Successful use of differential target multiplexed spinal cord stimulation for chronic postsurgical abdominal pain.

Introduction: Recent advances in stimulation techniques have improved the efficacy and expanded the applicability of spinal cord stimulation (SCS). Among these techniques, there are no reports on the efficacy of differential target multiplexed (DTM) SCS for chronic postsurgical pain (CPSP) after abdominal surgery. Therefore, we present the successful use of DTM SCS for CPSP after distal pancreatectomy. Methods: A 49-year-old man with hypertension and severe chronic low back pain presented with neuropathic CPSP involving the left abdomen in the area of a laparotomy incision. His pain was refractory to conservative treatment and was rated 10 on a numerical rating scale (NRS). He underwent permanent implantation of a pulse generator after a 14-day trial stimulation. Results: Chronic postsurgical pain was well controlled (NRS 1-2) at a 3-month follow-up with DTM SCS. Conclusion: Differential target multiplexed SCS can be a new treatment option for neuropathic CPSP that is resistant to conservative treatment. It is important to further examine the characteristics of CPSP and identify appropriate candidates for the successful use of DTM SCS.

[Successful detection of MYD88 L265P mutation in Waldenström's macroglobulinemia complicated with myelofibrosis using highly sensitive digital PCR].

A 78-year-old man with anemia (Hb 9.6 g/dl) and elevated serum immunoglobulin M (IgM 3,577 mg/dl) levels was referred to our hospital. Bone marrow aspiration yielded a dry tap, and bone marrow biopsy revealed the infiltration of CD20 positive lymphoplasmacytic lymphoma cells and myelofibrosis. The patient was diagnosed with Waldenström's macroglobulinemia complicated with myelofibrosis. TGF-ß plasma concentration was elevated. Further, after chemotherapy with bendamustine and rituximab, remission of both Waldenström's macroglobulinemia and myelofibrosis was achieved, and TGF-ß levels normalized. MYD88 L265P mutation was detected using highly sensitive digital PCR, which compared with currently used direct PCR product sequencing, has a superior sensitivity. The use of digital PCR has additional advantages toward MYD88 L265P detection, particularly when the available amount of sample DNA is limited owing to myelofibrosis.

[A Case of Essential Thrombocythemia with a JAK2V617F Mutation andPolymyalgia Rheumatica].

A patient with polymyalgia rheumatica(PMR)had increasing thrombocytosis. CRP levels, the ESR, and serum interleukin (IL)-6 levels were slightly elevated, and the patient tested negative for RF and anti CCP antibodies. Muscle pain was ameliorated with the administration of corticosteroids. Genetic analysis of the peripheral white blood cells demonstrated the presence of a JAK2V617F mutation. The muscle pain experienced by the patient was considered to be due to essential thrombocythemia( ET)of myeloproliferative neoplasms(MPNs)along with an inflammatory reaction. Unfortunately, the patient died suddenly because of cerebral infarction.

[A Case of Severe, Idiopathic Cytopenia of Undetermined Significance(ICUS)in an Elderly Patient].

Severe idiopathic cytopenia(initially neutropenia)of undetermined significance(ICUS)was identified in an elderly patient. Immature blasts and dysplastic cells were not observed, and the karyotypic analysis was normal. These hematological findings did not meet the minimal diagnostic criteria for myelodysplastic syndrome(MDS). Causative disease and drugs were excluded. Cases of ICUS that have the possibility of evolving into MDS are expected to increase in the elderly.

Identification of a hydrolyzable tannin, oenothein B, as an aluminum-detoxifying ligand in a highly aluminum-resistant tree, Eucalyptus camaldulensis.

Eucalyptus camaldulensis is a tree species in the Myrtaceae that exhibits extremely high resistance to aluminum (Al). To explore a novel mechanism of Al resistance in plants, we examined the Al-binding ligands in roots and their role in Al resistance of E. camaldulensis. We identified a novel type of Al-binding ligand, oenothein B, which is a dimeric hydrolyzable tannin with many adjacent phenolic hydroxyl groups. Oenothein B was isolated from root extracts of E. camaldulensis by reverse-phase high-performance liquid chromatography and identified by nuclear magnetic resonance and mass spectrometry analyses. Oenothein B formed water-soluble or -insoluble complexes with Al depending on the ratio of oenothein B to Al and could bind at least four Al ions per molecule. In a bioassay using Arabidopsis (Arabidopsis thaliana), Al-induced inhibition of root elongation was completely alleviated by treatment with exogenous oenothein B, which indicated the capability of oenothein B to detoxify Al. In roots of E. camaldulensis, Al exposure enhanced the accumulation of oenothein B, especially in EDTA-extractable forms, which likely formed complexes with Al. Oenothein B was localized mostly in the root symplast, in which a considerable amount of Al accumulated. In contrast, oenothein B was not detected in three Al-sensitive species, comprising the Myrtaceae tree Melaleuca bracteata, Populus nigra, and Arabidopsis. Oenothein B content in roots of five tree species was correlated with their Al resistance. Taken together, these results suggest that internal detoxification of Al by the formation of complexes with oenothein B in roots likely contributes to the high Al resistance of E. camaldulensis.

