Objective This study aimed to establish the clinical significance of positive blood cultures during the past 10 years in Saga University Hospital.
Methods All hospitalized patients with positive blood cultures in the gastroenterology, hepatology and respiratory wards in the Department of Internal Medicine, Saga University Hospital were evaluated by retrospective chart review between January 1999 and December 2008. The results were compared between period I (1999-2003) and period II (2004-2008).
Results During the study, 2,680 isolates from 22,694 samples (11.8%) were detected in Saga University Hospital: 106 (13.1%) isolates from 812 samples were detected in the gastroenterology ward; 71 (7.8%) from 914 in the hepatology ward; and 160 (6.0%) from 2,671 in the respiratory ward. The number of positive blood cultures increased during period II compared with period I in all three wards. The ratio of Gram-negative rods increased in the gastroenterology ward during period II (p<0.05). The ratio of Gram-positive cocci was higher in the respiratory ward compared with the other two wards (p<0.05 in each). In contrast, the ratio of Gram-negative rods was higher in the gastroenterology and hepatology wards (p<0.05 in each). Fungemia increased in the gastroenterology and respiratory wards in period II (p<0.05 in each).
Conclusion The trends in bacterial species in positive blood cultures differed between the gastroenterology, hepatology and respiratory wards. This could be important for decision making regarding antimicrobial therapy in the early therapeutic phase.

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Background The guidelines recommend combination therapy for patients who are unable to achieve target BP with monotherapy; some fixed dose therapies including an angiotensin II receptor blocker (ARB) and diuretics are available in Japan. However, to date there have been few reports on this long-term treatment and the patient profiles suited for this combination remain ambiguous.
Method The Aichi Research on Combination therapy for Hypertension Study was a multicenter, open-label, prospective observational study that investigated the efficacy and safety of 1-year treatment with the losartan-hydrochlorothiazide (HCTZ) combination tablet in patients with hypertension uncontrolled by either ARB monotherapy or combination therapy with a calcium channel blocker (CCB). An ARB was switched to a losartan-HCTZ tablet after a pre-observation period.
Results A total of 614 of 648 patients were evaluable (mean age, 66.3 years; 52.8% men; mean baseline blood pressure, BP, 157.7/87.9 mmHg). The BP had decreased significantly to 138.0/78.2 mmHg by month 3 (p<0.001, t-test), and 36.2% of the patients had achieved their target BP. The hypotensive effect lasted for 1 year and was found equally in the losartan-HCTZ arm and the losartan-HCTZ plus CCB arm. A stratified analysis showed significant hypotensive effects in patients with higher baseline BP, women, and patients who did not drink alcohol (p<0.001, unpaired t-test).
Conclusion The losartan-HCTZ combination tablet was found to have an early hypotensive effect, good tolerability, and stable long-term benefits in patients with hypertension uncontrolled by ARB monotherapy or combination therapy with a CCB.

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Background HMG-CoA reductase inhibitors (statins) inhibit cholesterol biosynthesis, and also decrease the formation of isoprenoid intermediates required for the activation of Rho kinase (ROCK) pathway. ROCK pathway plays pivotal roles in cardiovascular diseases including arteriosclerosis. It has been implicated that inhibition of ROCK can reverse vascular dysfunction in humans with atherosclerosis. However, it is not clear whether statins, at doses used to lower cholesterol levels, inhibit ROCK activity in humans with atherosclerosis.
Methods We treated 40 subjects with stable atherosclerosis with rosuvastatin 10 mg/day, or rosuvastatin 40 mg/day for 28 days in a randomized, double-blinded study. We assessed the change in the lipid levels, C-reactive protein (CRP), ROCK activity, and flow-mediated dilation (FMD) of the brachial artery before and after statins therapy.
Results Treatment with rosuvastatin 10 mg and 40 mg significantly reduced LDL cholesterol by 43.2% to 55.9% and increased FMD by 29.3% to 42.5% (p<0.05 for both compared with baselines). Both doses inhibited ROCK activity (p<0.05), and the extent of inhibition was greater with rosuvastatin 40 mg compared with 10 mg (p<0.05). Only rosuvastatin 40 mg significantly reduced hsCRP (p<0.05).There was no correlation between changes in ROCK activity and changes in low-density lipoprotein cholesterol (r=0.37, p>0.05 vs. r=0.41, p>0.05) among patients randomized to rosuvastatin 10 mg group or 40 mg group. There was a correlation between ROCK inhibition and change in FMD among patients with rosuvastatin 10 mg therapy (r=0.43, p<0.05), and 40 mg therapy (r=0.54, p<0.05). Correlation was found between changes in ROCK inhibition and changes in CRP in rosuvastatin 40 mg/day group (r=0.47, p<0.05).
Conclusion These results demonstrate that high dose rosuvastatin exerts greater effects on LDL-C, ROCK activity, and CRP than low dose rosuvastatin. These findings provide clinical evidence that statins are effective in improving endothelium dysfunction by a cholesterol-independent mechanism in patients with atherosclerosis.

