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R Munoz

Publications and source records attributed to R Munoz.

At least 19 recordsLinked to original sources
PubMed2007

A genome-wide scan for schizophrenia and psychosis susceptibility loci in families of Mexican and Central American ancestry.

Schizophrenia is a complex psychiatric disorder, likely to be caused in part by multiple genes. In this study, linkage analyses were performed to identify chromosomal regions most likely to be associated with schizophrenia and psychosis in multiplex families of Mexican and Central American origin. Four hundred and fifty-nine individuals from 99 families, containing at least two siblings with hospital diagnoses of schizophrenia or schizoaffective disorder, were genotyped. Four hundred and four microsatellite markers were genotyped for all individuals and multipoint non-parametric linkage analyses were performed using broad (any psychosis) and narrow (schizophrenia and schizoaffective disorder) models. Under the broad model, three chromosomal regions (1pter-p36, 5q35, and 18p11) exhibited evidence of linkage with non-parametric lod (NPL) scores greater than 2.7 (equivalent to empirical P values of less than 0.001) with the peak multipoint NPL = 3.42 (empirical P value = 0.00003), meeting genomewide evidence for significant linkage in the 1pter-p36 region. Under the narrow model, the same three loci showed (non-significant) evidence of linkage. These linkage findings (1pter-p36, 18p11, and 5q35) highlight where genes for psychosis and schizophrenia are most likely to be found in persons of Mexican and Central American ancestry, and correspond to recent linkages of schizophrenia or psychosis in other populations which were formed in part from emigrants from the Spanish empire of the 15th and 16th centuries.

Central America↗
PubMed2006

Do antidepressants influence mood patterns? A naturalistic study in bipolar disorder.

This prospective, longitudinal study compared the frequency and pattern of mood changes between outpatients receiving usual care for bipolar disorder who were either taking or not taking antidepressants. One hundred and eighty-two patients with bipolar disorder self-reported mood and psychiatric medications for 4 months using a computerized system (ChronoRecord) and returned 22,626 days of data. One hundred and four patients took antidepressants, 78 did not. Of the antidepressants taken, 95% were selective serotonin or norepinephrine reuptake inhibitors, or second-generation antidepressants. Of the patients taking an antidepressant, 91.3% were concurrently taking a mood stabilizer. The use of antidepressants did not influence the daily rate of switching from depression to mania or the rate of rapid cycling, independent of diagnosis of bipolar I or II. The primary difference in mood pattern was the time spent normal or depressed. Patients taking antidepressants frequently remained in a subsyndromal depression. In this naturalistic study using self-reported data, patients with bipolar disorder who were taking antidepressants--overwhelmingly not tricyclics and with a concurrent mood stabilizer--did not experience an increase in the rate of switches to mania or rapid cycling compared to those not taking antidepressants. Antidepressants had little impact on the mood patterns of bipolar patients taking mood stabilizers.

Adult↗
PubMed2006

[Fatal familiar insomnia: clinical, neurophysiological and histopathological study of two cases].

INTRODUCTION: Family prion diseases are caused by mutations in the gene coding the prion protein (PrP), originating an altered isoform called prion. One of the most uncommon is the fatal familial insomnia (FFI), an entity characterized by sleep disorders and that is associated to a mutation in codon 178. METHODS: We have studied two male patients, aged 43 and 49 years respectively, from the same family. RESULTS: The most significant symptoms were sleep disorders with agitation, fractionated sleep, snoring and daytime sleepiness. The evolution was brief, the patient dying at a few months of the clinical debut. Sleep registries showed destructuration with total loss of the normal cycle of the phases and great decrease of the sleep spindles and K complexes in both cases. The polygraphy showed tachycardia and apnea pauses. In the molecular study, a mutation in the codon 178 was detected, both being methionine/methionine homozygotes at position 129. The most outstanding neuropathological abnormalities were located in the thalamus with gliosis and neuronal loss of anterior and dorsomedial ventral nuclei and also intense neuronal loss in olive of the first case. CONCLUSIONS: This study describes two new cases of FFI with genotype D178N-129M and short course classical phenotype. The polysomnography is essential in the diagnostic strategy of this disease whose neuropathological substrate is the thalamic alterations and of the inferior olive. Molecular biology permits an exact diagnosis of FFI although there is still controversy on the phenotypal variability and physiopathogenic mechanisms.

Adult↗
PubMed2001

The human oncoprotein MDM2 uses distinct strategies to inhibit transcriptional activation mediated by the wild-type p53 and its tumor-derived mutants.

