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Biomedical subjects

A Lago

Publications and source records attributed to A Lago.

At least 19 recordsLinked to original sources
PubMed1999

Neurologic complications associated with hepatitis C virus infection.

A series of nine patients with neurologic complications of hepatitis C virus infection is reported. Seven patients presented a combination of chronic sensory polyneuropathy, multineuropathy, and encephalopathy related to cryoglobulinemia. The noncryoglobulinemic symptoms consisted of an anterior optic neuropathy and a restless legs syndrome with small-fiber neuropathy. Corticosteroids and cyclophosphamide were useful in controlling vasculitic episodes. Interferon-alpha caused remission in half of the treated patients.

Adult↗
PubMed1999

Prediction of the intestinal absorption of endothelin receptor antagonists using three theoretical methods of increasing complexity.

PURPOSE: Three new computational strategies have been evaluated for their ability to predict intestinal membrane permeability to a series of endothelin receptor antagonists. METHODS: The three methods were evaluated using a set of ten nonpeptide endothelin receptor antagonists. The simplest method, "the rule of five", is based on 2D parameters such as the number of potential hydrogen bonds, molecular weight and calculated lipophilicity. A method based on molecular mechanics calculations is used to calculate 3D parameters such as polar and non-polar parts of the molecular surface area. The third method uses quantum mechanics to calculate molecular properties related to the valence region. RESULTS: Descriptors derived by the latter two methods correlated well with permeability coefficients of the endothelin receptor antagonists. On the other hand, the rule of five failed to discriminate between drugs with high and low permeability. CONCLUSIONS: Molecular surface descriptors and descriptors derived from quantum mechanics are potentially useful for the virtual screening of the permeability of the intestinal membrane to endothelin receptor antagonists.

Animals↗
PubMed1998

Erythrocyte promotion of platelet reactivity decreases the effectiveness of aspirin as an antithrombotic therapeutic modality: the effect of low-dose aspirin is less than optimal in patients with vascular disease due to prothrombotic effects of erythrocytes on platelet reactivity.

BACKGROUND: Aspirin (acetylsalicylic acid, ASA) is widely used for secondary prevention of ischemic vascular events, although its protection only occurs in 25% of patients. We previously demonstrated that platelet reactivity is enhanced by a prothrombotic effect of erythrocytes in a thromboxane-independent manner. This diminishes the antithrombotic therapeutic potential of ASA. Recent data from our laboratory indicate that the prothrombotic effect of erythrocytes also contains an ASA-sensitive component. In accordance with this observation, intermittent treatment with high-dose ASA reduced the prothrombotic effects of erythrocytes ex vivo in healthy volunteers. In the present study, the effects of platelet-erythrocyte interactions were evaluated ex vivo in 82 patients with vascular disease: 62 patients with ischemic heart disease treated with 200 mg ASA/d and 20 patients with ischemic stroke treated with 300 mg ASA/d. METHODS AND RESULTS: Platelet activation (release reaction) and platelet recruitment (fluid-phase proaggregatory activity of cell-free releasates from activated platelets) were assessed after collagen stimulation (1 microg/mL) of platelets, platelet-erythrocyte mixtures, or whole blood. Platelet thromboxane A2 synthesis was inhibited by >94% by ASA administration in all patients. Importantly, platelet recruitment followed one of three distinct patterns. In group A (n=32; 39%), platelet recruitment was blocked by ASA both in the presence and absence of erythrocytes. In group B (n=37; 45%), recruitment was abolished when platelets were evaluated alone but continued in the presence of erythrocytes, indicating a suboptimal effect of ASA on erythrocytes of this patient group. In group C (n= 13; 16%), detectable recruitment in stimulated platelets alone persisted and was markedly enhanced by the presence of erythrocytes. CONCLUSIONS: In two thirds of a group of patients with vascular disease, 200 to 300 mg ASA was insufficient to block platelet reactivity in the presence of erythrocytes despite abolishing thromboxane A2 synthesis. Platelet activation in the presence of erythrocytes can induce the release reaction and generate biologically active products that recruit additional platelets into a developing thrombus. Insufficient blockade of this proaggregatory property of erythrocytes can lead to development of additional ischemic complications.

Adult↗
PubMed1998

[Acute myocarditis caused by varicella virus].

We describe a case of acute myocarditis subsequent to varicella virus infection. We comment on the rarity of the clinical entity together with the nonspecificity of the routine diagnostic technique (EKG, X-ray, echocardiography study, routine laboratory, etc.) linked with the excellent gain of antibodies cardiac gammagraphy joined with viral serology, after the primary suspicion factor prior to the presence of skin lesions, fever and thoracic pain.

Acute Disease↗
PubMed1998

Circadian variation in acute ischemic stroke: a hospital-based study.

