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Biomedical subjects

E Tolosa

Publications and source records attributed to E Tolosa.

At least 145 records · Page 8Linked to original sources
PubMed1994

Clinical diagnosis and diagnostic criteria of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome).

Progressive supranuclear palsy (PSP) is characterized clinically by supranuclear gaze palsy, neck dystonia, parkinsonism, pseudobulbar palsy, gait imbalance with frequent falls and frontal lobe-type dementia. In the advanced typical case, when supranuclear gaze palsy and other main features are present diagnosis is relatively easy. Diagnostic problems, though, are frequent in the early stages due to the variable clinical presentation and in those atypical cases in which gaze palsy does not develop or that present as a severe dementia disorder or as an isolated akinetic-rigid syndrome. In this review we summarize the clinical features of PSP and emphasize those aspects helpful in the differential diagnosis with Parkinson's disease and other motor and cognitive disorders that can pose difficult diagnostic problems. Clinical diagnostic criteria are also discussed and modifications of those currently in used are proposed.

Diagnosis, Differential↗
PubMed1994

Dopaminergic function in rat brain after oral administration of calcium-channel blockers or haloperidol. A microdialysis study.

Microdialysis technique was used to study the effects of both acute and repeated oral administration of calcium-channel blockers (flunarizine, cinnarizine, verapamil, nifedipine and nicardipine) in dopaminergic function in rat brain and to compare them to the effects of haloperidol. Acute flunarizine, nicardipine or haloperidol increased extracellular levels of dopamine (DA) or metabolites. After repeated (18 days) administration, nicardipine, nifedipine, verapamil or haloperidol increased and flunarizine decreased extracellular striatal levels of dopamine or metabolites. Chronic treatment with calcium-channel blockers or haloperidol failed to block K(+)-evoked release of dopamine. This suggests that the calcium-channel blockers used in this study do not influence calcium entry necessary for DA release. An acute challenge with haloperidol caused either no change or a decrease in extracellular levels of DA or metabolites after repeated administration of calcium-channel blockers or haloperidol. This is considered to be due to the lesser response of dopaminergic neurons because of treatment. A neuroleptic-like mechanism of action together with a decrease in firing activity and/or a reduced dopamine re-uptake of dopaminergic neurons are considered.

Action Potentials↗
PubMed1994

Identification and characterization of serotonin 5-HT4 receptor binding sites in human brain: comparison with other mammalian species.

Specific binding for the 5-HT4-selective radioligand [3H]GR 113808 has been identified in human and calf brain membranes. Using human tissue the distribution of the binding was heterogeneous throughout different brain regions, being highest in the caudate nucleus. For this region a Kd value of 0.59 +/- 0.08 nM and a Bmax of 225 +/- 2.6 fmol/mg were obtained. Other regions with substantial densities were the lenticular nucleus, the substantia nigra, the hippocampus and the frontal cortex, whereas no binding could be detected in the cerebellum. The ability of several standard compounds in displacing the radioligand was compatible with the labelling of 5-HT4 receptors. Correlation analysis showed no significant differences amongst data obtained for these compounds using human, calf and guinea-pig membranes.

Adult↗
PubMed1994

Characterization of neural cell adhesion molecule (NCAM) expression in thyroid follicular cells: induction by cytokines and over-expression in autoimmune glands.

NCAM (CD56) is a cell surface glycoprotein of the immunoglobulin superfamily expressed on neuroendocrine and natural killer (NK) cells which has considerable molecular heterogeneity due to differential splicing and post-translational modifications. NCAM has been detected in the thyroid follicular cells (thyrocytes) immunohistologically. We report here the molecular form, the modulation by cytokines and the levels of expression in thyroid pathology. By using a panel of MoAbs to NCAM on Western blots from thyrocyte extract we have determined that these cells express the 140- and 180-kD forms of NCAM. Exposure of primary cultures of thyrocytes to interferon-gamma (IFN-gamma), and even more, to the combination of IFN-gamma plus tumour necrosis factor-alpha (TNF-alpha) induced a clear increase in the expression of NCAM as assessed by FACS analysis. NCAM expression in thyrocytes was assessed by immunofluorescence in 59 surgical specimens of thyroid glands, and was found increased in 11/17 (64%) of Graves', in 5/25 (20%) of multinodular goitre (MNG) and in occasional adenoma glands. No correlation was found with the expression of HLA class I, class II or the degree of lymphocytic infiltration scored in adjacent sections, but it was often seen in areas infiltrated by macrophages. In conclusion, NCAM is an adhesion molecule whose expression is clearly increased in thyrocytes in autoimmune glands, probably as a consequence of exposure to cytokines locally released. Since one of the forms of NCAM expressed by thyrocytes has the capability to generate intracellular signal it may play a role in normal thyroid function. In addition, NCAM may facilitate the recognition of thyrocytes by lymphocytes, particularly by NK CD56+ lymphocytes.

