bluuebunny/crossref_metadata_2025 huggingface dataset:
Topical Nitric Oxide Treatment after Pull Through Operations for Hirschsprung Disease
Authors: Tiryaki Tuğrul , Demirbağ Suzi , Atayurt Halil , Çetinkurşun Salih
Published: February 2005

Aim:

The diagnosis and treatment of Hirschsprung disease are well standardized. Symptoms of obstruction after surgery for Hirschsprung disease may result from residual spasticity of the internal anal sphincter. Nitric oxide (NO) is the chemical messenger mediating relaxation of the internal anal sphincter and its exogenous application results in a relaxation response in smooth muscle. The purpose of this study was to investigate topical NO application for obstructive symptoms after surgery for Hirschsprung disease and to correlate the symptoms with manometric findings with a view to directing further management.

Materials and Methods:

The authors reviewed application of topical NO on six symptomatic children who were operated for Hirschsprung disease. Eighteen patients older than 3 years of age were evaluated for anorectal manometric, functional and clinical outcome. The symptoms included enterocolitis in three patients and constipation in three patients. NO ointment was applied twice daily for 6 weeks in symptomatic patients and manometry was repeated.

Results:

Anorectal manometric evaluation of six patients showed high internal anal sphincter tone without reflex relaxation on applying distending pressure to the rectum. Marked improvement of symptoms was noted after 6‐week application of topical NO and maximal internal anal resting pressure decreased significantly (35% reduction). After ceasing application of topical ointment, increased maximal anal resting pressure was seen again.

Conclusion:

Although anal sphincter hypertonicity is not thought to be the only cause of post‐operative obstructive symptoms, relaxation of the internal anal sphincter may improve the symptoms. Topical NO can be used for treatment of obstructive symptoms in Hirschsprung disease. We managed our symptomatic patients successfully with local NO application with a reversible chemical sphincterotomy. NO could be used as a therapeutic modality.
Multidisciplinary Management of Surgical Disorders of the Pancreas in Childhood
Authors: Stringer Mark D , Davison Suzanne M , McClean Paddy , Rajwal Sanjay , Puntis John W. L , Sheridan Maria , Ramsden William , Woodley Helen
Published: February 2005

Objectives:

To describe the frequency and range of pancreatic disorders in children requiring surgical intervention and to highlight the importance of multidisciplinary management.

Methods:

An audit of all children under 17 years of age referred with surgical disorders of the pancreas or pancreatitis to a regional pediatric gastroenterology unit in the United Kingdom during a 10‐year period. A retrospective chart review of clinical features, pathology and outcome was undertaken.

Results:

Surgical intervention was required for the following pancreatic disorders: persistent hyperinsulinemic hypoglycemia of infancy (n = 4), pancreatic tumors (n = 5), pancreaticobiliary malunion (n = 12), pancreatic trauma (n = 6) and pancreatitis (n = 10). The indications for surgery in acute pancreatitis were a persistent pseudocyst (n = 1) and treatment of an underlying cause of pancreatitis (n = 4); in chronic pancreatitis, surgery was used to treat symptomatic pancreatic duct strictures (n = 4). One child died of a progressive lymphoma but all others who underwent surgery are alive and well. All 33 children with acute pancreatitis, including four with pancreatic necrosis, survived.

Conclusions:

Surgery for pancreatic disorders in children is rarely required but may be necessary a) for definitive management of primary pancreatic pathology, b) to treat sequelae of acute or chronic pancreatitis and c) to treat an underlying cause of pancreatitis. There is a broad spectrum of potential pathologies. These patients are best managed by a multidisciplinary team approach.
Infected and Noninfected Ascites in Pediatric Patients
Authors: Vieira Sandra M. G , Matte Ursula , Kieling Carlos O , Barth Afonso L , Ferreira Cristina T , Souza Aline F , Taniguchi Adriano , da Silveira Themis R
Published: February 2005

Objectives:

To determine the prevalence of spontaneous bacterial peritonitis, ascites with bacterial infection and noninfected ascites in pediatric patients with portal hypertensive ascites and to compare the clinical and laboratory features of infected and noninfected ascites.

Methods:

Forty‐one episodes of portal hypertensive ascites (serum‐ascites albumin gradient >1.1 g/dL) in 31 patients were studied. Median age was 2.9 years. Twenty‐four (77.4%) patients were cirrhotic and 20 (83.3%) were classified as Child‐Pugh C. Median pediatric end‐stage liver disease score was 18.5. The following ascites features were assessed: polymorphonuclear neutrophil cell count, cytology, pH, concentration of glucose, lactic dehydrogenase, total protein and albumin, Gram stain and bacteriological culture. Blood was sampled for complete blood count, coagulation studies, liver and renal function tests. Groups were compared by Mann‐Whitney and χ2 tests (P < 0.05).

Results:

Noninfected ascites were observed in 29 of 41 samples, spontaneous bacterial peritonitis in eight of 41 and ascites with bacterial infection in four of 41. The most prevalent clinical features were fever, voluminous ascites and encephalopathy, but there were no significant differences in the clinical features of the groups. All patients with infected ascites were cirrhotic. There was no statistical difference in Child‐Pugh or pediatric end‐stage liver disease status between patients with infected and noninfected ascites. Culture of ascetic fluid was positive in four of eight cases of spontaneous bacterial peritonitis. Gram‐negative rods were the most prevalent bacteria cultured. Except for serum albumin, no statistical differences in biochemical markers were observed between patients with infected and noninfected ascites.

