Expression of MHC class I heavy chain and beta2-microglobulin in rat brainstem motoneurons and nigral dopaminergic neurons

We demonstrate here that motoneurons and nigral dopaminergic neurons in the brainstem of the adult rat, with the exception of motoneurons innervating ocular muscles, display high levels of both MHC class I heavy chain and beta2-microglobulin mRNAs. These neurons also display interferon-gamma receptor mRNA. We find it striking that these particular neurons are those which are vulnerable to neurodegeneration in diseases such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS).     

Sprouting of bladder nerves into cystoplastic cecal segment in the rat

Incorporation of bowel into the bladder (enterocystoplasty) has been widely used to increase bladder capacity. It has been reported by others that the response of smooth muscle from the cystoplastic segment of the intestine shifts from that of the intestine (relaxation to α-agonists and ATP) to that of the bladder (contraction to α-agonists and ATP). This suggests a functional integration of the intestinal muscle into the bladder; the mechanisms are unknown. The aims of the present study were (1) to elucidate if there are signs of bladder nerves sprouting across the anastomosis into the intestinal segment, and (2) to study what happens with the intrinsic innervation of the intestinal segment. As a model, we used cecocystoplasty in rats. The bladder was opened and a patch of cecum with intact vascular supply was anastomosed to the bladder. After two to 11 months the rats were sacrificed and the bladders mounted as wholemounts and stained for acetylcholinesterase-containing nerves, or embedded in paraffin for histology. A pronounced degeneration of the myenteric plexus was found in the cecal segments. In some areas, this had proceeded to the extent that the ganglia were isolated ovoid lumps of cells with no apparent connection to other ganglia. Areas lacking ganglia and nerve trunks but still with muscle could be found in all specimens. Abundant axon bundles were demonstrated sprouting from the cut bladder nerves close to the anastomosis. The bundles spread out in a fan-like pattern or were organized as fewer thicker nerves. There were many nerve bundles entering the cecal segment where they branched and the diameter decreased till they no longer became visible. Some nerves reached surviving lumps of myenteric ganglion cells. The results show that the bladder nerves sprout into the anastomosed cecal segment. It is reasonable to assume that these nerves are responsible for the changes in receptor pharmacological properties of the cecal smooth muscle towards that of bladder muscle. Received: 30 October 1998 / Accepted: 18 May 1999     

Higher levels of antibodies against the psoriasis-associated antigen pso p27 in cerebrospinal fluid from patients with low back pain and sciatica

STUDY DESIGN: A prospective study comparing the presence of antibodies against the psoriasis-associated antigen pso p27 in pain-free control subjects and patients with low back pain and/or sciatica. OBJECTIVES: To analyze the amount of local inflammation present in human lumbar disc disorders, using anti-pso p27 antibodies in the cerebrospinal fluid as a marker and to analyze whether pain intensity correlates with this marker of inflammation. SUMMARY OF BACKGROUND DATA: Pso p27 is a major antigen in psoriasis that is also present, mostly locally, in other inflammatory disorders, such as sarcoidosis, inflammatory bowel disease, and ankylosing spondylitis, inflammation is also thought to play a major role in the generation of lumbar and radicular pain in degenerative disc disorders. METHODS: Anti-pso p27 antibodies in cerebrospinal fluid were quantified using an indirect enzyme-linked immunosorbent assay with pso p27 obtained from patients with psoriasis for use as an antigen. Fifteen patients with spinal stenosis, 11 patients without myelographic disc herniation, 17 patients with disc herniation, and 24 pain-free patient control subjects were studied. RESULTS: Significantly higher levels of anti-pso p27 antibodies were found in patients with myelographic signs of disc herniation than in with patients with no signs of herniation, patients with spinal stenosis, and control subjects. Patients with no known signs of disc herniation and patients with myelographic signs of spinal stenosis (< 10 mm in diameter) caused by degenerative changes, had higher levels of anti-pso p27 antibodies than did control subjects. However, these differences reached only borderline statistical significance. CONCLUSIONS: The results support those in previous reports, that inflammation probably plays an important role in degenerative disk disorders, particularly in disk herniations. That there was no correlation between pain intensity and anti-pso p27 activity indicates that the antigen is probably not essential in pain generation per se. The results may indicate that pso p27 is expressed secondary to, not as an initiator of, inflammation.     

