Multi-pathogen serological survey of migratory caribou herds: A snapshot in time.

Pathogens can impact host survival, fecundity, and population dynamics even when no obvious disease is observed. Few baseline data on pathogen prevalence and diversity of caribou are available, which hampers our ability to track changes over time and evaluate impacts on caribou health. Archived blood samples collected from ten migratory caribou herds in Canada and two in Greenland were used to test for exposure to pathogens that have the potential to effect population productivity, are zoonotic or are emerging. Relationships between seroprevalence and individual, population, and other health parameters were also examined. For adult caribou, the highest overall seroprevalence was for alphaherpesvirus (49%, n = 722), pestivirus (49%, n = 572) and Neospora caninum (27%, n = 452). Lower seroprevalence was found for parainfluenza virus type 3 (9%, n = 708), Brucella suis (2%, n = 758), and Toxoplasma gondii (2%, n = 706). No animal tested positive for antibodies against West Nile virus (n = 418) or bovine respiratory syncytial virus (n = 417). This extensive multi-pathogen survey of migratory caribou herds provides evidence that caribou are exposed to pathogens that may have impacts on herd health and revealed potential interactions between pathogens as well as geographical differences in pathogen exposure that could be linked to the bio-geographical history of caribou. Caribou are a keystone species and the socio-economic cornerstone of many indigenous cultures across the North. The results from this study highlight the urgent need for a better understanding of pathogen diversity and the impact of pathogens on caribou health.

Parasites, stress and reindeer: infection with abomasal nematodes is not associated with elevated glucocorticoid levels in hair or faeces.

Stress hormones (glucocorticoids), incorporated into hair/fur and faeces, have been proposed as biomarkers of overall health in wildlife. Although such biomarkers may be helpful for wildlife conservation and management, their use has rarely been validated. There is a paucity of studies examining the variation of stress hormones in mammals and how they relate to other health measures, such as parasitism. Parasites are ubiquitous in wildlife and can influence the fitness of individual animals and populations. Through a longitudinal experiment using captive reindeer (Rangifer tarandus tarandus), we tested whether animals infected with Ostertagia gruehneri, a gastrointestinal nematode with negative impacts on fitness of the host, had higher stress levels compared with those that had been treated to remove infection. Faecal samples were collected weekly for 12 weeks (June-September) and hair was collected at the start and end of the study; glucocorticoids were quantified using enzyme immunoassays. Contrary to what was expected, infected reindeer had similar levels of cortisol in hair and slightly lower glucocorticoid metabolites in faeces compared with uninfected reindeer. Faecal corticosterone levels were higher than faecal cortisol levels, and only corticosterone increased significantly after a handling event. These results suggest that reindeer may use a tolerance strategy to cope with gastrointestinal nematodes and raise the question as to whether moderate infection intensities with nematodes are beneficial to the host. By removing nematodes we may have altered the gut microbiota, leading to the observed elevated faecal glucocorticoid metabolite levels in the treated reindeer. These findings demonstrate the importance of considering both cortisol and corticosterone in physiological studies, as there is mounting evidence that they may have different functionalities.

Testing the pluralist approach to sex: the influence of environment on synergistic interactions between mutation load and parasitism in Daphnia magna.

Both deleterious mutations and parasites have been acknowledged as potential selective forces responsible for the evolutionary maintenance of sexual reproduction. The pluralist approach to sex proposes that these two factors may have to interact synergistically in order to stabilize sex, and one of the simplest ways this could occur is if parasites are capable of causing synergistic epistasis between mutations in their hosts. However, the effects of both deleterious mutations and parasitism are known to be influenced by a range of environmental factors, so the nature of the interaction may depend upon the organisms' environment. Using chemically mutated Daphnia magna lines, we examined the effects of mutation and parasitism under a range of temperature and food regimes. We found that although parasites were capable of causing synergistic epistasis between mutations in their hosts, these effects were dependent upon an interaction between parasite genotype and temperature.

Degree of body weight in obesity and Rorschach personality aspects of mental distress.

