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Objective.The risk of clinically manifested major cardiovascular (CV) events in primary Sjögren syndrome (pSS) remains unclear. This study aimed to assess myocardial fibrosis in pSS and investigate the associated disease characteristics by cardiac magnetic resonance imaging (cMRI).Methods.We performed a cross-sectional study of patients with pSS without cardiac symptoms. Labial gland biopsy was documented in 44 patients (85%). Patients without CV risk factors underwent contrast-enhanced cMRI. Late gadolinium enhancement (LGE) was used to assess myocardial fibrosis. Myocardial edema was assessed using T2-weighted imaging (T2WI). We compared the left ventricular (LV) geometry and function between the groups with and without LGE. Further, we explored the associations of cMRI abnormalities with pSS characteristics.Results.Fifty-two women with pSS (median age 55, IQR 47.0–65.7 yrs) were enrolled in the study. LGE was observed in 10 patients (19%), two of whom showed high intensity on T2WI. High intensity on T2WI was observed in 3 patients (5.8%). LV mass index and LV mass/end-diastolic volume tended to be higher in the LGE-positive group than in the LGE-negative group (P = 0.078 and 0.093, respectively). Salivary gland focus score (FS) ≥ 3 was independently associated with LGE-positive in the multivariable analysis (OR 11.21, 95% CI 1.18–106.80).Conclusion.Subclinical myocardial fibrosis, as detected by cMRI, was frequent in patients with pSS without cardiac symptoms. Abnormal cMRI findings were associated with salivary gland FS ≥ 3.

Background: Influence of Helicobacter pylori infection and sex difference on leukocyte differentials was insufficiently understood. We therefore conducted the current study to evaluate influence of H. pylori and sex on peripheral leukocyte differentials as well as influence of Helicobacter pylori eradication. Methods: Dyspeptic patients and persons asked to examine gastroduodenal lesions at medical check were included. Total leukocytes, differentials, and anti-H.pylori IgG antibody were measured. Those change after eradication was also measured. H. pylori infection was assessed by anti-H. pylori IgG antibody, rapid urease test, and pathologic findings. H. pylori-uninfected patients and non-dyspeptic/seronegative persons were regarded as negative controls. Results: Totally 374 patients and 299 controls were evaluated, and 167 patients were successfully eradicated. Peripheral counts of neutrophil and monocyte elevated with H. pylori infection: 3221.7+/-1108.7 vs. 2911.9+/-1027.3/μL and 307.5+/-130.5 vs. 281.5+/-106.4/μL, (p­=.0002 and .0054). Compared to females, males manifested elevated counts of every leukocyte, but the difference was insignificant in basophil (p=.0089, 0.0316, Conclusions: We confirmed increases in neutrophils and monocytes in H. pylori-infected patients. Successful eradication reduced peripheral counts of neutrophil, lymphocyte, and monocyte, whereas it increased eosinophil counts. Males manifested elevated counts of every leukocyte, comparing to females. H. pylori infection influences systemic immune response and may not predispose to allergic disorders.Trial registration: The study protocol was registered on UMIN (University hospital Medical Information Network system) in Japan (R000017345) in 2014.

We report a 68-years-old woman with systemic sclerosis and interstitial pneumonia (IP). She had developed subacute progressively encephalopathy and dementia while treated with oral cyclophosphamide and prednisolone. She admitted to our hospital because of syncope. Laboratory tests indicated slight elevated cerebrospinal fluid protein, and levels of serum C-reactive protein (CRP), levels of soluble IL-2 receptor was normal. But, magnetic resonance imaging (MRI) of the brain showed multiple infarct-like lesions mainly in the white matter, which mimics progressive multiple leukoencephalopathy (PML). Twenty days after admission, the retested MRI of the brain disclosed initial lesions progressively enlarged and numbers of the lesions were increased. The polymerase chain reaction (PCR) for JC virus of cerebrospinal fluid was negative. To make diagnosis, brain biopsy was performed. Microscopic examination revealed that small vessels were filled with lymphoma cells (CD20+, CD79+, CD3-), and intravascular lymphoma (IVL) was diagnosed. She treated with regimens of R-CHOP. After chemotherapy her consciousness and dementia were gradually improved. IVL of central nerve system (CNS) is a rare disease, and its common symptoms are ischemia, infarction and dementia. Diagnosis of IVL of CNS is difficult when the lesion mimics PML, and patient with similar laboratory examinations and radiographic findings of PML should undergo brain biopsy detected malignant cell in small vessels, which is a value of diagnosis.

Background: Elderly acute myeloid leukemia (AML) patients and patients with higher-risk myelodysplastic syndromes (MDS) have a much poorer prognosis than younger patients despite intensive chemotherapy. Methods: Ten patients with higher-risk MDS and 12 patients with AML over 65 years of age were enrolled into this study and received oral induction therapy with cytarabine ocfosfate and etoposide. Results: The therapy response rates were 60% in the MDS group and 41.7% in the AML group. The difference in overall survival among MDS and AML patients was not statistically significant. The difference in the median survival times of the responsive and nonresponsive groups, which included MDS and AML patients, was statistically significant (790 and 174 days, respectively). Conclusions: Based on a comparison of the data of this therapy in elderly higher-risk MDS patients versus elderly AML patients, we conclude that this therapy is well tolerated and can be cost-effective and useful for higher-risk MDS in elderly patients.

Objectives Minodronic acid hydrate, an oral bisphosphonate, has a greater inhibitory effect on bone resorption than do other approved drugs; however, this has been studied only in patients with primary osteoporosis. Here, we administered minodronic acid hydrate to patients with steroid-induced osteoporosis who have been treated with steroids for rheumatoid arthritis or other collagen diseases, and the efficacy and safety of minodronic acid hydrate were prospectively investigated. Methods Twenty-five patients treated in our rheumatology clinic received minodronic acid hydrate 1 mg/day. The changes in bone mineral density (BMD) and bone turnover markers were investigated at 3 and 6 months, and adverse events, including the presence or absence of an incident osteoporotic fracture, were examined over a period of 6 months. Results Percent changes in BMD of the lumbar spine and femur significantly increased. The values of bone turnover markers significantly decreased. There were no patients with a radiographically apparent incident fracture. Adverse events included toothache for which the patient discontinued the treatment and three cases of gastrointestinal disorder that did not lead to discontinuation, and thus minodronic acid hydrate was well tolerated. Conclusions Here, we show that minodronic acid hydrate is effectively and safely used for treatment of steroid-induced osteoporosis.

