bluuebunny/crossref_metadata_2025 huggingface dataset:
Large hiatal hernia in patients with iron deficiency anaemia: a prospective study on prevalence and treatment
Authors: Panzuto F. , Di Giulio E. , Capurso G. , Baccini F. , D'Ambra G. , Delle Fave G. , Annibale B.
Published: March 2004

Background : Although large hiatal hernia may cause bleeding from Cameron erosions, its role in iron deficiency anaemia has been debated, and no data are available on the treatment of these patients with proton pump inhibitors.

Aims : To determine the prevalence of large hiatal hernia in out‐patients with iron deficiency anaemia and the role of proton pump inhibitors in the prevention of recurrence of anaemia.

Methods : Two hundred and twenty‐eight out‐patients underwent upper/lower endoscopy. Those with large hiatal hernia were given an oesophagogram, discontinued iron supplementation and received proton pump inhibitor treatment with (group 1) or without (group 2) surgery. Anaemia was re‐assessed during 1 year of follow‐up.

Results : Large hiatal hernia was the likely cause of anaemia in 21 patients (9.2%). The median haemoglobin and ferritin values at the diagnosis of anaemia were 7.9 g/dL and 6 µg/L, respectively. Cameron erosions were found in 33% of patients. Ten and eleven patients were included in groups 1 and 2, respectively. Haemoglobin values were 13.8 g/dL and 13.4 g/dL at 3 months of follow‐up, and 13.4 g/dL and 13.8 g/dL at 1 year of follow‐up, in groups 1 and 2, respectively.

Conclusions : Large hiatal hernia may cause iron deficiency anaemia, even without Cameron erosions. Surgery in combination with proton pump inhibitor therapy is no better than proton pump inhibitor therapy alone in preventing the recurrence of anaemia.
The prevalence and clinical course of functional dyspepsia
Authors: El‐Serag H. B. , Talley N. J.
Published: March 2004

Aim : To examine the prevalence of functional dyspepsia in the general population, and to evaluate the natural history/clinical course of patients with functional dyspepsia.

Methods : Full‐length published manuscripts during 1980–2002 were included if: (i) participants had uninvestigated or functional dyspepsia; (ii) dyspepsia was defined; (iii) for prevalence, population‐based samples were evaluated; (iv) for prognosis, the total number of the inception cohort and the total number of individuals available at the end of follow‐up were reported.

Results : Twenty‐two studies (1976–2002) that examined the prevalence of dyspepsia fulfilled the inclusion and exclusion criteria; 17 studies examined more than 1000 participants, but only two studies provided information sufficient to calculate the prevalence of functional dyspepsia (11.5–14.7%). The prevalence of uninvestigated dyspepsia was in the range 10–40%. When the definition of dyspepsia was restricted to participants with upper abdominal pain, irrespective of the presence of heartburn or acid regurgitation, the prevalence rate estimate was 5–12%. Thirteen studies examined the clinical course of functional dyspepsia (seven retrospective and six prospective). Sample sizes were small (n = 35–209). A follow‐up ascertainment of symptoms amongst individuals in the original cohorts was obtained in 92.5–98.2% of prospective studies and in 67.7–82.2% of retrospective studies. The follow‐up duration was in the range 1.5–10 years for prospective studies and 5–27 years for retrospective studies; the median follow‐up duration for all studies was approximately 5 years. A variable prognosis was reported. An outcome of symptom improvement or becoming asymptomatic was reported in at least one‐half of patients in 10 of the 13 studies, and in at least two‐thirds of patients in six of the 13 studies. Prognostic factors were inconsistent and, in general, poorly described.

Conclusions : Functional dyspepsia is prevalent world‐wide, but the prognosis remains poorly defined. There is a need for population‐based studies to examine the prevalence and clinical course of documented functional dyspepsia.
Helicobacter pylori eradication therapy vs. antisecretory non‐eradication therapy for the prevention of recurrent bleeding from peptic ulcer
Authors: Gisbert J. P. , Khorrami S. , Carballo F. , Calvet X. , Gene E. , Dominguez‐Muñoz E.
Published: March 2004

Aim : To perform a meta‐analysis comparing the efficacy of Helicobacter pylori eradication therapy vs. antisecretory non‐eradication therapy for the prevention of recurrent bleeding from peptic ulcer.

Methods : A search was made of the Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL and several congresses for controlled clinical trials comparing the efficacy of H. pylori eradication therapy vs. antisecretory non‐eradication therapy for the prevention of peptic ulcer re‐bleeding. Studies with all patients taking non‐steroidal anti‐inflammatory drugs were excluded. Extraction and quality assessment of the studies were performed by two reviewers.

Results : In the first meta‐analysis, the mean percentage of re‐bleeding in the H. pylori eradication therapy group was 4.5%, compared with 23.7% in the non‐eradication therapy group without long‐term antisecretory therapy [odds ratio, 0.18; 95% confidence interval (CI), 0.09–0.37; ‘number needed to treat’ (NNT), 5; 95% CI, 4–8]. In the second meta‐analysis, the re‐bleeding rate in the H. pylori eradication therapy group was 1.6%, compared with 5.6% in the non‐eradication therapy group with maintenance antisecretory therapy (odds ratio, 0.25; 95% CI, 0.08–0.76; NNT, 20; 95% CI, 12–100). When only patients with successful H. pylori eradication were included, the re‐bleeding rate was 1%.

