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Aim: This study aimed to assess the ability of preoperative axial computed tomography (CT) to predict surgical difficulty in bringing the ileal pouch to the level of the anus during restorative proctocolectomy (RPC)., Method: Patients who underwent RPC with an ileal pouch-anal anastomosis (or ileal pouch-anal canal anastomosis) in our institution between January 2008 and April 2014 were enrolled. The patients were divided into two groups, including those in whom CT indicated potential difficulty in extending the pouch downwards (extension difficult (ED) group) and patients with no CT evidence of potential difficulty (normal group). The groups were compared for clinical factors and the thickness of the slices of CT showing the root of the superior mesenteric artery, the point of communication of the ileocaecal artery with the marginal artery (tICA) and the anal verge (AV). Receiver-operating characteristic analysis was performed, and a cut-off value was calculated for predicting the degree of difficulty in bringing the ileal pouch down to the anal canal., Results: Thirty-four patients were entered in the study. The ED group included significantly taller patients and more with familial adenomatous polyposis than the normal group. The distance between tICA and AV was significantly longer in the ED group, with a cut-off of 21 cm giving a sensitivity of 100% and a specificity of 83.3%., Conclusion: The distance between tICA and AV measured by axial CT can be a useful predictor for the difficulty in bringing the ileal pouch down to the anus during RPC., (Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.)

The occurrence of traumatic abdominal wall hernia secondary to blunt trauma is uncommon, and laparoscopic repair of such hernias is very rare. A 53-year-old man, who had sustained injuries to his right thigh and right abdomen 8 months previously, visited a hospital because of a bulge in the right lateral abdomen. An abdominal computed tomography scan revealed a rupture in the lateral abdominal muscle and herniation of the cecum into the subcutaneous space. Accordingly, delayed traumatic abdominal wall hernia was diagnosed, which was successfully repaired laparoscopically. Thus, a laparoscopic tension-free mesh repair was safely and effectively performed for delayed traumatic abdominal wall hernia.

Understanding the mechanisms underlying the bystander effects of low doses/low fluences of low- or high-linear energy transfer (LET) radiation is relevant to radiotherapy and radiation protection. Here, we investigated the role of gap-junction intercellular communication (GJIC) in the propagation of stressful effects in confluent normal human fibroblast cultures wherein only 0.036-0.144% of cells in the population were traversed by primary radiation tracks. Confluent cells were exposed to graded doses from monochromatic 5.35 keV X ray (LET ~6 keV/μm), 18.3 MeV/u carbon ion (LET ~103 keV/μm), 13 MeV/u neon ion (LET ~380 keV/μm) or 11.5 MeV/u argon ion (LET ~1,260 keV/μm) microbeams in the presence or absence of 18-α-glycyrrhetinic acid (AGA), an inhibitor of GJIC. After 4 h incubation at 37°C, the cells were subcultured and assayed for micronucleus (MN) formation. Micronuclei were induced in a greater fraction of cells than expected based on the fraction of cells targeted by primary radiation, and the effect occurred in a dose-dependent manner with any of the radiation sources. Interestingly, MN formation for the heavy-ion microbeam irradiation in the absence of AGA was higher than in its presence at high mean absorbed doses. In contrast, there were no significant differences in cell cultures exposed to X-ray microbeam irradiation in presence or absence of AGA. This showed that the inhibition of GJIC depressed the enhancement of MN formation in bystander cells from cultures exposed to high-LET radiation but not low-LET radiation. Bystander cells recipient of growth medium harvested from 5.35 keV X-irradiated cultures experienced stress manifested in the form of excess micronucleus formation. Together, the results support the involvement of both junctional communication and secreted factor(s) in the propagation of radiation-induced stress to bystander cells. They highlight the important role of radiation quality and dose in the observed effects.

