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M A Morales

Publications and source records attributed to M A Morales.

At least 37 records · Page 2Linked to original sources
PubMed1999

Release-depletion and receptor-mediated neuronal internalization of endogenous neurotensin in the stellate ganglion of the cat.

The release and depletion of neurotensin in sympathetic preganglionic axon terminals and internalization in principal ganglion cells were investigated in the cat stellate ganglion by means of combined immunohistochemical staining, image analysis and confocal microscopy. Neurotensin stored in preganglionic boutons was released by 40 or 5 Hz electrical stimulation of preganglionic nerves, being depleted to 7.4 and 19.2% of control levels by continuous stimulation lasting 20 or 160 min (both stimuli delivered 48,000 pulses). Once released, neurotensin was internalized by the principal ganglion cells as evidenced by a ring of bright spot-like granules in the perinuclear region indicating the sites of intracellular neurotensin accumulation. Neurotensin internalization was time-dependent, thus, different content was found when the time between the end of stimulation and start of perfusion was varied. The onset of neurotensin internalization appeared in the first minutes, intracellular accumulation was evident at 20 min, maximal internalization occurred at 120 min and, 24 h later internalized neurotensin content had faded. Internalization was partially blocked by the nonpeptide neurotensin antagonist SR48692. These data provide evidence of presynaptic neurotensin release and depletion by electrical stimulation with varied frequencies. They also provide evidence for in situ receptor-mediated internalization of endogenously released neurotensin, raising the possibility that internalization may represent, in addition to some kind of turnover dynamics, an important part of the mechanisms of neuropeptide signaling.

Animals↗
PubMed1999

[Estimation of the neurologic demand in a health care area of Madrid, Spain (area 11, University Hospital, 12 of October)].

OBJECTIVES: To analyse the demand for neurologic care and the neurological resources in a health district. PATIENTS AND METHODS: Demographic, medical care aspects, neurologic care demands and neurological resources of the health district 11 of Madrid (University Hospital "12 de Octubre"), referred to 1996, were reviewed. RESULTS: The rate of aging (17%) and the consulting rates in the National Health System (86%) versus private care were high in this health district. The neurologic care demands were 17.5-18.1 and 36 consultations respectively per 1,000 inhabitants/year. There were 2 patient-care neurologists and 3.7 neurologic beds per 100,000 inhabitants. CONCLUSIONS: The neurologic care was considered high and with a tendency to increase. The available neurological resources were judged to be insufficient.

Catchment Area, Health↗
PubMed1999

Safety of ergotamine-ergic pharmacologic stress echocardiography for vasospasm testing in the echo lab: 14 year experience on 478 tests in 464 patients.

BACKGROUND: The safety of ergonovine/ergometrine stress testing for coronary vasospasm when performed outside the cath lab has vigorously been questioned. The aim of this study was to assess the value of ergonovine/ergometrine stress testing performed in the echo lab. METHODS: We retrospectively reviewed the data prospectively collected in the echo lab of the Institute of Clinical Physiology of Pisa (Italy) from January 1, 1985, to October 1, 1998, on 478 tests performed on 464 patients with either ergonovine or ergometrine stress echo testing. By selection, all patients had history of chest pain, consistent with vasospastic angina, negative or ambiguous exercise stress testing, and normal or near normal resting left ventricular function. Ergonovine or ergometrine maleate was injected up to a total cumulative dosage of 0.35 mg, under continuous 12 lead ECG and two-dimensional echo monitoring. RESULTS: There were no death, myocardial infarction, ventricular fibrillation or III degree atrioventricular block. One patient had non-sustained ventricular tachycardia associated with transient ST segment elevation 30 min after the test. Two patients had II degree atrioventricular block, associated with positive echocardiography test and promptly reversed by nitrate administration. Transient regional myocardial dysfunction occurred in 74 patients (15%). Limiting ischemia-independent side effects were present in 13 patients (3%): hypotension in 1, arterial hypertension in 5, nonsustained ventricular tachycardia in 2, and nausea/vomiting in 5. The overall feasibility was 97%. CONCLUSIONS: Pharmacological stress echocardiography with either ergonovine or ergometrine is highly feasible and can be safely performed in the echo lab in properly selected patients in whom coronary vasospasm is suspected. It is often the only way to document coronary vasospasm otherwise missed by conventional noninvasive stress test and even by coronary angiography.

Coronary Angiography↗
PubMed1999

Impaired sympathetic response before intradialytic hypotension: a study based on spectral analysis of heart rate and pressure variability.

