bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of promethazine on lumbar vertebral bone mass in postmenopausal women
Authors: TYAN M. L.
Published: August 2009

Abstract. Objectives. Work in mice suggests that the age‐related loss of bone mineral noted in that species is caused by an intrinsic defect in a haematopoietic cell population which results directly or indirectly in increased bone resorption. This age‐related loss of bone mineral is prevented or reversed by well‐tolerated doses of promethazine HCL. The present study was undertaken to determine if promethazine would retard or reverse bone loss in postmenopausal women.

Design. Postmenopausal women whose spine (L2 to L4) bone mineral content (BMC) was two standard deviations below young normal values were assigned randomly to receive calcium or promethazine and calcium daily. Subjects who had been taking oral oestrogen for more than 4 years also were assigned randomly but independently to the calcium or promethazine groups.

Setting. All subjects were seen in the out‐patient clinic of the Department of Medicine, School of Medicine, University of California, Los Angeles.

Subjects. Healthy, ambulatory postmenopausal females were recruited by word of mouth and by advertisement from the local community. Fifty‐four subjects completed the first 6 months of the study and 43 completed 30 months.

Interventions. The subjects were assigned randomly to receive 1000 mg calcium daily or promethazine 50 mg and calcium 1000 mg daily throughout the period of the study.

Main outcome measures. Bone mineral content of the lumbar vertebrae (L2 to L4) was determined by dual photon densitometry every 6 months. Dorsolumbar spine X‐rays were obtained yearly and at the completion of the study to detect new compression fractures.

Results. In the groups not taking oestrogen, BMC decreased at the rate of 1.53% year−1 in the group given only calcium; in contrast, BMC increased at 3.22% year−1 in the group given promethazine and calcium (P < 0.001). Among the women taking oestrogen, increases in mean BMC were noted in both groups, but those taking promethazine and calcium had a greater rate of increase than observed in the group taking only calcium (5.62% vs. 1.97% per year−1, P < 0.001).

Conclusions. These results suggest that promethazine can induce a modest increase in vertebral BMC in postmenopausal women who are not taking oestrogen and greater increases in those who are.
Effects of weight loss on pulmonary function in obese men with obstructive sleep apnoea syndrome
Authors: LARGERSTRAND L. , RÖSSNER S.
Published: August 2009

Abstract. The effects of long‐term behaviour modification of obesity on pulmonary function was studied in eight men with obstructive sleep apnoea syndrome (initial mean body mass index [BMI] 41.8 kg m−2) before and after a mean weight loss of 20 ± 7 (SD) kg. Mean arterial Pco2 fell from 6.3 ± 1.2 to 5.5 ± 0.6 kPa (P < 0.05) and concomitant significant improvements were found in vital capacity, total lung capacity, functional residual capacity and forced expired volume (FEV 1.0). The study suggests that weight loss per se, rather than the method of choice to achieve weight loss, results in clinically significant improvement of pulmonary function in obese men.
Progressive renal failure in patients with lupus nephritis
Authors: TANAKA H. , AKAMA H. , TOMINAGA N. , OSHIMA H. , ICHIKAWA Y. , IKEDA Y.
Published: August 2009

Abstract. Objective. To investigate the mode of progression to renal failure in patients with lupus nephritis in relation to disease activity and responsiveness to corticosteroid therapy.

Design. Retrospective clinical study.

Setting. University hospital.

Subjects. Twenty‐eight patients with progressive lupus nephritis (Cr ≥ 1.4 mg dl−1).

Interventions. Rapidity of progression was defined as the slope of the reciprocal of serum creatinine values. Lupus activity was scored using the systemic lupus erythematosus disease activity index system.

Main outcome measures. Improvement of serum creatinine values after 6 months of therapy.

Results. Rapidity of progression, which was calculated during the deterioration in kidney function, reflected systemic and serological disease activity, and moreover closely correlated with response to corticosteroid therapy.
Pathophysiological mechanisms for restenosis following coronary angioplasty: possible preventive alternatives
Authors: LÖVQVIST A. , EMANUELSSON H. , NILSSON J. , LUNDQVIST H. , CARLSSON J.
Published: August 2009

Abstract. Restenosis after successful percutaneous transluminal coronary angioplasty (PTCA) remains an unsolved medical problem. The search for the underlying pathophysiological mechanisms have identified intimal proliferation of smooth muscle cells (SMC) to be the prevailing cause of late restenosis, with endothelial cells (EC) and platelets being important participators in the process. According to the most accepted present theory, SMC would be stimulated to migrate and proliferate shortly after the angioplasty by the release of growth factors from injured EC and accumulated platelets. However, clinical trials of agents interfering with these mechanisms have not significantly diminished the rate of restenosis, which suggest both that our knowledge of the process is incomplete, and that new ways of administrating the agents may be required.
Antiphospholipid antibodies and ischaemic heart disease
Authors: JØRGENSEN P. , HANSEN P. R.
Published: August 2009

Abstract. Antiphospholipid antibodies (APA) have been detected in various conditions including venous and arterial thrombosis, recurrent fetal loss, thrombocytopenia and cardiac valvular lesions. APA were initially found in patients with systemic lupus erythematosus (SLE) but later have been demonstrated also in patients without connective tissue disease. We report the extensive evaluation of a 24‐year‐old otherwise healthy male with APA and a family history of SLE who presented with severe ischaemic heart disease requiring coronary by‐pass surgery.
Effects on glucose tolerance, insulin secretion, insulin‐like growth factor 1 and its binding protein, IGFBP‐1, in a randomized controlled diet and exercise study in healthy, middle‐aged men
Authors: HELLÉNIUS MAI‐LIS B. , BRISMAR KERSTIN E. , BERGLUND BO H. , de FAIRE ULF H.
Published: August 2009

Abstract. Objectives. To study the effects of advice on diet, exercise and their combination on oral glucose tolerance (OGTT), insulin secretion, insulin‐like growth factor‐1 (IGF‐1) and its binding protein, IGFBP‐1.