Conclusions:

The prevalence of infected ascites was 29.2%. With the exception of serum albumin, there were no differences in the clinical and biochemical features of patients with infected ascites and noninfected ascites.
Helicobacter pylori Status and Symptom Assessment Two Years after Eradication in Pediatric Patients from a High Prevalence Area
Authors: Magistà Anna Maria , Ierardi Enzo , Castellaneta Stefania , Miniello Vito Leonardo , Lionetti Elena , Francavilla Antonio , Ros Philippe , Rigillo Nicola , Di Leo Alfredo , Francavilla Ruggiero
Published: February 2005

Objectives:

To establish the rate of Helicobacter pylori reinfection in children from an H. pylori high prevalence area, possible clinical features predictive of reinfection and the usefulness of re‐treatment.

Methods:

65 consecutive children attending the authors' department between 1998 and 2000 who had proven successful H. pylori eradication were enrolled; 52 took part. Patients and family members were invited to undergo 13C‐urea breath testing and to complete a simple questionnaire regarding symptoms and socioeconomic status. Patients with H. pylori reinfection were offered treatment; eradication was assessed by 13C‐urea breath test 8 weeks after completion of treatment.

Results:

Of 52 children, 15 (28.8%) were H. pylori positive. Variables predictive of reinfection were age at primary infection and presence of an infected sibling. Although reinfected children were more frequently symptomatic than non‐reinfected patients, no specific symptom was associated with reinfection. Of the nine re‐treated patients who returned 8 weeks after completing therapy, the bacterium was eradicated in five (56%).

Conclusions:

The 12.8% per year reinfection rate in childhood at 2 years that we observed should prompt a re‐evaluation of H. pylori status even after a successful eradication. Living in an H. pylori high prevalence area increases the annual risk of reinfection by approximately fourfold over the annual risk in H. pylori low prevalence areas.
Chronic Abdominal Pain in Children: A Clinical Report of the American Academy of Pediatrics and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition
Authors: Di Lorenzo Carlo , Colletti Richard B , Lehmann Harold P , Boyle John T , Gerson William T , Hyams Jeffrey S , Squires Robert H , Walker Lynn S , Kanda Pamela T
Published: February 2005

Children and adolescents with chronic abdominal pain pose unique challenges to their caregivers. Affected children and their families experience distress and anxiety that can interfere with their ability to perform regular daily activities. Although chronic abdominal pain in children is usually attributable to a functional disorder rather than to organic disease, numerous misconceptions, insufficient knowledge among health care professionals and inadequate application of knowledge may contribute to a lack of effective management. This clinical report accompanies a technical report on childhood chronic abdominal pain and provides guidance for the clinician in the evaluation and treatment of children with chronic abdominal pain. The conclusions are based on the evidence reviewed in the technical report and on consensus achieved among subcommittee members.
Effects of Anticonvulsants on Human P450c17 (17α‐Hydroxylase/17,20 Lyase) and 3β‐Hydroxysteroid Dehydrogenase Type 2
Authors: Flück Christa E. , Yaworsky Dustin C. , Miller Walter L.
Published: February 2005

Summary:  Purpose: Women with epilepsy apparently have a higher incidence of polycystic ovary syndrome (PCOS) than do women without epilepsy. Whether the underlying disease or the antiepileptic drug (AED) treatment is responsible for this increased risk is unknown, although clinical reports implicate valproic acid (VPA) as a potential cause. The steroidogenic enzymes 3βHSDII (3β‐hydroxysteroid dehydrogenase) and P450c17 (17α‐hydroxylase/17,20 lyase) are essential for C19 steroid biosynthesis, which is enhanced during adrenarche and in PCOS.

Methods: To determine whether the AEDs VPA, carbamazepine (CBZ), topiramate (TPM), or lamotrigine (LYG) directly affect the activities of human 3βHSDII and P450c17, we added them to yeast expressing human P450c17 or 3βHSDII and assayed enzymatic activities in the microsomal fraction.

Results: Concentrations of VPA ≤10 mM had no effect on activities of P450c17; however, VPA inhibited 3βHSDII activity starting at 0.3 mM (reference serum unbound concentration, 0.035–0.1 mM) with an IC50 of 10.1 mM. CBZ, TPM, and LTG did not influence 3βHSDII or P450c17 activities at typical reference serum unbound concentrations, but did inhibit 3βHSDII and P450c17 at concentrations >10‐fold higher.

Conclusions: None of the tested AEDs influenced 3βHSDII or P450c17 activities at concentrations normally used in AED therapy. However, VPA started to inhibit 3βHSDII activity at concentrations 3 times above the typical reference serum unbound concentration. Because inhibition of 3βHSDII activity will shift steroidogenesis toward C19 steroid production when P450c17 activities are unchanged, very high doses of VPA may promote C19 steroid biosynthesis, thus resembling PCOS. CBZ, TPM, and LTG influenced 3βHSDII and P450c17 only at toxic concentrations.
Proteomic Identification of the Involvement of the Mitochondrial Rieske Protein in Epilepsy
Authors: Junker Heike , Späte Kira , Suofu Yalikun , Walther Reinhard , Schwarz Gerold , Kammer Winfried , Nordheim Alfred , Walker Lary C. , Runge Uwe , Kessler Christof , Popa‐Wagner Aurel
Published: February 2005

Summary: Purpose:Kindled seizures are widely used to model epileptogenesis, but the molecular mechanisms underlying the attainment of kindling status are largely unknown. Recently we showed that achievement of kindling status in the Sprague–Dawley rat is associated with a critical developmental interval of 25 ± 1 days; the identification of this long, well‐defined developmental interval for inducing kindling status makes possible a dissection of the cellular and genetic events underlying this phenomenon and its relation to normal and pathologic brain function.

