Medizin - Open Access LMU - Teil 20/22 Ludwig-Maximilians-Universität München

The International Consensus Conference on the treatment of primary breast cancer takes place every two years in St. Gallen, Switzerland.The panel in St. Gallen is composed of international experts from different countries. From a German perspective, it seems reasonable to interpret the voting results in the light of AGO-recommendations and S3-guidelines for everyday practice in Germany. Consequently, a team of eight breast cancer experts, of whom two are members of the international St. Gallen panel, commented on the voting results of the St. Gallen Consensus Conference (2013). The main topics at this year’s St. Gallen conference were surgical issues of the breast and axilla, radio-therapeutic and systemic treatment options, and the clinical relevance of tumour biology. The clinical utility of multigene assays for supporting individual treatment decisions was also intensively discussed.

Background/Aims: Surveillance colonoscopy is recommended afterpolypectomy of adenoma and surgery for colorectal cancer. The purpose ofthis study was to assess the frequency of advanced adenoma and cancer incolonoscopies performed for surveillance compared to screeningcolonoscopies. Methods: Analysis of relative frequencies of findings incolonoscopies performed for post-adenoma surveillance (post-ad),post-cancer surveillance (post-crc), screening, and follow-up of apositive fecal occult blood test (FOBT). Logistic regression was used toidentify the risk for advanced adenoma (adenoma mm, containinghigh-grade dysplasia, or villous histology) and cancer. Results: 324,912 colonoscopies were included in the analysis: 81,877 post-ad, 26,89 6post-crc, 178,305 screening, 37,834 positive FOBT. Advanced adenoma(cancer) was diagnosed in 8.0% (0.4%) of post-ad, 5.0% (1.0%) ofpost-crc, 7.4% (1.1%) of screening, and 11.7% (3.6%) of positiveFOBT colonoscopies. Compared to screening, the odds ratios for findingadvanced adenoma were 0.93 (95% CI 0.88-0.98) for post-ad, 0.96(0.86-1.08) for post-crc, and 1.18 (1.09-1.28) for positive FOBTcolonoscopies. The odds ratios for the diagnosis of cancer were 0.29(0.24-0.36) for post-ad, 0.81 (0.61-1.07) for post-crc, and 2.77(2.43-3.17) for positive FOBT. Conclusion: Colonoscopy for post-adsurveillance but not colonoscopy for post-crc surveillance is associatedwith a lower risk of diagnosis of advanced adenoma and cancer.

Background/Aims: Chronic kidney disease (CKD) patients on dialysis areprone to vitamin D insufficiency despite oral vitamin D supplementation.Here, we studied whether narrow-band ultraviolet B (NB-UVB) exposuresimprove vitamin D balance. Methods: 14 haemodialysis patients and 15healthy subjects receiving oral cholecalciferol 20 mu g daily got nineNB-UVB exposures on the entire body. Serum 25-hydroxyvitamin D (25(OH)D)was measured by radioimmunoassay. Cutaneous mRNA expression levels ofCYP27A1 and CYP27B1, two enzymes required for hydroxylation of vitamin Dinto its active metabolite, were also measured. Results: The baselineserum 25(OH)D concentration was 57.6 +/- 18.2 nmol/l in the CKD patientsand 74.3 +/- 14.8 nmol/l in the healthy subjects. The NB-UVB courseincreased serum 25(OH)D by 14.0 nmol/l (95% CI 8.7-19.5) and 17.0nmol/l (CI 13.7-20.2), respectively. At baseline the CKD patients showedsignificantly increased CYP27B1 levels compared to the healthy subjects.Conclusions: A short NB-UVB course is an efficient way to improvevitamin D balance in CKD patients on dialysis who are receiving oralvitamin D supplementation. The increased cutaneous CYP27B1 levels in theCKD patients suggest that the loss of renal activity of this enzyme isat least partially compensated for by the skin.

Background: First-episode schizophrenia (FE-SZ) and attention deficithyperactivity disorder (ADHD) are both neuropsychiatric disordersassociated with an impaired dopaminergic transmission. Though displayingdifferent clinical phenotypes, a common pathophysiological pathway isdiscussed controversially. Several studies using transcranial magneticstimulation (TMS) revealed abnormalities in human motor cortexexcitability in both schizophrenia and ADHD patients. Studies oncortical excitability comparing these two diseases directly are lacking.Method: In this study, a total of 94 subjects were analyzed.Twenty-fiveFE-SZ patients were directly compared with 28 ADHD patients and 41healthy controls (HC). We investigated cortical excitability (inhibitoryand facilitatory networks) with single- and paired-pulse TMS to the leftand right motor cortex. Results: Compared to HC, FE-SZ/ADHD patientsdisplayed an impaired cortical inhibition over the left hemisphere.Apart from an enhanced intracortical facilitation, FE-SZ patients didnot differ compared to ADHD patients in the main outcome measures. Bothpatient groups presented a dysfunctional hemispheric pattern of corticalinhibition and facilitation in comparison with HC. Conclusion: Theresults of this study indicate a pattern of cortical disinhibition andabnormal hemispheric balance of intracortical excitability networks intwo different psychiatric diseases. These effects might be associatedwith an imbalance in GABAergic and dopaminergic transmission and mightprovide evidence for a common pathophysiological pathway of bothdiseases.