Conclusions : The treatment of H. pylori infection is more effective than antisecretory non‐eradication therapy (with or without long‐term maintenance antisecretory treatment) in the prevention of recurrent bleeding from peptic ulcer. Consequently, all patients with peptic ulcer bleeding should be tested for H. pylori, and eradication therapy should be prescribed to infected patients.
Mucosal cytokine production during remission after resection for Crohn's disease and its relationship to future relapse
Authors: Yamamoto T. , Umegae S. , Kitagawa T. , Matsumoto K.
Published: March 2004

Aim : To examine whether mucosal cytokine production during remission after resection for Crohn's disease is a predictor of future relapse.

Methods : Thirty‐six patients who remained in remission after resection for terminal ileal or ileo‐caecal Crohn's disease were included. At enrolment, blood and mucosal (ileal and rectal biopsies) samples were collected. All patients were followed up regularly for 1 year after enrolment and the disease activity was assessed according to the Crohn's disease activity index.

Results : Twenty patients remained in remission and 16 patients relapsed during the 1‐year follow‐up. Interleukin‐1β, interleukin‐6 and tumour necrosis factor‐α levels in the ileal mucosa were significantly higher in relapsed patients than in patients in remission. These cytokine levels in the rectal mucosa were not associated with relapse. Conventional blood markers and plasma cytokine levels did not correlate with relapse. Amongst the clinical parameters, a younger age, short disease duration before operation and fistulating disease were risk factors for relapse. In multivariate analysis, only the ileal interleukin‐6 level was an independent significant predictor for relapse.

Conclusions : The interleukin‐6 level in the ileal mucosa during remission after resection for ileal or ileo‐caecal Crohn's disease is an independent significant predictor for future relapse.
Erythromycin for the treatment of chronic intestinal pseudo‐obstruction: description of six cases with a positive response
Authors: Emmanuel A. V. , Shand A. G. , Kamm M. A.
Published: March 2004

Background : Chronic intestinal pseudo‐obstruction, due to intestinal myopathy or neuropathy, is characterized by the signs and symptoms of intestinal obstruction in the absence of true obstruction. Episodes are resistant to medical therapy.

Aim : To determine the value of erythromycin treatment in chronic intestinal pseudo‐obstruction.

Methods : All patients with proven chronic intestinal pseudo‐obstruction treated with erythromycin were reviewed. Patients with symptomatic benefit are described in detail. Responders were compared with non‐responders to identify the factors associated with benefit.

Results : Fifteen consecutive patients (nine females; median age, 37 years; median follow‐up, 41 months) were treated with oral erythromycin, 1.5–2.0 g/day. Six patients (three primary visceral myopathy, two normal histology on light microscopy, one visceral myopathy secondary to scleroderma) responded, with decreased pain and vomiting, normalized bowel dysfunction and decreased episodes of ileus. Five of the six patients (83%) who responded to erythromycin were male, compared with two of the nine non‐responders (22%) (P = 0.04). Four of the six responders (67%) had histological or immunohistological visceral myopathy, compared with three of the nine patients (33%) who failed to respond. Responders were less likely than non‐responders to be taking long‐term opiates.

Conclusions : Erythromycin is effective for acute episodes of ileus and chronic symptoms in some patients with chronic intestinal pseudo‐obstruction.
A dynamic simulation model for powdery mildew epidemics on winter wheat*
Authors: Rossi V. , Giosuè S.
Published: March 2004

A system dynamic model for epidemics of Blumeria graminis (powdery mildew) on wheat was elaborated, based on the interaction between stages of the disease cycle, weather conditions and host characteristics. The model simulates the progress of disease severity, expressed as a percentage of powdered leaf area, on individual leaves, with a time step of one day, as a result of two processes: the growth of fungal colonies already present on the leaves and the appearance of new colonies. By means of mathematical equations, air temperature, vapour pressure deficit, rainfall and wind are used to calculate incubation, latency and sporulation periods, the growth of pathogen colonies, infection and spore survival. Effects of host susceptibility to infection, and of leaf position within the plant canopy, are also included. Model validation was carried out by comparing model outputs with the dynamics of epidemics observed on winter wheat grown at several locations in northern Italy (1991–98). Simulations were performed using meteorological data measured in standard meteorological stations. As there was good agreement between model outputs and actual disease severity, the model can be considered a satisfactory simulator of the effect of environmental conditions on the progress of powdery mildew epidemics.
Development and use of a forecasting model for Cydia pomonella*
Authors: Roubal C. , Rouzet J.
Published: March 2004

For more than 10 years, a forecasting model for Cydia pomonella in apple orchards, worked out by the French NPPO, has described the development of emergence cohorts in spring, and followed their development and descent, through the whole agricultural season. In homogeneous areas, this tool, still under development, can be used to define periods for effective treatment (ovicides, larvicides, mating disruption) and the tolerance for codling moth levels in various situations. Alternation of insecticides is provided for, so as to manage resistance phenomena. The reliability of the model is based on rigorous continuous biological checks on the forecasts made by the algorithm, on scientific surveillance by INRA and on regular collaboration between the advisers involved and the agrometeorological services. The model forms part of a wider decisional scheme, or expert system, in which the fruit grower and his adviser provide observations on the changes which cannot be provided by the model: installation of hail protection nets, night lights, fruit spreading. More parameters will be incorporated in future and the geographical validity of the model will be extended, particularly to more northerly areas.
Application of fuzzy logic for the simulation of Plasmopara viticola using agrometeorological variables*
Authors: Orlandini S. , Marta A. Dalla , D’Angelo I. , Genesio R.
Published: March 2004