Methods:By using proteomics on cerebral tissue from our new rat kindling model, we undertook a global analysis of protein expression in kindled animals. Some of the identified proteins were further investigated by using immunohistochemistry.

Results:We report the identification of a modified variant of the Rieske iron‐sulfur protein, a component of the mitochondrial cytochromebc1complex, whose isoelectric point is shifted toward more alkaline values in the hippocampus of kindled rats. By immunohistochemistry, the Rieske protein is well expressed in the hippocampus, except in the CA1 subfield, an area of selective vulnerability to seizures in humans and animal models. We also noted an asymmetric, selective expression of the Rieske protein in the subgranular neurons of the dorsal dentate gyrus, a region implicated in neurogenesis.

Conclusions:These results indicate that the Rieske protein may play a role in the response of neurons to seizure activity and could give important new insights into the molecular pathogenesis of epilepsy.
Removing Eye‐movement Artifacts from the EEG during the Intracarotid Amobarbital Procedure
Authors: Zhou Weidong , Gotman Jean
Published: February 2005

Summary:  Purpose: The EEG is often recorded during the intracarotid amobarbital procedure (IAP) to help in the assessment of the spatial extent and the duration of the effect of the drug. In scalp recordings, the EEG is always heavily contaminated with eye movement artifacts as the patient actively performs visual tasks.

Methods: Independent component analysis (ICA) is a new technique for blind source separation. In this study, we separated the EEG data recorded during the IAP into independent components using ICA. The EEG signal was reconstructed by excluding the components related to eye movement and eye blinks.

Results: EEGs from 10 IAP tests were analyzed. The experimental results indicate that ICA is very efficient at subtracting eye‐movement artifacts, while retaining the EEG slow waves and making their interpretation easier.

Conclusions: ICA appears to be a generally applicable and effective method for removing ocular artifacts from EEG recordings during IAP, although slow waves and ocular artifacts share similar frequency distributions.
Pharmacokinetic and Metabolic Investigation of Topiramate Disposition in Healthy Subjects in the Absence and in the Presence of Enzyme Induction by Carbamazepine
Authors: Britzi Malka , Perucca Emilio , Soback Stefan , Levy René H. , Fattore Cinzia , Crema Francesca , Gatti Giuliana , Doose Dennis R. , Maryanoff Bruce E. , Bialer Meir
Published: February 2005

Summary:  Purpose: To characterize the metabolic profile of topiramate (TPM) in humans and to assess the influence of enzyme induction by carbamazepine (CBZ) on the pharmacokinetics and metabolic profile of TPM.

Methods: Twelve healthy subjects received a single oral dose of TPM (200 mg) on two randomized occasions. On one occasion, TPM was administered alone, and on the other, it was given on day 18 of a 24‐day treatment with CBZ (maintenance dosage, 600 mg/day). Blood and urine samples were collected for ≥72 h after dosing. TPM and its metabolites were assayed in plasma and urine by a specific liquid chromatography–mass spectroscopy (LC‐MS) method.

Results: Mean TPM oral clearance (CL/F) increased from 1.2 L/h (control) to 2.2 L/h after CBZ treatment. Mean TPM half‐life decreased from 29 h to 19 h. TPM was excreted extensively in urine both under noninduced (56%) and CBZ‐induced conditions (40%). 2,3‐O‐Des‐isopropylidene‐TPM (2,3‐diol‐TPM) was identified as the most prominent urinary metabolite, with a recovery accounting for 3.2% and 7.9% of the TPM dose under noninduced and induced conditions, respectively. Corresponding recovery values for 10‐hydroxy‐TPM (10‐OH‐TPM) were 1.2% and 1.8%, respectively. The control AUCmetabolite/AUCdrug ratio for 2,3‐diol‐TPM and 10‐OH‐TPM were 1.5% and 0.6%, and they increased by threefold and twofold, respectively, after CBZ treatment.

Conclusions: TPM remains appreciably excreted unchanged in urine (41%) under CBZ‐induced conditions, even though TPM CL/F increased by twofold. Although 2,3‐diol‐TPM and 10‐OH‐TPM were measured in unconjugated form, the significant increases in their AUC and urinary excretion are consistent with the twofold increase in TPM clearance.
Peace History Intra‐Abrams: The Field from 1938 through His Work on the Nobel Peace Prize
Authors: Chatfield Charles
Published: February 2005

In the generation prior to Irwin Abram's (2001) second edition of The Nobel Peace Prize, the field of peace history has proliferated dramatically and has become ever more a comprehensive record of social reform, as well as a multi‐disciplinary approach using social mobilization analysis in innovative ways. The field has also become increasingly international, in terms or cooperative research across national boundaries, in its subject matter, and in its contribution to a global paradigm shift regarding war and peace.
Civil Society Promotion of Truth, Justice, and Reconciliation in Chile: Villa Grimaldi
Authors: Baxter Victoria
Published: February 2005