Purpose: We aimed to clearly visualize heterogeneous distribution of hypoxia-inducible factor 1α (HIF) activity in tumor tissues in vivo., Methods: We synthesized of (125)I-IPOS, a (125)I labeled chimeric protein probe, that would visualize HIF activity. The biodistribution of (125)I-IPOS in FM3A tumor-bearing mice was evaluated. Then, the intratumoral localization of this probe was observed by autoradiography, and it was compared with histopathological findings. The distribution of (125)I-IPOS in tumors was imaged by a small animal SPECT/CT scanner. The obtained in vivo SPECT-CT fusion images were compared with ex vivo images of excised tumors. Fusion imaging with MRI was also examined., Results: (125)I-IPOS well accumulated in FM3A tumors. The intratumoral distribution of (125)I-IPOS by autoradiography was quite heterogeneous, and it partially overlapped with that of pimonidazole. High-resolution SPECT-CT fusion images successfully demonstrated the heterogeneity of (125)I-IPOS distribution inside tumors. SPECT-MRI fusion images could give more detailed information about the intratumoral distribution of (125)I-IPOS., Conclusion: High-resolution SPECT images successfully demonstrated heterogeneous intratumoral distribution of (125)I-IPOS. SPECT-CT fusion images, more favorably SPECT-MRI fusion images, would be useful to understand the features of heterogeneous intratumoral expression of HIF activity in vivo.

To image hypoxia-inducible factor-1 (HIF-1)-active tumors, we previously developed a chimeric protein probe ([(123/125) I]IPOS) that is degraded in the same manner as HIF-1α under normoxic conditions. In the present study, we aim to show that the accumulation of radioiodinated POS reflects the expression of HIF-1. In vivo single-photon emission computed tomography (SPECT)/X-ray CT (CT) imaging, autoradiography, and double-fluorescent immunostaining for HIF-1α and pimonidazole (PIMO) were carried out 24 h after the injection of [(125) I]IPOS. Tumor metabolite analysis was also carried out. A tumor was clearly visualized by multi-pinhole, high-resolution SPECT/CT imaging with [(125) I]IPOS. The obtained images were in accordance with the corresponding autoradiograms and with the results of ex vivo biodistribution. A metabolite analysis revealed that 77% of the radioactivity was eluted in the macromolecular fraction, suggesting that the radioactivity mainly existed as [(125) I]IPOS in the tumors. Immunohistochemistry revealed that the HIF-1α-positive areas and PIMO-positive areas were not always identical, only some of the regions were positive for both markers. The areas showing [(125) I]IPOS accumulation were positively and significantly correlated with the HIF-1α-positive areas (R = 0.75, P < 0.0001). The correlation coefficient between [(125) I]IPOS-accumulated areas and HIF-1α-positive areas was significantly greater than that between the [(125) I]IPOS-accumulated areas and the PIMO-positive areas (P < 0.01). These findings indicate that [(125) I]IPOS accumulation reflects HIF-1 expression. Thus, [(123/125) I]IPOS can serve as a useful probe for the molecular imaging of HIF-1-active tumors., (© 2011 Japanese Cancer Association.)

We treated a woman with membranous nephropathy in whom serious nephrotic syndrome (NS) continued even after the introduction of hemodialysis (HD). No response was seen with conservative treatment, including administration of steroids and albumin transfusion and body fluid management with HD. Hypoalbuminemia continued, and management of her general condition was problematic because of the hypotension, edema, pleural and peritoneal effusions. We performed percutaneous renal artery embolization (RAE), voluntary urine output disappeared for a short time, and good clinical course was subsequently seen with sustainable serum albumin levels of around 3 g/dL.

We investigated the protective effect of several heterocyclic pyrimidine compounds against ultraviolet B (UVB)-induced damage in human keratinocyte HaCaT cells, as well as the inhibitory effect on melanogenesis in B16 melanoma cells. One of the compounds examined, 2-piperadino-6-methyl-5-oxo-5,6-dihydro(7H)pyrrolo[3,4d]pyrimidine maleate (MS-818), showed low cytotoxicity even at 500 microM. At 50-500 microM, MS-818 dose-dependently suppressed the UVB (100 mJ/cm(2))-induced elevation of tumor necrosis factor alpha (TNF-alpha), one of the trigger cytokines for cell death, in HaCaT cells. In addition, MS-818 (100 microM) markedly inhibited melanogenesis in B16 melanoma cells via downregulation of tyrosinase expression mediated by microphthalmia-associated transcription factor (MITF) and extracellular signal-regulated kinase (ERK). In conclusion, MS-818 protected epidermal cells from UVB-induced damage and also suppressed melanogenesis in melanoma cells. It appears to be a good candidate for a new UVB-protective and whitening agent for application in cosmetics.

