Thyroxine and triiodothyronine levels in hyperthyroid patients during treatment with propranolol

In the last few years, there has been an active effort in Italy to involve the population in solving health problems at the community level. This movement had its origin in the industrial setting, where workers succeeded in promoting legislation which gives them control over matters affecting their health. This experience lead to the development of a health education methodology based on the following principles: (a) the assessment of health needs must be based on the subjective experience of the people who have acquired knowledge and interest in health problems; (b) the evaluation of health needs by professionals serves to complement and integrate the assessment of needs as experienced by the community; (c) the self-diagnosis of the community -- in particular of homogenous community groups exposed to similar health risks and experiencing the same needs--and the diagnosis of the professionals must undergo cross-validation and be accepted by both parties; (d) on the basis of this mutual agreement, community health programmes should be planned and carried out jointly by the professionals and the people.     

Verbal and nonverbal abilities in the Williams syndrome phenotype: evidence for diverging developmental trajectories

One commonly cited feature of Williams syndrome is a characteristic dissociation between relatively spared language skills and severely impaired nonverbal abilities. However, the actual evidence for a dissociation between verbal and nonverbal abilities in Williams syndrome is equivocal. In two separate studies we examined these abilities in 16 individuals showing the Williams syndrome phenotype. When considered as a whole, the group did have significantly superior verbal abilities, but this difference was caused by a large discrepancy in abilities in only a small number of individuals. In both studies there was a clear, linear relation between individuals' verbal ability, and the magnitude of their verbal-nonverbal discrepancy. We suggest that these results are best explained in terms of verbal ability developing at a faster rate than nonverbal ability in this disorder. We discuss how this model of differential rates of development has the potential to reconcile the apparently inconsistent findings in this area.     

Functional outcome assessment of adults with right hemisphere brain damage

This article addresses functional outcome assessment of adults with cognitive-communicative disorders due to relatively focal right hemisphere brain damage (RBD). Our discussion observes the World Health Organization's orientation on the multidimensional consequences of health conditions. The WHO framework distinguishes specific deficits (impairments) from their functional consequences: disabilities, or restrictions in daily life activities and handicaps, or broader changes in life role participation. Although there is little evidence about the functional aftermath of RBD, especially in relation to cognitive-communicative disorders, we summarize the data and observations that are available and hypothesize about relationships among outcomes at different levels. We also describe some tools and procedures that may be useful for measuring functional outcomes after RBD, along with relevant caveats, and end with a discussion of research needs and future directions, emphasizing gaps that span the range from basic investigation to treatment research to instrument and procedure development.     

Wavelet image extension for analysis and classification of infarcted myocardial tissue

Some computer applications for tissue characterization in medicine and biology, such as analysis of the myocardium or cancer recognition, operate with tissue samples taken from very small areas of interest. In order to perform texture characterization in such an application, only a few texture operators can be employed: the operators should be insensitive to noise and image distortion and yet be reliable in order to estimate texture quality from the small number of image points available. In order to describe the quality of infarcted myocardial tissue, we propose a new wavelet-based approach for analysis and classification of texture samples with small dimensions. The main idea of this method is to decompose the given image with a filter bank derived from an orthonormal wavelet basis and to form an image approximation with higher resolution. Texture energy measures calculated at each output of the filter bank as well as energies of synthesized images are used as texture features in a classification procedure. We propose an unsupervised classification technique based on a modified statistical t-test. The method is tested with clinical data, and the classification results obtained are very promising. The performance of the new method is compared with the performance of several other transform-based methods. The new algorithm has advantages in classification of small and noisy input samples, and it represents a step toward structural analysis of weak textures.     

Cytochrome P450-mediated metabolism of the HIV-1 protease inhibitor ritonavir (ABT-538) in human liver microsomes

The HIV-1 protease inhibitor ritonavir (ABT-538) undergoes cytochrome P450-mediated biotransformation in human liver microsomes to three major metabolites, Ml, M2 and M11, with wide interindividual variation in the rates of metabolite formation. The structures of these metabolites were determined with the use of electrospray ionization mass spectrometry. Chemical inhibition, metabolic correlation, immunoinhibition and metabolism by microsomes derived from specific CYP cDNA-transfected B-lymphoblastoid cell lines indicated that the CYP3A subfamily of enzymes was the major contributor to the formation of M1 and M11, whereas both CYP3A and CYP2D6 contributed to the formation of M2. None of the typical CYP3A substrates/inhibitors (e.g., ketoconazole, troleandomycin) were able to completely inhibit ritonavir metabolism, even at high concentrations. Ritonavir was found to be a potent inhibitor of CYP3A-mediated biotransformations (nifedipine oxidation, IC50) = 0.07 microM; 17alpha-ethynylestradiol 2-hydroxylation, IC50 = 2 microM; terfenadine hydroxylation, IC50 = 0.14 microM). Ritonavir was also found to be an inhibitor of the reactions mediated by CYP2D6 (IC50 = 2.5 microM) and CYP2C9/10 (IC50 = 8.0 microM). The results of this study indicate the potential for in vivo inhibition of the metabolism by ritonavir of drugs that are CYP3A, CYP2D6 and, to a lesser extent, CYP2C9/10 substrates.     

Sarcomas of the female genital tract and pelvic soft tissues. A cluster of 14 cases in one year

We report ten uterine and four extrauterine sarcomas encountered in a twelve month period (1989-90). The seven new cases of uterine sarcomas represent an estimated one third of all cases of malignancy of the corpus uteri, which were diagnosed at the gynaecology departments of St James's and Adelaide hospitals in one year. Overall, the prognosis was poor in the uterine sarcoma group-only one patient in clinically tumour free and five have succumbed to their disease. Delay in diagnosis especially in younger women with fibroid uterus contributed to this outcome.     

New multimeric magnetic resonance imaging agents

RATIONALE AND OBJECTIVES: The authors investigated the effect of multimerization on the relaxivity of macrocyclic gadolinium (Gd) chelates. The objective was to develop more sensitive magnetic resonance imaging (MRI) contrast agents to study biochemical processes. METHODS: Covalently linked nonionic, macrocyclic, multimeric lanthanide chelates that belong to the classes of dimers, trimers, tetramers, hexamer, and octamer, in the molecular weight range approximately 1 to 5 KDa, were synthesized. The chemical linkage was based on either the amide bond or the 2-hydroxypropylidene bond. Relaxivity values, 20r1, on Gd3+ chelates and hydration numbers, Q, on Tb3+ chelates were determined. RESULTS: Relaxivity values increased with molecular weight and Q values were not affected, the increase in r1 in attributable to the expected increase in the overall rotational correlation time, tau r with an increase in molecular weight. The rigidity of the linkers, which is expected to affect the intrachelate rotational correlation time tau r* that makes a contribution to the overall correlation time, tau r, exerted a noticeable effect. The hydroxyl-based chelates generally had lower r1 values than the amide-based chelates. This is rationalized as arising from the longer and thereby rate-limiting effect of the tau m value for the hydroxyl chelates compared with that reported of the amide-based chelates. This rate limiting effect of tau m becomes a dominant factor controlling attainable enhanced relaxivity when multimers based on traditional chelate designs are used for MRI applications. CONCLUSIONS: Approaches aimed at enhancing relaxivity by modulating the water relaxation time, tau m, will be important for the future development of functional MRI contrast agents for the imaging of biochemical processes.