Expression profile of survivin in acute leukaemias: the importance of differential splicing.
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Biomedical subjects
Publications and source records attributed to I Castro.
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BACKGROUND: The site and distribution of inflammation in the airways of asthmatic patients has been largely investigated. Inflammatory cells are distributed in both large and small airways in asthma. It has been demonstrated that distal lung inflammation in asthma may significantly contribute to the pathophysiology of the disease. The upper airways have also been implicated in the overall asthmatic inflammation. Although it is now accepted that lung inflammation is not restricted to the intrapulmonary airways in asthma, little is known about cell distribution in the other lung compartments and their relation to the intrapulmonary airways. OBJECTIVE: We aimed to map the inflammatory process in fatal asthma (FA), from the upper airways to the lung parenchyma. METHODS: Eosinophil, neutrophil, mast cell and lymphocyte content were determined in nasal mucosa, the trachea, intrapulmonary airways and parenchyma (peribronchiolar and distal) of 20 patients with FA and 10 controls. RESULTS: Eosinophil content was higher in all studied areas in FA compared with controls (P<0.02). Mast cell content was higher in the outer area of larger airways, small membranous bronchioles and in peribronchiolar parenchyma of FA compared with controls (P<0.04). CD3+, CD4+and CD20+cells showed increased content in FA intrapulmonary airways compared with controls (P<0.05). There was a positive correlation between CD4+cell content in nasal mucosa and larger airways in asthmatics. Increased neutrophil content was observed only in peribronchiolar parenchyma of FA (P=0.028). CONCLUSION: Eosinophils present a widespread distribution within the respiratory tract in FA, from the nasal mucosa to the distal lung. The outer wall of small membranous bronchioles is the main site of inflammatory changes in FA. There is a localized distribution of alveolar inflammation at the peribronchiolar region for mast cells and neutrophils. Our findings provide further evidence of the importance of the lung periphery in the pathophysiology of FA.
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Measurement of radiation isocenter is a fundamental part of commissioning and quality assurance (QA) for a linear accelerator (linac). In this work we present an automated procedure for the analysis of the stars-shots employed in the radiation isocenter determination. Once the star-shot film has been developed and digitized, the resulting image is analyzed by scanning concentric circles centered around the intersection of the lasers that had been previously marked on the film. The center and the radius of the minimum circle intersecting the central rays are determined with an accuracy and precision better than 1% of the pixel size. The procedure is applied to the position and size determination of the radiation isocenter by means of the analysis of star-shots, placed in different planes with respect to the gantry, couch and collimator rotation axes.
OBJECTIVE: The effects of natural estradiol and progesterone replacement therapy on lipoprotein and cardiovascular parameters were assessed in 20 postmenopausal women with mild to moderate systemic arterial hypertension. DESIGN: After confirming hypertension in the absence of antihypertensive treatment, blood pressure control was achieved by administration of amlodipine at individually adjusted doses. Hormone replacement therapy (HRT) was introduced in a cyclic regimen (21 of 28 days) with percutaneous estradiol (1.5 mg/day) and vaginal micronized progesterone (100 mg/day). RESULTS: Blood pressure and mean heart rate remained unchanged during HRT. Serial echocardiograph scans showed no change in left ventricle mass, but a significant reduction in the thickness of the left ventricular posterior wall was observed. During treatment, patients showed little variation in total cholesterol levels (baseline: 199+/-10 mg/dl, 12 months: 202+/-11 mg/dl), as well as in high-density lipoprotein (53+/-2 to 50+/-3 mg/dl), low-density lipoprotein (122+/-10 to 118+/-11 mg/dl), and triglycerides (111+/-13 to 126+/-13 mg/dl). A subgroup of 10 patients with initial total cholesterol levels >200 mg/dl responded to HRT with a slight but significant decrease of cholesterol levels after 12 months (265+/-10 to 237+/-12 mg/dl, p<0.05, repeated measures ANOVA). HRT did not change mean antithrombin III levels and affected neither plasma renin activity nor aldosterone levels. CONCLUSION: These results suggest that the proposed HRT regimen with percutaneous estradiol associated with low-dose vaginal micronized progesterone could be a safe alternative for postmenopausal women with hypertension at least during the period required to treat menopausal symptoms.
