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Aim-Background: To review the rare entity of gastroenteropancreatic neuroendocrine tumours (GEP NETs) and to present multimodality therapeutic approaches for liver metastases in this group of patients. Case Report: We describe the case of a 57-year-old gentleman who presented at the Emergency Department with symptoms of complete large bowel obstruction due to a splenic flexure tumour. The patient underwent tumour extirpation by an extended left hemicolectomy with end colostomy (transverse colon), while multiple liver metastases (both lobes) were also palpated. His postoperative course was without any major complications and he was referred to a tertiary centre for further evaluation and treatment. Histology of the specimen was remarkable for low grade large bowel neuroendocrine carcinoma (G3 WHO 2010) pT3, N2b (TNM 2009). Results: Small NETs can be managed with local resection but larger tumours require formal resection of the involved organ with its adjacent lymph nodes, staging of the disease and planning of further treatment. Octreoscan identifies the need for adjuvant therapy with somatostatin analogues. Hepatectomy, with or without preoperative contralateral of the affected lobe portal vein embolisation, is performed on patients with metastases isolated to one lobe, while orthotopic liver transplantation is reserved for patients meeting standard criteria. Conclusions: The rarity of GEP-NETs along with the variations in their presenting symptoms is a challenging diagnosis for the attending physician. Surgical therapy remains the cornerstone of treatment, while numerous adjuncts (RFA, PRRT, SIRT, TACE) serve in the multimodality approach for patients with unresectable liver metastases. [ABSTRACT FROM AUTHOR]

The laboratory mouse, Mus musculus domesticus, has been the workhorse of the very successful laboratory study of mammalian immunology. These studies - discovering how the mammalian immune system can work - have allowed the development of the field of wild immunology that is seeking to understand how the immune responses of wild animals contributes to animals' fitness. Remarkably, there have hardly been any studies of the immunology of wild M. musculus domesticus (or of rats, another common laboratory model), but the general finding is that these wild animals are more immunologically responsive, compared with their laboratory domesticated comparators. This difference probably reflects the comparatively greater previous exposure to antigens of these wild-caught animals. There are now excellent prospects for laboratory mouse immunology to make major advances in the field of wild immunology. [ABSTRACT FROM AUTHOR]

Background: LIS1 is the main gene causing classical (isolated) lissencephaly predominating in the posterior brain regions (p>a). However, about 40% of patients with this malformation pattern show no abnormality after fluorescence in situ hybridisation (FISH) analysis of the 17p13.3 region and LIS1 sequencing. To investigate whether alternative gene(s) or genomic deletions/duplications of LIS1 may account for the high percentage of individuals who show no abnormalities on FISH and sequencing, we performed multiplex ligation dependent probe amplification assay (MLPA) in a series of patients. Methods: We initially performed DNA sequencing in 45 patients with isolated Iissencephaly with a p>a gradient, in whom FISH had revealed normal results. We subsequently performed MLPA in those who were mutation negative, and long range polymerase chain reaction (PCR) to characterise the breakpoint regions in patients in whom the deletions were small enough. Results: We found LIS1 mutations in 44% of patients (20/45) of the whole sample and small genomic deletions/ duplications in 76% of the remaining (19/25). Deletions were much more frequent than duplications (18 vs 1). Overall, small genomic deletions/duplications represented 49% (19/39) of all LIS1 alterations and brought to 87% (39/45) the number of patients in whom any involvement of LIS1 could be demonstrated. Breakpoint characterisation, performed in 5 patients, suggests that A/u mediated recombination is a major molecular mechanism underlying LIS1 deletions. Conclusions: LIS1 is highly specific for isolated p>a lissencephaly. The high frequency of genomic deletions/ duplications of LIS1 is in keeping with the over representation of Alu elements in the 17p13.3 region. MLPA has a high diagnostic yield and should be used as first line molecular diagnosis for p>a lissencephaly. [ABSTRACT FROM AUTHOR]

Between 1987 and 1990 a large series of at-risk individuals has been referred to our Huntington's disease (HD) presymptomatic testing programme. A detailed protocol for assessment and counselling has been followed. Out of 238 serious inquiries, 36% were potentially suitable for the testing programme, but 19% chose not to continue. Reasons for exclusion included the presence of clinical features of HD and being under the age of 18 years. Out of 40 final results given to 38 individuals, 23 indicated a lowered risk, 11 an increased risk, while five results were uninformative, two of these becoming informative on repeat testing. This series contained more women than men, and was disproportionately from the higher socio-economic groups. Motives for requesting a test principally related to child-bearing, informing existing children, and planning for the future. No significant psychiatric symptoms have been reported in the short term, but difficult counselling problems were presented by the high proportion of applicants who already showed clinical signs of HD. It is concluded that a detailed counselling protocol is essential in testing for HD, as many applicants are ill-prepared; this will assume even greater importance when the HD gene is identified and a test for specific mutations is available. The experience of presymptomatic testing for HD provides important general lessons which are likely to be applicable to other inherited neurological and psychiatric disorders. [ABSTRACT FROM AUTHOR]

The results of DNA analysis are presented for a series of 90 couples, with one partner at 50% risk for Huntington's disease (HD), who were referred for exclusion testing in pregnancy over a three year period. Thirty-seven couples were studied in detail. The aims of the study were to evaluate attitudes towards prenatal testing, before pregnancy and afterwards, and the effectiveness of our counseling and methods of organising the service. Problems which could arise in relation to presymptomatic testing are documented. It is concluded that exclusion testing is a valuable form of prediction for some couples, particularly where family structure does not permit prediction for the person at risk. The need for intensive counselling was highlighted by the difficulties experienced by many couples in understanding how the test worked. Particular ethical and organisational problems may arise which require careful consideration beforehand and some recommendations are made. The proportion of couples who will continue to request exclusion testing as pre-symptomatic testing becomes more widely applicable remains unknown. [ABSTRACT FROM PUBLISHER]

Thirteen South Wales kindreds with adult polycystic kidney disease have been studied for genetic linkage using the alpha globin and 3'HVR probes. A maximum lod score of 24.187 was found at a recombination fraction of 0.03. This study supports the existence of a single locus on chromosome 16 responsible for the disorder. [ABSTRACT FROM PUBLISHER]

The search for the Huntington's disease gene has recently concentrated on the telomere of the short arm of chromosome 4. The evidence suggesting this position has been based on single crossover events, but there is conflicting evidence regarding the position of the gene relative to the most terminal markers. We have found significant linkage disequilibrium between the markers D4S98 (probe BS731B-C) and D4S95 (probe BS674E-D) and HD, which supports a localisation for the gene proximal to D4S90 and makes a telomeric localisation unlikely. This disequilibrium may also prove to be important in the future in allowing modification of risk estimates based on genetic linkage. [ABSTRACT FROM PUBLISHER]

The autosomal dominant form of polycystic kidney disease (ADPKD) has been linked to the α-globin gene locus on 16p. Linkage studies between the autosomal recessive type (ARPKD) and the 3′ HVR of the α-globin gene cluster showed that the ARPKD and ADPKD are not allelic. [ABSTRACT FROM AUTHOR]