Ontogeny and cellular expression of MHC and leucocyte antigens in human retina

We have investigated the ontogeny of MHC class I, class II, CD45, and macrophage antigens in wholemounts of normal human fetal retina at 10–25 weeks gestation (WG) using monoclonal antibodies and immunogold histochemistry. MHC class I antigens were expressed on retinal vascular endothelial cells and provided a useful marker of vessel organization from 14–25 WG. Microglial cells expressed immunoreactivity to MHC class I, class II, and CD45 antigens from 10 WG (pre-vascularization) and macrophage S22 (Mac S22) antigen from 14 WG (post-vascularization), although none of the antigens tested were detected on neuronal or macroglial elements. Microglia expressing MHC, CD45, and macrophage antigens occurred in both ramified and rounded forms with no close correlation being observed between morphology and antigenicity. The numbers of immunoreactive cells labeled with each of the four markers increased steadily throughout gestation in all specimens studied. Equivalent numbers of microglia expressed MHC class I, class II, and CD45 antigens in retinae at similar gestational ages; however, our data indicate that microglia expressing Mac S22 antigen comprise approximately 40% or less of the population of MHC and CD45-immunoreactive cells during development. Topographical analyses suggest that MHC class I, class II, and CD45-positive microglia enter the retina from both the peripheral retinal margin and the optic disc from at least 10 WG; Mac S22-positive cells appear in association with the development of the retinal vasculature and enter the retina via the optic disc after 14 WG. © 1995 Wiley-Liss, Inc.     

Handling of asymmetrical dimethylarginine and symmetrical dimethylarginine by the rat kidney under basal conditions and during endotoxaemia.

BACKGROUND: Asymmetrical dimethylarginine (ADMA) is capable of inhibiting nitric oxide synthase enzymes, whereas symmetrical dimethylarginine (SDMA) competes with arginine transport. The potential role of inflammation in the metabolism of ADMA has been elucidated in an in vitro model using tumour necrosis factor-alpha, resulting in a decreased activity of the ADMA-degrading enzyme dimethylarginine dimethylaminohydrolase (DDAH). The kidney probably plays a crucial role in the metabolism of ADMA by both urinary excretion and degradation by DDAH. We aimed to further elucidate the role of the kidney in a rat model under basal conditions and during endotoxaemia. METHODS: Twenty-five male Wistar rats weighing 275-300 g were used for this study. The combination of arteriovenous concentration differences and kidney blood flow allowed calculation of net organ fluxes. Blood flow was measured using radiolabelled microspheres according to the reference sample method. Concentrations of ADMA, SDMA and arginine were measured by high-performance liquid chromatography. RESULTS: The kidney showed net uptake of both ADMA and SDMA and fractional extraction rates were 35% and 31%, respectively. Endotoxaemia resulted in a lower systemic ADMA concentration (P = 0.01), which was not explained by an increased net renal uptake. Systemic SDMA concentrations increased during endotoxaemia (P = 0.007), which was accompanied by increased creatinine concentrations. CONCLUSIONS: The rat kidney plays a crucial role in the regulation of concentrations of dimethylarginines, as both ADMA and SDMA were eliminated from the systemic circulation in substantial amounts. Furthermore, evidence for the role of endotoxaemia in the metabolism of dimethylarginines was obtained as plasma levels of ADMA were significantly lower in endotoxaemic rats.     

Venenthrombose und Lungenembolie Prophylaxe und Behandlung

Venöse Thromboembolien (VTE) stellen eine häufige Morbiditäts- und Mortalitätsursache dar; die jährliche Inzidenz wird mit etwa 1 : 1 000 angegeben. Dabei sind verschiedene Risikogruppen zu unterscheiden, die sowohl durch endogene Faktoren (z. B. genetisch deteminierte Thrombophilie), viel häufiger aber durch exogene Faktoren (zugrundeliegende Erkankung) charakterisiert werden. Diese Heterogenität resultiert in Besonderheiten bei Prophylaxe und Therapie von VTE, auf die in dieser Darstellung eingegangen werden soll.     

