Risk factors for linezolid-associated thrombocytopenia in adult patients.

OBJECTIVES: Thrombocytopenia (TP) is a common adverse effect of linezolid (LZD). However, risk factors for LZD-associated TP have been reported in Western patients with relatively heavy body weight. The aim of this study was to determine the risk factors for LZD-associated TP in Asian population. MATERIALS AND METHODS: A retrospective cohort study was conducted among 101 consecutive patients who received LZD therapy (1,200 mg/day) between July 2003 and December 2013 at a tertiary referral hospital in Tokyo, Japan. The patients with obvious other causes for TP were excluded. The information of target infectious disease, patients' age, gender, body weight, body mass index, baseline serum creatinine (SCr), baseline platelet count, and treatment duration was collected retrospectively. TP was defined as ≥ 50% decrease in platelet count from baseline. Bi- and multi-variate analyses were performed. RESULTS: A total of 101 patients were included (mean age [SD] 64 [18]; male gender [%], 57 [56]). Median duration [range] of LZD therapy was 14 days [1-67]. LZD-associated TP was identified in 42 patients (42%). For TP, adjusted odds ratio (OR) [95% CI] of daily per kg dose (DPKD) and SCr was 1.14 [1.05-1.26] and 1.51 [1.01-2.50], respectively. CONCLUSIONS: Higher DPKD and elevated SCr are significantly associated with LZD-associated TP. These findings suggest that daily dose of LZD should be adjusted using body weight, as typically done in pediatrics, in adults as well. Renal function also should be considered for dose adjustment.

Risk factors of mid-term mortality of patients with infective endocarditis.

In-hospital and long-term mortality of infective endocarditis (IE) are well noted, but the studies for mid-term (90-day) mortality of IE is still limited. We determine the mid-term mortality rate of IE and its significant predictors. Seventy patients with IE were hospitalised at St. Luke's International Hospital between January 1996 and March 2009, of whom 62 consecutive patients could be followed up for 90 days after diagnosis. We then calculated Kaplan-Meier (KM) estimates and performed time-to-event analysis. The mean (standard deviation, SD) age was 66.6 (15.3) years. Thirty-five patients (56%) were male. Blood cultures were positive in 87%. Causative microorganisms were: viridans group streptococci (23%), ß-streptococci (16%), Staphylococcus aureus (15%), including methicillin-resistant S. aureus (MRSA) (5%). Thirty-three cases (53%) had at least one complication such as heart failure (34%), central nervous system (CNS) complication (29%) or emboli peripheral to CNS (6%). KM estimates (95% CI) of the 90-day mortality was 14.5% (7.8-25%). In multiple regression analysis using the Cox proportional hazards model, hazard ratios of at least one complication for the 90-day mortality was 8.2 (1.4-155). Mid-term mortality of IE continues to be high and the presence of at least one complication may be considered as an independent risk factor of mid-term mortality.

PDA usage by Japanese resident physicians is low: a cross-sectional survey.

OBJECTIVES: Personal digital assistants (PDAs) are in widespread use by resident physicians in many countries, reaching as high as 95% in some reports. Uses are varied and include clinical decision support and support of evidence-based practice. Utilization by resident doctors in Japan has not been characterized. This study was conducted to determine practice patterns of PDA use by Japanese resident physicians. METHODS: A nationwide cohort survey study was distributed to all 1070 residency teaching programs in Japan. The survey included questions pertaining to use of PDAs in clinical practice. RESULTS: 1124 surveys were returned (response rate of approximately 75%). 297 (30.7%) respondents reported currently using PDAs, while 971 (86.4%) reported having used a PDA in the past. PDA users were more likely to be male (p <0.05), but no other significant differences were found when examining the following variables: age, training site (university hospital versus community teaching hospital), satisfaction with existing information technology access. CONCLUSIONS: Use of PDAs among Japanese resident physicians is much lower than their counterparts in other countries. In light of this, further research on patient outcomes in Japan and the impact of PDA usage on patient outcomes is urgently needed. If demonstrated to improve outcomes, barriers to adoption need to be identified and overcome.

