Does prior arthroscopic procedure impact outcomes of knee arthroplasty? A systematic review and meta-analysis.

OBJECTIVE: Despite generally favorable outcomes following knee arthroscopy, a certain subset of patients inevitably develops progression of knee disease, necessitating subsequent total knee arthroplasty (TKA). Therefore, the evaluation of TKA outcomes following arthroscopy has emerged as a major area of research. The aim of the current review is to measure the impact of prior arthroscopy on functional and adverse outcomes following TKA. MATERIALS AND METHODS: Literature search was conducted in the databases including Medline, EMBASE, PubMed Central, ScienceDirect, Google Scholar and Cochrane library from inception until April 2021. Meta-analysis with random-effects model was conducted to calculate pooled odds ratio (OR) or standardized mean difference (SMD) with 95% confidence interval (CI) depending on the type of outcome. RESULTS: In total, 9 studies with 185,013 participants were included in the review. The majority of the studies were conducted in the USA and China. Almost all the studies had low quality as per Newcastle Ottawa (NO) scale. The pooled SMD for functional outcome was -0.19 [95%CI: -0.30 to -0.09], while the pooled OR for revision rate was 1.53 (95% CI: 1.21 to 1.92). In terms of postoperative complications, the pooled OR for stiffness was 1.55 (95% CI: 0.92-2.61), infection was 1.39 (95%CI: 1.17-1.67), aseptic loosening was 1.93 (95% CI: 1.19-3.11), VTE was 1.06 (95% CI: 0.83-1.35), and MUA was 1.33 (95% CI: 1.13-1.57) respectively. CONCLUSIONS: Prior arthroscopy has significant impact on the functional and adverse clinical outcomes following TKA. Surgeons need to develop a comprehensive intervention plan to manage these high-risk patients and reduce the rate of postoperative complications.

Association between Intracranial Atherosclerotic Calcium Burden and Angiographic Luminal Stenosis Measurements.

BACKGROUND AND PURPOSE: Calcification of the intracranial vasculature is an independent risk factor for stroke. The relationship between luminal stenosis and calcium burden in the intracranial circulation is incompletely understood. We evaluated the relationship between atherosclerotic calcification and luminal stenosis in the intracranial ICAs. MATERIALS AND METHODS: Using a prospective stroke registry, we identified patients who had both NCCT and CTA or MRA examinations as part of a diagnostic evaluation for ischemic stroke. We used NCCTs to qualitatively (modified Woodcock Visual Score) and quantitatively (Agatston-Janowitz Calcium Score) measure ICA calcium burden and used angiography to measure arterial stenosis. We calculated correlation coefficients between the degree of narrowing and calcium burden measures. RESULTS: In 470 unique carotid arteries (235 patients), 372 (79.1%) had atherosclerotic calcification detectable on CT compared with 160 (34%) with measurable arterial stenosis on CTA or MRA (P < .001). We found a weak linear correlation between qualitative (R = 0.48) and quantitative (R = 0.42) measures of calcium burden and the degree of luminal stenosis (P < .001 for both). Of 310 ICAs with 0% luminal stenosis, 216 (69.7%) had measurable calcium scores. CONCLUSIONS: There is a weak correlation between intracranial atherosclerotic calcium scores and luminal narrowing, which may be explained by the greater sensitivity of CT than angiography in detecting the presence of measurable atherosclerotic disease. Future studies are warranted to evaluate the relationship between stenosis and calcium burden in predicting stroke risk.

Predictors of renal relapse in Korean patients with lupus nephritis who achieved remission six months following induction therapy.

