A new framework for the documentation and interpretation of oral food challenges in population-based and clinical research.

BACKGROUND: The conduct of oral food challenges as the preferred diagnostic standard for food allergy (FA) was harmonized over the last years. However, documentation and interpretation of challenge results, particularly in research settings, are not sufficiently standardized to allow valid comparisons between studies. Our aim was to develop a diagnostic toolbox to capture and report clinical observations in double-blind placebo-controlled food challenges (DBPCFC). METHODS: A group of experienced allergists, paediatricians, dieticians, epidemiologists and data managers developed generic case report forms and standard operating procedures for DBPCFCs and piloted them in three clinical centres. The follow-up of the EuroPrevall/iFAAM birth cohort and other iFAAM work packages applied these methods. RECOMMENDATIONS: A set of newly developed questionnaire or interview items capture the history of FA. Together with sensitization status, this forms the basis for the decision to perform a DBPCFC, following a standardized decision algorithm. A generic form including details about severity and timing captures signs and symptoms observed during or after the procedures. In contrast to the commonly used dichotomous outcome FA vs no FA, the allergy status is interpreted in multiple categories to reflect the complexity of clinical decision-making. CONCLUSION: The proposed toolbox sets a standard for improved documentation and harmonized interpretation of DBPCFCs. By a detailed documentation and common terminology for communicating outcomes, these tools hope to reduce the influence of subjective judgment of supervising physicians. All forms are publicly available for further evolution and free use in clinical and research settings.

Detection of relevant amounts of cow's milk protein in non-pre-packed bakery products sold as cow's milk-free.

BACKGROUND: Currently, there is no mandatory labelling of allergens for non-pre-packed foods in the EU. Therefore, consumers with food allergy rely on voluntary information provided by the staff. The aim of this study was to characterize allergic reactions to non-pre-packed foods and to investigate whether staff in bakery shops were able to give advice regarding a safe product choice. METHODS: Questionnaires were sent to 200 parents of children with a food allergy. Staff of 50 bakery shops were interviewed regarding selling non-pre-packed foods to food-allergic customers. Bakery products being recommended as 'cow's milk-free' were bought, and cow's milk protein levels were measured using ELISA. RESULTS: A total of 104 of 200 questionnaires were returned. 25% of the children experienced an allergic reaction due to a non-pre-packed food from bakery shops and 20% from ice cream parlours. Sixty percent of the bakery staff reported serving food-allergic customers at least once a month, 24% once a week. Eighty four percent of the staff felt able to advise food-allergic consumers regarding a safe product choice. Seventy three 'cow's milk-free' products were sold in 44 bakery shops. Cow's milk could be detected in 43% of the bakery products, 21% contained >3 mg cow's milk protein per serving. CONCLUSION: Staff in bakery shops felt confident about advising customers with food allergy. However, cow's milk was detectable in almost half of bakery products being sold as 'cow's milk-free'. Every fifth product contained quantities of cow's milk exceeding an amount where approximately 10% of cow's milk-allergic children will show clinical relevant symptoms.

[Quality rating of follow-up examinations conducted on breast cancer patients]. / Wertigkeit der routinemässig erfassten Nachsorgedaten bei Brustkrebspatientinnen.

For breast centre certification, follow-up care data have to be presented, although the further treatment is carried out outside of the hospital. An analysis of 2062 patients with their first operation (breast cancer and carcinoma in situ) occurring between 1.1.1984 and 31.12.1998 has been conducted. The tracking of follow-up results ended on 1.7.2007. The survival of breast cancer patients appears to be superior in the pure clinical register than with cross-linking with additional registers (Epidemiological Cancer Register and registration of address office). The outcome of this is that the completed feedback of the cases of death (Cancer Register) and of living patients (registration of address office) increases the qualitative statement. The compliance with the data security laws may be ensured by pseudo-anonymisation.

Co-expression and prognostic value of gross cystic disease fluid protein 15 and mammaglobin in primary breast cancer.

