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Biomedical subjects

A Muñoz

Publications and source records attributed to A Muñoz.

At least 199 records · Page 11Linked to original sources

Operative treatment of the anterior synostotic plagiocephaly: analysis of 45 cases.

An operative series of 45 patients with anterior synostotic plagiocephaly is analyzed. In the cases of six children it was not possible to visualize synostosis of the cranial sutures on plain X-ray films or three-dimensional CT. Primary procedures were performed at an average age of 14 months with an average postoperative follow-up of 47.5 months. Children were operated on either with lateral canthal advancement (5 cases), unilateral orbital advancement with "tongue in groove" (12 cases), or bilateral orbital advancement (28 cases). Excellent results were obtained in 33/45 patients, while 8/45 children required secondary minor revisions. Of the three different surgical techniques, the results achieved by the bilateral approach were considered better than those attained with the unilateral techniques. Osteotomies of the nasal bones are recommended in the cases of older children with severe nasal deviation associated with dislocation of the nasoethmoidal complex.

Congenital Abnormalities↗

In situ characterization of the Ca2+ sensitivity of large conductance Ca2+-activated K+ channels: implications for their use as near-membrane Ca2+ indicators in smooth muscle cells.

The Ca2+ sensitivity of large conductance Ca2+- and voltage-activated K+ channels (BKV,Ca) has been determined in situ in freshly isolated myocytes from the guinea pig urinary bladder. In this study, in situ denotes that BKV,Ca channel activity was recorded without removing the channels from the cell. By combining patch clamp recording in the cell-attached configuration and microfluorometry of fura-2, we were able to correlate BKV,Ca channel activity with changes in cytoplasmic intracellular [Ca2+] ([Ca2+]i). The latter were induced by ionomycin, an electroneutral Ca2+ ionophore. At 0 mV, the Hill coefficient (nH) and the [Ca2+]i to attain half of the maximal BKV,Ca channel activity (Ca50) were 8 and 1 microM, respectively. The data suggest that this large Hill number was not a consequence of the difference between the near-membrane [Ca2+] ([Ca2+]s) and the bulk [Ca2+]i, indicated by fura-2. High Hill numbers in the activation by Ca2+ of BKV,Ca channels have been seen by different groups (e.g., filled squares in Fig. 4 of Silberberg, S. D., A. Lagrutta, J. P. Adelman, and K. L. Magleby. 1996. Biophys. J. 70:2640-2651). However, such high nH has always been considered a peculiarity rather than the rule. This work shows that a high Ca2+ cooperativity is the normal situation for BKV,Ca channels in myocytes from guinea pig urinary bladder. Furthermore, the Ca50 did not display any significant variation among different channels or cells. It was also evident that BKV,Ca channel activity could decrease in elevated [Ca2+]i, either partially or completely. This work implies that the complete activation of BKV,Ca channels occurs with a smaller increment in [Ca2+]s than previously expected from in vitro characterization of the Ca2+ sensitivity of these channels. Additionally, it appears that the activity of BKV,Ca channels in situ does not strictly follow changes in near-membrane [Ca2+].

Animals↗

Syringe and needle exchange as HIV/AIDS prevention for injection drug users in Puerto Rico.

This study evaluated the effectiveness of the first needle exchange program (NEP) established in Puerto Rico. The data for this study were collected during the first months of the NEP from July 1995 to March 1996 in 13 communities of the San Juan metropolitan area. Subjects were the participants of two modalities of the NEP: a mobile team and a community-based drug treatment program. During the 3-week evaluation period, 2401 injection drug users (IDUs) were recruited, resulting in a total of 19,195 exchange contacts and 146,323 syringes exchanged. No significant change in drug injection was observed. However, the program was effective in reducing sharing of syringes and cookers. The study suggests that the NEP did help in reducing needle sharing in Puerto Rico. However, the HIV seropositivity in returned syringes suggests the need to continue aggressive prevention programs to arrest the epidemic among IDUs. However, factors related to the socio-cultural environment as well as cultural norms and traditions need to be considered when planning and expanding NEPs.

