Frequency of dermatological side effects of continuous subcutaneous insulin infusion in children and adolescents with type 1 diabetes.

BACKGROUND: The incidence of type 1 diabetes is rising, particularly in young infants. The treatment with continuous subcutaneous insulin infusion (CSII) offers certain benefits and has gained popularity. Insulin-pump therapy could be associated with cutaneous-adverse effects. The purpose of our study was to investigate the frequency and characterization of skin-related complications in patients with CSII. METHODS: In a single center setting, 54 patients (28 male, 26 female) on CSII therapy aged between 3 and 20 years participated in our study. Data including duration of diabetes, duration of CSII, pump model, catheter material, frequency of catheter switch and hygiene procedures at time of puncture were collected through a standardized questionnaire and photographs of affected areas of the skin were made. Statistical analysis was done to verify an association with gender, patients' age, HbA1c values, and body mass index. RESULTS: Our observation revealed skin complications at the site of catheter insertion in 43% (8 f, 15 m) of our patients. A frequent occurrence of scars (24%, 6 f, 7 m), lipohypertrophic areas (20%, 4 f, 7 m) and eczema (11%, 1 f, 5 m) was observed. Furthermore, 6% (1 f, 2 m) showed changes in pigmentation and 6% (1 f, 2 m) lipoatrophy. The catheter localization had to be switched due to skin-complications in 24% (6 f, 7 m) whereas none of our patients discontinued insulin-pump therapy. CONCLUSION: Skin-related complications during CSII are frequent and regular examination of the insertion sites is crucial. To verify the occurrence of lipoatrophy associated with insulin pump therapy - an otherwise rare complication - larger studies would be needed.

A prospective cohort study on the impact of darbepoetin alfa on quality of life in daily practice following anemia treatment guideline revisions.

OBJECTIVE: This study aimed to evaluate the impact of darbepoetin alfa (DA) on hemoglobin (Hb) levels and quality of life (QoL) in cancer patients with anemia in current daily practice following several revisions of anemia treatment guidelines. METHODS: This was a prospective, multi-center, observational study across Germany in non-myeloid cancer outpatients with chemotherapy-induced anemia treated with DA. Age, sex, cancer type, stage, and therapy, performance status, anemia status and treatment, and Hb concentrations were recorded for up to 18 weeks in a web-based registry. Optional QoL assessments were collected at baseline and at the end of DA treatment. MAIN RESULTS: Of 984 eligible patients, 978 had complete anemia data, 492 also had complete QoL data. In the 978 patients, mean age was 64 (standard deviation, SD 12) years, 62% of patients were women. Breast (26%) and gastrointestinal (22%) cancer were most prevalent. Therapy was palliative in 44% of patients and initiated with curative intent in 29%. Mean baseline Hb was 9.5 (SD 0.9) g/dL, which increased by an average of 1.2 g/dL. In 67% of patients Hb increased either to 10-12 g/dL or by ≥2 g/dL; no Hb response was seen in 219 patients (22%); increases of 0 to 1, >1 to 2, and >2 g/dl were seen in 216 (22%), 265 (27%), and 278 (28%) patients, respectively. Anemia treatment did not result in any significant differences of performance status. However, QoL improvements were significantly greater in Hb responders, although a linear relationship with Hb increments was lacking. None of 47 fatal cases was considered related to treatment with DA. CONCLUSION: Patients treated with DA in routine clinical practice had increases in Hb and reported improvement in QoL. Due to the uncontrolled design, no conclusions can be made regarding causality to treatment and the clinical relevance of the improvement.

Small lesions evaluation based on unsupervised cluster analysis of signal-intensity time courses in dynamic breast MRI.

An application of an unsupervised neural network-based computer-aided diagnosis (CAD) system is reported for the detection and characterization of small indeterminate breast lesions, average size 1.1 mm, in dynamic contrast-enhanced MRI. This system enables the extraction of spatial and temporal features of dynamic MRI data and additionally provides a segmentation with regard to identification and regional subclassification of pathological breast tissue lesions. Lesions with an initial contrast enhancement >/=50% were selected with semiautomatic segmentation. This conventional segmentation analysis is based on the mean initial signal increase and postinitial course of all voxels included in the lesion. In this paper, we compare the conventional segmentation analysis with unsupervised classification for the evaluation of signal intensity time courses for the differential diagnosis of enhancing lesions in breast MRI. The results suggest that the computerized analysis system based on unsupervised clustering has the potential to increase the diagnostic accuracy of MRI mammography for small lesions and can be used as a basis for computer-aided diagnosis of breast cancer with MR mammography.

