Effects of polypharmacy on the prevalence of adverse drug events resulting in outpatient visits and hospitalization.

A high proportion of hospitalizations is attributable to the prevalence of adverse drug events. This retrospective study included outpatients and inpatients to determine the prevalence of adverse drug events and if polypharmacy increases it. The prevalence, classification, and causality of adverse drug events were assessed based on medical records, laboratory values, and other data. Multivariate analysis (multiple logistic regression analysis) was performed with the presence or absence of adverse drug events at the time of the visit as the dependent variable and items for which the P-value was <0.25 in the univariate analysis as independent variables. The prevalence of adverse drug events was 13.0%, 10.9%, and 16.0% among all patients, the outpatient group, and the inpatient group, respectively. Multivariate analysis showed that polypharmacy (≥5 drugs) significantly increased the risk of adverse drug events in all patients. The prevalence of adverse drug events significantly increased with each additional drug used. We expect that minimizing the number of medications through moderation of the number of prescription drugs and elimination of polypharmacy will reduce the number of outpatient visits and hospitalizations due to adverse drug events.

Factors influencing the use of over-the-counter drugs and health foods/supplements.

Over-the-counter (OTC) drugs and health foods/supplements are used as means of self-medication with the aim of preventing diseases and maintaining health. No reports have yet addressed the relationship between healthcare systems and self-medication. Here, we carried out a retrospective survey to identify healthcare system factors affecting OTC drug and health food/supplement usage. Patients hospitalized at Gifu Municipal Hospital between October 1, 2014 and March 31, 2015 were given a survey. The items surveyed were age, gender, disease, alcohol intake/smoking status, insurance classification, and medical pharmaceuticals, OTC drugs, and health foods/supplements used immediately before hospitalization. We performed multiple logistic regression analysis using OTC drugs and health foods/supplements as dependent variables with patient attributes, medical insurance, etc. as independent variables. A total of 5,965 patients were analyzed. OTC users comprised 2.6 % (156 people) of the total. The use of OTC drugs was significantly higher for females and alcohol consumers than in other categories. In contrast, the use of OTC drugs was significantly lower for participants in public expense/medical subsidy programs. Health foods/supplements were used by 4.0 % of all subjects (240 people); their use was significantly higher among females and users of medical pharmaceuticals. On the other hand, the use of health foods/supplements was significantly lower for smokers, users of the latter-stage elderly healthcare system, and users of public expense/medical subsidy programs.

Risk factors for developing infusion reaction after rituximab administration in patients with B-cell non-Hodgkin's lymphoma.

Rituximab (RTX), a monoclonal antibody against CD20, is known to cause fewer side effects than conventional anti-cancer drugs; however, infusion reaction (IR), which is specific to monoclonal antibody therapy, is frequently triggered by RTX. Therefore, we designed this study to identify risk factors based on clinical test values for developing IR after RTX administration. Eighty-nine patients with B-cell non-Hodgkin's lymphoma who had received RTX for the first time between February 2010 and March 2013, at the Gifu Municipal Hospital were enrolled as subjects. Analysis of data was conducted for 87 patients, after excluding patients whose data were missing. Univariate analysis showed significant differences in the number of patients exhibiting a soluble interleukin-2 receptor (sLL-2R) level > 2,000 U/L and hemoglobin (Hb) < lower standard limit (LSL) between the IR and non-IR groups. Multivariate analysis showed significant differences with respect to slL-2R > 2,000 U/L [odds ratio (OR), 4.463; 95% confidence interval (Cl), 1.262-15.779; P = 0.020], Hb < LSL [OR, 3.568; 95% CI, 1.071-11.890; P = 0.038], and steroid administration [OR, 0.284; 95% Cl, 0.094-0.852; P = 0.025]. Our findings show that sIL-2R > 2,000 U/L, Hb < LSL, and a lack of steroid premedication are risk factors for developing IR following RTX treatment.

Induction of tissue-specific stem cells by reprogramming factors, and tissue-specific selection.