JAK2 46/1 haplotype is associated with JAK2 V617F-positive myeloproliferative neoplasms in Japanese patients.

Myeloproliferative neoplasms (MPNs) constitute a group of phenotypically diverse chronic myeloid malignancies, characterized by clonal hematopoiesis and excessive production of terminally differentiated myeloid blood cells. The MPNs include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), most of which are characterized by a somatic point mutation, V617F, in the janus kinase 2 (JAK2) gene. This mutation was recently shown to occur more frequently in a specific JAK2 haplotype, JAK2 46/1, in North American and European MPN patients. Little is known, however, about JAK2 haplotypes in Japanese MPN patients. Therefore, we examined 108 Japanese patients with MPN, including 19 with PV, 61 with ET, 10 with PMF, and 17 with unclassifiable MPN, as well as 104 control individuals for the JAK2 rs10974944(C/G) single nucleotide polymorphism, in which the G allele indicates the 46/1 haplotype. We found that the JAK2 46/1 haplotype was significantly more frequent in patients with V617F-positive MPN than in controls (odds ratio [OR], 3.6; 95 % confidence interval [CI], 2.2-5.8, p < 0.001), and in PV patients than in controls (OR, 6.3; 95 % CI, 3.0-29.4, p < 0.001). In conclusion, we demonstrated that the JAK2 46/1 haplotype is associated with JAK2 V617F-positive MPNs in Japanese patients.

Highly fluctuating thrombocytopenia developing in a patient with immune thrombocytopenia (ITP) while administering romiplostim.

A patient with immune thrombocytopenia (ITP) was administered a thrombopoietin (TPO) receptor agonist, romiplostim. After a step-wise increase the dose of romiplostim, the platelet count was highly fluctuated; it initially markedly increased, but then it subsequently steeply dropped. These fluctuations were observed three consecutive times. The administration of romipolostin was then discontinued. After the re-administration of romiplostim, the dose was gradually increased, and the platelet count rose steadily. The highly fluctuating platelet count in the present patient indicates the need for careful monitoring of the platelet count at the beginning of romiplostim administration.

[Severe immune thrombocytopenia caused by interferon-beta in a patient with malignant melanoma].

A 57-year-old woman was diagnosed with malignant melanoma three years ago. She received pre- and post-operative therapy with DAV chemotherapy and Feron (Feron®, interferon-b, IFN-b). Thereafter, she received a monthly local injection of Feron®. Severe thrombocytopenia developed three years later. Immune pathogenesis was suspected since platelet-associated immunoglobulin G (PAIGg) was increased and the administration of prednisolone (PSL) quickly ameliorated the thrombocytopenia. This is the first report of severe immune thrombocytopenia caused by IFN-b. Local injections of Feron® were resumed; however, thrombocytopenia was not observed.

[Acute leukemia of ambiguous lineage with monosomy 7 and Philadelphia chromosome].

A 67-year-old female was admitted with a diagnosis of acute leukemia. Immature blasts did not show cytoplasmic granules and were POX(-), ES(-), and PAS(+). Flow cytometry of leukemic cells demonstrated positivity for CD7, CD10, CD19, CD13, CD34, HLA-DR, and coexpression of CD7 and CD34, CD10 and HLA-DR, and CD19 and CD13. Cytogenetic analysis demonstrated -7 and t(9;22)(q34;q11.2), and genomic studies demonstrated minor BCR/ABL chimeric mRNA and rearrangements of IgH and TCR. These findings indicated the clonal proliferation of leukemic blasts that expressed a mixed phenotype. Acute leukemia of ambiguous lineage was diagnosed, although the significance of the specificity of lineage markers remains unclear. The differential diagnosis included CML and B-ALL. The patient was treated according to Ph+ALL. However, the hematological response was poor, with persistent residual blasts and severe pancytopenia. The subsequent administration of imatinib mesylate led to a complication of heart failure, and the patient died on the 19th hospital day.

[Neurological disturbance of the lower extremities by an extramedullary hematopoietic mass complicated with primary myelofibrosis].