Design. A 6‐month, randomized, controlled intervention study.

Setting. Primary health care centres in Sollentuna, Stockholm and the Department of Medicine, Karolinska Hospital, Stockholm, Sweden.

Subjects. One hundred and fifty‐seven normoglycaemic healthy men, mean age 46 years, range 35–60 years, with slightly to moderately raised cardiovascular risk factors.

Interventions. Advice on diet (D, n = 40), exercise (E, n = 39) a combination of both (DE, n = 39) and a control group (C. n = 39).

Main outcome measures. An OGTT, insulin secretion, IGF‐1 and its binding protein, IGFBP‐1.

Results. The number of pathological OGTTs in the intervention groups decreased from 42/118 to 33/118 whilst the number in the control group did not change. Fasting insulin levels decreased in groups E and DE from 8.8–7.4 mU L−1 (P < 0.01) and from 8.3–6.7 mU L−1 (P < 0.01), respectively. Accordingly, the insulin area under the curve decreased from 5278 to 4828 (P < 0.05) in group E, and from 5482 to 4809 (P < 0.01) in group DE. IGF‐1 only increased in group D. The most prominent changes were noted for IGFBP‐1, which increased in all three intervention groups and to the highest degree in group DE (from 33.7–42.6 μg L−1, P < 0.001).

Conclusions. A combination of increased exercise and improved diet, as well as increased exercise alone, favourably affect glucose and insulin homeostasis in middle‐aged men with moderately elevated cardiovascular risk factors. The most marked changes were noted for IGFBP‐1, possibly suggesting a decreased insulin secretion and an enhanced insulin sensitivity.
Clinical and virological findings in mixed cryoglobulinaemia
Authors: MAZZARO C. , TULISSI P. , MORETTI M. , MAZZORAN L. , PUSSINI E. , CROVATTO M. , SANTINI G. F. , POZZATO G.
Published: August 2009

Abstract. Objectives. As a close relationship has been established between mixed cryoglobulinaemia and hepatitis C virus (HCV) infection, the clinical, histological and virological findings of patients affected by mixed cryoglobulinaemia were determined.

Design. Hepatitis C virus infection was investigated by the presence of anti‐HCV antibodies and PCR amplification of the 5′ untranslated region (5′ UTR), and the genotype of HCV was also determined according to Okamoto. A bone marrow biopsy was performed in all patients and liver and kidney biopsies when indicated.

Subjects. Eighty‐two subjects affected by mixed cryoglobulinaemia were enrolled in this study.

Results. The prevalence of anti‐HCV antibodies was high (83%); PCR amplification of the 5′UTR region was performed in 52 subjects and in 44 of them (85%) the results were positive. In the same subjects, the Core region amplification was positive in 46 cases (88%). A high prevalence of genotype II was found (54%). Chronic liver disease was present in 55 patients (67%). Bone marrow biopsies showed the presence of low‐grade non‐Hodgkin's lymphomas in 11 cases (13%). Membrano‐proliferative glomerulonephritis was found in seven subjects (8%).

Conclusions. Mixed cryoglobulinaemia is associated with HCV infection in the nearly all cases. Several HCV genotypes are involved in the pathogenesis of this disease. Mixed cryoglobulinaemia is associated with a high prevalence of chronic liver disease, low‐grade non‐Hodgkin's lymphomas and membranoproliferative glomerulonephritis.
Immunopathogenesis and immunotherapy in rheumatoid arthritis: an area in transition
Authors: KLARESKOG L. , RÖNNELID J. , HOLM G.
Published: August 2009

Abstract. In years to come, new therapeutic modalities for the treatment of chronic arthritis will be launched for general clinical use. These therapies, until today only used in clinical studies, are based on knowledge obtained from animal models of chronic arthritis. This knowledge not only ushers therapeutic use in humans: in many settings, the animal studies have proven to be irreplacable tools to get insights into the pathogenesis of chronic arthritis. Rheumatoid arthritis (RA) shows a strong linkage of susceptibility to a certain epitope common to some HLA‐DRβ chains; this immunogenetic linkage is the strongest evidence for specific, T‐cell dependent immunity in the pathogenesis of the disease. Despite intense efforts, no unequivocal proofs of T‐cell specificity or oligoclonality have been found in RA. Therapeutic efforts directed against T‐cells or T‐cell functions have also at the best showed partial effects. As compared to the local production of T‐cell cytokines in the joint, monokine production is abundant. Therapies aimed at neutralizing the effects of the cartilage‐devastating monokine TNF‐a have showed remarkable results in small clinical trials. The possibility of increasing the presence of the regulatory cytokines IL‐4, IL‐10 and TGF‐β has also been explored, but only in animal studies. Immunology has also shed light on the mode of action of the commonly used ‘disease modifying’ drugs, and combinations of such drugs have shown increased potentials in recent clinical studies. The possibility of combining traditional anti‐arthritic drugs with recent immunological tools seem promising for the future. This review discusses recent advances in the understanding of pathogenesis and delineate new therapeutic approaches for chronic arthritis from the point of view of the immunologically oriented clinician.
Islet cell antibodies: variable immunostaining of pancreatic islet cells and carcinoid tissue
Authors: HALLBERG ANDERS , JUHLIN CLAES , BERNE CHRISTIAN , KÄMPE OLLE , KARLSSON F. ANDERS
Published: August 2009

Abstract. Objectives. Islet cell antibodies (ICA) in sera of patients with autoimmune diabetes mellitus generally stain not only the insulin‐producing beta cells but also the non‐beta cells of the islets of Langerhans. The antibodies have been reported to react also with the chromaffin cells of carcinoid tissue. In the present study, we examined in detail the reactivity of 10 ICA‐positive sera of patients with new onset insulin‐dependent diabetes mellitus (IDDM) and two sera of patients with stiff‐man syndrome.

