"Miniguts" from plucked human hair meet Crohn's disease.

Human pluripotent stem cells represent a powerful tool to study human embryonic development and disease but also open up novel strategies for cell replacement therapies. Their capacity to give rise to every cell type of the human body, meanwhile, enables researchers to generate high yields of mesodermal, ectodermal, but also endodermal-derived tissues such as hepatic, pancreatic, or intestinal cells. Another progress in the field came with the advent of 3-dimensional culture conditions, so-called organoids, which facilitate maturation of stem cells and in turn more faithfully recapitulate human tissue architecture. While several studies reported the derivation of organoid cultures from adult intestinal tissue, the derivation of intestinal organoids derived from plucked human hair of Crohn's disease patients has not been reported. The current research project reports such successful generation and characterization of induced pluripotent stem cells (iPSCs) derived from hair sheet keratinocyte cultures of a patient with Crohn's disease. Stepwise differentiation along the intestinal lineage showed no differences in intermediate stages such as definitive endoderm formation. We also directed the patterned primitive gut tube toward intestinal organoids resembling the cellular architecture of human "miniguts". As expected from current pathophysiological knowledge on Crohn's disease, there were no obvious morphological differences in the "miniguts" derived from healthy control and diseased patient-induced pluripotent stem cells. Taken together, our platform will enable for detailed and complementary phenotyping of the pathophysiology of Crohn's disease in a novel disease-in-a-dish format.

Determinants of eosinophil cationic protein in nasal lavages in children.

BACKGROUND: Nasal lavages are increasingly used to assess airways inflammation in children. However, there are no studies assessing how measurement error as well as biological influences contribute to the concentration of nasal inflammatory parameters in a population based survey. OBJECTIVE: To investigate determinants of concentration of eosinophil cationic protein (ECP) in nasal lavages we studied 147 schoolchildren (mean age 8.1 years, SD 0.6 years) by repeated nasal lavages/year over a 2 year period. METHODS: Standardized questionnaires were completed by the parents each year. A skin-prick test with seven aeroallergens (birch, cat, dog, hazel, weeds, Dermatophagoides pteronyssinus and D. farinae) was performed. One hundred and one children could perform valid lavages at least five times a year. As a measure of reproducibility the intraclass coefficient of reliability was calculated. RESULTS: The intraclass coefficient of reliability was 0.27 over all observations suggesting that about a quarter of total variance is due to between-subject variance. Taking means over each year increased reliability to 0.60. Linear regression analyses with ECP being the dependent variable demonstrated significant higher values for boys (beta=12.26; P < 0.01), children sensitized to seasonal (beta=34.27; P=0.02) but not to perennial allergens (beta=-4.44; P=0.57), and for children with a serous (beta=10.01; P=0.01) or purulent rhinitis (beta=22.45; P < 0.001). CONCLUSION: Assessment of inflammatory mediators in nasal lavages is a useful tool for epidemiological paediatric studies. However, due to the relatively high intraindividual variability of ECP concentrations multiple lavages are necessary to characterize the individual.

Fatal haemoptysis associated with invasive pulmonary aspergillosis treated with high-dose amphotericin B and granulocyte-macrophage colony-stimulating factor (GM-CSF).

Opportunistic pulmonary infections are a leading cause of morbidity and mortality in patients with chemotherapeutically treated neoplasias. With increasingly aggressive cytotoxic regimens causing prolonged neutropenia, the risk of systemic mycoses and in particular of invasive pulmonary aspergillosis has increased. We review the case of a 10-year-old child suffering from relapsed lymphoblastic leukaemia and from high-dose amphotericin B-treated invasive pulmonary aspergillosis acquired during long-standing neutropenia in the initial phase of remission induction chemotherapy. The patient died in remission after GM-CSF-induced bone marrow recovery and clinical and radiological improvement with stable plasmatic coagulation and normal thrombocyte count. Peracute massive pulmonary bleeding caused by the simultaneous arrosion of a greater pulmonary artery and a lobar bronchus by a liquefactive fungal focus was responsible. In patients with chemotherapeutically induced neutropenia and invasive aspergillosis, bone marrow recovery may lead to the liquefaction of pulmonary foci, and, in view of the well-known vasotropic nature of the infection, to a potentially lethal arrosion bleeding. With the emerging use of colony-stimulating factors for shortening and overcoming neutropenia, this so far rare complication may become of increasing importance.

[Eye manifestations of fetal alcohol syndrome]. / Augenveränderungen bei Alkoholembryopathie.

Alcohol is the most frequent and most important teratogenic agent causing mental and physical retardation in childhood. The alcohol fetal syndrome is characterized by pre- and postnatal growth retardation, hypotonia, hyperactivity, microcephalus, mental retardation and typical craniofacial malformations. The latter includes short palpebral fissures, a poorly developed philtrum, thin upper lip vermillion, short mandibles, a flattened midface structure and dysplastic ears. Ophthalmological signs occur in 90% and include epicanthus, ptosis, myopia, optic nerve hypoplasia and tortuous retinal vessels. Microphthalmus, coloboma and Peters' anomaly have also been described. Five children with alcohol embryopathy are presented. The histopathological findings of the enucleated eye of a 6th child with alcohol embryopathy which was sent to us for examination and which revealed an anterior staphyloma with Peters' anomaly is also described. Ophthalmologists should be aware of alcohol in pregnancy as a preventable cause of eye malformation.

[Histochemical and histomorphometric studies on growth fractions in human breast carcinoma]. / Histochemische und histomorphometrische Untersuchungen zum Wachstumsverhalten menschlicher Mammacarcinome.

Nucleolar organizer regions (NOR) can easily be recognized on paraffin sections of bioptic material with an argyrophilic stain. NORs are meant to to correlate with mitotic activity of proliferating cells. This study examine wether NOR-activity corresponds with the proliferations marker KI-67. 10 fibroadenomas and 40 invasive ductal breast carcinomas were studied. For objective tumor grading the size of the nuclei was determined morphometrically. NORs, KI-67 and nuclei sizes correlate closely in fibroadenomas. In carcinomas, however, a correlation between NORs, KI-67, and the size of the nuclei could not be found. NORs and KI-67 evidently mark different cell activities. For prognostic evaluation of malignant tumors they should therefore not be used alternatively but complementarily.

Microcirculatory disturbances during the early phase following experimental spinal cord trauma in the rat.

The early (primary) lesion of the microvasculature and neurons in the gray matter of the rat become mainfest within 0-3 min, long before the development of secondary ischemic-anoxic changes. The central hemorrhagic necrosis of the gray matter, induced by the impact injury, seems to depend primarily on theseverity of trauma. However, since the lesion is limited to the gray matter of one or two segments, these primary changes are not responsible for the irreversible transverse lesion. Additionally, the experimental cord injury in the rat demonstrates that secondary vascular changes (i.e., the pathological permeability of vessels in the white matter) produce a progressive edema that spreads into the necrotic zone and leads to definite transverse lesion. Not least of all, the increased pressure of the spinal tissue may promote the self-destructive process leading to irreversible damage to white matter.