A 59-year-old man with primary myelofibrosis developed motor and sensory neurological disturbance of the legs. Magnetic resonance imaging (MRI) demonstrated a mass lesion of the thoracic vertebra at Th4-6, and in the thoracic vertebral canal at Th4-9, which compressed the spinal cord. Needle biopsy of the mass lesion demonstrated extramedullary hematopoiesis. Initial treatment with bolus methylprednisolone was ineffective and, after subsequent radiation therapy, the mass lesion disappeared and the neurological symptoms ameliorated; however, regrowth of the extramedullary lesion was observed one month later. Surgical resection of the extramedullary lesion, laminectomy, and subsequent radiation were performed. The clinical course after the final treatment was good with no neurological symptoms, although the follow-up period is still short.

Massive ascites associated with all-trans retinoic acid treatment in therapy-related acute promyelocytic leukemia.

A 77-year-old man who developed pancytopenia was administered granulocyte colony-stimulating factor (G-CSF) by another doctor, and referred to us for the evaluation of pancytopenia. He had hepatocellular carcinoma and was treated with transcatheter arterial chemoembolization (TACE) containg epirubicin (total dose: 300 mg over the last two years). Bone marrow aspiration smear demonstrated hypercellular marrow with promyelocytes. Cytogenetic analysis demonstrated del(7), t(15;17)(q22;q12), and a fluorescence in-situ hybridization (FISH) study demonstrated chimeric fusion genes of PML-RAR-alpha. He was diagnosed with therapy-related acute promyelocytic leukemia (APL), and treated with all trans-retinoic acid (ATRA). He showed the progressive accumulation of ascites with liver damage, without pulmonary symptoms of ATRA differentiation syndrome. After 60 days of ATRA treatment, complete hematological and cytogenetic responses were achieved. However, the patient died of septic circulatory failure.

A case of acute promyelocytic leukemia showing transient thrombocytosis caused by increased interleukin-6 and thrombopoietin after treatment with all-trans retinoic acid and chemotherapy.

A patient with acute promyelocytic leukemia(APL)treated with all-trans retinoic acid(ATRA)and chemotherapy for remission induction developed marked thrombocytosis after bone marrow recovery. Thrombocytosis also occurred after post remission chemotherapies, although the degree of thrombocytosis gradually decreased. During thrombocytosis, plasma levels of interleukin-6(IL-6)were elevated while those of thrombopoietin(TPO)were not elevated. However, the plasma level of TPO was markedly elevated at the nadir after post remission chemotherapy. These findings suggest that in APL patients, thrombocytosis after treatment with ATRA and or chemotherapy may be caused by increased plasma levels of both of IL-6 and TPO.

Transient severe pancytopenia due to elevated tumor necrosis factor-alpha in overwhelming infection.

A 66-year-old woman complained of fever, sore throat, and neck pain due to pharyngitis and painful lymph node swelling. CBC revealed severe pancytopenia and markedly hypocellular marrow. The administration of antibiotics and granulocyte-colony stimulating factor (G-CSF) successfully ameliorated the inflammatory lesions, and hematopoiesis recovered. Causes for pancytopnenia was unlikely to be virus infection or drugs, and aplastic anemia was also unlikely since only the plasma levels of tumor necrosis factor-alpha (TNF-alpha) was markedly elevated, erythropoietin (EPO) was slightly elevated, interferon-gamma (IFN-gamma) was normal, and flow cytometric analysis for paroxysmal nocturnal hemoglobinuria (PNH)-type cells was negative. These results suggested that the cause of impaired hematopoiesis in the present patient might have been due to elevated TNF-alpha in overwhelming infection, although the pathogen was not identified.

[Multiple myeloma with variant type translocation, t(8;22)(q24;q11.2)].

A 68-year-old female complained of anemia and bone pain. Monoclonal increase of plasma IgA, lambda-type was observed, and immature plasma cells were detected in the bone marrow. These plasma cells showed intermediate differentiation on CD38 gating flow cytometry. Chromosomal analysis demonstrated complex abnormalities including repeats and translocation, t(8;22)(q24;q11.2) by G-banding, and breakpoint down stream of 3'c-MYC on fluorescence in situ hybridization. Multiple myeloma with variant type translocation was diagnosed. Treatment with continuous infusion of dexamethasone and oral administration of thalidomide effectively decreased IgA, plasma cells and chromosomal abnormality, facilitating complete remission.

Angioimmunoblastic T cell lymphoma associated with reversible myelofibrosis.

A 56-year-old man complained of fever, anemia, thrombocytopenia and lymph node swelling. Biopsy of the lymph node demonstrated angioimmunoblastic T cell lymphoma (AITL) with the loss of normal architecture, proliferation of neoplastic T cells, small vessels mixed with eosinophils and plasma cells. Aspiration of bone marrow was dry tap, and biopsy demonstrated myelofibrosis with increased proliferation of reticulin fiber. Markedly elevated plasma levels of transforming growth factor beta1 (TGF-beta1) and soluble interleukin-2 receptor (sIL-2R) were observed, and that of platelet growth factor (PDGF) AB was slightly elevated. After chemotherapy, remission of lymphoma was achieved. The aspiration of bone marrow became possible, and the level of TGF-beta1 and PDGF AB showed normalization; thus, myelofibrosis was reversible.