BACKGROUND AND PURPOSE: We investigated circadian rhythm in ischemic stroke onset and its subtypes, differentiating between first-ever stroke and recurrent stroke. METHODS: A consecutive series of 1223 patients with ischemic stroke was admitted at 2 reference hospitals; the time of onset of symptoms was obtained, differentiating between onset while asleep and awake. We compared circadian rhythm between stroke types and between first-ever and recurrent stroke. RESULTS: The onset time was known in 914 patients; 25.6% experienced onset on awakening [higher incidence in thrombotic and lacunar stroke (28.9% and 28.4%, respectively) than in embolic stroke (18.8%)]. For all stroke subtypes, there was a significant diurnal variation, with a morning peak between 6 AM and noon; after redistributing the hour of onset of patients awakening with stroke, the morning peak was minimal in all types of stroke. There were no differences in circadian rhythm between patients with first-ever and recurrent stroke. CONCLUSIONS: Only hospitalized patients were studied. There is a circadian rhythm in all types of stroke, with higher frequency during the day and lower frequency in the last hours in the evening. The highest incidence in the early hours of the morning can be overestimated, due to patients who awaken with stroke. There is no difference in circadian rhythm between first-ever stroke and recurrent stroke.

Acute Disease↗
PubMed1998

[Lacunar infarct and deep cerebral hemorrhage: a comparison of the risk factors].

INTRODUCTION: Lacunar infarcts (LI) and deep cerebral hemorrhages (DCH) have the same localization and a vasculopathy which appears to be similar, at the level of the small perforating arteries, classically attributed to arterial hypertension (AHT). OBJECTIVES: To compare the vascular risk factors of patients with lacunar ictus (LIc) and those with DCH, to try to determine how these may affect the appearance of one type of stroke or another. PATIENTS AND METHODS: We analyzed a prospective consecutive series of patients with cerebral vascular accidents (CVA), selecting 1,540 patients in the first 1,155 with a first CVA. We recorded demographic data and the following risk factors: previous transient ischemic accident (TIA), AHT, diabetes mellitus (DM), hypercholesterolemia, ischemic cardiopathy, atrial fibrillation and the presence of silent infarcts on CT. RESULTS: Two hundred and four patients had LIc and 163 had DCH. There was a significant dissociation between LIc and a history of TIA, DM, hypercholesterolemia and the presence of silent lacunar-type infarcts on CT. However, after multivariant analysis, DM did not continue to be an independent variable. Arterial blood pressure was found to be greater in the DCH group. CONCLUSIONS: The presence of different risk factors for LIc and DCH may be the key to understanding the mechanism which leads to one type or other of CVA.

Aged↗
PubMed1998

[Delayed hospitalization of the patient with acute stroke].

INTRODUCTION AND OBJECTIVE: We analyze the main factors influencing the time delay between onset and admission to the hospital in acute stroke. PATIENTS AND METHODS: Consecutive series of 1,344 patients with acute stroke or transient ischemic attack admitted at two reference hospitals of Valencia and included at the same stroke register. Factors assessed were age, sex, vascular risk factors, stroke onset and arrival at hospital, stroke severity and stroke subtype. RESULTS: In 30% of patients the stroke onset time was unknown. 70.7% of patients with acute stroke, and known onset, arrived to the hospital in the first six hours. The median time from onset to admission was: TIA, 2 hours; cerebral infarct, 3 hours (lacunar infarcts 5 hours, non-lacunar infarcts 2 hours) and intracerebral hemorrhage, 2 hours. Patients with severe stroke arrive earlier at the hospital (p < 0.001). Neither sex, age, nor vascular risk factors influence the delay time. CONCLUSIONS: The arrival time varies with stroke subtype: patients with intracerebral hemorrhage or TIA arrive earlier than those with cerebral infarct, and non-lacunar infarcts earlier than lacunar ones. Furthermore, patients with severe stroke are admitted sooner at the hospital.

Acute Disease↗
PubMed1997

[Primary intraventricular hemorrhage: an analysis of eight cases].

OBJECTIVE: Primary intraventricular haemorrhage (HIVP) is a rare condition, of diverse aetiology and variable course. We present a series of eight cases of HIVP diagnosed by CT and analyze the different aetiologies. MATERIALS AND METHODS: A retrospective series of 8 cases diagnosed by CT, the risk factors, clinical behaviour, complications and prognosis are evaluated. Neuroimaging findings (CT, MR and/or DIVAS) are described. RESULTS: The most commonly associated factor is arterial hypertension (75%). Clinically, presentation was uniform as evidence of sudden intracranial hypertension with signs of meningeal irritation with little or no neurological focal signs. The commonest complication was hydrocephalus (25%) and the chances of survival in most cases were good. Three causes of bleeding were found: an arteriovenous malformation, an aneurysm and a blood coagulation disorder. Three hypertensive patients with no obvious cause of bleeding had periependimary laguna infarcts. CONCLUSIONS: HIVP is an unusual condition of diverse aetiology, uniform clinical presentation and has a good short term prognosis. We suggest that pathology of the small vessels, induced by hypertension, may play a part in the aetiology of a subgroup of patients with no obvious cause of bleeding.

Adult↗
PubMed1997

[Transitory episode of laughter as the initial symptom of an ischemic stroke].

