Small-scale agricultural grassland management can affect soil fungal community structure as much as continental scale geographic patterns.

A European transect was established, ranging from Sweden to the Azores, to determine the relative influence of geographic factors and agricultural small-scale management on the grassland soil microbiome. Within each of five countries (factor 'Country'), which maximized a range of geographic factors, two differing growth condition regions (factor 'GCR') were selected: a favorable region with conditions allowing for high plant biomass production and a contrasting less favorable region with a markedly lower potential. Within each region, grasslands of contrasting management intensities (factor 'MI') were defined: intensive and extensive, from which soil samples were collected. Across the transect, 'MI' was a strong differentiator of fungal community structure, having a comparable effect to continental scale geographic factors ('Country'). 'MI' was also a highly significant driver of bacterial community structure, but 'Country' was clearly the stronger driver. For both, 'GCR' was the weakest driver. Also at the regional level, strong effects of MI occurred on various measures of the soil microbiome (i.e. OTU richness, management-associated indicator OTUs), though the effects were largely regional-specific. Our results illustrate the decisive influence of grassland MI on soil microbial community structure, over both regional and continental scales, and, thus, highlight the importance of preserving rare extensive grasslands.

Dialysis vintage time has the strongest correlation to psychosocial pattern of oral health-related quality of life - a multicentre cross-sectional study.

BACKGROUND: Aim of this cross-sectional, multicentre study was to investigate associations of dialysis vintage time in haemodialysis (CKD5D) patients with oral health-related quality of life (OHRQoL) and dental and periodontal treatment need. MATERIAL AND METHODS: CKD5D patients were divided into subgroups according to dialysis vintage time in different dialysis centres in Germany. OHRQoL was assessed with oral health impact profile (OHIP-G14). Dental treatment need was classified as presence of carious lesions. Periodontal treatment need was defined as periodontal screening index score (PSI) 3-4. RESULTS: In total, 190 participants were divided into the subgroups according to the time on CKD5D: 0 - 2 (n = 29), 3 - 5 (n = 35), 6 - 8 (n = 34), 9 - 12 (n = 29), 13 - 20 (n = 34) and >20 years (n = 29). The overall treatment need in the total cohort was 92% (dental 56%, periodontal 88%) with a total OHIP-G14 sum score of 4.17 [2; 0-5] without a significant correlation. Time on CKD5D was inversely correlated with the OHIP G14 score (p<0.01, R = -0.201). The pattern psychosocial impact was significantly associated with the dialysis duration (p<0.01) and showed a negative correlation to the OHIP-G14 (R = -0.283, Spearman's rho test p<0.01). For oral function also a negative correlation with OHIP-G14 was detected (Spearman's rho: -0.183). CONCLUSIONS: Patients with a prolonged dialysis vintage time show an improved OHRQoL, which might be mainly caused by the positive development of psychosocial pattern of OHRQoL. The oral health situation of HD patients seems unsatisfying, independently of dialysis vintage time and OHRQoL. Accordingly, an improvement in oral health situation of CKD5D patients is mandatory necessary. Thereby, consideration of psychosocial aspects especially at the beginning of CKD5D therapy and a sensitization regarding oral health issues with increasing vintage time might be recommendable.

Why, when and how should immunosuppressive therapy considered in patients with immunoglobulin A nephropathy?

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Lifelong mesangial deposition of IgA1 complexes subsist inflammation and nephron loss, but the complex pathogenesis in detail remains unclear. In regard to the heterogeneous course, classical immunosuppressive and specific therapeutic regimens adapted to the loss of renal function will here be discussed in addition to the essential common renal supportive therapy. Renal supportive therapy alleviates secondary, surrogate effects or sequelae on renal function and proteinuria of high intraglomerular pressure and subsequent nephrosclerosis by inhibition of the renin angiotensin system (RAASB). In patients with physiological (ΔGFR < 1·5 ml/min/year) or mild (ΔGFR 1·5-5 ml/min/year) decrease of renal function and proteinuric forms (> 1 g/day after RAASB), corticosteroids have shown a reduction of proteinuria and might protect further loss of renal function. In patients with progressive loss of renal function (ΔGFR > 3 ml/min within 3 months) or a rapidly progressive course with or without crescents in renal biopsy, cyclophosphamide with high-dose corticosteroids as induction therapy and azathioprine maintenance has proved effective in one randomized controlled study of a homogeneous cohort in loss of renal function (ΔGFR). Mycophenolic acid provided further maintenance in non-randomized trials. Differentiated, precise, larger, randomized, placebo-controlled studies focused on the loss of renal function in the heterogeneous forms of IgAN are still lacking. Prospectively, fewer toxic agents will be necessary in the treatment of IgAN.

