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Biomedical subjects

M Velasco

Publications and source records attributed to M Velasco.

At least 55 records · Page 3Linked to original sources
PubMed2000

Progastrin expression predisposes mice to colon carcinomas and adenomas in response to a chemical carcinogen.

BACKGROUND & AIMS: Processing intermediates of preprogastrin (gly-gastrin and progastrin), termed nonamidated gastrins, are mitogenic for several cell types including colonic epithelial cells. However, presently it is not known if nonamidated gastrins play a role in colon carcinogenesis and if the effects are similar to those of amidated gastrins. METHODS: Colon carcinogenesis in response to azoxymethane (AOM) was examined in transgenic mice overexpressing either progastrin (hGAS) or amidated gastrin (INS-GAS), compared with that in wild-type (WT) mice. RESULTS: In AOM-treated groups, the total number of tumors per colon was significantly higher in hGAS (4.8+/-0.34) than INS-GAS (3.0+/-0.16) and WT (2.7+/-0.35) mice. Total numbers of adenocarcinomas and adenomas per animal colon were also significantly higher in hGAS than INS-GAS and WT mice. The size of the tumors was greater in hGAS mice, resulting in a significantly higher tumor burden per mouse in the hGAS mice than INS-GAS and WT mice. Although >90% of the tumors were located in the distal half of the colon in INS-GAS and WT mice, a significant number (42%) were present at the proximal end of the colon in hGAS mice. CONCLUSIONS: The results suggest that the risk for developing colon carcinomas and adenomas in response to AOM is significantly increased in mice expressing high levels of progastrin, but not amidated gastrins.

Adenoma↗
PubMed2000

Predictors in the treatment of difficult-to-control seizures by electrical stimulation of the centromedian thalamic nucleus.

OBJECTIVE: To evaluate the efficacy of chronic electrical stimulation of centromedian thalamic nuclei (ESCM) in the treatment of difficult-to-control seizures. METHODS: Thirteen patients underwent ESCM for periods ranging from 12 to 94 months (mean, 41.2 mo) with electrodes stereotactically placed in both centromedian nuclei and connected to internalized stimulation systems. Electrode placement was guided by ventriculography and confirmed with magnetic resonance imaging before stimulation systems were internalized. Anatomic and electrophysiological confirmation of the electrodes' position was accomplished by plotting electrode position on anatomic sections of Schaltenbrand and Bailey's atlas, and testing cortical recruiting responses and electroencephalogram desynchronization elicited by acute low- or high-frequency stimulation, respectively. RESULTS: Improvement was highly significant for generalized tonicoclonic seizures and atypical absences. Better results were obtained for Lennox-Gastaut syndrome. These results were accompanied by a significant decrease in generalized spike-wave and secondary synchronous discharges, as well as focal spikes in the frontal regions. In contrast, ESCM reduced neither complex partial seizures nor focal spikes in temporal regions. Outcomes using ESCM for generalized epilepsy were better in patients in whom anatomic and electrophysiological confirmation of electrode placement was correct than in those in whom the target was missed bilaterally (P < 0.001). The effect was sustained during the observation period and was better for longer-term than for shorter-term stimulation periods. CONCLUSION: ESCM is an efficient and safe procedure for controlling certain seizure types, if patient selection and stereotactic placement are satisfactory.

Adolescent↗
PubMed2000

Subacute electrical stimulation of the hippocampus blocks intractable temporal lobe seizures and paroxysmal EEG activities.

