bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of inflammatory attacks in the classical type hyper‐IgD syndrome on immunoglobulin D, cholesterol and parameters of the acute phase response
Authors: Simon A. , Bijzet J. , Voorbij H. A. M. , Mantovani A. , Van Der Meer J. W. M. , Drenth J. P. H.
Published: August 2004

Background.  Classical type hyper‐immunoglobulin D (IgD) syndrome (HIDS) is an hereditary auto‐inflammatory disorder, characterized by recurrent episodes of fever, lymphadenopathy, abdominal distress and a high serum concentration of IgD. It is caused by mevalonate kinase deficiency.

Objective.  To further characterize the acute phase response during fever attacks in HIDS in order to improve diagnosis.

Subjects.  Twenty‐two mevalonate kinase‐deficient HIDS patients.

Methods.  Blood samples were drawn during and in between febrile attacks, and concentrations ofC‐reactive protein (CRP), ferritin, procalcitonin, pentraxin 3, IgD and cholesterol in several lipoprotein fractions were determined.

Results.  The marked acute phase response at the time of a fever attack in classical type HIDS is reflected by a rise in CRP accompanied by a moderate but statistically significant rise in procalcitonin and pentraxin 3. In only two of 22 patients, procalcitonin concentration rose above 2 ng mL−1 during fever attack, compatible with the noninfectious nature of these attacks. Ferritin does not reach the high concentrations found in adult‐onset Still's disease. Despite the defect in mevalonate kinase, a component of cholesterol metabolism, serum cholesterol did not change during attacks. IgD concentration is elevated regardless of disease activity, although there is appreciable variation during life. Its role in HIDS remains unclear.

Conclusion.  The combination of high CRP concentration plus procalcitonin concentration <2 ng mL−1 in a symptomatic HIDS patient might indicate a febrile attack without (bacterial) infection; this observation warrants further investigation for its usefulness as a marker in clinical practice.
Low birth weight in combination with catch‐up growth predicts the occurrence of the metabolic syndrome in men at late middle age: the Atherosclerosis and Insulin Resistance study
Authors: Fagerberg B. , Bondjers L. , Nilsson P.
Published: August 2004

Objectives.  To study the combined effects of a low birth weight and a pronounced weight increase up to early adulthood on the presence of cardiovascular risk factors constituting the metabolic syndrome in late middle age.

Design and setting.  A structured sample of 396 men, 58 years old from the general population. Birth weight and weight at 18 years were obtained from medical records and registers.

Main outcome measures.  Body mass index (BMI), waist : hip ratio (WHR), blood pressure, serum concentrations of insulin, triglycerides, HDL cholesterol and LDL particle size at age 58 years.

Results.  The ratio between weight at age 18 years and birth weight correlated with a number of characteristics at age 58 years: BMI (r = 0.24, P < 0.001), WHR (r = 0.24, P < 0.001), diastolic blood pressure (r = 0.13, P < 0.05), insulin (r = 0.14, P < 0.01), triglycerides (r = 0.10, P < 0.05), HDL cholesterol (r = −0.13, P < 0.01) and LDL particle size (r = −0.17, P < 0.05). The metabolic syndrome, according to current definitions, were more common at the age of 58 years in the third tertile of the weight at 18/birth ratio, than in the other tertiles (P = 0.008).

Conclusions.  The interaction between a low birth weight and an accelerated catch‐up growth to early adulthood is associated with the occurrence of the metabolic syndrome in the late middle age. These findings are in accord with the concept that the effects of genes are conditioned by fetal growth, and that the effects of a small body size at birth are conditioned by growth during childhood and by environmental factors in childhood and adult life.
Prospects of genetic research of mild cognitive impairment
Authors: van Duijn C. M.
Published: August 2004

Mild cognitive impairment (MCI) is a common problem in the elderly. Genetic research may yield valuable clues to improve the diagnostic and prognostic tools for MCI. As the majority of patients progress into Alzheimer's disease (AD) and other forms of dementia, the genetics of MCI cannot be separated from the genetics of AD and dementia in general. Follow‐up studies of carriers of mutations underlying AD may yield valuable clues for the development of new diagnostic tools for MCI. In particular, large‐scale studies of carriers of the apolipoprotein E 4 allele may still be of interest. Our knowledge of the genes involved in MCI is still very limited. In addition, we need powerful and carefully designed candidate gene studies aiming to discover new genes involved in the risk and progression of MCI. Although the genetics of MCI will be difficult to disentangle, there is ample opportunity to improve research of the genes involved.
CSF biomarkers for mild cognitive impairment
Authors: Blennow K.
Published: August 2004

