Association between N-methyl-D-aspartate Receptor Subunit 2B Gene Polymorphisms and Personality Traits in a Young Japanese Population.

OBJECTIVE: The N-methyl-D-aspartate receptor subunit 2B (GluN2B) is involved in regulation of anxiety and depression and nervous activity in the brain. Single nucleotide polymorphisms of the GluN2B gene (GRIN2B) are associated with human mental function and behaviour. We investigated whether four GRIN2B polymorphisms (rs7301328, rs1806201, rs1805247, and rs1805502) affect characterisation of personality traits. METHODS: In 248 young people, GRIN2B polymorphisms were analysed, and personality traits were assessed using the Neuroticism Extraversion Openness-Five Factor Inventory (NEO-FFI) and State-Trait Anxiety Inventory (STAI). RESULTS: There was no main effect of the GRIN2B polymorphisms on the NEO-FFI and STAI dimension scores. Interaction between polymorphism and sex was found in rs1805247 (p = 0.034) and rs1805502 (p = 0.040) in terms of the conscientiousness score of the NEO-FFI. However, post hoc simple main effect analysis showed no significant effect. The preliminary haplotype analysis indicated that haplotype CTT (rs1806201-rs1805247-rs1805502) in the haplotype block was associated with the extraversion score of the NEO-FFI in female participants (p = 0.044), but the significance was lost on correction for multiple testing. CONCLUSION: There was no significant association between selected GRIN2B polymorphisms and personality traits, but this may be due to low statistical power. Further studies involving a larger study population are needed to clarify this.

Comparison of neoadjuvant chemotherapy versus upfront surgery with or without chemotherapy for patients with clinical stage III esophageal squamous cell carcinoma.

Neoadjuvant chemotherapy (NAC) and chemoradiotherapy have been shown to extend postoperative survival, and preoperative therapy followed by esophagectomy has become the standard treatment worldwide for patients with esophageal squamous cell carcinoma (ESCC). The Japan Clinical Oncology Group 9907 study showed that NAC significantly extended survival in advanced ESCC, but the survival benefit for patients with clinical stage III disease remains to be elucidated. We compared the survival rates of NAC and upfront surgery in patients with clinical stage III ESCC. Consecutive patients histologically diagnosed as clinical stage III (excluding cT4) ESCC were eligible for this retrospective study. Between September 2002 and April 2007, upfront transthoracic esophagectomy was performed initially and, for patients with positive lymph node (LN) metastasis in a resected specimen, adjuvant chemotherapy using cisplatin and 5-fluororouracil every 3 weeks for two cycles was administered (Upfront surgery group). Since May 2007, a NAC regimen used as adjuvant chemotherapy followed by transthoracic esophagectomy has been administered as the standard treatment in our institution (NAC group). Patient characteristics, clinicopathological factors, treatment outcomes, post-treatment recurrence, and overall survival (OS) were compared between the NAC and upfront surgery groups. Fifty-one and 55 patients were included in the NAC and upfront surgery groups, respectively. The R0 resection rate was significantly lower in the NAC group than in the upfront surgery group (upfront surgery, 98%; NAC, 76%; P = 0.003). In the upfront surgery group, of 49 patients who underwent R0 resection and pathologically positive for LN metastasis, 22 (45%) received adjuvant chemotherapy. In the NAC group, 49 (96%) of 51 patients completed two cycles of NAC. In survival analysis, no significant difference in OS was observed between the NAC and upfront surgery groups (NAC: 5-year OS, 43.8%; upfront surgery: 5-year overall surgery, 57.5%; P = 0.167). Patients who underwent R0 resection showed significantly longer OS than did those who underwent R1, R2, or no resection (P = 0.001). In multivariate analysis using age, perioperative chemotherapy, depth of invasion, LN metastasis, surgical radicality, postoperative pneumonia, and anastomotic leakage as covariates, LN metastasis [cN2: hazard ratio (HR), 1.389; P = 0.309; cN3: HR, 16.019; P = 0.012] and surgical radicality (R1: HR, 3.949; P = 0.009; R2 or no resection: HR, 2.912; P = 0.022) were shown to be significant independent prognostic factors. In clinical stage III ESCC patients, no significant difference in OS was observed between NAC and upfront surgery. Although potential patient selection bias might be a factor in this retrospective analysis, the noncurative resection rate was higher after NAC than after upfront surgery. The survival benefit of more intensive NAC needs to be further evaluated.

