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In the matter of Cabrera.
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Extended Hubbard model: A cluster effective-medium approach.
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Decreasing xanthine oxidase-mediated oxidative stress prevents useful cellular adaptations to exercise in rats.
Reactive oxygen or nitrogen species (RONS) are produced during exercise due, at least in part, to the activation of xanthine oxidase. When exercise is exhaustive they cause tissue damage; however, they may also act as signals inducing specific cellular adaptations to exercise. We have tested this hypothesis by studying the effects of allopurinol-induced inhibition of RONS production on cell signalling pathways in rats submitted to exhaustive exercise. Exercise caused an activation of mitogen-activated protein kinases (MAPKs: p38, ERK 1 and ERK 2), which in turn activated nuclear factor kappaB (NF-kappaB) in rat gastrocnemius muscle. This up-regulated the expression of important enzymes associated with cell defence (superoxide dismutase) and adaptation to exercise (eNOS and iNOS). All these changes were abolished when RONS production was prevented by allopurinol. Thus we report, for the first time, evidence that decreasing RONS formation prevents activation of important signalling pathways, predominantly the MAPK-NF-kappaB pathway; consequently the practice of taking antioxidants before exercise may have to be re-evaluated.
A critical re-evaluation of systolic and diastolic overloading patterns.
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Restriction enzyme banding and in situ nick-translation on different types of hetero- and euchromatin.
We studied the role of chromatin accessibility and methylation in the banding patterns produced by means of in situ nick-translation (NT) and restriction enzyme (RE) banding techniques. For these studies we used the X chromosomes of Microtus cabrerae because of their large segment with four different types of constitutive heterochromatin and because in these chromosomes we can also compare active and inactive euchromatin. The results demonstrate that constitutive heterochromatin in the X chromosomes of M. cabrerae is methylated at specific sequences in both active and inactive Xs. They also show that NT-based techniques are suitable for detecting weak differences in chromatin accessibility, such as differences between active and inactive euchromatin, and are able to distinguish methylation only at the accessible sites. Thus, when methylation has to be mapped in situ, additional experiments have to be performed in order to distinguish findings due to differential accessibility. RE banding seems less sensitive to slight differences in chromatin accessibility, and might thus be more suitable than in situ NT-based techniques for methylation mapping. In harmony with these results, HpaII-based RE banding is able to distinguish between active and inactive euchromatin, possibly depending on its methylation status.
An epidemic in a coronary care unit caused by Pseudomonas species.
Five patients in a coronary care unit were involved in an epidemic caused by a nonfermenting Gram-negative bacillus, presumptively identified by our laboratory as Pseudomonas cepacia. All medications administered intravenously to these patients were cultured. Because morphine was the only such medication common to the treatment of all the patients involved, a vial used in the unit at that time was cultured, as were two previously-entered vials of saline solution and several sterile vials of distilled water used in the preparation of injectable medication. The Pseudomonas cepacia organism was recovered from one of the vials of saline solution. The epidemic ended as soon as the practice of re-entering the vials of sterile saline solution was discontinued.
Smoking and sickness absence among public health workers.
BACKGROUND: As well as causing sickness and death, smoking has high socio-economic costs. The aim of this paper was to examine how closely smoking is associated with sickness absence among healthcare workers. SUBJECTS AND METHODS: Cases and controls were paired by age, gender and occupation among primary healthcare workers in Tenerife, Canary Islands, Spain. Cases were selected from workers that had been absent from work due to sickness for 1 or more days in an entire year, regardless of the cause. Controls were those workers who were not absent due to sickness over the same period. Tobacco consumption was verified by telephone poll. Matched pairs analysis was performed. RESULTS: Among the 292 cases, 40% were smokers, compared with 31% of controls [odds ratio (OR)=1.51, 95% confidence intervals (CI)=1.06-2.14]. The association between smoking and sickness absence was stronger in those aged 30-45 years (OR=1.60, 95%CI=1.04-2.44) and among nurses (OR=2.08, 95%CI=1.05-4.14). When the cause of sickness absence was a respiratory disease, no association was found with smoking. However, an association was found with back pain (OR=5, 95%CI=1.45-17.27). Duration of tobacco consumption was higher in cases (a) when only current smokers were considered (P=0.002), and (b) when including the smoking duration of former smokers (P=0.0004). CONCLUSIONS: Smoking is associated with a higher risk of sickness absence among healthcare workers, particularly due to back pain. This could be used as an incentive to persuade healthcare workers to stop smoking and re-inforce the non-smoking message given to their patients.
