Early Control of PTH and FGF23 in Normophosphatemic CKD Patients: A New Target in CKD-MBD Therapy?

Background and objectives: Levels of parathyroid hormone (PTH) and the phosphaturic hormone FGF23, a fibroblast growth factor (FGF) family member, increase early in chronic kidney disease (CKD) before the occurrence of hyperphosphatemia. This short-term 6-wk dose titration study evaluated the effect of two phosphate binders on PTH and FGF23 levels in patients with CKD stages 3 to 4. Design, setting, participants, and measurements: Patients were randomized to receive over a 6-wk period either calcium acetate (n = 19) or sevelamer hydrochloride (n = 21). Results: At baseline, patients presented with elevated fractional excretion of phosphate, serum PTH, and FGF23. During treatment with both phosphate binders there was a progressive decline in serum PTH and urinary phosphate, but no change in serum calcium or serum phosphate. Significant changes were observed for FGF23 only in sevelamer-treated patients. Conclusions: This study confirms the positive effects of early prescription of phosphate binders on PTH control. Prospective and long-term studies are necessary to confirm the effects of sevelamer on serum FGF23 and the benefits of this decrease on outcomes. Clin J Am Soc Nephrol 5: 286-291, 2010. doi: 10.2215/CJN.05420709

Improving Alzheimer`s Disease Diagnosis with Machine Learning Techniques

There is not a specific test to diagnose Alzheimer`s disease (AD). Its diagnosis should be based upon clinical history, neuropsychological and laboratory tests, neuroimaging and electroencephalography (EEG). Therefore, new approaches are necessary to enable earlier and more accurate diagnosis and to follow treatment results. In this study we used a Machine Learning (ML) technique, named Support Vector Machine (SVM), to search patterns in EEG epochs to differentiate AD patients from controls. As a result, we developed a quantitative EEG (qEEG) processing method for automatic differentiation of patients with AD from normal individuals, as a complement to the diagnosis of probable dementia. We studied EEGs from 19 normal subjects (14 females/5 males, mean age 71.6 years) and 16 probable mild to moderate symptoms AD patients (14 females/2 males, mean age 73.4 years. The results obtained from analysis of EEG epochs were accuracy 79.9% and sensitivity 83.2%. The analysis considering the diagnosis of each individual patient reached 87.0% accuracy and 91.7% sensitivity.

Home blood pressure monitoring in blood pressure control among haemodialysis patients: an open randomized clinical trial

Background. It is not known if the adjustment of antihypertensive therapy based on home blood pressure monitoring (HBPM) can improve blood pressure (BP) control among haemodialysis patients. Methods. This is an open randomized clinical trial. Hypertensive patients on haemodialysis were randomized to have the antihypertensive therapy adjusted based on predialysis BP measurements or HBPM. Before and after 6 months of follow-up, patients were submitted to ambulatory blood pressure monitoring (ABPM) for 24 h, HBPM during 1 week and echocardiogram. Results. A total of 34 and 31 patients completed the study in the HBPM and predialysis BP groups, respectively. At the end of study, the systolic (SBP) and diastolic (DBP) blood pressure during the interdialytic period measured by ABPM were significantly lower in the HBPM group in relation to the predialysis BP group (mean 24-h BP: 135 +/- 12 mmHg/76 +/- 7 mmHg versus 147 +/- 15 mmHg/79 +/- 8 mmHg; P < 0.05). In the HBPM analysis, the HBPM group showed a significant reduction only in SBP compared to the predialysis BP group (weekly mean: 144 +/- 21 mmHg versus 154 +/- 22 mmHg; P < 0.05). There were no differences between the HBPM and predialysis BP groups in relation to the left ventricular mass index at the end of the study (108 +/- 35 g/m(2) versus 110 +/- 33 g/m(2); P > 0.05). Conclusions. Decision making based on HBPM among haemodialysis patients has led to a better BP control during the interdialytic period in comparison with predialysis BP measurements. HBPM may be a useful adjuvant instrument for blood pressure control among haemodialysis patients.