A correct clinical diagnosis of Alzheimer's disease (AD) early in the course of the disease is of importance to initiate symptomatic treatment with acetylcholine esterase inhibitors, and will be even more important when disease‐arresting drugs, such as β‐sheet breakers or γ‐secretase inhibitors, will reach the clinic. However, there is no clinical method to determine if a patient with mild cognitive impairment (MCI) has incipient AD, i.e. will progress to AD with dementia, or have a benign form of MCI without progression. Thus, there is a great clinical need for diagnostic biomarkers to identify incipient AD in MCI cases. Three cerebrospinal fluid (CSF) biomarkers; total‐tau (T‐τ), phospho‐tau (P‐τ) and the 42 amino acid form of β‐amyloid (Aβ42) have been evaluated in numerous scientific papers. These CSF markers have high sensitivity to differentiate early and incipient AD from normal ageing, depression, alcohol dementia and Parkinson's disease, but lower specificity against other dementias, such as frontotemporal and Lewy body dementia. However, if the CSF biomarkers are used in the right clinical context, i.e. together with the cumulative information from the clinical examination, standard laboratory tests and brain‐imaging techniques [single photon emission tomography (SPECT) and magnetic resonance tomography (MRT) scans], they may have a role in the clinical evaluation of MCI cases.
Mild cognitive impairment – beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment
Authors: Winblad B. , Palmer K. , Kivipelto M. , Jelic V. , Fratiglioni L. , Wahlund L.‐O. , Nordberg A. , Bäckman L. , Albert M. , Almkvist O. , Arai H. , Basun H. , Blennow K. , De Leon M. , DeCarli C. , Erkinjuntti T. , Giacobini E. , Graff C. , Hardy J. , Jack C. , Jorm A. , Ritchie K. , Van Duijn C. , Visser P. , Petersen R.C.
Published: August 2004

The First Key Symposium was held in Stockholm, Sweden, 2–5 September 2003. The aim of the symposium was to integrate clinical and epidemiological perspectives on the topic of Mild Cognitive Impairment (MCI). A multidisciplinary, international group of experts discussed the current status and future directions of MCI, with regard to clinical presentation, cognitive and functional assessment, and the role of neuroimaging, biomarkers and genetics. Agreement on new perspectives, as well as recommendations for management and future research were discussed by the international working group. The specific recommendations for the general MCI criteria include the following: (i) the person is neither normal nor demented; (ii) there is evidence of cognitive deterioration shown by either objectively measured decline over time and/or subjective report of decline by self and/or informant in conjunction with objective cognitive deficits; and (iii) activities of daily living are preserved and complex instrumental functions are either intact or minimally impaired.
Mild cognitive impairment as a diagnostic entity
Authors: Petersen R. C.
Published: August 2004

The concept of cognitive impairment intervening between normal ageing and very early dementia has been in the literature for many years. Recently, the construct of mild cognitive impairment (MCI) has been proposed to designate an early, but abnormal, state of cognitive impairment. MCI has generated a great deal of research from both clinical and research perspectives. Numerous epidemiological studies have documented the accelerated rate of progression to dementia and Alzheimer's disease (AD) in MCI subjects and certain predictor variables appear valid. However, there has been controversy regarding the precise definition of the concept and its implementation in various clinical settings. Clinical subtypes of MCI have been proposed to broaden the concept and include prodromal forms of a variety of dementias. It is suggested that the diagnosis of MCI can be made in a fashion similar to the clinical diagnoses of dementia and AD. An algorithm is presented to assist the clinician in identifying subjects and subclassifying them into the various types of MCI. By refining the criteria for MCI, clinical trials can be designed with appropriate inclusion and exclusion restrictions to allow for the investigation of therapeutics tailored for specific targets and populations.
Choice, participation and accountability: assessing the potential impact of legislation promoting patient and public involvement in health in the UK*
Authors: Sang Bob
Published: August 2004

Recent legislation enabling increased patient and public involvement in health decision‐making will increasingly interact with the maturing independent patient movement to open up accountability systems across healthcare. Lay people will develop new roles, building on learning from the independent advocacy sector, self management, and wider active participation. Inevitably, this means a profound cultural challenge for healthcare organizations, and for citizens, as they begin to understand the implications of the new policies, including patient choice.
Feedback from community pharmacy users on the contribution of community pharmacy to improving the public's health: a systematic review of the peer reviewed and non‐peer reviewed literature 1990–2002
Authors: Anderson Claire , Blenkinsopp Alison , Armstrong Miriam
Published: August 2004

Objective  To systematically review feedback from pharmacy users on their perceptions and experiences of health‐related advice and services provided from community pharmacies.

Methods  The focus of the review was community pharmacy activities in relation to promoting health and well‐being, preventing ill‐health and maintaining health. Searches were conducted for peer‐reviewed (international) and non‐peer‐reviewed (UK) research. Electronic databases searched included MEDLINE, EMBASE, Cochrane Library and International Pharmaceutical Abstracts; hand searches of key journals and conference abstracts, key informants. Key informants in the UK were contacted to identify unpublished studies. The inclusion period was 1990 onwards.

Data extraction and synthesis  Data were abstracted into a matrix by one author with a sample checked by a second. The Health Development Agency's Evidence Base 2000 standards and the evidence categories used by the Department of Health in the National Service Frameworks were applied to each item.

Main results  Seven peer reviewed papers and 13 non‐peer reviewed reports were identified for inclusion in the review. Consumer usage of pharmacies is almost universal with prescription supplies and purchase of over the counter medicines predominating. Evidence shows that not only is usage low for general health advice, but that pharmacists are perceived as ‘drugs experts’ rather than experts on health and illness. Emergency hormonal contraception and head lice management schemes have been well received. There is a need to consider privacy and confidentiality surrounding advice giving.