[Sympathetic reinnervation of the transplanted heart. Study using iodine-123 labeled meta-iodobenzylguanidine].
INTRODUCTION AND OBJECTIVES: Metaiodobenzylguanidine (MIBG) is an analogue of norepinephrine and its cardiac uptake shows sympathetic innervation. During the heart transplantation the allograft becomes completely denervated. The present study was conducted to assess the evolution of sympathetic re-innervation after transplantation, and to related re-innervation with functional status. PATIENTS AND METHODS: We studied 31 patients from 6 months to 12 years after transplantation by 123I-MIBG studies to evaluate re-innervation and by rest/exercise radionuclide ventriculography to evaluate cardiac function. Myocardial MIBG uptake was quantified by calculating a heart-to-mediastinum ratio (HMR). An HMR > 1.8 was considered normal, moderate between 1.8 and 1.6, mild between 1.6 and 1.3, and absent < 1.3. RESULTS: HMR correlated with time after transplantation (r = 0.607; p < 0.001). HMR of patients studied after 2 years of transplantation was significantly higher (1.62 +/- 0.2 vs 1.34 +/- 0.2; p < 0.05). MIBG uptake was in the anterior region in 3 patients, in the antero-lateral region in 25, and in the antero-lateral and septal regions in 3. From a functional point of view, peak filling rate at exercise was higher in patients studied 2 years after the transplantation (2.7 +/- 0.8 edv/s vs 2.16 +/- 0.5 edv/s; p = 0.02). These patients also showed a higher increase of heart rate with exercise (p < 0.005 vs p < 0.01). CONCLUSIONS: Sympathetic re-innervation increase with time after heart transplantation, and is more frequently seen 2 years after transplantation. Sympathetic re-innervation first appears in the anterior or the antero-lateral regions. A complete re-innervation of the transplanted heart does not occur 12 years after transplantation.
The mitochondrial lineage U8a reveals a Paleolithic settlement in the Basque country.
BACKGROUND: It is customary, in population genetics studies, to consider Basques as the direct descendants of the Paleolithic Europeans. However, until now there has been no irrefutable genetic proof to support this supposition. Even studies based on mitochondrial DNA (mtDNA), an ideal molecule for constructing datable maternal genealogies, have failed to achieve this. It could be that incoming gene flow has replaced the Basque ancient lineages but it could also be that these lineages have not been detected due to a lack of resolution of the Basque mtDNA genealogies. To assess this possibility we analyzed here the mtDNA of a large sample of autochthonous Basques using mtDNA genomic sequencing for those lineages that could not be unequivocally classified by diagnostic RFLP analysis and control region (HVSI and HVSII) sequencing. RESULTS: We show that Basques have the most ancestral phylogeny in Europe for the rare mitochondrial subhaplogroup U8a. Divergence times situate the Basque origin of this lineage in the Upper Palaeolithic. Most probably, their primitive founders came from West Asia. The lack of U8a lineages in Africa points to an European and not a North African route of entrance. Phylogeographic analysis suggest that U8a had two expansion periods in Europe, the first, from a south-western area including the Iberian peninsula and Mediterranean France before 30,000 years ago, and the second, from Central Europe around 15,000-10,000 years ago. CONCLUSION: It has been demonstrated, for the first time, that Basques show the oldest lineages in Europe for subhaplogroup U8a. Coalescence times for these lineages suggest their presence in the Basque country since the Upper Paleolithic. The European U8 phylogeography is congruent with the supposition that Basques could have participated in demographic re-expansions to repopulate central Europe in the last interglacial periods.
