Objective The aim of this study was to elucidate the efficacy of interferon (IFN)-beta monotherapy for elderly patients of ≥70 years with type C hepatitis (HCV) of genotype 2. Methods The present study was a retrospective cohort study. Inclusion criteria were type C hepatitis patients with HCV genotype 2a or 2b, ≥70 years, and IFN-beta monotherapy of within 24weeks. Thirty-one consecutive patients who satisfied the above criteria were enrolled in the present study. Independent factors that might have influenced the sustained virological response (SVR) were studied using logistic regression analysis. Results Background of clinical profiles was as follows: median (range) age =71 (70-76) years, male/female =13/18, and median (range) HCV-RNA=260 (<5-3,800) KIU/mL. Out of 31, 16 patients (51.6%) had SVR by the intention-to-treat analysis. The SVR was significantly associated with the serum HCV RNA level. Logistic analysis showed that SVR occurred when HCV RNA level was <100 KIU/mL (p=0.020). Based on the difference of the serum HCV RNA level, the SVR rate was 81.8% (9/11) in patients with a serum HCV RNA level of <100 KIU/mL and 35.0% (7/20) in patients with a serum HCV RNA level of ≥100 KIU/mL. Conclusion IFN-beta monotherapy of ≤24 week is a possible therapy selection for elderly patients of ≥70 years with type C hepatitis of genotype 2.
Background Gamma glutamyltransferase (GGT) or alanine aminotransferase (ALT) is reported to be an independent risk factor of diabetes and cardiovascular disease and proposed as a component of metabolic syndrome (MS). However, there are few studies examining the direct association between MS and GGT or ALT in Japanese men and women. Methods Direct associations between GGT or ALT and MS defined by revised NCEP criteria for Japanese and between GGT or ALT and Japanese MS (JMS) defined by the Examination Committee for the Criteria of Metabolic Syndrome were examined using medical check-up data from 1,880 men and 1,079 women. Results The prevalence of MS and JMS was significantly higher in subjects with the highest quartile of GGT or ALT than the subjects with the lowest quartile of GGT or ALT (p<0.0001 in men and p<0.0001 for MS and p<0.001 for JMS in women). The optimal cutoff points of GGT and ALT for diagnosing MS or JMS were 42 U/L or 41 U/L, respectively for GGT and both 25 U/L for ALT in men and 21 U/L or 23 U/L, respectively for GGT and 20 U/L or 25 U/L, respectively for ALT in women. Conclusion The prevalence of MS and JMS increases with the increase in blood levels of GGT or ALT even through the normal range of GGT or ALT in Japanese men and women.
Purpose This study was carried out to clarify the relationship of IgG phosphatidylserine-dependent anti-prothrombin antibody (aPS/PT), IgG beta 2 glycoprotein I-dependent anticardiolipin antibody (beta 2-GPI aCL), and lupus anticoagulant (LA) to cerebral infarction, using data from 93 patients who visited our hospitals. Materials and Methods We computed the positive rates for each of IgG aPS/PT, beta 2-GPI aCL, and LA in the 93 patients with cerebral infarction, and carried out logistic regression analysis with IgG aPS/PT as the outcome variable and with beta 2-GPI aCL, LA, and each risk factor as predictor variables in order to assess the relationship of IgG aPS/PT with each factor. Results IgG aPS/PT was more highly correlated with LA than beta 2-GPI aCL in IgG aPS/PT-positive patients with cerebral infarction. IgG aPS/PT itself appears to have high specificity as a marker for antiphospholipid syndrome (APS), because there were patients who were IgG aPS/PT-positive but both beta 2-GPI aCL- and LA-negative. Conclusion In IgG aPS/PT-positive patients with cerebral infarction, IgG aPS/PT is more highly correlated with LA than beta 2-GPI aCL. It is also strongly associated with APS. Measurement of IgG aPS/PT in patients with cerebral infarction could be of diagnostic value.
