Pulmonary defence mechanisms

Renal involvement occurs in the majority of patients with systemic lupus erythematosus. Contemporary therapeutic regimens for immunosuppression and for the treatment of hypertension, hyperlipidemia, infections, and seizures have likely contributed to improvements in the prognosis of these patients over the last four decades. Corticosteroids usually ameliorate the manifestations of lupus nephritis but achieve less complete and sustained remissions than do cytotoxic drugs. Among the cytotoxic drugs, pulse cyclophosphamide has one of the best profiles of efficacy and toxicity. Because each episode of exacerbation of lupus nephritis results in cumulative scarring, atrophy and fibrosis, we recommend continued maintenance treatment for 1 year beyond the point of complete remission of proliferative lupus nephritis. Studies are in progress to determine whether innovative treatment strategies will enhance efficacy and minimize toxicity associated with cytotoxic drug therapies. Lupus membranous nephropathy poses a lower risk of renal failure, but persistent nephrotic syndrome confers risks of cardiovascular events; this form of lupus nephritis is usually treated with less intensive regimens of corticosteroids, cytotoxic drugs, or cyclosporine. The prognosis and overall success of treatment for lupus nephritis seem to vary widely among geographically and racially diverse populations. The causes for the apparently worse prognosis and poorer responses to treatment of lupus nephritis in Black patients are currently unexplained and require further study. Until such data are available, caution is clearly warranted in extrapolating evidence, particularly about prognosis and effects of treatment, among different populations of patients with lupus nephritis.     

Protection of side-branches in coronary lesions with a new stent design

Although the association between transverse myelitis (TM) and systemic lupus erythematosus (SLE) has been reported previously, it remains a rare clinical condition. Our experience treating three women with lupus TM within a few months is presented. In each patient, spinal cord dysfunction was accompanied by laboratory or clinical evidence of SLE. Further neurologic manifestations, such as optic neuritis, developed in all patients, suggesting other diagnoses, including multiple sclerosis (MS), Devic's syndrome, and lupoid sclerosis. The outcomes for these three women were severe disability, death, and moderate disability, respectively. The severity of outcome did not seem to correlate with the timing or intensity of treatment. Physiatrists should be aware of the potential for neurologic progression in lupus TM, because patients with this condition invariably require rehabilitation.     

Flares in lupus nephritis: incidence, impact on renal survival and management

One of the characteristics of systemic lupus erythematosus (SLE) is the large inter- and intra-individual variability of the clinical course. Lupus nephritis is no exception. Some patients with kidney involvement may show rapid progression to renal failure, others may enter complete and stable remission after adequate therapy while a number of other patients, with similar clinical and histological pattern at presentation, may alternate periods of clinical quiescence with renal exacerbations of different severity. In this paper we focus on the incidence, the prognostic significance and the treatment of renal flares in patients with SLE nephritis.     

Systemic lupus erythematosus in children: the complex problems of diagnosis and treatment encountered in 101 such patients at the Mayo Clinic

Between 1945 and 1970, 101 children (86 girls and 15 boys) with systemic lupus erythematosus were evaluated at the Mayo Clinic. Only 9 children were less than 9 years old at the time of diagnosis. The most frequent presenting complaint was arthralgia; fever, fatigue, and a "butterfly" malar rash also were common. Renal involvement, found in more than 76 per cent of patients, was a prognostically poor sign. The overall survival of children with renal involvement is improved by the use of adequate steroid therapy.     

Lupus anticoagulants and antiphospholipid antibodies

In recent years, clinical syndromes involving lupus anticoagulants and antiphospholipid antibodies have come into increasing clinical prominence. Since the discovery that most antiphospholipid antibodies require the presence of anionic phospholipid-binding proteins such as B2-glycoprotein I and prothrombin, a large number of studies have attempted to delineate the specificity of these antibodies. Several mechanisms have been proposed to explain the hypercoagulable state associated with these antibodies. This review attempts to summarize these data and the challenges that confront efforts to delineate the pathogenesis of the prothrombotic state associated with the presence of these antibodies.     

