Biomedical subjects

E Sala

Publications and source records attributed to E Sala.

At least 37 records · Page 2Linked to original sources

PubMed2001

Methylation pattern of different regions of the MLH1 promoter and silencing of gene expression in hereditary and sporadic colorectal cancer.

Nonrandom, widespread promoter methylation of tumor suppressor genes is a common mechanism of gene inactivation during tumorigenesis. We examined the methylation status of two distinct regions of the MLH1 promoter (proximal and distal to the transcription start site) and the MLH1 gene expression by methylation-specific PCR and immunohistochemistry. A total of 72 colorectal tumors, both with (n = 51, 22 affected by hereditary nonpolyposis colorectal cancer, HNPCC, defined according to the international clinical criteria and 29 sporadic cases) and without microsatellite instability (MSI) (n = 21) were studied. Methylation was present in at least one of the two promoter regions in 86% of the sporadic MSI cases, in 33% of the cases lacking MSI, and in 23% of the HNPCC tumors. In the HNPCC cases with a known MLH1 mutation (n = 10) none of the two promoter regions was methylated. Hypermethylation in both MLH1 promoter regions was seen in 45% of the MSI sporadic cases vs. 5% of the MSI-negative cases and 0% of the HNPCC cases. The overall concordance between the two promoter regions regarding methylation status was good (P = 0.009), but no significant correlation between methylation and suppression of the MLH1 immunohistochemical expression was found. Our data confirm that mutation and hypermethylation are mutually exclusive mechanisms in inducing mismatch repair deficiency and support the hypothesis of methylation as a process evenly distributed along the different regions of the promoter.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Identification of a small supernumerary marker chromosome, r(2)(p10q11.2), and the problem of determining prognosis.

The identification of small supernumerary marker chromosomes (SMCs) and the elucidation of their clinical significance remain two of the problems in classical human cytogenetics. We observed a small supernumerary ring in amniotic fluid cell cultures and identified its origin as r(2)(p10q11.2) and its extent by means of fluorescent in situ hybridisation (FISH). Uniparental disomy (UPD) was excluded by microsatellite analysis using polymorphic markers localised in the same region. On the basis of normal ultrasonographic checks, the patient decided to continue the pregnancy. A normal female was delivered at term and subsequent neonatal follow-ups confirmed the normal phenotype and development. In the present case, genetic counselling was not helpful because of the absence of reference cases. Detailed characterisation made it possible to correlate the normal baby phenotype with the trisomic 2p10-2q11.2 genomic region. Further molecular cytogenetic investigations of SMCs classified by DNA content and pregnancy outcome data should improve genetic counselling and risk evaluation.

Adult↗

PubMed2001

Multicenter study of a commercial, automated polymerase chain reaction system for the rapid detection of Mycobacterium tuberculosis in respiratory specimens in routine clinical practice.

A cooperative study was conducted among six laboratories to compare the performance of the Cobas Amplicor (CA) polymerase chain reaction (PCR) system (Roche Molecular Systems, USA) for the detection of Mycobacterium tuberculosis with that of microscopy and culture in routine clinical laboratory diagnosis. A total of 5,221 decontaminated respiratory specimens were tested. The use of an internal control allowed detection of PCR inhibition in 144 (2.8%) specimens. Only two culture-positive samples were CA PCR inhibitory and therefore could not be detected by PCR testing. Of the 333 culture-positive specimens, 278 (83.5%) were positive by the CA PCR. Of the 4,744 culture-negative specimens, 52 (1.1%) were positive by the CA PCR. After analysis of discrepancies, 40 of the 52 culture-negative, CA PCR-positive specimens were classified as true positive. Thus, the overall sensitivities of culture, CA PCR and microscopy were 89.3%, 85.2% and 55.5%, respectively. The overall specificity of the CA PCR was 99.7%. Five of the six centers found similar performances for the CA PCR, with sensitivities ranging from 85.7 to 90.9%. The CA PCR was more sensitive for smear-positive samples, exhibiting overall sensitivities of 96.1% and 71.7% for smear-positive and smear-negative specimens, respectively. These results indicate that the Cobas Amplicor system enables microbiology laboratories with reasonable previous experience in molecular biology testing to perform PCR and to detect Mycobacterium tuberculosis in more than 70% of specimens obtained from infected patients.