Antibodies, Monoclonal↗
PubMed1994

Indolent anti-Hu-associated paraneoplastic sensory neuropathy.

Paraneoplastic sensory neuropathy (PSN) usually runs a subacute progressive course, leaving the patient with severe sensory dysfunction in weeks to months. We describe five patients with PSN, high titers of anti-Hu antibodies (type 1 antineuronal nuclear autoantibodies), and an indolent clinical course. The patients had a median age of 55 years (range, 41 to 72). Four had small-cell (3) or undifferentiated large-cell (1) lung cancer. Patients presented with mild, asymmetric sensory symptoms; in two, the neuropathy was predominant in the arms. Two patients also had a visceral neuropathy causing gastrointestinal dysfunction. The PSN was stable or progressed very slowly without treatment for a median of 18 months (range, 5 to 32) and remained so after treatment with immunoglobulins (1 patient), chemotherapy (3), or both therapies (1). All patients were ambulatory, leading an independent life up until the time of the last visit or until death from the tumor (2 patients). The median follow-up was 36 months (range, 22 to 52). A paraneoplastic origin should be considered in patients with mild, very slowly progressive sensory neuropathies.

Adult↗
PubMed1994

[Compression of the spinal cord by the amyloid tissue in the thoracic vertebral amyloidoma].

Solitary amyloidoma consists of amyloid tissue deposits in the absence of systemic amyloidosis or plasma cell dyscrasia. Single vertebral amyloidoma is an unusual cause of spinal cord compression. We present the case of a 72-year-old man with medullar compression by amyloidoma affecting the sixth dorsal vertebra and with nuclear magnetic resonance images that were indistinguishable from epidural metastasis. The patient improved notably after resection.

Aged↗
PubMed1994

Mid-stage parkinsonism with mild motor fluctuations.

Most patients with Parkinson's disease who undergo levodopa therapy eventually develop fluctuations in the diurnal control of their symptoms. These fluctuations, when mild, consist mostly of the "wearing-off" effect--the re-emergence of symptoms several hours after the ingestion of each dose of levodopa. In some patients, "wearing-off" in the daytime is preceded by, or associated with, the development of nocturnal and early morning akinesia. Some patients at this stage also have mild (mostly peak dose or square-wave) choreoathetoid dyskinesias. In patients with "wearing-off," "on" periods tend to occur when plasma levels of levodopa are high; nocturnal and early morning akinesia and diurnal "off" periods tend to occur at times when plasma levodopa levels are low, reflecting insufficient concentrations of dopamine in the striatum. Treatment strategies in patients with mid-stage parkinsonism and mild fluctuations are primarily directed toward enhancing dopaminergic transmission in the striatum. This is achieved by increasing the supply of levodopa to the brain or by administering drugs that either prolong the effect of synaptic dopamine from levodopa, or activate postsynaptic dopamine receptors. This presentation will discuss the advantages and possible drawbacks of these different strategies, which include the use of controlled-release levodopa preparations, deprenyl, and the new monoamine oxidase (MAO)-B inhibitors, catechol-O-methyl transferase (COMT) inhibitors, and the various "direct" dopamine agonists.

Catechol O-Methyltransferase Inhibitors↗
PubMed1993

[Cerebral metastasis of melanoma: study of 48 patients].

BACKGROUND: Malignant melanoma is a frequent cause of cerebral metastases (CM). In the present study the characteristics of primitive melanomas of patients with CM, their forms of clinical presentation and treatment were analyzed. METHODS: A retrospective study of the patients with melanoma and CM diagnosed between 1982 and 1991 was carried out. RESULTS: Out of 786 patients with melanoma 48 were identified with CM. In 65% of the melanoma originated in cutaneous areas BANS (of bad prognosis). The median thickness of the tumor (Breslow's index) was of 3.6 mm. The median period of latency between diagnosis of the melanoma and the detection of CM was 22 months. Although recent hemorrhage of the CM was observed in the cranial computerized tomography in 20 of the 48 patients, only 7 presented clinical symptoms of ictus. In 23 patients the CM were the only evidence of metastases of the melanoma. The median survival was one month in the patients treated with only dexamethasone, 3.5 months in the chemotherapy group, 2.5 months for the group given radiotherapy and 6 months for those undergoing surgery. CONCLUSIONS: Most of the patients with cerebral metastasis had a primitive melanoma with criteria of bad prognosis. The presence of hemorrhage in computerized tomography did not always correlate with clinical symptoms of ictus. Surgical treatment must be considered in patient with sole cerebral metastasis without evidence of distant disease.