The purpose of this study was to evaluate the autonomic response to standard haemodialysis and the changes associated with the onset of intradialytic hypotension in 12 normotensive patients with uraemia. Power spectra of R-R interval and of blood pressure fluctuations were obtained during a standard dialysis session and estimated in the low-frequency (LF, 30-150 mHz) and high-frequency (HF, 150-400 mHz) range. The absolute power of the LF component of blood pressure variations and the LF/HF ratio of R-R interval were assumed as indexes of sympathetic activity. Standard haemodialysis induced hypotension in six patients (unstable) while a minor pressure decline was present in the other six (stable). Normalized blood volume before dialysis and percentage volume reduction were similar in the two groups. Tachycardia in response to pressure and volume decrease was more pronounced in stable than in unstable patients, as evidenced by a higher slope of the relation between R-R interval and systolic blood pressure (7.9 versus 0.9 ms/mmHg, P<0.01). Sympathetic tone was enhanced during early dialysis in all patients (+2+/-1 for R-R LF/HF ratio, +2.4+/-0.6 mmHg2 and +7.2+/-2 mmHg2 for absolute LF power of diastolic and of systolic blood pressure respectively, P<0.05), compared with baseline predialysis values. During late dialysis, unstable patients showed an impairment of sympathetic activation which preceded hypotension and was maximal during the crisis (-2.9+/-1.4 for R-R LF/HF ratio, -2.7+/-1.4 mmHg2 and -8.6+/-4.0 mmHg2 for absolute LF power of diastolic and of systolic blood pressure respectively, P<0.05). On the contrary, stable patients showed constantly elevated indexes (+3.7+/-1.4 for R-R LF/HF ratio, +5.9+/-2.7 mmHg2 and +13.3+/-6.2 mmHg2 for LF of diastolic and of systolic blood pressure, P<0.05). Values returned to predialysis levels after the end of the dialysis session in all patients. We conclude that standard haemodialysis activates a marked and reversible sympathetic response in both stable and unstable uraemic patients. However, in unstable patients, such activation is impaired in late dialysis, therefore contributing to the onset of the hypotensive crisis.

Aged↗
PubMed1998

Signal-averaged ECG abnormalities in haemodialysis patients. Role of dialysis.

BACKGROUND: Late potentials (LP) on the signal-averaged electrocardiogram (SAECG) are predictive of malignant ventricular arrhythmias and sudden cardiac death in patients with ischaemic and non-ischaemic cardiomyopathy. Cardiac dysfunction, both regional and global, as well as supraventricular and ventricular arrhythmias are reported in a high percentage of patients with end-stage renal failure (ESRF). The aim of the study was to assess the prevalence of LP and the effects of haemodialysis on the SAECG of ESRF patients. METHODS: SAECG was recorded immediately before and within 30 min after the end of dialysis in 48 patients in sinus rhythm, free of conduction disturbances on ECG and of signs of congestive heart failure. Serum electrolytes were sampled together with the SAECG recordings. An echo-Doppler exam was performed within 2 weeks of the study. SAECGs were adequate for analysis in 45/48 patients. LP were present when at least two of the following criteria were fulfilled: QRS duration < or = 115 ms, LAS40 < or = 38 ms, RMS40 > or = 38 microV at 40 Hz high pass bidirectional filter, and noise <0.7 microV. RESULTS: LP were detected in 12/45 patients (25%) on the SAECG before dialysis; of these 12 patients, seven had a history of a previous myocardial infarction and two had documented coronary artery disease (CAD). A significant greater wall motion score index--calculated on a 16 segment model--was reported in patients with LP (1.20+/-0.20 vs 1.01+/-0.03, P<0.01), while left ventricular mass was comparable in the two groups of patients. At the end of dialysis, a significant prolongation of fQRS duration was found both at 25 and 40 Hz filters (from 98+/-11 to 106+/-16 ms and from 97+/-12 s to 102+/-13 ms, respectively, P<0.001). A significant inverse relationship was seen between the percentage of dialysis-induced serum potassium reduction and fQRS changes at 40 Hz (r=-0.68, P<0.001). CONCLUSIONS: LP were detected in a significant proportion of dialysis patients, probably related to underlying CAD with left ventricular dysfunction. Prolongation of fQRS after dialysis could be explained by the acute reduction in serum potassium levels.

Aged↗
PubMed1998

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Attitude of Health Personnel↗
PubMed1997

Topographic relationship of neurotensin-containing axon terminals with cardiac and noncardiac principal ganglion cells in the stellate ganglia of the cat.