COMPUTER-AIDED DIAGNOSIS AND VISUALIZATION BASED ON CLUSTERING AND INDEPENDENT COMPONENT ANALYSIS FOR BREAST MRI.

Computer-aided diagnosis and simultaneous visualization based on independent component analysis and clustering are integrated in an intelligent system for the evaluation of small mammographic lesions in breast MRI. These techniques are tested on biomedical time-series representing breast MRI scans and enable the extraction of spatial and temporal features of dynamic MRI data stemming from patients with confirmed lesion diagnosis. By revealing regional properties of contrast-agent uptake characterized by subtle differences of signal amplitude and dynamics, these methods provide both a set of prototypical time-series and a corresponding set of cluster assignment maps which further provide a segmentation with regard to identification and regional subclassification of pathological breast tissue lesions. Both approaches lead to an increase of the diagnostic accuracy of MRI mammography by improving the sensitivity without reduction of specificity.

Analysis of dynamic susceptibility contrast MRI time series based on unsupervised clustering methods.

We compare five different unsupervised clustering techniques as tools for the analysis of dynamic susceptibility contrast MRI time series. The study included four subjects: two subjects with stroke and two subjects without focal neurological deficit. The goal was to determine the robustness and reliability of clustering methods in providing a self-organized segmentation of perfusion MRI data sharing common properties of signal dynamics. For this purpose, the relative signal reduction time series was computed for each pixel. Clustering of the resulting high-dimensional feature vectors was performed by minimal free-energy deterministic annealing, self-organizing maps, two variants of fuzzy c-means clustering (FVQ and FSM), and the neural gas algorithm. Clustering results were evaluated by visual assessment of cluster assignment maps and corresponding signal time curves as well as by quantitative comparison of cluster assignment maps with conventional pixel-specific perfusion parameter maps based on quantitative receiver operating characteristic (ROC) curve analysis. Clustering methods provided a functional segmentation with respect to vessel size, detected side asymmetries of contrast-agent first pass, and identified regions of perfusion deficits in subjects with stroke. As confirmed by quantitative ROC analysis, the clustering approach can detect regions of reduced brain perfusion with high accuracy when compared to conventional analysis by pixel-specific cerebral blood volume and mean transit time maps. We conclude that by unveiling differences of signal dynamics and amplitude, clustering is a useful tool to analyze and visualize regional properties of brain perfusion. Thus, it may contribute to the computer-aided diagnosis of cerebral circulation deficits by noninvasive neuroimaging.

Ericksonian hypnosis in tinnitus therapy: effects of a 28-day inpatient multimodal treatment concept measured by Tinnitus-Questionnaire and Health Survey SF-36.

For the first time, the therapeutic effects on subacute and chronic tinnitus of an inpatient multimodal treatment concept based on principles of Ericksonian hypnosis (EH) were examined by standardized criteria of the Tinnitus Questionnaire (TQ) and Health Survey (SF-36) within a controlled prospective, longitudinal study. A total of 393 patients were treated within an inpatient closed-group 28-day-setting based on a resource-oriented, hypnotherapeutic concept. The severity of tinnitus was assessed by TQ at times of admission, discharge and also at a 6- and 12-month follow-up. Health-related quality of life was evaluated before and after therapy using the SF-36. After therapy, a decrease in TQ score was seen in 90.5% of the patients with subacute tinnitus and in 88,3% of those with chronic tinnitus. Assessment of the TQ score at the end of therapy revealed highly significant improvements of 15.9/14.1 points in mean. Effect sizes in the treatment groups (0.94/0.80) were superior to those in the waiting-list controls (0.14/0.23). The TQ score remained stable in the follow-up controls. Significant improvement in health-related quality of life has been observed within the treatment groups depending on initial level of tinnitus serverity I-IV according to TQ. Using a multimodal treatment concept with emphasis on resource-activating approaches of EH the annoyance of tinnitus can be significantly reduced while health-related quality of life is enhanced within a comparatively short treatment period of 28 days.

Cluster analysis of dynamic cerebral contrast-enhanced perfusion MRI time-series.

We performed neural network clustering on dynamic contrast-enhanced perfusion magnetic resonance imaging time-series in patients with and without stroke. Minimal-free-energy vector quantization, self-organizing maps, and fuzzy c-means clustering enabled self-organized data-driven segmentation with respect to fine-grained differences of signal amplitude and dynamics, thus identifying asymmetries and local abnormalities of brain perfusion. We conclude that clustering is a useful extension to conventional perfusion parameter maps.

Traceless multipole moment densities and transformations in macroscopic electromagnetism.