Objectives It is known that the risk of cerebral stroke recurrence in post-stroke patients is comparatively higher than in normal subjects, and it is suggested that autonomic nervous system dysfunctions elevate this risk. We investigated the anti-hypertensive effects of cilnidipine, a Ca antagonist which suppresses sympathetic nerve activation, in hypertensives with chronic-stage cerebrovascular disease in a comparison with amlodipine. Methods Amlodipine 5-7.5 mg/day, or cilnidipine 5-10 mg/day was administered to 78 hypertensive subjects (greater than 140 mmHg systolic, or 90 mmHg diastolic) undergoing outpatient treatment. Amlodipine or cilnidipine was also administered similarly, to 30 subjects having hypertension associated with a cerebral infarct which occurred more than one month earlier due to cerebral thrombosis or embolism. After 3 months administration, the subjects' blood pressures and pulse rates were recorded with an ambulatory blood pressure monitor over 24 hours. Results No difference was recognized in patient age, gender, and systolic and diastolic blood pressure before treatment between the groups. In the cilnidipine groups, no difference in average 24-hour or waking systolic blood pressure values was seen between cerebrovascular disease (CVD) subjects and non-CVD subjects, although in the amlodipine groups, CVD subjects had significantly higher blood pressure values than non-CVD subjects. In the cilnidipine group, the coefficient of variation values of pulse rate were significantly higher in CVD subjects than in non-CVD subjects (p<0.05). Conclusion In patients with recent stroke, a Ca antagonist with no sympathetic nerve suppression had weaker blood pressure-lowering effects. Significantly increased pulse rate variability, shown in the CVD subjects administered cilnidipine, suggests that cilnidipine enhanced the parasympathetic function in hypertensive patients with CVD.
Objective Endothelial dysfunction is present in ankylosing spondylitis (AS). However, the etiology of events is still unclear. The aim of the present study was to investigate whether there are abnormalities in nitric oxide (NO) metabolism and endothelin-1 (ET-1) in AS patients. Methods Subjects without any classical cardiovascular (CV) risk factors were studied. Fasting glucose, serum lipids, high sensitive CRP (hsCRP), ESR, asymmetric dimethylarginine (ADMA) and ET-1 were studied. Patients were also evaluated with the Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Functional Index, and the Bath Ankylosing Spondylitis Disease Activity Index. Results A total of 48 AS patients (38.6±10.6 years; 36M/12F) and 38 controls (36.4±11.1 years; 27M/11F) were studied. Acute phase reactants including hsCRP, and ESR were significantly increased in the patients group (p<0.05). Serum ADMA concentrations were also significantly higher in AS than in controls. Plasma levels of ET-1 did not differ between the groups (p>0.05). Comparison of three groups (conventional and anti-TNF treatment groups and controls) revealed that ADMA was significantly higher in the conventional treated AS than in controls. The levels of ADMA were not different between anti-TNF group and healthy subjects. Plasma ET-1 concentrations were similar between groups (p>0.05). Correlation analysis yielded significant correlations between ADMA, hsCRP, LDL cholesterol, HDL cholesterol and triglycerides (p<0.05). Conclusion The increased ADMA levels obtained in a group of relatively young AS patients who did not have classical CV risk factors suggest that NO metabolism is impaired in AS. On the other hand, anti-TNF treatments may have a beneficial effect on vascular function in AS.
Background The overuse of antibiotics results in the unnecessary spread of resistant strains. A common setting for antibiotic overuse is in the treatment of upper respiratory tract infections (URIs), which are predominantly due to viruses. Objective To investigate the type and frequency of antibiotic prescription for URI without apparent bacterial infection in Japan, based on both visits and facilities. Design Cross-sectional analysis of insurance claims submitted to an employer-sponsored health insurance plan in Japan between January and March, 2005 for diagnoses of URI. Claims having a potentially valid reason for antibiotic prescription (e.g., secondary diagnosis of pneumonia) were excluded. Outcome Measures Antibiotics prescribed for these URI visits. Results From a total of 24,134 claims, 2,577 claims (non-bacterial URI, one visit per claim) were analyzed; antibiotics were prescribed in 60% of these visits. Third-generation cephalosporins were the most commonly-prescribed drug class (46%), followed by macrolides (27%) and quinolones (16%). In general, visits to physician offices were more likely to result in an antibiotic prescription than visits to hospital outpatient clinics. No statistically significant difference was identified among hospital types, including private and public ownership or teaching hospital status. Analysis of the frequency of antibiotic prescription by facility revealed two peaks in distribution, with one group prescribing to about 90% of URI patients and the second appearing to prescribe to about 40% of patients. Conclusion Antibiotics are frequently prescribed to URI patients in Japan. Although overuse results from the difficulty in accurately distinguishing viral from bacterial URIs, some facilities appear to attempt to differentiate the underlying cause of the URI while others do not.
