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Biomedical subjects

P Muñoz

Publications and source records attributed to P Muñoz.

At least 19 recordsLinked to original sources

A GEE moving average analysis of the relationship between air pollution and mortality for asthma in Barcelona, Spain.

Several studies have assessed the association between air pollution and hospital admissions or emergency room visits for asthma. Because of both the presence of missing data and the small number of observations, the relationship between air pollution and mortality for respiratory causes has been rarely analysed, and when it has, the results are very inconclusive or even inconsistent. The objective of this study is to assess the relation between levels of air pollutants (black smoke, sulphur dioxide, nitrogen dioxide and ozone), meteorological variables (24th average temperature and relative humidity) and daily mortality for asthma (ICD-9 493, 2 to 45 years old) in Barcelona, Spain, during the period 1986-1989. Since the range of daily mortality for asthma (2 to 45 years old) during the period 1986-1989 was 0-1), we have preferred to consider this variable as dichotomous. First, the relationship between air pollutants, meteorological variables and daily mortality (controlled for the occurrence of asthma epidemics) was estimated using logistic regression models. As was expected, the residuals from this regression were autocorrelated, showing a complex moving average (MA) structure. If covariates were not time dependent the so-called generalized linear mixed models, could be applied. In our case the covariates vary. As a consequence the likelihood is numerically intractable because it involves the evaluation of n-fold integral. An alternative method that avoids these numerical problems is the generalized estimating equations method (GEE). It is a multivariate analogue of quasi-likelihood estimation. In the absence of a likelihood function the parameters can be estimated by solving a multivariate analogue of the quasi score function. We have modified the GEE method in this paper, allowing for a different structure in the error covariance matrix (MA). Both air pollutants and meteorological variables are related with the occurrence of a death for asthma. In this sense, nitrogen dioxide, NO(2) (ss=0.037, p<0. 05), ozone, O(3) (ss=0.021, p<0.06) and high temperature (the ss's were in the range (0.098-0.182), p<0.05) increased the probability of dying for asthma in Barcelona during the period 1986-1989.

Adolescent

Immunohistochemical reactivity of polyclonal antibodies against Sphaerospora testicularis and Ceratomyxa labracis (Myxosporea: Bivalvulida), with other myxosporean parasites.

Immunological staining with rabbit antibodies raised against Sphaerospora testicularis and Ceratomyxa labracis was used to characterise their specificity and their reactivity towards other fish parasites. Polar capsules and valves of S. testicularis and C. labracis were labelled with their homologous antibody and cross reaction was observed with all the myxosporean parasites assayed from marine and freshwater fish hosts. All polar capsules were stained with both antibodies, except those of Zschokkella mugilis, which were not labelled with anti-S. testicularis serum. These observations suggest that polar capsules may be very conserved structures in myxosporean parasites from different hosts.

Animals

Benfluorex improves muscle insulin responsiveness in middle-aged rats previously subjected to long-term high-fat feeding.

It has been reported that benfluorex ameliorates the insulin resistance induced by high-fat feeding when its administration is initiated at the same time as the change in diet. Here we have examined whether benfluorex reverses insulin resistance when this is established in middle-aged rats chronically maintained on a high-fat diet. Untreated 12-month-old rats that had been subjected to a high-fat diet for the last 6 months showed markedly lower insulin-induced stimulation of 2-deoxyglucose uptake by strips of soleus muscle and a reduced expression of GLUT4 glucose carriers in skeletal muscle. However, animals subjected to the same protocol but treated with benfluorex during the last month of high-fat feeding showed marked improvement in insulin-stimulated glucose transport by soleus muscle. Benfluorex treatment caused a substantial increase in the content of GLUT4 protein in white muscle; however, GLUT4 levels in red muscle remained low. Our results indicate: (i) that benfluorex treatment in middle-aged rats reverses the insulin resistance induced by high-fat feeding in soleus muscle; (ii) benfluorex is active even when it is administered once the insulin-resistant state is already established; (iii) reversion of muscle insulin resistance by benfluorex can occur independently of modifications in GLUT4 protein expression.

Aging

Myocardial Epstein-Barr virus-associated cardiac smooth-muscle neoplasm arising in a cardiac transplant recipient.

Epstein-Barr virus-associated smooth muscle proliferations have been reported in immunosuppressed patients with acquired immunodeficiency syndrome and after organ transplantation. We report here a case of a histologically benign case arising in a 48-year-old male who had received immunosuppressive therapy 4 years earlier, after cardiac transplantation. In the necropsy performed for unrelated reasons, an incidental left intramyocardial tumor was discovered. The presence of Epstein-Barr virus was confirmed by EBER-1 in situ hybridization and polymerase chain reaction. To the best of our knowledge, this is the first case of an Epstein-Barr virus-associated smooth muscle proliferation arising in the heart after cardiac transplantation and should be added to the potential complications of this kind of procedure.