Renal relapse in patients with lupus nephritis (LN) is a risk factor for poor renal function. Therefore, there is a need to identify clinical and serological risk factors for renal relapse. A total of 108 patients with LN were enrolled in this study. All the subjects had achieved complete remission or partial remission following six months of induction therapy. We retrospectively analyzed their clinical and laboratory indices, final renal function, and kidney biopsy findings. The median follow-up period after LN diagnosis was 81 months. Renal relapse had occurred in 36 patients; it occurred in 38% and 46% of patients within five and 10 years after achievement of renal remission, respectively. There was no difference between the relapsed rate in patients with complete remission and that in those with partial remission. Clinical variables at LN onset and renal biopsy findings in the patients with sustained remission and relapsed patients were also not different. The probability of renal relapse was significantly higher in patients with an earlier age of onset of systemic lupus erythematosus (SLE) (≤ 28 years versus >28 years; HR 7.308, P=0.001), seronegativity for anti-Ro antibody (seronegativity versus seropositivity; HR 3.514, P=0.007), and seropositivity for anti-dsDNA antibody at six months after initiation of induction therapy (HR 8.269, P=0.001). Our study demonstrated that early onset of SLE, seronegativity for anti-Ro antibody and increased anti-dsDNA antibody following six months of induction therapy independently predict renal relapse among the LN patients.

Pancreatic adenocarcinoma upregulated factor, a novel endothelial activator, promotes angiogenesis and vascular permeability.

Pancreatic adenocarcinoma upregulated factor (PAUF) was recently reported to be a metastasis factor for pancreatic cancer cells. Here, we demonstrate a novel role for PAUF as a potent endothelial activator, promoting both angiogenesis and vascular permeability. Overexpression of PAUF in a mouse pancreatic cancer model resulted in increased tumor vascularity. Recombinant PAUF (rPAUF) enhanced proliferation, migration and capillary-like tube formation of human endothelial cells (ECs), consistently with increased neovascularization in vivo. rPAUF also increased endothelial permeability through the disruption of vascular endothelial-cadherin-facilitated cell-cell junctions in vitro and induced vascular leakage in mouse skin. These effects were attenuated upon treatment with an antibody against PAUF. Moreover, PAUF evoked a time- and dose-dependent activation of extracellular signal-regulated kinase (ERK)1/2, AKT and endothelial NO synthase (eNOS) in ECs, which are closely linked to rPAUF-induced angiogenesis. Finally, rPAUF upregulated the expression of C-X-C chemokine receptor 4 (CXCR4) in ECs and potentiated the in vitro and in vivo EC angiogenic responses to stromal cell-derived factor-1 (SDF-1), a ligand for CXCR4. Taken together, these data demonstrate that PAUF has a novel function in promoting angiogenesis and vascular permeability. Our findings suggest new possibilities for PAUF's role in the pathogenesis of angiogenesis-dependent diseases.

VDUP1 potentiates Ras-mediated angiogenesis via ROS production in endothelial cells.

Vitamin D3 up-regulated protein 1 (VDUP1) is a tumor suppressor of which expression is reduced in a variety of cancer cells, and enforced expression inhibits the tumor cell proliferation. It inhibits the activity of thioredoxin, thus contributing cellular ROS generation. Since ROS is a critical factor for angiogenesis, we investigated the role of VDUP1 in angiogenesis and endothelial proliferation. The expression of VDUP1 was upregulated by overexpression of an oncogene, Ras. Enforced expression of VDUP1 increases ROS production and proliferation of Ras-overexpressing endothelial cells. Overexpression of VDUP1 increases the resistance to the anchorage-dependent cell death and tube formation of the Ras-overexpressing endothelial cell. In addition, the removal of ROS by ROS scavenger attenuates the effect of VDUP1 on tube formation. These results suggest that VDUP1 is involved in Ras-mediated angiogenesis via ROS generation in endothelial cells.

