A novel mutation in the antithrombin gene (insT 7429-30) causes superior mesenteric vein thrombosis.
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Antithrombins↗
Biomedical subjects
I Sánchez
Publications and source records attributed to I Sánchez.
Multislice CT in graft vascular disease. A pilot study.
INTRODUCTION: Graft vessel disease (GVD) is one of the main long-term complications in heart transplant (HT) patients. At present, the diagnosis of this complication requires invasive procedures. Multislice CT is an emerging technique that allows visualization of the coronary anatomy, including the vascular lumen and wall thickness. Our objective was to establish the value of 16-detector multislice CT in the detection of GVD, compared with angiography and intravascular ultrasound (IVUS). PATIENTS AND METHODS: We studied 32 HT patients, who had a mean follow-up of 2016 days. CT was performed 24 hours prior to angiography, associated with IVUS if the latter proved normal. Comparisons were subsequently made using contingency tables to establish the sensitivity, specificity, and predictive values of the CT. RESULTS: Angiography was not performed on two patients, and eight were excluded from CT assessment due to serum creatinine values >1.5 mg/dL. Comparison of the CT findings with the invasive techniques yielded a sensitivity of 50%, a specificity of 81%, a negative predictive value of 81%, a positive predictive value of 50%, and a precision of 72%. CONCLUSIONS: Our results suggested good performance of the technique in screening for GVD because a high negative predictive value was recorded. We plan to increase the number of patients and use the 64-detector CT system to ensure greater time and spatial resolution.
Follow-Up Studies↗
[Home ventilatory assistance in Chilean children: 12 years' experience].
OBJECTIVE: Home ventilatory support systems are a treatment option for patients with severe chronic respiratory failure. The objective of the present study was to characterize the children admitted to a home ventilatory assistance program. PATIENTS AND METHOD: The home ventilation program was created by our hospital to coordinate professional and technological support for chronic ventilator-dependent children. We revised and updated information on patient characteristics, type of assisted ventilation, respiratory morbidity, and equipment failures between 1993 and 2004. RESULTS: Follow-up of 35 children (18 male) was carried out by our hospital staff. Median age upon admission to the program was 12 months (range, 5 months to 14 years). Median length of time in the program was 21 months and we were able to wean 40% of patients from ventilators. Six patients died. The main indications for assisted ventilation were neuromuscular disease (12 cases), airway abnormality (11 cases), cardiopulmonary disease (7 cases), and hypoventilation syndrome (5 cases). The types of assisted ventilation used were continuous positive airway pressure (in 17 cases), bilevel positive pressure (in 8 cases), and synchronized intermittent mandatory ventilation (in 10 cases). Invasive ventilation via a tracheostomy was used in 26 cases. The use of noninvasive ventilation increased in the last 4 years. Respiratory morbidity (pneumonia and bacterial tracheitis) was the most frequent cause of hospitalization and the annual rate of such episodes was 1.6 per child. The annual rate of hospitalization due to equipment failures was 0.1 per child. CONCLUSION: The program provides safe and necessary home ventilatory assistance for children with severe chronic respiratory failure. The professional support that home hospitalization offers had a positive effect on outcome in these children. It is important to take our experience into account in creating a Chilean national home ventilatory assistance program.
Adolescent↗
Dobesilate inhibits the activation of signal transducer and activator of transcription 3, and the expression of cyclin D1 and bcl-XL in glioma cells.
OBJECTIVES: Because fibroblast growth factor (FGF) causes the intracellular accumulation of activated signal transducer and activator of transcription 3 (STAT3), we assessed whether dobesilate, a synthetic FGF inhibitor that has been reported to show antiproliferative and proapoptotic activities in glioma cell cultures, down-regulates the STAT3 signaling pathway in growing cultures of those cells. Because STAT3 signaling pathway plays pleiotropic roles in tumor proliferation, maintenance of STAT3 in its inactive state may prevent glioma growth and spreading. METHODS: Rat glioma C6 cells were treated with dobesilate and cultures were evaluated immunocytochemically for STAT3 activation and enhancement of the expression rate of cyclin D1 and bcl-XL. RESULTS: Dobesilate abrogates the accumulation of activated STAT3 in glioma cells. The decrease in the intracellular levels of activated STAT3 by the dobesilate treatment runs parallel with a significant attenuation of cyclin D1 and bcl-XL expression. CONCLUSION: Treatment with inhibitors of FGF down-regulates the STAT3 signaling pathway. These alterations could be correlated to the already observed inhibition of cell proliferation and promotion of apoptosis in glioma cell cultures by dobesilate. The reported results may open new avenues for developing new treatments against these tumors.