To evaluate the influence of Helicobacter pylori and sex difference on peripheral platelet counts, dyspeptic patients without immunohaematologic disorders were evaluated. H. pylori infection was verified with the rapid urease test and serum anti-H. pylori IgG antibody. Platelet counts were analysed with a reference to H. pylori infection and sex difference. Among H. pylori-eradicated patients, changes in platelet counts were separately evaluated. Totally, 655 patients were enrolled: 340 patients were infected with H. pylori and 178 patients received eradication therapy, with a success rate of 88.2% (157/178). Females with H. pylori infection definitely manifested elevated platelet counts (infected vs. uninfected 244 ± 57 vs. 219 ± 54 × 109/l; p < 0.0001). H. pylori eradication reduced peripheral platelets by 8 weeks, 5–6 months, 1, 2 and ≧3 years after eradication in females from 248 ± 54 to 237 ± 49, 237 ± 54, 229 ± 48, 238 ± 61 and 232 ± 50 × 109/l (p = 0.0003, 0.0182, 0.0041, 0.0398 and 0.0289), respectively. In males, the reduction was verified by 8 weeks, 1 year and ≧3 years from 226 ± 52 to 217 ± 47, 214 ± 44 and 200 ± 49 × 109/l (p = 0.0464, 0.0164 and 0.0016), respectively. In conclusion, H. pylori infection upregulates platelet counts mainly in females, and eradication reduced peripheral platelets in both sexes. Females appeared more susceptible to H. pylori infection than males with regard to upregulation of platelet counts.

d Kanifukuoka-Kyodo Clinic, Fujimino, Japan Abstract Helicobacter pylori infection has been reported to be inversely associated with allergic disorders. We by chance experienced a patient with atrophic gastritis who presented marked elevations of both nonspecific serum immunoglobulin E and eosinophil counts after H. pylori eradication. A 49-year-old Japanese man received eradication of H. pylori using lansoprazole 60 mg/day, amoxicillin 1,500 mg/day, and clarithromycin 400 mg/day for 7 days. Serum immunoglobulin E increased to more than four times its pretreatment level, 306 ) 485 ) 1,325 U/ml, and peripheral eosinophil counts increased to more than three times, 99 ) 139 ) 298 per μl. Deducing from the current case, H. pylori eradication might develop allergic disorders in some patients.

Although the effects of angiotensin II receptor blockers (ARBs) on non-diabetic glomerulonephritis have been reported, studies of their effects on collagenvascular diseases, particularly lupus nephritis, are limited. In this retrospective, observational study, systemic lupus erythematosus (SLE) patients ( n = 7) with lupus nephritis and uncontrolled proteinuria were treated with an angiotensin-converting enzyme inhibitor followed by the ARB losartan (25–50 mg/day). Urinary protein excretion and renal function were evaluated. After 12 months of losartan, mean urinary protein excretion decreased significantly by 84.8%. Mean systolic and diastolic blood pressures also decreased significantly during the 12 months of losartan treatment, although not in normotensive patients. Complement 4, total complement activity and anti-dsDNA antibody levels, which are indices of SLE activity, and serum creatinine levels, which is an index of renal function, showed no change in response to losartan treatment. A more extensive evaluation of the effects of ARBs in patients with lupus nephritis and poorly controlled proteinuria is required.

Objective We have observed alterations of quantitative (q)-EEG findings occurring in interferon (IFN)-α treated chronic hepatitis C (CH-C) patients, and found patient's age to be one factor influencing such EEG alterations. In the present study we evaluated the correlation between q-EEG alterations during IFN-α treatment and the severity of hepatitis based on liver biopsies. Methods A total of 102 CH-C patients underwent blind, prospective and serial q-EEG examinations. The IFN-α was administered under the same therapeutic regimen to all patients. Serial EEGs were obtained before, at 2 and 4 weeks, and at 2-3 days after the conclusion of treatment. The absolute powers of each frequency band in different periods were determined by q-EEG. Staging (of fibrosis) and grading (of inflammatory cell infiltration) were scaled according to Desmet's classification. We evaluated the relationship between q-EEG and scales of staging or grading. Results Age distributions did not differ significantly among stages or grades. As the stage or grade increased, the alterations of EEG during IFN-α treatment became more pronounced, and significant (repeated-measures analysis of variances; both, p

Discrepant outcomes of Helicobacter pylori eradication in patients with idiopathic thrombocytopenic purpura have been reported. Here patients with dyspepsia and no other complications underwent gastroendoscopic examination and evaluation for Helicobacter pylori infection. Helicobacter pylori-infected patients with gastritis and gastric ulcer received eradication therapy: lansoprazole (60 mg/day), clarithromycin (400 mg/day), and amoxicillin (1500 mg/day) for 1 week. Lansoprazole 30 mg/day was administrated additional 7 weeks. Peripheral platelets were counted before treatment, 8 weeks after initiation of therapy, and at follow-up periods. Platelet counts in patients with both gastritis and gastric ulcer were evaluated with reference to the presence of Helicobacter pylori infection. Eighty-seven patients with gastritis and 35 of those with gastric ulcer underwent successful eradication therapy. Peripheral platelet counts in patients with gastritis decreased from 235+/-55 to 228+/-58 (10(3)/microL) (p=0.0337), and those with gastric ulcer decreased from 248+/-60 to 232+/-48 (10(3)/microL) (p=0.020) 8 weeks after initiation of therapy. Non-eradicated patients did not show such a tendency. Helicobacter pylori eradication reduced peripheral platelet counts in patients with gastritis and gastric ulcer. Amelioration of thrombocytopenia by eradicating Helicobacter pylori appears to involve mechanisms specific to idiopathic thrombocytopenic purpura.