The pattern of association between neurotensin (NT)-immunoreactive (NTIR) preganglionic nerve terminals and cardiac and noncardiac neurons in the stellate ganglion of the cat is analyzed, based on the finding of an excitatory modulation effect of exogenous NT on cardiac functions. For this purpose, NT-containing terminals were labeled by immunohistochemistry, and ganglion cells were detected by retrograde labeling of cardiac and vertebral nerves to identify cardiac and noncardiac neurons. To determine a possible regional localization of NTIR terminals and ganglion cells, the ganglia were divided into four areas: caudal, dorsomedial, cranial, and ventromedial, related to the two major afferent nerves (thoracic white rami 3 [T3WR] and 2 [T2WR]) and the two efferent nerves (vertebral and cardiac). NTIR terminals were widespread in the complete ganglion tissue; they covered practically all the regions explored, although two clusters of high concentration of NTIR terminals were detected in the cranial and caudal areas. By retrograde labelling it was found that cardiac cells were arranged around the exit of the cardiac nerve and that the vertebral neurons were extended from the exit of the vertebral nerve to the entrance of T3WR. The finding of association of NTIR terminals with cardiac neurons may account for the cardioregulatory effect of NT; however, since the presence of NTIR terminals close to the noncardiac neurons is notorious, other regulatory functions of NT must be considered.

Animals↗
PubMed1997

Prognostic value of dobutamine-atropine stress echocardiography early after acute myocardial infarction. Echo Dobutamine International Cooperative (EDIC) Study.

OBJECTIVES: The aim of this multicenter, multinational, prospective, observational study was to assess the relative value of myocardial viability and induced ischemia early after uncomplicated myocardial infarction. BACKGROUND: Dobutamine-atropine stress echocardiography allows evaluation of rest function (at baseline), myocardial viability (at low dose) and residual ischemia (peak dose, up to 40 micrograms with atropine up to 1 mg) in one test. METHODS: Dobutamine-atropine stress echocardiography was performed 12 +/- 5 days (mean +/- SD) after a first uncomplicated acute myocardial infarction in 778 patients (677 men; mean age 58 +/- 10 years) with technically satisfactory rest echocardiographic study results. Patients were followed-up for 9 +/- 7 months. RESULTS: Dobutamine-atropine stress echocardiographic findings were positive for myocardial ischemia in 436 of patients (56%) and negative in 342 (44%). During follow-up, there were 14 cardiac-related deaths (1.8% of the total cohort), 24 (2.9%) nonfatal myocardial infarctions and 63 (8%) hospital readmissions for unstable angina. One hundred seventy-four patients (22%) underwent coronary revascularization (bypass surgery or coronary angioplasty). Spontaneous events occurred in 61 of 436 patients with positive and 40 of 342 patients with negative findings on dobutamine-atropine stress echocardiography (14% vs. 12%, p = 0.3). When only spontaneously occurring events were considered, the most important predictor was myocardial viability (chi-square 9.7). Using the Cox proportional hazards model, only the presence of myocardial viability (hazard ratio [HR] 2.0, p < 0.002) and age (HR 1.03, p < 0.001) were predictive of spontaneously occurring events. When only hard cardiac events were considered, age was the strongest predictor (chi-square 3.6, p = 0.056), followed by wall motion score index (WMSI) at peak dose (chi-square 3.3, p = 0.06) and remote ischemia (chi-square 2.25, p = 0.1). When cardiac death was considered, WMSI at peak dose was the best predictor (HR 9.2, p < 0.0001). CONCLUSIONS: During dobutamine stress, echocardiographic recognition of myocardial viability is more prognostically important than echocardiographic recognition of myocardial ischemia for predicting unstable angina, whereas WMSI at peak stress was the best predictor of cardiac-related death. Different events can be recognized with different efficiency by various stress echocardiographic variables.

Adult↗
PubMed1997

Immunoreactive prolactin forms colocalize with vasopressin in neurons of the hypothalamic paraventricular and supraoptic nuclei.