The purpose of this article is to explore a civil society initiative that seeks to promote truth, justice, and reconciliation in the post‐transitional society of Chile. The article will describe the role of civil society in promoting a site of memory on Villa Grimaldi, a former torture center in Santiago, Chile. The site of memory demonstrates the role that a nongovernmental organization (NGO) actor can play in complementing and in extending the work of a formal transitional justice process (i.e., a truth and reconciliation commission) in promoting truth about a past period of human rights abuses and promoting a sense of justice and reconciliation, particularly for survivors of the abuses. The case also outlines many of the relative advantages and disadvantages of civil society involvement in such initiatives.
Characterizing the Role of Design in New Product Development: An Empirically Derived Taxonomy*
Authors: Perks Helen , Cooper Rachel , Jones Cassie
Published: February 2005

This article empirically explores the nature of the role of design in the new product development process. The investigation adopts a multiple case study methodology. Data were collected through a six‐month interview program carried out with mid‐size to large U.K. manufacturing companies. The researchers articulate the scope and detailed nature of actions undertaken by design across all phases of the new product development process. Design functional, integration, and leadership actions are unraveled from the data. A taxonomy characterizing three roles for design in new product development is developed and explained. In the first role, design is explored as a functional specialism.

The second categorization develops the role of design as part of a multifunctional team. The third role depicts the designer as process leader. Detailed actions and skills associated with each role are discussed and illustrated. Contextual factors explaining and influencing each design role are unraveled. These are articulated as speed of development process, innovativeness of the product development effort, and use of external design agencies. The implications of these findings for the development of design skills and capabilities are discussed in terms of recruitment, training, and educational policies.
The Impact of User‐Oriented Design on New Product Development: An Examination of Fundamental Relationships*
Authors: Veryzer Robert W. , Borja de Mozota Brigitte
Published: February 2005

Design offers a potent way to position and to differentiate products and can play a significant role in their success. In many ways it is the focus on deep understanding of the customer or user—what may be termed user‐oriented design (UOD)—that transforms a bundle of technology with the ability to provide functionality into a “product” that people desire to interact with and from which they derive benefits. Even though the importance of this type of design is gaining recognition, several fundamental relationships between user‐oriented design contributions and the new product development (NPD) process and outcomes (i.e., product) remain unresearched, although they are assumed. This article examines the fundamental relationships underlying the incorporation of a user orientation into the NPD process. The discussion is organized around UOD's impact in terms of enhancing collaborative new product development (process oriented), improving idea generation (process oriented), producing superior product or service solutions (product oriented), and facilitating product appropriateness and adoption (product oriented). Each of these is developed and presented in the form of a research proposition relating to the impact of user‐oriented design on product development. The fundamental relationships articulated concerning UOD's impact on NPD form a conceptual framework for this approach to product design and development.

For practitioners, the article suggests how user‐oriented design can improve NPD through its more grounded and comprehensive approach, along with the elevated appreciation of design challenges and heightened sense of possibilities for a product being developed. For scholars, the article identifies four important areas for UOD research. In addition to the rich avenues offered for research by each of these, the framework presented provides a foundation for further study as well as the development of new measures and tools for enhancing NPD efforts.
Managing the Design Innovation–Brand Marketing Interface: Resolving the Tension between Artistic Creation and Commercial Imperatives*
Authors: Beverland Michael B.
Published: February 2005

The relationship between design and marketing is an uneasy one. Managing this tension is critical for luxury marketers, whose point of differentiation is a combination of design excellence and market execution. This article explores the tensions between marketing and design and the integration of design into the brand management process in luxury wine firms. The results of the investigation describe five design‐based values held by luxury winemakers: remaining true to craft, expressions of place, stylistic consistency, living up to the brand's heritage, and remaining current. Five methods of integrating design into the firm are identified. These are top leadership support and integration at the strategic level, simultaneous loose–tight coupling, being in the marketplace versus being of the marketplace, intergenerational teams, and deliberate decoupling. This last is a novel solution and involves designers walking a fine line between their commitment to their values and the ongoing evolution of the brand. Essentially, designers of luxury wine products downplay their scientific expertise, market knowledge, and responsiveness in favour of appealing to their five espoused values.
A placebo‐controlled screening trial of tiagabine, sertraline and donepezil as cocaine dependence treatments
Authors: Winhusen Theresa M. , Somoza Eugene C. , Harrer Judy M. , Mezinskis Juris P. , Montgomery Margaret A. , Goldsmith R. Jeffrey , Coleman Florence S. , Bloch Daniel A. , Leiderman Deborah B. , Singal Bonita M. , Berger Paul , Elkashef Ahmed
Published: February 2005

Aims  To conduct a preliminary evaluation of the safety and efficacy of tiagabine, sertraline or donepezil versus an unmatched placebo control as a treatment for cocaine dependence.

Design  A 10‐week out‐patient study was conducted using the Cocaine Rapid Efficacy and Safety Trial (CREST) study design.

Setting  This study was conducted at the Cincinnati Medication Development Research Unit (MDRU) and at an affiliated site in Dayton, Ohio.

Participants  Participants met Diagnostic and Statistical Manual version IV (DSM‐IV) criteria for cocaine dependence. Sixty‐seven participants were enrolled with 55 completing final study measures.

Intervention  The targeted daily doses of medication were tiagabine 20 mg, sertraline 100 mg and donepezil 10 mg. All participants received 1 hour of manualized individual cognitive behavioral therapy on a weekly basis.