Short stature is related to high body fat composition despite body mass index in a Mexican population.
BACKGROUND: Mexico has a high prevalence of short stature (SS) population; thus, body mass index (BMI) criteria for diagnosis of obesity should be different from that in a tall stature (TS) population. The aim of this study was to determine whether SS at the same BMI would have greater body fat mass than those with TS. METHODS: We studied 116 individuals, 58 with SS (women < or =1.50 m and men < or =1.60 m) matched by gender, age (+/-5 years), and BMI (+/-2). Body fat was measured by bioelectrical impedance analysis. RESULTS: Paired comparisons between matched subjects showed that SS have greater body fat percentage than TS (Delta = 1.40%, p = 0.04). Subjects with BMI > or =25 and SS showed higher difference (Delta = 4.2%, p = 0.004) in body fat percentage. Subjects with SS have more body fat percentage than TS. CONCLUSIONS: This finding supports the hypothesis that in SS population BMI for diagnosis of obesity must be re-evaluated; from these results, we propose that diagnosis of obesity in SS be from BMI of 25.
[Post-radiation pneumonitis in a case of Hodgkin's lymphoma assessed with PET-FDG by residual mediastinal mass].
The PET-FDG is a useful method to assess the post-radiotherapy residual masses in supradiaphragmatic lymphoma patients. We present the case of a patient with residual mediastinic mass revealed by CT after the patient had completed treatment for Hodgkin's disease and in whom the PET study demonstrated a typical pattern of post-radiation pneumonitis. When these patients are re-assessed early after radiotherapy, the different tracer uptake patterns should be taken into account in order to identify the existence of radiotherapy sequela and avoid false positive results.
[Magnetic resonance imaging and lung perfusion scintigraphy in tetralogy of Fallot following surgery].
OBJECTIVE: To evaluate pulmonary arteries in patients with tetralogy of Fallot following surgery with quantified lung perfusion scintigraphy and magnetic resonance imaging. MATERIAL AND METHODS: From January 1985 to December 1999, 47 patients who underwent surgery between 1985 and 1999 were studied. To obtain values of normality, 45 infants with no pulmonary artery disease were assessed with lung perfusion scintigraphy (right lung flow: 54-61%, left lung flow: 38.7-46%) and magnetic resonance imaging axial view (right/left pulmonary artery branch diameter ratio: 1-1.1). Patients with stenosis underwent catheterization. RESULTS: Group 1: 27 patients with normal parameters. Group 2: nine patients with left pulmonary branch stenosis and irregularities in all parameters; left/right branch diameter ratio 0.51 and left lung perfusion 26.3 +/- 7.9%, r correlation ratio 65%, p < 0.005, left branch pressure gradient 34.4 +/- 17.9 mm Hg, rate-gradient r 89%, p < 0.001. Group 3: five patients with right pulmonary branch stenosis and irregularities in all parameters; right/left branch diameter ratio 0.52, reduced right lung perfusion 32 +/- 11%, with a stenotic branch gradient of 40 +/- 19 mm Hg., rate/gradient ratio r 72%, p < 0.005; gradient/perfusion ratio r 82%, p < 0.003. Group 4: Six patients with bilateral stenosis, reduced diameter in the stenotic area with normal perfusion in both lungs and bilateral gradient. Eighteen patients with stenosis underwent re-operation, with favorable outcome in 14. CONCLUSION: Magnetic resonance imaging and quantified lung perfusion scintigraphy provide useful information in the follow-up of tetralogy of Fallot.
[Effects of monaural and binaural stimulation on middle latency auditory evoked responses].