A mechanistic model called PLASMO was developed earlier to simulate grapevine downy mildew (Plasmopara viticola) and has been applied in several viticultural areas of Italy since 1988 by the collaboration of several research institutions of Firenze. In this study, a new simulation model based on fuzzy logic has been developed for the same structure (biological cycle of P. viticola). This approach allows classical quantitative information to be used together with qualitative information. Vague concepts can also be handled. Agrometeorological data is used, with an hourly time step, starting from budbreak to the end of the growing season. Air temperature, relative humidity, rainfall and leaf wetness are required. The simulated processes are the growth of grapevine leaf area and the main phases of the biological cycle of the pathogen: incubation, sporulation, germination, spore survival and inoculation. The main epidemiological outputs are timing of infection events and disease intensity. The performance of the model is evaluated and the mechanistic and fuzzy logic approaches are compared.
A model estimating the risk of Fusarium head blight on wheat*
Authors: Rossi V. , Giosuè S. , Pattori E. , Spanna F. , Del Vecchio A.
Published: March 2004

A dynamic simulation model for the risk of Fusarium head blight on wheat was elaborated based on systems analysis. The model calculates a daily infection risk based on sporulation, spore dispersal and infection of host tissue of the four main species causing the disease (Gibberella zeae, Fusarium culmorum, Gibberella avenacea, Monographella nivalis). Spore yield and dispersal are calculated as functions of temperature, rainfall and relative humidity, while the main factors affecting the infection rate are temperature, wetness and the host growth stage. The model also calculates a risk for mycotoxin production by G. zeae and F. culmorum in the infected head tissue. First validations against field data, collected in some wheat‐growing areas in northern Italy and not used in model elaboration, produced satisfactory results.
Estimating the potential development of Diaporthe helianthi epidemics in Italy*
Authors: Battilani P. , Rossi V. , Girometta B. , Delos M. , Rouzet J. , André N. , Esposito S.
Published: March 2004

Diaporthe helianthi is the causal agent of a severe sunflower disease but, in Italy, disease outbreaks are sporadic with no significant losses. The present work investigates the role of meteorological conditions on the potential development of D. helianthi epidemics in Italy, using the French model Asphodel, which simulates the effect of air temperature, relative humidity and rainfall on ascospore maturation and dispersal, infection establishment, disease onset and severity during the period of host susceptibility. Meteorological data measured in eight stations distributed from north to south Italy, over a 5‐year period (1995–99), was used as model input. Results showed that meteorological conditions in Italy are frequently favourable for D. helianthi infections on sunflower, and severe epidemics are possible. Therefore, climatic conditions are not a limiting factor for disease development in the Italian sunflower‐growing areas. The lack of disease epidemics in Italy may be related to differences in the pathogen populations compared with the French ones.
Early warning system for grapevine in South Moravia (Czech Republic)*
Authors: Hrubý R.
Published: March 2004

South Moravia is a very important agricultural region with 12 000 ha of fruiting vineyards. The forecasting and warning service for vineyards in this region was created in 2000 as a PHARE Project which was part of a large‐scale programme ‘Cross‐border Cooperation between Czech Republic and Austria’. The aim of the project is ecological wine production. Forty automatic meteorological stations, located in the target area, create a network linked to a central computer. Meteorological data forecasts the development of Plasmopara viticola, Erysiphe necator and Botryotinia fuckeliana on bunches. The output can be used by growers to determine the time of fungicide application. The experiences and possibilities of improvement of the warning service are presented.
VIPS – a web‐based decision support system for farmers, agricultural extension services and agricultural scientists*
Authors: Folkedal A. , Brevig C.
Published: March 2004

In Norway, the new web‐based warning system called VIPS aims to give open access to all the information needed for farmers to reduce their reliance on plant protection products. VIPS calculates warnings for 70 weather stations for several pests in selected fruits, vegetables and cereals. Registered users may adjust the climatic data used in the models and record field observations to get private warnings. They may also use the system to record farm practices. VIPS is unique in several aspects: (1) it has a general user interface for all crops and pests, and the user gets a quick overview of which pests to look out for; (2) all warnings are site‐specific and linked to an authorized weather station which supplies validated meteorological data. The extension service supplies the validated biological data necessary to run the models; (3) the presentation is layered under the weather stations of each county. The first level gives information of danger (red), possible danger (yellow) and no danger (green) for each model (past 5 days/coming 5 days). The next three levels give information of the specific model, historical data and exact values of the input parameters used in the models for the calculations.
Agrogis: a computer‐based program for collecting information on pests of plants in Poland*
Authors: Wójtowicz A.
Published: March 2004

A computer system Agrogis has been developed to record information on pest infestation of plants in different regions of Poland. Data can be entered manually or from disks, and can be displayed in the form of charts and maps. Agrogis will be made available on the Internet.
Bio‐economic modelling of potato brown rot in the Netherlands*
Authors: Breukers A. , Oude Lansink A. , Van Der Werf W. , Huirne R.
Published: March 2004

