Kazuhiro Okafuji

A familial factor XIII subunit B deficiency

A 32‐year‐old woman with a bleeding tendency born of a consanguineous marriage, was found to have factor XIII subunit B deficiency. An abnormally low level of factor XIII activity was initially noticed and this finding led to further studies of the proband and her family. The notable features were: undetectable subunit B of factor XIII in the proband and her brother and reduced levels of subunit B, 34–52%, in her parents and children. The probands brother had a markedly decreased level of subunit A protein. The level of factor XIII subunit A in platelets of the proband was normal. The half‐life of subunit A determined from the disappearance curve of infused factor XIII subunit A concentrate was approximately 3 d and this is the shortest estimate of the half‐life of factor XIII to date. From these results, it is suggested that subunit A is unstable in plasma deficient in subunit B and subunit B stabilizes the A protein.

Effect of granulocyte colony‐stimulating factor on neutropenia due to chemotherapy for non‐Hodgkin's lymphoma

The authors administered recombinant human granulocyte colony‐stimulating factor (rhG‐CSF) to 16 patients with advanced non‐Hodgkins lymphoma treated with combination chemotherapy. Groups of three to five patients were treated with 50, 100, 200, and 400 μ/m2 per day of rhG‐CSF by intravenous infusion for 14 days, beginning 3 days after chemotherapy. There was a strong linear relationship between the dose and the area under the curve over this dose range. The rhG‐CSF was rapidly cleared from serum, with a mean half‐life of 5.97 hours for the second phase (t1/2). In patients treated with a dose of more than 100 μg/m2 per day, the duration of neutropenia (P < 0.01) and the duration of fever (P < 0.05) were significantly decreased. The rhG‐CSF was well tolerated and the only clinical observation that appeared relating to rhG‐CSF administration was slight bone pain. This study strongly suggests that an optimum dose of rhG‐CSF in patients after chemotherapy is 100 to 200 μg/m2. Our study shows that rhG‐CSF is a clinically useful drug for patients treated with myelosuppressive chemotherapy.

Ipragliflozin lowers small, dense low-density lipoprotein cholesterol levels in Japanese patients with type 2 diabetes mellitus

Highlights • Small dense LDL-C (sd LDL-C) convey cardiovascular risk in type 2 diabetes (T2D).• Ipragliflozin reduced sd LDL-C levels in Japanese patients with T2D.• Changes in body weight, TG and LDL-C levels contributed to sd LDL-C reduction.

Acute Nonlymphocytic Leukemia Complicated by Garcin’s Syndrome

A 15-year-old girl was diagnosed as having acute nonlymphocytic leukemia (ANLL, FAB M2) in January 1990 and achieved complete remission with chemotherapy. She was readmitted to our hospital with a hearing disturbance and hoarseness in October 1990. A suprapharyngeal tumor was found on cranial MRI, and bone marrow leukemic cells were slightly increased in number. Involvement of leukemic cells was proven by biopsy of the tumor. Therefore, we made a diagnosis of ANLL relapse with Garcins syndrome. To our knowledge, this is the first reported case of leukemia complicated by Garcins syndrome.

Switching from atorvastatin to rosuvastatin lowers small, dense low-density lipoprotein cholesterol levels in Japanese hypercholesterolemic patients with type 2 diabetes mellitus.