The expression of IL-12 p40 and its homologue, Epstein-Barr virus-induced gene 3, in inflammatory bowel disease.

BACKGROUND: It has recently been suggested that Crohn's Disease (CD) is associated with an exaggerated T helper 1 cytokine response as manifest by increased production of interleukin-12 (IL-12) and interferon-gamma (IFN-gamma). Epstein-Barr virus-induced gene 3 (EBI3) encodes a 34-kDa glycoprotein that is 27% identical to the p40 unit of IL-12 and has recently been reported to be up-regulated in ulcerative colitis (UC). AIM: To determine whether mucosal expression of IL-12 p40 or EBI3 correlates with inflammatory bowel disease (IBD). PATIENTS/METHODS: mRNA expression in colonic mucosa from patients with UC, Crohn's disease (CD) and non-IBD controls was measured by reverse-transcribed real-time polymerase chain reaction (PCR). RESULTS: EBI3 was significantly increased in both involved and uninvolved colonic mucosa in patients with UC. Although IL-12 p40 was increased in some patients with CD relative to non-IBD controls, the increase was not statistically significant. However, 5-aminosalicylic acid (5-ASA) use was significantly correlated with reduced IL-12 p40 levels in the patients with CD, but not in UC cases. A similar reduction was not seen in 5-ASA-treated UC patients. CONCLUSION: IL-12 p40 expression in CD is heterogeneous. In contrast, expression of the IL-12 p40 homologue, EBI3, is up-regulated in nearly all UC cases and in a subset of CD.

A combination therapy with simvastatin and ursodeoxycholic acid is more effective for cholesterol gallstone dissolution than is ursodeoxycholic acid monotherapy.

Inhibitors of 3-hydroxy,3-methylglutaryl coenzyme A (HMG-CoA) reductase have been reported to decrease the cholesterol saturation index (CSI) in duodenal bile in humans and to prevent formation of cholesterol gallstones in animal studies. We performed a prospective study to evaluate the role of HMG-CoA reductase inhibitors as gallstone-dissolving agents. Fifty patients with radiolucent gallstones in a gallbladder opacifying at drip infusion cholecystography were treated with either 10 mg/day simvastatin plus 600 mg/day ursodeoxycholic acid (group 1, n=26) or 600 mg/day ursodeoxycholic acid alone (group 2, n=24) for 12 months. The ratio of solitary to multiple gallstone cases was 21:29. Plasma lipid levels were assessed and ultrasonographic examination of the gallbladder was performed at baseline and at 3-month intervals during treatment. Duodenal bile sampling was performed in five patients in each group at baseline and after 12 months of treatment. Plasma cholesterol decreased significantly in group 1 but not in group 2. In solitary gallstone cases, no significant difference in dissolution rates was observed between groups 1 (3 of 9, 33%) and 2 (4 of 12, 33%). In contrast, the dissolution rate in multiple gallstone cases was significantly higher in group 1 (12 of 17, 71%) than in group 2 (3 of 12, 25%) (p < 0.01). Bile cholesterol saturation index was significantly decreased (p < 0.01) but did not significantly differ between the two groups. These results suggest that combination therapy with simvastatin and ursodeoxycholic acid is more effective for cholesterol gallstone dissolution than ursodeoxycholic acid monotherapy in patients with multiple gallstones.

An interleukin 12-related cytokine is up-regulated in ulcerative colitis but not in Crohn's disease.