Measurements  Primary outcome measures of efficacy included urine benzoylecgonine (BE) level, Cocaine Clinical Global Impression Scale–Observer and self‐report of cocaine use. Safety measures included adverse events, ECGs, vital signs and laboratory tests.

Findings  Subjective measures of cocaine dependence indicated significant improvement for all study groups. Generalized estimating equations analysis indicated that the tiagabine group showed a trend toward a significant decrease in urine BE level from baseline to weeks 5–8 (P = 0.10) and non‐significant changes for the other study groups. No pattern of physical or laboratory abnormalities attributable to treatment with any of the medications was identified. There were three serious adverse events reported, none of which were related to study procedures.

Conclusions  The present findings suggest that tiagabine may be worthy of further study as a cocaine dependence treatment.
Outcome of radioiodine‐131 therapy in hyperfunctioning thyroid nodules: a 20 years’ retrospective study
Authors: Ceccarelli Claudia , Bencivelli Walter , Vitti Paolo , Grasso Lucia , Pinchera Aldo
Published: February 2005

Objective  To investigate the risk of hypothyroidism after radioiodine (131I) treatment for hyperfunctioning thyroid nodules.

Design  Retrospective analysis of patients treated with 131I for hyperfunctioning thyroid nodules and followed up for a maximum of 20 years.

Patients  A total of 346 patients treated with 131I in the years 1975–95, for a single hyperfunctioning nodule.

Measurements  Hypothyroidism was defined as TSH levels > 3·7 mU/l. Kaplan–Meier survival analysis was used to analyse permanence of euthyroidism after 131I. A stepwise Cox proportional hazard model was used to identify factors influencing the progression to hypothyroidism.

Results  The cumulative incidence of hypothyroidism was 7·6% at 1 year, 28% at 5 years, 46% at 10 years and 60% at 20 years. Age (P < 0·01), 24‐th 131I uptake (P < 0·05) and previous treatment with methimazole (MMI, P < 0·1) were associated with a faster progression towards hypothyroidism, while thyroid and nodule size, thyroid status at diagnosis and degree of extranodular thyroid parenchymal suppression had no influence. In hyperthyroid patients with partial parenchymal suppression, however, previous MMI treatment was the most important prognostic factor (P < 0·01).

Conclusions  After 20 years of follow‐up, 60% of patients treated with 131I for a single hyperfunctioning nodule are hypothyroid. Factors increasing the risk of hypothyroidism are age, 131I uptake and MMI pretreatment. The prognostic value of this last factor, however, depends on the degree of suppression of the extranodular thyroid parenchyma at the scan.
The relative importance of genetic and environmental factors in the aetiology of thyroid nodularity: a study of healthy Danish twins
Authors: Hansen Pia Skov , Brix Thomas Heiberg , Bennedbæk Finn Noe , Bonnema Steen Joop , Iachine Ivan , Kyvik Kirsten Ohm , Hegedüs Laszlo
Published: February 2005

Background  A large proportion of healthy, euthyroid, nongoitrous individuals have thyroid nodules. The aetiology of these ultrasonographically detected morphological abnormalities is largely unknown. Factors such as age, gender, iodine intake, smoking and parity are associated with nodularity of the thyroid. Whether there is a genetic susceptibility is unclear.

Aim  To gain insight into the aetiology of thyroid nodularity by investigating a large cohort of healthy euthyroid monozygotic and dizygotic twins.

Design  A cross‐sectional twin study.

Participants  A representative sample of self‐reported healthy twin pairs was identified through the Danish Twin Registry. A total of 520 individuals divided into 104 monozygotic (MZ), 107 dizygotic same sex (DZ) and 49 opposite sex (OS) twin pairs were investigated.

Measurements  Probandwise concordance and tetrachoric correlations. Quantitative genetic modelling was used to elucidate the relative importance of genetic and environmental effects for the variation in the liability of nodularity.

Results  A higher concordance rate for thyroid nodularity was found in MZ twins [0·57 (95% CI 0·36–0·76)] than in DZ twins [0·36 (95% CI 0·17–0·56, P = 0·074)]. The same was true for tetrachoric correlations: 0·67 (95% CI 0·34–0·87) in MZ twins and 0·17 (CI – 0·28–0·56, P = 0·053) in DZ twins. The difference, although not significant, was more pronounced for multiple nodules than for solitary nodules. Controlling for covariates (age, gender and smoking habits), it was calculated that genetic factors accounted for 67% (95% CI 35–87%) and environmental factors for 33% (95% CI 13–65%) of the individual differences in the liability to thyroid nodularity.

Conclusions  This study suggests that genetic factors are of aetiological importance for thyroid nodularity in clinically healthy and euthyroid individuals, and indicates a difference in the aetiology of solitary and multiple thyroid nodules.
Facilitated nitration and oxidation of LDL in cigarette smokers
Authors: Yamaguchi Y. , Haginaka J. , Morimoto S. , Fujioka Y. , Kunitomo M.
Published: February 2005

Background  Cigarette smoking increases the risk of developing atherosclerosis and ischaemic heart disease. Smoking‐induced oxidative stress is considered to favour oxidation of low‐density lipoprotein (LDL) and subsequently promotes the atherogenic process. We investigated whether peroxynitrite, a reaction product of cigarette smoke, is involved in facilitated oxidation of LDL in smokers.

