Usefulness and accuracy of segmental adrenal venous sampling on localisation and functional diagnosis of various adrenal lesions in primary aldosteronism.

AIM: To clarify the usefulness and accuracy of segmental adrenal venous sampling (sAVS) on localisation and functional diagnosis of various adrenal lesions in primary aldosteronism. MATERIALS AND METHODS: Consecutive patients (n=162) who underwent adrenalectomy and 138 patients indicated for medication following sAVS were analysed retrospectively. Based on immunohistopathological diagnosis, the positive predictive value (PPV) of computed tomography (CT)-detectable aldosterone-producing adenoma (APA) was calculated. Moreover, endocrinological and sAVS characteristics were analysed quantitatively and qualitatively among APA, CT-undetectable aldosterone-producing nodules (APNs), multiple aldosterone-producing micronodules (MAPM), and medication groups. RESULTS: The PPV of APA by sAVS was 137/141 (97.1%; 95% confidence interval, 92.9-99.2%). Compared to the medication cases, the APA group showed stronger disease activity clinically and significant differences in adrenal hormones, such as a higher aldosterone level and aldosterone-to-cortisol ratio, and lower cortisol levels in the adrenal central vein and aldosterone maximum tributaries on the dominant side after cosyntropin stimulation. The APA group shows focal aldosterone hypersecretion, such as mean number of aldosterone elevated segments (1.7 ± 0.7 versus 2 ± 0.9, p=0.003) and presence of aldosterone-not-elevated segments (93% versus 41%, p<0.001). Clinically and in terms of sAVS, APN and MAPM showed similar characteristics to APA and to the medication cases, respectively. CONCLUSION: sAVS can localise functionally active tissues of CT-detectable and CT-undetectable lesions enabling decisions on surgical or medical treatment.

Sputum-to-serum hydrogen sulphide ratio as a novel biomarker of predicting future risks of asthma exacerbation.

BACKGROUND: Increased level of hydrogen sulphide (H2 S) in sputum is reported to be a new biomarker of neutrophilic airway inflammation in chronic airway disorders. However, the relationship between H2 S and disease activity remains unclear. OBJECTIVE: We investigated whether H2 S levels could vary during different conditions in asthma. METHOD: H2 S levels in sputum and serum were measured using a sulphide-sensitive electrode in 47 stable asthmatic subjects (S-BA), 21 uncontrolled asthmatic subjects (UC-BA), 26 asthmatic subjects with acute exacerbation (AE-BA) and 15 healthy subjects. Of these, H2 S levels during stable, as well as exacerbation states, were obtained in 13 asthmatic subjects. RESULTS: Sputum H2 S levels were significantly higher in the AE-BA subjects compared to the UC-BA and healthy subjects (P < .05). However, serum H2 S levels in the AE-BA subjects were lower than in the S-BA subjects (P < .001) and similar to those in healthy subjects. Thus, the sputum-to-serum ratio of H2 S (H2 S ratio) in the AE-BA subjects was significantly higher than in the S-BA, UC-BA and healthy subjects (P < .05). Among all subjects, sputum H2 S levels showed a trend to decrease with FEV1 %predicted and significantly positive correlations with sputum neutrophils (%), sputum IL-8 and serum IL-8. A multiple linear regression analysis showed that sputum H2 S was independently associated with increased sputum neutrophils (%) and decreased FEV1 %predicted (P < .05). The cut-off level of H2 S ratio to indicate an exacerbation was ≥0.34 (area under the curve; 0.88, with a sensitivity of 81.8% and specificity of 72.7%, P < .001). Furthermore, half of the asthmatic subjects with H2 S ratios higher than the cut-off level experienced asthma exacerbations over the following 3 months after enrolment. CONCLUSIONS: The H2 S ratio may provide useful information on predicting future risks of asthma exacerbation, as well as on obstructive neutrophilic airway inflammation as one of the non-Th2 biomarkers, in asthma.

Key factors for school health policy implementation in Thailand.

