Precipitation and temperature drive continental-scale patterns in stream invertebrate production.

Secondary production, the growth of new heterotrophic biomass, is a key process in aquatic and terrestrial ecosystems that has been carefully measured in many flowing water ecosystems. We combine structural equation modeling with the first worldwide dataset on annual secondary production of stream invertebrate communities to reveal core pathways linking air temperature and precipitation to secondary production. In the United States, where the most extensive set of secondary production estimates and covariate data were available, we show that precipitation-mediated, low-stream flow events have a strong negative effect on secondary production. At larger scales (United States, Europe, Central America, and Pacific), we demonstrate the significance of a positive two-step pathway from air to water temperature to increasing secondary production. Our results provide insights into the potential effects of climate change on secondary production and demonstrate a modeling framework that can be applied across ecosystems.

What is causing my arthritis, doctor? A glimpse beyond the usual suspects in the pathogenesis of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common, but heterogeneous, disease. Usually, when it comes to the pathogenesis of RA the physician faces a complex network of cytokines and cells of the immune system-the so-called effector level. However, is this network 'the cause' of the disease? Or is this rather the level most physicians are somewhat familiar with, as modern anti-rheumatic medications are having their targets there? In this review, we are looking beyond the usual culprits from the physician's perspective and discuss how other factors, such as genes, epigenetics, environmental factors, local joint characteristics or processes of aging might influence the clinical phenomenon RA.

Factors influencing skin autofluorescence of patients with peritoneal dialysis.

Skin autofluorescence (SAF) measurement is a simple, noninvasive method to assess tissue advanced glycation end products (AGE). In patients with end-stage renal disease and in those on hemodialysis AGE production is increased. Less is known about those treated with peritoneal dialysis (PD). In this study we tested if SAF is influenced by clinical and treatment characteristics in PD patients.This cross-sectional study included 198 PD patients (of those, 128 were on traditional glucose-based solutions and 70 patients were partially switched to icodextrin-based PD). SAF measurements were done with a specific AGE Reader device. The impact of patients' age, gender, current diabetes, duration of PD, cumulative glucose exposure, body mass index, smoking habits and use of icodextrin on SAF values were tested with multiple regression analysis.Our analysis revealed that patients' age, current diabetes and icodextrin use significantly increase patients' SAF values (p = 0.015, 0.012, 0.005, respectively). AGE exposure of PD patients with diabetes and on icodextrin solution is increased. Further investigation is required whether this finding is due to the icodextrin itself or for a still unspecified clinical characteristic of PD population treated with icodextrin.

[Safety of immunosuppressants]. / Sicherheit der Immunsuppressiva.

METABOLISM: Cyclosporin A and leflunomide may increase the blood pressure, whereas administration of prednisolone and tacrolimus may cause hyperglycemia. Azathioprine, chloroquine, methotrexate and mycophenolate mofetil seem to be metabolically neutral. Tocilizumab and tumor necrosis factor (TNF) alpha blockers have a negative effect on the lipid profile. INFECTIONS: The overall infection risk for prednisolone is estimated to be 1.3. This risk for methotrexate is also 1.3 compared to other disease modifying antirheumatic drugs (DMARDs). Regarding biologics, the highest risk of serious infections was associated with certolizumab pegol and tocilizumab, in contrast to abatacept and rituximab which showed the lowest risk. CANCER RISK: Azathioprine and cyclosporin A are associated with a markedly increased risk of non-melanoma skin cancer. According to the RABBIT registry no significant increase in tumor rate has been reported for biologics. PREGNANCY: Azathioprine, chloroquine, cyclosporin A, prednisolone, sulfasalazine, tacrolimus and cyclophosphamide (only after the second trimester) may be administered during pregnancy. Biologics should be avoided unless there is a treatment need in cases of uncontrolled disease activity. BREAST FEEDING: Only chloroquine, prednisolone, sulfasalazine and tacrolimus may be taken during breast feeding. There are insufficient data on the safety of biologics.

Development of a disease activity index for the assessment of reactive arthritis (DAREA).

OBJECTIVES: The objectives of this study were to investigate and validate individual variables and to develop a composite score for disease activity measurement in patients with reactive arthritis (REA). METHODS: In the first cross-sectional part, the clinical and laboratory evaluation of 45 patients was used to elaborate the most important individual disease activity measures. In the second prospective part, these variables as well as a composite score for disease activity measurement of REA were prospectively validated in 23 patients at two points in time. RESULTS: The following variables emerged as the most useful for the composite measure: number of swollen and tender joints, patient's pain and global assessment, and C-reactive protein. The score was calculated by simple addition of the individual figures. CONCLUSION: DAREA constitutes a reliable score which can easily be assessed on a day-to-day office work basis.

