Etoposide-containing conditioning regimen reduces the occurrence of hemophagocytic lymphohistiocytosis after SCT.

Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages that secrete high amounts of inflammatory cytokines. HLH occurring after SCT is difficult to diagnose. It is characterized by severe clinical manifestations and high mortality. Despite current therapeutic approaches, outcomes remain poor. We analyzed the incidence and risk factors of HLH after SCT and the response to treatment and prognosis of 554 patients with HLH after SCT. The cumulative incidence of HLH after SCT was 4.3% (24/554). Use of etoposide in the conditioning regimen was only factor that reduced HLH after SCT (P=0.027). All patients who received autologous transplantation were successfully treated. Patients with liver dysfunction (for example, high total bilirubin level, prolonged prothrombin time and high level of fibrinogen degradation products) had a poor response to treatment for HLH. Physicians should be cautious of HLH, while not using etoposide for conditioning regimen.

[Rib-originated fibrous dysplasia: report of a case].

The incidence of fibrous dysplasia (FD) is not frequent in the case of benign bone tumors of the chest wall, and differential diagnosis between FD and the malignancy on the basis of imaging findings is difficult. We report a case of a painful FD lesion (size, 9×8 cm) that originated from the 5th rib of a 52-year-old man and was surgically resected. His symptoms improved after the operation. Painful and large FD lesions should be resected because of a difficulty in differential diagnosis from malignant tumors.

Roles of neuronal nitric oxide synthase, oxidative stress, and propofol in N-methyl-D-aspartate-induced dilatation of cerebral arterioles.

BACKGROUND: It remains unclear whether N-methyl-D-aspartate (NMDA) receptors contribute to cerebral parenchymal vasodilatation, and any effects of clinically used anaesthetics on the dilatation. The present study was designed to examine whether NMDA induces neuronal nitric oxide synthase (NOS)-mediated dilatation, in the cerebral parenchymal arterioles, and whether propofol and superoxide modulate the dilatation in relation to the NMDA receptor activation. METHODS: The cerebral parenchymal arterioles within rat brain slices were monitored by a computer-assisted microscopy, and the vasodilatation in response to NMDA (10(-7) to 10(-5) M) was evaluated. Immunofluorescence analysis to neuronal and endothelial NOS and measurement of levels of superoxide and nitric oxide within the arteriole were simultaneously performed. RESULTS: Propofol, an NMDA receptor antagonist MK801, and a neuronal NOS antagonist S-methyl-l-thiocitrulline (SMTC) reduced NMDA-induced dilation, whereas a superoxide inhibitor, Tiron, and NADPH oxidase inhibitor, gp91ds-tat, augmented NMDA-induced dilatation. Immunofluorescence analysis revealed distribution of neuronal NOS in both endothelial and smooth muscle cells in addition to neuronal cells. NMDA-induced superoxide and nitric oxide within the parenchymal arterioles. The increased superoxide within the arteriole was similarly inhibited by MK801, SMTC, gp91ds-tat, propofol, and a neuronal NOS antagonist vinyl-l-NIO, whereas the level of nitric oxide was reduced by MK801, SMTC, propofol, and vinyl-l-NIO, and it was augmented by gp91ds-tat. CONCLUSIONS: NMDA dilates cerebral parenchymal arterioles possibly via neuronal NOS activation, whereas it produces superoxide via NADPH oxidase. In these arterioles, propofol reduces both the dilatation and superoxide production in response to NMDA.

Cerebral oxygenation in the beach chair position before and during general anesthesia.