Conclusions  Users of community pharmacy‐based health development initiatives express a high level of satisfaction. If community pharmacies are to be used to their full extent, then actions to extending the public's awareness and acceptance of the pharmacist's role in giving advice will be crucial. Further research will be needed to measure any change in premises development on the public's perception of the level of privacy in pharmacies.
What does it mean to involve consumers successfully in NHS research? A consensus study
Authors: Telford Rosemary , Boote Jonathan D. , Cooper Cindy L.
Published: August 2004

Objective  To obtain consensus on the principles and indicators of successful consumer involvement in NHS research.

Design  Consensus methods were used. An expert workshop, employing the nominal group technique was used to generate potential principles and indicators. A two‐round postal Delphi process was used to obtain consensus on the principles and indicators.

Setting and participants  Participants were drawn from health, social care, universities and consumer organizations. A purposive sampling strategy was used to identify people who had experience and/or knowledge of consumer involvement in NHS research. Six researchers and seven consumers participated in an expert workshop. Ninety‐six people completed both rounds of the Delphi process.

Main outcome measures  Consensus on principles and indicators of successful consumer involvement in NHS research.

Results  Eight principles were developed through an expert workshop and Delphi process, and rated as both clear and valid. Consensus was reached on at least one clear and valid indicator by which to measure each principle.

Conclusions  Consensus has been obtained on eight principles of successful consumer involvement in NHS research. They may help commissioners, researchers and consumers to deepen their understanding of this issue, and can be used to guide good practice.
Perceptions around concordance – focus groups and semi‐structured interviews conducted with consumers, pharmacists and general practitioners
Authors: Bajramovic Jasmina , Emmerton Lynne , Tett Susan E.
Published: August 2004

Background  Achieving concordance by identifying beliefs about illness, treatment and medicine‐taking should impact positively on behaviour and consumer satisfaction with respect to treatment, and health outcomes may be improved.

Objective  To explore, in the Australian context, beliefs and expectations of general practitioners (GPs), consumers and pharmacists in relation to concordance to allow further exploration of the implementation of principles of concordance in Australia.

Design  Qualitative analysis of focus group and semi‐structured interview data.

Setting and participants  Focus groups were held with seven consumers and nine pharmacists and, in‐depth, semi‐structured interviews were held with 10 GPs between February and May 2003, in Brisbane (Australia).

Results  This explorative study identified a variety of issues. Consumers expressed the need for more input from health professionals – being given more information on their treatments and conditions, more time spent in discussion, and establishing a system where harmonious relationships between health professionals could take place, which would result in a more consumer‐friendly health care system. The main issues voiced by the pharmacists were about the idea of organizing the health care system in a way that would accommodate more quality information sharing between all partners. GPs’ issues included better and unlimited information‐sharing, having more time to promote quality in health care and receiving remuneration for increased verbal contact with other health care professionals. Suggestions were made about ways to achieve concordance by improved information‐sharing and shared decision‐making.

Conclusion  The data from this study will lead to the development of models to explore and attempt to incorporate principles of concordance in Australian pharmacy and medical practice.
A systematic review of the research on communication between patients and health care professionals about medicines: the consequences for concordance
Authors: Stevenson Fiona A. , Cox Kate , Britten Nicky , Dundar Yenal
Published: August 2004

Objectives  We draw on a systematic review of research on two‐way communication between patients and health practitioners about medicines in order to determine the extent to which concordance is, or is not, being put into practice.

Data sources  Six electronic databases were searched using the following categories of search terms: health care professionals, patients/consumers, medicine‐taking/prescribing and communication. Articles were also identified from handsearches of journals, article reference lists and the Concordance website.

Review methods  Studies published between 1991 and 2000 were included. Studies were not excluded on the basis of design, methods or language employed. Abstracts of identified articles were assessed by at least two reviewers and the full articles were assessed by one reviewer and checked by at least one other reviewer. Data on the design, analysis and relevant findings were extracted.

Results  A total of 11 801 abstracts were reviewed and 470 full articles were retrieved. Of the 134 articles subsequently included, 116 were descriptive studies. All but 10 of the papers were written in English. There were mixed findings about the extent to which patients feel that their beliefs, experience and preferences about medicines can be shared. Doctors tend to dominate discussions in consultations, although patient participation is associated with positive outcomes. Health care professionals’ behaviour can impede as well as enhance patient involvement.

Conclusions  There is little research that examines fundamental issues for concordance such as whether an exchange of views takes place. It is possible that interventions are needed to facilitate the development of concordance in practice.
Reasons underpinning patients' preferences for various angina treatments
Authors: Lambert Nigel , Rowe Gene , Bowling Ann , Ebrahim Shah , Laurence Michael , Dalrymple Jamie , Thomson Richard
Published: August 2004

Objective  To elicit patients’ preferences for the treatment of angina.

Design  Angina patients were interviewed in order to elicit their personal reasons underlying preferences for various treatment options. Interviews followed a general repertory grid technique, in which seven treatment options were presented to patients in triads. Treatments considered ranged from medication to invasive revascularization therapies, with a ‘no treatment’ option.

Setting  Two general practices in Norwich, Norfolk.

Subjects  Twenty‐one patients with diagnosed angina, which was both mild and stable.