Inflammation markers in nasal lavage, and nasal symptoms in relation to relocation to a newly painted building: a longitudinal study

Introduction: There is a need to evaluate possible health effects of ventilation improvements and emissions from new buildings, in longitudinal studies. New methods to study biological effects on the eyes and upper airways are now available. Material and methods: A longitudinal study was performed on 83 trained social workers in two offices in Uppsala, Sweden. The exposed group (n= 57) moved to a newly redecorated building nearby. Low emitting building material had been used, including a new type of solvent-free water-based paint. The control group (n= 26) worked in the same office during the study period (November 1995 to February 1996). Hygiene management was carried out in both offices, at the beginning and the end of the investigation. Tear film stability (BUT) was measured. Nasal patency was measured by acoustic rhinometry, and eosinophilic cationic protein (ECP), myeloperoxidase (MPO), lysozyme and albumin were analyzed in nasal lavage fluid (NAL). Results: The relocation resulted in an increase in the personal outdoor airflow rate from 11 to 22 l/s. Indoor concentrations of terpenes were higher in the new building, and powdering of the new linoleum floor was observed. Measurements showed low levels of volatile organic compounds (VOC), formaldehyde, carbon dioxide (CO₂), nitrogen dioxide, respirable dust, and microorganisms in the air of all buildings. The move resulted in an increased nasal patency and an increase of ECP and lysozyme in NAL, after adjusting for changes in the control group. No changes were observed for nasal or ocular symptoms. A seasonal effect, with a decrease of ECP, was observed in the control group. Conclusion: A well-ventilated office building can be redecorated without any major ocular or nasal effects, or measurable increase of indoor air pollution if low-emitting building materials are selected. In agreement with previous evidence, the improved ventilation flow may explain the increase of nasal patency. The increase of ECP and lysozyme in NAL suggested an inflammatory effect in the new building. Since this building had increased ventilation flow, increased concentrations of terpenes, and powdering from the polish on the new linoleum floor, identification of causative agents was difficult. The hygiene measures did not give any evidence that emissions from the new type of solvent-free water-based paints or building dampness were responsible for the observed nasal effects. Considering the higher emissions of VOC reported from older types of water-based latex paints and solvent-based wall paints, the new type of solvent-free water-based paint seems to be a good choice from the hygiene point of view. Received: 21 December 1998 / Accepted: 20 June 1999     

Retrospective versus original information on physical and psychosocial exposure at work

OBJECTIVES: Retrospective exposure assessments are often performed in epidemiologic studies. The presence of an eventual misclassification, both nondifferential and differential, is debated but can rarely be investigated. The aim of this study was to compare self-reported information on the same physical and psychosocial work exposures with 25 years' difference. METHODS: In 1969-1970 a survey of randomly chosen men and women in Stockholm county, concerning, among other things, work exposures, was undertaken. During 1993-1994, 280 subjects participated in a reexamination, regarding psychosocial and physical factors at work and musculoskeletal disorders. The questions were all formulated in the same way as in 1969-1970. RESULTS: When self-reported information on work exposures, collected with a 25-year interval, was compared, acceptable, although not high, agreement was found for 3 out of 4 physical factors and for 4 out of 10 physical environmental factors. Questions measuring psychosocial load had somewhat lower agreement. Current exposure status influenced the memory of past exposures. Study subjects who reported low-back disorders at the reexamination tended to show a better agreement in their assessments of retrospective exposures than those without current symptoms. When relative risks from original and retrospective data were calculated, hardly any influence on the estimates due to that differential misclassification could be found. For persons with and without neck or shoulder symptoms no apparent differences in assessments were found. CONCLUSIONS: Retrospective assessments of exposures at the workplace showed misclassifications to a certain degree. However, the influence of the misclassifications on the risk estimates was limited.     