AIM: Ischemic brain damage related to the beach chair position is a matter of concern. The current study was designed to evaluate whether the beach chair position before and during general anesthesia differentially induces changes in cerebral oxygenation as determined by near-infrared spectroscopy (NIRS) in surgical patients. METHODS: We evaluated brain tissue oxygen index (TOI) values using the NIRS monitor NIRO-200TM in the beach chair position the day before and during general anesthesia. Thirty patients with normal preoperative TOI values undergoing shoulder surgery were enrolled. The initial TOI measurement in the supine position after 10 min rest or 10 min after tracheal intubation was followed by measurements after 5 min each in the 30-degree and subsequently 60-degree head-up tilt positions. During general anesthesia, patients were mechanically ventilated to obtain normocapnia under inhalation of 1.5% sevoflurane in 50% oxygen. Mean blood pressure (MAP) was measured non-invasively in the arm at heart level and was maintained above 60 mmHg with phenylephrine. RESULTS: Preoperative TOI values and preoperative MAP were within the normal range in the study population. MAP decreased upon anesthesia but did not further change when the patient was placed in the 30- and 60-degree head-up tilt positions. Heart rate also decreased upon anesthesia. However, TOI values did not change with induction of general anesthesia or placement of the patients in the beach chair position. CONCLUSION: Under general anesthesia, the beach chair position does not alter cerebral oxygenation in patients showing normal preoperative cerebral TOI values.

Immunohistochemical examination of epiphyseal growth plates of Japanese Brown cattle with chondrodysplasia.

A new type of inherited chondrodysplasia is described in Japanese Brown cattle, but the basic defects of the epiphyseal growth plate (EGP) in the limb long bones, and proliferation and differentiation of the chondrocytes in the EGP, are not yet understood. In the present study, the EGPs of the limb long bones in eight cases of chondrodysplasia and four normal (control) cattle were examined histologically and immunohistochemically. In the control cattle, proliferative chondrocytes (PCs) and hypertrophic chondrocytes (HCs) were arranged in columns parallel to the long axis of the bone, and HCs were situated on the metaphyseal side of the EGP. In all the affected cattle, many chondrocytes with a hypertrophic appearance were detected in the inner areas of the central portion of the EGP. The PC columns were short and arranged irregularly. Bone tissue and small blood vessels were found frequently in these areas. Six affected cattle showed complete EGP-closure. Backscattered electron (BSE) imaging showed that the calcified cartilage matrix was restricted to the lower region of the hypertrophic zone (HZ) of the EGP in the control cattle, while the calcified cartilage matrix and bone tissue were scattered in the inner areas of the EGP in all the chondrodysplastic cattle. Immunohistochemistry revealed type X collagen in the HCs and cartilage matrix of the HZ in the control cattle. In all the affected cattle, type X collagen was detected in apparently hypertrophic chondrocytes in the inner areas of the EGP. Type II collagen was detected in the entire EGP in all the affected cattle, as in the controls. BrdU (5-bromo-2'-deoxyuridine), injected intravenously 1h before euthanasia was detected in many PCs in the EGP in the control cattle; none, however, was detected in the central portion of the EGP in any affected animal. These observations indicate that differentiation into HCs and calcification of cartilage matrix occur in the inner areas of the central portion of the EGP in chondrodysplasia of Japanese Brown cattle. Differentiation into the HCs at this abnormal site may be caused by the inadequate proliferation and disorganization of the PCs. Premature EGP-closure, observed commonly in chondrodysplasia of Japanese Brown cattle, was thought to be caused by replacement of the calcified cartilage in the inner areas of the EGP by bone tissue.

New strategy of therapy for functional dyspepsia using famotidine, mosapride and amitriptyline.

BACKGROUND: In functional gastrointestinal (GI) disorders including functional dyspepsia (FD) and irritable bowel syndrome (IBS), there might be no small extent of contributions of psychosomatic factors. As a therapy for IBS patients, the effectiveness of antidepressants has been reported. AIM: In this study, we evaluated the efficacy of H2-receptor antagonist (famotidine) and 5-HT4 receptor agonist (mosapride citrate). In addition, the effect of antidepressants was assessed as the second-step therapy. METHODS: Patients complaining upper GI symptoms were diagnosed as FD excluding organic diseases. Randomized patients received 20 mg/day of famotidine or 15 mg/day of mosapride citrate for 4 weeks and the efficacy was compared between the two groups based on a 10-point visual analogue scale. When symptoms were not relieved (score improvement 0-2 points), patients received amitriptyline (30 mg/day) or no medication for 4 weeks randomly. Patients who had depression in psychological test (SDS) were omitted. RESULTS: As the first-step therapy, both famotidine and mosapride showed beneficial effects regardless of FD subtypes, age and gender. The efficacy of these two drugs in relieving FD symptoms was not significantly different. In patients who failed in the first-step therapy, amitriptyline showed beneficial effects. CONCLUSIONS: These findings might be clinically important in view of the efficient relief of symptoms in FD patients.

