Organ Involvement In Patients Research Articles

Association of circulating endothelial cells with flow mediated vasodilation and disease activity in patients with systemic lupus erythematosus

Objectives The aim of this study was to determine the correlation between CEC count and endothelial function, disease activity, and organ involvement in patients with SLE. Background Premature atherosclerosis in patients with systemic lupus erythematosus (SLE) is not explained by traditional risk factors. Circulating endothelial cells (CEC) have been identified as a surrogate marker of endothelial dysfunction Methods The present study included 30 premenopausal women with SLE and 20 age and sex matched healthy controls (HC). Endothelial function was studied by flow mediated vasodilation (FMD%) in the brachial artery. Serum levels of VCAM-1, ICAM-1 were measured. Results FMD% was lower in patients with SLE than HC (3.5 ± 0.4 vs 9.7 ± 3.2, p p r = 0.97), and negatively with FMD% ( r = −0.94). Serum levels of VCAM-1 and ICAM-1 were significantly elevated in patients with SLE compared to HC ( p p p p Conclusion CEC is associated with endothelial dysfunction, disease activity and increased VCAM-1 levels in patients with SLE. These findings suggest a potential role of CEC in the pathophysiology of cardiovascular disease in these patients.

Correlation of Circulating Glucocorticoid-Induced TNFR-Related Protein Ligand Levels with Disease Activity in Patients with Systemic Lupus Erythematosus

The aim of this paper is to investigate the correlation of glucocorticoid-induced tumor necrosis factor receptor- (TNFR-) related protein ligand (GITRL) with disease activity and organ involvement in patients with systemic lupus erythematosus (SLE). Serum GITRL levels were measured in 58 patients with SLE and 30 healthy controls matched for age and sex. Patients were assessed for clinical and laboratory variables. Correlations of serum GITRL levels with SLEDAI, laboratory values, and clinical manifestations were assessed. Serum GITRL levels were determined by ELISA. Serum GITRL levels were markedly increased in patients with SLE compared with healthy controls (mean 401.3 ng/mL and 36.59 ng/mL, resp.; P < 0.0001). SLE patients with active disease showed higher serum GITRL levels compared to those with inactive disease (mean 403.3 ng/mL and 136.3 ng/mL, resp; P = 0.0043) as well as normal controls (36.59 ng/mL; P < 0.0001). Serum GITRL levels were positively correlated with SLEDAI, titers of anti-dsDNA antibody, erythrocyte sedimentation rate (ESR), and IgM and negatively correlated with complement3 (C3). Serum GITRL levels were higher in SLE patients with renal involvement and vasculitis compared with patients without the above-mentioned manifestations.

Preoperative Plasma Fibrinogen Level Is a Useful Predictor of Adjacent Organ Involvement in Patients with Advanced Gastric Cancer

PurposeThe aim of the present study was to assess the association between the pre-operative plasma fibrinogen level and the adjacent organ involvement in advanced gastric cancer.Materials and MethodsA total of 923 pre-operative plasma samples were obtained from 923 patients diagnosed clinically as having advanced gastric cancer, and fibrinogen levels were measured by immunoassay. Associations between fibrinogen levels and clinicopathologic findings (depth of tumor, adjacent organ involvement, and lymph node metastasis), along with survival were examined by univariate and multivariate analyses.ResultsTumor size, tumor depth, and the presence of lymph node metastasis were found to be positively correlated with the preoperative plasma fibrinogen levels (P<0.001). Fifty (5.4%) patients had adjacent organ involvement. Lymphatic invasion (P<0.001), tumor size (P<0.001), clinical T (depth of invasion) stage (P<0.001), and clinical nodal stage (P=0.018) were found to be associated with adjacent organ involvement. Univariate and multivariate regression analyses showed that a preoperatively elevated plasma fibrinogen level was associated with adjacent organ involvement (P<0.001, 0.028), and Kaplan-Meier analysis showed that it was associated with poorer survival (P<0.001).ConclusionsPlasma fibrinogen was found to be a clinically useful marker of adjacent organ involvement and overall survival. When a high fibrinogen level is encountered, preoperatively, adjacent organ involvement should be suspected in clinically advanced gastric cancer.

