bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the E‐cadherin/catenin complex in colorectal carcinoma cell lines
Authors: El‐Bahrawy Mona , Poulsom S. Richard , Rowan Andrew J. , Tomlinson Ian T. , Alison Malcolm R.
Published: May 2004

The E‐cadherin/catenin complex is a prime mediator of cell–cell adhesion. APC mutations can result in loss of β‐catenin downregulation and an accumulation of β‐catenin in the cell. β‐CATENIN mutations can have a similar effect. The aim of this study was to investigate the effect of β‐CATENIN and APC mutations on the expression and assembly of the E‐cadherin/catenin complex. Five colorectal carcinoma cell lines with different APC and β‐CATENIN gene status were selected and mutations were confirmed. The expression of members of the E‐cadherin/catenin complex was studied by immunohistochemistry and Western blotting. Complex assembly was investigated by immunoprecipitation. It is shown that E‐cadherin and catenins are expressed in colorectal carcinoma cell lines with the predominant complex assembly being E‐cadherin/β‐catenin/α‐catenin. The subcellular distribution of the proteins is influenced by cell–cell contact, resulting in membranous localization. The expression and assembly of the E‐cadherin/catenin complex does not appear to be affected by the presence of APC and or β‐CATENIN mutations.
A population‐based epidemiologic study of irritable bowel syndrome in South China: stratified randomized study by cluster sampling
Authors: Xiong L. S. , Chen M. H. , Chen H. X. , Xu A. G. , Wang W. A. , Hu P. J.
Published: May 2004

Background : The detailed population‐based data on irritable bowel syndrome in South China are lacking.

Aims : To assess the prevalence of irritable bowel syndrome in South China and its impact on health‐related quality of life.

Subjects and methods : A face‐to‐face interview was carried out in South China to assess the prevalence of irritable bowel syndrome. Random clustered sampling of permanent inhabitants aged 18–80 years was carried out under stratification of urban and suburban areas. The impact of irritable bowel syndrome on health‐related quality of life was evaluated using the Chinese version of SF‐36.

Results : A total of 4178 subjects (1907 male and 2271 female) were interviewed. The adjusted prevalence of irritable bowel syndrome in South China is 11.50% according to the Manning criteria and 5.67% according to the Rome II criteria. Factors including history of analgesic use such as non‐steroidal anti‐inflammatory drug (odds ratio 3.83), history of food allergies (odds ratio 2.68), psychological distress (odds ratio 2.18), life events (odds ratio 1.89), history of dysentery (odds ratio 1.63) and negative coping style (odds ratio 1.28) were significantly associated with the presence of irritable bowel syndrome (P < 0.05). Irritable bowel syndrome was significantly associated with a decrement in health‐related quality of life score.

Conclusion : Irritable bowel syndrome is a common disorder in South China and has a negative impact on health‐related quality of life.
Serological testing for coeliac disease in patients with symptoms of irritable bowel syndrome: a cost‐effectiveness analysis
Authors: Mein S. M. , Ladabaum U.
Published: May 2004

Background: Patients diagnosed with irritable bowel syndrome may have coeliac disease.

Aim: To evaluate the cost‐effectiveness of coeliac disease testing in suspected irritable bowel syndrome.

Methods: We used decision analysis to estimate the number of coeliac disease cases detected, quality‐adjusted life‐years gained, and costs resulting from testing suspected irritable bowel syndrome patients for tissue transglutaminase antibody or an antibody panel (tissue transglutaminase, gliadin, total immunoglobulin A). Positive tests prompted endoscopic biopsy. A gluten‐free diet improved quality of life in coeliac disease.

Results: Assuming a coeliac disease prevalence of 3%, tissue transglutaminase detected 28 and the panel detected 29 of 30 coeliac disease cases among 1000 suspected irritable bowel syndrome patients. The cost/case detected was $4600 with tissue transglutaminase and $8800 with the panel. The cost/quality‐adjusted life‐year gained with tissue transglutaminase was $7400, and the incremental cost/quality‐adjusted life‐year gained for the panel vs. tissue transglutaminase was $287 000. Tissue transglutaminase cost under $100 000/quality‐adjusted life‐year gained at a coeliac disease prevalence ≥1.1%, assuming a modest utility gain of 0.005 with coeliac disease diagnosis.

Conclusions: Testing for coeliac disease in patients with suspected irritable bowel syndrome is likely to be cost‐effective even at a relatively low coeliac disease prevalence and with small improvements in quality of life with a gluten‐free diet.
Cost‐effectiveness of screening for hepatocellular carcinoma in patients with cirrhosis due to chronic hepatitis C
Authors: Lin O. S. , Keeffe E. B. , Sanders G. D. , Owens D. K.
Published: May 2004

Background : Screening for hepatocellular carcinoma in cirrhotic patients using abdominal ultrasonography and alpha‐foetoprotein levels is widely practiced.

Aim : To evaluate its cost‐effectiveness using a Markov decision model.

Methods : Several screening strategies with abdominal ultrasonography or computerized tomography and serum alpha‐foetoprotein at 6–12‐month intervals in 40‐year‐old patients with chronic hepatitis C and compensated cirrhosis were simulated from a societal perspective, resulting in discounted costs per quality‐adjusted life‐year saved. Extensive sensitivity analysis was performed.