Successful induction of immune tolerance in a patient with haemophilia B with inhibitor.

We describe successful induction of immune tolerance (IT) in a 10-month-old boy with severe haemophilia B. Urticaria developed soon after starting prophylactic treatment and was associated with an inhibitor at 7 Bethesda units mL(-1). Initially, we tried low dose factor IX therapy to induce IT with only a transient effect. The patient experienced an intracranial haemorrhage. A simple bolus dose of FIX eradicated the inhibitor. Thereafter he has been free from inhibitor and nephrotic syndrome for more than 5 years, although he receives FIX three times a week.

Successful unrelated cord blood transplantation in Philadelphia chromosome positive acute lymphoblastic leukemia during pulmonary aspergillosis treated by anti-fungal therapy, granulocyte colony-stimulating factor-mobilized granulocytes and surgical resection: case report.

A 3-year-old girl with Philadelphia chromosome positive acute lymphoblastic leukemia developed pulmonary aspergillosis during severe neutropenia by re-induction therapy. She was treated by intravenous fluconazole, oral itraconazole with plasma level monitoring and surgical resection of the focus for 3 months after clinical diagnosis of fungal infection was made. Once she had recovered from surgery we attempted to induce remission with anti-fungal treatment. She developed fever and neutropenia and appeared unlikely to remit with conventional chemotherapy. Unrelated one-antigen-mismatched cord blood (CB) transplantation was performed 2 months after the induction therapy. Her pulmonary aspergillosis was reactivated during subsequent conditioning. Anti-fungal drugs were switched to amphotericin B and granulocyte colony-stimulating factor-mobilized granulocyte concentrates were transfused. She obtained engraftment and has maintained complete hematological and molecular remission without signs of aspergillus infection for 13 months so far after transplantation. Even very high-risk transplantation in pediatric patients could be successfully supported by carefully designed intense comprehensive medical care.

Detection of human herpesvirus 6 and JC virus in progressive multifocal leukoencephalopathy complicating follicular lymphoma.

Progressive multifocal leukoencephalopathy (PML), a demyelinating infectious disease caused by JC virus (JCV), occurs almost exclusively in immunocompromised patients usually with malignant diseases. We report here a Japanese female with follicular lymphoma who subsequently developed PML. In addition to JCV, human herpesvirus 6 (HHV-6) was detected in the affected brain lesions of the patient by polymerase chain reaction and by in situ hybridization. HHV-6, recognized as a neurotropic virus, is known to be reactivated during immunosuppression and can cause fatal complications such as encephalitis/encephalopathy. It is likely that impaired immunity associated with lymphoma and the additional immunosuppression following cytopenia-inducing chemotherapies predisposed the patient to reactivated HHV-6 infection. Although it remains to be clarified whether HHV-6 plays an important role as a co-agent with JCV in causing demyelination of the brain, our observation alerts physicians to the possible association of HHV-6 with the pathogenesis of PML.

Lactate dehydrogenase production and release in a newly established human myeloma cell line.

Aggressive multiple myeloma with high serum lactate dehydrogenase (LDH) often has unusual clinical features and is considered to be a distinct clinical entity of multiple myeloma. A myeloma cell line, designated Maska-98, was established from the bone marrow of a patient with aggressive myeloma with extremely high serum LDH that was resistant to conventional chemotherapy. Maska-98 cells had morphological features of immature plasma cells, and immunophenotypic analysis showed that the cells expressed the plasma cell-associated surface antigens including CD38, 49d, and 56, but no T- or B-cell antigens, such as CD2, 3, 4, 8, 19, and 20. Maska-98 cells contained cytoplasmic immunoglobulin (IgG lambda). By utilizing this cell line we demonstrated that the myeloma cells produce and release a large amount of LDH, since (i) abundant LDH was found in the culture supernatant of Maska-98, (ii) immunocytochemical analysis showed that cytoplasm of the cells was strongly stained with anti-LDH monoclonal antibody, and (iii) Maska-98 cells expressed a greater amount of LDH mRNA than the T-cell line TALL-1, as shown by reverse transcription-polymerase chain reaction. As far as we know, there is no report of a myeloma cell line producing excess LDH. Therefore, Maska-98 would provide a novel source for further studies of the pathogenesis of aggressive multiple myeloma with high serum LDH.