HIV Infections↗

Identification of a thyroid hormone response element in the promoter region of the rat lipocalin-type prostaglandin D synthase (beta-trace) gene.

We have previously reported that mRNA levels for the rat lipocalin-type prostaglandin (PG) D synthase/beta-trace (PGDS) gene, the enzyme responsible for the production of PGD2 in the central nervous system, are regulated by thyroid hormone in vivo. In this study, we describe the identification of a thyroid hormone (T3) response element (T3RE) in the 5'-flanking region of the rat PGDS gene. By radioimmunoprecipitation of genomic fragments using thyroid hormone receptor (TR) protein and specific anti-TR antibodies, gel-shift, foot-printing, mutational analysis, and transactivation assays we have identified a spaced four imperfect direct repeat (DR4) element, GGTTCACTTCAGGGTA (positions -586/-571), which functions as a T3RE when fused to a heterologous promoter. Our results suggest that thyroid hormone regulates the expression of the rat lipocalin-type PGDS gene through this element. Remarkably, the element identified also confers regulation by retinoic acid. Giving the important roles proposed for the PGDS enzyme and its product, PGD2, the major PG in the mammalian brain, the altered expression of the PGDS gene may contribute to the deleterious effects of hypothyroidism in the central nervous system.

5' Untranslated Regions↗

Developmental expression of the tenascin-C is altered by hypothyroidism in the rat brain.

Tenascin-C is an extracellular matrix glycoprotein involved in cell adhesion and migration, and neurite outgrowth. Since these processes have been found to be under thyroid control in the developing rat brain, we have investigated the effect of congenital hypothyroidism on tenascin-C expression. At birth, in situ hybridization studies in hypothyroid rats show an abnormal up-regulation of tenascin-C in some areas (caudate-putamen, geniculate nuclei, ependymal epithelium of the lateral ventricles, hippocampus) and down-regulation in others (occipital and retrosplenial cortex, subiculum). With subsequent development, hypothyroid animals show higher tenascin-C expression also in the upper layers of the cerebral cortex and subplate, and the Bergmann glia of the cerebellum. Significantly, thyroxine treatment of hypothyroid rats led to normalization of tenascin-C levels in most areas. In agreement with the messenger RNA data, hypothyroid rats contain an uniformly higher level of immunoreactive tenascin-C protein throughout the brain, particularly in the cerebellum. Suggesting a direct cellular effect, thyroid hormone also decreases tenascin-C expression in two glial cell lines (C6, B3.1) expressing thyroid receptors. Our results show that congenital hypothyroidism causes specific alterations in the pattern of tenascin-C expression in the rat brain which may at least partially be responsible for some of the developmental disturbances observed in this syndrome.

Aging↗

Necrotizing external otitis caused by Aspergillus fumigatus: computed tomography and high resolution magnetic resonance imaging in an AIDS patient.

Most necrotizing (malignant) external otitis (NEO) occurs in diabetic patients and is commonly caused by Pseudomonas aeruginosa. We report an acquired immunodeficiency syndrome (AIDS) patient with NEO caused by Aspergillus fumigatus in which computed tomography (CT) showed destructive petrous bone involvement and magnetic resonance imaging (MRI) of the ear discovered extensive soft tissue and facial nerve involvement. Dedicated MRI studies of the ear in this type of pathology provide new insights relating to nerve dysfunction, that cannot be obtained with CT.

AIDS-Related Opportunistic Infections↗

Megatherapy in children with high-risk Ewing's sarcoma in first complete remission.

To improve the prognosis of patients with metastatic or high-risk localized sarcoma in first CR, we explored the role of consolidation therapy with megatherapy and hematopoietic rescue. From 1986 to 1995, of 72 patients with Ewing's sarcoma from three pediatric departments, 30 were diagnosed as high-risk patients. Of these 30 patients, six did not achieve complete remission and four refused megatherapy and received multimodal treatment (chemotherapy + surgery and/or radiotherapy). The remaining 20 patients received megatherapy. There were 15 males and five females with a median age of 10.8 years (range 2-18 years). Five patients had metastatic disease at initial diagnosis, nine patients had primary tumor in the pelvis and 13 had a tumor volume greater than 100 ml. Overall disease-free survival was 62.7+/-11%; 40+/-21.9% for those with metastatic disease, 76.2+/-12.2% for those with tumor volume greater than 100 ml and 64.8+/-16.5% for those with tumor in pelvic bones. In conclusion, megatherapy has improved the outcome of this group of patients relative to that expected following conventional therapy.