INTRODUCTION: Pathological laughter occurs in pseudobulbar paralysis, in psychiatric disorders and as a sign of convulsions (gelastic crisis). An extremely rare form is the "fou rire prodromique' a pathological episode of laughter preceding a stroke. The pathogenesis is unknown and classically differentiated from gelastic crises. "Fou rire prodromique' has been described in subcortical ischaemic or haemorrhagic strokes, not in cortical strokes. CLINICAL CASE: We describe a patient with an ischaemic cerebrovascular accident due to embolism of the left Sylvian artery. The clinical picture started with a short episode of pathological laughter which preceded sensitive aphasia and weakness of the right limbs. CONCLUSIONS: We suggest that in the case described it is impossible to differentiate between the "fou rire prodromique' and a gelastic crisis as a first sign of an embolic cerebrovascular accident.

Aged↗
PubMed1997

[Analysis of the situation of Valencian neurology by the Commission of Analysis of the Quality of Valencian Neurological Society].

INTRODUCTION: The Comision de Analisis de la Calidad de la Sociedad Valenciana de Neurologia has made a proposal of Neurology care requirements, based on the findings of various studies done in this region. There studies suggest that there should be a proportion of 3 neurologists per 100,000 inhabitants. METHOD: An analysis of requirements was made, based on evaluation of the public health service, private practice and trainee specialists (MIR) regarding this problem. The need for emergency neurological attention, and the place of a hierarchy and a system for referral was also considered. RESULTS: It was calculated that 109 neurologists are required, 11 in Castellon, 63 in Valencia and 35 in Alicante. This would mean a proportion of 2,66 neurologists per 100,000 inhabitants in Castellon, 2,90 in Valencia and 2,70 in Alicante. The total figure for the whole Community would be 2,82 per 100,000 inhabitants. CONCLUSIONS: At the present time neurological care is expensive, since a lack of specialists means waiting lists, poor patient care and high costs due to inappropriate use of technical resources.

Emergency Medical Services↗
PubMed1996

Nonpeptide endothelin receptor antagonists. VI: Pharmacological characterization of SB 217242, a potent and highly bioavailable endothelin receptor antagonist.

This study describes the pharmacological characterization of SB 217242, a highly potent orally bioavailable nonpeptide antagonist of both endothelin type A (ETA) and endothelin type B (ETB) receptors. In human cloned ETA and ETB receptors, SB 217242 produced concentration-dependent displacement of [125]I-endothelin-1 (ET-1) in both receptor subtypes with Ki values of 1.1 and 111 nM, respectively. SB 217242 produced concentration-dependent, parallel rightward shifts in the ET-1 concentration-response curves in rat isolated aorta and human isolated pulmonary artery (ETA receptor-mediated vascular contraction) with Kb values of 4.4 and 5.0 nM, respectively. SB 217242 was 4-, 62- and 125-fold more potent as an ETA receptor antagonist than the previously reported compounds BQ-123, PD 142893 and Ro 46-2005, respectively. SB 217242 (10 microM) did not produce significant effects against contraction produced by other vasoactive agents. SB 217242 produced concentration-dependent antagonism of responses produced by ETB receptor activation as demonstrated by antagonism of sarafotoxin S6c-mediated contraction in the rabbit isolated pulmonary artery with a Kb value of 352 nM. In vitro cell monolayers of Caco-2 cells had high permeability to SB 217242. In vivo pharmacokinetics in the rat confirmed that SB 217242 was rapidly absorbed from the gastrointestinal tract with a bioavailability of 66%. The SB 217242 plasma half-life in rats after intraduodenal administration was 3.3 hr, with a systemic clearance of 27.3 ml/min/kg. Orally administered SB 217242 (0.3-30 mg/kg) produced dose-dependent inhibition of the pressor response to exogenous ET-1 in conscious rats; with a dose of 30 mg/kg p.o., inhibition was observed for at least 5.5 hr. The present study demonstrates that SB 217242 is a highly potent antagonist of both ETA and ETB receptors. In addition, SB 217242 has high in vitro permeability and high oral bioavailability. SB 217242 represents a new orally active pharmacological tool that should assist in the elucidation of the chronic role of endothelin in pathophysiology.

Animals↗
PubMed1994

SB 209670, a rationally designed potent nonpeptide endothelin receptor antagonist.

An extremely potent and highly specific non-peptide, subnanomolar endothelin (ET) receptor antagonist, SB 209670, has been synthesized and characterized. SB 209670, which was rationally designed using conformational models of ET-1, selectively inhibits binding of 125I-labeled ET-1 to cloned human ET receptor subtypes ETA and ETB (Ki = 0.2 and 18 nM, respectively). SB 209670 produces concentration-dependent inhibition of ET-1-mediated vasoconstriction in isolated vascular tissues and in vivo following either intravenous or intraduodenal administration. SB 209670 produces a dose-dependent reduction in blood pressure in hypertensive rats, protects from ischemia-induced neuronal degeneration in a gerbil stroke model, and attenuates neointima formation following rat carotid artery balloon angioplasty. SB 209670 will be useful in characterizing and classifying the physiological and pathophysiological effects of ET.

Animals↗