Effects of ketamine on voltage-dependent calcium currents and membrane potentials in single bullfrog atrial cells.

PURPOSE: This study was undertaken to assess the effect of ketamine on L-type calcium channel current (I(Ca)) and membrane action potential in the bullfrog single atrial myocyte. METHODS: Bullfrog single atrial myocytes were prepared by enzymatic dispersion. Whole-cell voltage-clamp technique and current clamp technique were used to monitor I(Ca), membrane resting potential, and action potential. RESULTS: Ketamine (10(-5)-10(-3) M) showed dose-dependent inhibition of I(Ca) in a reversible manner. The 50% inhibitory concentration (IC(50)) of ketamine on I(Ca) was estimated to be 0.92 x 10(-5) M. Use-dependent block of I(Ca) was not observed. The resting membrane potential was depolarized at a high concentration (10(-4) M) of ketamine. Reduction of the plateau phase and prolonged duration of the action potential were observed in the presence of a high concentration of ketamine (10(-4) M). CONCLUSION: Ketamine has an inhibitory effect on I(Ca) in the bullfrog single atrial myocyte, and a high dose (10(-4) M) of ketamine prolonges the duration of the action potential. The mechanism of inhibition of I(Ca) seems to be a direct effect on the L-type calcium channel, not like an open channel blocker.

[Transcatheter arterial embolization of aneurysmal-type renal arteriovenous fistula: a case report].

We report a case of aneurysmal-type renal arteriovenous fistula, which was successfully treated with transcatheter arterial embolization (TAE). A 73-year-old woman was referred to our hospital because of an incidental abnormal renal mass detected by computed tomography (CT). CT scan showed a round mass (4 x 3 x 3 cm) in the right kidney. Magnetic resonance (MR)-angiography and angiography revealed an aneurysmal type renal arteriovenous fistula (AVF). The patient was treated with TAE using detachable coils. CT, MR-angiography and angiography are useful means for the diagnosis of renal arteriovenous fistula. TAE is a powerful treatment for renal arteriovenous fistula.

[A case of Legionella pneumonia successfully treated intravenously with both erythromycin and ciprofloxacin].

A 54-year-old man was admitted to our hospital complaining of a high fever and watery diarrhea. The chest radiograph on admission revealed a homogeneous consolidation of the left upper lobe. Laboratory findings included proteinuria, oligouria, hematuria, myoglobinuria, hyponatremia, and serum CPK elevation. On the basis of these findings, a tentative diagnosis of Legionella pneumonia was made. He was treated with sulbactam/cefoperazon and erythromycin, but his high fever remained and the consolidation shadow deteriorated. He was therefore given both erythromycin and ciprofloxacin intravenously. After several days the fever had returned to normal, the appearance of the chest radiograph had improved, and his symptoms were quickly relieved. This case suggests that intravenous administration of ciprofloxacin and erythromycin can be an effective treatment against Legionella pneumonia.

Effects of propofol on contractile response and electrophysiological properties in single guinea-pig ventricular myocyte.

Effects of propofol on contractile response, action potential, resting membrane potential and L-type voltage-dependent calcium channel current were examined in guinea-pig single cardiac myocyte. Propofol (10(-4) M) inhibited contractile response induced by electrical stimulation (83.6% of control, n = 5), but did not change the resting membrane potential. On the other hand, propofol reduced the overshoot of action potential (10(-4) M), and shortened the duration of action potential (10(-5) and 10(-4) M). Whole-cell voltage clamp experiment showed inhibition of L-type calcium channel current (ICa, 10(-5) M: 90.8+/-1.39, 10(-4) M: 83.4+/-1.53% of control, n = 5). In addition, propofol showed use-dependent block of ICa. It is concluded that negative inotropic effect of propofol is caused by suppression of action potential, and that inhibition of ICa plays a role in shortening of the duration of action potential.