Animals↗
IGF-I and vasoactive intestinal peptide (VIP) regulate cAMP-response element-binding protein (CREB)-dependent transcription via the mitogen-activated protein kinase (MAPK) pathway in pituitary cells: requirement of Rap1.
In previous studies we demonstrated that vasoactive intestinal peptide (VIP) mediation, and interactions between mitogen-activated protein kinase (MAPK) and cAMP/protein kinase A (PKA) signaling pathways are implicated in insulin-like growth factor I (IGF-I)- and VIP-induced lactotroph proliferation. These facts led us to investigate the intracellular mechanisms involved in IGF-I- and VIP-induced lactotroph proliferation. Exposure of cultured male rat pituitary cells to IGF-I (10(-7) M) or VIP (10(-7) M) stimulated the MAPK cascade. Studies in GH4C1 cells, with an expression vector for Rap1 GTPase-activating protein (Rap1 GAP1), demonstrated reduced VIP-induced MAPK activation, indicating that VIP-dependent activation of the extracellular signal-regulated kinase (ERK) pathway requires PKA-Rap1 signaling. IGF-I induced cAMP-response element (CRE)-binding protein (CREB) phosphorylation through the Ras-MAPK pathway, whereas VIP phosphorylated CREB directly via PKA. The mechanisms that regulate IGF-I-and VIP-CREB-dependent gene transcription were examined using GH4C1 cells transiently transfected with a CRE reporter gene. IGF-I and VIP stimulation of CRE-mediated transcription required activation of both Ras-MAPK and cAMP/PKA signaling. This activation was blocked in the presence of Rap1 GAP1. In summary, we showed that IGF-I and VIP stimulated MAPK activity and the phosphorylation of CREB in pituitary cells. Furthermore, VIP-dependent activation of PKA-Rap1-ERK pathways mediated VIP and IGF-I effects on CREB-dependent transcription in GH4C1 cells. Thus, it is possible that VIP- and IGF-I-induced lactotroph proliferation may involve Rap1.
Animals↗
[Utility of bronchoalveolar lavage in immunocompromised children: diagnostic yield and complications].
OBJECTIVE: Immunocompromised children are at high risk for developing pneumonia due to opportunistic pathogens. The role of bronchoalveolar lavage (BAL) in the evaluation of such patients is still controversial. MATERIAL AND METHOD: We reviewed the hospital records of immunosuppressed patients with respiratory symptoms who had undergone BAL in the pediatric department of the Hospital Clinico de la Pontificia Universidad Católica of Chile. RESULTS: Sixty-eight BAL were performed on 54 children (mean age: 7.5 years) receiving wide-spectrum antibiotic treatment. The most frequent respiratory signs and symptoms were fever (90%) and cough and respiratory distress (81%); 18% had neutropenia and 43% thrombocytopenia. A specific pathogen was identified in BAL samples for 25 patients (37%). The pathogens isolated were bacteria in 21 cases, viruses in 6, Pneumocystis carinii in 5, fungi in 4, and Mycobacterium tuberculosis in one. Fourteen (19%) of the children who underwent BAL were on mechanical ventilation. Outcome was satisfactory in all cases. Twenty-one complications were recorded, 17 of which were minor (mild hypoxemia or fever) and 4 major, requiring tracheal intubation. No deaths were recorded. CONCLUSIONS: Evaluation by fiberoptic bronchoscopy together with BAL proved to be a safe procedure with an adequate diagnostic yield that made it possible to determine the etiology of the pulmonary infiltrates seen in chest x-rays. Both positive and negative results of BAL were useful for treating the patients.
Adolescent↗
Relevance of the pH probe in sleep study analysis in infants.
