bluuebunny/crossref_metadata_2025 huggingface dataset:
Chloroplast biogenesis during rehydration of the resurrection plantXerophyta humilis: parallels to the etioplast–chloroplast transition
Authors: INGLE ROBERT A. , COLLETT HELEN , COOPER KEREN , TAKAHASHI YUICHIRO , FARRANT JILL M. , ILLING NICOLA
Published: September 2008

De‐etiolation of dark‐grown seedlings is a commonly used experimental system to study the mechanisms of chloroplast biogenesis, including the stacking of thylakoid membranes into grana, the response of the nuclear‐chloroplast transcriptome to light, and the ordered synthesis and assembly of photosystem II (PSII). Here, we present the xeroplast to chloroplast transition during rehydration of the resurrection plantXerophyta humilisas a novel system for studying chloroplast biogenesis, and investigate the role of light in this process. Xeroplasts are characterized by the presence of numerous large and small membrane‐bound vesicles and the complete absence of thylakoid membranes. While the initial assembly of stromal thylakoid membranes occurs independently of light, the formation of grana is light dependent. Recovery of photosynthetic activity is rapid in plants rehydrated in the light and correlates with the light‐dependent synthesis of the D1 protein, but does not require de novo chlorophyll biosynthesis. Light‐dependent synthesis of the chlorophyll‐binding protein Lhcb2 and digalactosyldiacylglycerol synthase 1 correlated with the formation of grana and with the increased PSII activity. Our results suggest that the molecular mechanisms underlying photomorphogenic development may also function in desiccation tolerance in poikilochlorophyllous resurrection plants.
Chromogranin A‐, serotonin‐, synaptophysin‐ and vascular endothelial growth factor‐positive endocrine cells and the prognosis of colorectal cancer: An immunohistochemical and ultrastructural study
Authors: Gulubova Maya , Vlaykova Tatyana
Published: September 2008

Background and Aim:  Endocrine differentiation in colorectal adenocarcinoma has been reported but its significance as a prognostic marker remains uncertain. The aim of the present study was to analyze the prognostic significance of endocrine differentiation in colorectal cancer.

Methods:  The presence of endocrine cells (EC) was determined in 137 colorectal cancers using light and electron immunohistochemistry and the immunogold method with chromogranin A, serotonin and synaptophysin. Vascular endothelial growth factor (VEGF) expression in tumor biopsies was also analyzed applying anti‐VEGF antibodies.

Results:  EC labeled with at least one of the studied markers were detected in 47 (34.3%) primary colorectal cancers (30% chromogranin A‐positive, 33% synaptophysin‐positive and 18% serotonin‐positive). In 23% of tumor biopsies, VEGF‐positive EC were also detected. The immunostaining on serial sections showed that some chromogranin A‐, synaptophysin‐ or serotonin‐positive EC also contained VEGF immune deposits. By the immunogold method, the presence of VEGF was localized to the granules of EC. Tumors with VEGF‐positive EC appeared to have significantly higher vascularization, detected as systematic microvessel density (28.89 vs 15.22 vessels/mm2, P = 0.044, Mann–Whitney U‐test) compared to those without VEGF‐positive EC. Ultrastructurally, EC in the tumor tissue displayed some features different from those in the normal colon. The survival analyses revealed that patients with EC in primary tumor tissues had a worse prognosis after surgical therapy than those without endocrine cell differentiation (P < 0.05, log–rank test).

Conclusions:  Endocrine differentiation is not an uncommon event in primary colorectal cancer and it could be a useful marker for a worse prognosis after the surgical therapy. Tumors positive for VEGF and containing VEGF‐positive EC have higher vascularization, which probably also contributes to the unfavorable prognosis of patients.
Pulmonary hypertension responding to hyperthyroidism treatment
Authors: HEGAZI Mohamed Osama , EL SAYED Amin , EL GHOUSSEIN Hussam
Published: September 2008

Abstract:  Pulmonary hypertension in adults with hyperthyroidism is increasingly being reported. Although the mechanism is uncertain, the reversal of pulmonary hypertension following restoration to an euthyroid state supports a causal relationship. This case report is of a 43‐year‐old woman who presented with Graves disease and right ventricular failure. Echocardiography showed severe pulmonary hypertension, moderate to severe tricuspid regurgitation, normal left heart function and a negative bubble contrast study. Carbimazole therapy was instituted along with diuretics and captopril. The patient was followed for a period of 14 months. Clinical and biochemical euthyroidism was attained after 4 months of treatment. Resolution of right ventricular failure and normalization of pulmonary artery pressure occurred 11 and 14 months after initiation of therapy, respectively. Investigating thyroid status in patients with pulmonary hypertension is recommended. In patients with hyperthyroidism and (otherwise unexplained) pulmonary hypertension, restoration of euthyroidism may cure right ventricular failure and restore normal pulmonary artery pressure.
Relationship between field walking tests and incremental cycle ergometry in COPD
Authors: LUXTON Nia , ALISON Jennifer A. , WU Judy , MACKEY Martin G.
Published: September 2008

Background and objective:  Cycle ergometer training is an important component of pulmonary rehabilitation for patients with COPD. However, incremental cycle tests from which individualized cycle training intensity can be prescribed may not be readily available to clinicians. The aims of the study were to (i) investigate the physiological and psychophysical responses to the 6‐min walk test (6MWT), incremental shuttle walk test (ISWT) and cycle ergometer test (CET); and (ii) determine whether the distance walked in either the 6MWT or the ISWT could be used to estimate peak work rate on a cycle ergometer.