Thailand formulated a National School Health Policy (NSHP) in 1998, and it has been widely implemented but has not been evaluated. This case study aimed to identify factors that have influenced the implementation of NSHP in Thailand. For this purpose, we conducted a document review and key informant interviews. We selected key interviewees, from NSHP implementers at national, provincial and school levels in four geographical areas. We adopted a content analysis method, using a framework of 12 influential components of successful policy implementation and triangular policy framework. This study showed that NSHP was well-disseminated and implemented at whole country. We identified seven positive factors influencing NSHP implementation, namely matching with ongoing educational strategy, competition and encouragement by an awarding system, sustainable human capacity building at school level, participation of multiple stakeholders, sufficient understanding and acceptance of school health concepts, sharing information and collaboration among schools in the same clusters and functional fund raising activities. In addition, we identified three negative factors, namely lack of institutional sustainability, vague role of provincial officers and diverse health problems among Thai children. The government should clarify the role of provincial level and set up institutionalized capacity-building system as measures to strengthen monitoring and evaluation activities.

Lipid-laden bronchoalveolar macrophages in asthma and chronic cough.

BACKGROUND: The presence of lipids in alveolar macrophages (AMs) may impair their phagocytic response, and determine airway inflammation and obstruction. OBJECTIVE: To determine the factors such as severity of asthma, chronic cough, airway inflammation and obesity that may influence the presence of lipids in lung macrophages. METHODS: Bronchoalveolar lavage fluid (BALF) was obtained from 38 asthmatics (21 severe and 17 mild/moderate), 16 subjects with chronic cough and 11 healthy control subjects. The presence of lipids in macrophages was detected using an Oil-red-O stain and an index of lipid-laden macrophages (LLMI) was obtained. RESULTS: LLMI scores were higher in healthy subjects (median 48 [IQR 10-61]) and the severe asthma group (37 [11.5-61]) compared to mild/moderate asthmatics (7 [0.5-37]; p < 0.05 each). Subjects reporting a history of gastro-oesophageal reflux disease (GORD) had higher LLMI values (41.5 [11.3-138] versus 13 [0-39.3], p = 0.02). There was no significant correlation between LLMI and chronic cough, BAL cell differential counts, FEV1, FEV1/FVC or body mass index (BMI). CONCLUSIONS: The reduced LLMI in mild/moderate asthma may be related to lower incidence of GORD. However, this was not related to the degree of airflow obstruction, obesity or airway inflammation.

A single-blood-sample method using inulin for estimating feline glomerular filtration rate.

BACKGROUND: Application of a multisample method using inulin to estimate glomerular filtration rate (GFR) in cats is cumbersome. OBJECTIVES: To establish a simplified procedure to estimate GFR in cats, a single-blood-sample method using inulin was compared with a conventional 3-sample method. ANIMALS: Nine cats including 6 clinically healthy cats and 3 cats with spontaneous chronic kidney disease. METHODS: Retrospective study. Inulin was administered as an intravenous bolus at 50 mg/kg to cats, and blood was collected at 60, 90, and 120 minutes later for the 3-sample method. Serum inulin concentrations were colorimetrically determined by an autoanalyzer method. The GFR in the single-blood-sample method was calculated from the dose injected, serum concentration, sampling time, and estimated volume of distribution on the basis of the data of the 3-sample method. RESULTS: An excellent correlation was observed (r = 0.99, P = .0001) between GFR values estimated by the single-blood-sample and 3-sample methods. CONCLUSIONS AND CLINICAL IMPORTANCE: The single-blood-sample method using inulin provides a practicable and ethical alternative for estimating glomerular filtration rate in cats.

Estimation of glomerular filtration rate in rabbits by a single-sample method using iodixanol.

To estimate the glomerular filtration rate (GFR) in conscious rabbits, a single-sample method using the non-ionic contrast medium iodixanol was compared with a three-sample method using the standard agent inulin. Iodixanol and inulin were co-administered intravenously to male New Zealand White rabbits at 60 mg I/kg and 40 mg/kg, respectively, and blood was collected 30, 60, 90 and 120 min later. Serum iodixanol and inulin concentrations were separately determined by high performance liquid chromatography and colorimetry, respectively. Serum urea nitrogen (UN) and creatinine concentrations were also determined. Based on the data from healthy and cisplatin-treated rabbits, the GFR estimated by iodixanol was well consistent with that by inulin. Further, when the GFR decreased to more than 60% of the reference value, serum creatinine concentrations became elevated. However, serum UN concentrations exhibited wide fluctuations, presumably due to a difference in renal handlings. The single-sample method using iodixanol was considered to be an expedient tool in both clinical and research settings, because the stress due to a multi-sample method was reduced.