Adult↗
PubMed1993

[Surgical treatment combined with radiotherapy and chemotherapy in an unselected population of patients with malignant glioma].

BACKGROUND: Malignant gliomas are tumors of bad prognosis with a mean survival of 12 months. In the present report 74 patients diagnosed of malignant glioma were studied with the following aims: 1) evaluate how many could receive combined radiotherapy (RT) and chemotherapy (BCNU) treatment following surgery and 2) analyze whether the patients treated presented a survival similar to that described in the literature. METHODS: The records of 74 patients operated on for malignant glioma between 1987-1990 and consecutively included in a protocol of treatment with RT and BCNU were reviewed. RESULTS: Out of the total of 74 patients, 29 (39%) were considered evaluable. The medians of progression free interval and survival were of 10 and 16 months, respectively in these patients. Forty-five (61%) patients could not fulfill the protocol mainly because of tumoral progression prior to completion of RT and severe post surgical complications. The evaluable patients were significantly younger (p = 0.004) and tumoral exeresis wider (p = 0.0003) than in those who were not evaluable. CONCLUSIONS: Most of the patients operated on for malignant glioma may not receive treatment considered as standard, principally due to tumor progression in the first weeks following surgery and the presence of severe post surgical complications.

Adult↗
PubMed1993

Delayed appearance of anti-myelin-associated glycoprotein antibodies in a patient with chronic demyelinating polyneuropathy.

A patient who had a polyneuropathy compatible with a chronic inflammatory demyelinating polyneuropathy and was initially negative for anti-myelin-associated glycoprotein (MAG) antibodies developed a double monoclonal gammopathy, IgM kappa and IgM lambda, two years after the diagnosis. The IgM kappa, but not the IgM lambda, exhibited strong anti-MAG antibody activity. The late appearance of the anti-MAG immunoreactivity suggests that in patients with an initial diagnosis of chronic inflammatory demyelinating polyneuropathy, the search for anti-MAG antibodies should be repeated during the course of the neuropathy.

Autoantibodies↗
PubMed1993

Blood B, T, CD4+ and CD8+ lymphocytes in female Wistar rats.

We have established reference values of peripheral blood lymphocyte subsets in healthy female Wistar rats under highly standardized conditions. Using monoclonal antibodies and flow cytometry, T lymphocytes (OX19+), B lymphocytes (OX6+ and anti-Ig+), T-helper/inducer (W3/25+), and T-suppressor/cytotoxic subsets (OX8+) were determined, from week 11 to week 21 after birth. The mean percentages of T and B lymphocytes with respect to total lymphocytes were 78.5% and 18%, respectively; the mean percentages of T-helper/inducer and T-suppressor/cytotoxic cells in relation to T lymphocytes were 59% and 25%, respectively (n = 48). No difference in total leukocyte count, differential leukocyte analysis, or lymphocyte subsets was observed during the 10 weeks the rats were studied under standard housing conditions. Therefore, the period considered seems the most appropriate in which to carry out experiments that could involve lymphocyte subset disturbances.

Animals↗
PubMed1993

Absence of REM sleep, altered NREM sleep and supranuclear horizontal gaze palsy caused by a lesion of the pontine tegmentum.

A 27-year-old woman with a mass lesion confined to the pontine tegmentum had absence of rapid eye movement (REM) sleep and abnormal nonrapid eye movement (NREM) sleep with no sleep spindles when the sole neurologic manifestation was a bilateral supranuclear horizontal gaze palsy. This study suggests that the tegmentum nuclei associated with REM sleep generation in humans and the pathways that control horizontal eye movements are closely related. Furthermore, these findings indicate that bilateral damage of the pontine tegmentum is necessary for REM sleep abolition. Interruption of connections between the tegmentum of the pons and the reticular nuclei of the thalamus could be the cause of the absence of sleep spindles.

Adult↗
PubMed1993

Gamma delta lymphocytes in endocrine autoimmunity: evidence of expansion in Graves' disease but not in type 1 diabetes.