To evaluate the vulnerability of the central nervous system (CNS) in patients with systemic lupus erythematosus (SLE).Forty-eight patients with SLE, 58 with schizophrenia in remission and 39 healthy controls were enrolled in the study. Patients vocally generated 100 numbers in a random fashion, using numbers 0 to 9, and were evaluated with seriality scores. Patients with SLE were subgrouped according to differences in the presence of Raynaud's phenomenon, anti-phospholipid antibody, lupus activity, and a history of neuropsychiatric (NP) lupus, and these patients were also evaluated by comparison with their counterparts.In general, patients with SLE showed lower seriality scores than patients with schizophrenia, and higher seriality scores than normal controls. The scores of the patients with a history of NP lupus matched those with schizophrenia, and the scores of never having NP lupus matched those of the healthy controls.CNS vulnerability may be prolonged in patients who have a history of NP lupus even when they appear to be in normal NP status. The damage in random number generation (RNG) observed in patients with a history of NP lupus seemed equal to that found in those with schizophrenia, whereas those patients never having NP lupus appeared to be equal to the controls. The current study suggests a heterogeneous nature of SLE and prolonged damage, especially in CNS vulnerability, when evaluating with RNG.

We report a rare case of systemic lupus erythematosus (SLE) complicated by alveolar hemorrhage and cytomegalovirus (CMV) colitis. Despite the successful treatment of lupus nephritis by steroid pulse therapy, the patient developed an acute alveolar hemorrhage 2 months later. Cyclophosphamide pulse therapy ameliorated the hemorrhage. One month later, she suddenly developed melena secondary to CMV colitis. Antiviral therapy was successful. We emphasize the importance of timely and precise differential diagnosis for successful management of complicated SLE.

Objective To examine whether Coxiella burnetii (C. burnetii) is involved in chronic fatigue syndrome (CFS), we administered tetracycline antibiotics to subjects with CFS, and followed changes in clinical symptoms, PCR findings, and C. burnetii antibody titers.Patients and Methods The subjects were 8 patients with CFS and 213 with nonspecific complaints such as chronic fatigue and low-grade fever for several months or longer but not meeting the diagnostic criteria for CFS. All were examined for C. burnetii infection by nested PCR and the indirect immunofluorescence test (IF).Results Four CFS patients (the CFS group) and 54 controls [the post-Q fever fatigue syndrome (QFS) group] positive for C. burnetii were treated mainly with minocycline or doxycycline (100 mg/day) for 3 months. After treatment, all 58 patients tested negative for C. burnetii infection. In the CFS group, no significant difference was noted between the mean pre- and post-treatment temperatures or headache scores. Similarly, there was no significant improvement in performance status (PS) scores. In the QFS group, however, mean temperatures and headache scores were significantly decreased after treatment (p

We report the case of a 32-year-old man who developed Wegener's granulomatosis complicated with refractory intestinal ulceration. In August 2001, he presented with a high fever, nasal bleeding, and bilateral leg numbness. These symptoms worsened, which prompted him to consult his home doctor on February 18, 2002. In spite of treatment with antibiotics, his symptoms did not improve. Furthermore, abdominal pain and melena occurred as additional symptoms in March 2002. He was admitted to our hospital on April 5, 2002. A deformed nose condition (the so-called saddle nose) was observed at this time. Laboratory data showed a high erythrocyte sedimentation rate (103 mm/h) and a high level of serum C-reactive protein (14.98 mg/dl), and hematuria and proteinuria were also observed. The patient was positive for an antineutrophil cytoplasmic antibody specific for proteinase-3 (PR3-ANCA). A chest computed tomography (CT) scan revealed multiple pulmonary nodules in the lung field. A biopsied-specimen from the nasal mucosa showed necrotizing granulomatosis with giant cells. Together with his symptoms and the laboratory and pathological findings, the patient was diagnosed as having Wegener's granulomatosis. A colon fiberscopy showed multiple ulcerations with bleeding from the terminal ileum to the ascending colon, and nodular lesions at the terminal ileum. We started a combination therapy of prednisolone (60 mg/day) and cylophosphamide (100 mg/day) orally. The patient's gastrointestinal symptoms disappeared and abnormal serological indicators improved. Although Wegener's granulomatosis complicated with refractory intestinal ulceration is rare, this case indicates that the gastrointestinal region is also a target organ of Wegener's granulomatosis.

A 65-year-old Japanese woman was diagnosed in 1996 with a pathological fracture of the left femur caused by immunoglobulin D-type myeloma (IgD myeloma). She responded well to combination chemotherapy followed by irradiation. The patient experienced renal failure and became dependent on haemodialysis. In 1999, large plasmacytomas developed in the abdomen and left humerus. The abdominal tumour appeared to induce gastroduodenal ulcers and jejunal obstruction. We initiated irradiation therapy without chemotherapy to prevent further growth of the plasmacytoma, although treatment-resistant gastroduodenal ulcers developed. Continued blood loss from the gastroduodenal ulcers resulted in a deterioration in the patient's health, which prevented successful haemodialysis. An autopsy showed that the plasmacytoma had undergone coagulation necrosis. We conclude that the use of combination chemotherapy with topical irradiation was an acceptable treatment measure against IgD plasmacytoma; irradiation without chemotherapy was the most likely cause of the coagulation necrosis seen in the plasmacytoma at autopsy.

To clarify the prevalence of subclinical renal tubular acidosis (RTA) and its association with clinical and laboratory parameters in primary and secondary Sjögren's syndrome (SS), an acid-loading test was conducted. Subclinical RTA was found in 32% of patients with SS. The prevalence of subclinical RTA in primary and secondary SS was about the same (31.6% and 33.3%, respectively). Significant longer duration of illness, more severely decreased salivary excretion, decreased lymphocyte number, higher serum levels of IgG and IgA, and higher frequency of anti-SS-A (Ro) and SS-B (La) antibodies were found in patients with subclinical RTA. These results suggested that subclinical RTA may be a characteristic manifestation both in primary and secondary SS, along with the progression of immunologic dysfunction, when the illness seemed to be indolent.

A 40-year-old woman with amyopathic dermatomyositis (ADM) developed acute pneumonitis. Despite pulse methylprednisolone therapy, the pneumonitis worsened. We therefore initiated cyclosporin-A (Cy-A) therapy with success, although Pneumocystis carinii (PC) pneumonia occurred. Coexistence of dermatomyositis (DM)-related pneumonitis and PC pneumonia was diagnosed by means of chest X-ray findings, KL-6, and polymerase chain reaction (PCR) for PC. We thus continued Cy-A therapy to ameliorate the pneumonitis. Cy-A appeared to be effective for corticosteroid-resistant pneumonitis in a patient with DM.

