Safety and usefulness of a novel eMotion electric mesh nebulizer in children with asthma.

BACKGROUND: A new electronic mesh nebulizer, eMotion is known to have higher performance compared to conventional nebulizers. However, there are some concerns about whether too much delivered dose might cause side effects with higher frequency. METHODS: To evaluate the safety and usefulness of the nebulizer, we measured changes in heart rates and lung functions of 73 asthmatic children when they inhaled 1 microg/kg of procaterol with eMotion or a conventional nebulizer, Junior BOY. RESULTS: In 34 children with mild asthma exacerbation, physical findings, lung function and transcutaneous oxygen saturation levels were improved after inhalation using both nebulizers. No adverse effects including significant increase of heart rate were found. Improvements in the rates of the parameters were comparable. When response to beta2-agonist inhalation was checked in 39 children in stable condition, similar degrees of improvement in lung function were observed, and heart rates did not change after inhalation with either nebulizers. CONCLUSIONS: Safety and efficacy was comparable between eMotion and a conventional nebulizer when it was used to administer beta2-agonists in asthmatic children. However, from the fact that eMotion needs only 3-4 minutes to inhale 2 mL solution, eMotion could be more useful for most children who usually do not prefer longer inhalation time with conventional compressor nebulizers.     

Allelic homogeneity due to a founder mutation in Japanese patients with lattice corneal dystrophy type IIIA

Lattice corneal dystrophies (LCDs) are caused by mutations of the transforming growth factor beta-induced gene (TGFBI, formerly betaig-h3). LCD type IIIA (LCDIIIA) has been reported mostly from Japan. In this study, we demonstrate allelic homogeneity for Japanese patients with LCDIIIA, using intragenic polymorphic markers. When exon 11 of TGFBI was analyzed, all 18 patients examined were found to be heterozygous for both a P501T mutation and an IVS10-3C --> T variation. On the other hand, none of 54 normal Japanese control subjects had the P501T, and 5 of the controls were heterozygous for IVS10-3C --> T. Haplotype analysis of the patients revealed that both P501T and IVS10-3C --> T were located on the same chromosome, and a significant linkage disequilibrium (P < 0.001, Fisher's exact probability test) was observed between LCDIIIA (P501T) and IVS10-3C --> T. When exon 8 of the gene was analyzed, all these patients possessed the "G allele" of a 1028G/A polymorphism. A significant linkage disequilibrium (P < 0.003; chi-square test) was also observed between P501T and the G allele in the patients. These results suggest that allelic homogeneity seen in Japanese patients with LCDIIIA may result from a single founder mutation.     

Artificial Liver: Present and Future

Early in 1956, the first model of a biological artificial liver, using a live dog's liver incorporated in a cross-hemodialyzer, was placed in an experimental animal with portocaval encephalopathy. This "biological artificial liver," a hybrid artificial liver in the present terminology, was the first in the world. In October 1958, the first human patient, a young male patient in hepatic coma due to liver cirrhosis, was placed on the laboratory-made biological artificial liver composed of four parabiotic cross-hemodialyzers connected with four live dogs' livers to which the "hepatic reactors" for ammonium adsorption and acid-base balance were additionally equipped. This first case was very successful, resulting in the patient's recovery from coma. This article introduces the past history of the artificial liver, research of which has mainly been conducted in Japan since the early 1950s by the author, M. Mito, and Y. Nosé. Until recently, little progress has been made in this field through the application of blood purification principles such as hemoadsorption, plasmapheresis, and other modifications and combinations. Accumulation of clinical experiences with such conventional methods has stimulated the third generation of the artificial liver to a return to a hybrid organ applying modern science and technology. A concept of hybrid organs in comparison with organ transplants is introduced. The Japanese national project of developing a new artificial liver system, as conducted by the author as the chairman and his associates, is introduced.     

Polymerization of methacrylic acid esters with the aged system of lanthanum versatate and p-chlorobenzenediazonium tetrafluoroborate

The aged system of lanthanum versatate ( 1 ) and p-chlorobenzenediazonium tetrafluoroborate ( 2 ) was found to initiate effectively the radical polymerization of acrylic monomers including alkyl methacrylates, butyl acrylate and acrylonitrile, although its initiating activity is lower than that of the non-aged system. The polymerization of methyl methacrylate ( 3 ) with the aged 1/2 system was studied kinetically in acetone. The initial polymerization rate (R_p) is expressed by R_p = Kċ[aged 1/2 ]^0.80 ċ [ 3 ]^1.1 at 50°C. The overall activation energy of the polymerization is 59.0 kJ ċ mol⁻¹. The molecular weight of the resulting poly( 3 ) formed in the early stage increases with increasing conversion. The polymerization system involves a persistent radical showing a four-line EPR spectrum with a g-value of 2.004. A three-line spectrum due to the nitroxyl radical was also observed at lower monomer concentrations. The total concentration of persistent radicals was found to correspond well to the instantaneous polymerization rate. The copolymerization of styrene (M₁) and 3 (M₂) with the aged initiator system was examined at 50°C in acetone. r₁ and r₂ are 0.19 and 0.47, respectively. The former is considerably smaller than that (0.52) reported for the conventional radical polymerization.     