PURPOSE: To investigate the clinical, electroencephalographic (EEG), and histopathologic effects of subacute electrical stimulation of the hippocampal formation or gyrus (SAHCS) on 10 patients with intractable temporal lobe seizures. METHODS: Bilateral, depth, hippocampal or unilateral, subdural, basotemporal electrodes were implanted in all 10 patients for a topographic diagnosis of the site and extent of the epileptic focus before a temporal lobectomy. In all patients, antiepileptic drugs (AEDs) were discontinued from 48 to 72 h before a program of continuous SAHCS, which was performed for 2-3 weeks. Stimulation parameters were biphasic Lilly wave pulses, 130/s in frequency, 450 micros in duration, and 200-400 microA in amplitude. The stimuli were delivered 23 of every 24 h for the 2-3-week SAHCS period. The effects of SAHCS on the number of clinical seizures per day and the percentage of interictal EEG spikes per 10-second samples of maximal paroxysmal activity at the epileptic focus were determined daily during the 16 days of SAHCS. At the completion of this program, patients underwent an en bloc temporal lobectomy, and the histopathologic effects of SAHCS on the stimulated tissue were analyzed by means of light-microscopy studies. RESULTS: In seven patients whose stimulation electrode contacts were placed within the hippocampal formation or gyrus and who experienced no interruption in the stimulation program, SAHCS abolished clinical seizures and significantly decreased the number of interictal EEG spikes at the focus after 5-6 days. The most evident and fast responses were found by stimulating either the anterior pes hippocampus close to the amygdala or the anterior parahippocampal gyrus close to the entorhinal cortex. Other surface, hippocampal, and basotemporal EEG signs predicted and accompanied this antiepileptic response. These included an electropositive DC shift and monomorphic delta activity at the medial hippocampal and parahippocampal regions, and a normalization of the background EEG activity and signs of slow-wave sleep in surface. depth, and subdural regions. In contrast, no evident antiepileptic responses or no responses at all were found in three patients when stimulation was either interrupted or when it was administered outside the hippocampus. Light microscopy analysis of the stimulated hippocampal tissue showed histopathological abnormalities attributable to the depth-electrode penetration damage or to the pial surface reaction to the subdural, Silastic electrode plate. However, no evident histopathological differences were found between the stimulated and nonstimulated hippocampal tissue. CONCLUSIONS: SAHCS appears to be a safe procedure that can suppress temporal lobe epileptogenesis with no additional damage to the stimulated tissue.

Adult↗
PubMed2000

Mice overexpressing progastrin are predisposed for developing aberrant colonic crypt foci in response to AOM.

Recent studies show that nonamidated gastrins (Gly-gastrin and progastrin) stimulate colonic proliferation. However, the role of nonamidated vs. amidated gastrins in colon carcinogenesis has not been defined. We measured intermediate markers of carcinogenesis in transgenic mice overexpressing either progastrin (hGAS) or amidated gastrin (INS-GAS) in response to azoxymethane (AOM). The hGAS mice showed significantly higher numbers of aberrant crypt foci (140-200% increase) compared with that in wild-type (WT) and INS-GAS mice (P < 0.05) after AOM treatment. The bromodeoxyuridine-labeling index of colonic crypts also was significantly elevated in hGAS mice vs. that in WT and INS-GAS mice. The results therefore provide evidence for a mitogenic and cocarcinogenic role of nonamidated gastrins (progastrin), which is apparently not shared by the amidated gastrins. Although nonamidated gastrins are now believed to mediate mitogenic effects via novel receptors, amidated gastrins mediate biological effects via different receptor subtypes, which may explain the difference in the cocarcinogenic potential of nonamidated vs. amidated gastrins. In conclusion, our results provide strong support for a cocarcinogenic role for nonamidated gastrins in colon carcinogenesis.

Animals↗
PubMed2000

Evaluation of the polymerase chain reaction for the detection of Mycobacterium tuberculosis.

The development of nucleic acid-based technologies has improved the sensitivity, specificity and speed of detection of Mycobacterium tuberculosis in clinical samples. Both commercially available and 'in-house' polymerase chain reaction (PCR) systems are in use, and a significant number of reports compare such systems with more traditional diagnostic tools for tuberculosis. Few studies, however, have focused on the reproducibility of the results when submitting a sample batch to PCR in different laboratories, especially in developing countries. Consequently, PCR results obtained from six laboratories in six different Latin American countries for samples reconstituted with defined amounts of M. tuberculosis cells were evaluated. Each laboratory used specific conditions of sample processing, nucleic acid amplification and amplicon detection. Analysis of results allowed large differences in sensitivity and specificity to be observed. We conclude that in its present setting, in-house PCR cannot be used as a single diagnostic tool for tuberculosis, and that special care needs to be taken upon interpretation of results by inclusion of a proper number of positive and negative controls.