Sequential therapy with cyclophosphamide and mycophenolic acid in patients with progressive immunoglobulin A nephropathy: a long-term follow-up.

In progressive immunoglobulin (Ig)A nephropathy (IgAN), cyclophosphamide pulse therapy (CyP), high-dose intravenous immunoglobulins (IVIg) and mycophenolic acid (MPA) have been used to stop progressive loss of renal function, but disease progression may occur after the end of the initial treatment. Here, we report the long-term follow-up of patients with progressive IgAN with MPA as maintenance therapy after CyP (CyP-MPA). In a median observation time of 6·2 years, we analysed the slopes of the loss of renal function of 47 patients with biopsy-proven IgAN and treated with CyP. Thirty-one patients with further progression were treated with MPA maintenance for a median time of 5·2 years. Follow-up was compared with symptomatic therapy and IVIg as historically matched control groups. Median loss of renal function was reduced significantly from 0·9 ml/min to 0·1 ml/min per month with CyP (P < 0·05), and with MPA in patients with a relapse from -0·4 ml/min to -0·1 ml/min per month (P < 0·05) until the end of the study. Proteinuria decreased significantly from 1·6 g/l to 1·0 g/l after CyP, and during MPA treatment to 0·6 g/l (P = 0·001 Friedman test). Median renal survival time was in patients with CyP 10·5 years (range = 3·2-17·8), with CyP-MPA 10·7 years (range = 8·3-13·1), with IVIg 4·7 years (range = 2·6-6·6), and in untreated patients 1·2 years (range = 0·8-1·6; log-rank test P < 0·01). In patients with progressive IgAN, our long-term follow-up observation indicates that sequential CyP-MPA therapy maintains renal survival significantly.

Hydronephrosis Resulting from Bilateral Ureteral Stenosis: A Late Complication of Polyoma BK Virus Cystitis?

We report here a case of acute lymphoblastic leukemia in remission presenting a late-onset bilateral hydronephrosis probably due to polyoma BK virus-induced proliferation of bladder endothelium on both ostii. The diagnosis was made virologically by BK virus Polymerase Chain Reaction (PCR) detection in the absence of any other bladder disease. Awareness of this late complication is necessary not only in patients after renal transplantation but also in patients after hematopoietic stem cell transplantation from matched unrelated donor.

[Interstitial nephritis]. / Interstitielle Nephritis.

Drugs such as antibiotics, non-steroidal anti-inflammatory drugs and proton pump inhibitors, infections and systemic diseases can trigger interstitial nephritis. The clinical outcome varies from asymptomatic progression to acute kidney injury. Interstitial nephritis often leads to characteristic and detectable partial tubular disorders such as tubular proteinuria (alpha(1)-microglobulin), phosphaturia with hypophosphatemia, aminoaciduria, diminished H(+) secretion with metabolic acidosis with inadequate high urinary pH, glucosuria and salt loss. The main principle of treatment is avoidance of the inducing agent. In addition corticosteroids have been proven usable after exclusion of an infection so that a good prognosis can be expected for acute nephritis in the majority of cases. In chronic forms the interstitial nephritis involves the glomeruli as well as potentially resulting in end-stage renal failure in the long run. Supportive therapies are then required in the sense of chronic renal failure in order to prevent further functional loss up to end-stage renal disease.