Although induced pluripotent stem (iPS) cells have significant implications for overcoming most of the ethical issues associated with embryonic stem (ES) cells, there are still several unresolved issues related to the use of iPS cells for clinical applications, such as teratoma formation. In this study, we were able to generate tissue-specific stem (induced tissue-specific stem; iTS) cells from the pancreas (iTS-P) or liver (iTS-L) by transient overexpression of reprogramming factors, combined with tissue-specific selection. The generation of iTS cells was easier than that of iPS cells. The iTS-P/iTS-L cells express genetic markers of endoderm and pancreatic/hepatic progenitors and were able to differentiate into insulin-producing cells/hepatocytes more efficiently than ES cells. Subcutaneous transplantation of both types of iTS cells into immunodeficient mice resulted in no teratoma formation. The technology used for the transient overexpression of reprogramming factors and tissue-specific selection may be useful for the generation of other tissue-specific stem cells, and the generation of iTS cells could have important implications for the clinical application of stem cells.

Paraneoplastic cerebellar degeneration caused by ovarian clear-cell carcinoma.

Paraneoplastic cerebellar degeneration is a paraneoplastic neurological syndrome caused by the remote effect of certain systemic cancers and is characterized by subacute cerebellar symptoms. A 62-year-old woman suffering from unidentified cerebellar symptoms was admitted to our hospital. Paraneoplastic cerebellar degeneration was suspected and ovarian cancer was detected after the systemic examination for malignancy. The symptoms of vertigo and dysarthria were improved a little after surgical operation and treatments of γ-globulin, steroid pulse and tacrolimus hydrate. The cerebellar symptoms of paraneoplastic cerebellar degeneration are often evident prior to detection of malignancy. It is important to perform systemic examination for malignancy in case of unidentified cerebellar symptoms.

Effect of intra-articular lesions on the outcome of periacetabular osteotomy in patients with symptomatic hip dysplasia.

In order to clarify how intra-articular lesions influence the survival of a periacetabular osteotomy in patients with dysplasia of the hip, we performed an observational study of 121 patients (121 hips) who underwent a transposition osteotomy of the acetabulum combined with an arthroscopy. Their mean age was 40.2 years (13 to 64) and the mean follow-up was 9.9 years (2 to 18). Labral and cartilage degeneration tended to originate from the anterosuperior part of the acetabulum, followed by the femoral side. In all, eight hips (6.6%) had post-operative progression to Kellgren-Lawrence grade 4 changes, and these hips were associated with the following factors: moderate osteoarthritis, decreased width of the joint space, joint incongruity, and advanced intra-articular lesions (subchondral bone exposure in the cartilage and a full-thickness labral tear). Multivariate analysis indicated subchondral bone exposure on the femoral head as an independent risk factor for progression of osteoarthritis (p = 0.003). In hips with early stage osteoarthritis, femoral subchondral bone exposure was a risk factor for progression of the grade of osteoarthritis. Although the outcome of transposition osteotomy of the acetabulum was satisfactory, post-operative progression of osteoarthritis occurred at a high rate in hips with advanced intra-articular lesions, particularly in those where the degenerative process had reached the point of femoral subchondral bone exposure.

Long-term results of Tokyo Children's Cancer Study Group trials for childhood acute lymphoblastic leukemia, 1984-1999.

We report the long-term results of Tokyo Children's Cancer Study Group's studies L84-11, L89-12, L92-13, and L95-14 for 1846 children with acute lymphoblastic leukemia, which were conducted between 1984 and 1999. The value of event-free survival (EFS)+/-s.e. was 67.2+/-2.2% at 10 years in L84-11, which was not improved in the following two studies, and eventually improved to 75.0+/-1.8% at 10 years in L95-14 study. The lower EFS of the L89-12 reflected a high rate of induction failure because of infection and delayed remission in very high-risk patients. The L92-13 study was characterized by short maintenance therapy; it resulted in poor EFS, particularly in the standard-risk (SR) group and boys. Females did significantly better than males in EFS in the early three studies. The gender difference was not significant in overall survival, partly because >60% of the males survived after the testicular relapse. Randomized studies in the former three protocols revealed that intermediate- or high-dose methotrexate therapy significantly reduced the testicular relapse rate. In the L95-14 study, gender difference disappeared in EFS. Contrary to the results of larger-scale studies, the randomized control study in the L95-14 reconfirmed with updated data that dexamethasone 8 mg/m(2) had no advantage over prednisolone 60 mg/m(2) in the SR and intermediate-risk groups. Prophylactic cranial irradiation was assigned to 100, 80, 44, and 44% of the patients in the studies, respectively. Isolated central nervous system relapse rates decreased to <2% in the last two trials. Secondary brain tumors developed in 12 patients at 8-22 years after cranial irradiation. Improvement of the remission induction rates and the complete omission of irradiation are currently main objectives in our studies.