The incidence, treatment and prognosis of cervical carcinoma in young women: a retrospective analysis of 4,975 cases in Japan.

OBJECTIVE: To determine the clinical characteristics of patients (young women) with cervical carcinoma aged less than 35 years. METHODS: Data from patients who were treated for cervical carcinomas from 1990 to 2000 in the Kinki District were retrospectively investigated for clinical stage, histologic type, treatment procedure and prognosis. RESULTS: Of a total of 4,975 cases, 441 patients were aged less than 35 years old. The incidence of cervical carcinoma in these women was 7.9% from 1990 to 1995, 9.1% from 1996 to 2000, and 9.5% from 2001 to 2005. FIGO Stage I included 374 cases, followed by, 49 in Stage II, 11 in Stage III, and seven in Stage IV. Squamous cell carcinoma incidence was 80.7% and non-squamous cell carcinoma incidence was 19.3%. Several types of surgery were performed in patients with Stage I and II, while patients with Stage III and IV were treated with radiotherapy and/or chemotherapy without any type of surgery. In patients who underwent lymphadenectomy, 21.1% cases had nodal involvement. The 5-year survival rate was 95% for Stage I disease, 73% for Stage II, 68% for Stage III, and 19% for Stage IV. CONCLUSION: The incidence of cervical carcinoma in young women slightly increased from 1990 to 2005. The prognosis of cervical carcinoma tends to be better in young women than in older patients, especially in Stage III disease.

Antifouling properties of tough gels against barnacles in a long-term marine environment experiment.

In the marine environment, the antifouling (AF) properties of various kinds of hydrogels against sessile marine organisms (algae, sea squirts, barnacles) were tested in a long-term experiment. The results demonstrate that most hydrogels can endure at least 2 months in the marine environment. In particular, mechanically tough PAMPS/PAAm DN and PVA gels exhibited AF activity against marine sessile organisms, especially barnacles, for as long as 330 days. The AF ability of hydrogels toward barnacles is explained in terms of an 'easy-release' mechanism in which the high water content and the elastic modulus of the gel are two important parameters.

Chronic osmotic stimuli increase salusin-beta-like immunoreactivity in the rat hypothalamo-neurohypophyseal system: possible involvement of salusin-beta on [Ca2+]i increase and neurohypophyseal hormone release from the axon terminals.

Salusin-alpha and -beta were recently discovered as bioactive endogenous peptides. In the present study, we investigated the effects of chronic osmotic stimuli on salusin-beta-like immunoreactivity (LI) in the rat hypothalamo-neurohypophyseal system. We examined the effects of salusin-beta on synaptic inputs to the rat magnocellular neurosecretory cells (MNCs) of the supraoptic nucleus (SON) and neurohypophyseal hormone release from both freshly dissociated SONs and neurohypophyses in rats. Immunohistochemical studies revealed that salusin-beta-LI neurones and fibres were markedly increased in the SON and the magnocellular division of the paraventricular nucleus after chronic osmotic stimuli resulting from salt loading for 5 days and dehydration for 3 days. Salusin-beta-LI fibres and varicosities in the internal zone of the median eminence and the neurohypophysis were also increased after osmotic stimuli. Whole-cell patch-clamp recordings from rat SON slice preparations showed that salusin-beta did not cause significant changes in the excitatory and inhibitory postsynaptic currents of the MNCs. In vitro hormone release studies showed that salusin-beta evoked both arginine vasopressin (AVP) and oxytocin release from the neurohypophysis, but not the SON. In our hands, in the neurohypophysis, a significant release of AVP and oxytocin was observed only at concentrations from 100 nm and above of salusin-beta. Low concentrations below 100 nm were ineffective both on AVP and oxytocin release. We also measured intracellular calcium ([Ca(2+)](i)) increase induced by salusin-beta on freshly-isolated single nerve terminals from the neurohypophysis devoid of pars intermedia. Furthermore, this salusin-beta-induced [Ca(2+)](i) increase was blocked in the presence of high voltage activated Ca(2+)channel blockers. Our results suggest that salusin-beta may be involved in the regulation of body fluid balance by stimulating neurohypophyseal hormone release from nerve endings by an autocrine/paracrine mechanism.

