Experimental infection by Yersinia ruckeri O1 biotype 2 induces brain lesions and neurological signs in rainbow trout (Oncorhynchus mykiss).

Pathological manifestations in rainbow trout (Oncorhynchus mykiss) following experimental waterborne infection with Yersinia ruckeri serotype O1 biotype 2 (strain 07111224) were investigated. Rainbow trout were exposed to 8 × 107  CFU/ml of Y. ruckeri by bath for 6 hr, and mortality was then monitored for 22 days post-infection (dpi). Organs were sampled at 3 dpi and also from moribund fish showing signs of severe systemic infection such as bleeding, exophthalmia or erratic swimming behaviour. Y. ruckeri was observed in the meninges and diencephalon of the brain, and lamina propria of olfactory organ at 3 dpi. At 12 dpi, Y. ruckeri had spread throughout the brain including cranial connective tissues and ventricles and the infection was associated with haemorrhages and an infiltration with leucocytes. Y. ruckeri infection and associated with leucocyte infiltration were observed at 13 dpi. In conclusion, Y. ruckeri strain 07111224 causes encephalitis in the acute phase of infection, which could explain why Y. ruckeri-affected fish show exophthalmia and erratic swimming known as signs of ERM.

Sleep quality improves with endoscopic sinus surgery in patients with chronic rhinosinusitis and nasal polyposis.

BACKGROUND: Chronic Rhinosinusitis with Nasal Polyposis (CRSwNP) is a chronic disease that has a major impact on generic and disease-specific quality of life. Little is known about the influence of CRSwNP on sleep and what effect surgery for CRSwNP has on sleep quality. The aim of the study was to investigate sleep quality in patients with CRSwNP before and after endoscopic surgery. METHODOLOGY: Forty-two patients filled out four validated sleep questionnaires and one sino/nasal, disease specific quality of life questionnaire before surgery and three months later. A healthy control group filled out the same questionnaires at baseline and after three months. RESULTS: An impact on sleep patterns was found in all sleep questionnaires and surgery clearly improved the quality of sleep. The Sino-nasal outcome test sum score decreased from median 51,5 to 26,5. Epworth sleepiness scale showed a decline in score from score 7.5 to 6.0. Surgery also reduced the risk for obstructive sleep apnoea in 13 patients evaluated by the Berlin Questionnaire and Multivariable Apnea Prediction Index. CONCLUSIONS: Patients with CRSwNP had impaired sleep quality, daytime sleepiness, nasal patency, and risk for sleep apnea, all of which improved after corrective surgery.

Concurrent palliative chemoradiation leads to survival and quality of life benefits in poor prognosis stage III non-small-cell lung cancer: a randomised trial by the Norwegian Lung Cancer Study Group.

BACKGROUND: The palliative role of chemoradiation in the treatment of patients with locally advanced, inoperable non-small-cell lung cancer stage III and negative prognostic factors remains unresolved. METHODS: Patients not eligible for curative radiotherapy were randomised to receive either chemoradiation or chemotherapy alone. Four courses of intravenous carboplatin on day 1 and oral vinorelbin on days 1 and 8 were given with 3-week intervals. Patients in the chemoradiation arm also received radiotherapy with fractionation 42 Gy/15, starting at the second chemotherapy course. The primary end point was overall survival; secondary end points were health-related quality of life (HRQOL) and toxicity. RESULTS: Enrolment was terminated due to slow accrual after 191 patients from 25 Norwegian hospitals were randomised. Median age was 67 years and 21% had PS 2. In the chemotherapy versus the chemoradiation arm, the median overall survival was 9.7 and 12.6 months, respectively (P<0.01). One-year survival was 34.0% and 53.2% (P<0.01). Following a minor decline during treatment, HRQOL remained unchanged in the chemoradiation arm. The patients in the chemotherapy arm reported gradual deterioration during the subsequent months. In the chemoradiation arm, there were more hospital admissions related to side effects (P<0.05). CONCLUSION: Chemoradiation was superior to chemotherapy alone with respect to survival and HRQoL at the expense of more hospital admissions due to toxicity.

