When can a drug be considered synergic with radiotherapy?

The combination of radiotherapy with chemotherapy is now considered the standard treatment for a number of tumors. However frequently, within radiotherapy as well as medical oncology, considerable skepticism has been expressed about the real impact of this therapeutic modality, in spite of the improvement in terms of outcome seen in numerous trials concerning head and neck, lung, esophageal cancer and tumors of the anal canal, the uterine cervix and pancreas. Considering the evident clinical advantages achieved in the last 2-3 decades, a close collaboration between basic, preclinical and clinical research is desirable to further optimize the outcomes based on the present radiobiological knowledge. As for the preclinical evaluation different methods should be concomitantly used to analyze the pharmacokinetics and mechanism of action; the method of tumor growth delay should be used especially in neoadjuvant clinical settings; the method of tumor control should be used when chemoradiation is aimed at the local cure of the patient independently of subsequent surgery.     

Endoscopic dilation of gastroesophageal anastomosis stricture after gastric bypass

Background: The management of strictures after gastric bypass procedure using balloon dilation is described. Methods: A retrospective review of all dilations performed is presented. Balloon dilators were used, and all strictures were dilated initially up to 12 to 15 mm for 1 min. Results: The review included 24 patients with a mean age of 42.8 years and a mean body mass index of 49.6. All the patients except one were women. In terms of procedure, 67% required one dilation and 30% required two. In the first 3 months after surgery, 21 patients developed the stricture. Three patients (13%) had leaks. There was no endoscopic appearance suggesting the need for a repeated procedure. All the dilations were successful, and weight loss compared well with that in the rest of the patients. Conclusions: A successful technique for the treatment of anastomotic strictures after gastric bypass is presented. Most of the patients required one dilation. Most strictures appeared during the first 3 months after surgery. Female gender and leak may be high risk factors for the development of stricture.     

Prognostic value of clinical variables at presentation in patients with non-ST-segment elevation acute coronary syndromes: results of the Proyecto de Estudio del Pronóstico de la Angina (PEPA)

Patients with suspected non-ST-segment elevation acute coronary syndromes (NSTEACS) constitute a heterogeneous population with variable outcomes. Risk stratification in this population of patients is difficult due to the complexity in patient risk profile. We conducted this study to characterize the value of clinical and electrocardiographic variables for risk stratification in an unselected population of consecutive patients with NSTEACS on admission. Thirty-five clinical and electrocardiographic variables at presentation in the emergency room of 18 hospitals were prospectively analyzed in 4,115 patients with NSTEACS and related with the outcomes at 90 days. We also developed a risk score using the variables found to be independent predictors of ischemic events to facilitate risk stratification. Cardiovascular mortality was 4.3% and the rate for the outcome of either cardiovascular death or nonfatal myocardial infarction was 6.9%. The only independent predictors of mortality were age, diabetes, peripheral vascular disease, postinfarction angina, Killip class > or = 2, ST-segment depression, and elevation of cardiac markers. A risk profile using the variables found to be independent predictors of events was calculated for cardiovascular mortality and for the combination of either death or nonfatal myocardial infarction. Event rates increased significantly in all subgroups of patients based on the number of independent risk factors as the risk score increased. Using these factors, 90-day mortality ranged from as low as 0.4% in patients with no risk factors to 21.1% for those with more than 4 risk factors. In conclusion, simple clinical and electrocardiographic data obtained at hospital admission allow an accurate risk stratification of patients with NSTEACS. In the PEPA registry, simple variables easy to obtain at admission appear to be a valuable tool in discerning between patients at very low and very high risk according to the cluster of factors for each patient. The risk score developed was obtained from an unselected population, representative of the whole spectrum of patients with NSTEACS, allowing identification of patients at different risks for adverse outcomes, and, therefore, permitting optimization of therapy.     

Ultrasonic backscatter and diastolic function in hypertensive patients

This study was designed to assess whether ultrasonic reflectivity, evaluated by a real-time integrated backscatter analysis, was related to the severity of diastolic dysfunction, as studied by Doppler echocardiography in patients with essential hypertension. One hundred nine subjects were included in the study. Diastolic function was assessed by mitral-inflow Doppler ultrasound recordings. Backscatter cyclic variation and maximal intensity were measured in 6 regions throughout the left ventricle. The subjects were classified in 5 groups according to blood pressure and diastolic function: 29 normotensives with normal diastolic function (group 1), 18 hypertensives with normal diastolic function (group 2), 47 hypertensives with a delayed relaxation pattern (group 3), 11 hypertensives with a pseudonormal filling pattern (group 4), and 4 hypertensives with a restrictive filling pattern (group 5). The highest cyclic variation was found in groups 1 and 2, the lowest in groups 4 and 5 (5.7+/-0.2 dB in group 1 and 5.7+/-0.2 dB in group 2 versus 2.9+/-0.3 dB in group 4 and 2.1+/-0.4 dB in group 5; P<0.001), with intermediate values in group 3 (5.2+/-0.2 dB). Cyclic variation was inversely correlated with left ventricular chamber stiffness (P<0.05) and directly correlated with midwall fractional shortening (P<0.02) in all hypertensives. No differences in maximal intensity were found among the 5 groups of subjects. These results show an association between diminished cyclic variation of backscatter and deterioration of diastolic function in hypertensive patients. Thus, alterations in this parameter may be useful for the assessment of diastolic dysfunction in hypertension.     