The role of mitochondria-derived reactive oxygen species in the pathogenesis of non-steroidal anti-inflammatory drug-induced small intestinal injury.

Non-steroidal anti-inflammatory drugs (NSAIDs) have been implemented in clinical settings for a long time for their anti-inflammatory effects. With the number of NSAID users increasing, gastroenterological physicians and researchers have worked hard to prevent and treat NSAID-induced gastric mucosal injury, an effort that has for the large part being successful. However, the struggle against NSAID-induced mucosal damage has taken on a new urgency due to the discovery of NSAID-induced small intestinal mucosal injury. Although the main mechanism by which NSAIDs induce small intestinal mucosal injury has been thought to depend on the inhibitory effect of NSAIDs on cyclooxygenase (COX) activity, recent studies have revealed the importance of mitochondria-derived reactive oxygen species (ROS) production, which occurs independently of COX-inhibition. ROS production is an especially important factor in the increase of small intestinal epithelial cell permeability, an early stage in the process of small intestinal mucosal injury. By clarifying the precise mechanism, together with its clinical features using novel endoscopy, effective strategies for preventing NSAID-induced small intestinal damage, especially targeting mitochondria-derived ROS production, may be developed.

An open-label, dose-escalation, safety, and pharmacokinetics phase I study of ombrabulin, a vascular disrupting agent, administered as a 30-min intravenous infusion every 3 weeks in Japanese patients with advanced solid tumors.

PURPOSE: To determine ombrabulin's maximum tolerated dose and dose recommended for Japanese patients with advanced solid tumors and to assess its antitumor activity and overall safety and pharmacokinetic profiles. METHODS: This was a multi-center, open-label, sequential-cohort, dose-escalation phase I study of ombrabulin, a vascular disrupting agent, administered once every 3 weeks. Patients were treated with 15.5, 25, 35, or 50 mg/m(2) ombrabulin over a 30-min intravenous infusion. The recommended dose was the highest dose at which <33 % of all evaluable patients experienced dose-limiting toxicities (DLTs) during the first treatment cycle or 50 mg/m(2) (recommended in Caucasian patients) if the previous definition was not met. RESULTS: Fifteen patients were treated. No DLT occurred with 15.5, 25, or 35 mg/m(2) ombrabulin. In the 50 mg/m(2) group, one patient had Grade 3 lymphopenia, and another experienced Grade 2 hypertension and Grade 3 diarrhea judged as DLTs. The most frequent related adverse events in this group were diarrhea, nausea, and hypertension. Two patients had Grade 3 anemia, one at the 15.5 mg/m(2) and the other at the 50 mg/m(2). No AEs necessitating dose reduction or Grade 4 AEs were observed. Overall, five patients had stable disease. Pharmacokinetic parameters were comparable to those in non-Japanese patients. CONCLUSIONS: Ombrabulin treatment once every 3 weeks was well tolerated in Japanese patients with advanced solid tumors. The dose recommended is 50 mg/m(2), as in Caucasian patients. The safety and pharmacokinetic profiles were comparable between Japanese and Caucasian patients (funded by Sanofi; ClinicalTrials.gov number, NCT00968916).

Phase I study of TAS-102 treatment in Japanese patients with advanced solid tumours.

BACKGROUND: TAS-102 consists of α, α, α-trifluorothymidine (TFT) and an inhibitor of thymidine phosphorylase (TPI). We conducted a dose-escalation phase I study in Japanese patients with advanced solid tumours. METHODS: TAS-102 was administered twice daily on days 1-5 and days 8-12 in a 28-day cycle to patients with solid tumours refractory to standard chemotherapy, to determine its maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and pharmacokinetics (PKs). MTD was evaluated in cycle 1. RESULTS: Safety and PKs were evaluated in 21 patients treated with TAS-102 at 30, 40, 50, 60, or 70 mg m(-2) per day. DLTs, such as grade 4 leucopenia, grade 4 neutropenia, and grade 4 thrombocytopenia, were observed in two patients at doses of 30 and 70 mg m(-2). α, α, α-trifluorothymidine and TPI exposures increased dose dependently, and the percentage of decrease in neutrophil count and TFT exposure were significantly correlated. The disease control rate was 50.0% with a median progression-free survival of 2.4 months in 18 colorectal cancer patients. The dose of TAS-102 was not increased above 70 mg m(-2) per day because of the increased tendency for grade 3 and 4 neutropenia, and 70 mg m(-2) per day was the recommended dose for phase II studies. CONCLUSIONS: TAS-102 at 70 mg m(-2) per day was tolerated in Japanese patients with advanced solid tumours. Phase II studies are ongoing in patients with colorectal cancer.