A long-term study in Angora goats experimentally infected with Mycobacterium avium subsp paratuberculosis: Clinical disease, faecal culture and immunological studies

Two longitudinal experiments involving Angora goats challenged with either bovine or ovine strains of Mycobacterium avium subspecies paratuberculosis (Map) have been conducted over a period of 54 and 35 months, respectively. Blood samples for the interferon-gamma (IFN-gamma) test and the absorbed ELISA and faecal samples for bacteriological culture were taken pre-challenge and monthly post-challenge. Persistent shedding, IFN-gamma production, seroconversion and clinical disease occurred earlier with the bovine Map gut mucosal tissue challenge inoculum than with cultured bacteria. The IFN-gamma responses of the gut mucosal tissue and bacterial challenge groups were substantially and consistently higher than those of the control group. The in vivo and cultured cattle strains were much more pathogenic for goats than the sheep strains with persistent faecal shedding, seroconversion and clinical disease occurring in the majority of bovine Map challenged goats. With the ovine Map, 3 goats developed persistent antibody responses but only one of these goats developed persistent faecal shedding and clinical disease. However, there was no significant difference between the IFN-gamma responses of the tissue challenged, bacterial challenged and control groups. Compared with sheep, the ELISA appeared to have higher sensitivity and the IFN-gamma test lower specificity. (C) 2005 Elsevier B.V. All rights reserved.

Prevalence of diabetic peripheral neuropathy and relation to glycemic control therapies at baseline in the BARI 2D cohort

We evaluated the associations between glycemic therapies and prevalence of diabetic peripheral neuropathy (DPN) at baseline among participants in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial on medical and revascularization therapies for coronary artery disease (CAD) and on insulin-sensitizing vs. insulin-providing treatments for diabetes. A total of 2,368 patients with type 2 diabetes and CAD was evaluated. DPN was defined as clinical examination score > 2 using the Michigan Neuropathy Screening Instrument (MNSI). DPN odds ratios across different groups of glycemic therapy were evaluated by multiple logistic regression adjusted for multiple covariates including age, sex, hemoglobin A1c (HbA1c), and diabetes duration. Fifty-one percent of BARI 2D subjects with valid baseline characteristics and MNSI scores had DPN. After adjusting for all variables, use of insulin was significantly associated with DPN (OR = 1.57, 95% CI: 1.15-2.13). Patients on sulfonylurea (SU) or combination of SU/metformin (Met)/thiazolidinediones (TZD) had marginally higher rates of DPN than the Met/TZD group. This cross-sectional study in a cohort of patients with type 2 diabetes and CAD showed association of insulin use with higher DPN prevalence, independent of disease duration, glycemic control, and other characteristics. The causality between a glycemic control strategy and DPN cannot be evaluated in this cross-sectional study, but continued assessment of DPN and randomized therapies in BARI 2D trial may provide further explanations on the development of DPN.

The Use of Smell Identification Tests in the Diagnosis of Parkinson`s Disease in Brazil

Smell identification tests may be of routine clinical value in the differential diagnosis of PD but are subject to cultural variation and have not been systematically evaluated in the Brazilian population. We have applied culturally adapted translations of the University of Pennsylvania 40-item smell identification test (UPSIT-40) and the 16-item identification test from Sniffin` Sticks (SS-16) to nondemented Brazilian PD patients and controls. Pearson`s correlation coefficient between the test scores was 0.76 (95% CI 0.70-0.81, n = 204, P < 0.001). To calculate reliability measures for each test we used the diagnosis (either PD or control) as outcome variable for separate logistic regression analyses using the score in the UPSIT-40 or the SS-16 as a covariate. The SS-16 specificity was 89.0% with a sensitivity of 81.1% (106 PD and 118 controls). The UPSIT-40 specificity was 83.5% and its sensitivity 82.1% (95 PD and 109 controls). Regression curves were used to associate an individual`s smell test score with the probability of belonging to the PD, as opposed to the control group. Our data provide support for the use of the UPSIT-40 and SS-16 to help distinguish early PD from controls. (c) 2008 Movement Disorder Society

