Chronic inflammation predicts long-term mortality in patients with Raynaud's phenomenon.

BACKGROUND: Subclinical chronic inflammation could be the driving force behind the recently revealed association between abnormal nailfold capillaries as well as autoantibodies and long-term mortality in patients with incipient Raynaud's phenomenon. Whether laboratory markers that reflect a chronic inflammatory process are directly related to mortality in Raynaud's phenomenon is not known. METHODS: In total, 2958 patients with incipient Raynaud's phenomenon without previously known connective tissue disease (CTD) were enrolled. At their initial presentation, laboratory tests for C-reactive protein (CRP), leucocytes, fibrinogen and the haemoglobin concentration were obtained. In addition, nailfold capillaries and antinuclear antibodies (ANA) were assessed. Patients' mortality was recorded through a median follow-up period of 9.3 years. RESULTS: Baseline CRP, fibrinogen and haemoglobin concentration were associated with long-term mortality in an individual analysis of patients with incipient Raynaud's phenomenon. In a multivariable model including patients' age, nailfold capillaries and ANA, a low haemoglobin concentration remained independently related to future mortality. Amongst potential predictors for mortality in patients with Raynaud's phenomenon, a low haemoglobin concentration was most strongly related to patients' mortality risk. CONCLUSION: In Raynaud's phenomenon, laboratory markers that can be attributed to a chronic inflammatory state independently yield prognostic information in addition to the presence of abnormal nailfold capillaries and ANA. Amongst all prognostic markers, the haemoglobin concentration is most strongly related to patients' mortality in Raynaud's phenomenon.

Associations of nailfold capillary abnormalities and immunological markers in early Raynaud's phenomenon.

OBJECTIVES: Nailfold capillaroscopy (NC) and laboratory tests for antinuclear antibodies (ANA) are routinely used in parallel for detection of emerging connective tissue disease (CTD) in patients with Raynaud's phenomenon (RP). The aim of this study was to assess the associations between distinct nailfold capillary abnormalities and concomitant autoantibodies in patients with incipient RP without previously known CTD. METHOD: Patients with incipient RP without previously known CTD were included in this retrospective analysis. We analysed the association of particular capillary abnormalities (reduced density, avascular fields, dilations, giant capillaries, haemorrhages, tortuosity, ramifications, oedema) with ANA and ANA subsets (anti-Scl-70, anti-CENP-B, anti-U1-RNP, anti-dsDNA, anti-SSA(Ro), anti-SSB(La), anti-Sm, and anti-Jo-1 antibodies). We also developed a score that allows the estimation of each patient's individual probability for the presence of an ANA titre ≥ 1:160. RESULTS: The final analysis comprised 2971 patients. Avascular fields, giant capillaries, reduced capillary density, and capillary oedema were closely related to an ANA titre ≥ 1:160. Both giant capillaries and avascular fields were associated with anti-Scl-70 and anti-CENP-B antibodies. Only a weak association was found between giant capillaries and anti-U1-RNP antibodies. Each patient's individual probability for the presence of an ANA titre ≥ 1:160 can be represented by a sum score comprising giant capillaries, reduced density, avascular fields, ramifications, and oedema as well as patients' sex and age. CONCLUSION: In patients with incipient RP, anti-Scl-70 and anti-CENP-B antibodies are related most specifically to distinct capillary alterations. Although a sum score can represent the patient's probability for elevated ANA titres, NC cannot substitute for immunological tests in patients with incipient RP.

Abatacept (CTLA-4IG) treatment reduces the migratory capacity of monocytes in patients with rheumatoid arthritis.