Methods:  A repeated measures study was undertaken in COPD patients in a stable condition. The 6MWT, ISWT and CET were performed in random order, and physiological responses, rate of perceived exertion and dyspnoea were measured.

Results:  Twenty‐two patients with COPD completed the study. There was no significant difference in peak oxygen uptake between the 6MWT, ISWT and CET. The significant correlation between the 6MWD and incremental shuttle walk distance with peak watts on the CET (r = 0.63, P = 0.002 and r = 0.75, P < 0.001, respectively) was strengthened by the inclusion of weight, age and gender (r = 0.89 P = 0.001 and r = 0.91, P < 0.001). Bland–Altman analysis demonstrated a strong agreement between peak work rate measured on the CET and that estimated from either the 6MWT or the ISWT.

Conclusions:  The significant relationships found between the three exercise tests, and the regression equations predicting peak work rate on the CET from the 6MWT or the ISWT, may allow for the estimation of intensity of cycle exercise training from walk tests in COPD patients.
Association between polymorphisms of microsomal epoxide hydrolase and COPD: Results from meta‐analyses
Authors: HU Guoping , SHI Zhe , HU Jinxing , ZOU Guoming , PENG Gongyong , RAN Pixin
Published: September 2008

Background and objective:  COPD is a complex polygenic disease in which gene–environment interactions are very important. The gene encoding microsomal epoxide hydrolase (EPHX1) is one of several candidate loci for COPD pathogenesis and is highly polymorphic. Based χ on the polymorphisms of EPHX1 gene (tyrosine/histidine 113, histidine/arginine 139), the population can be classified into four groups of putative EPHX1 phenotypes (fast, normal, slow and very slow). A number of studies have investigated the association between the genotypes and phenotypes of EPHX1 and COPD susceptibility in different populations, with inconsistent results. A systematic review and meta‐analysis of the published data was performed to gain a clearer understanding of this association.

Methods:  The MEDLINE database was searched for case–control studies published from 1966 to August 2007. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.

Results:  Sixteen eligible studies, comprising 1847 patients with COPD and 2455 controls, were included in the meta‐analysis. The pooled result showed that the EPHX1 113 mutant homozygote was significantly associated with an increased risk of COPD (OR 1.59, 95% CI: 1.14–2.21). Subgroup analysis supported the result in the Asian population, but not in the Caucasian population. When the analysis was limited to only the larger‐sample‐size studies, studies in which controls were in Hardy–Weinberg equilibrium and studies in which controls were smokers/ex‐smokers, the pooled results supported the conclusion. The EPHX1 139 heterozygote protected against the development of COPD in the Asian population, but not in the Caucasian population. The other gene types of EPHX1 113 and EPHX1 139 were not associated with an increased risk of COPD. The slow activity phenotype of EPHX1 was associated with an increased risk of COPD. The fast activity phenotype of EPHX1 was a protective factor for developing COPD in the Asian population, but not in the Caucasian population. However, the very slow activity phenotype of EPHX1 was a risk for developing COPD in the Caucasian population, but not in the Asian population.

Conclusions:  The polymorphisms of EPHX1 113 and EPHX1 139 are genetic contributors to COPD susceptibility in Asian populations. The phenotypes of EPHX1 were contributors to overall COPD susceptibility.
Cross‐sectional and longitudinal construct validity of the Saint George's Respiratory Questionnaire in patients with IPF
Authors: PENG Shouchun , LI Zhenhua , KANG Jian , HOU Xianming
Published: September 2008

Background and objective:  This study was performed to confirm the cross‐sectional and longitudinal construct validity of the Saint George's Respiratory Questionnaire (SGRQ) for the measurement of health‐related quality of life (HRQoL) in patients with IPF.

Methods:  Sixty‐eight patients with IPF responded to the SGRQ and pulmonary function tests (PFT), dyspnoea testing, arterial blood gas analysis, 6‐min walk tests (6MWT) and high‐resolution computed tomography were performed in a baseline study. A follow‐up study was performed on 45 of these patients.

Results:  In the baseline study HRQoL as measured by the SGRQ was substantially impaired in IPF patients, especially in symptoms and activity domains. A significant decline in HRQoL was observed in the activity domain during follow up. TLC and changes in TLC showed the most significant inverse correlations with each SGRQ domain (r < −0.3, P < 0.05). In a stepwise multiple regression analysis, TLC contributed most significantly to each SGRQ component baseline score. Similar results were also observed during follow up. There was a significant correlation between total CT scores and each component of the SGRQ (r > 0.3, P ≤ 0.001). Changes in ground‐glass opacity on CT (CT‐alv) were also correlated with changes in each SGRQ domain (r > 0.3, P ≤ 0.001). Stepwise multiple regression analysis showed that interstitial opacity on CT (CT‐fib) contributed to variation in the baseline activity score, and that changes in CT‐alv independently contributed to overall changes in the SGRQ domains during follow up. The dyspnoea score, and changes in the dyspnoea score, correlated significantly with the SGRQ sores, with the exception of the symptoms score, in both the baseline and follow‐up studies.

Conclusions:  HRQoL as assessed by the SGRQ showed good cross‐sectional and longitudinal construct validity in patients with IPF. However, additional studies are required to analyse the reliability and responsiveness so that the SGRQ can be used in patients with IPF.
Lung transplantation in Hong Kong: 12 years of experience
Authors: WONG Chi Fong , FUNG Siu Leung , YAN See Wan , LEE Joseph , CHENG Lik Cheung , CHIU Clement S.W.
Published: September 2008

Background and objective:  A lung transplant programme was launched in August 1994 at Grantham Hospital in Hong Kong with the first single‐lung transplant performed in July 1995. A retrospective study was undertaken of all patients who had undergone lung transplantation and their outcomes analysed.

