Iron Fortification of Flours in Venezuela

This paper reviews a conference about the impact of the iron fortification program in Venezuela; it was presented at the Pan American Health Organization regional technical meeting: "Iron Fortification: Where Are We in Terms of Iron Compounds," held in Washington January 10–12, 2001. Some of the data presented were published in the American Journal of Clinical Nutrition , including stimulating results about the impact of fortification of precooked corn and white wheat flours, as well as the prevalence of anemia and iron deficiency in the Venezuelan population. This article reports results from three surveys carried out in 1997, 1998, and 1999 on the same age and socioeconomic group that had been evaluated in 1990, 1992, and 1994. This article also shows the impact of iron fortification programs and the influence of other factors on the prevalence of iron deficiency and anemia during the last 7 years.     

Effects of verapamil on the pharmacokinetics and metabolism of epirubicin

Summary Experimental data suggest that multidrug resistance in cancer may be overcome by using an increased dose of anticancer agent(s) in combination with a resistance-modifying agent (RMA). We studied the pharmacokinetics and metabolism of both epirubicin (EPI) and verapamil (VPL) to explore the possible pharmacokinetic interactions between these two drugs. Ten patients with advanced breast cancer were given EPI (40 mg/m² in a daily i.v. bolus for 3 consecutive days), and five of them also received VPL (4×120 mg/daily p.o. for 4 consecutive days). The data indicated a significant interaction between these two drugs that affected their metabolism. The areas under the concentration-time curves (AUC) obtained for epirubicin glucuronide, epirubicinol glucuronide, and both of the 7-deoxy-aglycones were higher in the EPI+VPL group as compared with the EPI group. The AUC, terminal half-life, mean residence time, volume of distribution at steady state, and plasma clearance of EPI alone as compared with EPI+VPL did not differ significantly. These results suggest either an induction of enzymes necessary for drug metabolism or an increase in the liver blood flow, resulting in an enhanced generation of metabolites with time or in an inhibition of excretion processes. Comparisons of the AUC values obtained for EPI and its metabolites after the first, second, and third injections of EPI revealed a cumulative effect for the metabolites that was more pronounced in the EPI+VPL group, being significant (P<0.05) for epirubicin glucuronide in both treatment groups and for epirubicinol glucuronide in the EPI+VPL group. Maximal concentrations of VPL and nor-VPL reached 705±473 and 308±122 ng/ml, respectively, with the steady-state concentrations being 265±42 ng/ml for VPL and 180±12 ng/ml for nor-VPL.This study was supported by the Erich und Gertrud Roggenbuck-Stiftung zur Förderung der Krebsforschung (Hamburg). The anthracycline metabolites were kindly provided by Dr. A. Suarato (Farmitalia, Milano, Italy); nor verapamil was provided by Dr. Traugott (Knoll, Ludwigshafen, Germany)     

Angiotensin Converting Enzyme Inhibitors: Animal Experiments Suggest a New Pharmacological Treatment for Alcohol Abuse in Humans

The prevalence of heavy alcohol consumption is a major problem of increasing proportions throughout the world. Although alcohol sensitizing drugs and more recently serotonin uptake inhibitors are drug interventions with some following, their long term beneficial consequences have yet to be demonstrated. In recent years, we have demonstrated that manipulating activity in the renin-angiotensin system will dramatically alter voluntary alcohol consumption in rats. Based on these findings, the present study evaluated the ability of a class of drugs known as the angiotensin converting enzyme inhibitors to reduce voluntary alcohol drinking in laboratory animals. These drugs prevent the conversion of angiotensin I to angiotensin II. They have been licensed for use in Europe and North America and are indicated in the treatment of hypertension. Our experiments showed that both captopril (Capoten, Squibb) and enalapril (Vasotec, Merck Sharpe & Dohme) can reduce alcohol drinking in both normotensive and hypertensive animals regardless of whether the pattern of intake is in a bout or of a less exaggerated nature. Furthermore, this change in alcohol intake can occur without concomitant changes in blood pressure, plasma renin activity, overall fluid balance, or the distribution and metabolism of alcohol. Taken together these findings suggest that the angiotensin converting enzyme inhibitors should be evaluated in a clinical setting for they may prove to be a useful new treatment or treatment adjunct for alcohol abuse in humans.     

Pulmonary valve insertion during reoperation for tetralogy of Fallot

Our experience with pulmonary valve insertion during reoperation for residual lesions after initial open repair of tetralogy of Fallot in 15 patients is reported. Preoperatively, 14 patients were in moderate to severe congestive heart failure, and all 15 had decreased right ventricular (RV) function at cardiac catheterization. All 15 patients had pulmonary insufficiency but not as an isolated finding. The most common residual lesions encountered were ventricular septal defect in 9, tricuspid insufficiency in 11, and peripheral pulmonary arterial stenosis in 6. Tissue valves were inserted in all patients. Mean peak RV-left ventricular pressure ratio measured in the operating room decreased from 0.61 +/- 0.10 (+/- the standard deviation) to 0.47 +/- 0.17 (p less than 0.05). There were no operative deaths. At follow-up (mean, 33 months), all but 1 patient were in New York Heart Association Class I or II. Pulmonary valve insertion should be considered during reoperation for tetralogy of Fallot when pulmonary insufficiency and RV failure are present.     

APACHE II score and abdominal sepsis. A prospective study

Therapeutic trials for intra-abdominal sepsis require pretreatment stratification; physiologic scoring has been recently proposed for this purpose. We have prospectively tested the validity of one such scoring system, namely, the Acute Physiology and Chronic Health Evaluation (APACHE II). As part of a larger database, we correlated APACHE II scores with mortality in 100 patients hospitalized for generalized peritonitis or abdominal abscess. Use of steroids was recorded because of our suspicion that steroids increase mortality but blunt the physiologic response to sepsis. Thirty-one patients died, including 12 of 19 patients receiving steroids. Stepwise discriminant analysis revealed that the APACHE II score and steroid use were each independently associated with the rate of mortality. We report a prospective validation of pretreatment APACHE II scoring in abdominal sepsis. Steroid use is an independent risk factor.