J. de Gracia

Genotype-phenotype correlation for pulmonary function in cystic fibrosis

Background: Since the CFTR gene was cloned, more than 1000 mutations have been identified. To date, a clear relationship has not been established between genotype and the progression of lung damage. A study was undertaken of the relationship between genotype, progression of lung disease, and survival in adult patients with cystic fibrosis (CF). Methods: A prospective cohort of adult patients with CF and two CFTR mutations followed up in an adult cystic fibrosis unit was analysed. Patients were classified according to functional effects of classes of CFTR mutations and were grouped based on the CFTR molecular position on the epithelial cell surface (I–II/I–II, I–II/III–V). Spirometric values, progression of lung disease, probability of survival, and clinical characteristics were analysed between groups. Results: Seventy four patients were included in the study. Patients with genotype I–II/I–II had significantly lower current spirometric values (p<0.001), greater loss of pulmonary function (p<0.04), a higher proportion of end-stage lung disease (p<0.001), a higher risk of suffering from moderate to severe lung disease (odds ratio 7.12 (95% CI 1.3 to 40.5)) and a lower probability of survival than patients with genotype I–II/III, I–II/IV and I–II/V (p<0.001). Conclusions: The presence of class I or II mutations on both chromosomes is associated with worse respiratory disease and a lower probability of survival.

Time of exposure as a prognostic factor in avian hypersensitivity pneumonitis

Spirometric values were subsequently evaluated in 22 patients suffering from hypersensitivity pneumonitis caused by avian problems. First spirometric values were abnormal in 18/22 (82%) of patients. A restrictive pattern was observed in 16/22 (72%) of patients and an obstructive pattern in 6/22 (27%). The TLCO was reduced in all cases (12/12). Improvement or normalization of the respiratory function occurred 3.4 +/- 2.4 months after the avian contact had ceased. At the end of the follow-up, parameters were normal in 13/22 (59%) of patients. The restrictive pattern remained unchanged in 7/22 (32%), and the obstructive pattern persisted in 4/22 (18%) of the patients. The TLCO was normal in 6/12 (50%) of patients. Neither age nor treatment with corticosteroids (13 patients) had a significant influence upon the evolution of the lung function. However, total recovery or significant improvement was observed in 12/12 (100%) of patients who had been in contact with birds less than 2 years, in contrast to 6/10 (60%) of patients with more than 2 years of contact (P = 0.002).

Increased risk of tuberculosis transmission in families with microepidemics

In the present study, we analysed: 1) prevalence of TB infection and incidence of disease among family contacts of a cohort of patients with TB; 2) differential characteristics of families with microepidemics and families with < or = 1 new case of TB; and 3) efficacy of chemoprophylaxis in this group of contacts. Three thousand and seventy one family contacts of 635 patients with TB were studied. The study consisted of tuberculin skin testing and chest radiography in all cases, and bacteriological studies when active disease was suspected. Contacts were classified as belonging to: families with microepidemics (FME) (those with > or = 2 new cases of TB); families with one new case; and families with with no new cases. Chemoprophylaxis was prescribed in contacts following standard recommendations; all were followed up for 12-18 months. Rates of TB infection and disease among families, as well as the incidence of TB disease between those compliant and noncompliant with chemoprophylaxis were compared. Among the 3,071 contacts, 1,264 (41%) were infected and 176 (6%) had TB. Twenty two families with FME (3%) yielded 55 new cases of TB. The prevalence of infection (excluding the TB cases) was 80% in families with FME, 52% in families with one new case, and 41% in families with no new case (odds ratio (OR) 3.7; 95% confidence interval (95% CI) 2.1-6.5). Sputum smears were positive in 53% of cases in FME and 24% in non-FME families (OR 3.4; 95% CI 1.7-6.5). Bronchial sample cultures were positive in 84% of patients from FME families but in only 40% of those from non-FME families (OR 7.5; 95% CI 3.6-15.8). Chemoprophylaxis was prescribed in 356 contacts, of whom 296 complied and generated only one new case of TB, whilst there were 13 new cases among the 60 who did not comply (OR 81.6; 95% CI 26.7-248.7). This study showed the prevalence of infection and incidence of tuberculosis among family contacts of patients with newly diagnosed tuberculosis to be very high. A small number of families with microepidemics accounted for most new cases of tuberculosis, which were also more infectious. The extremely high risk of transmission in these families, together with the proven efficacy of chemoprophylaxis, justifies prescription of chemoprophylaxis to all their members, regardless of age.

Skin tests in bird breeder's disease.

The diagnostic value of skin tests was assessed in 35 patients affected by bird breeders disease by comparing the results with those obtained in a group of 27 symptomless breeders and 10 symptomless unexposed individuals. Sterilised and diluted serum and lyophilised extracts of faeces prepared from the breeders own birds were injected intradermally. Skinprick tests using the same materials were carried out simultaneously. The intradermal test using serum showed a positive reaction in 18 out of 20 patients tested and in three out of 20 symptomless breeders (p less than 0.0005); later reactions occurred in eight of the patients and one of the symptomless breeders (p less than 0.01). A delayed reaction was seen in five of the patients and one of the symptomless breeders (p = 0.09). No positive reactions were recorded in symptomless unexposed individuals. Intradermal skin testing using extracts of faeces yielded an immediate reaction in 19 of 21 patients and in three of 11 symptomless breeders tested (p less than 0.001); a late reaction was seen in 18 of the patients and in five of the symptomless breeders (p less than 0.05). Delayed reactions occurred in 11 of the 21 patients tested, whereas no positive responses were seen in symptomless breeders (p less than 0.025). Skinprick tests gave negative results in all cases. Skin testing constitutes a simple, quick, and safe procedure that can assist the differential diagnosis between individuals with bird breeders disease and symptomless breeders, the immediate reaction being similar in its sensitivity to testing for serum precipitins but possessing greater specificity.