Bacterial endophytes contribute to abiotic stress adaptation in pepper plants (Capsicum annuum L.).

Endophytes are nonpathogenic plant-associated bacteria that can play an important role in plant vitality and may confer resistance to abiotic or biotic stress. The effects of 5 endophytic bacterial strains isolated from pepper plants showing 1-aminocyclopropane-1-carboxylate deaminase activity were studied in sweet pepper under in vitro conditions. Four of the strains tested showed production of indole acetic acid. Plant growth, osmotic potential, free proline content, and gene expression were monitored in leaves and roots under control and mild osmotic stress conditions. All indole acetate producers promoted growth in Capsicum annuum L. 'Ziegenhorn Bello', from which they were isolated. Osmotic stress caused an increase in the content of free proline in the leaves of both inoculated and noninoculated plants. Inoculated control plants also revealed higher proline levels in comparison with noninoculated control plants. Differential gene expression patterns of CaACCO, CaLTPI, CaSAR82A, and putative P5CR and P5CS genes during moderate stress were observed, depending on the bacterium applied. Inoculation with 2 bacterial strains, EZB4 and EZB8 (Arthrobacter sp. and Bacillus sp., respectively), resulted in a significantly reduced upregulation or even downregulation of the stress-inducible genes CaACCO and CaLTPI, as compared with the gene expression in noninoculated plants. This indicates that both strains reduced abiotic stress in pepper under the conditions tested.

Association of lipopolysaccharide-binding protein and coronary artery disease in men.

OBJECTIVES: In this study we tested the hypothesis that lipopolysaccharide-binding protein (LBP) might be able to be used as a biomarker for coronary artery disease (CAD). BACKGROUND: The mechanisms by which the innate immune recognition of pathogens could lead to atherosclerosis remain unclear. Lipopolysaccharide-binding protein is the first protein to encounter lipopolysaccharide and to deliver it to its cellular targets, toll-like receptors; therefore, its presence might be a reliable biomarker that indicates activation of innate immune responses. METHODS: A total of 247 men undergoing elective coronary angiography were studied, and the extent of coronary atherosclerosis was assessed by 2 established scores: "extent score" and "severity score." Levels of LBP, markers of inflammation, and traditional risk factors for CAD were assessed. RESULTS: Serum LBP concentration was significantly increased in 172 patients with angiographically confirmed CAD compared with 75 individuals without coronary atherosclerosis (20.6 +/- 8.7 pg/ml vs. 17.1 +/- 6.0 pg/ml, respectively; p = 0.002). Moreover in multivariable logistic regression analyses, adjusted for established cardiovascular risk factors and markers of systemic inflammation, LBP was a significant and independent predictor of prevalent CAD (p < 0.05 in all models). CONCLUSIONS: Lipopolysaccharide-binding protein might serve as a novel marker for CAD in men. The present results underlie the potential importance of innate immune mechanisms for CAD. Further studies are warranted to bolster the data and to identify pathogenetic links between innate immune system activation and atherosclerosis.

Single daily dose of cyclosporine in patients with primary glomerulonephritis and nephrotic syndrome.

AIMS: Single daily dose cyclosporine (SDD-CsA) might be a new option providing comparable efficacy, increased compliance and less nephrotoxicity compared to standard twice-daily dose cyclosporine (TDD-CsA). The aim of this trial was to prove the feasibility of SDD-CsA as primary and secondary maintenance therapy in patients with nephrotic syndrome. METHODS: We treated 25 adult patients with nephrotic syndrome and chronic primary glomerulonephropathy with SDD-CsA for a period of 12 months or more. 12 patients were pre-treated with twice-daily dose cyclosporine (TDD-CsA) and were then switched secondarily to a single daily dose after a median period of 8 months (sSDD-CsA). 13 patients were treated primarily with single daily dose cyclosporine (pSDD-CsA). RESULTS: In primary SDD-CsA patients, proteinuria decreased significantly from 9.2 - 0.8 g/l (p = 0.02) and serum protein increased significantly from 54 - 71 g/l (p = 0.03) during the study period. In secondary SDD-CsA patients, serum protein increased further (64 - 69, p = 0.04) after switching to SDD-CsA. In secondary SDD-CsA patients, the median total daily CsA dose was significantly lower (200 mg) with SDD-CsA compared to previous twice-daily dosing (300 mg, p = 0.01). Serum creatinine did not differ significantly before and after therapy and between the groups. CONCLUSIONS: SDD-CsA is effective in patients with nephrotic syndrome as primary and secondary maintenance therapy. SDD-CsA allows for significantly lower total daily doses, probably with less nephrotoxicity.

