Interface and temperature dependent magnetic properties in permalloy thin films and tunnel junction structures.

Magnetization dynamics and field dependent magnetization of different devices based on 25-30 nm thick Permalloy (Py) films: such as single Py layers (Py/MgO; Py/CoFeB/Al2O3) and Py inserted as a magnetic layer in magnetic tunnel junctions (Py/CoFe/Al2O3/CoFe; Py/CoFeB/Al2O3/CoFe; Py/MgO/Fe) have been extensively studied within a temperature range between 300 K down to 5 K. The dynamic response was investigated in the linear regime measuring the ferromagnetic resonance response of the Py layers using broadband vector network analyzer technique. Both the static and the dynamic properties suggest the possible presence of a thermally induced spin reorientation transition in the Py interface at temperatures around 60 K in all the samples investigated. It seems, however, that the details of the interface between Py and the hardening ferromagnet/insulator structure, the atomic structure of Py layers (amorphous vs. textured) as well as the presence of dipolar coupling through the insulating barrier in the magnetic tunnel junction structures could strongly influence this low temperature reorientation transition. Our conclusions are indirectly supported by structural characterization of the samples by means of X-Ray diffraction and high resolution transmission electron microscopy techniques. Micromagnetic simulations indicate the possibility of strongly enhanced surface anisotropy in thin Py films over CoFe or CoFeB underlayers. Comparison of the simulations with experimental results also shows that the thermally-induced spin reorientation transition could be influenced by the presence of strong disorder at the surface.

Efficacy of nitroglycerine infusion versus sublingual nifedipine in severe pre-eclampsia: a randomized, triple-blind, controlled trial.

1. Information regarding the use of continuous i.v. administration of nitroglycerine as an antihypertensive agent in the management of pre-eclampsia is scarce. In the present study, i.v. nitroglycerine or sublingual nifedipine were administered to 32 women with severe pre-eclampsia who were being managed with controlled plasma volume expansion and MgSO(4) loading and maintenance doses. Maternal blood pressure and heart rate responses, fetal heart rate responses and perinatal fetal-maternal adverse effects were evaluated using classical parametric and non-parametric data analysis and data modelling by mixed models. 2. An important hypotensive response was observed in both groups, although this reponse was greater, faster and exhibited less variability (more precision) in the nitroglycerine-treated group. Heart rate also increased in both the nitroglycerine- and nifedipine-treated groups (4.6 +/- 4.4 vs 8.6 +/- 5.3 b.p.m., respectively), although the increase in the nifedipine-treated group was almost twofold that in the nitroglycerine-treated group. There were no significant changes in fetal heart rate in response to vasodilator therapy. The frequency of perinatal fetal-maternal adverse effects was similar in both groups at 40% and the adverse effects observed included flushing, headache, palpitations and nausea. 3. In conclusion, i.v. infusion of nitroglycerine is an effective, safe and alternative therapy for severe pre-eclampsia.

Human MUC4 mucin induces ultra-structural changes and tumorigenicity in pancreatic cancer cells.

MUC4 is a type-1 transmembrane glycoprotein and is overexpressed in many carcinomas. It is a heterodimeric protein of 930 kDa, composed of a mucin-type subunit, MUC4alpha, and a membrane-bound growth factor-like subunit, MUC4beta. MUC4 mRNA contains unique 5' and 3' coding sequences along with a large variable number of tandem repeat (VNTR) domain of 7-19 kb. A direct association of MUC4 overexpression has been established with the degree of invasiveness and poor prognosis of pancreatic cancer. To understand the precise role of MUC4 in pancreatic cancer, we engineered a MUC4 complementary DNA construct, mini-MUC4, whose deduced protein (320 kDa) is comparable with that of wild-type MUC4 (930 kDa) but represents only 10% of VNTR. Stable ectopic expression of mini-MUC4 in two human pancreatic cancer cell lines, Panc1 and MiaPaCa, showed that MUC4 minigene expression follows a biosynthesis and localisation pattern similar to the wild-type MUC4. Expression of MUC4 resulted in increased growth, motility, and invasiveness of the pancreatic cancer cells in vitro. Ultra-structural examination of MUC4-transfected cells showed the presence of increased number and size of mitochondria. The MUC4-expressing cells also demonstrated an enhanced tumorigenicity in an orthotopic xenograft nude mice model, further supporting a direct role of MUC4 in inducing the cancer properties. In conclusion, our results suggest that MUC4 promotes tumorigenicity and is directly involved in growth and survival of the cancer cells.

