Interstitial and vascular pancreas rejection in relation to graft survival

To examine the incidence of interstitial and vascular rejection in pancreas allografts and its impact on graft survival, we studied 36 percutaneous pancreas biopsies and 10 pancreas transplantectomy specimens from 32 patients who had undergone simultaneous pancreas-kidney transplantation. Interstitial rejection (IR) was predominantly found in the biopsies, while vascular rejection (VR) was most prominent in the transplantectomies. Pancreas graft survival was significantly decreased for pancreas grafts that had suffered from vascular rejection when compared to those with only interstitial rejection. Potential rejection markers, i. e., serum amylase, glucose, creatinine, and urinary amylase, did not correlate with histological signs of rejection, although increased levels of serum amylase were, in all but one case, associated with rejection.We conclude that a percutaneous pancreas biopsy remains the most reliable method to determine pancreas rejection, and that by distinguishing between IR andVR, a pancreas biopsy may provide important diagnostic as well as prognostic information. Received: 6 March 1997 Received after revision: 5 June 1997 Accepted: 30 June 1997     

Respiratory health status in swine producers using respiratory protective devices

A cross-sectional survey on respiratory health in swine producers showed that 30% of 301 examined men usually used a dust mask when working inside a barn. They did not differ significantly from dust mask nonusers in respect to respiratory symptoms and lung function. This analysis was undertaken to determine whether the respiratory health of dust mask users was associated with reasons why they had started individual respiratory protection. The subjects were recontacted in order to identify those who started using a mask to deliberately prevent symptoms (42 men) and those who started protection because of pre-existing respiratory symptoms (44 men). Not unexpectedly, betweengroup comparisons of respiratory symptoms and lung function suggest that swine producers who wear dust masks for preventive purposes have better respiratory health than those who wear dust masks because of symptoms or those who do not use individual respiratory protection. The individual reasons for starting dust mask usage should be examined among potential determinants of the outcomes of prospective studies which can then provide more valid assessment of the effect of individual respiratory protection. © 1993 Wiley-Liss, Inc.     

N-acetylaspartate is an axon-specific marker of mature white matter in vivo: a biochemical and immunohistochemical study on the rat optic nerve.

Axonal pathology is a major cause of neurological disability in multiple sclerosis. Axonal transection begins at disease onset but remains clinically silent because of compensatory brain mechanisms. Noninvasive surrogate markers for axonal injury are therefore essential to monitor cumulative disease burden in vivo. The neuronal compound N-acetylaspartate, as measured by magnetic resonance spectroscopy, is currently the best and most specific noninvasive marker of axonal pathology in multiple sclerosis. The possibility has been raised, however, that N-acetylaspartate is expressed also by oligodendroglial lineage cells. In order to investigate N-acetylaspartate specificity for white matter axons, transected rat optic nerves were analyzed by high-performance liquid chromatography and immunohistochemistry. In transected adult nerves, N-acetylaspartate and N-acetyl aspartylglutamate decreased in concordance with axonal degeneration and were undetectable 24 days posttransection. Nonproliferating oligodendrocyte progenitor cells, oligodendrocytes, and myelin were abundant in these axon-free nerves. At 24 days posttransection, N-acetylaspartate was increased (42%; p = 0.02) in nontransected contralateral nerves. After transection at postnatal day 4, total N-acetylaspartate decreased by 80% (P14; p = 0.002) and 94% (P20; p = 0.003). In these developing axon-free nerves, 25 to 33% of oligodendrocyte progenitor cells were proliferating. These data validate magnetic resonance spectroscopy measurements of N-acetylaspartate as an axon-specific monitor of central nervous system white matter in vivo. In addition, the results indicate that neuronal adaptation can increase N-acetylaspartate levels, and that 5 to 20% of the N-acetylaspartate in developing white matter is synthesized by proliferating oligodendrocyte progenitor cells.     

Hydrocephalus and cavernoma of the cauda equina

The association of a tumor of the cauda equina and hydrocephalus is unusual. We report a case of hydrocephalus with normal pressure associated with an equally rare affliction, a cavernous angioma of the cauda equina, which regressed after surgical ablation. The physiological mechanism involved is discussed.     

Obstacles and Opportunities for Multi-disciplinary Working in Drug Misuse: a case study

This paper examines the lack of congruence between national policy documents and local practice in multi-disciplinary working with drug users, by reporting on a case study within one English county. It gives an analysis of the roles and responsibilities of generic service providers and a minority of specialists, based on 100 interviews and questionnaires with representatives from professional groups involved with drug issues. The respondents worked with a range of young people and adults. Whilst professionals worked well within broad disciplines such as health or education, they did not operate as well across disciplinary boundaries. Many of the respondents were unsure about the specific role of their own profession, and which group they should target for drug interventions. There was a lack of clarity about what approach was appropriate to their traditional target group in terms of drugs, and consequently many did not utilize their established approach for that group. When the reasons for the lack of co-working were examined, it was found that there were many misconceptions among professionals concerning what other professional groups actually did in response to drugs. The authors clarify the reasons for the apparent confusion and highlight the possibility that a traditional generic approach and target group may not provide an appropriate match in terms of drug intervention. They make recommendations for overcoming these obstacles to multi-disciplinary working and consider the implications for training.     