Protein phosphatase 1 nuclear targeting subunit is a hypoxia inducible gene: its role in post-translational modification of p53 and MDM2.

p53, the most commonly mutated tumor suppressor gene in human cancers, is a master regulator of apoptosis in many types of cells. Recently, protein phosphatase-1 (PP1) has emerged as a key phosphatase of p53, which modulates the interaction of p53 with its regulatory protein mouse double minute 2 (MDM2) and transcriptional activity. In the present study, we demonstrate the potential role of PP1 nuclear targeting subunit (PNUTS) in regulating the phosphorylation and apoptotic activities of p53. Hypoxia significantly increased mRNA and protein expression of PNUTS in various cell lines concomitantly with increases in p53. Promoter analysis confirmed the presence of hypoxia response elements in the promoter region of the PNUTS gene, which respond to hypoxia and forced expression of hypoxia-inducible factor 1 alpha. Overexpression of PNUTS markedly increased cell death in response to hypoxia, with increased expression of Bax, an apoptosis-related gene induced by p53. Consistently, PNUTS increased the nuclear localization, phosphorylation, and transcriptional activity of p53 as well as the ubiquitin-dependent proteosomal degradation of MDM2. However, the W401A mutant form of PNUTS, which is incapable of binding to PP1, failed to induce these events. Taken together, our findings suggest that PNUTS may play an important role in controlling cell death in response to cellular stresses such as hypoxia through the post-translational modification of p53 and MDM2.

A case of cholestatic autoimmune hepatitis and acute liver failure: an unusual hepatic manifestation of mixed connective tissue disease and Sjögren's syndrome.

Although hepatomegaly is reported to occur occasionally in patients with mixed connective tissue disease (MCTD) or Sjögren's syndrome (SS), autoimmune liver diseases such as primary biliary cirrhosis, sclerosing cholangitis, and autoimmune hepatitis in association with MCTD or SS have rarely been described. We report a case of severe cholestatic autoimmune hepatitis presenting with acute liver failure in a 40-yr-old female patient suffering from MCTD and SS. The diagnosis of MCTD and SS was made at the age of 38. The patient presented severe jaundice and elevation of conjugated bilirubin. The patient denied alcohol and drug use and had no evidence of viral hepatitis. On the 8th day of her hospitalization, the patient developed grade III hepatic encephalopathy. She was diagnosed as autoimmune hepatitis presenting with acute liver failure based on clinical features, positive FANA and anti-smooth muscle antibodies, negative anti-mitochondrial antibodies, high titers of serum globulin, liver biopsy findings, and a good response to corticosteroid therapy, The patient was managed with prednisolone and the clinical symptoms, liver function test results, and liver biopsy findings showed much improvement after steroid therapy.

Vascular endothelial growth factor levels in the serum and synovial fluid of patients with rheumatoid arthritis.

OBJECTIVE: To determine the vascular endothelial growth factor (VEGF) concentrations in serum and synovial fluid (SF) from patients with rheumatoid arthritis (RA) and to search for relationships between VEGF levels and clinical and laboratory variables. METHODS: We measured VEGF levels using an enzyme-linked immunosorbent assay. Serum samples were obtained from 99 RA patients, 49 osteoarthritis (OA) patients, and 80 normal controls. Paired samples of serum and SF were collected from 32 patients with RA and 15 with OA. RESULTS: The mean serum VEGF concentration was 590.1 pg/ml for RA patients, 286.7 pg/ml for OA patients, and 265.8 pg/ml in controls. The serum VEGF concentration was significantly higher in the RA patients than in the OA patients or the controls (both p < 0.001). Furthermore, the VEGF levels in SF from RA patients were significantly higher than in SF from OA patients (p = 0.017). However, there was no correlation between VEGF levels in serum and SF from the same RA patients. The serum VEGF concentration was correlated with the ESR, serum CRP concentration, serum rheumatoid factor, number of tender and swollen joints, Modified Health Assessment Questionnaire, and patient and physician global assessments of disease activity in RA patients. CONCLUSION: These results suggest that VEGF level is related to RA disease activity, suggesting that VEGF may play some role in the pathogenesis of RA.

A soluble auxin-binding protein, ABP57. Purification with anti-bovine serum albumin antibody and characterization of its mechanistic role in the auxin effect on plant plasma membrane H+-ATPase.

