Reproducibility of the parameters of the on-transient cardiopulmonary responses during moderate exercise in patients with chronic obstructive pulmonary disease

To be clinically useful as indices reflective of altered physiological function consequent to interventions in patients with chronic obstructive pulmonary disease (COPD), the time constant (τ) and steady-state amplitude of the kinetic responses for oxygen uptake ( ) carbon dioxide output ( ) ventilation ( ) and heart rate (HR) have to be appropriately differentiable and reproducible. We therefore assessed the reproducibility of τ and steady state amplitude values in 41 patients with severe COPD [mean (SD)] [forced expiratory volume in 1 s=41 (7)% predicted], aged 64 (5) years. Of the total, 6 of the patients (15%) did not produce breath-by-breath data of sufficient quality to warrant kinetic analysis. The remaining 35 patients completed two moderate-intensity 10 min square-wave exercise tests separated by 2 h, both before and after an endurance training programme. Tests were conducted on an electromagnetically-braked cycle ergometer at an exercise intensity corresponding to 80% of the estimated lactate threshold (θ_La) or 50% of peak oxygen uptake if θ_La was insufficiently differentiable. Breath-by-breath measurements of , , and HR were averaged into 10 s bins and the on-transient response kinetics were estimated using a mono-exponential model. Analysing the pre-training and the post-training test 1 and test 2 comparisons together, the test 1 –test 2 differences were not significantly different from 0 for either τ or A. The standard deviation of the test 1 –test 2 differences allowed us to define the magnitude of change that would reach statistical significance. For τ, this averaged some 8, 10, 11 and 8 s, for , , and HR, respectively, for a one-tailed paired-comparisons test (i.e. appropriate for assessing hypothesised improvements resulting from an intervention); for a two-tailed comparison, the differences were approximately 2 s greater. The corresponding one-tailed values for A were 100 ml·min^–1, 95 ml·min^–1, 2.5 1·min^–1 and 4 beats·min^–1, respectively; the two-tailed values were 10%–15% greater. We therefore conclude that both τ and A for moderate-intensity exercise can be reproducibly estimated in patients with COPD when the data set provides a sufficiently large amplitude of response and sufficiently low sample variability to allow appropriate parameter estimation. Electronic Publication     

Reactivity of different LH and FSH standards and preparations in the world health organization matched reagents for enzyme-linked immunoassays of gonadotrophins

The immunoreactivity of various LH and FSH calibration standards and recombinant preparations in the enzyme-linked immunoassay (EIA) systems for gonadotrophins developed for the Special Programme of Research in Human Reproduction of the World Health Organization (WHO) were compared. The preparations tested included three LH and two FSH pituitary standards (calibrated against LH 80/552 and 68/40 and FSH 78/549 respectively) provided with the EIA or radioimmunoassay WHO matched reagent kits, the pituitary preparation LER-907, and recombinant human LH (rhLH) and FSH (rhFSH). Simultaneous curve fitting of the EIA dose-response curves revealed no significant differences among the slopes generated by the WHO LH standards and LER-907; in contrast, no parallelism was found between the curves of rhLH and the pituitary-derived LH standards. No significant differences were found among the slopes of the curves elicited by the pituitary and recombinant FSH preparations. Each LH preparation exhibited a high degree of charge heterogeneity. Considerable variations in charge isoform distribution among the WHO LH standards, rhLH and LER-907 were also evident. In contrast, the FSH preparations were less heterogeneous and exhibited minor differences in charge distribution. Despite the existing differences in charge isoform distribution, all the pituitary-derived preparations as well as rhFSH seem appropriate for using as calibration standards in this particular EIA system.     

Using Bayesian networks in the construction of a bi-level multi-classifier. A case study using intensive care unit patients data

Combining the predictions of a set of classifiers has shown to be an effective way to create composite classifiers that are more accurate than any of the component classifiers. There are many methods for combining the predictions given by component classifiers. We introduce a new method that combine a number of component classifiers using a Bayesian network as a classifier system given the component classifiers predictions. Component classifiers are standard machine learning classification algorithms, and the Bayesian network structure is learned using a genetic algorithm that searches for the structure that maximises the classification accuracy given the predictions of the component classifiers. Experimental results have been obtained on a datafile of cases containing information about ICU patients at Canary Islands University Hospital. The accuracy obtained using the presented new approach statistically improve those obtained using standard machine learning methods.     

