Objective When patients with Graves' disease show severe allergic cutaneous reactions, physicians often suggest that they undergo radioiodine therapy instead of receiving propylthiouracil (PTU), another antithyroid drug, because anti-neutrophil cytoplasmic antibody (ANCA) -related vasculitis can occur with PTU, especially with long-term use. However, some patients refuse radioiodine therapy and chose PTU. Sometimes PTU treatment may be prolonged. Since the frequency of adverse effects of methimazole (MMI) is dose-related, there is a possibility that we can re-administer a low dose without adverse effects to patients well-controlled with PTU who once experienced an allergic reaction to MMI.

Methods I prospectively re-administered a low dose of MMI to patients who previously experienced an allergic reaction to MMI at initial treatment. The dose of re-administered MMI ranged from 5 mg twice a week to 5 mg daily.

Patients Nine patients with Graves' disease who developed urticaria at initial treatment with MMI and had been treated with PTU for 6 to 21 years were recruited.

Results Eight of the 9 patients were successfully controlled with MMI without allergic cutaneous reactions. Only one patient felt itchiness 2 days after switching to MMI. However, skin change was not observed.

Conclusion If the patients show allergic cutaneous reactions as a side effect of MMI at the initial treatment for Graves' disease, then there is a strong possibility that such patients can tolerate a low dose of MMI without adverse effects after the disease activity has subsided.

Objective The adverse effects of selective sodium-glucose co-transporter 2 (SGLT2) inhibitors generally appear within about two or three months after treatment initiation in Japan. Therefore, we investigated the impact of tofogliflozin, a class of SGLT2 inhibitors, on glycemic control and body composition during this period in Japanese patients with type 2 diabetes mellitus.

Methods This single-arm open-label study enrolled 20 patients. Patients received tofogliflozin 20 mg once daily for 8 weeks. At week 8, changes from baseline in body weight, serum metabolic markers, and body composition were evaluated.

Results A total of 17 patients completed the 8-week administration of tofogliflodin. No serious adverse events were noted. Hemoglobin A1c (HbA1c) decreased significantly, from 7.8% to 7.3% with 8-week administration of tofogliflozin. Both the body weight and body mass index (BMI) also decreased. In addition, a decreased renal function of the boundary zone and hemoconcentration were detected. As for body composition, the free fat mass, total body water, extracellular water and intracellular water were all decreased significantly. Interestingly, the amount of fat mass did not change. The degree of improvement in HbA1c was correlated with the baseline fat mass and BMI.

Conclusion An eight-week administration of tofogliflozin improved glycemic control and reduced the body weight and free fat mass in type 2 diabetic patients without affecting the fat mass. In this period, the hematocrit level and renal function should be monitored to guard against hemoconcentration and renal impairment, respectively.

Objective The effects of febuxostat therapy on hyperuricemia in patients with and without type 2 diabetes were compared in this retrospective observational study after pair-matching using the propensity scores.

Methods In total, 160 patients with hyperuricemia were studied as the treated set, and the 155 subjects in whom the administration of febuxostat was not discontinued during the observation period were investigated in the full analysis. The study subjects were divided into two groups based on the style of initiation of febuxostat: initial and switching therapy from allopurinol administration.

Results The reduction in the serum uric acid (sUA) levels at six months after the initiation of febuxostat administration did not significantly differ between the patients with and without diabetes in both the initial (206±114 and 226±113 μmol/L in patients with and without diabetes, respectively) and switching (154±91 and 129±90 μmol/L in patients with and without diabetes, respectively) therapy groups. The eGFR values were significantly increased compared to the baseline levels only in the patients without diabetes. The changes in the eGFR values were significantly associated with the presence of diabetes and sUA at baseline in a multivariate analysis. The frequency of adverse events was not significantly different between the patients with and without diabetes.

Conclusion Although febuxostat exerted a similar sUA-lowering effect against hyperuricemia in patients with type 2 diabetes compared to those without, the renoprotective effect was attenuated in those with diabetes compared to nondiabetic subjects.