Mortality and medical morbidity beyond 2 years after allogeneic hematopoietic stem cell transplantation: experience at a single institution.

Long-term follow-up data on patients who underwent allogeneic hematopoietic stem cell transplantation in our institution between 1990 and 2007 were evaluated for mortality and morbidity beyond 2 years post-transplantation. Follow-up data were obtained annually from medical records or by mail to the relevant hospitals, or to the patients themselves. In total, 369 patients survived more than 2 years, but 72 patients died thereafter. Relapse was the most common cause of death, followed by pulmonary complications and infections. Second malignancy was the cause of death in seven patients. Chronic kidney disease was one of the most serious complications, and seven patients needed regular dialysis or kidney transplantation. Hypertension and diabetes were reported in 19 and 11.2% patients, respectively. Second malignancies were observed in 14 patients beyond 2 years after transplantation, and the oral mucosa, tongue, esophagus and colon were the main organs involved. We recommend that physicians caring for allogeneic hematopoietic stem cell transplant patients should at a minimum examine kidney function and gastrointestinal tract for secondary malignancy, in addition to hematological status. Such information will be useful for optimizing outcomes through the detection and prevention of complications.

Phase 1 study of conatumumab, a pro-apoptotic death receptor 5 agonist antibody, in Japanese patients with advanced solid tumors.

PURPOSE: Conatumumab is a fully human monoclonal agonist antibody against human death receptor 5 (DR5). The primary objectives of this phase 1 study were to assess the safety, tolerability, and pharmacokinetics (PK) of conatumumab in Japanese patients with advanced solid tumors. METHODS: This is an open-label ascending dose study with a starting dose level of 3 mg/kg. Subsequent doses of 10 and 20 mg/kg were planned. Six patients were enrolled into 1 of 3 dose cohorts (3, 10, or 20 mg/kg) of conatumumab administered intravenously once every 2 weeks as a single agent. No conatumumab was administered on day 43 to allow the assessment of terminal PK parameters. The primary endpoints were the incidence of dose-limiting toxicities (DLTs) and assessment of PK parameters of conatumumab. RESULTS: Eighteen patients received at least 1 dose of conatumumab. There were no DLTs observed as defined in the protocol. No patients had an adverse event leading to conatumumab discontinuation. Conatumumab demonstrated dose-linear kinetics. A best response of stable disease was reported in nine patients. Monocytes were found to express DR5 and showed a high degree of conatumumab receptor occupancy after treatment at all dose levels. CONCLUSIONS: Conatumumab administered up to 20 mg/kg once every 2 weeks was well tolerated in Japanese patients with advanced solid tumors. Adverse events and PK in these patients were similar to those in the first in human (FIH) study.

Weekly paclitaxel in patients with recurrent or metastatic head and neck cancer.

PURPOSE: To evaluate the efficacy and safety of weekly paclitaxel in patients with recurrent or metastatic head and neck cancer (HNC) by combined analysis of early and late phase II trials. METHODS: Eligibility criteria included histologically proven HNC with recurrent or metastatic disease, measurable disease, PS 0-2, and one or no prior chemotherapy regimens. Treatment consisted of a 1-h infusion of paclitaxel at a dose of 100 mg/m(2) weekly for 6 weeks of a 7-week cycle. A total of 74 patients were enrolled: 37 between February and November 2004 in an early phase II trial and 37 between October 2005 and July 2006 in a late phase II trial. RESULTS: The median number of treatment cycles was two, and median dose intensity was 84.2 mg/m(2)/week. The most common grade 3-4 adverse events were leukopenia (37.5%), neutropenia (30.6%), anemia (12.5%), constipation (8.3%), peripheral neuropathy (5.6%), anorexia (5.6%), and pneumonitis (5.6%). Overall response rate was 29.0% according to RECIST. The median duration of response, median time to progression, and median survival time were 7.4, 3.4, and 14.3 months, respectively. CONCLUSIONS: This study demonstrates that weekly paclitaxel has promising activity with acceptable toxicity in the treatment of recurrent or metastatic HNC.