Methods:  Data were collected from hospital and outpatient records.

Results:  There were 12 transplants (two single‐lung and 10 double‐lung) performed in the 12 years to December 2006. No postoperative or early mortality was observed. In addition to the usual complications there were two cases of early pulmonary tuberculosis and one rare case of delayed fungal sternotomy infection. The 1‐year, 3‐year and 5‐year survival rates were 100%, 100% and 76.2%, respectively. All fatalities were related to the consequences of chronic rejection or its treatment.

Conclusions:  Despite the limited experience and the small case volume, the survival of patients was good and comparable with international experience.
Effects of Th2 pulmonary inflammation in mice with bleomycin‐induced pulmonary fibrosis
Authors: HIRATA Hirokuni , ARIMA Masafumi , FUKUSHIMA Yasutsugu , ISHII Yoshiki , TOKUHISA Takeshi , FUKUDA Takeshi
Published: September 2008

Background and objective:  Leucocytes, especially lymphocytes and neutrophils, as well as alveolar macrophages, that infiltrate into the lung are involved in the development of pulmonary fibrosis. However, the role of T helper (Th)2‐type inflammation, mediated by Th2 cells and eosinophils, in fibrosis remains unknown. Transgenic mice deficient in the transcriptional repressor, Bcl6, display an attenuation of Th2 cytokine production. We studied the effects of Th2‐type pulmonary inflammation on bleomycin‐induced pulmonary fibrosis using Bcl6 transgenic mice.

Methods:  Bleomycin was administered to ovalbumin (OVA)‐sensitized Bcl6 transgenic and wild‐type mice by intratracheal instillation during sequential OVA antigen challenge. Concentrations of transforming growth factor‐β1 in the BAL fluid were measured 2 weeks after bleomycin administration. At the same time lung tissue was examined histopathologically, and homogenized to assess collagen levels and Th1/Th2 cytokine mRNA expression.

Results:  Although OVA‐sensitized, bleomycin‐treated Bcl6 transgenic mice had markedly lower numbers of eosinophils in both BAL and lung tissue compared with OVA‐sensitized, bleomycin‐treated wild‐type mice, the development of pulmonary fibrosis in response to bleomycin was similar in Bcl6 transgenic mice and wild‐type mice.

Conclusion:  These results suggest that Th2‐dominant inflammation in the lung is not essential for the development of bleomycin‐induced pulmonary fibrosis.
Transbronchial biopsy is clinically useful in classifying patients with interstitial pneumonia associated with polymyositis and dermatomyositis
Authors: MOCHIMARU Hiroshi , KAWAMOTO Masashi , ENOMOTO Tatsuji , SAITOH Yoshinobu , ABE Shinji , NEI Takahito , FUKUDA Yuh , KUDOH Shoji
Published: September 2008

Background and objective:  The histological type of intraluminal fibrosis is an important prognostic factor for interstitial pneumonia. We therefore examined whether transbronchial lung biopsy (TBLB) specimens are useful for predicting the clinical course and prognosis of patients with interstitial pneumonia associated with polymyositis and dermatomyositis (PM/DM), with particular attention to the different types of intraluminal fibrosis.

Methods:  Twenty‐five cases of interstitial pneumonia associated with PM/DM were classified according to the pattern of intraluminal fibrosis as assessed by TBLB, and the clinical course and response to treatment were compared. Interstitial fibrosis was evaluated by sequential thin‐section CT scans.

Results:  In 19 of 25 (76%) cases, there was sufficient intraluminal fibrosis to perform an evaluation. Intraluminal fibrosis was classified as bud (polyp) type or mural incorporation type (either alone or mixed with bud type). The bud type was seen in five cases and these improved following treatment with corticosteroids only. The mural incorporation type was seen in 14 cases. In 11 of these 14 cases, progressive long‐term fibrosis developed and four cases were fatal, in spite of corticosteroid and immunosuppressive therapy. The response to drugs (P < 0.01) and survival (P < 0.05) were significantly greater in patients with bud‐type than mural incorporation‐type intraluminal fibrosis.

Conclusions:  Classification of the pattern of intraluminal fibrosis as assessed by TBLB is useful for predicting the response to treatment, clinical course and prognosis of interstitial pneumonia associated with PM/DM.
Underlying aetiology of pulmonary hypertension in 191 patients: A single centre experience
Authors: FRUCHTER Oren , YIGLA Mordechai
Published: September 2008

Background and objective:  The aim of this study was to describe the prevalence and annual incidence, as well as the aetiology of pulmonary hypertension (PHT) in a PHT clinic, so as to assist in future assessments of the economic burden of PHT.

Methods:  The medical records for all new cases of PHT, defined as systolic pulmonary artery pressure >45 mm Hg as measured by Doppler echocardiography, or as mean pulmonary artery pressure >25 mm Hg measured at cardiac catheterization, between January 1998 and December 2005, were reviewed. The aetiology of the PHT was recorded and separate mean annual incidences were calculated.