Automation↗

PubMed2001

Objective analysis of vocal warm-up with special reference to ergonomic factors.

Vocal warm-up was studied in terms of changes in voice parameters during a 45-minute vocal loading session in the morning. The voices of a randomly chosen group of 40 female and 40 male young students were loaded by having them read a novel aloud. The exposure groups (5 females and 5 males per cell) consisted of eight combinations of the following factors: (1) low (25 +/- 5%) or high (65 +/- 5%) relative humidity of ambient air; (2) low [< 65 dB(SPL)] or high [> 65 dB(SPL)] speech output level during vocal loading; (3) sitting or standing posture during vocal loading. Two sets of voice samples were recorded: a resting sample before the loading session and a loading sample after the loading session. The material recorded consisted of /pa:ppa/ words produced normally, as softly and as loudly as possible in this order by all subjects. The long /a/ vowel of the test word was inverse-filtered to obtain the glottal flow waveform. Time domain parameters of the glottal flow [open quotient (OQ), closing quotient (CQ), speed quotient (SQ), fundamental frequency (F0)], amplitude domain parameters of the glottal flow [glottal flow (fAC) and its logarithm, minimum of the first derivative of the glottal flow (dpeak) and its logarithm, amplitude quotient (AQ), and a new parameter, CQAQ], intraoral pressure (p), and sound pressure level (SPL) values of the phonations were analyzed. Voice range profiles (VRP) and the singer's formant (g/G, a/A, cl/c, e1/e, g1/g for females/males) of the loud phonation were also measured. Statistically significant differences between the preloading and postloading samples could be seen in many parameters, but the differences depended on gender and the type of phonation. In females the values of CQ, AQ, and CQAQ decreased and the values of SQ and p increased in normal phonations; the values of fAC, dpeak, and SPL increased in soft phonations; the values of AQ and CQAQ decreased in loud phonations; the harmonic energy in the singer's formant region increased significantly at every pitch. In males the values of OQ and AQ decreased and the values of dpeak, F0, p, and SPL increased in normal phonations; the values of fAC and p increased in soft phonations. The changes could be interpreted as signs of a shift toward hyperfunctional voice production. Low humidity was associated with more hyperfunctional changes than high humidity. High output was associated with more hyperfunctional changes than low output. Sitting position was associated with an increasing trend at both margins of male VRP, whereas the case was the opposite for standing position.

Adolescent↗

PubMed2001

The prevalence of voice disorders among day care center teachers compared with nurses: a questionnaire and clinical study.

The acceptance of voice disorders by day care center teachers as an occupational disease is not an invariably established practice. This is due to the lack of reliable evidence of a higher risk for voice disorders in this profession. To find out the risk of voice disorders, an epidemiological study was conducted among day care center teachers (n = 262), using hospital nurses (n = 108) as a control group. Symptoms were charted by a questionnaire. In a clinical examination made by a laryngologist, the voice quality was assessed and the laryngeal status noted. Teachers at day care centers had significantly more voice disorders than did nurses. Vocal nodules and laryngitis findings appeared significantly more frequently among day care center teachers than among those in the control group. The results prove voice disorders to be more frequent among day care center teachers than among control group subjects, and also that the main cause for this may be a higher vocal loading among day care center teachers than among control group subjects.

Adult↗

PubMed2001

Mammographic parenchymal patterns and breast cancer natural history--a case-control study.

The relationship between tumour size, malignancy grade and dense mammographic parenchymal patterns was evaluated by using a nested case-control design with 875 breast cancer cases and 2 601 matched controls. Wolfe's classification was used to assess mammographic parenchymal patterns. The dense P2/DY mammographic parenchymal patterns were significantly associated with invasive ductal grade 3 carcinoma (OR = 2.03; 95%, CI 1.13-3.62, p = 0.016). Stratified by tumour size, we found that the odds ratio for grade 3 invasive ductal NOS breast cancer measuring 15-19 mm associated with P2/DY mammographic parenchymal patterns was 3.46 (95% CI 1.12-10.68). For tumours larger than 30 mm, the odds ratio was 10.09 (95% CI 1.27-79.93). The highest risk of grade 3 cancers being in tumours measuring 30 mm + may be due to dedifferentiation of missed cancers, but there is some excess even in the < 20 mm tumours, suggesting an increased risk in association with dense mammographic patterns of some aggressive cancers which are grade 3 at inception. Our results are consistent with the model that breast cancer is a progressive disease, whose development can be arrested by screening, and that the point at which individual tumour progression is stopped is crucial for prognosis not simply in terms of stage of disease, but also of histological grade.

