Norethisterone Treatment, a Major Risk-Factor for Veno-Occlusive Disease in the Liver After Allogeneic Bone Marrow Transplantation

In this single-center study, we retrospectively analyzed incidenceand risk factors for hepatic veno-occlusive disease (VOD) in 249 consecutive patients who underwent allogeneic hematopoietic stem celltransplantation between January 1990 and June 1995. Twenty-four of the249 transplanted patients developed VOD. The probabilities ofdeveloping VOD were 17% among women and 7% in men (P = .01). In women treated with norethisterone, the incidence was 27%compared with 3% in women without this treatment (P = .007).One-year survival rates were 17% and 73% in patients with (n = 24)or without VOD (n = 225), respectively. The use of heparin prophylaxis (100 IE/kg/24 hours for 1 month) did not alter the incidence or 1-year mortality of VOD. In multivariate analysis, thefollowing risk factors were significant: norethisterone treatment (P < .001), bilirubin >26 µmol/L before bone marrowtransplantation (BMT) (P = .002), one HLA-antigen mismatch(P = .003), previous abdominal irradiation (P = .02), and conditioning with busulphan (P = .02). Ourconclusion is that norethisterone treatment should not be used inpatients undergoing BMT and heparin prophylaxis did not affect theincidence or mortality of VOD.     

Grafted neural stem cells develop into functional pyramidal neurons and integrate into host cortical circuitry

In vitro expanded neural stemprogenitor cells can undergo region-specific differentiation after transplantation to the developing or adult brain, and display morphologies and markers characteristic of mature neurons. Here we have used patch-clamp techniques to explore whether grafted stem cells also can develop physiological properties of mature neurons and become functionally integrated within host neural circuitry. The immortalized neural progenitor cell line, RN33B, prelabeled with GFP by using a lentiviral vector, was transplanted into the cortex or hippocampus of neonatal rats. We found that the grafted GFP-positive cells differentiated into cells with morphological features of cortical or hippocampal pyramidal neurons, and that many of them had established appropriate cortico-thalamic and contralateral hippocampal connections, respectively, as revealed by retrograde tracing. Whole-cell patch-clamp recordings from grafted cells with morphological characteristics of pyramidal neurons showed that they were able to generate action potentials, and received functional excitatory and inhibitory synaptic inputs from neighboring cells. These data provide evidence that grafted neural progenitors can differentiate into morphologically mature pyramidal projection neurons, establish appropriate long-distance axonal projections, exhibit normal electrophysiological properties, and become functionally integrated into host cortical circuitry.     

Motility index measured by magnetic resonance enterography is associated with sex and mural thickness

BACKGROUND Recently, a technique has been developed to use magnetic resonance enterography(MRE) for the evaluation of small bowel motility. The hypothesis was that assessment of the motility index(MI) should reflect differences in motility between clinical conditions.AIM To aim of the present observational, cross-sectional study was to evaluate the use of the MI in daily clinical practice.METHODS All consecutive patients aged 18-70 years who were referred for MRE at the Department of Radiology during a 2-year period were asked to participate. Healthy volunteers were included as controls. MRE was prepared and conducted in accordance with clinical routines. On the day of examination, all the participants had to complete the visual analog scale for irritable bowel syndrome(IBS) and IBS-symptom severity scale. Maps of MI were calculated from dynamic MR images. ANOVA was used to evaluate differences in MI between groups, classified as healthy, Crohn's disease, ulcerative colitis, IBS, other assorted disorders and dysmotility. Logistic and linear regression were applied to the MI values. All medical records were scrutinized for medical history.RESULTS In all, 224 examinations were included(inclusion prevalence 76.3%), with 22 controls and 202 patients. There was a significant difference in the MI of the jejunum(P = 0.021) and terminal ileum(P = 0.007) between the different groups. The MI was inversely associated with the mural thickness of the terminal ileum in men(P 0.001) and women(P = 0.063) after adjustments, and tended to be lower in men than in women(P = 0.056). Subjectively observed reduction of motility on MRI was accomplished by reduced MI of terminal ileum in men(P 0.001) and women(P = 0.030). In women, diarrhea was inversely associated with the MI of the jejunum(P = 0.029), and constipation was positively associated with the MI of the terminal ileum(P = 0.039).CONCLUSION Although MIs differ across diseases, a lower MI of the terminal ileum is mainly associated with male sex and an increased mural thickness. Symptoms are weakly associated with the MI.     

The effect of body mass and physical activity on the development of guinea pig osteoarthrosis

We quantitatively evaluated the morphological and biochemical effects of body mass and physical activity on spontaneously developing guinea pig osteoarthrosis (OA). 6-month-old male guinea pigs were allocated to 3 groups: controls (C) living under standard laboratory conditions with food ad libitum; mobilized animals (M) allowed unrestricted motion in large rooms with food ad libitum; and a diet group (D) weight-matched with the M-group. At 9- and 12-months of age they were killed and the left proximal tibia was processed for quantitative histology and the right tibial articular cartilage for analyses of glycosaminoglycan (GAG). OA mostly occurred on the medial condyleos central part not covered by the meniscus. The thinnest cartilage was found in 12-month-old M-animals (M12), which had 60% of the central cartilage surface affected by lesions that extended down to the mineralized cartilage. C12 had 25% exposed mineralized cartilage and D12, 2%. Subchondral bone density followed the loading patterns N the highest in M12 and lowest in D12. M12 had the lowest cartilage GAG concentrations. Load appears to be a key external factor in guinea pig OA. An increase in physical activity may be chondroprotective in the early phase, but harmful when fibrillations eventually have developed. This is underscored by the extensive OA changes in M12, although these animals weighed about the same as D12 (which had the least extensive OA). Therefore, a reduction in body mass seems to retard the progression of OA in animals, which are mainly subjected to a static load (C12 and D12), but not sufficiently in animals with a more dynamic load (M12). Changes in morphological patterns are paralleled by changes in GAG concentration, which probably reflect the metabolic capacity of the cartilage.