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Biomedical subjects

J Ortiz

Publications and source records attributed to J Ortiz.

At least 55 records · Page 3Linked to original sources

Effect of atmospheric pollution on the respiratory system.

Santiago de Chile has a high level of air pollution with ozone (O3), carbon monoxide (CO) and particles equal or smaller than 10 microns (PM10) usually exceeding the accepted standards. This situation should be noxious for the exposed population and particularly--in the case of O3 and PM10--for the respiratory system. However, such an effect is rather difficult to demonstrate and it depends on the type of population under study.

Air Pollution↗

[Molecular diagnosis in an Argentinian family with multiple endocrine neoplasia type-1 (MEN-1)].

MEN-1 is a hereditary autosomal dominant syndrome characterized by the involvement of parathyroid glands, pancreatic islet cells and anterior pituitary gland. Today molecular genetics permit gene carrier analysis to compare the data obtained with the clinical biochemical tests. The twenty living members of the first, second and third generation of a family with MEN-1 were studied to determine the presence of genetic markers in MEN-1 loci 11q13, by linkage analysis and in affected individuals by biochemical tests and clinical examination. Two very informative polymorphic markers immediately flanking the MEN-1 gene on chromosome 11 band q13 were detected: PYGM and D11S987, haplotypes segregated by two members of the second generation, inherited from their father and two of the third generation: the affected one and one presymptomatic. The third generation had the affected member with renal stones and elevated PTH, PRL and glucagon. The presymptomatic carrier of MEN-1 allele showed elevated PTH. Among the members who inherited the normal allele we found one with elevated gastrin, one with elevated glucagon and one with elevated PTH, all asymptomatic. Of one Argentine family studied, molecular diagnosis allowed us to detect one presymptomatic carrier in the members at risk. As suggested by the available literature, accuracy of molecular diagnosis seems to make it the test of choice to exclude those members at risk for MEN-1 inheriting the normal allele.

Adult↗

Continuous versus inpatient prophylaxis of the first episode of spontaneous bacterial peritonitis with norfloxacin.

Cirrhotic patients with ascites and low ascitic fluid total protein and/or high serum bilirubin levels are at high risk to develop the first episode of spontaneous bacterial peritonitis during long-term follow-up. The aim of the present study was to determine the efficacy of continuous long-term selective intestinal decontamination with norfloxacin in the prevention of this complication. One hundred nine cirrhotic patients with ascites and ascitic fluid total protein levels of < or = 1 g/dL or serum bilirubin levels of > 2.5 mg/dL without previous spontaneous bacterial peritonitis were prospectively randomized into two groups: group 1 (n = 56) received norfloxacin, 400 mg daily administered orally, and group 2 (n = 53) was the long-term control group, receiving norfloxacin only during hospitalization. During a mean follow-up of 43 +/- 3 weeks, there was one spontaneous bacterial peritonitis (1.8%) in group 1 and 9 (16.9%) in group 2 (P < .01). The incidence of community-acquired spontaneous bacterial peritonitis was lower in group 1 (1.8% vs. 13.2%, P < .05), whereas the incidence of nosocomial spontaneous bacterial peritonitis (0% vs. 3.7%) and the incidence of extraperitoneal infections (25% vs. 24.5%) were similar in both groups (P = NS). The actuarial probability of survival at 18 months was 75% in group 1 and 62% in group 2 (P = NS). Resistance to norfloxacin was observed in 9 of 10 (90%) Escherichia coli isolated in infections from group 1 and in 4 of 11 (36.3%) from group 2 (P < .05). The overall incidence of infections caused by norfloxacin-resistant bacteria was higher in group 1 (19.6% vs. 15%), but it did not reach statistical significance. Continuous long-term selective intestinal decontamination with norfloxacin is effective in preventing the first spontaneous bacterial peritonitis in cirrhotic patients at high risk. However, the emergence of infections caused by norfloxacin-resistant bacteria must be weighed carefully against the benefits of continuous long-term prophylaxis.

Anti-Infective Agents↗

Early microbiologic diagnosis of spontaneous bacterial peritonitis with BacT/ALERT.