Evaluation Studies as Topic↗
PubMed2000

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine induces a higher number of aberrant crypt foci in Fischer 344 (rapid) than in Wistar Kyoto (slow) acetylator inbred rats.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine carcinogen in the human diet and is a colon carcinogen in the rat. N-Acetyltransferase-2 (NAT2) catalyzes the conversion of PhIP and other heterocyclic amines to a DNA-reactive form. NAT2 has a polymorphic distribution in humans and other mammals, including rats. The rapid NAT2 genotype has been shown to be associated with increased colorectal cancer risk in some, but not all, human epidemiological studies. This investigation was designed to study the role of acetylator genotype in PhIP-induced colon carcinogenesis using aberrant crypt foci (ACF) as an intermediate biomarker. Five-week-old male, rapid-acetylator Fischer 344 (F344) rats and slow-acetylator Wistar-Kyoto (WKY) rats were fed the semipurified AIN76A diet with 0.01% PhIP, 0.04% PhIP, or no PhIP (control) for 8 weeks. PhIP induced ACF in both rapid- and slow-acetylator rats; 0.04% PhIP induced more ACF than 0.01% PhIP. There was no difference in the number of ACF between rapid- and slow-acetylator rats that were fed 0.01% PhIP. However, 0.04% PhIP induced 2-fold higher ACF and a greater dose-dependent increase in PhIP-induced ACF in the rapid-acetylator F344 rats compared with the slow-acetylator WKY rats. The results support human epidemiological studies showing higher risk for colorectal cancer in rapid acetylators who frequently consume meat that is very well done.

Acetylation↗
PubMed2000

Efficacy of potential chemopreventive agents on rat colon aberrant crypt formation and progression.

We assessed the effects of 78 potential chemopreventive agents in the F344 rat using two assays in which the inhibition of carcinogen-induced aberrant crypt foci (ACF) in the colon was the measure of efficacy. In both assays ACF were induced by the carcinogen azoxymethane (AOM) in F344 rats by two sequential weekly injections at a dose of 15 mg/kg. Two weeks after the last AOM injection, animals were evaluated for the number of aberrant crypts detected in methylene blue stained whole mounts of rat colon. In the initiation phase protocol agents were given during the period of AOM administration, whereas in the post-initiation assay the chemopreventive agent was introduced during the last 4 weeks of an 8 week assay, a time when ACF had progressed to multiple crypt clusters. The agents were derived from a priority listing based on reports of chemopreventive activity in the literature and/or efficacy data from in vitro models of carcinogenesis. During the initiation phase carboxyl amidoimidazole, p-chlorphenylacetate, chlorpheniramine maleate, D609, diclofenac, etoperidone, eicosatetraynoic acid, farnesol, ferulic acid, lycopene, meclizine, methionine, phenylhexylisothiocyanate, phenylbutyrate, piroxicam, 9-cis-retinoic acid, S-allylcysteine, taurine, tetracycline and verapamil were strong inhibitors of ACF. During the post-initiation phase aspirin, calcium glucarate, ketoprofen, piroxicam, 9-cis-retinoic acid, retinol and rutin inhibited the outgrowth of ACF into multiple crypt clusters. Based on these data, certain phytochemicals, antihistamines, non-steroidal anti-inflammatory drugs and retinoids show unique preclinical promise for chemoprevention of colon cancer, with the latter two drug classes particularly effective in the post-initiation phase of carcinogenesis.

Animals↗
PubMed1999

Treadmill exercise-induced stress causes a rise of blood histamine in normotensive but not in primary hypertensive humans.

We have previously shown an interaction between noradrenergic and histamine-containing neurons in the rat vas deferens. As a generalized phenomenon, this interaction is involved in a novel peripheral reflex that, in an inhibitory way, modulates sympathetic activity and arterial pressure. Consistent with this, an activation of postganglionic sympathetic neurons causes a rise in rat blood histamine. In the present study, we showed that enhanced sympathetic activity due to treadmill exercise in normotensive humans, is accompanied by a rise in blood histamine, suggesting the presence of a similar neuronal interaction in humans. In contrast, the rise in blood histamine does not occur in primary hypertensive humans during the same degree of physical exercise, suggesting that this interaction is faulty in such hypertensives and could be involved in the pathophysiology of the disease.

Adult↗
PubMed1999

Reversible mechanical fixation of eye position in awake head-restrained pigeons (Columba livia).