BACKGROUND: To establish the relationship between sleep apnoea and gastro-oesophageal reflux in infants and describe the clinical, demographic and pHmetric profile and the characteristic of the sleep polysomnography with a pH probe. METHODS: A total of 102 consecutive patients were evaluated. Parents were requested to fill out a questionnaire about symptoms and previous therapy. Gastro-oesophageal reflux was considered abnormal when the percentage of time with pH less than 4 was higher than 4% of total sleep time. RESULTS: A total of 102 infants were enrolled, 53% males. Seventy-four per cent of the infants were full-term babies. At the moment of the polysomnography, the mean age of the sample was 2.6 months. Suspicion of apnoea was the most common clinical diagnosis prior to the study. Only two infants have abnormal electroencephalogram. Mild gastro-oesophageal reflux was seen in 37 (36%) infants, while 22 (21.5%) did not have any reflux episode, and the remaining 43 (42%) infants had reflux index in the pathologic range. Only one patient had an unequivocal temporal relationship between acid oesophageal reflux and respiratory pause with oxygen desaturation. DISCUSSION: Infants with history of apnoea or acute life threatening event frequently had gastro-oesophageal reflux episodes which did not correlated with respiratory events, suggesting that gastro-oesophageal reflux and apnoea often occur in the same infant as two separate events.
Chile↗
Polyphasic study of the genetic diversity of lactobacilli associated with 'Almagro' eggplants spontaneous fermentation, based on combined numerical analysis of randomly amplified polymorphic DNA and pulsed-field gel electrophoresis patterns.
AIMS: The goal of this study was to assess the genetic diversity of lactic acid bacteria (LAB) from the complex natural ecosystem present in the spontaneous fermentation of 'Almagro' eggplants by a polyphasic approach based on molecular techniques. METHODS AND RESULTS: Randomly amplified polymorphic DNA (RAPD) and pulsed-field gel electrophoresis (PFGE) were applied to 149 Lactobacillus isolates obtained from that fermentation process. Two random primers, OPL-05 and ArgDei-For, and two rare-cutting enzymes, SfiI and SmaI, chosen after preliminary testing on the basis of band intensity and distribution, were used. RAPD and PFGE generated electrophoretic patterns suitable for strain discrimination, but further discrimination was achieved when combined numerical analysis of the results from both methods and the results previously obtained by SDS-PAGE whole cell protein analysis, was carried out. The findings indicated a considerable degree of genomic diversity in the LAB microbiota studied and especially in the Lactobacillus plantarum isolates. In terms of species assignment, the polyphasic study allowed a definite and well-founded identification of 98.7% of the isolates. CONCLUSIONS: The combined numerical analysis of RAPD and PFGE patterns represented a useful tool to discriminate the diversity of the Lactobacillus strains responsible for the spontaneous fermentation of this pickle. The species identification and strain typing results from the polyphasic study were regarded as the most exact compromise yielding the fewest contradictions based on the available data. SIGNIFICANCE AND IMPACT OF THE STUDY: Combined numerical analysis of RAPD-PCR and PFGE patterns has not yet been employed to study the genetic diversity of LAB from an ecosystem like that found in fermenting vegetables.
Cluster Analysis↗
IGF-I inhibits apoptosis through the activation of the phosphatidylinositol 3-kinase/Akt pathway in pituitary cells.
In previous studies we demonstrated that IGF-I induces proliferation of pituitary lactotrophs. In addition to its mitotrophic actions, IGF-I is known to prevent apoptosis induced by diverse stimuli in several cell types. In this study, we investigated the action of IGF-I on pituitary cell survival and the intracellular signaling transduction pathway implicated in this effect. Treatment of cultured male rat pituitary cells with IGF-I (10(-7) M) for 24 h prevented pituitary cell death induced by serum deprivation. The protective effect of IGF-I was blocked by phosphoinositide 3-kinase (PI3-kinase) inhibitor, LY294002, but was unaffected by PD98059, which inhibits MAP/ERK kinase (MEK1). IGF-I activation of PI3-kinase induced the phosphorylation and activation of the serine/threonine kinase Akt. Moreover, IGF-I increased the phosphorylation of the pro-apoptotic factor Bad and the levels of the anti-apoptotic protein Bcl-2 through the PI3-kinase pathway in primary pituitary cells.
Animals↗
Evaluation of the impact of a pharmaceutical care program in children with asthma.