BACKGROUND & AIMS: Interleukin 12 (IL-12) is a heterodimeric, macrophage-derived cytokine that is elevated in Crohn's disease (CD). Epstein-Barr virus-induced gene 3 (EBI3) is a recently characterized human glycoprotein that is homologous to the 40-kilodalton chain of IL-12 and forms a heterodimer with the 35-kilodalton chain of IL-12. We investigated the expression of EBI3 in colonic mucosa of normal control subjects, patients with ulcerative colitis (UC), and patients with CD. METHODS: Colonic tissue was analyzed for messenger RNA (mRNA) expression by quantitative polymerase chain reaction and for protein expression by immunohistology and Western blotting. RESULTS: EBI3 mRNA was present in intestinal biopsy specimens from healthy subjects and patients with CD but was elevated only in active UC. EBI3 levels in UC specimens correlated with histological scores of activity and T-cell infiltration. EBI3-positive cells that had a shape consistent with that of macrophages were identified in the lamina propria, and protein was detected by Western blotting. CONCLUSIONS: EBI3 is a novel IL-12-related cytokine that is expressed by macrophage-like cells in normal intestine and CD and has enhanced expression in active UC but not in active CD.

Fulminant hepatitis following bone marrow transplantation in hepatitis B virus carrier siblings.

A 19-year-old male healthy hepatitis B virus (HBV) carrier developed fulminant hepatitis following allogenic bone marrow transplantation (BMT) from his brother, who was also a healthy HBV carrier, during the first complete remission of acute myelogenic leukemia (M1, FAB classification). Serum markers related to both HBV and hepatitis C virus (HCV) were elevated during active liver injury when a point mutation in the precore (pre-C) region occurred in the HBV. The patient received low-dose interferon alpha (IFN-alpha), while the dose of cyclosporin A was tapered; the patient eventually recovered from the liver injury. Fulminant hepatitis due to HBV and/or HCV following BMT is rare, and it is considered to have a very poor prognosis. The rationale for the use of low-dose IFN-alpha with cyclosporin A (CyA) is discussed.

Crohn's disease associated with pancreatitis of unknown etiology: a case report.

Pancreatitis is generally regarded to be an extra-intestinal complication of Crohn's disease unless the duodenum is directly involved. Some reports in the recent literature, however, suggested a possible association of pancreatitis with Crohn's disease. In this report, we describe a 25-year-old male with Crohn's disease and pancreatitis, the etiology of which was uncertain. The pancreatitis resolved along with the clinical improvement in Crohn's disease. This case supports the concept of an association between Crohn's disease and pancreatitis.

Factor V deficiency in a patient with rheumatoid arthritis.

Factor V deficiency associated with rheumatoid arthritis was found in a 54-year-old woman. Hereditary factor V deficiency is very rare; only about 150 cases have been reported since its discovery in 1943. This appears to be the first case report of factor V deficiency associated with rheumatoid arthritis in the literature.

Erythrocyte superoxide dismutase in various hematological diseases.

We measured superoxide scavenging activity (SSA) of erythrocytes with the recently developed chemiluminescence method by Nakano et al in Down syndrome and various hematological diseases. Hematological disorders were aplastic anemia, myelodysplastic syndrome, multiple myeloma, malignant lymphoma and chronic myelogenous leukemia. The SSA of erythrocytes was 1.7 times higher in Down syndrome, which was consistent with values reported in the previous publications. The erythrocyte SSA in patients of multiple myeloma treated with interferon-alpha was higher than that in healthy volunteers. The erythrocyte SSA in myelodysplastic syndrome, malignant lymphoma and chronic myelogenous leukemia did not differ from that in healthy volunteers. The mean value of erythrocyte SSA in aplastic anemia also remained within normal range. However, when an individual's hemoglobin concentration was compared with his or her own erythrocyte SSA, there was a clear correlation between them. Namely erythrocyte SSA increased when anemia was severe. There was no correlation between erythrocyte SOD activity and ageing.

A case of IgA nephropathy associated with adeno- and herpes simplex viruses.

We report here an adult case of IgA nephropathy associated with episodes of recurrent tonsillitis. Various kinds of viral antigens were examined in the renal and tonsillar tissues by immunofluorescence. Granular depositions of adeno- and herpes simplex viral antigens were detected in the glomerular mesangial areas and in the tonsillar epithelial cells by immunofluorescence. IgA and IgA1 deposits were also observed in the glomerular mesangial areas. It was suggested that IgA nephropathy might be caused by multiple antigenic substances, including adeno- and/or herpes simplex viruses, located in the tonsillar regions.