Gross cystic disease fluid protein (GCDFP-15) and mammaglobin are both widely used and accepted markers for epithelia of breast origin. We aimed to evaluate their relation of expression on parallel whole tissue sections in primary breast cancer by immunohistochemistry and also to correlate it with clinico-pathological parameters including patient survival. Primary breast carcinomas from 165 patients with a mean clinical follow-up of 73 months were immunostained using commercially available antibodies against GCDFP-15 and mammaglobin. An immunoreactive score (IRS) was calculated based on the cytoplasmic staining intensity and the number of cells stained. Cytoplasmic expression of GCDFP-15 and mammaglobin was observed in 73.3% and 72.1% of invasive breast carcinomas respectively. 91.8% of breast cancer cases expressed at least one of both markers. Both markers strongly correlated with each other and were significantly associated with lower tumour grading. Additionally, GCDFP-15 negativity was significantly associated with shortened disease-free survival times in univariate and multivariate analyses. We demonstrated the strong correlation of GCDFP-15 and mammaglobin with each other and showed that only very few primary breast cancers are completely negative for both markers. The significantly longer disease free survival times for patients with GCDFP-15 positive tumours clearly warrants further study.

ALCAM/CD166 is overexpressed in colorectal carcinoma and correlates with shortened patient survival.

BACKGROUND: Activated leucocyte cell adhesion molecule (ALCAM) has been implicated in tumorigenesis and tumour progression of malignant melanoma and prostate cancer. AIMS: To clarify the expression patterns of ALCAM in colon cancer and to correlate these with clinicopathological parameters, including patient survival. METHODS: One hundred and eleven colorectal carcinomas were immunostained for ALCAM (clone MOG/07) using a standard detection system. Cytoplasmic and membranous immunoreactivity were scored semiquantitatively. Fisher's exact test, chi2 test for trends, Kaplan-Meier analysis, and Cox's regression were applied. RESULTS: In colorectal cancer, 58.6% and 30.6% of cases showed strong cytoplasmic and membranous expression of ALCAM, respectively. No significant correlation with patient age, tumour grade, stage, or nodal status was apparent. In survival analyses, membranous ALCAM expression correlated significantly (Cox's regression, p=0.028; relative risk, 2.3) with shortened patient survival. CONCLUSIONS: ALCAM is frequently upregulated in colorectal cancer and is a new independent prognostic marker, underscoring the importance of ALCAM in tumour progression in this disease.

Clinical value of echocardiographic tissue characterization in the diagnosis of myocarditis.

Inflammatory changes in the myocardium have been visually observed as alterations on echocardiograms. The goal of this study was to determine how these myocardial changes affect the texture of echocardiographic images, and how these could be described through quantitative texture analysis. The results of 142 endomyocardial biopsies were compared with those of texture analysis in echocardiograms of 106 patients suspected of having myocarditis. There were 52 cases of biopsy-proven acute myocarditis, 12 of persistent myocarditis, nine of healed myocarditis without fibrosis, 17 of healed myocarditis with fibrosis, and 35 cases of cardiomyopathy. Eight myocardial biopsies exhibited no pathological changes and nine patients had other cardiac problems. The echocardiograms of a control group of 24 healthy subjects were also evaluated by texture analysis. Three texture parameters were able to differentiate between normal and abnormal myocardium. The mean grey value, i.e. average brightness, was appreciably higher in cases of myocarditis than in control subjects, whereas one co-occurrence and one run length feature had markedly decreased. We conclude that myocarditis and fibrosis induce changes in echocardiographic image texture, i.e. increases in brightness, heterogeneity, and contrast. Performing digital image texture analysis of echocardiograms makes it possible to distinguish between myocarditis and normal myocardium.

Circadian rhythms of dopamine and cholecystokinin in nucleus accumbens and striatum of rats--influence on dopaminergic stimulation.

The concentrations of cholecystokinin (CCK) and dopamine (DA) were determined in the nucleus accumbens (anterior, posterior) and striatum of rats every 2 h during a period of 24 h. For both substances, a circadian rhythm was found, which was best fitted by a dominant 24-h period superimposed by the second (12 h) and fourth (6 h) harmonics. The rhythms in CCK and DA were negatively correlated because of a difference in phase position by approximately 3 h. A dominant DA peak was found in the light phase coinciding with a trough in CCK and vice versa in the dark phase. Based on these data, CCK and DA were determined in rats treated with gamma-butyrolactone (GBL; inhibitor of DA release) or thyrotropin-releasing hormone (TRH; stimulator of DA release) at 0900 h or 1300 h to study a putative time-dependency in drug effects. After GBL treatment, CCK as well as DA increased by up to 200% whereas TRH administration led to a rather complex alteration, inasmuch as CCK was increased or decreased, depending on circadian time, whereas the rhythmic pattern in DA remained relatively unaffected. Comparing the drug effects obtained at 0900 h with the response seen at 1300 h revealed significant quantitative as well as qualitative differences. The results demonstrate that the neurotransmission system investigated changed its level of activity depending on time of day. No changes were obtained that convincingly may be ascribed to colocalization of DA and CCK. It is concluded that the chronobiological data indicate a close interaction of CCK and DA in various areas of the rat brain, independent of colocalization.