Editorial

Aim: Wall stress‐independent signalling pathways were studied for endothelin‐1 (ET‐1)‐induced c‐fos expression in rat intact mesenteric small arteries. Methods: Arteries were kept unmounted in Krebs buffer, equilibrated for 1 h and stimulated with vasoactive substances for 15–60 min. The c‐fos mRNA expression was determined by real‐time polymerase chain reaction. Results: Stimulation with fetal bovine serum (FBS), phorbol 12‐myristate 13‐acetate (PMA) and ET‐1 caused about a doubling of c‐fos mRNA. The ET‐1‐induced c‐fos expression was steady (15–60 min) and was inhibited by the inhibitor of the ET_A receptor, BQ‐123. Platelet‐derived growth factor‐B, angiotensin II and U46619 did not cause increased c‐fos mRNA levels. The broad specificity inhibitor staurosporine inhibited the response to ET‐1, but inhibitors of Rho‐A kinase and phosphatidylinositol 3‐kinase had no effect. However, inhibitors to tyrosine kinases, the MAP kinases [extracellular signal‐regulated kinase 1/2 (ERK1/2), c‐Jun amino‐terminal kinase, p38], and to conventional protein kinase C showed no inhibition. Consistent with these findings, ET‐1 did not cause activation of ERK1/2, a finding also seen in vessels held under pressure. In contrast, ET‐1‐induced c‐fos expression was inhibited by the calcium chelator BAPTA, suggesting a role for intracellular calcium. This possibility was supported by the finding that raising the extracellular K⁺ concentration caused increased expression of c‐fos in a concentration‐dependent manner. Conclusion: The results suggest that in the absence of wall stress, ET‐1 is able to induce increased expression of c‐fos independent of traditional growth pathways, such as MAP kinase. The mechanism appears to be calcium‐dependent.     

Assessment of nutritional status in children with cystic fibrosis: conventional anthropometry and bioelectrical impedance analysis. A cross-sectional study in Dutch patients

BACKGROUND: Assessment of nutritional status in children with cystic fibrosis (CF) is clinically relevant. Methods to measure nutritional status should be reliable and non-invasive, and reference values should be available. AIM: To compare weight and height measurements and measurements of specific body compartments in children with CF. METHODS: In a cross-sectional survey of 58 children with CF (28 females), we compared height and weight (expressed as: weight-for-height, body mass index (BMI), height-for-age and weight-for-age) with fat mass (skinfold sum (SFS)), muscle mass (upper arm circumference (UAC)) and bioelectrical impedance analysis (BIA). Results were expressed as Z-scores, using Dutch reference values. RESULTS: BMI and weight-for-height were within the normal range (mean Z-score (range): -0.13 (-1.5, 2.7) and -0.02 (-1.7, 2.8)). Weight and height corrected for age were below normal (mean Z-score (range): -0.79 (-2.4, -0.05) and -1.2 (-2.8, 1.4) (P<0.01)). Lean body mass by skinfold sum (LBM(sfs)), UAC and BIA were also significantly below reference values (mean Z-score (range): -0.9 (-2.2, 1.8), -0.95 (-2.4, 1.8) and -1.1 (-3.6, 1.0) (P<0.01)). Lean body mass (LBM) by BIA correlated with LBM(sfs). BIA systematically underestimated LBM in both CF patients and in control subjects. CONCLUSION: Nutritional status of children with CF must be evaluated, using age-corrected weight and height expressed in Z-score. LBM estimated by SFS, UAC and by BIA appear to be useful, although longitudinal studies in CF children should be performed to evaluate their clinical significance in detecting changes in nutritional status.     

MRI of transplanted pancreatic islets.