Simultaneous Involvement of Nervous and Gastrointestinal Systems in Behçet's Disease

Simultaneous Involvement of Nervous and Gastrointestinal Systems in Behçet's Disease

Clinical Features and Outcomes of Renal Mycetoma Complicated byCandidaSepsis in Newborn Infants

Purpose: The kidney is a common site of end organ involvement in patients with candidemia. This study was undertaken to inves- tigate clinical features and outcomes of renal mycetoma complicated by Candida sepsis in neonates. Methods: A retrospective analysis of the medical records and radiologic images was conducted in a neonatal intensive care unit over a 9-year period (2002-2010). Results: During the study period, there were 69 episodes of Candida sepsis. C. albicans was the most common pathogen (49.2%), and C. parapsilosis was the second (42%), but emerging. Of the 42 patients who underwent ultrasound examination in early phase of infection, renal mycetoma was observed in 8 cases (19.1%). Renal mycetoma was more frequently developed in patients with C. albicans sepsis than those with non-albicans candidemia, but the result was not significant. The demographic characteristics of the two groups of patients who had Candida sepsis (with renal mycetoma vs. without renal mycetoma) were similar. Candiduria was more common in the mycetoma group (P<0.01). In addition, the duration of antifungal medication was longer in patients with mycetoma (P<0.001). On follow-up ultrasounds, improvement and resolution of renal echogenic lesions took a median time of 2 and 5 months respectively for the mycetoma group. Conclusion: Candiduria may be an initial sign of renal mycetoma complicated by Candida sepsis in newborn infants. Echogenic foci on the renal ultrasound are persistent for a considerable period after antifungal therapy, and therefore follow-up evaluations are important.

Early systemic sclerosis: assessment of clinical and pre-clinical organ involvement in patients with different disease features

To assess internal organ involvement in early SSc at presentation. One hundred and fifteen patients admitted to a tertiary centre because of RP, who did not present any routinely detectable scleroderma-related internal organ involvement, were investigated for ANA and videocapillaroscopy, and underwent history and physical examination to detect symptoms/signs suggestive of SSc. Patients were then subdivided into three groups: (i) early SSc, constituted by patients without clinical manifestations other than RP, but with scleroderma marker autoantibodies and/or typical capillaroscopic abnormalities; (ii) probable SSc, constituted by patients with the same autoantibody and/or capillaroscopic status as early SSc patients, but with any of the following manifestations: digital ulcers/scars, puffy fingers, arthritis, telangiectasia, dysphagia/heartburn, shortness of breath; (iii) UCTD, constituted by patients with a specific (i.e. disease antibody marker) ANA and capillaroscopic findings plus any disease manifestation. All patients were investigated by lung functional study and B-mode echo-Doppler-cardiography. Patients who consented underwent oesophageal manometry. An inverted mitral E : A ratio (i.e. early scleroderma cardiac involvement) and/or a diffusing lung capacity for CO <80% of the predictive value (i.e. early lung involvement) and/or basal low oesophageal sphincter pressure <15 mmHg (i.e. early oesophageal involvement) were detected in 37/51 probable SSc patients (72%), 8/19 early SSc patients (42%) and 12/45 UCTD patients (27%). A scleroderma-related internal organ involvement was detected in patients from each group and, more importantly, was pre-clinical in a number of cases.