Main outcome measures  Treatment preferences verbalized by patients during interview, and the underlying reasons for these.

Results  Attitudes voiced towards the range of treatments for angina were diverse; 27 different reasons underlying patients’ preferences were identified. Patients’ preferences were largely justified by reasons associated with the conditional effectiveness or otherwise of treatments. When presented with treatment triads, medication (drug) treatments were over 2.5 times more likely to be chosen as a most preferred option than invasive or surgical treatments. Although surgical treatments were generally considered to be ‘effective’, it was perceived that they were more appropriate for situations when the condition became life‐threatening. There were occasions, however, when preferences were driven by other reasons, such as a desire to avoid surgery because it was perceived negatively as ‘invasive’ and ‘frightening’. Drug treatments were viewed as ‘quick’, ‘easy’ and reversible. Personal experiences of the effectiveness or otherwise of treatments were frequently cited as reasons for stated preferences. However, patients often commented that they would prefer the doctor to make the decision about their treatment.

Conclusions  Patients choices among treatments was largely driven by perceptions of their effectiveness or otherwise. Although surgery was perceived as ‘effective’ it was also seen as conditionally so, dependent upon severity of the condition – which is not necessarily the case, as the risks of adverse events and surgical complications increase for emergency cases. As such, access to better information about the effectiveness and timeliness of interventions is needed. Although respondents held anxieties about treatment, particularly invasive or surgical treatments, fewer choices were driven by emotional and lifestyle factors unrelated to ‘effectiveness’, such as fear or ease of treatment.
Clinical and biochemical study of 28 patients with mucopolysaccharidosis type VI
Authors: Azevedo ACMM , Schwartz IV , Kalakun L , Brustolin S , Burin MG , Beheregaray APC , Leistner S , Giugliani C , Rosa M , Barrios P , Marinho D , Esteves P , Valadares E , Boy R , Horovitz D , Mabe P , Da Silva LCS , De Souza ICN , Ribeiro M , Martins AM , Palhares D , Kim CA , Giugliani R
Published: August 2004

This paper presents data collected by a Brazilian center in a multinational multicenter observational study of patients with mucopolysaccharidosis type VI (MPS VI), aiming at determining the epidemiological, clinical, and biochemical profile of these patients. Twenty‐eight south‐American patients with MPS VI were evaluated through medical interview, physical exam, echocardiogram, electrocardiogram, ophthalmologic evaluation, quantification of glycosaminoglycans (GAGs) in urine, and measurement of the activity of N‐acetylgalactosamine‐4‐sulfatase (ARSB) in leukocytes. 92.9% of patients were Brazilian. Mean age at diagnosis and at evaluation was 48.4 months and 97.1 months, respectively. 88% of patients had onset of symptomatology before the age of 36 months. Consanguinity was reported by 27% of the families. Mean weight and height at birth were 3.481 kg and 51.3 cm, respectively. The most frequently reported clinical manifestations were short stature, corneal clouding, coarse facial features, joint contractures, and claw hands. All patients presented with echocardiogram changes as well as corneal clouding. Mean ARSB activity in leukocytes was 5.4 nmoles/h/mg protein (reference values: 72–174), and urinary excretion of GAGs was on average 7.9 times higher than normal. The number of clinical manifestations did not show a significant correlation with the levels of urinary GAGs nor with the ARSB activity. Also, no significant correlation was found between the levels of urinary GAGs and the ARSB activity. It was concluded that MPS VI has high morbidity and that, when compared with data published in the literature, patients in our study were diagnosed later and presented with a higher frequency of cardiological findings.
A previously undescribed frameshift deletion mutation of HFE (c.del277; G93fs) associated with hemochromatosis and iron overload in a C282Y heterozygote
Authors: Barton JC , West C , Lee PL , Beutler E
Published: August 2004

A 62‐year‐old white man with a hemochromatosis phenotype was found to be heterozygous for the C282Y mutation of the HFE gene. The H63D and S65C mutations of HFE were not present. As most C282Y heterozygotes do not develop a hemochromatosis phenotype, the coding region of the patient's HFE gene was sequenced and a previously undescribed frameshift mutation was identified in exon 2 (c.del277; G93fs) that resulted in a premature stop‐codon. There were no coding region mutations of the ferroportin gene (FPN1). We performed human leukocyte antigen (HLA) typing of the patient and his brother who was heterozygous for the C282Y HFE mutation unassociated with a hemochromatosis phenotype. They shared only C282Y and the HLA haplotype A*03, B*14; hence, the c.del277 mutation was linked to the HLA haplotype A*02, B*44 and therefore not on the same chromosome as the C282Y mutation. Thus, the present patient's only intact HFE protein is C282Y, and this may explain his hemochromatosis phenotype.
TP63 mutation and clefting modifier genes in an EEC syndrome family
Authors: Ray AK , Marazita ML , Pathak R , Beever CL , Cooper ME , Goldstein T , Shaw DF , Field LL
Published: August 2004