Noninvasive diagnosis of cardiac rejection through echocardiographic tissue characterization.

Ultrasonic tissue characterization is based on the assumption that microscopic tissue structures are identifiable by their acoustic properties. Our study group consisted of 23 cardiac recipients. Two-dimensional images were obtained within 2 hours of endomyocardial biopsy. The end-diastolic echo frames were digitized into the matrix of an image-processing system. A region of interest was placed into the anteroseptal segment of the left ventricle. The texture within the region of interest was analyzed using four major groups of texture analysis (first-order histogram, co-occurrence matrix, run-length statistic, and power spectrum). A total of 408 echocardiographic examinations were compared with histologic findings. The 117 initially calculated texture parameters were reduced incrementally using a series of discriminant analyses. A set of three texture parameters (inverse difference moment undirected, run-length nonuniformity vertical, and sector sum) was able to describe changed echocardiographic texture when rejection occurred. Using these three parameters, echocardiographic sensitivity was 89.0% and specificity was 83.6% for moderate rejection. We conclude that cardiac rejection is associated with echocardiographic texture alterations and that serial echocardiographic texture analysis can reliably identify rejection.

Measuring left ventricular function after heart transplantation via digitization of M-mode echocardiograms.

The aim of the study was to assess the usefulness of M-mode echocardiography for noninvasive diagnosis of cardiac rejection. For this purpose, 292 M-mode images of 26 heart transplant recipients were analyzed. The echocardiographic images were digitized into an image analysis system. The curves of left ventricular diameter changes were obtained and its first differential calculated. A total of 23 parameters were measured. The most important parameters were: peak velocity of systolic diameter change, peak velocity of diastolic diameter change, time to peak velocity of systolic diameter change, time to peak velocity of diastolic diameter change (TPEAK-D), isovolumetric relaxation time (IVRT), rapid filling time (RFT), shortening fraction (SF), and mean velocity of circumferential fiber shortening (MVCF). The echocardiographic parameters were compared to biopsy results. In 18 patients, 23 biopsy-proven moderate rejections occurred. When rejection occurred, IVRT decreased 23% +/- 6% (P < 0.05), SF decreased 13% +/- 14% (P<0.05), MVCF decreased 18% +/- 18% (P<0.05), and TPEAK-D increased 27% +/- 27% (P<0.05). We concluded that the analysis of digitized M-mode images can identify heart transplant rejection.

Correlative circadian rhythms of cholecystokinin and dopamine content in nucleus accumbens and striatum of rat brain.

Due to contrary results concerning the interaction of cholecystokinin and dopamine (CCK/DA) circadian variations in CCK/DA concentration were investigated in forebrain nuclei of rats (Nc. accumbens, striatum) in order to assess the influence of time of day on neurotransmission. CCK was determined by a radioimmunoassay, DA was measured by electrochemical detection after HPLC separation. A distinct circadian rhythm, superimposed by harmonics (12 h, 6 h) was found in the content of both DA and CCK. A trough was shown for CCK during the light phase and a crest during the late afternoon and the dark phase, respectively. For DA the opposite was found. Caused by a phase-shift of about 3-4 h, the CCK/DA rhythms are negatively correlated. The differences are significant at 11.00 h, 13.00 h, 21.00 h, and 03.00 h. The results indicate that circadian processes are involved in neuronal transmission of CCK and DA.

The clinical value of ultrasonic tissue characterization in the management of heart transplant patients.