Human MDM2 (hMDM2) inhibits transcriptional activation mediated by wild-type p53 and its tumor-derived mutants. We present evidence to show that hMDM2 interacts with the tumor-derived mutants of p53 and inhibits transcriptional activation of the human c-myc promoter mediated by the tumor-derived mutants of p53 through two domains. These two domains of hMDM2 are able to function independent of each other. Interaction with either of the domains is sufficient for inhibition of mutant p53-mediated transactivation. One of these domains is the same as the wild-type p53 interaction domain of hMDM2, whereas a second domain is situated within amino acid 190 and 276 residues and is specific for mutant p53. hMDM2 does not inhibit transcriptional activation mediated by the transcriptional activator VP16, suggesting that the inhibition is not mediated by inactivation of a general transcription factor. The transactivation and the oligomerization domains of mutant p53 are dispensable for its interaction with hMDM2. Thus, both hMDM2 and p53 recognize each other through unique domains. These observations suggest that forms of hMDM2 incapable of interacting with the wild-type p53, and are often expressed in transformed cells, would inhibit mutant p53-mediated transactivation and antagonize the tumorigenic function of mutant p53. This inhibitory function of hMDM2 may account for infrequent co-occurrence of p53 mutation and hMDM2 overexpression in cancer cells. Our results also suggest distinct mechanisms for wild-type and mutant p53-mediated transcriptional activation.

Biomarkers, Tumor↗
PubMed2000

Whole blood ionized magnesium: age-related differences in normal values and clinical implications of ionized hypomagnesemia in patients undergoing surgery for congenital cardiac disease.

OBJECTIVES: We sought to (1) determine reference values for whole blood ionized magnesium concentrations in newborns, children, and young adults and (2) evaluate the frequency and clinical implications of ionized hypomagnesemia in patients undergoing surgery for congenital heart disease. METHOD: We prospectively measured ionized magnesium concentrations in 299 subjects (113 control subjects and 186 patients undergoing surgery for congenital heart disease). Subjects were categorized by age. In the surgical group blood samples were obtained before bypass, during bypass (cooling and rewarming), after bypass, and during admission to the intensive care unit. Ionized hypomagnesemia was defined as ionized magnesium level 2 standard deviations below the mean of control subjects in the same age group. Patients were analyzed, controlling for cardiopulmonary bypass time. RESULTS: In the control group ionized magnesium concentrations differed by age. Neonates and adults showed lower ionized magnesium concentrations compared with those of other age groups. Infants exhibited the highest ionized magnesium concentration. In the surgical group patients older than 1 month showed a higher proportion of ionized hypomagnesemia compared with that found in neonates at baseline (P <.001), after bypass (P =. 03), and at admission to the intensive care unit (P =.02). Controlling for cardiopulmonary bypass time, patients older than 1 month who were hypomagnesemic during bypass showed longer intubation time (P =.001) and longer intensive care stay (P =.01) and tended to have a higher pediatric severity of illness score on intensive care admission (P =.14) compared with patients without ionized hypomagnesemia. CONCLUSIONS: There are age-related differences in normal ionized magnesium concentrations. Ionized hypomagnesemia is a common and clinically relevant occurrence among patients older than 1 month of age undergoing surgery for congenital heart disease.

Adolescent↗
PubMed2000

Changes in whole blood lactate levels during cardiopulmonary bypass for surgery for congenital cardiac disease: an early indicator of morbidity and mortality.

OBJECTIVE: Our objective was to evaluate the change in lactate level during cardiopulmonary bypass and the possible predictive value in identifying patients at high risk of morbidity and mortality after surgery for congenital cardiac disease. METHODS: We prospectively studied lactate levels in 174 nonconsecutive patients undergoing cardiopulmonary bypass during operations for congenital cardiac disease. Arterial blood samples were taken before cardiopulmonary bypass, during cardiopulmonary bypass (cooling and rewarming), after cardiopulmonary bypass, and during admission to the cardiac intensive care unit. Complicated outcomes were defined as open sternum as a response to cardiopulmonary instability, renal failure, cardiac arrest and resuscitation, extracorporeal membrane oxygenation, and death. RESULTS: The largest increment in lactate level occurred during cardiopulmonary bypass. Lactate levels decreased between the postbypass period and on admission to the intensive care unit. Patients who had circulatory arrest exhibited higher lactate levels at all time points. Nonsurvivors had higher lactate levels at all time points. A change in lactate level of more than 3 mmol/L during cardiopulmonary bypass had the optimal sensitivity (82%) and specificity (80%) for mortality, although the positive predictive value was low. CONCLUSIONS: Hyperlactatemia occurs during cardiopulmonary bypass in patients undergoing operations for congenital cardiac disease and may be an early indicator for postoperative morbidity and mortality.