Dermal collagen matrices for ventral hernia repair: comparative analysis in a rat model.

PURPOSE: The purpose of this study was to compare inflammatory responses, tissue integration, and strength of the acellular dermal collagen matrices AlloDerm(®)* Regenerative Tissue Matrix, Permacol™**Surgical Implant (Permacol), and CollaMend™*** Implant in a rat model for ventral hernia repair. METHODS: Rats were randomized into four groups and abdominal wall defects repaired with an inlay graft of AlloDerm, Permacol, or CollaMend. Rats were sacrificed at six time points and the defect area was removed and analyzed for tissue integration and physical strength. RESULTS: Variable cell infiltration was seen for the three implant groups. At of the all time points examined, cellular infiltration was most rapid in the AlloDerm implants and slowest for CollaMend. At 14 days, significant cell infiltration along with putative blood vessel formation was observed for AlloDerm, while Permacol implants exhibited a moderate level of infiltration. Very few cells penetrated CollaMend implants at 2 weeks. Cells had reached the center of the Permacol implants by 1 month, whereas CollaMend implants were encapsulated with a loose coat of disconnected cells, with very few cells infiltrating past the surface. At 6 months, AlloDerm and Permacol had evidence of cell penetration throughout the implants, while the CollaMend samples exhibited limited infiltration. Animals for each implant developed seromas: AlloDerm 40%, Permacol 33%, and CollaMend 83%. Mechanical testing revealed that AlloDerm at 6 months showed the lowest tensile strength, CollaMend the highest, and Permacol an intermediate level. CONCLUSIONS: The three biologics exhibited different patterns and rates of cellular and vascular permeation in our rat model. AlloDerm implants exhibited the most rapid and extensive cellular infiltration, followed by Permacol. However, on gross examination, the AlloDerm implants thinned significantly by 6 months. In contrast, the Permacol and CollaMend implants appeared to be largely intact.

Road traffic accident risk in patients with diabetes mellitus receiving blood glucose-lowering drugs. Prospective follow-up study.

AIM: To investigate, at a national level, whether patients using insulin or oral glucose-lowering agents had an increased risk of road traffic accidents compared with non-users. METHODS: All Norwegians aged 18-69 years (3.1 million) were followed from April 2004 until September 2006. Information on drug prescriptions, road traffic accidents and emigration/death was obtained from the following population-based registries: the Prescription Database, the Road Accident Registry and the Central Population Registry. The exposure period was the time from the first prescription of insulin or oral glucose-lowering agent during the study period. The incidence of accidents in the exposed person-time was compared with the incidence of accidents in the unexposed person-time by standardized incidence ratio (SIR). RESULTS: During the study period, 20 494 road traffic accidents with personal injuries were registered in Norway. One hundred and eighty-three accidents were registered for insulin users not taking oral glucose-lowering agents and 219 for users of oral blood glucose-lowering drugs without insulin. The SIR (95% confidence interval) for all ages and both genders combined were: insulin 1.4 (1.2-1.6), oral glucose-lowering agents 1.2 (1.0-1.3) and users of drugs for peptic ulcer and gastro-oesophageal reflux disease (negative comparators) 1.3 (1.2-1.4). The highest SIRs were found among the youngest insulin users (18-34 years old). CONCLUSIONS: A slightly increased risk of being involved in a road traffic accident was observed for drivers prescribed insulin, while no increased risk was observed for drivers prescribed oral glucose-lowering agents. The increased risk observed for insulin users was similar to that observed for users of drugs for peptic ulcer and gastro-oesophageal reflux disease.

Cellular, hemostatic, and inflammatory parameters of the surgical stress response in pigs undergoing partial pericardectomy via open thoracotomy or thoracoscopy.