Impact of hemoglobin level on survival in definitive chemoradiotherapy for T4/M1 lymph node esophageal cancer.

We retrospectively investigated the impact of the pre-chemoradiotherapy hemoglobin level (pre-CRT Hb level) for T4 and/or M1 lymph node (LYM) squamous cell carcinoma of the esophagus. Chemotherapy consisted of protracted infusion with 5-fluorouracil (5-FU) at 400 mg/m(2)/day on days 1-5 and 8-12, combined with cisplatin at 40 mg/m(2)/day on days 1 and 8, repeated twice at a 5-week interval. Concurrent radiation therapy was started on day 1 and delivered at 2 Gy/day for five days a week for a total radiation dose of 60 Gy, with a two-week break after a cumulative dose of 30 Gy. Several factors considered to be related with treatment outcome were evaluated by univariate and multivariate analysis. A total of 48 patients with T4/M1 LYM (lymphocyte) esophageal cancer treated with chemoradiotherapy (CRT) between September 2002 and April 2005 were enrolled. The complete response rate to this regimen was 44% and median survival time was 13.6 months, with a median follow-up period of 26.8 months. Median pre-CRT Hb level was 13.5 (10.4-15.3) g/dL. The CR rate in patients with a pre-CRT Hb level of 13 g/dL or less was only 24% but it was 60% in those with a level that was more than 13 g/dL (P=0.01). As for survival, anovarevealed that a pre-CRT Hb of 13 g/dL or less was a significant prognostic factor with a hazard ratio of 0.45 (95% confidence interval [CI]); 0.21-0.97, P=0.04), while on manova, including performance status, tumor size, TNM stage and pre-CRT Hb level, a pre-CRT Hb level of 13 g/dL or less was the only significant prognostic factor, with a hazard ratio of 0.35 (95% CI; 0.13-0.90, P=0.03). In conclusion, the pre-CRT Hb level may be an important determinant of outcome in patients with T4/M1 LYM squamous cell carcinoma of the esophagus.

Differential effects of angiotensin II versus endothelin-1 inhibitions in hypertrophic left ventricular myocardium during transition to heart failure.

BACKGROUND: In view of their mutual crosstalk, the roles of angiotensin II (Ang II) and endothelin-1 (ET-1) in the myocardium are assumed to be synergistic and supplemental. METHODS AND RESULTS: In the phase of compensated left ventricular (LV) hypertrophy of Dahl salt-sensitive rats, Ang II peptide and the ACE mRNA in the LV were increased by 1.6- and 3.8-fold, respectively. In contrast, ET-1 peptide and the preproET-1 mRNA remained unchanged. In subsequent congestive heart failure (CHF), Ang II and ACE mRNA did not show further increases. But ET-1 and the mRNA were increased de novo by 5.3- and 4.1-fold, respectively. In ascending aorta-banded rats, the local activations of Ang II and ET-1 also showed a differential time course between LV hypertrophy and CHF. Long-term treatments of Dahl salt-sensitive rats with temocapril (an ACE inhibitor) and with bosentan (a mixed ET receptor blocker) equally improved long-term survival. Temocapril reduced the LV/body weight ratio and ameliorated LV fractional shortening. Conversely, although bosentan equally improved fractional shortening, it did not reduce the increase in LV mass. Combined treatment with these 2 drugs further ameliorated the animal's survival without additional decreases in systolic pressure. CONCLUSIONS: The pathophysiological roles in the myocardium during the transition to CHF differ qualitatively between Ang II and ET-1. Thus, long-term therapy with a combination of ACE inhibition and ET antagonism may provide a new approach for heart failure in humans.

Treatable subsets in cancer of unknown primary origin.