Evaluation of natural computation techniques in the modelling and optimization of a sequential injection flow system for colorimetric iron(III) determination

Abstract The present study shows and gives evidence of the applicability of natural computation techniques in the modelling and optimization of a sequential injection flow system of analysis for colorimetric iron(III) determination in water samples. The reaction with thiocyanate is used as reagent colour. A neural network consisting of two hidden layers, each one formed by eight neurons, was used to model the system. Optimization of the system in terms of sensitivity, linearity and sampling rate was carried out by using jointly the neural network and genetic algorithms. The latter were used with a set of 50 crossed and mutated chromosomes over 100 generations. In the system thus developed, 140 μl of sample and 70 μl of reagent were sequentially introduced into the holding coil and propelled toward the detector at a flow of 5 ml/min. The system gave a sampling rate of 110 samples per hour. A comparison of the results obtained in the analysis of six samples with those obtained using the reference method (atomic absorption spectrophotometry) showed the high quality of results provided.

Use of mathematical models to describe dynamic behaviour of potentiometric biosensors: Comparison of deterministic and empirical approaches to an urea flow-through biosensor

Abstract The response of a flow-through biosensor is the consequence of complex interrelations between the dilution of the sample in a continuous stream (governed by physical variables) and the phenomena involved in the reactions between enzyme and substrate (governed by diffusion and kinetic processes). These interrelations make it difficult to know in advance the influence of manifold parameters in the biosensor response. If a reliable model of these processes is attainable, it will be possible to test rapidly, by computer, the effect of the variation of different operating variables on the response of the biosensor. This paper presents the results obtained when two models are applied to describe dynamic behaviour of a potentiometric flow-through urea biosensor. One of these models uses an empirical approach based on neural networks, while the other proposes a deterministic approach that takes into account reaction-diffusion equations.

Antibody deficiency in bronchiectasis

To the Editors: nnWe have read with interest the article by van Kessel et al . 1 on impaired antibody response to the pneumococcal polysaccharides of Streptococcus pneumoniae in patients with bronchiectasis of unknown aetiology. Several aspects of this work are controversial and there is no unanimous agreement on some of their conclusions. The first aspect that merits attention is the lack of a control group to establish the normal total antibody response and the isotypes to the vaccine, and, consequently, the diagnostic criteria of impaired antibody response. There are no universal criteria for adequate antibody response to polysaccharides and each laboratory should establish its own 2. This is particularly important because of the therapeutic implications. Treatment of symptomatic patients with a lack of antibody response is performed with periodic administration of intravenous immunoglobulins (Ig) at a high cost, dependent on healthcare centres and potential side-effects 3. For this reason, strict diagnostic criteria must be established.nnIt is interesting to note that van Kessel et al . 1 used different criteria for the response with total antibodies to the serotypes 3, 4 and 9V, in which the post-vaccination titre should be >20 U·mL−1 with at least a two-fold increase for two of the three …

Application of natural computation techniques to optimal design of flow injection systems

Abstract Flow injection (FI) systems are widely used for on-line monitoring of chemical processes. Several approaches have been made in order to achieve the optimal design of the FI system, mainly based on the approach of deterministic models that describe the process using the mass balances around the system and the corresponding kinetic relations. Although, good results have been obtained with this approach, the complexity of the system and the effort necessary to calculate the parameters that characterize the FI system using a deterministic model, have led to the consideration of more empirical approaches to obtain a model of the process. In this paper, the authors present the results obtained in the application of two techniques, known as natural intelligence techniques, in the optimal design of a flow injection sandwich system for glucose and glycerol analysis. The optimization is performed using a genetic algorithm, in which a population evolves combining the genetic code of the most capable individuals of the previous generation. To evaluate the performance of each individual an artificial neural network is used. The results obtained with this approach are comparable with the one previously developed using a deterministic description of the FI system.

Evaluation of a mathematical model to simulate dynamic response of tubular potentiometric sensors in flow-injection systems

Abstract Potentiometric detectors based on ion-selective electrodes are specially suited to flow measurements because of their low cost and high selectivity. Simultaneously in flow analysis the use of tubular-electrode configuration seems ideal as the flow characteristics can be kept constant throughout the system. The design of very simple manifolds, which increases the robustness and the system reliability, is constrained by the knowledge of the influence of hydrodynamic parameters in the detector response. With the aim to optimize the design of this kind of systems a mathematical model, that simulates the response of tubular potentiometric detectors in flow-injection systems, has been developed and tested. Results provided by simulation are compared with experimental ones, and the model capabilities are discussed.

Insect Cell Culture Medium Selection and Optimisation Based on Monitoring and Economical Considerations

The culture of insect cells is currently done using different media specifically developed for these cells (among them, IPL-41, Graces, and TC-100). The growth of a Sf9 cell line was studied in each of these media, and IPL-41 showed the best results. Nevertheless, this medium contains various carbohydrates as carbon and energy sources, and this fact supposes a complication for the monitoring of the culture. In order to make possible the control of the sugar exhaustion, its formulation was simplified to a unique saccaride source, as it was seen that one of this nutrients was sufficient to enable an efficient growth of the cells.