A comparative study for detecting CYP3A induction by CYP3A probe drugs and endogenous markers in cynomolgus monkeys.

CYP3A probe drugs such as midazolam and endogenous markers, and plasma 4ß-hydroxycholesterol (4ß-OHC) and urinary 6ß-hydroxycortisol-to-cortisol ratios (6ß-OHC/C) have been used as markers of CYP3A induction in cynomolgus monkeys, as with humans. However, there is limited information on their sensitivity and ability to detect CYP3A induction, as most studies were evaluated only at a high dose of the inducer, rifampicin (RIF; 20 mg/kg). In the present study, the CYP3A induction by RIF over a range doses of 0.2, 2 and 20 mg/kg (n = 4) was examined using CYP3A probe drugs (midazolam, triazolam and alprazolam) and the plasma and urinary endogenous CYP3A markers (4ß-OHC and 6ß-OHC/C). The sensitivity and relationship for detecting CYP3A induction was compared among the markers. Four days repeated oral administration of rifampicin to cynomolgus monkeys reduced the area under the plasma concentration-time curve of all CYP3A probe drugs in a rifampicin dose-dependent manner. Although the endogenous CYP3A markers (4ß-OHC and 6ß-OHC/C) were also changed for the middle (2 mg/kg) and high (20 mg/kg) doses of rifampicin, the fold-changes were relatively small, and CYP3A induction could not be detected at the lowest dose of rifampicin (0.2 mg/kg). In conclusion, CYP3A probe drugs are more sensitive for detecting CYP3A induction than endogenous CYP3A markers in cynomolgus monkeys, even for a short experimental period.

Design and synthesis of selective CDK8/19 dual inhibitors: Discovery of 4,5-dihydrothieno[3',4':3,4]benzo[1,2-d]isothiazole derivatives.

To develop a novel series of CDK8/19 dual inhibitors, we employed structure-based drug design using docking models based on a library compound, 4,5-dihydroimidazolo[3',4':3,4]benzo[1,2-d]isothiazole 16 bound to CDK8. We designed various [5,6,5]-fused tricyclic scaffolds bearing a carboxamide group to maintain predicted interactions with the backbone CO and NH of Ala100 in the CDK8 kinase hinge region. We found that 4,5-dihydrothieno[3',4':3,4]benzo[1,2-d]isothiazole derivative 29a showed particularly potent enzymatic inhibitory activity in both CDK8/19 (CDK8 IC50: 0.76nM, CDK19 IC50: 1.7nM). To improve the physicochemical properties and kinase selectivity of this compound, we introduced a substituted 3-pyridyloxy group into the scaffold 8-position. The resulting optimized compound 52h showed excellent in vitro potency (CDK8 IC50: 0.46nM, CDK19 IC50: 0.99nM), physicochemical properties, and kinase selectivity (only 5 kinases showed <35% unbound fraction at 300nM. CDK19: 4.6%, CDK8: 8.3%, HASPIN: 23%, DYRK1B: 27%, HIP1: 32%). Based on a docking model of 52h bound to CDK8, we could explain the highly specific kinase activity profile found for this compound, based on the interaction of the pyridyl group of 52h interacting with Met174 of the CDK8 DMG activation loop. In vitro pharmacological evaluation of 52h revealed potent suppression of phosphorylated STAT1 in various cancer cells. The high oral bioavailability found for this compound enabled in vivo studies, in which we demonstrated a mechanism-based in vivo PD effect as well as tumor growth suppression in an RPMI8226 human hematopoietic and lymphoid xenograft model in mouse [T/C: -1% (2.5mg/kg, qd)].

Studies of CDK 8/19 inhibitors: Discovery of novel and selective CDK8/19 dual inhibitors and elimination of their CYP3A4 time-dependent inhibition potential.