Gastric effects of methylnaltrexone on mu, kappa, and delta opioid agonists induced brainstem unitary responses

In this study, we evaluated the gastric effects of methylnaltrexone, an opioid receptor antagonist that does not cross the blood-brain barrier in vivo, on mu, kappa and delta opioid agonists induced brainstem unitary responses in an in vitro neonatal rat brainstem-gastric preparation. Single units in the medial subnucleus of the nucleus tractus solitarius (NTS), responding to electrical stimulation of subdiaphragmatic vagal fibers, were recorded. Selective opioid receptor agonists and antagonists were applied only to the gastric compartment of the bath chamber and thus, the brainstem functions of the preparation were not affected by the drugs. The peripheral gastric effects of a mu opioid receptor agonist, DAMGO, and a kappa opioid receptor agonist, U-50,488H, were evaluated on 58 tonic units that received the subdiaphragmatic vagal inputs. For approximately 78% of the units observed, DAMGO (1.0 microM) and U-50,488H (1.0 microM) induced a concentration-dependent inhibition of 62.1+/-9.3% (mean +/- SE) and 49.2+/-6.5% of the control level of the NTS neuronal activity, respectively. Methylnaltrexone competitively antagonized the DAMGO-induced brainstem neuronal effects. Methylnaltrexone at an 18.8-fold higher concentration also reversed U-50,488H-induced NTS neuronal responses. Naloxone, a non-selective opioid receptor antagonist, reversed the inhibitory effects of DAMGO and U-50,488H at much lower concentrations (3.8% and 0.5%, respectively) compared to methylnaltrexone. Only 18% of the NTS neurons evaluated showed inhibitory responses to a delta receptor agonist, DPDPE, (19.7+/-5.0% at 10 microM), and this inhibition could not be reversed by methylnaltrexone in the concentration range we tested. In addition, when methylnaltrexone (1.0 microM) alone was applied to the gastric compartment, there was an activation (8.5+/-2.1%) of the NTS neurons receiving subdiaphragmatic vagal inputs, suggesting an endogenous gastric opioid action in the modulation of brainstem neuronal activities.     

Utilization of cardiovascular drugs (blood pressure lowering drugs, lipid lowering drugs and nitrates) and mortality from ischaemic heart disease and stroke An ecological analysis based on Sweden's municipalities

Objective: To perform an ecological study in an effort to generate questions concerning the preventive impact of various cardiovascular drugs on mortality from stroke and ischaemic heart disease (IHD) in the community, and to explore the association between sales of nitrates and mortality from stroke and IHD. Methods: Out-patient drug utilization (sales) of blood pressure lowering drugs, lipid lowering drugs and nitrates were categorized in four groups of equal size by quartiles and compared with mortality from IHD and stroke, using the group of municipalities with the lowest utilization as reference, from 1989 to 1993 in 283 of Sweden's 288 municipalities, by Poisson regression. Adjustments were made for population size, age and gender proportions, the utilization rate of cardiovascular drugs other than the tested drug group and location of the municipality. Results: Compared with the group of municipalities with the lowest sales and adjusting only for population size, mortality from IHD and stroke increased with the extent of utilization of blood pressure lowering drugs and nitrates. In contrast, mortality decreased with increased utilization of lipid lowering drugs. After further adjustments by percentage of men, age structure, geographical location (mid-points) of the municipalities, and, as a proxy for cardiovascular disease, the sales of cardiovascular drugs other than the tested drug group, the increased risk associated with blood pressure lowering drugs disappeared, and there was a dose-response association between sales of diuretics and old antihypertensives and decreasing mortality, sales of nitrates continued to be associated with an increased risk, and the low mortality risk associated with sales of lipid lowering drugs persisted. Conclusion: Lipid lowering drugs may have a preventive impact in the general population, but the preventive impact of blood pressure lowering drugs, with the exception of diuretics and old antihypertensives, may be low in many municipalities. The safety of nitrates needs more investigation at the individual level. Received: 16 April 1998 / Accepted in revised form: 10 November 1998     