Autosomal dominant EEC syndrome consists of ectrodactyly, ectodermal dysplasia, and cleft lip with or without cleft palate (CL/P). We investigated an EEC kindred with 10 affected persons in three generations in order to map the causative mutation in this family and to map modifier genes that contribute to the expression of facial clefting in the phenotype. DNA from 15 family members was genotyped for 388 genome screen markers. Analysis revealed maximal linkage between EEC and chromosome 3q27, which contains a known EEC gene – tumor protein 63 (TP63). Sequencing showed a CGT→TGT missense mutation (R280C) in exon 7, previously reported to cause EEC in four families, and ectrodactyly alone (split hand‐foot malformation) in one sporadic case and one large kindred. Analysis of the clefting phenotype in this EEC family demonstrated maximal linkage to two regions on chromosomes 4q and 14, which multiple studies have implicated in non‐syndromic CL/P. In conclusion, this study demonstrates that the mutation of TP63 is the major (Mendelian) EEC gene in this kindred and suggests that additional minor modifying genes which predispose to non‐syndromic CL/P could also contribute to the expression of the clefting component of the syndrome in this family.
Cholesteryl ester transfer protein promoter single‐nucleotide polymorphisms in Sp1‐binding sites affect transcription and are associated with high‐density lipoprotein cholesterol
Authors: Thompson JF , Lloyd DB , Lira ME , Milos PM
Published: August 2004

Genetic variation in the human cholesteryl ester transfer protein (CETP) promoter has been shown to be associated with high‐density lipoprotein cholesterol (HDL‐C) levels and cardiovascular disease. Some of this variation occurs in Sp1/Sp3 binding sites in the proximal promoter. We find that both the known promoter polymorphism at −629 and the previously uncharacterized polymorphism at −38 are associated with HDL‐C levels in vivo and affect transcription in vitro. While the −629 polymorphism is common in all ethnic groups, the −38 polymorphism is found at significant levels (6.4%) only among African Americans. Those homozygous for the less common −38A allele have higher HDL‐C levels than those with the more frequent −38G allele. This association was found in a population of African Americans at risk of cardiovascular disease and then replicated in a different population chosen from among patients with extremes of HDL‐C. When studied in vitro, the most transcriptionally active allele (−629C/−38G) yields 51% more reporter protein than the least active allele (−629A/−38A) in HepG2 cells. These transcriptional effects reflect the projected impact of increased CETP expression on HDL‐C phenotypes seen in vivo.
Genetic analysis of lethal congenital malformations causing perinatal mortality at Nizwa Hospital, Oman
Authors: Sawardekar KP
Published: August 2004

An analysis of lethal congenital malformations (LCM) – which contributed to perinatal mortality at Nizwa Hospital, Oman – is presented for a 10‐year period from January 1993 through December 2002. Single gene, chromosomal or multifactorial inheritance accounted for 86.1% of the cases. LCM‐related perinatal deaths were higher in Omani, compared to those in non‐Omani births (p < 0.001). This could possibly be attributed to high consanguinity, low female literacy and high fertility rates in the Omani population. Forty per cent of LCM‐related perinatal deaths in the study had potential options for prevention. Integration of a community‐based genetic service into the existing health‐care delivery system is suggested.
Management strategies for gastroesophageal reflux disease
Authors: BAK YOUNG‐TAE
Published: August 2004

Abstract  In the treatment of gastroesophageal reflux disease (GERD), the most effective treatment option is the use of proton pump inhibitor (PPI), which minimizes the effect of gastric acid on the distal esophagus. Both the step‐up and step‐down treatment strategies have advantages and disadvantages. Most physicians would like to choose the step‐down therapy rather than the step‐up therapy. The ‘No‐step’ PPI therapy (i.e. continuous PPI therapy) is another relevant option. After an initial remission, long‐term PPI therapy is an appropriate form of maintenance therapy in many patients.

As a treatment plan for non‐erosive reflux disease, a standard dose of PPI for 4–8 weeks followed by either the step‐down strategy or the on‐demand treatment strategy is acceptable. When treating erosive esophagitis, PPI is better than H2 receptor blockers in healing mucosal breaks and relieving symptoms. Long‐term maintenance PPI therapy is reported to be very effective in maintaining the remission of reflux esophagitis for up to 5 years. On‐demand PPI is also another good option for a maintenance therapy in erosive esophagitis. In Barrett's esophagus, symptoms seem to be well‐controlled with PPIs. Unfortunately, however, PPIs have no effect on the shortening of Barrett's esophagus or in preventing the progression to dysplasia and adenocarcinoma.

In summary, after reviewing existing guidelines a rather simple guideline on the management of GERD is suggested – PPI should be given for 4–8 weeks followed by either on‐demand or maintenance PPI therapy according to the clinical severity.
Definition and diagnosis of gastroesophageal reflux disease
Authors: WONG WAI‐MAN , WONG BENJAMIN CHUN‐YU
Published: August 2004

Abstract  With widespread treatment of Helicobacter pylori infection, and that peptic ulcer diseases are no longer considered a chronic illness and are declining in most parts of the world, gastroesophageal reflux disease (GERD) predominates the upper gastrointestinal disease spectrum. GERD is a well‐defined condition. More innovative research in GERD in recent years led us to new conceptual frameworks on pathogenesis and novel diagnostic tests. The proton pump inhibitor test has evolved to become the diagnostic test of choice for the investigation of patients with the disease spectrum of GERD. Multi‐channel intraluminal impedance with pH sensor allows the detection of pH episodes irrespective of their pH values (acid and nonacid reflux). It is useful to measure gastroesophageal reflux in the postprandial period, and in patients with persistent symptoms while on therapy and those with atypical symptoms.
Extraesophageal and atypical manifestations of GERD
Authors: WONG WAI‐MAN , FASS RONNIE
Published: August 2004