The purpose of this study was to investigate the treatable subsets in cancer of unknown primary origin (CUP). Fifty patients (27 males and 23 females; median age, 53 years) with CUP diagnosed between April 1992 and June 1999 were analyzed retrospectively. Of the 50 patients, 39 received chemotherapy: platinum-based in 31, non-platinum-based in 4, and clinical trials of new agents in 4. Of the 39 patients, 13 (33.3%; 95% confidence interval: 19.1 - 50.2%) showed objective responses, with 4 complete responders. Patients with poorly differentiated carcinomas in whom beta-subunit of human chorionic gonadotropin (beta-HCG) was elevated more than 10 mIU / ml and female patients with peritoneal adenocarcinomatosis achieved high response rates (83.3% and 80%, respectively) with platinum-based chemotherapy, as compared with only a 15.3% response rate in the remaining patients. Platinum-based chemotherapy provided promising results in patients with poorly differentiated carcinomas and in female patients with peritoneal adenocarcinomatosis. Significantly elevated serum levels of beta-HCG in patients with poorly differentiated carcinoma might predict a better response to platinum-based chemotherapy. However, the investigation of novel chemotherapeutic approaches is warranted for other groups of patients with CUP.

Adenovirus is a key pathogen in hemorrhagic cystitis associated with bone marrow transplantation.

Late-onset hemorrhagic cystitis (HC) is a well-known complication of bone marrow transplantation (BMT) that is mainly attributed to infection with BK virus (BKV) and adenovirus (AdV). From 1986 through 1998, 282 patients underwent BMT, and 45 of them developed HC. Urine samples tested positive for AdV in 26 patients, of which 22 showed virus type 11. Among patients who underwent allogeneic BMT, logistic regression analysis revealed acute graft-versus-host disease (grade, > or = 2) to be the most significant predictive factor for HC (P < .0001). In addition, a total of 193 urine samples regularly obtained from 26 consecutive patients who underwent allogeneic BMT were examined for BKV, JC virus (JCV), and AdV by means of polymerase chain reaction. Of patients without HC, approximately 30% of the specimens tested positive for BKV (58 samples) and JCV (55 samples), whereas 5 (3%) tested positive for AdV. Of the 3 samples obtained from patients with HC, the numbers of positive results for BKV, JCV, and AdV were 3, 1, and 1, respectively; the numbers of positive results increased to 14 of 17, 9 of 17, and 10 of 17, respectively, when we added another 14 samples obtained from 14 patients with HC (P < .0001, P = .026, and P < .0001, respectively). In conclusion, there was significant correlation between AdV and HC in the patients we studied.

Dose-escalation study of CHOP with or without prophylactic G-CSF in aggressive non-Hodgkin's lymphoma.

BACKGROUND: CHOP is accepted as the gold standard for first line chemotherapy of aggressive non-Hodgkin's lymphoma (NHL). A dose-escalation study of CHOP was conducted to determine the maximal tolerated dose (MTD) and toxicity profile of CHOP at three-week intervals with or without prophylactic recombinant human granulocyte colony-stimulating factor (rHuG-CSF) in patients with aggressive NHL. PATIENTS AND METHODS: The doses of drugs were escalated from 50 mg/m2 to 70 mg/m2 for doxorubicin and from 750 mg/m2 to 2250 mg/m2 for cyclophosphamide, with conventional doses of vincristine and oral prednisolone. After the MTD was determined without rHuG-CSF, dose escalation was conducted with prophylactic rHuG-CSF. RESULTS: Thirty-three patients with NHL were enrolled into the study. The MTD without prophylactic rHuG-CSF was 70 mg/m2 of doxorubicin and 1250 mg/m2 of cyclophosphamide, with neutropenia as a dose-limiting toxicity. The MTD with prophylactic rHuG-CSF was 70 mg/m2 of doxorubicin and 2250 mg/m2 of cyclophosphamide. The overall response rate was 100% (76% complete response and 24% partial response). Progression-free survival and overall survival at five years were 45% and 66%, respectively. CONCLUSIONS: Significant dose escalation of doxorubicin and cyclophosphamide was feasible with prophylactic rHuG-CSF. The efficacy of dose-escalated CHOP should be compared with that of standard CHOP.

Study of dose escalation and sequence switching of administration of the combination of docetaxel and doxorubicin in advanced breast cancer.