Objective Adult patients with pertussis rarely show typical symptoms, such as paroxysmal coughing, inspiratory "whoop", or post-tussive vomiting. While a culture is regarded as the gold standard for diagnosis, the sensitivity is very low. Therefore, the diagnosis of pertussis in adults in clinical practice is mostly based on single-sample serology using an enzyme-linked immunosorbent assay (ELISA) with the pertussis toxin antigen. Various cut-off values for the anti-pertussis toxin IgG (PT-IgG) have been proposed. It has been reported that concentrations of PT-IgG fall below the defined cut-off about 4.5 months after infection on average, and within 1 year in most patients. We investigated the distribution and time course of the PT-IgG levels.

Methods The data were collected from the medical records.

Patients The study retrospectively identified subjects who had visited Ikebukuro Otani Clinic, which is a specialized clinic for patients with cough. We retrospectively reviewed 406 patients with PT-IgG measurements to investigate the age distribution of PT-IgG levels. The changes in PT-IgG levels over time were assessed in the 205 patients who had more than one PT-IgG measurement.

Results PT-IgG levels were ≥100 EU/mL in more than 15% of subjects. The PT-IgG levels of a few subjects had diminished over a long period of time.

Conclusion A PT-IgG level greater than the defined cut-off value simply indicates past infection or immunization in most subjects. As such, a single measurement of PT-IgG using the cut-off values might lead to overdiagnosis of pertussis. Further data collection and analysis are required.

A 29-year-old woman who underwent the Fontan procedure at 10 years of age had an incidental finding of liver masses on abdominal ultrasonography. Subsequent gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid magnetic resonance imaging showed a 15 mm hypervascular mass with washout in the hepatobiliary phase in liver segment 4 (S4), and an 18 mm hypervascular mass without washout in the hepatobiliary phase in liver segment 2 (S2). The S2 liver mass was pathologically diagnosed to be a regenerative nodule by an ultrasound-guided needle biopsy, and the S4 liver mass was pathologically diagnosed as a poorly differentiated hepatocellular carcinoma after partial hepatectomy.

The patient was a 67-year-old female with liver cirrhosis due to hepatitis C. She was administered furosemide at 20 mg/day and spironolactone at 25 mg/day, but the ascites did not improve. Despite the additional administration of tolvaptan at 3.75 mg/day, the response to ascites was still poor. While the dose of tolvaptan was thereafter increased to 7.5 mg/day on the 7th hospital day, the ascites still persisted. However, she continued to receive tolvaptan (7.5 mg/day) because the worsening of her subjective symptoms was mild and she wished to do so. The ascites was later found to have almost completely disappeared on computed tomography (CT) at 6 months.

A 23-year-old asymptomatic woman was referred to our hospital for further examination of a systolic ejection murmur with fixed splitting of the second heart sound auscultated at the third left sternal border. Initial echocardiography could not detect the cause. Subsequently performed low-dose computed tomography, however, ruled out the possibility of any congenital heart diseases, but revealed a markedly shortened anteroposterior diameter of the chest, which led us to a diagnosis of straight back syndrome. A vertically oriented "pancake" appearance of the heart, straight vertebral column, and compression of the right ventricular outflow tract were clearly demonstrated on the reconstructed images.

A 57-year-old man with antithrombin III deficiency with deep vein thrombosis and pulmonary thromboembolism after surgery for colon cancer was managed with warfarin and inferior vena cava filtration. After starting chemotherapy for liver metastasis, the control of his prothrombin time-international normalized ratio in response to warfarin began to fluctuate. Warfarin was changed to edoxaban (an oral direct Factor Xa inhibitor), and he had no recurrence of venous thromboembolism or bleeding for approximately 1 year. We conclude that edoxaban could be a useful treatment option for complicated patients with deep vein thrombosis.

A 79-year-old man was diagnosed with sudden deafness. He had previously experienced a suspected episode of angina pectoris. At a local hospital, after 500 mg of hydrocortisone and 80 mg adenosine triphosphate (ATP) were administered, he became aware of chest discomfort. An electrocardiogram revealed serious ST-segment depressions. He was diagnosed with a non-ST elevated myocardial infarction (NSTEMI). Emergency coronary angiography revealed triple vessel disease, and the lesion was successfully stented. The mechanisms whereby the stable effort angina pectoris destabilized in this case were thought to include a reduction of the local blood flow because of an ATP product and probable thrombus formation in response to the administered steroids.