We consider whether use of traceless multipole moment densities in macroscopic electromagnetism can yield physically acceptable results. For harmonic plane wave fields it is shown that a traceless electric quadrupole density yields linear constitutive relations for which the dynamical material constants (permittivity and magnetoelectric coefficients) and response fields are unphysical. We further show that, within multipole theory, these constitutive relations cannot be transformed into physically acceptable relations. Specifically, the transformed response field D is unphysical for all orders beyond the electric dipole. This contrasts with use of primitive (traced) moment densities, for which unphysical constitutive relations have been successfully transformed up to electric octopole-magnetic quadrupole order, thereby providing also the leading contribution to the ac permeability.

Comparison of three triple regimens with omeprazole or ranitidine bismuth citrate for Helicobacter pylori eradication.

BACKGROUND: Regimens with ranitidine bismuth citrate (RBC) or omeprazole (O) are effective in eradicating Helicobacter pylori. This randomized, open, multicentre trial compares three different regimens with these drugs. METHODS: Consecutive H. pylori +ve outpatients were included. The alternative regimens were: 1) O 20 mg, clarithromycin (C) 250 mg and metronidazole (M) 500 mg (O.C.M), 2) RBC 400 mg, C 250 mg and M 500 mg (RBC.C.M), 3) RBC 400 mg, tetracycline (T) 1000 mg and M 500 mg [RBC.T.M]. All drugs were given twice daily for 7 days. H. pylori infection was assessed with H. pylori urea breath tests. RESULTS: 426 H. pylori +ve patients were included (mean age 58 years [range 18-88], male/female: 244/182). The eradication rates (intention to treat) in the O.C.M, RBC.C.M and RBC.T.M groups were 117/137 (85%), 141/146 (97%) and 117/143 (82%), respectively (P < 0.001, overall assessment). There were no significant differences in side effects between the alternatives. CONCLUSION: In this trial, RBC.C.M was the most effective one, it was well tolerated and compliance was satisfactory. RBC.T.M is an alternative to regimens with clarithromycin.

Protection of the photosynthetic apparatus against damage by excessive illumination in homoiohydric leaves and poikilohydric mosses and lichens.

Experimental work on the control of photosystem II in the photosynthetic apparatus of higher plants, mosses and lichens is reviewed on a background of current literature. Transmembrane proton transport during photoassimilatory and photorespiratory electron flows is considered insufficient for producing the intrathylakoid acidification necessary for control of photosystem II activity under excessive illumination. Oxygen reduction during the Mehler reaction is slow. Together with associated reactions (the water-water cycle), it poises the electron transport chain for coupled cyclic electron transport rather than acting as an efficient electron sink. Coupled electron transport not accompanied by ATP consumption in associated reactions provides the additional thylakoid acidification needed for the binding of zeaxanthin to a chlorophyll-containing thylakoid protein. This results in the formation of energy-dissipating traps in the antennae of photosystem II. Competition for energy capture decreases the activity of photosystem II. In hydrated mosses and lichens, but not in leaves of higher plants, protein protonation and zeaxanthin availability are fully sufficient for effective energy dissipation even when photosystem II reaction centres are open. In leaves, an additional light reaction is required, and energy dissipation occurs not only in the antennae but also in reaction centres. Loss of chlorophyll fluorescence during the drying of predarkened poikilohydric mosses and lichens indicates energy dissipation in the dry state which is unrelated to protonation and zeaxanthin availability. Excitation of photosystem II by sunlight is not destructive in these dry organisms, whereas photosystem II activity of dried leaves is rapidly lost under strong illumination.

Hydration-dependent photosynthetic production of lichens: what do laboratory studies tell us about field performance?

Extensive investigations made in the past two decades on lichen photosynthesis in relation to water content have shown two features of particular interest: first, the depression of net photosynthesis at high water contents, suprasaturation (i.e. the lichen contains more water than necessary to saturate photosynthesis), and, second, the ability of green algal lichens to regain photosynthetic activity by uptake of water from humid air. Evidence from several investigators is presented to confirm that both phenomena are now well substantiated through laboratory investigations. It has been questioned whether these features do actually occur in nature and, if they do, to what extent. Recent work is summarized that demonstrates that for many of the lichens studied suprasaturation is of major importance and can result in depressed photosynthesis for around a third of the time that the lichens are photosynthetically active. Reactivation of photosynthesis of green algal lichens by high humidity is also, apparently, very common in some environments, for example, humid temperate rainforests, occurring almost every night. It is possible that the dominance of green algal lichens, rather than cyanobacterial species, in these habitats is a result of their ability to utilize water vapour. If so, then the phenomenon must have major ecological importance for lichen productivity. In general, laboratory studies seem to be able to predict extremely well the behaviour of lichens in their natural habitat.