Breast↗

PubMed2001

Estimation of disease progression parameters from case-control data: application to mammographic patterns and breast cancer natural history.

BACKGROUND: Estimations of mean sojourn time (MST) and sensitivity (S) in disease screening have been previously calculated from case-control data, using simple models which did not include covariates. Many studies have shown an effect of mammographic parenchymal pattern (MPP) on breast-cancer risk and tumour histology. We have expanded previous models on these to estimate MST and S with the effects of MPP as a covariate. METHODS: Data were from a nested case-control study within the East Anglian screening programme, with 875 cases and 2,601 controls. Estimates of disease progression and screening parameters were based on conditional likelihood calculation, using a Markov process model. Ninety-five per cent confidence intervals (CI) were calculated using the profile likelihood wherever possible and using a numerical estimate of the information matrix or the area under the likelihood curve where necessary. RESULTS: We obtained estimates of the incidence of preclinical disease, rate of transition from preclinical to clinical and screening sensitivity, and evaluated the association of these parameters with mammographic parenchymal pattern. A higher incidence of preclinical disease was found for high-risk MPP [relative incidence = 1.62 (95% CI: 0.89; 2.73)]. However, no difference in progression rate from preclinical to clinical disease between different MPP was found. Dense MPPs were associated with decreased sensitivity [relative sensitivity = 0.24 (95% CI: 0.06; 15)]. Wide CIs were found, probably being a consequence of the relative sparsity of interval cancer data. DISCUSSION: It is possible to estimate multiple parameters of disease progression and screening quality from case-control data. The reduction in sensitivity of the screening process associated with high-risk patterns presented here, could be of paramount interest for proposing new screening strategies, such as possible additional screening tools.

Breast Neoplasms↗

PubMed2001

Impaired muscle oxygen transfer in patients with chronic renal failure.

We hypothesized that impaired O2 transport plays a role in limiting exercise in patients with chronic renal failure (CRF). Six CRF patients (25 +/- 6 yr) and six controls (24 +/- 6 yr) were examined twice during incremental single-leg isolated quadriceps exercise. Leg O2 delivery (QO2(leg)) and leg O2 uptake (VO2(leg)) were obtained when subjects breathed gas of three inspired O2 fractions (FI(O2)) (0.13, 0.21, and 1.0). On a different day, myoglobin O2 saturation and muscle bioenergetics were measured by proton and phosphorus magnetic resonance spectroscopy. CRF patients, but not controls, showed O2 supply dependency of peak VO2 (VO2(peak)) by a proportional relationship between peak VO2(leg) at each inspired O2 fraction (0.59 +/- 0.20, 0.47 +/- 0.10, 0.43 +/- 0.10 l/min, respectively) and 1) work rate (933 +/- 372, 733 +/- 163, 667 +/- 207 g), 2) QO(2leg) (0.80 +/- 0.20, 0.64 +/- 0.10, 0.59 +/- 0.10 l/min), and 3) cell PO2 (6.3 +/- 5.4, 1.7 +/- 1.3, 1.2 +/- 0.7 mmHg). CRF patients breathing 100% O2 and controls breathing 21% O2 had similar peak QO2(leg) (0.80 +/- 0.20 vs. 0.79 +/- 0.10 l/min) and similar peak VO2(leg) (0.59 +/- 0.20 vs. 0.57 +/- 0.10 l/min). However, mean capillary PO2 (47.9 +/- 4.0 vs. 38.2 +/- 4.6 mmHg) and the capillary-to-myocite gradient (40.7 +/- 6.2 vs. 34.4 +/- 4.0 mmHg) were both higher in CRF patients than in controls (P < 0.03 each). We conclude that low muscle O2 conductance, but not limited mitochondrial oxidative capacity, plays a role in limiting exercise tolerance in these patients.

Adult↗

PubMed2001

Muscle angiogenic growth factor gene responses to exercise in chronic renal failure.