BACKGROUND: Thoracoscopy has been shown to reduce the inflammatory and immunologic response to surgical stress, as compared with corresponding open procedures in humans. The influence on the hemostatic system, however, has not been thoroughly evaluated. The current study aimed to compare the perioperative and immediate postoperative changes in cellular, hemostatic, and inflammatory parameters after a partial pericardectomy performed by either thoracoscopy or thoracotomy. METHODS: For this study, 16 pigs were randomly assigned to have a partial pericardectomy performed thoracoscopically or by thoracotomy. Blood was collected intraoperatively, then 10 min, 3 h, and 6 h after surgery. Whole ethylenediaminetetraacetic acid (EDTA)-stabilized blood and plasma were examined for cellular, hemostatic, and inflammatory parameters, respectively, and thromboelastography (TEG) was performed on citrated whole blood. RESULTS: No significant difference in any of the parameters measured was found between the two groups except for the TEG parameter R-time, which was significantly shorter in the thoracoscopic group 3 h postoperatively. In both groups, a significant postoperative state of hypercoagulability and increase in inflammatory parameters was found. Additionally, pig blood showed a high degree of hypercoagulability in preoperative measurements, as compared with other species. CONCLUSIONS: Partial pericardectomy performed by thoracotomy or thoracoscopy in pigs produces a surgical stress response of equal magnitude, as measured by cellular, hemostatic, and inflammatory changes.

Unrestricted weight bearing and intensive physiotherapy after uncemented total hip arthroplasty.

BACKGROUND AND AIMS: The effectiveness of partial weightbearing after hip surgery has been questioned as well as the need of intensive physiotherapy. MATERIAL AND METHODS: 36 patients (average age 54.4, 19 women) operated with uncemented hip arthroplasty were randomized either to unrestricted weightbearing (UWB) combined with intensive physiotherapy or to partial weightbearing (PWB) for 3 months combined with a short self-training program. The load during walking and the muscle strength (MS) in abduction was measured preoperative and subsequent up to 12 months. RESULTS: The average peak load on the operated leg at one week was 39.0 kg for the UWB and 25.8 for the PWB group (P = 0.009) while at three months 70.0 and 31.7 (P = 0.001) respectively. At 6 and 12 months there were no differences between the groups. The muscle strength increased in both groups up to six months but there were no differences between the groups. CONCLUSIONS: Even though patients applied more load than the recommended 15 kg most patients were able to comply with partial weightbearing fairly well. The effect of intensive physiotherapy on the muscle strength after hip arthroplasty is questionable.

Subsurface tile drainage loss of modern pesticides: field experiment results.

The concentration and loss of two herbicides (bentazone and MCPA), two fungicides (fenpropimorph and propiconazole) and two insecticides (dimethoate and pirimicarb) were measured in tile drainage water from a 2,813 m2 experimental grass field from May to August 2001. Three different pesticides were applied to the field and subsequently a rainfall of 10 mm was simulated during the first experiment and 16 mm during the second experiment. Bromide was applied as a conservative tracer in the first experiment and the concentration of bromide and suspended sediment was also measured in tile drainage water. In the first experiment, maximum concentrations of bentazone, fenpropimorph and dimethoate in drainage water were 5.8 microg l(-1), 0.33 microg l(-1) and 2.29 microg l(-1), respectively. In the second experiment, maximum concentrations for MCPA, propiconazole and pirimicarb were 3.6 microg l(-1), 0.065 microg l(-1), 2.3 microg l(-1), respectively. The loss:applied ratio was highest for bentazone (0.088%) and declined in the order of dimethoate (0.057%), pirimicarb (0.050%), propiconazole (0.0031%) and fenpropimorph (0.00042%). Exposure of the macroinvertebrate species Gammarus pulex to pesticides in the drainage water during the second experiment (exposure time: 7 hours) showed significant mortality/inactivity as compared to an upstream and downstream control.

Different versions of the anatomical therapeutic chemical classification system and the defined daily dose--are drug utilisation data comparable?