Application of several types of substrates to ficin-catalyzed peptide synthesis.

The capability of ficin, a cystine protease, to form peptide bonds was investigated using several types of N-Boc-amino acid phenyl and naphthyl esters as acyl donor components. Enzyme-catalyzed peptide synthesis was carried out under optimized reaction conditions of pH, acyl acceptor concentration and selection of the best yield organic solvent. It used a condensation of N-Boc-Ala-OpGu and Ala-pNA as a model reaction. The products were obtained in 72-96% yield using 10 different substrates, within a few minutes of reaction time.

Therapy-related myelodysplastic syndrome in childhood: a retrospective study of 36 patients in Japan.

We report here a retrospective analysis of 36 children with therapy-related myelodysplastic syndrome (t-MDS) diagnosed between 1990 and 1999 in Japan. Their median age was 7.7 years and the median latency period for the development of t-MDS was 38.5 months. The primary tumors were hematologic in 15 of the cases and nonhematologic in 21. Chromosomal abnormalities were detected in 32/34(94%) patients: abnormalities of chromosomes 5and/or 7 in 41% and notably, 11q23 abnormalities in 31%. The prognosis of children with t-MDS was very poor as compared to children with primary MDS (5 year survival: 16% versus 54%, p<0.0001).

Spontaneous recanalization of functionally occluded bilateral internal thoracic artery T graft.

Functional occlusion of the left internal thoracic artery T graft is reported. The patient underwent triple coronary artery bypass grafting with bilateral internal thoracic artery, anastomosing in situ to the left internal thoracic artery to the left anterior descending artery, free right internal thoracic artery to the obtuse marginal and posterolateral branch of the left circumflex artery. Early angiography showed occlusion of the in situ left internal thoracic artery to the moderately stenosed left anterior descending artery and patent side arm to circumflex. However, mid-term angiography revealed restoration of the left internal thoracic artery flow. A negative exercise stress test was noted throughout the postoperative period. Flow competition with a native coronary artery may be responsible for functional occlusion of the left internal thoracic artery.

Clinical results of aortic arch replacement using a four branched prosthetic graft.

AIM: The aim of this study was to evaluate the operative techniques of total arch replacement, the clinical results and the survival curves of patients following this procedure. METHODS: Since December 2001, 92 patients have undergone surgical treatment for aortic dissection and aneurysm. The total aortic arch replacement was performed in 24 of these patients. There were 16 men and 8 women, and the age range was 42 to 81 years with a mean age of 59.4 years. As the operative technique for total arch replacement, we used the 4-branched prosthetic graft, selective cerebral perfusion (SCP), continuous cold blood cardioplegia (CCBC), and open distal anastomosis under circulatory arrest. The combined operations were coronary bypass grafting in 4 patients, aortic valve suspension in 1 patient and a Bentairs procedure in 1 patient. Eleven (73.3%) patients with acute dissection required emergency operation. RESULTS: The hospital mortality rate was 25% (6 of the 24 patients). The causes of death were multiple organ failure (MOF) due to renal and mesenteric ischemia in 3 patients, cerebral infarction in 2 patients, myonephropathic metabolic syndrome (MNMS) in 1 patient, respectively. The data concerning extracorporeal circulation was 204+/-53 min in total pump time, 136+/-43 min in aortic cross clamp time, 83+/-14 min in SCP time and 48+/-10 min in circulatory arrest time, respectively. The long-term result in actuarial survival rate was 76% for 5 years. CONCLUSION: We consider the technique of total arch replacement using 4-branched prosthetic graft, SCP, CCBC, and open distal anastomosis is a useful operative method in patients with aortic aneurysm.

Transtrochanteric valgus osteotomy for the treatment of osteoarthritis of the hip secondary to acetabular dysplasia.