Patients with chronic renal failure (CRF) have impaired exercise capacity even after erythropoietin treatment. We recently showed that although this is explained in part by reduced convective O(2) delivery to muscles, there is also an impairment of O(2) transport from muscle capillaries to the mitochondria. Given the importance of the capillary surface area for capillary mitochondrial O(2) transport and reports of reduced capillarity in CRF, we hypothesized that the angiogenic gene response to exercise is impaired in such patients. Six patients with CRF and six control subjects matched for age, size, and sedentary lifestyle exercised on a single occasion for 1 h at similar work intensities averaging 50% of maximal capacity. Exercise was confined to the knee extensors of a single leg by means of a specially designed leg-kick ergometer. A percutaneous biopsy of the quadriceps was taken within 30 min of cessation of exercise and compared with a similar biopsy done at different times without any prior exercise for 24 h. Conventional Northern blots were prepared and probed for vascular endothelial growth factor (VEGF; the major putative angiogenic growth factor for muscle), basic fibroblast growth factor (bFGF), and transforming growth factor (TGF)-beta(1). Data during both rest and exercise were successfully obtained in four subjects of each group. We also assessed muscle capillarity and mitochondrial oxidative capacity to relate to these changes. Mitochondrial oxidative capacity was normal, whereas capillary number per fiber was 12% lower than in normal subjects. VEGF mRNA abundance was increased after exercise by about one order of magnitude, with no reduction in response in CRF. For bFGF and TGF-beta(1), exercise elicited no response in either group. Reduced muscle capillarity in CRF does not, therefore, stem from reduced transcription of VEGF. To the extent that VEGF is important to exercise-induced angiogenesis in muscle, we suspect a posttranscriptional aberration in this response occurs in CRF to explain reduced capillarity.

Adolescent↗

PubMed2001

Supported discharge shortens hospital stay in patients hospitalized because of an exacerbation of COPD.

This prospective, controlled, but not formally randomized study investigates the feasibility and efficiency of an alternative to standard hospitalization for patients with exacerbated chronic obstructive pulmonary disease (COPD), based upon supported discharge with nurse supervision at home. Over a 12-month period, emergency physicians, not directly involved in the study, admitted 205 patients with exacerbated COPD to the authors' respiratory unit. Patients were included in the supported discharge group (n=105) if they voluntarily chose to participate in the programme and lived in the city of Palma de Mallorca (where adequate home support could be provided). Patients not fulfilling these criteria (mainly residents outside the city) served as controls (n=100). Inpatient treatment was standardized in all patients and included oxygen therapy, bronchodilators, antibiotics and steroids. Both groups were comparable in terms of age (mean +/- SD: 70 +/- 10 versus 65 +/- 11 yr for supported discharge and control group, respectively), severity of airflow obstruction (forced expiratory volume in one second 45 +/- 18% reference versus 46 +/- 19% ref.), comorbidity and socioeconomic status. Length of hospital stay (LOS) in the supported discharge group was shorter (5.9 +/- 2.8 versus 8.0 +/- 5.1 days, p < 0.001). After discharge, a respiratory nurse visited supported discharge patients at home during 7.3 +/- 3.8 days. Only one patient (1%) required hospital readmission during this period of time. The reduced LOS resulted in a lower utilization of hospital beds at any given point in time throughout the study period. Within the framework and potential limitations of this study, the results indicate that the supported discharge programme in Spain: 1) allows a significant reduction in the length of hospital stay of patients hospitalized because of an exacerbation of chronic obstructive pulmonary disease; 2) does not result in an inappropriately increased rate of hospital readmissions; and 3) reduces the utilization of hospital resources.

Aged↗

PubMed2001

Pulmonary gas exchange responses to histamine and methacholine challenges in mild asthma.