A promising treatment method for type 1 diabetes mellitus is transplantation of pancreatic islets containing beta-cells. The aim of this study was to develop an MR technique to monitor the distribution and fate of transplanted pancreatic islets in an animal model. Twenty-five hundred purified and magnetically labeled islets were transplanted through the portal vein into the liver of experimental rats. The animals were scanned using a MR 4.7-T scanner. The labeled pancreatic islets were clearly visualized in the liver in both diabetic and healthy rats as hypointense areas on T2*-weighted MR images during the entire measurement period. Transmission electron microscopy confirmed the presence of iron-oxide nanoparticles inside the cells of the pancreatic islets. A significant decrease in blood glucose levels in diabetic rats was observed; normal glycemia was reached 1 week after transplantation. This study, therefore, represents a promising step toward possible clinical application in human medicine.     

Fusion and failure following anterior cervical plating with dynamic or rigid plates: 6-months results of a multi-centric, prospective, randomized, controlled study

Anterior cervical plate fixation is an approved surgical technique for cervical spine stabilization in the presence of anterior cervical instability. Rigid plate design with screws rigidly locked to the plate is widely used and is thought to provide a better fixation for the treated spinal segment than a dynamic design in which the screws may slide when the graft is settling. Recent biomechanical studies showed that dynamic anterior plates provide a better graft loading possibly leading to accelerated spinal fusion with a lower incidence of implant complications. This, however, was investigated in vitro and does not necessarily mean to be the case in vivo, as well. Thus, the two major aspects of this study were to compare the speed of bone fusion and the rate of implant complications using either rigid- or dynamic plates. The study design is prospective, randomized, controlled, and multi-centric, having been approved by respective ethic committees of all participating sites. One hundred and thirty-two patients were included in this study and randomly assigned to one of the two groups, both undergoing routine level-1- or level-2 anterior cervical discectomy with autograft fusion receiving either a dynamic plate with screws being locked in ap - position (ABC, Aesculap, Germany), or a rigid plate (CSLP, Synthes, Switzerland). Segmental mobility and implant complications were compared after 3- and 6 months, respectively. All measurements were performed by an independent radiologist. Mobility results after 6 months were available for 77 patients (43 ABC/34 CSLP). Mean segmental mobility for the ABC group was 1.7 mm at the time of discharge, 1.4 mm after 3 months, and 0.8 mm after 6 months. For the CSLP- group the measurements were 1.0, 1.8, and 1.7 mm, respectively. The differences of mean segmental mobility were statistically significant between both groups after 6 months (P = 0.02). Four patients of the CSLP-group demonstrated surgical hardware complications, whereas no implant complications were observed within the ABC-group (P = 0.0375). Dynamic plate designs provided a faster fusion of the cervical spine compared with rigid plate designs after prior spinal surgery. Moreover, the rate of implant complications was lower within the group of patients receiving a dynamic plate. These interim results refer to a follow-up period of 6 months after prior spinal surgery. Further investigations will be performed 2 years postoperatively.     

Sumatriptan nasal spray in the acute treatment of migraine in adolescents and children

About 4-10% of children and adolescents suffer from migraine. In the last few years, several studies have been performed to assess the efficacy and safety of triptans for the acute treatment of migraine in children and adolescents. Only sumatriptan nasal spray has been approved for the treatment of acute migraine with or without aura in adolescents aged 12-17 years in Europe. This review describes the results of the studies with sumatriptan nasal spray that have been performed in children and adolescents, including a study performed in the Netherlands.     

Agenesis of permanent incisors in a mediaeval maxilla and mandible: aetiological aspects

A paleopathological maxilla and mandible with tooth agenesis were analyzed, focussing on the aetiology of the condition. The jaw material, derived from an adult mediaeval male, was examined by standard anthropological analyses, including radiography. In the maxilla there was agenesis of three permanent incisors and one premolar, and in the mandible of one permanent incisor and two permanent molars. Absence or marked reduction of the incisive foramen and the nasopalatine canal was found. The pattern of tooth agenesis was similar to the pattern observed in contemporary individuals, except for the agenesis of one permanent maxillary centreal insisor. It is suggested that the pronounced lack of the premaxillary area of the nasopalatine canals and the incisive foramen. As the condition can be ascribed to deviations in the prenatal developments, this investigation shows that embryological developmental patterns, which form the basis for the pattern of tooth agenesis, should be taken into account when evaluation dry bonde patholgy.