The objectives of the present study were to evaluate whether a schedule-dependent pharmacokinetic and/or pharmacodynamic interaction exists between two sequences of docetaxel and doxorubicin administration and to determine the maximal tolerated dose (MTD) of this combination. Patients with chemotherapy-naïve metastatic or recurrent advanced breast cancer were enrolled. In the crossover design, tandem dose escalation of docetaxel and doxorubicin was performed. Docetaxel, in doses ranging from 50-70 mg/m2, was administered for 1 h by drip infusion either just before or after a 5-min bolus i.v. injection of doxorubicin at dosages from 40-50 mg/ m2. The sequence of drug administration was switched after the first course in each patient, and the sequence of drug administration thereafter depended on the patient's choice. Twenty-five patients were initially assessable for toxicity. The MTD in the sequence of doxorubicin after docetaxel was 40 and 50 mg/m2, respectively, with the dose-limiting toxicity of neutropenia. On the other hand, the MTD of the sequence of docetaxel after doxorubicin was 70 and 50 mg/m2, respectively. The dose-limiting toxicities in this sequence were neutropenia and diarrhea. Duration of grade 4 neutropenia in the sequence of docetaxel followed by doxorubicin was significantly longer than that in the alternate sequence (P = 0.0062). However, there was no difference in pharmacokinetic parameters of docetaxel, doxorubicin, and doxorubicinol between the two sequences. The sequence of 50 mg/m2 doxorubicin followed by 60 mg/m2 docetaxel is recommended for subsequent clinical trials for practical reasons.

[Clinical effects of combination therapy with cefozopran and tobramycin for severe infections in patients with hematologic diseases].

We studied clinical effect of a combination therapy with cefozopran (CZOP) and tobramycin (TOB) for infections in 80 patients with hematologic diseases in 15 institutes. Combined doses with CZOP 2 g and TOB 60-90 mg twice a day had been given intravenously. Of the 80 patients, 61 patients (42 with acute leukemia, 10 with malignant lymphoma, 3 with aplastic anemia, 2 with chronic myeloid leukemia, 2 with multiple myeloma, and 2 with myelodysplastic syndrome) were evaluable. Those consisted of 6 patients with septicemia, 49 with suspected septicemia, 3 with pneumonia, and 3 with other infections. Clinical efficacy by the treatment was excellent in 24, good in 17, fair in 9, and poor in 11 patients, and the overall efficacy rate including excellent and good was 67.2%. Microbiologically, 5 of the 6 patients with septicemia (1 coagulase negative Staphylococcus, 2 S. pneumoniae, 1 S. oralis, and 1 E. coli) were responded. The efficacy rate in patients with severe granulocytopenia showing 100/microliter or lesser neutrophil counts during the drug administration was 57.1% (12/21). Side effects and abnormal changes of clinical laboratory findings were observed in 5 patients, and 16 patients, respectively, but most of them were mild. The findings above suggested that the combination therapy with CZOP and TOB is useful as an empiric therapy for severe infections in patients with hematologic diseases.

Apoptosis during iron chelator-induced differentiation in F9 embryonal carcinoma cells.

We have previously demonstrated that three potent iron chelators, hinokitiol, dithizone and deferoxamine, induce differentiation of F9 embryonal carcinoma cells, as do other well-known morphogens such as retinoic acid (RA) and sodium butyrate (NaB). In this study, we compared the patterns of cell proliferation, cell death and cell cycle arrest during the process of differentiation induced by these five agents. When F9 cells were cultured with the agents at their individual differentiation-inducing concentrations, cell proliferation was rapidly inhibited by treatment with the iron chelators and NaB. In contrast, RA did not influence the rate of increase of cell number at the concentration of 1 microm. The three chelators also caused a marked reduction in cell viability, and the treated cells exhibited internucleosomal DNA fragmentation, whereas cells treated with NaB showed no apoptotic characteristics. RA induced apoptosis weakly at 1 microm and strongly at higher concentrations. In addition, all the iron chelators hindered cell cycle progression, resulting in an arrest at the G1-S interface or S phase. The phenomena observed in chelator-treated cells were considerably different from those in RA- or NaB-treated cells. It is concluded that the three iron chelators cause both severe apoptotic cell death and cell cycle arrest of proliferating F9 cells via cellular iron deprivation, and that this apoptotic change may be independent of the process of differentiation.