Results:  The study population included 191 patients ranging in age from 16 to 90 years. Respiratory disorders were the leading aetiology for PHT, accounting for 31% of cases, followed by collagen vascular diseases (19%), idiopathic (12%), haemodialysis (13%), chronic thromboembolism (8%), haematological diseases (7%), liver cirrhosis (6%) and hypoventilation syndrome (4%). The mean annual incidence of PHT was 15.9 new cases per million citizens per year, with a mean annual incidence due to respiratory disease of 4.82 (COPD, 3.83), collagen vascular disease 3.08, haemodialysis 2.08, idiopathic 1.92, chronic thromboembolism 1.33, haematological disease 1.17, liver disease 0.92 and hypoventilation syndrome 0.58. The mean annual incidence of PAH and chronic thromboembolic PHT that fitted the guidelines for therapy was 8.58 cases per year per million citizens.

Conclusion:  The current data may help in estimating the economic burden of PHT.
Phosphoinositide 3‐kinase δ inhibitor as a novel therapeutic agent in asthma
Authors: PARK Seoung J. , MIN Kyung H. , LEE Yong C.
Published: September 2008

Abstract:  Multiple signal transduction pathways are involved in airway inflammation with one of the key signalling pathways being phosphoinositide 3‐kinase (PI3K). Numerous components of the PI3K pathway play an important role in the expression and activation of inflammatory mediators, inflammatory cell recruitment, immune cell function, airway remodelling and corticosteroid insensitivity in asthma. More recently studies exploring the specific roles of different PI3K catalytic subunit isoforms in asthma have been initiated. Several of these have highlighted the importance of p110δ isoform as a novel target for therapeutic intervention in asthma. In this review the biological role of PI3Ks, especially PI3Kδ, are highlighted and the therapeutic potential of selective PI3Kδ inhibitor in asthma discussed.
Limited role for outpatient parenteral antibiotic therapy for community‐acquired pneumonia
Authors: INGRAM Paul R. , CERBE Lana , HASSELL Marilyn , WILSON Moira , DYER John R.
Published: September 2008

Background and objective:  This study examined the potential utility of outpatient parenteral antibiotic therapy (OPAT) as a means of reducing the excessive number of patients hospitalized with low‐risk community‐acquired pneumonia (CAP).

Methods:  A prospective feasibility study was conducted, in which a selection algorithm was applied to a cohort of patients admitted with suspected CAP, to identify a group in whom admission may have been prevented by the use of OPAT. Numbers of potentially suitable patients, inpatient bed days saved and frequency of adverse events that may have led to readmission were measured.

Results:  There were 118 inpatients treated with confirmed CAP during the study period, of whom 27 had low‐risk disease (Pneumonia Severity Index grades I–III). Application of the selection algorithm identified eight (30% of those with low‐risk disease) patients who were potentially suitable for OPAT, and this group commonly experienced adverse events during follow up which may have resulted in readmission to hospital.

Conclusions:  In many hospitalized patients with CAP, outpatient therapy is precluded by either disease severity or active medical and psychosocial factors. This limits the role of OPAT as a tool for reducing the inpatient burden of CAP.
Radiological diagnosis of small pulmonary nodules detected on low‐dose screening computed tomography
Authors: TSUSHIMA Kenji , SONE Shusuke , HANAOKA Takaomi , KUBO Keishi
Published: September 2008

Background and objective:  Early detection and treatment of small malignant pulmonary lesions can improve survival; however, screening by CT detects many false positives. This study retrospectively evaluated a protocol for the diagnostic work‐up of nodules detected by low‐dose CT (LDCT) that are ≤ 10 mm in diameter.

Methods:  A health screening programme included LDCT. Lesions detected were allocated to one of four categories: negative, semi‐negative, positive and semi‐positive. Positive and semi‐positive categories included non‐calcified nodules without a polygonal shape, and these patients had an initial diagnostic HRCT and were then followed up using high‐resolution CT (HRCT) at intervals determined by the characteristics of the lesion on screening LDCT and the initial diagnostic HRCT.

Results:  There were 275 nodules detected on screening LDCT; 84 patients had lesions classified as positive and 99 as semi‐positive. Thirteen nodules detected on screening LDCT were only determined to be polygonal and benign following the diagnostic HRCT. The sensitivity and specificity of the screening CT, when compared with diagnostic HRCT, for determining if nodules should be classified as positive were 100% and 97%. The sensitivity and specificity of the initial diagnostic HRCT for being able to predict lung cancer were 87.5% and 91.7% respectively.

Conclusions:  Following the detection of a pulmonary lesion on screening LDCT, a diagnostic HRCT is necessary to determine the timing of follow‐up HRCT. Diagnostic HRCT is needed to rationalize the screening for lung cancer to reduce the frequency of unnecessary follow‐up scans.
Bronchodilator reversibility, airway eosinophilia and anti‐inflammatory effects of inhaled fluticasone in COPD are not related
Authors: REID David W. , WEN Yudong , JOHNS David P. , WILLIAMS Trevor J. , WARD Chris , WALTERS E. Haydn
Published: September 2008

Background and objective:  Bronchodilator reversibility (BDR) is common in smoking‐related COPD, but the airway pathology underlying this has not been described. In particular, it is not known whether BDR is associated with underlying airway eosinophilia and whether BDR is predictive of a better response to inhaled corticosteroid (ICS) treatment.

Methods:  A double‐blind, placebo‐controlled, randomized 2 : 1 study of fluticasone propionate (FP), 500 µg twice daily versus placebo over 6 months was performed in subjects with mild to moderate COPD. Subjects with a clinical history of asthma were excluded, but not on BDR criteria alone. Induced sputum, BAL and endobronchial biopsies (EBB) were performed in 36 subjects at baseline, and 30 of these provided a second full set of samples (FP, n = 19; placebo, n = 11).

