Incidence of multiple sclerosis in Hordaland, western Norway: a fluctuating pattern

The incidence of multiple sclerosis (MS) was studied in the county of Hordaland, western Norway. A significant increase in incidence in the period 1958-1987, a decline followed by a gradual increase in mean age at onset, geographic differences in time trends and a biphasic pattern revealed by a birth cohort analysis support the theory of real time-space fluctuations in the incidence of MS over time.     

Adeno-associated virus vector-mediated systemic delivery of IFN-beta combined with low-dose cyclophosphamide affects tumor regression in murine neuroblastoma models.

PURPOSE: Type I IFNs (IFN-alpha/beta) have shown significant antitumor activity in preclinical models but limited efficacy and significant toxicity in clinical trials. We hypothesized that the antitumor activity of type I IFNs could be enhanced by chronic, low-dose systemic delivery and sought to test this in murine neuroblastoma models. EXPERIMENTAL DESIGN: Continuous liver-generated expression of human IFN-beta (hINF-beta) was achieved through a gene therapy-mediated approach using adeno-associated virus vectors encoding hIFN-beta (AAV hINF-beta). Orthotopic localized retroperitoneal and disseminated models of neuroblastoma were established using three different xenografts. Immunohistochemical analysis and ELISA were used to evaluate the antiangiogenic effect of therapy. RESULTS: The development of both localized orthotopic (retroperitoneal) and disseminated neuroblastoma was prevented in all mice expressing hINF-beta. Continued growth of established retroperitoneal tumors, treated with AAV hINF-beta as monotherapy, was significantly restricted, and survival for mice with established, disseminated disease was significantly prolonged following administration of AAV hINF-beta. Analysis of treated tumors revealed a significant antiangiogenic effect. Mean intratumoral vessel density was diminished and expression of the angiogenic factors vascular endothelial growth factor and basic fibroblast growth factor were both decreased. Finally, combination therapy in which AAV hIFN-beta was used together with low-dose cyclophosphamide resulted in regression of both established retroperitoneal and disseminated disease. CONCLUSIONS: AAV-mediated delivery of hIFN-beta when used as monotherapy was able to restrict neuroblastoma growth due in part to inhibition of angiogenesis. When used in combination with conventional chemotherapy, AAV hIFN-beta was able to effect complete tumor regression.     

Systemic endotoxin and gastric mucosal pH are the best parameters to predict lethal outcome in a porcine model of abdominal sepsis according to multivariate analysis.

This study was devised to identify sepsis-relevant parameters that early and reliably predict a lethal outcome in intra-abdominal sepsis. In 18 Duroc pigs, peritonitis was induced through standardized gastrotomy. Twelve hours later the defect was oversewn and the abdominal cavity lavaged thoroughly. Sepsis relevant parameters were measured before initiating therapy, and 30 min later animals were extubated and observed for a period of 6 days under adequate analgesia with free access to water and food. All parameters were correlated with survival postoperatively. In the treatment group, 7 out of 18 pigs (39%) died within the observation period. Endotoxin level at 30 min after initiation of therapy [17.9 EU/mL (+/- 12.1) vs. 110.9 EU/mL (+/- 21); p <.001] and Delta pHi [0.015 (+/- 0.011) vs. -0.039 (+/- 0.013); p =.016] were identified as the two parameters with highest predictive power regarding mortality in a multivariate analysis. In conclusion measurement of endotoxin and gastric tonometry should gain wider clinical application in septic patients.     

Simultaneous en-bloc allotransplantation of pancreas and kidney in the animal model. Comparison of separate organ and en-bloc pancreas/kidney transplantation in swine]

The high technical complication rate of pancreas transplantation requires large animal models to improve clinical transplant survival rates. The pig is a very suitable animal due to its anatomy, physiology and immunology which are similar to humans. In this study a model of en-bloc simultaneous pancreas and kidney transplantation was established which--in contrast to separate transplantation of both organs--decreases preservation time, operation time, and clamp time. Furthermore, the rates of intra- and postoperative complications were reduced compared with separate transplantation. The donor aorta (encompassing celiac axis, superior mesenteric artery, and left renal artery) is anastomosed en-bloc to the recipients aorta in a an oblique-to-side fashion. The portal vein is anastomosed end-to-side to the left common iliac vein. The exocrine pancreatic secretions are drained via duodenocystostomy to allow for monitoring of urinary amylase for rejection. The en-bloc technique is an alternative for pediatric donor organs since the risk of vascular complications is lower compared with separate implantation of the donor vessels. Based on our results in a large animal model the en-bloc technique could be used in adult uremic diabetic patients who receive a combined pancreas-kidney transplant from a pediatric cadaver donor.     