A research project is being undertaken to design a bio‐economic model of potato brown rot (Ralstonia solanacearum) in the Netherlands. The first part of the project consists of an analysis of the past and current brown rot policy for its effectiveness and costs. Then, a stochastic, bio‐economic model will be designed that shows the relationship between the costs of control measures and their effect on the probability of brown rot. This model will eventually be used to determine optimal control strategies and to make recommendations for improvement of the Dutch brown rot policy.
proPlant expert.com – an online consultation system on crop protection in cereals, rape, potatoes and sugarbeet*
Authors: Newe M. , Meier H. , Johnen A. , Volk T.
Published: March 2004

The internet‐based system proPlant expert.com assists farmers in making field‐specific decisions on fungicide and growth regulator application in cereals, insecticide and growth regulator application in rape, and fungicide application in potatoes and sugarbeet. Any consultation is based on both agricultural data and weather reports drawn from official meteorological services. Together with information on the infestation level, the system processes this data to develop a recommendation on the application of a specific plant protection product, if necessary. Farmers and consultancies have been using the service in Germany and other European countries since 2001. Before starting the service in other countries, parts of the software had to be altered to meet the specific requirements of our partners outside Germany.
A web‐based decision support system for integrated management of weeds in cereals and sugarbeet*
Authors: Rydahl P.
Published: March 2004

A Danish decision support system (DSS) named Crop Protection Online (CPO) for integrated management of weeds in cereals and beet has been developed during the past 20 years. CPO is based on a model that runs in three main steps: model step 1 quantifies the level of weed control needed on a field level, model step 2 selects candidate herbicides and calculates dose rates to meet the need, and model step 3 calculates tank mixtures of herbicides with two to four mixing components, if advantageous. CPO has been developed in cereals and beet, and various prototype versions have been validated in 1679 field tests. CPO secured yield potentials, and the level of residual weeds was not increased when compared with reference treatments. The potential of CPO to reduce herbicide use has been observed in all model crops, but the potential was greatest in cereals. In spring cereal field trials highly infested with weeds, the present version of CPO suggested 35% of one full herbicide dose on average and in winter cereals CPO suggested 44% on average of one full dose. The results from validation trials demonstrate that CPO is capable of suggesting robust treatment options with a low input of herbicides. The system architecture of CPO has been exported to Poland and the Baltic countries, and the system is expected to be suitable for export to other countries too.
Decision support systems used in the Netherlands for reduction in the input of active substances in agriculture
Authors: Bouma E.
Published: March 2004

Since the middle of the 1980s, Dutch farmers have been using decision support systems (DSS) as an aid in the control of pests. This started with EPIPRE, then weather‐related potato blight warning systems were developed (Prophy and Plant‐Plus). In the 1990s, many weather‐based DSS were developed against pests of orchards, flower bulbs, arable crops and field‐produced vegetables. Also, a DSS was developed to predict and check the effect of meteorological conditions on the effectiveness of application timing of plant protection products (GEWIS). The use of these systems resulted in more sustainable crop protection: sustainable because the use of DSS led to a lower risk of crop damage and, in many cases, to a lower input of active substances, by optimization of the product and dose to actual phytosanitary and meteorological conditions. The use of GEWIS to ensure application at the right time of day further reduced the input of active substances and increased efficacy.
The Pacific Pest List Database for agricultural trade facilitation
Authors: Vernon R.
Published: March 2004

The Pest List Database for the Pacific is a user‐friendly database that provides information on agricultural pest occurrences within a country as required to facilitate trade in terms of the International Plant Protection Convention and International Standards For Phytosanitary Measures. Its main outputs are: (a) a pest list for any specified crop intended for export and (b) a list of pest incursions detected on imported goods from any selected country. The system is designed for use by the 22 Pacific Island countries and territories that the Secretariat of the Pacific Community serves and is so far installed in five countries with a new one being delivered every 3–4 months. It is typically delivered with a few thousand known pest occurrence records of that country, and look‐up lists of several thousand Pacific pests and a few hundred crops.
User interfaces and system architecture of a web‐based decision support system for integrated pest management in cereals*
Authors: Rydahl P. , Hagelskjær L. , Pedersen L. , Bøjer O. Q.
Published: March 2004

A Danish decision support system (DSS) on integrated pest management (including pathogens and weeds) has been developed during the past 20 years. This DSS is distributed as an integrated part of the ‘Danish Integrated Farm Management System’, which is a PC program, of which the plant protection module presently has about 2500 subscribers in Denmark. This program has been designed to propose relevant options for treatment with plant protection products according to observations from a field inspection. The new object‐oriented web‐based system architecture of this DSS was developed in 2001. This allows local (national) adaptation of the DSS in terms of language, crops, pests, products and features. Model complexity and DSS algorithms can also be adjusted to local conditions. The system has been implemented in a relational database structure (Microsoft SQL Server) and a dynamic web application (Java and Jscript in Active Server Pages on an Internet Information Server). The system architecture has been designed with emphasis on a high level of flexibility for future adjustments due to agronomic and legal requirements. The DSS models have been linked to a pest identification module and to a comprehensive database on label information on plant protection products.
Image analysis for the identification of the quarantine pest Tilletia indica*
Authors: Chesmore D. , Bernard T. , Inman A. J. , Bowyer R. J.
Published: March 2004