Fundus autofluorescence after full macular translocation surgery for myopic choroidal neovascularization

BACKGROUND: To investigate fundus autofluorescence (FAF) findings in patients who underwent full macular translocation surgery with 360-degree retinotomy (MT360) for myopic choroidal neovascularization (CNV). METHODS: Observational case series. Thirty-one eyes of 31 patients who underwent MT360 for myopic CNV from February 1999 through September 2005 were included. We measured the best-corrected visual acuity and obtained color fundus photographs, optical coherence tomography (OCT) images, and fluorescein angiography images. FAF imaging by confocal scanning laser ophthalmoscope was obtained postoperatively in all study eyes and preoperatively in two study participants. FAF features at the new macula were qualitatively evaluated and compared with preoperative lesions associated with CNV. The FAF features at the retinal pigment epithelial (RPE) area with preoperative CNV also were evaluated. RESULTS: The mean interval between MT360 and the final FAF examination was 58 months (range, 8-94 months). FAF imaging was almost normal in five eyes (16%), the increased FAF was well defined at the new macula area in 23 eyes (74%), and the FAF was decreased in three eyes (10%). Neither newly developed CNV nor subretinal fluid was seen at the new macular region in any eyes on fluorescein angiography or OCT imaging. The configurations of well-defined increased FAF in 23 eyes corresponded with the preoperative CNV in two eyes (9%) and subretinal hemorrhages in five eyes (22%). Well-defined increased FAF larger than the CNV or subretinal hemorrhage was seen in 16 eyes (69%). The RPE area located at the area of the preoperative CNV had a FAF defect or decreased FAF in 30 eyes (97%) on postoperative FAF imaging; there were no increased FAF changes. CONCLUSIONS: Well-defined increased FAF at the new macula after MT360 suggests that FAF reflects not only fluorophores in the RPE but also in the neurosensory retina. These fluorophores may result from interactions between the retina and CNV/pathologic RPE.     

ABCA4 gene mutations in Japanese patients with Stargardt disease and retinitis pigmentosa

PURPOSE: To evaluate photoreceptor cell-specific adenosine triphosphate (ATP)-binding cassette transporter (ABCA4) gene mutations in Japanese patients with Stargardt disease (STGD) and the correlation of these mutations to clinical phenotypes. METHODS: Serum was obtained from 10 unrelated Japanese patients with STGD and 96 unrelated Japanese patients with autosomal recessive retinitis pigmentosa (arRP). All 50 ABCA4 gene exons of the patients with STGD were screened for mutations by a combination of single-strand conformation polymorphism analysis and polymerase chain reaction (PCR) direct-sequencing techniques. By restriction enzyme digestion, primer extension analysis, and PCR direct sequencing techniques, the patients with arRP were screened for three segregated, presumably null ABCA4 gene mutations observed in Japanese patients with STGD. RESULTS: Three novel, presumably null mutations of the ABCA4 gene, IVS7-45_952delinsTCTGACC, IVS12+2T-->G, and 1894delA, were identified. The Arg2149stop mutation that had been found in a white patient with STGD in a prior study was also found in a Japanese patient. Two arRP-affected siblings and two unrelated patients with STGD were found to be homozygous for the same IVS12+2T-->G mutation, and three other arRP-affected siblings were carriers of the IVS12+2T-->G mutation and/or the IVS7-45_952delinsTCTGACC mutation. These three siblings with arRP showed only atrophic degeneration in the macula early after the onset of the disease, and STGD had been diagnosed. CONCLUSIONS: Three novel ABCA4 gene mutations were identified in Japanese patients with STGD and arRP. Mutations in the ABCA4 gene can cause panretinal degeneration that changes its clinical appearance from STGD to arRP over time.     