Adolescent↗

Recombinant human erythropoietin (rh-Epo) administration to normal child bone marrow donors.

We have evaluated the efficacy of administering recombinant human erythropoietin (rh-Epo) to 11 healthy bone marrow donors weighing less than 30 kg. Three weeks before harvesting, the donors received 100 units/kg/day rh-Epo subcutaneously and oral iron supplementation (2.5 mg/kg twice daily). Six children with hematocrit values below the normal ranges for their ages after bone marrow harvesting received 150 units/kg rh-Epo three times a week for 2 weeks and oral iron supplementation at the same dose. No rh-Epo side-effects were observed. Hematocrit values before harvesting increased to between 5.7 and 18.5 (mean 10.6 +/- 1.2) above the baseline values (P = 0.0001). Hematocrit after harvesting decreased to between 4 and 19.5% (mean, 11.1) below the day 0 pre-harvest values. On day + 15 all but one patient had a hematocrit value > or = baseline value. No patient required transfusion during or after bone marrow harvest. Our results show that rh-Epo administration can avoid transfusion and has no side-effects in low weight child bone marrow donors.

Administration, Cutaneous↗

Autologous bone marrow transplantation with monoclonal antibody purged marrow for children with acute lymphoblastic leukemia in second remission. Spanish Working Party for BMT in Children.

The purpose of this study was to evaluate the outcome of children with acute lymphoid leukemia (ALL) in second remission who have undergone high-dose chemotherapy and radiotherapy and autologous bone marrow transplantation (ABMT) with monoclonal antibody purged marrow, and to determine the main prognostic factors. From 1987 to 1992, 55 children with ALL in second remission underwent ABMT. The conditioning regimen consisted of total body irradiation (TBI) plus cyclophosphamide in 21 patients and TBI plus cyclophosphamide plus cytarabine or VP-16 in 28 patients; the remaining six patients were treated with chemotherapy alone (cyclophosphamide and busulfan, and/or VP-16). The marrow was purged using monoclonal antibodies and complement or magnetic microspheres in all cases. All patients engrafted. Three patients (5%) died early post transplant from infections. Twenty-six patients (47%) relapsed (median 150 days); 26 patients (47%) are alive and in complete remission (CR) at a median of 36 months. The Kaplan-Meier estimation showed a probability of event-free survival (EFS) of 46 +/- 0.007%. In the univariate analysis, first CR length and conditioning with TBI plus two or more cytotoxic drugs were found to be the most significant predictors of EFS. ABMT with purged marrow is a treatment modality which offers a chance of cure in children with ALL after relapse, including children who relapse early.

Adolescent↗

Prenatal diagnosis of testicular torsion.

A case of the prenatal diagnosis of testicular torsion at 39 weeks' gestation is presented. The affected testicle was observed as a small rounded area of hypoechogenicity with a peripheral echogenic ring without hydrocele. The appearance was suggestive of the chronic phase of testicular torsion. The neonatal genital exploration confirmed the diagnosis.

Adult↗

The c-erbA alpha protooncogene induces apoptosis in glial cells via a protein kinase C- and bcl-2-suppressible mechanism.