OBJECTIVE: To investigate whether published drug utilisation studies contain satisfactory references to the ATC/DDD version applied and thus are usable for comparative purposes. METHODS AND RESULTS: A literature survey of drug utilisation studies was made. Seventy-three articles were identified by two Medline searches, one in 1996 and another in 1998. The articles were classified into four different groups. Groups 1 and 2 give proper references to the defined daily doses (DDDs) used in the studies, either by full reference to the version of the ATC Index with DDDs or by listing the actual DDDs used. The articles in groups 1 and 2 represent 46% of the articles in the survey. The articles classified in groups 3 and 4 give references only to general articles about the anatomical therapeutic chemical classification (ATC)/DDD system or no references at all. Fifty-four percent of the articles in the survey were classified in these groups. In these articles it is not possible to identify which DDDs have been used in the presentation of drug consumption data. CONCLUSIONS: According to the results from our literature survey, it is not common practice to include the ATC codes and the DDD values used or to make reference to the versions of the ATC/DDD index used when results from drug utilisation studies are published. One possible reason for this might be little or no knowledge about the ATC/DDD system as a dynamic system in which alterations are made annually. The lack of references to the actual DDDs used in the studies make comparisons between different data sets difficult and misleading.

[Decentralized special training in pulmonary medicine. A project using telemedicine]. / Desentralisert spesialistutdanning i lungesykdommer. Et prosjekt med bruk av telemedisin.

In arctic Norway, where there is a lack of specialists in pulmonary medicine two postgraduate students, already qualified as specialists in internal medicine at Tromsø Regional Hospital, applied to continue their training at their respective local hospitals. The regional hospital in Tromsø has a long tradition of telemedicine, with network links to local hospitals in the region, and is equipped for interactive consultation and the bilateral transmission of x-rays and video recordings, and digital transmission of x-rays. Accordingly, supported by their supervisor, the two postgraduate students applied to the committee for postgraduate education in pulmonary medicine to have a year's work at their respective local hospitals, supervised via the telemedicine facilities, accepted as equivalent to a six-month module of the normal syllabus. The project was approved and executed as planned. The registrars, who were responsible for pulmonary service at their local hospitals, served four days a month at the regional hospital, and their supervisor visited the local hospitals one day each month. All internal education at the regional hospital was made available by means of a weekly interactive televised link-up, x-rays being displayed on screen as transmitted digitally; bronchoscopies were shown by video, and ad hoc tutorials arranged as needed. Evaluated by the national committee, the project was found satisfactory, and the registrars were duly qualified.

Synovial fluid cytokines in patients with rheumatoid arthritis or other arthritic lesions.

The synovial fluid (SF) of rheumatoid arthritis (RA) patients contains a mixture of inflammatory mediators. In order to determine whether certain cytokine patterns locally in the joint are specifically related to the chronic inflammation in RA, the concentrations of interleukin (IL)-1alpha, IL-1beta, IL-6, IL-10, transforming growth factor-beta (TGF-beta), tumour necrosis factor-alpha (TNF-alpha) and IgG2b-inducing factor (IgG2bIF) were measured in SF from 22 patients with RA and 22 patients with other types of arthritic lesions. High levels of IL-10, latent and active TGF-beta and the presence of IgG2bIF are significantly correlated with RA when corrected for age. As these factors have the capacity to promote antibody production, they might contribute to the maintenance of local antibody production in RA synovial tissues. All RA-SF samples contained detectable levels of IL-10 and all except one contained IL-1beta, while concentrations in several non-RA-SF samples were below detection limits. IL-6 and TGF-beta were present in all SF samples from both RA and non-RA patients. The presence of IgG2bIF was strongly correlated with high levels of IL-10 and IL-1beta in SF. However, no distinct cytokine profile specific for the chronic inflammation characteristic of RA was found.

Autoantibody patterns in synovial fluids from patients with rheumatoid arthritis or other arthritic lesions.

Patients with rheumatoid arthritis (RA) produce a variety of autoantibodies, not only demonstrable in the circulation, but also locally in the inflamed joint. We investigated the local production of several autoantibodies in the synovial fluid (SF) of 24 patients with RA and of 26 patients with other arthritic lesions. RA patients had higher titres of immunoglobulin M (IgM) and immunoglobulin G (IgG) rheumatoid factors (RFs) and of collagen type II antibodies in SF, whereas there were no demonstrable differences between groups with regard to antibodies against double-stranded (ds) DNA, C1q or the hapten 2,4,6-trinitrobenzene sulfonic acid (TNP). No differences were observed for total synovial levels of IgM or IgG. There was no autoantibody pattern that was typical of RA patients, except for the local presence of RF, primarily in seropositive RA patients. Our findings therefore support the notion that RF and collagen type II antibodies are induced by immunogenic material present in the local inflamed environment. In the accompanying paper we studied various synovial fluid cytokines in the same patient groups. Here we correlated the level of these cytokines with autoantibody titres in SF, but no specific cytokine associated with the production of RF was found. Hence, we conclude that several different inflammatory mediators might contribute to the chronic inflammation and autoantibody production in the joint of RA patients. An inverse correlation was established between concentrations of tumour necrosis factor-alpha (TNF-alpha) and levels of total IgG.