Results:  Baseline BDR was not related to airway eosinophilia and did not predict response to ICS. Post‐bronchodilator FEV1 increased in the FP group compared with the placebo group (P = 0.05), and there were within‐treatment group reductions in total symptom scores with FP (P < 0.05). Compared with placebo, FP reduced macrophage numbers but increased neutrophil numbers in EBB (P = 0.01 and P = 0.003, respectively). BAL neutrophil and epithelial cell numbers were also reduced with FP (P = 0.03 for both). There were within‐treatment group reductions in the numbers of EBB mast cells and CD8+ve lymphocytes with FP (P = 0.007).

Conclusions:  BDR was not related to any particular inflammatory phenotype or any clinical or anti‐inflammatory response to ICS in these subjects with mild to moderate COPD.
Epidemiology of primary systemic vasculitis in the Australian Capital Territory and south‐eastern New South Wales
Authors: Ormerod A. S. , Cook M. C.
Published: September 2008

Background:  The aim of the study was to determine the epidemiology of primary systemic vasculitis in the Australian Capital Territory and the surrounding rural region between 1995 and 2005.

Methods:  Cases were ascertained by a medical record search according to international consensus classification criteria. For antineutrophil cytoplasmic antibody‐associated vasculitides, ascertainment was corroborated by a search of all positive antineutrophil cytoplasmic antibody serology during the study period. Denominators were obtained from region‐specific census data collected during the study period. Prevalence, incidence and patient characteristics for primary systemic vasculitides were determined for two 5‐year periods, 1995–1999 and 2000–2004.

Results:  We identified 41 cases of primary systemic vasculitides (Wegener’s granulomatosis (WG), microscopic polyangiitis (MPA), Churg–Strauss syndrome or polyarteritis nodosa) between 1995 and 1999 and 67 between 2000 and 2004, giving prevalences of 95/million (95% confidence interval (CI) 76.9–116.1) and 148/million (95%CI 125.1–173.9), respectively. Annual incidence was similar in both periods (approximately 17/year per million adult population). Disease‐specific incidences (per million per year) for each of the two periods were 8.8 and 8.4 for WG, 2.3 and 5.0 for MPA, 2.3 and 2.2 for Churg–Strauss syndrome and 2.3 and 1.1 for polyarteritis nodosa. The rural incidence of MPA was 13.9 (95%CI 7.7–23.5) compared with 1.6 (95%CI 0.2–7.2) in the city and there was a trend towards a higher incidence of WG in rural than urban areas.

Conclusion:  The overall incidence of primary systemic vasculitides is similar to that reported from other developed countries. WG is more common in south‐eastern Australia than in southern Europe, whereas MPA is less common. There was a trend towards higher incidence of antineutrophil cytoplasmic antibody‐associated vasculitides in rural than urban areas.
Cardiac magnetic resonance imaging in the evaluation of cardiac sarcoidosis: an Australian single‐centre experience
Authors: Manins V. , Habersberger J. , Pfluger H. , Taylor A. J.
Published: September 2008

Background:  Cardiac involvement in systemic sarcoidosis is common; however, current diagnostic tools are imprecise. Recognition of cardiac sarcoidosis (CS) is important as it has a relatively poor prognosis. Gadolinium‐enhanced cardiac magnetic resonance imaging (Gad‐CMR) is emerging as an excellent technique in determining the presence of and extent to which cardiac muscle is affected by sarcoidosis.

Methods:  A retrospective analysis was performed on all patients with biopsy‐proven systemic sarcoidosis referred for Gad‐CMR scanning to evaluate potential cardiac involvement. All patients also underwent an electrocardiogram, Holter monitor and echocardiography. Gallium‐67 radionuclide investigation, positron emission tomography and cardiac biopsy were ordered at the discretion of the treating physician.

Results:  Eleven of the 20 patients had Gad‐CMR images supportive of the diagnosis of CS. Eight of these 11 patients met the Japanese Ministry of Health and Welfare (JMHW) criteria for the diagnosis of CS; three abnormal Gad‐CME scans consistent with diagnosis of CS were seen in patients who did not meet JMHW criteria. No patients with normal Gad‐CMR scan met JMHW criteria for CS.

Conclusion:  These findings suggest that Gad‐CMR is potentially superior to the JMHW criteria in the diagnosis of cardiac sarcoidosis.
Nephrotoxic effects of iodixanol and iopromide in patients with abnormal renal function receiving N‐acetylcysteine and hydration before coronary angiography and intervention: a randomized trial
Authors: Juergens C. P. , Winter J. P. , Nguyen‐Do P. , Lo S. , French J. K. , Hallani H. , Fernandes C. , Jepson N. , Leung D. Y. C.
Published: September 2008

Background:  The use of contrast agents during coronary intervention can result in nephropathy, particularly in patients with renal dysfunction. We aimed to determine whether the use of iso‐osmolar iodixanol is less nephrotoxic than that of low‐osmolar iopromide when patients are adequately prehydrated and have received N‐acetylcysteine.

Methods:  We conducted a randomized, double‐blind, multicentre study of patients with impaired renal function undergoing a coronary interventional procedure. Primary end‐point was the incidence of contrast‐induced nephropathy (CIN) on day 2, defined as an increase in serum creatinine concentration of ≥44 μmol/L (0.5 mg/dL) or by a relative increase of ≥25% from baseline. Secondary end‐points included peak increase in serum creatinine between baseline and day 7.