OBJECTIVE: The binding of abatacept (CTLA-4Ig) to the B7 ligands CD80 and CD86 prevents the engagement of CD28 on T cells and thereby prevents effector T cell activation. In addition, a direct effect of CTLA-4Ig on antigen-presenting cells (APCs) could contribute to the therapeutic effect. To further elucidate the mechanism of CTLA-4Ig, we performed phenotype and functional analyses of APCs in patients with rheumatoid arthritis (RA) before and after the initiation of CTLA-4Ig therapy. METHODS: Peripheral blood mononuclear cells were analyzed before and at 2 and 4 weeks after the initiation of CTLA-4Ig therapy. Proportions of APCs were determined by flow cytometry. CD14+ monocytes were further analyzed for the expression of costimulatory and adhesion molecules and for their transendothelial migratory capacity in vitro. In addition, CD14+ monocytes from healthy controls were analyzed for their migratory and spreading capacity. RESULTS: Proportions and absolute numbers of monocytes were significantly increased in RA patients treated with CTLA-4Ig. The expression of several adhesion molecules was significantly diminished. In addition, monocytes displayed a significant reduction in their endothelial adhesion and transendothelial migratory capacity upon treatment with CTLA-4Ig. Likewise, isolated monocytes from healthy controls revealed a significant reduction in their migratory and spreading activity after preincubation with CTLA-4Ig or anti-CD80 and anti-CD86 antibodies. CONCLUSION: We describe direct effects of CTLA-4Ig therapy on phenotype and functional characteristics of monocytes in RA patients that might interfere with the migration of monocytes to the synovial tissue. This additional mechanism of CTLA-4Ig might contribute to the beneficial effects of CTLA-4Ig treatment in RA patients.

A rare polymorphism in the gene for Toll-like receptor 2 is associated with systemic sclerosis phenotype and increases the production of inflammatory mediators.

OBJECTIVE: To investigate whether polymorphisms in Toll-like receptor (TLR) genes, previously reported to be associated with immune-mediated diseases, are involved in systemic sclerosis (SSc). METHODS: We genotyped 14 polymorphisms in the genes for TLRs 2, 4, 7, 8, and 9 in a discovery cohort comprising 452 SSc patients and 537 controls and a replication cohort consisting of 1,170 SSc patients and 925 controls. In addition, we analyzed 15-year followup data on 964 patients to assess the potential association of TLR variants with the development of disease complications. We analyzed the functional impact of the associated polymorphism on monocyte-derived dendritic cells. RESULTS: In the discovery cohort, we observed that a rare functional polymorphism in TLR2 (Pro631His) was associated with antitopoisomerase (antitopo) positivity (odds ratio 2.24 [95% confidence interval 1.24-4.04], P=0.003). This observation was validated in the replication cohort (odds ratio 2.73 [95% confidence interval 1.85-4.04], P=0.0001). In addition, in the replication cohort the TLR2 variant was associated with the diffuse subtype of the disease (P=0.02) and with the development of pulmonary arterial hypertension (PAH) (Cox proportional hazards ratio 5.61 [95% confidence interval 1.53-20.58], P=0.003 by log rank test). Functional analysis revealed that monocyte-derived dendritic cells carrying the Pro63His variant produced increased levels of inflammatory mediators (tumor necrosis factor α and interleukin-6) upon TLR-2-mediated stimulation (both P<0.0001). CONCLUSION: Among patients with SSc, the rare TLR2 Pro631His variant is robustly associated with antitopoisomerase positivity, the diffuse form of the disease, and the development of PAH. In addition, this variant influences TLR-2-mediated cell responses. Further research is needed to elucidate the precise role of TLR-2 in the pathogenesis of SSc.

ACE gene polymorphism and proliferative retinopathy in type 1 diabetes: results of a case-control study.