Hand impairment in systemic sclerosis: association of different hand indices with organ involvement

Objective: To evaluate the association between the assessment tools used to quantify hand impairment and organ involvement in patients with systemic sclerosis (SSc).Methods: Eighty consecutive SSc patients were assessed for hand impairment using the Hand Anatomic Index (HAI), finger-to-palm distance in flexion (FTP), and the Hand Mobility in Scleroderma (HAMIS) test. Cluster analysis was used to identify patients having similar characteristics on the basis of the pattern of organ involvement in order to create clinically homogeneous groups, and to correlate these clusters with the measures of hand involvement. Finally, we evaluated the discriminating ability of the indices to identify the patients whose clinical condition was more severe.Results: Two major clusters were identified by cluster analysis on the basis of organ involvement. The first (cluster A) included 61 patients and the second (cluster B) 19 patients characterized by minor and major extent of organ involvement, respectively. The extent of organ involvement and the hand impairment were related. The scores of hand indices were lower in cluster B. The area under the receiver operating characteristic (ROC) curve (C-index) for the logistic model including all three indices was 0.85 (95% confidence interval 0.74–0.95).Conclusion: The seriousness of hand involvement as measured by the three indices was associated with the extent of organ involvement. Further studies of hand impairment scales are needed to provide validated guidance as meaningful clinical measures.

Clinical characteristics of patients with chronic eosinophilic leukaemia (CEL) harbouring FIP1L1‐PDGFRA fusion transcript—results of Polish multicentre study

A small subgroup of patients with hypereosinophilic syndrome (HES) demonstrates imatinib-sensitive fusion transcript-the FIP1L1-PDGFRA (F/P+). These cases are currently diagnosed as chronic eosinophilic leukaemia (CEL). In this paper, we screened 77 patients to estimate the frequency of FIP1L1-PDGFRA transcript among patients with unexplained, long-term hypereosinophilia exceeding 1.5 x 10(9)/L and to analyse the clinical and serological features in F/P+ CEL population. The FIP1L1-PDGFRA chimeric protein was detectable in 16 (14 males and 2 females) out of 77 examined HES patients (20%) by RT-PCR. Two patients suffered from cough at diagnosis. Three out of 16 (18%) patients had no organ involvements, in 5-one organ was affected and in the remaining eight cases-at least two. Eosinophilic organ damage/dysfunction identified splenomegaly in the majority of studied patients. We compared clinical and serological features between CEL F/P+ (n = 16) and HES (n = 61) patients. F/P+ cases had significantly increased WBC and absolute eosinophil count (AEC) at diagnosis (p = 0.008 and 0.02), whereas platelet count was decreased in this population (p = 0.03). Serum B12 and tryptase levels were increased (p = 0.002 and 0.004) in CEL F/P+ patients when compared to HES cases whereas serum IL-5 levels were significantly increased in the latter group (p = 0.01). Male gender and splenomegaly occurred more frequent in CEL F/P+ population (p = 0.002 and 0.0007, respectively). Additionally, patients with F/P+ CEL (n = 16) were compared with F/P- CEL (n = 8). The latter group, was significantly older, had lower AEC and higher platelet count. In conclusion, significant clinical symptoms are infrequent present and splenomegaly remains the most common organ involvement in patients with CEL expressing F/P fusion transcript. Our study confirmed the long-term remission on imatinib in this patient population.

A retrospective randomly selected cohort study of D-penicillamine treatment in rapidly progressive diffuse cutaneous systemic sclerosis of recent onset

Several uncontrolled studies in systemic sclerosis have shown that D-penicillamine may cause improvement in skin sclerosis, decrease the rate of new visceral organ involvement, and improve overall survival. To undertake a single-centre retrospective randomly selected cohort study to examine the effects of D-penicillamine treatment on skin and visceral organ involvement in patients with rapidly progressive systemic sclerosis of recent onset. Eighty-four patients with diffuse cutaneous systemic sclerosis who had received D-penicillamine within 24 months of clinically detectable onset of skin sclerosis were randomly selected from the systemic sclerosis cohort followed at the Scleroderma Center of Thomas Jefferson University. Employing a previously described severity scale, disease severity and skin involvement were compared from initiation of D-penicillamine to end of study and a correlated matched t-test was used to establish statistical significance. At a mean+/-SD duration of D-penicillamine therapy of 29.2+/-5.5 months and at a median dose of 750 mg per day statistically significant improvement in skin (P<0.01) and cardiac, pulmonary and renal involvement (P<0.05) was observed. At last follow-up, 17 (20%) patients were still receiving D-penicillamine, 25 (30%) had discontinued it owing to disease improvement, and 18 (21%) had discontinued it owing to side-effects. In a population of patients with diffuse cutaneous systemic sclerosis, with progressive disease of recent onset, D-penicillamine treatment at a median dose of 750 mg per day caused a statistically significant reduction in skin involvement and improvement of renal, cardiac and pulmonary involvement.