Here we describe a method to fix gaze positions and to significantly reduce saccadic oscillations in pigeons. The procedure consists of a mechanical immobilization of the eye through the use of an electromagnet that exerts a radial force upon a small metal rectangle glued to the dorsal part of the eye. The method can be used in avian visual neurophysiology in order to hold the eye immobilized for periods of time, long enough to map the properties of visual receptive fields and investigate the possible functions of saccadic oscillations.

Animals↗
PubMed1999

[Multiple coronary aneurysms in a young man. A diagnostic approach via different technics].

Coronary aneurysms are uncommon. The most frequent etiologies are atherosclerotic and congenital, although there are several other rare causes. Myocardial infarction and sudden death may be the initial manifestations which are usually a consequence of aneurysm complications such as rupture or distal embolization. Although coronariography is the gold standard diagnostic technique, coronary aneurysm may also be detected by non-invasive methods such as ultrasonography and nuclear magnetic resonance. We report the case of a young male with hypercholesterolemia who presented cardiac arrest as the first clinical manifestation. Ultrasonography and MRI revealed the presence of multiple coronary aneurysm. This case illustrates the usefulness of non-invasive techniques for the diagnosis of coronary aneurysm.

Adult↗
PubMed1999

Fulminant herpes hepatitis in a healthy adult: a treatable disorder?

Hepatitis due to herpes simplex virus (HSV) is a potentially fatal disorder that is often not considered in the differential diagnosis of acute hepatitis. This disease occurs most often in patients with impaired immunity and is very uncommon in healthy patients. HSV hepatitis presents with a wide clinical spectrum, and the clinical diagnosis is difficult. We describe a case of disseminated herpes virus infection with fulminant hepatitis mimicking an acute human immunodeficiency virus infection in a 33-year-old healthy man. Preliminary studies suggest that early treatment of HSV hepatitis with acyclovir may be beneficial in these patients. A high index of suspicion and the availability of early diagnostic tools, such as HSV DNA detection, may dramatically improve the clinical outcome of severe HSV hepatitis.

Acute Disease↗
PubMed1999

Effects of amlodipine and enalapril on platelet function in patients with mild to moderate hypertension.

OBJECTIVE: The aim of this study was to compare the effect of amlodipine and enalapril on platelet aggregation, and platelet production of malondialdehyde in patients with mild to moderate arterial hypertension. PATIENTS AND METHODS: A parallel, double-blind, placebo-controlled study was carried out in 24 patients (2 groups of 12 patients each). Initially all patients received placebo for four weeks; then amlodipine, 5 mg daily or enalapril 20 mg daily taken once a day at 7 am. Dosage was doubled after 4 weeks when diastolic blood pressure was > 90 mmHg in sitting position, the treatment was continued for 12 weeks. At the end of placebo and active phases a platelet aggregation test, using adenosine diphosphate, collagen and adrenaline, and a platelet malondialdehyde production test, either in basal conditions (MDA-basal) and after the stimulation of arachidonic acid pathway by adding ethylmaleimide (MDA-activated) were carried out. RESULTS: Blood pressure was reduced by both agents, enalapril and amlodipine. Enalapril controlled 58.3% of hypertensive patients with an average dosage of 31.7 mg/daily. Amlodipine controlled 75% of patients with a dosage of 7.1 mg/daily. Platelet aggregation was reduced by amlodipine in 15.9% for ADP (10 microM); 17.4% for collagen (2 microg/ml) and 19.9% for adrenaline (2 microM) (p < 0.025). Meanwhile enalapril slightly increased platelet aggregation by 6.7%, 1.3% and 5.6% for the three agents, respectively (p > 0.05, ns). Malondialdehyde was reduced by amlodipine in 45.33% (p < 0.05) for MDA-basal; 3.76% (p > 0.05) for MDA-activated; and the ratio MDA-basal:MDA-activated in 36.79% (p < 0.005). Meanwhile enalapril increased MDA-basal in 2.89%; MDA-activated in 3.58% and reduced the ratio MDA-basal:MDA-activated, in 10.34% (p > 0.05). CONCLUSION: Both agents, enalapril and amlodipine, reduced blood pressure, but only amlodipine reduced platelet aggregation and platelet production of malondialdehyde, indicating its action on the arachidonic acid metabolic pathway.