The effects of air pollution on hospitalizations for cardiovascular disease in elderly people in Australian and New Zealand cities

OBJECTIVE: The goal of this study was to estimate the associations between outdoor air pollution and cardiovascular hospital admissions for the elderly. DESIGN: Associations were assessed using the case-crossover method for seven cities: Auckland and Christchurch, New Zealand; and Brisbane, Canberra, Melbourne, Perth, and Sydney Australia. Results were combined across cities using a random-effects meta-analysis and stratified for two adult age groups: 15-64 years and >= 65 years of age (elderly). Pollutants considered were nitrogen dioxide, carbon monoxide, daily measures of particulate matter (PM) and ozone. Where multiple pollutant associations were found, a matched case-control analysis was used to identify the most consistent association. RESULTS: In the elderly, all pollutants except 03 were significantly associated with five categories or cardiovascular disease admissions. No associations were found for arrhythmia and stroke. For a 0.9-ppm increase in CO, there were significant increases in elderly hospital admissions for total cardiovascular disease (2.2%), all cardiac disease (2.8%), cardiac failure (6.0%), ischemic heart disease (2.3%), and myocardial infarction (2.9%). There was some heterogeneity between cities, possibly due to differences in humidity and the percentage of elderly people. In matched analyses, CO had the most consistent association. CONCLUSIONS. The results suggest that air pollution arising from common emission sources for CO, NO2, and PM (e.g., motor vehicle exhausts) has significant associations with adult cardiovascular hospital admissions, especially in the elderly, at air pollution concentrations below normal health guidelines. RELEVANCE TO CLINICAL AND PROFESSIONAL PRACTICE: Elderly populations in Australia need to be protected from air pollution arising from outdoor sources to reduce cardiovascular disease.

Association between Parkinson`s disease and glucocerebrosidase mutations in Brazil

Objective: To evaluate the association between parkinsonism and mutations in the glucocerebrosidase gene (GBA) in Brazilian patients. Methods: We searched for three GBA common mutations (N370S, L444P and G377S) in 65 Brazilian patients affected by PD with disease onset before the age of 55 and compared the results to 267 age- and sex-matched controls. Results: GBA mutations were detected at a significantly higher frequency among Parkinson`s disease patients (2/65 = 3%), when compared to the control group (0/267): P = 0.0379. Conclusion: These results provide further evidence for GBA mutations being a possible hereditary risk factor for PD. (C) 2007 Elsevier Ltd. All rights reserved.

Uveitis in celiac disease with an excellent response to gluten-free diet: third case described

To describe the case of a patient with celiac disease who achieved a complete response to a gluten-free diet. A 28-year-old woman presented with diarrhea, oral ulcers, and refractory uveitis of 2.5-years duration. She was treated with prednisone, mydriatic drops, and infliximab with no response. She was referred to our hospital at which point her previous diagnosis of uveitis was confirmed; she was also diagnosed with right-sided sacro-iliitis. The patient did not have arthritis or any skin conditions. Three tests for fecal parasites and a fecal leukocyte were negative. Endoscopy revealed atrophic appearance of the duodenal mucosa. Biopsy showed atrophy of the duodenal villi with intra-epithelial lymphocytes, hyperplasia of the crypts, and chronic inflammatory infiltrate. The search for antiendomysial antibody was > 1/1,280. The patient was started on a gluten-free diet and after 3 months demonstrated significant improvement of gastrointestinal symptoms and uveitis, as well as a reduction of antiendomysial antibodies (1/80). After 6 months, there was complete remission of gastrointestinal symptoms and total control of uveitis. The antiendomysial antibody was negative at that time. Clinical uveitis as a manifestation of celiac disease has been described in only two cases in the literature. This case study is the third to demonstrate that uveitis is a clinical symptom that can be addressed in patients with celiac disease.