OBJECTIVE: To study the relationship between degree of obesity and personality measures of mental distress. METHOD: The Rorschach method (Comprehensive System) and the Beck Depression Inventory. General descriptors were also included. Participants were 120 obese patients with a mean body mass index (BMI) of 41 (+/- SD 6) kg/m2. RESULTS: Depression, stress or psychopathology such as distortions in perception and cognitions were not related to the degree of obesity. Body concern and body-related anxiety (An+Xy) were more common in relatively lower degrees of obesity. According to general descriptors heavier patients had lower educational and socio-economic level, and more bodily pain problems. DISCUSSION: Depression was not related to body weight, in spite of findings of more depression in obesity compared to normal weights. Other factors than severity of obesity would account for the mental distress in obese patients. The differences in body concern and anxiety in varying degrees of obesity could be related to the social and educational context, where attitudes toward obesity differ. Less Rorschach signs of body concern in the morbidly obese contrasted with more self-reported bodily pain problems.

The effect of brimonidine tartrate on retinal blood flow in patients with ocular hypertension.

PURPOSE: To study the effects of topical brimonidine tartrate 0.2%, an alpha(2)-agonist ocular hypotensive drug, on retinal capillary blood flow in patients with ocular hypertension. METHODS: The study was a double-masked, randomized, placebo-controlled trial set in a tertiary eye center. Ocular hypertensive patients with repeatable intraocular pressures greater than 21 mm Hg and normal visual fields and optic disks were consecutively recruited. After an eye examination, baseline retinal blood flow measurements were made with confocal scanning laser Doppler flowmetry in one study eye. Patients were then randomly assigned to receive either brimonidine or placebo (saline) twice daily for 8 weeks. Blood flow and intraocular pressure measurements were then repeated after 4 and 8 weeks. RESULTS: Seventeen patients were randomly assigned to receive brimonidine, and 14 received placebo. One patient in each group failed to complete the study. The mean group differences in baseline age and intraocular pressure were not statistically significant (59. 23 [+/-10.24] and 52.23 [+/-16.46] years, respectively, and 24.84 [+/-2.08] and 24.56 [+/-2.85] mm Hg, respectively). Brimonidine reduced intraocular pressure by 17.90% and 16.17% at 4 and 8 weeks, respectively, with a significant difference in treatment effect compared with the placebo group (P <.007). The group difference in treatment effect in any of the three hemodynamic parameters velocity, volume, and flow was within 8% and not significantly different at 4 or 8 weeks (P.360). Based on a type I error of 0.05, our study had a power greater than or equal to 75% to detect group differences in treatment effect of greater than or equal to 15% to 20%. CONCLUSIONS: Brimonidine reduces intraocular pressure without altering retinal capillary blood flow in patients with ocular hypertension.

Prediction of functional disability, recurrences, and chronicity after 1 year in 180 patients who required sick leave for acute low-back pain.

The aim of the study was to identify factors that predict low-back pain outcome at 12 months and thus to identify patients at risk for poor long-term outcomes. One hundred-eighty patients, all disabled by acute low-back pain, were included. Outcome (dependent) variables were Oswestry disability score, recurrences during the study year, and chronicity defined as 90 or more days off work for low-back pain during the study year, or a disease-specific sick-leave rate (a variable created by the authors) of more than 25%. Stepwise logistic regression analysis was performed. Thirty-three percent of the patients had an Oswestry score greater than 25, indicating moderate disability at the 1-year follow-up evaluation. Pain on coughing at study entry predicted a high likelihood of disability at 1 year, with a threefold risk. Many work days missed as a result of low-back pain in the past 2 years and lack of stimulating work tasks predicted recurrences during the year. A high Oswestry score assessed at study entry was the only factor that predicted chronicity. The factors revealed in the current study should help the clinician to identify patients at risk. The authors propose that the revealed predictors should be investigated extensively at the patient's first visit for acute low-back pain.

An exploratory study of agreement between therapists' goals and patients' problems revealed by the rorschach.