Background: Conjugated linoleic acids (CLA) in general, and in particular the trans-10, cis-12 (t10, c12-CLA) isomer are potent modulators of milk fat synthesis in dairy cows. Studies in rodents, such as mice, have revealed that t10, c12-CLA is responsible for hepatic lipodystrophy and decreased adipose tissue with subsequent changes in the fatty acid distribution. The present study aimed to investigate the fatty acid distribution of lipids in several body tissues compared to their distribution in milk fat in early lactating cows in response to CLA treatment. Effects in mammary gland are further analyzed at gene expression level. Methods: Twenty-five Holstein heifers were fed a diet supplemented with (CLA groups) or without (CON groups) a rumen-protected CLA supplement that provided 6 g/d of c9, t11-and t10, c12-CLA. Five groups of randomly assigned cows were analyzed according to experimental design based on feeding and time of slaughter. Cows in the first group received no CLA supplement and were slaughtered one day postpartum (CON0). Milk samples were taken from the remaining cows in CON and CLA groups until slaughter at 42 (period 1) and 105 (period 2) days in milk (DIM). Immediately after slaughter, tissue samples from liver, retroperitoneal fat, mammary gland and M. longissimus (13th rib) were obtained and analyzed for fatty acid distribution. Relevant genes involved in lipid metabolism of the mammary gland were analyzed using a custom-made microarray platform. Results: Both supplemented CLA isomers increased significantly in milk fat. Furthermore, preformed fatty acids increased at the expense of de novo-synthesized fatty acids. Total and single trans-octadecenoic acids (e. g., t10-18:1 and t11-18:1) also significantly increased. Fatty acid distribution of the mammary gland showed similar changes to those in milk fat, due mainly to residual milk but without affecting gene expression. Liver fatty acids were not altered except for trans-octadecenoic acids, which were increased. Adipose tissue and M. longissimus were only marginally affected by CLA supplementation. Conclusions: Daily supplementation with CLA led to typical alterations usually observed in milk fat depression (reduction of de novo-synthesized fatty acids) but only marginally affected tissue lipids. Gene expression of the mammary gland was not influenced by CLA supplementation.

Background: Since the times of domestication, cattle have been continually shaped by the influence of humans. Relatively recent history, including breed formation and the still enduring enormous improvement of economically important traits, is expected to have left distinctive footprints of selection within the genome. The purpose of this study was to map genome-wide selection signatures in ten cattle breeds and thus improve the understanding of the genome response to strong artificial selection and support the identification of the underlying genetic variants of favoured phenotypes. We analysed 47,651 single nucleotide polymorphisms (SNP) using Cross Population Extended Haplotype Homozygosity (XP-EHH). Results: We set the significance thresholds using the maximum XP-EHH values of two essentially artificially unselected breeds and found up to 229 selection signatures per breed. Through a confirmation process we verified selection for three distinct phenotypes typical for one breed (polledness in Galloway, double muscling in Blanc-Bleu Belge and red coat colour in Red Holstein cattle). Moreover, we detected six genes strongly associated with known QTL for beef or dairy traits (TG, ABCG2, DGAT1, GH1, GHR and the Casein Cluster) within selection signatures of at least one breed. A literature search for genes lying in outstanding signatures revealed further promising candidate genes. However, in concordance with previous genome-wide studies, we also detected a substantial number of signatures without any yet known gene content. Conclusions: These results show the power of XP-EHH analyses in cattle to discover promising candidate genes and raise the hope of identifying phenotypically important variants in the near future. The finding of plausible functional candidates in some short signatures supports this hope. For instance, MAP2K6 is the only annotated gene of two signatures detected in Galloway and Gelbvieh cattle and is already known to be associated with carcass weight, back fat thickness and marbling score in Korean beef cattle. Based on the confirmation process and literature search we deduce that XP-EHH is able to uncover numerous artificial selection targets in subpopulations of domesticated animals.