We studied isotype-specific rheumatoid factors (RFs) to clarify their significance in rheumatoid arthritis (RA) and to verify the difference in RF isotypes between RA and chronic liver diseases (CLD). Isotype-specific RFs in RA and in CLD were measured by enzyme-linked immunosorbent assay (ELISA). Most sera (n = 51, 94.1%) from RA patients contained some kind of RF isotypes (92.1% for IgM RF, 76.4% for IgG RF, and 43.1% for IgA RF), and seronegative RA by ELISA was seen in only 11.8% (n = 6). The most characteristic combination of RF isotypes in active RA was IgG, IgA, and IgM. This combination of RF isotypes changed to IgG plus IgM, according to the diminution of RA activity; then, we found only IgM RF in inactive RA. The titers of each RF isotype also decreased in parallel with the activity of RA. IgA RF seemed to be the most sensitive factor for evaluating the activity of RA. In CLD, almost the same high frequency (n = 49, 89.8% for IgM RF, 59.2% for IgG RF), with the same titer levels seen in RA, was observed. On the other hand, IgA RF was significantly lower in frequency (n = 9, 18.4%) and in titer, compared with the finding in RA. Surprisingly, even in CLD, true seronegativity by ELISA was also found in very few patients (n = 4, 8.1%). In CLD, positive RFs detected by agglutination assay were seen more often in chronic hepatitis than in liver cirrhosis. In RA patients, significant associations of IgA RF and the serum concentration of IgA, and IgG RF and the serum concentration of IgG, were observed. On the other hand, in CLD patients, significant associations of IgG RF and the serum IgG concentration, and of IgM RF and the serum IgM concentration, were observed. These results indicated that IgA RF in active RA is the most characteristic RF isotype distinguishing it from other nonrheumatic diseases, as well as from inactive RA. RF isotypes reflected the background polyclonal B-cell activation in different manners in both diseases. In CLD, RF isotypes seemed to be disease-related immunological disorders reflecting disease progression.

Objectives - To estimate the effect of brain function due to IFN-alpha in chronic hepatitis C patients by the quantitative EEG. Methods - 56 chronic hepatitis C patients were administered IFN-alpha intramuscularly at 9×10 6 IU daily for the first 4 weeks and then 3 times/week for the next 20 weeks. Serial EEGs were obtained in each subject before, at 2 and 4 weeks, and after completing the treatment. Resting EEG without artifacts was selected for quantitative EEG analysis, which was performed blindly. The frequency range was divided into delta to beta. The absolute and relative powers of each frequency band in each subject were calculated and the differences of these powers at different stages were analyzed statistically. Results - The absolute powers of slow waves (delta, theta 1, and theta 2) increased while alpha 2 and fast wave (beta) decreased significantly at all locations during IFN-alpha administration. The total power and alpha 1 values revealed no significant alterations. The relative power revealed the same alteration during treatment. These changes disappeared following the treatment. Such diffuse slowing in the EEG was revealed by the total change in the whole subjects. Conclusions - Diffuse slowing in the EEG was induced by IFN-alpha, was reversible, and was evident as the total change in the subjects. These findings suggested mild IFN-alpha-induced encephalopathy.

We have encountered five hemodialysis patients who had received enteral nutrition and recovered from erythropoietin-resistant anemia with neutropenia after the correction of copper deficiency. We reduced the required doses of recombinant human erythropoietin (rHuEPO) to maintain the target hematocrit levels and three patients were finally weaned from the rHuEPO therapy. Thus, copper deficiency is involved in erythropoietin-resistant anemia in hemodialysis patients.

Beyond the obvious step of limiting use of non-steroidal anti-inflammatory drugs (NSAIDs), the treatment of ulcers induced by NSAIDs remains controversial. We evaluated the efficacy of the proton-pump inhibitor lansoprazole on NSAID-induced ulcers. Ulcers were endoscopically diagnosed in 47 NSAID users. These patients received 30 mg/day lansoprazole, orally, for 6 or 8 weeks (6 weeks for duodenal ulcers and 8 weeks for other ulcers). Ulcer healing was assessed using an established classification system. The presence of immunoglobulin G antibody against Helicobacter pylori was also evaluated. The antibody was present in the sera of 51% of patients (24/47). Most of the ulcers reached scarring stages S1 (healing) or S2 (good healing), and the S2 healing rate was 35%. Two H. pylori seropositive patients did not reach these stages; their ulcers were improved by H. pylori eradication therapy, followed, in one case, by medication with misoprostol. Lansoprazole seemed to be useful for most patients with NSAID-induced ulcers, but a few needed additional treatments.

We investigated the role of melatonin in the induction of gastric lesions induced by water immersion restraint stress or centrally administered thyrotropin-releasing hormone (TRH). Melatonin (0.1-1 ng) injected intracisternally (i.c) 30 min prior to stress dose-dependently inhibited the induction of gastric lesions by water immersion restraint stress, while 100 micrograms/kg, i.p. failed to protect the gastric mucosa. Preadministration of melatonin (1 ng, i.c.) significantly reduced (83%) the severity of gastric lesions induced by a TRH analogue (500 ng, i.c.). Serum melatonin concentrations 30 min after administration of 1 ng melatonin i.c. did not differ from those of rats receiving i.c. vehicle. These results suggest that melatonin plays a protective, anti-stress, role in the gastric mucosa via a mechanism involving the central nervous system.

A 59-year-old patient with schizophrenia developed Sjögren's syndrome. She also presented with the lupus anticoagulant attributed to long-term medication with chlorpromazine. Serial plasmapheresis treatments were performed to decrease the anti-coagulant activity. As a result, the activated partial thromboplastin time was temporarily improved, but the lupus anti-coagulant activity did not change. Because of her unstable emotional state, she continued to require chlorpromazine, but took a low dose of aspirin (87 mg/day) and never manifested any signs of thrombotic events. In view of the potential anti-thrombotic effects of chlorpromazine, it may not be necessary to use plasmapheresis in an attempt to reduce anti-coagulant activity among patients with chlorpromazine-induced lupus anti-coagulant.

