in patients with platelet-refractory disease and only 2.5% in the other patients (p < 0.0001). Ten patients with subdural hematoma did not have surgery and eight had significant clinical improvement associated with reduction or resolution of the hematoma, confirmed by CT scan in six patients. The subdural hematoma was the cause of death in only one patient. This study shows that the frequency of the different neurologic complications varies among types of BMT. Patients undergoing autologous BMT for AML with platelet refractoriness have an increased risk of subdural hematoma that may be treated with conservative measures.

Adolescent↗

Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop.

To improve the specificity and sensitivity of the clinical diagnosis of progressive supranuclear palsy (PSP, Steele-Richardson-Olszewski syndrome), the National Institute of Neurological Disorders and Stroke (NINDS) and the Society for PSP, Inc. (SPSP) sponsored an international workshop to develop an accurate and universally accepted set of criteria for this disorder. The NINDS-SPSP criteria, which were formulated from an extensive review of the literature, comparison with other previously published sets of criteria, and the consensus of experts, were validated on a clinical data set from autopsy-confirmed cases of PSP. The criteria specify three degrees of diagnostic certainty: possible PSP, probable PSP, and definite PSP. Possible PSP requires the presence of a gradually progressive disorder with onset at age 40 or later, either vertical supranuclear gaze palsy or both slowing of vertical saccades and prominent postural instability with falls in the first year of onset, as well as no evidence of other diseases that could explain these features. Probable PSP requires vertical supranuclear gaze palsy, prominent postural instability, and falls in the first year of onset, as well as the other features of possible PSP. Definite PSP requires a history of probable or possible PSP and histopathologic evidence of typical PSP. Criteria that support the diagnosis of PSP, and that exclude diseases often confused with PSP, are presented. The criteria for probable PSP are highly specific, making them suitable for therapeutic, analytic epidemiologic, and biologic studies, but not very sensitive. The criteria for possible PSP are substantially sensitive, making them suitable for descriptive epidemiologic studies, but less specific. An appendix provides guidelines for diagnosing and monitoring clinical disability in PSP.

Humans↗

Autosomal recessive Wolfram syndrome associated with an 8.5-kb mtDNA single deletion.

Wolfram syndrome (MIM 222300) is characterized by optic atrophy, diabetes mellitus, diabetes insipidus, neurosensory hearing loss, urinary tract abnormalities, and neurological dysfunction. The association of clinical manifestations in tissues and organs unrelated functionally or embryologically suggested the possibility of a mitochondrial implication in the disease, which has been demonstrated in two sporadic cases. Nonetheless, familial studies suggested an autosomal recessive mode of transmission, and recent data demonstrated linkage with markers on the short arm of human chromosome 4. The patient reported here, as well as her parents and unaffected sister, carried a heteroplasmic 8.5-kb deletion in mtDNA. The deletion accounted for 23% of mitochondrial genomes in lymphocytes from the patient and approximately 5% in the tissues studied from members of her family. The presence of the deletion in the patient in a proportion higher than in her unaffected parents suggests a putative defect in a nuclear gene that acts at the mitochondrial level.

Base Sequence↗

Hyperinducibility of HLA class II expression of thyroid follicular cells from Graves' disease. A primary defect?

Thyroid follicular cells (thyrocytes) from Graves' disease (GD) patients' thyroid glands express HLA class II molecules "ectopically." This phenomenon has been attributed to induction by locally produced cytokines and may be relevant to disease pathogenesis. We have compared IFN-gamma-mediated induction of HLA class II in thyrocytes from glands affected with GD and a nonautoimmune disease (MNG), to investigate a possible differential regulation of HLA expression between these two pathologies. HLA induction has been measured in primary thyrocyte cultures and control autologous macrophages stimulated or not stimulated with IFN-gamma. Comparison of flow cytometric data using an improved algorithm demonstrated that expression of HLA class II molecules is more readily induced in thyrocytes from GD than from MNG thyroid glands. This higher inducibility was parallel to a faster and stronger induction of HLA class II message in GD thyrocytes but did not correlate with the levels of HLA class II or class I originally expressed by thyrocytes in the tissue or with the degree of lymphocytic infiltration of the gland. There was no association with a particular HLA class II allele or with the presence of IFN-gamma and IL-2 in the tissue, as assessed by reverse transcription-PCR. No differences in the induction of class II were found in macrophages from each group of patients. These results suggest that an intrinsic feature of thyrocytes from GD patients is an up-regulation of HLA class II expression and that this is a characteristic that may facilitate the triggering of autoimmunity to "hyperinducible" thyroid glands.

Adolescent↗

Neuronal changes in the substantia nigra with aging: a Golgi study.

In order to recognize substantia nigra neuronal changes occurring in aging, 20 human control brains from 13 males and 7 females with a mean age of 61 years (range 20 to 93 years) without neurological disease were examined using the Golgi method. A quantitative study of dendrites and dendritic spines was performed as well as a statistical analysis of obtained data. Parallel sections to the impregnated material were histologically and immunohistologically studied with the aim to identify possible neuronal cytoskeletal abnormalities. Results were compared to changes of substantia nigra reported in other conditions such as Parkinson's disease (PD) and methyl-4-phenylpyridine (MPTP) experimental toxicity. Three different substantia nigra neuronal types were observed. Morphological changes during aging consisted of distorted profile of the cell body and swelling and beading of dendritic branches. The quantitative assessment of changes observed in neuronal types showed a significant loss of dendrites and dendritic spines, especially in the oldest cases. These findings were similar to those previously described in other cerebral areas during aging, but a specific vulnerability of the largest substantia nigra neuronal type could be observed. Nodulations and beaded aspects of dendrites are reminiscent of those changes previously described in MPTP toxicity. Dendritic varicosities found in the oldest cases have also been found in dendrites of large substantia nigra neurons in PD. Cytoskeletal abnormalities have been described in PD but were not found in the present study. Therefore, other pathophysiological mechanisms different from the cytoskeletal compromise occurring in some neurodegenerative diseases should be involved in aging.

