First-line treatment for severe aplastic anemia in children: bone marrow transplantation from a matched family donor versus immunosuppressive therapy

The current treatment approach for severe aplastic anemia in children is based on studies performed in the 1980s, and updated evidence is required. We retrospectively compared the outcomes of children with acquired severe aplastic anemia who received immunosuppressive therapy within prospective trials conducted by the Japanese Childhood Aplastic Anemia Study Group or who underwent bone marrow transplantation from an HLA-matched family donor registered in the Japanese Society for Hematopoietic Cell Transplantation Registry. Between 1992 and 2009, 599 children (younger than 17 years) with severe aplastic anemia received a bone marrow transplant from an HLA-matched family donor (n=213) or immunosuppressive therapy (n=386) as first-line treatment. While the overall survival did not differ between patients treated with immunosuppressive therapy or bone marrow transplantation [88% (95% confidence interval: 86–90) versus 92% (90–94)], failure-free survival was significantly inferior in patients receiving immunosuppressive therapy than in those undergoing bone marrow transplantation [56% (54–59) versus 87% (85–90); P<0.0001]. There was no significant improvement in outcomes over the two time periods (1992–1999 versus 2000–2009). In multivariate analysis, age <10 years was identified as a favorable factor for overall survival (P=0.007), and choice of first-line immunosuppressive therapy was the only unfavorable factor for failure-free survival (P<0.0001). These support the current algorithm for treatment decisions, which recommends bone marrow transplantation when an HLA-matched family donor is available in pediatric severe aplastic anemia.     

Comparison of high-dose and low-dose corticosteroid therapy for refractory Mycoplasma pneumoniae pneumonia in children

Background

Mycoplasma pneumoniae pneumonia (MPP) is generally a self-limiting disease, but it may become refractory. It is thought that refractory MPP is linked to the excessive immunologic responses of the host. Consequently, the use of adjunctive systemic corticosteroids may have beneficial effects. In this study, we compared the effects of high- and low-dose corticosteroid therapy in a pediatric population with refractory MPP.

Muscarinic agonist binding in rat brain following chronic nicotine treatment

Carbamylcholine binding was determined from competition experiments with [3H] quinuclidinyl benzilate in the rat brain chronically treated with nicotine. The nicotine group exhibited about two-fold lower affinity for the agonist binding toward a high-affinity site (or state) in the cerebral cortex, as compared with the control group. However, no alteration in the agonist binding was observed in the hypothalamus/thalamus and brainstem after chronic nicotine treatment.     

Mutation analysis of a Japanese patient with fucosidosis

Fucosidosis is a rare autosomal recessive disorder resulting from a deficiency of α-L-fucosidase. Recently, various mutations have been reported in this disease, but it is difficult to elucidate the phenotype from the genetic mutations. We report a patient with chronic infantile type fucosidosis, with a compound heterozygote of a nonsense mutation (W148X, Trp at codon 148 to stop codon) and a large deletion, including all exons. This is the first report of a large deletion demonstrated in fucosidosis. It is interesting that this patient has a relatively mild clinical course despite the absence of the mRNA. This case also indicates the difficulty in determining the phenotype from the genotype in fucosidosis. Received: February 19, 1999 / Accepted: April 16, 1999     

Responses of bradykinin sensitive tooth-pulp driven neurons in cat cerebral cortex

Summary The properties of single cortical neurons responding to electrical stimulation of the tooth-pulp and to intrapulpal application of bradykinin were studied in the cat. The activities of tooth-pulp driven neurons (TPNs) were recorded from the middle and anterior parts of the coronal gyrus of the cerebral cortex. Bradykinin-sensitive tooth-pulp driven neurons (BK-TPNs) were located in layer IV of area 3b of the anterior part of the coronal gyrus. These neurons had a large cutaneous oro-facial receptive field and received a nociceptive input from the facial skin as well as from the tooth-pulp. The BK-TPNs had a higher threshold and longer latency to electrical stimulation than TPNs insensitive to bradykinin (non BK-TPNs). These findings suggest that BK-TPNs in this cortical area may be involved in sensory processing of noxious information from trigeminal regions.     

Selective potentiation of extracellular Ca2+-dependent contraction by neuropeptide Y in rabbit mesenteric arteries

1. Neuropeptide Y (NPY) potentiated the contractile responses induced by electrical transmural stimulation, noradrenaline and KCl in the rabbit mesenteric artery. 2. In preparations treated with noradrenaline or KCl in Ca2+ free medium, NPY also potentiated the contractile response induced by resupplementation of Ca2+. 3. 3H-efflux from the arteries preincubated with [3H]-noradrenaline was not affected by NPY. 4. These results suggest that NPY selectively acts on the postsynaptic membrane and potentiates the contractions mediated through receptor-operated and voltage-dependent Ca channels.     

Treatment of metastatic bone lesions in the upper extremity: indications for surgery

Pathological fractures caused by metastatic malignant disease have been the subject of increasing interest in recent years. This article describes our experience with the treatment of metastatic bone disease of the upper extremity and our attempt to clarify the indications for different surgical procedures. Of 53 patients with metastatic lesions to the upper extremity, 20 who had been surgically treated were analyzed retrospectively. These comprised 13 men and 7 women with a mean patient age of 62 years. The most common primary tumors to metastasize were lung and liver, with the humerus involved in 12 cases and the scapula and forearm in 4 cases each. Four patients with scapula and forearm involvement underwent tumor resection due to uncontrollable tumor size, while 3 were successfully treated by selective arterial embolization. Three metastases to the humeral head were reconstructed with endoprosthesis, but functional restriction was noted. Five cases with metastases to the humeral shaft were treated with tumor curettage, internal fixation using intramedullary nailing, adjuvant cryosurgery, and cementing. This achieved good results for pain relief and functional restoration with minimal complications. Two metastases to the humeral condyle were unable to be stabilized with plate and locking screws. Metastatic lesions to the scapula and forearm are commonly treated nonsurgically, but some patients with uncontrollable tumor mass require surgical resection. Endoprosthetic replacement is recommended if the lesion involves the humeral head or condyle. Most patients with the humeral shaft lesion are likely to benefit from tumor curettage, intramedullary nailing with locking screw, and cementing.