ABP(57) is an auxin-binding protein that possesses receptor function. In this study, a protocol for ABP(57) purification was developed on the basis of cross-reactivity shown between ABP(57) and antisera raised against bovine serum albumin, which enabled us to purify ABP(57) with a high yield and to further characterize it. ABP(57) activates plant plasma membrane H(+)-ATPase (PM H(+)-ATPase) via direct interaction. The binding of indole-3-acetic acid (IAA) to the primary binding site on ABP(57) caused a marked increase in the affinity of ABP(57) for PM H(+)-ATPase, which was accompanied by a change in ABP(57) conformation. Meanwhile, additional IAA binding to the secondary site on ABP(57) nullified the initial effect without inducing further conformational change. When ABP(57) with IAA occupying only the primary site interacted with PM H(+)-ATPase, no IAA could access the secondary site. These results suggest that IAA-induced biphasic alteration in the affinity of ABP(57) for PM H(+)-ATPase correlates with a bell-shaped dose response of the enzyme to IAA. There is also a possibility that, whereas the stimulation phase of the response is associated with a conformational change of ABP(57), the destimulation phase probably results from hindrance arising directly from the presence of IAA at the secondary site.

Intramedullary tuberculosis manifested as Brown-Sequard syndrome in a patient with systemic lupus erythematosus.

A 25-year-old girl presented with progressive deterioration of right side weakness with decreased sensation on the left trunk. She had been treated with high dose steroid due to autoimmune thrombocytopenia for 2 months. Clinical, laboratory and immunologic studies revealed that she had systemic lupus erythematosus (SLE), MRI of spinal cord showed marginal contrast enhancing and fluid containing mass in the cord of the C5-6 level, suggesting intramedullary abscess. She underwent surgery of mass removal with biopsy. The pathologic findings from cord tissues revealed numerous acid fast bacilli (AFB) in necrotic tissues. After surgery and anti-tuberculous treatment, her neurologic symptoms were markedly improved with restoration of right side motor weakness. To our knowledge, this is the first case report of intramedullary tuberculosis in a patient with SLE. Since intramedullary tuberculosis may sometimes mimic neurologic complication of SLE itself, it may pose diagnostic and therapeutic confusion for clinicians. We report a case of spinal cord tuberculosis affecting C5, 6 level which was manifested as Brown-Sequard syndrome in a patient with SLE.

IgG antibodies to type II collagen reflect inflammatory activity in patients with rheumatoid arthritis.

OBJECTIVE: To determine the clinical significance of IgG antibodies to type II collagen (CII) and to define any correlation of antibodies to CII with the inflammatory response in patients with rheumatoid arthritis (RA). METHODS: IgG antibodies to native human type II collagen (IgG anti-CII) were measured in sera and synovial fluid (SF) from patients with RA, patients with osteoarthritis (OA), and healthy controls by an improved ELISA. Demographic, clinical, and laboratory data including tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) levels were also obtained at the time of sampling in patients with RA. RESULTS: The median level and positivity for circulating IgG anti-CII were higher in patients with RA (n = 297) than patients with OA (n = 34) and healthy controls (n = 50) (p < 0.001). The titers of IgG anti-CII in SF were also higher in RA (n = 45) than in OA (n = 16) (p < 0.001). In paired samples, the levels of IgG anti-CII were significantly higher in SF compared to the sera in patients with RA (n = 45) (p < 0.001), but levels were not different in patients with OA (n = 16). Circulating IgG anti-CII converted from positive to negative in 13 patients (10.7%) and from negative to positive in 18 patients (14.8%) among 122 patients with RA in whom IgG anti-CII were monitored sequentially at a mean interval of 12.2 months. IgG anti-CII positive patients (n = 98) had shorter disease duration (p = 0.04) and less frequent deformity (p = 0.013), and higher median erythrocyte sedimentation rate (ESR) (p = 0.001) and C-reactive protein (CRP) (p < 0.001) than IgG anti-CII negative patients (n = 120). The levels of IgG anti-CII correlated with CRP (r = 0.270) and ESR (r = 0.253). CRP decreased significantly in patients (n = 13) who converted from IgG anti-CII positive to negative (p = 0.013). IgG anti-CII positive patients (n = 40) had higher levels of TNF-alpha and IL-6 than negative patients (n = 40) (p < 0.001). Levels of IgG anti-CII correlated well with TNF-alpha (r = 0.617) and IL-6 (r = 0.347). CONCLUSION: Increased IgG anti-CII in sera and SF in RA correlated directly with acute phase reactants and the proinflammatory cytokines TNF-alpha and IL-6. Our data suggest that IgG anti-CII could reflect inflammatory activity with a potential to destroy cartilage in the early stages of RA.