Diagnosis of the teliospores of Tilletia indica (Karnal bunt) detected in wash tests is complicated by the fact that wheat grain can be contaminated by ‘look‐alike’ species, namely Tilletia walkeri (ryegrass bunt) and Tilletia horrida (rice smut). Although morphological diagnosis is possible when there are relatively large numbers of teliospores present, it is difficult with only a few spores as there are significant overlaps in the characteristics of each species. Molecular methods can confirm presumptive identifications, but these take 2–3 weeks. Image analysis offers the potential for more rapid confirmation. An image analysis system was developed for use on bleached spores. Bleaching spores reveals additional morphological characters (spore profile and spore wall layers) that may be used in an image analysis system to discriminate species. The image‐processing software automatically locates spores on a given image and calculates perimeter, surface area, number of spines and spine size, maximum and minimum ray radius, aspect ratio and roundness. Principal components analysis (PCA) is performed on the parameters to obtain a linear separation of spore species. Accuracy of 97% in separating T. indica and T. walkeri has been achieved in preliminary tests using PCA, but further evaluation is required.
Computer‐aided information systems of the Lithuanian NPPO*
Authors: Bernotas S.
Published: March 2004

The computerized information system of the Lithuanian NPPO connects all its subdivisions into a single network, including the Central Authority, the Regional Plant Protection and Quarantine Posts and the Plant Quarantine Border Posts. Besides covering the main administration, inspection and certification functions of the NPPO, it also includes the Phytosanitary Register, an information system on pest distribution, and a system on quality control of imported and exported fresh fruits and vegetables.
Identifying weather‐related covariates controlling grape berry moth dynamics*
Authors: Schmidt K. , Hoppmann D. , Holst H. , Berkelmann‐Löhnertz B.
Published: March 2004

The use of plant protection products requires precise forecasting of the susceptible larval stages of the grape berry moths Lobesia botrana and Eupoecilia ambiguella as these dynamics vary with the weather pattern of a particular year. The objective of this research has been to partition the relative influence of specific climatic factors on the dynamics of these insects. Data taken from 7 years of continuous monitoring of the flight occurrence of male adults, and of the following development stages (i.e. eggs and larvae), was analysed by a generalized Leslie process. The model type reduces the population to three probabilities: development, survival and fertility. Each probability can be modelled as a function of the associated weather factors, while the functional relationships and the model parameters are established. The analysis started with the simplest approach and, in a step‐by‐step procedure, model complexity was added until a sufficient fit to the overall data set was achieved. Within the magnitude of the model, development rates were controlled solely by temperature, but the duration of single stages (i.e. survival) was found to be affected by a combination of temperature and relative humidity. The model represents a combination of mechanisms within a season with empirical components.
Mapping potential exposure to drift of plant protection products*
Authors: Golla B. , Enzian S. , Gutsche V.
Published: March 2004

A proposal for a practical, site‐specific approach for farmers has been developed to fulfil the drift restrictions and directions imposed on a registered plant protection product. The approach is based on exposure potential maps, primarily taking account of regional and local application conditions that reduce non‐target exposure. Firstly, the maps are focused on the spray drift exposure pathway. Using geographically referenced data, we have developed four exposure indicators that allow classification of potential non‐target exposure on the basis of local application conditions. This enables us to manage product application restrictions on a field‐to‐field basis by means of the exposure class to which each field is assigned. This easy‐to‐understand information can be distributed as paper maps or as digital maps to the farmer. The farmer himself no longer needs to assess whether local conditions reduce non‐target exposure. All calculations are carried out using very detailed topographic data which suit scales from 1:10 000 to 1:25 000. Processing and analysis of the GeoData is realized through GIS technology.
Changes in blood carnitine and acylcarnitine profiles of very long‐chain acyl‐CoA dehydrogenase‐deficient mice subjected to stress
Authors: Spiekerkoetter U. , Tokunaga C. , Wendel U. , Mayatepek E. , Exil V. , Duran M. , Wijburg F. A. , Wanders R. J. A. , Strauss A. W.
Published: March 2004

Background  In humans with deficiency of the very long‐chain acyl‐CoA dehydrogenase (VLCAD), C14–C18 acylcarnitines accumulate. In this paper we have used the VLCAD knockout mouse as a model to study changes in blood carnitine and acylcarnitine profiles under stress.

Design  VLCAD knockout mice exhibit stress‐induced hypoglycaemia and skeletal myopathy; symptoms resembling human VLCADD. To study the extent of biochemical derangement in response to different stressors, we determined blood carnitine and acylcarnitine profiles after exercise on a treadmill, fasting, or exposure to cold.

Results  Even in a nonstressed, well‐fed state, knockout mice presented twofold higher C14–C18 acylcarnitines and a lower free carnitine of 72% as compared to wild‐type littermates. After 1 h of intense exercise, the C14–C18 acylcarnitines in blood significantly increased, but free carnitine remained unchanged. After 8 h of fasting at 4 °C, the long‐chain acylcarnitines were elevated 5‐fold in knockout mice in comparison with concentrations in unstressed wild‐type mice (P < 0·05), and four out of 12 knockout mice died. Free carnitine decreased to 44% as compared with unstressed wild‐type mice. An increase in C14–C18 acylcarnitines and a decrease of free carnitine were also observed in fasted heterozygous and wild‐type mice.