High-dose intravenous immunoglobulin pulse therapy in patients with progressive immunoglobulin A nephropathy: a long-term follow-up.

In progressive immunoglobulin A nephropathy (IgAN), intravenous immunoglobulin (IVIg) treatment has been used to delay disease progression, but the long-term efficacy is largely unknown. We report the clinical outcomes after IVIg therapy in six male patients with progressive IgAN [median glomerular filtration rate (GFR) 31 ml/min per 1.73 m(2)] followed for a median observation period of 8 years. In this single-arm, non-randomized study, IVIg was given monthly at a dose of 2 g/kg body weight for 6 months. The course of renal function was assessed by linear regression analysis of GFR and proteinuria, and was compared to eight patients with IgAN (median GFR 29 ml/min per 1.73 m(2)) without IVIg as a contemporaneous control group. IgAN disease progression was delayed after IVIg therapy on average for 3 years. The mean loss of renal function decreased from -1.05 ml/min per month to -0.15 ml/min per month (P = 0.024) and proteinuria decreased from 2.4 g/l to 1.0 g/l (P = 0.015). The primary end-point (GFR < 10 ml/min or relapse) occurred 5.2 years (median; range 0.4-8.8) after the first IVIg pulse, and after 1.3 years (median; range 0.8-2.4) in the control group (P = 0.043). In Kaplan-Meier analysis, the median renal survival time with IVIg was prolonged by 3.5 years (IVIg 4.7 years versus control 1.2 years; P = 0.006). IVIg pulse therapy may be considered as a treatment option to reduce the loss of renal function and improve proteinuria in patients with progressive IgAN.

Serum antibody positivity for distinct Helicobacter pylori antigens in benign and malignant gastroduodenal disease.

Infection with Helicobacter pylori may be associated with a variety of gastroduodenal diseases. Although H. pylori infection is common, peptic ulcer disease and gastric cancer occur in only a small minority of infected persons. This work was intended to correlate the pathological findings with the serological response to certain H. pylori antigens. Serum samples were taken from 285 patients who underwent gastroscopy. H. pylori infection was diagnosed by histology, culture or rapid urease test (RUT). Serum IgG reactivity against H. pylori-specific antigens was studied by Western blot. There was a significant association between the diagnosis of gastric cancer and the presence of IgG antibodies against the 19.5, 33 and 136 kDa (CagA) antigens. Comparing all H. pylori-positive patients with the gastric cancer group for the presence of the 19.5, 33 and 136 kDa (CagA) antigens, the results were as follows: chi2: 17.482, p < 0.001, power P = 0.994, odds ratio (OR) for the presence of gastric cancer: 19.5 (95% confidence interval (CI): 4.11-92.56). Antibodies against CagA alone or other bands (except 33 and 19.5 kDa antigens), as well as the age of patients were not related to a diagnosis of gastric cancer. Male patients were more likely to develop duodenal ulcer. IgG antibodies against the 19.5, 33 and 136 kDa (CagA) antigens could be helpful to identify patients at enhanced risk for the development of gastric cancer.

Dose adjustment of ciprofloxacin in renal failure: reduce the dose or prolong the administration interval?