Autophagy is one of the major processes involved in the degradation of intracellular materials. Here, we examined the potential impact of heavy ion irradiation on the induction of autophagy in irradiated C2C12 mouse myoblasts and their non-targeted bystander cells. In irradiated cells, ultrastructural analysis revealed the accumulation of autophagic structures at various stages of autophagy (i.e. phagophores, autophagosomes and autolysosomes) within 20 min after irradiation. Multivesicular bodies (MVBs) and autolysosomes containing MVBs (amphisomes) were also observed. Heavy ion irradiation increased the staining of microtubule-associated protein 1 light chain 3 and LysoTracker Red (LTR). Such enhanced staining was suppressed by an autophagy inhibitor 3-methyladenine. In addition to irradiated cells, bystander cells were also positive with LTR staining. Altogether, these results suggest that heavy ion irradiation induces autophagy not only in irradiated myoblasts but also in their bystander cells.

Low- or intermediate-dose gamma radiation appears to have the capacity to ameliorate certain types of diseases, including allergic conditions, when examined under specific exposure conditions and with specific animal models, though the molecular mechanisms involved remain to be fully clarified. We investigated the anti-inflammatory effects of intermediate-dose gamma radiation by examining its effects on the activation state of p38 MAPK and the production of cytokines in mouse macrophage RAW264.7 cells. Dephosphorylation of both ERK1/2 and p38 MAPK was observed at 15 min after irradiation (0.5-1 Gy from a (137)Cs source) concomitant with a significant increase in the expression of MKP-1, which dephosphorylates ERK1/2 and p38 MAPK. Since activated p38 MAPK mediates TNF-alpha production, we examined the effect of radiation on LPS-induced activation of p38 MAPK and TNF-alpha production. The activation of p38 MAPK and production of TNF-alpha induced by LPS treatment were both suppressed in preirradiated cells. LPS-induced production of TNF-alpha was enhanced by knockdown of MKP-1. These results indicate that 0.5 Gy gamma radiation would cause up-regulation of MKP-1, leading to inactivation of p38 MAPK and suppression of TNF-alpha production, in cells of mouse macrophages cell line.

Chlorinated derivatives of bisphenol A (ClBPAs) have been detected in wastewater from waste paper recycling plants. We previously reported that bisphenol A (BPA) and ClBPAs [3-chlorobisphenol A, 3,3'-dichlorobisphenol A, and 3,3',5-trichlorobisphenol A] irradiated with ultraviolet (UV) B or UVC (not with UVA) induced inhibition of cell growth, and that 3-hydroxybisphenol A (3-OHBPA) was detected in the photoproducts [Mutou, Y., Ibuki, Y., Terao, Y., Kojima, S., Goto, R., 2006b. Chemical change of chlorinated bisphenol A by ultraviolet irradiation and cytotoxicity of their products on Jurkat cells. Environmental Toxicology and Pharmacology, 21, 283-289]. The formation of hydroxylated BPAs by UV irradiation might contribute to the inhibition of cell growth, but the mechanism of the growth inhibition is not clarified. In this study, we investigated whether BPA and ClBPAs exposed to UVA, UVB, or UVC, and 3-OHBPA could induce the death of Jurkat cells and whether the pattern of cell death was apoptosis. ClBPAs exposed to UVB and UVC induced significant cell death, but those exposed to UVA and BPA did not. The cell death was apoptosis because chromatin condensation and DNA fragmentation were detected. Activation of caspase-3, -8, and -9 and cytochrome c release indicated that ClBPAs exposed to UVB or UVC induced apoptosis via typical apoptotic pathways. In addition, 3-OHBPA induced apoptosis similar to UVB- or UVC-irradiated ClBPA. These results suggested that the photoproducts of ClBPAs generated by UV irradiation, containing 3-OHBPA, contributed to the induction of apoptosis.

Background: Atopic dermatitis (AD) is a common pruritic inflammatory skin disease, which occurs primarily in childhood. Recently, narrow-band ultraviolet B (UVB) phototherapy has been used to treat AD, but the mechanism involved is unknown. In this study, we investigated whether UVB irradiation influences AD in the NC/Nga mouse., Methods: The mice were separated into three groups: control, AD-control (immunized with mite antigens), and AD+UVB-irradiated (immunized with mite antigens and UVB irradiation) groups. The mice in the irradiation group were exposed to 1 kJ/m(2)/day twice a week from 6 to 12 weeks of age. Animals in the control and AD-control groups were shaved, but not irradiated., Results: In the AD+UVB-irradiated group, the atopy score, ear thickness, and total immunoglobulin E (IgE) were increased in comparison with the AD-control group. On day 40, the levels of interleukin (IL)-4, IL-5, and IL-10 in the spleen lymphocytes were significantly increased compared with the AD-control group, resulting in a marked decrease of the interferon (IFN)-gamma/IL-4 ratio compared with the AD-control group. In addition, the levels of IL-6, tumor necrosis factor (TNF)-alpha, and NO(x) production by peritoneal macrophages were significantly elevated., Conclusion: These results indicate that UVB irradiation promotes the development of AD-like skin lesions in NC/Nga mice.