The synthetic progestin, norethisterone (NET), has been reported as a contragestational postcoital agent in humans, rodents and rabbits. The effect and molecular mechanisms of NET and its A-ring reduced metabolites, 5alpha-NET and 3beta5alpha-NET, on the acrosome reaction (AR) are unknown. The aim of this study was to assess the effect of these compounds on an in vitro progesterone-induced AR in porcine spermatozoa. The spermatozoa were obtained from semen ejaculated by proven fertile adult pigs. Seminal plasma removed and incubated under capacitating conditions was performed in TALP-Hepes medium for 4 h. Progesterone (P4) and three different progestins: norethisterone (NET), 5alpha-norethisterone (5alpha-NET) and 3beta5alpha-NET were then added at equimolar doses, and the spermatozoa were incubated for 15 min. Double-staining with PSA-FITC and Hoechst-33258 assessed the AR and sperm viability. Both P4 and NET induced the AR, while 5alpha-NET not only did not induce this process, but was able to block the effect of P4 on the spermatozoa. 3beta5alpha-NET was not able to inhibit P4 action. These results suggest that NET and its A-ring reduced metabolites act in different ways on the progesterone-induced AR in porcine spermatozoa.
A multicentre, prospective, controlled study compared the clinical efficacy, safety and economic impact of a pharmacist intervention to promote sequential intravenous to oral clindamycin conversion. A total of 473 patients receiving intravenous clindamycin for at least 72 hours were included in the study. Two groups were established: an intervention group (204 patients) in which an informative sheet recommending the sequential treatment was provided, and a control group (269 patients). Clindamycin was prescribed for respiratory infections in 38.9% and for prophylaxis in surgery in 25.4% of the patients (71% were contaminated surgery). No difference between groups regarding sex, infection severity, health status or clinical progress was observed. Both the step-down treatments after 72 hours of intravenous clindamycin and the change to the oral route later on, were significantly increased with the intervention (p < 0.001, p < 0.001 respectively). No significant differences between both groups were found in the number of patients with adverse effects associated with the i.v. therapy, although the incidence tended to be lower in the intervention group (49/204 intervention versus 85/269 control, p = 0.07). Compliance with the recommended clindamycin dosing regimen was significantly higher in the intervention group, in which 1.3 days reduction of intravenous therapy provided an average cost savings of PTA5246 (95% CI 2556-7935) per treatment. A higher reduction of 1.7 days was achieved in those patients candidates for switch therapy on the third day of intravenous clindamycin. A sequential program with clindamycin may provide a cost-effective alternative to conventional therapy and the introduction of an information sheet is a cost-effective strategy to promote it.
AIM: An intensive 2-year field study of 65 hihi (or stitchbirds) on Mokoia Island provided an opportunity to investigate the causes of mortality of this endangered species in a free-living environment. METHODS: The birds were observed daily during the breeding season (October to March) and every 4 weeks during the remainder of the year. Any abnormalities in behaviour, voice and body weight were recorded and all sick or dead birds which could be recovered were taken to the laboratory for necropsy. RESULTS: Thirty-one birds died during the period of this study. Aspergillosis was found to be the cause of death in six of nine adult birds examined post mortem. Some of the affected birds experienced subtle voice changes before becoming ill and all birds had granulomatous lesions in airsacs or lungs at necropsy. A further eight birds for which carcasses could not be found or which were autolysed showed similar clinical signs before death or disappearance. CONCLUSION: Because Aspergillus is an opportunist pathogen it seems likely that affected birds were immunosuppressed. This may have occurred during the breeding season which in this species is highly stressful. The presence of fungal material in bronchial exudate and the occurrence of the disease in mates, raises the possibility that aspergillosis in hihi may be contagious.