Design. The sera were analysed by immunofluorescence and by immunoperoxidase staining of human islets as well as by immunoprecipitations using 35S‐methionine labelled rat islet lysates. In addition, immunofluorescence analyses of carcinoid tissues were carried out.

Results. Eight of the 10 IDDM‐positive sera reacted with all islet endocrine cells, whereas two sera showed staining restricted to the beta cells, as did the two sera of the patients with stiff‐man syndrome. All beta cell ‘selective’ sera, but only 6 of 8 ‘whole’ islet positive sera, immunoprecipitated the 64 kDa glutamic acid decarboxylase (GAD) antigen. The staining of carcinoid tissue was variable and did not correlate with the ‘whole’ or ‘selective’ staining pattern of islets.

Conclusion. The data underline a heterogeneity of ICA and indicate the presence of a separate, non‐GAD antigen in islet cells. It is possible that in future studies, a resolution of ICA titres with respect to different types of islet cellular reactivity might provide insights into the pathogenesis of IDDM and improve the prognostic implications of antibody determinations.
Dramatic responses to intravenous immunoglobulin in vasculitis*
Authors: BOMAN S. , BALLEN J. L. , S. Seggev Joram
Published: August 2009

Abstract. Intravenous immunoglobulin (IVIG) has been successfully used to treat autoimmune diseases. We report dramatic, rapid and sustained responses to its use in two cases of vasculitis: a patient with primary angiitis of the central nervous system; and a patient with hepatitis‐B‐antigen‐related polyarteritis nodosa, who failed treatment with corticosteroids. Improvement in gait and a marked decrease in serum creatinine, respectively, were observed within 24 h of the first dose of IVIG. Both patients remained stable for several months. We conclude that IVIG should be considered in patients with vasculitis who fail corticosteroids, or when a rapid response is required.
Mitochondrial medicine
Authors: Luft Rolf , LANDAU B. R.
Published: August 2009

Abstract.In the mitochondrion, inherited defects have been identified in the electron transport system by which ATP is formed, as well as in the transport and metabolism of fuels. Clinical findings in diseases due to these defects can be related to abnormal accumulations of metabolic intermediates and inadequate or inefficient ATP generation. In the oxidative process within the mitochondrion, chemical oxidants are generated, which can cause cellular damage. As the body's defences against the oxidants decline, oxidative damage appears to contribute to the ageing process itself as well as to age‐related degenerative diseases. Understanding in this area has accelerated with knowledge of the synthesis, structure and function of the mitochondrion and its specific DNA. The frontier is expected to advance rapidly as causal relationships between these diseases and mitochondrial dysfunction, and the potential role of antioxidants in therapy, are better defined.
Influence of compensated radioiodine therapy on thyroid volume and incidence of hypothyroidism in Graves' disease
Authors: Nygaard Birte , HEGEDÜS L. , GERVIL M. , HJALGRIM H. , HANSEN B. M. , SØE‐JENSEN P. , HANSEN J. M.
Published: August 2009

Abstract. Objectives. To investigate the long‐term effect of radioactive iodine (131I) on thyroid function and size in patients with Graves' disease.

Setting. Out‐patient clinic in Herlev Hospital.

Subjects. One hundred and seventeen consecutive patients (104 women) with Graves' disease selected for 131I treatment and followed for a minimum of 12 months (range 1–10 years, median 5 years).

Interventions. 131I dose was calculated based on thyroid volume and 24‐h 131I uptake.

Main outcome measures. Standard thyroid function variables and ultrasonically determined thyroid volume before treatment as well as 0.75, 1.5, 3, 6 and 12 months after treatment, and then once a year were investigated.

Results. Seventy‐eight patients were cured by one 131I dose and 30 by two doses, while the remaining nine patients received additional doses (range one to five doses, median one dose). Within one year, 25% developed hypothyroidism, and hereafter, hypothyroidism developed at a constant rate of 3% per year independent of antithyroid pretreatment. The cumulative 10‐year risk of hypothyroidism was 60%. Initial median thyroid volume was 33 mL (range 9–106 mL). At 12 months after the last 131I dose, median thyroid volume was reduced to 14 mL (range 6–36 mL) (P < 0.00001). The median reduction being 58% (range 0–80%,), hereafter no further reduction occurred. A significant reduction in thyroid volume was also noted in patients needing subsequent 131I doses and in those developing hypothyroidism within the first year.

Conclusions. 131I normalizes thyroid volume in patients with Graves' disease. Hypothyroidism seems an inevitable end result of this treatment. The present study suggests that it will be impossible to modify 131I therapy in a way to achieve both early control of hyperthyroidism and a low incidence of hypothyroidism.
Relationship between symptom pattern, assessed by the PAGI‐SYM© questionnaire, and gastric sensorimotor dysfunction in functional dyspepsia
Authors: Kindt S. , Dubois D. , Van Oudenhove L. , Caenepeel P. , Arts J. , Bisschops R. , Tack J.
Published: August 2009