Expression Levels of Renal Organic Anion Transporters (OATs) and Their Correlation with Anionic Drug Excretion in Patients with Renal Diseases

PURPOSE: Because the urinary excretion of drugs is often decreased in renal diseases, dosage regimens are adjusted to avoid adverse drug reactions. The aim of present study was to clarify the alteration in the levels of renal drug transporters and their correlation with the urinary drug excretion in renal diseases patients. METHODS: We quantified the mRNA levels of human organic anion transporters (hOATs) by real-time polymerase chain reaction and examined the excretion of the anionic drug, cefazolin, in renal disease patients. Moreover, transport of cefazolin by hOAT1 and hOAT3 were examined using HEK293 transfectants. RESULTS: Among four hOATs, the level of hOAT1 mRNA was significantly lower in the kidney of patients with renal diseases than in the normal controls. The elimination constant of cefazolin showed a significant correlation with the values of phenolsulfonphthalein test and mRNA levels of hOAT3. The uptake study using HEK293 transfectants revealed that cefazolin and phenolsulfonphthalein were transported by hOAT3. CONCLUSIONS: These results suggest that hOAT3 plays an important role for anionic drug secretion in patients with renal diseases and that the expression levels of drug transporters may be related to the alteration of renal drug secretion.     

HERPES SIMPLEX ESOPHAGITIS IN THE ELDERLY

Herpes simplex esophagitis (HSE) occurs mostly in immunocompromised patients and rarely in immunocompetent patients. We encountered an elderly patient, a biologically immunocompromised patient with HSE who had characteristic endoscopic features and responded to acyclovir therapy. An 82‐year‐old woman presented with high‐grade fever and epigastric discomfort for several days. A diagnosis of bacterial pneumonia was made based on imaging studies and cultures. Despite antibiotic treatment, epigastric discomfort persisted. Endoscopy revealed multiple exudative and circumscribed shallow ulcers with slightly raised edges in the mid‐distal esophagus. Esophageal biopsy specimens showed multinucleated giant cells with Cowdry type A intranuclear inclusion bodies in epithelial cells, which were positive for herpes simplex virus‐type 1 DNA by polymerase chain reaction. Because a diagnosis of HSE was made, she was treated with acyclovir, resulting in esophageal mucosal healing. In elderly patients with esophageal symptoms, HSE should be considered.     

Cytochemical and cytological properties of perineuronal oligodendrocytes in the mouse cortex

Neuronal cell bodies are associated with glial cells collectively referred to as perineuronal satellite cells. One such satellite cell is the perineuronal oligodendrocyte, which is unmyelinating oligodendrocytes attaching to large neurons in various neural regions. However, little is known about their cellular characteristics and function. In this study, we identified perineuronal oligodendrocytes as 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase‐positive cells attaching to neuronal perikarya immunostained for microtubule‐associated protein 2, and examined their cytochemical and cytological properties in the mouse cerebral cortex. 2′,3′‐Cyclic nucleotide 3′‐phosphodiesterase‐positive perineuronal oligodendrocytes were immunonegative to representative glial markers for astrocytes (brain‐type lipid binding protein and glial fibrillary acidic protein), microglia (Iba‐1) and NG2⁺ glia. However, almost all perineuronal oligodendrocytes expressed glia‐specific or glia‐enriched metabolic enzymes, i.e. the creatine synthetic enzyme S‐adenosylmethionine:guanidinoacetate N‐methyltransferase and l ‐serine biosynthetic enzyme 3‐phosphoglycerate dehydrogenase. As to molecules participating in the glutamate–glutamine cycle, none of the perineuronal oligodendrocytes expressed the plasmalemmal glutamate transporters GLAST and GLT‐1, although nearly half of the perineuronal oligodendrocytes were immunopositive for glutamine synthetase. Cytologically, perineuronal oligodendrocytes were mainly distributed in deep cortical layers (layers IV–VI), and attached directly and tightly to neuronal cell bodies, making a long concave impression to the contacting neurons. Interestingly, they attached more to glutamatergic principal neurons than to GABAergic interneurons, and this became evident at postnatal day 14, when the cerebral cortex develops and maturates. These cytochemical and cytological properties suggest that perineuronal oligodendrocytes are so differentiated as to fulfill metabolic support to the associating principal cortical neurons, rather than to regulate their synaptic transmission.     

Limitation of apoptosis induced by gefitinib in a long-surviving postoperative recurrent lung cancer case

Although gefitinib is known to possess an effect inducing apoptosis against lung cancer, it is not clear how clinically effective it is in this regard in patients with lung cancer. Therefore, we tried to reduce its administration from every to every other day in a 73-year-old woman in good condition over 5 years after the recurrence of lung cancer. As a result, her CEA serum level then commenced to increase to the abnormal range within a month. Apoptosis induced by gefitinib was thought not sufficient to kill all lung cancer cells even though well controlled by it for a long period.