Guilherme Geib

Serum magnesium and proton-pump inhibitors use: a cross-sectional study

OBJECTIVE The aim of this study was to evaluate the association of serum magnesium levels with proton pump inhibitors (PPIs) use and other factors. METHODS This was a cross-sectional study of 151 patients admitted with acute diseases in the Internal Medicine Division of the Hospital de Clinicas de Porto Alegre, after the exclusion of conditions that are commonly associated with hypomagnesemia: diarrhea; vomiting; chronic alcohol use; severely uncompensated diabetes mellitus; and chronic use of laxatives, diuretics or other drugs causing magnesium deficiency. RESULTS All patients had normal serum magnesium levels. Serum albumin and creatinine levels were positively associated with serum magnesium levels, after adjusting for confounders. There was no difference between mean serum magnesium levels of PPI users and non-users, nor between men and women; there was also no correlation among age, serum phosphorus, and potassium levels with serum magnesium levels. Limitations of this study include the absence of an instrument for measuring adherence to PPI use and the sample size. CONCLUSION The association of PPI use and hypomagnesemia is uncommon. Congenital defects in the metabolism of magnesium may be responsible for hypomagnesemia in some patients using this drug class.

Androgen-Dependent Expression of c-jun and c-fos in Human Non-Transformed Epithelial Prostatic Cells: Association with Cell Proliferation

Objective: To assess the effect of dihydrotestosterone (DHT) on the gene expression of c-fos and c-jun and on the proliferation of human non-transformed epithelial prostatic (HNTEP) cells. Methods: Cell proliferation (MTT) and c-fos and c-jun mRNA expression (RT-PCR) were determined in cells treated with DHT (10–8, 10–10, and 10–13M) or with control medium. Results: DHT 10–13 M had a significant stimulatory effect on cell proliferation (p < 0.05) and c-fos and c-jun gene expression when compared to cells treated with higher concentrations of this hormone (10–10 and 10–8M) or with the control group. Conclusions: Our data demonstrate that the increase in c-fos and c-jun expression and cell growth in HNTEP cells is maximal with the lowest DHT concentration (10–13M). These proto-oncogenes may play a role in the control of hormone responsiveness and cell proliferation in HNTEP cells.

Superoxide dismutase activity in doxorubicin-induced cardiotoxicity in humans: A novel tool for risk stratification

8036 Background: oxidative stress has been implicated in doxorubicin-induced cardio toxicity in experimental studies. The role of oxidative pathways in clinical doxorubicin-induced cardiotoxicity, however, is poorly characterized. We investigated if systemic antioxidant markers predict cardiac dysfunction in patients eligible for doxorubicin use. METHODS we prospectively evaluated oncology patients eligible for doxorubicin chemotherapy, with no prior history of cardiovascular disease. Blood samples for enzymatic (super oxide dismutase activity [SOD-U/mg protein]) and non-enzymatic antioxidants (total radical trapping antioxidant potential [TRAP-μmol of Trolox/mg protein]) were collected at baseline (B), third (T) and final (F) cycles. Left ventricular ejection fraction (LVEF) was assessed by radionuclide ventriculography. RESULTS Fifty-one patients (49±12 years, 90% female) underwent 5.9 ± .9 chemotherapy cycles and received 301 ± 52 mg/m2 of doxorubicin, mostly for breast cancer (80%). Overall, LVEF decreased from 60.7 ± 6.1% at baseline to 56.4 ± 7.4 % after treatment (p<0.001), but only 6 (12%) patients developed significant LV systolic dysfunction (LVEF<50%). SOD activity increased significantly during treatment (4.5 ± 1.8 [B], 6.0 ± 2.1 [T], 5.6 ± 2.2 [F]; p<0.01), while TRAP values were unchanged (302 ± 120 [B], 312 ± 119 [T], 299 ± 99 [F], NS). Interestingly, baseline SOD values from patient who developed LV systolic dysfunction were significantly higher than those who maintained a normal LVEF (5.9 ± 1.8 versus 4.3 ± 1.7; p<0.05). We also observed a trend toward greater change in SOD values over time in patients who did not developed LV systolic dysfunction (1.7 ± 2 [LVEF≥50%] versus 0.2 ± 3.3 [LVEF<50%]; p=0.14). In multivariate analysis, adjusted for age and doxorubicin dose, baseline SOD activity remained an independent predictor of LV dysfunction. CONCLUSIONS high baseline SOD activity predicts doxorubicin-induced cardio toxicity in humans, in part because recruitment of enzymatic anti-oxidant defense mechanisms may be limited. Non-enzymatic pathways (TRAP) were not predictive of cardiac dysfunction. [Table: see text].

Stage III Non–Small-Cell Lung Cancer Treated With Concurrent Chemoradiation Followed or Not by Consolidation Chemotherapy: A Survival Analysis From a Brazilian Multicentric Cohort

Purpose Of newly diagnosed patients with non–small-cell lung cancer (NSCLC), stage III accounts for 30%. Most patients are treated with concurrent chemoradiation therapy, but the addition of consolidation chemotherapy (CC) is debatable. We examined the effect of CC in Brazilian patients with stage III NSCLC treated in routine clinical practice. Methods We retrospectively collected data for patients from five different Brazilian cancer institutions who had stage III NSCLC and who were treated with chemoradiation therapy followed or not by CC. Eligible patients were age 18 years or older and must have been treated with cisplatin-carboplatin plus etoposide, paclitaxel, or vinorelbine, concurrently with thoracic radiation therapy (RT). Patients treated with surgery or neoadjuvant chemotherapy were excluded. The primary end point was overall survival (OS). Associations between CC and clinical variables and demographics were evaluated by using Pearson’s χ2 test. Survival curves were calculated by using the Kaplan-Meier method and were compared using the log-rank test. Univariable and multivariable analysis used a Cox proportional hazards model. Results We collected data from 165 patients. Median age was 60 years. Most patients were male (69.1%), white (77.9%), current or former smokers (93.3%), and had stage IIIB disease (52.7%). Adenocarcinoma was the most common histology (47.9%). Weight loss of more than 5% was observed in 39.1% and Eastern Cooperative Oncology Group performance status of 2 was observed in 14.6%. The only variable associated with CC was T stage (P = .022). We observed no statistically significant difference in OS between patients treated or not with CC (P = .128). A total delivered RT dose ≥ 61 Gy was the only variable independently associated with improved survival (P = .012). Conclusion Brazilian patients with locally advanced NSCLC who were treated with standard treatment achieved OS similar to that reported in randomized trials. CC did not improve OS in patients with stage III NSCLC after concurrent chemoradiation therapy. An RT dose of less than 61 Gy had a negative effect on OS.