Abstract  The patient assessment of upper gastrointestinal symptom severity index (PAGI‐SYM) questionnaire was recently developed and validated for the evaluation of therapeutic responsiveness in functional dyspepsia (FD). Functional dyspepsia is a heterogeneous disorder, with different pathophysiological mechanisms underlying the symptom pattern. The relationship between PAGI‐SYM scores and putative pathophysiological mechanisms has not been studied. The aim of this study was to evaluate the relationship between PAGI‐SYM subscales and gastric emptying, gastric sensitivity and gastric accommodation in FD. A total of 161 consecutive FD patients underwent Helicobacter pylori (HP), gastric barostat and standardized gastric emptying testing (n = 126), and completed the PAGI‐SYM questionnaire. Relationships between scores for the six subscales (heartburn/regurgitation, nausea/vomiting, fullness/satiety, bloating, upper abdominal pain, lower abdominal pain) and gastric function were analysed using Pearson’s linear correlation, multiple regression analysis, chi‐square and Student’s t‐tests. Gastric emptying was significantly correlated with scores for heartburn/regurgitation (r = 0.26), nausea/vomiting (r = 0.19), fullness/satiety (r = 0.20), bloating (r = 0.21) and lower abdominal pain (r = 0.22; all P < 0.05). Patients with delayed emptying had significantly higher scores for each of these subscales (all P < 0.05). Discomfort volume during gastric distension was significantly correlated with scores for fullness/satiety (r = −0.27), bloating (r = −0.23), heartburn/regurgitation (r = −0.21), and upper abdominal pain (r = −0.20). Patients with hypersensitivity to distension had significantly higher scores for fullness/satiety (P < 0.05). At different cut‐off levels of symptom severities, consistent associations were found between fullness/satiety and gastric discomfort volume, between preprandial volumes and upper abdominal pain, compliance and upper abdominal pain, and between bloating and gastric discomfort volume. Multiple regression analysis revealed that gastric emptying rate contributed significantly to models for the severity of these subscales. The importance of discomfort volume disappeared in favour of gender when sex was included in the model. No significant correlations were found with HP status or with gastric accommodation. PAGI‐SYM scores are mainly correlated with gastric emptying rate and with gastric hypersensitivity. Multivariate analysis suggests that the questionnaire may be useful in the evaluation of gastroprokinetics. Its role in the evaluation of drugs that alter gastric sensitivity is less clear.
MicroRNAs in common diseases and potential therapeutic applications
Authors: Tsai Louis M , Yu Di
Published: August 2009

1. Evidence gathered in recent years has revealed microRNAs (miRNAs) fine‐tune gene expression and play an important role in various cellular processes, including cell growth, differentiation, proliferation and apoptosis.

2. The present review summarizes current knowledge of miRNA pathways in the pathogenesis of cancer, cardiac diseases, neurodegenerative diseases, diabetes, autoimmune/inflammatory diseases and infection.

3. There is considerable potential to target miRNAs as a novel approach in the treatment of human diseases. Currently, miRNA‐based therapies are being examined in both animal models and human clinical trials.
Guanylate cyclase regulates ileal longitudinal muscle contractions induced by neurogenic nitrergic activity in the rat
Authors: Oliveira Jorge MA , Gonçalves Jorge
Published: August 2009

1. Nitrergic neurons regulate gastrointestinal (GI) activity and their dysfunction has been associated with various GI diseases. Nitric oxide (NO) typically relaxes GI smooth muscle, but nitrergic contractions also occur. Although guanylate cyclase is well established as mediating nitrergic GI relaxation, its role in contraction remains uncertain.

2. We used electrical field stimulation (EFS; 0.3 msec pulses, three trains of 1.2 s width, 2 Hz, at 30 s intervals) to evoke biphasic contraction–relaxation responses in rat ileum strips (longitudinal muscle–myenteric plexus preparations), mediated by the endogenous nitrergic transmitter, under non‐adrenergic, non‐cholinergic (NANC) conditions (1 μmol/L atropine and 4 μmol/L guanethidine).

3. All EFS responses were abolished by tetrodotoxin (1 μmol/L). Inhibition of NO synthase withNω‐nitro‐l‐arginine‐methyl‐ester (l‐NAME; 100 and 300 μmol/L) prevented both EFS‐evoked contractions and relaxations.l‐Arginine (3 mmol/L) reversedl‐NAME inhibition, primarily restoring contractions and suggesting that these require lower nitrergic transmitter levels than relaxations.

4. Pretreatment of preparations with subrelaxant concentrations of sodium nitroprusside (1 μmol/L) selectively desensitized EFS‐evoked contractions without affecting relaxations, suggesting different downstream mechanisms. Nevertheless, the selective guanylate cyclase inhibitor 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (3 and 10 μmol/L) inhibited both nitrergic contractions and relaxations, indicating that guanylate cyclase activation is required for both responses.

5. The results of the present study support the hypothesis that the endogenous nitrergic transmitter differentially regulates guanylate cyclase, leading to either contractions or relaxations depending on its concentrations, thus providing additional insight into the regulation of ileum contractility by nitrergic activity.
Multidrug resistance protein 4 mediates cAMP efflux from rat preglomerular vascular smooth muscle cells
Authors: Cheng Dongmei , Ren Jin , Jackson Edwin K
Published: August 2009

1. Previous studies have shown that stimulation of adenylyl cyclase in preglomerular vascular smooth muscle cells (PGVSMC) increases extracellular cAMP; however, the mechanism by which PGVSMC transport intracellular cAMP into the extracellular milieu is unknown.

2. We hypothesize that multidrug resistance protein (MRP) 4 is the primary transporter mediating efflux of intracellular cAMP from PGVSMC.

3. Both reverse transcription–polymerase chain reaction and real‐time polymerase chain reaction detected MRP4 mRNA in PGVSMC in culture. Moreover, western blotting using an antibody specific for MRP4 gave rise to a 150 kDa signal, consistent with the presence of MRP4 protein in PGVSMC.

4. Specifically designed short interference (si) RNA reduced MRP4 mRNA expression by 71% (P = 0.0075) and MRP4 protein by 80% (P = 0.0004).

