General anesthesia for dental treatment in a Williams syndrome patient with severe aortic and pulmonary valve stenosis: suspected episode of postoperatively malignant hyperthermia

A 28-month-old boy (height, 76 cm; weight, 9.4 kg) diagnosed as having Williams syndrome presented for dental care. We report a case of postoperatively suspected malignant hyperthermia after the administration of general anesthesia for dental treatment in this patient with severe supravalvular aortic stenosis and pulmonary artery hypoplasia. Anesthesia was maintained through the inhalation of nitrous oxide and sevoflurane with oxygen. The patient was hemodynamically stable and no other abnormalities were observed. After the completion of the dental treatment, he was transferred to the pediatric ward. On arrival at the ward, the patient's core temperature increased to 39.5 degrees C and tachypnea (RR, 30 breaths/min) was observed. The SPO2 during inhalation was slightly low (92%-93%). Serum biochemistry revealed an elevated CK level (1345 U/L) but no other abnormal findings. Twelve hours after the dental treatment, the patient's core temperature fell to 37.4 degrees C. After hospitalization for 4 days, the patient was discharged in good condition. In the present case, general anesthesia was employed for dental treatment despite severe supravalvular aortic stenosis and peripheral pulmonary artery hypoplasia, because conventional dental therapy was very difficult as a result of the patient's mental retardation and hyperkinesia. The present case suggests that the use of volatile agents that could trigger malignant hyperthermia should be avoided wherever possible.     

PD-L1 blockade exhibits anti-tumor effect on brain metastasis by activating CD8+ T cells in hematogenous metastasis model with lymphocyte infusion

Brain metastases are common complication in cancer patients. Immune checkpoint inhibitors show therapeutic benefits also in patients with central nervous system (CNS) metastases. However, their antitumor effects on metastatic tumors and their underlying mechanisms are still poorly understood. In this study we investigated the antitumor effect of anti-programmed death-ligand 1 (PD-L1) antibody on metastatic brain tumors and evaluated immune responses during treatment. We employed a hematogenous brain metastasis xenograft model using immunodeficient mice with murine lymphocyte infusions. A human non-small-cell lung cancer (NSCLC) cell line stably expressing NanoLuc^® reporter (Nluc-H1915) was inoculated from the internal carotid artery of SCID mice. After metastases were established (24 days after inoculation), splenocytes prepared from H1915-immunized BALB/c mice were injected intravenously and mouse IgG or anti-PD-L1 antibody treatment was started (day 1). Evaluated by Nluc activity, tumor volume in the brain on day 14 was significantly lower in anti-PD-L1-treated mice than in mouse IgG-treated mice. Furthermore CD8⁺ cells were primarily infiltrated intratumorally and peritumorally and anti-PD-L1 treatment induced a significantly higher proportion of Granzyme B (GzmB)⁺ cells among CD8⁺ T cells. The antitumor effect of anti-PD-L1 antibody on brain metastasis is thought to be achieved by the enhanced activation of infiltrated CD8⁺ T cells into metastatic brain tumor. These results suggest that anti-PD-L1 antibody-containing regimens may be promising treatment options for cancer patients with brain metastases.

     

Effects of thyroid hormones on cartilage sulphation in sex-linked dwarf chickens

The present investigation was undertaken to see if exogenous thyroid hormome could stimulate cartilage sulphation in vivo and in vitro in sex-linked dwaft chickens B-thyroxine or 1-3,5,5-triiodothyronine injection for 7 consecutive days stimulated in vivo 35SO2-4 incorporation into trachea cartilages of the dwarf chicken. Both thyroid hormones added to the incubation medium with or without 2.5% dwarf chicken serum also stimulated in vitro 35SO2-4 incorporation into pelvic rudiment from 11-day chick embryos. These data demonstrate that thyroid hormones, like insulin-like growth factor 1, might be responsible for the reduced growth rate of dwarf chickens.     

Aplastic anaemia with 13q-: a benign subset of bone marrow failure responsive to immunosuppressive therapy

In an attempt to determine the pathological significance of a long arm deletion of chromosome 13 (13q-) in bone marrow failure syndrome, we reviewed the clinical records of nine patients who were initially diagnosed with aplastic anaemia due to bone marrow hypoplasia without dysplasia. Six patients responded to immunosuppressive therapy and the other three improved with steroids. None of the patients developed acute leukaemia (follow up: 54-129 months) and the estimated 5-year survival was 78%. These findings indicate that pancytopenia with 13q- represents bone marrow failure of a benign nature, similar to aplastic anaemia without karyotypic abnormalities, rather than preleukaemia.     

Watershed infarcts in a multiple microembolic model of monkey

It has long been debated whether watershed infarcts are caused by hemodynamic or embolic mechanisms. In the present study, we investigated microembolic roles in the pathogenesis of watershed infarcts by examining MRI in a macaque monkey model of multiple microinfarcts. 50 μm microbeads were injected into each internal carotid artery twice with a month interval. Monkeys (n = 4) injected with 2250–2800 microbeads per unilateral side showed both cortical and internal watershed infarcts in the acute phase and atrophic changes with microbleeds in the chronic phase. These results suggest embolic pathogenesis can contribute to the genesis of both cortical and internal watershed infarcts in primates.     

Twenty Years’ Experience in Allogeneic Hematopoietic Stem Cell Transplantation for Philadelphia Chromosome—Positive Acute Lymphoblastic Leukemia in the Nagoya Blood and Marrow Transplantation Group

Between October 1981 and December 2000, 46 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) underwent allogeneic hematopoietic stem cell transplantation (HSCT) in the Nagoya Blood and Marrow Transplantation Group. The median age was 28.5 years (range, 4-51 years). All but one patient achieved engraftment. Grade II-to-IV acute graft-versus-host disease (GVHD) developed in 32.5% of patients, and chronic GVHD developed in 40.5%. The incidences of relapse and treatment-related mortality (TRM) at 5 years were 65% and 26%, respectively. The estimated overall survival rate at 5 years was 23%. Univariate analysis showed that improved disease-free survival (DFS) was independently associated with complete remission (CR) at transplantation (39%), compared with non-CR (8%) (P = .023). Non-CR at transplantation was associated with a higher risk of relapse. Donor type, acute GVHD, and time from diagnosis to HSCT all had a significant effect on TRM. In a multivariate analysis, 9 months or more from diagnosis to HSCT was the only variable statistically significant for DFS (relative risk, 3.22; P = .01). This study demonstrates that allogeneic HSCT cures a significant population of patients with Ph+ ALL. Relapse is the major obstacle limiting the success of HSCT. Early transplantation during CR from donors, including unrelated persons or mismatched relatives, may offer improved long-term DFS.