Results : For the least efficacious strategy, annual alpha‐foetoprotein/ultrasonography, the incremental cost‐effectiveness ratio (vs. no screening) was $23 043/quality‐adjusted life‐year. Biannual alpha‐foetoprotein/annual ultrasonography, the most commonly used strategy in the United States, was more efficacious, with a cost‐effectiveness ratio of $33 083/quality‐adjusted life‐year vs. annual alpha‐foetoprotein/ultrasonography. The most efficacious strategy, biannual alpha‐foetoprotein/ultrasonography, resulted in a cost‐effectiveness ratio of $73 789/quality‐adjusted life‐year vs. biannual alpha‐foetoprotein/annual ultrasonography. Biannual alpha‐foetoprotein/annual computerized tomography screening resulted in a cost‐effectiveness ratio of $51 750/quality‐adjusted life‐year vs. biannual alpha‐foetoprotein/annual ultrasonography screening.

Conclusions : Screening for hepatocellular carcinoma is as cost‐effective as other accepted screening protocols. Of the strategies evaluated, biannual alpha‐foetoprotein/annual ultrasonography gives the most quality‐adjusted life‐year gain while still maintaining a cost‐effectiveness ratio <$50 000/quality‐adjusted life‐year. Biannual alpha‐foetoprotein/annual computerized tomography screening may be cost‐effective.
Cognitive dissonance and undergraduate nursing students’ knowledge of, and attitudes about, smoking
Authors: Clark Eileen , McCann Terence V. , Rowe Kathy , Lazenbatt Anne
Published: May 2004

Background.  Smoking is a major cause of morbidity and mortality. Although nurses have an important role in health promotion, and are well placed to see the harmful effects of tobacco smoking, studies suggest that they smoke at much the same rate as the general population.

Aim.  The aim of this paper is to report a study examining undergraduate nursing students’ knowledge about the impact of smoking on health, and their attitudes towards smokers and smoking.

Methods.  The study took place in 2001, using a non‐probability sample of 366 undergraduate nursing students from an Australian university. Participants completed the Smoking and Health Promotion instrument. Festinger's theory of cognitive dissonance provided an explanatory framework for the findings.

Results.  Most respondents who were still smoking began the habit while in high school. Students had greater generic than specialized knowledge about the effects of smoking on health, and there was no significant difference between second and third year students’ knowledge. Those who still smoked had less favourable attitudes towards smoking‐related health promotion than those who had never smoked or stopped smoking. Non‐smokers were more supportive of non‐smokers’ rights than those who continued to smoke, while those who had stopped smoking were undecided. There was minimal association between levels of knowledge and attitudes about being sensitive to smoking‐related health risks.

Conclusion.  The findings have implications for both high school education and undergraduate nursing education, and for the recruitment of students to undergraduate nursing programmes. More attention needs to be given in undergraduate nursing programmes to smoking and smoking‐related illnesses, and to nurses’ role in smoking health promotion.
Making portfolios work in practice
Authors: Scholes Julie , Webb Christine , Gray Morag , Endacott Ruth , Miller Carolyn , Jasper Melanie , McMullan Mirjam
Published: May 2004

Background.  A portfolio captures learning from experience, enables an assessor to measure student learning, acts as a tool for reflective thinking, illustrates critical analytical skills and evidence of self‐directed learning and provides a collection of detailed evidence of a person's competence.

Aims.  This paper reports data on how assessors and nursing students match learning outcomes and/or competencies to their practice and then reconstruct those experiences into the format required by the portfolio documentation. The data were gathered as part of a larger study to evaluate the use of portfolios in the assessment of learning and competence in England.

Methods.  This three phase stakeholder evaluation was designed to gain the views of those involved in designing, implementing and using portfolios in nurse education. In phase 2, 122 students and 58 nurse teachers were interviewed about their perceptions of portfolio use, and a further 32 students and 26 assessors were interviewed after they had been observed taking part in an assessment process. Thematic data analysis was used.

Findings.  Assessors and students underwent a complex process of deconstructing learning outcomes/competences to fit these to their practice. These then had to be reconstructed through the written medium to fit the structure of the portfolio. Confirmation that this met teachers’ expectations was essential to allay feelings of insecurity.

Conclusions.  To achieve maximum benefit from the portfolio as a learning tool to link theory and practice, there needs to be a clear fit between the model of portfolio and the professional practice that is to be assessed. Outcomes and competences, as well as the type of evidence required to demonstrate their achievement, and integration of the whole experience should match the students’ stage of professional and academic development. Over‐complex approaches to practice assessment, particularly in the early stages of students’ careers, can detract from clinical learning in favour of learning how to complete the portfolio successfully.
‘The good nurse’: visions and values in images of the nurse
Authors: Fealy Gerard M.
Published: May 2004

Background.  The various ways in which the nurse has been publicly portrayed do not merely reflect the value of nursing in society, but also define the boundaries of nursing, and reveal the ideologies and systems of power‐brokerage at work in shaping nursing. Therefore, it is of profound interest to the profession to continue to examine the ways in which the nurse is and has been portrayed.

Aim.  This paper aims to present a historical analysis of the image of the nurse in public discourses in Ireland.

Methods.  Using a framework of critical discourse analysis within the method of historical research, the paper draws on documentary primary sources to present an analysis of discourse concerning the ‘good nurse’.

Findings.  In exposing the diverse ways in which the nurse has been depicted in Irish public discourses, the origins of the ‘good nurse’ ideal are identified, the reasons for its continued promotion are critically examined, and the effects of the ideal on the development of nursing in Ireland are considered.