Urinary bladder involvement in patients with systemic lupus erythematosus: with review of the literature.

OBJECTIVES: To investigate the etiologies of urinary bladder involvement in patients with systemic lupus erythematosus (SLE), the clinicoradiologic features of gastrointestinal tract manifestations and clinical outcomes in patients with lupus cystitis accompanied by gastrointestinal manifestations. METHODS: We conducted a retrospective chart review on 413 patients with SLE. Patients were selected for review on the basis of lower urinary tract symptoms including urinary frequency, urgency and urinary incontinence. Radiologic studies were analyzed in patients with lupus cystitis. RESULTS: Ten consecutive patients, complicated with lower urinary tract symptoms, were identified. Underlying etiologies were as follows: lupus cystitis in five, neurogenic dysfunction secondary to transverse myelitis in three, cyclophosphamide-induced cystitis in one and tuberculous cystitis in one patient. All patients with lupus cystitis showed gastrointestinal manifestations, such as abdominal pain, nausea, vomiting and/or diarrhea during the periods of cystitis symptoms. In all patients with lupus cystitis, paralytic ileus was demonstrated on plain abdominal X-ray and ascites, bilateral hydroureteronephrosis and thickened bladder wall were identified on abdominal ultrasound or CT. Abdominal CT revealed bowel wall thickening in four of the five patients. The main sites of thickened bowel on abdominal CT were territory supplied by superior mesenteric artery. Two of five patients with lupus cystitis expired during the follow-up period. CONCLUSION: Diverse etiologies may cause lower urinary tract symptoms in patients with SLE. Lupus cystitis is strongly associated with gastrointestinal involvement and abdominal CT can be a useful radiologic tool to investigate the gastrointestinal tract involvement in patients with lupus cystitis.

Systemic mononuclear inflammatory vasculopathy associated with Sjögren's syndrome in a patient with primary biliary cirrhosis.

We report a 46-year-old woman with primary biliary cirrhosis (PBC) presenting with Sjögren's syndrome and systemic mononuclear inflammatory vasculopathy. Biopsy specimens of sural nerve showed findings consistent with vasculitic neuropathy. Perivascular inflammatory mononuclear cell infiltration was observed on muscle biopsy specimen. The findings of abdominal computed tomography and brain magnetic resonance imaging were suggestive of vasculitis. Clinical manifestations and radiologic findings were improved after high dose prednisolone therapy.

Divergent effect of cyclosporine on Th1/Th2 type cytokines in patients with severe, refractory rheumatoid arthritis.