BACKGROUND/AIMS: Inoculation of ascitic fluid into conventional blood culture bottles is more sensitive than conventional culture in the diagnosis of spontaneous bacterial peritonitis. BacT/ALERT is an automated colorimetric microbial detection system that has been shown to be faster than conventional blood culture bottles in the diagnosis of bacteremia. The aim of the study was to compare the BacT/ALERT system with the conventional culture and the conventional blood culture bottles method in the diagnosis of spontaneous bacterial peritonitis. METHODS: All the ascitic fluid samples from patients with cirrhosis hospitalized in our Department between September 1992 and May 1994 (n=1032) were prospectively evaluated. In all cases, an aliquot of ascitic fluid was sent for Gram's stain and conventional culture, and 20 ml were inoculated at the bedside into blood culture bottles: 10 ml into conventional blood culture bottles and 10 ml into BacT/ALERT. RESULTS: Thirty ascitic fluid infections (23 spontaneous bacterial peritonitis and 7 neutrocytic ascites) and 20 bacterascites were diagnosed. Conventional culture was positive in 10/30 ascitic fluid infections (33.3%), conventional blood culture bottles in 22/30 (73.3%) (p<0.01 compared to conventional culture) and BacT/ALERT in 20/30 (66.6%) (p<0.05 compared to conventional culture, pNS compared to conventional blood culture bottles). The time elapsed for culture positivity was 43.4+/-34.2 h for conventional blood culture bottles and 13.3+/-9.2 h for BacT/ALERT (p<0.001). Thirteen of the 23 cases of spontaneous bacterial peritonitis (56.5%) were detected within the first 12 h with BacT/ALERT, as compared to only three (13%) with conventional blood culture bottles (p<0.03). CONCLUSION: The automated system BacT/ALERT provides an earlier microbiologic diagnosis of spontaneous bacterial peritonitis than conventional blood culture bottles with similar sensitivity.

Anti-Bacterial Agents↗

Azidothymidine triphosphate determination using micellar electrokinetic capillary chromatography.

There is a need to perform pharmacokinetic studies in the pediatric population utilizing antiretroviral drugs, which have shown effectiveness for the treatment of human immunodeficiency virus (HIV). In order to establish a relationship between efficacy and toxicity, we need to detect and quantitate these antiretroviral nucleosides and their metabolites at the intracellular level. Micellar electrokinetic capillary chromatography (MECC) was used for the separation of five nucleotides: cytidine triphosphate (CTP), adenosine triphosphate (ATP), thymidine triphosphate (TTP), guanosine triphosphate (GTP) and azidothymidine triphosphate (AZT-TP). Attomoles of these nucleotides were satisfactorily resolved in short run times with high peak efficiencies. In addition, nanoliters of sample volume were used to perform the analysis using ultraviolet (UV) detection at 254 nm.

Anti-HIV Agents↗

The Saccharomyces cerevisiae kinetochore.

Accurate chromosome segregation is dependent on a specialized chromosomal structure, the kinetochore/centromere. The only essential constituent of the S. cerevisiae kinetochore established today is CBF3, a multisubunit complex that binds to S. cerevisiae centromere DNA. Therefore CBF3 and its four components, Cbf3a, Cbf3b, Cbf3c and Cbf3d, will form the centerpiece of this review. In addition, we will describe proteins that are putatively involved in kinetochore function specifically in the context with CBF3 interaction. Furthermore, we discuss the role of the S. cerevisiae kinetochores in a putative cell cycle checkpoint control and in microtubule attachment.

Base Sequence↗

Biochemical adaptations in the mesolimbic dopamine system in response to repeated stress.

We have demonstrated previously that chronic administration of morphine, cocaine, or ethanol produces some common biochemical adaptations in the ventral tegmental area (VTA) and nucleus accumbens (NAc), components of the mesolimbic dopamine system implicated in the reinforcing and locomotor activating properties of these drugs of abuse. Because this neural pathway is also regulated by stress, and because stress has been shown to influence an animal's behavioral responses to drugs of abuse, it was of interest to determine whether repeated exposure to stress results in similar biochemical adaptations. By use of immunoblot analysis, we show here that a course of chronic "unpredictable" stress, like chronic drug exposure, increased levels of immunoreactivity of tyrosine hydroxylase and glial fibrillary acidic protein and decreased levels of immunoreactivity of neurofilament proteins in the VTA. Chronic unpredictable stress also increased levels of cyclic AMP-dependent protein kinase activity and decreased levels of immunoreactivity of the G protein subunit, Gi alpha, in the NAc. These effects required long-term exposure to stress and were in most cases not seen in the substantia nigra and caudate-putamen, components of the nigrostriatal dopamine system studied for comparison. The biochemical effects of chronic stress in the VTA and NAc differed among three strains of rat studied. Fischer 344 rats were the most responsive in that they exhibited all of the aforementioned adaptations, whereas Lewis rats were the least responsive in that they exhibited none of these adaptations; Sprague-Dawley rats exhibited an intermediate number of responses. Taken together, the results of the present study demonstrate that chronic exposure to stress results in biochemical adaptations in the mesolimbic dopamine system that resemble the chronic actions of several drugs of abuse. These adaptations could contribute to the convergent behavioral effects induced by treatments that are mediated via the VTA-NAc pathway.

