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Biomedical subjects

A Castro

Publications and source records attributed to A Castro.

At least 163 records · Page 9Linked to original sources
PubMed2000

Comparison of intravenously administered dofetilide versus amiodarone in the acute termination of atrial fibrillation and flutter. A multicentre, randomized, double-blind, placebo-controlled study.

AIMS: This study compared the efficacy and safety of intravenous dofetilide with amiodarone and placebo in converting atrial fibrillation or flutter to sinus rhythm. METHODS AND RESULTS: One hundred and fifty patients with atrial fibrillation or flutter (duration range 2 h-6 months) were given 15-min intravenous infusions of 8 microg. kg(-1)of dofetilide (n=48), 5 mg. kg(-1)of amiodarone (n=50), or placebo (n=52) and monitored continuously for 3 h. Sinus rhythm was restored in 35%, 4%, and 4% of patients, respectively (P<0.001, dofetilide vs placebo;P=ns, amiodarone versus placebo). Dofetilide was more effective in atrial flutter than in atrial fibrillation (cardioversion rates 75% and 22%, respectively;P=0.004). The mean time to conversion with dofetilide was 55+/-15 min. Dofetilide prolonged the QTc interval (+16% at 20 min). Amiodarone substantially decreased the ventricular rate in non-converters (-18 beats. min(-1)at 30 min). Two patients given dofetilide (4%) had non-sustained ventricular tachycardias, and four (8%) had torsade de pointes, in one case requiring electrical cardioversion. CONCLUSION: Intravenous dofetilide is significantly more effective than amiodarone or placebo in restoring sinus rhythm in patients with atrial fibrillation or flutter. However, when infused intravenously at this dose and rate, dofetilide causes a significant incidence of torsade de pointes.

Acute Disease↗
PubMed2000

Gastric fundus relaxation and emetic sequences induced by apomorphine and intragastric lipid infusion in healthy humans.

OBJECTIVES: Experimental animal studies have suggested that gastric relaxation precedes emesis, whether induced by peripheral or central stimuli. We aimed to quantify the gastric relaxatory and symptomatic responses to a standardized emetic inductor. METHODS: In healthy volunteers, we measured the gastric and symptomatic response to two different proemetic stimuli: a peripheral stimulus (intragastric infusion at 5 ml/min of 50% fat emulsion in water) and a central stimulus (s.c. apomorphine at 0.01 mg/kg). Proximal gastric tone was continuously recorded by an electronic barostat. Symptoms were simultaneously quantified by a graded questionnaire. RESULTS: Lipid-induced gastric relaxation occurred in 17/17 subjects and was followed by nausea in 12/17. The total amount of intragastric fat required to trigger gastric relaxation was 139 +/- 34 ml and to induce nausea, 258 +/- 32 ml. Gastric relaxation after subcutaneous apomorphine occurred in 13/14, and nausea/emesis, in the same 13/14. As expected, timing of events after stimulation was much shorter in response to the central than to the peripheral stimulus. Thus, gastric relaxation began 4.0 +/- 0.6 min after subcutaneous apomorphine and 28 +/- 7 min after the onset of lipid infusion (p < 0.05); likewise, the symptomatic response to central stimulation with apomorphine was 8.5 +/- 1.8 min versus 52 +/- 6 min for lipid infusion, p < 0.05. However, the magnitude of gastric relaxation was quite similar for both stimuli (apomorphine: 208 +/- 35 ml; intragastric lipid: 235 +/- 23 ml). No correlation was observed between the symptomatic response and the magnitude of the gastric relaxation, whether elicited by intragastric infusion of lipids or by subcutaneous apomorphine. Specifically, when symptomatic and gastric motor responses were compared in each of the 14 subjects who received both stimuli, no significant correlation between individual responses was detected. CONCLUSIONS: Gastric relaxation invariably precedes nausea and emesis and is of the same magnitude whether induced by apomorphine (central stimulus) or intragastric lipid infusion (peripheral stimulus). Nevertheless, in some instances and depending on the nature of the stimulus, fundic relaxation is a physiological event unassociated with nausea.

Adult↗
PubMed2000

Comparison of the Serodia Treponema pallidum particle agglutination, Captia Syphilis-G, and SpiroTek Reagin II tests with standard test techniques for diagnosis of syphilis.