Segmental polymorphisms in the proterminal regions of a subset of human chromosomes

The subtelomeric domains of chromosomes are probably the most rapidly evolving structures of the human genome. The highly variable distribution of large duplicated subtelomeric segments has indicated that frequent exchanges between nonhomologous chromosomes may have been taking place during recent genome evolution. We have studied the extent and variability of such duplications using in situ hybridization techniques and a set of well-defined subtelomeric cosmid probes that identify discrete regions within the subtelomeric domain. In addition to reciprocal translocation and illegitimate recombination events that could explain the observed mosaic pattern of subtelomeric regions, it is likely that homology-based recombination mechanisms have also contributed to the spread of distal subtelomeric sequences among particular groups of nonhomologous chromosome arms. The frequency and distribution of large-scale subtelomeric polymorphisms may have direct implications for the design of chromosome-specific probes that are aimed at the identification of cryptic subtelomeric deletions. Furthermore, our results indicate that the relevance of some of the telomere closures proposed within the present Human Genome Sequence draft are restricted to specific allelic variants of unknown frequencies.     

Ultrastructural and morphometric study of the Sertoli cell of the viscacha (Lagostomus maximus maximus) during the annual reproductive cycle

Changes in the morphology of viscacha Sertoli cells were studied during the annual reproductive cycle. Sertoli cells exhibited marked nuclear and cytoplasmic changes. Seasonal variation in nuclear size and shape, chromatin texture, and nucleolus characteristics was observed. The seasonal patterns of the volume densities of the endoplasmic reticulum (ER), mitochondria, Golgi complex, dense bodies and lipid inclusions were distinct. Morphometric analysis revealed that the Golgi complex is the organelle most sensitive to seasonal change. It declined drastically in the regressed testes and its recovery was slow. The ER and mitochondria exhibited seasonal variations in their pattern and content, that was minimal during winter. In contrast, an accumulation of lipid and dense bodies, such as primary and secondary lysosomes, accompanied the spermatogenic arrest. The volume densities of both organelles were maximum during the restoration of spermatogenesis. The length and organization of the inter-Sertoli junctions also changed with the reproductive cycle. The Sertoli cell number per tubular cross section decreased significantly during the testicular regression, coincident with the presence of Sertoli cells with marked signs of involution. The degree of regression and recovery exhibited by the viscacha Sertoli cells was closely related to that shown by the associated germ cells. Therefore, seasonal endocrine fluctuations and local factors could be involved in the regulation of the morphological and functional characteristics of the viscacha Sertoli cells. These hormonal fluctuations are synchronized by the photoperiod through the pineal gland and its hormone, melatonin.     

GLP-1 signalling and effects on glucose metabolism in myocytes from type 2 diabetic patients

Changes in the activity of glycogen synthase a and related kinases (phosphatidylinositol-3-kinase, protein kinase B, p44/42 MAP kinases and p70s6 kinase) evoked by GLP-1 in human myocytes from normal subjects were recently implied in the effect of this hormone upon D-glucose transport and glycogen synthesis in the same cells. The major aims of the present study were i) to investigate the possible extension of this knowledge to myocytes obtained from type 2 diabetic patients, ii) to compare in these patients the response to GLP-1, insulin or the structurally related GLP-1 peptides, exendin (1-39)amide and exendin(9-39)amide, and iii) to explore possible differences in the responsiveness to these agents between normal and diabetic subjects. Apart from the much higher basal PI3K activity and impaired response to insulin of p44/42 MAP kinases in the diabetic patients, the changes in enzyme activity caused by either hormone or peptide, although not identical, were essentially comparable. Nevertheless, significant differences in glucose transport and metabolism parameters were observed in the diabetic patients vs. normal subjects: in the diabetic patients, basal 2-deoxy-glucose uptake and glycogen synthase a activity were lower, accompanied by a similar increasing effect of GLP-1 or insulin; yet, the basal value for glycogen synthesis was higher, coinciding with a lesser relative increment in response to GLP-1 or insulin.     

Nutritional characterization by anthropometrics of institutionalized and non-institutionalized elderly Venezuelan

In order to evaluate nutritional status by anthropometry, a group of elderly (60 to 83 years old) was studied: 63 institutionalized and 37 non-institutionalized elderly from Valencia city, Venezuela. Weight, height, triceps skinfold and mid-arm circumference were measured and the body mass index (weight/height2) was calculated. The average age for the institutionalized group was 77.3 +/- 7.5 years old and 69.5 +/- 7.6 years old for the free-living elderly group. Tricipital skinfold (TSF) and mid-arm circumference (MAC) means were within the normal reference range for both groups, without significant differences by sex. Body mass index (BMI) was higher in the institutionalized group. Lower BMI and MAC were found in older elderly (> or =80 y). According to the nutritional classification by BMI, 16% of nutritional deficit, 45% of normal status and 39.7% with of excess weight were found in institutionalized elderly; while in free-living elderly, prevalences were 8%, 62% and 29.7% respectively. Even though normal nutritional status was highly prevalent, institutionalized elderly showed higher prevalences of nutritional alterations (underweight and overweight).