5. Isoproterenol (1 μmol/L) increased intracellular cAMP, which resulted in efflux of cAMP into the medium. The siRNA knockdown of MRP4 significantly reduced basal extracellular cAMP and nearly abolished isoproterenol‐induced increases in extracellular cAMP (P = 0.0143, interaction between isoproterenol and MRP4 siRNA in two‐factor analysis of variance). In isoproterenol‐treated cells, MRP4 siRNA decreased the ratio of extracellular cAMP to intracellular cAMP by 72% (P = 0.0019).

6. We conclude that MRP4 is the dominant cAMP transporter in PGVSMC.
Peripheral arterial disease is associated with coronary artery spasm as assessed by an intracoronary acetylcholine provocation test
Authors: Chen Kang‐Yin , Rha Seung‐Woon , Li Yong‐Jian , Poddar Kanhaiya L , Jin Zhe , Minami Yoshiyasu , Wang Lin , Li Guang‐Ping , Saito Shigeru , Park Jae‐Hyoung , Na Jin‐Oh , Choi Cheol Ung , Lim Hong‐Euy , Kim Jin‐Won , Kim Eung‐Ju , Park Chang‐Gyu , Seo Hong‐Seog , Oh Dong‐Joo
Published: August 2009

1. Both peripheral arterial disease (PAD) and coronary artery spasm (CAS) are associated with endothelial dysfunction. Thus, a higher incidence of CAS may be expected in patients with PAD. In the present study, we evaluated the incidence and characteristics of CAS in patients with PAD.

2. A total of 78 patients with PAD and 241 age‐ and gender‐matched patients without PAD who had chest pain with normal coronary appearance on coronary angiograms underwent intracoronary acetylcholine (ACh) provocation test. Acetylcholine was injected into the left coronary artery in incremental doses of 20, 50 and 100 μg/min. Significant CAS was defined as a transient > 70% luminal narrowing with concurrent chest pain and/or ST segment changes.

3. Patients with PAD had a significantly higher incidence of ACh‐induced significant CAS than those without PAD (60.3 vs 34.0%, respectively P < 0.001), as well as chest pain and ST segment changes during the ACh provocation test. Patients with PAD were more sensitive to lower doses of ACh and had a higher incidence of multivessel spasm than those without PAD. Multivariable logistic analysis showed that age, current smoking, PAD and myocardial bridge were independent predictors of ACh‐induced significant CAS. Moreover, of these factors, PAD was the strongest independent predictor (odds ratio 4.25; confidence interval 1.33–13.54; P = 0.014).

4. In patients with chest pain, the presence of arterial disease at another site should still push the clinician towards treating the chest pain as angina, even if the coronary anatomy is normal on a coronary angiogram.
Peroxisome proliferator‐activated receptor‐γ coactivator‐1α in muscle links metabolism to inflammation
Authors: Handschin Christoph
Published: August 2009

1. In higher eukaryotes, metabolism and immunity are tightly coupled. However, whereas in evolutionary terms a compromised immune response due to undernourishment has been the predominant problem, the inflammatory response to obesity and other lifestyle‐associated diseases has increased in relevance in Western societies in the past 100 years.

2. Traditionally, fat tissue has been considered as the major source of pro‐inflammatory secreted factors in these pathologies. However, in recent years the contribution of other tissues to disease‐causing chronic inflammation has been increasingly appreciated.

3. Peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α) is one of the key regulatory factors in active skeletal muscle. Aberrant expression of PGC‐1α in inactive muscle fibres could be linked to a sedentary lifestyle, persistent systemic inflammation and a higher risk for many chronic diseases. Accordingly, modulation of PGC‐1α activity in skeletal muscle may have a broad range of therapeutic effects. Here, recent advances in the understanding of the role of muscle PGC‐1α in health and disease are reviewed.
Radical prostatectomy for high‐risk prostate cancer: Biochemical outcome
Authors: Kawamorita Naoki , Saito Seiichi , Ishidoya Shigeto , Ito Akihiro , Saito Hideo , Kato Masanori , Arai Yoichi
Published: August 2009

Objectives:  To determine the biochemical outcome following radical prostatectomy alone in patients with high‐risk prostate cancer.

Methods:  Between January 2002 and August 2007, 252 patients underwent radical retropubic prostatectomy. Those who received neoadjuvant hormone therapy were excluded from this analysis. Based on pre‐operative data, we stratified the patients into low, intermediate, and high‐risk groups according to the risk criteria of the National Comprehensive Cancer Network in 2003, respectively. Prostate‐specific antigen (PSA) failure was defined as any detectable PSA level higher than 0.2 ng/mL.

Results:  The PSA failure‐free survival rate for the high‐risk group (n = 46) was 64.5% after a median follow‐up period of 39 months. Among patients with high‐risk disease, none with pathologically organ‐confined cancer (n = 19) and a negative surgical margin had PSA failure. The PSA failure‐free rate in patients with non organ‐confined cancer (n = 27) was 39.5%. Among the pretreatment variables, a positive biopsy core percentage (the number of positive biopsy cores/total biopsy core) ≥30 was a significant independent predictor of extra prostatic extension.

Conclusions:  Radical prostatectomy is feasible in high‐risk prostate cancer patients, only if they have a pathologically organ‐confined disease.
An audit of genetic testing in diagnosis of inherited retinal disorders: a prerequisite for gene‐specific intervention
Authors: Pradhan Monika , Hayes Ian , Vincent Andrea
Published: August 2009

Abstract

Background:  There has been an exponential increase in the number of genes implicated in inherited retinal disease over the last decade, but the genetic and phenotypic heterogeneity limited mutation detection. The high cost of sequencing and long turn around times meant that gene testing was not a viable option, particularly in New Zealand. Recently, advancements including development of micro‐array‐based mutation analysis and non‐for‐profit laboratories have resulted in affordable and time‐efficient testing. This has enabled genetic diagnostics to become an integral component of the work‐up for inherited retinal disease.

