bluuebunny/crossref_metadata_2025 huggingface dataset:
Radioiodine treatment for benign thyroid disorders: results of a nationwide survey of UK endocrinologists
Authors: Vaidya Bijay , Williams Graham R. , Abraham Prakash , Pearce Simon H. S.
Published: October 2007

Background  A survey of physicians’ practice relating to radioiodine administration for hyperthyroidism was carried out in the UK over 15 years ago and showed wide variations in patient management. This led to the development of national guidelines for the use of radioiodine in hyperthyroidism. As there have been significant advances in the field since that survey, we carried out another survey to study the prevalent practices relating to radioiodine therapy for benign thyroid disorders across the UK.

Subjects and methods  We mailed 698 UK consultant endocrinologists a questionnaire on radioiodine treatment based on three patient scenarios: hyperthyroid Graves’ disease, subclinical hyperthyroidism and nontoxic goitre.

Results  The response rate was 40%. For the scenario of an initial presentation of Graves’ disease, 80%, 19% and 0·4% of respondents preferred thionamide, radioiodine or thyroidectomy, respectively. There were inconsistencies in respondents’ recommendations on radioiodine dose, the use of pre‐ and post‐radioiodine supplementary treatments, timing of a repeat dose, and the use of radioiodine in thyroid eye disease. For the case of subclinical hyperthyroidism, one‐third of respondents would generally initiate treatment. The majority were more likely to treat subclinical hyperthyroidism in the presence of paroxysmal atrial fibrillation or osteoporosis. If a decision were made to treat subclinical hyperthyroidism, 63%, 35%, 1% and 0·4% would recommend radioiodine, thionamide, beta‐blocker and thyroidectomy, respectively. For the scenario of nontoxic goitre, 62%, 21%, 13% and 5% favoured observation, thyroidectomy, radioiodine and thyroxine, respectively.

Conclusions  There remain significant differences in several aspects of clinical practice relating to the use of radioiodine treatment for benign thyroid disorders in the UK.
Evaluation of adrenal function using the human corticotrophin‐releasing hormone test, low dose Synacthen test and 9am cortisol level in children and adolescents with central adrenal insufficiency
Authors: Maguire Ann M. , Biesheuvel Cornelis J. , Ambler Geoffrey R. , Moore Bin , McLean Mark , Cowell Christopher T.
Published: October 2007

Background  The insulin tolerance test (ITT) has become less popular in paediatrics because of the risks associated with hypoglycaemia. Human corticotrophin‐releasing hormone (hCRH) test results correlate with the ITT and may be an acceptable method to test for central adrenal insufficiency (CAI). Simpler tests, such as the low dose Synacthen test (LDST) and 9am cortisol, have also been proposed.

Objective  To compare the ability of the hCRH test, LDST, 9am cortisol level and 24‐h cortisol profiles to diagnose CAI in a paediatric population.

Design and setting  A cross‐sectional study in a tertiary paediatric endocrine clinic.

Participants  Thirty‐one children and adolescents (aged 2·3–18·3 years) with CAI risk factors had an hCRH test, LDST, 9am cortisol and 24‐h cortisol profile performed.

Results  Of 23 patients with confirmed CAI (hCRH peak cortisol < 400 nmol/), 19 failed the LDST (peak cortisol < 267 nmol/l, i.e. 10th percentile for controls). Nineteen would have failed based on the 10th percentile cut point for 9am cortisol (< 140 nmol/l). Using receiver operating characteristic (ROC) curve coordinates, a 9am cortisol < 108 nmol/l was sensitive (83%) and specific (99%) for CAI. The 9am cortisol levels measured on two occasions were repeatable (94%) and correlated (r = 0·83, P = 0·01). All eight adrenally sufficient patients (hCRH peak cortisol ≥ 400 nmol/l) passed the LDST. Seven had normal 9am cortisol (≥ 140 nmol/l). The 24‐h cortisol area under the curve (AUC) for these patients was within the 10th–90th percentiles for control subjects’ AUC. The peak cortisol to hCRH and LDST were correlated (r = 0·88, P = 0·01), with no difference between the peaks (mean difference –5·3 nmol/l, P = 0·69).

Conclusions  In children with CAI risk factors, the diagnosis can be made if unstressed 9am cortisol is < 108 nmol/l. As cortisol levels > 381 nmol/l are highly suggestive of normal hypothalamic–pituitary–adrenal (HPA) function, stimulation testing need only be performed if 9am cortisol is 108–381 nmol/l. The LDST should be interpreted cautiously because mild CAI may be missed. When stimulation results are marginal, 24‐h cortisol profiles can provide reassurance of normal cortisol status.
Identification of molecular mechanisms related to nonthyroidal illness syndrome in skeletal muscle and adipose tissue from patients with septic shock
Authors: Rodriguez‐Perez Alfonso , Palos‐Paz Fernando , Kaptein Ellen , Visser Theo J. , Dominguez‐Gerpe L. , Alvarez‐Escudero Julian , Lado‐Abeal Joaquin
Published: October 2007

Objective  Septic shock is one of various causes of nonthyroidal illness syndrome (NTIS). In humans, the molecular mechanisms involved in NTIS are mostly unknown. The aim of this study was to investigate, in patients with NTIS secondary to septic shock, changes in the expression of genes involved in the actions of thyroid hormones and in the activity of deiodinase enzymes, in two tissues important for protein and energy metabolism, skeletal muscle (SM) and subcutaneous adipose tissue (SAT).

Design  Hospitalized patients were divided into a control and a septic shock NTIS group.