Resistance to thyroid hormone (RTH) is a genetic disorder characterized by reduced tissue responsiveness to thyroid hormone. We herein describe a 60-year old man who presented with the clinical features of cardiomyopathy, diabetes mellitus and elevated thyroid hormones with unsuppressed thyroid stimulating hormone. A genetic analysis of thyroid hormone receptor (TR) revealed a missense mutation (A268D) in the TRβ gene. Clinical manifestations of RTH may be variable due to different tissue distributions of TR subtypes and different actions of mutant receptors. The current case demonstrates that patients with a TRβ mutation may have impaired his glucose metabolism and a reduced cardiac function, although patients appear clinically euthyroid.

We herein present a 60-year-old man with adrenocortical carcinoma who had gynecomastia. An endocrinological examination revealed increased levels of serum estradiol and dehydroepiandrosterone-sulfate (DHEA-S) and reduced levels of free testosterone. Magnetic resonance imaging showed an adrenal tumor with heterogeneous intensity. Iodine-131 adosterol scintigraphy showed an increased uptake at the same site. Because feminizing adrenocortical carcinoma was suspected, right adrenalectomy was performed; the pathological diagnosis was adrenocortical carcinoma. The results of immunostaining indicated a virilizing tumor. Aromatase activity was identified on RT-PCR. As disorganized steroidogenesis is pathologically present in adrenocortical carcinoma, this diagnosis should be made with caution.

A patient presented with hyperthyroidism and end-stage renal disease requiring hemodialysis that was difficult to control despite increased dosages of anti-thyroid drugs. The condition could finally be controlled by ¹³¹I radioactive iodine therapy (RIT) and hemodialysis provided under a hospital-linkage system. During three hemodialysis sessions after the oral administration of ¹³¹I, we measured the radioactivity released from the patient and the radioactivity of the devices/tools used. The radioactivity of the devices/tools was managed by allowing the isotope to decay into non-radioactive elements. Our experience suggests that outpatient RIT may provide a safe and convenient means of treating Graves' disease, even in patients receiving hemodialysis.

Calciphylaxis is rare cutaneous manifestation associated with painful skin ulceration and necrosis. It primarily occurs in patients with end-stage chronic kidney disease. In this report, we would like to show our experience with a male patient presenting with minimal change nephrotic syndrome that was sequentially complicated by acute kidney injury and painful ulcerative cutaneous lesions due to calciphylaxis. There seemed to be several contributing factors, including a disturbance of the patient's mineral metabolism and the systemic use of glucocorticoids and warfarin. Various concerns regarding the diagnostic and therapeutic conundrums that were encountered in the present case are also discussed.

We herein describe the first known case of diffuse alveolar hemorrhage (DAH) associated with the administration of Makyo-kanseki-to, a Chinese herbal drug. A 64-year-old man with bronchial asthma presented with persistent cough. Makyo-kanseki-to was prescribed as an adjunctive treatment for bronchial asthma. Immediately after drug ingestion, the patient expectorated bloody sputum. DAH was diagnosed based on the presence of bilateral ground-glass opacity which was identified on chest computed tomography and bloody bronchoalveolar lavage fluid. We diagnosed that the administration of Makyo-kanseki-to was the responsible medication because the hemorrhage developed immediately after drug ingestion and resolved after the cessation of such medication with no subsequent recurrence.

Pulmonary sarcomatoid carcinoma is a rare subtype of non-small cell lung cancer with a poor prognosis. We herein report on a case of pulmonary sarcomatoid carcinoma that was treated successfully by concurrent chemoradiotherapy. A 65-year-old man was diagnosed to have pulmonary pleomorphic carcinoma (clinical T4N2M0 stage IIIB). He received concurrent chemoradiotherapy (60 Gy of radiotherapy in 30 fractionations and two courses of chemotherapy with carboplatin and paclitaxel). After chemoradiotherapy, a significant reduction of the tumor size was observed. Two courses of adjuvant chemotherapy were performed. He is currently alive at 15 months after the first treatment without any recurrence or metastasis.

Post-intubation tracheal stenosis accounts for the greatest proportion of whole-cause tracheal stenosis. Treatment of post-intubation tracheal stenosis requires a multidisciplinary approach. Surgery or an endoscopic procedure can be used, depending on the type of stenosis. However, the efficacy of cryotherapy in post-intubation tracheal stenosis has not been validated. Here, we report a case of recurring post-intubation tracheal stenosis successfully treated with bronchoscopic cryotherapy that had previously been treated with surgery. In this case, cryotherapy was effective in treating web-like fibrous stenosis, without requiring more surgery. Cryotherapy can be considered as an alternative or primary treatment for post-intubation tracheal stenosis.