OBJECTIVE: To evaluate the relationship between the ACE insertion/deletion polymorphism and proliferative diabetic retinopathy in patients with type 1 diabetes of long duration. Based on epidemiological and pathophysiological findings, risk factors apart from glycemic control and duration of disease are likely to be involved in the development of proliferative retinopathy. RESEARCH DESIGN AND METHODS: In this case-control study, we compared 81 patients with longstanding (> or =20 years) type 1 diabetes who had nonproliferative (mild or moderate background) retinopathy with 95 patients with diabetes of similar duration and HbA1c who had proliferative retinopathy. To avoid the confounding effect of nephropathy, patients with overt nephropathy were excluded, and microalbuminuria was introduced into the multiple logistical regression model. The polymorphic region in intron 16 of the ACE gene (17q23) was analyzed using the polymerase chain reaction. RESULTS: The ACE genotype distribution in patients with proliferative retinopathy (DD 39.4%, ID 48.9%, II 11.7%) was significantly different (P < 0.001) from that of patients with nonproliferative retinopathy (DD 17.3%, ID 54.3%, II 28.4%). In a multiple logistical regression analysis, the adjusted relative risk for proliferative retinopathy in a patient with a DD genotype compared with a patient with an II genotype was 6.6 (95% CI 2.2-19.5), P = 0.0026. In addition to genotype, systolic blood pressure (odds ratio 1.027 [95% CI 1.0-1.1], P = 0.0093) but not microalbuminuria (< or =20 vs. > or =20 microg/min) reached statistical significance in the multiple regression model. Because subjects were matched regarding diabetes duration and HbA1c, we did not interpret the respective parameter estimates. CONCLUSIONS: These data provide evidence that deletion in the ACE gene is associated with the prevalence of proliferative retinopathy in type 1 diabetes and suggest that the DD genotype confers susceptibility to proliferative retinopathy independent of diabetic nephropathy

High turnover bone disease following lung transplantation.

Recipients of lung transplants are at very high risk for significant bone loss. Nevertheless, data on bone disease after lung transplantation are still limited. We, therefore, retrospectively evaluated the data of 33 patients surviving at least 1 year after lung transplantation (LTx) who were seen in our outpatient clinic for osteologic evaluation. Results of clinical evaluations, radiographs, and dual-energy X-ray absorptiometry (DXA) were related to each other, to clinical variables, and to serum levels of osteocalcin, parathyroid hormone (PTH), and 25-hydroxyvitamin D: 14 of 33 patients (42%) had vertebral fractures, 9 of whom were diagnosed within 2 years after transplantation. Bone mineral density values (DXA) were markedly decreased and predictive of compression fractures. 25-Hydroxyvitamin D levels were low in 13 patients (39%) and PTH was elevated in 7 (21%). Despite corticosteroids and low 25-hydroxyvitamin D, serum osteocalcin was elevated in 12 patients (36%). This was only partially explained by hyperparathyroidism, low sex hormones, and impaired renal function, and may partly be caused by cyclosporin A. We thus conclude that severe symptomatic bone disease is common in lung transplant recipients and due to a complex situation including high turnover bone loss and hypovitaminosis D. DXA can be used to estimate fracture risk for individual patients.

Gastric perforation of a left lobe amoebic liver abscess.

Liver abscess is the most common extra-intestinal manifestation of invasive amoebiasis. Perforation of the abscess is a potential life-threatening complication. We report a case where perforation into the stomach was successfully managed conservatively. The initial diagnosis in this case was made by gastroscopy and biopsy. To our knowledge, only five cases of gastric perforation of an amoebic liver abscess have been reported in the English literature. In none of these cases was the diagnosis established by histology of gastric biopsy specimens.

A prospective evaluation of the medical consultation system CADIAG-II/RHEUMA in a rheumatological outpatient clinic.

To evaluate the performance of CADIAG-II/RHEUMA as consultant in the primary evaluation of patients visiting a rheumatological outpatient clinic, a CADIAG-II/RHEUMA consultation was done for 54 patients and the list of generated diagnostic hypotheses was compared to each clinical discharge diagnosis. For 26 of a total of 126 rheumatological discharge diagnoses, no matching CADIAG-II/RHEUMA diagnosis was available. 94% of all other discharge diagnoses were found in the list of CADIAG-II/RHEUMA hypotheses, 82% among the first third of the list of hypotheses and 48% among the first five hypotheses. We identified the following factors limiting the ability of CADIAG-II/RHEUMA to generate a comprehensive and correctly ranked list of diagnostic hypotheses: (1) a large percentage of patients with early stages of not clearly identified rheumatological conditions; (2) the limited number of CADIAG-II/RHEUMA diagnoses compared to the large number of known rheumatological conditions; (3) the fact that rheumatological diseases are rarely characterized by a single pathognomonic feature but are usually diagnosed by combinations of rather unspecific findings.