Expression of adhesion molecules on synovial fluid and peripheral blood monocytes in patients with inflammatory joint disease and osteoarthritis.

OBJECTIVE: To determine the presence of adhesion molecules on monocytes/macrophages (Mphi) from peripheral blood (PB) and synovial fluid (SF) in patients with osteoarthritis (OA) and inflammatory joint diseases (rheumatoid (RA) and reactive arthritis (ReA)) in order to improve our understanding of the possible mechanisms underlying the inflammatory process. METHODS: Whole blood and SF cells were stained with monoclonal antibodies against CD11a (LFA-1), CD15 s (sialyl-Lewis X), CD44, CD54, VLA-4, and HLA-DR counterstained with anti-CD14 antibodies as a Mphi marker for dual fluorescence analysis by flowcytometry. RESULTS: On PB-Mphi, CD15s was markedly increased in both RA as well as ReA compared with OA. Furthermore, in the PB LFA-1, CD44, and HLA-DR showed a higher surface density on Mphi in ReA than in OA. Comparison between SF and PB showed significantly higher CD44 and CD54 expression on SF-Mphi. These molecules play an important part in lymphocyte-Mphi interaction. CONCLUSION: In PB from patients with inflammatory joint diseases, Mphi are activated, allowing recruitment into the synovial compartment. These disorders, in contrast with OA seem to be "systemic" in nature. Within the SF, different adhesion molecules are expressed on CD14(+) Mphi as compared with PB.

Cytokine production by synovial T cells in rheumatoid arthritis.

OBJECTIVE: To investigate the production of cytokines by T cells in patients with rheumatoid arthritis (RA), reactive arthritis (REA) and osteoarthritis (OA). METHODS: The lymphokines interleukin (IL)-2, IL-4, interferon gamma (IFN-gamma) and tumour necrosis factor beta (TNF-beta), as well as the monokines IL-1, IL-6 and TNF-alpha, were measured by immunoassays in sera and synovial fluid (SF) from patients with RA, REA and OA. In addition, cytokine expression was studied by immunohistochemistry in synovial membrane tissue sections from patients with RA and OA. RESULTS: Almost 60% of RA sera contained at least one of the cytokines investigated, though in low concentrations, whereas cytokines were generally not detectable in sera from REA and OA patients. In contrast, cytokines were found in virtually all SF; thus, the majority of SF from RA patients contained IFN-gamma (median level 17 pg/ml) in addition to the monokines IL-6 (4700 pg/ml) and TNF-alpha (157 pg/ml). IFN-gamma and IL-6 (but not TNF-alpha) were also frequently measured in SF from REA patients, whereas OA samples typically contained only IL-6. Immunohistochemical analysis of tissue sections from RA patients revealed lymphokine expression in 0.1-0.3% of T cells, particularly IL-2 and IFN-gamma, and to a lesser extent also IL-4. Interestingly, the expression of TNF-alpha and IL-6 by synovial T cells was also observed. The majority of cytokine-expressing T cells were CD4-positive T-helper cells typically found in perivascular areas, whereas cytokine-producing CD8-positive T cells were found distributed throughout the synovium. As expected, in specimens from OA patients, T cells were much less abundant and expression of cytokines could not be detected. CONCLUSION: These data clearly demonstrate production of cytokines by T cells in RA synovial tissue, indicating that activated T cells play a role in the pathophysiological events of RA.

Tumour necrosis factor alpha and its soluble receptors parallel clinical disease and autoimmune activity in systemic lupus erythematosus.