Adaptation, Physiological↗

Drugs of abuse and stress increase the expression of GluR1 and NMDAR1 glutamate receptor subunits in the rat ventral tegmental area: common adaptations among cross-sensitizing agents.

Behavioral and electrophysiological evidence suggests that glutamatergic neurotransmission plays an important role in some of the long-term effects of cocaine and other drugs of abuse on brain function. We therefore examined the effect of repeated cocaine treatment on glutamate receptor subunit expression in central dopamine (DA) pathways implicated in many of cocaine's behavioral actions. By immunoblotting procedures using subunit-specific antibodies, we found that repeated, but not acute, cocaine treatment increased the levels of immunoreactivity of GluR1 (an AMPA receptor subunit) and NMDAR1 (an NMDA receptor subunit) in the ventral tegmental area (VTA), a nucleus containing mesolimbic DA neurons. In contrast, chronic cocaine treatment did not alter levels of GluR2 (an AMPA receptor subunit), NMDA2A/B (NMDA receptor subunits), or GluR6/7 (kainate receptor subunits) in this brain region. Moreover, GluR1 and NMDAR1 levels were not regulated in other regions of the mesolimbic or nigrostriatal DA pathways, including the substantia nigra. Because several drugs of abuse and stress can elicit common and cross-sensitizing effects on mesolimbic DA function, we next examined whether repeated morphine and stress treatments would regulate these proteins similarly in the VTA. Although morphine delivered by subcutaneous pellet implantation had no significant effect on subunit levels, morphine delivered intermittently by subcutaneous injections of escalating doses elevated GluR1 levels in the VTA. Repeated restraint stress also paradigm (2 stressors/d under variable conditions) increased both GluR1 and NMDAR1 levels in this brain region. Unlike cocaine, morphine, and stress, repeated treatment with other psychotropic drugs (haloperidol, raclopride, sertraline, and desipramine) that lack reinforcing or sensitizing properties did not regulate GluR1 or NMDAR1 subunit levels in the VTA. Increased glutamate receptor subunit expression in the VTA may represent an important molecular mechanism by which drugs of abuse and stress exert common, long-term effects on mesolimbic DA function.

Animals↗

Atrial defibrillation using temporary epicardial defibrillation stainless steel wire electrodes: studies in the canine sterile pericarditis model.