Methods:  Genetic testing for inherited retinal disorders was initiated via the Ocular Genetic Clinic in Auckland 2 years ago. A retrospective audit of genetic testing over this period was carried out. The results of these tests and outcomes are discussed.

Results:  Thirty‐five probands have undergone genetic testing for retinal disorders. This has included X‐Linked Retinoschisis, Leber Congenital Amaurosis, Retinitis Pigmentosa, Albinism, Achromatopsia, Usher syndrome, Stargardt disease and Mitochondrial disease. Of these, 54% of tests (19/35) showed a rare variant or pathogenic mutation. Three couples have proceeded to investigate the options of prenatal diagnosis and/or pre‐implantation genetic diagnosis.

Conclusion:  The introduction of genetic testing, largely via disease arrays, has been highly successful at clarifying disease genotype in our cohort. It is now a timely and cost‐effective investigation that should be elemental to the assessment of inherited retinal disease. Genetic testing in an opportune fashion permits genetic counselling, enables families to make reproductive choices and might allow the possibility of gene therapy interventions.
Relationship between myopia and allergen‐specific serum IgE levels in patients with allergic conjunctivitis
Authors: Mimura Tatsuya , Yamagami Satoru , Usui Tomohiko , Funatsu Hideharu , Noma Hidetaka , Honda Norihiko , Amano Shiro
Published: August 2009

Abstract

Purpose:  Various exogenous allergens can cause allergic conjunctivitis, whereas refractive errors are also related (as an endogenous factor) to the pathogenesis of allergic conjunctivitis. However, little is known about the interaction between exogenous and endogenous factors in patients with allergic conjunctivitis. We investigated the relationship between refractive errors and exogenous allergens in patients with allergic conjunctivitis.

Methods:  Sixty patients with allergic conjunctivitis and 60 healthy subjects (non‐allergy patients) were enrolled. Refraction was carried out in all subjects. In addition, total immunoglobulin E (IgE) and specific IgE levels for 12 inhaled allergens were measured by the capsulated hydrolic carrier polymer system.

Results:  The patients who were positive for‐specific IgE to indoor allergens had higher myopia than those who were negative, including those positive for house dust IgE (−3.66 ± 2.95 vs. −1.05 ± 3.39, P = 0.0015), Dermatophagoides pteronyssinus (D. pteronyssinus) IgE (−3.50 ± 2.91 vs. −1.01 ± 3.46, P = 0.0021), and acarus IgE (−3.45 ± 2.21 vs. −1.51 ± 3.73, P = 0.0087), whereas antibody‐positive and antibody‐negative patients for outdoor allergens showed no significant differences of refraction. Refractions in indoor group (−3.58 ± 3.42) and indoor/outdoor (−3.70 ± 2.64) group were higher than those in outdoor group (−0.84 ± 2.30, P = 0.0047 and P = 0.0032) and the non‐allergy group (−1.30 ± 1.48, P = 0.0082 and P = 0.0054) [‐refraction] was significantly correlated with total IgE (r = 0.333, P = 0.0093), house dust (r = 0.355, P = 0.0054) and D. pteronyssinus (r = 0.379, P = 0.0028), while no correlation between refractive error and outdoor allergens was proven.

Conclusion:  These results suggest that specific IgE levels for indoor allergens, such as house dust, might be associated with refractive errors.
Rotation of the head might not be recommended for internal jugular puncture in infants and children
Authors: ARAI TOSHIMI , MATSUDA YOSHIFUMI , KOIZUKA KYOKO , YASUOKA ASAKO
Published: August 2009

Background:  Traditionally, we have been puncturing the internal jugular vein (IJV) with the head rotated. However, in adults it has been suggested that rotation of the head increases the magnitude of an overlapping of the IJV to the carotid artery (CA). Therefore, in infants and children, we have examined anatomic relationship between the IJV and the CA under the head in midline and head in rotated position.

Method:  Eleven infants and 51 children were included. Under general anesthesia, the patient was positioned in the Trendelenburg position with a shoulder roll to allow extension of the neck. At first, the head was placed in the midline position. The ultrasound probe was placed perpendicular to the skin, and images of the right IJV and CA were collected at the level of the cricoid cartilage. Then, the head was rotated to the left at 45°. The images were collected in the same way. The position of the right IJV relative to the CA was defined as anterior (A), anterolateral (AL), or lateral (L).

Results:  Rotation of the head increased the magnitude of an overlapping because of more changes from L → AL, L → A, or AL → A (P < 0.05, Wilcoxon t‐test).

Conclusion:  We conclude that the rotation of the head increases the magnitude of an overlapping of the IJV to the CA in infants and children.
A prospective multicentre study to investigate percutaneous tibial nerve stimulation for the treatment of faecal incontinence
Authors: Govaert B. , Pares D. , Delgado‐Aros S. , La Torre F. , Van Gemert W. G. , Baeten C. G.
Published: August 2009

Aim  Percutaneous tibial nerve stimulation (PTNS) is a minimal invasive treatment that can be performed in the outpatient clinic. This is a pilot study to investigate PTNS in the treatment of faecal incontinence.

Method  Percutaneous tibial nerve stimulation was performed by insertion of a needle electrode near the posterior tibial nerve. Patients were treated twice a week. Evaluation of faecal incontinence and quality of life was performed at baseline, 6 weeks, 3 months, 6 months and 1 year. Quality of life was estimated using SF‐36 and FIQL questionnaires.