Medicamentos disponibles en pediatría para el tratamiento de la enfermedad por reflujo gastroesofágico / Paediatric drugs available for the treatment of the gastroesophageal reflux disease

Se analiza la oferta del mercado farmacéutico español a la hora de cubrir el tratamiento de la Enfermedad por Reflujo Gastroesofágico (ERGE) en la población pediátrica. Para ello se realiza una revisión de las especialidades correspondientes a los grupos A03AF, A02BA y A02BC, a partir del catálogo de especialidades farmacéuticas del Consejo General de Colegios Farmacéuticos, en la que se atendió a: - Dosis indicada en el niño, en caso de ser un fármaco de uso pediátrico.- Formas farmacéuticas en que se presentan estos fármacos. A partir de esta revisión se establecen dos grupos: El 44 por ciento de los fármacos implicados en el tratamiento de la ERGE no se dispone de estudios en la población pediátrica. El 33 por ciento de los AH2 y el 40 por ciento de los IBP son utilizables en niños. Ningún IBP posee presentación correctamente diseñada para la población pediátrica. Se llega a la conclusión, de que el mercado actual no dispone de medicamentos correctamente diseñados para pediatría en las terapias más efectivas en el tratamiento de la ERGE (AU)

Intrinsic fluorescence of enzymes and fluorescence of chemically modified enzymes for analytical purposes: a review.

In recent years our research group has developed new alternatives for fluorescence enzymatic determinations. First, we observed that the intrinsic fluorescence of enzymes changes during enzymatic reactions, proportionally to the substrate concentration, avoiding the combination of the enzymatic reaction with a fluorophore-involving reaction. The main disadvantage of this method is that the excitation and emission wavelengths of the enzymes are in the UV region of the spectrum. An alternative to overcome this problem consisted of covalently bonding the enzyme to a fluorophore. In this paper, an overview is given of all of the applications and future developments on both types of alternatives that we have developed. Apart from the analytical characteristics of the methods, we have also reviewed all of the information about mathematical models we have elaborated to date.

Efficacy of human recombinant DNase in pediatric patients with cystic fibrosis.

BACKGROUND: Most respiratory complications in cystic fibrosis (CF) arise from abnormally viscid mucus, and rhDNase has shown to be effective in enhancing mucous clearance. We explored the responses to rhDNase in a Mexican population of CF patients. METHODS: Patients with CF received aerosolized rhDNase (2.5 mg daily) during 3 months, followed by daily aerosolized placebo during 3 months. RESULTS: A total of 21 CF patients entered the study (11.1 +/- 0.5 years of age, mean +/- SEM, 10 girls): 15 patients (71%) had basal forced vital capacity (FVC) higher than the 70% predicted value, and the remainder of the patients had an FVC of between 30 and 70%. As a group, rhDNase progressively increased the forced expiratory flow at 1 sec (FEV1) as well as the FVC, reaching statistical significance (p <0.005) at the end of the third month of treatment. Sputum production and difficulty to expectorate or to breathe also improved during the rhDNase treatment period (p <0.05 to p <0.001). All these changes progressively decreased to basal values after 3 months with aerosolized placebo. Adverse reactions were almost null, with a sole patient reporting dysphonia. CONCLUSIONS: Aerosolized rhDNase was effective in progressively improving respiratory function and symptoms in most CF patients.

Fetal amniotic adhesions. Their topographic concordance with regionally clustered malformations.

BACKGROUND: The amniotic band disruption complex (ABDC) has been segregated recently into various phenotypes. In view of the pathogenic mechanisms that have been proposed, this study was designed to assess if it is one variable process or is composed of several distinct complexes. METHODS: The 48 cases of fetuses with bands or placenta attached to fetal parts cited in this paper included nine new cases and 39 from the literature. They were organized first according to the embryonal topography of the malformations, then according to the position of the adhesions, and finally by the assessment of distances between the cases and between the malformations using the squared Euclidean distances for binary variables and cluster analysis. RESULTS: In all three analyses, three groups were identified: 1) fetuses with cephalo-thoracic anomalies; 2) fetuses with caudal anomalies, and 3) fetuses with mixed anomalies. Nonetheless, overlap among the three groups was apparent. Thus, while fetuses with amniotic bands form three clusters, it appears that these are part of a spectrum and should be considered as variable manifestations of a single entity resulting from a single pathogenetic mechanism. An association was established between the localization of the adhesions and the malformations in various axes. Abdominoschisis, however, was not particularly related to adhesions at one or the other end of the fetus; a short umbilical cord was an almost universal finding. Single umbilical artery (SUA) was especially related to caudal adhesions and malformations (p = 0.004 and 0.001), as well as abdominoschisis (p = 0.002) and agenesis of the abdominal organs (p = 0.008). CONCLUSIONS: The association between amniotic adhesions to the fetus and multiple malformations occurring predominantly in the same area suggest that the former are the cause of the latter. The association of abdominoschisis, as well as a short umbilical cord, with malformations and adhesions in all areas, suggests that these are secondary phenomena to generalized embryonal and fetal tension. SUA, however, with a specifically regional association, is more likely to be due to disruption from exposure in cases with abdominoschisis, often accompanying the loss of abdominal organs.