We compared the microhemagglutination assay for Treponema pallidum (MHA-TP), a treponemal test, with two other treponemal tests, the Serodia Treponema pallidum particle agglutination (TP-PA) assay and the Captia Syphilis-G enzyme immunoassay, using 390 clinical serum samples. We also compared two nontreponemal tests, the rapid plasma Reagin (RPR) card test and the SpiroTek Reagin II test. Agreements of the MHA-TP with the TP-PA test and the Syphilis-G test were 97.4 and 97.7%, respectively. There was 89.2% agreement between the RPR and Reagin II tests. The Reagin II test was more apt to be reactive if the treponemal test was also reactive. We conclude that either the Serodia TP-PA test or the Captia Syphilis-G test is an appropriate substitute for the MHA-TP and that the Spirotek Reagin II test could substitute for the RPR test as a screening test.

Antibodies, Bacterial↗
PubMed2000

Evaluation of brain natriuretic peptide in the diagnosis of heart failure.

A diagnosis of heart failure (HF) can be difficult, especially in patients with mild symptomatology. The purpose of this study was to evaluate the significance of brain natriuretic peptide (BNP) in the diagnosis of HF with systolic or isolated diastolic ventricular dysfunction. One hundred patients and 9 controls were included in the study. Eighty-five patients were diagnosed with HF, based on clinical and echocardiographic findings. BNP levels were accurate for the diagnosis of HF, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.92. In addition, BNP levels showed an excellent accuracy for the diagnosis of isolated diastolic HF (AUC = 0.89). These data suggest that the measurement of BNP levels may be helpful in the diagnosis of HF and in selecting patients for further evaluation. Furthermore, BNP measurement can play an important role in the diagnosis of isolated diastolic HF.

Aged↗
PubMed2000

Thienothiadiazine 2,2-dioxide acyclonucleosides: synthesis and antiviral activity.

The synthesis of acyclonucleosides derived from thieno[3,2-c] and thieno[2,3-c][1,2,6]thiadiazine 2,2-dioxides was achieved following the silylation method. Lipase-mediated methodology was employed for deprotection of the acyclic moieties. The antiviral effects were determined against a broad spectrum of viruses, including cytomegalovirus (CMV) and varicella zoster virus (VZV). Only minor antiviral activity against VZV was observed for those acyclonucleosides carrying a benzyl group.

Antiviral Agents↗
PubMed2000

Endocrine and paracrine-autocrine regulation of the human corpus luteum during the mid-luteal phase.

Human corpora lutea undergo an extremely rapid period of growth, development and regression during the course of non-fertile cycles. The tissue consists of steroidogenic (parenchymal) and non-steroidogenic (stromal) cells. In women and other primates, steroid hormone production by corpora lutea depends on the presence of pituitary-derived LH. Nevertheless, there is also intra-luteal regulation of steroid synthesis. Steroidogenic luteal cells and non-steroidogenic cells interact via endocrine and paracrine pathways, and by contact-dependent pathways (gap junctions). Thus, hormones and locally produced factors including steroids, growth factors, cytokines, reactive oxygen species and nitric oxide may modulate luteal lifespan. The factors regulating regression and rescue of the corpus luteum are not understood completely. This review describes the expression of two representative intragonadal peptides that may influence luteal regression (interleukin 1 beta) and luteal rescue (steroidogenic acute regulatory protein).

Animals↗
PubMed2000

Electrophysiology of atrial fibrillation: evolving insights.

In the last few years many studies have been performed to better understand the pathophysiological nature of atrial fibrillation (AF). These recent observations provide new insights into the initiation and perpetuation of AF, underlying the importance of the pulmonary veins as major sources of atrial triggers and introducing new concepts such as atrial electrical remodeling and spatial heterogeneity of the electrophysiologic characteristics of this arrhythmia. The purpose of this review was to provide current knowledge about AF electrophysiology in an effort to unite old models and new concepts.

Animals↗
PubMed2000

Population frequency distribution of HumF13A01, HumFXIIIB, and HumLIPOL loci in the Basque Country (Northern Spain).

A population study of unrelated individuals from the Basque Country (Northern Spain) was carried out using the GenePrint STR System. The PCR products were separated on denaturing polyacrylamide gels and visualized by silver staining. Three tetrameric loci were evaluated: HumF13A01, HumFXIIIB, and HumLIPOL. All loci fit Hardy-Weinberg expectations, and independence of alleles was found between these STR loci. A comparison with other population groups indicated allele frequencies are well conserved in Caucasians, but differ from other racial groups. The calculated parameters a priori probability of exclusion (Pex) and "power of discrimination" (PD) show how informative these loci are for the determination of identity and relatedness of individuals.

Ethnicity↗
PubMed2000

[Microdeletion of Y chromosome in severe olygozoospemic infertile patient].