The role of vaccines in the control of STDs: HPV vaccines

Prophylactic vaccines for genital human papillomavirus (HPV) infection have been shown to be feasible in animal models, and suitable vaccine material based on virus-like particles can be produced in bulk at reasonable cost. Initiation of phase III clinical trials will follow definition of trial outcome measures through further epidemiological studies, and development-of assays of host protective immunity. Vaccines could in principle eliminate HPV-related disease, as the human race is the only natural host for the relevant papillomaviruses (PVs). Therapeutic vaccines for genital HPV infection are also possible, but have not yet been demonstrated as feasible in practice because the choice of vaccine antigens is difficult, the method of their optimal delivery is uncertain, and the nature of the relevant antiviral immunity is unknown. PV species specificity will require trials to be conducted in man, which will slow definition of an ideal vaccine.

Long-term administration of IgG2a anti-NK1.1 monoclonal antibody ameliorates lupus-like disease in NZB/W mice in spite of an early worsening induced by an IgG2a-dependent BAFF/BLyS production

The role of natural killer (NK) T cells in the development of lupus-like disease in mice is still controversial. We treated NZB/W mice with anti-NK1.1 monoclonal antibodies (mAbs) and our results revealed that administration of either an irrelevant immunoglobulin G2a (IgG2a) mAb or an IgG2a anti-NK1.1 mAb increased the production of anti-dsDNA antibodies in young NZB/W mice. However, the continuous administration of an anti-NK1.1 mAb protected aged NZB/W mice from glomerular injury, leading to prolonged survival and stabilization of the proteinuria. Conversely, the administration of the control IgG2a mAb led to an aggravation of the lupus-like disease. Augmented titres of anti-dsDNA in NZB/W mice, upon IgG2a administration, correlated with the production of BAFF/BLyS by dendritic, B and T cells. Treatment with an anti-NK1.1 mAb reduced the levels of interleukin-16, produced by T cells, in spleen cell culture supernatants from aged NZB/W. Adoptive transfer of NK T cells from aged to young NZB/W accelerated the production of anti-dsDNA in recipient NZB/W mice, suggesting that NK T cells from aged NZB/W are endowed with a B-cell helper activity. In vitro studies, using purified NK T cells from aged NZB/W, showed that these cells provided helper B-cell activity for the production of anti-dsDNA. We concluded that NK T cells are involved in the progression of lupus-like disease in mature NZB/W mice and that immunoglobulin of the IgG2a isotype has an enhancing effect on antibody synthesis due to the induction of BAFF/BLyS, and therefore have a deleterious effect in the NZB/W mouse physiology.

Abnormal chronotropic reserve and heart rate recovery in patients with SLE: a case-control study

Abnormal heart-rate (HR) response during or after a graded exercise test has been recognized as a strong and an independent predictor of all-cause mortality in healthy and diseased subjects. The purpose of the present study was to evaluate the HR response during exercise in women with systemic lupus erythematosus (SLE). In this case-control study, 22 women with SLE (age 29.5 perpendicular to 1.1 years) were compared with 20 gender-, BMI-, and age-matched healthy subjects (age 26.5 +/- 1.4 years). A treadmill cardiorespiratory test was performed and HR response during exercise was evaluated by the chronotropic reserve (CR). HR recovery (Delta HRR) was defined as the difference between HR at peak exercise and at both first (Delta HRR1) and second (Delta HRR2) minutes after exercising. SLE patients presented lower peak VO(2) when compared with healthy subjects (27.6 perpendicular to 0.9 vs. 36.7 perpendicular to 1.1 ml/kg/min, p = 0.001, respectively). Additionally, SLE patients demonstrated lower CR (71.8 +/- 2.4 vs. 98.2 +/- 2.6%, p = 0.001), Delta HRR1 (22.1 +/- 2.5 vs. 32.4 +/- 2.2%, p = 0.004) and Delta HRR2 (39.1 +/- 2.9 vs. 50.8 +/- 2.5%, p = 0.001) than their healthy peers. In conclusion, SLE patients presented abnormal HR response to exercise, characterized by chronotropic incompetence and delayed Delta HRR. Lupus (2011) 20, 717-720.

