Distant relations: business interruption insurance and business closure insurance.

This article looks at COVID-19-related issues in the context of commercial and industrial insurance cover taken out against the risk of infectious disease. The focus is on government action taken and regulation passed in the U.K. and in Germany, respectively, to redress the pandemic. The insurance market offers business interruption (BI) cover (in the U.K. and internationally) as well as business closure (BC) cover (mainly in Germany) to protect against the impact of infectious diseases on commercial enterprises. The insurance law issues that came to be analysed in relation to the COVID-19 pandemic formed the subject matter of widespread litigation in both countries. Judgements were rendered in the Supreme Court in the U.K. (the FCA test case) and in the German Federal Supreme Court and now provide some authoritative legal guidance. However, the outcome of these court battles was totally different, insofar as policyholders were concerned. This article, next to offering some historical legal analysis of BI and BC insurance cover, attempts to explain why policyholders won in court in the U.K. and lost the legal argument in Germany and seeks to reconcile these diverse outcomes. The article ends with a brief outlook on how the pertinent COVID-19 insurance law issues might come to be revisited, both by the markets and in the legal community, in the context of reinsurance coverage.

Primary signet ring cell mucinous ovarian carcinoma: a case report and literature review.

A 24-year-old female patient presented with an extremely rare primary signet cell carcinoma of the right ovary 1 year after surgery for a mucinous borderline tumour of the left ovary. Relaparotomy was carried out with right adnexectomy, appendectomy and partial omentectomy. Surgery was followed by 6 courses of paclitaxel/carboplatinum chemotherapy. After an initial response, the patient again developed increasing ascites. The patient was transferred to our hospital and a re-relaparotomy was carried out, completing the operation. After 3 courses of pegylated doxorubicin/trabectedin, the clinical course showed a positive response and a decline of the tumour marker CEA in peripheral blood. After 5 months, ascites developed in the retroperitoneum so that the chemotherapy had to be changed. In spite of a positive response with the new chemotherapy, the patient died of a very rare pulmonary complication after 1 month within 2 days.

[Superior vena cava syndrome by cardiac tumor]. / Sekundäres kardiales Non-Hodgkin-Lymphom als Differentialdiagnose des Vena-cava-superior-Syndroms.

CASE REPORT: A 59-year-old man with a 4-week history of dyspnea, coughing, and chest discomfort was referred to hospital for further evaluation. Moreover, he reported fever and fatigue. There were neither cardiovascular risk factors nor drug medication. 6 months earlier, a deep vein thrombosis of his left lower limb was diagnosed followed by an anticoagulation for 4 weeks. Physical examination revealed a dilatation of the neck veins with a present Kussmaul sign and a diastolic murmur at the left lower sternal border. The findings on the rest of his physical examination were unremarkable. Electrocardiography showed normal sinus rhythm, low voltage, and anterolateral T wave inversion. Initial laboratory results were remarkable for elevated lactate dehydrogenase level. Transthoracic echocardiography revealed a small pericardial effusion with a large intracardiac mass adjacent to the right atrium. Thoracic computed tomography confirmed the tumor mass and showed enlargement of mediastinal lymph nodes. The patient underwent transesophageal echocardiography-guided transvenous biopsy of the tumor. The immunohistology of the specimen revealed non-Hodgkin's lymphoma. The patient subsequently received a chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone. His clinical response after the first cycle was remarkable with total regression of the superior vena cava syndrome. After the third cycle of therapy, both tumor and pericardial effusion had disappeared. CONCLUSION: A cardiac tumor is a rare cause of a superior vena cava syndrome. Tissue biopsy is warranted to guide diagnosis and therapy. Transvenous biopsy is generally safe when guided by echocardiography.

Homozygous WNT3 mutation causes tetra-amelia in a large consanguineous family.

Tetra-amelia is a rare human genetic disorder characterized by complete absence of all four limbs and other anomalies. We studied a consanguineous family with four affected fetuses displaying autosomal recessive tetra-amelia and craniofacial and urogenital defects. By homozygosity mapping, the disease locus was assigned to chromosome 17q21, with a maximum multipoint LOD score of 2.9 at markers D17S931, D17S1785, D17SS1827, and D17S1868. Further fine mapping defined a critical interval of approximately 8.9 Mb between D17S1299 and D17S797. We identified a homozygous nonsense mutation (Q83X) in the WNT3 gene in affected fetuses of the family. WNT3, a human homologue of the Drosophila wingless gene, encodes a member of the WNT family known to play key roles in embryonic development. The Q83X mutation truncates WNT3 at its amino terminus, suggesting that loss of function is the most likely cause of the disorder. Our findings contrast with the observation of early lethality in mice homozygous for null alleles of Wnt3. To our knowledge, this is the first report of a mutation in a WNT gene associated with a Mendelian disorder. The identification of a WNT3 mutation in tetra-amelia indicates that WNT3 is required at the earliest stages of human limb formation and for craniofacial and urogenital development.

Immunoscintigraphy of septic loosening of knee endoprosthesis: a retrospective evaluation of the antigranulocyte antibody BW 250/183.