Conclusions  Long‐chain acylcarnitines in blood increase in knockout mice in response to different stressors and concentrations correlate with the clinical condition. A decrease in blood free carnitine in response to severe stress is observed in knockout mice but also in wild‐type littermates. Monitoring blood acylcarnitine profiles in response to different stressors may allow systematic analysis of therapeutic interventions in VLCAD knockout mice.
Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey
Authors: Mehta A. , Ricci R. , Widmer U. , Dehout F. , Garcia de Lorenzo A. , Kampmann C. , Linhart A. , Sunder‐Plassmann G. , Ries M. , Beck M.
Published: March 2004

Background  Fabry disease is a rare X‐linked disorder caused by deficient activity of the lysosomal enzyme α‐galactosidase A. Progressive accumulation of the substrate globotriaosylceramide in cells throughout the body leads to major organ failure and premature death. In response to the recent introduction of enzyme replacement therapy, the Fabry Outcome Survey (FOS) was established to pool data from European clinics on the natural history of this little‐known disease and to monitor the long‐term efficacy and safety of treatment. This paper presents the first analysis of the FOS database and provides essential baseline data against which the effects of enzyme replacement can be measured.

Design  Baseline data from a cohort of 366 patients from 11 European countries were analysed in terms of demography and clinical manifestations of Fabry disease.

Results  Misdiagnosis of Fabry disease is common, and the mean delay from onset of symptoms to correct diagnosis was 13·7 and 16·3 years in males and females, respectively. Although previously thought to have serious manifestations only in hemizygous men, the FOS database has confirmed that females heterozygous for Fabry disease are similarly affected. Furthermore, signs and symptoms of Fabry disease may be present from early childhood.

Conclusions  With the advent of enzyme replacement therapy, it is important that general practitioners and physicians in a range of specialties recognize the signs and symptoms of Fabry disease so that effective treatment can be given. Baseline data from FOS demonstrate that enzyme replacement therapy should not be restricted to hemizygous men, but should be considered for both heterozygous females and children.
Gender, age and seasonal effects on IgA deficiency: a study of 7293 Caucasians
Authors: Weber‐Mzell D. , Kotanko P. , Hauer A. C. , Goriup U. , Haas J. , Lanner N. , Erwa W. , Ahmaida I. A. , Haitchi‐Petnehazy S. , Stenzel M. , Lanzer G. , Deutsch J.
Published: March 2004

Background  The frequency of serum IgA deficiency (SIgAD) differs between populations. We examined the prevalence of SIgAD in healthy Caucasians.

Materials and methods  Serum immunoglobulin A (SIgA) was measured in 7293 volunteers (2264 women, 5029 men) aged 30 ± 14·2 years (mean ± SD; range: 12–66). Serum immunoglobulin A and subnormal SIgA levels were defined by a SIgA level < 0·07 g L−1, and between 0·07 and 0·7 g L−1, respectively. Means were compared by analysis of variance (anova) and analysis of covariance (ancova); frequencies by the χ2 test.

Results  Fifteen subjects (0·21%; one woman, 14 men) had SIgAD. Subnormal SIgA levels were found in 155 persons (2·13%): 21 females (0·93% of the females) and 134 males (2·66% of the males; difference: 1·74%; 95% CI: 1·12–2·33%; P < 0·001). Males were more likely to have subnormal SIgA levels or SIgAD (odds ratio 3·09, 95% CI: 1·97–4·85). The prevalence of SIgAD and subnormal SIgA was lowest in winter (χ2 = 14·8; P = 0·002; 3 d.f.; and χ2 = 43·2; P < 0·001; 3 d.f., respectively).

Serum immunoglobulin A concentrations were significantly higher during winter. Serum immunoglobulin A levels increased with age on average by 0·2 ± 0·06 g L−1 per decade of life (P < 0·001). Taking into account the influence of age, SIgA concentration was lower in females as compared with males.

Conclusion  The prevalence of SIgAD and subnormal SIgA levels is increased in males. There exists a significant influence of gender, age and seasons on SIgA levels.
Intracellular lipid accumulation, low‐density lipoprotein receptor‐related protein expression, and cell survival in vascular smooth muscle cells derived from normal and atherosclerotic human coronaries
Authors: Llorente‐Cortés V. , Otero‐Viñas M. , Berrozpe M. , Badimon L.
Published: March 2004

Background  Vascular smooth muscle cell (VSMC) regulation during atherosclerotic plaque progression is determinant for plaque stability.

Aims  To study lipid accumulation, low‐density lipoprotein receptor‐related protein (LRP) expression, and cell survival in VSMCs isolated from nonatherosclerotic areas (normal VSMCs) and advanced atherosclerotic plaques (plaque‐VSMCs) of human coronaries.

Design  Normal or plaque‐VSMCs were obtained from the intima by modification of the explant technique.

Results  Aggregated low‐density lipoprotein (agLDL) (100 µg mL−1) internalization induced higher intracellular cholesteryl ester (CE) accumulation in plaque‐VSMC compared with normal VSMCs (89·28 ± 6·1 vs. 60·34 ± 4·1 µg CE mg−1 of protein; P < 0·05). This internalization was associated with LRP expression, as plaque‐VSMCs show higher levels of LRP mRNA (6·06 ± 0·55 vs. 3·87 ± 0·28; P < 0·05) and LRP protein expression than normal VSMCs. However, plaque‐VSMCs showed a lower proliferative response than normal VSMCs (6536 ± 636 vs. 11151 ± 815 c.p.m. [3H]thymidine; P < 0·05) and did not respond to platelet‐derived growth factor BB (PDGF‐BB) stimulus. In agreement, the Bcl2/BAX ratio was significantly lower in plaque‐VSMCs compared with normal VSMCs (0·14 ± 0·05 vs. 0·51 ± 0·07; P < 0·05) and it was independent of lipid loading.