INTRODUCTION: Middle latency evoked potentials include a series of evoked responses which encompass/include myogenic potentials (which translate the existence of sonomotor reflexes), and others which are clearly of neurogenic origin. The latter are the most useful from the clinical point of view. OBJECTIVE: To evaluate the effects of monoaural (MA) and binaural (BA) stimulation on middle latency auditory evoked potentials. PATIENTS AND METHODS: We studied 15 healthy people, aged between 18 and 52 years, in whom Cz recording electrodes had been fitted to both short-circuited external ears with Fpz as earth. The stimuli used were alternate clicks of condensation and rarefication of 90 dBHL, first BA and them MA. The auditory evoked response from the brain stem was also recorded. RESULTS: We found more stability of most of the components evaluated during biauricular stimulation. All subjects had Pa waves and 93% had Pb waves. Statistically significant differences were only found for the amplitude of Po and Pa (BA against RE) (Wilcoxon test, p < 0.05). CONCLUSION: The use of BA stimulation to obtain middle latency evoked potentials is more useful for study of the more rostral parts of the auditory path, since its components are more stable.
[Aortic coarctation: different anatomo-clinical forms depending on the age of presentation].
OBJECTIVE: To analyse the anatomo-clinical characteristics of the coarctation of the aorta at different ages of presentation as well as the findings and results of its surgical correction at different periods. PATIENTS AND METHODS: We retrospectively studied the clinical and angiographic data, as well as the intraoperative findings and surgical outcomes of 82 consecutive patients (54 M and 28 F) with coarctation of the aorta. Mean age was 16.2 +/- 13.7 years (1 month to 63 years). The patients were divided into three groups according to age: Group A (n = 10) under 1 year; Group B (n = 30) from 1 to 12 years and Group C (n = 42) over 12 years. RESULTS: A preductal form was found in 20.7% cases (50.0%, 30.0% and 7.1% of groups A, B, and C respectively; p = 0.003). An associated left-to-right shunt was present in 19.5% (40.0%, 16.7% and 16.7% of groups A, B and C respectively; p = NS). The first manifestation of the disease was different in groups A, B and C. Among group A patients, congestive heart failure was the most frequent presentation (70.0%). In group B, the most frequent presentation (30%) was as an incidental finding in an asymptomatic patient. Finally, systemic hypertension or its complications predominated among group C patients (38.0%). Left ventricular hypertrophy on ECG was present in 0.0%, 30.0% and 54.7% of patients in groups A, B and C (p = 0.003) respectively. Postoperative complications including death, hypertensive crisis and re-coarctation were observed in 90.0%, 33.3% and 21.4% in groups A, B and C (p = 0.01) respectively. CONCLUSIONS: Among patients with coarctation of the aorta, the age of clinical presentation allows us to define groups of patients with different anatomical characteristics, clinical course and postoperative outcome.
A phase I study of hydralazine to demethylate and reactivate the expression of tumor suppressor genes.
BACKGROUND: The antihypertensive compound hydralazine is a known demethylating agent. This phase I study evaluated the tolerability and its effects upon DNA methylation and gene reactivation in patients with untreated cervical cancer. METHODS: Hydralazine was administered to cohorts of 4 patients at the following dose levels: I) 50 mg/day, II) 75 mg/day, III) 100 mg/day and IV) 150 mg/day. Tumor biopsies and peripheral blood samples were taken the day before and after treatment. The genes APC, MGMT; ER, GSTP1, DAPK, RARbeta, FHIT and p16 were evaluated pre and post-treatment for DNA promoter methylation and gene expression by MSP (Methylation-Specific PCR) and RT-PCR respectively in each of the tumor samples. Methylation of the imprinted H19 gene and the "normally methylated" sequence clone 1.2 was also analyzed. Global DNA methylation was analyzed by capillary electrophoresis and cytosine extension assay. Toxicity was evaluated using the NCI Common Toxicity Criteria. RESULTS: Hydralazine was well tolerated. Toxicities were mild being the most common nausea, dizziness, fatigue, headache and palpitations. Overall, 70% of the pretreatment samples and all the patients had at least one methylated gene. Rates of demethylation at the different dose levels were as follows: 50 mg/day, 40%; 75 mg/day, 52%, 100 mg/day, 43%, and 150 mg/day, 32%. Gene expression analysis showed only 12 informative cases, of these 9 (75%) re-expressed the gene. There was neither change in the methylation status of H19 and clone 1.2 nor changes in global DNA methylation. CONCLUSION: Hydralazine at doses between 50 and 150 mg/day is well tolerated and effective to demethylate and reactivate the expression of tumor suppressor genes without affecting global DNA methylation.
