Alveolar hemorrhage, glomerulonephritis and anti-cytoplasmic polynuclear antibodies]

The value of antineutrophilic cytoplasmic antibodies (ANCA) was assessed in the diagnosis and chronic treatment of 7 patients with microscopic polyarteritis or Wegener's granulomatosis. All patients had oligoimmune glomerulonephritis with segmental and focal necrosis and presented with anaemia. Five of them had alveolar haemorrhage with haemoptysis and infiltrates at radiography. ANCA were assayed by indirect immuno-fluorescence on ethanol-fixed neutrophils and were strongly positive, with a cycloplasmic aspect in 5 cases and a perinuclear aspect in 2 cases. Initial remission with fall in ANCA titres was obtained with corticosteroids, cyclophosphamide and sometimes plasmapheresis (5 patients), but frequent relapses with re-elevation of ANCA titre occurred when treatment was reduced. It is concluded that ANCA are very helpful in the diagnosis of systemic vasculitis, notably in cases with first-time alveolar haemorrhage. They also facilitate monitoring and therapeutic decisions, since relapses are frequent.     

Mediastinal adenopathies and presence of anti-cytoplasmic antibodies of diffuse type polynuclear neutrophils]

We report a case of sarcoidosis with mediastinal and pulmonary localizations associated with diffuse antineutrophil cytoplasmic antibodies (c-ANCA). This led to discuss the differential diagnosis with vascularitis and the specificity of c-ANCA in Wegener's granulocytosis.     

Cytomegalovirus associated diseases of the heart]

Latent cytomegalovirus (CMV) infection is not uncommon in the juvenile and adult population. The full blown disease is mostly restricted to immunosuppressed and immunodeficient patients, but may also occur in healthy individuals. The acute CMV-myocarditis often takes a mild course with only transient changes of left ventricular hemodynamics or a pericardial effusion as assessed by echocardiography. In our patient population it was characterized by the presence of anti-interfibrillary antibodies. In acute myocarditis the virus genome can be detected by in-situ hybridization in 42% (40% in the myocytes, 21% in the interstitial cells and 41% in endothelial cells). In patients with perimyocarditis CMV-DNA is found in 24% of patients in the myocytes, in 24% of patients in the interstitial cells and in 50% of patients in the endothelium. In healthy controls CMV-DNA could be assessed only in interstitial and endothelial cells (70% and of the infected 30% of positive cases) but not in the myocytes. In dilated cardiomyopathy (DC) CMV-DNA can be found in 48%. Particularly in myocytes in 45% of cases, in interstitial cells in 50% and in the endothelium of small vessels in 68%. An induction of the disease by a chronic local stimulation of the immune system is a likely pathogenetic explanation of the immuno phenomena observed in parallel to the viral persistence. Additive damage by chronic CMV infection can be caused by the infection of the endothelium and smooth muscle cells of the intima of coronary arteries. There are some reports of CMV-DNA detection in the arterial walls or atherosclerotic plaques of patients with atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anti-CD20 monoclonal antibodies and associated viral hepatitis in hematological diseases

Over the past decade, the administration of anti-CD20 monoclonal antibodies such as rituximab has demonstrated various degrees of effectiveness and has improved patients’ outcomes during the treatment of autoimmune hematological disorders and hematological malignancies. However, the depletion of B-cells, the distribution of T-cell populations, and the reconstruction of host immunity resulting from the use of anti-CD20 monoclonal antibodies potentially lead to severe viral infections, such as hepatitis B virus (HBV), hepatitis C virus (HCV), parvovirus B19, and herpes viruses, in patients who are undergoing immune therapy or immunochemotherapy. Of these infections, HBV- and HCV-related hepatitis are a great concern in endemic areas because of the high morbidity and mortality rates in untreated patients. As a result, prophylaxis against HBV infection is becoming a standard of care in these areas. Parvovirus B19, a widespread pathogen that causes red blood cell aplasia in immunocompromised hosts, also causes hepatitis in healthy individuals. Recently, its association with hepatitis was recognized in a patient treated with rituximab. In addition, adenovirus, varicella-zoster virus, hepatitis E virus, and rituximab itself have been linked to the occurrence of hepatitis during or after rituximab treatments. The epidemiologies and pathogeneses of these etiologies remain unknown. Because of the increasing use of anti-CD20 monoclonal antibodies for the treatment of hematological malignancies or autoimmune hematological disorders, it is imperative that physicians understand and balance the risks of hepatotropic virus-associated hepatitis against the benefits of using anti-CD20 monoclonal antibodies.     