[Fluorosis in primary dentition in a region with endemic water fluoride]. / Fluorosis en dentición temporal en un área con hidrofluorosis endémica.

OBJECTIVE: The aim of the present study was to estimate the prevalence of dental fluorosis in primary dentition of a San Luis Potosi children population, and its association to fluoride concentration in drinking water and urine. An additional objective was, to develop, validate, and test a specific index for dental fluorosis in primary dentition. MATERIAL AND METHODS: From May 1997, to January 1999, we conducted a cross-sectional study to assess the prevalence of dental fluorosis in primary dentition. Study subjects were 100 children aged 3-6 years, selected at random from three kindergartens in three risk areas of San Luis Potosi. The specific index of dental fluorosis for primary dentition (Dental Fluorosis for Primary Dentition Index--DFPDI) was validated by estimating fluoride concentrations in enamel of teeth with and without dental fluorosis. The Kruskal-Wallis test was used to assess the association between fluoride concentrations in drinking water and urine, with dental fluorosis; the association between risk area and dental fluorosis was assessed with the Mantel-Haenszel chi 2 test. RESULTS: The prevalence of dental fluorosis in primary dentition was 78%; primary molars were most affected in both maxillae and the predominant color was a non-glossy white appearance. We found a strong direct correlation (r = 0.93) between fluoride concentrations in primary teeth and the DFPDI. Associations were found between fluoride concentrations of drinking water and urine, with dental fluorosis (Kruskal-Wallis p = 0.00001), and between risk area and dental fluorosis (Mantel-Haenszel chi 2 p = 0.00001). CONCLUSIONS: DFPDI allowed adequate identification and grading of dental fluorosis in primary dentition. It is important to detect the initial toxic effects of fluoride exposure to predict dental fluorosis in permanent dentition and skeletal fluorosis.

[Consistency and validity of the evaluation of the clinical chart]. / Consistencia y validez en la evaluación del expediente clínico.

OBJECTIVE: Assess the degree of external consistency and validity of the EXP CLIN instrument has for measuring the quality information contained in medical charts. MATERIAL AND METHODS: In a transverse comparative study, two hundred and twelve clinical charts were randomly selected belonging to patients seen at a pediatric hospital. The charts were assessed using the EXP-CLIN for phases: 1) internal assessment: by hospital personnel of the pediatric hospital, and, II) external assessment: by personnel from other hospitals. The results were analyzed using the concordance method. RESULTS: The concordance percentages were found to be 76% for medical charts and medical notes related with the process of diagnosis-treatment, as well as the general characteristics of the clinical chart. The concordance percentages average was 88%, supporting the idea that when the EXP-CLIN instrument is applied twice to the same chart, good concordance is obtained between the two measures. CONCLUSIONS: Given that the application of the instrument documented a good level of external consistency, its use is justified for assessing the quality of the information contained in the charts of the patients seen at our unit.

[Classification by levels of clinico-epidemiological research designs]. / Clasificación en niveles de los diseños de investigación clínico-epidemiológicos.

The objective was to identify the characteristics of epidemiologic designs enabling their classification. A critical review of the literature in the clinical epidemiologic area was done to establish the main differences between designs. A meeting with experts to discuss this controversial topic and obtain criteria by consensus was organized. We propose an integral classification based on levels with two fundamental shafts: intervention and explanatory reasoning.

Behavioral and physiological sex differences observed in an animal model of fulminant hepatic encephalopathy in the rat.

Hepatic encephalopathy is characterized by a number of neuropsychiatric and motor disturbances observed in patients with liver dysfunction. The purpose of this study is to fully characterize behavioral and physiological sex differences in an animal model of fulminant hepatic encephalopathy (FHE). Male and female rats were administered thioacetamide (600 mg/kg) via i.p. (intraperitoneal) injection at Hours 0 and 24 and allowed to progress into the four stages of FHE. Male rats reached all four stages of FHE significantly earlier than female rats (p < 0.05). The performance of the male rats deteriorated more quickly (p < 0.05) than that of the females in all of the sensory and motor behavioral tests. Sex differences were observed in the liver enzymes of the FHE rats. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase were significantly greater (p < 0.05) in male rats in all four stages of FHE. Significant increases were also observed in the levels of direct and total bilirubin (p < 0.05). Neuronal damage was observed in the CA1 and CA2 regions of the hippocampus. In the CA1 region, male rats displayed greater pathological changes in Stages III and IV (p < 0.05) than female rats. The damage in the CA2 region was only observed in Stage IV male rats. Our data indicate that observable behavioral and physiological sex differences occur in thioacetamide-induced FHE in the rat.