Phototolerance of lichens, mosses and higher plants in an alpine environment: analysis of photoreactions.

Adaptation to excessive light is one of the requirements of survival in an alpine environment particularly for poikilohydric organisms which in contrast to the leaves of higher plants tolerate full dehydration. Changes in modulated chlorophyll fluorescence and 820-nm absorption were investigated in the lichens Xanthoria elegans (Link) Th. Fr. and Rhizocarpon geographicum (L.) DC, in the moss Grimmia alpestris Limpr. and the higher plants Geum montanum L., Gentiana lutea L. and Pisum sativum L., all collected at altitudes higher than 2000 m above sea level. In the dehydrated state, chlorophyll fluorescence was very low in the lichens and the moss, but high in the higher plants. It increased on rehydration in the lichens and the moss, but decreased in the higher plants. Light-induced charge separation in photosystem II was indicated by pulse-induced fluorescence increases only in dried leaves, not in the dry moss and dry lichens. Strong illumination caused photodamage in the dried leaves, but not in the dry moss and dry lichens. Light-dependent increases in 820-nm absorption revealed formation of potential quenchers of chlorophyll fluorescence in all dehydrated plants, but energy transfer to quenchers decreased chlorophyll fluorescence only in the moss and the lichens, not in the higher plants. In hydrated systems, coupled cyclic electron transport is suggested to occur concurrently with linear electron transport under strong actinic illumination particularly in the lichens because far more electrons became available after actinic illumination for the reduction of photo-oxidized P700 than were available in the pool of electron carriers between photosystems II and I. In the moss Grimmia, but not in the lichens or in leaves, light-dependent quenching of chlorophyll fluorescence was extensive even under nitrogen, indicating anaerobic thylakoid acidification by persistent cyclic electron transport. In the absence of actinic illumination, acidification by ca. 8% CO2 in air quenched the initial chlorophyll fluorescence yield Fo only in the hydrated moss and the lichens, not in leaves of the higher plants. Under the same conditions, 8% CO2 reduced the maximal fluorescence yield Fm strongly in the poikilohydric organisms, but only weakly or not at all in leaves. The data indicate the existence of deactivation pathways which enable poikilohydric organisms to avoid photodamage not only in the hydrated but also in the dehydrated state. In the hydrated state, strong nonphotochemical quenching of chlorophyll fluorescence indicated highly sensitive responses to excess light which facilitated the harmless dissipation of absorbed excitation energy into heat. Protonation-dependent fluorescence quenching by cyclic electron transport, P700 oxidation and, possibly, excitation transfer between the photosystems were effectively combined to produce phototolerance.

A comparison of two indirect methods for estimating average levels of gene flow using microsatellite data.

We compare the performance of Nm estimates based on FST and RST obtained from microsatellite data using simulations of the stepwise mutation model with range constraints in allele size classes. The results of the simulations suggest that the use of microsatellite loci can lead to serious overestimations of Nm, particularly when population sizes are large (N > 5000) and range constraints are high (K < 20). The simulations also indicate that, when population sizes are small (N /= 50) and many loci (nl >/= 20), RST performs better than FST for most of the parameter space. However, FST-based estimates are always better than RST when sample sizes are moderate or small (ns

The symptomatic effect of cisapride in patients with irritable bowel syndrome and constipation.

BACKGROUND: Cisapride improves symptoms in patients with idiopathic constipation. This trial compares the effect of cisapride with that of placebo in patients with irritable bowel syndrome (IBS) and constipation. METHODS: Seventy patients were randomized to 12 weeks' treatment with 5 mg cisapride three times daily or placebo in a double-blind trial. The dose could be doubled after 4 weeks in patients without satisfactory improvement. The patients scored their symptoms on a 100-mm visual analogue scale (VAS) (0 = best, 100 = worst), and the investigators evaluated the symptomatic effect. RESULTS: The dose was doubled in 17 and 23 patients in the cisapride and placebo groups, respectively, after 4 weeks. The patients' mean VAS score for global evaluation of IBS symptoms in the cisapride and placebo groups was 73 and 71 mm, respectively, at the start of treatment and 47 and 41 mm at the end. The difference between cisapride and placebo at the end was 6 mm in favour of placebo (95% confidence interval (CI), -6, 18) (NS). The investigators evaluated the effect as good or excellent in 39.2% and 58.8% in the cisapride and placebo groups, respectively. The difference in favour of placebo was 19.5% (95% CI, -5, 44) (NS). Nor were any statistically significant differences seen between cisapride and placebo in the other effect factors. CONCLUSIONS: The trial seems to exclude a clinically significant effect of 15-30 mg cisapride daily in patients with IBS and constipation during a 12-week treatment period.