Patients' and doctors' perception of long-term morbidity in patients with testicular cancer clinical stage I

Patient-based questionnaires were designed with the aim to identify and rank long-term somatic and psychosocial morbidity in patients with low-stage testicular cancer. A further intention was to compare patients' assessments with experienced doctors' general opinion on quality of life items in cured testicular cancer patients. In pilot study I, 103 tumour-free patients ranked items of physical and psychosocial morbidity after having had various kinds of treatment. Though the ranking procedure appeared to cause some difficulties amongst the patients and subsequently was abandoned, the results indicated considerable differences between the patients' and doctors' evaluations. In pilot study II patients were asked to score the different items. The questionnaire of pilot study II was completed by 107 patients from the Norwegian Radium Hospital (NRH) and 99 relapse-free patients from the Royal Marsden Hospital (RMH) with testicular cancer stage I at least 1 year after infradiaphragmatic radiotherapy (n = 94) or adjuvant chemotherapy (2 cycles,n=26), or patients who had been followed on the surveillance program (n = 86). A total of 93 doctors completed a similar questionnaire, thereby expressing their general opinion on long-term morbidity in comparable testicular cancer patients as seen during routine clinical follow-up. Both the irradiated patients and those on the surveillance program reported slight degrees of Raynaud-like phenomena, neurotoxicity and ototoxicity, most probably representing background morbidity in an age-matched general male population. Doctors tended to underestimate their patients' somatic morbidity, but often overestimated the degree of psychological distress, in particular in patients on the surveillance program. Significant differences between RMH and NRH patients with regard to sexual problems and to leisure time activity may be explained by cultural differences in the two countries. The items presented in the questionnaire used identify important issues for patients cured of testicular cancer which may be used in future multicentre trans-cultural studies assessing these patients' quality of life. This will provide sufficient data for psychometric testing and, together with the findings from patients' free comments, support the final design of a testicular cancer quality of life module.     

Pituitary adenylate cyclase-activating peptide-immunoreactive nerve fibers in the cat eye

Purpose: To study the occurrence and distribution of the neuropeptide pituitary adenylate cyclase-activating peptide (PACAP) in ocular and orbital structures of the cat. Methods: Immunocytochemistry to localize PACAP and double immunostaining to detect co-localization of PACAP with other neuropeptides. Results: Numerous PACAP-immunoreactive nerve fibers were observed in the lacrimal gland, choroid and retroocular arteries. There was a sparse supply of PACAP-containing nerve fibers in the iris, ciliary body and conjunctiva. Subpopulations of PACAP-containing nerve fibers stored vasoactive intestinal peptide (VIP) or calcitonin gene-related peptide (CGRP). Around 10% of the ganglion cells in the sphenopalatine ganglion harbored PACAP immunoreactivity. In the trigeminal ganglion around 5% of the neuronal cell bodies and in the ciliary ganglion only occasional ganglion cells contained PACAP immunoreactivity. PACAP immunoreactivity co-localized with VIP in the sphenopalatine ganglion and with CGRP in the trigeminal ganglion. Conclusion: PACAP-containing nerves in the eye and associated structures demonstrate a distribution pattern resembling that of VIP. Subpopulations of nerve fibers containing PACAP immunoreactivity store VIP or CGRP immunoreactivity. Neuronal PACAP in the eye and orbit may take part in regulation of smooth muscle tone, glandular secretion and sensory processing.     

Does the service at a large oncologic out-patient clinic satisfy the patients' perceived need?

Describes the physical status and quality of life in ambulatory oncologic patients seen at the Norwegian Radium Hospital (NRH) and assesses their satisfaction with the out-patient service. During a two-week period in 1993 517 consecutive patients completed a qualify-of-life questionnaire (EORTC QLQ-C30) during their out-patient visit at the NRH. The results of the EORTC QLQ-C30 were compared with those from a similar study performed in 1991 (211 patients evaluated during one week).