Results  A total of 22 patients were included. The mean age was 60.4 ± 11.7 years. After 6 weeks, 18 continued the treatment; 13 patients had a > 50% decrease in incontinence episodes. Overall incontinence episodes fell from 19.6 ± 21.0 at baseline to 9.9 ± 15.5 (P = 0.082) at 6 weeks and to 3.6 ± 4.8 (P = 0.029) at 1 year. Postponement time and quality of life increased significantly during follow up.

Conclusion  Percutaneous tibial nerve stimulation is simple and can be used in the outpatient setting. Good results can be obtained and sustained during maintenance treatment.
Clinical features’ diagnostics and treatment of Hirschsprung’s disease in adults
Authors: Vorobyov G. I. , Achkasov S. I. , Biryukov O. M.
Published: August 2009

Aim  Hirschsprung’s disease first diagnosed in adulthood is symptomatic from early childhood in most cases. However, the condition is frequently masked when constipation is managed effectively by enemas and aperients. One third of the patients will experience progressive symptoms or complications, requiring urgent surgical intervention.

Method  Ninety patients with adult Hirschsprung’s disease were observed by a combination of investigations: barium enema, anorectal physiology, estimation of acetylcholinesterase activity and a 60 mm full‐thickness strip biopsy. The latter two modalities were performed in selected patients where there was diagnostic uncertainty. Single‐staged resections, mostly modified Duhamel procedures, were performed in patients who were stable and fit, and with only a limited degree of megacolon present, and no other complications. Otherwise patients were temporarily defunctioned prior to staged resection. All patients underwent surgical treatment. Long‐term functional outcomes were expressed as good, satisfactory or poor.

Results  Median age was 24.5 years, range 14–47 years, and 72.2% were men. Almost three quarters (73.3%) of the patients had symptoms dating from early childhood. Barium enema was diagnostic in 84.3%, and 36.2% had a positive, but weak rectoanal inhibitory reflex. Acetylcholinesterase staining was positive in 85.7%, but full‐thickness strip biopsy was positive in 100% of equivocal cases. A separate cadaveric study of unaffected individuals determined the true length of the normal physiological hypoganglionic zone, mean 24.4 mm and range 7.5–50 mm. Supra‐anal short segment Hirschprung’s disease was found in 5.6% patients, rectal involvement in 54.4%, rectosigmoid in 38.9% and total aganglionosis of the colon in 1.1%. Resection of the aganglionic zone and proximally dilated colon was performed as a single‐staged procedure in 67.8%. Staged surgery was carried out in 32.2%. A modified Duhamel procedure was performed in 91.2% of cases. A good or satisfactory functional outcome was achieved in 96.7%. Long‐term functional outcome after resection depends on the degree of preoperative megacolon present. Megacolon limited to the sigmoid colon was associated with a good outcome in 89.7%, but in only 66.7% with more proximal dilatation (P < 0.05).

Conclusion  Occasionally, Hirschsprung’s disease presents in adulthood, with ongoing symptoms from early childhood or with the development of functional obstruction, faecal impaction and megacolon in later life. Diagnosis often requires multimodal investigation. A 60 mm full‐thickness strip biopsy confirms aganglionosis in 100%. A modified Duhamel procedure is the operation of choice.
Open muscle biopsy in suspected myopathy: diagnostic yield and clinical utility
Authors: Lai C.‐H. , Melli G. , Chang Y.‐J. , Skolasky R. L. , Corse A. M. , Wagner K. R. , Cornblath D. R.
Published: August 2009

Background:  The purpose of the study was to investigate the diagnostic yield and clinical utility of open muscle biopsy and to identify pre‐biopsy factors that might predict useful clinical results for suspected myopathy.

Methods:  Two‐hundred fifty‐eight muscle biopsies, performed for investigation of suspected myopathy, were evaluated.

Results:  A specific clinical diagnosis following muscle biopsy was made in 43% of cases. As a result of the biopsy, clinical diagnosis was changed in 47% and treatment was changed in 33% of cases. Results either led to a specific clinical diagnosis or changed the diagnosis/treatment in 74% of patients. Positive family history of myopathy and findings of myopathic irritability on electromyography had a negative predictive value for diagnosis change.

Conclusions:  Open muscle biopsy is useful in myopathy evaluation in the modern genetic era.
The CST3 B haplotype is associated with frontotemporal lobar degeneration
Authors: Benussi L. , Ghidoni R. , Galimberti D. , Boccardi M. , Fenoglio C. , Scarpini E. , Frisoni G. B. , Binetti G.
Published: August 2009

Background and purpose:  Frontotemporal lobar degeneration (FTLD) is a common cause of early‐onset dementia. Given the role of cystatin C in brain neurodegeneration and neuroregeneration, the aim of this study was to determine whether the cystatin C gene (CST3) was genetically associated with FTLD.

Methods:  Hundred and eighty‐six FTLD patients and 457 controls underwent CST3 analysis by PCR and KspI enzyme digestion.

Results:  In FTLD patients negative for the presence of PGRN mutations, we found an over‐representation of the CST3 haplotype B [odds ratio (OR = 1.619, P = 0.002)] and of AB/BB genotypes (OR = 1.704, P = 0.008) in FTLD patients.