Histamine (HIST) produces greater changes in bronchial and pulmonary vasculature, and so may produce more gas exchange abnormalities, than methacholine (MTH) after inhalational challenge. The goals of this study were to compare the effects of HIST and MTH challenge on pulmonary gas exchange in patients with mild asthma at an equivalent degree of bronchoconstriction. Eleven patients were studied (mean+/-SEM age, 22+/-1 yr; forced expiratory volume in one second (FEV1), 91+/-5% pred) using a randomized, double-blind cross-over design. Respiratory system resistance (Rrs), arterial blood gases, and ventilation-perfusion distributions were measured before and after HIST/MTH challenges when cumulative doses caused a 30% fall in FEV1. Compared with baseline, HIST and MTH provoked similar moderate to severe increases in Rrs (p<0.005 each), and mild to moderate decreases in arterial oxygen tension (Pa,O2) due to ventilation-perfusion abnormalities (dispersion of pulmonary blood flow -log SDQ-, 0.40+/-0.03-0.71+/-0.08 and 0.47+/-0.04-0.89+/-0.06; normal values <0.60-0.65), respectively, similar to those shown in mild to moderate acute asthma, without differences between them. For the same degree of airflow obstruction, both histamine and methacholine bronchoprovocations induce, in patients with mild asthma, very similar disturbances in ventilation-perfusion distribution and respiratory system resistance, suggesting similar mechanisms of airway narrowing.

Adult↗

PubMed2001

A fast and easy screening method for voice disorders among teacher students.

A recent study concerning voice disorders among future teachers showed that about 20% of the students had a voice disorder. Most of the disorders were organic. In the current study, we describe a voice-screening method that can be administered by the health care personnel in order to select students for further examination by the speech language therapist and/or phoniatrician. The screening method consists of a perceptual assessment of voice quality and a questionnaire concerning vocal symptoms. As criterion for further medical investigation and voice therapy, we selected a score of 35 mm or above on a visual analogue scale assessing Grade, i.e. overall grade of hoarseness and/or two or more weekly or more often occurring vocal symptoms. The results showed that health care personnel with some training in assessing voices using the questionnaire are competent to perform a rough voice screening on students.

Adult↗

PubMed2000

Modelling the reproducibility of acoustic rhinometry.

This paper presents an application of a linear model with correlated errors to the assessment of the precision of acoustic rhinometry in clinical medicine. The design of the reproducibility study involved 20 healthy subjects measured by five investigators with three replicate measurements of four variates taken from the right and left nasal cavities, altogether 2400 measurements. The parametric model may be structured to account for random variation between subjects, serial correlation within subjects and measurement error. The model-based reproducibility correlation coefficient was estimated to be fair both for the nasal volume measurements and for the nasal minimal cross-sectional area measurements with an overall average of 0.65. An alternative measure, the within-subject coefficient of variation, averaged 15 per cent. The choice between the measures of reproducibility depends on the degree of heterogeneity of the studied populations, the presence of time trend and the scale of measurement of the rhinometric variates. In clinical practice, repeated measurements should always be made to attain a reasonable level of reproducibility in acoustic rhinometry.

Adult↗

PubMed2000

Size, node status and grade of breast tumours: association with mammographic parenchymal patterns.

A case-control study was designed to assess the association of mammographic parenchymal patterns with the risk of in-situ and invasive breast cancer. In addition, the relationship between tumour characteristics and mammographic patterns were also investigated. A total of 875 patients with breast cancer were selected and matched with 2601 controls. Mammographic parenchymal patterns of breast tissue were assessed according to Wolfe's classification, and statistical analysis was by conditional logistic regression. Relative to the N1 pattern, the odds ratios of having an invasive breast cancer associated with the P2 and DY patterns were 1.8 and 1. 4, respectively. In addition, the odd ratios of having an invasive grade 3 breast cancer associated with the P2 and DY patterns were 2. 8 and 3.9, respectively. Relative to the combined N1/P1 pattern, the odd ratios of having a breast cancer smaller than 14 mm, 15-29 mm, or larger than 30 mm associated with the combined high-risk P2/DY pattern (P2 + DY) were 1.2, 1.6, and 2.0, respectively. Finally, women with the P2/DY pattern were twice as likely to have a breast cancer which had already spread to the axillary nodes, compared to women with women with the N1/P1 pattern (odds ratios of 2.1 and 1.4, respectively). Our results confirm previous findings suggesting that mammographic parenchymal patterns may serve as indicators of risk for breast cancer. Our results also suggest that mammographic parenchymal patterns are associated with the stage at which breast cancer is detected.

Breast Neoplasms↗

PubMed2000

A study of repeated measures of softest and loudest phonations.

