Nestor H Garcia

Renal tubular acidosis and vasculitis associated with IgE deposits in the kidney and small vessels

We report a woman with a history of allergies, polyuria, polydipsia, proteinuria, renal loss of electrolytes, renal tubular acidosis, nephrocalcinosis, and palpable purpura. A proximal defect was excluded by a normal bicarbonate reabsorption curve, and a distal tubular defect was shown because urine pH did not decrease to less than 6.4 despite ammonium chloride-induced systemic acidosis. Moreover, furosemide failed to improve urinary acidification. Urine-to-blood PCO(2) gradient was less than 14 mm Hg, although the urine bicarbonate level reached values as high as 89 mEq/L. Combining bicarbonate and neutral phosphate infusions increased the urine-to-blood PCO(2) gradient to only 20 mm Hg. These subnormal PCO(2) gradient values point to proton-pump dysfunction in the collecting tubule. Histological evidence of tubulointerstitial disease accompanied the tubular defects. The striking histological feature was the presence of immunoglobulin E (IgE) deposits in glomeruli, tubuli, and vessels. Concurrent with these findings, she had high serum IgE titers and CD23 levels. IgE antibodies from her serum were reactive against human renal tubuli, with binding to two regions that matched two different proteins present in cortex and medulla. One of these proteins corresponded to carbonic anhydrase II (31 kd); the second, to an unidentified protein that seems attached to cell membranes. We suggest that these IgE antibodies could have had a pathogenic role in this patients glomerular, tubular, and small-vessel disease.

Adding carotid total plaque area to the Framingham risk score improves cardiovascular risk classification

Introduction Cardiovascular events (CE) due to atherosclerosis are preventable. Identification of high-risk patients helps to focus resources on those most likely to benefit from expensive therapy. Atherosclerosis is not considered for patient risk categorization, even though a fraction of CE are predicted by Framingham risk factors. Our objective was to assess the incremental value of combining total plaque area (TPA) with the Framingham risk score (FramSc) using post-test probability (Ptp) in order to categorize risk in patients without CE and identify those at high risk and requiring intensive treatment. Material and methods A descriptive cross-sectional study was performed in the primary care setting in an Argentine population aged 22–90 years without CE. Both FramSc based on body mass index and Ptp-TPA were employed in 2035 patients for risk stratification and the resulting reclassification was compared. Total plaque area was measured with a high-resolution duplex ultrasound scanner. Results 57% male, 35% hypertensive, 27% hypercholesterolemia, 14% diabetes. 20.1% were low, 28.5% moderate, and 51.5% high risk. When patients were reclassified, 36% of them changed status; 24.1% migrated to a higher and 13.6% to a lower risk level (κ index = 0.360, SE κ = 0.16, p < 0.05, FramSc vs. Ptp-TPA). With this reclassification, 19.3% were low, 18.9% moderate and 61.8% high risk. Conclusions Quantification of Ptp-TPA leads to higher risk estimation than FramSc, suggesting that Ptp-TPA may be more sensitive than FramSc as a screening tool. If our observation is confirmed with a prospective study, this reclassification would improve the long-term benefits related to CE prevention.

Risk of vascular disease in premenopausal women with diabetes mellitus.

PURPOSE The aims of this study were (1) to estimate the prevalence of cardiovascular disease risk factors among premenopausal and menopausal Argentinean women with and without type 2 diabetes mellitus and (2) to assess the contribution of total plaque area (TPA) to risk stratification when added to Framingham risk scores. METHODS A descriptive cross-sectional study in primary prevention in 1257 women (ages 19-84 years) from Argentina. TPA was measured by ultrasonography. Framingham sex-specific risk equations were used to predict the risk of developing cardiovascular disease, coronary heart disease, and stroke during the next 10 years. Patients were divided into diabetic (n = 293) and control groups (n = 964), and then each group was divided according to age (>40, 40-49, 50-59, and ≥60 years). FINDINGS No difference was observed between diabetic and control groups in the incidence of smoking or the presence of early family cardiovascular event. Overall, diabetic patients had higher body mass index, blood pressure, and TPA versus the control group. The Framingham risk score was higher in the diabetic group in all age groups. The mean (SD) coronary heart disease scores for the diabetic group at <40, 40 to 49, 50 to 59, and ≥60 were 6% (1.7%), 19% (2.5%), 38% (2.0%), and 60% (1.5%), respectively, whereas the scores in the control group 3% (0.8%), 7% (0.9%), 17% (0.9%), and 40% (0.9%), respectively. The stroke score was also enhanced in diabetic women, independent of their age. These data indicate that diabetic women in the premenopausal age or the early years of menopause age (40-50 years) are at intermediate or higher risk of developing a cardiovascular event. IMPLICATIONS Premenopausal diabetic women should be considered at possibly high risk of cardiovascular events compared with nondiabetic women. Direct assessment of atherosclerotic burden, such as TPA, should be used early in this population instead of relying on traditional risk scores.

High Concentrations of Sodium Chloride Improve Microbicidal Activity of Ibuprofen against Common Cystic Fibrosis Pathogens

Ibuprofen (IBU-H), a widely used anti-inflammatory, also shows a marked antimicrobial effect against several bacterial species, including those involved in cystic fibrosis such as Pseudomona aeruginosa, methicillin resistant Staphylococcus aureus and Burkholderia cepacia complex. Additionally, our results show significant synergy between water soluble Na-ibuprofen (IBU-Na) and ionic strength. Salt concentrations above 0.5 M modify the zeta potential promoting the action of Na-IBU; thus, with 1 M sodium chloride, IBU-Na is ten times more efficient than in the absence of ionic strength, and the minimum effective contact time is reduced from hours to minutes. In short time periods, where neither IBU-Na nor controls with 1 M NaCl show activity, the combination of both leads to a reduction in the bacterial load. We also analyzed whether the changes caused by salt on the bacterial membrane also promoted the activity of other microbicide compounds used in cystic fibrosis like gentamicin, tobramycin and phosphomycin. The results show that the presence of ionic strength only enhanced the bactericidal activity of the amphipathic molecule of IBU-Na. In this respect, the effect of saline concentration was also reflected in the surface properties of IBU-Na, where, in addition to the clear differences observed between 145 mM and 1 M, singular behaviors were also found, different in each condition. The combination of anti-inflammatory activity and this improved bactericidal effect of Na-IBU in hypertonic solution provides a new alternative for the treatment of respiratory infections of fibrotic patients based on known and widely used compounds.