Our study describes the mid-term clinical results of the use of transtrochanteric valgus osteotomy (TVO) for the treatment of osteoarthritis of the hip secondary to acetabular dysplasia. The operation included valgus displacement at the level of the lesser trochanter, and lateral displacement of the greater trochanter by inserting a wedge of bone. We reviewed 70 hips. The mean age of the patients at operation was 44 years (14 to 59). Most (90%) had advanced osteoarthritis. The scores for pain and gait had improved significantly at a mean follow-up of 9.4 years. The rate of survival until an endpoint of a further operation during a follow-up of ten years was 82%. The survival rate was 95% in patients with unilateral involvement who were less than 50 years of age at operation. TVO is a useful form of treatment for advanced osteoarthritis of the hip, particularly in young patients with unilateral disease.

Tuberculous aortitis, ruptured 48 years after therapeutic implantation of synthetic balls.

A case of tuberculous aortitis, ruptured 48 years after an implantation of synthetic balls into the extrapleural space was reported. Those balls were implanted as a therapeutic alternative to artificial pneumothorax for treating pulmonary tuberculosis. Free perforation was triggered by debridement of an expanding cold abscess. A tuberculous abscess adjacent to the arterial wall should be carefully managed even in the absence of the blood flow by image analysis.

Bone marrow fat cell enlargement and a rise in intraosseous pressure in steroid-treated rabbits with osteonecrosis.

The etiology of steroid-induced osteonecrosis (ON) is unclear. This study was designed to determine whether bone marrow fat cell size, intraosseous pressure, and blood flow rate differed between steroid-treated rabbits with ON and those without. Twenty-nine rabbits were intramuscularly injected once with 20 mg/kg of methylprednisolone acetate (MPSL), and five rabbits were injected once with physiologic saline (PS) as a control. Intraosseous pressure and blood flow rate in the proximal femur were determined before and at 2 weeks after the injection. After these measurements, both femora and humeri were histopathologically examined for the presence of ON, and size of bone marrow fat cells were morphologically examined. At 2 weeks after steroid injection, the intraosseous pressure was significantly higher in rabbits with ON than in those without (p = 0.0251), and the blood flow rate had decreased significantly more in rabbits with ON than in those without (p = 0.0051). The size of the bone marrow fat cells was significantly (p = 0.0004) larger in rabbits with ON (diameter, 63.5 +/- 5.8 microm) than in those without (diameter, 53.3 +/- 6.9 microm). Injection of PS (5 rabbits), 1 (10 rabbits), 5 (10 rabbits), and 20 (10 rabbits) mg/kg of body weight of MPSL showed that a larger dose of steroid increased both fat cell size and prevalence of ON. These results suggest that bone marrow fat cell enlargement and a rise in intraosseous pressure may be important when considering the pathophysiology of steroid-induced ON in rabbits.

Plasma concentration of tissue inhibitor of matrix metalloproteinase 1 in patients with colorectal carcinoma.

BACKGROUND: The expression of tissue inhibitor of matrix metalloproteinase (TIMP) 1 in tumour tissue from patients with colorectal carcinoma has been reported to be related to disease progression. However, the clinical significance of plasma TIMP-1 has not been fully elucidated. METHODS: The plasma level of TIMP-1 protein was determined by enzyme-linked immunosorbent assay in samples from 54 patients who underwent resection of the primary tumour. RESULTS: Plasma TIMP-1 levels were associated significantly with depth of invasion and metastasis to lymph nodes and liver. Circulating TIMP-1 levels were significantly higher in patients with serosal invasion, liver metastases and Dukes' stage C tumours. Using a cut-off value of 160 ng/ml, serosal invasion and Dukes' C stage could be predicted with an accuracy of 68.5 per cent. With a cut-off value of 170 ng/ml, metastasis to the lymph node and liver could be predicted with an accuracy of 66.7 and 70.4 per cent respectively. These values were greater than those for carcinoembryonic antigen and CA19-9. CONCLUSION: These data suggest that the plasma concentration of TIMP-1 correlates with both invasion and metastasis in patients with colorectal carcinoma.

Generation of cytotoxic T lymphocytes against autologous lung cancer cells resistant to apoptosis.