Mannose binding lectin gene polymorphisms and asthma.

BACKGROUND: Bronchial asthma is a chronic inflammatory disorder of the airways. Recently, it has been suggested that complement plays significant roles in asthma. Mannose-binding lectin (MBL) is one of the key molecules in complement activation pathways that are associated with several infectious and immune disorders. SUBJECTS AND METHOD: To investigate whether MBL plays roles in asthma, we analysed MBL2 polymorphisms (allele B, H/L and Y/X) and plasma MBL levels in a Japanese adult population including 232 healthy controls and 579 asthmatics. RESULTS: Although there was linkage disequilibrium among the three polymorphisms, each polymorphism significantly affects serum MBL levels independently. However, there were no significant differences between asthmatics and controls in MBL2 genotype distribution and in MBL concentrations [1.47+/-0.07(SE) mg/L for asthmatics and 1.66+/-0.14 mg/L for controls, P=0.2]. MBL levels and genotype have no significant relationship with serum IgE, pulmonary functions, and the severity of asthma. CONCLUSION: Although plasma MBL levels depend on the MBL2 polymorphisms, these polymorphisms and plasma MBL levels are not associated with the asthma phenotype.

Effects of the short chain sugar acid 2-buten-4-olide on the hypothalamo-pituitary-adrenal axis in normal and adjuvant-induced arthritic rats.

The effects of intraperitoneal (i.p.) administration of 2-buten-4-olide (2-B4O), an endogenous sugar acid, on the hypothalamo-adenohypophysial system were examined in Lewis rats that were normal and in adjuvant-induced arthritic (AA) rats. In comparison with vehicle-treated rats, the plasma corticosterone and c-fos mRNA levels in the paraventricular nucleus (PVN) of normal rats increased significantly after i.p. administration of 2-B4O. Dual immunostaining revealed that almost all corticotrophin-releasing factor (CRF)-immunopositive neurones in the parvocellular division of the PVN exhibited Fos-like immunoreactivity (LI) 120 min after i.p. administration of 2-B4O (100 mg/kg). In the AA rats, repeated i.p. administration of 2-B4O (100 mg/kg) after immunisation significantly suppressed the expression of clinical symptoms and significantly increased plasma concentrations of corticosterone. Further, repeated i.p. administration of 2-B4O significantly increased CRF mRNA levels in the PVN and pro-opiomelanocortin mRNA levels in the anterior pituitary; however, they did not change arginine vasopressin mRNA levels in the parvocellular division of the PVN. These results suggest that i.p. administration of 2-B4O activates the hypothalamo-pituitary-adrenal (HPA) axis via the activation of CRF neurones in the PVN, and the activation of the HPA axis by i.p. administration of 2-B4O may be associated with the inhibition of AA in rats.

Risk stratification for in-hospital mortality in spontaneous intracerebral haemorrhage: a Classification and Regression Tree analysis.

BACKGROUND: Risk stratification for mortality in intracerebral haemorrhage (ICH) helps guide care, but existing clinical prediction rules are too cumbersome for clinical practice because of their complexity. AIM: To develop a simple decision tree model of in-hospital mortality risk stratification for ICH patients. METHODS: We collected information on spontaneous ICH patients hospitalized in a teaching hospital in Japan from August, 1998 to December, 2001 (n = 374). All variables were abstracted from data available at the time of initial evaluation. A prediction rule for in-hospital mortality was developed by the Classification and Regression Tree (CART) methodology. The accuracy of the model was evaluated using the area under receiver-operator characteristic curve. RESULTS: Overall in-hospital mortality rate was 20.2%. The CART methodology identified four groups for mortality risk, varying from low (2.1%) to high (58.9%). Level of consciousness (coma) was the best single predictor for mortality, followed by high ICH volume (cut-off 10.4 ml), and then age (cut-off 75 years). The accuracy of our CART model (0.86) exceeded that of a multivariate logistic regression model (0.81). DISCUSSION: ICH patients can easily be stratified for mortality risk, based on three predictors available on admission. This simple decision tree model provides clinicians with a reliable and practical tool.