Aortic Aneurysm, Abdominal

Rhodococcus equi infection in transplant recipients: case report and review of the literature.

BACKGROUND: Rhodococcus equi is an opportunistic pathogen that usually causes infection in immunocompromised hosts, mainly human immunodeficiency virus-positive patients, yet solid organ transplant recipients may be affected as well. Infections in this group of patients have not been sufficiently analyzed. METHODS: We report an R equi pneumonia in a heart transplant recipient and review another 11 cases. RESULTS: Infection appeared a mean of 49 months (range 1-180) after transplantation. Lung was primarily involved in 10 cases (83.3%). The remaining two cases presented with a paravertebral abscess and a purulent pericarditis. Invasive techniques were necessary to reach the diagnosis in nine cases. One patient healed with surgical resection of the lesion; the remaining 11 received antimicrobial agents. Six of them required additional surgical treatment. Three patients died. CONCLUSIONS: Clinicians should consider R equi when evaluating a solid organ recipient with an asymptomatic lung nodule. Microbiology laboratories should be alerted in these cases because it could be mistaken for a contaminant diphtheroid and will not respond to the standard empirical therapy.

Actinomycetales Infections

Immunohistochemical characterization of a polyclonal antibody against Sphaerospora dicentrarchi (Myxosporea: Bivalvulida), a parasite from sea bass (Dicentrarchus labrax L.) (Teleostei: Serranidae).

Rabbit antibody was raised against Sphaerospora dicentrarchi, a histozoic parasite of sea bass (Dicentrarchus labrax L.). Light and electron immunohistological staining were used to characterize its specificity and possible reactivity toward other fish parasites. In light immunohistochemistry the polar capsules and valves of the S. dicentrarchi spores appeared strongly stained, whereas developmental stages were not. Electron microscopic histochemistry revealed intense labeling in valves and some developmental stages. Cross-reaction was observed with all the myxosporean parasites assayed, even with those belonging to other genera. Polar capsules of all the myxosporean species except Polysporoplasma sparis were the main structures stained by the polyclonal antibody. These observations could reveal the existence of conserved antigenic epitopes in polar capsules of different Myxosporea.

Animals

Pneumonia after heart transplantation: a multi-institutional study. Spanish Transplantation Infection Study Group.

A multiinstitutional study of 307 heart transplant recipients was carried out to determine the clinical, radiographic, and prognostic characteristics, the incidence, and the etiology of pneumonias in the first year after transplantation. There were 21.1 cases of pneumonia per 100 heart transplantations. Seventy-five percent of the cases occurred in the first trimester. Eighty-two causal agents were identified, of which 60% were opportunistic, 25% were nosocomial, and 15% were community-acquired. The most frequent isolates were cytomegalovirus (20), Aspergillus species (13), and Pneumocystis carinii (11). Hemoptysis occurred more frequently in aspergillus pneumonias than in other pneumonias (54% vs. 6%, respectively; P < .05); aspergillus pneumonia was the only type of pneumonia during which cavitated nodules were noted on thoracic radiographs. The overall mortality rate was 30.8%; the independent factors of a poor prognosis were aspergillus infection (relative risk [RR], 7.4; 95% confidence interval [CI], 5.8-9.1) and bilateral pulmonary infiltrates (RR, 10; 95% CI, 8.5-11.4).

Adult

Hypersensitivity of Ku-deficient cells toward the DNA topoisomerase II inhibitor ICRF-193 suggests a novel role for Ku antigen during the G2 and M phases of the cell cycle.

Ku antigen is a heterodimer, comprised of 86- and 70-kDa subunits, which binds preferentially to free DNA ends. Ku is associated with a catalytic subunit of 450 kDa in the DNA-dependent protein kinase (DNA-PK), which plays a crucial role in DNA double-strand break (DSB) repair and V(D)J recombination of immunoglobulin and T-cell receptor genes. We now demonstrate that Ku86 (86-kDa subunit)-deficient Chinese hamster cell lines are hypersensitive to ICRF-193, a DNA topoisomerase II inhibitor that does not produce DSB in DNA. Mutant cells were blocked in G2 at drug doses which had no effect on wild-type cells. Moreover, bypass of this G2 block by caffeine revealed defective chromosome condensation in Ku86-deficient cells. The hypersensitivity of Ku86-deficient cells toward ICRF-193 was not due to impaired in vitro decatenation activity or altered levels of DNA topoisomerase IIalpha or -beta. Rather, wild-type sensitivity was restored by transfection of a Ku86 expression plasmid into mutant cells. In contrast to cells deficient in the Ku86 subunit of DNA-PK, cells deficient in the catalytic subunit of the enzyme neither accumulated in G2/M nor displayed defective chromosome condensation at lower doses of ICRF-193 compared to wild-type cells. Our data suggests a novel role for Ku antigen in the G2 and M phases of the cell cycle, a role that is not related to its role in DNA-PK-dependent DNA repair.