OBJECTIVE: To assess the changes in ventricular evoked responses (VER) produced by the decrease in left ventricular outflow tract gradient (LVOTG) in patients with hypertrophic obstructive cardiomyopathy (HOCM) treated with dual-chamber (DDD) pacing. METHODS: A pulse generator Physios CTM (Biotronik, Germany) was implanted in 9 patients with severe drug-refractory HOCM. After implantation, the following conditions were assessed: 1) Baseline evaluation: different AV delay (ranging from 150 ms to 50 ms) were sequentially programmed during 5 to 10 minutes, and the LVOTG (as determined by Doppler echocardiography) and VER recorded; 2) standard evaluation, when the best AV delay (resulting in the lowest LVOTG) programmed at the initial evaluation was maintained so that its effect on VER and LVOTG could be assessed during each chronic pacing evaluation. RESULTS: LVOTG decreased after DDD pacing, with a mean value of 59 +/- 24 mmHg after dual chamber pacemaker, which was significantly less than the gradient before pacing (98 + 22 mmHg). An AV delay > 100 ms produced a significantly lower decrease in VER depolarization duration (VERDD) when compared to an AV delay < or = 100 ms. Linear regression analyses showed a significant correlation between the LVOTG values and the magnitude of VER (r = 0.69; p < 0.05) in the 9 studied patients. CONCLUSION: The telemetry obtained intramyocardial electrogram is a sensitive means to assess left ventricular dynamics in patients with HOCM treated with DDD pacing.
PURPOSE: To evaluate the value of recurrent anginal symptoms combined with seriation of conventional EKG in detecting coronary restenosis (renarrowing > or = 50% at the site dilated) after PTCA. Two hundred and seventy patients (204 men, mean age 53.1 +/- 9.4 years) with angina who submitted to successful PTCA of single-vessel coronary disease were followed and restudied angiographically 5.2 +/- 1.6 months after the procedure. At any moment from PTCA to follow-up: 1) typical angina pectoris was classified as either absent or present; 2) a 12-lead EKG was classified as improved, unchanged or worsened in comparison with the EKG either before or early after PTCA on the basis of ST-T alterations; 3) all patients underwent coronariography and were then classified as either having or lacking restenosis. The sensitivity and predictive positive value of recurrent angina, worsened EKG, or both, in detecting restenosis were respectively: 74.6% and 68.6%, 44.3% and 85.3%, and 55.9 and 91.7%. The specificity and predictive negative value of no recurrence of angina, improved EKG, or both, in detecting the absence of restenosis were respectively: 85.8% and 89.1%; 69.6% and 91.0%; and 75.6% and 93.9%. CONCLUSION: In single-vessel coronary disease, the detection of coronary restenosis after PTCA based on behavior of the symptoms plus rest EKG seriation shows acceptable degrees of sensitivity, specificity and mainly of predictive values when comparison with respective historical values of the ergometric test is considered.
Organic extracts representing 48 species included in 30 families of Costa Rican tropical plants were evaluated for their ability to neutralize hemorrhagic activity induced by the venom of the snake Bothrops asper. A bioassay in mice was used, based on intradermal injection of either venom or venom-extract mixtures followed by the measurement of hemorrhagic areas. Total inhibition of hemorrhage was observed with the ethanolic, ethyl acetate and aqueous extracts of Bursera simaruba, Clusia torresii, C. palmana, Croton draco, Persea americana, Phoebe brenesii, Pimenta dioica, Sapindus saponaria, Smilax cuculmeca and Virola koschnyi. Chemical analysis of these extracts identified catequines, flavones, anthocyanines and condensated tannins, which may be responsible for the inhibitory effect observed, probably owing to the chelation of the zinc required for the catalytic activity of venom's hemorrhagic metalloproteinases.