Measurement  Serum collection for biochemical measurements, and SM and SAT biopsies for mRNA expression analysis of thyroid hormone receptors (THRB1, THRA1), retinoid X receptors (RXRA, RXRB, RXRG), nuclear receptor corepressor (NCOR1), silencing mediator of retinoid and thyroid hormone receptor (SMRT), steroid receptor coactivator (SRC1), type 1 and 2 deiodinases (D1, D2), monocarboxylate transporter 8 (MCT8), SECIS binding protein 2 (SBP2) and uncoupling protein 3 (UCP3) as well as D1, D2 and D3 enzyme activity measurements.

Results  The NTIS group had lower serum TSH, and free T3 and higher rT3 than controls. D1 and D3 were detected in SAT, with no differences found between the two groups; SM had very low D2 activity and again no differences were found between groups; D3 activity in SM was higher in NTIS than controls. SM expression of THRB1, RXRG and D2 was lower and RXRA higher in NTIS than controls. SAT from NTIS patients had lower MCT8, THRB1, THRA1, RXRG and SMRT, and higher UCP3 expression than controls.

Conclusions  In patients with septic shock NTIS tissue responses are orientated to decrease production and increase degradation (muscle) or decrease uptake (adipose tissue) of T3, as well as to decrease thyroid hormone actions.
Association of ENPP1 (PC‐1) K121Q polymorphism with obesity‐related parameters in subjects with metabolic syndrome
Authors: González‐Sánchez José L. , Zabena Carina , Martínez‐Larrad María T. , Martínez‐Calatrava María J. , Pérez‐Barba Milagros , Serrano‐Ríos Manuel
Published: October 2007

Background  The metabolic syndrome (MS), a cluster of several metabolic disorders, is increasingly being recognized as a risk factor for cardiovascular disease. Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), originally described as a plasma cell allo‐antigen and named plasma cell membrane glycoprotein (PC‐1), is an inhibitor of insulin‐induced activation of the insulin receptor. The single nucleotide polymorphism (SNP) K121Q in the ENPP1 gene has been studied in relation to obesity, insulin resistance and other features of MS in several populations with conflicting results.

We therefore investigate the role of the K121Q SNP in the ENPP1 gene in MS in Caucasians from the province of Segovia in Central Spain (Castille).

Design and methods  We recruited 794 unrelated persons (46·5% males and 53·5% females), ages 35–74 years from a cross‐sectional population‐based epidemiological survey in the province of Segovia in Central Spain (Castille). Obesity‐related anthropometric measurements included BMI, waist circumference, blood pressure and lipid profile. MS was defined by International Diabetes Federation (IDF) guidelines. K121Q PC‐1 genotypes were determined by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP).

Results  The 121Q allele was associated with an increased BMI and waist circumference among subjects fulfilling the criteria for MS. These differences remained statistically significant even after the adjustment for sex, age and degree of glucose tolerance (β = 1·347, P = 0·017 and β = 2·824, P = 0·046; for BMI and waist circumference, respectively). Moreover, among type 2 diabetic patients those carrying the 121Q allele had higher BMI and higher leptin levels than subjects carrying the K121K genotype.

Conclusions  Our results suggest that the ENPP1121Q allele might contribute to the genetic susceptibility to abdominal obesity among subjects with MS.
The Anti‐Ghrelin Spiegelmer NOX‐B11‐3 Blocks Ghrelin‐ but not Fasting‐Induced Neuronal Activation in the Hypothalamic Arcuate Nucleus
Authors: Becskei C. , Bilik K. U. , Klussmann S. , Jarosch F. , Lutz T. A. , Riediger T.
Published: October 2007

The hypothalamic arcuate nucleus (Arc) is the presumed target site for the orexigenic hormone ghrelin, which is secreted from the stomach during fasting. Ghrelin directly activates Arc neurones. Similar to exogenous ghrelin, overnight food deprivation also induces c‐Fos expression in the Arc of mice. In the present study, we tested the role of endogenous ghrelin in the fasting‐induced c‐Fos expression in the Arc of mice. We used NOX‐B11‐3, the latest generation of the recently developed ghrelin‐binding compounds, so‐called RNA Spiegelmers (SPM) to block endogenous ghrelin action during food deprivation. The specificity and potency of this compound was also tested in electrophysiological and immunohistological experiments. In electrophysiological in vitro single cell recordings, NOX‐B11‐3 effectively blocked the excitatory effect of ghrelin in the medial Arc (ArcM) of rats whereas the biologically inactive control SPM had no effect. Furthermore, NOX‐B11‐3 (15 mg/kg i.p.) potently suppressed ghrelin‐induced (25 µg/kg s.c., 12 h after SPM injection) c‐Fos expression in the Arc. However, when injected at the beginning of a 14‐h fasting period, the same dose of NOX‐B11‐3 had no effect on the c‐Fos expression in the Arc of mice. These results demonstrate that NOX‐B11‐3 is a long‐acting compound, which effectively blocks the effect of exogenous ghrelin on neuronal activity in the Arc under in vitro and in vivo conditions. Furthermore, increased ghrelin signalling does not appear to be a necessary factor for the activation of Arc neurones during food deprivation or other fasting‐related signals might have masked or compensated for the loss of the ghrelin effect.
Histamine H3 Receptor and Orexin A Expression During Daily Torpor in the Djungarian Hamster (Phodopus sungorus)
Authors: Herwig A. , Ivanova E. A. , Lydon H. , Barrett P. , Steinlechner S. , Loudon A. S.
Published: October 2007