Animals

Stimulation of membrane serine-threonine phosphatase in erythrocytes by hydrogen peroxide and staurosporine.

Indirect evidence has suggested that K-Cl cotransport in human and sheep erythrocytes is activated physiologically by a serine-threonine phosphatase. It is activated experimentally by H2O2 and by staurosporine, a kinase inhibitor. Activation by H2O2 and staurosporine is inhibited by serine-threonine phosphatase inhibitors, suggesting that the activators stimulate the phosphatase. The present study shows that sheep and human erythrocytes contain membrane-associated as well as cytosolic serine-threonine phosphatases, assayed from the dephosphorylation of 32P-labeled glycogen phosphorylase. In cells from both species, the relatively low sensitivity of the membrane enzyme to okadaic acid suggests it is type 1 protein phosphatase. The cytosolic phosphatase was much more sensitive to okadaic acid. Membrane-associated phosphatase was stimulated by both H2O2 and staurosporine. The results support earlier conclusions that the membrane-associated type 1 phosphatase identified here is regulated by phosphorylation and oxidation. The results are consistent with the phosphatase, or a portion of it, being responsible for activating K-Cl cotransport.

Animals

Effect of ethanol ingestion on renal regulation of water and electrolytes.

Ethanol may alter the homeostasis of water and electrolytes before the occurrence of liver damage able to explain these disorders. How the kidney may become involved in water diuresis or sodium and potassium retention has not been well elucidated. During the last decade, an increasing body of evidence has guided interest toward the relevance of the biochemical basis of ethanol-induced injury to the kidney. Multiple functional abnormalities of renal tubules may be associated with ethanol-induced changes in membrane composition and lipid peroxidation of these epithelial cells. Ethanol interferes with the carrier function by decreasing (Na+K)-ATPase activity, but this activity is enhanced by chronic exposure. Recently, it was reported that ethanol oxidation by the kidney is favored in chronic ethanol-treated rats, thereby suggesting a pathogenic role for acetaldehyde in the nephrotoxic effect of ethanol ingestion. Also, increased reactive oxygen species, partly generated from acetaldehyde oxidation, may contribute to the occurrence of oxidative stress. The pathophysiology of renal regulation of water and electrolytes of alcoholic disease is analyzed on the basis of recent advances in our knowledge concerning the biochemical effects of ethanol on the kidney.

Alcohol Drinking

Haemophilus species bacteremia in adults. The importance of the human immunodeficiency virus epidemic.

BACKGROUND: Until the late 1970s, invasive infections caused by Haemophilus species were thought to occur mainly in children and only infrequently in adults. OBJECTIVE: To report the largest series to date of Haemophilus species bacteremia (HB) from a single center. DESIGN: Retrospective. SETTING: Large, tertiary care, general teaching hospital. METHODS: We reviewed the charts of adult patients with HB detected from January 1, 1986, to December 31, 1994. Haemophilus strains were serotyped, and the antimicrobial resistance pattern was analyzed. RESULTS: One hundred sixteen patients had HB (0.26 cases per 1000 admissions). Thirty-eight children and 16 adults were excluded. Human immunodeficiency virus (HIV) infection was the most common underlying condition (n = 18 [29%]), followed by malignant neoplasms (n = 12 [19%]) and chronic obstructive pulmonary disease (n = 12 [19%]). Prevalence in HIV-positive patients was 5 cases per 1000 admissions vs 0.2 cases per 1000 admissions in HIV-negative patients. Infection was nosocomial in 16 patients (26%). Focal diseases were pneumonia in 41 patients (66%), cholangitis in 5 patients (8%), endocarditis in 3 patients (5%), meningitis and septic arthritis each in 1 patient (2%), and primary bacteremia in 9 patients (14%). The HIV-positive patients were significantly younger and presented more frequently with pneumonia (P < .05). Overall, 14 patients died (22%). Bacteremia was polymicrobial in 11 patients (18%). Haemophilus influenzae was isolated in 53 patients (85%). Rates of antimicrobial resistance were 11% to chloramphenicol sodium succinate, 48% to ampicillin sodium, 78% to erythromycin stearate, 76% to combined sulfamethoxazole and trimethoprim, 15% to rifampin, and 57% to clarithromycin. CONCLUSIONS: Infection with HIV has become the most common underlying disease in adults with HB in our hospital. Therapeutic approaches must take into account the high rate of antimicrobial resistance.

AIDS-Related Opportunistic Infections

Regulation of glucose transport, and glucose transporters expression and trafficking in the heart: studies in cardiac myocytes.