Cytokines are believed to play an important role in the pathogenesis of systemic lupus erythematosus (SLE). However, for tumour necrosis factor alpha (TNF-alpha) both beneficial and deleterious effects have been reported. To obtain information about the involvement of this cytokine in the pathophysiology of SLE, serum levels of TNF-alpha, the soluble forms of the 55 and 75 kDa tumour necrosis factor receptors (TNF-R55 and TNF-R75), and interleukin-6 (IL-6) were measured by ELISA in nine female patients over a period of 2 yr. Compared to healthy controls, levels of TNF-alpha (median 47 pg/ml, range < 15-222 pg/ml), TNF-R55 (median 1.9 ng/ml, range 0.8-10.8 ng/ml), TNF-R75 (median 4.7 ng/ml, range 1.5-15 ng/ml) and IL-6 (median 3.5 pg/ml, range < 3.5-52 pg/ml) were significantly elevated in SLE patients (P < 0.0001 vs controls in all cases). There were strong correlations between TNF-alpha and its soluble receptors (P < 0.0001). Moreover, TNF-alpha and both TNF-Rs strongly correlated with clinical and serological parameters of disease activity, such as the European Consensus Lupus Activity Measurement (ECLAM) score, anti-dsDNA antibodies, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and anaemia (P < 0.0001 for all comparisons). TNF-alpha and TNF-R75 also correlated with IL-6 (P < 0.0001). However, no correlation between IL-6 and ECLAM was found, and the correlation of IL-6 with anti-dsDNA was relatively weak; in contrast, IL-6 correlated strongly with CRP and ESR (P < 0.0001). Although these data do not allow us ultimately to discriminate between beneficial and deleterious effects of TNF-alpha, they nevertheless suggest a central role for the TNF system in the pathophysiology of SLE.

Folic acid and cyanocobalamin levels in serum and erythrocytes during low-dose methotrexate therapy of rheumatoid arthritis and psoriatic arthritis patients.

OBJECTIVE: To compare folic acid (FA) levels in patients being treated with methotrexate (MTX) with those of untreated patients in order to investigate potential folate depletion by MTX and its possible relationship to the drug's efficacy. METHODS: In 33 patients on low-dose MTX therapy and in 24 controls, FA and cyanocobalamin (B12) levels were determined in serum and red blood cells (RBC). In addition, MTX levels in the RBC and serum were measured, and clinical and laboratory measures of disease activity were evaluated. RESULTS: MTX treated patients had lower FA levels than controls (median 4.36 vs 7.37 ng/ml, p < 0.001). A significant correlation between serum FA and MTX/RBC (p < 0.01) and between the weekly dose and MTX/RBC (p < 0.01) was seen. There was apparently no correlation between FA and the cumulative total MTX. MTX patients had lower B12/RBC levels than the controls (p < 0.001); the serum levels of B12 were not different. Clinical features, ESR and CRP did not correlate with FA, B12 or MTX levels. CONCLUSIONS: The degree of folate depletion during MTX therapy depends primarily upon the weekly administered dose. Folate depletion may be related to B12 deficiency in RBC. Since FA levels were not related to parameters of disease activity it is conceivable that MTX does not exert its action in RA primarily by inhibiting dihydrofolatereductase. Therefore, additional folate compounds, if necessary, should not lead to a reduction in the efficacy of MTX.

Autoimmune response to the spliceosome. An immunologic link between rheumatoid arthritis, mixed connective tissue disease, and systemic lupus erythematosus.

OBJECTIVE: To assess the significance of autoantibodies to RA33, the A2 protein of the heterogeneous nuclear ribonucleoproteins (hnRNP), and to the related hnRNP proteins A1, B1, and B2 in rheumatic diseases. METHODS: Using a partially purified preparation of hnRNP-A and hnRNP-B proteins, sera from 303 patients with various rheumatic diseases were investigated by immunoblotting. For the analysis of cross-reactivities, autoantibodies were affinity purified by blot elution. RESULTS: Anti-A2/RA33 was found in 35% of rheumatoid arthritis (RA) patients, 38% of mixed connective tissue disease (MCTD) patients, 23% of systemic lupus erythematosus (SLE) patients, and, apart from single exceptions, not in patients with other rheumatic diseases. All anti-A2/RA33-positive sera were also reactive with B1 and B2, and anti-A2/RA33 antibodies cross-reacted with both proteins. Antibodies to hnRNP-A1 were found less frequently; moreover, the majority of anti-A1-positive sera also contained anti-A2/RA33 antibodies. In anti-A1, anti-A2/RA33 double-positive sera, cross-reactivity between the 2 antibodies was generally observed. In SLE patients, the presence of anti-A2/RA33 was correlated with the presence of anti-(U1) small nuclear RNP (snRNP) and anti-Sm (P < 0.0001 and P < 0.005, respectively), but there was no evidence for cross-reactivity between antibodies to hnRNP and antibodies to snRNP antigens. CONCLUSION: Since both hnRNPs and snRNPs are essential components of the spliceosome, the data show that the immune systems of patients with RA, SLE, and MCTD react to this functional complex. However, compared with MCTD and SLE patients, RA patients have a more restricted immune response to the spliceosome: they react to hnRNP proteins, particularly to hnRNP-A2/RA33, but not to snRNPs.