This study describes and classifies goals as formulated by psychodynamically oriented psychotherapists, and examines the agreement between the therapists' goals and the patients' problems revealed by the Rorschach. One hundred thirty treatment plans were rated with regard to content, and five of the goal categories were compared to corresponding Rorschach clusters. Personality differences were examined between patients with low agreement between the therapists' goals and patients' problems and those with relatively high agreement. Patients with low agreement were characterized by a high degree of problem complexity and psychopathology, especially in thinking. They also showed signs of psychological defenses that might have obstructed the communication of their psychological problems to the therapists. The results suggest that the Rorschach may provide information about aspects of patients' psychological functioning which they are not able to communicate or which are not paid attention to by the therapists.

The effect of brimonidine tartrate on retinal blood flow in patients with ocular hypertension [corrected].

PURPOSE: To study the effects of topical brimonidine tartrate 0.2%, an alpha2-agonist ocular hypotensive drug, on retinal capillary blood flow in patients with ocular hypertension. METHODS: The study was a double-masked, randomized, placebo-controlled trial set in a tertiary eye center. Ocular hypertensive patients with repeatable intraocular pressures greater than 21 mm Hg and normal visual fields and optic disks were consecutively recruited. After an eye examination, baseline retinal blood flow measurements were made with confocal scanning laser Doppler flowmetry in one study eye. Patients were then randomly assigned to receive either brimonidine or placebo (saline) twice daily for 8 weeks. Blood flow and intraocular pressure measurements were then repeated after 4 and 8 weeks. RESULTS: Seventeen patients were randomly assigned to receive brimonidine, and 14 received placebo. One patient in each group failed to complete the study. The mean group differences in baseline age and intraocular pressure were not statistically significant (59.23 [+/-10.24] and 52.23 [+/-16.46] years, respectively, and 24.84 [+/-2.08] and 24.56 [+/-2.85] mm Hg, respectively). Brimonidine reduced intraocular pressure by 17.90% and 16.17% at 4 and 8 weeks, respectively, with a significant difference in treatment effect compared with the placebo group (P < .007). The group difference in treatment effect in any of the three hemodynamic parameters velocity, volume, and flow was within 8% and not significantly different at 4 or 8 weeks (P > .360). Based on a type I error of 0.05, our study had a power greater than or equal to 75% to detect group differences in treatment effect of greater than or equal to 15% to 20%. CONCLUSIONS: Brimonidine reduces intraocular pressure without altering retinal capillary blood flow in patients with ocular hypertension.

Serum Gm allotype development during childhood.

Gm allotypes are genetic variants of the immunoglobulin heavy G chains (IGHG) of IgG molecules, coded from chromosome 14q32, characterized by differences in amino acid epitopes of the constant heavy G chains and inherited in the Mendelian manner. Gm allotypes have influence on IgG subclass levels, and serum Gm allotype levels have been given for different Gm genotypes in adults. Four hundred and thirty healthy children, aged 1-15 years, were examined for serum Gm allotypes and IgG subclasses from the six most common Gm genotypes and different age groups were measured using competitive enzyme-linked immunosorbant assay and radial immunodiffusion methods. Quantities (in g/l) of G1m(a) and G1m(f) of IgG1, G2m(n) and G2m(-n) of IgG2 and G3m(g), and G3m(b) of IgG3 are given. Different maturation rates of the alternative Gm allotypes within IgG1, IgG2 and IgG3 were shown. G2m(n) development was strikingly retarded compared with G2m(-n) from the gamma2 locus. This was found comparing IgG2 levels from homozygous G2m(-n-n) and G2m(nn) individuals, but was also seen in heterozygous G2m(n-n) genotypes. From the gamma1 locus G1m(f) levels dominated significantly, but inconstantly, over G1m(a) levels in heterozygous G1m(af) individuals. In homozygous G1m genotypes, G1m(aa) compared with G1m(ff) of the same age, one or the other dominated, sometimes significantly. Serum levels of G3m(b) from the gamma3 locus of homozygous G3m(bb) individuals were increased significantly compared with G3m(g) levels of homozygous G3m(gg) individuals, in ages over 3 years. However, in heterozygous G3m(gb) individuals G3m(b) dominance was not evident. There is a relatively rapid development of G1m(f) molecules and a retarded development of G2m(n) in the Gm(f;n;b) haplotype. In comparison, G1m(a) is retarded and G2m(-n) is enhanced in the Gm(a;-n;g) haplotype. The retarded serum G2m(n) development is comparable with serum IgA development during childhood. Different maturation rates of Gm allotypes within the same IgG subclass provide further explanation for the variation of the antibody response during childhood. Quantitative Gm allotype determinations give information of the activity from IGHG genes. The genetic variation constitutes an additional basis for evaluation of IgG antibodies in different diseases in childhood.