Emergency situations in drug addicts. Classification, diagnostic and therapeutic measures

In drug addicts emergency situations can occur which differ only slightly in symptoms but require different therapeutic measures, depending on type of the drug and symptomatology. Diagnostic and therapeutical difficulties in emergency situations, especially the not unfrequent late complications and the considerable danger of suicidal actions require in general the immediate hospitalization. Intensive care and surveillance are necessary. The adequate therapy of ventilatory and circulatory functions is of great importance and should be started by the first consulted physician before transport to the hospital.     

Pediatric airway in health and disease

The most common cause of pediatric anesthetic morbidity is the failure to adequately oxygenate. Problems with pediatric airways are the major cause of this inability to provide adequate oxygenation. Problems with pediatric airways and the diseases that affect them require not only knowledge about their pathophysiology but also considerable hands-on experience and respect for the complications that subsequently occur. It is hoped that by sharing knowledge and experiences, pediatricians can improve the care all of us strive to give our young patients.     

Acute oxygen therapy

Tissues require oxygen for survival. Its delivery depends on adequate ventilation, gas exchange and distribution in the circulation. Many causes of hypoxaemia can be corrected by adding oxygen to the inspired air but response is variable and must be measured.     

Indications for, and use of, cytotoxic agents in SLE

Over the past decade, cytotoxic drugs have come to assume an increasingly important role in the management of systemic lupus erythematosus. Intravenous cyclophosphamide has become the standard treatment for lupus affecting major organs, in particular lupus nephritis. Cytotoxics with less potential for adverse side effects such as azathioprine and methotrexate are widely used in the management of non-major organ lupus and as an adjunct to reduce corticosteroid requirements. Recent clinical experience in lupus with newer cytotoxic drugs such as cyclosporin A, adenosine analogues, and mycophenolate mofetil appear promising and may offer improvements in lupus management in the future.     

Differential roles of the anti-ribosomal P antibody and antineuronal antibody in the pathogenesis of central nervous system involvement in systemic lupus erythematosus

OBJECTIVE: To compare the role of antibodies against the ribosomal P protein (anti-P) with that of antibodies against neuronal cells (anti-N) in the pathogenesis of central nervous system (CNS) involvement in systemic lupus erythematosus (SLE). METHODS: Sera from 87 SLE patients (27 with non-CNS SLE, 34 with lupus psychosis, and 26 with nonpsychotic CNS lupus) and from 20 control patients with neurologic manifestations without SLE and cerebrospinal fluid (CSF) from 41 patients with CNS lupus and from the 20 control patients were assayed for IgG anti-P and anti-N by an enzyme-linked immunosorbent assay (ELISA) using ribosomal P synthetic peptides and by a cell ELISA using paraformaldehyde-fixed SK-N-MC neuroblastoma cell lines, respectively. RESULTS: Serum anti-P levels were significantly elevated in patients with lupus psychosis compared with those with non-CNS SLE or those with nonpsychotic CNS lupus, whereas there were no significant differences in serum anti-N levels among these 3 groups. In contrast, CSF anti-N levels were significantly elevated in patients with lupus psychosis compared with those with nonpsychotic CNS lupus and compared with non-SLE controls, whereas CSF anti-P were not detected in most of the patients. CONCLUSION: The results indicate that anti-P in the systemic circulation and anti-N in the CSF are involved in the development of lupus psychosis.     

Highly cationic anti-DNA antibodies in patients with lupus nephritis analyzed by two-dimensional electrophoresis and immunoblotting

The relationship between chemical properties of anti-DNA antibodies (Abs) and lupus nephritis was investigated. The anti-DNA Abs in sera from systemic lupus erythematosus (SLE) patients were separated by two-dimensional electrophoresis (2-DE) and immunoblotting with goat anti-human IgG Abs. Highly cationic anti-DNA Abs were detected in deoxyribonuclease I (DNase I)-treated sera from patients with lupus nephritis (in 8 of 9 cases) but not in the sera from SLE patients without nephritis (in 0 of 9 cases), normal subjects, or patients with other renal diseases (in 0 of 7 cases). The mean titers of anti-dsDNA Abs in patients with lupus nephritis were not significantly different from those in SLE patients without nephritis. The highly cationic anti-DNA Abs in the sera disappeared after incubation with heparin-Sepharose. These results suggest that highly cationic anti-DNA Abs are specific for lupus nephritis and may be involved in development of lupus nephritis via the binding to glycosaminoglycans on the endothelial cell surface.     