We are reporting a 37 year old male with severe oligozoospermia and a history of infertility for thirteen years and surgery for severe unilateral varicocele. The hormonal levels for FSH, LH and T, and karyotype were within the normal range. Multiplex PCR revealed the presence of a de novo microdeletion in the azoospermia factor (AZF) c region involving the deleted in azoospermia (DAZ) and basic protein Y-2 (BPY2) genes. These results suggest that severe oligozoospermia should be considered for the screening of microdeletions of Yq involving the AZFc region even in the presence of a varicocele.

Adult↗
PubMed1999

Development of immunoreactivity to neuropeptide Y in the brain of brown trout (Salmo trutta fario).

The development of neuropeptide Y-immunoreactive (NPY-ir) neurons in the brain of the brown trout, Salmo trutta fario, was studied by using the streptavidin-biotin immunohistochemical method. Almost all NPY-ir neurons found in the brain of adults already appeared in embryonic stages. The earliest NPY-ir neurons were observed in the laminar nucleus, the locus coeruleus, and the vagal region of 9-mm-long embryos. In the lateral area of the ventral telencephalon, habenula, hypothalamus, optic tectum, and saccus vasculosus, NPY-ir cells appeared shortly after (embryos 12-14 mm in length). The finding of NPY-ir cells in the saccus vasculosus and the vagal region expand the NPY-ir structures known in teleosts. Among the regions of the trout brain most richly innervated by NPY-ir fibers are the hypothalamus, the isthmus, and the complex of the nucleus of the solitary tract/area postrema, suggesting a correlation of NPY with visceral functions. Two patterns of development of NPY-ir populations were observed: Some populations showed a lifetime increase in cell number, whereas, in other populations, cell number was established early in development or even diminished in adulthood. These developmental patterns were compared with those found in other studies of teleosts and with those found in other vertebrates. J. Comp. Neurol. 414:13-32, 1999.

Animals↗
PubMed1999

Chlorophenylmethyl benzothiadiazine dioxides derivatives: potent human cytomegalovirus inhibitors.

Modifications of our previously reported lead compounds, acyclonucleosides derived from 2,1,3-benzothiadiazine dioxides, in the search for inhibitors of human cytomegalovirus (HCMV), lead us to identify the chlorophenylmethyl benzothiadiazine dioxides derivatives as potent HCMV inhibitors. The synthesis and antiviral data of this second-generation of benzothiadiazine dioxide compounds are reported.

Anti-Infective Agents↗
PubMed1999

A comparison of the bronchodilatory effect of 50 and 100 microg salbutamol via Turbuhaler and 100 microg salbutamol via pressurized metered dose inhaler in children with stable asthma.

AIM: The aim of the study was to compare the efficacy of single doses of salbutamol Turbuhaler (50 and 100 microg), salbutamol pressurized metered dose inhaler (pMDI) (100 microg) and placebo in children with stable chronic reversible airway obstruction. Primary efficacy variable (FEV1-av) was calculated as the area under the curve of forced expiratory volume in one second (FEV1) (AUC, 0-4 h) and divided by the observed time. DESIGN: The study was of a randomized, single-dose, crossover and double-blind design. Seven centres participated. FEV1 was measured pre-dose and at 15 min, 0.5, 1, 1.5, 2, 3 and 4 h post study dose. PATIENTS: Forty asthmatic children (9 girls) with a mean age of 9 years (range: 6-12), mean FEV1 of 1.6 l (range: 0.9-2.4) and a mean FEV1 in percentage of predicted normal value of 80% (range: 61-109) were randomized into the study. The mean reversibility 30 min after inhaling 2x100 microg salbutamol from pMDI was 20% (range: 9-45) or 15% (range: 8-27) in percentage of predicted normal value. RESULTS: The mean FEV1-av was 1.63 l for placebo, 1.71 l for 50 microg salbutamol Turbuhaler, 1.76 l for 100 microg salbutamol Turbuhaler and 1.76 for 100 microg salbutamol pMDI. Corresponding values for maximum FEV1 were 1.76, 1. 85, 1.87 and 1.87 l, respectively. There were no statistically significant differences between the active treatments in FEV1-av or maximum FEV1. All active treatments were significantly better than placebo. CONCLUSION: No significant differences in bronchodilating effect between 50, 100 microg salbutamol Turbuhaler and 100 microg salbutamol pMDI in children, aged 6-12 years, with stable asthma could be demonstrated. All active treatments were significantly better than placebo.

Albuterol↗
PubMed1999

Novel potential agents for human cytomegalovirus infection: synthesis and antiviral activity evaluation of benzothiadiazine dioxide acyclonucleosides.