OBJECTIVE: To investigate the effect of cyclosporine on cytokine production, especially on T helper 1 (Th1) and T helper 2 (Th2) type cytokines, in patients with rheumatoid arthritis (RA). METHODS: A 16 week randomized, double blind, placebo controlled study of cyclosporine (2.5 to 4 mg/kg/day) was conducted in 40 patients with severe, refractory RA who had residual inflammation and disability despite partial responses to prior maximal tolerated dose of methotrexate (MTX; < 15 mg/week) and low dose prednisone (< 10 mg/day). Clinical and laboratory variables, and circulating levels of interleukin 2 (IL-2), IL-4, IL-10, IL-12, tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) measured by ELISA were compared between patients (cyclosporine group) treated with cyclosporine plus MTX and those (placebo group) treated with placebo plus MTX at entry and at 16 weeks. RESULTS: At 16 weeks, the cyclosporine group (n = 17), compared with the placebo group (n = 17), had greater decreases in tender joints, swollen joints, patient global assessment, patient self-assessed disability, and C-reactive protein, as well as having more patients with > 20% improvement. Comparison of circulating cytokines at entry and at 16 weeks showed significant decreases of IL-2 (median -61 vs 7 pg/ml; p = 0.004) ("+" denotes increase, "-" denotes decrease), IL-12 (median -313 vs -14 pg/ml; p = 0.002), TNF-alpha (median -55 vs 5 pg/ml; p < 0.001), and IFN-gamma (median -21 vs 5 pg/ml; p = 0.003), and a significant increase of IL-10 (median 55 vs -12 pg/ml; p < 0.001) in the cyclosporine group compared with the placebo group. The degree of IL-10 increases correlated strongly with the degree of IL-12 decreases in the cyclosporine group (r = 0.572, p = 0.016). However, there was no change in circulating IL-4 between the 2 groups. Within the cyclosporine group, the improved patients (n = 10) compared to the non-improved patients (n = 7) had a greater increase in circulating IL-10 (median 172.0 vs 85.2%; p = 0.01). The rate of increase of IL-10 strongly correlated with the rate of improvement of joint scores (r = 0.718, p = 0.001) after administration of cyclosporine. CONCLUSION: Our results suggest that the therapeutic effect of cyclosporine is achieved by correcting a Th1/Th2 imbalance (a shift of Th1 type to Th2 type), which may be involved in the pathogenesis of RA; and that circulating IL-10 is useful to assess the clinical improvements in patients with RA after administration of cyclosporine.

Causes of death in Korean patients with systemic lupus erythematosus: a single center retrospective study.

OBJECTIVE: To determine the causes of death in Korean patients with systemic lupus erythematosus (SLE). METHODS: We evaluated retrospectively Korean SLE patients who were monitored in the Center for Rheumatic Disease in Kang-Nam St. Mary's Hospital from 1993 to 1997 and who died. RESULTS: Forty-three (7.9%) of 544 patients died. Comparison of demographics and disease activity indices between the deceased and the survivors showed that the age was older and C3 at presentation was lower in the deceased (n = 40) than the survivors (n = 453) (age: 33.8 +/- 13.6 versus 28.3 +/- 10.6 years, p = 0.02, C3: 36.8 +/- 21.4 versus 49.7 +/- 20.8 mg/dl, p = 0.03). Among 40 patients who died, the frequency and causes of death were as follows: 13 from infection (32.5%), 10 SLE-related factors (25.0%), 6 pulmonary hypertension (15.0%), 4 cerebrovascular accidents (10.0%), and 3 thrombotic thrombocytopenic purpura (7.5%). The majority of the SLE-related deaths were non-renal in origin, including 3 cerebral nervous system disease, 2 TTP, 2 acute pulmonary hemorrhage syndrome, 1 acute myocarditis, and 1 multi-system illness. SLE-related renal causes were responsible for only death. The major organisms of infection were gram negative bacilli (69.2%), primarily manifesting as sepsis or bacteremia (76.9%). The patients (n = 13) who died from infection had lower levels of complement and higher levels of anti-ds DNA antibody at presentation than those (n = 27) who died from the other causes (C3: 24.7 +/- 17.8 versus 41.7 +/- 21.5 mg/dl, p = 0.02, anti-dsDNA antibody: 68.0 +/- 73.5 versus 27.0 +/- 35.3 IU, p = 0.04). The mean steroid dose being administered one month before death was also higher in the patients who died of infection (30.5 +/- 15.2 versus 15.2 +/- 7.7 mg/day, p = 0.03). Patients who died of pulmonary hypertension, the third most common cause of mortality, showed extremely high pulmonary pressures at the initial diagnosis, with a short interval to death, and had less major organ involvement at death. There were no deaths due to coronary heart disease or neoplasm in this cohort. CONCLUSION: The most common cause of death in 544 Korean lupus patients was infection, mainly manifesting as gram negative bacterial sepsis. SLE-related factors (mostly non-renal) were the next most frequent cause. Death from infection was associated with higher disease activity at presentation and a higher dose of steroid used previously. Death due to pulmonary hypertension was common, whereas death due to coronary heart disease was absent.