Diagnostic Value of Peripheral Lymph Node Biopsy in Sarcoidosis: A Report of 67 Cases

A peripheral lymph node (PLN) 1 cm or greater was found in 79 of 546 sarcoidosis patients (14.5%) between 1972 and 2005. Seventy-two of the 79 sarcoidosis patients had a lymph node biopsy performed. Sixty-seven of these biopsy specimens were histologically diagnosed as sarcoidosis, whereas five patients had a reactive adenopathy. For patients with histological diagnosis of sarcoidosis, localizations of the biopsies were as follows: cervical (n=21), supraclavicular (n=20), inguinal (n=11), axillary (n=8), epitrochlear (n=5) and submandibular (n=2). At the time of biopsy, 12 patients had stage 0 disease, 37 patients had stage I disease, 14 patients had stage II disease and four patients had stage III disease. Skin involvement (16.4%) was the most frequently observed type of organ involvement in patients who had enlarged PLNs due to sarcoidosis. In the presence of an enlarged PLN in sarcoidosis, biopsy had a greater diagnostic value compared with other methods, as well as having a relatively low cost (approximately US$120) in Turkey. No procedure-related complications were observed. In conclusion, it is recommended that PLNs be thoroughly examined when sarcoidosis is suspected. If an enlarged PLN is found, biopsy should be routinely performed because it is an easy, convenient and practical method, with a low complication risk and a high sensitivity.

Immunohistochemical Expression of Activated Caspase-3 as a Marker of Apoptosis in Glomeruli of Human Lupus Nephritis

The role of apoptosis in lupus nephritis (LN) is still controversial. One of the key events in the process of apoptosis is activation of caspase-3. Studies of experimental models suggested that activated caspase-3 is a reliable indicator of apoptotic rate, with a favorable comparison against terminal transferase-mediated DNA nick-end labeling (TUNEL) assay. Our aim is to study apoptosis in various forms of LN and its relationship to histomorphological changes and selected laboratory findings by using activated caspase-3 as a novel marker of apoptosis. We investigated glomerular cell apoptosis in 51 biopsy specimens from patients with LN classified according to the International Society of Nephrology/Renal Pathology Society classification by using the TUNEL method and immunohistochemistry against activated caspase-3. In addition, activity and chronicity indices were calculated and anti-Ki-67 antibody was used to estimate proliferative activity. Activated caspase-3-positive cells were present in glomeruli of 88.2% of cases, observed in the glomerular tuft and cellular and fibrocellular crescents. In the glomerular tuft, they were found mainly in segments with active inflammatory lesions. There was good correlation between apoptotic index assessed by using activated caspase-3 immunolabeling and the TUNEL method (r = 0.72; P < 0.01). We observed a significant positive correlation between apoptotic index and LN class (P < 0.001). Apoptotic index correlated significantly with activity index, proliferation index, and daily protein excretion (P < 0.001), but not chronicity index, creatinine concentration, or anti-DNA antibody-binding activity in serum. Apoptotic rate is greater in severe active glomerular lesions in human LN, suggesting that apoptosis may be involved in augmenting inflammation in human LN.