Treatment of autoimmune diseases and graft rejection with anti-CD4 antibodies]

Based on the experience that T helper lymphocytes play an important part in the initiation and maintenance of various autoimmune diseases and also in graft rejection, novel therapeutic approaches have been developed and are under investigation. They are aimed at selective inhibition of T cells whose activation is unwanted. Useful tools for this purpose are monoclonal antibodies to cell surface molecules which are restricted to certain cell populations. In this review the concept of treatment with antibodies to CD4-a surface molecule characteristic of T helper lymphocytes-is discussed. Encouraged by experimental experiences obtained during the past years, a series of case reports were published and clinical pilot studies have been performed, the preliminary results of which are now becoming available. Anti-CD4 therapy appears to be a promising approach. Short-lasting effects can be separated from long-lived effects. The latter are not easy to explain, although hypotheses have been developed still requiring more detailed experimental confirmation.     

Heart valve surgery and associated diseases in aged subjects]

The object of this study was to assess the additional risk related to associated pathology in patients aged 70 or over undergoing valvular heart surgery. Two hundred and thirty nine patients aged 70 to 87 years (average 74.6 +/- 3.2) underwent this form of surgery between October 1979 and June 1989. Sixty seven had coronary artery disease, 26 had atherosclerotic occlusive peripheral arterial disease, and 149 had one or more extracardiovascular pathology. Two hundred and thirteen patients underwent monovalvular and 26 bivalvular replacement. Coronary bypass was associated in 25 cases. Eighteen patients (7.5%) died in the 30 days following surgery. The perioperative mortality was not significantly greater in patients with extra-cardiac pathology (9.4% vs 4.4%; NS), in patients with coronary artery disease (11.9% vs 5.8%; NS), in patients with respiratory failure and FEV1 < 1 litre (1 death out of 20 cases) or in patients with renal failure and serum creatinine levels > or = 175 mumol/l (20% vs 6.3%, NS). Respiratory failure was the only extra-cardiac variable identified with increased perioperative morbidity. The perioperative mortality of elderly patients with valvular heart disease is greater than that of patients under 70 years of age (6.4% vs 2.1%) in our experience of the last 6 years p < 0.01). Associated arterial and extra-cardiac pathology does not significantly increase the mortality and strict selection of elderly inoperable patients together with improved surgical techniques and postoperative care has considerably reduced perioperative morbidity and mortality in this group of patients.     

特异性抗膜突蛋白抗体在结缔组织病肺部受累早期诊断中的意义

目的 探讨特异性的自身抗体对结缔组织病(CTD)相关肺部损伤的临床意义.方法 以重组膜突蛋白作为抗原,应用酶联免疫吸附试验(ELISA)和免疫印迹法检测40例系统性硬化症(SSc)患者和38例混合性结缔组织病(MCTD)患者外周血抗膜突蛋白抗体.比较不同肺脏受累的CTD患者之间抗膜突蛋白抗体的差异.结果 ELISA和免疫印迹法检测发现21例(52%)SSc患者和15例(39%)MCTD患者抗膜突蛋白抗体阳性.CTD合并肺脏受累组抗膜突蛋白抗体的滴度均显著高于无肺脏受累组(0.23±0.14与0.12±0.35,P=0.001).在肺功能检查方面,抗膜突蛋白抗体阳性患者组与阴性患者组比较,肺总量[(82±10)%与(90±14)%,P=0.027],用力肺活量[(76±13)%与(85±17)%,P=0.040],一氧化碳弥散量[(58±16)%与(72±23)%,P=0.014]均显现显著降低.结论 抗膜突蛋白抗体在SSc和MCTD患者中具有较高的阳性率,并与CTD合并肺脏受累显著相关,可能早期提示结缔组织病肺脏损害.