Conclusions.  While the ways in which Irish nurses have been depicted in public discourses have similarities with international nursing imagery, the ‘good nurse’ ideal has a uniquely Irish expression, indicating that the image of the nurse is both culture‐specific and changes to reflect the underlying sociocultural context, and prevailing system of political power and influence.
Structure and potential C‐terminal dimerization of a recombinant mutant of surfactant‐associated protein C in chloroform/methanol
Authors: Luy Burkhard , Diener Alexander , Hummel Rolf‐Peter , Sturm Ernst , Ulrich Wolf‐Rüdiger , Griesinger Christian
Published: May 2004

The solution structure of a recombinant mutant [rSP‐C (FFI)] of the human surfactant‐associated protein C (hSP‐C) in a mixture of chloroform and methanol was determined by high‐resolution NMR spectroscopy. rSP‐C (FFI) contains a helix from Phe5 to the C‐terminal Leu34 and is thus longer by two residues than the helix of porcine SP‐C (pSP‐C), which is reported to start at Val7 in the same solvent. Two sets of resonances at the C‐terminus of the peptide were observed, which are explained by low‐order oligomerization, probably dimerization of rSP‐C (FFI) in its α‐helical form. The dimerization may be induced by hydrogen bonding of the C‐terminal carboxylic groups or by the strictly conserved C‐terminal heptapeptide segment with a motif similar to the GxxxG dimerization motif of glycophorin A. Dimerization at the heptapeptide segment would be consistent with findings based on electrospray ionization MS data, chemical cross‐linking studies, and CNBr cleavage data.
Bacterial IscU is a well folded and functional single domain protein
Authors: Adinolfi Salvatore , Rizzo Francesca , Masino Laura , Nair Margie , Martin Stephen R. , Pastore Annalisa , Temussi Piero A.
Published: May 2004

Iron–sulfur clusters are widely represented in most organisms, but the mechanism of their formation is not fully understood. Of the two main proteins involved in cluster formation, NifS/IscS and NifU/IscU, only the former has been well studied from a structural point of view. Here we report an extensive structural characterization of Escherichia coli IscU. We show by a variety of physico‐chemical techniques that E. coli IscU construct can be expressed to high purity as a monomeric protein, characterized by an αβ fold with high α‐helix content. The high melting temperature and the reversibility of the thermal unfolding curve (as measured by CD spectroscopy) hint at a well ordered stable fold. The excellent dispersion of cross peaks in the 1H‐15N correlation spectrum is consistent with these observations. Monomeric E. coli IscU is able to provide a scaffold for Iron–sulfur cluster assembly, but has no direct interaction with either Fe(II) or Fe(III) ions, suggesting the need of further partners to achieve a stable interaction.
Poneratoxin, a neurotoxin from ant venom
Authors: Szolajska Ewa , Poznanski Jaroslaw , Ferber Miguel López , Michalik Joanna , Gout Evelyne , Fender Pascal , Bailly Isabelle , Dublet Bernard , Chroboczek Jadwiga
Published: May 2004

Poneratoxin is a small neuropeptide found in the venom of the ant Paraponera clavata. It is stored in the venom reservoir as an inactive 25‐residue peptide. Here we describe both chemically synthesized poneratoxin and poneratoxin obtained by expression in insect cells. When expressed in insect cells, poneratoxin was observed attached to cell membranes. Both synthetic and recombinant ponerotoxins were soluble below pH 4.5. The structure of synthetic poneratoxin was characterized by circular dichroism and solved by nuclear magnetic resonance. In an environment imitating a lipid bilayer, at pH within the range of insect hemolymph, synthetic poneratoxin has a V shape, with two α‐helices connected by a β‐turn. Insect larvae were paralyzed by injection of either of the purified toxins, with the recombinant one acting faster. The recombinant toxin‐producing baculovirus reduced the average survival time of the insect host by 25 h compared with unmodified virus. Mass spectrometry analysis showed that the recombinant toxin has an N‐terminal 21‐residue extension, possibly improving its stability and/or stabilizing the membrane‐bound state. The potential use of poneratoxin for the construction of biological insecticide is discussed.
Interaction of sweet proteins with their receptor
Authors: Tancredi Teodorico , Pastore Annalisa , Salvadori Severo , Esposito Veronica , Temussi Piero A.
Published: May 2004

The mechanism of interaction of sweet proteins with the T1R2‐T1R3 sweet taste receptor has not yet been elucidated. Low molecular mass sweeteners and sweet proteins interact with the same receptor, the human T1R2‐T1R3 receptor. The presence on the surface of the proteins of ‘sweet fingers’, i.e. protruding features with chemical groups similar to those of low molecular mass sweeteners that can probe the active site of the receptor, would be consistent with a single mechanism for the two classes of compounds. We have synthesized three cyclic peptides corresponding to the best potential ‘sweet fingers’ of brazzein, monellin and thaumatin, the sweet proteins whose structures are well characterized. NMR data show that all three peptides have a clear tendency, in aqueous solution, to assume hairpin conformations consistent with the conformation of the same sequences in the parent proteins. The peptide corresponding to the only possible loop of brazzein, c[CFYDEKRNLQC(37–47)], exists in solution in a well ordered hairpin conformation very similar to that of the same sequence in the parent protein. However, none of the peptides has a sweet taste. This finding strongly suggests that sweet proteins recognize a binding site different from the one that binds small molecular mass sweeteners. The data of the present work support an alternative mechanism of interaction, the ‘wedge model’, recently proposed for sweet proteins [Temussi, P. A. (2002) FEBS Lett.526, 1–3.].
Black house spiders are unlikely culprits in necrotic arachnidism: a prospective study
Authors: Isbister G. K. , Gray M. R.
Published: May 2004

Abstract

Twenty‐five patients with definite bites by Badumna spp. spiders were recruited prospectively. Bites occurred across Australia, 92% from October to March, and most during daylight. Pain occurred in all cases, was severe in seven cases, with a median duration of 5 min. Other effects included: puncture marks (24%), swelling (12%) and erythema (68%). Minor systemic effects occurred in 4 bites. No patient had a necrotic ulcer (0%; 97.5% confidence interval 0−14%). Black house spiders (Badumna spp.) are unlikely to cause necrosis, contrary to reports of suspected bites. Patients can be reassured and do not require any further investigation or treatment. (Intern Med J 2004; 34: 287−289)
Neurological manifestations of cardiac myxoma: a review of the literature and report of cases
Authors: Ekinci E. I. , Donnan G. A.
Published: May 2004

Abstract

Background and aims: Cardiac myxoma is a rare but important cause of stroke, which affects young people. More recently the diagnosis has been enhanced by the use of echocardiograms. We aimed to review the neurological presentations, including stroke, of cardiac myxoma in this modern era of diagnosis and management.