We encountered a 45-year-old man who presented with marked eosinophilia as the first manifestation of sclerosing cholangitis. He was found to have a liver dysfunction during a regular physical check up and thereafter consulted our hospital. The laboratory data on admission indicated an elevation of AST (96 IU/L), ALT (136 IU/L) and ALP (1,025 IU/L). Furthermore, the leukocyte count was 18,190/mm3 and he also showed marked eosinophilia (54.5%, 9,914/mm3). There were no atypical findings in the eosinophils. Other diseases causing eosinophilia, including parasite infection, allergic disorders, hypereosinophilic syndromes, drug-induced eosinophilia, malignancies, etc. were all investigated and ruled out. A liver biopsy revealed marked eosinophilic infiltration in the portal area and interlobular bile duct injury. Magnetic resonance cholangiopancreatography (MRCP) demonstrated a slight dilatation of the left intrahepatic bile ducts, but no clear diagnosis could be made at that time. A follow-up liver biopsy and endoscopic retrograde cholangiopancreatography (ERCP) finally revealed a diagnosis of secondary sclerosing cholangitis due to eosinophilic cholangiopathy. According to previous Japanese reports, eosinophilia of more than 5% was reported in 39 of 142 (27.0%) primary sclerosing cholangitis (PSC) patients. Eosinophilic cholangiopathy could cause a condition mimicking PSC and it might be confused as PSC with eosinophilia. The literature contains only about 40 case reports on eosinophilic cholangiopathy, and therefore, to date little attention has been paid to this condition. We should therefore pay attention to this condition when making a differential diagnosis of either PSC or IgG4-related sclerosing cholangitis.
We describe the case of a 43-year-old primiparous woman who had acute myocardial infarction. She underwent successful primary percutaneous coronary intervention. Elective cesarean section was performed uneventfully at 32 weeks gestation.
Interferon (IFN) therapies, including IFN, peginterferon (PEG-IFN) and ribavirin (RBV) plus PEG-IFN combination, are widely used for patients with chronic hepatitis C. We encountered a patient with chronic hepatitis C in whom previous IFN or PEG-IFN alone had not induced type 1 diabetes (T1D), while the addition of RBV to PEG-IFN did induce T1D. The patient had HLA types conferring highly susceptibility to T1D. Thus, adding RBV to PEG-IFN may render chronic hepatitis C patients, with T1D-susceptible HLA types, more prone to developing T1D than IFN or PEG-IFN alone. To prevent T1D development, we recommend HLA typing prior to initiating RBV plus PEG-IFN administration.
We report a case of diabetic ketoacidosis (DKA) and severe hypertriglyceridemia who developed cardiac arrest due to hypophosphatemia. He was diagnosed with diabetes and hyperlipidemia, indicating metabolic syndrome. Hypophosphatemia was caused by large insulin doses received while treating DKA, which were required because of insulin resistance owing to hypertriglyceridemia. Metabolic syndrome may have accelerated serum phosphate depletion. We suggest frequent monitoring of serum phosphate and phosphate replacement for patients with DKA and severe hypertriglyceridemia. Although such a critical condition has not been reported, it may occur during treatment of patients with poorly controlled type 2 diabetes with DKA.
Glycohemoglobin, also known as hemoglobin (Hb) A1c, is a marker of long-term glycemic control in patients with diabetes. We present two South-Asian diabetic patients whose HbA1c peaks were not measurable using high performance liquid chromatography (HPLC). Further investigations showed that these patients were homozygous for a hemoglobin variant, HbE (β26 Glu→Lys). Because of the increasing numbers of immigrants in Japan, area-specific hemoglobinopathies are now encountered more frequently than before. Thus, if discrepant results are found on an HbA1c assay or if the HbA1c value cannot be measured, such patients should be screened for hemoglobinopathies and alternative measurements for monitoring diabetes should be considered.