Adult↗

Early prediction of stroke severity. Role of the erythrocyte sedimentation rate.

BACKGROUND AND PURPOSE: Early predictors of functional outcome after stroke are necessary for better planning of treatment and care. METHODS: We evaluated prospectively early clinical predictors of short-term functional outcome in a group of patients with ischemic cerebral infarction and explored whether the intensity of the acute-phase response provided further information concerning the short-term functional outcome. We evaluated a group of 208 ischemic stroke patients using the Mathew scale at entry. All patients had neuroimaging studies and routine blood tests, including erythrocyte sedimentation rate (ESR), within 72 hours from clinical onset. At discharge, functional outcome was graded according to a Stroke Outcome Scale. RESULTS: Larger infarcts, more embolic infarcts, and fewer lacunar infarcts were observed in the poor-outcome group. Vascular risk factors, radiological findings not related to the index stroke, time to admission, and treatment were similar in the two outcome groups. Variables with statistically significant differences between outcome groups included the following: age > 65 years, female sex, admission Mathew score < 75, worsening at clinical presentation, infarct volume > 6 cm3, complicating infections, fasting glucose > 110 mg, nonfasting glucose > 130 mg, and elevated ESR. With stepwise logistic regression analysis, Mathew score on admission, infarct volume, mode of clinical presentation, and ESR remained in the predictive model of stroke outcome, with a sensitivity and specificity of 89.91% and 85.71%, respectively. After removing the computed tomographic information from the model the same variables remained, with a sensitivity and specificity of 83.05% and 94.29%, respectively. CONCLUSIONS: Infarct size and clinical severity on admission are the stronger predictors of short-term functional outcome. Mode of clinical presentation, clinical evolution during the first day of stroke, and ESR are also independent predictors of short-term stroke outcome. These findings might be indicative of an inadequate collateral profile and/or a more pronounced prothrombotic state.

Adult↗

Early anticoagulation after large cerebral embolic infarction: a safety study.

OBJECTIVE: To assess whether hemorrhage after early anticoagulation in nonseptic embolic infarction is related to clinical severity and infarction size. BACKGROUND: Explicit clinical criteria and timing of anticoagulation after large embolic infarctions are unknown. METHODS: Out of 171 patients receiving anticoagulation between July 1992 and December 1993, 83 patients with hemispheric embolisms received heparin within 72 hours from onset (activated partial thromboplastin time [aPTT] 1.5 times control value). Stratified by age and sex, a "high-risk" group (46 patients) was defined as those having stroke symptoms involving three or more CNS domains, Mathew Scale score < or = 74, or hemorrhagic infarction on initial CT, and a "low-risk" group (37 patients) as those having stroke symptoms involving fewer than three cortical domains, or Mathew Scale score > 74, and CT showing no blood. Loss of consciousness, seizures, or history of bleeding were exclusion criteria. Repeated CTs (100%) and MRIs (36%) detailed infarctions according to standard maps and evaluated all unexplained clinical worsening. RESULTS: Prior to therapy, high-risk patients had more severe clinical deficits (p < 0.01), larger infarctions on CT (p < 0.01), and more mass effect (p < 0.01). Hemorrhagic conversion (26% in the high-risk group versus 22% in the low-risk group) and hemorrhagic worsening (4% in the high-risk group versus 13% in the low-risk group) were unrelated to admission clinical severity or infarction size, but they were related to an excessive prolongation of the aPTT (p < 0.01). CONCLUSIONS: Infarction size and clinical severity in alert patients with nonseptic embolic stroke carries no additional bleeding complications after early anticoagulation. If anticoagulants are deemed necessary, treatment delay seems unjustified. However, rigorous monitoring of the aPTT is strongly advised to keep the level at 1.5 to 2 times control values.

Aged↗

[Wolfram's syndrome: correlation of clinical signs and neurological images].

Wolfram's syndrome is defined by the association of diabetes mellitus, diabetes insipidus, optic atrophy and nerve deafness. Other neurological anomalies, such as ataxia, nystagmus, tonic pupil, dizziness, dysarthria, dysphagia and epilepsy are rarely described and tend to appear later than the primary manifestations. We describe a patient with Wolfram's syndrome whose magnetic resonance image (MRI) of the head showed brainstem and cerebellar atrophy years before the appearance of clinical signs of brainstem disfunction. We conclude that alterations in MRI precede neurological symptoms by several years in Wolfram's syndrome.

Adult↗

Laparoscopy-assisted colonoscopic polypectomy.

One of the most feared complications in the removal of moderate-sized or large sessile polyps is colonic perforation. Complete colonoscopic total excision of these kinds of polyps can be safely undertaken using laparoscopic assistance, which enables prompt diagnosis and treatment of perforation. Laparoscopy-assisted endoscopic polyp excision can be safely performed, avoiding critical septic complications and can also help in the selection of patients to appropriate colonic resection without increasing morbidity or mortality.

Colon↗