We herein describe a patient with Behçet's disease in whom we followed the development and resolution of pulmonary artery aneurysms. He presented with intermittent hemoptysis, pulmonary thromboembolism was initially diagnosed, and anticoagulant therapy was started. Over the next several months, the expansion of pulmonary arteries was noted. Five months after his initial admission, he was readmitted for massive hemoptysis, and further examinations revealed that he had Behçet's disease. Corticosteroids and intravenous cyclophosphamide were started. Over the next five months, the pulmonary artery aneurysms and thrombosis resolved. The development of pulmonary artery aneurysms led to the diagnosis of Behçet's disease, and they resolved after immunosuppressive therapy.

We herein report a rare chromosomal abnormality observed in an acute promyelocytic leukemia (APL) patient. She had several APL derivative clones including a clone with i(17)(q10) abnormality, which consists of two kinds of structural abnormalities, a cryptic translocation of t(15;17) and an isochromosome of 17q. Although an obvious microscopic t(15;17) change was not observed on either arms of the isochromosome, PML/RARα fusion signals were detected on an interphase fluorescence in situ hybridization analysis. By several cytogenetic analyses of her bone marrow cells, it was confirmed that the i(17)(q10) clone was derived from the classic t(15;17) clone via another intervening clone, cryptic t(15;17).

We herein present a case of acquired hemophilia A with a normal activated partial thromboplastin (aPTT), intramuscular hematoma and cerebral hemorrhage occurring in a 73-year-old man. The patient visited our emergency department with gait disturbance, pain and swelling in his right leg. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed intramuscular hematoma and intracranial hemorrhage. The results of initial coagulation studies were normal, but repeated coagulation studies revealed an isolated prolongation of the aPTT. Additional laboratory tests confirmed the diagnosis of acquired hemophilia A. If the initial aPTT is normal, we should therefore repeat the aPTT and also perform other coagulation studies including a mixing study, factor VIII level and inhibitor, to investigate the underlying diseases in elderly patients with spontaneous hemorrhaging of unknown etiology.

The prognosis for myelodysplastic syndrome with bone marrow fibrosis (MDS-F) is worse than the prognosis of MDS without fibrosis. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy; however, the indications and the procedures involved in HSCT remain unclear. We herein describe a 69-year-old Japanese man with MDS-F who received haploidentical HSCT and post-transplantation cyclophosphamide. Although the first HSCT resulted in secondary graft failure, the second HSCT using PTCy led to successful engraftment after early improvement in fibrosis. Since the incidence of graft failure is high in myelofibrosis patients, a secondary HSCT using PTCy may be successful if employed.

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by segmental vasospasm and it is often accompanied by either posterior reversible encephalopathy syndrome or stroke. However, other MRI abnormalities have rarely been reported. A 28-year-old woman presented with a thunderclap headache immediately after delivery; MRI showed segmental vasoconstriction and an abnormal signal in the splenium of the corpus callosum. Neuroimaging abnormalities normalized 20 days after the first examination. Only two cases of RCVS with transient splenial lesions (TSL) have so far been reported. Both cases occurred postpartum like ours, indicating that delivery may be a trigger for the development of both TSLs and RCVS.

We herein report the case of a 72-year-old man demonstrating myasthenia gravis (MG) with a dropped head and acute respiratory insufficiency. There was no ocular, bulbar, or limb involvement. The patient was seronegative for anti-acetylcholine receptor (AChR) antibodies and anti-muscle-specific tyrosine kinase (MuSK) antibodies. Subsequent tests showed seropositivity for anti-low-density lipoprotein receptor-related protein 4 (LRP4) antibodies. The addition of steroid pulse therapy resulted in a full remission of his respiratory symptoms. This presentation suggests that LRP4-positive MG should be considered in the differential diagnosis of patients presenting with acute respiratory insufficiency without either cranial or limb involvement.