Endocrine autoimmune disorders are mediated by T cell-dependent responses to organ-specific antigens, but the mechanisms initiating the process remain unknown. Lymphocytes which use the gamma delta heterodimer as T cell receptor (TCR) for antigen constitute a distinct subset of T cells whose function remains elusive. In order to investigate their possible involvement in endocrine autoimmunity we have determined the proportion of gamma delta T cells in the peripheral blood of 23 patients with type 1 (insulin-dependent) diabetes mellitus (type-1 DM) and 30 patients with autoimmune thyrotoxicosis (Graves' disease). T lymphocyte TCR expression was assessed by fluorescence-activated flow cytometry on peripheral blood mononuclear cells using MoAbs UCHT1 (CD3), TCR delta 1 (gamma delta TCR), WT31 and beta F1 (alpha beta TCR) and both the percentage of T cells expressing gamma delta and the ratio gamma delta/alpha beta were calculated. In the diabetic patients gamma delta cells were not significantly different from the control group (7.7 +/- 54% versus 8.0 +/- 5.5% of T cells, P NS). There was no relation between the proportion of gamma delta lymphocytes and the presence of islet cell antibodies (ICA) in the sera. The Graves' patients showed a tendency towards a higher proportion of gamma delta T lymphocytes than the controls (gamma delta/alpha beta ratios: 0.095 +/- 0.047 versus 0.063 +/- 0.022, P = 0.03). In 14 Graves' patients the number of gamma delta were measured in paired samples of peripheral and intrathyroidal lymphocytes, demonstrating an expansion of gamma delta within the thyroid glands (0.21 +/- 0.3 versus 0.095 +/- 0.047, P = 0.032). Immunohistochemical studies showed that gamma delta cells were scattered among the predominant alpha beta lymphocytes infiltrating the thyroid gland and that they account for 10% of intraepithelial lymphocytes. No relation was found between the increase of gamma delta lymphocytes and any clinical features.

Adolescent↗
PubMed1993

Mitochondrial respiratory chain activity in skeletal muscle from patients with Parkinson's disease.

Different abnormalities in mitochondrial electron transport chain activity have been demonstrated in muscle and other tissues of patients with idiopathic Parkinson's disease (PD). We studied eight Spanish patients with PD to evaluate the functional activity of the electron transport chain in muscle mitochondria from patients of this country. We found lower complex I activity (nmol.min-1.mg-1) in patients (245.8 +/- 42.8) than in controls (331.6 +/- 60.1) (p = 0.004) and lower complex IV activity in patients (46.1 +/- 9) than in controls (144.1 +/- 42.3) (p = 0.00001). Complex V activity was also decreased in two patients and complex II and III activities were normal in all of them. Although these results strongly suggest an alteration in mitochondrial DNA in PD, the various electron transport chain defects in different tissues seem to be nonspecific.

Aged↗
PubMed1993

Hyperintense globus pallidus on T1-weighted MRI in cirrhotic patients is associated with severity of liver failure.

Hyperintense globus pallidus on T1-weighted MRI is present in most patients with advanced liver disease. We evaluated the relationship between the signal intensity of the globus pallidus and clinical or laboratory data of 77 patients eligible for liver transplantation. There was a significant correlation between the intensity of the signal and the Child-Pugh score (as indication of severity of liver disease), presence of postural tremor, previous episodes of variceal bleeding or hepatic encephalopathy, prothrombin activity, serum aspartate and alanine aminotransferase, bilirubin, and the indocyanine green (ICG) hepatic clearance, a very sensitive marker of liver function. The multivariate analysis disclosed that the ICG hepatic clearance and previous episodes of variceal bleeding were independently associated with the signal intensity in the globus pallidus. MRI repeated in 21 patients 10 to 20 months after transplant showed a disappearance of the lesion in all cases. We conclude that the hyperintense globus pallidus is secondary to the severity of the liver disease, and is reversible when liver function returns to normal.

Adult↗
PubMed1993

Prognostic impact of mutated K-ras gene in surgically resected non-small cell lung cancer patients.

Mutated K-ras oncogenes have been detected in a third of lung adenocarcinomas, located usually in codon 12, its presence correlating negatively with survival. To further define the role of K-ras point mutations in non-small cell lung cancer, we studied the presence of mutated K-ras genes in surgical specimens from 66 patients. Polymerase chain reaction was performed from sections of formalin-fixed paraffin-embedded tissue. We screened for point mutations in codons 12, 13 and 61 of the K-ras gene by dot blot hybridization analysis with mutation-specific oligonucleotide probes. Ras gene mutations were present in 13 of 66 carcinomas (20%), nine in codon 12 and four in codon 61. Three squamous cell carcinomas harbored two different point mutations in K-ras codon 12. Mutated K-ras genes were found more frequently in squamous cell carcinomas (eight of 38) than in adenocarcinoma (three of 22). Analysis of nucleotide sequence disclosed a multifarious mutation pattern of K-ras codon 12, where the most common conversion was from glycine (GGT) to valine (GTT). K-ras point mutation positive subset had poorer survival, nine of the 13 patients died during the follow-up period as compared with 22 of 53 patients with no mutation in the K-ras gene (P = 0.01). The difference was also strikingly significant when stratified according to node status.

Adult↗