Lung manifestation in asymptomatic patients with primary Sjögren syndrome: assessment with high resolution CT and pulmonary function tests.

The authors studied 37 consecutive patients with primary Sjögren syndrome and normal chest radiographs. Thin-section CT images were analyzed using a semiquantitative grading system. The presence, distribution, and severity of 9 morphologic parameters were assessed. In 34 patients, CT findings were correlated to pulmonary function tests (PFTs). Abnormal high resolution CT (HRCT) findings were seen in 24 of 37 patients (65%): interlobular septal thickening, n = 9; micronodules, n = 9; ground glass attenuation n = 4; parenchymal cysts, n = 5. Intralobular opacities, honey combing, bronchial wall thickening, bronchiectasis, and pleural irregularities were less frequent. Both HRCT and PFTs were normal in 10 patients. Computed tomography was normal in four patients with PFTs that indicated the presence of small airway disease. High resolution CT abnormalities were found in seven patients with normal PFT. The overall correlation between HRCT and PFTs was poor. High resolution CT and PFTs appear to be sensitive for both the early detection of parenchymal abnormalities and a decreases in lung function in asymptomatic patients with primary Sjögren syndrome. However, abnormal HRCT findings do not necessarily indicate a substantial alteration in PFTs.

Characteristics of joint involvement and relationships with systemic inflammation in systemic sclerosis: results from the EULAR Scleroderma Trial and Research Group (EUSTAR) database.

OBJECTIVE: To determine the prevalence of and independent factors associated with joint involvement in a large population of patients with systemic sclerosis (SSc). METHODS: This study was cross-sectional, based on data collected on patients included in the European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) registry. We queried this database to extract data regarding global evaluation of patients with SSc and the presence of any clinical articular involvement: synovitis (tender and swollen joints), tendon friction rubs (rubbing sensation detected as the tendon was moved), and joint contracture (stiffness of the joints that decreased their range of motion). Overall joint involvement was defined by the occurrence of synovitis and/or joint contracture and/or tendon friction rubs. RESULTS: We recruited 7286 patients with SSc; their mean age was 56 +/- 14 years, disease duration 10 +/- 9 years, and 4210 (58%) had a limited cutaneous disease subset. Frequencies of synovitis, tendon friction rubs, and joint contractures were 16%, 11%, and 31%, respectively. Synovitis, tendon friction rubs, and joint contracture were more prevalent in patients with the diffuse cutaneous subset and were associated together and with severe vascular, muscular, renal, and interstitial lung involvement. Moreover, synovitis had the highest strength of association with elevated acute-phase reactants taken as the dependent variable. CONCLUSION: Our results highlight the striking level of articular involvement in SSc, as evaluated by systematic examination in a large cohort of patients with SSc. Our data also show that synovitis, joint contracture, and tendon friction rubs are associated with a more severe disease and with systemic inflammation.

Clinical, endoscopic, and histologic spectrum of nonsteroidal anti-inflammatory drug-induced lesions in the colon.