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Objective This study retrospectively analyzed clinical outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelofibrosis (MF) in a single institution.
Methods During the past 20 years, 6 patients with MF have undergone allo-HSCT in our institution. We investigated the clinical characteristics and follow-up course of these patients.
Patients Median age was 47 years (range, 40-52 years). The median interval between diagnosis and allo-HSCT was 12.5 months (range, 5-97 months).
Results Among these 6 patients, 4 patients were categorized in the high-risk group according to the International Prognostic Scoring System. All 6 patients received myeloablative conditioning regimens, but most of them eventually died of relapse.
Conclusion In this small series, allo-HSCT resulted in dismal outcomes. Our experience clearly indicates the need for studies with a larger series of patients to evaluate the efficacy of this modality.

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Objective Antidepressants have been recommended for the treatment of post-stroke depression (PSD). The purpose of this study was to evaluate the effect of fluvoxamine maleate, a selective serotonin re-uptake inhibitor (SSRI), on depressive state, sleep disturbance, and serum melatonin levels in patients with depressive state after cerebral infarction.
Methods Nineteen patients who were hospitalized for cerebral infarction and scored 40 points or higher on the Self Depression Scale (SDS) were enrolled in this study. Nine of the 19 patients received fluvoxamine as a treatment group and the other 10 patients were used as untreated controls. Before and after commencing the drug therapy, the patients were assessed by the SDS, Pittsburgh Sleep Quality Index (PSQI), Japan Stroke Scale for Depression (JSSD), and Japan Stroke Scale for Emotional Disturbance (JSSE), and their serum melatonin levels were measured. The control group underwent the same evaluations as the treatment group.
Results The SDS score improved in the treatment group at 1 week after the start of drug treatment, and in the control group at 1 and 2 weeks into the observation period. In the treatment group, the JSSD and PSQI scores improved and serum melatonin levels increased.
Conclusion The administration of fluvoxamine to patients with depressive state after cerebral infarction alleviated both the depressive state and sleep disturbances. Increased melatonin levels by the administration of fluvoxamine may contribute to improvement in sleep disturbance, one of the major symptoms of depression.

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Objective Although a lot of people have recently reported headaches provoked after watching 3-D videos, the clinical features of the so-called "3-D headache" have not been clarified. In this study, we investigated the clinical features of headaches provoked after watching 3-D videos.
Methods We conducted a questionnaire survey by email to cases who described headaches caused by watching 3-D videos on a Weblog. We established the diagnostic criteria for 3-D headaches, which are as follows for a definite 3-D headache: A) Provoked after watching 3-D videos, but was never provoked by 2-D videos, B) Never experienced previously, C) Unclassifiable by the ICHD-II. A possible 3-D headache was one that met the criteria of A) and B) the same as above, C) Classified as a "probable" subform by the International Classification of Headache Disorders-2nd Edition (ICHD-II).
Results We received answers from 16 cases (5 males, 11 females, average age of 35.8 years old). Eleven of the 16 cases had experienced an entirely new type of headache after watching 3-D videos. Of these 11 cases, 5 were diagnosed as having a definite "3-D headache". The other 6 cases were diagnosed as having possible 3-D headaches. The remaining 5 of 16 cases were suspected to be attacks of primary headaches that the cases were accustomed to having experienced. The common characteristics of the 5 definite 3-D headaches were that they were bilateral and non-pulsating, and the duration was from 10 minutes to 24 hours. The intensity of the 3-D headache was as follows; severe in 2 cases, moderate in 2 cases, and mild is one case. Three of the 4 cases with moderate to severe headache had nausea.
Conclusion The headaches provoked after watching 3-D videos include not only the attacks of primary headaches but also the headache attacks unclassifiable by the ICHD-II.

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Background We compared the usefulness of tuberculin skin test (TST) and three interferon-gamma release assays (IGRAs) [QuantiFERON-TB Gold (QFT-2G), QuantiFERON-TB Gold In-tube (QFT-3G), T-SPOT.TB] as the supportive method for diagnosing pulmonary tuberculosis (TB).
Methods The subjects were 66 patients who required clinical differentiation of pulmonary TB. The final clinical diagnosis of pulmonary TB in 22 patients and non-pulmonary TB in 44 patients was established by clinical specimens.
Results In 22 patients with pulmonary TB, the positive response rate was 59.1% on TST, 81.8% on QFT-2G, 86.4% on QFT-3G and 95.5% on T-SPOT.TB. In 44 patients with non-pulmonary TB disease, the positive response rate was 40.9% on TST, 6.8% on QFT-2G, 6.8% on QFT-3G, 13.6% on T-SPOT.TB. Indeterminate results on three IGRAs were recognized in one patient each on QFT-2G and QFT-3G among patients with pulmonary TB and in two patients each on QFT-2G and QFT-3G among patients with non-pulmonary TB. However, there were no indeterminate results on T-SPOT.TB in either patient group. Patients with false-negative or indeterminate results on IGRAs had severe underlying diseases or were receiving immunosuppressive treatments.
Conclusion There were no significant differences among the three IGRA tests in this study. However, because the three IGRA tests showed a significantly higher positive response rate for patients with pulmonary TB and a lower positive response rate for patients with non-pulmonary TB than TST, the three IGRA tests seemed to be more useful than TST for the differentiation of patients with pulmonary TB.