PURPOSE: Multicenter, open and non-controlled study to evaluated the efficacy and the tolerability of a low-dose combination of two anti-hypertensive agents: a cardioselective beta-blocker, bisoprolol (2.5 and 5.0 mg) with 6.25 mg of hydrochlorothiazide. METHODS: One hundred and six patients in the stage I and stage II of the systemic hypertension (mild to moderate) were given the bisoprolol/hydrochlorothiazide combination once daily and the diastolic and systolic blood pressures were monitored during the 8-week trial. RESULTS: The bisoprolol/hydrochlorothiazide combination reduced the initial mean values of systolic and diastolic blood pressures, respectively, from the 157.4 mmHg and 98.8 mmHg to 137.3 mmHg and 87.4 mmHg. At the end of the treatment period, 61% of the patients normalized blood pressure values (< 90 mmHg) and 22.9% of them had responded to the treatment, resulting in a total response rate (normalized + responsive) of 83.9% of cases. Adverse events were described only in 18.9% of the patients and dizziness and headache were the most common. There were no clinically significant changes on plasma levels of potassium, uric acid, glucose, or in the lipid profile. CONCLUSION: The combination of low dosages of bisoprolol and hydrochlorothiazide may be considered an effective, well tolerated and rational alternative for the initial treatment of the patients with mild to moderate hypertension.
A correlation between urinary tract infection, vesicoureteral reflux and voiding disorders has increasingly been reported. Voiding dysfunction increases the incidence of recurrent urinary tract infection, induces and perpetuates vesicoureteral reflux, even after surgical antireflux treatment, and may result in permanent renal damage. The resolution of the primary cause with voiding normalization is essential to achieve good results in the treatment of secondary problems such as urinary tract infection and vesicoureteral reflux. Thirty seven children with vesicoureteral reflux secondary to voiding disorders were diagnosed and treated between 1990 and 1995 (five years). Forty-nine ureters were studied. The subjects became symptomatic between 1 month and 13 years of age, with the occurrence of urinary tract infection. All children were neurologically and morphologically normal. Symptoms suggesting bladder instability were detected in 34 (91.9%) and dysfunctional sphincter obstruction in three (8.1%). These patients were all evaluated with a renal/bladder sonogram and voiding cystogram, complemented in 17 (45.9%) with urodynamic testing that confirmed clinical diagnosis. 99mTc-dimercaptosuccinic acid renal scans performed on 29 (78.4%) children revealed renal damage in 26 (89.6%). A treatment program of bladder retraining and bowel habit normalization was encouraged in every child, anti-cholinergic drugs were associated in 23 (62.2%), muscle-relaxant drugs in three (8.1%), phenoxybenzamine and intermittent catheterization were used in one child (2.7%). Urinary tract infection prophylaxis was instituted in 34 (91.9%) children. Urinary tract infection was completely resolved in 35 (94.6%) patients, and its frequency decreased in two (5.4%). Thirty-two children (86.5%) with vesicoureteral reflux were cured and four (10.8%) were improved. Evidence of voiding disfunction ceased in 22 (59.5%) cases and improved in 14 (37.8%) with a reduction in the frequency and intensity of complaints. Urgency syndrome and vesicoureteral reflux remained unchanged in one child (2.7%). These findings imply that detection and treatment of bladder/sphincter disfunction are essential in every child with the complex of recurrent urinary tract infection and vesicoureteral reflux.
BACKGROUND: Identification of high-risk patients and defining prognostic factors may be useful in the treatment of head and neck cancer. The role of the lymph node reactivity is still obscure. The value of the node reactivity pattern as a predictor of tumor control in oral cavity cancer was analyzed. METHODS: Retrospective analysis of patients with oral cavity squamous cell carcinoma (OCSCC), submitted to tumor resection and neck dissection, with pathologic negative lymph nodes (pN0). Dominant node reactivity pattern was defined as lymphocytic predominance (LP), germinal centers (GC), normal (NL), sinus hystiocytosis (SH), and lymphocytic depletion (LD). Clinical and pathological characteristics of patients free of disease (DF) were compared with those of patients with control failure (CF), which included local, regional, and distant recurrences. RESULTS: Of the 26 patients with pN0 OCSCC, prevalence of SH was found in 10 cases, GC in 13, and LD, NL and PL in 1 case each. Comparing CF and DF groups, there was no significant statistical difference regarding: age, gender, performance status index, weight loss, smoking and drinking habits, complementary treatment, average follow-up, tumor grade or thickness, margins, or tumor inflammatory and desmoplastic reaction. Although there was a higher proportion of perineural invasion and larger tumors in the CF group, the difference was not statistically significant either. Germinal centers or LP were noted in only 27% of the CF group and in 73% of the DF group. Collectively, NL, SH, or LD patterns were observed in 73% of CF. This incidence was statistically different from 27% of the DF group (P <0.05). CONCLUSIONS: Lymph node reactivity pattern seems to be a prognostic index in pN0 OCSCC patients. Prospective analysis is advised to confirm these results. Prophylactic neck dissection as a staging procedure could select high-risk patients even when no metastasis is found.