Abstract  Extraesophageal manifestations of gastroesophageal reflux disease (GERD) are essentially complications of GERD that primarily involve organs that are in proximity to the esophagus. Non‐cardiac chest pain (NCCP) is an atypical manifestation of GERD, because symptoms originate in essence from the esophagus. In both atypical and extraesophageal manifestation of GERD frequent heartburn is uncommon and lack of GERD symptoms is not unusual. Esophageal mucosal injury is rarely present making upper endoscopy a low‐yield procedure in both conditions. While association with GERD has been commonly reported, the extent of causality remains unknown. In NCCP, the usefulness of the proton pump inhibitor (PPI) test in diagnosing GERD‐related NCCP has been established. Similar value in extraesophageal manifestations of GERD has been proposed, but rarely studied. While treatment of extraesophageal manifestations of GERD remains a challenge, PPIs in at least double the standard dose, should be considered for the initial therapy. Properly designed therapeutic studies are still lacking as well as the exact role of antireflux surgery in this patient population.
Clinical practice pattern of gastroenterologists, primary care physicians, and otolaryngologists for the management of GERD in the Asia–Pacific region: The FAST survey
Authors: WONG WAI‐MAN , LIM PAUL , WONG BENJAMIN CHUN‐YU
Published: August 2004

Background and Aim:  The clinical practice patterns of gastroenterologists, primary care physicians, and otolaryngologists for the management of gastroesophageal reflux disease (GERD) in the Asia–Pacific region are unknown. Respective medical professionals from seven countries of the Asia–Pacific region were invited to participate in a questionnaire survey.

Methods:  Five hundred and eighty‐five medical professionals (221 gastroenterologists, 205 primary care physicians, and 159 otolaryngologists) participated in the survey. Three different versions of the questionnaire were used for each medical specialty. The questionnaire inquired about the prevalence, diagnosis, and management strategy of GERD for the respective medical professionals.

Results:  All three medical specialties agreed that GERD is increasing and the most common diagnostic strategy used for patients with mild symptoms of GERD was ‘treat before testing’. Gastroenterologists preferred ‘test before treating’ for patients with severe symptoms, but primary care physicians and otolaryngologists preferred ‘treat before testing’ for severe cases. Most medical professionals had heard of the proton pump inhibitor (PPI) empiric trial but only 33–52% of them had used it before. For mild and severe cases of GERD, gastroenterologists preferred the use of PPIs, while primary care physicians and otolaryngologists reserved PPIs for severe cases of GERD. Gastroenterologists preferred ‘step down’ approach, while the other two specialties preferred ‘step‐up’ approach for the management of GERD. The preferred maintenance strategy for GERD was daily maintenance therapy among the three medical specialties.

Conclusion:  A clear evidence‐based management strategy for the management of GERD is warranted in the Asia–Pacific region.
Changing epidemiology of gastroesophageal reflux disease in the Asian–Pacific region: An overview
Authors: GOH KL
Published: August 2004

Abstract  Gastroesophageal reflux disease (GERD) is a common disease in the West, which now appears to be also increasing in prevalence in the Asian Pacific region. The reasons for this changing epidemiology are two‐fold: an increased awareness among doctors and patients, and/or a true increase in the prevalence of the disease. Prevalence rates of reflux esophagitis (RE) of up to 16% and prevalence of GERD symptoms of up to 9% have been reported in the Asian population. However, the frequency of strictures and Barrett's esophagus remain very low. Non‐erosive reflux disease (NERD) appears to be the most common form of GERD among Asian patients accounting for 50–70% of cases with GERD. Among Asian patients differences can also be discerned among different ethnic groups. For example, in Malaysia where a multiracial society exists, RE is significantly more common among Indians compared to Chinese and Malays whereas NERD is more frequently seen in the Indian and Malays compared to the Chinese. The reasons for these differences are not known but may indicate both genetic factors and environmental factors peculiar to the particular racial group. GERD has also been increasing in the region demonstrating a time‐lag phenomenon compared to the West. Differing predisposition to GERD among different ethnic groups would mean that such an increase would be more prominent among certain racial groups.
Review Article: Efficacy and safety of rabeprazole in treating gastroesophageal reflux disease
Authors: LIM PWY , GOH KL
Published: August 2004

Abstract  Proton pump inhibitors (PPI) are the mainstay of gastroesophageal reflux disease (GERD) treatment. They have a good efficacy and short‐ and long‐term safety profile. Rabeprazole is a second generation PPI with rapid onset of action that quickly relieves symptoms of GERD. Rabeprazole consistently and profoundly inhibits gastric acid secretion. Its metabolism is less dependent on CYP4502C19 system and therefore is the least affected among all PPIs by CYP4502C19 genetic polymorphism. Recent studies have also indicated that rabeprazole on‐demand is cost effective in preventing non‐erosive reflux disease (NERD) symptom relapse.
Overexpression of the acidic dehydrin WCOR410 improves freezing tolerance in transgenic strawberry leaves
Authors: Houde Mario , Dallaire Sylvain , N'Dong Daniel , Sarhan Fathey
Published: August 2004