Results:  Of 191 patients recruited, 15% (95% CI: 8–22) of the patients receiving iopromide and 12% (95% CI: 5–19) of the patients receiving iodixanol developed CIN (95% CI of the difference: 13 to −7, P = 0.56). When including peak serum creatinine on day 7, CIN developed in 23% of patients receiving iopromide and in 27% of patients receiving iodixanol (95% CI of the difference: 8 to −16, P = 0.48). The peak increase in serum creatinine concentration at day 7 was similar in both groups (patients receiving iopromide, 18.4 ± 24.4 μmol/L, vs patients receiving iodixanol, 21.9 ± 24.2 μmol/L; P = 0.33).

Conclusion:  There remains a high incidence of CIN despite prehydration and routine use of N‐acetylcysteine in patients with pre‐existing renal dysfunction undergoing coronary interventional procedures. Although our study is underpowered, iodixanol was not associated with a statistically significant lower incidence of CIN when compared with iopromide.
An opportunity to reinforce ethical values: declarations made by graduating medical students in Australia and New Zealand
Authors: Macneill P. U. , May A. N. , Dowton S. B.
Published: September 2008

Background:  The aim of the study was to ascertain the use of declarations of ethical commitment made by medical students graduating from the final‐year class of 2006 in Australia and New Zealand, the extent of student contribution to the process and the manner in which those declarations were declared.

Methods:  Information was obtained, by telephone interview and email, from officers or responsible academic staff of faculties of medicine (or medicine and health sciences) in Australia and New Zealand.

Results:  Of 20 medical faculties in Australia and New Zealand, seven were established recently and are yet to graduate students. Thirteen faculties graduated medical students in 2006 and students in 10 of those faculties made declarations on graduating. Of those, six faculties consulted with students in formulating and/or in deciding on the declaration and four gave students major responsibility for writing the declaration. Three faculties invited graduating students to modify the declaration each year. Students in two of those faculties had done so on occasion and, in the third, they had rewritten the declaration each year.

Conclusion:  An increasing proportion of faculties of medicine in Australia and New Zealand provide for a declaration of ethical values on graduating. We emphasize educational opportunities for reinforcing these values by encouraging students to formulate their ‘own’ declaration, modify the declaration each year, read the declaration in a formal ceremony and by presenting graduating students with a plaque or printed declaration suitable for framing, which is signed by the Dean and graduating student.
Assessment and management of hypertension in patients with type 2 diabetes
Authors: Thomas M. C. , Atkins R.
Published: September 2008

Background:  Hypertension is a major risk factor for adverse outcomes in type 2 diabetes and an important target for intervention. Despite this, the management of blood pressure (BP) remains suboptimal, particularly in patients at increased risk for cardiovascular and chronic kidney disease. The aim of this study was to estimate the frequency of hypertension and its management in consecutive clinic‐based samples of patients with type 2 diabetes in Australian primary care.

Methods:  BP levels and antihypertensive management strategies were compared in patients with type 2 diabetes recruited as part of the Developing Education on Microalbuminuria for Awareness of reNal and cardiovascular risk in Diabetes (DEMAND) study in 2003 (n = 1831) and the National Evaluation of the Frequency of Renal impairment cO‐existing with Non‐insulin‐dependent diabetes (NEFRON) study in 2005 (n = 3893). Systolic BP levels and the use of antihypertensive therapies were examined in patients with and without chronic kidney disease.

Results:  The patient characteristics in both studies were similar in that more than 80% of patients in both studies were hypertensive. Systolic BP targets of ≤130 mmHg were achieved in approximately half of all treated patients in both studies. However, the use of antihypertensive therapy either alone or in combination increased from 70.4% in DEMAND to 79.5% in NEFRON 2 years later (P < 0.001). Despite this, antihypertensive therapy continued to be underutilized in high‐risk groups, including in those with established chronic kidney disease.

Conclusion:  The DEMAND and NEFRON studies both show that BP control is achievable in Australian general practice, with more than half of all patients seeing their general practitioners achieving a target systolic BP ≤130 mmHg. However, more needs to be done to further reduce BP levels, particularly in patients at high risk of adverse outcomes.
Are children just small adults? The differences between paediatric and adult sleep medicine
Authors: Robinson P. D. , Waters K.
Published: September 2008

Several important physiological and maturational changes occur in sleep development during the paediatric age range, particularly during infancy and in early childhood. As the pathology of sleep apnoea is superimposed onto a developing and often plastic physiological system, children often show a different pathophysiology to their adult counterparts. These factors need to be incorporated into the evaluation of a child’s sleep problems. Particular attention should be paid to the developmental stage of the child. Investigation, interpretation and subsequent management provide further unique challenges and during successive reviews predicted normal changes must also be taken into account. This review article discusses the important physiological and maturational changes that occur in sleep during childhood, some common paediatric sleep conditions and their presentation and the appropriate evaluation and management of these conditions. In the course of the discussion, we have stressed important differences between paediatric and adult sleep medicine.
Safe general anesthesia in a hyperkalemic infant
Authors: SHUKRY MOHANAD , DE ARMENDI ALBERTO J.
Published: September 2008

A 10‐day‐old boy treated in the intensive care unit and operating room due to hyperkalemia and renal failure. After admission to the intensive care unit and treatment for hyperkalemia, the patient required insertion of dialysis catheter in the operating room. Treatment for hyperkalemia continued while the patient was under general anesthesia. The operation was carried out successfully and cardiac signs and symptoms of hyperkalemia did not occur despite of potassium blood levels of 8.1 mEq·l−1. General anesthesia could be safe in hyperkalemic patients as long as the treatment for hyperkalemia is initiated before and during the surgery and hyperkalemia inducing agents are avoided.
Alteration of anion gap and strong ion difference caused by hydroxyethyl starch 6% (130/0.42) and gelatin 4% in children
Authors: WITT LARS , OSTHAUS WILHELM ALEXANDER , JÜTTNER BJÖRN , HEIMBUCHER CHRISTIAN , SÜMPELMANN ROBERT
Published: September 2008

Background:  Synthetic colloid administration is a common practice for preventing perioperative hypovolemia and consecutive circulatory failure in children. This prospective, randomized study was conducted to investigate the effects of two different unbalanced synthetic colloid solutions on acid–base equilibrium in children.

