Shuhei Karakawa

Continuous Intravenous Infusion of Ketamine and Lidocaine as Adjuvant Analgesics in a 5-Year-Old Patient with Neuropathic Cancer Pain

For difficult to treat neuropathic pain from cancer, adjuvant analgesics are often used with opioids. We present the case of a 5-year-old girl who was diagnosed with meningitis caused by malignant T-cell lymphoma. She had severe neuropathic pain not relieved by increasing doses of a fentanyl infusion. Intravenous administration of ketamine and lidocaine in combination with fentanyl provided excellent analgesia without significant side effects. Ketamine and lidocaine can be safely infused together with concomitant opioids for the treatment of refractory neuropathic pain caused by cancer.

Decreased Expression in Nuclear Factor-κB Essential Modulator Due to a Novel Splice-Site Mutation Causes X-linked Ectodermal Dysplasia with Immunodeficiency

X-linked ectodermal dysplasia with immunodeficiency (XL-ED-ID) is caused by hypomorphic mutations in NEMO, which encodes nuclear factor-kappaB (NF-κB) essential modulator. We identified a novel mutation, 769−1 G>C, at the splicing acceptor site of exon 7 in NEMO in a Japanese patient with XL-ED-ID. Although various abnormally spliced NEMO messenger RNAs (mRNAs) were observed, a small amount of wild-type (WT) mRNA was also identified. Decreased NEMO protein expression was detected in various lineages of leukocytes. Although one abnormally spliced NEMO protein showed residual NF-κB transcription activity, it did not seem to exert a dominant-negative effect against WT-NEMO activity. CD4+ T cell proliferation was impaired in response to measles and mumps, but not rubella. These results were consistent with the clinical and laboratory findings of the patient, suggesting the functional importance of NEMO against specific viral infections. The 769−1 G>C mutation is responsible for decreased WT-NEMO protein expression, resulting in the development of XL-ED-ID.

Transient pseudothrombocytopenia in a neonate: Transmission of a maternal EDTA-dependent anticoagulant

EDTA-dependent pseudothrombocytopenia (PTCP) is characterised by a low platelet count caused by autoantibodies in the serum reacting with EDTA-anticoagulated blood. EDTA-dependent PTCP is caused by a factor that retains EDTA anticoagulation activity in the serum. We report here that a neonate from a mother with PTCP presented with transient low platelet counts when EDTA was used as an anticoagulant. To confirm the transmission of a maternal serum factor to the neonate, we examined to add the maternal serum into the normal blood. Platelet count decreased significantly after adding maternal serum. Clumped platelets were also observed in the smears of mixed samples.

Adult-onset primary cyclic autoimmune neutropenia: a case report: ADULT-ONSET PRIMARY CYCLIC AIN

A few cases of primary autoimmune neutropenia (AIN) have been reported in adults, but cyclic primary AIN, which is characterized by the periodic oscillation of neutrophils, is uncommon in adults.

Anti‐human neutrophil antigen‐1a, ‐1b, and ‐2 antibodies in neonates and children with immune neutropenias analyzed by extracted granulocyte antigen immunofluorescence assay

Anti‐human neutrophil antigen (HNA) antibodies have been implicated in the development of neonatal alloimmune neutropenia (NAN) and autoimmune neutropenia (AIN). There are many conventional assay methods that detect anti‐HNA antibodies. However, a method to measure multiple samples and detect several anti‐HNA antibodies simultaneously is needed.

Azacitidine successfully maintained the second remission in an infant with KMT2A‐rearranged acute lymphoblastic leukemia who relapsed after unrelated cord blood transplantation

The outcome for infants with KMT2A (MLL)‐rearranged acute lymphoblastic leukemia (MLL‐r ALL) is dismal despite intensive therapy, including hematopoietic stem cell transplantation (HSCT). Epigenetic dysregulation is considered a key driver of MLL‐r leukemogenesis, which theoretically supports the use of epigenetic modifiers as a treatment option. We report an infant MLL‐r ALL case with post‐HSCT relapse. After achieving a second remission, which was maintained for 10 months using only the DNA methyltransferase inhibitor, azacitidine, the patient successfully received the second HSCT. This report describes the clinical effectiveness of azacitidine for the treatment of infant MLL‐r ALL.

Neutropenia (In Infancy and Childhood)

Neutropenia is defined as a decrease in the number of circulating neutrophils in the peripheral blood with absolute neutrophil count less than 1000–1500/μL. Chronic neutropenia in pediatric patients is divided into three groups. Extrinsic factors, such as antibodies, some drugs, and nutritional deficiencies, lead to excessive destruction of neutrophils. Autoimmune neutropenia is a benign form of neutropenia shown in infancy to early childhood. Spontaneous recovery of neutropenia usually occurs within a few months to a few years. Acquired disorders of myeloid and stem cells present hypoplasia of myeloid cells. Congenital neutropenia is intrinsic defects in granulocytes or their progenitors and includes a heterogenous group of disorders. More than ten responsible gene mutations have been identified in congenital neutropenia. Most common congenital neutropenia is due to the gene mutation of neutrophil elastase. The hallmark of profound neutropenia is increased susceptibility to bacterial infections, cutaneous cellulitis, deep tissue abscesses, pneumonia, and septicemia. Almost patients with congenital neutropenia have been responded to administration of G-CSF. However, long-term use of G-CSF has the risk of the development of MDS/AML, suggesting the necessity of the careful follow-up. Hematopoietic stem cell transplantation should be considered for the curable treatment in severe congenital neutropenia.