The prolactin (PRL) gene is expressed in the hypothalamo-neurohypophyseal system as revealed by the detection of the PRL mRNA and of PRL-like immunoreactive and biologically active proteins in hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei and in the neurohypophysis. We have investigated the distribution of cells containing PRL-like molecules in the PVN and SON by immunocytochemistry with a specific antiserum directed against the 16-kD N-terminal fragment of PRL. PRL-positive cells were found to be concentrated throughout the ventral SON and in the lateroposterior region of the PVN. The cellular distribution of PRL-immunoreactive cells resembled more closely that of vasopressin (VP) than that of oxytocin magnocellular neurons. Moreover, double immunofluorescence labelling, followed by confocal microscopy, indicated the coexistence of PRL- and VP-related antigens within the same neurons of the PVN and SON. Pre-embedding immunoperoxidase on the ultrastructural level showed a PRL-like product in granular-type particles within the neural soma and projections in the SON and PVN. These findings are consistent with the expression and secretion of PRL-like molecules by vasopressinergic neurons of the hypothalamo-neurohypophyseal system.

Animals↗
PubMed1996

Role of endothelium in the vasodilating effect of progestins and androgens on the rat thoracic aorta.

1. In the rat thoracic aorta, contractions induced by noradrenaline were inhibited by the steroids progesterone, pregnanolone, testosterone and 5 alpha- and 5 beta-dihydrotestosterone. 2. Removal of endothelium did not prevent relaxation to the steroids, suggesting that the vasodilating effect of steroids occurred on the smooth muscle cells. 3. gamma-Aminobutyric acid (GABA) did not modify noradrenaline-induced contraction. Thus, the vasodilation elicited by steroids is not apparently mediated by GABA receptors. 4. On the basis that noradrenaline opens receptor-operated calcium channels to induce contraction, we suggest that relaxation by steroids involves a blockade of this type of channels.

Androgens↗
PubMed1996

Plasma HIV-1 RNA as a predictor of the efficacy of adding zalcitabine to a previous regimen with zidovudine.

The objective of this study was to determine whether or not plasma HIV-1 RNA levels, the syncytium-inducing phenotype assay or mutations at codon 215 of the gene encoding HIV-1 reverse transcriptase could have prognostic value in patients already undergoing therapy with zidovudine who were started on combination therapy with zidovudine and zalcitabine. A prospective study was performed in 37 HIV-1-infected individuals who had received at least 6 months (mean: 9 months; range: 6-24 months) of zidovudine to which zalcitabine was added. The mean initial CD4 cell count was 330 cells/mm3 (range: 20-520 cells/mm3). At baseline and at the end of the study (12 months), we analysed CD4 and CD8 cell counts, plasma HIV-1 RNA levels, the syncytium-inducing phenotype of virus isolated from peripheral blood mononuclear cells and mutations at codon 215 of the gene encoding reverse transcriptase. These variables were studied by Fisher's exact and U Mann-Whitney tests. There were statistically significant differences between progressor and non-progressor groups at baseline and after a 12-month period in the following parameters: CD4 and CD8 cell counts and HIV-1 RNA level (P < 0.05). Clinical progression occurred significantly more often in patients with CD4 cell counts < or = 300 cells/mm3 and HIV-1 RNA > 30000 copies/ml at baseline (P = 0.003). Moreover, we found that progression to AIDS only occurred in those patients whose viral load increased during the follow-up period and who had a CD4 cell count < 300 cells/mm3. Our results show the usefulness of HIV-1 RNA level as a surrogate marker for clinical outcome.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Effects of glycine on the mouse neuromuscular junction.

Glycine was applied at a range of different concentrations to test possible effects at the neuromuscular junction of the mouse. The presynaptic control of acetylcholine (ACh) release and the postsynaptic activation of the nicotinic receptor have been analysed by means of extracellular recording with an EPC7 Patch Clamp amplifier. The results indicated that glycine did not modify in a significant manner the release of ACh and the postsynaptic cholinergic receptor function. Nevertheless, a significant increase in the rate of the conformational change of the receptor-ion channel complex seemed to be noteworthy. Glycine at 30 and 300 microM increased in a dose dependent manner the decay time of the spontaneous miniature current. Concentrations of glycine exceeding 10mM completely blocked the activity of the end-plate in this preparation. In conclusion, we proved that glycine does not affect most of the parameters of neurotransmission in the mouse but, it increases the conformational change of the postsynaptic complex, perhaps inhibiting the acetylcholinesterase activity.

Animals↗
PubMed1995

Localization of choline acetyltransferase in rat peripheral sympathetic neurons and its coexistence with nitric oxide synthase and neuropeptides.