Seasonal animals use different strategies to reduce energy expenditure in the face of reduced seasonal food availability. For example, the ground squirrel enters a hibernation state with reduced metabolism, hypothermia and suppressed central nervous system activity, whereas the Djungarian hamster (Phodopus sungorus) employs daily bouts of torpor associated with reduced body temperature and energy expenditure. Studies in the hibernating ground squirrel implicate an increase in histamine synthesis and histamine H3 receptor expression in the brain as a central mechanism governing hibernation. In the present study, we demonstrate an up‐regulation of H3 receptors in several brain nuclei in the Djungarian hamster during bouts of daily torpor, a shallow form of hypothermia, suggesting that histaminergic pathways may play a general role in maintaining low body temperature and torpor state in mammals. These regions include the arcuate nucleus, dorsomedial hypothalamus, suprachiasmatic nucleus, dorsal lateral geniculate nucleus and tuberomammilary nucleus. Interestingly, expression of the mRNA for orexins, a group of neuropeptides that increase wakefulness, remains unchanged during the arousal from daily torpor, suggesting that this classic ‘arousal’ pathway is not involved in the transition from a hypothermic to the euthermic state.
Adaptive differences in gene expression in European flounder (Platichthys flesus)
Authors: LARSEN PETER F. , NIELSEN EINAR E. , WILLIAMS TIMOTHY D. , HEMMER‐HANSEN JAKOB , CHIPMAN JAMES K. , KRUHØFFER MOGENS , GRØNKJÆR PETER , GEORGE STEPHEN G. , DYRSKJØT LARS , LOESCHCKE VOLKER
Published: October 2007

Population structure was previously believed to be very limited or absent in classical marine fishes, but recently, evidence of weakly differentiated local populations has been accumulating using noncoding microsatellite markers. However, the evolutionary significance of such minute genetic differences remains unknown. Therefore, in order to elucidate the relationship between genetic markers and adaptive divergence among populations of marine fishes, we combined cDNA microarray and microsatellite analysis in European flounders (Platichthys flesus). We demonstrate that despite extremely low levels of neutral genetic divergence, a high number of genes were significantly differentially expressed between North Sea and Baltic Sea flounders maintained in a long‐term reciprocal transplantation experiment mimicking natural salinities. Several of the differentially regulated genes could be directly linked to fitness traits. These findings demonstrate that flounders, despite little neutral genetic divergence between populations, are differently adapted to local environmental conditions and imply that adaptation in gene expression could be common in other marine organisms with similar low levels of population subdivision.
Colleterial glands of Sesamia nonagrioides as a source of the host‐recognition kairomone for the egg parasitoid Telenomus busseolae
Authors: DE SANTIS FEDERICA , CONTI ERIC , ROMANI ROBERTO , SALERNO GIANANDREA , PARILLO FRANCESCO , BIN FERDINANDO
Published: October 2007

Abstract The maize stemborer Sesamia nonagrioides glues its egg masses under the leaf sheaths or ear bracts using colleterial gland secretion. In spite of such concealed oviposition sites, these eggs are parasitized by Telenomus busseolae. The colleterial glands of S. nonagrioides are investigated as a possible source of the host‐recognition kairomone for T. busseolae. This secretion, applied on glass beads, elicits intense antennal drumming and oviposition probing behaviour in the parasitoid. Through an histochemical study, neutral and acid glycoconjugates are identified as components of the secretion. Finally, using ultrastructural techniques, the colleterial glands are described and classified as comprising class 3 secretory cells.
Polyethism and nestmate recognition in the alarm reaction of Atta leaf‐cutting ants
Authors: VELOSO FRANCELINO MÁRCIO R. , DE LIMA MENDONÇA ADRIANA , DO NASCIMENTO RUTH R. , DE MENDONÇA FERNANDO A. C. , DA SILVA EDLEIDE L. , DE FREITAS MARIA DO ROSÁRIO T. , CABRAL CYRO R. , DA SILVA CARLOS EDUARDO , RIBEIRO JOSÉ H. S. , SANTANA ANTÔNIO EUZÉBIO G.
Published: October 2007

Abstract Ethological studies are conducted under laboratory conditions using workers of Atta sexdens sexdens and Atta opaciceps collected from field colonies to investigate the mechanisms involved in the alarm response and intra‐specific recognition in leaf‐cutting ants. Hexane extracts from the heads of gardeners and generalist workers elicit higher levels of alarm response in foragers from the same colony than do mandibular gland extracts from foragers and soldiers, indicating that gardeners, generalists and foragers are primarily responsible for the production of alarm pheromone. Foragers subjected to extracts from non‐nestmates exhibit significantly greater alarm responses than are induced by similar extracts derived from nestmate workers, suggesting that the alarm pheromone may have a role in nestmate recognition.
Exhumation across the Indus Suture Zone: a record of back sliding of the hanging wall
Authors: Zeilinger Gerold , Seward Diane , Burg Jean‐Pierre
Published: October 2007

The Kohistan Arc Complex is an integral part of the NW Himalayan collision system and is bounded by two major suture zones, the Indus Suture Zone (ISZ) and the Northern Suture in the south and north respectively. Fission‐track analyses on samples collected along the Indus River across the arcuated ISZ in the Besham region are presented here. The footwall yields zircon and apatite fission‐track (FT) ages of ∼23 Ma and ∼3.7 Ma respectively; the hanging wall ages range from 24 to 42 Ma for zircon and ∼10 Ma for apatite. Thus, the change in ISZ kinematics from thrusting to normal faulting was not later than Oligocene and normal faulting on this ISZ segment was still active at least into early Pliocene times. At this time normal faulting had already ended at other ISZ segments, but it was still (or again) active across the ISZ in the Besham region most likely as a local phenomenon caused by the growth of the Indus Syntaxis, a transverse antiform parallel to the Nanga Parbat Syntaxis.
Using SHRIMP zircon dating to unravel tectonothermal events in arc environments. The early Palaeozoic arc of NW Iberia revisited
Authors: Abati Jacobo , Castiñeiras Pedro , Arenas Ricardo , Fernández‐Suárez Javier , Gómez Barreiro Juan , Wooden Joseph L.
Published: October 2007