BACKGROUND: [corrected] Non-small cell lung cancer (NSCLC) is resistant to conventional treatment; so the development of a new therapy is urgent. MATERIALS AND METHODS: 50 patients with NSCLC and malignant effusion were enrolled in this study. Seventeen autologous lung cancer cell lines were established. Peripheral lymphocytes and irradiated autologous tumor cell lines were co-cultured to generate cytotoxic T lymphocytes (CTL). Expression of apoptosis-related molecules were analysed by RT-PCR or FACS. RESULTS: CTL lines were established in 2 patients. Both CTL lines were CD3+, CD8+ and MHC class I-restricted T cells and showed cytotoxic activities not only against autologous tumor cell lines but against allogenic cancer cell lines. Two lung cancer cell lines were established from one patient before and after cisplatin-based chemotherapy. The tumor cell line established after chemotherapy was apoptosis-resistant, but was sensitive to cytotoxicity of CTL. CONCLUSION: CTL-based immunotherapy may be one of the candidates for future therapies against NSCLC.

Should scirrhous gastric carcinoma be treated surgically? Clinical experiences with 233 cases and a retrospective analysis of prognosticators.

BACKGROUND/AIMS: The prognosis of patients with scirrhous gastric carcinoma has been poorest. METHODOLOGY: To clarify the role of surgical treatment, 233 patients with a primary scirrhous gastric carcinoma were retrospectively analyzed. RESULTS: Of the 233 patients, 182 underwent surgical resection, while the other 51 did not. The median survival time of those with unresectable tumors was 88.0 +/- 15.3 days and that of those who underwent resection was 380.0 +/- 41.8 days. In the 182 patients who underwent resection, multivariate analysis revealed four significant factors; lymphatic invasion, serosal invasion, curability, and lymph node dissection. Of these, curability was the most significant. The median survival time of patients whose tumor were curatively resected was 727.0 +/- 116.3 days, significantly longer than 272 +/- 34.9 days for those whose resection ended noncuratively. In 65 patients whose tumor was curatively resected, subset analyses of factors by multivariate analyses revealed an absence of serosal invasion as the single significant prognosticator. The 5-year survival rate was 55.6% in patients with scirrhous cancer without serosal invasion. CONCLUSIONS: For patients with scirrhous gastric carcinoma, palliative resection should not be attempted for poor outcome. However, if curative resection seems feasible, radical surgery would be justified, especially for tumors without serosal exposure.

Sequential computed tomography images demonstrating characteristic changes in fibrous dysplasia.

Images of fibrous dysplasia (FD) on computed tomography (CT) or magnetic resonance imaging (MRI) vary depending on the relative proportions of the fibrous and osseous components. Based on analysis of the literature, Camilleri suggested that structural changes revealed by conventional radiography may be indicative of the progression of FD. Here we describe the case of a boy who presented at 12 years of age with monostotic FD located in the right maxilla. The lesion first appeared as a lamellar, "onion peel"-like structure on CT; then over the course of the next five years, the structure became what has been termed an "egg-shell lesion", before eventually assuming the form of a "ground-glass lesion".

Postoperative vestibular-evoked myogenic potentials in cases with vestibular schwannomas.

Although still the subject of discussion, vestibular-evoked myogenic potentials (VEMPs) have been considered to reflect the function of the saccular and, more recently, the cochlear tracts. To accurately determine the precise afferent pathway carrying VEMPs, we studied the outcomes of VEMPs and other examinations in patients with unilateral vestibular schwannomas. Eleven patients with unilateral vestibular schwannomas resected using a middle cranial fossa approach were included in the study. Patients underwent pure-tone threshold audiometry, caloric tests and analysis of auditory brainstem responses (ABRs) and VEMPs pre- and postoperatively. The results were compared with those obtained in patients with intact superior or inferior vestibular and cochlear nerves. Among the 11 patients studied, 4 retained their VEMPs postoperatively. Three of the 10 patients with inferior vestibular schwannomas exhibited normal VEMPs, preserved hearing levels (20 dB HL) and anatomically intact superior vestibular nerves. In all of these cases, ABRs more closely correlated with VEMPs than with caloric responses. In one of the cases with inferior vestibular schwannomas, VEMPs were preserved postoperatively and VEMP latencies were shortened, which indicates the preoperative presence of a conduction block in either the cochlear or superior vestibular nerve. VEMPs may be conducted in both the superior vestibular and cochlear nerves, as well as in the inferior vestibular nerve. Thus, evaluation of saccular nerve function should be performed carefully, especially in cases where hearing is preserved. It appears that cochlear conduction may proceed along two pathways, one direct and the other via the brainstem, but this remains to be verified.