Adolescent↗
PubMed2000

Reconstruction of 3-dimensional right ventricular shape and volume from 3 orthogonal planes.

This study validates a reconstructive technique that describes 3-dimensional right ventricular (RV) shape and volume with the use of 3 standard echocardiographic planes. The volume of 24 cast models of lamb right ventricles (12 normal, 12 hypertensive) was determined by water displacement. Reconstruction of the cast shapes was calculated from 2 sets of digitized data: cast cross-sectional digitized tracings and echocardiographic cross-sectional tracings. Regional volume ratios from both data sets were assessed to quantitatively specify RV regional volume differences between normotensive and hypertensive right ventricles. This method described the 3-dimensional RV shape with no differences between reconstructed volumes and true volumes for either normotensive or hypertensive casts. Between hypertensive and normal groups, regional volume ratios yielded a difference in free wall ratios that was observed to be greater in the hypertensive cast group (P =.007).

Animals↗
PubMed1995

Beta-Lactam antibiotic resistance in gram-positive bacterial pathogens of the upper respiratory tract: a brief overview of mechanisms.

Streptococcus pneumoniae and Group A Streptococci are frequent colonizers and major causative agents of disease in the upper respiratory tract of humans. In spite of the immense and common selective pressure of beta-lactam antibiotics against both of these bacterial species during the last four to five decades, penicillin-resistant strains of group A streptococci have not been described in the clinical literature as of 1994. This is particularly puzzling since penicillin-resistant mutants of this bacterium have been isolated repeatedly in the laboratory and such mutants carry altered penicillin-binding proteins (PBPs) with reduced drug affinities, i.e., a basic mechanism identical to the one seen in penicillin-resistant isolates of Streptococcus pneumoniae that have emerged in large numbers and at numerous locations and have spread explosively all over the globe by the beginning of the 1990s. The reasons for this contrasting situation are not clear. In Streptococcus pneumoniae the resistance mechanism to penicillin appears to originate in recombinational events between ancestral pneumococcal cells and as yet unidentified extra species DNA donors and probably involves the process of genetic transformation for which this bacterium has a remarkable hormonally controlled mechanism. The integration of foreign DNA sequences in the pneumococcal PBP genes leads to the remodeling of at least four of the five PBPs that change in their kinetic properties and increase in the penicillin resistance level of the bacteria also seems to involve increased production of the low-affinity binding proteins.

Animals↗
PubMed1995

Progressive magnesium deficiency increases mortality from endotoxin challenge: protective effects of acute magnesium replacement therapy.

OBJECTIVES: To study the effects of endotoxin on magnesium homeostasis; to determine if progressive magnesium deficiency alters outcome from endotoxin challenge; and to evaluate the efficacy of magnesium therapy in reducing endotoxin-induced mortality. DESIGN: Prospective, placebo-controlled, randomized, multiexperiment studies. SETTING: Research laboratory of a university hospital. SUBJECTS: Male Sprague Dawley rats (n = 299). INTERVENTIONS: Experiment 1 was designed to test if endotoxin alters magnesium homeostasis. Circulating total and ionized magnesium (estimated by ultrafilterable values) concentrations were determined in blood samples collected from animals after the randomized administration of placebo or 0.3, 3.0, or 30 mg/kg of endotoxin. A baseline blood sample was collected and then a second blood sample was obtained at 5, 15, 30, 60, 120, or 180 mins after endotoxin or placebo administration. In experiment 2, animals were randomized to receive magnesium-sufficient diets or magnesium-deficient diets for 6 wks. After 6 wks, the effects of the randomized administration of 3.0 mg/kg endotoxin or placebo were evaluated on mortality and analyte values (pH and blood gases, sodium, potassium, chloride, glucose, ionized calcium, hematocrit, total and ultrafilterable magnesium concentrations) in the three study groups (magnesium-sufficient, 3-wk magnesium-deficient, or 6-wk magnesium-deficient). In experiment 3, magnesium-deficient animals were randomized to receive 50 mmol/kg magnesium chloride or placebo, before or after the administration of 3.0 mg/kg of endotoxin. Baseline and 24-hr analyte determinations were performed and outcome was analyzed. MEASUREMENTS AND MAIN RESULTS: Experiment 1: Significant increases (p < .05) in circulating total magnesium concentrations were found in animals that received 30 mg/kg of endotoxin, at 120 mins (0.79 +/- 0.10 vs. 0.60 +/- 0.05 mmol/L), and 180 mins (0.74 +/- 0.04 vs. 0.56 +/- 0.04 mmol/L) compared with baseline values. Similarly, significant increases (p < .05) in ionized magnesium concentrations were observed 120 and 180 mins after 3.0 and 30 mg/kg of endotoxin compared with baseline values. Experiment 2: Magnesium deficiency was strongly (p < .02) associated with increased mortality from endotoxin challenge. Endotoxin administration (3.0 mg/kg) was lethal in 10 (43%) of 23 magnesium-sufficient animals, 15 (65%) of 23 3-wk magnesium-deficient animals, and 20 (83%) of 24 6-wk magnesium-deficient animals. Experiment 3: In magnesium-deficient animals, rats treated with magnesium replacement therapy had significantly increased survival from endotoxin administration (15 [52%] of 29 vs. five [17%] of 29, p < .01) compared with placebo-treated animals. CONCLUSIONS: a) Endotoxin challenge causes significant increases in circulating total and ionized magnesium concentrations. b) Progressive magnesium deficiency is strongly associated with increased lethality, and magnesium replacement therapy provides significant protection from endotoxin challenge. c) These experimental results support the concept that cellular injury is probably associated with increases in circulating magnesium concentrations. Furthermore, these experimental findings suggest that magnesium deficiency predisposes to worse outcome from endotoxin challenge, and that replacement therapy in the setting of magnesium deficiency may be warranted, especially in critically ill subjects.

