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Biomedical subjects

J Pascual

Publications and source records attributed to J Pascual.

At least 73 records · Page 4Linked to original sources

Combined therapy for migraine prevention? Clinical experience with a beta-blocker plus sodium valproate in 52 resistant migraine patients.

The aim was to explore whether combining a beta-blocker and sodium valproate could lead to an advantage in efficacy in patients with migraine previously resistant to the two medications in monotherapy. Fifty-two patients (43 women) with a history of episodic migraine with or without aura, and previously unresponsive to beta-blockers and sodium valproate in monotherapy, were treated with a combination of propranolol or nadolol and sodium valproate in an open-label fashion. Eight patients (15%) discontinued due to adverse events. Fifteen (29%) did not respond. The remaining 29 cases (56%) showed response (> 50% reduction in migraine days). The response was excellent in nine (17%). From this open trial, combination therapy with a beta-blocker and sodium valproate appears to be a good migraine preventative in some previously resistant migraine cases. Controlled trials are now necessary to determine the true advantage in efficacy of this combination in difficult to treat migraineurs.

Adrenergic beta-Antagonists↗

Topiramate for patients with refractory migraine: an observational, multicenter study in Spain.

INTRODUCTION: The efficacy of current preventive migraine treatments is limited. In addition, tolerability problems are not infrequent. OBJECTIVES: To check our experience with topiramate in the treatment of patients with refractory migraine. PATIENTS AND METHODS: We offered treatment with topiramate to patients with the diagnosis of International Headache Society (IHS) migraine who had not responded to or tolerated beta-blockers, amitriptyline, flunarizine and/or valproate. This series is made up of 115 patients (88 women), between 16 and 81 years. Most of them (n=79) fulfilled the Silberstein et al. criteria for transformed migraine. The parameters analyzed were "response" (reduction in migraine frequency>50%), excellent response (>75%) and tolerability. RESULTS: After 3 months, the maintenance doses of topiramate ranged from 25 to 400 mg, though most patients took 100 mg. Twenty-four (21%) patients withdrew due to adverse events, mostly cognitive difficulties, that had already occurred with doses as low as 25-50 mg, while 26 (23%) found topiramate ineffective. The remaining 65 (56%) patients responded, 34 with excellent response. Sixteen patients (10 obese) lost weight (3-13 kg). CONCLUSIONS: Topiramate seems to be a good therapeutic option for about half of the patients with refractory migraine. In these patients response is usually excellent. Intolerance due to adverse events appears in one-fifth of the cases early and at low doses.

Adolescent↗

Brighter yellow blue tits make better parents.

Whether or not bird ornaments are a signal for direct (e.g. good parents) or indirect (e.g. good genes) benefits to prospective partners in sexual selection is controversial. Carotene coloration in Parus species is directly related to the ingestion of caterpillars, so that a brightly carotene-coloured tit may be signalling its ability to find caterpillars, a main high-quality food source for good fledgling development, and hence its parental abilities. If carotene-based plumage coloration is related to the good-parent hypothesis, we predict that yellow plumage brightness of tit fathers should be positively correlated to their investment in offspring provisioning. Here, we use cross-fostering experiments in blue tits (Parus caeruleus) to show that chick development (as measured by tarsus length) is related to yellowness of the foster father, but not to that of the genetic parents. Using these data, we were able to measure, for the first time to our knowledge, the separate contribution of genetic and environmental factors (i.e. parental plumage coloration) to chick development, and hence parental investment. Our data, which relate carotenoid coloration to models of good parents, and data from other authors, which relate ultraviolet coloration to good-genes models, stress that different kinds of coloration within an individual may provide different units of information to prospective females.

Animals↗

Episodic ataxia type 2. Three novel truncating mutations and one novel missense mutation in the CACNA1A gene.

We analysed the CACNA1A gene, located on chromosome 19p13, in three unrelated families and one sporadic case with episodic ataxia type 2 (EA-2). In two of the families and the sporadic patient, novel truncating mutations, which disrupt the reading frame and result in a premature stop of the CACNA1A protein, were identified in exons 14, 16 and 26. In the remaining family, a novel missense mutation (H253Y) was found. Of the twenty two EA-2 mutations identified thus far, including those of the present study, seventeen are truncating mutations and five are missense mutations, all resulting in an EA-2 clinical phenotype.