[Effective splenectomy in a patient with HIV-associated thrombocytopenia].

A 31-year-old man presented with a 3-month history of petechial hemorrhages. Physical examination revealed no splenomegaly. The patient's platelet count was 1.0 x 10(9)/l and bone marrow aspiration showed an elevated number of megakaryocytes. A diagnosis of HIV-associated thrombocytopenia was made on the basis of HIV seropositive results. The CD4 cell count was 400 x 10(6)/l. No opportunistic infections indicating AIDS were detected. Initially the patient was treated with predonisolone, but showed only a transient response. He also failed to respond to zidovudine, lamivudine, or indinavir. Following splenectomy, however, his platelet count rose above 80 x 10(9)/l (normal level: 150-350 x 10(9)/l).

[Hemolytic uremic syndrome after bone marrow transplantation].

One hundred and thirteen patients who underwent autologous or allogeneic bone marrow transplantation (BMT) were investigated for the subsequent development of hemolytic uremic syndrome (HUS). HUS developed in seven patients (four males and three females, five acute lymphocytic leukemia (ALL), one acute myelogenous leukemia, one non-Hodgkin's lymphoma) between 36-196 days after BMT. Four patients were recipients of autologous BMT and three were those of allogeneic BMT. Six patients were preconditioned with the regimens including fractionated total body irradiation (TBI). ALL and preconditioning regimen with TBI were suspected to be the risk factors for the development of HUS. Cyclosporin A (CSP) administration was discontinued in three patients who had been given CSP for graft-versus-host disease prophylaxis. Predonisolone was given to the three patients and plasma exchange was performed in one patient. Both hemolytic anemia and thrombocytopenia were resolved in virtually all patients, while creatinine elevation has persisted along with hypertension in one patient.

Utility and safety of Hickman catheters for venous access after bone marrow transplantation.

Hickman catheters are useful for vascular access after bone marrow transportation because they can handle large volume and allow for easy transfusions and blood drawing through wide double lumens making it easier to case for patients under sterile conditions in a clean room. However, the safety of Hickman catheters as compared to Silastic catheters in marrow transplants has never been discussed. We therefore retrospectively reviewed the complications of two catheters in 71 allogeneic bone marrow transplant recipients between September 1986 and August 1994. The complication and infection rates of Hickman catheters were 0.21 and 0.09 per 100 device-life days, and rate of temperature >38 degrees C during leukocytopenia (<1,000 white blood cells) was 0.18. These rates were not different from those of Silastic catheters suggesting that Hickman catheters are safe and acceptable in marrow transplantation. The benefits and drawbacks of Hickman catheters relevant to catheter choice were also discussed.

Incidence and influence of GB virus C and hepatitis C virus infection in patients undergoing bone marrow transplantation.

Markers of GB virus C (GBV-C) and hepatitis C virus (HCV) were sought in 80 patients before and after they underwent BMT in a metropolitan hospital in Tokyo between 1990 and 1996. RNA of GBV-C was detected in 14 (18%) patients before BMT. Of the 55 patients who had been transfused, 14 (25%) possessed GBV-C RNA at a frequency significantly higher than in the 25 untransfused patients who were all negative (P < 0.01). HCV RNA was detected in three of the 55 (5%) transfused patients, but in none of the 25 untransfused patients. Sera at 3 months after BMT were available for 57 patients. GBV-C RNA persisted in all 10 patients who were infected before BMT, while it was detected in five of the remaining 47 (11%) patients who were not. However, persistent and/or ongoing GBV-C infection had no appreciable influence on patient morbidity or mortality. Two of the 57 patients were positive for HCV RNA before BMT and this persisted after BMT in both. HCV RNA became positive in eight of the remaining 55 (15%) patients who were negative before BMT. Of the 14 patients who received transfusions screened by the first-generation test at BMT, seven (50%) became positive for HCV RNA, a rate significantly higher than the one of 41 (2%) patients who received transfusions screened by the second-generation test (P < 0.001). These results indicate that BMT patients are at increased risk of GBV-C infection transmitted by transfusions received before and at the time of BMT, and that the risk of HCV infection has decreased after the implementation of the second-generation anti-HCV test.