Primary lymphoma of the bladder is quite rare; primarily, it is extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT-lymphoma). There is only one case report of primary diffuse large B-cell lymphoma (DLBCL) of the bladder, accompanied by diffuse wall thickening of the bladder. Here, we report a second case of primary DLBCL of the bladder in a 75-year-old woman patient, whose initial presentation was acute renal failure. Three courses of R-CHOP chemotherapy were effective to treat acute renal failure caused by post-renal obstruction and to attain clinical remission.
Coronary aneurysm is rare in SLE and confirmation of etiology is usually made at postmortem examination. We encountered a giant aneurysm with multiple stenotic segments of the coronary arteries in a patient with SLE who had previous history of AAA/TAA. Resection of the aneurysm and coronary artery bypass graft were successfully performed. Histology of the coronary arterial wall showed severe damage of the media with inflammatory cell infiltration, indicating that the aneurysm was caused by arteritis. The aneurysm may have developed during the long course of inactive stage of SLE, emphasizing the need for screening of coronary lesions in the management of SLE.
We herein report a Japanese family lineage, possibly demonstrating Birt-Hogg-Dubé (BHD) syndrome. A 29-year-old nonsmoking woman was admitted to our hospital due to spontaneous pneumothorax. A chest CT showed multiple lung cysts, and breast cancer was simultaneously detected that needed priority surgical treatment. In the family history, the patient's father and half brother also experienced recurrent pneumothorax, and both had similar findings in their chest CT. In a genetic analysis of her half brother, the mutation of the BHD gene was identified. BHD syndrome is a rare autosomal and dominantly inherited disorder, which has three characteristics: multiple lung cysts that may be associated with pneumothorax, skin fibrofolliculomas, and renal neoplasm. For multiple-cystic disease of the lungs with an unknown etiology, or pneumothorax, as seen in a family history, it is necessary to consider the possibility of BHD syndrome.
The RTX respirator is a biphasic external cuirass-style ventilator that supports both inspiration and expiration at various cycle rates and pressures, as well as allowing application of the vibration and cough modes. With this respirator, the duration and pressure can be altered in both the inspiratory and expiratory phases, and it can promote the removal of secretions by switching between the vibration mode (which involves external high-frequency oscillation: EHFO) and the cough mode. We used this respirator to remove secretions in two elderly patients with extensive atelectasis. They were nursed in the lateral decubitus position with the cuirass attached to one side of the chest only. The vibration mode removed secretion to reduce the viscosity of secretions and loosen impacted bronchial secretions. The cough mode interrupts the vibration mode and forces secretions towards the pharynx. The lateral decubitus position was useful for postural drainage. The extensive atelectasis of both patients was improved by this procedure. The RTX respirator may be a useful tool for the management of elderly patients with sputum retention.
A 68-year-old man was admitted to our hospital for indistinct consciousness, progressive dyspnea, night sweats and fever of 2 weeks duration. Hypoxemia, thrombocytopenia, and elevated serum lactate dehydrogenase were found. Computed tomography was negative except for a small bilateral pleural effusion. Chest perfusion scintigraphy showed inhomogeneous perfusion thought unlikely to be pulmonary artery thromboembolism. Intravascular large B-cell lymphoma was suspected, and a pulmonary microvascular cytology specimen was obtained that contained numerous large lymphoma cells. Because the patient's condition was rapidly deteriorating, we started chemotherapy on the basis of the pulmonary microvascular cytology findings, and he improved. Later, atypical lymphocytes similar to those in the pulmonary microvascular cytology specimen were found in a bone marrow specimen. He was diagnosed as having diffuse large B-cell lymphoma. Because lymphoma cells were found in the pulmonary microvasculature, intravascular lymphoma was also diagnosed. Pulmonary microvascular cytology was helpful to detect lymphoma cells in the pulmonary microvasculature.