Bisphenol A (BPA) and chlorinated bisphenol A (ClBPAs) were detected in wastewater from waste paper recycling plants. In previous study, we showed the acute cytotoxicity of oxidized products of BPA and ClBPAs generated by ultraviolet (UV) irradiation. However, estrogenic activities of these photoproducts have not been studied. Therefore, we investigated change of estrogenic activities of BPA and ClBPAs [3-chlorobisphenol A (3-ClBPA), 3,3'-dichlorobisphenol A (3,3'-diClBPA) and 3,3',5-trichlorobisphenol A (3,3',5-triClBPA)] after UVB irradiation using yeast two-hybrid assay. The agonist activities of ClBPAs were higher than that of BPA in the absence of S9. ClBPAs irradiated with UVB lost agonist activities. The addition of S9 also completely erased the activity. The antagonist activities of BPA and ClBPAs with or without UVB irradiation were not detected both in the absence or presence of S9. UVB irradiation (0-100 J/cm2) decreased the agonist activity of 3,3'-diClBPA in proportion to increase of released chloride ion. The agonist activity was completely lost at 50 J/cm2 of UVB, of which dose could dissociated almost all chlorine. These findings suggested that UVB irradiation could decrease the estrogenic activity of chlorinated compounds, which was due to the selective release of chloride ion.

Chlorinated derivatives of bisphenol A (ClBPAs) have been detected in wastewater from waste paper recycling plants. BPA and ClBPAs are always exposed to ultraviolet (UV) radiation in the environment and consequently various photoproducts might be produced. Acute cytotoxicity of photoproducts of BPA and ClBPAs are not known. In this study, we investigated the cytotoxicity and chemical structure of photoproducts of BPA and ClBPAs (3-chlorobisphenol A (3-ClBPA), 3,3'-dichlorobisphenol A (3,3'-diClBPA) and 3,3',5-trichlorobisphenol A (3,3',5-triClBPA)) after UV irradiation (UVA, UVB and UVC). The toxicities of photoproducts on Jurkat cells were determined by Alamar Blue assay, and the chemical structures of the photoproducts were identified using GC/MS. The cytotoxicities of 3-ClBPA and 3,3'-diClBPA were higher than that of BPA and 3,3',5-triClBPA. In addition, the toxicities of ClBPAs were increased by the irradiation of UVB and UVC at 100J/cm(2) and decreased at 1000J/cm(2) in comparison with those at 100J/cm(2), indicating that their structures had changed. 3-Hydroxybisphenol A (3-OHBPA) was detected in the photoproducts of 3-ClBPA irradiated with UVB and UVC at 100J/cm(2), and 3-OHBPA and 3-chloro-3'-hydroxybisphenol A (3-Cl-3'-OHBPA) were detected in those of 3,3'-diClBPA. However, these hydroxylated BPAs were not detected in the photoproducts exposed to 1000J/cm(2). The cytotoxicity of 3-OHBPA was the almost same as ClBPAs after UVB and UVC irradiation. These results indicate that the formation of hydroxylated BPAs might contribute to the increase in toxicity caused by UV irradiation.

It has been speculated that the use of hydroxy-methyl-glutaryl coenzyme A reductase inhibitors (statins) is associated with the risk of malignant diseases. Considering their immunosuppressive activities, malignant diseases that are associated with an immunosuppressive status seem feasible to examine the association. We therefore examined the association between statin use and development of lymphoid malignancies in a case-control study. Cases were 221 consecutive incident cases with histopathologically proven lymphoid malignancies (lymphoma and myeloma), hospitalized in the Department of Hematology of Toranomon Hospital (Tokyo, Japan) between 1995 and 2001. Two independent control groups, comprising 442 and 437 inpatients without malignancies from the Departments of Orthopedics and Otorhinolaryngology of the same hospital, were selected to test for consistency of association. Controls were matched individually with cases for age, sex and year of admission. Subject information, including statin use, was abstracted from medical records at the time of hospitalization. Strength of association was evaluated as an adjusted odds ratios (aOR) using a conditional logistic regression model. A higher frequency of statin use was found among patients with lymphoid malignancies in comparison with both orthopedic (aOR 2.11, 95% CI 1.20-3.69, P = 0.009) and otorhinolaryngology patients (aOR 2.59, 95% CI 1.45-4.65, P = 0.001), the significance being maintained when the two control groups were combined (aOR 2.24, 95% CI 1.37-3.66, P = 0.001). In conclusion, we observed an elevated risk of lymphoid malignancy with statin use among Japanese patients. Further evaluations in different populations are required to draw conclusions as to the carcinogenicity of lymphoid malignancies with statin use.