In this article, synthetic studies around a pyridylacrylamide-based hit compound (1), utilizing structure-based drug design guided by CDK8 docking models, is discussed. Modification of the pendant 4-fluorophenyl group to various heteroaromatic rings was conducted aiming an interaction with the proximal amino acids, and then replacement of the morpholine ring was targeted for decreasing potential of time-dependent CYP3A4 inhibition. These efforts led to the compound 4k, with enhanced CDK8 inhibitory activity and no apparent potential for time-dependent CYP3A4 inhibition (CDK8 IC50: 2.5nM; CYP3A4 TDI: 99% compound remaining). Compound 4k was found to possess a highly selective kinase inhibition profile, and also showed favorable pharmacokinetic profile. Oral administration of 4k (15mg/kg, bid. for 2weeks) suppressed tumor growth (T/C 29%) in an RPMI8226 mouse xenograft model.

IgE Abs to Der p 1 and Der p 2 as diagnostic markers of house dust mite allergy as defined by a bronchoprovocation test.

BACKGROUND: Limited information is available regarding the clinical usefulness of measuring the levels of IgE to allergen components from house dust mites (HDMs) in the diagnosis of genuine HDM allergy. METHODS: To evaluate the diagnostic usefulness of measuring levels of serum IgE antibodies (Abs) to allergen components from Dermatophagoides pteronyssinus (DP) as a predictor of immediate asthmatic response (IAR) to bronchoprovocation, we studied 55 DP-sensitized asthmatic patients who underwent a bronchoprovocation test using crude DP extract. The levels of IgE Abs to crude DP, nDer p 1, rDer p 2, and rDer p 10 in patients who showed IAR (n = 41) were compared with those in patients who showed no IAR (n = 14). RESULTS: While the frequencies of positivity for IgE Abs to nDer p 1 and rDer p 2 among the entire study population were 89 and 86%, respectively, all patients with IAR tested positive for both of them with high IgE concentrations. The areas under the receiver operating characteristic curves for IgE to nDer p 1 and rDer p 2 as predictors of IAR were 0.913 and 0.906, respectively. The specificity of IgE to nDer p 1 and rDer p 2 was higher than IgE to crude DP even at low cut-off points. CONCLUSIONS: IgE to nDer p 1 and/or rDer p 2 was highly predictive of allergen-induced IAR. These findings validate the clinical usefulness of measuring the levels of IgE to nDer p 1 and rDer p 2 as a diagnostic tool for genuine HDM allergy.

Development of vascular smooth muscle contractility by endothelium-derived transforming growth factor ß proteins.

It is well established that the release of vasodilators and vasoconstrictors from vascular endothelium regulates vascular smooth muscle contraction. In this report, we investigate the role of the endothelium in the development and maintenance of constitutive vascular contractility. For that purpose, contractile activity of cultured bovine aortic smooth muscle cells (BASMCs) embedded in collagen gels was monitored by changes in gel diameter. After culturing for 5 days, ATP- and high KCl solution-induced contractions were significantly enhanced in the gels that were overlaid with bovine aortic endothelial cells (BAECs) or were cultured with conditioned medium of cultured BAECs. ATP-induced Ca(2+) transients, recorded in BASMCs cultured with conditioned medium of BAECs, were markedly augmented, but high KCl-induced Ca(2+) transients were not affected. BASMCs in control gels were spindle shaped, and those in endothelium-treated gels were more elongated and interconnected. The endothelial conditioned medium also strongly affected the intracellular distribution of actin fibers. Conditioned medium of BAECs contained TGFß1 and TGFß2. The TGFß receptor antagonist SB431542 as well as simultaneous treatment with TGFß1 and TGFß2 neutralizing antibodies completely reversed the above effects of endothelial conditioned medium on BASMCs. BAECs medium induced phosphorylation of Smad2 and increased ATP-induced phosphorylation of myosin light chain in BASMCs. The present results indicate that the release of TGFß1 and TGFß2 from vascular endothelium affects the contractility of vascular smooth muscle cells by altering their morphology and agonist-induced Ca(2+) mobilization.

Effect of dalteparin, a low-molecular-weight heparin, as adjunctive therapy in patients with Kawasaki disease: a retrospective study.