A 53-year-old man developed possible transfusion-related acute lung injury (TRALI) after red cell component transfusion. The patient developed autoimmune neutropenia with the expression of neutrophil antibodies. Neutrophil aggregation, endothelial damage, and development of a large thrombus containing platelets were observed post mortem in his pulmonary vessels. The patient also had subacute organizing pneumonia. He received blood components treated with universal pre-storage leuko-reduction. Even though leukocytes in the blood components are reduced to a few million by this process, TRALI can be fatal, as was the case for this recipient, who had subacute organizing pneumonia in conjunction with immune-mediated neutropenia.
Contraception is recommended during imatinib therapy based on the teratogenicity data in rats. However, patients may become pregnant and here we describe a successful pregnancy and labor without any congenital anomaly in a patient with chronic myeloid leukemia (CML) under treatment with imatinib. The patient had received imatinib for 53 months before she became pregnant, with a complete cytogenetic response achieved after 6 months of therapy and a major molecular response (MMR) after 28 months. CML was in MMR at discovery of pregnancy and the fetus had been exposed to imatinib for 5 weeks. Treatment was discontinued, but MMR persisted during gestation.
Biphenotypic acute leukemia (BAL) is a rare entity that comprises 0.5-3% of all acute leukemias and probably arises from multipotent progenitor cells. The optimal approach for BAL therapy is unknown. Thus, it is important to elucidate the origin of the neoplastic cells for determination of the appropriate therapy. We report the case of a 41-year-old man with BAL having myeloid and T-lymphoid lineage phenotypes. Strangely, neither CD34 nor TdT expression nor rearrangement of TCR-α/β, δ/γ genes were shown. This pattern is rarely encountered and suggests that the blast cells were possibly considered immature with aspects of differentiation indicating myeloid lineage, rather than T-lymphoid lineage.
CD20-positive T-cell malignancy is a rare disease. We report a case of CD20-positive T-cell large granular lymphocyte leukemia (T-LGLL). The leukemic cells were positive for CD20 and T cell markers, such as CD3, CD4, CD5, CD8 and CD57. A monoclonal rearrangement of the T-cell receptor (TCR) β chain gene was detected. Twenty-three cases of well-documented CD20-positive T-cell malignancies were reviewed. Most cases were mature T-cell malignancies, especially exhibiting a cytotoxic T-cell phenotype, despite a diversity of the pathological diagnoses. Additional cases must be evaluated to clarify the implications of CD20 expression on T-cell malignancies and to elucidate whether such cases constitute a distinct biologic and clinical disease entity. The accumulation of cases will help to facilitate provision of a proper treatment for CD20-positive T-cell malignancies in the future.
Idiopathic thrombocytopenic purpura (ITP) is a hemorrhagic disease that often occurs in the elderly. It generally presents as a chronic disease with insidious onset, and is frequently resistant to various therapies. Compared to patients less than 40 years old, those older than 60 years tend to show a higher rate of ITP-related mortality. The present report describes a 73-year-old patient with acute ITP who experienced diffuse alveolar hemorrhage that responded well to high-dose intravenous immunoglobulin therapy combined with corticosteroid pulse therapy.
We describe a case of encephalomyelitis mimicking multiple sclerosis associated with chronic graft-versus-host disease (GVHD) occurring after allogeneic bone marrow transplanation (BMT) for myelodysplastic syndrome. Immunosuppressive therapy, consisting of a therapeutic dose of cyclosporine A and a maintenance dose of methylprednisolone, was effective in treating symptoms. Although central nervous system GVHD is very rare and remains controversial, presentation of neurological symptoms after allogeneic BMT warrants consideration of GVHD in the differential diagnosis.
A 74-year-old woman presented with abducens nerve palsy, postganglionic Horner syndrome and sensory disturbance in the territory of the ophthalmic nerve on the left side. Cranial magnetic resonance imaging demonstrated a gadolinium-enhanced lesion within the left cavernous sinus. Thereafter, uterine cervical cancer was detected as the origin of this intra-cavernous sinus metastasis. We emphasize that the combination of abducens nerve palsy and ipsilateral postganglionic Horner syndrome may indicate a lesion located within the posterior portion of the cavernous sinus or in its vicinity. Moreover, this is the first reported case of uterine cervical cancer with intra-cavernous sinus metastasis.