Timing of breast cancer surgery during the luteal menstrual phase may improve prognosis.

A meta-analysis has been performed of available retrospective reports concerning the 5-15 year disease-free survival of 5,353 premenopausal breast cancer patients operated on either during the follicular or luteal phases of the menstrual cycle. Patients with surgery performed during the luteal phase (d 14-23+) had an overall mean 5% benefit compared to those operated on the follicular phase determined by date of onset of their last menstrual period p = 0.02 by Wilcoxon 2-tailed test. When nodal invasion was reported, node-negative patients had a 5 +/- 2% SEM benefit. Patients with positive nodes had a 34 +/- 3% SEM increase in survival (p = .05), including both estrogen and progesterone-receptor negative as well as positive neoplasms. In 3 of 4 reports from major cancer treatment centers, each containing 249-1175 cases, risk of recurrent cancer and/or death increased 5 to 6-fold after 10 years for women receiving surgery during d 7-14 of their cycle, compared to those resected during d 21-36. Improvement in prognosis was greatest for patients with the highest risk of recurrence due to node-invasive disease and receptor dysfunction. Several cell-mediated immunologic factors inimical to metastasis are maximal in the luteal phase of the menstrual cycle, including natural killer cell activity. A new drug which augments natural killer cell activity may extend any beneficial survival results to post-menopausal breast cancer patients in the future. We conclude that accurate menstrual histories should be included in the medical record from now on for all premenopausal women receiving any surgical procedure upon the breast, preferably using an objective method of determining the date of last ovulation. Prospective randomized clinical trials are necessary to determine the full extent of survival benefits of late luteal surgical timing.

Timing of breast cancer surgery during the luteal menstrual phase may improve prognosis.

A meta-analysis has been performed of available retrospective reports concerning the 5-15 year disease-free survival of 5,353 premenopausal breast cancer patients operated on either during the follicular or luteal phases of the menstrual cycle. Patients with surgery performed during the luteal phase (d14-23+) had an overall mean 5% benefit compared to those operated on the follicular phase determined by date of onset of their last menstrual period p=0.02 by Wilcoxon 2-tailed test. When nodal invasion was reported, node-negative patients had a 5 + 2% SEM benefit. Patients with positive nodes had a 34 + 3% SEM increase in survival (p = .05), including both estrogen and progesterone-receptor negative as well as positive neoplasms. In 3 of 4 reports from major cancer treatment centers, each containing 249-1175 cases, risk of recurrent cancer and/or death increased 5 to 6-fold after 10 years for women receiving surgery during d7-14 of their cycle, compared to those resected during d21-36. Improvement in prognosis was greatest for patients with the highest risk of recurrence due to node-invasive disease and receptor dysfunction. Several cell-mediated immunologic factors inimical to metastasis are maximal in the luteal phase of the menstrual cycle, including natural killer cell activity. A new drug which augments natural killer cell activity may extend any beneficial survival results to post-menopausal breast cancer patients in the future. We conclude that accurate menstrual histories should be included in the medical record from now on for all premenopausal women receiving any surgical procedure upon the breast, preferably using an objective method of determining the date of last ovulation. Prospective randomized clinical trials are necessary to determine the full extent of survival benefits of late luteal surgical timing.

Growth hormone-releasing hormone depletion in the female rat: similarities to aging.

The age-related decline in growth hormone (GH) secretion has been largely attributed to age-related degeneration of hypothalamic growth hormone-releasing hormone (GHRH)-producing neurons. GH decline has recently been linked to age-related bone changes in humans. Bone loss and decreased bone strength are common in aging rats and humans, but density of remaining mineral tissue is known to be increased. The effect of induced hypothalamic GHRH deficiency on bone was assessed, and similarities between bone changes encountered and those taking place in aging were identified. Female rats received monosodium glutamate (MSG) following birth, and they were euthanized at 19 weeks of age. Femurs from MSG-treated rats had greater mineral density (p < .05), greater mineral/matrix ratio (p < .01), lower mineral apposition rate (p < .005), and lower bone formation rate (p < .05). These results suggest that hypothalamic GHRH decline plays a substantial role in the development of bone pathology similar to that observed in aging individuals.

