Functional outcome of patients with chronic obstructive pulmonary disease and exercise hypercapnia

Chronic hypercapnia is associated with a poor prognosis in chronic obstructive pulmonary disease (COPD). Some patients are normocapnic at rest but retain CO2 during exercise. The significance of this abnormality on the course of the disease is unknown. Sixteen stable COPD patients (13 males and 3 females, aged 60 +/- 5 yrs, mean +/- SD) who had previously undergone pulmonary function tests and progressive exercise testing with arterial blood sampling at rest and maximal capacity, entered the study. At first evaluation (E1), subjects were normocapnic at rest (arterial carbon dioxide tension (Pa,CO2): 4.9-5.7 kPa, (37-43 mmHg)) and all presented exercise-induced hypercapnia (end-exercise Pa,CO2 > 5.7 kPa (43 mmHg) with a minimal 0.5 kPa (4 mmHg) increase from resting value). The subjects were re-evaluated 24-54 months later (34 +/- 8 months) (second evaluation (E2)). At E2, forced expiratory volume in one second (FEV1) had decreased from 42 +/- 13 to 38 +/- 15% of predicted values, and mean resting Pa,CO2 had increased from 5.2 +/- 0.3 to 5.7 + 0.4 kPa. Maximal exercise capacity (Wmax) decreased between E1 and E2 from 76 +/- 30 to 56 +/- 22 W. Even if Wmax was lower at E2, end-exercise, Pa,CO2 was higher than at E1 (6.6 +/- 0.8 vs 6.4 +/- 0.5 kPa). At E2, eight subjects presented resting hypercapnia (group H), whilst the others remained normocapnic (Group N). Group H subjects had higher Pa,CO2, at Wmax than Group N and lower Wmax than Group N at E2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Quantifying characteristics of information-technology applications based on expert knowledge for detection of oestrus and mastitis in dairy cows

Expert opinions were elicited about the characteristics at the commercial-farm level of on-line information technology (IT) applications that are able to detect oestrus and mastitis in dairy cows. Since actual data of these characteristics are not available, judgmental data provided an alternative means to interpret the implications of research results for commercial farms. Applications included were activity measurement, milk-production measurement, electrical conductivity of quarter milk, automated concentrate feeders and milk-temperature measurement. Sensitivity and specificity of detection of oestrus (OD), clinical-mastitis (CMD) and subclinical-mastitis (SCMD) were ascertained. Conjoint-analysis was used to assess the effect of each application indirectly by decomposing the evaluated overall detection characteristics of a predefined number of IT combinations. The individual experts were consistent in evaluating the alternatives, but there was variation in estimates among experts. Estimations of the main effects of the applications and important first-order interactions were incorporated into the detection models. Implementation of all applications under study resulted in overall sensitivities and specificities of 82% and 90%, 73% and 87%, 58% and 82% for OD, CMD and SCMD, respectively. Further research is necessary that should take into account costs and benefits of the different detection systems based on the current status of farm performance (e.g. OD and mastitis incidence) and farm structure (e.g. farm size, years in operation of the milking parlour and parlour layout). Research to do this is currently in progress.     

Use of fuzzy logic to describe constraints derived from engineeringjudgment in genetic algorithms

Engineering optimization frequently runs into difficulties due to constraints. If an application is insufficiently constrained, it will not yield a unique optimal solution. Traditionally, underconstrained problems may be solved manually, applying engineering judgment to select the most plausible of a range of solutions which meet the initial set of constraints. The engineering judgment used to select good solutions is often qualitative and may even include contradictory elements. This paper addresses the issue of incorporating engineering judgment into the objective function of an optimizer in order to restrict the range of solutions. Fuzzy logic is used to represent engineering judgment since it is able to represent the qualitative nature of the knowledge and give an assessment of the overall quality of each solution. The approach has been used successfully to match a physically based gas turbine blade cooling design model to experimental results     

Tracer kinetic modeling of the 5-HT1A receptor ligand [carbonyl-11C]WAY-100635 for PET