Methods:  Fifty pediatric patients (aged 0–12 years) scheduled for major pediatric surgery were randomized to receive either 10 ml·kg−1 of 6% hydroxyethyl starch solution 130/0.42 (HES) or 4% modified fluid gelatin (GEL) to maintain adequate systemic hemodynamics. Before and after colloid administration, a blood sample was collected to analyze hemoglobin, hematocrit, electrolytes, and acid–base parameters. The anion gap and the strong ion difference (SID) were calculated using standard formulas.

Results:  Both HES and GEL administration caused a significant increase in plasma chloride concentration (P < 0.01) and an accompanying decrease in SID (P < 0.01). In the HES group, the anion gap decreased significantly (P < 0.01) whereas the anion gap remained stable in the GEL group. In both groups, initial actual base excess and pH did not change significantly after colloid administration.

Conclusions:  Moderate intraoperative plasma replacement with unbalanced synthetic colloids HES and GEL leads to a decrease in SID and, in the case of HES, to a significant decrease in the anion gap in children. These alterations may result in a possible misinterpretation when the anion gap and SID are used for differential diagnosis of metabolic disturbances during major pediatric surgery.
Paracetamol (Acetaminophen): mechanisms of action
Authors: ANDERSON BRIAN J.
Published: September 2008

Paracetamol has a central analgesic effect that is mediated through activation of descending serotonergic pathways. Debate exists about its primary site of action, which may be inhibition of prostaglandin (PG) synthesis or through an active metabolite influencing cannabinoid receptors. Prostaglandin H2synthetase (PGHS) is the enzyme responsible for metabolism of arachidonic acid to the unstable PGH2. The two major forms of this enzyme are the constitutive PGHS‐1 and the inducible PGHS‐2. PGHS comprises of two sites: a cyclooxygenase (COX) site and a peroxidase (POX) site. The conversion of arachidonic acid to PGG2is dependent on a tyrosine‐385 radical at the COX site. Formation of a ferryl protoporphyrin IX radical cation from the reducing agent Fe3+at the POX site is essential for conversion of tyrosine‐385 to its radical form. Paracetamol acts as a reducing cosubstrate on the POX site and lessens availability of the ferryl protoporphyrin IX radical cation. This effect can be reduced in the presence of hydroperoxide‐generating lipoxygenase enzymes within the cell (peroxide tone) or by swamping the POX site with substrate such as PGG2. Peroxide tone and swamping explain lack of peripheral analgesic effect, platelet effect, and anti‐inflammatory effect by paracetamol. Alternatively, paracetamol effects may be mediated by an active metabolite (p‐aminophenol).p‐Aminophenol is conjugated with arachidonic acid by fatty acid amide hydrolase to form AM404. AM404 exerts effect through cannabinoid receptors. It may also work through PGHS, particularly in areas of the brain with high concentrations of fatty acid amide hydrolase.
Urodynamic evaluation of sacral neuromodulation for urge urinary incontinence
Authors: Groenendijk Pieter M. , Lycklama à Nyeholt August A.B. , Heesakkers John P.F.A. , Van Kerrebroeck Philip E.V. , Hassouna Magdy M. , Gajewski Jerzy B. , Cappellano Francesco , Siegel Steven W. , Fall Magnus , Dijkema Hero E. , Jonas Udo , Van Den Hombergh Ubi ,   Representing the Sacral Nerve Stimulation Study Group
Published: September 2008

OBJECTIVE

To evaluate the urodynamic data before and 6 months after implantation of sacral neuromodulation (SNM, an established treatment for voiding dysfunction, including refractory urge urinary incontinence, UI) and to assess the correlation between the urodynamic data and clinical efficacy in patients with UI.

PATIENTS AND METHODS

In all, 111 patients with a >50% reduction in UI symptoms during a percutaneous nerve evaluation test qualified for surgical implantation of SNM. Patients were categorized in two subgroups, i.e. those with UI with or without confirmed detrusor overactivity (DO) at baseline. At the 6‐month follow‐up all patients had a second urodynamic investigation, with the stimulator switched on.

RESULTS

At baseline, there was urodynamically confirmed DO in 67 patients, while 44 showed no DO. A review of filling cystometry variables showed a statistically significant improvement in bladder volumes at first sensation of filling (FSF) and at maximum fill volume (MFV) before voiding for both UI subgroups, compared with baseline. In 51% of the patients with UI and DO at baseline, the DO resolved during the follow‐up. However, those patients were no more clinically successful than those who still had DO (P = 0.73). At the 6‐month follow‐up, 55 of 84 implanted patients showed clinical benefit, having a ≥50% improvement in primary voiding diary variables. Patients with UI but no DO had a higher rate of clinical success (73%) than patients with UI and DO (61%), but the difference was not statistically significant.