Materials and methods  Plasma LDL was obtained from 10 healthy asymptomatic cigarette smokers and 10 healthy nonsmokers. The state of enhanced oxidative stress in the plasma was assessed by LDL subfraction assay using anion‐exchange high‐performance liquid chromatography (AE‐HPLC) and measurements of thiobarbituric acid‐reactive substances (TBARS), 8‐hydroxydeoxyguanosine (8‐OHdG), vitamin E, 3‐nitrotyrosine and 3‐chlorotyrosine.

Results  Smokers showed a significantly higher level of TBARS and 8‐OHdG as well as a significantly lower level of vitamin E than nonsmokers, even after stopping smoking for 10 h or more. The LDL subfraction assay demonstrated an increase in oxidatively modified LDL, as expressed by lower levels of LDL1 and higher levels of LDL2. The 3‐nitrotyrosine levels in apolipoprotein B in LDL were significantly higher in smokers than nonsmokers, while the 3‐chlorotyrosine levels remained unchanged. In addition, these changes observed in the smokers were further accelerated within 30 min after resumption of cigarette smoking when compared with the levels before smoking resumption.

Conclusion  The present study suggests that peroxynitrite plays a significant role in oxidative modification of plasma LDL induced by cigarette smoking.
Comparative chromosomal studies of E. caballus (ECA) and E. przewalskii (EPR) in a female F1 hybrid
Authors: Ahrens E. , Stranzinger G.
Published: February 2005

Previous research revealed that the karyotypes of Equus przewalskii (2n = 66) and Equus caballus (2n = 64) differ by one pair of metacentric chromosomes, present in ECA but not in EPR, and two pairs of acrocentric chromosomes found only in the EPR karyotype. The formation of a trivalent during meiosis in a male F1 hybrid and the homologies in G‐banding patterns suggest that ECA 5 corresponds to two acrocentric EPR chromosomes resulting from a Robertsonian fusion or fission event. Chromosomal investigations of a female interspecies F1 hybrid including banded karyograms and fluorescence in situ hybridization (FISH) studies focusing on the p and q arm of ECA 5 were conducted. Q‐ and G‐banding patterns of E. caballus, E. przewalskii and the hybrid revealed interspecies homology between all chromosome pairs except for ECA 5, EPR 23 and EPR 24, which were unique for that particular species. Furthermore, they indicated homology between ECA 5p and EPR 23 as well as between ECA 5q and EPR 24. FISH revealed hybridization of the BACs laminin beta 3 (LAM B3) and laminin gamma 2 (LAM C2) to ECA 5p and EPR 23. However, nuclear factor I (NFIA) and immunoglobulin lambda (IGL@), primarily assigned to ECA 5q, mapped to ECA 7 and EPR 6 respectively. Thus the karyotypes of E. caballus and E. przewalskii differ solely by one Robertsonian translocation (ECA 5 =EPR 23 + EPR 24).
Close genetic relationship of early Neolithic cattle from Ziegelberg (Freising, Germany) with modern breeds
Authors: Kühn R. , Ludt C. , Manhart H. , Peters J. , Neumair E. , Rottmann O.
Published: February 2005

In 2003 a variety of crafts and bone specimens were found during excavations of a Neolithic settlement near Freising, the southernmost site of the Linear Pottery Culture in Bavaria. Six cattle bones were used to extract ancient DNA (aDNA). Applying nested and touchdown PCR, two fragments of the mitochondrial (mt) DNA control region could be amplified from specimen 533/III which yielded a total of 230 base pairs (bp). The sequence was compared with the homologous part of 40 extant breeds of Bos taurus and B. indicus and related species, such as Banteng (B. javanicus), Gaur (B. gaurus), the European bison (Bison bonasus) and the aurochs (B. primigenius). A neighbour joining tree was constructed based on the appropriate model of sequence evolution. The control region sequence of the 533/III cattle bone, whose age was determined by radiocarbon dating, clusters close to the extant European breeds, but distinctly apart from the basal aurochs and far distant from the B. indicus group. The archaeological and genetic analyses of Bos Ziegelberg demonstrate that domesticated cattle reached southern Bavaria at least 7000 years ago.
Genetic variability of seven dog breeds based on microsatellite markers
Authors: Schelling C. , Gaillard C. , Dolf G.
Published: February 2005

The present study, compared the genetic variability of seven dog breeds and a test sample from Switzerland by means of 26 microsatellite markers. Five loci were excluded from further analyses because one was monomorphic, one not in Hardy–Weinberg equilibrium in all breeds and three in linkage disequilibrium with linked loci. The proportion of shared alleles at the individual level of the remaining 21 microsatellite markers combined with the neighbour‐joining method allowed for the clustering of the large majority of the individuals in accordance to their breed. The results were confirmed by analyses using a Bayesian approach for clustering and a Monte Carlo re‐sampling method for individual assignment or exclusion to a given population.
Seclusion of children and adolescents: Psychopathological and family factors
Authors: Gullick Karen , McDermott Brett , Stone Prue , Gibbon Peter
Published: February 2005

ABSTRACT:  This paper describes the use of seclusion in a child and adolescent inpatient unit, including precipitating events, management strategies, details of seclusion episodes and individual and family risk factors. Inpatient ward documentation of seclusion episodes, demographic data and measures of individual psychopathology and impairment, parent mental health, life events and family functioning were used to compare secluded, non‐secluded and outpatient groups. Secluded individuals had elevated psychopathology compared with non‐secluded inpatients and outpatients. Their families reported poorer parental mental health and family functioning and more recent stressful life events. The results indicate that seclusion is most common among high‐risk inpatients.
Nurses under threat: A comparison of content of 28 aggression management programs
Authors: Farrell Gerry , Cubit Katrina
Published: February 2005