[Carbonyl-11C]WAY-100635 is a promising PET radioligand for the 5-HT1A receptor, having demonstrated more favorable characteristics for in vivo imaging than the previously available [O-methyl-11C]WAY-100635. The current study evaluates different tracer kinetic modelling strategies for the quantification of 5-HT1A receptor binding in human brain. Mathematical modelling of the carbonyl-labeled radiotracer is investigated using compartmental structures, including both plasma input and reference tissue approaches. Furthermore, the application of basis function methods allows for the investigation of parametric imaging, providing functional maps of both delivery and binding of the radioligand. Parameter estimates of binding from normal volunteers indicate a low intra- versus a high intersubject variability. It is concluded that a simplified reference tissue approach may be used to quantify 5-HT1A binding either in terms of ROI data or as parametric images.     

Pharmacological activities of trimetoquinol and 1-benzyl halogen-substituted analogues on rat beta-adrenoceptor subtypes

The beta-adrenoceptor activity profile of trimetoquinol and its 1-benzyl halogen-substituted analogues was studied in rat tissues containing primarily beta 1 (atria)-, beta 2 (trachea)- and atypical beta/beta 3 (distal colon and brown adipose tissue)-adrenoceptors. Functional biological activity resided in the (-)-isomer of trimetoquinol which was 112-, 275-, 372- and 513-fold more potent than (+)-trimetoquinol in trachea, right atria, distal colon and brown adipose tissue, respectively. (+/-)-Trimetoquinol was equally or slightly less active than (-)-trimetoquinol. The 1-benzyl halogen-substituted analogues of trimetoquinol exhibited differential activation of beta-adrenoceptor subtypes. In functional assays, 3'-iodotrimetoquinol was a potent activator of all beta-adrenoceptor subtypes. 3',5'-Diiodotrimetoquinol was 10-fold more potent as an agonist in tissues containing atypical beta/beta 3-adrenoceptors than those tissues containing beta 1- and beta 2-adrenoceptor sites. Furthermore, this drug was a partial agonist as compared to (+/-)-trimetoquinol and 3'-iodotrimetoquinol on beta 1-adrenoceptors. Pharmacological properties of the compounds on rat beta 3-adrenoceptors expressed in Chinese hamster ovary (CHO) cells were consistent with results observed in functional assays. 3',5'-Diiodotrimetoquinol possessed the greatest potency for activation of adenylyl cyclase. Rank order of affinity for rat beta 3-adrenoceptor was 3'-iodotrimetoquinol = 3',5'-diiodotrimetoquinol > (+/-)-trimetoquinol > (-)-isoprenaline. These results suggest that 3',5'-diiodotrimetoquinol is a promising drug for further chemical modification in the development of selective beta 3-adrenoceptor ligands.     

Breathing of awake goats during prolonged dysfunction of caudal M ventrolateral medullary neurons

Recent scientific studies have demonstrated the efficacy of various forms of immunotherapy for the treatment of allergic diseases. Traditional subcutaneous immunotherapy, sublingual, oral, and intranasal immunotherapy have been shown to significantly reduce symptoms and favorably modulate the immune response. Outcome studies that use patient response data from standardized surveys represent the next challenge to all practicing allergists.     

The P300 component of the auditory evoked potential in the posttraumatic vegetative state

The dynamic studies of P300 component of the acoustic evoked potential were conducted in 12 patients in posttraumatic state of the autonomic system. The amplitude and time parameters of P300 were analyzed, its spatial distribution over the cortex, and features of generation. The obtained results were compared with the normative data. Significant changes in P300 in comparison with the normal characteristics were revealed in patients with the absence of conscious mental activity. These changes were maximally expressed when the state of patients was irreversible. In case of patients' outcome from the studied state the amplitude-temporal and topographic response characteristics tended to normalization but did not reach it completely. The obtained results allow us to consider the P300 component as one of the most informative indices in consciousness recovery after severe brain injury.