Acute low-back-pain patients exhibit a fourfold increase in sick leave for other disorders: a case-control study.

One hundred eighty patients with acute low-back pain (LBP) were compared to 608 age- and sex-matched controls with regard to somatic and personality characteristics. The low-back-pain group had a fourfold increase (median) in sick-leave episodes for reasons other than spinal morbidity during the preceding 2 years. In the same period, the median number of episodes of sick leave for LBP was 1 in the patients and 0 in the controls. The mean number of days off for other reasons was 34 (median = 20.5) in the patients compared to 9 (median = 0) in the controls, and days off for LBP were 20 (median = 5) and 5 (median = 0), respectively. Analysis of other factors than those directly related to LBP disclosed significant differences in marital status and smoking habits between patients and controls. Furthermore, LBP patients estimated their work to be physically heavier. We conclude that medical intervention should focus not only on the spine, but also on a wide range of other aspects of the patient's situation. Even in the acute phase of LBP, the previous sick-leave records should be analyzed to provide adequate measures to prevent future sick leaves. Presently, the sociomedical costs for a subset of the population who repeatedly seek help for LBP are significantly higher than those for the non-LBP population.

Alternative G1m, G2m and G3m allotypes of IGHG genes correlate with atopic and nonatopic pathways of immune regulation in children with bronchial asthma.

Most genetic studies of bronchial asthma deal with IgE responsiveness. The manner by which allergens trigger IgE production and activate mast cells suggests that several genetic loci may be involved. Several reports of candidate genes include chromosome 6 and HLA antigens, chromosome 14q11 and the alpha chain of the T cell receptor, chromosome 11q32 and the beta chain of the high-affinity IgE receptor and chromosome 5 and the gene cluster for IL-4, respectively. In addition, the immunoglobulin heavy chain G (IGHG) genes on chromosome 14q32 have been associated with both atopic and non atopic bronchial asthma in children. In order to further investigate the role of IGHG genes in asthmatic children, the phenotypes of patients with homozygous but alternative IGHG genes were investigated. IGHG gene expression of patients with childhood asthma was determined by serum Gm allotypes with a quantitative competitive indirect ELISA method. The groups consisted of 24 children with the homozygous G3m(b/b)-G1m(f/f)-G2m(n/n) and 16 with the alternative G3m(g/g)-G1m(a/a)-G2m(-n/-n) genes. The two different genotypes were investigated for serum IgE (PRIST), serum IgG subclass levels (radial immunodiffusion), Gm allotype levels (competitive ELISA), IgA and IgM levels (radial immunodiffusion), peripheral blood eosinophils, specific IgE antibodies (skin prick test, SPT, or radioallergosorbent test, RAST), number of peripheral blood CD lymphocyte markers (flow cytometry) and serum IL-4 and IFN-gamma levels (ELISA). Comparison of the two genotypes in children with bronchial asthma revealed significantly increased IgE (p < 0.001), increased specific IgE (p < 0.001), as investigated by SPT or RAST (n = 10 allergens tested), increased number of peripheral blood eosinophils (p < 0.01), increased serum IgG1(f/f)(p < 0.001), IgG2(n/n) (p < 0.001) and IgG3(b/b)(p < 0.01) levels, and decreased CD8 given in percent of the total number of peripheral lymphocytes, (p < 0.02) in the G3m(b/b)-G1m(f/f)-G2m(n/n) genotype. The asthmatic children with the G3m(g/g)-G1m(a/a)-G2m(-n/-n) genes instead showed low IgE levels, practically no specific IgE antibodies, a lower number of peripheral blood eosinophils, lower IgG1(a/a), IgG2(-n/-n) and IgG3(g/g) serum levels and higher CD8 lymphocyte numbers. The results show that the IGHG3(b/b)-IGHG1(f/f)-IGHG2(n/n) genes are in linkage disequilibrium with allergen-specific high-responding IGHE genes and present the atopic phenotype of bronchial asthma, while the IGHG3(g/g)-IGHG1(a/a)-IGHG2(-n/-n) genes present the nonatopic phenotype of childhood asthma. The two genotypes with different amino acid epitopes of their constant heavy gamma1, gamma2 and gamma3 chains presented qualitatively different IgG1, IgG2 and IgG3 molecules, respectively, and also different serum IgG1, IgG2 and IgG3 levels, together with different numbers of peripheral blood eosinophils and CD8 lymphocytes. The two IGHG genotypes represent different pathways of human immune regulation. An association of atopic IGHG genotype with other candidate genes for atopy could be suggested.