Isolation and functional analysis of the CjNdly gene, a homolog in Cryptomeria japonica of FLORICAULA/LEAFY genes.

We report the isolation and characterization of CjNdly, a homolog in Japanese cedar (Cryptomeria japonica D. Don) of the FLORICAULA/LEAFY (FLO/LFY) genes. We determined the entire nucleotide sequence of CjNdly, including short 5'- and 3'-untranslated regions. The deduced amino acid sequence was similar to those of the products of the FLO/LFY genes from other species. The nucleotide sequence showed the closest homology to that of the NEEDLY gene in Pinus radiata D. Don. Although no proline-rich region has been reported previously in homologous gene products from gymnosperms, we found such a region at the amino-terminal end of the deduced amino acid sequence encoded by CjNdly. We detected the expression of CjNdly in both reproductive and vegetative tissues and organs of C. japonica. Heterologous expression of CjNdly in transgenic tobacco plants induced precocious flowering of regenerating shoots on agar-solidified medium and flowers with an abnormal phenotype, namely, petal-like stamens. Our findings suggest that the CjNdly gene may have important roles in flower development in Japanese cedar, resembling those of its angiosperm homologs.

Sarcoidosis acutely involving the musculoskeletal system.

A 69-year-old man complained of knee pain, subsequent polyarthralgia, and pains of the muscles of the pelvic girdle and thighs. At the same time, erythema of the face and hands appeared. Biopsy of the skin and muscle revealed non-caseating granuloma of epithelioid cells. The level of serum angiotensin-converting enzyme was normal, but that of lysozyme was elevated. Chest X-ray and CT did not show bilateral hilar lymphadenopathy (BHL) but revealed infiltrative ground glass appearance-like shadows of both lungs, and a Ga scintigram disclosed accumulation in the right hilar region, but not in the muscles. These complaints were quickly ameliorated by the administration of prednisolone. The present patient represented a rare case of acute musculoskeletal system involvement in sarcoidosis not typical of Löfgren's syndrome.

Acute myeloblastic leukemia in a patient with hereditary protein C deficiency.

The patient had been diagnosed with hereditary protein C deficiency. She recently developed acute myeloblastic leukemia (AML). Chemotherapy for AML by cytosine arabinoside, aclarubicin followed by granulocyte colony-stimulating factor (CAG) was started. Disseminated intravascular coagulation (DIC) was observed, however thromboembolic complication was not observed during the hospital course. Hematological remission was not obtained, and the patient died of pseudomembranous pancolitis. Whether the development of these rare disorders of hereditary protein C and AML are coincidental, or involve a causal relationship remains unknown.

T-gamma delta large granular lymphocyte leukemia preceded by pure red cell aplasia and complicated with hemophagocytic syndrome caused by Epstein-Barr virus infection.

A 51-year-old man developed anemia, and was diagnosed with pure red cell aplasia through the absence of erythroid progenitors. Initially, he was treated with cyclosporine and prednisolone for 6 months but they were ineffective. Large granular lymphocyte (LGL) leukemia with the T-cell gamma delta phenotype evolved after 6 months showing CD2+, CD3+, CD8- and CD56- with the T-cell receptor beta gene rearrangement, clonalities of gamma and delta genes and complex chromosome abnormality simultaneously with hemophagocytic syndrome (HPS). Epstein-Barr virus (EBV) genomic DNA was detected in the bone marrow cells. Administration of bolus methylprednisolone was ineffective, and the patient died one month later. In the present patient, it seemed that lymphoproliferative disease of large granular lymphocytes (LDGL) manifested initially as PRCA, gammadelta LGL leukemia evolved, and finally fatal HPS become complicated, presumably caused by the EBV reactivation in the immunodeficiency state with the administration of immunosuppressants.

A breast cancer patient with myelodysplastic syndrome postoperatively treated by radiation and tamoxifen administration--a case report.

A 72-year-old female developed pancytopenia 4 years after breast cancer surgery. She had received regional radiation postoperatively, and tamoxifen for 4 years. Bone marrow examination demonstrated immature myeloblasts and dysplastic cells. Myelodysplastic syndrome (MDS) of refractory anemia with excess blasts (RAEB) was diagnosed, and the patient died of cerebral hemorrhage 4 months after the diagnosis of RAEB. Radiation and the administration of tamoxifen were suspected to have played a role in the development of secondary MDS.