We reviewed medical records of 256 patients to investigate the frequency and characteristics of hemorrhagic cystitis (HC) associated with reduced-intensity stem cell transplantation (RIST) as opposed to conventional stem cell transplantation (CST); 137 patients underwent CST and 119 RIST. Diagnosis of HC was made based on two or more episodes of sterile, macroscopic hematuria with normal coagulation profiles, without any evidence of renal stones or genitourinary malignancy. Actuarial frequency of HC development in RIST group was 7.6% (9/119), which gave a cumulative annual incidence of 11.7%. In CST group, 13 of 137 patients (9.5%) developed HC, giving an estimated annual incidence of 9.7%. The probability of developing HC was similar between the two groups (P=0.77). The viral etiologies of HC, adenovirus (n=12) and BK virus (n=2), were documented in eight patients after RIST and in six after CST. HC was milder and of a shorter duration, with less blood transfusion requirements, in RIST group than in CST group. A multivariate analysis revealed that HC was associated with antiadenovirus antibody positivity in the recipients, total dose of busulfan, and chronic GVHD. Although HC following RIST is less severe than that following CST, it is still a significant problem.

A 59-year-old man with liver cirrhosis due to hepatitis B virus infection received non-myeloablative stem-cell transplantation (NST) for the treatment of adult T-cell lymphoma. The preparative regimen consisted of cyclophosphamide and fludarabine. While the pharmacokinetics of these drugs was altered in this patient, his clinical course was uneventful without the development of severe hepatic damage. Complete remission was achieved on day 56. Although he finally died of hemorrhage from esophageal varices on day 68, this case suggests that ATL may be a good candidate for allogeneic HSCT, and that NST may be feasible for patients with hepatic impairment.

A 54-year-old man with chronic myelocytic leukemia in blastic phase received reduced-intensity transplantation (RIST) from an HLA-identical unrelated donor. The preparative regimen consisted of busulfan, fludarabine, and anti-thymocyte globulin. Graft-versus-host disease (GVHD) prophylaxis was cyclosporine alone. Because he had a high risk of relapse, we discontinued cyclosporine on day 37, but he did not develop any signs of acute GVHD. To induce GVHD and augment a graft-versus-leukemia effect, we initiated interferon-alpha therapy on day 80 to a maximum dosage of three million units five times a week. He achieved molecular remission on day 94 followed by the development of extensive chronic GVHD the severity of which paralleled to the dose of interferon-alpha GVHD gradually subsided after discontinuation of interferon-alpha and the patient remains in molecular remission 18 months after transplantation. This case suggests that early withdrawal of cyclosporine and the prophylactic use of interferon-alpha are promising in RIST for high-risk leukemia., (Copyright 2002 Wiley-Liss, Inc.)

To evaluate the diagnostic value of a halo on computed tomography (CT) in the diagnosis of invasive pulmonary aspergillosis (IPA), we retrospectively reviewed chest CT scans and autopsy reports for patients who had been admitted to our hospitals for the treatment of hematological malignancy. Pulmonary complications were suspected in all patients and chest CT scans were taken within a month of death. We examined the association between autopsy and CT findings in 48 patients who were diagnosed as IPA (n = 17), candidosis (n = 4), zygomycosis (n = 2), infiltration of hematological malignancy (n = 12), bacterial pneumonia (n = 6), cytomegalovirus pneumonia (n = 2), pulmonary hemorrhage (n = 2), or pulmonary congestion (n = 1). Patients with IPA showed a variety of CT findings, including halo (n = 13), nodules (n = 14), granular shadows (n = 3), masses (n = 6), consolidations (n = 9), wedge-shaped consolidations (n = 1), and cavitation (n = 2). In contrast, 0, 11 and two of the 31 patients without IPA showed halo, nodules and masses, respectively. These signs were more frequently observed in IPA patients than in non-IPA patients. The CT halo, especially, seemed to be specific for IPA in hospitalized neutropenic patients with hematological malignancies who developed antibiotic-resistant fever. For CT findings other than these three signs, there were no significant differences between IPA- and non-IPA patients.

