Practical guide for the diagnosis and management of primary ciliary dyskinesia.

OBJECTIVE: Primary ciliary dyskinesia (PCD) is a relatively rare genetic disorder that affects approximately 1 in 20,000 people. Approximately 50 genes are currently known to cause PCD. In light of differences in causative genes and the medical system in Japan compared with other countries, a practical guide was needed for the diagnosis and management of Japanese PCD patients. METHODS: An ad hoc academic committee was organized under the Japanese Rhinologic Society to produce a practical guide, with participation by committee members from several academic societies in Japan. The practical guide including diagnostic criteria for PCD was approved by the Japanese Rhinologic Society, Japanese Society of Otolaryngology-Head and Neck Surgery, Japanese Respiratory Society, and Japanese Society of Pediatric Pulmonology. RESULTS: The diagnostic criteria for PCD consist of six clinical features, six laboratory findings, differential diagnosis, and genetic testing. The diagnosis of PCD is categorized as definite, probable, or possible PCD based on a combination of the four items above. Diagnosis of definite PCD requires exclusion of cystic fibrosis and primary immunodeficiency, at least one of the six clinical features, and a positive result for at least one of the following: (1) Class 1 defect on electron microscopy of cilia, (2) pathogenic or likely pathogenic variants in a PCD-related gene, or (3) impairment of ciliary motility that can be repaired by correcting the causative gene variants in iPS cells established from the patient's peripheral blood cells. CONCLUSION: This practical guide provides clinicians with useful information for the diagnosis and management of PCD in Japan.

Nedaplatin as a Single-Agent Chemotherapy May Support Palliative Therapy for Patients with Adenoid Cystic Carcinoma: A Case Report.

Adenoid cystic carcinoma (ACC) is a rare form of adenocarcinoma, which is a broad term describing any cancer that begins in the glandular tissues. It can be found in the head and neck. We report a patient with recurrent ACC arising from the submandibular gland, treated with 100 mg/m2 nedaplatin every 4 weeks. Although our patient's lactate dehydrogenase levels, which is produced by ACC, showed a rising trend throughout the treatment, the level decreased for approximately 2 weeks immediately after administration of nedaplatin every 4 weeks. Thus, there is a possibility that the agent may be effective. Complications such as anorexia and nausea were observed, but they were tolerated and manageable. Nedaplatin may be considered as a supportive agent during palliative therapy for patients with ACC. More clinical trials regarding nedaplatin are necessary, as this study may indicate that a medical approach works well for ACC.

[A Case of Merkel Cell Carcinoma Complicated with Severe Thrombocytopenia Treated with Carboplatin/Etoposide Regimen after Surgery].

Thrombocytopenia is often caused by myelosuppression during chemotherapy. However, when platelet transfusions are required, pathological conditions such as idiopathic thrombocytopenic purpura(ITP)and thrombotic thrombocytopenic purpura( TTP)also occur. We report a case of Merkel cell carcinoma complicated with severe thrombocytopenia treated with carboplatin/etoposide regimen after surgery. The patient's platelet count did not increase in spite of platelet transfusions. However, the platelet count increased after steroid treatment was chosen under the diagnosis of ITP. Subsequent examinations revealed that the patient had HLA antibody, which caused the platelet transfusion refractoriness. When the platelet count does not increase in spite of platelet transfusions during chemotherapy, the possibility that the platelet transfusion refractoriness is due to the presence of HLA antibody should be considered.

Dual antiplasmodial activity of vitamin D3 and its analog, 22-oxacalcitriol, by direct and indirect mechanisms.

Recent evidence suggests that 1α,25-dihydroxyvitamin D3 (calcitriol, VD3), the active form of vitamin D (VD), can inhibit the proliferation of microorganisms. In the present study, we conducted in vitro experiments and utilized in vivo murine models to investigate the antimalarial activity of VD3 and its analog, 22-oxacalcitriol (22-OCT), which was designed to cause less hypercalcemia than VD3. VD3 and 22-OCT treatments effectively resolved a Plasmodium chabaudi (Pc) infection in wild-type mice. Reduced parasitemia was observed during the acute phase of infection in the presence of VD3 and 22-OCT, followed by a delayed peak during the chronic stage of infection. Some anti-Pc activity was observed in VD receptor knockout (KO) mice. VD3 and 22-OCT also completely inhibited the proliferation of P. falciparum (Pf) in human red blood cells in vitro. Plasma levels of interferon (IFN)-γ in VD3-treated B10 and B6 mice were lower than those in vehicle-treated animals, and VD3 resolved a Pc infection in IFN-γ-KO mice, which greatly improved survival. These data suggest that the protective effects of VD3 are elicited through an IFN-γ-independent mechanism. Effective antiplasmodial doses of VD3 and 22-OCT resulted in a loss of body weight in mice. This loss in body weight occurred concomitantly with the development of hypercalcemia. Zoledronic acid partially attenuated VD3-induced hypercalcemia and abrogated the antiparasitic effects of VD3. This study highlights a potential therapeutic role for VD3 in the treatment of malarial infections and shows that hypercalcemia is excellent indicator of the antiplasmodial activity of VD3.