The c-erbA protooncogene encodes the thyroid hormone (3,5,3'-triiodothyronine; T3) receptor alpha1 (TR alpha1). c-erbA/TR alpha1 is expressed in many cell types including glial cells, particularly in the immature state. We show here by morphological and biochemical criteria that c-erbA induces apoptosis of glial B3.1 cells in serum-deprived conditions. This effect is mostly T3 independent. Growth factors such as platelet-derived growth factor, basic fibroblast growth factor, or transforming growth factor-alpha prevent B3.1 + TR alpha1 cell death. Protein kinase C (PKC) activators also prevent the apoptosis phenomenon, an effect that was blocked by the PKC-specific inhibitor GF109203X. Expression of an exogenous bcl-2 gene led also to B3.1 + TR alpha1 cell survival. Neither a series of inhibitors including GF109203X nor T3 inhibits bcl-2 action, indicating that bcl-2 blocks a downstream step in the death-promoting process. B3.1 + TR alpha1 cell apoptosis is not blocked by caspase-1 or poly-ADP-ribosyltransferase inhibitors, suggesting that the activation of these classic pathways is not involved in the apoptotic mechanism. In addition, direct interaction with specific neuronal cells but not incubation with their conditioned medium inhibits also apoptosis of B3.1 + TR alpha1 cells. Our results show that c-erbA promotes an apoptotic process in glial B3.1 cells that is suppressible by PKC activation and bcl-2, probably by distinct mechanisms.

Animals↗

Repercussions of acidosis on postnatal erythrocyte deformability in term and preterm newborns.

Erythrocyte deformability in newborns, a determining factor in neonatal blood hyperviscosity, is also often responsible for decreased blood flow in the microcirculation of several organs, such as the brain, kidneys, and digestive tract. In 70 neonates classified by gestational age and by the presence or absence of acidosis, we analyzed the filterability of erythrocytes in suspension through 5 polycarbonate membranes and its relation with gasometric determinations, Anion-GAP, plasma viscosity, plasma osmolality, erythrocyte volumes, and plasma lipids. Using a logistic regression analysis, controlling gestational age (p = 0.17), mean corpuscular volume (MCV) (p = 0.63), and mean corpuscular hemoglobin concentration (MCHC) (p = 0.21), the presence of acidosis (p = 0.0049, odds ratio: 3.60) is a risk factor for an increased rigidity index in newborns. Metabolic and respiratory acidosis were significantly related with lower erythrocyte deformability in the early neonatal period (below 5 days of age). Decreased plasma bicarbonate and increased Anion-GAP (even in compensated metabolic acidosis), as well as increased pCO2 in respiratory acidosis, were significantly related with decreased erythrocyte filterability. In newborns under 32 weeks of gestational age the increase in erythrocyte rigidity index is more related to the low gestational age and increased MCV than to the presence of acidosis. These factors can produce changes in the microcirculation of these patients.

Acidosis↗

Left-truncated data with age as time scale: an alternative for survival analysis in the elderly population.

BACKGROUND: The standard approach for survival analysis of the elderly population is to define the survival time as the elapsed time from entry into the study until death, and to adjust by age using stratification and regression procedures. However, the interest is in the study of the aging process and the risk factors related to it, not in the use of time-on-study as the time scale. Here, we present methods to use age as the time scale and compare inferences and interpretations with those obtained using the standard approach. METHODS: A total of 1,315 individuals aged 65 years or older from the city of Barcelona, Spain, were interviewed in 1986 (baseline). The vital status of the cohort was assessed in October 1994. To illustrate the usefulness of age as time scale (alternative approach) instead of time-on-study in the survival analysis of the elderly population, both methods were used to assess the relationship between baseline functional capacity and mortality. RESULTS: Using the alternative approach, we observed that 50% of the sample died at age 80.6 years; this information could not be estimated with the standard approach. Using age as a covariate in the standard analysis with time-on-study as the time scale and using age as the time scale in the alternative analysis, the association of functional capacity at baseline and mortality was of similar magnitude under both analyses. Nevertheless, using the alternative approach, relative risks were slightly lower, and the adjustment by age was tight and was not subject to the inherent assumptions in regression models of the functional relationship of independent variables with outcome. We illustrated the methods with fixed covariates (i.e., gender) and baseline values of time-dependent covariates (i.e., functional capacity), but we discussed the extension of our methods for the analysis of time-dependent covariates measured at several visits in a cohort study. Methods proposed here are easily implemented with widely available statistical software packages. CONCLUSIONS: Although the use of standard survival analysis generally produces correct estimates, the use of age as time scale is deemed more appropriate for survival analysis of the elderly: Inferences are easier to interpret and final models are simpler. We therefore recommend the use of age as time scale for survival analysis of the elderly population.

Aged↗