We compared a CMV virus load determined by real-time PCR with an antigenemia value to analyze the correlation between these two methods. We also compared the values for virus load determined by the two distinct real-time PCR methods, which amplify the US17 region and immediate-early (IE) gene of CMV, respectively, to evaluate the reliability of these methods. Two hundred and sixty-five samples were obtained weekly from 29 patients, who had engraftment after unrelated bone marrow transplantation or HLA-mismatched related blood stem cell transplantation. CMV infection was detected in 115 samples from 22 patients by US17-PCR and 69 samples from 20 patients by the antigenemia assay. Fifty-eight samples were positive for both assays, but 57 and 11 samples were positive only for US17-PCR and antigenemia, respectively. A good correlation of the results of US17-PCR and antigenemia was demonstrated (r = 0.61). All antigenemia-positive samples and randomly selected antigenemia-negative samples were subjected to IE-PCR. The results of IE-PCR showed a good correlation with those of antigenemia (r = 0.64). Furthermore, the best correlation was observed between US17-PCR and IE-PCR (r = 0.83). In conclusion, both real-time PCR methods showed a good correlation with the antigenemia assay, and could be used to monitor CMV infection after hematopoietic stem cell transplantation.

A 27-year-old man with aplastic anemia and renal insufficiency requiring dialysis underwent allogeneic PBSCT. The preparative regimen consisted of melphalan, ATG and TLI. GVHD prophylaxis consisted of cyclosporine and prednisolone. He was dialyzed prior to administration of melphalan and at 24 and 72 h after it. Otherwise, the dialysis schedule was unchanged, at three times a week. Engraftment was rapid. Regimen-related toxicity was minimal. Pharmacokinetic parameters of melphalan were not significantly altered with its plasma half-life 1.5 h. Patients with renal failure can receive allogeneic HSCT, and a combination of melphalan, ATG and TLI may serve as an alternative to CY and ATG.

A 23-year-old man with chronic myelocytic leukemia (CML) in the first chronic phase underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from his HLA-identical sibling. Pretransplant evaluations showed that he had a low risk of transplantation-related mortality and that the interval between the diagnosis of CML and PBSCT was only 6 months. However, he developed a variety of complications, including acute renal failure requiring hemodialysis, severe hepatic damage, hemorrhagic cystitis, and gastrointestinal hemorrhage leading to hypovolemic shock. Pathological examination of the colonic mucosa showed vascular endothelial damage and thrombotic lesions, leading to the diagnosis of thrombotic microangiopathy. Later, we found that he had the constitutional abnormality XYY. XYY syndrome is a frequent congenital abnormality, and mental disorders and congenital abnormalities of kidney and liver are common manifestations. Considering his clinical course, it was interesting that complications were severe in the organs which are frequently involved in cases of XYY syndrome. These organs may have poor function or poor reserves and may be more vulnerable to endothelial damage caused by high-dose cytotoxic chemotherapy. Patients with XYY syndrome might have a high risk of transplantation-related mortality.

To investigate the utility of blood culture of invasive fungal infections in patients with haematological malignancies, an autopsy survey was conducted in 720 patients who were treated between 1980 and 1999. We identified 252 patients with invasive mycosis. These included Candida (n = 94), Aspergillus (n = 91), Zygomycetes (n = 34), Cryptococcus (n = 7), Trichosporon (n = 11), Fusarium (n = 1), and unknown fungi (n = 20). Of the 94 patients with invasive candidiasis, 20 had positive blood cultures. Of the 11 patients with invasive trichosporonosis, seven had positive blood cultures. The sensitivities of blood cultures were 1.1%, 0% and 14% for detecting invasive aspergillosis, zygomycosis and cryptococcosis respectively. Multiple regression analysis showed a significant correlation between results of Candida blood cultures and some variables, including prophylactic use of absorbable antifungals (P = 0.0181) and infection by Candida albicans (P = 0.0086). The sensitivity of blood cultures decreased when patients received antifungal chemoprophylaxis. Unless these agents are inactivated in culture bottles, conventional blood cultures might produce false-negative results.

