No abstract

Fetal outcome in systemic lupus erythematosus (SLE) was retrospectively analysed in 242 pregnancies in 112 unselected patients, and the outcome was compared with that of 417 pregnancies in 192 control women matched for age, parity and socio-economic status. Relative risk for fetal loss after the diagnosis of SLE was 2.5 (95% confidence interval (CI), 1.4-4.5), for prematurity 5.8 (3.2-10.5) and for intra-uterine growth retardation (IUGR) 8.6 (3.0-24.3). Fetal outcome of pregnancy in patients with pre-existing stable lupus nephritis was no worse than in other SLE pregnancies. Relations of three lupus anticoagulant (LA) assays and tree anticardiolipin (aCL) enzyme-linked immunosorbent assays to fetal outcome were studied. Patients positive by any LA assay had a previous fetal loss more often than patients negative by all LA assays (odds ratio 3.4; 95% CI, 1.3-9.0; P = 0.01). Of the 41 patients whose antiphospholipid antibody (aPL) tests were all negative, five (12%) had a history of fetal loss (16% in controls). As a group, aCL was more sensitive for fetal loss than LA (64% vs 50%), but LA was more specific (77% vs 52%). Combinations of one aCL assay with one LA assay had a 41-73% sensitivity and a 64-73% specificity for a history of fetal loss. aPL did not correlate to prematurity or fetal growth retardation. In conclusion, fetal loss in SLE is 2.5 times more prevalent than in the normal population. The presence of LA indicates a high risk for fetal loss, and the absence of aPL is an indication of a favorable pregnancy outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

We describe immunization of two mothers against a new platelet alloantigen, designated Tua, in association with thrombocytopenia in their first born children. The platelet-specific antibodies were identified by a glycoprotein-specific platelet protein assay with husband's platelets. Monoclonal antibodies against glycoprotein complex IIb/IIIa (AP2) and against glycoprotein IIb (SZ22) could be used to immobilize the antigen bearing protein. When monoclonal antibodies against glycoprotein Ib/IX (FMC25) or Ia/IIa (Gi9) were used, no platelet-specific antibodies were detectable. The previously described alloantigens on the glycoprotein IIb/IIIa complex (HPA 1,3,4, Sra and Vaa) were not responsible for the reaction. Immunochemical analysis by an immunoblot assay showed that the Tua antigen resides on GPIIIa but the antigen was destroyed by reduction of the protein. Altogether 10 individuals belonging to three unrelated families were shown to carry the antigen. The family studies within three generations indicated autosomal codominant inheritance. Thus the Tua antigen is apparently different from all previously published platelet alloantigens. One Tua positive blood donor was identified in a population study of approximately 150 individuals. This indicates a low frequency in the Finnish population. Extended population studies will be required to determine a more exact frequency of Tua antigen.

The occurrence of cardiac manifestations and their relationship with the lupus anticoagulant (LA) in SLE was studied in 74 patients who were followed up for 22 years (median), of which 16 years were after the initial LA testing. Pericarditis was the most common cardiac event occurring in 16 (22%) patients but it did not correlate with LA. Valvular heart disease, coronary artery disease, left ventricular failure and/or cor pulmonale were observed in 16 (22%) patients. Taken together, their occurrence was associated with a history of leg ulcers (odds 3.8, P = 0.028) but not with LA or other common clinical manifestations of the antiphospholipid syndrome. Valvular heart disease in five patients was significantly associated with LA (P = 0.05). Cor pulmonale due to chronic pulmonary embolism was present in two patients with LA. Myocardial infarctions in five patients occurred late in the course of disease but in relatively young patients (mean 43 years). Fatal myocardial infarction in the absence of atherosclerosis in two LA-positive patients supports a pathogenetic role for LA in these cases. In conclusion, of the various cardiac complications in SLE, valvular heart disease and cor pulmonale appear to be connected with the antiphospholipid syndrome. Both conditions should be actively sought in patients with LA to decrease possible adverse events (arterial emboli and right ventricular failure) affecting the patients' prognosis.

Methicillin-resistant Staphylococcus aureus (MRSA) has become a significant acute and chronic respiratory pathogen. While vancomycin is effective against MRSA, its relatively poor penetration into lung secretions and dose-limiting renal toxicity make it less effective in the respiratory setting. As inhaled administration of vancomycin would overcome these limitations, we developed a dry powder formulation suitable for inhalation (AeroVanc). Here, we report a phase I, single-dose, dose-escalating study aimed at demonstrating safety and tolerability of AeroVanc. In part I, 18 healthy subjects received a single dose of 16 mg, 32 mg, or 80 mg of AeroVanc. Two subjects also received a 250-mg dose of intravenous vancomycin. In part 2 of the study, 32 mg and 80 mg AeroVanc were administered to subjects with cystic fibrosis as single doses. There were no serious side effects. A small drop in forced expiratory volume in 1 s (FEV1) was observed in 3 subjects with cystic fibrosis, one of whom required salbutamol. Vancomycin was rapidly absorbed after inhalation. Peak and mean plasma concentrations of vancomycin were dose proportional. The average minimum concentration of vancomycin in sputum remained above the usual MIC values for MRSA for up to 24 h (minimum sputum concentration [Cmin], 32-mg dose = 3.05 μg/ml, 80-mg dose = 8.0 μg/ml). In conclusion, AeroVanc was well tolerated and achieved high levels in sputum with a mean systemic absorption of 49%, making it a potential therapeutic strategy for respiratory infection with MRSA.