Comparison of the efficacy and safety of ciclesonide 160 μg once daily vs. budesonide 400 μg once daily in children with asthma

Ciclesonide is an onsite-activated inhaled corticosteroid (ICS) for the treatment of asthma. This study compared the efficacy, safety and effect on quality of life (QOL) of ciclesonide 160 microg (ex-actuator; nominal dose 200 microg) vs. budesonide 400 microg (nominal dose) in children with asthma. Six hundred and twenty-one children (aged 6-11 yr) with asthma were randomized to receive ciclesonide 160 microg (ex-actuator) once daily (via hydrofluoroalkane metered-dose inhaler and AeroChamber Plus spacer) or budesonide 400 microg once daily (via Turbohaler) both given in the evening for 12 wk. The primary efficacy end-point was change in forced expiratory volume in 1 s (FEV1). Additional measurements included change in daily peak expiratory flow (PEF), change in asthma symptom score sum, change in use of rescue medication, paediatric and caregiver asthma QOL questionnaire [PAQLQ(S) and PACQLQ, respectively] scores, change in body height assessed by stadiometry, change in 24-h urinary cortisol adjusted for creatinine and adverse events. Both ciclesonide and budesonide increased FEV1, morning PEF and PAQLQ(S) and PACQLQ scores, and improved asthma symptom score sums and the need for rescue medication after 12 wk vs. baseline. The non-inferiority of ciclesonide vs. budesonide was demonstrated for the change in FEV1 (95% confidence interval: -75, 10 ml, p = 0.0009, one-sided non-inferiority, per-protocol). In addition, ciclesonide and budesonide showed similar efficacy in improving asthma symptoms, morning PEF, use of rescue medication and QOL. Ciclesonide was superior to budesonide with regard to increases in body height (p = 0.003, two-sided). The effect on the hypothalamic-pituitary-adrenal axis was significantly different in favor of ciclesonide treatment (p < 0.001, one-sided). Both ciclesonide and budesonide were well tolerated. Ciclesonide 160 microg once daily and budesonide 400 microg once daily were effective in children with asthma. In addition, in children treated with ciclesonide there was significantly less reduction in body height and suppression of 24-h urinary cortisol excretion compared with children treated with budesonide after 12 wk.     

Calcification and ossification of chronic encapsulated intracerebral haematoma: case report.

We report a case of calcified chronic encapsulated intracerebral haematoma (ICH) in a 29-year-old female who presented with progressive left sided weakness and intermittent seizures since childhood. The preoperative magnetic resonance (MR) imaging of the head initially suggested that a partially thrombosed aneurysm or vascular malformation was present. However, no vascular stain was found on the digital subtraction angiography (DSA) of both the carotid and vertebral arteries. The excised mass was histologically diagnosed as a chronic ICH. We traced the patient's medical history and found that at the age of one she sustained a head injury after a fall. So far, to our knowledge, no case of epilepsy secondary to a calcified chronic encapsulated ICH occurring 28 years after head injury has been reported. Calcified chronic encapsulated ICH concomitant with new bone formation within is even rarer. The possible pathogenesis of this case is discussed.     

Expression profiling identifies the CRH/CRH-R1 system as a modulator of neurovascular gene activity.

Corticotropin-releasing hormone receptor type 1 (CRH-R1)-deficient mice display reduced anxiety-like behavior, a chronic corticosterone deficit, and an impaired neuroendocrine stress response caused by disruption of the hypothalamic-pituitary-adrenocortical (HPA) axis. The molecular substrates and pathways of CRH/CRH-R1-dependent signaling mechanisms underlying the behavioral phenotype as well as the consequences of lifelong glucocorticoid deficit remain largely obscure. To dissect involved neuronal circuitries, we performed comparative expression profiling of brains of CRH-R1 mutant and wild-type mice using our custom made MPIP (Max Planck Institute of Psychiatry) 17k cDNA microarray. Microarray analysis yielded 107 genes showing altered expression levels when comparing CRH-R1 knockout mice with wild-type littermates. A significant proportion of differentially expressed genes was related to control of HPA and hypothalamic-pituitary-thyroid (HPT) axes reflecting not only the disturbance of the HPA axis in CRH-R1 mutant mice but also the interplay of both neuroendocrine systems. The spatial analysis of regulated genes revealed a prevalence for genes expressed in the cerebral microvasculature. This phenotype was confirmed by the successful cross-validation of regulated genes in CRH overexpressing mice. Analysis of the cerebral vasculature of CRH-R1 mutant and CRH overexpressing mice revealed alterations of functional rather than structural properties. A direct role of the CRH/CRH-R1 system was supported by demonstrating Crhr1 expression in the adult murine cerebral vasculature. In conclusion, these data suggest a novel, previously unknown role of the CRH/CRH-R1 system in modulating neurovascular gene expression and function.