Methods : Records of patients with neurological presentations at the Austin and Repatriation Medical Centre and The Northern Hospital were retrieved from 1985 to late 2001, using International Classification of Diseases codes for atrial myxoma. Published literature reports were obtained by using Medline search database. An iterative process of bibliography review was utilised to identify reports not found by primary search. Case demographics, neurological presentations, investigations, treatment and outcome were recorded.

Results : From the Austin and Repatriation Medical Centre and The Northern Hospital, 6 cases were reported in detail and 107 cases from the published literature were analysed. The mean age of all cases was 43 (range 6−82). There was a female to male predominance (3:2). While there were overlapping neurological presentations, the most common presentation was ischaemic stroke (83% of all patients) most often in multiple sites (41%). The other presentations included syncope (28%), psychiatric presentations (23%), headache (15%) and seizures (12%). Commonest means of reaching the diagnosis was by echocardiography. The myxoma was surgically resected in 69% of cases. Of all cases, 24% were autopsy reports, almost all prior to availability of echocardiograms (in mid‐1970s).

Conclusions : Patients who presented with neurological complications of cardiac myxoma were young and stroke was by far the most common single presentation. Importantly, when all clinical manifestations were considered, almost half were potentially reversible. In recent years, echocardiography has made significant contribution to establishing the diagnosis less invasively. There is uncertainty about the role of anticoagulants. The treatment of choice remains surgical excision, although the timing post stroke is debatable. There is a need for large scale collaborative studies to help refine management strat­egies. (Intern Med J 2004; 34: 243−249)
Renal‐related deaths in Australia 1997−1999
Authors: Li S. Q. , Cunningham J. , Cass A.
Published: May 2004

Abstract

Background:  Despite marked increases in cases of treated end‐stage renal disease in Australia, little is known about renal disease mortality.

Aims:  To quantify the contribution of renal diseases to mortality in Australia and to explore the relationship between renal disease and other common diseases as causes of death.

Methods:  Data from the Australian Bureau of Statistics on underlying and associated causes of death (based on death certificates) were examined for deaths occurring in 1997−1999 and registered by the end of 1999. Causes of death were coded according to the International Classification of Diseases, 10th Revision (ICD‐10). Several causes outside the ICD‐10 chapter on diseases of the genito‐urinary system (e.g. diabetic renal disease, hypertensive renal disease and congenital malformations of the kidney) were included as renal.

Results:  Of 378 832 recorded deaths, renal disease was coded as the underlying cause for 7888 (2.1%) and as an associated cause for an additional 28 012 (7.4%). Almost all renal deaths (98.4%) had at least one other cause of death recorded on the death certificate.

Conclusions:  The contribution of renal disease to Australian mortality has been underestimated because of historical reliance on a single (underlying) cause of death. Deaths involving renal disease usually occur in the context of multiple coexisting chronic and/or acute conditions. (Intern Med J 2004; 34: 259−265)
Changes in prevalence and site of care of diabetes in a health district 1991–2001
Authors: Whitford D. L. , Roberts S. H.
Published: May 2004

Aims  Alongside a rising prevalence of known diabetes, patterns of care for diabetes have been changing in the United Kingdom. The aim of this study is to describe the changes in the prevalence of known diabetes and shift in site of care of patients in a single health district over a 10‐year period.

Methods  Repeat cross‐sectional study over 10 years of patients with diabetes resident in North Tyneside district.

Results  The crude prevalence of known diabetes in North Tyneside rose from 1.1 to 3.0% between 1991 and 2001. The proportion of patients receiving their diabetes care wholly in primary care rose significantly from 608/2236 (27%) in 1991 to 3995/5809 (69%) in 2001 (χ2 = 968, 1 d.f., P < 0.001). The number of patients attending secondary care also rose by 14% over this period of time from 1508 to 1712 patients.

Conclusions  Most of the extra workload of the rising prevalence of diabetes has been met in primary care. However, hospital care has not seen a drop in workload. This has important implications for health care planning, as an increase in resources will be required within both primary and secondary care to meet the needs of the diabetic population.
Increased levels of triglycerides, BMI and blood pressure and low physical activity increase the risk of diabetes in Swedish women. A prospective 18‐year follow‐up of the BEDA*study
Authors: Dotevall A. , Johansson S. , Wilhelmsen L. , Rosengren A.
Published: May 2004

Aim  To investigate risk factors for the development of diabetes in middle‐aged women.

Methods  A random population sample of 1351 women without prior diabetes or cardiovascular disease, aged 39–65 years, took part in a screening study in 1979–1981 with questionnaires, physical examination and blood sampling. Development of diabetes up to 1998 was identified at a second examination in 1997–1998.