Immunoscintigraphy with the use of the antigranulocyte antibody BW 250/183 is a reliable method for detecting infection, especially in septic loosening of hip prostheses, for which purpose quantitative interpretation of the time-activity course is employed. Therefore, we retrospectively studied whether similar results could be achieved in knee prostheses. We verified 28 scintigraphic examinations in 26 patients by histology. Scintigraphy was performed during an early (4-6 h post injection) and a late phase (23-25 h post injection). Infection was diagnosed when activity around the knee prosthesis increased by more than 10% compared with bone marrow. We found a sensitivity and a negative predictive value of 100%, a specificity of 80%, a positive predictive value of 81% and an accuracy of 89%. Specificity and accuracy are lower than in the evaluation of hip prostheses; however, in comparison to other scintigraphic modalities, scintigraphy with the antigranulocyte antibody BW 250/183 is superior in excluding infection and has better specificity and accuracy. Therefore, as in the case of hip prostheses, the described methodology appears to be the scintigraphic modality of choice for knee prostheses.

Genomic gain of PIK3CA and increased expression of p110alpha are associated with progression of dysplasia into invasive squamous cell carcinoma.

PIK3CA, encoding the catalytic subunit p110alpha of phosphatidylinositol 3-kinase (PI3K), is activated in malignant diseases. However, the role of the PIK3CA gene aberrations for tumourigenesis of head and neck squamous cell carcinoma (HNSCC) is to date unclear. The present study was designed to determine the genomic aberration of PIK3CA in invasive HNSCC and dysplastic precursor lesions by fluorescence in situ hybridization (FISH) with a YAC probe, containing the PIK3CA gene, on isolated interphase nuclei from histomorphologically well-defined regions of formalin-fixed tissue sections and to compare these data with protein and mRNA expression of p110alpha. The mRNA and protein levels of p110alpha were assessed, respectively, by in situ hybridization and immunohistochemistry on consecutive tissue sections. Copy number gains at 3q26 were observed in one of six low-to-moderate dysplasias (17%) and in seven of nine high-grade dysplasias (78%), as well as in 11 carcinomas (100%). In addition, one of seven high-grade dysplasias (14%) and 6 of 11 carcinomas (55%) had amplifications of 3q26. The majority of cases with copy number gain in more than 50% of the cells and/or amplification in more than 10% of cells showed increased p110alpha mRNA and protein expression, whereas only two cases (18%) (one high-grade dysplasia and one carcinoma) with no gain or low-level gain displayed increased p110alpha protein expression. These data suggest that 3q26 copy number gain and amplification represent early genomic aberrations in HNSCC carcinogenesis. In addition, p110alpha mRNA and protein expression in HNSCC may be regulated by these genomic aberrations as well as by epigenetic events.

Calcitonin receptor-like receptor: identification and distribution in human peripheral tissues.

We report here on the characterization and immunohistochemical localization in human tissues of calcitonin receptor-like receptor (CRLR) which was recently found to mediate the effects of both calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM). Western blot analysis using antibodies raised against the first extracellular loop and the carboxy-terminal part of hCRLR, respectively, detected two major bands corresponding to about 70 and 60 kDa in membrane preparations of cultured endothelial cells and numerous organs including lung, heart ventricle and kidney. Immunohistochemical analysis of the cardiovascular system revealed CRLR-like immunoreactivity (CRLR-LI) in the endothelium of all blood vessels including large and small arteries, veins and capillaries, and in heart muscle cells and endocardium. The lung showed intense staining over the alveolar capillaries. Within the digestive tract, staining was observed over the cells lining the excretory ducts of the parotid gland, over the epithelium of the fundic glands of stomach, endocrine cells of the duodenum and ileum and some myenteric ganglia. The kidney presented staining of the juxtaglomerular arteries, the glomerular capillaries and chief cells of the collecting duct. Within the endocrine organs, a strong CRLR-LI signal was observed over the Langerhans islets, and weak immunoreactivity in the Leydig cells of testis. Spleen showed intense staining in trabecular veins and sinuses. Macrophages displayed a variable immunoreactivity. Our data demonstrate a wide distribution of CRLR throughout the human body and suggest CRLR to be involved in the mediation of a variety of actions in addition to vascular control.

Testing of skeletal implant surfaces with human fetal osteoblasts.

The effect of standard orthopaedic implant materials on osteoblast proliferation and differentiation was investigated using a human osteoblast cell culture system. Human fetal osteoblasts 1.19 were cultured on stainless steel, cobalt-chrome-molybdenum, and commercially pure titanium for 12 days. Tissue culture polystyrene was used as a control. Cell proliferation was measured by electronic cell counting and by a colorimetric proliferation assay. To assess the degree of differentiation, levels of alkaline phosphatase activity, collagen Type I, and osteocalcin production were measured. Osteocalcin gene expression was measured by reverse transcriptase-polymerase chain reaction. Electronic cell counting and proliferation assays showed lower cell numbers and delayed proliferation on stainless steel and cobalt-chrome-molybdenum compared with titanium and polystyrene. Alkaline phosphatase and osteocalcin were measured higher on titanium than on stainless steel or cobalt-chrome-molybdenum. Differences in collagen Type I production were not found. Reverse transcriptase-polymerase chain reaction showed the highest osteocalcin gene expression on titanium. The human fetal osteoblast cell line 1.19 provides a rapidly proliferating and differentiating system for testing biomaterials in which differences in osteoblast proliferation and differentiation on orthopaedic implant materials could be revealed, suggesting that the chemistry of biomaterials has a dynamic effect on proliferation and differentiation of human osteoblasts.