BACKGROUND: Dalteparin, a low-molecular-weight heparin, has anticoagulant and anti-angiogenic activity. This study investigated whether dalteparin reduced coronary artery lesion (CAL) prevalence, and resistance to intravenous immunoglobulin (IVIG) therapy in Kawasaki disease (KD). METHODS: This retrospective study comprised two parts. In the first cohort, 126 patients with KD (68 male, 58 female; median age: 22 months, range: 1-67 months) admitted to Nihon University Nerima-Hikarigaoka Hospital from January 2004 to June 2008, received either dalteparin 75 IU/kg/day, IVIG 400 mg/kg/day for 5 consecutive days, and aspirin 30 mg/kg/day, or dalteparin 75 IU/kg/day and aspirin 30 mg/kg/day, until clinical improvement. Control data came from the 2005-6 Nationwide KD survey. In the second cohort, 112 patients with KD (59 male, 53 female; median age: 19 months, range: 1-66 months) admitted from June 2010 to February 2012, received either dalteparin 75 IU/kg/day, IVIG 2.0 g/kg over 12 h, and aspirin 30 mg/kg/day, or dalteparin 75 IU/kg/day and aspirin 30 mg/kg/day. Control data came from the 2009-10 Nationwide KD survey. No patients enrolled in the nationwide surveys received dalteparin. All patients at our institution were given dalteparin in their combination therapy. RESULTS: A comparison of the first cohort with controls in the nationwide survey showed that the prevalence of initial administration of IVIG was 80.2% versus 86.0%; the rate of additional IVIG administration was 7.1% versus 14.0% (p = 0.03); CAL prevalence in the acute period was 4.8% versus 11.9% (p < 0.01); and the prevalence of cardiovascular sequelae was 0% versus 3.8% (p < 0.05). A comparison of the second cohort with controls in the nationwide survey showed that the rate of initial administration of IVIG was 92.9% versus 89.5%; the rate of additional IVIG administration was 8.9% versus 17.1% (p = 0.02); the prevalence of resistance to IVIG was 3.6% versus 14.9% (p < 0.001); and CAL prevalence in the acute period was 2.7% versus 8.6% (p = 0.03). CONCLUSIONS: This study found that adjunctive dalteparin was associated with a lower prevalence of IVIG resistance and CAL in young children with KD. TRIAL REGISTRATION UMIN-CTR: UMIN000010349.

[Comparison of exhaled nitric oxide levels measured by two offline methods and the NO breath® method in Japan].

BACKGROUND: The fraction of exhaled nitric oxide (FeNO) is a useful marker of eosinophilic airway inflammation in asthmatics. Clinical application of FeNO measurement in Japan is expected increase because the procedure is now covered through health insurance. However, the measurement system used is known to affect FeNO results, and it remains unknown whether results from offline methods correlate with those from traditional online methods, such as NO breath®. METHODS: The study population comprised 48 patients at our hospital. FeNO levels were measured by using two offline methods (Sievers and CEIS) and a standard online method, NO breath® RESULTS: FeNONO breath levels were significantly correlated with FeNOSievers(r=0.875) and FeNOCEIS(r=0.888) levels. FeNONO breath levels were nearly equal to FeNOSievers results (FeNONO breath=1.05×FeNOSievers), but both of these levels were lower (p=0.02) than FeNOCEIS data (FeNONO breath=0.74×FeNOCEIS). A Bland-Altman plot of values obtained by the NO breath® and Sievers methods revealed that the NO breath® result was lower than the Sievers level when FeNO was low but was higher than the Sievers level when FeNO was high. CONCLUSION: Differences exist in the levels of FeNO measurement by three methods (two offline methods and NO breath®): conversion equations are needed to compare the FeNO levels obtained by using these three methods. In addition, NO breath® may be more useful to distinguish asthmatic patients from non-asthmatics, compared with Sievers method.

Oxidative addition of a strained C-C bond onto electron-rich rhodium(I) at room temperature.

The C-C bond of cyclobutanones undergoes oxidative addition to a T-shape rhodium(I) complex possessing a PBP pincer ligand at room temperature. The remarkable propensity of the rhodium complex for oxidative addition is attributed to the highly electron-donating nature of the boron ligand as well as the unsaturation on the rhodium center.

Cough variant and cough-predominant asthma are major causes of persistent cough: a multicenter study in Japan.