Vertebral arteries (VAs) are vulnerable to mechanical stress between the atlas and axis, and subsequent VA dissection can cause posterior circulation infarction. We herein present a rare but informative case of bilateral VA aneurysms that caused recurrent stroke. The localization of the aneurysms and dynamic angiography with neck movement suggested a pathogenesis related to chronic mechanical injury of the VAs, though no skeletal abnormality was detected. The recurrences stopped and both aneurysms shrank after neck collar fixation and after the combination use of antithrombotics. For patients with posterior circulation infarction of unknown origin, a careful evaluation of VAs with physicians paying special attention to the atlantoaxial joint level is therefore recommended.

This report describes a rare case of recurrent bilateral focal myositis and its successful treatment via methotrexate. A 38-year-old man presented myalgia of the right gastrocnemius in May 2005. Magnetic resonance imaging showed very high signal intensity in the right gastrocnemius on short-tau inversion recovery images. A muscle biopsy revealed inflammatory CD4+ cell-dominant myogenic change. Focal myositis was diagnosed. The first steroid treatment was effective. Tapering of prednisolone, however, repeatedly induced myositis relapse, which progressed to multiple muscle lesions of both lower limbs. Initiation of methotrexate finally allowed successful tapering of prednisolone, with no relapse in the past 4 years.

A 40-year-old man complaining of progressive body weight loss was diagnosed to have acquired immunodeficiency syndrome. Within 2 weeks after the initiation of combination antiretroviral therapy, he developed fever, massive cervical lymphadenopathy and a protruding subcutaneous abscess. A lymph node biopsy and abscess drainage revealed non-caseous granuloma and mycobacterium. The mycobacterium belonged to Runyon II group, but it showed no matches to any previously reported species. According to sequence analyses, the strain was identified as Mycobacterium shigaense. After six months of antimycobacterial treatment, the lesions were all successfully cured. This is the third case report of the novel mycobacterium, M. shigaense, presenting in associatioin with immune reconstitution syndrome.

We herein report the case of a 63-year-old man who presented with a 3-month history of a cutaneous nodular lesion of his jaw, low grade fever, lethargy and progressive cognitive impairment. He had a 30-year history of multiple sclerosis and had been treated with fingolimod for the previous 2 years. Laboratory data revealed CD4 lymphocytopenia and a tissue culture of the skin nodule was positive for Cryptococcus neoformans. Cerebrospinal fluid and serum cryptococcal antigen tests were also positive and we diagnosed him to have disseminated cryptococcosis. This dissemination might be associated with fingolimod-induced CD4 lymphocytopenia. The risk of an opportunistic infection should therefore be considered when encountering fingolimod-treated patients.

Fluorodeoxyglucose (FDG)-positron emission tomography with computed tomography (FDG-PET/CT) is useful in disease monitoring of malignancies after therapy, while an FDG uptake may also be present in benign diseases. We herein demonstrate a case of disseminated Mycobacterium tuberculosis mimicking systemic metastasis of prostate cancer. This case highlights that clinicians should consider Mycobacterium tuberculosis in patients with prostate cancer who demonstrate multifocal FDG uptakes masquerading as metastasis, even when the chest photographs reveal a normal appearance and a sputum examination demonstrates negative results. An invasive surgical biopsy may be required and a pathological analysis would be critical in the diagnosis of Mycobacterium tuberculosis.

A 58-year-old Japanese man with a high parasitemia of Plasmodium falciparum, returning from Uganda, was admitted to our hospital since his consciousness level rapidly deteriorated after the initial dose of mefloquine. Despite the parasitemia was cleared by quinine by day 7, the coma remained unchanged and diffuse leukoencephalopathy was detected on magnetic resonance image. Steroid pulse therapy was initiated on day 8. Subsequently, the neurological manifestations improved and he was discharged on day 73 without any sequelae. Pathogenesis of P. falciparum causing cerebral malaria is diverse and complex. If neurological symptoms unusually prolong, steroid may be an effective treatment option.

Tetanus is a potentially fatal infection. Approximately 100 cases are reported in Japan each year; however, little is known about its clinical course and outcomes in the current era of treatment. We herein report three cases of tetanus in elderly patients who survived after mechanical ventilation and intensive care. These patients, together with six other similar cases, had a median weaning period of 31 days and median length of stay of 77 days. In elderly patients, severe systemic forms of tetanus require prolonged mechanical ventilation and hospitalization. To improve prevention, tetanus vaccination should be promoted more aggressively among those who are susceptible to the disease.