Assessment of radiologic progression in rheumatoid arthritis. A randomized, controlled trial

Radiologic assessment of progressive joint destruction in rheumatoid arthritis is generally considered to be the ultimate standard for evaluation of treatment. We compared alternative radiologic techniques by performing a randomized, controlled trial in which hand films of rheumatoid arthritis patients were read by several skilled observes. The number of joints evaluated (34 versus 18) was found to make relatively little difference, but the number of readers and their experience level was critical. Films should be read in pairs. Joint space narrowing and erosion scores were shown to contribute independent information. Use of recommended techniques can reduce the number of patients required and, thus, can reduce the cost of a clinical trial by more than half and can substantially increase the sensitivity and efficiency of a trial. Therefore, critical selection of the method of assessing study endpoint is of great importance.     

A canadian study of the total medical costs for patients with systemic lupus erythematosus and the predictors of costs

Objective. We conducted a cost identification analysis on 164 consecutive patients with systemic lupus erythematosus (SLE) who entered the Montreal General Hospital Lupus Registry between January 1977 and January 1990, compared their costs to the population of Quebec, and determined the predictors of cost. Methods. In January 1990 and 1991, participants completed questionnaires on health services utilization and on employment history over the preceding 6 months, as well as on functional, psychological, and social well-being. The societal burden of SLE was determined in terms of direct costs (all resources consumed in patient care) and indirect costs (wages lost due to lack of work force participation because of morbidity). Results. The mean total annual cost for 1989, as assessed in January 1990 and expressed in 1990 Canadian dollars, was $13,094. Although only 44% of the patients were fully employed, indirect costs were responsible for 54% of this total ($7,071). Ambulatory costs, primarily diagnostic procedures, medications, and visits to health care professionals, comprised 55% of direct costs ($3,331). The results of the 1990 cost determination were similar. On average, hospitalizations among SLE patients were 4 times more frequent than among the general population of Quebec (matched for age and sex), and the number of ambulatory visits to physicians was double that for the average resident of Quebec. Higher 1989 values of creatinine and a poorer level of physical functioning were the best predictors of higher 1990 direct costs (R² = 0.29). A poorer SLE well-being score, a combination of education and employment status, and a weaker level of social support were the best predictors of higher indirect costs (R² = 0.29). Conclusion. The direct and indirect costs for patients with SLE are substantial, and their respective predictors are distinct. Direct costs arise from organic complications which induce functional disability. Predictors of indirect costs are potentially amenable to psychological or social interventions and may be more easily modified than the determinants of direct costs, thereby improving patient outcome while simultaneously reducing disease costs.     

Enamel and dental anomalies in latent‐transforming growth factor beta‐binding protein 3 mutant mice

Latent‐transforming growth factor beta‐binding protein 3 (LTBP‐3) is important for craniofacial morphogenesis and hard tissue mineralization, as it is essential for activation of transforming growth factor‐β (TGF‐β). To investigate the role of LTBP‐3 in tooth formation we performed micro‐computed tomography (micro‐CT), histology, and scanning electron microscopy analyses of adult Ltbp3‐/‐ mice. The Ltbp3‐/‐ mutants presented with unique craniofacial malformations and reductions in enamel formation that began at the matrix formation stage. Organization of maturation‐stage ameloblasts was severely disrupted. The lateral side of the incisor was affected most. Reduced enamel mineralization, modification of the enamel prism pattern, and enamel nodules were observed throughout the incisors, as revealed by scanning electron microscopy. Molar roots had internal irregular bulbous‐like formations. The cementum thickness was reduced, and microscopic dentinal tubules showed minor nanostructural changes. Thus, LTBP‐3 is required for ameloblast differentiation and for the formation of decussating enamel prisms, to prevent enamel nodule formation, and for proper root morphogenesis. Also, and consistent with the role of TGF‐β signaling during mineralization, almost all craniofacial bone components were affected in Ltbp3‐/‐ mice, especially those involving the upper jaw and snout. This mouse model demonstrates phenotypic overlap with Verloes Bourguignon syndrome, also caused by mutation of LTBP3, which is hallmarked by craniofacial anomalies and amelogenesis imperfecta phenotypes.     

Einzelreferate und Buchbesprechungen

Ohne Zusammenfassung     

Versuche einer chemischen Charakterisierung und Reindarstellung des Trichophytins (des aktiven,antigenen Prinzips pathogener Hautpilze)

Ohne Zusammenfassung     

Virtual endocast of Ignacius graybullianus (Paromomyidae,Primates) and brain evolution in early primates

Extant primates are distinctive among mammals in having relatively large brains. As stem primates, Paleogene plesiadapiforms provide direct information relevant to the earliest stages in the evolution of this characteristic. Here we describe a virtual endocast reconstructed from ultra high resolution X-ray computed tomography data for the paromomyid plesiadapiform Ignacius graybullianus (USNM 421608) from the early Eocene of Wyoming. This represents the most complete endocast known for a stem primate, allowing for an unprecedented study of both size and fine details of anatomy. Relative to fossil and extant euprimates, I. graybullianus had large olfactory lobes, but less caudal development of the cerebrum and a poorly demarcated temporal lobe, suggesting more emphasis on olfaction and a less well developed visual system. Although its brain was small compared to those of extant primates, the encephalization quotient of I. graybullianus is higher than that calculated for Paleocene Plesiadapis cookei and overlaps the lower portion of the range documented for fossil euprimates. Comparison to the basal gliroid Rhombomylus suggests that early primates exhibited some expansion of the cerebrum compared to their ancestors. The relatively small brain size of I. graybullianus, an arboreal frugivore, implies that neither arboreality nor frugivory was primarily responsible for the expanded brains of modern primates. However, the contrasts in features related to the visual system between I. graybullianus and fossil and extant euprimates suggest that improvements to these portions of the brain contributed to increases in brain size within Euprimates.