OBJECTIVE: Persistent cough is a frequent cause of doctor and hospital visits, and its incidence may be increasing. However, diagnosis of the cause of cough remains difficult. Because different causes of cough have different treatments, accurate diagnosis of the cause of cough is critical. To gain a better understanding of the causes of cough in Japan, we performed a multicenter epidemiological study of Japanese patients. METHODS: The study involved seven institutions in five different areas of Japan, and was conducted over 1 year from March 2009. Patients aged ≥16 years attending the participating centers for the first time complaining of cough persisting for ≥3 weeks were eligible. Patients with chest X-ray abnormalities responsible for cough, fever or blood-stained sputum were excluded, while those with wheeze or shortness of breath were included. Frequency and severity of cough were assessed using questionnaires, and laboratory tests were performed to enable differential diagnoses. RESULTS: Among the 313 patients evaluated, mean duration of cough symptoms was 192.1 ± 558.4 days. Cough variant asthma (CVA) was the most common cause of prolonged/chronic cough (42.2%), followed by cough-predominant asthma (CPA) (28.4%), atopic cough (7.3%) and chronic obstructive pulmonary disease (6.7%). Patients with an unclear diagnosis were treated with tulobuterol, a transdermal ß2-agonist preparation, for 1-2 weeks. Transdermal tulobuterol improved assessments of cough in patients with CVA or CPA, enabling rapid diagnosis of these diseases. CONCLUSIONS: These findings show that CVA and CPA are the main causes of cough persisting for ≥3 weeks.

A 4-year-old girl with clinically mild encephalopathy with a reversible splenial lesion associated with rotavirus infection.

Rotavirus is a common cause of severe gastroenteritis in children. It is known that rotavirus gastroenteritis may be accompanied by neurological manifestations, including encephalitis/encephalopathy and seizures. We report a case of a 4-year-old girl with clinically mild encephalopathy with a reversible splenial lesion associated with rotavirus infection. She was admitted to our hospital because of reduced level of consciousness, seizures, diarrhea, and vomiting. Fecal rotavirus antigen testing was positive. Cell counts in the cerebrospinal fluid (CSF) were normal. She had a normal serum sodium level on admission. Brain computed tomography showed no cerebral edema. However, electroencephalography showed generalized high-voltage slow waves, and diffusion-weighted magnetic resonance imaging demonstrated a transient abnormality in the splenium of the corpus callosum. We diagnosed clinically mild encephalopathy with a reversible splenial lesion associated with rotavirus infection. She recovered well and exhibited no neurological sequelae. Rotavirus RNA and antigen were not detected in the CSF, suggesting that the reversible splenial change was caused by indirect effects on the central nervous system subsequent to viral infection. Her normal serum sodium level indicates that this change can occur without hyponatremia.

Age-specific characteristics of inpatients with severe asthma exacerbation.

BACKGROUND: The characteristics of inpatients with severe asthma exacerbation remain unclear. It is considered that the characteristics of inpatients with severe asthma vary depending on age. However, these are rarely investigated. The objective of this study is to investigate the differences in characteristics among different age groups. We considered that it is necessary to understand the characteristics of each age group so that we can establish strategies in preventing severe asthma exacerbation. METHODS: All asthma inpatients who were hospitalized between 2004 and 2011 with SpO2 <90% (in room air), were breathless at rest, and showed increased respiratory rate and pulse rate were examined. We compared the characteristics among the young age group, middle age group, and advanced age group. RESULTS: The total number of patients was 204. In the young age group, the percentages of patients with irregular visits and non visits to a medical institution were high. This group showed high percentages of smokers and pet owners. The percentage of continuous ICS users in this group was 25.9%. The middle age group had high rates of aspirin-intolerant asthma. The percentage of continuous ICS users in this group was 60.2%. In the advanced age group, the percentages of patients with hypertension/heart disease, diabetes mellitus, and COPD were high. This group showed good treatment adherence. The percentage of continuous ICS users in this group was 77.4%. CONCLUSIONS: The characteristics of inpatients with severe asthma vary depending on age. We need to establish countermeasures for asthma exacerbation according to the characteristics of patients depending on age.

Rapid effectiveness of minocycline or doxycycline against macrolide-resistant Mycoplasma pneumoniae infection in a 2011 outbreak among Japanese children.