PURPOSE: It has become increasingly clear that nonsteroidal anti-inflammatory drugs may cause damage not only to the upper gastrointestinal tract but also to the small and large intestine. Although the colon may be readily investigated by endoscopy, drug-induced lesions are not well known, probably because they are considered to occur only rarely. In the present study we describe endoscopic, histologic, and gross characteristics of nonsteroidal anti-inflammatory drug-induced colonic damage. Furthermore, pathogenetic mechanisms and therapeutic options are discussed. METHODS: The histories of all patients diagnosed as having nonsteroidal anti-inflammatory drug colitis during the last two years at the department of gastroenterology or the department of pathology at our hospital were reviewed. Endoscopic, histologic, and gross pathologic findings were systematically recorded. In addition, data on duration and type of nonsteroidal anti-inflammatory drug intake and time from onset of symptoms to diagnosis were collected. Therapy and outcome of our patients, if available, are reported. RESULTS: During the study period 11 patients were diagnosed as having nonsteroidal anti-inflammatory drug colitis. Most patients presented with diarrhea with or without blood loss and complained about diffuse abdominal pain. Endoscopy revealed flat ulcers in the entire colon being more severe in the right colon in the three cases with acute onset of diarrhea. In four cases concentric "diaphragm-like" strictures were seen, all located in the right colon. In the remainder endoscopy showed nonspecific erosions and was normal in one patient. Histology revealed findings similar to ischemic colitis. Additionally, in two cases collagenous colitis was found. Diclofenac slow release was the most commonly involved drug. The median time from onset of symptoms to diagnosis was 1.8 (range, 0-11.5) years. CONCLUSIONS: Nonsteroidal anti-inflammatory drug colitis is a clinically significant disease, which may present with diarrhea, anemia, and nonspecific abdominal complaints. Careful history taking, together with awareness of endoscopic and histologic findings, allows a timely diagnosis of this disease.

Thermographic parameters in the diagnosis of secondary Raynaud's phenomenon.

OBJECTIVE: To determine the major infrared thermographic parameters in discriminating between patients with and without secondary Raynaud's phenomenon. DESIGN: A cross-sectional study. SETTING: Outpatient clinic of a university department of physical medicine and rehabilitation in Vienna. PATIENTS: Consecutive sample of 86 patients (72 women, 14 men) referred from the Division of Rheumatology for the clarification of a possible secondary Raynaud's phenomenon. MAIN OUTCOME MEASURES: According to color changes induced by cold exposure, clinical classification of Raynaud's phenomenon was performed as follows: no, unlikely, probable, and definite Raynaud's phenomenon. The following thermographic parameters were applied to a stepwise logistic regression analysis: the absolute temperature of the fingertips before, 10, and 20 minutes after cold challenge (Tpre, T10, T20); the longitudinal temperature difference before, 10, and 20 minutes after cold challenge (LTDpre, LTD10, LTD20); the mean area under the rewarming curve of the fingertips; the recovery index 20 minutes after cold challenge (RI20); and the most rapid phase of rewarming of the fingertips of both hands (Gmax right, Gmax left). The sensitivity of thermographic classification into the 4 groups of clinical evaluation was assessed by discriminant analysis using significant parameters from logistic regression analysis. RESULTS: Only LTDpre reached the level of significance (p < .0001). Using LTDpre, 22 of 23 subjects without clinical Raynaud's phenomenon and 20 of 26 patients with definite clinical Raynaud's phenomenon were classified correctly. Patients with unlikely or probable Raynaud's phenomenon were classified as no Raynaud's phenomenon or definite Raynaud's phenomenon. CONCLUSION: LTDpre is the major thermographic parameter to discriminate between patients with and without definite Raynaud's phenomenon by clinical history.

[Pleural and pulmonary changes within the scope of rheumatoid arthritis]. / Pleurale und pulmonale Veränderungen im Rahmen der rheumatoiden Arthritis.

Pulmonary complications caused by rheumatoid arthritis are a clinically relevant aspect of this chronic arthropathy. Those complications can involve all parts of the thorax, including the lung parenchyma, the pleura, and the thoracic cage. The most common complications are necrobiotic nodules, pleural abnormalities, Caplan's syndrome, parenchymal fibrosis, bronchiolitis obliterans, and iatrogenic damage of lung the parenchyma. This article reviews pulmonary abnormalities induced by rheumatoid arthritis and their clinical and radiological findings. In addition, the role of different imaging modalities in the diagnostic work-up of pulmonary complications caused by rheumatoid arthritis is discussed.

Soluble intercellular adhesion molecule-1 (sICAM-1) in patients with rheumatoid arthritis and systemic lupus erythematosus.