Abstract Dating of zircon cores and rims from granulites developed in a shear zone provides insights into the complex relationship between magmatism and metamorphism in the deep roots of arc environments. The granulites belong to the uppermost allochthonous terrane of the NW Iberian Massif, which forms part of a Cambro‐Ordovician magmatic arc developed in the peri‐Gondwanan realm. The obtained zircon ages confirm that voluminous calc‐alkaline magmatism peaked around 500 Ma and was shortly followed by granulite facies metamorphism accompanied by deformation at c. 480 Ma, giving a time framework for crustal heating, regional metamorphism, deformation and partial melting, the main processes that control the tectonothermal evolution of arc systems. Traces of this arc can be discontinuously followed in different massifs throughout the European Variscan Belt, and we propose that the uppermost allochthonous units of the NW Iberian Massif, together with the related terranes in Europe, constitute an independent and coherent terrane that drifted away from northern Gondwana prior to the Variscan collisional orogenesis.
Sweet delivery – sugar translocators as ports of entry for antisense oligodeoxynucleotides in plant cells
Authors: Sun Chuanxin , Ridderstråle Karin , Höglund Anna‐Stina , Larsson Lars‐Gunnar , Jansson Christer
Published: October 2007

Antisense oligodeoxynucleotides (ODNs) are short (12–25 nt long) stretches of single‐stranded DNA that may be delivered to a cell, where they hybridize to the cognate mRNA in a sequence‐specific manner, thereby inhibiting gene expression. Here we used confocal microscopy to monitor the uptake and trafficking of ODNs in barley tissues. We conclude that uptake of ODNs across the plant plasma membrane is mediated by active transport of mono‐ or disaccharides through sugar translocators. We demonstrate that sugar transport can deliver ODNs to barley seeds, and that this strategy may be employed to suppress gene activity in endosperm cells by antisense ODN inhibition. We further found that sucrose compared favorably with oligofectamine as a vehicle for ODN delivery to human cells in a low‐serum environment.
Common characteristics of upper and lower airways in rhinitis and asthma: ARIA update, in collaboration with GA2LEN
Authors: Cruz A. A. , Popov T. , Pawankar R. , Annesi‐Maesano I. , Fokkens W. , Kemp J. , Ohta K. , Price D. , Bousquet J. ,   on behalf of ARIA Initiative Scientific Committee
Published: October 2007

This update aimed to review the new evidence available to support or refute prior Allergic Rhinitis and its Impact on Asthma (ARIA) statements. A Medline search of publications between 2000 and 2005 was conducted, with articles selected by experts. New evidence supports previous ARIA statements, such as: (i) allergic rhinitis (AR) is a risk factor for asthma; (ii) patients with persistent rhinitis should be evaluated for asthma; (iii) most patients with asthma have rhinitis; (iv) a combined strategy should be used to treat the airways and (v) in low‐ to middle‐income countries, a different strategy may be needed. The increased risk of asthma has also been found among sufferers from non‐AR. Recent reports show AR is a global problem. Many studies demonstrated parallel increasing prevalence of asthma and rhinitis, but in regions of highest prevalence, it may be reaching a plateau. Factors associated with a reduced risk of asthma and AR have been identified, confirming previous findings of protection related to exposure to infections. Treatment of rhinitis with intranasal glucocorticosteroids, antihistamines, leukotriene antagonists or immunotherapy may reduce morbidity because of asthma. To take advantage of the paradigm of unified airways, there is a need to rationalize diagnosis and treatment to optimize management.
Effects of cumulus cells on rabbit oocyte in vitro maturation
Authors: Tao Y. , Cao C. , Zhang M. , Fang F. , Liu Y. , Zhang Y. , Ding J. , Zhang X.
Published: October 2007

Cumulus cells (CCs) are of great importance in oocyte development and maturation in many species, but detailed influence of CCs has not been extensively examined, especially on rabbit. The present study was designed to investigate the effects of CCs and the elongation of in vitro maturation (IVM) time on rabbit oocyte nuclear and ooplasmic maturation and survival. Cumulus oocyte complexes (COCs) and naked oocytes (NOs) were recovered directly from rabbits super‐ovulated with eCG. Corona‐enclosed oocytes (COs) and denuded oocytes (DOs) were obtained from COCs after removing a part or whole of CCs. The oocytes were cultured in the following seven groups. (i) Cumulus cell enclosed oocytes (CEOs) were cultured alone (CEOs); (ii) COs were cultured alone (COs); (iii) DOs were cultured alone (DOs); (iv) NOs were cultured alone; (v) DOs were co‐cultured with COCs [DOs(COCs)]; (vi) DOs were co‐cultured with CCs [DOs(CCs)]; (vii) NOs were co‐cultured with CCs [NOs(CCs)]. After the oocytes were cultured for 24 and 30 h, the nuclear maturation was evaluated by first polar body (PB1) extrusion while the ooplasmic maturation was evaluated by the cleavage rate after parthenogenetic activation. The results showed that the nuclear maturation rate of CEOs, COs, DOs(COCs) and DOs(CCs) after 24 h incubation were significantly different from each other (p ≤ 0.05), the rate of DOs(CCs) was similar to that of DOs (p ≥ 0.05). The cleavage rates in the first two groups were significantly higher than those of the others (p < 0.05). For oocytes cultured for 30 h, the nuclear maturation rates were significantly different for each culture model (p < 0.05). The cleavage rates in first two groups were significantly higher than those of others (p < 0.05). Both the nuclear and cleavage rates significantly increased when the culture time of DOs(COCs) was prolonged from 24 to 30 h. DOs(CCs) nuclear maturation was significantly improved when the culture time was prolonged from 24 to 30 h, but the ooplasmic maturation was not. Few NOs incubated with or without CCs accomplished nuclear maturation (approximately 2% both), even when the culture time was prolonged from 24 to 30 h. The oocyte degeneration rates were significantly different for each culture model after both 24 and 30 h incubation (p ≤ 0.05). There was no significant difference in oocyte degeneration in the same groups between 24 and 30 h incubation (p > 0.05). The results suggest that rabbit CCs affect oocyte nuclear and ooplasmic maturation, and their survival. The prolongation of the culture time of rabbit oocyte from 24 to 30 h improves the nuclear and ooplasmic maturation differently in the present system. Rabbit oocytes free of CCs, especially NOs, show weak meiotic resumption potential and compromised viability, which cannot be improved by co‐culture with dispersed CCs. The degeneration mostly happens at early time of IVM.
Tomographic assessment of therapeutic response to uveitic macular oedema
Authors: Sivaprasad Sobha , Ikeji Felicia , Xing Wen , Lightman Sue
Published: October 2007