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Objective Dehydration is a common condition and frequent cause of hospitalization in older people, despite the caregiver's high attention in attempt to avoid its occurrence. In this study, various physical signs were examined as clinical signs of dehydration in elderly.
Methods A prospective observational study was conducted in an acute care teaching hospital. Consecutive elderly patients who were admitted to the Department of Medicine were evaluated. Dehydration was defined as a calculated serum osmolality above 295 mOsm/L. The patients diagnosed as dehydrated or not dehydrated were observed for physical signs of dehydration. Data of blood and urine chemistry analysis were also compared between the two groups.
Results A total of 27 elderly patients admitted with acute medical conditions were included in this study. For the physical signs, dry axilla had moderate sensitivity (44%) and excellent specificity (89%) to detect dehydration. Sunken eyes and delayed capillary refill time also showed relatively good specificity (83%). For laboratory data, the mean concentrations of serum sodium of the dehydrated group (146 mEq/L) was significantly higher (p<0.01) than those of the non-dehydrated group (134 mEq/L).
Conclusion Physical signs of dehydration in elderly showed relatively good specificity but poor sensitivity. The evaluation of the axillary moisture could help assess dehydration as well as laboratory data analysis such as serum sodium concentration.

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A 41-year-old woman was referred with epigastric discomfort. She had a 20-year history of SLE. Esophagogastroduodenoscopy (EGD) examination showed severe atrophic gastritis in the stomach and a protruding lesion was detected. Histological examination showed a carcinoid tumor with cytoplasmic staining with chromogranin-A. Using an endoscopic submucosal dissection (ESD) technique, en bloc resection of the tumor was performed. No recurrence has been found for 3 years after the treatment. Type I gastric carcinoid can occur at an earlier age with AIG and autoimmune diseases such as systemic lupus erythematosus (SLE). This is the first report of gastric carcinoid that was treated by ESD.

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Shock patients with restrictive cardiomyopathy due to cardiac amyloidosis are refractory to medical treatment. Here, we report a case of early initiation of intra-aortic balloon pumping (IABP) in a patient with cardiac amyloidosis who developed postoperative shock. Continuous hemodiafiltration was also applied to control circulating fluid volume. The mechanical treatments allowed reduction of the doses of catecholamine and diuretics and resulted in full recovery. It is reasonable to initiate IABP and hemofiltration dialysis during the early stages for the appropriate control of hemodynamics and fluid in shock patients with cardiac amyloidosis.

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We report a middle-aged Japanese man who had a past history of malignant lymphoma with tubulointerstitial nephritis (TIN) presenting a high serum immunoglobulin G4 (IgG4) concentration and bilateral kidney enlargement and swelling of many lymph nodes. Although lymph node biopsy was not evident of a recurrence of lymphoma, kidney biopsy showed prominent infiltration of IgG4-positive plasma cells in a tubulointerstitial lesion but not in glomeruli. We made a diagnosis of IgG4-related TIN and lymphadenopathy; administration of oral prednisolone improved his physical and laboratory parameters. This is the first report of a case of IgG4-related TIN and lymphadenopathy after therapy for malignant lymphoma.

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A 67-year-old man, on oral therapy for type 2 diabetes mellitus since 1990, had sustained proteinuria since 2005. When hematuria was first discovered in 2008, renal dysfunction [creatinine (Cr), 1.2 mg/dL], inflammation [C-reactive protein (CRP), 12 mg/dL] and high myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA) levels [546 ELISA units (EU)] were observed. Renal biopsy showed the diagnosis of ANCA-associated nephritis combined with diabetic nephropathy. For this patient, there was pathological proof of the combination of diabetic nephropathy and ANCA-associated vasculitis.

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A 68-year-old Japanese woman with asthma of recent onset and a long history of membranous glomerulonephropathy (MN) was admitted because of multifocal pulmonary infiltrates, marked eosinophilia, mild renal dysfunction, a rash on her feet, and right median nerve paralysis. Although MPO- and PR3-ANCA were negative, skin biopsy demonstrated leukocytoclastic vasculitis and Churg-Strauss Syndrome (CSS) was diagnosed. She also had salivary gland swelling and a high serum IgG4 level. Renal biopsy revealed MN with eosinophil-rich tubulointerstitial nephropathy. Her symptoms resolved after the start of corticosteroid therapy. The present case shows that ANCA-negative CSS can have a clinical condition similar to IgG4-related kidney disease.