Familial neurological disorders

ic revolution. The increase in genetic information is occurring at an exponential rate. This new knowledge is leading to major advances in the understanding of disease; in areas of research ranging from inherited abnormalities to the genetics of cancer, we are gaining insight that is leading to new treatment paradigms. Most inherited diseases affecting the central nervous system have been defined by the gene alterations involved. Although many of these genetic diseases have no neurosurgical issues, neurosurgeons do need to be familiar with those syndromes that lead to neurosurgically treatable disease. In addition, neurosurgeons may become involved in the treatment of some of these diseases as the physicians delivering genetic therapy to the brain. This issue of Neurosurgical Focus is devoted to inherited diseases. Review articles covering some of the more common disorders, such as neurofibromatosis and tuberous sclerosis, are included. Both the genetic alterations leading to the syndrome and the molecular events responsible for the abnormalities seen are described. In addition, articles about rare disorders such as Cowden disease are presented. The association of Lhermitte::Duclos syndrome with this disease is of great importance, because of the widespread organ involvement in patients with Cowden disease. Given the complexity of brain development, the finding that there is a genetic basis to malformations that occur during cortical development is not surprising. Included here is an excellent review of the cortical dysplasias and what is known about the genetic alterations leading to these abnormalities. Neurosurg Focus 20 (1):Intro, 2006

Immune‐Neuroendocrine Interactions and Autoimmune Diseases

The relationship between immune-neuroendocrine system is firmly established. The messengers of this connection are hormones, neuropeptides, neurotransmitters and cytokines. The immune-neuroendocrine system have the capacity to synthesize and release these molecules, which, in turn, can stimulate or suppress the activity of immune or neuroendocrine cells by binding to receptors. In fact, hormones, neuropeptides and neurotransmitters participate in innate and adaptive immune response.Autoimmune rheumatic diseases (ARD) are characterized by aberrant production of pro-inflammatory cytokines, which are a potent activator of the HPA axis. In consequence, high levels of pro-inflammatory hormones such as estrogens and prolactin, and low levels of glucocorticoids, an anti-inflammatory hormone, have been described in the active phase of ARD. In addition, high levels of pro-inflammatory hormones and cytokines have also been frequently detected in organ involvement of patients with ARD, suggesting an abnormal local neuroendocrine immune interaction. There is evidence that hormonal changes may appear before the symptomatic phase of the disease. Therefore, it is possible that a pro-inflammatory hormone favors the rupture of tolerance, which is a key feature of autoimmune diseases. The interactions between the immune-neuroendocrine system have a major impact on our understanding of the pathogenic mechanisms, diagnosis and therapy of ARD.

Predictive Markers for Development of Severe Organ Involvement in Patients with Systemic Sclerosis

Prognosis of systemic sclerosis (SSc) is associated with the extent of skin involvement and the presence of lung, heart, kidney, and/or digestive tract damage. Most patients do not require disease-modifying therapy. However, to avoid irreversible tissue injury, early detection of visceral involvement is crucial for prompt initiation of therapy. The aim of this study is to identify, among initial investigations performed at time of diagnosis, predictive markers for the development of severe organ involvement (SOI). We retrospectively reviewed the medical records of 41 patients with SSc who were followed for 5 years after diagnosis, including those who died because of SSc within this 5-year period. We considered 68 clinical, biological, and technical parameters obtained at time of diagnosis and studied their association with development of SOI during this 5-year period, using a multivariate logistic regression. Eighteen patients (44%) developed SOI, with a median delay of 1.5 years following diagnosis. Three independent markers were identified: reduced vital capacity, fulfilment of American College of Rheumatology criteria at diagnosis, and presence of rheumatoid factor. To identify patients at risk for developing severe disease, given the short delay between diagnosis of SSc and development of SOI, we recommend monitoring these markers at diagnosis.

IL-6 levels predict disease variant and extent of organ involvement in patients with mastocytosis

Mastocytosis is often associated with organ involvement and hematological disorders. Patients may also exhibit elevated levels of plasma IL-6. To gain insight into the relevance of this observation, we correlated plasma levels of IL-6 and soluble IL-6 receptor (sIL-6R) with multiple disease parameters in 29 patients with mastocytosis. Mean plasma IL-6 levels were elevated in patients compared to healthy controls ( P < 0.0001). Disease category significantly correlated with plasma IL-6 levels, as did severity of bone marrow pathology, organomegaly, and extent of skin involvement. In plasma, there was a positive correlation of IL-6 to total tryptase, alkaline phosphatase, IgM, white blood cell count, prothrombin time, partial thromboplastin time, and neutrophil numbers. There was an inverse correlation to hemoglobin. sIL-6R levels were not elevated. These observations demonstrate that IL-6 is a useful surrogate marker of severity of hematologic disease and suggest that IL-6 contributes to pathology.