Background Primary Sjogren syndrome (pSS) shares many clinical, inflammatory, and immunological features with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Both SLE and RA are characterized by a high risk of cardiac involvement. However, there are limited data on the risk of overt cardiac involvement in pSS. Objectives We sought to use a cardiac magnetic resonance imaging (CMR) approach to assess cardiac involvement and determine its association with disease characteristics in pSS patients without cardiac symptoms. Methods Consecutive pSS patients, according to ACR classification criteria (2012), without a history or clinical findings of hypertension, cardiovascular disease, diabetes, or dyslipidemia underwent contrast CMR. Late gadolinium enhancement (LGE) was used for the assessment of myocardial fibrosis. Using a black-blood T2-weighted image (T2-WI), myocardial inflammation could be assessed. Sjogren syndrome disease activity index (ESSDAI) was determined. Eighty percent patients had documentation of a minor salivary gland biopsy. Salivary gland biopsy data were classified by focus score (FS). We investigated the patients in terms of prevalence of CMR abnormalities and explored possible associations between CMR abnormalities and pSS disease characteristics. Results Thirty-seven female pSS patients were enrolled (mean age: 55.5 ± 7.0 years). On an average, cardiovascular risk was low for the group, with patients demonstrating no ECG abnormalities, and the patients had generally low traditional cardiovascular risk factors, with a mean Framingham 10-year hard cardiovascular risk score of 4 ± 2%. The mean ESSDAI was 3.3 ± 2.1. Thirteen patients (35%) demonstrated myocardial abnormalities. Myocardial edema was seen in 5 patients (13%) on T2-WI. LGE was found in 11 patients (29%), 3 of whom demonstrated edema on T2-WI. The main finding observed in 7 among 11 LGE-positive patients (63%) was a linear LGE pattern without coronary distribution. A patchy nodular LGE pattern was observed in 4 among 11 patients (37%). The patients with CMR abnormalities showed no significant difference of ESSDAI, compared with those with no CMR abnormalities. Antibodies to La/SSB antigens were significantly higher in LGE-positive than LGE-negative patients (p=0.003). Raynaud phenomenon was significantly associated with LGE-positive and T2-WI-positive patients (p=0.001 and p=0.04, respectively). Other pSS characteristics such as disease duration, commodities, and cardiovascular risk factors were not significantly associated with myocardial abnormalities. The greatest relative difference between LGE-positive and -negative patients was observed in FS >3, with an adjusted odds ratio of 3.0. After adjusting for confounding by age, pSS duration, and anti-SSB antigen, the association of LGE with Reynaud phenomenon remained significant (p=0.02). Conclusions Subclinical myocardial involvement, as detected by CMR, was frequent in pSS patients without cardiac symptoms. Our results suggest that Raynaud phenomenon has a role in promoting cardiac involvements in patients with pSS. Disclosure of Interest None declared

An alcohol abuser with hepatitis C developed multibacterial sepsis. His mean 100% alcohol intake reached 400 ml/day. In January 2001, he suddenly experienced fever (39°C) with no other symptoms. One week later, he was admitted to our hospital and was subsequently diagnosed with sepsis associated with four species of bacteria (Streptococcus constellatus, Fusobacterium mortiferum, Bacteroides thetaiotaomicron, and non-spore-forming anaerobic gram-positive bacillus). A drip infusion of imipenem/cilastatin was administrated, resulting in a successful therapeutic outcome. No underlying disorder was found except for gastric ulcers and hepatic cirrhosis. Damagedgastric mucosa was assumed to be the possible cause and route for the bacterial invasion.(Internal Medicine 42: 208-210, 200

To investigate the clinical characteristics and risk factors of Pneumocystis jirovecii pneumonia (PCP) in rheumatoid arthritis (RA) patients treated with adalimumab.We conducted a multicenter, retrospective, case-control study to compare RA patients treated with adalimumab with and without PCP. Data from 17 RA patients who were diagnosed with PCP and from 89 RA patients who did not develop PCP during adalimumab treatment were collected.For the PCP patients, the median age was 68 years old, with a median RA disease duration of eight years. The median length of time from the first adalimumab injection to the development of PCP was 12 weeks. At the onset of PCP, the median dosages of prednisolone and methotrexate were 5.0 mg/day and 8.0 mg/week, respectively. The patients with PCP were significantly older (p0.05) and had more structural changes (p0.05) than the patients without PCP. Computed tomography of the chest revealed ground-glass opacity without interlobular septal boundaries in the majority of the patients with PCP. Three PCP patients died.PCP may occur early in the course of adalimumab therapy in patients with RA. Careful monitoring, early diagnosis, and proper management are mandatory to secure a good prognosis for these patients.

Despite many suicidal cases in patients with systemic lupus erythematosus (SLE), literature on this subject is lacking. To elucidate and prevent this phenomenon, we re-evaluated the clinical records of seven suicidal patients with SLE. Six patients had photosensitivity and insomnia. At the time of the suicide attempt, hypocomplementemia was observed in five of six patients. Diffuse slowing on electroencephalograms were observed in four of five patients. One patient successfully committed suicide while on no therapy while five patients made their attempts under the tapering courses of steroids. Five patients manifested psychoses whereas two patients displayed no psychotic findings. All patients attempted suicide shortly after admission (mean time 20 days). The subsequent courses of the survivors who received more medication were favorable. Therefore, it appears that disease activity was not fully controlled in these patients. Furthermore, signs of an imminent suicide attempt were missed in some cases. Psychosis, insomnia, history of photosensitivity, an incompletely controlled disease state, receiving tapering steroid dose, diffuse slowings on electroencephalograms and the presence of hypocomplementemia appeared to be risks for attempting suicide in SLE. We would recommend that such patients be under psychiatric care for at least 2 months to prevent suicide. When the patient is still psychotic or unstable, further medical care will be required.

Two women with rheumatoid arthritis who had experienced miscarriages became pregnant while they were under etanercept treatment. One stopped etanercept after 3 weeks with increased doses of prednisolone, and the other restarted etanercept at a half doses 3 months later. They delivered a healthy baby at full term, and no problems in both expecting mothers and babies were observed. The use of etanercept in patients with rheumatoid arthritis seemed safe for pregnant mothers and their fetuses.