[Experience with Palmaz stent in pulmonary branch stenosis].
INTRODUCTION AND OBJECTIVES: Since 1989, the balloon expandable Palmaz stent (Johnson & Johnson Interventional Systems) has been used for the treatment of congenital heart disease. This study reports the results and the technique used for its implantation in native and post surgical retraction pulmonary branch stenosis. MATERIALS AND METHODS: From february 1995 to june 1996, we have performed this technique in 11 symptomatic children/adolescents with pulmonary branch stenosis, the mean age was 11 +/- 2 years. Fourteen procedures were made and 16 stents were implanted. The mean condition of the patients was: 7 with tetralogy of Fallot after a previous complete correction, 1 with Noonan syndrome and a surgically corrected atrial septal defect, 1 with pulmonary trunk aneurysm and a previous surgical correction for pulmonary valve and branch stenosis, 1 with pulmonary atresia and an intact septum who underwent a surgical valvotomy and posterior percutaneous valvuloplasty with a good ventricular development, and final was a tricuspid atresia with a previous Waterston anastomosis which produced a stenosis at the right pulmonary branch who underwent a modified Fontan operation with the result of a severe stenosis at the medial and inferior right pulmonary artery. The branch ostium was affected in five cases, and in one case with diffuse hypoplasia of the right branch, the stenosis was at both sites. The stenosis was native in nine cases and post surgery in the other five (2 Waterston, 1 Blalock-Taussig, 1 Fontan). We used the right and/or left femoral vein in all cases except two, in which we used the internal jugular vein. We followed the technique reported by the Boston-Houston experience, with an extra stiff guide and Mullins sheath towards the site of the stenosis. RESULTS: The procedure was effective in all cases except one. The mean pulmonary branch and balloon diameter was 11 +/- 3 mm and 14 +/- 2 mm, respectively, rate 1.2. The stenosis diameter rose from 4.8 +/- 1 to 11 +/- 2 mm (p < 0.001) with a percentage fall from 63 +/- 5 to 2 +/- 1% (p < 0.001). The pressure gradient fell from 30 +/- 5 to 5 +/- 1 mmHg (p < 0.001) and the right ventricle systolic pressure fell from 77 +/- 6 to 48 +/- 3 mmHg (p < 0.01). The mean followup was 10 +/- 3 months, a symptomatic and pulmonary perfusion improvement was seen. After 8 +/- 4 months, we evaluated six patients/nine stents with angiography, and we excluded thrombosis, aneurysms and occlusion of lobar or segmental branches. One case had a proximal stent re-stenosis as it did not cover the whole stenosis, so a new stent was implanted. Three patients/four stents underwent redilatation getting a slightly higher diameter than previously. COMPLICATIONS: One patient had a stent migration and he underwent surgical stent retrieval. CONCLUSIONS: Implantation of the Palmaz stent is a useful procedure for the treatment of native or post-operative pulmonary stenosis. It is possible to apply it to hypoplastic and ostial pulmonary stenosis. We confirm the effectiveness of redilatation at mid term.
[Echocardiographic follow-up of insulin-dependent diabetics].
Results of echocardiographic test made on 29 patients with Diabetes Mellitus type I, under 14 years of age, on two occasions with an average of 33 months between test are presented. Anomalies were detected in approximately 30% of patients and persisted in re-evaluations of those patients with more than three altered parameters. Decrease of septal movement, as an index of myocardial contractibility affectation, is the only parameter which increased rate with time. Authors do not find any correlation between echocardiographic anomalies and age, sex, duration of diabetes, insulin doses and glycohemoglobin values. Due to high incidence of echocardiographic anomalies detected, they recommend these test be conducted periodically on type I diabetics, even though relation between control of the illness and long-term complications still appears to be uncertain.