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A 52-year-old woman was diagnosed with Blau syndrome and rheumatoid arthritis and was treated with prednisolone and methotrexate. Joint pain and skin ulcers were poorly controlled; therefore, mizoribine (MZ; 150 mg/day) was administered once daily from March 2011. In early July 2011, the patient was hospitalized because of acute kidney injury (AKI) and acute pancreatitis. We reasoned that AKI resulted from hyperuricemia during MZ administration because serum concentrations of uric acid (31.6 mg/dL) and MZ (trough level, 5.14 μg/mL) were markedly elevated on admission. MZ should be administered with caution because of the risk of marked hyperuricemia leading to AKI.

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We describe a case of a 67-year-old man with systemic lupus erythematosus who presented with progressive left hemiplegia. Although the cerebral spinal fluid (CSF) polymerase chain reaction (PCR) for the JC virus was negative, a brain biopsy confirmed the diagnosis of progressive multifocal leukoencephalopathy (PML). The tapering of prednisone and the use of cidofovir could not arrest the disease progression. Administration of mefloquine stopped the extension of the lesion, and resulted in obvious clinical improvement. The CSF nested PCR for the JC virus also became negative. This widely used drug should be tried for the treatment of non-HIV PML.

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A 24-year-old woman presented with headache and left-sided focal signs following multiple episodes of right monocular visual impairment. Magnetic resonance angiography revealed a decreased vascular image intensity due to a suspicious stenosis in the right internal carotid artery (ICA). The stenosis was not demonstrated on duplex sonography as it was beyond the field of view of the investigation. Intravascular ultrasound (IVUS) revealed that the outer vessel diameter was significantly reduced during stenosis, supporting the presence of vasospasm. Idiopathic recurrent extracranial ICA vasospasm was diagnosed. Recurrent vasospasms of extracranial ICA may be a distinct entity that can cause ischemic stroke.

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A 50-year-old woman received two weeks of cefozopran and two weeks of imipenem for streptococcal endocarditis and vertebral osteomyelitis. Subsequently she received four weeks of oral levofloxacin and eight weeks of oral clarithromycin due to persistent elevation of C-reactive protein. Finally, she was admitted to our hospital due to massive hematuria. Abdominal CT showed rupture of an aneurysm in the right kidney and emergent coil embolization was performed. Multiple sets of blood culture grew Streptococcus oralis, and transthoracic echocardiography revealed vegetation at the aortic valve. Retrospective review of the abdominal images revealed the emergence of the aneurysm during the treatment.

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Diaphragmatic paralysis is commonly caused by surgical and traumatic injuries, malignant neoplasm, and neurodegenerative disorders. However, in rare instances, diaphragmatic paralysis due to herpes-zoster virus infection has been reported. Here, we describe an 85-year-old woman who developed left hemidiaphragmatic paralysis within 19 days of the appearance of a typical herpes-zoster rash involving the C4-5 dermatome on the left side. Clinical and radiological findings revealed no local causes of phrenic nerve lesion. The hemidiaphragmatic paralysis was thought to be caused by herpes-zoster virus infection.

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A 19-year-old man with Philadelphia chromosome-positive acute lymphoblastic leukemia received an allogeneic hematopoietic cell transplant with unrelated bone marrow. On day 20, the patient developed impaired consciousness and disorientation. Examination of the cerebrospinal fluid showed 2×10⁴ copies/mL of HHV6B. HHV6 encephalitis was diagnosed, as had HHV6 myelitis based on symptoms that included lancinating pain/pruritus in the lower limbs and dysuria/dyschezia. Concurrently, he showed sinus tachycardia. Even after clearance of the HHV6 genome from the plasma and CSF was achieved by treatment with foscarnet, sinus tachycardia persisted for another 100 days. We suspected prolonged sinus tachycardia due to dysautonomia caused by HHV6 encephalomyelitis.

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Primary mediastinal seminoma is a rare tumor usually with nonspecific symptoms such as chest pain, dyspnea and hoarseness, but superior vena cava syndrome (SVCS) is an extremely uncommon syndrome. We report a 25-year-old man who presented with superior vena cava syndrome for 1 month and a 1-week history of retrosternal chest pain. Thorax computerized tomography demonstrated a soft tissue mass in the anterior mediastinum with stippled calcifications compressing the superior vena cava and other major vessels. Transthoracic biopsy showed primary seminoma of the anterior mediastinum. Combined chemoradiotherapy was performed and the patient was considered to have a partial response to treatment.

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