Serum levels of the soluble form of the intercellular adhesion molecule-1 (sICAM-1) have been advocated as a parameter of clinical relevance in determining the activation of the immune system in inflammatory disease(s). We have determined sICAM-1 levels in 46 patients with rheumatoid arthritis (RA), in 53 patients with systemic lupus erythematosus (SLE), and in 82 healthy controls using a commercially available ELISA system. When compared to the healthy controls, sICAM-1 levels of the patients did not differ statistically significantly nor was there any difference between the patient groups. However, there was a strong correlation within the patient groups between sICAM-1 levels and conventional measures of disease activity. Thus, although sICAM-1 may be of theoretical interest with regard to immune activation, our results do not support the view of sICAM-1 providing additional information to the clinical rheumatologist when it is compared to more conventional measures such as acute-phase proteins or clinical activity scores.

[AV-block II and arthritis as manifestations of Lyme borreliosis]. / AV-Block II und Arthritis als Manifestationen der Lyme-Borreliose.

A 23-year old patient suffered from transient oligoarthritis and second degree AV block. The diagnosis of stage II systemic Lyme borreliosis was supported by a history of tick bites and the detection of both IgG and IgM borrelia antibodies in the patient's serum. The ECG-findings (bradyarrhythmia and AV block II) were detected several weeks after the onset of arthritis, whilst the patient reported no cardiac symptoms. Treatment was started with ceftriaxone and then continued with doxycycline because of an allergic reaction to the first antibiotic.

Functional and molecular aspects of transient T cell unresponsiveness: role of selective interleukin-2 deficiency.

Defects of T cell (Tc) proliferation have been demonstrated in several autoimmune diseases. Detailed mechanisms governing activation and proliferation of Tc are still not completely known. Here we show that under certain conditions human peripheral blood lymphocytes, once activated by anti-CD3, fail to respond to a subsequent restimulation via the Tc-receptor. Peripheral blood mononuclear cells (PBMC) were preactivated by anti-CD3 for 96 h following restimulation by anti-CD3, interleukin (IL)-2 and other mitogens. In control experiments unstimulated PBMC were incubated in medium alone. Immunophenotypes were analysed by flow cytometry. Cytokine production was determined by reverse transcription-polymerase chain reaction and intracellular signalling protein contents of Tc were compared by Western blotting. Furthermore, apoptosis was detected by terminal deoxyribose transferase-mediated deoxyuridine triphosphate nick end labelling assay. Unstimulated PBMC proliferate well after subsequent stimulation with anti-CD3, whereas IL-2 induces only limited proliferation. In contrast, preactivated cells respond only minimally to restimulation with anti-CD3, but IL-2 induces a marked proliferation. Both preactivated and unstimulated Tc respond well to restimulation by phytohaemagglutinin (PHA). In contrast, preactivated Tc show only a weak response to concanavalin A. Interestingly, when cells have been allowed to rest for 168 h, the responsiveness of preactivated Tc is restored. Immunoblots reveal that preactivated cells have a higher intracellular content of zeta-chain and p56lck. No differences are found concerning apoptosis after restimulation with anti-CD3 or the expression of ERK 1/2. The unresponsiveness to restimulation is due to an impairment of the transcription of the IL-2 gene and this defect is temporary. Despite the lack of proliferation, preactivated Tc phenotypically maintain an intermediate stage of activation. These data show how the same cell population can change its functional phenotype into a non-responder state.

What have mast cells to do with edema formation, the consecutive repair and fibrinolysis?

Mast cells (MC) have been implicated in the activation of vascular endothelial cells, capillary leak formation, transmigration of white blood cells, and translocation of fibrinogen (and other plasma molecules) into the tissues, with consecutive edema formation. However, the mechanisms of repair that lead to tissue reconstitution after MC activation and edema formation have not been defined so far. In the present article, the possible contribution of MC to repair, in particular fibrinolysis, is discussed. Thus, accumulating evidence exists that human MC express and release the tissue-type plasminogen activator (tPA) in a constitutive manner. MC also express the urokinase receptor (uPAR) and heparin. Most importantly, however, MC lack plasminogen activator inhibitors (PAI-1, PAI-2, PAI-3). In line with this 'pro-fibrinolytic' profile of antigens, MC supernatants induce plasminogen-to-plasmin conversion and fibrin clot lysis in vitro. The c-kit ligand SCF upregulates uPAR expression, and the release of tPA from MC. These observations point to an important role of MC in endogenous fibrinolysis, a hitherto unrecognized (repair) function of this cell.