Adult↗

Birth seasonality in Jujeño (north-west Argentina) altitude populations.

Seasonality of births has been related to multiple factors, including environmental, biological and sociocultural ones, in populations of diverse geographic and cultural origin. However, the relationship between this variable of bioanthropologic interest and geographic altitude has not been adequately explored. The aim of this study was to analyse the monthly distribution pattern of birth rates in Jujeño (north-west Argentina) populations located at different geographic altitude levels. Data were provided by the Statistical Reports on Liveborns (n = 110,404) in the province of Jujuy, 1985-1992. Records were grouped by birthplace into the four geographic regions of the province: Ramal (350 m.a.s.l.), Valle (1200 m.a.s.l.), Quebrada (2500 m.a.s.l.) and Puna (3500 m.a.s.l.). Henry's coefficients of seasonality were estimated. A chi-square test for goodness of fit (chi2) was used to identify statistically significant seasonal variations. Edwards' test was used to detect simple harmonic cycles in birth distribution. Statistically significant seasonal patterns were found in the four geographic regions and they respond to a cyclic model of simple harmonic variation. The greatest Henry coefficients were observed in spring and summer in the higher regions (Puna and Quebrada). whereas they were seen in autumn and winter in the lowlands (Valle and Ramal). It is suggested that these patterns reflect the influence of environmental and socioeconomic altitude-related factors and inter-regional cultural diversity, rather than the influence of geographical altitude per se.

Altitude↗

Body weight changes and the A-6G polymorphism of the angiotensinogen gene.

BACKGROUND: The objective of the study was to analyze the relationship of polymorphisms of the angiotensinogen gene with changes in body weight during 3 y of antihypertensive treatment, in a group of young adults with essential hypertension. METHODS: Essential hypertensives, less than 50 y old, never previously treated with antihypertensive drugs and in the absence of diabetes mellitus were included. After the initial evaluation, patients were treated using only non-pharmacological measures (n=29), beta-blockers (n=40) or angiotensin-converting enzyme inhibitors (n=66). Resting blood pressure, biochemical profile and body weight at the beginning and yearly were measured. The polymorphism A-6G of the angiotensinogen gene located in the promoter region was analyzed. RESULTS: One-hundred and thirty-five patients were included. Genotypes of the A-6G polymorphism of the AGT gene were in Hardy-Weinberg equilibrium (AA 34, AG 63, GG 38). No significant differences were observed among genotypes in terms of age, body mass index, body weight, systolic or diastolic blood pressure. No significant differences in the genotype distribution or in the allele frequencies were observed, although the A allele was most frequent among the obese subjects. During the 3 y of antihypertensive treatment, there was a trend to increase weight despite the dietary recommendations. The slopes of body weight over time, adjusted by age and baseline BMI, differed significantly among the homozygote genotypes (P=0.006). The highest were for those with the AA genotype and the lowest for the GG genotype (1.180+/-0.25 and -0.128+/-0.24 kg/y; P=0.0001). The influence of the genotype in the changes on body weight remained significant after considering its interaction with the kind of antihypertensive treatment, although among subjects carrying the AA genotype those treated with ACEi showed the least body weight change. Furthermore, A-6G genotypes had the largest influence on weight changes, accounting for 19% of the variance, when age, sex and initial body mass index were included in the model. CONCLUSIONS: In a group of young adult hypertensive subjects, there was a trend to increase weight despite dietary recommendations. Subjects with the AA genotype were those with the largest weight gain, but this effect was modified by the antihypertensive treatment.

Adrenergic beta-Antagonists↗

Cardiovascular effects of peptide kinin B2 receptor antagonists in rats.