Abstract

Purpose:  To evaluate the therapeutic effects on the different morphological patterns of uveitic macular oedema and central macular thickness using optical coherence tomography (OCT).

Methods:  Retrospective observational case series. Fifty consecutive patients with a clinical diagnosis of new or recurrent macular oedema due to uveitis were examined with serial OCTs for 1 year. The correlation between different patterns of macular oedema (diffuse macular oedema, inner cystoid oedema, outer cystoid oedema, oedema involving both inner and outer layers of retina and serous retinal detachment) and change in logMAR visual acuity and the recorded variables including age, gender, systemic disease associated with uveitis, location and duration of uveitis, and duration of macular oedema were examined. Response to treatment was measured as change in logMAR visual acuity and evolution of patterns of macular oedema.

Results:  Diffuse macular oedema, external cystoid and serous retinal detachment responded well to treatment. Cysts in the inner retinal layers were more resistant to treatment. The cysts in the outer layers disappeared faster than cysts in the inner layers in patients with cysts in both layers at baseline. Multivariate analysis showed that cystoid macular oedema (all types) (P = 0.03) and inner cystoid oedema (P = 0.031) were the variables significantly associated with final visual acuity.

Conclusion:  Assessment of patterns of uveitic macular oedema by OCT gives useful information on the prognosis. Inner retinal cystoid oedema is more resistant to treatment than any other patterns of oedema.
Global analysis of nitrogen and phosphorus limitation of primary producers in freshwater, marine and terrestrial ecosystems
Authors: Elser James J. , Bracken Matthew E.S. , Cleland Elsa E. , Gruner Daniel S. , Harpole W. Stanley , Hillebrand Helmut , Ngai Jacqueline T. , Seabloom Eric W. , Shurin Jonathan B. , Smith Jennifer E.
Published: October 2007

The cycles of the key nutrient elements nitrogen (N) and phosphorus (P) have been massively altered by anthropogenic activities. Thus, it is essential to understand how photosynthetic production across diverse ecosystems is, or is not, limited by N and P. Via a large‐scale meta‐analysis of experimental enrichments, we show that P limitation is equally strong across these major habitats and that N and P limitation are equivalent within both terrestrial and freshwater systems. Furthermore, simultaneous N and P enrichment produces strongly positive synergistic responses in all three environments. Thus, contrary to some prevailing paradigms, freshwater, marine and terrestrial ecosystems are surprisingly similar in terms of N and P limitation.
Frequency‐dependence stabilizes competitive interactions among four annual plants
Authors: Harpole W. Stanley , Suding Katharine N.
Published: October 2007

It is the combination of large fitness differences and strong stabilizing mechanisms that often constitute niche‐based explanations for species abundance patterns. Despite the importance of this assumption to much of community ecology, empirical evidence is surprisingly limited. Empirical tests are critical because many abundance patterns are also consistent with neutral‐based alternatives (that assume no fitness differences or stabilization). We quantified interactions of four annual grassland species in two‐species mixtures at varying frequencies. We found evidence of strong negative frequency‐dependent stabilization, where scaled population growth rates increased with decreasing frequency for all four species. There was also a consistent competitive hierarchy among these species indicative of strong fitness differences that, in most cases, suggested potential competitive exclusion despite the observed strong stabilization.
Interactions between microvascular and macrovascular disease in diabetes: pathophysiology and therapeutic implications
Authors: Krentz Andrew J. , Clough Geraldine , Byrne Christopher D.
Published: October 2007

Convention partitions the complications of diabetes into two main subtypes. First are the diabetes‐specific microvascular complications of retinopathy, nephropathy and neuropathy; second are the atherothrombotic macrovascular complications that account for the majority of premature deaths. Pathological interactions between microvascular and macrovascular complications, for example, nephropathy and macrovascular disease, are common. Similar mechanisms and shared risk factors drive the development and progression of both small and large vessel disease. This concept has therapeutic implications. Mounting evidence points to the need for multifactorial strategies to prevent vascular complications in subjects with diabetes and/or the metabolic syndrome. We advocate a combined therapeutic approach that addresses small and large vessel disease. Preferential use should be made of drug regimens that (i) maximize vascular protection, (ii) reduce the risk of iatrogenic vascular damage and (iii) minimize the increasing problem of polypharmacy.
Patient selection determines the prostate cancer yield of dynamic contrast‐enhanced magnetic resonance imaging‐guided transrectal biopsies in a closed 3‐Tesla scanner
Authors: Singh Anurag K. , Krieger Axel , Lattouf Jean‐Baptiste , Guion Peter , Grubb Robert L. , Albert Paul S. , Metzger Greg , Ullman Karen , Smith Sharon , Fichtinger Gabor , Ocak Iclal , Choyke Peter , Ménard Cynthia , Coleman Jonathan
Published: October 2007

OBJECTIVE

To evaluate the cancer yield of transrectal prostate biopsies in a 3‐T magnetic resonance imaging (MRI) scanner in patients with elevated prostate specific antigen (PSA) levels and recent negative transrectal ultrasonography (TRUS)‐guided prostate biopsies.