Conclusions  These results indicate that higher intracellular lipid deposition in plaque‐VSMCs is related to higher LRP expression levels. However, LRP‐mediated agLDL internalization is not directly related to the reduced survival of plaque‐VSMCs.
Association between human‐Pneumocystis infection and small‐cell lung carcinoma
Authors: De La Horra C. , Varela J. M. , Fernández‐Alonso J. , Medrano F. J. , Respaldiza N. , Montes‐Cano M. A. , Calderón E. J.
Published: March 2004

Background  Tobacco smoking is the most important but not the only risk factor in lung carcinoma. There is evidence that certain infections, which cause chronic inflammatory reactions, can also induce tumour development. It has recently been shown that patients with chronic pulmonary diseases present a high rate of subclinical Pneumocystis infection, and that the latter is able to induce inflammatory responses and alveolar cell alterations. The possible role of Pneumocystis infection in the development of lung neoplasms thus deserves consideration.

Material and methods  Polymerase chain reaction has been used to analyze the presence of DNA of two independent loci of the Pneumocystis genome: the mitochondrial region (mtLSU rRNA) and the gene encoding for the dihydropteroate synthase enzyme, in paraffin‐embedded tissue blocks of 10 cases of small cell lung carcinoma (SCLC) and 10 cases of nonsmall cell lung carcinoma (NSCLC) with similar demographic and clinical characteristics. Five cases without lung pathology, and two cases of Pneumocystis pneumonia were also analyzed as controls.

Results  DNA of the microorganism was found in all the cases of SCLC but in only two of the NSCLC, and in none of the controls without pulmonary disease – thus implying a statistically significant association (P < 0·0001) between subclinical Pneumocystis infection and SCLC.

Conclusions  While the nature of this association is not clear, it nevertheless constitutes an important finding – either the infection is specifically facilitated by this tumour or induces the development of this type of neoplasm in combination with other factors.
Use of an artificial neural network to predict Graves’ disease outcome within 2 years of drug withdrawal
Authors: Orunesu E. , Bagnasco M. , Salmaso C. , Altrinetti V. , Bernasconi D. , Del Monte P. , Pesce G. , Marugo M. , Mela G. S.
Published: March 2004

Background  Graves’ disease (GD) is an autoimmune disorder characterized by hyperthyroidism, which can relapse in many patients after antithyroid drug treatment withdrawal. Several studies have been performed to predict the clinical course of GD in patients treated with antithyroid drugs, without conclusive results. The aim of this study was to define a set of easily achievable variables able to predict, as early as possible, the clinical outcome of GD after antithyroid therapy.

Methods  We studied 71 patients with GD treated with methimazole for 18 months: 27 of them achieved stable remission for at least 2 years after methimazole therapy withdrawal, whereas 44 patients relapsed. We used for the first time a perceptron‐like artificial neural network (ANN) approach to predict remission or relapse after methimazole withdrawal. Twenty‐seven variables obtained at diagnosis or during treatment were considered.

Results  Among different combinations, we identified an optimal set of seven variables available at the time of diagnosis, whose combination was useful to efficiently predict the outcome of the disease following therapy withdrawal in approximately 80% of cases. This set consists of the following variables: heart rate, presence of thyroid bruits, psycological symptoms requiring psychotropic drugs, serum TGAb and fT4 levels at presentation, thyroid‐ultrasonography findings and cigarette smoking.

Conclusions  This study reveals that perceptron‐like ANN is potentially a useful approach for GD‐management in choosing the most appropriate therapy schedule at the time of diagnosis.
Bradycardia and sinus arrest during percutaneous ethanol injection therapy for hepatocellular carcinoma
Authors: Ferlitsch A. , Kreil A. , Bauer E. , Schmidinger H. , Schillinger M. , Gangl A. , Peck‐Radosavljevic M.
Published: March 2004

Background  Percutaneous ethanol injection (PEI) is an established method in the treatment of hepatocellular carcinoma (HCC) and considered a safe procedure, with severe complications occurring rarely. Cardiac arrhythmias have not been reported to date. Aim of the study was to investigate the occurrence of dysrhythmias during PEI.

Patients and methods  Twenty‐six consecutive patients with inoperable HCC were included. During ultrasound‐guided PEI with 95% ethanol, electrocardiogram (ECG) monitoring was performed before starting and continuously during PEI.

Results  During PEI a significant reduction in mean heart rate (> 20%) was seen in 15 of 26 (58%) patients. In 11 of 26 patients (42%) occurrence of sinuatrial block (SAB) or atrioventricular block (AVB) was observed after a median time of 9 s (range 4–50) from the start of PEI with a median length of 24 s (range 12–480). Clinical symptoms were seen in two patients, including episodes of unconsciousness, seizure‐like symptoms in both and a respiratory arrest during PEI in one patient, requiring mechanical ventilation. In four of 12 patients with repeat interventions, dysrhythmias were reproducible during monthly performed procedures. There was a significant association between the occurrence of SAB or AVB and the amount of instilled alcohol (P = 0·03) and post‐PEI serum ethanol levels (P = 0·03).