The purpose of this study was to evaluate the rejection process by ultrasonic tissue characterization. Serial 2D echocardiographic images were obtained within 24 h prior to an endomyocardial biopsy. The end-diastolic echoframes were digitized into a computer matrix. A region of interest was placed into the anteroseptal segment of each scan. Image texture was analysed by four major groups of texture analysis (first-order histogram, co-occurrence matrix, run-length statistic, power spectrum). In 23 patients, 408 biopsies were taken after each examination, so that correlation between the ultrasonic tissue measurements and the histological state of the tissue could be determined. When rejection occurred, heterogeneity, brightness and contrast of texture increased. Of 117 texture parameters originally claculated, three parameters (inverse difference moment, run-length non-uniformity, ring sums of power spectrum) that characterized rejection were determined by means of discriminance analysis. Compared with biopsy findings, echocardiographic sensitivity for moderate rejection was 93.3% and specifity 83.6%. Our study indicates that acute rejection is associated with changes in echocardiographic texture. Serial echocardiographic texture analysis can reliably identify heart transplant rejection.

[The oculocardiac reflex during vitrectomy under neuroleptanalgesia]. / Untersuchungen des okulokardialen Reflexes bei Vitrektomien in Neuroleptanalgesie.

Oculocardiac reflex (OCR) is a frequently occurring complication in eye operations. It is a trigemino-vagal reflex characterised by the clinical occurrence of bradycardia and other cardiac rhythm disturbances following manipulations on the eye and its surroundings especially after traction of the external eye muscles. In this paper based on an analysis of 402 anaesthesia records, a bradycardia frequency (f = less than 60/min) of 31.8% was noted while other rhythm disturbances occurred in 5.7%. Predisposition facts were identified as age over 50, hypertension and cardiac diseases requiring medication with cardiac drugs. The frequency of OCR is considerably lowered by diabetes mellitus. Examination of 159 traction measurements made at the lateral rectus muscle revealed that the first manipulation made at the rectus bulbi superior muscle resulted in a statistically significantly stronger reflex activity than at the other muscles. In a further series of investigations in which rectus bulbi superior muscle was tested last, this muscle again showed the biggest frequency deviation. Only determination of the percentage heart rate decrease is suitable for characterising reflex activity. The frequency of the reflex occurring in our study was 71.7%, the result being reduced by the high proportion of diabetics, who are relatively reflex insensitive.

[The individual variability of pyramidal neurons in the neocortex of the rat]. / Zur individuellen Variabilität von Pyramidenneuronen im Neocortex der Ratte.

In Golgi-Kopsch impregnated pyramid neurons of the neocortex (regio precentralis agranularis and area striata) of adult rats the individual variability was investigated. As parameters served the dendritic lengths, spine numbers and spine densities along the dendritic orders (basal and apical), within single dendritic fields, the apical and basal parts of the dendritic tree and of the whole neuron. The statistical tests gave the following results: Pyramid neurons in the regio precentralis agranularis are more variable than pyramid neurons in the area striata. Within the area striata the lamina III-pyramid neurons are more invariable than the lamina V-pyramid neurons. The basal dendrites are statistically more invariable than the apical dendrites. The dendritic lengths are less variable than the spine values. In general, the variability is different in particular subdivisions of the neurons analyzed as well as for the parameter chosen. The variability of neuronal structures depends from genetical factors and from a functional training. The knowledges about this variability are still insufficient. They are of considerable importance for the planning of experiments followed by statistical analyses.

[Individual variability of lamina V pyramidal neurons in the cingulate area of the rat]. / Zur individuellen Variabilität von Lamina V-Pyramidenneuronen der Regio cingularis der Ratte.

Lamina V-pyramidal neurons of regio precentralis agranularis in Golgi-Kopsch impregnated frontal series of the brains of four adult male rats were analyzed quantitatively in order to estimate the degree of individual variability. As parameters served the dendritic lengths, spine numbers and spine densities along the dendritic orders, within single dendritic fields and within the apical and basal parts of the dendritic tree or of the whole neuron. The significance of individual differences in these parameters between the animals was proven by the tests of Mann and Whitney or of Kruskal and Wallis. The variability turned out to be different in particular subdivisions of the neuron analyzed as well as for the parameter chosen. The basal single dendritic field showed a relative high degree of constancy in its data and the dendritic lengths were statistically more invariable than the spine values. The knowledge about high or less variable parameters in strictly selected neurons is of considerable importance for the planning of experiments followed by quantitative analyses of neurons. The application of the most suitable statistical method is also discussed.