Relationships between bone mass measurements and lifetime physical activity in a Swedish population.

Lifetime occupational and leisure time activities were assessed by a questionnaire in order to evaluate their relationship to bone mass measurements and biochemical markers of bone metabolism in a population of 61 women and 61 men, randomly selected from a Swedish population register, to represent ages between 22 and 85 years. We also considered possible confounders by using questions about smoking habits, milk consumption, hormone replacement therapy (HRT), and menopausal age. Bone mineral density (BMD) and bone mineral content (bone mass, BMC) of the total body, lumbar spine, and proximal femur (neck, trochanter, Ward's triangle) were measured by dual energy X-ray absorptiometry (DXA), and BMD of the forearm with single energy X-ray absorptiometry (SXA). In addition, both DXA and SXA provided information on bone area. Quantitative ultrasound measurements (QUS) at the heel were performed to assess the speed of sound (SOS) and broadband ultrasound attenuation (BUA). Fasting blood samples were analyzed for biochemical markers of bone metabolism as well as parathyroid hormone (PTH) and total serum calcium. After adjustment for confounding factors, neither BMD nor QUS measurements were consistently related to lifetime leisure time or occupational activities; nor were there any consistent patterns relating biochemical markers of bone metabolism to bone mass measurements. However, physical activity seemed to influence bone mass, area, and width more than density. In men, high levels of leisure time activity were associated with raised values for lumbar spine area (6.2%) and width (3.3%) as well as for femoral neck area (5.5%) compared with their low activity counterpart. Men exposed to high levels of occupational activity demonstrated lower lumbar spine BMD (10.9%) and area (5.3%) than men with low activity levels. Within an unselected Swedish population, estimation of lifetime occupational and sport activities as well as bedrest, using a questionnaire, demonstrated no major effects on bone density. However, the association between high levels of lifetime activity and raised values for bone mass, area, and width indicate that geometrical changes in bone may provide better estimations of mechanically induced bone strength than bone density, at least in men.

Coxarthrosis and farm work: a case-referent study.

The purpose of this case-referent study was to analyze the association between coxarthrosis and occupation. The study was performed in a Swedish agricultural county and comprised 269 cases of radiologically verified arthrosis of osteoarthritis (< 3 mm joint space) that were compared to 538 randomly selected controls in the same region, matched for age, sex, and place of residence. Farmers and agricultural workers showed an increased risk of coxarthrosis and the observed risk increased with increasing number of years of farming. Tractor driving and milking were associated with coxarthrosis, whereas no association with other types of machine work could be demonstrated. An association between coxarthrosis and heavy physical work before the age of 16 years was also observed. The results give only limited information on the external causes of coxarthrosis, however. More detailed studies of groups of individuals with coxarthrosis in order to obtain more information about contributing and underlying factors would therefore be valuable.

Appendicitis followed by reactive arthritis in an HLA B27-positive man after infection with Yersinia enterocolitica, diagnosed by serotype specific antibodies and antibodies to Yersinia outer membrane proteins.

A case of appendicitis followed by reactive arthritis in an HLA B27-positive, 29-year-old man after infection with Yersinia enterocolitica is reported. Infection with Y. enterocolitica was diagnosed by determination of serotype specific antibodies and antibodies to Yersinia outer membrane proteins. Bacteriological cultures from the appendix were not made. Although reactive arthritis is a well-known complication of Yersinia-associated enteric disease, there are only few reports of patients with Y. enterocolitica pseudo-appendicitis complicated by arthritis during follow-up.