AIMS This open-label, randomized, parallel-group comparative study compared the efficacy of rosuvastatin (5mg/day) and atorvastatin (10mg/day) for reduction of small dense low-density lipoprotein cholesterol (sd LDL-C) levels in Japanese patients with type 2 diabetes mellitus (T2DM). METHODS Patients with T2DM and hypercholesterolemia with detectable sd LDL-C after receiving 10mg/day atorvastatin for ≥ 24 weeks were randomly assigned to receive rosuvastatin (5mg/day; switched treatment) or atorvastatin (10mg/day; continued treatment) for 12 weeks. The primary endpoints were changes in sd LDL-C levels and sd LDL-C/total LDL-C ratio evaluated using the LipoPhor AS(®) system. RESULTS There were no significant percent changes from baseline for LDL-C levels between the switched (n=55) and the continued treatment group (n=56). However, the former group exhibited a statistically significant reduction from baseline of sd LDL-C levels, sd LDL-C/total LDL-C ratio compared with the latter group (-3.8 mg/dL vs. -1.4 mg/dL, p=0.014; -2.3% vs. -0.6%, p=0.004, respectively). Multiple regression analysis among all subjects revealed that independent factors contributing to the reduction in sd LDL-C levels were a change in LDL-C (p=0.003) and triglyceride (TG) levels (p=0.006), treatment group (the switched group=1, the continued group=0; standard coefficient=-1.2, p=0.034) and baseline glycated hemoglobin A1c (HbA1c) (p=0.045), respectively. CONCLUSION Switching from 10mg atorvastatin to 5mg rosuvastatin may be a useful therapeutic option to reduce sd LDL-C levels in Japanese hypercholesterolemic patients with T2DM.

Effects of Ca2+ Antagonist, Nicardipine, on Experimental Asthma With Special Reference to Slow Reacting Substance of Anaphylaxis

Slow reacting substance of anaphylaxis (SRS‐A) is an important chemical mediator of bronchial asthma. Leukotriene C4 is a component of SRS‐A and is synthesized from arachidonic acid. Its synthesizing and releasing processes are found to he Ca2+‐dependent. We developed an in vivo inhalation asthma model, mainly mediated by SRS‐A, and elucidated the relationship between a Ca2+‐antagonist, nicardipine, and SRS‐A. In the asthmatic model, mediated by endogenous SRS‐A induced by antigen inhalation, continuous intravenous infusion of nicardipine 7 μg/kg/min depressed the open airway pressure by about 60% compared with the saline‐treated group. Inhibition of mean pulmonary resistance (RL) was about 50% and that of the inverted value of dynamic compliance (1/Cdyn) about 36%. However, the same concentration of nicardipine did not significantly affect the airway response in the asthmatic model induced by the inhalation of leukotriene C4. These results suggest that nicardipine, at the concentration used in the present study, did not block the direct effect of SRS‐A on the smooth muscle, but blocked the Ca2+ influx required for the synthesis of SRS‐A and its release.

Salvage chemotherapy of refractory non-Hodgkin's lymphoma with aclacinomycin, behenoyl ara-C, etoposide, and prednisolone.

SummaryA total of 40 patients with recurrent non-Hodgkins lymphoma were treated with ABEP combination chemotherapy (aclarubicin,N4-behenoyl-1-β-d-arabinofuranosylcytosine, etoposide, and prednisolone). A complete remission (CR) was achieved in 37.5% of the patients and partial remission, in 15.0%. The ABEP regimen proved to be effective in T-cell as well as B-cell lymphoma. It appears that the ABEP regimen may be partially non-cross-resistant with front-line doxorubicin-containing combinations. Survival for 39 months was achieved in 42.0% of the CR responders compared with 6.7% of partial responders (PRs) and nonresponders (NRs) (P<0.01). Diesease-free survival for 45 months was seen in 66% of the CR patients. The ABEP regimen was effective in the treatment of patients with recurrent or refractory lymphoma, enabling hope for long-term survival in the majority of CR cases.

Trisomy 14 with thrombocytosis and monocytosis.

It has been reported that trisomy 14 is associated with myeloid malignancies, but a case with increased platelet count has also been reported. However, the clinical significance of trisomy 14 is still uncertain. We report a patient with trisomy 14 with thrombocytosis and a gradual increase in monocytosis. He was treated with hydroxyurea, cytarabine and aclarubicin in low doses and his quality of life was maintained for a period of about 1 year from blastic crisis. Hydroxyurea, cytarabine or aclarubicin in low doses may be the treatment of choice for trisomy 14 patients with respect to the patients’ quality of life.