OBJECTIVES: This study sought to determine whether temporary epicardial wire electrodes can be used safely and effectively to defibrillate the atria with low energy shocks in the absence of anesthesia. BACKGROUND: Atrial fibrillation after open heart surgery is a significant clinical problem. METHODS: Twelve dogs with sterile pericarditis were studied. In the first group (6 dogs, bilateral thoracotomy group), a wire electrode, insulated except for the distal 6 cm, was placed on the epicardial free wall of each atrium. Each end of the bare wire was then sutured to the parietal pericardium. In the second group (6 dogs, median sternotomy group), the wire electrodes were kept in place by a double loop of Prolene placed around the distal tip of the bare wire and sewn to the overlying parietal pericardium. In the bilateral thoracotomy group, atrial defibrillation thresholds (defined as < 90% and > 10% successful defibrillation of 20 shocks at a given delivered energy) were obtained in anesthetized dogs using the wire electrodes with the chest closed and open and using two transvenously placed catheters with coil electrodes in the distal 6 cm (one in the coronary sinus and the other in the right atrial appendage) with the chest open. In the median sternotomy group, thresholds were obtained in minimally sedated animals without reopening the chest. A 25% increase above threshold shock was also used to determine a new percent success. After 4 days, the wire electrodes were removed by pulling on the external ends. At the time of removal, blood pressure and heart rate were monitored for 30 min, after which dogs were killed and their hearts sent for histopathologic study. For all dogs, chest radiographs were obtained postoperatively and on study days. RESULTS: Atrial defibrillation using the wire electrodes was successful in all dogs at a mean (+/- SE) voltage of 112 +/- 9 V, with an energy level of 0.46 +/- 0.07 J and an impedance of 59.3 +/- 5 ohms. The mean percent success at the atrial defibrillation threshold was 36 +/- 5%. The 25% increase in defibrillation voltage improved the mean percent success to 73% (mean energy 0.66 +/- 0.19 J). No clinical or hemodynamic complications were observed during shock delivery, and no ventricular arrhythmias were induced during the shocks. No complications followed wire electrode removal. Histopathologic analysis showed no structural damage. CONCLUSIONS: The atrial defibrillation threshold obtained using temporary epicardial wire electrodes for atrial defibrillation is < 1 J in dogs. Atrial defibrillation using temporary epicardial wire electrodes can be performed safely, quickly and reliably without the need for anesthesia or antiarrhythmic agents. The wire electrodes can be removed without adverse hemodynamic or structural consequences. These data provide a basis for testing atrial defibrillation using epicardial wire electrodes in patients after open heart surgery.

Algorithms↗

Pilomatrixoma: a description of two cases diagnosed by fine-needle aspiration.

The present work reports on the findings obtained by fine-needle aspiration of two pilomatrixomas located on the upper limbs whose diagnosis was confirmed histologically. In both cases, the cytology disclosed a proliferation of small round basaloid cells that were dispersed and grouped in clusters together with squamous cells and abundant multinucleate giant cells. The differential diagnosis with other neoplasms is discussed.

Adult↗

Biochemical actions of chronic ethanol exposure in the mesolimbic dopamine system.

In previous studies, we have demonstrated that chronic administration of morphine or cocaine produces some common biochemical adaptations in the ventral tegmental area (VTA) and nucleus accumbens (NAc), components of the mesolimbic dopamine system implicated in the reinforcing actions of these and other drugs of abuse. Since this neural pathway is also implicated in the reinforcing actions of ethanol, it was of interest to determine whether chronic ethanol exposure results in similar biochemical adaptations. Indeed, as seen for chronic morphine and cocaine treatments, we show here that chronic ethanol treatment increased levels of tyrosine hydroxylase and glial fibrillary acidic protein immunoreactivity, and decreases levels of neurofilament protein immunoreactivity, in the VTA. Also like morphine and cocaine, ethanol increases levels of cyclic AMP-dependent protein kinase activity in the NAc. These actions of ethanol required long-term exposure to the drug, and were in most cases not seen in the substantia nigra or caudateputamen, components of the nigrostriatal dopamine system studied for comparison. Altered levels of tyrosine hydroxylase in catecholaminergic cells frequently reflect altered states of activation of the cells. Moreover, increasing evidence indicates that ethanol produces many of its acute effects on the brain by regulating NMDA glutamate and GABAA receptors. We therefore examined the influence of chronic ethanol treatment on levels of expression of specific glutamate and GABA receptor subunits in the VTA. It was found that long-term, but not short-term, ethanol exposure increased levels of immunoreactivity of the NMDAR1 subunit, an obligatory component of NMDA glutamate receptors, and of the GluR1 subunit, a component of many AMPA glutamate receptors; but at the same time, long-term ethanol exposure decreased immunoreactivity levels of the alpha 1 subunit of the GABAA receptor complex. These changes are consistent with an increased state of activation of VTA neurons inferred from the observed increase in tyrosine hydroxylase (TH) expression. These results demonstrate that chronic ethanol exposure results in several biochemical adaptations in the mesolimbic dopamine system, which may underlie prominent changes in the structural and functional properties of this neural pathway related to alcohol abuse and alcoholism.

Adenylyl Cyclases↗

Strain-selective effects of corticosterone on locomotor sensitization to cocaine and on levels of tyrosine hydroxylase and glucocorticoid receptor in the ventral tegmental area.