CONCLUSION

These urodynamic results show a statistically significant improvement in FSF and MFV in patients with UI with or with no DO after SNM. Although there was a urodynamic and clinical improvement in both groups, patients with UI but no DO are at least as successful as patients with UI and DO. Therefore in patients with UI, DO should not be a prerequisite selection criterion for using SNM.
Adeno‐associated viral vector transduction of green fluorescent protein in kidney: effect of unilateral ureteric obstruction
Authors: Ito Keiichi , Chen Jie , Khodadadian Jonathan J. , Vaughan E. Darracott , Lipkowitz Michael , Poppas Dix P. , Felsen Diane
Published: September 2008

OBJECTIVE

To evaluate adeno‐associated virus (AAV) mediated renal gene transfer, by examining the localization and time course of gene expression in the kidneys of mice with unilateral ureteric obstruction (UUO) and controls. AAV is a replication‐defective virus that has the potential to deliver genes into the kidney to improve renal damage after UUO.

MATERIALS AND METHODS

An AAV vector carrying a green fluorescent protein (GFP) reporter gene (rAAV‐GFP) was used. In control mice, GFP expression was evaluated at 4, 7, 14 and 28 days after intrapelvic injection of rAAV or phosphate‐buffered saline (PBS). In mice with UUO, the left ureter was obstructed, and 24 h later either rAAV or PBS was injected; GFP expression was evaluated 4, 7 and 14 days later by direct fluorescence.

RESULTS

In the control mice, at least 7 days was required to detect GFP expression, whereas after UUO, GFP expression was already evident at 4 days after injection. GFP was localized mainly to the medullary tubules.

CONCLUSIONS

This study shows successful transduction of GFP into mouse kidney using an AAV vector; GFP was expressed sooner in UUO kidneys than in the controls. These results show the feasibility of using AAV to transduce GFP into the obstructed kidney, and suggest that it might be useful in transducing therapeutically active agents.
Inhibitory effects of nicorandil, a KATPchannel opener and a nitric oxide donor, on overactive bladder in animal models
Authors: Kamiyama Yutaka , Muto Satoru , Masuda Hitoshi , Ide Hisamitsu , Ishizuka Nobuhiko , Saito Keiji , Horie Shigeo
Published: September 2008

OBJECTIVES

To investigate the effects of nicorandil, an ATP‐sensitive potassium (KATP) channel opener with a nitric oxide (NO) donor property, on overactive bladder (OAB) in animal models. Nicorandil is currently used clinically to treat ischaemic heart disease.

MATERIALS AND METHODS

Three animal OAB models were used: (i) C‐fibre mediated bladder overactivity by infusion of a low concentration of acetic acid (AA) into the bladder in female Wistar rats; (ii) bladder outlet obstruction (BOO) created by partial urethral obstruction in female Wistar rats; and (iii) neuronal NO synthase (nNOS) knockout (KO) mice with urinary frequency. The effects of nicorandil and KRN2391, both of which act as KATPchannel openers and NO donors, on the OAB models were examined.

RESULTS

Cystometry showed that intravesical instillation of nicorandil and KRN2391 successfully inhibited OAB induced by intravesical instillation of AA. In the BOO model compared with untreated BOO rats, both nicorandil (1 and 3 mg/kg, orally) and KRN2391 (1 mg/kg, orally) significantly reduced the voiding frequency. Compared with wild‐type mice, nNOS KO mice had urinary frequency with no change in the total urine volume. Nicorandil (3 mg/kg, orally) and KRN2391 (1 mg/kg, orally) significantly reduced the voiding frequency in nNOS KO mice.

CONCLUSIONS

Ourin vivoresults show that nicorandil, a KATPchannel opener with a NO donor property, can suppress OAB from both neurogenic and myogenic causes. Nicorandil appears to be a promising candidate for clinical use in patients with OAB.
Response to docetaxel/carboplatin‐based chemotherapy as first‐ and second‐line therapy in patients with metastatic hormone‐refractory prostate cancer
Authors: Nakabayashi Mari , Sartor Oliver , Jacobus Susanna , Regan Meredith M. , McKearn David , Ross Robert W. , Kantoff Philip W. , Taplin Mary‐Ellen , Oh William K.
Published: September 2008

OBJECTIVES

To evaluate the efficacy of docetaxel/carboplatin (DC)‐based chemotherapy as first‐ and second‐line chemotherapy for patients with hormone‐refractory prostate cancer (HRPC).

PATIENTS AND METHODS

We retrospectively identified all patients with HRPC treated with DC‐based chemotherapy at the Dana‐Farber Cancer Institute. Regimens either included estramustine (EDC) or not (DC). We identified patients who received EDC as first‐line chemotherapy and patients who received DC as second‐line or subsequent chemotherapy. Patients treated with EDC received 20–70 mg/m2docetaxel every 1–4 weeks, estramustine 140 mg three times daily and carboplatin (area under the curve, AUC), (4–6) every 3–4 weeks. Patients treated with DC received docetaxel 50–70 mg/m2and carboplatin AUC (4–6) every 3–4 weeks.

RESULTS

In all, the study included 54 patients; 24 received EDC and 30 DC (median age 62.8 and 66.9 years, respectively); their prostate‐specific antigen (PSA) level at the start of chemotherapy was 112.7 and 213.3 ng/mL, respectively. There were declines of ≥50% in PSA level in 88% and 20% in the two groups, respectively. The median overall survival was 17.7 and 14.9 months in the EDC and DC groups, respectively. The most common reversible grade 4 toxicity with either regimen was neutropenia (4% and 7% in EDC and DC, respectively).

CONCLUSIONS

DC‐based chemotherapy is well tolerated and active in HRPC. Adding carboplatin to docetaxel provides an additional activity in 20% of patients as a second‐line or subsequent chemotherapy.