Photopheresis treatment enhances CD95 (fas) expression in circulating lymphocytes of patients with systemic sclerosis and induces apoptosis.

We investigated the effects of photopheresis in systemic sclerosis by analysing its influence on lymphocytes with regard to apoptosis and expression of bcl-2 and fas. Peripheral blood lymphocytes isolated immediately before and 24 h after photopheresis were investigated for apoptosis, bcl-2 and fas expression by fluorocytometry, and compared to controls. In addition, leucocytes from systemic sclerosis patients taken directly from the photopheresis system were tested for apoptosis after 24 h in culture. fas expression was similar in controls and patients with systemic sclerosis just before photopheresis, but increased 24 h after photopheresis, mainly due to an increase of CD4+CD95+ cells. bcl-2 was overexpressed in scleroderma peripheral lymphocytes, but not influenced by photopheresis. As compared to healthy controls, the percentage of apoptotic cells 24 h after photopheresis was high in cultured lymphocytes, but not ex vivo. The significant increase in fas on peripheral lymphocytes observed in this study may be a major operative mechanism of photopheresis in addition to (and possibly related to) the induction of apoptosis.

Discrete lung involvement in systemic lupus erythematosus: CT assessment.

PURPOSE: To study the computed tomographic (CT) appearance of early lung involvement in systemic lupus erythematosus (SLE). MATERIALS AND METHODS: In a prospective study, 48 patients with serologically confirmed SLE but no prior clinical evidence of lung involvement underwent chest radiography, CT, and lung function tests. Radiographs and CT scans were compared, and CT scans were evaluated for signs suggestive of parenchymal and pleural disease. Extent and distribution of disease were determined. CT findings were correlated with clinical and functional data. RESULTS: Of 45 patients with normal chest radiographs, 17 (38%) had abnormal CT findings. Extent of disease was statistically significantly correlated with duration of clinical history (r = .93) and decreased single-breath diffusing capacity for carbon monoxide (r = .8) and ratio of forced expiratory volume in 1 second to forced vital capacity (r = .77). CONCLUSION: CT is superior to chest radiography for detection of functionally relevant pulmonary disease and is an important adjunct in early assessment of SLE.

Angiotensin-converting enzyme polymorphism in patients with terminal renal failure.

An insertion/deletion polymorphism has been described for the gene that encodes the angiotensin-converting enzyme. The deletion allele is associated with higher angiotensin-converting enzyme plasma levels, which ultimately might lead to increased angiotensin II concentrations. Because angiotensin II is a mediator for progressive renal injury, this study determined the frequency of distribution of the angiotensin-converting enzyme insertion/deletion polymorphism in 106 hemodialysis patients and in a group of 95 healthy control patients. There was no difference between the two groups as far as the distribution of the insertion and deletion allele was concerned. Of the total hemodialysis population, 26.4% exhibited the deletion/deletion genotype, as compared with 37.9% of the healthy control population. Also, when patients with terminal renal failure as a result of glomerular disease were analyzed separately, the frequency of the deletion/deletion genotype was identical to that of the control group. Furthermore, the frequency of hypertension, coronary artery disease, left ventricular hypertrophy, and dilated cardiomyopathy, were analyzed according to the angiotensin-converting enzyme genotype, but the deletion allele could not be defined as a risk factor in the study's hemodialysis population. It was therefore concluded that the angiotensin-converting enzyme insertion/deletion polymorphism is not a major risk factor for development of end-stage renal failure. Additionally, in hemodialysis patients, there is no association between the risk for cardiovascular diseases and the angiotensin-converting enzyme genotype.