Animals↗
PubMed1995

Paediatric perfusion practice in North America: an update.

In August 1994, an updated survey questionnaire was mailed to each paediatric open-heart surgery programme in North America as a follow-up to the 1989 paediatric survey. The survey requested demographic data, equipment selection criteria and specific perfusion techniques for paediatric patients. The earlier survey revealed a wide range of clinical practice. Data from the recent survey were compared with the 1989 survey to identify current programme demographics and trends in equipment use and techniques. Responses were received from 125 hospitals (110 active programmes and 15 programmes that do not perform paediatric open-heart surgery) for a response rate of 74%. Of the 110 active centres, 77 perform both adult and paediatric cardiac surgery, and 33 perform paediatric surgery exclusively. Forty-three centres reported that they perform paediatric cardiac transplantation, an increase from 35 centres in 1989. Total caseload increased by more than 8% per year from 1988 to 1994. In 1994, 18% of the patients were operated upon during the first month of life (versus 15% in 1989), and 46% were operated on during the first year of life (versus 45% in 1989). While the 1989 survey was characterized by a high degree of heterogeneity in equipment and techniques, the recent survey reveals a trend toward homogeneity among respondents. The use of membrane oxygenation and arterial line filtration has become universal, and there was an increase in the use of all types of safety devices in the cardiopulmonary bypass circuit.

Adolescent↗
PubMed1995

Cranio-mandibular disorder in children.

A study of frequency of occurrence of signs and symptoms of temporomandibular dysfunction (TMD) by means of questionnaires and clinical examination was performed at New York University College of Dentistry. Ninety children, ages 3 to 16, were examined.

Adolescent↗
PubMed1994

Alternative method of ultrafiltration after cardiopulmonary bypass.

A revised circuit design for modified ultrafiltration is presented rendering the technique more convenient for use after cardiopulmonary bypass when blood cardioplegia is used. The procedure employs a hollow-fiber ultrafiltration device attached to the cardioplegia circuit. A bubble trap, heat exchanger, and a pressure monitor are incorporated as safety features. The technique has been used in 80 patients (30 pediatric and 50 adult) and has been associated with relevant increases in colloid osmotic pressure and hematocrit.

Adult↗
PubMed1994

Ultrafilterable hypomagnesemia in neonates admitted to the neonatal intensive care unit.

OBJECTIVE: To evaluate the frequency and clinical correlates of ultrafilterable hypomagnesemia in neonates admitted to the neonatal intensive care unit (ICU). DESIGN: Prospective, observational study. SETTING: Massachusetts General Hospital and Mount Auburn Hospital. PATIENTS: A total of 117 patients (84 neonatal ICU patients and 33 normal newborns) studied over a 2-yr period of time. MEASUREMENTS: Blood samples were collected during the first 48 hrs after admission. The concentrations of magnesium (total and ultrafilterable), ionized calcium, parathyroid hormone, electrolytes, glucose and arterial blood gases were determined. RESULTS: Ultrafilterable circulating magnesium concentrations were determined in 74 of 84 neonatal ICU patients. On admission to the neonatal ICU, 23 (31.1%) of 74 neonates had ultrafilterable hypomagnesemia; two (2.7%) of 74 patients had ultrafilterable hypermagnesemia. Neonatal ICU patients had significantly lower (p < .001) ultrafilterable magnesium concentrations compared with normal neonates. Hypomagnesemic ICU patients required mechanical ventilatory support more frequently than did normomagnesemic ICU neonates (p < .05). Ionized hypocalcemia was a common finding in our patients (34 [42%] of 81). However, ultrafilterable hypomagnesemia was not statistically associated with ionized hypocalcemia (p > .05). Despite the below normal serum concentrations of ultrafilterable magnesium observed in our study, there was no impairment in parathyroid hormone secretion. CONCLUSIONS: Ultrafilterable hypomagnesemia is a common finding in neonates admitted to the ICU. Ultrafilterable hypomagnesemia is associated with the need for mechanical ventilation. To our knowledge, this is the first report of ultrafilterable magnesium concentrations in normal and sick neonates.