Risk factors for avascular bone necrosis in systemic lupus erythematosus

OBJECTIVE: To study the predictive factors for avascular necrosis (AVN) of bone in patients with systemic lupus erythematosus (SLE). METHOD: The records of 38 SLE patients who developed clinically apparent AVN during the course of their disease were reviewed. Information on clinical presentation, corticosteroid usage and autoantibody profiles was obtained, and comparison was made between these patients and 143 consecutive control SLE patients who did not have AVN. RESULTS: The point prevalence of AVN in our SLE population was 12%. Patients with AVN, when compared with controls, had a significantly higher incidence of neurological disease (39% vs 14%; P < 0.001) and Cushingoid body habitus after steroid treatment (79% vs 53%; P = 0.004). The highest cumulative prednisolone dose in 1 and 4 months was significantly higher in the AVN group than the controls (1.8 vs 1.1 and 4.5 vs 2.8 g, respectively; P < 0.01 in both) and showed a linear trend with the incidence of AVN (chi2 test for trend, P < 0.01 in both). Lupus anticoagulant was associated with AVN (P = 0.02, odds ratio 2.88 [1.14-7.28]). Logistic regression analysis revealed that the highest cumulative prednisolone dose administered in 4 months, the maximum and mean daily prednisolone dosage, and the lupus anticoagulant were independent risk factors for AVN. CONCLUSIONS: Corticosteroid remains the major predisposing factor for AVN in SLE. Patients who require an initial high-dose steroid for disease control are at risk of AVN, especially if they are positive for the lupus anticoagulant or develop Cushingoid habitus after steroid treatment. High-risk patients should be closely monitored so that early AVN can be diagnosed by sensitive techniques such as magnetic resonance imaging and radioisotope bone scanning.     

Lupus pregnancy, its effect on the course of lupus nephritis and the evaluation of fetal loss frequency

The subject of analysis were data concerning the 101 pregnancies in 43 patients with systemic lupus erythematodes observed in years 1965-1990. The evaluation proved that pregnancy does not deteriorate the course of lupus nephritis that is in the remission before the conception. In lupus patients the risk of fetal loss and stillbirth is high, especially in the presence of anticardiolipin antibodies. The course of active lupus occurring during pregnancy is frequently severe and its effect on the pregnancy is very harmful.     

Early aspects of the intrarenal distribution of mercury after the intravenous administration of mercuric chloride

It is generally considered that the clinical manifestations of human and canine systemic lupus erythematosus (SLE) are similar in many respects. However, there are differences in serological markers of SLE between the two species, which has led to much discussion on which immunopathological criteria might be appropriate in the diagnosis of the canine disorder. Further studies on canine SLE will need to address these issues, so that definitive diagnostic indices may be employed. Areas which require to be re-assessed, in particular, include the applicability of assays for antibodies to double-stranded DNA--a hallmark of human SLE, a re-evaluation of the anaemia associated with canine SLE and an index of the clinical activity of the disease process.     

Upregulation of cathepsin D expression in the dedifferentiating salamander limb regenerates and enhancement of its expression by retinoic acid

The antiphospholipid antibodies (aPL) present in "antiphospholipid-protein syndrome and autoimmune disorders" are associated with thromboembolic episodes, such as venous and/or arterial thrombosis and fetal loss. Patients with antiphospholipid antibodies have, by definition, laboratory abnormalities in either coagulation assays or various solid phase immunoassays ELISA or radioimmunoassays (RIA). These assay systems were initially thought to detect antibodies against phospholipids. The problem was complicated when it was reported that phospholipid is not the sole antigen but only a part of it, the other contribution being due to b2-glycoprotein I (b2-GP I). More findings, demonstrate that the aPL are in fact anti-b2-GP I antibodies directed against a epitope which is expressed when b2-GP I is bound to anionic phospholipid or another suitable surface. Recent studies have demonstrated that antibodies related to lupus anticoagulant (LA) induce an anticoagulant activity in b2-GP I. Some of these LA require binding to phospholipid. However, not all LA require b2-GP I as a cofactor. Human prothrombin is an antigen for some LA IgG's. Finally, a subclassification of phospholipid-dependent coagulation test anticoagulants is described, there appear to be several subclasses of LA, and the clinical and laboratory criteria required to establish the diagnosis of antiphospholipid-protein syndrome is emphasised.     