The first acyclonucleosides based on the benzothiadiazine dioxide system were synthesized following the silylation procedure. Several acyclic moieties, including acetoxyethoxymethyl, benzyloxymethyl, and propargyloxymethyl groups, were introduced. Two synthetic strategies were designed to selectively obtain the N-1 or N-3 derivatives. Lipase-mediated deacylation was used for the deprotection of the acyclonucleosides. Some of the benzothiadiazine dioxide acyclonucleosides, in particular 16, proved active against human cytomegalovirus (CMV) at concentrations slightly higher than that found for ganciclovir [50% inhibitory concentration (IC50) = 3. 5-3.7 micrograms/mL, cytotoxicity (CC50) >/= 40 micrograms/mL, MCC = 20 micrograms/mL]. Additionally, compound 16 inhibited the replication of human immunodeficiency virus type 1 (HIV-1) and HIV-2 in CEM cells at concentrations that were 5-fold lower than its cytotoxic concentration.

Anti-HIV Agents↗
PubMed1999

Selective, tight-binding inhibitors of integrin alpha4beta1 that inhibit allergic airway responses.

Integrin alpha4beta1 mediates leukocyte recruitment, activation, mediator release, and apoptosis inhibition, and it plays a central role in inflammatory pathophysiology. High-affinity, selective inhibitors of alpha4beta1, based on the Leu-Asp-Val (LDV) sequence from the alternatively spliced connecting segment-1 (CS-1) peptide of cellular fibronectin, are described that employ a novel N-terminal peptide "cap" strategy. One inhibitor, BIO-1211, was approximately 10(6)-fold more potent than the starting peptide and exhibited tight-binding properties (koff = 1.4 x 10(-4) s-1, KD = 70 pM), a remarkable finding for a noncovalent, small-molecule inhibitor of a protein receptor. BIO-1211 was also 200-fold selective for the activated form of alpha4beta1, and it stimulated expression of ligand-induced epitopes on the integrin beta1 subunit, a property consistent with occupancy of the receptor's ligand-binding site. Pretreatment of allergic sheep with a 3-mg nebulized dose of BIO-1211 inhibited early and late airway responses following antigen challenge and prevented development of nonspecific airway hyperresponsiveness to carbachol. These results show that highly selective and potent small-molecule antagonists can be identified to integrins with primary specificity for peptide domains other than Arg-Gly-Asp (RGD); they confirm the generality of integrins as small molecule targets; and they validate alpha4beta1 as a therapeutic target for asthma.

Animals↗
PubMed1999

IL-4 selectively inhibits IL-2-triggered Stat5 activation, but not proliferation, in human T cells.

IL-2 activates several distinct signaling pathways that are important for T cell activation, proliferation, and differentiation into both Th1 and Th2 phenotypes. IL-4, the major cytokine that promotes differentiation of Th2 cells, has been shown to block signaling of the Th1-promoting cytokine IL-12. As IL-2 synergizes with IL-12 in promoting Th1 differentiation, the effects of IL-4 on IL-2 signal transduction were investigated. IL-4 suppressed activation of DNA binding and tyrosine phosphorylation of the transcription factor Stat5 by IL-2, and suppressed the expression of the IL-2-inducible genes CD25, CIS, the PGE2 receptor, and cytokine responsive (CR) genes CR1 and CR8. Activation of Stat5 by cytokines that share a common gamma receptor subunit, IL-2, IL-7, and IL-15, was suppressed by preculture in IL-4. Activation of the Jak1 and Jak3 kinases that are proximal to Stat5 in the IL-2-Jak-STAT signaling pathway was suppressed, and this correlated with inhibition of IL-2Rbeta subunit expression. In contrast to suppression of Stat5, proliferative responses to IL-2 were augmented in IL-4-cultured cells, and activation of proliferative pathways leading to activation of mitogen activated protein kinases, induction of expression of Myc, Fos, Pim-1, and cyclin D3, and decreased levels of the cyclin-dependent kinase inhibitor p27 were intact. These results identify molecular mechanisms underlying interactions between IL-4 and IL-2 in T cells and demonstrate that one mechanism of regulation of IL-2 activity is selective and differential modulation of signaling pathways.

Base Sequence↗
PubMed1999

Bacillus cereus prosthetic valve endocarditis.

Bacillus cereus is a ubiquitous organism that often contaminates microbiological cultures but rarely causes serious infections. Reports of B. cereus endocarditis are infrequent. Infection in patients with valvular heart disease is associated with significant mortality and morbidity. We describe a case of B. cereus endocarditis involving a mechanical mitral prosthesis that resolved after replacement of the prosthetic valve. We also review the previous cases reported in the literature.

Bacillaceae Infections↗