Bias↗
PubMed1993

Hormonal responses to surgical stress in children.

The hormonal responses to surgical stress in adults are well characterized. We hypothesized that children have age-related differences in the "stress responses" to surgery. To test this hypothesis we prospectively studied 98 children (aged 2 to 20 years) undergoing elective surgical procedures under general anesthesia. Preoperative and postoperative (1 hour postoperation) blood samples were obtained and serum prolactin and cortisol concentrations were measured. Patient data were stratified by patient age and length of operation. All patients had significant (P < .05) increases in serum cortisol and prolactin concentrations 1 hour postoperatively as compared with preoperative values. However, there were no significant differences in prolactin and cortisol responses to surgery based on the age, anesthetic technique, or length of operation. Females had higher mean (+/- SD) serum prolactin concentrations (78.41 +/- 62.23 micrograms/L) as compared with males postoperatively (39.8 +/- 21.75 micrograms/L) (P < .05). We conclude the following: (1) children have significant increases in circulating prolactin and cortisol concentrations following surgery and anesthesia, and that those increases are not affected by age, length of surgery, or anesthetic technique; and (2) females have greater prolactin responses to surgery and anesthesia than males.

Adolescent↗
PubMed1992

Geographic distribution of penicillin-resistant clones of Streptococcus pneumoniae: characterization by penicillin-binding protein profile, surface protein A typing, and multilocus enzyme analysis.

Examination of several hundred penicillin-resistant clinical isolates of Streptococcus pneumoniae has revealed extensive strain-to-strain variation in the number and molecular size of penicillin-binding proteins (PBPs). This polymorphism has been used to classify resistant isolates into groups (PBP families) that share distinct electrophoretic profiles. We describe herein properties of four such PBP families: two from Spain (and/or Ohio) and one each from Hungary and Alaska. We have discovered that representative isolates assigned to each PBP family also share capsular serotype, antibiotic resistance pattern, pneumococcal surface protein A type, and multilocus enzyme genotype. The results demonstrate independent clonal origin for strains assigned to each PBP family. Each resistant clone occurs with uniquely high incidence within specific geographic areas.

Alaska↗
PubMed1992

Favorable effects of hyperosmotic reperfusion on myocardial edema and infarct size.

Myocardial water content and infarct size were studied in 39 pigs randomly assigned to a nonintervention group, a group with an intracoronary infusion of a control solution, and a group with a hyperosmotic infusion to 450 mosM by the addition of D-mannitol. The intracoronary solutions were selectively infused into the left anterior descending coronary artery just distal to the occlusion site starting 48 min after occlusion. Reperfusion was performed 3 min later and the infusion rate progressively tapered off over the following 33 min. Multiple myocardial fragments were then obtained in nine pigs, from endocardial, mesocardial, and epicardial regions of the ischemic and control myocardium. Water content measured after 48 h of dessication was significantly greater in the reperfused [530 +/- 7 ml/100 (mean +/- SE) g dry wt] compared with control myocardium (374 +/- 3; P less than 0.0001) and similar in reperfused control and isotonic infusion groups (556 +/- 7 and 543 +/- 8 ml/100 g dry wt); it was 491 +/- 11 with intracoronary D-mannitol infusion, representing 35% less increase (P less than 0.001). In the 30 remaining pigs, area at risk and infarct size were measured 24 h later by in vivo fluorescein and in vitro triphenyltetrazolium chloride. Infarct size was similar in control and in the isotonic reperfused hearts, 6.80 +/- 1.05 and 6.22 +/- 0.76% of ventricular weight, and smaller with D-mannitol, 4.46 +/- 0.46 (P less than 0.05). The ratio of infarct size to area at risk was also smaller [0.415 +/- 0.029 vs. 0.543 +/- 0.052 and 0.547 +/- 0.045 (P less than 0.02)].(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