BACKGROUND: Mycoplasma pneumoniae is a major pathogen causing community-acquired pneumonia in children and young adults. Outbreaks typically occur at intervals of several years. In 2011, a widespread outbreak was associated with macrolide-resistant M. pneumoniae (MRMP) in Japanese children, often those of school age. METHODS: Two hundred fifty-eight children were diagnosed with M. pneumoniae-associated pneumonia based on chest radiography, real-time polymerase chain reaction (PCR), and antibody titers between January and December 2011. Mycoplasma pneumoniae cultures obtained from nasopharyngeal samples using appropriate broth were subjected to real-time PCR, by which decreases in M. pneumoniae in patients treated with minocycline (MIN), doxycycline (DOX), or tosufloxacin (TFX) were calculated. Mutations of the 23S ribosomal RNA gene that confer high resistance to macrolides in M. pneumoniae were identified by DNA sequencing. RESULTS: Among 202 M. pneumoniae isolates from M. pneumoniae-associated pneumonia patients, 176 (87.1%) were MRMP. Macrolide-resistant M. pneumoniae infection was significantly related to school age (P < .01) and initial administration of macrolides (P < .01). Minocycline or DOX (n = 125) or TFX or levofloxacin (n = 15) was used for definitive treatment of MRMP patients. Minocycline or DOX was significantly more effective than TFX (P ≤ .05) in achieving defervescence within 24 hours and in decreasing numbers of M. pneumoniae DNA copies 3 days after initiation. CONCLUSIONS: Macrolides are inappropriate as first-choice agents against MRMP in terms of shortening the clinical course and decreasing M. pneumoniae. Control and prevention of MRMP outbreaks in children require early decreases in M. pneumoniae as well as improvement of clinical findings.

Investigation of drug-drug interactions caused by human pregnane X receptor-mediated induction of CYP3A4 and CYP2C subfamilies in chimeric mice with a humanized liver.

The induction of cytochrome P450 (P450) enzymes is one of the risk factors for drug-drug interactions (DDIs). To date, the human pregnane X receptor (PXR)-mediated CYP3A4 induction has been well studied. In addition to CYP3A4, the expression of CYP2C subfamily is also regulated by PXR, and the DDIs caused by the induction of CYP2C enzymes have been reported to have a major clinical impact. The purpose of the present study was to investigate whether chimeric mice with a humanized liver (PXB mice) can be a suitable animal model for investigating the PXR-mediated induction of CYP2C subfamily, together with CYP3A4. We evaluated the inductive effect of rifampicin (RIF), a typical human PXR ligand, on the plasma exposure to the four P450 substrate drugs (triazolam/CYP3A4, pioglitazone/CYP2C8, (S)-warfarin/CYP2C9, and (S)-(-)-mephenytoin/CYP2C19) by cassette dosing in PXB mice. The induction of several drug-metabolizing enzymes and transporters in the liver was also examined by measuring the enzyme activity and mRNA expression levels. Significant reductions in the exposure to triazolam, pioglitazone, and (S)-(-)-mephenytoin, but not to (S)-warfarin, were observed. In contrast to the in vivo results, all the four P450 isoforms, including CYP2C9, were elevated by RIF treatment. The discrepancy in the (S)-warfarin results between in vivo and in vitro studies may be attributed to the relatively small contribution of CYP2C9 to (S)-warfarin elimination in the PXB mice used in this study. In summary, PXB mice are a useful animal model to examine DDIs caused by PXR-mediated induction of CYP2C and CYP3A4.

Allergenicity and cross-reactivity of booklice (Liposcelis bostrichophila): a common household insect pest in Japan.

