Tolerance in the absence of autoantigen

Regulatory T (T(reg)) cells show promise for treating autoimmune diseases, but their induction to elevated potency has been problematic when the most optimally derived cells are from diseased animals. To circumvent reliance on auto-antigen reactive T(reg) cells, stimulation to vaccine antigens (Ags) may offer a viable alternative while maintaining potency to protect against proinflammatory diseases. Our Salmonella vaccine expressing colonization factor Ag I (CFA/I) possesses anti-inflammatory properties, evident by elevated Th2 cell responses, reduced inflammatory cell infiltrates in the Peyer's patches, and an absence of proinflammatory cytokine production by infected macrophages. Given these findings, we hypothesized whether this vaccine would be protective against experimental autoimmune encephalomyelitis (EAE). As such, Salmonella-CFA/I protected in both prophylactic and therapeutic paradigms against proteolipid protein (PLP(139-151))-mediated EAE in SJL mice. The protected mice showed significantly reduced clinical disease and subsequent resolution when compared to PBS-treated controls. Histopathological studies showed reduced demyelination and no inflammation of spinal cords when compared to PBS- or Salmonella vector-treated mice. To ascertain whether the observed immune deviation was in part supported by T(reg) cells, analysis revealed involvement of FoxP3(+) CD25(+) CD4(+) T cells. Adoptive transfer of induced TGF-beta (+) T(reg) cells from vaccinated mice showed complete protection against PLP(139-151) challenge, but not by naive T(reg) cells. Partial protection to EAE was also achieved by the adoptive transfer of CD25(-) CD4(+) T cells, suggesting that Th2 cells also contributed. Thus, these data show that T(reg) cells are induced by oral vaccination with Salmonella-CFA/I contributing to the efficacious treatment of autoimmune disease.     

Treatment With Cinacalcet of Secondary Hyperparathyroidism After Renal Transplantation

Background

The treatment of posttransplant secondary hyperparathyroidism (SHP) with vitamin D analogues is determined by their effectiveness to reverse hypercalcemia. Calcimimetics inhibit parathyroid hormone (PTH) secretion by modulating the calcium-sensing receptor in the parathyroid gland. Cinacalcet, a calcimimetic drug, has proven its effectiveness for the treatment of SHP among patients in phase V of chronic renal disease.

Patients and Methods

This retrospective analysis included 48 patients with SHP who were treated with cinacalcet. The initial dose of 30 mg/d could be increased to 180 mg, administering calcitriol also, depending on the serum calcium and PTH levels. The objectives were a PTH level between 75 and 125 pg/mL or a decrease >40%, and a serum calcium level below 10.5 mg/dL.

Results

The average PTH at baseline was 244 pg/mL, decreasing to 131 pg/mL at 1 year (P < .01). The average calcium at baseline was 10.1 mg/dL descending to 9.2 mg/dL at 1 year (P < .01). Among patients with hypercalcemia, the calcium decreased from 11 to 9.6 mg/dL at 1 year (P < .01). Seventy percent of patients without hypercalcemia reached the desired value of PTH, and 100% of those with hypercalcemia. Among patients with hypercalcemia, the desired calcium level was reached in 91% of cases. Ten patients developed hypocalcemia. In 3 cases we stopped the treatment with cinacalcet due to digestive intolerance.

Conclusions

Treatment with cinacalcet controlled hyperparathyroidism and hypercalcemia among patients with posttransplant SHP. It was a safe drug, with a low incidence of side effects.     

Cardiac Hemodynamic Profiles and Pro-B-Type Natriuretic Peptide in Cirrhotic Patients Undergoing Liver Transplantation

Background

The aim of our study was to determine concentrations of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with cirrhosis, thereby describing the hemodynamic and cardiac profiles to verify the existence of cirrhotic cardiomyopathy.

Methods

Clinical data, NT-proBNP levels, echocardiography, and right heart hemodynamic measurements were performed on all patients undergoing liver transplantation for cirrhosis.