Progress in freezing tolerance (FT) improvement through plant breeding approaches has met with little success in the last 50 years. Engineering plants for greater FT through plant transformation is one possible way to reduce the damage caused by freezing. Here, we report an improvement of the selection procedure and the transfer of the wheat Wcor410a acidic dehydrin gene in strawberry. The encoded protein has previously been shown to be associated with the plasma membrane, and its level of accumulation has been correlated with the degree of FT in different wheat genotypes. The WCOR410 protein was expressed in transgenic strawberry at a level comparable with that in cold‐acclimated wheat. Freezing tests showed that cold‐acclimated transgenic strawberry leaves had a 5 °C improvement of FT over wild‐type or transformed leaves not expressing the WCOR410 protein. However, no difference in FT was found between the different plants under non‐acclimated conditions, suggesting that the WCOR410 protein needs to be activated by another factor induced during cold acclimation. These data demonstrate that the WCOR410 protein prevents membrane injury and greatly improves FT in leaves of transgenic strawberry. A better understanding of the limiting factors allowing its activation may open up the way for engineering FT in different plant organs, and may find applications for the cryopreservation of human tissues and organs.
Increased zinc content in transplastomic tobacco plants expressing a polyhistidine‐tagged Rubisco large subunit
Authors: Rumeau Dominique , Bécuwe‐Linka Noëlle , Beyly Audrey , Carrier Patrick , Cuiné Stéphan , Genty Bernard , Medgyesy Peter , Horvath Eva , Peltier Gilles
Published: August 2004

Rubisco is a hexadecameric enzyme composed of two subunits: a small subunit (SSU) encoded by a nuclear gene (rbcS), and a large subunit (LSU) encoded by a plastid gene (rbcL). Due to its high abundance, Rubisco represents an interesting target to express peptides or small proteins as fusion products at high levels. In an attempt to modify the plant metal content, a polyhistidine sequence was fused to Rubisco, the most abundant protein of plants. Plastid transformation was used to express a polyhistidine (6×) fused to the C‐terminal extremity of the tobacco LSU. Transplastomic tobacco plants were generated by cotransformation of polyethylene glycol‐treated protoplasts using two vectors: one containing the 16SrDNA marker gene, conferring spectinomycin resistance, and the other the polyhistidine‐tagged rbcL gene. Homoplasmic plants containing L8‐(His)6S8 as a single enzyme species were obtained. These plants contained normal Rubisco amounts and activity and displayed normal photosynthetic properties and growth. Interestingly, transplastomic plants accumulated higher zinc amounts than the wild‐type when grown on zinc‐enriched media. The highest zinc increase observed exceeded the estimated chelating ability of the polyhistidine sequence, indicating a perturbation in intracellular zinc homeostasis. We discuss the possibility of using Rubisco to express foreign peptides as fusion products and to confer new properties to higher plants.
DEAD‐box RNA helicases in Arabidopsis thaliana: establishing a link between quantitative expression, gene structure and evolution of a family of genes
Authors: Mingam Annaïck , Toffano‐Nioche Claire , Brunaud Véronique , Boudet Nathalie , Kreis Martin , Lecharny Alain
Published: August 2004

The model genome of Arabidopsis thaliana contains a DEAD‐box RNA helicase family (RH) of 58 members, i.e. almost twice as many as in the animal or yeast genomes. Transcript profiling using real‐time quantitative polymerase chain reaction (PCR) has been obtained for 20 AtRHs from nine different organs. Two AtRHs exhibited plant‐specific profiles associated with photosynthetic and sink organs. The other 18 AtRHs had the same transcript profile, and the levels of transcription of these ‘housekeeping’AtRHs were under strict quantitative control over a large range of values. Transcript levels may be very different between the most recently duplicated genes. The master regulatory element in the definition of the transcript level is the simultaneous presence of a TATA‐box and an intron in the 5′ untranslated region (UTR). There is a positive and highly significant correlation between the size of the 5′ UTR intron and the transcription level, as long as a characteristic TATA‐box is present. Our work on the housekeeping AtRHs suggests a scenario for the evolution of duplicated genes, leading to both highly and poorly transcribed genes in the same terminal branch of the phylogenetic tree. The general evolutionary drive of the AtRH family, after duplication of a highly transcribed ancestral AtRH, was towards an alteration of the transcriptional activity of the divergent duplicates through successive events of suppression of the TATA‐box and/or the 5′ UTR intron.
Spider dragline silk proteins in transgenic tobacco leaves: accumulation and field production
Authors: Menassa Rima , Zhu Hong , Karatzas Costas N. , Lazaris Anthoula , Richman Alex , Brandle Jim
Published: August 2004