ABSTRACT:  Staff who work in the health service are now recognized as a high‐risk group for assault in the workplace. Recently, professional and industrial organizations have begun to suggest appropriate curricula for training staff in aggression management. However, there is currently a plethora of aggression management training programs (AMP) available, varying both in content and in duration. In this paper, 28 programs were evaluated against 13 major content areas derived from the recommendations made from key professional and industrial organizations, and what may be today considered appropriate/ideal content areas for AMP. Information on programs available in English was sought via standard databases, the Internet, program providers, and through networking with colleagues and professional organizations. The majority of the programs reviewed covered personal safety issues for staff and patients, together with legal issues. The use of restraint, pharmacological management of aggression and seclusion were features of programs specifically addressing the needs of health care staff in mental health settings. Most programs appeared not to address the psychological and organizational costs associated with aggression in the workplace. This is surprising since the literature suggests that the effects of violence are wide and varied, including increased absenteeism and sick leave, property damage, decreased productivity, security costs, litigation, workers’ compensation, reduced job satisfaction together with recruitment and retention issues. Also, few programs were based on a systematic evaluation of their outcomes. Suggestions for program development and their teaching are discussed.
Providing emergency mental health care to asylum seekers at a time when claims for permanent protection have been rejected
Authors: Procter Nicholas G.
Published: February 2005

ABSTRACT:  In total, 90% of ‘boat people’ who make it to Australia's migration zone are assessed as legitimate refugees and given Temporary Protection Visas (TPV) allowing them to stay in Australia for 3 years in the first instance. With an increasing number of individuals and families on TPV having their claims for a Permanent Protection Visa (PPV) rejected, this paper argues using the National Mental Health Plan 2003–2008 as a guide, for interventions that are culturally and linguistically appropriate, thus, aiming to minimize risk from exposure to extreme mental stressors in the event of an application for a PPV being rejected. Continuity and integration of mental health care involving key stakeholders is best achieved by bridging discrete elements through preparing for visa appeals and reviews, news from home and ongoing psychosocial stressors – in the context of different episodes, interventions by different providers, and changes in mental distress. To help strengthen continuity and integration of mental health supports for TPV holders, well resourced care must be experienced as connected and coherent.
Effect of simvastatin given alone and in combination with valsartan or enalapril on blood pressure and the structure of mesenteric resistance arteries and the basilar artery in the genetically hypertensive rat model
Authors: Ledingham Janet M , Laverty Richard
Published: February 2005

1. The aims of the present study were to investigate, in the New Zealand genetically hypertensive (GH) rat model, the effects of treatment with simvastatin, alone or in combination with valsartan or enalapril, on blood pressure (BP) and structural remodelling of mesenteric resistance arteries (MRA) and of the basilar artery, an artery that plays a major role in the regulation of cerebral resistance.

2. Genetically hypertensive rats were treated with simvastatin at two dose levels (5 and 10 mg/kg per day) and simvastatin in combination with valsartan or enalapril (also 5 and 10 mg/kg per day) from the age of 7 to 12 weeks. Systolic BP and bodyweight were measured weekly.

3. At the end of the experiment, following fixation by perfusion, MRA and the basilar artery were excised and embedded in Technovit (a glycol methacrylate medium; Heraeus Kulzer, Werheim, Germany). Serial sections were cut and stereological techniques used to determine tunica media width and cross‐sectional area (CSA), lumen diameter and the ratio of media width/lumen diameter.

4. Simvastatin monotherapy did not lower BP at either dose. In the high‐ and low‐dose groups, the combination of simvastatin + enalapril lowered BP more than with enalapril alone; this was also true for the simvastatin + valsartan combination in the lower‐dose group.

5. The MRA were hypotrophically remodelled by the 10 mg/kg per day dose of simvastatin; the 5 mg/kg per day dose caused hypotrophic remodelling with decreased media/lumen ratio. Valsartan and enalapril caused hypotrophic remodelling together with outward remodelling of the lumen in the 10 mg/kg per day valsartan group and, in all groups, a reduction in the media/lumen ratio, with the greatest effect observed in the high‐dose groups.

6. The combination treatments of simvastatin + valsartan and simvastatin + enalapril did not have any consistent extra effect on MRA remodelling.

7. In the basilar artery, high‐dose simvastatin had a hypotrophic effect on the media and both doses reduced the media/lumen ratio independently of any change in BP.

8. Simvastatin given in combination with valsartan produced a slight further reduction in medial CSA, media width and ratio. In combination with enalapril, there was little consistent additional effect.

9. Simvastatin monotherapy hypotrophically remodelled the media of the basilar artery in the GH rat model, even in the absence of changes in BP. A similar structural effect may explain, in part, the reduction in stroke seen in patients treated with statins.
Oral implant restoration for enhanced oral function
Authors: Henry Patrick J
Published: February 2005

1. The present paper reviews the clinical applications of implant‐anchored restorations replacing teeth and defects of the craniofacial skeleton resultant from congenital, traumatic and surgical tissue loss.