1.1 T helper cell subset Helicobacter pylori (H. pylori) and smoking are well known risk factors for gastric ulcer, and both are classified as definite carcinogens. Interestingly, the two also reportedly share common immune response features. With recent advances in immunology, various functions of T lymphocytes (T cells) have been discovered. T cells are divided into suppressor and helper on the basis of immunological functionings, and T helper cells are now known to consist of two distinct groups, as demonstrated using mouse models in the 1980s [Reiner, 2008; Mosman & Coffman, 1989]. Both groups are derived from naive T cells: interleukin-12 (IL-12) causes naive T helper cells to differentiate into type 1 (Th1) cells, while augmentation of IL-4 around naive T cells leads to Th2 differentiation. Th1 cells produce IL-2 and interferonγ (IFN-γ) to maintain cell mediated immunity against intracellular organisms such as viruses and mycobacteria, and Th2 cells produce IL-4 and IL-13 promoting the differentiation of B cells to plasma cells and the induction of class-switching resulting in IgE production. Differentiated plasma cells produce immunoglobulins which participate in mucosal defense against extracellular organisms including H. pylori. Groundbreaking research inspired subsequent studies which finally led to the discovery of Th17 cells [Steinman, 2007] and T regulatory cells (Treg) [Sakaguchi et al., 1995, 2008]. As a consequence of this pioneering research, T helper cells, at present, are sub-grouped into 4 types according to the differences in their cytokine productions (Table 1).

To evaluate the influence of Helicobacter pylori and sex difference on peripheral platelet counts, dyspeptic patients without immunohaematologic disorders were evaluated. H. pylori infection was verified with the rapid urease test and serum anti-H. pylori IgG antibody. Platelet counts were analysed with a reference to H. pylori infection and sex difference. Among H. pylori-eradicated patients, changes in platelet counts were separately evaluated. Totally, 655 patients were enrolled: 340 patients were infected with H. pylori and 178 patients received eradication therapy, with a success rate of 88.2% (157/178). Females with H. pylori infection definitely manifested elevated platelet counts (infected vs. uninfected 244 ± 57 vs. 219 ± 54 × 10(9)/l; p0.0001). H. pylori eradication reduced peripheral platelets by 8 weeks, 5-6 months, 1, 2 and ≥3 years after eradication in females from 248 ± 54 to 237 ± 49, 237 ± 54, 229 ± 48, 238 ± 61 and 232 ± 50 × 10(9)/l (p = 0.0003, 0.0182, 0.0041, 0.0398 and 0.0289), respectively. In males, the reduction was verified by 8 weeks, 1 year and ≥3 years from 226 ± 52 to 217 ± 47, 214 ± 44 and 200 ± 49 × 10(9)/l (p = 0.0464, 0.0164 and 0.0016), respectively. In conclusion, H. pylori infection upregulates platelet counts mainly in females, and eradication reduced peripheral platelets in both sexes. Females appeared more susceptible to H. pylori infection than males with regard to upregulation of platelet counts.

The incidence of systemic fungal infections has risen, as shown by increases in the numbers of immunosuppressed or immunocompromised patients. The consequences of these fungal infections are occasionally serious. However, the efficacy of antifungal prophylaxis in patients receiving corticosteroid treatment has not been well investigated, even though they are susceptible to severe fungal infections. Therefore, we retrospectively evaluated the prophylactic efficacy of an antifungal agent—oral itraconazole solution (ITCZ-OS)—for immunosuppressed patients receiving corticosteroids in a single institution. Of 39 patients, 18 received prophylaxis with ITCZ-OS at a dose of 200 mg/day, and 21 did not. As a result, no fungal infections developed in the prophylactic group, but 7 of the 21 patients (33%) in the non-prophylactic group suffered from fungal infections consisting of 3 non-invasive candidiases, 2 invasive candidiases, and 2 invasive pulmonary aspergilloses. Among the non-prophylactic group, aging and hypoalbuminemia were statistically significantly associated with incidence of invasive fungal infections. Of the four patients with invasive fungal infections, three had concomitant chronic illness such as diabetes. Toxicity among the prophylactic group was not statistically significantly different from that of the non-prophylactic group. In addition, none needed discontinuation of the drug. These results indicate the potential antifungal prophylactic effect of ITCZ-OS for a subset of patients treated with moderate or high doses of corticosteroids.

Helicobacter pylori eradication is becoming a first-line therapy against idiopathic thrombocytopenic purpura (ITP) and its long term efficacy has already been reported. In contrast, eradication therapy reduced peripheral platelets in non-ITP patients 8 weeks later. To confirm the long term efficacy of Helicobacter eradication on platelet counts in non-ITP patients, we evaluated changes in peripheral platelet counts in endoscopically diagnosed patients with Helicobacter infection. Endoscopically diagnosed patients with Helicobacter infection received eradication therapy using amoxicillin (1500 mg/day), clarithromycin (400 mg/day) and lansoprazole (60 mg/day). The changes in platelet counts after Helicobacter eradication were serially evaluated for as long as 3 years or more. In total, 294 patients were enrolled: 243 patients successfully received eradication therapy and 51 were unsuccessfully treated. As a whole, peripheral platelet counts significantly decreased after Helicobacter eradication, being reduced by more than 1.0 × 10⁹/l by 5-6 months, 1 year, 2 years and 3 years or more (from 24.2+/-5.6 to 23.1+/-5.0, 23.0+/-5.0, 22.1+/-4.5, 22.4+/-5.6, and 21.6+/-5.3 × 10⁹/l: p =0.0001,0.0001, 0.0001, 0.0052, and0.0001, respectively). Helicobacter pylori eradication finally reduced peripheral platelet counts around 2.0 × 10⁹/l in non-ITP patients. There was a definite difference in platelet regulation by Helicobacter pylori between ITP and non-ITP patients. These bivalent effects, upregulation and downregulation, on the peripheral platelet induced by Helicibacter pylori infection appeared to originate from quite different mechanisms.

Precise mechanism of developing neuropathic arthropathy known as Charcot's joint is not fully understood.A 55-year-old Japanese woman with neurofibromatosis-1 complained of right gonalgia in December 2001. Physical examination revealed a huge tumor in the right lower leg without signs of inflammation. Laboratory findings were unremarkable. Radiographic examination disclosed the presence of osteoarthropathy in the right knee joint. In contrast, radiologic findings of the right foot and ankle were compatible with neuropathic arthropathy. Further investigations could not reveal abnormal findings in the nervous system. To improve patient's quality of life, partial resection of the tumor was performed. The resected tissues were compatible with neurofibromatosis without malignant transformation. The patient newly noticed pains in the right ankle and tarsal joints one year after the operation. Restricted mobility and insufficient blood supply in the right knee arising from the huge tumor might accelerate development of osteoarthropathy through malnutrition of the chondrocytes. Because the patient did not experience the arthralgia before the operation, the tumor might damage the peripheral nerves unabling to receive afferent signals from such joints resulting in neuropathic arthropathy.The damaged peripheral nerves might be contributory to developing or accelerating neuropathic arthropathy.