Results  Seventy‐three women (5.4%) were diagnosed with diabetes during follow‐up. As expected, obesity resulted in a rising age‐adjusted risk with hazards ratio 3.2 [95% confidence interval (CI) 1.3, 8.1] at body mass index (BMI) 24–27 kg/m2, and 8.3 (3.5, 19.7), at BMI ≥ 27, compared with BMI < 22 kg/m2. S‐triglycerides (TG) carried a steeply increasing age‐adjusted risk with hazards ratio 4.0 (95% CI 2.1, 7.6) already at s‐TG 1.0–1.4 mmol/l, 7.1 (3.6, 14.0) at s‐TG 1.5–1.9 mmol/l and 9.3 (4.3, 20.2) at s‐TG ≥ 2.0 mmol/l compared with s‐TG < 1.0 mmol/l. Increasing systolic blood pressure (SBP) to 130–144, 145–159 and ≥ 160 mmHg escalated the hazards ratio of diabetes to 1.6 (0.8, 3.3), 3.6 (1.7, 7.4) and 5.6 (2.7, 11.4), respectively, compared with SBP < 130 mmHg. Also, low physical activity predicted diabetes, with hazards ratio 2.1 (1.3, 3.3) for sedentary compared with non‐sedentary activity. Smoking was not associated with increased risk of diabetes. After adjustment for BMI, SBP and physical activity, increasing TG level remained a strong and significant risk factor for diabetes [hazards ratio 3.0 (1.6, 5.7), 3.7 (1.8, 7.7) and 4.5 (2.0, 10.0), P < 0.001].

Conclusions  Among middle‐aged Swedish women even very slightly elevated s‐TG resulted in a considerably enhanced risk of developing diabetes, which was independent of age, BMI, blood pressure and physical activity.
Schizophrenia, the metabolic syndrome and diabetes
Authors: Holt R. I. G. , Peveler R. C. , Byrne C. D.
Published: May 2004

The prevalence of diabetes is increased in patients with schizophrenia. Although many reasons, including hereditary and lifestyle factors, contribute to this association, recently there has been heightened interest in the subject because of the link between the use of the newer atypical anti‐psychotic drugs and the development of diabetes. These drugs cause significant weight gain and this may be one of the mechanisms by which they increase incident diabetes. The increased prevalence of diabetes among people with schizophrenia has implications for the delivery of care by psychiatrists, diabetologists and primary care.
Vascular endothelium and inflammatory process, in patients with combined Type 2 diabetes mellitus and coronary atherosclerosis: the effects of vitamin C
Authors: Antoniades C. , Tousoulis D. , Tountas C. , Tentolouris C. , Toutouza M. , Vasiliadou C. , Tsioufis C. , Toutouzas P. , Stefanadis C.
Published: May 2004

Aims  Type 2 diabetes mellitus (DM) and coronary artery disease (CAD) are both associated with endothelial dysfunction and elevated oxidative and inflammatory state. We examined the effect of vitamin C on endothelial function and levels of soluble vascular cell adhesion molecule (sVCAM‐1), interleukin‐6 (IL‐6) and tumour necrosis factor (TNF‐α), in DM patients with or without CAD and in non‐diabetic subjects.

Methods  Thirty‐seven patients with DM + CAD, 17 patients with DM without CAD and 21 non‐diabetic subjects were divided into groups receiving vitamin C 2 g/day or no anti‐oxidant for 4 weeks. Forearm blood flow was determined using venous occlusion gauge‐strain plethysmography. Forearm vasodilatory response to reactive hyperemia was considered as index of endothelium‐dependent dilation.

Results  Baseline levels of IL‐6 and TNF‐α were significantly higher in patients with DM + CAD compared with patients with DM (P < 0.01) or non‐diabetic subjects (P < 0.01). IL‐6 and TNF‐α levels were also higher in DM compared with non‐diabetic subjects (P < 0.05). sVCAM‐1 levels were lower in non‐diabetic controls compared with DM + CAD (P < 0.05) or DM (P < 0.05). Reactive hyperaemia was higher in non‐diabetic controls compared with DM + CAD (P < 0.001) or DM (P < 0.001). Vitamin C significantly increased reactive hyperaemia only in the DM + CAD group, while it had no effect on serum levels of sVCAM‐1, TNF‐α and IL‐6 in any of the groups.

Conclusions  Type 2 diabetes mellitus is associated with impaired endothelial function and increased levels of TNF‐α, IL‐6 and sVCAM‐1, especially in patients with DM and CAD. Vitamin C significantly increased forearm vasodilatory response to reactive hyperaemia only in patients with combined DM and CAD.
The advantages and disadvantages of a ‘herbal’ medicine in a patient with diabetes mellitus: a case report
Authors: Wood D. M. , Athwal S. , Panahloo A.
Published: May 2004

Background  Patient‐initiated alternative treatments in the management of chronic conditions are common and increasing in the United Kingdom. To date, there have been no reports of herbal medicine use alone in the management of diabetes mellitus. We report here the case of a man who attained excellent glycaemic control using a ‘herbal’ medicine and reveal how important it was to identify the products of active constituents.

Case report  A 48‐year‐old man attending our clinic in Tooting, South London with known Type 2 diabetes, with evidence of both micro‐ and macro‐vascular diabetes‐related complications, was poorly controlled despite a drug regimen consisting of oral metformin and twice daily insulin. He went to India for at least 1 year and on returning to the clinic had excellent glycaemic control off all diabetic medication. While away he had started himself on a regimen of three different ‘herbal’ balls. Samples of blood were found to contain chlorpropamide in a therapeutic concentration; chlorpropamide was also found in one of the balls. He has been counselled on the potential risks associated with chlorpropamide and his treatment reverted to a more conventional treatment regimen.