The objective of this study was to evaluate the impact of a pharmaceutical care program on children with asthma. A comprehensive asthma education and monitoring program that includes basic asthma knowledge, symptoms and exacerbation evaluation, pharmacotherapy assessment including inhaler technique, and quality of life measurements was developed and applied in an outpatient paediatric clinic of the Catholic University of Chile. All patients with moderate asthma scheduled for outpatient visits with their internist over a 1-year period were referred for pharmacist intervention. Patients (aged 7-17) with moderate asthma attending the clinic were allocated to the intervention (group A) or control group (group B). Intervention patients were educated on their disease, pharmacotherapy, self-management, and inhalation techniques. The group B were children with their regular treatment for asthma but without pharmaceutical intervention. A paediatric asthma quality of life questionnaire (PAQLQ) was applied to both groups at 0, 2, and 9 weeks to assess the quality of life. Spirometry was done at the beginning and at the completion of the 9-week study. Beta-agonists used by each patient were also recorded. Eleven children (10.0+/-0.7 years) were included in the pharmaceutical care program, and ten children (9.9+/-0.6 years) in group B. For the individual domains of activities (A), emotions (E), and symptoms (S) there was a significant improvement in the children who received pharmaceutical care in comparison with those who did not receive it. The scores of group B did not change during the 9 weeks of follow-up. There were no significant changes in spirometric values in either group.
Analysis of Variance↗
Tracheal and lung sounds repeatability in normal adults.
Tracheal and lung sounds measurements for clinical applications depends on their intrasubject repeatability. Our objectives were to characterize tracheal and lung sounds and to investigate the temporal variability in normal adults. Tracheal sounds were studied in 7 subjects and lung sounds in 10 adults. Acoustic measurements were done in five occasions over a month for tracheal sounds and on seven occasions over a year for lung sounds. Sounds were recorded using contact sensors on the suprasternal notch and on the posterior right lower lobe. Subjects breathed through a pneumotachograph at flows of 0.9-1.1 l/s. Signals were low-pass filtered, amplified and Fourier analysis was applied to sounds within a target flow range. We measured the frequencies below which 25% (F25), 50% (F median), 75% (F75) and 99% (SEF99) of the spectral power between 100 and 2000 Hz. There were no differences between the measurements obtained at different days comparing each subject (P = ns, ANOVA). Our results show that the spectral pattern of tracheal and lung sounds are stable with low intrasubject variability.
Adult↗
New advances in the field of calcium channel antagonists: cardiovascular effects and structure-activity relationships.
In the last 15 years, calcium channel blockers have been widely used for treating cardiovascular diseases. These agents are a heterogeneous group of drugs with differing cardiovascular effects, and are effective in the treatment of angina and hypertension. These synthetic compounds bind separately with receptor sites located in or near the calcium channel, at molecular sites still to be fully identified. Verapamil, nifedipine and diltiazem are the most representative calcium channel blockers and used as prototypes for the design and development of new anticalcium molecules with potential efficacy and reduced toxic effects. There are three different types of voltage-operated calcium channels (VOCs): L-type, T-type and N-type, which are considered extra-cellular, but some anti-calcium agents as bepridil possess potential intracellular calcium activity. Many synthetic compounds containing heterocyclic ring in their structures have attracted considerable interest since current studies revealed their mechanisms and sites of action. This article reviews the new advances in the calcium channel antagonist group, showing new structures with longer-acting and higher vascular selectivity.
Angina Pectoris↗
[Role of flexible bronchoscopy in the re-expansion of persistent atelectasis in children].
OBJECTIVE: To evaluate the efficacy of flexible bronchoscopy plus bronchoalveolar lavage for the reexpansion of persistent atelectasis (course longer than 3 weeks) in children. PATIENTS AND METHODS: Retrospective review of the records of 83 children who underwent flexible fiberoptic bronchoscopy plus bronchoalveolar lavage for persistent atelectasis. Three categories of evolution were established for radiologic assessment: a) full re-expansion (full improvement over the initial image); b) partial re-expansion (decreased atelectasis of between 50% and 100%); and c) no change (if the decrease was less than 50% of the initial image). RESULTS: Endoscopy revealed mucus plugs in 54 patients (65%); bronchial malformations in 16 (19%); bronchial stenosis in 5 (6%); normal airways in 5 (6%) and other findings in 3 (4%). Radiologic changes after bronchoscopy showed full expansion for 34 patients (41%), partial re-expansion for 28 (34%) and no changes for 21 (25%). CONCLUSION: Flexible bronchoscopy plus bronchoalveolar lavage for the re-expansion of persistent atelectasis is useful in a high percentage of children.