[Follow up after potential curative surgery of colorectal cancer. Guidelines from the Norwegian Gastrointestinal Cancer Group]. / Kontrollopplegg etter potensiell kurativ operasjon for kolorektalcancer. Anbefaling fra Norsk Gastrointestinal Cancer Gruppe.

In Norway, about 2,800 cases of colorectal cancer are diagnosed every year. Two-thirds of the patients undergo potentially curative surgery and almost half of them develop local or distant metastases. The follow-up of colorectal cancer patients involves four strategies: Educating the patients about the disease, symptoms of relapse, and risk of hereditariness; Early diagnosis of relapse, to make curative re-surgery possible; Diagnosis of metachronous/synchronous cancer(s); Recording the results of current surgical techniques. The Norwegian Gastrointestinal Cancer Group recommend a four-year follow-up programme (every third month for two years and then twice a year) of colorectal cancer patients. It is suggested that patients treated with low anterior resection are followed regularly by means of rectoscopy and local examination (digital or by ultrasound) undertaken by specialist (surgeon or gastroenterologist). The others should be followed up mainly by general practitioners. Carcinoembryonic antigen (CEA)-monitoring is suggested every third month for two years, and then every sixth month. Colonoscopy is recommended at one and four year follow-up. Patients with normal CEA levels prior to surgery should be evaluated by ultrasound of the liver every sixth month for four years.

Do secondary substances in the thallus of a lichen promote CO2 diffusion and prevent depression of net photosynthesis at high water content?

Many lichens show seriously depressed net photosynthesis (NP) at high thallus water contents due to increased carbon dioxide diffusion resistance through blockage of diffusion pathways by water. The soil lichen Diploschistes muscorum, however, shows no depression and NP is close to maximal even at the highest thallus water content. We investigated whether lichen substances (lecanoric and diploschistesic acids) in the cortex and medulla contributed to this ability to maintain high NP. Dry thalli were extracted with water-free acetone and, after this treatment, were found to be fully viable to the extent of continued growth after replanting in the field. No differences were found in the response of NP to thallus water content between the normal and extracted thalli, in fact the response curves were often nearly identical. Thus, in this species it seems that lichen substances did not maintain the water-free diffusion pathways and some other explanation, possibly structural, needs to be sought.

Sequestration of lichen compounds by lichen-feeding members of the Arctiidae (Lepidoptera).

A survey for the presence of sequestered lichen compounds in 103 wild-caught imagines representing eight different genera and 16 different species of the Arctiidae was conducted. Known lichen compounds were detected for the first time in 24 of the analyzed specimens (representing five different genera and 11 different species) based on their HPLC retention times and on their UV-absorption spectra. The anthraquinone parietin, the depside atranorin, as well as a hydrolytic cleavage product of the latter were among the lichen compounds most frequently detected in wild-caught imagines. The observed variation of sequestered lichen compounds in wild-caught imagines with unknown feeding history may be due to several reasons. Lack of lichen compounds in imagines may have been caused, for example, by larvae feeding on lichens with no or only minute amounts of phenolic products. The age of the specimens analyzed may also influence the results obtained. Avoidance of lichen compounds by selective feeding on those parts of lichen thalli that have no or little lichen products may be another reason for the lack of lichen compounds in imagines. Preliminary feeding experiments conducted with larvae ofEilema complana, for example, indicated that the larvae fed exclusively on the algal layer and cortex of the lichenCladonia pyxidata, whereas the medulla, which is rich in fumarprotocetrarie acid, was avoided. As expected, imagines hatching from the larvae were free of this lichen compound. Any ecological role of the sequestered lichen compounds for the herbivores is unknown. It is possible, however, that sequestered lichen compounds may be utilized for the chemical defense of arctiid moths or against microbial pathogens.

Effect of wheat fibre supplements on duodenal ulcer recurrence.

In the present study the prophylactic effect of concentrated wheat fibre on duodenal ulcer recurrence was evaluated. Eleven grams of fibre (Fiberform) or placebo was added to an ordinary Norwegian diet for 1 year after endoscopic healing of duodenal ulcer. The ulcer recurrence rates were 84% (31 of 37 patients) in the fibre-supplemented group and 85% (30 of 36 patients) in the placebo group (NS). The effect on ulcer symptoms was similar in both groups. Side effects were infrequently seen. A concentrated wheat fibre supplement seems to have no preventive effect when given to duodenal ulcer patients living on a traditional Norwegian diet.