Results

Our patients showed a hyperdynamic circulation with elevated left-sided pressures despite high cardiac outputs. This observation suggested abnormalities in left ventricular diastolic compliance. We verified these results, because our cohort showed a significant left ventricular mass index and, consequently, diastolic dysfunction. Mean NT-proBNP levels were high. The great expansion of central volume may explain these results and the later development of left ventricular hypertrophy.

Conclusion

We concluded that elevated concentrations of NT-proBNP indicated the presence of hyperdynamic syndrome and cardiac dysfunction.     

Validación de la versión en español del cuestionario “Epidemiology of Prolapse and Incontinence Questionnaire-EPIQ”

IntroductionOne out of three women suffers from pelvic floor disorders. Thus, an instrument to evaluate this pathology in common clinical practice would be very useful. In this study the psychometric characteristics of the Spanish version of the US questionnaire “Epidemiology of Prolapse and Incontinence Questionnaire-EPIQ” have been evaluated, in order to test its equivalence to the original and allow for its use in Spain.Material and Methods60 women with pelvic floor pathology and 60 control women filled in the Spanish version of the EPIQ. The questionnaire was validated following the statistical procedure used in the validation of the original form.Results: Factibility113 women filled in all questionnaire items and 7 leaved some of them blank. Validity: 7 dimensions were indentified: quality of life (QoL), overactive bladder (OAB), anal incontinence (AI), micturition difficulty/pain (MD/P), functional defecation disorders (FDD), stress urinary incontinence (SUI), and pelvic organ prolapse (POP). The validity of contents was proved comparing the mean scores for each dimension in patients and control (T-student test). Positive and negative predictive values were POP=92,3% and 82,52%; SUI= 54,34% and 84,93%; OAB=60,6% and 84,52% and AI=24,32% and 92,68%. Reliability: Global Cronbach´s-alfa was 0,94 and for the different dimensions: 0,96 (QoL); 0,91 (OAB); 0,63 (AI); 0,72 (MD/P); 0,75 (FDD) y 0,61 (SUI).DiscussionThe Spanish version of the EPIQ questionnaire presents adequate factibility, validity and reliability to evaluate pelvic floor pathology in clinical practice.     

Gastrojejunal Anastomotic Stenosis in Laparoscopic Gastric Bypass with a Circular Stapler (21 mm): Incidence, Treatment and Long-term Follow-up

Background  

One of the keys to the long-term success of laparoscopic gastric bypass (LGBP) is performing a small-diameter gastrojejunal anastomosis, which occasionally involves an increased incidence of stenosis.     

Cross-country disparities in health-care expenditure: a factor decomposition

This note investigates the sources of international differences in the levels of per capita health-care expenditure, using data on the OECD countries between 1975 and 2003. To that end, we use Theil's second measure of inequality for decomposing cross-country disparities in per capita health-care expenditure into the contributions of various factors: health-care expenditure expressed as a share of GDP, labour productivity, employment rate, activity rate and the ratio of working-age population to total population. Our results show that cross-country differences in the share of GDP devoted to health-care expenditure and labour productivity are the main determinants of the level of dispersion in per capita health-care expenditure. On the contrary, existing disparities in the remaining explanatory factors considered play a less relevant role in this context. In any event, the analysis performed reveals that the overall inequality in per capita health-care expenditure decreased throughout the study period. This was due to the process of international convergence observed in most of the factors used to break down the level of per capita health-care expenditure.     

Age-dependent association of KIBRA genetic variation and Alzheimer's disease risk

An association between memory performance in healthy young, middle aged an elderly subjects and variability in the KIBRA gene (rs17070145) has been recently described. We analyzed this polymorphism in 391 sporadic Alzheimer's disease (AD) patients and 428 cognitively normal control subjects. The current study reveals that KIBRA (rs17070145) T allele (CT and TT genotypes) is associated with an increased risk (OR 2.89; p=0.03) for very-late-onset (after the age of 86 years) AD.