Bone metabolism in endurance trained athletes: a comparison to population-based controls based on DXA, SXA, quantitative ultrasound, and biochemical markers.

In general, physical exercise appears to have favorable effects on the skeleton. However, a few recent reports have described negative effects, including reduced bone density (BMD) and high bone turnover in runners. The aim of our study was to compare endurance runners to controls with respect to BMD at different sites and ultrasound transmission through the peripheral skeleton, and to use PTH, total serum calcium, and biochemical markers of bone metabolism as a complement in evaluating the effects of endurance running on bone. Thirty runners (mean age 32 years, range 19-54 years) participated in the study. Their main form of training consisted of endurance running at moderate intensity for about 7 hours (range 2-12 hours) per week, and they had been active in their sport for about 12 years (range 1-21 years). For a comparison, 30 age- and sex-matched population based controls were investigated. BMD values, measured by dual energy X-ray absorptiometry (DXA), were higher in runners than in controls for the total body (3.6%; P = 0.03), legs (9.6%; P = 0. 001), femoral neck (10.0%; P = 0.01), trochanter (9.9%; P = 0.01), and Wards triangle (11.8%; P = 0.02), but not in the lumbar spine or in the forearm measured by single energy X-ray absorptiometry (SXA). The quantitative ultrasound measurement of the calcaneus also revealed higher values in runners than in controls for both broadband ultrasound attenuation (9.2%; P = 0.002) and speed of sound (3.1%; P = 0.0001). At all sites, BMD was related to ultrasound measurements in controls, but no such relationship was evident in runners. Concentrations of parathyroid hormone (PTH) were lower (23.2%; P = 0.02) in runners than in controls, whereas total serum calcium concentrations were slightly higher (3.0%; P = 0.003). The levels of PICP (bone formation) and ICTP (bone resorption) in serum were lower (18.0%; P = 0.03 and 22.2%; P = 0.004, respectively) in runners than in controls, but no differences were seen for osteocalcin or bone specific alkaline phosphatase (b-ALP). In conclusion, BMD at the focus of strain for running, that is, the legs, is higher in endurance runners when compared to matched controls. Low bone turnover in runners, indicated by lower levels of PTH and biochemical markers of bone metabolism, point to an influence of endurance running at the cellular level.

Fibronectin and lymphocytes in inflammatory tissue. Studies of blood and synovial fluid lymphocytes from patients with rheumatoid arthritis and other inflammatory arthritides.

Lymphocytes infiltrating tissues under chronic inflammatory conditions are often surrounded by deposits of fibronectin. We have studied the possibility that this reflects capacity of lymphocytes to synthesize fibronectin and compared lymphocytes from blood and synovial fluid with respect to fibronectin interactions. In vitro activated blood lymphocytes exhibited synthesis of a fibronectin-like molecule. Synovial fluid cells appeared to synthesize the same high molecular weight component spontaneously. Activated blood lymphocytes have cell surface fibronectin and surface components of lower molecular weight which could be immunoprecipitated with anti-fibronectin antibodies as well as by insolubilized collagen. Synovial fluid cells showed cell surface fibronectin as revealed by immunocytochemical detection but seemed to lack or have relatively small amounts of the low-molecular weight fibronectin-like surface components. Synovial fluid T cells from arthritis patients showed adhesion to fibronectin. Immunocytochemistry demonstrated presence of alpha 4 and alpha 5 beta 1 integrins at the surface of the synovial fluid T cells and RGD and LDV peptides inhibited adhesion of the cells to fibronectin. Noteworthy, a portion of synovial fluid cells with lymphocyte markers also bound to plastic. Blood lymphocytes from the same arthritis patients displayed relatively poor or negligible adhesion to fibronectin unless activated to blast transformation and did not attach to plastic. Taken together these results suggest that activated lymphocytes from blood and synovial fluid may use fibronectin of exogenous or endogenous origin when interacting with tissues during inflammatory processes. Furthermore, the presence at the lymphocyte surface of components of different molecular weight precipitated by anti-fibronectin antibodies suggests that fibronectin or its fragments can bind to the lymphocyte surface.