PATIENTS AND METHODS

Between July 2004 and November 2005, patients with at least one previous negative prostate biopsy within the previous 12 months had MRI‐guided biopsy of the prostate in a 3‐T MRI scanner. Patients with previous positive biopsies for cancer were excluded. Target selection was based on T2‐weighted imaging and dynamic contrast‐enhanced (DCE) imaging studies.

RESULTS

Thirteen patients were eligible; their median (range) age was 61 (47–74) years and PSA value 4.90 (1.3–12.3) ng/mL. Most patients had one previous negative biopsy (range 1–4). Four patients had a family history of prostate cancer. There were 37 distinct targets based on T2‐weighted imaging. Fifteen of 16 distinct DCE abnormalities were co‐localized with a target based on T2‐weighted imaging. Despite this correlation, only one of 13 patients had a directed biopsy positive for cancer. Including systematic biopsies, two of 13 patients had a biopsy positive for prostate cancer. One patient had prostate intraepithelial neoplasia and one had atypical glands in the specimen.

CONCLUSION

The prostate‐cancer yield of transrectal biopsies in a 3‐T MRI scanner, among patients with recent negative TRUS‐guided prostate biopsies, is similar to repeat systematic TRUS‐guided biopsy. DCE correlates with T2‐imaging but does not appear to improve prostate cancer yield in this population.
A phase II trial of cisplatin, fixed dose‐rate gemcitabine and gefitinib for advanced urothelial tract carcinoma: results of the Cancer and Leukaemia Group B 90102
Authors: Philips George K. , Halabi Susan , Sanford Ben L. , Bajorin Dean , Small Eric J. ,   Cancer and Leukaemia Group B
Published: October 2007

OBJECTIVE

To conduct a phase II trial to determine the efficacy of cisplatin, a fixed dose‐rate infusion of gemcitabine and gefitinib (an orally active epidermal growth factor receptor tyrosine kinase inhibitor) in patients with advanced urothelial carcinoma.

PATIENTS AND METHODS

Eligible patients had previously untreated measurable disease, an Eastern Cooperative Oncology Group performance status of 0–2 and creatinine clearance of >50 mL/min. The treatment regimen consisted of cisplatin 70 mg/m2 on day 1, gemcitabine 1000 mg/m2 on day 1 and 8, administered at a fixed dose rate of 10 mg/m2/min, given every 3 weeks concurrent with gefitinib 500 mg/day orally for a maximum of six cycles. Maintenance gefitinib 500 mg/day was continued for responding or stable disease.

RESULTS

In all, 27 patients were accrued before the study was halted because the dose‐limiting toxicity (DLT) exceeded pre‐established stopping rules. The DLT events were two grade 5 (one infection, one cardiovascular accident) and three with grade 4 non‐haematological toxicity. In 25 evaluable patients there were nine objective responses, for an overall response rate of 36% (95% confidence interval, CI, 18–57%). The median (95% CI) survival time was 11.1 (5.2–35.3) months.

CONCLUSION

The combination of cisplatin, fixed dose‐rate gemcitabine and gefitinib is active in advanced TCC, although the relative contribution of gefitinib cannot be determined. However, this regimen was associated with excessive toxicity.
Independent assessment of a wide‐focus, low‐pressure electromagnetic lithotripter: absence of renal bioeffects in the pig
Authors: Evan Andrew P. , McAteer James A. , Connors Bret A. , Pishchalnikov Yuri A. , Handa Rajash K. , Blomgren Philip , Willis Lynn R. , Williams James C. , Lingeman James E. , Gao Sujuan
Published: October 2007

OBJECTIVE

To assess the renal injury response in a pig model treated with a clinical dose of shock waves (SWs) delivered at a slow rate (27 SW/min) using a novel wide focal zone (18 mm), low acoustic pressure (<20 MPa) electromagnetic lithotripter (Xi Xin‐Eisenmenger, XX‐ES; Xi Xin Medical Instruments Co. Ltd., Suzhou, PRC).

MATERIALS AND METHODS

The left kidneys of anaesthetized female pigs were treated with 1500 SWs from either an unmodified electrohydraulic lithotripter (HM3, Dornier MedTech America, Inc., Kennesaw, GA, USA; 18 kV, 30 SW/min) or the XX‐ES (9.3 kV, 27 SW/min). Measures of renal function (glomerular filtration rate, GFR, and renal plasma flow) were collected before and after SW lithotripsy, and kidneys were harvested for histological quantification of vascular haemorrhage, expressed as a percentage of the functional renal volume (FRV). A fibre‐optic probe hydrophone was used to characterize the acoustic field, and the breakage of gypsum model stones was used to compare the function of the two lithotripters.

RESULTS

Kidneys treated with the XX‐ES showed no significant change in renal haemodynamic function and no detectable tissue injury. Pigs treated with the HM3 had a modest decline from baseline (≈ 20%) in both GFR (P > 0.05) and renal plasma flow (P = 0.064) in the treated kidney, but that was not significantly different from the control group. Although most HM3‐treated pigs showed no evidence of renal tissue injury, two had focal injury measuring 0.1% FRV, localized to the renal papillae. The width of the focal zone for the XX‐ES was ≈ 18 mm and that of the HM3 ≈ 8 mm. Peak positive pressures at settings used to treat pigs and break model stones were considerably lower for the XX‐ES (17 MPa at 9.3 kV) than for the HM3 (37 MPa at 18 kV). The XX‐ES required fewer SWs to break stones to completion than did the HM3, with a mean (sd) of 634 (42) and 831 (43) SWs, respectively (P < 0.01). However, conditions were different for these tests because of differences in physical configuration of the two machines.