Spider dragline silk is a unique biomaterial and represents nature's strongest known fibre. As it is almost as strong as many commercial synthetic fibres, it is suitable for use in many industrial and medical applications. The prerequisite for such a widespread use is the cost‐effective production in sufficient quantities for commercial fibre manufacturing. Agricultural biotechnology and the production of recombinant dragline silk proteins in transgenic plants offer the potential for low‐cost, large‐scale production. The purpose of this work was to examine the feasibility of producing the two protein components of dragline silk (MaSp1 and MaSp2) from Nephila clavipes in transgenic tobacco. Two different promoters, the enhanced CaMV 35S promoter (Kay et al., 1987) and a new tobacco cryptic constitutive promoter, tCUP (Foster et al., 1999) were used, in conjunction with a plant secretory signal (PR1b), a translational enhancer (alfalfa mosaic virus, AMV) and an endoplasmic reticulum (ER) retention signal (KDEL), to express the MaSp1 and MaSp2 genes in the leaves of transgenic plants. Both genes expressed successfully and recombinant protein accumulated in transgenic plants grown in both greenhouse and field trials.
Specific cysteine protease inhibitors act as deterrents of western flower thrips, Frankliniella occidentalis (Pergande), in transgenic potato
Authors: Outchkourov Nikolay S. , De Kogel Willem Jan , Schuurman‐de Bruin Antje , Abrahamson Magnus , Jongsma Maarten A.
Published: August 2004

In this study, the effects of the accumulation of cysteine protease inhibitors on the food preferences of adult female western flower thrips, Frankliniella occidentalis (Pergande), were investigated. Representative members of the cystatin and thyropin gene families (stefin A, cystatin C, kininogen domain 3 and equistatin) were expressed in potato (Solanum tuberosum) cv. Impala, Kondor and Line V plants. In choice assays, a strong time‐ and concentration‐dependent deterrence from plants expressing stefin A and equistatin was observed. Cystatin C and kininogen domain 3 were not found to be active. All tested inhibitors were equally or more active than stefin A at inhibiting the proteolytic activity of thrips, but, in contrast with stefin A, they were all expressed in potato as partially degraded proteins. The resistance of cysteine protease inhibitors against degradation in planta by endogenous plant proteases may therefore be relevant in explaining the observed differences in the deterrence of thrips. The results demonstrate that, when given a choice, western flower thrips will select plants with low levels of certain cysteine protease inhibitors. The novel implications of the defensive role of plant cysteine protease inhibitors as both deterrents and antimetabolic proteins are discussed.
Over‐expression of a transcription factor regulating ABA‐responsive gene expression confers multiple stress tolerance
Authors: Kim Jin‐Baek , Kang Jung‐Youn , Kim Soo Young
Published: August 2004

Unfavourable environmental conditions, such as drought, freezing and high salinity, are major limiting factors of plant productivity. Plants perceive and respond adaptively to such ‘abiotic stress’ conditions, and the adaptive process is controlled mainly by the phytohormone, abscisic acid (ABA). The hormone, whose level increases under various stress conditions, functions as a signal to trigger adaptive responses that include changes in gene expression patterns. We have recently reported transcription factors that regulate the ABA‐responsive gene expression. As ABA mediates adaptation to several common abiotic stresses, we investigated whether the transcription factors are involved in various stress responses. Here, we report that over‐expression of ABF3, one of the factors, confers tolerance to chilling, freezing, high temperature and oxidative stress in addition to drought. Our results indicate that ABF3 is involved in multiple stress responses, and that it may be a useful genetic resource for the engineering of plant stress tolerance.
Personal Services in the Post‐industrial Economy: Adding Nonprofits to the Welfare Mix
Authors: Graefe Peter
Published: August 2004

This article develops linkages between two separate fields of research, namely work on post‐industrial welfare states, and work on nonprofit organizations. It pays particular attention to the emphasis on personal services and the “cost disease” hypothesis found in the former, which places strong constraints on improving pay and job quality in the nonprofit sector. At the same time, it argues that the post‐industrial welfare states literature, despite its emphasis on personal services, has largely ignored the significant and growing role of nonprofits in delivering these services, and thus the potential of these organizations to shape their relevant labour markets. This poses the question about the relative weight of productivity‐related wage restraints in personal services versus the capacity for agency by nonprofits. The final section of the paper engages in a critique of the “cost disease” hypothesis to suggest that space exists to improve pay and job quality in nonprofit personal services, despite productivity‐related constraints.
Human Motivation and Professional Practice: of Knights, Knaves and Social Workers
Authors: Martin Graham P. , Phelps Kay , Katbamna Savita
Published: August 2004

Efforts to improve the efficiency and responsiveness of public services by harnessing the self‐interest of professionals in state agencies have been widely debated in the recent literature on welfare state reform. In the context of social services, one way in which British policy‐makers have sought to effect such changes has been through the “new community care” of the 1990 NHS and Community Care Act. Key to this is the concept of care management, in which the identification of needs and the provision of services are separated, purportedly with a view to improving advocacy, choice and quality for service users. This paper uses data from a wide‐ranging qualitative study of access to social care for older people to examine the success of the policy in these terms, with specific reference to its attempts to harness the rational self‐interest of professionals. While care management removes one potential conflict of interests by separating commissioning and provision, the responsibility of social care professionals to comply with organizational priorities conflicts with their role of advocacy for their clients, a tension rendered all the more problematic by the perceived inadequacy of funding. Moreover, the bureaucracy of the care management process itself further negates the approach's supposedly client‐centred ethos.