Invasive aspergillosis is a common form of fungal infection in patients with hematological malignancies. Because Aspergillus species have angioinvasive properties, they frequently disseminate from the lung to a variety of organs via hematogenous spread. Extra-pulmonary involvement occurs at an advanced stage of invasive aspergillosis, and represents an ominous sign. However, few reports have been published on extra-pulmonary involvement in cases of aspergillosis. Its clinical features have not been fully clarified. We experienced a patient who developed thyrotoxicosis and fatal airway obstruction caused by invasive aspergillosis of the thyroid. A 26-year-old man was admitted to our hospital for the treatment of non-Hodgkin's lymphoma. During myelosuppression following the chemotherapy, he developed cervical swelling and hyperthyroidism. We suspected lymphoma infiltration to the thyroid, and irradiated it with a total of 26 Gy. However, the cervical lesion enlarged rapidly, and he complained of wheezing and dyspnea. We underwent immediate tracheostomy to secure the airway, but he died. Autopsy findings were striking. Extensive necrosis with diffuse infiltration of Aspergillus hyphae was observed in the thyroid gland. Necrotic tissues of the thyroid protruded into the tracheal lumen, causing airway obstruction. This case demonstrated that invasive aspergillosis of the thyroid can lead to medical emergency.

A 53-year-old man who had a history of fluminant hepatitis caused by precore mutant hepatitis B virus (HBV) was admitted to our hospital for the treatment of relapsed non-Hodgkin's lymphoma in July 2000. At admission, serum levels of aspartate aminotransferase and alanine aminotransferase were normal, but he tested positive for HBs antigen. The titer was 64-fold by radioimmunoassay. We initiated lamivudine at a daily dose of 75 mg to prevent HBV proliferation during chemotherapy. By September 2000, he had received six courses of rituximab at 375 mg/m(2) and four courses of fludarabine and mitoxantrone. No hepatic damage was observed from the initiation of treatment until March 2001. At present, four months after the completion of chemotherapy, he continues lamivudine, and the titer of HBs antigen is low at 4-fold. Rituximab is usually associated with mild toxicity, usually limited to infusion periods. The drug is not generally associated with increased incidence of opportunistic infections. However, some case reports have been recently published on severe viral infections following administration of rituximab. These include fluminant hepatitis caused by HBV, pure red cell aplasia due to parvovirus B19 and fatal varicella-zoster infection. While it remains unknown whether rituximab can be safely administered in patients with chronic HBV infection, this case report suggested that prophylactic administration of lamivudine is beneficial for suppressing reactivation of HBV during chemotherapy including rituximab. Rituximab should be used cautiously for patients with HBV infection, but prophylactic administration of lamivudine may be beneficial for preventing reactivation of HBV., (Copyright 2001 Wiley-Liss, Inc.)

We developed a new quantitative system for diagnosis of invasive pulmonary aspergillosis (IPA) using real-time automated polymerase chain reaction (PCR). Intra-assay and interassay precision rates for in vitro examination were 2.53% and 2.20%, respectively, and the linearity of this assay was obtained when there were >20 copies/well. We examined 323 samples taken from 122 patients with hematological malignancies, including 33 patients with IPA and 89 control patients. Blood samples were subjected to PCR antigen detection methods, using enzyme-linked immunosorbent assay (ELISA) and determination of plasma (1-->3)-beta-D-glucan (BDG) concentration. The sensitivities of PCR, ELISA, and BDG measurement for diagnosis of IPA were 79%, 58%, and 67%, respectively; the specificities were 92%, 97%, and 84%. Positive findings on PCR preceded those of computed tomography by -0.3+/-6.6 days, those of BDG measurement by 6.5+/-4.9 days, and those of ELISA by 2.8+/-4.1 days. Real-time PCR was sensitive for IPA diagnosis, and quantitation was accurate.

A 63-year-old man received high-dose cyclophosphamide for peripheral blood stem-cell (PBSC) harvest. He received 200 mg fluconazole. On day 3, atrial fibrillation developed with blood pressure declining to 78 mmHg. The rapid adrenocorticotropin (ACTH) test showed blunted adrenal responses. He was suspected as having adrenal failure, and fluconazole was discontinued. The rapid ACTH test became normal on Day 14, and PBSCs were successfully harvested. To clarify the association between adrenal failure and fluconazole, we resumed 400 mg fluconazole on Day 16 and repeated the test on Day 21, which showed blunted adrenal responses. This case demonstrates that prophylactic use of fluconazole can cause adrenal insufficiency., (Copyright 2001 Wiley-Liss, Inc.)