17 beta-Estradiol inhibits the production of dopamine by the tuberoinfundibular dopaminergic neurons of the male rat.

Previous work in our laboratory suggests that the indirect stimulation of prolactin gene transcription observed in male rats between 3 and 6 h following estrogen injection results from an inhibition of dopamine release from the tuberoinfundibular dopaminergic neurons. To evaluate further the role of dopamine in the regulation of prolactin gene transcription by estrogens, we have examined the acute effects of 17 beta-estradiol (E2) on dihydroxyphenylalanine accumulation in the arcuate median eminence region and the amount of dopamine associated with the arcuate median eminence region. Dihydroxyphenylalanine accumulation in the arcuate median eminence region was unaffected when examined 2 h following a single injection of E2 (10 micrograms), and was reduced by 60% when examined 4 h following E2 treatment. When examined 4 h after E2 injection, dopamine content in the arcuate median eminence region was significantly increased. These data suggest that estrogens exert acute inhibitory effects on the tuberoinfundibular dopaminergic neurons of the male rat, and further support the assertion that the indirect stimulatory actions of estrogens on prolactin gene transcription result from inhibition of hypothalamic dopamine production.

A quantitative evaluation of magnetic resonance image signal changes of the brain in chronic hepatic encephalopathy.

Hyperintensity in the basal ganglia of patients with serious liver disease is a common finding on T1-weighted magnetic resonance images. In this study, we used optical densitometry to quantitatively evaluate the hyperintense magnetic resonance image signal changes in the various regions of the brain of patients with chronic hepatic encephalopathy. The incidence and morphological distribution of the magnetic resonance signal changes were evaluated from T1-weighted magnetic resonance images of the brain from seven non-alcoholic patients and six healthy controls. Significant differences (p < 0.05) between the patient group and controls were found in the limbic system (hippocampus, temporal lobe, cingulate gyrus, and fornix), extrapyramidal system and associated myelinated pathways (lentiform nucleus, tectum, tegmentum, cerebral peduncles, internal capsule and the corpus callosum). No measurable differences were observed in the frontal, parietal, and occipital cortex, or the dorsomedial thalamus. The presence of the high signal intensity changes on T1-weighted magnetic resonance image suggests that characteristics alterations occur in functional regions of the brain in chronic hepatic encephalopathy.

Distribution of zinc metallothionein I mRNA in rat brain using in situ hybridization.

Metallothionein (MT) isoforms I and II were first identified and characterized in our laboratories in several regions of brain, in hippocampal neurons in primary culture, and in retinoblastoma and neuroblastoma cell lines. In this study, by having employed the MT-I cDNA as a probe, we sought to gain additional insight about the function of MT by discerning the regional distribution of its mRNA. Northern blot analyses of brain mRNA revealed that the administration of zinc enhanced dramatically MT-I mRNA (570 bp). The in situ hybridization study revealed that MT-I mRNA was located in several areas of brain, with the highest concentrations found in the cerebellum, hippocampus, and ventricles. The results of these studies are interpreted to suggest that zinc enhances the synthesis of MT mRNA and MT in turn may participate in zinc associated functions in neurons.

Is glutamate-induced reduction in growth hormone-releasing hormone a neuroendocrine model of aging in the rat?

Decreases in serum growth hormone (GH) associated with aging may be a result of age-related degenerative changes in neurons of the hypothalamus resulting in a decrease of growth hormone-releasing hormone (GHRH). This study tests the utility of glutamate-induced hypothalamic neuronal degeneration in the rat as a neuroendocrine model of aging. Sprague-Dawley female rats received three 4-mg/g monosodium glutamate (MSG) subcutaneous injections during the first 5 days following birth. Animals were anesthetized at 60 days of age and challenged with GHRH. Blood samples were assayed for GH. Serum GH levels following GHRH challenge in the MSG-treated group rose more slowly and to a lower peak than in controls (P < 0.05). There was no difference in total GH release over the 1-hr interval following challenge. MSG-treatment of animals resulted in lower gross body (P < 0.05) and kidney (P < 0.05) weights with no difference in ovary or adrenal weights. There were also no differences in pituitary GH or total protein content between the groups. Analysis of femurs in the MSG animals revealed both a lower bone strength (P < 0.05) and maximum mid-shaft diameter (P < 0.05), but no difference in length, mineral/matrix ratio, or tissue density. Our data suggest that the degree of neuroendocrine disruption resulting from neonatal MSG administration mimics in part systemic changes commonly observed in aged animals. Hence, definite similarities exist between MSG treatment and the documented aging-related changes in hypothalamic GHRH content and GH regulation in the rat.