Conclusions  General practitioners and hospital physicians should be alert to those patients returning from abroad on effective ‘herbal’ medications that these may in fact contain an active ingredient.
The value of the Rydel‐Seiffer tuning fork as a predictor of diabetic polyneuropathy compared with a neurothesiometer
Authors: Kästenbauer T. , Sauseng S. , Brath H. , Abrahamian H. , Irsigler K.
Published: May 2004

Aims  The aim of the study was to investigate the predictive value of the Rydel‐Seiffer tuning fork for detecting diabetic neuropathy and to compare it with an electronic neurothesiometer.

Methods  In 2022 consecutive diabetic subjects, peripheral polyneuropathy was diagnosed by vibration perception threshold (VPT) at the tip of both great toes using a 128‐Hz tuning fork and a neurothesiometer, by simple bedside tests and by the presence of neuropathic symptoms. These evaluations were further combined to diagnose peripheral nerve dysfunction (abnormal bedside tests) and symptomatic neuropathy. VPT was also measured in 175 non‐diabetic control subjects to define normal values.

Results  VPT was normal in 1917 subjects and abnormal in 105 (5.2%) patients when measured by the tuning fork. Patients with an abnormal vibration test were significantly (P < 0.0001) older than subjects with a normal vibration sense, while diabetes duration and HbA1c of the former were also significantly elevated. The same was true for the percentages of an abnormal 10‐g monofilament test (66.7% vs. 7.2%, P < 0.0001) and a missing Achilles’ tendon reflex (68.6% vs. 24.8%, P < 0.0001). Finally, the VPT measured by the neurothesiometer was 2.5 times higher in patients with an abnormal tuning fork test (32.0 ± 9.8 vs. 12.5 ± 6.4 V, P < 0.0001). The plot of the difference of both methods against their mean yielded a good agreement of the two VPT measurements, and the tuning fork had a high sensitivity and positive predictive value for the diagnosis of abnormal bedside tests and for symptomatic neuropathy.

Conclusion  The tuning fork reliably detected peripheral neuropathy in comparison with the neurothesiometer. A tuning fork is a useful screening test for diabetic neuropathy.
Cyprus’ Accession to the European Union and Educational Change: a critique
Authors: ANGELIDES PANAYIOTIS , LEIGH JAMES
Published: May 2004

Cyprus will soon become a member of the European Union. The negotiations for its the access have ended and as from next year it will represent one of the countries that will expand the EU. The member countries of the EU have progressed in the field of education, they have high requirements from their schools and offer quality education (although there is no homogeneity amongst their educational systems). Therefore, the future accession of Cyprus to the EU raises many questions regarding the situation of its education system in comparison to the other Members. With a focus on change, this article studies the situation that prevails in Cyprus and examines the different barriers that hamper the development of its educational system. The authors then discuss a number of ways to achieve educational change.
Conjugate Priors Represent Strong Pre‐Experimental Assumptions
Authors: Gutiérrez‐Peña Eduardo , Muliere Pietro
Published: May 2004

Abstract. It is well known that Jeffreys’ prior is asymptotically least favorable under the entropy risk, i.e. it asymptotically maximizes the mutual information between the sample and the parameter. However, in this paper we show that the prior that minimizes (subject to certain constraints) the mutual information between the sample and the parameter is natural conjugate when the model belongs to a natural exponential family. A conjugate prior can thus be regarded as maximally informative in the sense that it minimizes the weight of the observations on inferences about the parameter; in other words, the expected relative entropy between prior and posterior is minimized when a conjugate prior is used.
Causal Reasoning from Longitudinal Data*
Authors: Arjas Elja , Parner Jan
Published: May 2004

Abstract.  This paper reviews some of the key statistical ideas that are encountered when trying to find empirical support to causal interpretations and conclusions, by applying statistical methods on experimental or observational longitudinal data. In such data, typically a collection of individuals are followed over time, then each one has registered a sequence of covariate measurements along with values of control variables that in the analysis are to be interpreted as causes, and finally the individual outcomes or responses are reported. Particular attention is given to the potentially important problem of confounding. We provide conditions under which, at least in principle, unconfounded estimation of the causal effects can be accomplished. Our approach for dealing with causal problems is entirely probabilistic, and we apply Bayesian ideas and techniques to deal with the corresponding statistical inference. In particular, we use the general framework of marked point processes for setting up the probability models, and consider posterior predictive distributions as providing the natural summary measures for assessing the causal effects. We also draw connections to relevant recent work in this area, notably to Judea Pearl's formulations based on graphical models and his calculus of so‐called do‐probabilities. Two examples illustrating different aspects of causal reasoning are discussed in detail.
A rare course of Whipple's disease with atypical cardiac manifestation
Authors: GUNIA S. , BEHRENS M. H. , STOSIEK P.
Published: May 2004

Whipple's disease (WD) is a rare disorder caused by the gram‐positive actinomycete Tropheryma whippelii (1). An oral route of acquisition is presumed (2). WD is a chronic systemic infection morphologically characterized by foamy PAS‐positive macrophages. This case report depicts the diagnosis and clinical management of a woman who presented with atypical cardial manifestations of WD and died from severe cardiac impairment by Tropheryma whippelii which was confirmed by polymerase chain reaction. Histological assessment of myocardial specimens obtained at autopsy showed PAS‐positive macrophages accumulating within foci of interstitial myocardial fibrosis. Immunohistochemical staining demonstrated myocarditis with lymphocytes and neutrophilic granulocytes, which has not been reported so far in the course of WD.
A longitudinal study of caries onset in initially caries‐free children and baseline salivary mutans streptococci levels: a Kaplan–Meier survival analysis
Authors: Kopycka‐Kędzierawski Dorota T. , Billings Ronald J.
Published: May 2004