Scarce availability and risk of transmission of infections and diseases (HIV, hepatitis B, Chagas' disease) limit the use and benefits of homologous blood transfusions for surgical purposes. Recent trials of perfluorocarbon-based hemosubstitutes (PFC-HSs) in experimental cardiopulmonary bypass (CPB) have demonstrated their ability to improve brain oxygenation, as compared with conventional crystalloid priming solutions. The objective of the project described here is to test different formulations of PFC-HSs and optimize their formulation and dosage for use in CPB. The project includes: (1) study the feasibility of implementing a laboratory for small scale production of PFC-HSs; (2) evaluate the efficacy of use of PFC-HSs in an animal model of CPB; and (3) evaluate the safety of use of PFC-HSs in an animal model of hemorrhagic shock. Several in-house PFC-HSs and outside PFC-HSs are being evaluated. The current state of the project is: (1) the feasibility study has been completed and several PFCs, emulsifiers and surfactants are being tested; (2) and (3) the animal models have been implemented are being used to test in-house and outside PFC-HSs as priming solutions in CPB and reinfusion fluids in hemorrhagic shock respectively. Some preliminary results are presented.
The state of art in the treatment of silent myocardial ischemia is reviewed in such a way as to provide with the cardiologist information for the correct decision to be made in patients with ischemia, but without clinical symptoms of angina and its equivalents. Previewed-required, the concept, the classification and the diagnostic methods were reviewed. The prognosis, pharmacological treatment, intervention procedures and their results on the natural history of the disease are emphasised. It is recommended that the treatment of silent ischemia be done, at first, with primary and secondary prevention, and with pharmacological therapy. It is assumed that with the reduction of general ischemic episodes, survival can be individualized. New techniques have been introduced that modify the results in both the short and long term of these procedures.
The immune response of people infected by the protozoan parasite Trypanosoma cruzi varies in indeterminate or chronic periods of infection, according to the course of the disease. Apparently, the antibody pattern is different in asymptomatic patients than in patients with cardio-myopathy. The study of those differences for clinical purposes depends on the availability of adequate antigenic preparations. We studied the behavior of crude and partially purified antigens of T. cruzi in acute and chronically infected patients. The level of total antibodies was measured by conventional serology (indirect immunofluorescence, IF, and indirect hemagglutination, HA) and the level of antibodies against different fractions of antigens obtained by analytical chroma-tofocusing, by using enzymatic immunoassay (ELISA). Chronic patients were classified according to Kuschnir et al. in: Group 0 (G0) or Group 1 (G1) according to the absence or presence of electrocardiographic alterations. In acute patients, conventional serology was negative in most cases. However, the ELISA performed with the soluble fraction of the lysate of parasites, showed positive results in 60% of patients. By classical serology, the behavior of chronic patients sera was different in the two groups when assayed by IF; G1 showing more elevated titles than G0. On the other hand, by HA the results were similar in both groups. When the sera were studied by ELISA using the different fractions, the fraction collected at pH 4-4.5, named F IV, detected distinct reactivity in some of, but not in all, the patients of G1. In that subgroup, the highest ELISA indes (optical density of sera vs OD of negative controls) was observed. By associating IF plus FIV-ELISA the results became more apparent: 22% of sera showed titles by IF equal or more than 1:128 and ELISA index equal or more than 3.5, whereas only 2% of G0 showed this characteristic and all the sera with index equal or more than 4 belonged to G1. With lesser antibody titles it was not possible to differentiate between the two groups. It can be concluded that the study of the pattern of antibodies by using different antigens and serological methodologies can offer useful information in the different periods of Chagas disease, by adding the higher sensitivity of methods using crude antigens with the more specific and discriminative results obtained by the use of purified or synthetic antigens.
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