Soluble receptors for tumor necrosis factor and interleukin-2 in serum and synovial fluid of patients with rheumatoid arthritis, reactive arthritis and osteoarthritis.

OBJECTIVE: To compare levels of soluble tumor necrosis factor receptor (TNF-R) and soluble interleukin 2 receptor (sIL-2R) in sera and synovial fluids (SF) of patients with rheumatoid arthritis (RA), reactive arthritis (ReA), and osteoarthritis (OA) in order to investigate the usefulness of soluble cytokine receptors for differentiation diagnosis and their involvement in the pathophysiology of rheumatic diseases. METHODS: Soluble TNF-R (55 kDa), sIL-2R, and TNF-alpha were measured by ELISA in sera and SF of patients with RA, ReA, and OA and correlated with serological and clinical disease activity variables. RESULTS: Serum TNF-R was significantly (p < 0.0001) elevated in RA (4.6 +/- 2.1 ng/ml, mean +/- SD) compared to ReA (2.5 +/- 0.6 ng/ml), OA (2.2 +/- 0.7 ng/ml), and healthy controls (2.0 +/- 0.4 ng/ml). In SF mean TNF-R levels were 21 +/- 9.3 ng/ml in RA, 12.5 +/- 5.1 ng/ml in ReA, and 8.7 +/- 3.7 ng/ml in OA (p < 0.0001 for RA vs ReA or OA; p < 0.02 for ReA vs OA). SF levels were significantly higher in rheumatoid factor (RF) positive than in RF negative patients with RA. In patients with RA, correlations were found between TNF-R and TNF-alpha in SF (r = 0.32, p < 0.01), and between TNF-R and early morning stiffness (r = 0.4, p < 0.003 in serum; r = 0.29, p < 0.05 in SF). However, there was no correlation with disease activity variables such as Ritchie index, erythrocyte sedimentation rate (ESR) or C-reactive protein. Serum levels of IL-2R were elevated in RA and ReA, but a significant difference was found only for RA versus OA and controls (p < 0.0005), whereas in SF significant differences existed between all 3 patient groups (RA/ReA: p < 0.004; RA/OA: p < 0.0001; ReA/OA: p < 0.0003); both in serum and SF, levels of RF positive patients with RA were higher than those of RF negative patients. In patients with RA, IL-2R correlated weakly with ESR (r = 0.24, p < 0.05), iron concentration (r = -0.35, p < 0.005), and CRP (r = 0.24, p < 0.05). CONCLUSION: In RA, in contrast to ReA and OA, TNF-R and IL-2R were not only elevated in the joint fluid but also in serum. This indicates general activation of the immune system in RA, but not in ReA and OA. Therefore the soluble receptors, especially TNF-R, might become useful diagnostic variables to distinguish RA from ReA and OA.

Acidic particles and lung function in children. A summer camp study in the Austrian Alps.

Epidemiological studies have repeatedly demonstrated the effects of acidic particles on lung function. Three consecutive panels of children participating in a summer camp in the Austrian Alps were investigated. On-site pollution assessment consisted of 24-h measurements of particulate matter < 10 microns and the hydrogen, sulfate, and ammonium ion components. The 24-h maximums of ozone and daily pollen counts were also established. For 47, 45, and 41 subjects, daily FEV1, FVC, and peak expiratory flow were recorded. Fifteen percent, 11%, and 5% of participants, respectively, reported current asthma medication, indicating a markedly increased prevalence of respiratory disease. Mean levels of ambient pollutants were approximately 15% higher for the first panel than for the other two panels, but the hydrogen ion (H+) component was twice as high for Panel 1. The maximum H+ exposure during Panel 1 was 84 nmol/m3 (4 micrograms/m3 H2SO4 equivalent). For FEV1 in Panel 1, a significant decrease of -0.99 ml per nmol/m3 H+ (p = 0.01) was observed. For Panel 2, the FEV1/H+ coefficient was found to be similar (-0.74 ml per nmol/m3 H+; p = 0.28), while for Panel 3 it was in the opposite direction (0.10 ml per nmol/m3 H+; p = 0.83). The decrease in FEV1 observed in Panel 1 was more pronounced when the mean exposure during the previous 4 d was considered (-2.99 ml FEV1 per nmol/m3 H+; p = 0.004). We conclude that summer haze acidic particles may be associated with transient decreases in lung function in children.

High incidence of asymptomatic urogenital infection in patients with uveitis anterior.