Central apnea and acute cardiac ischemia in a sheep model of epileptic sudden death.

The etiology of sudden death in patients with epilepsy remains unclear. Previous studies in a well-established sheep model of status epilepticus showed that more than one-third of the unsedated animals died within 5 minutes of seizure onset due to hypoventilation. The relative contributions of airway obstruction and central hypoventilation could not be determined because airway flow and respiratory effort were not monitored. In this study, status epilepticus was induced in unsedated sheep with tracheostomies monitored by electrocardiography, electroencephalography, arterial line, serial blood gases, and airway flowmeter. All 8 animals demonstrated central apnea and hypoventilation, which resulted in the death of 1 and contributed to the death of another. A third animal died of acute heart failure within 2 minutes of seizure onset, accompanied by a large septal myocardial hemorrhage, contraction bands, and signs of global cardiac ischemia. More subtle contraction bands, subendocardial hemorrhage, and signs of acute myocardial ischemia were seen in other animals as well, none of which died of cardiac causes. Malignant arrhythmia was not seen in any of the sheep. Central hypoventilation and apnea accompany generalized status epilepticus and may be an important cause of sudden death in epileptics. Acute cardiac failure may also be a cause of epileptic sudden death.

Decreased tumour necrosis factor-beta production in TNFB*2 homozygote: an important predisposing factor of lupus nephritis in Koreans.

Low TNF production and its association with TNF gene restriction fragment length polymorphism (RFLP) was demonstrated in (NZW/NZB) F1 mice. However, little is known about the significance of TNF production in association with TNF gene polymorphism in human SLE. This study was designed to evaluate the role of TNF production of peripheral blood mononuclear cells (PBMC) and its association with TNFB gene polymorphism in SLE, particularly lupus nephritis. TNFB gene polymorphism was defined by PCR-NcoI RFLP. TNF productions of phytohemagglutinin (PHA)-stimulated PBMC and T cells were examined by bioassay using L929 cell line and ELISA. The PBMC stimulated by PHA from patients with SLE (n = 60) tended to secrete less amounts of TNF by bioassay (1032 +/- 184 pg/ml vs 1524 +/- 224 pg/ml, P = 0.094), and TNF-beta by ELISA (P = 0.0082) than that from normal controls (n = 38). The low TNF-alpha producer was more frequent in nephritis than non-nephritis (34.4% vs 7.1% respectively, P < 0.01). TNF-beta also revealed similar results (53.1% vs 21.4%, P < 0.05). In SLE, mean production of TNF-beta was decreased in TNFB*2 homozygote (n = 18) than that in TNFB*1 homozygote (n = 9) (1126.3 +/- 145 pg/ml) vs 642 +/- 118.4 pg/ml, respectively, P = 0.021), whereas TNF-alpha production showed little difference between the two groups (710.1 +/- 56.4 vs 542.4 +/- 71.1 pg/ml, respectively, P = 0.149). Our results demonstrate that decreased TNF production of PBMC, which was significantly associated with TNFB*2 homozygosity, could be an important predisposing factor of lupus nephritis in Koreans.

Bronchiolitis obliterans organizing pneumonia as an initial manifestation in patients with systemic lupus erythematosus.

Diverse pleuropulmonary manifestations including diaphragmatic dysfunction, pleural effusion, acute lupus pneumonitis, pulmonary hemorrhage, pulmonary hypertension, and diffuse interstitial lung disease have been described in patients with systemic lupus erythematosus (SLE). Bronchiolitis obliterans organizing pneumonia (BOOP) as an initial manifestation of SLE is rarely reported. We describe 2 patients who had SLE concurrent with the onset of BOOP. Their respiratory symptoms, followup pulmonary function tests, and radiologic findings showed much improvement after steroid therapy.