Conservative treatment in patients sick-listed for acute low-back pain: a prospective randomised study with 12 months' follow-up.

We evaluated three different conservative treatment methods for acute low-back pain patients in groups following a manual therapy programme, an intensive training programme, or a general practitioner programme, the latter serving as the control group. Patients aged 19-64 years on sick leave for low-back pain with or without sciatica were included in a prospective randomised study evaluating outcomes such as impairment, pain, functional disability, socio-economic disability and satisfaction with the treatment or explanations. Evaluation by unbiased observers was performed at 1, 3 and 12 months. The three treatment groups were comparable at baseline. With regard to satisfaction, the patients in the manual therapy programme and those in the intensive training programme were more satisfied with the treatment than those in the general practitioner programme at all follow-ups. With regard to the explanations of current low-back pain episodes, the patients in the manual therapy programme were more satisfied than those in the general practitioner programme at all follow-ups. The manual therapy programme group were also more satisfied with the explanations than those in the intensive training programme at the 1-month follow-up. However, no differences were revealed between the groups with respect to outcomes on measures of impairment, pain, functional disability or socioeconomic disability. All three study groups showed rapid improvement. After 1 month a significant improvement was noted in all outcome values compared with the values on entry to the study. Within the limitations discussed in our study, it is concluded that (1) patients sick listed with acute low-back pain, with or without sciatica, will be significantly improved after 1 month regardless of conservative treatment programme; (2) they will be more satisfied with the treatment if they are referred to a manual treatment programme or a training treatment programme; (3) they will be more satisfied with the explanations of the acute low-back problem if they are referred to one of the above groups, especially the manual treatment group; (4) they will not show any other differences with respect to subjective and objective variables, either at short-term or at long-term follow-ups.

Linkage of IgA deficiency to Gm allotypes; the influence of Gm allotypes on IgA-IgG subclass deficiency.

IgA deficiency (IgAD) is the most common immunodeficiency, characterized by an arrest in B cell differentiation. It has a sporadic occurrence or variable inheritance pattern, and is also linked to the HLA genes. IgA deficiency is sometimes associated with IgG subclass deficiency. In this study the Gm allotypes, as genetic characteristics of the IgG1, IgG2 and IgG3, were analysed in 83 Caucasian IgAD individuals. Half of the patients presented with IgG4 < 0.01 g/l compared with 5% (P < 0.001) in a healthy population. Three of the 83 had significantly low IgG2 and four had significantly low IgG3 levels. Gm allotype frequencies in IgAD deviated compared with a normal population. Of the 83 patients, 44 (53%) showed homozygous G2 m(",") expression on the IgG2 locus (33% in controls, P < 0.01). In IgAD the Gm(a,",g) haplotype was more frequent (43%) compared with controls (31%, P < 0.01). The Gm homozygous phenotype Gm(a,",g/a,",g) was most common, found in 20 of 83 patients (24%, P < 0.05) compared with controls (14%). On the other hand the Gm(f,n,b) haplotype of IgAD was rare (28%) compared with controls (45%, P < 0.001). The low IgG4, < 0.01 g/l, found in 50% of the patients, was even more frequent (56-69%) among the G2 m(",") phenotypes. IgG subclass levels were given for different Gm phenotypes of the IgAD group and compared with controls. Significantly low IgG4 was revealed in the Gm(a,",g/a,",g) phenotype (P < 0.01) and significantly low IgG2 in the Gm(a,",g/f,",b) phenotype (P < 0.01). The Gm(a,",g/f,",b) phenotype contained the three patients found with IgG2 levels < -2 s.d., and the four patients with IgG3 levels < -2 s.d. were present among those with the homozygous Gm(a,",g/a,",g) phenotype; both phenotypes with G2 m(",") on the IgG2 locus. The 'compensatory' increase of IgG was significant for both IgG1 and IgG3 in all Gm phenotypes, but in the Gm(a,",g/f,",b). Thus, the susceptibility of IgAD with the additional IgG antibody deficiencies, down-regulated IgG4 and IgG2/IgG3, is associated with Gm allotypes, especially the homozygous G2 m(",") expression on the IgG2 locus.