BACKGROUND: Booklice (Liposcelis bostrichophila) are a common household insect pest distributed worldwide. Particularly in Japan, they infest 'tatami' mats and are the most frequently detected insect among all detectable insects, present at a frequency of about 90% in dust samples. Although it has been hypothesized that they are an important indoor allergen, studies on their allergenicity have been limited. METHODS: To clarify the allergenicity of booklice and the cross-reactivity of this insect allergen with allergens of other insects, patients sensitized to booklice were identified from 185 Japanese adults with allergic asthma using skin tests and IgE-ELISA. IgE-inhibition analysis, immunoblotting and immunoblotting-inhibition analysis were performed using sera from these patients. Allergenic proteins contributing to specific sensitization to booklice were identified by two-dimensional electrophoresis and two-dimensional immunoblotting. RESULTS: The booklouse-specific IgE antibody was detected in sera from 41 patients (22% of studied patients). IgE inhibition analysis revealed that IgE reactivity to the booklouse allergen in the sera from one third of booklouse-sensitized patients was not inhibited by preincubation with extracts from any other environmental insects in this study. Immunoblotting identified a 26-kD protein from booklouse extract as the allergenic protein contributing to specific sensitization to booklice. The amino acid sequence of peptide fragments of this protein showed no homology to those of previously described allergenic proteins, indicating that this protein is a new allergen. CONCLUSIONS: Sensitization to booklice was relatively common and specific sensitization to this insect not related to insect panallergy was indicated in this population.

A 7-year-old girl with subcutaneous emphysema, pneumomediastinum, pneumothorax, and pneumoretroperitoneum caused by Mycoplasma pneumoniae pneumonia.

A 7-year-old girl presented with subcutaneous emphysema, pneumomediastinum (PM), pneumoretroperitoneum, and pneumothorax caused by Mycoplasma pneumoniae (MP). The patient had been treated with clarithromycin for pneumonia at another hospital; however, her condition deteriorated and complications developed. Soon after admission to our hospital, we started the patient on minocycline and prednisolone, and the complications improved promptly. Laboratory data showed serum ferritin and urinary beta-2-microglobulin levels were greatly elevated. We therefore speculated that the patient might have underlying hypercytokinemia. Prednisolone is an effective treatment for hypercytokinemia. We therefore recommend prednisolone treatment for cases of severe M. pneumoniae pneumonia that do not respond to antimicrobial agents.

Posterior reversible encephalopathy syndrome in childhood: report of four cases and review of the literature.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a recently described disorder with typical radiological findings of bilateral gray and white matter abnormalities in the posterior regions of the cerebral hemispheres and cerebellum. Its clinical symptoms include headache, decreased alertness, mental abnormalities such as confusion, diminished spontaneity of speech, and changed behavior ranging from drowsiness to stupor, seizures, vomiting, and abnormalities of visual perception such as cortical blindness. In this study, the clinical and radiological findings of 4 children with this syndrome due to a variety of conditions are reported. METHODS: The records of 4 children with a diagnosis of PRES were retrospectively analyzed. RESULTS: PRES is associated with a disorder of cerebrovascular autoregulation of multiple etiologies. Four patients with PRES who had primary diagnoses of severe aplastic anemia, nephritic syndrome, Henoch-Schönlein purpura, and acute poststreptococcal glomerulonephritis are presented. This syndrome has been described in numerous medical conditions, including hypertensive encephalopathy, eclampsia, and with the use of immunosuppressive drugs. CONCLUSIONS: Early recognition of PRES as a complication during different diseases and therapies in childhood may facilitate precise diagnosis and appropriate treatment.

Acute encephalopathy with pandemic (H1N1) 2009 virus infection.

OBJECTIVES: In April 2009, a novel influenza A (H1N1) pdm virus was identified in Mexico and spread quickly around the world. However, the clinical features of acute encephalopathy associated with 2009 pandemic influenza have not yet been elucidated. METHODS: We treated 8 patients (3 boys and 5 girls) aged 4 to 11 years (average age, 8 y 3 months) with influenza virus-associated encephalopathy, who presented at our 2 hospitals between July 2009 and March 2010. We investigated the clinical characteristics, treatments, and outcomes in the patients. RESULTS: In all patients, brain computed tomography showed mild to severe diffuse cerebral edema, and electroencephalography revealed diffuse high-voltage slow waves. They were all treated with oseltamivir and methylprednisolone pulse therapy. Six patients recovered without any sequelae; however, the remaining 2 had residual neurological sequelae. These 2 patients presented with severe disturbance of consciousness, and their central nervous system symptoms appeared within 12 hours after the onset of fever. One patient had periventricular leukomalacia and symptomatic epilepsy by perinatal brain hypoxia, and the other patient had 1 complex febrile and 2 febrile seizures. CONCLUSIONS: This study showed that patients with influenza-associated encephalopathy caused by influenza A (H1N1) pdm infection were all older than those with seasonal influenza. Underlying neurological disease or history may be associated with poor prognosis.