Adolescent↗
Efficacy of nebulized epinephrine versus salbutamol in hospitalized infants with bronchiolitis.
We enrolled 30 infants (median age 3 months, range 1-12 months), hospitalized for bronchiolitis in a randomized double-blind trial, to examine the efficacy and safety of nebulized epinephrine compared to salbutamol. Once admitted, patients were treated with either nebulized 0.5 mg of an 0.1% epinephrine solution (0.5 mL in 3.5 mL normal saline (NS)) or 2.5 mg nebulized salbutamol (0.5 mL in 3.5 mL NS). They were evaluated daily before and after nebulization until discharge. The outcome measures used were: baseline clinical score (based on respiratory rate, subcostal retraction, presence of wheezing, and O2 requirement), change in clinical O2 score after nebulization, duration of O2 therapy, and duration of hospitalization. A significant improvement in the clinical score was noted on the first day of hospitalization in subjects receiving epinephrine (P = 0.025); that change was not seen in those on salbutamol (P = 0.6). Nebulized epinephrine decreased the baseline clinical score faster than salbutamol (P = 0.02), though on the fourth study day there was no significant difference between the two scores. On the fourth and fifth days of study there were more patients hospitalized in the salbutamol group than in the epinephrine group (P = 0.03 vs. P = 0.025). No adverse effects were associated with nebulized therapy. We conclude that nebulized epinephrine is a more effective agent than salbutamol in the initial treatment of bronchiolitis and is equally safe.
Administration, Inhalation↗
In vitro cytotoxicity of flavonoids against MK2 and C6 tumour cells.
The cytotoxic effect of five flavonoids isolated from the aerial parts of the Asteraceae family of plants were studied in vitro using LLC-MK2 and C6 glial cells. Agehoustin A was shown to be cytotoxic for both cells (71% or 67% cell death). Agehoustin B and artemetin, which lack a methoxy group at C-8 (RI), were not cytotoxic for the cells (19% and 16% cell death). The three flavonoids showed considerable suppressive effects on LLC-MK2 and C6 cell growth. Lucidin-dimethylether and gnaphaliin were also not cytotoxic for cells but they had no suppressive effect on cell growth. The results show a structure-cytostatic activity relationship. We suggest that the methoxy group on C-8 and on the B ring are responsible for death cell.
Animals↗
[Pilot study with the monoclonal antibody IOR-C5 as a potential agent of radioimmunoscintigraphy in colorectal cancer].
UNLABELLED: IOR C-5 is a G1 immunoglobulin type intact murine monoclonal antibody (MAb) that was developed in the Center of Molecular Immunology in Havana City, Cuba. In immunohistochemical studies, this demonstrated a significant affinity for the epithelial tissues so that it was used in a pilot clinical study to perform a radioimmunoscintigraphy of the colorectal primary tumors and their locoregional recurrences. It was labeled with 99mTc using the Schwarz method, with a > 95% performance. Planar images of the chest, abdomen and pelvis were performed at 10 minutes, 4-6 hours and 18-24 hours post-injection in the anterior and posterior projections and the SPECT was performed 4-6 hours and 18-24 hours post-injection of 1.85 GBq 99mTC. This study has aimed to verify in vivo the capacity of ior-C5 MAb to accumulate in the malignant colorectal lesions. ior-C5 accumulated in 5 out of the 7 patients who were studied and who were suffering from colorectal cancer or in whom there was suspicion of recurrence. There was a negative case of primary tumors, which was an adenocarcinoma in situ in a tubular-papillary adenoma. The second case with a negative radioimmunoscintigraphy was a true negative case. CONCLUSIONS: It can be concluded that even though the number of patients is quite low, ior-C5 fulfilled the expectations of recognizing the epitope expressed in colorectal tumors in an in vivo human environment.
Adenocarcinoma↗
Antitumor agents. Synthesis and biological evaluation of new compounds related to podophyllotoxin, containing the 2,3-dihydro-1,4-benzodioxin system.
New compounds with naphtho-fused systems were synthesized and evaluated as antitumor agents. The naphtho-fused systems 6 and 7, synthesized from the hydroxy-acetal, exhibit antitumor activity. The bis(phenylthio) derivatives were considered as possible precursors for lignan lactones (11). The hydroxy-naphthalen 6 showed a significant antineoplastic activity.
Antineoplastic Agents↗