Acute anterior uveitis (AAU) may be associated with systemic infectious or inflammatory disease. We examined 92 patients with the first attack of acute anterior uveitis; all patients were free of any extraocular symptoms. A thorough clinical examination did not reveal any systemic underlying disease. In the course of microbiological examination, however, a high incidence of asymptomatic infection of the urethra and/or cervix with ureaplasma urealyticum, chlamydia trachomatis and mycoplasma hominis was found. Infections with ureaplasma were significantly more frequent in patients with AAU when compared with a sex- and age-matched control group. There was no statistically valid association of these infections with the HLA-B27 phenotype in the patients. The higher rate of urogenital infections in patients with AAU may reflect a higher rate of sexual promiscuity. Transmission of infectious agents seems to be one possible factor in the pathogenesis of AAU.

Psychological health, self-reported physical health and health service use. Risk differential observed after one year of unemployment.

One year after the closure of a furniture factory the health consequences of long-term unemployment were studied among the 215 former employees and an interviewer-administered questionnaire was used to measure psychological health, self-perceived physical health and health service use. Those remaining unemployed 12 months after the closure were found to be 8 times more likely to report poor psychological health than were the re-employed (Odds ratio (OR): 8.5; 95% CI: 4.2-17.0). Self-reported physical ill-health was generally thought be respondents to be due to former work (56 percent of all disorders were related by subjects to former work history) and was also found to be associated with current employment status (OR 5.6; 95% CI: 2.7-11.5). Health services were over-utilized by the unemployed (OR 2.2; 95% CI: 1.2-4.1) and this differential was demonstrated to be even greater for the older and those reporting more diseases. Given the increasing proportion of long term unemployed in many Western countries this health service over-utilization will impose a substantial burden on public health expenditures unless other means of psychological and social support are provided.

Effect of infusion of salmon calcitonin on the secretion of somatostatin and gastrin in man.

In vitro and animal studies have pointed out complex interrelations between gastrointestinal hormones and calcitonin. To analyse the acute effects of calcitonin in more detail, patients undergoing surgery were infused intravenously with synthetic salmon calcitonin, a potent analog of the human hormone. Samples were taken after 0, 30 and 60 minutes from the hepatic, portal and a peripheral vein. Somatostatin and gastrin were determined by radioimmunoassay. The mean basal levels of somatostatin in peripheral and hepatic venous plasma (14.2 and 15.6 pg/ml) were significantly lower than in portal plasma (45.6 pg/ml), indicating effective removal by the liver. After infusion of calcitonin there was a general rise in somatostatin levels and an increase in the gradient between hepatic and portal blood. Basal gastrin levels were highest in the portal vein when compared intraindividually. The differences disappeared after calcitonin infusion with a concomitant systemic reduction of gastrin levels. Thus, calcitonin is able to stimulate the secretion of somatostatin from the gastrointestinal tract and does reduce gastrin secretion, possibly via the stimulation of somatostatin secretion.

[Experiences with a non-inflammable tube in laser surgery of the larynx]. / Erfahrungen mit einem unbrennbaren Tubus in der Laserchirurgie des Kehlkopfes.

With the recently developed noncombustible copper-tube dangerous damages caused by tube-ignition in the larynx will certainly be avoided.

[Observation of the radiologic course in long-term artificial respiration]. / Radiologische Verlaufsbeobachtung bei Langzeitbeatmung.

In a retrospective study, 108 patients were followed up who had to undergo artificial respiration treatment because of respiratory insufficiency. X-ray diagnosis showed a shock lung in all the patients. X-ray morphology correlates with the pathologicoanatomical substrate which develops progressively in phases. 24 patients (22%) could be saved, which is a remarkable success in view of the usually fatal prognosis. It was encouraging to find that follow-up examinations of the surviving patients did not reveal any detectable sequels of the "shock lung"; likewise, no unfavourable effects of the respiratory therapy were noticed.

[A method for prediction of outcome in patients with critical abdominal diseases under artificial ventilation (author's transl)]. / Ein Prognoseverfahren für Beatmungsfälle in der abdominellen Intensivmedizin.

Patients critically ill from abdominal diseases under controlled ventilation showed statistically significant differences in some vital signs and measurements immediately after admission to the intensive care unit, when grouped according to survivors (34 patients) and nonsurvivors (40 patients). On the basis of a stepwise linear discriminant analysis a practicable method of prognosis from data of the first 24 hours could be achieved, which enables a correct prediction of outcome in 91% of the survivors and 79% of the nonsurvivors.