[Analysis of inpatients with pneumonia due to influenza (H1N1) 2009--clinical aspects based on the presence or absence of respiratory complications].

We retrospectively analyzed the clinical aspects of inpatients with pneumonia caused by influenza (H1N1) 2009 after classifying them into two groups based on the presence or absence of respiratory complications. The study population--121 (5.6%) of 1,777 subjects diagnosed with influenza (H1N1) 2009 using a rapid influenza diagnostic kit or real-time reverse-transcription PCR-were hospitalized from August 2009 to May 2010 as detailed from admission to discharge in hospital medical charts. Of these, 72 had respiratory symptoms and most -56, or 3.2%, of the total-were diagnosed with pneumonia in chest radiography. The mean age of those with pneumonia was 6.9 years, 35.7% had a history of bronchial asthma and 80.4% were admitted within three days of onset. Some 75% of those with pneumonia, or 42, had respiratory distress (SpO2 < or = 93%) requiring supplementary oxygen. Significant lymphopenia and neutrophil increase were observed in blood tests of those admitted within three days of onset. Almost all were given an antiviral agent for 5 days. Among pneumonia cases, 14 (25%) also had severe respiratory complications such as pneumomediastinum and atelectasis, designated the complications group. They also had significantly lower oxygen saturation and significantly more elevated non-specific IgE on admission than those in the non-complications group (n = 42). Those with complications were hospitalized for significantly longer, and were administered isopretenol. All inpatients with influenza (H1N1) 2009 were discharged as healthy. Based on our retrospectively analyzed results in those with influenza (H1N1) 2009 pneumonia, we concluded that the following medical circumstances covered by the Japanese insurance system help lead to good outcomes: i) visiting the hospital soon after onset, ii) being diagnosed early using a rapid identification kit, iii) under-going systemic whole-body management, and iv) being administered antiviral and antibacterial agents.

Persistent airflow obstruction in young adult asthma patients.

BACKGROUND: Lung function determined by spirometry and the severity of dyspnea correlate weakly in asthma patients. We attempted to determine the risk factors in asthma patients having persistent airway obstruction despite of having only mild subjective symptoms, and to examine the possibility of improving FEV1 by treating asthma on the basis of the bronchodilator change in FEV1. METHODS: We examined asthma patients in their 20s and who visited Sagamihara National Hospital for the first time over a period of four years, by reviewing their clinical records. They underwent tests on the bronchodilator change in FEV1 and a test of airway hyperresponsiveness to histamine dihydrochloride. RESULTS: One hundred thirty-eight subjects (mean age, 25.6 years; 51 males, 87 females; current smoking, 30.4%; history of childhood asthma, 48.6%) were enrolled. Among them, 18.8% (26/138) showed persistent airway obstruction (postbronchodilator FEV1/FVC (%) <80%). Using the multiple logistic regression model, we found that history of childhood asthma and smoking history were the significant isolated risk factors for persistent airway obstruction. Moreover, we determined that the factors associated with the reversibility of airway obstruction in asthma patients without subjective symptoms were history of childhood asthma. CONCLUSIONS: In this study, patients not undergoing treatment for asthma were examined. History of childhood asthma and smoking history may be the risk factors for persistent airway obstruction in the asthma patients with mild subjective symptoms. Tests on the bronchodilator change in FEV1 should be performed in patients with history of childhood asthma and smoking history, even if they have only mild subjective symptoms.

Isolation of a PBP-pincer rhodium complex stabilized by an intermolecular C-H σ coordination as the fourth ligand.

A little help from my friends: a highly reactive, 16-electron square-planar rhodium complex was isolated. This species displays an intermolecular interaction between the rhodium and the C-H bond of another molecule as the fourth ligand to form an infinite network in the crystal lattice. The complex undergoes oxidative addition to the O-H bond of phenol or a primary alkyl alcohol to give the corresponding hydrido-phenoxido Rh(III) complex or carbonyl Rh(I) complex, respectively.