We report the cases of a father and his son with spinocerebellar ataxia type 7 (SCA7), a disorder rarely reported in Japan. The father had noticed dysarthria at age 38, and gait instability at age 46. Visual disturbance was noted 3 years later. Neurological examination at age 54 revealed visual disturbance, dysarthria, and cerebellar ataxia in all four extremities and the trunk. Cranial MRI showed moderate atrophy of the brain stem and cerebellar hemispheres. However, no retinal degeneration was found. The son was 16 years old at our first examination. Since age 6, his visual acuity began to decrease; at age 10, he noticed clumsiness in his hands. Six years later he began to experience gait instability. Neurological examination revealed visual disturbance and cerebellar ataxia. He was diagnosed with SCA7 by genetic analysis. His ophthalmologic examination showed retinal degeneration without pigmented spots, which is different from those of retinal phenotypes previously described in SCA7.
A 34-year-old Japanese man was admitted to an outside hospital with an elevated creatinine kinase level and suspected myositis. He was treated with high dose methylprednisolone, which caused severe aggravation of muscle weakness. He was transferred to our hospital at that time. On admission, chest computed tomography (CT) and the presence of anti-acetylcholine receptor antibodies supported a diagnosis of myasthenia gravis and thymoma. Laboratory findings showed hypokalemia, low plasma renin activity and high serum aldosterone. Further studies, including abdominal CT and adrenal venous sampling suggested primary aldosteronism. At first, thymectomy was performed, and one month later, he was treated with laparoscopic adrenalectomy. Immediately after this procedure, he suffered from myasthenic crisis, which was successfully managed with mechanical ventilation and steroid pulse therapy followed by oral prednisolone. This case presented a serious difficulty in differentiating from various myopathies and giving proper treatment because of a rare combination of independent diseases and their masquerading clinical features.
We present a patient who developed carbamazepine (CBZ)-induced Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome associated with high serum procalcitonin (PCT). The presentation (high fever, hepatosplenomegaly, leukocytosis), high PCT and CRP initially suggested sepsis, and he was treated with antibiotics, while CBZ was continued. The rash and hepatitis worsened. After withdrawal of CBZ, corticosteroid therapy was administered and the patient recovered with normalization of PCT. This case demonstrates that PCT may be increased in patients with DRESS. This is the first report of CBZ-induced DRESS associated with high PCT, and the second case of increased PCT in DRESS.
A 19-year-old Japanese man who had been diagnosed with Crohn's disease (CD) suffered from dry cough and fever over 38°C for three days prior to hospitalization. On admission, his colonic CD condition was stable, neither active nor in remission. Computed tomography of the chest showed small elevated tracheobronchial lesions. Bronchoscopy showed diffuse whitish granular lesions in the trachea and bronchi. The pathological findings in the biopsy showed inflammatory infiltration suggesting Crohn's tracheobronchitis. Thereafter, he was treated with inhaled Fluticasone propionate 400 μg/day. After one week his dry cough improved, and after two weeks bronchoscopic findings were improved.
The sentence in page 1175, abstract, line 8,"a sandwich enzyme-linked immunosorbent assay (ELISA) system, respectively" should be "a latex particle- enhanced turbidimetric assay, respectively". The sentence in page 1176, right column, line 20,"a sandwich enzyme-linked immunosorbent assay(ELISA) system, (adiponectin ELISA kit, Otsuka Pharmaceutical Co., Tokushima, Japan)(11)" should be "a latex particle-enhanced turbidimetric assay (Otsuka Pharmaceutical and Mitsubishi Chemical Medience, Tokyo, Japan )(11)". The reference 11 in page 1180, should be "11.Nishimura A, Sawai T, Determination of adiponectin in serum using a latexparticle-enchanced turbidimetric immunoassay with an automated analyzer. Clin Chim Acta 371:163-168,2006".