Genetic linkage analysis of pulmonary fibrotic response to silica in mice.

Inter-individual variations in the development of silicosis, even within the same environments, have been reported, which suggest the contribution of genetic factors in silicosis aetiology. The aim of the present study was to determine whether there is any significant genetic influence on the development of silicosis. Furthermore, which genetic loci are responsible for the pulmonary response to silica exposure? Eight strains of inbred mice were used to examine the genetic influence on the lung fibrotic response to silica exposure. After intercross-breeding between the most susceptible and most resistant strains, a genome-wide linkage analysis of quantitative trait loci (QTL) was performed. Hydroxyproline was applied as an index, and genotypes of 167 marker genes were analysed by fragment analysis using a capillary-type sequencer. There was significant inter-strain difference in the mean concentration of hydroxyproline contents among the eight strains of mice. Breeding studies were conducted between the most susceptible, C57BL/6J, and the most resistant strain, CBA/J. A genome-wide linkage analysis of silica-exposed intercrossed cohorts identified significant QTL on chromosome 4 and suggestive QTL on chromosomes 3 and 18. The present study demonstrates that genetic factors may play a significant role in fibrotic-lung responses to silica; one significant and two suggestive quantitative trait loci were identified.

The rubble-pile asteroid Itokawa as observed by Hayabusa.

During the interval from September through early December 2005, the Hayabusa spacecraft was in close proximity to near-Earth asteroid 25143 Itokawa, and a variety of data were taken on its shape, mass, and surface topography as well as its mineralogic and elemental abundances. The asteroid's orthogonal axes are 535, 294, and 209 meters, the mass is 3.51 x 10(10) kilograms, and the estimated bulk density is 1.9 +/- 0.13 grams per cubic centimeter. The correspondence between the smooth areas on the surface (Muses Sea and Sagamihara) and the gravitationally low regions suggests mass movement and an effective resurfacing process by impact jolting. Itokawa is considered to be a rubble-pile body because of its low bulk density, high porosity, boulder-rich appearance, and shape. The existence of very large boulders and pillars suggests an early collisional breakup of a preexisting parent asteroid followed by a re-agglomeration into a rubble-pile object.

Detailed images of asteroid 25143 Itokawa from Hayabusa.

Rendezvous of the Japanese spacecraft Hayabusa with the near-Earth asteroid 25143 Itokawa took place during the interval September through November 2005. The onboard camera imaged the solid surface of this tiny asteroid (535 meters by 294 meters by 209 meters) with a spatial resolution of 70 centimeters per pixel, revealing diverse surface morphologies. Unlike previously explored asteroids, the surface of Itokawa reveals both rough and smooth terrains. Craters generally show unclear morphologies. Numerous boulders on Itokawa's surface suggest a rubble-pile structure.

Touchdown of the Hayabusa spacecraft at the Muses Sea on Itokawa.

After global observations of asteroid 25143 Itokawa by the Hayabusa spacecraft, we selected the smooth terrain of the Muses Sea for two touchdowns carried out on 19 and 25 November 2005 UTC for the first asteroid sample collection with an impact sampling mechanism. Here, we report initial findings about geological features, surface condition, regolith grain size, compositional variation, and constraints on the physical properties of this site by using both scientific and housekeeping data during the descent sequence of the first touchdown. Close-up images revealed the first touchdown site as a regolith field densely filled with size-sorted, millimeter- to centimeter-sized grains.

Prolactin-releasing peptide is a potent mediator of stress responses in the brain through the hypothalamic paraventricular nucleus.