Bradykinin (BK) is a vasoactive peptide reputed to play an important role in cardiovascular homeostasis. In this study, we describe the cardiovascular changes (mean blood pressure (BP) and heart rate (HR)) induced by the i.v. administration (left jugular vein) of two selective kinin B2 receptor antagonist, namely icatibant (0.1-1 micromol/kg as a bolus) and MEN1 1270 (0.1-1 micromol/kg as a bolus or 1 micromol/kg infused in 15 or 60 min), in urethane-anaesthetized or conscious rats with an indwelling catheter implanted in the right carotid artery for BP measurements. In conscious rats, icatibant at 0.1 or 0.3 micromol/kg did not change BP but at 0.1 micromol/kg increased HR at 30 min from administration. MEN1 1270 at 0.1 or 0.3 micromol/kg induced a dose-related increase in BP and a concomitant bradycardia (significant at 0.3 micromol/kg) lasting for 5 or 30 min, respectively. Icatibant at 1 micromol/kg induced a slight (P < 0.05) increase in BP that resolved in 5 min and a biphasic tachycardia (peaks at 30 and 90 min from administration). MEN1 1270 at 1 micromol/kg induced a triphasic change in HR (tachycardia in the first 5 min, bradycardia at 30 min, and tachycardia at 90 and 120 min) and a biphasic change in BP (hypotension at 15 min and hypertension at 30 min). The i.v. infusion of MEN1 1270 (1 micromol/kg in 15 or 60 min) produced hypertension, whereas HR was increased only following the 15-min infusion. In urethane-anaesthetized rats, both icatibant and MEN1 1270 (0.1 micromol/kg as a bolus) increased BP and the onset for this effect was correlated with the time course of the antagonism of BK-induced hypotension, where the effect of MEN1 1270 was more rapid than that of icatibant. These results indicate that kinin B2 receptor antagonists can induce acute cardiovascular effects, and the reason for the different haemodynamic profile between icatibant and MEN1 1270 could be putatively attributed to kinetic characteristics.

Animals↗

[Profile of the antimigraine drug almotriptan].

Triptans are the most relevant advance in the symptomatic treatment of migraine in the last decade. In this paper the basic properties as well as the efficacy and tolerability data of the last launched triptan, almotriptan, are reviewed. Almotriptan exhibits the highest bioavailability among triptans, this absorption being unaffected by sex, the presence of food in the stomach or by a migraine attack. At the recommended dose of 12.5 mg, almotriptan shows a rapid onset of effect, at 30 minutes, with efficacy parameters comparable to those of placebo. The potential advantages of almotriptan seem to be three: recurrence rate in the low range, lack of interactions with other drugs and a placebo-like tolerability profile, with a very low rate of chest symptoms. This balanced profile between efficacy and tolerability makes almotriptan 12.5 mg a good option for the symptomatic treatment of migraine.

English Abstract↗

[Renal expression of intercellular adhesion molecule-1 (ICAM-1) in IgA deposit mesangial nephropathy. A tubulointerstitial lesion marker].

BACKGROUND: The aim of this study was to determine the significance of the renal expression of ICAM-1 in IgA nephropathy (IgAN). PATIENTS AND METHOD: First, we identified ICAM-1 (CD54) expression in tubular epithelial cells and interstitial leucocytes in renal biopsies from 45 patients with IgAN and 29 patients with non-glomerulonephritis nephropathy (non-GN). We then analysed the relationship between this expression and both histological and clinical data at the time of renal biopsy and after 2.4 (2) (X [SD]) years in IgAN, and 1.8 (1.5) years in non-GN. RESULTS: In IgAN, tubular ICAM-1 positive staining was seen in 25 (55%) biopsies; it was associated with extracapillary proliferation, glomerulosclerosis involving less than 50% of glomerular area, interstitial cell infiltration and tubular atrophy. ICAM-1 positive interstitial leucocytes were 234 (307)/mm2; this expression correlated with glomerulosclerosis, tubular atrophy, interstitial fibrosis and serum creatinine (Cr) level. In patients with 50% increase in Cr level, ICAM-1 positive interstitial leucocytes were 516 (360)/mm2 as compared with 66 (87.8)/mm2 (U = 16; p < 0.005) in patients with stable Cr. In non-GN, tubular ICAM-1 expression was observed in 7 (24%) biopsies. CONCLUSIONS: Tubular and Interstitial expression of ICAM-1 can be a marker of tubulointerstitial damage in IgAN. Interstitial ICAM-1, rather than tubular ICAM-1, may predict the progression of this disease.

Adult↗