Urination Frequency and Cystic Pressure Resistance After Fractionated whole or Partial Irradiation of the Rabbit Urinary Bladder

Urination frequency and cystic pressure resistance have been used as end-points to assess x-ray-induced changes of bladder function. Whole or half bladders of adult male rabbits were irradiated, caudally or cranially. The absorbed dose was 33 Gy, 36 Gy or 39 Gy, given in 5 daily fractions. Animals which received a whole bladder dose of 39 Gy or 36 Gy showed increased urination frequency and enhanced bladder pressure resistance during the whole follow-up time of 100 weeks, compared with the sham-irradiated controls. At half bladder irradiation, only the highest doses (39 Gy to the cranial part of the bladder and 39 Gy or 36 Gy to the caudal part) gave rise to a slight increase in frequency at about 20 weeks after exposure.     

Association of human polyomavirus JC with peripheral blood of immunoimpaired and healthy individuals

JC virus (JCV) infection is regularly asymptomatic in healthy individuals. In contrast, in immunocompromised individuals, highly activated virus replication may lead to PML. Peripheral blood cells (PBCs) are found to habor JCV DNA in healthy and diseased individuals and it is discussed that they might be responsible for dissemination of the virus to the central nervous system (CNS) during persistence. To better understand the role of JCV DNA in PBCs for persistent infection and pathogenesis, the authors characterized the extent of JCV infection in Ficoll-gradient purified blood cells (peripheral blood mononuclear cells [PBMCs]) of healthy and human immunodeficiency virus type 1 (HIV-1)-infected individuals. Virus activation in PBMCs from healthy JCV-infected individuals was found at a rate of 0% to 38% at low polymerase chain reaction (PCR) sensitivity. In progressive multifocal leukoencephalopathy (PML) patients, a stronger signal was found, indicating increased virus activation. JCV DNA was regularly detected in T and B lymphocytes and in monocytes at low levels. However, granulocytes were shown to be the predominant reservoir of JCV DNA harboring high copy numbers. Although the overall distribution of viral genomes holds true for the population studied, in the individual, a markedly changed pattern of distribution can be found.     

Staphylococcus epidermidis as a cause of postoperative wound infection after cardiac surgery: assessment of pathogenicity by a wound-scoring method

Wound infection after clean surgery prolongs hospital stay but the organism most commonly isolated from wound discharge, Staphylococcus epidermidis, is often dismissed as a contaminant or commensal. The wounds of 517 patients were assessed, after cardiac surgery, by a wound-scoring method ('ASEPSIS') and a close comparison was made of the appearance and clinical outcome of 89 wounds, from which bacteria were isolated. There was no significant difference in the scores of 49 wounds, where S. epidermidis was the sole isolate (9.5 per cent of all wounds, 95 per cent CI 6.9-12.0 per cent), and 13 wounds infected with Staphylococcus aureus (2.5 per cent, 95 per cent CI 1.2-3.9 per cent). Repeat cultures were obtained from 21 of the 49 wounds and, in 16 of these, the second isolate showed the same biochemical reactions and antibiotic resistance pattern as the first. Infection of sternal wounds is commoner with coagulase-negative staphylococci than with S. aureus and, clinically, is just as severe.     

Assistierte Reproduktion

Assisted reproduction (IVF/ICSI) is an established method for the treatment of infertility, though it entails a number of risks and limiting factors for the children and their families that really have to be considered and resolved. They also must be part of informative consultations before applying the selected (methods)/techniques. The following risks are of prime importance: 1. The increasing number of multiple pregnancies. Every multiple pregnancy has to be regarded as a complication of reproductive medicine: the rate of neonatal morbidity and mortality is higher compared to single pregnancies, and the emotional, logistic, and financial factors are significant for the concerned families. To limit these risks, it is preferable to perform only a single embryo transfer even though a lower rate of resulting pregnancies is to be expected. Of course it must be simultaneously provided that methods are developed and applied to transfer an embryo with high implantation potency. Based on existing/present results, the highest priority should not be given to pregnancy rates as high (as possible) but to the lowest possible complication rate for the infant with an acceptable pregnancy rate comparable to that achieved in fertile couples. 2. In assisted reproduction, the risk of fetal abnormalities seems to be elevated, but in some studies, according to the German IVF register, the selected method (ICSI) and other factors such as family abnormalities and environmental factors are relevant. Additional studies are required to clarify this subject and develop possible preventive strategies. 3. The children's psychomotoric development is normal as a rule. The risk of handicaps (retarded development spastic cerebral palsy) increases in accordance with the reduction of gestational period/age and the decrease of birth weight. This in turn is of particular significance in multiple pregnancies.