We have studied biochemical and behavioral effects of chronic corticosterone administration in two inbred rat stains (Fischer 344 and Lewis), known to differ in their hypothalamic-pituitary-adrenal axis and in their behavioral responses to drugs of abuse. First, we studied corticosterone regulation of phosphoproteins in the ventral tegmental area of sham- and corticosterone-treated Fischer and Lewis rats, by means of back-phosphorylation and two-dimensional gel electrophoresis and Western blotting analysis. Corticosterone administration upregulated tyrosine hydroxylase immunoreactivity and decreased glial-fibrillary acidic protein phosphorylation state in the ventral tegmental area of Fischer rats only, with no changes seen in Lewis rats. We also studied corticosterone effects on locomotor sensitization to cocaine, a behavior known to be regulated by the ventral tegmental area. In Fischer rats, chronic corticosterone pretreatment resulted in development of cocaine sensitization, which was absent in sham-pretreated Fischer rats. In contrast, Lewis rats developed cocaine sensitization either with or without corticosterone pretreatment. Thus, both biochemical and behavioral effects of corticosterone observed in Fischer rats were absent in Lewis rats. We next studied the possibility that certain transcription factors, thought to play a role in tyrosine hydroxylase expression, could be involved in these strain-selective effects of corticosterone. Corticosterone treatment decreased levels of glucocorticoid receptor immunoreactivity in the ventral tegmental area of Lewis rats, but not of Fischer rats. In addition, drug-naive Fischer rats showed higher ventral tegmental area levels of immunoreactivity of cyclic AMP response element binding protein than Lewis rats, with no effect of corticosterone observed in either strain. These findings suggest that hypothalamic-pituitary-adrenal axis modulation of responses to drugs of abuse is a genetically determined characteristic seen in Fischer rats, but absent in Lewis rats. We propose that corticosterone administration down-regulates the glucocorticoid receptor in the ventral tegmental area of Lewis rats, and thereby prevents other adaptations to corticosterone treatment, while in the ventral tegmental area of Fischer rats the lack of glucocorticoid receptor down-regulation and the high basal levels of cyclic AMP response element binding protein could facilitate the transcriptional, biochemical and behavioral actions of glucocorticoids.

Animals↗

One-year mortality prognosis in heart failure: a neural network approach based on echocardiographic data.

OBJECTIVES: This study sought to assess the usefulness and accuracy of artificial neural networks in the prognosis of 1-year mortality in patients with heart failure. BACKGROUND: Artificial neural networks is a computational technique used to represent and process information by means of networks of interconnected processing elements, similar to neurons. They have found applications in medical decision support systems, particularly in prognosis. METHODS: Clinical and Doppler-derived echocardiographic data from 95 consecutive patients with diffuse impairment of myocardial contractility were studied. After 1 year, data regarding survival or death were obtained and produced the prognostic variable. The data base was divided randomly into a training data set (47 cases, 8 deaths) and a testing data set (48 cases, 7 deaths). Results of artificial neural network classification were compared with those from linear discriminant analysis, clinical judgment and conventional heuristically based programs. RESULTS: The study group included 57 male (47 survivors) and 38 female patients (33 survivors). Linear discriminant analysis was not efficient for separating survivors from nonsurvivors because the accuracy at the ideal cutoff value was only 67.4%, with a sensitivity of 67.5%, positive predictive value of 27.8% and negative predictive value of 91.5%. In contrast, all artificial neural networks were able to predict outcome with an accuracy of 90%, specificity of 93% and sensitivity of 71.4%, for the best artificial neural network. Both clinical judgment and automatic heuristic methods were also inferior in performance. CONCLUSIONS: The artificial neural network method has proved to be reliable for implementing quantitative prognosis of mortality in patients with heart failure. Additional studies with larger numbers of patients are required to better assess the usefulness of artificial neural networks.

Adolescent↗

On-line telemetry: prospective assessment of accuracy in an all-volunteer emergency medical service system.