Worse renal outcome of lupus nephritis in male patients: a case-control study

Background: Progression and long-term renal outcome of lupus nephritis (LN) in male patients is a controversial subject in the literature. The aim of this study was to evaluate the influence of male gender on the renal outcome of LN. Methods: All male (M) LN patients who fulfilled American College of Rheumatology lupus criteria and who were referred for a kidney biopsy from 1999 to 2009 were enrolled in the study. Subjects with end-stage renal disease at baseline, or follow-up time below 6 months, were excluded. Cases were randomly matched to female (F) patients according to the class of LN, baseline estimated glomerular filtration rate (eGFR, Modification of Diet in Renal Disease simplified formula) and follow-up time. Treatment was decided by the clinical staff based on usual literature protocols. The primary endpoint was doubling of serum creatinine and/or end-stage renal disease. The secondary endpoint was defined as a variation of glomerular filtration rate (GFR) per year (Delta GFR/y index), calculated as the difference between final and initial eGFR adjusted by follow-up time for each patient. Results: We included 93 patients (31 M : 62 F). At baseline, M and F patients were not statistically different regarding WHO LN class (II 9.7%, IV 71%, V 19.3%), eGFR (M 62.4 +/- 36.4 ml/min/1.73 m(2) versus F 59.9 +/- 32.7 ml/min/1.73 m(2)), follow-up time (M 44.2 +/- 27.3 months versus F 39.9 +/- 27.9 months), and 24-hour proteinuria (M 5.3 +/- 4.6 g/day versus F 5.2 +/- 3.0 g/day), as well as age, albumin, C3, antinuclear antibody, anti-DNA antibody and haematuria. There was no difference in the primary outcome (M 19% versus F 13%, log-rank p = 0.62). However, male gender was significantly associated with a worse renal function progression, as measured by Delta GFR/y index (beta coefficient for male gender -12.4, 95% confidence interval -22.8 to -2.1, p = 0.02). The multivariate linear regression model showed that male gender remained statistically associated with a worse renal outcome even after adjustment for eGFR, proteinuria, albumin and C3 complement at baseline. Conclusion: In our study, male gender presented a worse evolution of LN (measured by an under GFR recovering) when compared with female patients with similar baseline features and treatment. Factors that influence the progression of LN in men and sex-specific treatment protocols should be further addressed in new studies. Lupus (2011) 20, 561-567.

Mechanisms of biocontrol by Pantoea dispersa of sugar cane leaf scald disease caused by Xanthomonas albilineans

Albicidins, a family of phytotoxins and antibiotics produced by Xanthomonas albilineans, are important in sugar cane leaf scald disease development. The albicidin detoxifying bacterium Pantoea dispersa (syn. Erwinia herbicola) SB1403 provides very effective biocontrol against leaf scald disease in highly susceptible sugar cane cultivars. The P. dispersa gene (albD) for enzymatic detoxification of albicidin has recently been cloned and sequenced. To test the role of albicidin detoxification in biocontrol of leaf scald disease, albD was inactivated in P. dispersa by site-directed mutagenesis. The mutants, which were unable to detoxify albicidin, were less resistant to the toxin and less effective in biocontrol of leaf scald disease than their parent strain. This indicates that albicidin detoxification contributes to the biocontrol capacity of P. dispersa against X. albilineans. Rapid growth and ability to acidify media are other characteristics likely to contribute to the competitiveness of P. dispersa against X. albilineans at wound sites used to invade sugar cane.