Conclusions  Bradycardia and block formation occur frequently during PEI. These symptoms could be explained by a vasovagal reaction and/or the direct effect of ethanol on the sinus node or the right atrial conduction system. Ethanol dose is an important factor for the occurrence of SAB/AVB. ECG‐monitoring seems mandatory during PEI. Prophylactic use of intravenously administered Atropine might be useful.
Characterization of expression of protein kinase C isozymes in human B‐cell lymphoma: Relationship between its expression and prognosis
Authors: Kamimura Katsuhito , Hojo Hiroshi , Abe Masafumi
Published: March 2004

Protein kinase C (PKC) enzymes play a major role in signal transduction and contribute to the regulation of cellular differentiation and proliferation. However, little is known about subtype‐specific intracellular expression of PKC in human malignant lymphoma. To characterize the relationship between expression of PKC and B‐cell lymphomas based on the different subspecies, we investigated the expression of four subspecies (α, βII, γ and δ) in five cases of reactive lymphoid tissues, 77 cases of human B‐cell lymphoma and 17 human lymphoma cell lines. In the reactive lymphoid tissues, PKC βII‐positive cells were found in the mantle zones and marginal zones, and centroblasts and centrocytes in the germinal centers showed cytoplasmic staining with strong intensity against PKC δ. The present study is the first report to examine the expression of PKC δ in reactive lymphoid tissues. In interfollicular areas, a small number of T‐cells were positive for PKC α. Protein kinase C γ‐positive cells were not found in these lymphoid tissues. Eight cases of Burkitt lymphoma (BL) (8/10; 80%) showed the overexpression of PKC α (P < 0.01), but other B‐cell lymphoma cases except three cases of diffuse large B‐cell lymphoma did not express PKC α. In addition, six and eight out of nine BL cell lines expressed the protein and mRNA of PKC α, respectively. These results indicate that PKC α was predominantly expressed on BL in comparison with other types of lymphoma. The expression of PKC γ was observed in only five cases of BL. The overall survival of PKC γ‐positive BL was significantly better than that of PKC γ‐negative BL (P < 0.05). The expression of PKC γ seems to be associated with a better prognosis in the limited number of BL cases in the present study.
Intravascular large B‐cell lymphoma presenting with mass lesions in the central nervous system: A report of five cases
Authors: Imai Hiroshi , Kajimoto Kazuyoshi , Taniwaki Masashi , Miura Ikuo , Hatta Yoshihiro , Hashizume Yoshio , Watanabe Masatoshi , Shiraishi Taizo , Nakamura Shigeo
Published: March 2004

We have encountered five cases of intravascular large B‐cell lymphoma (IVL) presenting with central nervous system (CNS) mass lesions during their clinical course. The age of the patients ranged from 50 to 74 years and three patients were male. All of these cases histopathologically showed typical intravascular localization of the neoplastic cells in the initial biopsy specimens obtained from sites other than the CNS. Despite multiagent chemotherapy, patients suffered from single or multiple CNS mass lesions 5–44 months after the initial diagnosis of IVL, except for one case in which IVL and the CNS mass lesion were diagnosed at the same time. The subsequent biopsy and autopsy specimens obtained from the CNS mass lesions revealed diffuse infiltration of the tumor cells with perivascular spreading, but minimal or no intravascular components. Immunohistochemical analysis of intravascular tumor cells and CNS mass lesions revealed expression of CD20, CD79a, bcl‐2 and negative for CD3e and Epstein–Barr virus encoded RNA. The overall features of the CNS mass lesions were very similar to or indistinguishable from those of the primary CNS lymphomas. This implies that CNS mass lesions in the IVL cases can be correctly diagnosed only by careful attention to clinical and pathological findings. Moreover, there is the possibility that some cases previously diagnosed as primary CNS lymphomas may have include IVL cases. Further investigation is needed to explore this unusual phenomenon.
Significance of histological subtypes of Kikuchi's disease: Comparative immunohistochemical and apoptotic studies
Authors: Kuo Tseng‐tong , Lo Sing Kai
Published: March 2004

Kikuchi's disease (KD) is a self‐limiting lymphadenitis mostly affecting the cervical lymph nodes of young individuals. It has been classified into three histological subtypes and postulated to progress from the proliferative type (PT) to the necrotizing type (NT) and finally resolve into the xanthomatous type (XT). Since KD has been shown to be an apoptotic disease, the apoptotic activity was studied by the TUNEL method on 6, 12, and 6 cases of PT, NT, and XT, respectively, to see if the apoptotic activity could be shown to decrease in the order of the postulated sequence of evoluation. Significant statistical difference among the three subtypes was found (P = 0.050). Further analysis revealed that PT versus NT was significant (P = 0.010), but NT versus XT (P = 0.385) or PT versus XT (P = 0.310) was not. Analysis of three stages of NT was also significant (P = 0.019). Immunohistochemical study showed that abundant CD8+ T cells and cytotoxic protein positive cells were present in PT and NT, but were relatively low in XT. Our results showed progression of PT to NT, but not from NT to XT. Xanthomatous type was not the resolving stage of KD, but seemed to be a distinctive histological variant of KD caused by either different etiology or an unusual host reaction.