Conclusions:  The present study indicated the CST3 B haplotype as a putative risk factor for FTLD in PGRN mutations negative patients. The reduced level of cystatin C, previously associated with the B haplotype, might represent the molecular factor responsible for the increased risk. Long‐term depletion of neurotrophic factors, such as cystatin C and progranulin proteins, seem to be a common theme in FTLD: boosting the expression of such proteins might be a promising therapeutic strategy for FTLD.
Capnellene, a natural marine compound derived from soft coral, attenuates chronic constriction injury‐induced neuropathic pain in rats
Authors: Jean Yen‐Hsuan , Chen Wu‐Fu , Sung Chun‐Sung , Duh Chang‐Yih , Huang Shi‐Ying , Lin Chan‐Shing , Tai Ming‐Hon , Tzeng Shun‐Fen , Wen Zhi‐Hong
Published: August 2009

Background and purpose: Natural compounds obtained from marine organisms have received considerable attention as potential sources of novel drugs for treatment of human inflammatory diseases. Capnellene, isolated from the marine soft coralCapnella imbricate, 4,4,6a‐trimethyl‐3‐methylene‐decahydro‐cyclopenta[]pentalene‐2,3a‐diol (GB9) exhibited anti‐inflammatory actions on activated macrophagesin vitro. Here we have assessed the anti‐neuroinflammatory properties of GB9 and its acetylated derivative, acetic acid 3a‐hydroxy‐4,4,6a‐trimethyl‐3‐methylene‐decahydro‐cyclopenta[]pentalen‐2‐yl ester (GB10).

Experimental approach: Effects of GB9 or GB10 on the expression of inducible nitric oxide synthase (iNOS), and cyclooxygenase‐2 (COX‐2) in interferon‐γ (IFN‐γ)‐stimulated mouse microglial BV2 cells were measured by Western blot. Thein vivoeffects of these compounds were examined in the chronic constriction injury (CCI) rat model of neuropathic pain, measuring thermal hyperalgesia, and microglial activation and COX‐2 protein in lumbar spinal cord, by immunohistochemistry.

Key results: In BV2 cells, GB9 and GB10 inhibited the expression of iNOS and COX‐2, stimulated by IFN‐γ. Intrathecal administration of GB9 and GB10 inhibited CCI‐induced nociceptive sensitization and thermal hyperalgesia in a dose‐dependent manner. Intraperitoneal injection of GB9 inhibited CCI‐induced thermal hyperalgesia and also inhibited CCI‐induced activation of microglial cells and up‐regulation of COX‐2 in the dorsal horn of the lumbar spinal cord ipsilateral to the injury.

Conclusion and implications: Taken together, these data indicate that the marine‐derived capnellenes, GB9 and GB10, had anti‐neuroinflammatory and anti‐nociceptive properties in IFN‐γ‐stimulated microglial cells and in neuropathic rats respectively. Therefore, capnellene may serve as a useful lead compound in the search for new therapeutic agents for treatment of neuroinflammatory diseases.
Re-Founding Representation: Wider, Broader, Closer, Deeper
Authors: Taylor Lucy
Published: August 2009

This article challenges conventional understandings and methodologies associated with the study of political representation. It imagines representation as a power relationship and shifts attention from elections to a closer examination of the interface between representatives and those they claim to represent. It argues for the need to make representation studies wider, moving our focus to study polities beyond the confines of prosperous, established democracies. Secondly, we should broaden our understanding of representation agents in two ways. We should consider how non-voters are represented and we should include diverse forms of social organisations, problematising relationships of representation within these groups and taking their political-representational role seriously. Thirdly, we should move closer, conducting not only macro-level analyses but also micro-level studies, exploring representation among and between individuals and groups in order to understand the complex relationships, motives and dynamics of power at work. Finally we need to go deeper, looking at our own subject positions as scholars critically and challenging the neutrality of the ideas and assumptions that we use as intellectual tools. Moreover, we should promote deeper relationships of representation, reconnecting it to ideas and practices of participation, and promoting the role of accountability in ‘closing the loop’ and enhancing democracy.
GYMNODINIUM COROLLARIUM SP. NOV. (DINOPHYCEAE)—A NEW COLD‐WATER DINOFLAGELLATE RESPONSIBLE FOR CYST SEDIMENTATION EVENTS IN THE BALTIC SEA1
Authors: Sundström Annica M. , Kremp Anke , Daugbjerg Niels , Moestrup Øjvind , Ellegaard Marianne , Hansen Regina , Hajdu Susanna
Published: August 2009

A naked dinoflagellate with a unique arrangement of chloroplasts in the center of the cell was isolated from the northern Baltic proper during a spring dinoflagellate bloom (March 2005). Morphological, ultrastructural, and molecular analyses revealed this dinoflagellate to be undescribed and belonging to the genus Gymnodinium F. Stein. Gymnodinium corollarium A. M. Sundström, Kremp et Daugbjerg sp. nov. possesses features typical of Gymnodinium sensu stricto, such as nuclear chambers and an apical groove running in a counterclockwise direction around the apex. Phylogenetic analyses based on partial nuclear‐encoded LSU rDNA sequences place the species in close proximity to G. aureolum, but significant genetic distance, together with distinct morphological features, such as the position of chloroplasts, clearly justifies separation from this species. Temperature and salinity experiments revealed a preference of G. corollarium for low salinities and temperatures, confirming it to be a cold‐water species well adapted to the brackish water conditions in the Baltic Sea. At nitrogen‐deplete conditions, G. corollarium cultures produced small, slightly oval cysts resembling a previously unidentified cyst type commonly found in sediment trap samples collected from the northern and central open Baltic Sea. Based on LSU rDNA comparison, these cysts were assigned to G. corollarium. The cysts have been observed in many parts of the Baltic Sea, indicating the ecologic versatility of the species and its importance for the Baltic ecosystem.
The Free‐Market Economy Is Fundametally Healthy
Authors: BECKER GARY , MYERSON ROGER , SCHOLES MYRON
Published: August 2009

Though another Great Depression seems to have been averted for the moment, great geo‐economic shifts are in the works as a result of the global meltdown emanating from Wall Street. Four Nobel laureates in economics take a look at where we are headed.