Ultrasonic backscatter and serum marker of cardiac fibrosis in hypertensives

Elevations in the serum concentration of the carboxy-terminal propeptide of procollagen type I (PIP) >127 microg/L have been found to predict severe myocardial fibrosis in hypertensive patients. This study was designed to assess whether ultrasonic reflectivity, evaluated by a real-time integrated backscatter analysis, was related to the severity of myocardial fibrosis as estimated by serum PIP. Thirty-four subjects were included in the study. Serum PIP was measured by specific radio immunoanalysis. Backscatter cyclic variation and maximal intensity were measured in 6 regions throughout the left ventricle. The subjects were divided into 3 groups: 14 normotensives with PIP <127 microg/L (group 1), 12 hypertensives with PIP <127 microg/L (group 2), and 8 hypertensives with PIP >127 microg/L (group 3). The highest cyclic variation was found in group 1 and the lowest in group 3 (5.78+/-0.25 versus 4.70+/-0.33 dB, P<0.05), with intermediate values in group 2 (5.10+/-0.27 dB). No differences in maximal intensity were found among the 3 groups of subjects. Using receiver operating characteristics curves, we observed that a cutoff of 2.90 dB for cyclic variation measured in the apex provided 75% sensitivity and 63% specificity for predicting PIP >127 microg/L in hypertensives, with a relative risk of 2.50 (95% CI, 0.72 to 34.70). These results show an association between diminished cyclic variation of backscatter and increased serum concentration of PIP in hypertension. Thus, the combination of these 2 parameters may be useful for the diagnosis of severe myocardial fibrosis associated with hypertension.     

Interaction between the C(-344)T polymorphism of CYP11B2 and age in the regulation of blood pressure and plasma aldosterone levels: cross-sectional and longitudinal findings of the Olivetti Prospective Heart Study

OBJECTIVE: To study the interaction between the C(-344)T polymorphism and known determinants (age, body mass and dietary sodium) of blood pressure and plasma aldosterone. DESIGN: Cross-sectional and longitudinal (1980-1995) survey of male workers in southern Italy. SETTING: Medical centre of the Olivetti factories. PARTICIPANTS: In 1995, the C(-344)T polymorphism was characterized in 811 untreated men. A subgroup of 280 participants already seen in 1980 was the object of longitudinal analysis. MAIN OUTCOME MEASURES: Blood pressure, demographic, anthropometric and biochemical variables (serum and urinary electrolytes and plasma aldosterone) and frequency of the C(-344)T polymorphism. RESULTS: In the whole population, there was no difference among genotypes for any of the variables examined. However, multiple regression showed a significant interaction between age (but not body mass or sodium intake) and genotype with regard to systolic (P = 0.03) and diastolic ( P= 0.02) pressure variability independently of covariates. Diastolic pressure increased linearly with age in carriers of the T allele (TT, P<0.001 and TC, P= 0.005), but not in CC homozygotes ( P= 0.848). In T carriers - but not in CC homozygotes - blood pressure and serum potassium increased and plasma aldosterone and serum sodium decreased across quintiles of age (P< 0.001 for all trends). In the longitudinal study, diastolic pressure increased significantly over time only in T carriers (TC+TT: +2.6 +/- 0.6, versus CC: -0.4 +/- 1.5 mmHg, P= 0.04). CONCLUSION: Inter-individual variation of blood pressure and plasma aldosterone is affected by the interaction of C(-344)T polymorphism and ageing, thus supporting a role for this variant in mechanisms affecting blood pressure regulation.     

Biomonitoring of Multiple Mycotoxins in Urine by GC–MS/MS: A Pilot Study on Patients with Esophageal Cancer in Golestan Province,Northeastern Iran

A pilot study to investigate the occurrence of 10 mycotoxins (deoxynivalenol, DON; 3-acetyldeoxynivalenol, 3-ADON; 15-acetyldeoxynivalenol, 15-ADON; fusarenon-X, FUS-X; diacetoxyscirpenol, DAS; nivalenol, NIV; neosolaniol, NEO; zearalenone, ZON; zearalanone, ZAN; T-2 toxin, T-2; and HT-2 toxin, HT-2) in esophageal cancer patients was performed with the urinary biomarkers approach in Golestan, Iran. Urine multimycotoxin analysis was performed by dispersive liquid–liquid microextraction and gas chromatography–tandem mass spectrometry (GC–MS/MS) analysis, and values were normalized with urinary creatinine (μg/g). Four mycotoxins, namely NEO (40%), HT-2 (17.6%), DON (10%), and HT-2 (5.8%), were detected in the analyzed urine samples. DON was only detected in the control group (5.09 μg/g creatinine), while T-2 (44.70 μg/g creatinine) was only present in the esophageal cancer group. NEO and HT-2 were quantified in both control and case groups, showing average of positive samples of 9.09 and 10.45 μg/g creatinine for NEO and 16.81 and 29.09 μg/g creatinine for HT-2, respectively. Mycotoxin co-occurrence was observed in three samples as binary (NEO/HT-2 and T-2/HT-2) and ternary (DON/NEO/HT-2) combinations, reaching total concentrations of 44.58, 79.13, and 30.04 µg/g creatinine, respectively. Further investigations are needed to explore a causal association between mycotoxin contamination and esophageal cancer. For this pilot study in Golestan, the low sample size was a very limiting factor.