CONCLUSION

The absence of renal injury with the wide focal zone XX‐ES lithotripter operated at low shock pressure and a slow SW rate suggests that this lithotripter would be safe when used at the settings recommended for patient treatment. That the injury was also minimal using the Dornier HM3 lithotripter at a slow SW rate implies that the reduced tissue injury seen with these two machines was because they were operated at a slow SW rate. As recent studies have shown stone breakage to be improved when the focal zone is wider than the stone, a wide focal zone lithotripter operated at low pressure and slow rate has the features necessary to provide better stone breakage with less tissue injury.
Muscarinic and purinergic receptor expression in the urothelium of rats with detrusor overactivity induced by bladder outlet obstruction
Authors: Kim Joon Chul , Yoo Jae Suk , Park Eun Young , Hong Sung Hoo , Seo Seong Il , Hwang Tae‐Kon
Published: October 2007

OBJECTIVE

To investigate the expression of muscarinic and purinergic receptors in rat urothelium, and changes in their distribution and expression following detrusor overactivity induced by bladder outlet obstruction (BOO).

MATERIALS AND METHODS

Thirty Sprague‐Dawley rats were divided into control (10) and BOO groups (20). Partial BOO was induced for 3 weeks and the rats assessed by cystometrography. A portion of the bladder was stained using immunofluorescence for M2 and M3 muscarinic receptors, and P2X3 purinergic receptors. The remainder was dissected into bladder urothelium and the smooth muscle layer, and the expression of the receptor proteins analysed by Western blotting.

RESULTS

Cystometrography showed a significant decrease in contraction interval and increase in contraction pressure in the BOO group. On immunofluorescence staining, muscarinic and purinergic receptors were localized in both the urothelium and the muscle layer. Immunoreactivity of M2 and M3 muscarinic receptors was greater in the urothelium of the BOO group than in the control group; there was a smaller increase in P2X3 immunoreactivity. On Western blotting, the expression of M2, M3 and P2X3 receptors was increased in the urothelium of the BOO group, and there was increased M3 receptor expression in the muscle layer of the BOO group.

CONCLUSIONS

There were detectable changes in muscarinic and purinergic receptors with bladder overactivity induced by BOO. Our results suggest that changes in urothelium receptor expression could have a role in mediating the afferent sensory responses in the urinary bladder.
Blood pressure changes during sexual stimulation, ejaculation and midodrine treatment in men with spinal cord injury
Authors: Courtois Frédérique J. , Charvier Kathleen F. , Leriche Albert , Vézina Jean‐Guy , Côté Magalie , Bélanger Marc
Published: October 2007

Associate Editor

Michael G. Wyllie

Editorial Board

Ian Eardley, UK

Jean Fourcroy, USA

Sidney Glina, Brazil

Julia Heiman, USA

Chris McMahon, Australia

Bob Millar, UK

Alvaro Morales, Canada

Michael Perelman, USA

Marcel Waldinger, Netherlands

OBJECTIVES

To explore the effectiveness of various sources of self‐stimulation, including oral midodrine, in triggering ejaculation in men with spinal cord injury (SCI), and to document the systematic variations in blood pressure at ejaculation and consider a revised definition of autonomic dysreflexia.

PATIENTS AND METHODS

The study included 62 men with SCI lesions from C2 to L2. Ejaculation potential was assessed with various sources of stimulation, beginning with natural stimulation, followed, if the test was negative, by penile vibrator stimulation (PVS) followed, if the test was again negative, by PVS combined with oral midodrine, started at 5 mg and increased in 5 mg steps up to 25 mg. The success rate of ejaculation was recorded, as were blood pressure (BP) changes measured at baseline and at ejaculation (or on the last trial if the test was negative). Reported sensations were also recorded and compared during positive and negative tests.

RESULTS

Overall, 89% of the patients reached ejaculation with one mode or another of stimulation. When patients had a negative result with natural stimulation, 56% were salvaged by PVS, and when PVS was negative, another 22% were salvaged by midodrine combined with PVS. The mean systolic BP increased by 35 mmHg at ejaculation during PVS and by 11 mmHg after midodrine, and a subsequent 29 mmHg at ejaculation during PVS combined with midodrine. By contrast, negative tests showed a relatively stable BP; the difference in changes in BP during positive and negative tests was significant (P < 0.01). Increases in BP during positive tests declined significantly more often within the limits of autonomic dysreflexia than negative tests (P < 0.01).

CONCLUSION

These results support the view that most men with SCI can obtain an ejaculation when a wide spectrum of stimulation is used, including natural stimulation, PVS, and PVS combined with oral midodrine. Positive tests were associated with significant increases in BP, in contrast to negative tests, where BP was relatively stable. This suggests that significant changes in BP are required for ejaculation and that insignificant changes are predictive of future failure. As most changes in BP during positive tests also fall within the criterion of autonomic dysreflexia, a revised definition of autonomic dysreflexia should be considered to encourage safe experiences with ejaculation and safe use of midodrine.
A dual physiological character for sexual function: the role of serotonergic receptors
Authors: Motofei Ion G.
Published: October 2007