A 71-year-old male was diagnosed as having pyothorax-associated lymphoma (PAL), a rare hematological malignancy associated with artificial pneumothorax for the treatment of pulmonary tuberculosis. Because of the low incidence, its clinical features have not been fully clarified. The PAL lesion in this patient disappeared after local radiotherapy and corticosteroid treatment. However, 8 months after the initial diagnosis, he developed a variety of neurological disorders and low-grade fever. Neither recurrence of the primary pulmonary lesion nor nodal enlargement was observed. Immediate magnetic resonance imaging of the brain revealed a ring-enhanced mass, suggesting a brain abscess. However, through a stereotactic biopsy of the brain lesion, infiltration of PAL cells was identified. The brain lesion rapidly enlarged despite intensive radiotherapy, and he finally died of lymphoma progression. This case demonstrates that PAL may progress as a type of extranodal lymphoma, and that brain lesions may produce a ring-enhanced pattern on computed tomography.

Intradermal stitch blepharoplasty is one of the most frequently performed aesthetic surgeries in Japan. The major disadvantage of this method is the general feeling that it is nonpermanent. Mutou and Mutou [1] first published this technique in 1972. From 1957 to 1997, they have performed 20,098 cases of this procedure. The aim of this study was to furnish a retrospective analysis of a failure rate after intradermal double-eyelid operations that had been performed by a single surgeon (Y. Mutou). We evaluated consecutive patients (male 115, female 1,457) from 1986 to 1993 who underwent intradermal blepharoplasty at Sapporo Chuo Keisei Geka Clinic. Fifty patients (male 3, female 47) revisited our clinic complaining of the "disappearance" or loss of the fold. The estimated disappearing rate was 3.43%. Thirty percent of the disappearance occurred within 1 year. Eighty-eight percent of the disappearances occurred within 5 years postoperatively.

Shaving off the sweat glands and hair follicles with a single-use safety razor is described.

A 62-year-old woman with IgA-lambda type monoclonal gammopathy had been followed up since January 1988. In March 1991, multiple myeloma (IgA-lambda) was diagnosed on the basis of bone marrow biopsy findings and increased serum IgA levels. She was treated intermittently with melphalan and prednisolone over a perioa of about 6 years, but was eventually admitted due to renal dysfunction, hypercalcemia, increased serum IgA and the formation of subcutaneous masses. During chemotherapy she underwent emergency surgery for obturative ileus. Histological examination of the resected tissues revealed invasion of myeloma cells into the small intestine and peritoneum. Despite continued chemotherapy, the patient's soft tissue masses enlarged, and new lesions appeared in other organs. In the terminal stage, lower serum IgA levels were observed despite an increase in Bence-Jones protein levels in urine. The patient died five months after admission. An autopsy found infiltration by atypical myeloma cells in multiple organs. An immunohistochemical examination revealed and increase in lambda-light chain positive cells relative to the number of alpha-heavy chain positive cells. The terminal course was considered to be representative of aggressive phase multiple myeloma. The case was rare in that the patient's ileus was caused by invasion of myeloma cells into the small intestine.

Cases of acute exacerbation in chronic liver disease ("acute-on-chronic") in Japan were surveyed by questionnaire method since 1986 and 220 cases were collected. 73 pathological specimens of 102 cases which were autopsied were subjected to morphological analysis. The cases were divided according to causes of acute exacerbations: namely super-imposed viral infection or drugs (Group I), unknown causes or post immunosuppressant therapy (Group II), alcohol abuse (Group III), operation, digestive tract hemorrhage or post TAE etc, (Group IV). Area of hepatic necrosis was large and regeneration of hepatocytes were significantly strong in Group I and II compared with cases of Group IV. Regeneration was also inhibited in liver of habitual alcohol drinker. Significant difference was shown in cases of Group IV. Pathologically liver of 10 cases of Group III divided to florried cirrhosis (3 cases), alcoholic liver cirrhosis (4 cases) and alcoholic hepatitis combined with post hepatitic liver cirrhosis (3 cases, all HBV carriers).

A technique is presented for correction of supratarsal depression in the upper lids of orientals, using silicone bag-gel prostheses.