Patients with SLE show in a variety of neuropsychiatric symptoms, although we could not use standardized methods for evaluating and making diagnosis of the syndromes. ACR felt to develop objective and valuable tools for the diagnosis and classification of neuropsychiatric lupus, therefore, they proposed a new tentative set of nomenclatures describing neuropsychiatric lupus syndromes in accordance with 4th edition of Diagnostic and Statistical Manual of Mental Disorders provided by American Psychiatric Association. For this purpose, The Ad Hoc Committee collected and evaluated 108 case presentations of neuropsychiatric lupus from USA, Canada, and UK. Re-evaluation of the tentative nomenclatures selected 19 neuropsychiatric syndrome to facilitate and enhance clinical research. They grouped into peripheral and central nervous system lupus, and central nervous system lupus was divided into neurologic syndromes and diffuse psychiatric/ neuropsychological syndromes. Instead of organic brain syndrome, a term of acute confusional state was introduced.

Known causes of eosinophilia include parasitic infections, allergic diseases, autoimmune diseases, neoplasms, and drug allergies.[1] Corticosteroid derivatives such as prednisone, prednisolone, methylprednisolone, dexamethasone, etc. are often used as first-line drugs to ameliorate the condition.[2] The ESR is used as an evaluation of lupus activity in rheumatic diseases. This report documents a patient with systemic lupus erythematosus (SLE) in whom accelerated ESR and eosinophilia were resolved by substituting prednisolone for methylprednisolone.

We evaluated the vulnerability of central nervous system (CNS) in patients with systemic lupus erythematosus (SLE) using exploratory eye movement analysis and random number generation (RNG), and compared the tests in evaluating CNS vulnerability. Nineteen patients received the tests more than a month after SLE onset in nonpsychotic status. Exploratory eye movements were analyzed using an eye-mark recorder that detects corneal reflection of infrared light, and numbers of eye fixations were counted to calculate responsive search score (RSS). Using digits 0 through 9, 100 numbers were vocally generated at a random fashion. “Seriality score” was calculated from the recorded 100 numbers. RSS of SLE patients was similar to that of normal individuals, irrespective of neuropsychiatric lupus history. Seriality score of patients having a history of neuropsychiatric lupus was higher than that of never having it (p

Proton-pump inhibitors have been reported to influence the human immune system, we therefore evaluated the effect of lansoprazole, a proton-pump inhibitor, on humoral immunity. Patients with gastric ulcer received lansoprazole 30 mg/day for 8 weeks, and serum immunoglobulins were evaluated before and upon completion of the treatment. There were 79 patients with gastric ulcer; 51 were H. pylori-infected and 28 were H. pylori-uninfected. Eighteen patients positive for H. pylori were receiving at least one non-steroidal anti-inflammatory drug, and 12 patients negative for H. pylori received one non-steroidal anti-inflammatory drug. H. pylori-infected patients showed significant increases in serum immunoglobulins G and M 8 weeks after the start of lansoprazole treatment ( P

Background Rheumatoid arthritis (RA) is a multi-organ inflammatory disorder associated with high cardiovascular morbidity and mortality. Importantly, cardiac involvements are typically clinically silent, only manifesting as myocardial abnormalities after an extended subclinical phase. Myocardial abnormalities may arise from a number of distinct processes, including myocardial inflammation (myocarditis), and/or myocardial fibrosis, any of which may be active in RA. Objectives We sought to assess cardiac involvement using a cardiac magnetic resonance imaging (CMR) approach and to determine its association with disease characteristics in RA patients without cardiac symptoms. Methods Consecutive RA patients and controls without cardiac symptoms were enrolled. RA patients and control subjects with no history and/or clinical findings of systemic and pulmonary hypertension, coronary artery disease, valvular heart disease, atrial fibrillation, diabetes mellitus, and dyslipidemia underwent CMR. RA patients received conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biologic DMARDs (bDMARDs). Late gadolinium enhancement (LGE) was obtained for the assessment of myocardial fibrosis. Using a black-blood T2-weighted image (T2-WI), myocardial inflammation could be assessed. Left ventricular geometry was classified into four categories: concentric remodeling, concentric or eccentric hypertrophy, or normal. We compared the patients and controls in terms of prevalence of CMR abnormalities, and explored possible associations between CMR abnormalities and RA disease characteristics. Results Sixty patients (mean age, 55.2±1.3 years; 85% female) and 20 controls (mean age 52.6±2.3 years; 86% female) were enrolled. Thirty RA patients received csDMARDs [25, methotrexate (MTX) (8.7±2.1mg); 5, other drugs)] and 30 RA patients received bDMARDs [(15, infliximab 3 mg/kg; 15, tocilizumab 8 mg/kg plus methotrexate (8.6±1.4 mg) mg/kg]. The control group showed no myocardial abnormalities. Twenty RA patients (33%) demonstrated myocardial abnormalities. T2-WI was seen in seven RA patients (11%). LGE was found in 19 RA patients (32%), six of whom also demonstrated T2-WI. Simplified Disease Activity Index (SDAI) scores were significantly higher in LGE-positive compared to LGE-negative (p=0.011). LGE was significantly associated with high NT-proBNP and eccentric hypertrophy (p=0.005, p=0.018, respectively). The use of bDMARDs was significantly associated with LGE-negative findings (p=0.0017). Other RA characteristics such as disease duration, autoantibody status, and cardiovascular risk factors were not significantly associated with myocardial abnormalities. After adjusting for confounding by age, RA duration, rheumatoid factor, and bDMARDs, the association of LGE with SDAI remained significant (p=0.023), in which the SDAI scores were, on average, 10.9 units higher in LGE-positive than in LGE-negative. Conclusions Subclinical myocardial inflammation and fibrosis are common in active RA patients without cardiac manifestation. Abnormal CMR findings were associated with higher RA disease activity, suggesting a role for inflammation in the pathogenesis of myocardial involvement in RA. Disclosure of Interest None declared