Tarsal–conjunctival disease associated with Wegener's granulomatosis

Objective To describe the clinical characteristics of tarsal–conjunctival disease in a cohort of patients with Wegener's granulomatosis (WG). Design Retrospective, case-controlled study. Participants The medical records of 82 consecutive WG patients who underwent an eye examination between January 1996 and June 2002 at the National Institutes of Health were reviewed. Methods Details of the ophthalmic examination, results of medical therapy, and histopathologic analysis results were recorded. Tarsal–conjunctival disease was defined by (1) conjunctival hyperemia and granuloma formation, areas of necrosis, or active fibrovascular changes in the tarsus or conjunctiva, or (2) evidence of inactive fibrovascular scar. The association of tarsal–conjunctival disease with major organ system involvement was assessed using Bayesian methods. Main outcome measures The occurrence and clinical characteristics of tarsal–conjunctival disease in a cohort of patients with WG and associations with major organ system involvement. Results Tarsal–conjunctival disease occurred in 13 of 82 patients (16%) with WG examined over a 6.5-year period. The palpebral surface of the upper lid was involved most commonly, showing conjunctival hyperemia in seven patients, granulomatous lesions in three patients, tarsal–conjunctival necrosis in four patients, active fibrovascular proliferation in six patients, and inactive fibrous scar tissue in seven patients. Histopathologic analysis of eyelid biopsy specimens showed granulomatous inflammation, focal necrosis, and areas of occlusive vasculitis in the tarsus and conjunctiva. In reviewing the patterns of organ involvement in patients with and without tarsal–conjunctival disease, the association of subglottic stenosis and nasolacrimal duct obstruction with tarsal–conjunctival disease showed a high probability of clinical significance. Conclusions Tarsal–conjunctival disease, a previously uncommon finding in patients with WG, was characterized by inflammation of the palpebral conjunctiva and tarsus followed by a fibrovascular proliferation and scar formation. Because of the important association of tarsal–conjunctival disease with subglottic stenosis, which can progress and lead to laryngeal obstruction and respiratory failure, patients with tarsal–conjunctival disease should be referred to an otolaryngologist for evaluation.

Fibromyalgia in Indian patients with SLE.

One hundred and fifty-eight patients with SLE were prospectively studied at a tertiary referral centre in India to ascertain the prevalence and clinical profile of fibromyalgia (FM) in Indian patients with lupus. An attempt was made to determine whether socio-demographic factors or disease characteristics differ in SLE patients with and without FM. Only 13 patients (8.2%) in our cohort were found to have fibromyalgia. Their clinical profiles were similar to that reported in other series. Corticosteroid withdrawal or dose reduction was the probable precipitating factor in nearly one-third of our patients. Age, sex, marital status, educational level, disease duration, disease activity and the organ involvement in patients with SLE and FM were comparable to those in patients not having FM. Fibromyalgia appears to be distinctly uncommon in Indian patients with lupus. A strong family support system, the virtual lack of disability benefits and/or racial variations in pain threshold could be the likely factors responsible for the low prevalence of the disease observed in Indian patients with SLE.

Investigation of the prevalence and clinical associations of antibodies to human fibronectin in systemic lupus erythematosus.