Cardiac muscle is characterized by a high rate of glucose consumption. In the absence of insulin, glucose transport into cardiomyocytes limits the rate of glucose utilization and therefore it is important to understand the regulation of glucose transporters. Cardiac muscle cells express 2 distinct glucose transporters, GLUT4 and GLUT1; although GLUT4 is quantitatively the more important glucose transporter expressed in heart, GLUT1 is also expressed at a substantial level. In isolated rat cardiomyocytes, insulin acutely stimulates glucose transport and translocates both GLUT4 and GLUT1 from an intracellular site to the cell surface. Recent evidence indicates the existence of at least 2 distinct intracellular membrane populations enriched in GLUT4 with a different protein composition. Elucidation of the intracellular location of these 2 GLUT4 vesicle pools in cardiac myocytes, their role in GLUT4 trafficking, and their relation to insulin-induced GLUT4 translocation needs to be addressed.

Animals

Chronic high-fat feeding and middle-aging reduce in an additive fashion Glut4 expression in skeletal muscle and adipose tissue.

The interaction of middle-aging and chronic high-fat feeding on glucose transport in skeletal muscle and adipose tissue was examined. To this end, we studied the effects of 6 month treatment with a high-fat diet in 12-month old rats. Chronic high-fat feeding led to a substantial reduction in GLUT4 glucose transporter expression both in adipose tissue and in skeletal muscle, which was additive to the reduction in GLUT4 protein content detected in aged rats. In parallel, the high-fat diet led to a reduced insulin-stimulated glucose transport in the incubated soleus muscle and isolated adipocytes; insulin resistance induced by high-fat feeding was superimposed to the decreased insulin response detected in aged rats. Different mechanisms were responsible for GLUT4 repression in response to high-fat feeding or aging in skeletal muscles and adipose tissue.

Adipose Tissue

[The prediction of the degree of metabolic control by minimal technical norms in a diabetes program].

OBJECTIVE: To assess whether scores on the minimum technical norms (MTN) of the diabetes mellitus programme are of use in determining the level of metabolic control achieved. DESIGN: A retrospective study. SETTING: Two teaching health centres in the city of Santander. PATIENTS AND OTHER PARTICIPANTS: 204 patients, the total chosen by the Santander area management for the 1994 annual evaluation of the Diabetes programme. MEASUREMENTS AND RESULTS: The values reached by the variables of the MTN were measured. For a control criterion we took the value of glycosylated haemoglobin HbA1C or over. 52% of patients fulfilled the criteria of good control, 20% acceptable and 28% bad. CONCLUSIONS: Scoring on the MTN has little value in predicting lower values of HbA1C and is no use in assessing the level of metabolic control achieved by the Diabetes programme. The evaluation of the programme should include results indicators.

Community Health Centers

Insulin-induced recruitment of glucose transporter 4 (GLUT4) and GLUT1 in isolated rat cardiac myocytes. Evidence of the existence of different intracellular GLUT4 vesicle populations.

UNLABELLED: Using isolated rat cardiomyocytes we have examined: 1) the effect of insulin on the cellular distribution of glucose transporter 4 (GLUT4) and GLUT1, 2) the total amount of these transporters, and 3) the co-localization of GLUT4, GLUT1, and secretory carrier membrane proteins (SCAMPs) in intracellular membranes. Insulin induced 5.7- and 2.7-fold increases in GLUT4 and GLUT1 at the cell surface, respectively, as determined by the nonpermeant photoaffinity label [3H]2-N-[4(1-azi-2,2,2-trifluoroethyl)benzoyl]-1, 3-bis-(D-mannos-4-yloxy)propyl-2-amine. The total amount of GLUT1, as determined by quantitative Western blot analysis of cell homogenates, was found to represent a substantial fraction ( approximately 30%) of the total glucose transporter content. Intracellular GLUT4-containing vesicles were immunoisolated from low density microsomes by using monoclonal anti-GLUT4 (1F8) or anti-SCAMP antibodies (3F8) coupled to either agarose or acrylamide. With these different immunoisolation conditions two GLUT4 membrane pools were found in nonstimulated cells: one pool with a high proportion of GLUT4 and a low content in GLUT1 and SCAMP 39 (pool 1) and a second GLUT4 pool with a high content of GLUT1 and SCAMP 39 (pool 2). The existence of pool 1 was confirmed by immunotitration of intracellular GLUT4 membranes with 1F8-acrylamide. Acute insulin treatment caused the depletion of GLUT4 in both pools and of GLUT1 and SCAMP 39 in pool 2. IN CONCLUSION: 1) GLUT4 is the major glucose transporter to be recruited to the surface of cardiomyocytes in response to insulin; 2) these cells express a high level of GLUT1; and 3) intracellular GLUT4-containing vesicles consist of at least two populations, which is compatible with recently proposed models of GLUT4 trafficking in adipocytes.

Animals