[Dynamics of prostate-specific antigen as prognostic factors in endocrine treatment for prostate cancer].

Prostate-specific antigen values provide important and unique information about prostate cancer to clinicians. However, there is conflicting information about the prognostic significance of the dynamics of PSA decline and elevation after treatment. To provide further insight into the dynamics of PSA as prognostic factors, we herein studied various PSA values as possible prognostic factors in 93 patients with prostate cancer treated with endocrine therapy. Thirteen (14.0%) had stage B tumors, 20 (21.5%) had stage C tumors, and 60 (64.5%) had stage D tumors. The overall 5-year survival rate was 41.2%. Relapse was observed in 32 (34.4%) patients. The influence of pre- and post-treatment PSA (both absolute and percentage values) on survival was analyzed. Normalization of PSA value was associated with prolonged survival regardless of interval to reach the lowest PSA level. The absolute value of PSA at 3 or 6 months following treatment was a significant discriminator, while the pre-treatment PSA level and percentage values of post-treatment PSA were not. These data show that the PSA nadir and PSA value at 3 or 6 months following treatment provide important prognostic information.

Cytotoxic and porphyrinogenic effects of diphenyl ethers in cultured rat hepatocytes: chlornitrofen (CNP), CNP-amino, chlomethoxyfen and bifenox.

We studied the cytotoxic and porphyrinogenic effects of four diphenyl ethers (DPEs), chlornitrofen (CNP), CNP-amino, chlomethoxyfen and bifenox, in rat hepatocytes cultured on Matrigel. Cytotoxicity was determined as a decrease in viability measured by the release of lactate dehydrogenase. Of the DPEs examined. CNP-amino was the most cytotoxic, with an LC50 value of 0.36 mM (95% confidence interval, 0.33-0.40 mM). CNP also reduced the viability in a concentration-dependent manner at the concentrations of 0.50 mM or above. In contrast, no concentration-dependent decrease in viability was observed in the chlomethoxyfen- and bifenox-treated hepatocytes at the concentrations up to 1.0 mM. To identify the enzyme involved in the metabolic activation of CNP-amino, inhibition studies were carried out using SKF 525-A (0.050 mM) and methimazole (1.0 mM). SKF 525-A, a cytochrome P450 inhibitor. quickened the onset of cell killing by CNP-amino, while methimazole, an inhibitor of flavin-containing monooxygenase (FMO), partially suppressed the cytotoxicity of CNP-amino. These results suggest that FMO plays an important role in the cytotoxicity induced by CNP-amino, while cytochrome P450 participates in the detoxification, possibly via the ring-hydroxylation. The maximum porphyrin accumulation was observed at 0.13 mM for chlomethoxyfen (18-fold) and at 0.25 mM for CNP and bifenox (17- and 21-fold, respectively). In contrast to these DPEs, the porphyrinogenic effect of CNP-amino was weak, with the maximum accumulation at 0.13 mM (at least fivefold). The predominant species was protoporphyrin IX in all of the DPE-treated cultures. These results suggest that all of the DPEs examined, possibly including CNP-amino, inhibit protoporphyrinogen oxidase, resulting in the accumulation of protoporphyrin IX.

[Giant vesico-vaginal stone: a case report].

A 74-year-old female with the chief complaint of lower abdominal and anal pain had been suffering from total incontinence due to cerebral palsy since her childhood. A giant stone was palpable on vaginal examination. A radiograph showed a giant calcification in the pelvis. Magnetic resonance imaging (MRI) revealed a giant vesico-vaginal stone, which occupied most of the bladder and vagina. Cystolithotomy was performed. The removed stone weighed 435 g, and measured 9.0 x 6.5 x 5.5 cm, and was composed of magnesium ammonium phosphate. To our knowledge only eight cases of female giant vesical stone have been reported. We herein report a rare case of vesico-vaginal stone unrelated to gynecological procedures.