The effects of i.c.v. administration of prolactin-releasing peptide on neurons in the paraventricular nucleus of rats and plasma corticosterone levels were examined by measuring changes in Fos-like immunoreactivity, c-fos mRNA using in situ hybridization histochemistry, and plasma corticosterone using a specific radioimmunoassay. Approximately 80% of corticotropin-releasing hormone immunoreactive cells exhibited Fos-like immunoreactivity in the parvocellular division of the paraventricular nucleus 90 min after i.c.v. administration of prolactin-releasing peptide. The greatest induction of the c-fos mRNA expression in the paraventricular nucleus was observed 30 min after administration of prolactin-releasing peptide, and occurred in a dose-related manner. Plasma corticosterone levels were also significantly increased 30 min after administration of prolactin-releasing peptide. Next, the effects of restraint stress, nociceptive stimulus and acute inflammatory stress on the expression of the prolactin-releasing peptide mRNA in the dorsomedial hypothalamic nucleus, nucleus of the solitary tract and ventrolateral medulla were examined using in situ hybridization histochemistry for prolactin-releasing peptide mRNA. Restraint stress and acute inflammatory stress upregulated the prolactin-releasing peptide mRNA expression in the nucleus of the solitary tract and ventrolateral medulla. Nociceptive stimulus upregulated the prolactin-releasing peptide mRNA expression in the ventrolateral medulla. Finally, we observed that pretreatment (i.c.v. administration) with an anti-prolactin-releasing peptide antibody significantly attenuated nociceptive stimulus-induced c-fos mRNA expression in the paraventricular nucleus. These results suggest that prolactin-releasing peptide is a potent and important mediator of the stress response in the brain through the hypothalamic paraventricular nucleus.

HER-2 codon 655 polymorphism in cervical carcinogenesis.

HER-2 codon 655 polymorphism together with human papillomavirus (HPV) types were examined in a total of 279 cervical smear samples. Forty-nine patients with high-grade squamous intraepithelial lesion had higher frequency of high-risk HPV than 167 patients with low-grade squamous intraepithelial lesion and 63 controls. There was no statistical difference in the frequencies of HER-2 Ile/Ile, Ile/Val, and Val/Val genotypes between squamous intraepithelial lesions (SILs) and controls. When the Ile/Ile genotype was compared to the Ile/Val + Val/Val genotypes, there was also no statistical difference in the genotype prevalence between SILs and controls either in 91 or 188 patients with or without high-risk HPV, respectively. These results suggest that the HER-2 polymorphism at codon 655 in cervical cell samples is unlikely to be associated with HPV status and the onset of cervical cancer in a Japanese population.

Expression of immediate early genes and vasopressin heteronuclear RNA in the paraventricular and supraoptic nuclei of rats after acute osmotic stimulus.

Monitoring the expression of immediate early genes (IEGs) is useful for following stress-induced cellular responses in the neuroendocrine system. We have examined the transcriptional activities of four IEGs (c-fos, junB, NGFI-A and NGFI-B) and of the arginine vasopressin (AVP) gene in the hypothalamic paraventicular (PVN) and supraoptic nuclei (SON) of rats after acute osmotic stimuli, using in situ hybridization histochemistry. After intraperitoneal (i.p.) administration of hypertonic saline (2% body weight, 900 mOsm/kg), the expression levels of all IEG mRNAs were increased significantly both in the PVN and SON at as early as 10 min, peaked at 30 min and remained elevated until 60 min. The expression of AVP heteronuclear (hn)RNA also peaked at 30 min, and remained elevated until 180 min. Thirty min after i.p. administration of hypertonic saline (600 mOsm/kg), the expression levels of all IEG mRNAs in the PVN and SON were significantly increased in comparison with those after i.p. administration of isotonic saline (290 mOsm/kg). Regression analysis revealed that expression levels of the IEG mRNAs and AVP hnRNA were positively correlated with the plasma concentration of sodium, and the rates of increase of the expression levels of all IEG mRNAs were similar. The expression levels of all IEG mRNAs examined are useful markers for following the changes of the AVP gene transcription in the PVN and SON after acute osmotic stimuli in rats.