Abstract –  Objectives: To apply survival analysis to a longitudinal study of the relationship between salivary mutans streptococci (MS) levels at baseline in initially caries‐free children and caries onset in deciduous, mixed, and permanent dentition. Methods: The Kaplan–Meier survival analysis method was used to compare survival times to caries onset for initially caries‐free children with low levels of MS at baseline with survival times to caries onset for initially caries‐free children with high levels of MS at baseline. Results: Data from a 6‐year longitudinal study of caries risk in initially caries‐free children in Rochester and the Finger Lakes Region of western New York were utilized for this study. Of 464 children analyzed, 327 had a low level of MS and 137 had a high level of MS at baseline. Survival analyses showed that children with a low level of MS at baseline remained caries‐free for a longer period than children with a high level of MS at baseline. Statistically significant relationships [hazard ratios (HR)] with onset of caries in deciduous, mixed and permanent teeth were found with high and low levels of salivary MS. Conclusions: Based on our analysis, we concluded that children who were caries‐free at baseline and who had high salivary MS levels at baseline would be at greater risk, i.e. more susceptible to caries onset, at any given time than caries‐free children who had low salivary MS levels at baseline. Survival functions for deciduous, mixed and permanent dentitions with their 95% confidence limits have been calculated. Survival analysis for the exploration of longitudinal caries studies has an advantage over traditional statistical methods, as it takes into account censored observations and incorporates the concept of risk over time. Hence, survival analysis is well suited for studying transitions from one health state to another, in this case, from a caries‐free state to a caries‐active state.
MODULI SPACES OF TOPOLOGICAL CALIBRATIONS, CALABI–YAU, HYPERKÄHLER, G2and SPIN(7) STRUCTURES
Authors: GOTO RYUSHI
Published: May 2004

This paper focuses on a geometric structure defined by a system of closed exterior differential forms and develops a new approach to deformation problems of geometric structures. We obtain a criterion for unobstructed deformations from a cohomological point of view (Theorem 1.7). Further we show that under a cohomological condition, the moduli space of the geometric structures becomes a smooth manifold of finite dimension (Theorem 1.8). We apply our approach to the geometric structures such as Calabi–Yau, HyperKähler, G2and Spin(7) structures and then obtain a unified construction of smooth moduli spaces of these four geometric structures. We generalize the Moser's stability theorem to provide a direct proof of the local Torelli type theorem in these four geometric structures (Theorem 1.10).
MICROSTRUCTURES AND STRAIN RELAXATION IN MODULATION-DOPED AlxGa1-xN/GaN HETEROSTRUCTURES
Authors: TAN W. S. , SHEN B. , SHA H. , CAI H. L. , WU X. S. , ZHENG Y. D. , JIANG S. S. , ZHENG W. L. , JIA Q. J. , HE Q.
Published: May 2004

Modulation-doped Al 0.22 Ga 0.78 N / GaN heterostructures with various thickness of Si-doped Al 0.22 Ga 0.78 N barrier (n- AlGaN ) were deposited on (0001)-oriented sapphire (α- Al 2 O 3) by atmosphere-pressure metal-organic chemical vapor deposition (MOCVD). The reciprocal space mappings (RSMs) of symmetric reflection (0002) and asymmetric reflection [Formula: see text] were measured by means of the high resolution X-ray diffraction (HRXRD). The results indicate that the microstructures and the strain status of the n- AlGaN barrier correlate to those of the underlying i- GaN layer. The strained n- AlGaN barrier starts to relax when its thickness is 75 nm. It is found that there exists an "abnormal" relaxation state (the strain parameter γ>1) in modulation-doped Al 0.22 Ga 0.78 N / GaN heterostructures, which maybe results from the internal defects in Al 0.22 Ga 0.78 N barrier and the strain relaxation status at the i- GaN /α- Al 2 O 3 interfaces.
THEORETICAL STUDY OF INHOMOGENEOUSLY-BROADENED-LINE SHAPES OF LUMINESCENT AND LASER f-ELEMENT TRANSITIONS IN SEMICONDUCTOR AND DIELECTRIC DIES
Authors: ZOLOTOVSKY A. A.
Published: May 2004

The many-body problem is solved for f-element complexes in solids. Multielectron orbitals are constructed from single-electron ones. Complexes of f-ions surrounded by sulphur, oxygen and fluoride ligands (atoms or ions) are employed as a model of radiating centres in order to describe the optoelectronic behavior of materials in the cluster approximation. Probabilities and intensities of luminescent- and laser-transition Stark components are calculated. Inhomogeneous broadening of line shapes in solids is studied for various excitation regimes.
METAL–INSULATOR TRANSITIONS IN TETRAHEDRAL SEMICONDUCTORS UNDER LATTICE CHANGE
Authors: SHUKLA SHAILESH , KUMAR DEEPAK , SHUKLA NITYA NATH , PRASAD RAJENDRA
Published: May 2004

Although most insulators are expected to undergo insulator to metal transition on lattice compression, tetrahedral semiconductors Si, GaAs and InSb can become metallic on compression as well as by expansion. We focus on the transition by expansion which is rather peculiar; in all cases the direct gap at Γ point closes on expansion and thereafter a zero-gap state persists over a wide range of lattice constant. The solids become metallic at an expansion of 13% to 15% when an electron Fermi surface around L-point and a hole Fermi surface at Γ-point develop. We provide an understanding of this behavior in terms of arguments based on symmetry and simple tight-binding considerations. We also report results on the critical behavior of conductivity in the metal phase and the static dielectric constant in the insulating phase and find common behavior. We consider the possibility of excitonic phases and distortions which might intervene between insulating and metallic phases.
FREELY INDECOMPOSABLE GROUPS ACTING ON HYPERBOLIC SPACES
Authors: KAPOVICH ILYA , WEIDMANN RICHARD
Published: May 2004

