LUPUS AND NON-LUPUS CUTANEOUS MANIFESTATIONS IN SYSTEMIC LUPUS ERYTHEMATOSUS

Abstract Mucocutaneous manifestations occur frequently in systemic lupus erythematosus (SLE). Common non-lupus dermatoses may be confused with lupus rashes, with important clinical consequences. A study of 84 consecutive patients with SLE was performed to determine the comparative frequency of lupus and non-lupus mucocutaneous abnormalities, the comparative sensitivity of routine histology and immunofluorescence in the diagnosis of lupus rashes, and the association of skin manifestations with other clinical and serological features. Thirty-five patients had dermatoses attributable to SLE (mean 3.7 per patient) and 58 had derrnatoses which were not directly attributable to SLE (mean 2.1 per patient), highlighting the need for accurate diagnosis of skin rashes in SLE patients. Routine histology confirmed the clinical diagnosis of typical cutaneous lupus in 100% of malar lupus rashes and in approximately 90% of subacute cutaneous and discoid lupus rashes. Direct immunofluorescence of the affected skin provided supportive evidence of cutaneous lupus in 60% of malar lupus rashes and approximately 50% of subacute cutaneous and discoid lupus rashes. This reaffirmed the poor sensitivity of immunofluorescence, compared with routine histology, in the diagnosis of lupus rashes. The association of subacute cutaneous lupus with anti-Ro antibodies was confirmed. (Aust NZ J Med 1987; 17: 501–506).     

von Willebrand disease (VWD): evidence‐based diagnosis and management guidelines,the National Heart,Lung, and Blood Institute (NHLBI) Expert Panel report (USA)1

Summary. von Willebrand disease (VWD) is a commonly encountered inherited bleeding disorder affecting both males and females, causing mucous membrane and skin bleeding symptoms, and bleeding with surgical or other haemostatic challenges. VWD may be disproportionately symptomatic in women of child‐bearing age. It may also occur less frequently as an acquired disorder (acquired von Willebrand syndrome). VWD is caused by deficiency or dysfunction of von Willebrand factor (VWF), a plasma protein that mediates platelet haemostatic function and stabilizes blood coagulation factor VIII. The pathophysiology, classification, diagnosis and management of VWD are relatively complex, but understanding them is important for proper diagnosis and management of patients with VWD. These evidence‐based guidelines for diagnosis and management of VWD from the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel (USA) review relevant publications, summarize current understanding of VWD pathophysiology and classification, and present consensus diagnostic and management recommendations based on analysis of the literature and expert opinion. They also suggest an approach for clinical and laboratory evaluation of individuals with bleeding symptoms, history of bleeding or conditions associated with increased bleeding risk. This document summarizes needs for further research in VWF, VWD and bleeding disorders, including clinical research to obtain more objective information about bleeding symptoms, advancements in diagnostic and therapeutic tools, and enhancement in the education and training of clinicians and scientists in bleeding and thrombotic disorders. The NHLBI Web site ( http://www.nhlbi.nih.gov/guidelines/vwd ) has a more detailed document, a synopsis of these recommendations, and patient education information.     

INTESTINAL ABSORPTION OF CAPTOPRIL AND TWO THIOESTER ANALOGS IN RATS AND DOGS

The objectives of this study were (i) to determine whether the reduced absorption of captopril from the colon of humans also occurs in rats and (ii), after confirmation of the relevance of a new rat model, to evaluate the intestinal absorption of captopril and several of its analogs. A model was developed and validated in which specific sites within the GI tract of rats were surgically implanted with a cannula such that animals could be dosed while conscious and unrestrained. The absorption of captopril after administration into the lower GI tract of rats was significantly reduced relative to the upper GI tract, which was consistent with results reported previously in humans. In rats, the absorption of the S-benzoyl thioester prodrug of captopril (SQ-25868) from the lower GI tract was substantially greater than that of captopril. However, the absorption of the S-benzoyl thioester prodrug of 4-phenyl thio-captopril (SQ-26991) from the lower GI tract was only marginally better than that of captopril. In additional studies in dogs, a 12 h controlled-release formulation of SQ-25868 provided sustained blood levels of captopril while maintaining acceptable bioavailability (>80%). Two approaches were tried, without success, to stabilize captopril in vivo: (i) complexation with zinc (SQ-26284) and (ii) use of ascorbic-acid-buffered (pH 3·5) vehicle. The zinc complex might have failed because it has very low solubility, whereas the pH-3·5-buffered vehicle was quickly neutralized within the colonic lumen in rats, and did not stabilize captopril against oxidation. Rapid neutralization might explain why the colonic bioavailability of captopril was not substantially increased when this pH-3·5-buffered vehicle was tried in humans. © 1997 by John Wiley & Sons, Ltd.     

Lip morphology and area changes associated with surgical correction of mandibular prognathism

Changes in lip morphology and area, measured in two dimensions from standardized lateral head films, were assessed in a series of twenty adults at three times: pre-surgically, 8--14 months post-surgically, and a long-term follow-up at 5--7 years. All individuals received the same, single surgical procedure (Obwegeser sagittal split for correcting mandibular prognathism. Upper and lower lip changes were quantified as millimetres displacement of the lip centroid vertically and horizontally, plus changes in cross-sectional area. Direction and amount of change, its dependency on the amount and kind of surgically induced symphyseal changes, and the intercorrelations among lips and among lip and symphysis variables were statistically evaluated, both univariately and multivariately. Three measures are made of symphysis change: horizontal and vertical repositioning and amount and direction of rotation. Horizontal repositioning primarily affected the lengthening and areal increase of the upper lip. Vertical repositioning had its major influence in the height and cross-sectional area of the lower lip: a superior shift of the mandible made the lower lip shorter, more protrusive and smaller in area; an inferior shift produced an increase in lower lip height with increased area. The third variable, symphyseal rotation, had its greatest influence on the labial-lingual shift of the upper lip's centroid. The long-term follow-up showed little change from the 1 year post-operative conditions; equilibrium of the soft tissue components was then achieved fairly soon after surgery.