Amlodipine↗
PubMed1999

Inhaled dopamine induces bronchodilatation in patients with bronchial asthma.

OBJECTIVE: To determine the probable bronchodilating effect of dopamine administered by inhalation route in patients with crisis of bronchial asthma and the effect of dopamine on bronchial motor tone. DESIGN AND METHOD: We have studied eighteen (18) patients with crisis of bronchial asthma, ten (10) subjects with bronchial hyperreactivity and ten (10) healthy subjects. Patients with other pulmonary or cardiac disease were excluded. All received by inhalation placebo (0.9% saline solution), dopamine at 0.5 microg/kg/min (controlled by heart rate and arterial pressure with a dynamap), and placebo. Respiratory parameters: forced vital capacity (FVC), forced expiratory volume at the first second (FEV1), forced maximal expiratory flow (FEFmax) and forced expiratory flow at the 50% of vital capacity (FEF50) were measured in each protocol period. Student's paired t test, Wilcoxon and Mann Whitney analysis were performed. RESULTS: After dopamine inhalation, there was an increase of FVC by 23% (p<0.001); an increase of FEV1 by 39% (p<0.0001); an increase of FEF50 by 33% (p<0.001) and an increase of FEFmax by 31% (p<0.001). There were no respiratory parameter changes in both, subjects with bronchial hyperreactivity and normal after dopamine inhalation. CONCLUSIONS: Inhaled dopamine induces bronchodilatation in patients with crisis of bronchial asthma. Inhaled dopamine neither alters basal bronchial tone in healthy subjects nor in subjects with bronchial hyperreactivity.

Administration, Inhalation↗
PubMed1998

Simultaneous intestinal leishmaniasis and mycobacterial involvement in a patient with acquired immune deficiency syndrome.

Gastrointestinal involvement is reported in approximately 50% to 93% of patients with human immunodeficiency virus. It is frequently the result of coinfection with several microorganisms. Selective Leishmania intestinal involvement presents with atypical symptoms for visceral leishmaniasis, and may appear as a relapse or as the first manifestation of the disease. The authors present a patient with acquired immune deficiency syndrome who has a history of treated leishmaniasis and gastrointestinal infection by showed Mycobacterium avium intracellulare (MAI). After the new onset of abdominal pain, an intestinal biopsy showed the presence of both MAI and Leishmania in duodenum. Intestinal infection by Leishmania must be included in the differential diagnosis in patients with a previous history of leishmaniasis or travel to an endemic area.

AIDS-Related Opportunistic Infections↗
PubMed1998

Metoclopramide and domperidone block the antihypertensive effect of bromocriptine in hypertensive patients.

This study was conducted in normotensive and hypertensive subjects at the Vargas Hospital of Caracas. Normotensive subjects received, in a cross-over fashion, placebo, metoclopramide (MTC), or domperidone (DOMP), 40 mg of each drug, daily for 1 week. The first group of patients under placebo for 1 week received a single 2.5-mg oral dose of bromocriptine (Br). The second group of patients received 30 mg MTC daily (divided into three doses) for 1 week. At the end of the period a single dose of 2.5 mg Br was administered to each patient. The third group of eight hypertensive patients received DOMP for 1 week at 30 mg/d and then a single 2.5-mg Br dose. Cardiovascular and biochemical parameters including arterial pressure, heart rate, plasma renin activity, and plasma aldosterone were evaluated during the 6-hour period before and after the administration of Br. Neither DOMP nor MTC significantly modified blood pressure and heart rate in normotensive patients. Br reduced both systolic and diastolic arterial pressure in hypertensive subjects. The peak of the antihypertensive effect appeared 3 hours after drug administration, but reduction of arterial pressure lasted approximately 6 hours. At the same time, Br reduced plasma aldosterone levels and plasma renin activity. MTC and DOMP reversed the antihypertensive effect of Br and its effect on aldosterone levels and plasma renin activity. We conclude from these findings that Br acts as an antihypertensive agent at peripheral and central levels by stimulating dopamine-2 receptors, which are involved in the aldosterone and renin secretion.

Adult↗