2. Different categories of tooth and tissue loss were treated in controlled multicentre prospective clinical trials. More recent developments have been the subject of limited pilot studies.

3. Long‐term results and meta‐analysis reviews have shown that osseointegrated implant‐supported restorations were at least equal to, and in some applications superior to, traditional treatment methods.

4. Based on the outcome of a 30 year research and development programme and validation in numerous clinical trials, osseointegrated implant dental rehabilitation has become a viable treatment alternative for missing teeth and, for some applications, is considered to be a standard of care.
Does permanent carotid artery occlusion produce a ‘preconditioning‐like’ effect towards more severe hypotension in energy metabolites? Role of cerebral adenosine
Authors: Plaschke Konstanze , Kreutzer Stefan , Sommer Clemens , Martin Eike , Bardenheuer Hubert J
Published: February 2005

1. The aim of the present study was to investigate the potential energy preserving effect of permanent bilateral common carotid artery occlusion (BCCAO) towards additional systemic hypotension of severe duration (30 min). In addition, the role of adenosine A1 receptors in cerebral ischaemic preconditioning was investigated in male Wistar rats. Thus, oligaemic rats were assigned randomly to continuous treatment with the adenosine A1 receptor agonist 2‐chloro‐N6‐cyclopentyladenosine (CCPA) or the adenosine A1 receptor antagonist 8‐cyclopentyl‐1,3‐dimethylxanthine (CPT), receiving daily intraperitoneal infusions of 0.1 mg/kg bodyweight CCPA or CPT or placebo (200 µL aqueous 2‐hydropropyl‐β‐cyclodextrin) at a delivery rate of 0.5 µL/h over 14 days.

2. Haemodynamic parameters and arterial blood gases were monitored. Rat cortical energy metabolites ATP, ADP, AMP, phosphocreatine and adenosine were measured using HPLC techniques. Adenosine A1 receptor expression was determined by immunhistochemistry and quantified by western blotting.

3. Two weeks of permanent BCCAO induced an ‘energy saving’ effect in rat cortical ATP concentrations. Under subchronic conditions, significant increases were detected in ADP and AMP concentrations after CCPA compared with placebo. Because similar changes were also seen after CPT, this adenosine A1 receptor‐mediated effect does not seems to be specific. Furthermore, no differences in adenosine A1 receptor expression could be detected.

4. Adenosine was not specifically involved in the ‘preconditioning‐like’ effect via the modulation of the adenosine A1 receptor in the present oligaemia model. Obviously, adenosine A1 receptor‐specific effects after delayed cerebral ischaemic preconditioning do not seem to play an essential role if BCCAO is followed by a prolonged additional severe ischaemic event.
Comparative study of genotype B and C hepatitis B virus‐induced chronic hepatitis in relation to the basic core promoter and precore mutations
Authors: WATANABE KOJI , TAKAHASHI TORU , TAKAHASHI SUMIO , OKOSHI SHOGO , ICHIDA TAKAFUMI , AOYAGI YUTAKA
Published: February 2005

Background: The clinicopathological profiles and outcome of chronic hepatitis B can differ by hepatitis B virus (HBV) genotypes. In Japan, genotype B and C are two major HBV genotypes. The basic core promoter and precore mutations are other known viral factors for disease activity, although the relationship between HBV genotypes and these mutations is not fully understood.

Methods: The HBV genotypes in 90 patients with chronic hepatitis B were determined using an ELISA. Obtained data were correlated with clinicopathological parameters, basic core promoter, precore and the nucleotide 1858 mutations of the HBV genome.

Results: Among 90 cases, 20 (22.2%) had genotype B and 70 (77.8%) had genotype C HBV. Genotype B patients were older than genotype C patients (44.0 ± 13.9 vs 34.7 ± 11.0 P = 0.0022). The HBeAg was more prevalent in genotype C than B patients (P = 0.0008) while anti‐HBe was more common in genotype B than C patients (P = 0.0002). Serum aspartate aspartate aminotransferase/alanine aminotransferase levels (B: 220.7 ± 612.8/257.0 ± 498.0 IU/L vs C: 111.3 ± 122.8/201.6 ± 229.4 IU/L, P = 0.16/0.48) and HBV viral loads in blood (B: 6.1 ± 3.1 log genome equivalent [LGE]/mL vs C: 6.7 ± 2.3 LGE/mL, P = 0.42) were equivalent. The seroconversion from HBeAg to anti‐HBe occurred significantly earlier in genotype B than C patients (62 ± 53 months vs 136 ± 54 months, P = 0.0028) during the mean observation period of 149 ± 82 months even under various therapeutic modalities. The categories III and IV of the histological activity index in genotype C were higher (III: P < 0.005, IV: P < 0.05, n = 68) than that in B patients whereas category II was higher in genotype B than C patients (P < 0.05). The double mutation (1762T/1764A) in the basic core promoter was more frequently found in genotype C than in B HBV (P = 0.0068), whereas the precore mutation (1896A) was more common in genotype B than C HBV (P = 0.0233). The incidence of 1858C that was complementary to the precore mutation site in the stem‐loop structure ∈, was equally rare in both genotype B and C HBV.

Conclusions: Genotype B patients were older, had earlier HBeAg seroconversion and exhibited more severe lobular necroinflammation, less portal inflammation and fibrosis than genotype C patients. This genotypic difference is related to the basic core promoter and precore mutations irrespective of 1858C.

© 2004 Blackwell Publishing Asia Pty Ltd