Efficacy of oral cytarabine ocfosfate and etoposide in the treatment of elderly patients with higher-risk myelodysplastic syndromes compared to that in elderly acute myeloid leukemia patients.

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.

Successful childbearing in two women with rheumatoid arthritis and a history of miscarriage after etanercept treatment.

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.

Clinical characteristics and risk factors for Pneumocystis jirovecii pneumonia in patients with rheumatoid arthritis receiving adalimumab: a retrospective review and case-control study of 17 patients.

OBJECTIVES: To investigate the clinical characteristics and risk factors of Pneumocystis jirovecii pneumonia (PCP) in rheumatoid arthritis (RA) patients treated with adalimumab. METHODS: 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. RESULTS: 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 (p < 0.05) and had more structural changes (p < 0.05) 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. CONCLUSIONS: 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.

Helicobacter pylori upregulates peripheral platelet counts mainly in female patients.

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; 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 × 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.

Efficacy and safety of antifungal prophylaxis with oral itraconazole solution among patients receiving corticosteroids: who should be given prophylaxis?

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.

Salivary Gland Focus Score Is Associated With Myocardial Fibrosis in Primary Sjögren Syndrome Assessed by a Cardiac Magnetic Resonance Approach.

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.

Long term changes in platelet counts after H. pylori eradication in non-ITP patients.

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, and <0.0001, 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.

Unilateral developments of osteoarthritis and Charcot's joint in a patient with neurofibromatosis.

BACKGROUND: Precise mechanism of developing neuropathic arthropathy known as Charcot's joint is not fully understood. CASE REPORT: 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. CONCLUSIONS: The damaged peripheral nerves might be contributory to developing or accelerating neuropathic arthropathy.

[Neuropsychiatric lupus (CNS lupus and PNS lupus)].

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.

Eye movement and random number in NP lupus evaluation.

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 < 0.05). No relations were confirmed between RSS and seriality score. The current study suggested heterogeneous nature of SLE in CNS vulnerability when evaluating with seriality score, but not with RSS. There seemed to be a difference between exploratory eye movement analysis and RNG in evaluating CNS vulnerability. Each test seemed to evaluate different aspects of brain function.

Efficacy and safety of minodronic acid hydrate in patients with steroid-induced osteoporosis.

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.

A case of systemic lupus erythematosus complicated by alveolar hemorrhage and cytomegalovirus colitis.

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.

Low-dose epoprostenol improved pulmonary hypertension in a patient with systemic lupus erythematosus.

A 43-year-old Japanese woman was referred to our hospital in 1997 because of Raynaud's phenomenon. Systemic lupus erythematosus was diagnosed on the basis of the presence of antinuclear antibody (1:1,280), anti-DNA antibody (1:640), anti-Sm antibody, antiphospholipid antibody, lymphopenia, and proteinuria. She developed pulmonary fibrosis in 1999 and pulmonary hypertension in 2001. In October 2002, a 24-hr continuous infusion of epoprostenol was started. Dyspnea, Raynaud's phenomenon, and pulmonary hypertension improved with low-dose epoprostenol (3.0 to 4.0 ng kg(-1) min(-1)). The patient could not tolerate larger doses of epoprostenol so 4.0 ng kg(-1) min(-1) was selected as the maintenance dose. The clinical course was uneventful at this dosage. It appears that pulmonary hypertension can be controlled with low-dose epoprostenol such as 3.0 to 4.0 ng kg(-1) min(-1) in some rheumatic patients.

Correlation between quantitative-EEG alterations and age in patients with interferon-alpha-treated hepatitis C.

The authors recently observed alterations in the quantitative EEG findings in patients with chronic hepatitis C who were treated with interferon-alpha (IFN-alpha). However, the factors that influenced such EEG alterations remain unclear. The authors evaluated the correlation between QEEG alterations that occurred during IFN-alpha treatment and the age of 98 patients with chronic hepatitis C. These patients underwent blind, prospective, and serial quantitative EEG examinations. IFN-alpha was administered intramuscularly at 9 x 10 IU daily for the first 4 weeks and then three times per week for the next 20 weeks. Serial EEGs were obtained before, at 2 and 4 weeks, and at 2 to 3 days after the treatment. The absolute powers of each frequency band at different stages of the treatment were determined by QEEG. The ages of the patients were classified into five groups: 20 to 29, 30 to 39, 40 to 49, 50 to 59, and > or =60 years. The relationship between the alterations in power values and age was statistically evaluated. As the age of the patients increased, the alterations in power values for the slow waves, alpha 2, and fast waves during IFN-alpha treatment became more remarkable, and significant (repeated-measure analysis of variance; P < 0.0001). The alterations of EEG occurring during IFN-alpha treatment were marked in older patients.

Exacerbation of rheumatoid arthritis following Helicobacter pylori eradication: disruption of established oral tolerance against heat shock protein?

A 62-year-old Japanese woman with RA received an eradication therapy against Helicobacter pylori in November 1999. Eight weeks later, successful eradication was confirmed by negative results for rapid urease test, pathologic findings, and a fall in anti-H. pylori IgG antibody titer. During the course, parameters for RA activity were exacerbated: C-reactive protein 1.1-4.2 mg/dL, rheumatoid arthritis precipitation antigen 2560-5120 dils., erythrocyte sedimentation rate 52-123 mm/h, and complements CH50 50 to over 60 U/mL. Lansbury index increased from 70% to 105%. Two more weeks later, the patient noticed right shoulder pain. She also complained of bilateral gonalgia two months later, and physical examination revealed increased fluid in the knee joints. Prednisolone was required to control the disease activity. The results of this case suggested that RA patients might experience a deleterious effect on the disease activity following H. pylori eradication possibly through disruption of the established oral tolerance against stress protein such as mycobacterial heat shock protein 65.

Treatment of chronic fatigue syndrome with antibiotics: pilot study assessing the involvement of Coxiella burnetii infection.

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<0.001). PS scores were also improved. CONCLUSION: These results suggest the possibility of direct involvement of C. burnetii in the pathological state of CFS to be low, despite the C. burnetii infection rate being high in CFS patients. This is a pilot study and further larger investigations are necessary to confirm our preliminary results.

Adult Kawasaki disease unrelated to epstein-barr virus and group A Streptococcus.

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.