OBJECTIVE: To evaluate the need for on-line telemetry control in an all-volunteer, predominantly advanced emergency medical technician (A-EMT) ambulance system. METHODS: Emergency medical service (EMS) advanced life support (ALS) providers were asked to transmit the ECG rhythms of monitored patients over a six-month period in 1993. The ECG rhythm interpretations of volunteer EMS personnel were compared with those of the on-line medical control physician. All discordant readings were reviewed by a panel of physicians to decide whether the misdiagnosis would have resulted in treatment aberrations had transmission been unavailable. RESULTS: Patients were monitored and rhythms were transmitted in 1,825 cases. 1,642 of 1,825 rhythms were correctly interpreted by the EMS providers (90%; 95% CI 89-91%). The accuracy of the EMS providers was dependent on the patient's rhythm (chi-square, p < 0.00001), the chief complaint (chi-square, p = 0.0001), and the provider's level of training (chi-square, p = 0.02). Correct ECG rhythm interpretations were more common when the out-of-hospital interpretation was sinus rhythm (95%), ventricular fibrillation (87%), paced rhythm (94%), or agonal rhythm (96%). The EMS providers were frequently incorrect when the out-of-hospital rhythm interpretation was atrial fibrillation/flutter (71%), supraventricular tachycardia (46%), ventricular tachycardia (59%), or atrioventricular block (50%). Of the 183 discordant cases, 124 (68%) involved missing a diagnosis of, or incorrectly diagnosing, atrial fibrillation/flutter. Review of the discordant readings identified 11 cases that could have resulted in treatment errors had the rhythms not been transmitted, one of which might have resulted in an adverse outcome. CONCLUSIONS: In this all-volunteer, predominantly A-EMT ALS system, patients with a field interpretation of a sinus rhythm do not require ECG rhythm transmission. Field interpretations of atrial fibrillation/flutter, supraventricular tachycardia, ventricular tachycardia, and atrioventricular blocks are frequently incorrect and should continue to be transmitted.

Chi-Square Distribution↗

Extracellular signal-regulated protein kinases (ERKs) and ERK kinase (MEK) in brain: regional distribution and regulation by chronic morphine.

Quantitative blot immunolabeling techniques were used to determine the concentrations of ERK1 (M(r) 44 kDa) and ERK2 (M(r) 42 kDa), the two major extracellular signal-regulated protein kinases, in different regions of rat brain. The aggregate ERK concentrations (ERK1 and ERK2) were relatively high in each of the brain regions studied, ranging from approximately 0.35 ng/microgram protein in cerebellum to approximately 1.2 ng/microgram protein in nucleus accumbens. However, differences in the regional distributions of ERK1 and ERK2 resulted in ratios of their relative abundance that differed by close to 10-fold among the regions studied. The ratios of ERK1 protein to ERK2 protein varied along a rostral-caudal gradient from a low of 0.16 in frontal cortex to a high of 1.5 in pons/medulla. In hypotonic homogenates from regions at either extreme of the gradient, ERK1 and ERK2 were both found to be predominantly (> 80%) soluble. In subcellular fractions prepared from sucrose homogenates of frontal cortex and pons/medulla, both ERK1 and ERK2 were enriched in the synaptosomal and cytosolic fractions, whereas ERK2 was also enriched in the microsomal fraction. By contrast, in subfractions containing purified nuclei, levels of ERK1 and ERK2 were about one-third of those seen in homogenates and, in subfractions enriched in mitochondria, both ERK1 and ERK2 were barely detectable. The catalytic activity of the ERKs paralleled their protein levels in all of the brain regions except the hippocampus, in which the activity and phosphotyrosine content were disproportionately high. As a possible explanation for this apparent disparity, the regional distribution of ERK kinase (MEK), which phosphorylates and activates the ERKs, was also investigated. The levels of immunoreactivity of the M(r) 45 kDa ERK kinase band differed by about threefold among the brain regions, with the highest levels being present in nucleus accumbens, hippocampus, substantia nigra, and caudate/putamen. Therefore, a higher concentration of ERK kinase immunoreactivity did not appear to account for the disproportionate levels of ERK activity and phosphotyrosine content in the hippocampus. Potential regulation of ERK and ERK kinase levels was also investigated in rats subjected to chronic morphine treatment. ERK1 and ERK2 levels were increased selectively in locus coeruleus and caudate/putamen after chronic morphine treatment, whereas ERK kinase immunoreactivity remained unchanged in all of the brain regions analyzed. In summary, the regional differences in ERK and ERK kinase expression and the region-specific regulation of ERK expression suggest that ERK-related signaling may play an important role in CNS function and its adaptive responses.

Animals↗