One common way to describe one's voice in an objective way is to measure the sound levels of the softest (pianissimo) and loudest possible (fortissimo) phonations at given pitches (voice range profile measurement). However, the reliability of the measurement has not been thoroughly investigated. The aim of the present study was to describe the repeatability and reproducibility of the sound level measurement in statistical terms, focusing on five target frequencies within the estimated speaking pitch range. Ten healthy female university students volunteered as test subjects. The voice range profiles within the speaking pitch range were defined 10 times in succession and in five sample sessions between 45-minute-long oral readings. Our study followed the ideas of the Gage repeatability and reproducibility design. The results showed that the method used was reliable in fortissimo phonations at four of the measured frequencies. Better reliability can be achieved by measuring three successive phonations at each pitch prior to the next target tone.

Adult↗

PubMed2000

Prevalence of voice disorders among future teachers.

An epidemiological study was conducted in order to find out the prevalence of voice disorders among students studying to be teachers. Vocal symptoms were inquired of 226 students. Their voices were assessed perceptually by a speech therapist and those who had abnormal voice quality or reported several vocal symptoms were referred to a clinical examination by a laryngologist. The results showed that 20% of this population reported two or more vocal symptoms during the previous year and that 19% had an organic voice disorder. This reinforces the need for clinical evaluation of students with vocal symptoms and more vocal training in the teacher education programs.

Adult↗

PubMed2000

High risk mammographic parenchymal patterns and diet: a case-control study.

Mammographic parenchymal patterns are related to breast cancer risk and are also thought to be affected by diet. We designed a case-control study comprising 200 cases with high-risk (P2 and DY) mammographic parenchymal pattern and 200 controls with low-risk (N1 and P1) patterns in order to investigate the effect of food and nutrient intake on mammographic patterns. Mammograms were evaluated according to the Wolfe classification system. Dietary data were obtained from 7-day food diaries. Mean daily intake of nutrients was computed from standard UK food tables. The adjusted odds ratio (OR) of having a high-risk pattern in women in the highest tertile of total protein and carbohydrate intake was twice that of women in the lowest tertile (OR = 2.00; 95% confidence interval (CI) 1.06-3.77; P = 0.04 and OR = 1.93; 95% CI 1.03-3.59; P = 0.04 respectively). There was no excess risk for fat intake. In addition, there was no association between intake of vitamins and mammographic parenchymal patterns. Total meat intake was strongly and positively associated with high-risk patterns among post-menopausal women (OR = 2.50, 95% CI 1.09-5.69, P = 0.03). Our study suggests that certain macronutrients and foods such as protein, carbohydrate and meat intake influence the risk of breast cancer through their effects on breast tissue morphology, whereas fat and vitamins do not affect mammographic density. It seems that parenchymal pattern acts as an informative biomarker of the effect of some macronutrient and foodstuffs intake on breast cancer risk.

Adipose Tissue↗

PubMed2000

High-risk mammographic parenchymal patterns, hormone replacement therapy and other risk factors: a case-control study.

BACKGROUND: Mammographic parenchymal patterns are of particular interest because the denser patterns reduce screening sensitivity as well as increasing breast cancer risk, and because they have been shown to be affected by exogenous oestrogens. METHODS: We designed a case-control study comprising 200 cases with high-risk (P2 and DY) pattern and 200 controls with low-risk (N1 and P1) pattern. Mammograms were evaluated according to the Wolfe classification. RESULTS: Parity, body mass index (BMI) and current smoking were inversely and independently associated, whereas late age of menarche and history of benign breast disease were positively associated with high-risk mammographic patterns. Current-users of hormone replacement therapy (HRT) were more than twice as likely to have a high-risk pattern than never-users (OR = 2.48, 95% CI : 1.32-4.61). Women who used HRT for more than 5 years were almost three times more likely to have a high-risk pattern than never-users (OR = 2.77, 95% CI : 1.11-6.91). Relative to never-users, women who started HRT before the menopause were more than twice as likely to have a high-risk pattern (OR = 2.53, 95% CI : 1.31-4.87). CONCLUSIONS: Careful clinical and mammographical follow-up might be appropriate in women undergoing HRT. The HRT-induced mammographic pattern might be regarded as a new baseline and changes with respect to this new pattern could then be monitored over time.

Aged↗