Quantitation of Gm allotypes.

A method for quantitation of Gm allotypes is described. Alternative Gm allotypes of the three IgG subclasses, IgG1, IgG2 and IgG3, were investigated for the six most common Caucasian Gm phenotypes. Quantitation of G1m(a), G1m(f) of IgG1, G2m(n) of IgG2 and G3m(b) of IgG3 was performed with specific monoclonal antisera and purified myeloma proteins of different Gm allotypes. Mean +/- SD are given as percentage of a normal serum pool and in g/l for the Gm allotypes G1m(a), G1m(f), G2m(n) and G3m(b). For homozygous individuals the G2m(",") values are equal to the IgG2 levels and the G3m(g,g) values equal to the IgG3 levels. For heterozygous individuals the value for G2m(") is calculated as IgG2 minus G2m(n) and for G3m(g) as IgG3 minus G3m(b). Homozygous individuals have about double the amounts of the Gm allotype compared with heterozygous individuals. The gene activity of heterozygous individuals is given by quotients, mean +/- SD for G1m(a)/G1m(f) of IgG1, G2m(n)/G2m(") of IgG2 and G3m(b)/G3m(g) of IgG3 in different Gm phenotypes. Heterozygous individuals on all three IgG subclass loci have at least six different qualities of IgG molecules compared with three for homozygous individuals.

Personality in patients with long-term patellofemoral pain syndrome.

Personality characteristics in patients with long-term patellofemoral pain were compared to those of matched controls and other groups both of non-patients and of psychiatric outpatients with character disorders. Personality was described using the self-administered dependency and alexithymia scales, the Karolinska Scales of Personality and the Rorschach inkblot method. The hypothesis was that the patellofemoral pain patients would have higher levels of anxiety, depression, helplessness, aggression and alexithymic characteristics than the matched controls. There were only a few significant differences between the knee patients and the matched controls. The Rorschach measures suggested significantly greater depression, hostility and passive attitude in the knee patients as compared to the reference data. There were no indications of the hypothesised alexithymic characteristics in the knee patients. If patellofemoral pain patients do not improve as expected, referral to a pain clinic with psychological expertise could be considered.

Gm phenotype linkage to subsets of juvenile chronic arthritis (JCA) with influence on IgG subclass response.

The serum hyper IgG of 76 JCA patients of different clinical subsets, 8 systemic, 37 polyarticular and 31 oligoarticular, were investigated by IgG subclass quantitation and Gm allotype determination. The well known increased serum IgG in JCA was confirmed as increased IgG1, IgG2 and IgG3 in the whole group. Investigating the clinical subsets IgG1 was significantly increased in all subsets while IgG2 and IgG3 increased only in the polyarticular form. In search of a genetic linkage for the clinical JCA subsets and the different IgG subclass patterns found, the alternative Gm allotypes G1m(a), G1m(f) for IgG1, G2m(n), G2m(") for IgG2 and G3m(g) , G3m(b) for IgG3 gene loci were investigated. The Gm (a,",g) haplotype was significantly increased in the whole JCA group and in the polyarticular subset. In the systemic subset the Gm (a,",g/a",g) phenotype was significantly increased, but the Gm (a,'h,g/f,n,b) phenotype was increased in the oligoarticular subset. The number of JCA patients with G1m(f,f)-,G3m(b,b)-phenotypes were significantly decreased. In such phenotypes, remission was more common. The susceptibility of JCA, its different clinical subsets and outcome of the disease is determined by Gm allotypes, affecting characteristic IgG subclass patterns.