To assess the prevalence of antibodies to human fibronectin (anti-Fn) in sera of patients with certain connective tissue diseases and to determine their association with disease activity and the pattern of organ involvement in patients with systemic lupus erythematosus (SLE). A capture enzyme linked immunosorbent assay (ELISA) was developed to quantify anti-Fn antibodies in serum samples from 65 patients with well characterised SLE, 50 with rheumatoid arthritis (RA), 15 with Behçet's disease (BD), 15 with systemic vasculitis and 36 healthy subjects. An anti-Fn antibody titre greater than mean + 3SD of the healthy control log values after back transformation to the normal scale was considered positive. Disease activity in SLE patients was scored using the British Isles Lupus Assessment Group (BILAG) Index. Erythrocyte sedimentation rate (ESR), concentrations of anti-dsDNA antibody, soluble interleukin-2 receptors (sIL-2R), C3, C4, C3 degradation products (C3dg) and immunoglobulin, and antinuclear antibody (ANA) titres were measured in blood samples from SLE patients; neopterin concentration was measured in corresponding urine samples. Anti-Fn antibodies were found in 22 of 65 SLE patients (33.8%), seven of 50 with RA (14%), one of 15 with BD (6.6%) and none of the 15 subjects with vasculitis. Thirty SLE patients had active disease and 35 had inactive disease; their median anti-Fn concentrations were 117 u/ml (range 47-450) and 68 u/ml (range 17-334), respectively (p = 0.0001). The presence of anti-Fn did not correlate with immunoglobulin concentrations or ANA titres in these sera. No significant difference was found between SLE patients with disease activity in one major organ system compared with multiple organ involvement, as defined by BILAG (p = 0.19). However, patients with musculoskeletal manifestations had consistently greater anti-Fn concentrations compared with patients with other clinical manifestations. There were significant correlations between amounts of anti-Fn in SLE sera and ESR (rs = 0.25, p = 0.045), sIL-2R (rs = 0.28, p = 0.024) and urine neopterin (rs = 0.3, p = 0.016) but not with serum anti-dsDNA antibody titres, plasma C3, C3dg or C4. However multiple regression analysis showed a low significant correlation only with sIL-2R and BILAG score (p = 0.047 and 0.042, respectively). Anti-Fn antibodies were detected in 34% of SLE patients and in small proportions of RA and BD patients. An association between serum anti-Fn and disease activity in SLE has been identified and most SLE patients with musculoskeletal involvement had increased anti-Fn antibody concentrations.

Serum thrombomodulin. A novel marker of disease activity in systemic lupus erythematosus.

Soluble thrombomodulin (sTM), a proposed serum marker of endothelial cell injury, was investigated as a parameter of disease activity in patients with systemic lupus erythematosus (SLE). Levels of sTM were determined by enzyme-linked immunosorbent assay. Disease activity was assessed using 3 established scoring systems: the American College of Rheumatology (ACR), the New York Hospital for Special Surgery (NYHSS), and the Systemic Lupus Activity Measure (SLAM) systems. A close correlation was found between sTM levels and disease activity as assessed with all 3 scoring systems: r = 0.52 by the ACR, 0.75 by the NYHSS, and 0.82 by the SLAM. We found that sTM is a sensitive serologic marker of organ involvement in patients with SLE. Furthermore, sTM may prove to be an important marker for vasculitis in general.

Detection of paradoxical cerebral echo contrast embolization by transcranial Doppler ultrasound.

Contrast echocardiography has been shown to be a sensitive method for detecting patent foramen ovale in embolic stroke, implying paradoxical embolization. However, not all two-dimensional echocardiographic studies are of diagnostic quality, and direct evidence for paradoxical cerebral embolization remains lacking. We addressed these problems by simultaneously using transcranial Doppler ultrasound and contrast echocardiography to compare relative sensitivity and concordance in the detection of right-to-left vascular shunting. Forty-six patients with stroke, transient neurologic defect, or question of atrial septal defect underwent study at rest and during Valsalva strain. Two-dimensional echocardiography detected shunting in 26% at rest and 15% during Valsalva strain, whereas transcranial Doppler study returned rates of 41% and 41%, respectively. Concordance was 82% and 75%, respectively. Discordant studies almost always had evidence of paradoxical contrast embolization by transcranial Doppler and intermediate findings by two-dimensional echocardiography. Transcranial Doppler is a sensitive, unambiguous technique for the detection of anatomic substrates and target organ involvement in patients suspected to have paradoxical cerebral embolization.