BACKGROUND: Dose adjustments of antimicrobial drugs are necessary in renal failure. One method of dose adjustment is to reduce the dose and the other is to prolong the administration interval in proportion to the reduced drug clearance. Pharmacokinetically, both methods involve an identical drug exposure but pharmacodynamically there may be differences. It is not known which dose adjustment method is preferable in patients with renal failure. METHODS: We performed simulations using a published mechanism-based pharmacokinetic/ pharmacodynamic model of ciprofloxacin effects on growth and death of Escherichia coli bacteria. Ciprofloxacin 500 mg every 12 hrs was selected as the standard dose. In renal failure either the dose was reduced (250 mg every 12 hrs) or the administration interval was prolonged (500 mg every 24 hrs) in proportion to the reduced ciprofloxacin clearance. Simulations were done with use of a commercial software package. RESULTS: In normal renal function, using the standard dose, bacterial eradication was predicted on day 3. In renal failure, bacterial eradication was predicted on day 3 when using the interval prolongation scheme but only on day 6 when using the dose reduction scheme. The relationship between the efficacies of these 3 dosage schemes could have been predicted by AUC above MIC and AUIC, but not by AUC/MIC or time above MIC. CONCLUSION: Prolongation of the administration interval may be the preferable dose adjustment method in renal failure with ciprofloxacin. We hypothesize that these results may be transferable to other so-called dose-dependent antimicrobial drugs.

Pharmacokinetics and pharmacodynamics of lispro-insulin in hemodialysis patients with diabetes mellitus.

OBJECTIVE: Lispro-insulin, after subcutaneous injection in patients with normal renal function, is absorbed faster and has a faster onset of action when compared to regular insulin. However, the pharmacokinetics and pharmacodynamics of lispro-insulin in renal failure have not yet been investigated. PATIENTS AND METHODS: Eight patients with diabetes mellitus on long-term hemodialysis received an individualized dose of regular insulin or lispro-insulin in a crossover design. Blood glucose and insulin concentrations were measured before and after the subcutaneous insulin injections. RESULTS: Plasma insulin concentrations increased faster (time of maximum concentration tmax 20 vs 40 minutes, p = 0.01) and were higher (standardized maximum concentration Cmax/D 13.6 vs 6.1 microU/ml/U, p = 0.01) after lispro-insulin compared to regular insulin. The area under the curve, clearance and parameters of the hypoglycemic action for the 2 insulin products did not differ significantly, but there was a trend to minimum blood glucose level (time of the blood glucose minimum, Gtmin) to occur earlier with lispro-insulin (120 vs 210 minutes, p > 0.05). Differences in elimination half-life and volume of distribution were explained by flip-flop pharmacokinetics in the case of regular insulin. CONCLUSIONS: In hemodialysis patients with diabetes mellitus, lispro-insulin is absorbed faster than regular insulin. Differences in the effects of lispro-and regular insulin can be explained by the differences in pharmacokinetics.

Tonsillectomy does not prevent a progressive course in IgA nephropathy.

BACKGROUND: IgA nephropathy, or Berger's disease, is a primary mesangioproliferative glomerulonephritis, usually with a favourable prognosis. PATIENTS AND METHODS: To investigate the effect of tonsillectomy we conducted a retrospective investigation on renal outcome in 55 patients with IgA nephropathy in an outpatient university clinic between 1968 and 1994. Established risk factors for progressive IgA nephropathy were equally distributed in 16 patients subjected to tonsillectomy and in 39 patients without tonsillectomy. Renal survival and impact of risk factors were estimated by Kaplan-Meier analysis and Cox regression model. RESULTS: Seen in terms of the bivariate Kaplan-Meier analysis the probability of renal survival 10 years after biopsy was 0.37 for the 16 patients with tonsillectomy and 0.63 for the 39 patients without tonsillectomy (log-rank test p = 0.49, not significant). In the multivariate Cox regression model with 6 independent clinical covariates, initially high serum creatinine concentration had the strongest impact on renal outcome (p = 0.002), with a hazard ratio of 8.9 (95% CI: 2.3-35.0). Tonsillectomy had no significant influence in the Cox model (p = 0.37), displaying a hazard ratio of 1.7 (95% CI: 0.5-5.7). CONCLUSION: In conclusion, tonsillectomy does not reduce the risk of developing renal failure or prevent a progressive course of IgA nephropathy.