Anatomically, sexual reflexes are mixed (somatic‐autonomic) circuits, represented by emission (sympathetic centre and somatic afferents), expulsion (parasympathetic centre and somatic efferents) and erection (parasympathetic centre and somatic afferents). Physiologically, ejaculation has a dual autonomic mediation, consisting of two distinct and opposite autonomic centres (emission and expulsion), both with a positive contribution to the respective function. Experimentally, serotonin (5HT) has two distinct, opposite and positive effects on sexual function, with 5HT‐1Aagonists decreasing intravaginal ejaculatory latency and erection, and 5HT‐2Cagonists increasing both erection and ejaculatory latency. In this review I assume that 5HT modulates sexual reflexes, establishing a functional connection between the involved somatic and autonomic structures. The 5HT‐1Areceptors are assumed to make the connection between somatic pathways and sympathetic centres while the 5HT‐2Creceptors could establish the connection between somatic pathways and parasympathetic centres. Further studies will develop the cerebral sexual duality, explaining the implication of psychological factors in sexual function and the role of sexuality in psychosocial behaviour.
Rationale and clinical implication of combined chemotherapy with cisplatin and oestrogen in prostate cancer: primary evidence based on methylation analysis of oestrogen receptor‐α
Authors: Moriyama‐Gonda Nobuko , Shiina Hiroaki , Terashima Masaharu , Satoh Kazumi , Igawa Mikio
Published: October 2007

OBJECTIVE

To determine whether oestrogen enhances platinum sensitivity, and if promoter CpG methylation of the oestrogen receptor‐α (ER‐α) gene determines the potential of cisplatin‐induced apoptosis in prostate cancer, as the high‐mobility group 1 (HMG1) preferentially binds to cisplatin‐modified DNA and is up‐regulated after oestrogen treatment in breast cancer cell line MCF‐7.

MATERIALS AND METHODS

The study comprised prostate cancer cell lines (LNCaP and PC‐3), 156 pathologically confirmed 156 radical prostatectomy samples and eight hormone‐refractory prostate cancer (HRPC) samples (from needle biopsy). Expression of HMG1 in cell lines was analysed by Western blotting or differential reverse‐transcription‐polymerase chain reaction (PCR). The methylation status of ER‐α was analysed by methylation‐specific PCR using bisulphite DNA as a template or bisulphite DNA sequencing.

RESULTS

In LNCaP cells, treatment with oestrogen increased HMG1 expression and co‐treatment with cisplatin and oestrogen reduced cell viability by accelerating apoptosis, compared with cisplatin alone. However, in PC‐3, oestrogen did not up‐regulate HMG1 or accelerate the cisplatin‐induced apoptosis. Although ER‐β was expressed in both LNCaP and PC‐3, ER‐α was expressed only in LNCaP. Bisulphite DNA sequencing of the ER‐α promoter showed partial methylation in LNCaP but complete methylation in PC‐3. ER‐α AS transfection diminished the cisplatin‐induced apoptosis in oestrogen‐treated LNCaP cells. In clinical samples there was ER‐α hypermethylation in 40% of prostate cancers this correlated with Gleason score (GS, 31% for GS < 7, 50% for GS = 7 and 56% for GS > 7). In addition, five of eight HRPC samples showed ER‐α hypermethylation.

CONCLUSION

These findings suggest that HMG1 induction as an enhancer of platinum sensitivity is mediated through interaction between oestrogen and ER‐α. As CpG hypermethylation of the ER‐α promoter is a frequent event in aggressive prostate cancer, negative conversion of ER‐α methylation is essential to achieve the most beneficial effect when combined chemotherapy of cisplatin with oestrogen is used in patients with prostate cancer.
Percutaneous nephrolithotomy made easier: a practical guide, tips and tricks
Authors: Ko Raymond , Soucy Frédéric , Denstedt John D. , Razvi Hassan
Published: October 2007

Percutaneous nephrolithotomy (PCNL) plays an integral role in managing large renal stones. Establishing percutaneous renal access is the most crucial step in the procedure and requires a thorough understanding of renal, retroperitoneal and thoracic anatomy to minimize the risk of complications. Moreover, access to fluoroscopy and the proper equipment are critical to ensuring complete stone removal. In this review we describe the technique of PCNL used in a high‐volume endourology centre, where the urologist is involved in all aspects of the procedure.
Comparison of the precision of transurethral endoscopic versus ultrasound‐guided application of injectables
Authors: Mitterberger Michael , Pinggera Germar M. , Pelzer Alexandre , Bartsch Georg , Colleselli Daniela , Neuwirt Hannes , Gradl Johann , Pallwein Leo , Aigner Friedrich , Frauscher Ferdinand , Strasser Hannes
Published: October 2007

OBJECTIVE

To compare the precision of transurethral endoscopic‐ vs ultrasound (US)‐guided injections, as transurethral application of various injectables under endoscopic view are widely used to treat urinary incontinence.

MATERIAL AND METHODS

Bovine collagen was injected into the lower urinary tract in 20 dead female pigs. In each pig five depots of collagen were injected and there were five pigs in each group. In group I collagen was injected into the urethral wall under endoscopic control. In group II collagen depots were injected periurethrally under endosocopic guidance. In group III collagen was injected into the urethral wall under US control. In group IV collagen depots were injected periurethrally under US guidance. A transurethral US probe (6 F, 15 MHz) and injection device were used for transurethral US‐guided injections. In all pigs the urethra and the periurethral tissue were removed after injection and investigated using anatomical preparations and histological sections.

RESULTS

In group I only two collagen depots were actually located in the urethral wall in two pigs (two of 25 depots, 8%). In group II five depots in two pigs were located in the urethral wall (five of 25 depots, 20%). The periurethral collagen depots were found to spread out in the loose connective and fat tissue around the urethra. In group III all US‐guided injections of collagen were situated in the urethral wall and in group IV they were all located periurethrally.

CONCLUSIONS

The present study shows that endoscopic application of injectables is an inaccurate technique, while US‐guided injections are precise. US‐guided injection enables excellent control of the therapeutic procedure.