We obtain a number of finiteness results for groups acting on Gromov-hyperbolic spaces. In particular we show that a torsion-free locally quasiconvex hyperbolic group has only finitely many conjugacy classes of n-generated one-ended subgroups.
UNAVOIDABLE SETS OF CONSTANT LENGTH
Authors: CHAMPARNAUD JEAN-MARC , HANSEL GEORGES , PERRIN DOMINIQUE
Published: May 2004

A set of words X is called unavoidable on a given alphabet A if every infinite word on A has a factor in X. For k,q≥1, let c(k,q) be the number of conjugacy classes of words of length k on q letters. An unavoidable set of words of length k on q symbols has at least c(k,q) elements. We show that for any k,q≥1, there exists an unavoidable set of words of length k on q symbols having c(k,q) elements.
ON PRODUCTS OF QUASICONVEX SUBGROUPS IN HYPERBOLIC GROUPS
Authors: MINASYAN ASHOT
Published: May 2004

An interesting question about quasiconvexity in a hyperbolic group concerns finding classes of quasiconvex subsets that are closed under finite intersections. A known example is the class of all quasiconvex subgroups [1]. However, not much is yet learned about the structure of arbitrary quasiconvex subsets. In this work we study the properties of products of quasiconvex subgroups; we show that such sets are quasiconvex and their finite intersections have a similar algebraic representation and, thus, are quasiconvex too.
Involvement of the mitogen-activated protein kinase cascade in peroxynitrite-mediated arachidonic acid release in vascular smooth muscle cells
Authors: Upmacis Rita K. , Deeb Ruba S. , Resnick Matthew J. , Lindenbaum Rochelle , Gamss Caryn , Mittar Dev , Hajjar David P.
Published: May 2004

Eicosanoid production is reduced when the nitric oxide (NO·) pathway is inhibited or when the inducible NO synthase gene is deleted, indicating that the NO· and arachidonic acid pathways are linked. We hypothesized that peroxynitrite, formed by the reaction of NO· and superoxide anion, may cause signaling events leading to arachidonic acid release and subsequent eicosanoid generation. Western blot analysis of rat arterial smooth muscle cells demonstrated that peroxynitrite (100–500 μM) and 3-morpholinosydnonimine (SIN-1; 200 μM) stimulate phosphorylation of extracellular signal-regulated kinase (ERK), p38, and cytosolic phospholipase A2 (cPLA2). We found that peroxynitrite-induced arachidonic acid release was completely abrogated by the mitogen-activated protein/ERK kinase (MEK) inhibitor U0126 and by calcium chelators. With the p38 inhibitor SB-20219, we demonstrated that peroxynitrite-induced p38 phosphorylation led to minor arachidonic acid release, whereas U0126 completely blocked p38 phosphorylation. Addition of arachidonic acid caused p38 phosphorylation, suggesting that arachidonic acid or its metabolites are responsible for p38 activation. KN-93, a specific inhibitor of Ca2+/calmodulin-dependent kinase II (CaMKII), revealed no role for this kinase in peroxynitrite-induced arachidonic acid release in our cell system. Together, these results show that in response to peroxynitrite the cell initiates the MEK/ERK cascade leading to cPLA2 activation and arachidonic acid release. Thus studies investigating the role of the NO· pathway on eicosanoid production must consider the contribution of signaling pathways initiated by reactive nitrogen species. These findings may provide evidence for a new role of peroxynitrite as an important reactive nitrogen species in vascular disease.
PKC-δ and CaMKII-δ2 mediate ATP-dependent activation of ERK1/2 in vascular smooth muscle
Authors: Ginnan Roman , Pfleiderer Paul J. , Pumiglia Kevin , Singer Harold A.
Published: May 2004

ATP, a purinergic receptor agonist, has been shown to be involved in vascular smooth muscle (VSM) cell DNA synthesis and cell proliferation during embryonic and postnatal development, after injury, and in atherosclerosis. One mechanism that ATP utilizes to regulate cellular function is through activation of ERK1/2. In the present study, we provide evidence that ATP-dependent activation of ERK1/2 in VSM cells utilizes specific isoforms of the multifunctional serine/threonine kinases, PKC, and Ca2+/calmodulin-dependent protein kinase II (CaMKII) as intermediates. Selective inhibition of PKC-δ activity with rottlerin, or adenoviral overexpression of kinase-negative PKC-δ, attenuated the ATP- and phorbol 12,13-dibutyrate (PDBu)-stimulated ERK1/2 activation. Inhibition of PKC-α activity with Gö-6976, or adenoviral overexpression of kinase-negative PKC-α, was ineffective. Alternatively, treatment with KN-93, a selective inhibitor of CaMKII activation, or adenoviral overexpression of kinase-negative CaMKII-δ2, inhibited ATP-dependent activation of ERK1/2 but had no effect on PDBu- or PDGF-stimulated ERK1/2. In addition, adenoviral overexpression of dominant-negative ras (Ad.HA-RasN17) partially inhibited the ATP- and PDBu-induced activation of ERK1/2 and blocked ionomycin- and EGF-stimulated ERK1/2, and inhibition of tyrosine kinases with AG-1478, an EGFR inhibitor, or the src family kinase inhibitor PP2 attenuated ATP-stimulated ERK1/2 activation. Taken together, these data indicate that PKC-δ and CaMKII-δ2 coordinately mediate ATP-dependent transactivation of EGF receptor, resulting in increased ERK1/2 activity in VSM cells.