Indirect immunofluorescence methods using a mouse monoclonal antibody raised to rat choline acetyltransferase (ChAT) revealed dense networks of ChAT-immunoreactive fibers in the superior cervical ganglion, the stellate ganglion, and the celiac superior mesenteric ganglion of the rat. Numerous and single ChAT-immunoreactive cell bodies were observed in the stellate and superior cervical ganglia, respectively. The majority of ChAT-immunoreactive fibers in the stellate and superior cervical ganglia were nitric oxide synthase (NOS) positive. Some ChAT-immunoreactive fibers contained enkephalin-like immunoreactivity. Virtually all ChAT-positive cell bodies in the stellate ganglion were vasoactive intestinal polypeptide (VIP)-positive, and some were calcitonin gene-related peptide (CGRP)-positive. After transection of the cervical sympathetic trunk almost all ChAT- and NOS-positive fibers and most enkephalin- and CGRP-positive fibers disappeared in the superior cervical ganglion. The results suggest that most preganglionic fibers are cholinergic and that the majority of these in addition can release nitric oxide, some enkephalin, and a few CGRP. Acetylcholine, VIP, and CGRP are coexisting messenger molecules in some postganglionic sympathetic neurons.

Animals↗
PubMed1995

Vasorelaxant effect of the analgesic clonixin on rat aorta.

1. A novel vasorelaxant effect of clonixinate of L-lysine (Clx), analgesic and anti-inflammatory, was studied in rat aortic rings. 2. Clx completely relaxed aortic rings contracted by KCl 70 mM and together with its analog flunixin exhibited lesser potency but equal efficacy than verapamil. In comparison, indomethacin, which is a more potent cyclo-oxygenase inhibitor relaxed only about 40% of the maximal contraction of aortic rings. 3. Furthermore, Clx antagonized Ca2+ dependent aortic contraction and BAY K-8644 induced aortic contraction suggesting its calcium antagonist character. 4. From these results it can be concluded that the hypotensive effect seen in rats in vivo after Clx i.v. injection arises because of vasodilatory effect of Clx and gives further support to the proposal that the pharmacological mechanism of action of Clx should be calcium antagonism.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1995

Ergonovine-echo test to assess the significance of chest pain at rest without ECG changes.

The aim of this study was to assess the feasibility and diagnostic role of ergonovine maleate infusion under continuous two-dimensional echocardiographic monitoring for the identification of vasospastic myocardial ischaemia in patients with chest pain at rest not associated with diagnostic ECG changes. One hundred and twenty-eight consecutive patients, selected on the basis of absence of ischaemic ECG changes during angina at rest before or during hospitalization, were enrolled in the study. Ergonovine maleate was i.v. administered in scaled doses (from 0.025 to 0.2 mg at 10 min intervals) under echocardiographic, electrocardiographic and systemic blood pressure monitoring. Wall motion asynergies were observed in 33 patients, accompanied by typical chest pain in 24 patients and by ECG changes in 25 (ST elevation in 13 patients, ST depression in seven, T wave changes in five). All patients were able to complete the test. Non life-threatening ventricular arrhythmias were observed in four patients exclusively in association with ischaemia. In seven patients with a positive test, coronary artery spasm was documented at angiography. In 16 patients with a positive test, the vasospastic event was reproduced by a hyperventilation-echo test or a second ergonovine maleate-echo test performed within 3 days of the first examination. In none of the patients with a negative test was documentation of myocardial ischaemia due to a primary reduction in coronary blood flow. Thus, in patients who do not show ECG changes during chest pain at rest, the ergonovine maleate-echo test is feasible and safe; it permits the recognition of ischaemic episodes on the basis of wall motion abnormalities when conventional 12-lead ECG-recorded chest pain is non-diagnostic.

Adult↗
PubMed1995

Non-invasive monitoring of hemodynamic parameters during hemodialysis.

We studied in 13 hemodialysis patients intradialytic variations of blood volume (BV) and cardiac output, by means of non-invasive methods. We found a weak correlation, r 0.2 or less, between BV variations and intradialysis blood pressure variations. The sensitivity of the former in describing the variations of the latter was only 32%. During the 30 min preceeding the hypothensive crisis the percent BV variations did not show any predictive trend. On the contrary, refilling increased as blood pressure dropped and a weak inverse relation (r -0.35) was found between these two parameters. Unstable patients had predialytic blood volume values significantly lower than stable ones and comparable to healthy subjects. On the contrary, the correlation between percent variations of cardiac output index and MAP was 0.68 with a sensitivity and specificity of 90% and 59%, respectively. Unfortunately these promising results were obtained only with an estimate of cardiac output obtained by echocardiography and not by transthoracic impedance cardiography, which is much more feasible than the former as on-line monitoring of cardiac output. On-line monitoring of hemodynamic parameters is an appealing but still unsolved task.

Aged↗