Acute transverse myelitis in systemic lupus erythematosus: a case of rapid diagnosis and complete recovery

Acute transverse myelitis is a rare and serious complication of systemic lupus erythematosus. Delay in diagnosis and treatment is associated with significant morbidity and mortality. Earlier diagnosis is facilitated by magnetic resonance imaging. Treatment of systemic lupus erythematosus-related acute transverse myelitis remains controversial. The use of steroids alone may result in incomplete recovery. We report a patient who was promptly diagnosed with systemic lupus erythematosus-related acute transverse myelitis by magnetic resonance imaging. The patient had complete resolution of her symptoms following aggressive treatment with steroids and cyclophosphamide. Review of published treatment of systemic lupus erythematosus-related acute transverse myelitis suggests aggressive therapy with steroids and cyclophosphamide may provide the best outcome.     

Enhanced expression of bcl-2 inhibits apoptosis in cultured human keratinocytes

Intravenous heparin followed by oral warfarin sodium is effective for preventing recurrent thromboembolism in patients who have pulmonary embolism or proximal vein thrombosis. The effectiveness of intravenous heparin depends on obtaining an adequate anticoagulant response early during therapy. A validated heparin protocol should be used to ensure that an adequate anticoagulant response is obtained as soon as possible. Low molecular weight heparin has the practical advantage that it does not require monitoring and dose finding. If thrombolytic therapy is indicated, it is safer for many patients to base management on the noninvasive diagnosis rather than performing pulmonary angiography. In patients suspected to have pulmonary embolism who have nondiagnostic lung scan and adequate cardiorespiratory reserve, serial noninvasive leg testing is a practical approach that avoids pulmonary angiography, identifies patients who have proximal vein thrombosis requiring treatment, and avoids the risks of anticoagulant treatment in the majority of patients.     

The effect of phosphorylation and site-specific mutations in the immunodominant epitope of the human ribosomal P proteins

The immunodominant epitope recognized by lupus antiribosomal P protein antibodies (anti-P antibodies) is located within the 11 C-terminal residues common to the three P proteins. This epitope contains a potential phosphorylation site for casein kinase II and clusters of acidic and hydrophobic amino acids. To determine the role of each of these features in antigen recognition, lupus anti-P sera were tested for binding to phospho- and dephospho- forms of the P proteins and to synthetic peptide antigens in which site-specific modifications had been introduced. Immunoblot analysis revealed that anti-P antibodies specific for the phospho- form of the P proteins represented only a minor population of anti-P antibodies and, in many cases, were absent altogether. In contrast, when charged substitutions were introduced into either the acidic or hydrophobic clusters and tested by ELISA, striking reductions of 64-86% were observed. Conservative Gly-->Pro substitutions also produced a 73% average reduction in anti-P binding whereas substitution of either Ser-105 or the C-terminal Asp-115 resulted in a < 35% reduction in binding. These findings suggest that phosphorylation of the P proteins does not play a role in antibody recognition but that anti-P antibodies require both the acidic and hydrophobic clusters for optimal binding to synthetic peptide antigens. The remarkable degree of specificity demonstrated by these antibodies supports the view that anti-P autoantibodies result from a highly specific (at the B cell level) immune response to self antigen.     

Deep venous thrombosis in pregnant women

The main risk factors for deep vein thrombosis in pregnancy and after delivery are preeclampsia, operative delivery, adiposity, prolonged bed rest, and haemostatic defects (antithrombin, protein C and protein S deficiencies), activated protein C resistance, lupus anticoagulant/antiphospholipid antibodies. Hyperhomocystinaemia is a general risk factor for deep vein thrombosis. The clinical diagnosis of deep vein thrombosis is difficult and must be confirmed by imaging techniques. Positive D-dimer has high sensitivity, but low specificity to detect acute thrombosis. Standard treatment is unfractionated heparin intravenously for 7-10 days, followed by subcutaneous injections. Anticoagulant treatment is prolonged for 6-12 weeks after delivery, usually with warfarin. During pregnancies associated with high risk of thrombosis, low molecular heparin prophylaxis is given during pregnancy and 6-12 weeks after delivery. Thrombosis in pregnancy must be followed by adequate investigation for an underlying thrombotic predisposition.