Background Polymyositis (PM) and dermatomyositis (DM) are inflammatory diseases; up to 70% affected patients (pts) show cardiac involvement, which may be fatal. However, the diagnosis, based on electrocardiogram, laboratory, and imaging investigations, is difficult because of nonspecific clinical presentation and the lack of standardized criteria. Cardiac magnetic resonance (CMR) is currently the best technique for diagnosing cardiac fibrosis and inflammation. Objectives To evaluate cardiac involvement in PM/DM pts without cardiac manifestations by using CMR. Methods Sixteen consecutive female PM/DM pts (age, 51.9±11.0 years; 7 DM, 9 PM) and 16 gender/age-matched healthy controls without cardiac symptoms (age, 52.6±5.3 years) underwent CMR. Pts and control subjects had no history and/or clinical findings of systemic/pulmonary hypertension, coronary artery disease, valvular heart disease, atrial fibrillation, diabetes mellitus, and dyslipidemia. Late gadolinium enhancement (LGE) was considered to indicate myocardial fibrosis, and black-blood T2WI was used for assessing myocardial inflammation. Left ventricular geometry was classified into concentric remodeling, concentric hypertrophy, eccentric hypertrophy, or normal. We compared the pts and controls regarding prevalence of CMR abnormalities, and explored the possible associations between CMR abnormalities and PM/DM disease characteristics. Group comparisons were made using the Wilcoxon chi-square test, Tukey–Kramer test, and Fisher exact test. Results PM/DM pts had normal inflammatory indices (erythrocyte sedimentation rate, C-reactive protein level), muscle enzyme assays, and improved muscle strength tests. LGE and T2WI were similar between PM and DM. LGE was seen in 8 pts (50%). Three of these 8 pts also had positive T2WI. Enhancement patterns observed were linear in middle layer, linear in subepicardial layer, nodular in middle layer, and patchy in middle layer (3, 1, 3, 1 pts, respectively). T2WI was observed in the same areas with LGE. No difference LGE positivity and T2WI findings was observed between PM (56% and 11%, respectively) and DM (43% and 29%, respectively) pts. Ejection fraction (EF) was similar between pts and controls (p=0.23). Of note, 7 pts showed concentric remodeling, and 75% of these pats showed LGE. PM/DM pts had higher NT-proBNP levels than controls. LGE was significantly correlated with concentric remodeling in PM/DM pts (p=0.04). Anti-Jo1 Ab positivity was correlated with LGE (p=0.03). However, T2WI was not associated with disease characteristics. Adjustment for disease duration, anti-Jo1 Ab, and LGE did not modify the association with concentric remodeling. Conclusions PM/DM pts without cardiac symptoms have a high prevalence of cardiac abnormalities. PM/DM pts with LGE are associated with abnormal morphology even with normal EF. Moreover, anti-Jo1 Ab positivity may be associated with LGE. Further studies are needed to determine whether CMR abnormalities affect prognosis or treatment strategy. Disclosure of Interest None declared

Background Systemic sclerosis (SSc) has an increased prevalence of cardiac involvement despite often being clinically silent. When clinically evident, cardiac involvement decreased the 70% 5-year mortality of SSc. Cardiac magnetic resonance imaging (CMR) is useful in SSc beause it focuses on late gadolinium enhancement (LGE) abnormalities and ventricular morphology and function. Objectives We aimed to assess the prevalence of subclinical myocardial involvement by left ventricular (LV) function and structure on CMR. We evaluated the relation between myocardial abnormalities and LV geometry. Methods This study compared consecutive female SSc patients without cardiac symptoms and healthy female controls with no history or clinical findings of systemic and pulmonary hypertension by echocardiography, coronary artery disease, valvular heart disease, atrial fibrillation, diabetes mellitus, and dyslipidemia. All underwent non-contrast or contrast CMR on a 3.0-T scanner. LV function was measured using ejection fraction (EF), end-systolic volume (ESV), end-diastolic volume (EDV), stroke volume (SV), and cardiac output (CO). LV hypertrophy was measured by absolute LV mass (LVM) and LVM index (LVMI) determined by LVM/body surface area. LGE was obtained to assess myocardial fibrosis. Myocardial inflammation was assessed by black- blood T2WI. Serum BNP concentrations were measured simultaneously. Results There were 44 SSc patients with a mean age of 57.1±8.7 years; 20 had diffuse type and 24 had limited type. There were 20 healthy controls with a mean age of 56.9±3.1 years. There were no significant differences in terms of age, gender, and cardiovascular risk factors. Compared with the control, SSc patients had a significantly higher EDV with tendency towards a high LVMI. There was no difference in EF. LGE (+) was detected in 25 of 44 (57%) SSc patients; LGE was in a linear pattern without coronary distribution in 13 (52%) SSc patients. T2WI was observed in 11 of 44 (25%) SSc patients. There were no differences in LGE and T2WI between the diffuse and limited type. The BNP level of the SSc group was significantly higher than that of the control group (P=0.04). The mean BNP level of SSc patients with LGE was significantly higher than that of SSc patients without LGE (P Conclusions SSc patients without cardiac symptoms have a high prevalence of cardiac abnormalities. Our data suggest that SSc-specific autoimmunity against Scl-70 mediates these changes. SSc patients with LGE had cardiac abnormalities associated with LVMI and serum BNP, leading to cardiac remodeling and possible development of cardiac involvement, even with a normal EF. Disclosure of Interest None declared

A 23-year-old Japanese woman with a fever and generalized skin eruptions was referred to our hospital in July 1999. At admission, her temperature was 38.9 degrees C, and she had fluctuating symptoms including erythema of the extremities, conjunctival hyperemia, strawberry tongue, and generalized skin eruptions, but lymphadenopathy was not verified. An initially elevated urine leukocyte count (more than 100 per high power field) later returned to normal range without antibiotic therapy. Adult Kawasaki disease was diagnosed on the basis of the above symptomology. Echocardiograph showed transient effusion in the pericardium. Using the Harada scoring system for treatment of Kawasaki disease, we gave the patient aspirin and did not administer intravenous immunoglobulin. The clinical course was uneventful, and on the day of discharge (day 22 after onset), the laboratory test results were nearly normal. Laboratory test results were negative for both Epstein-Barr virus and group A Streptococcus.