Metformin monitoring and change in serum creatinine levels in patients undergoing radiologic procedures involving administration of intravenous contrast media

STUDY OBJECTIVES: To evaluate the prevalence and magnitude of serum creatinine level elevations in patients receiving metformin who underwent radiologic procedures involving administration of intravenous contrast media, and to evaluate the efficacy of an electronic consultation in promoting timely evaluation of renal function after the procedure. DESIGN: Retrospective evaluation. SETTING: Veterans Affairs Medical Center. PATIENTS: Ninety-seven patients receiving metformin who underwent a radiologic procedure involving administration of intravenous contrast media over a 27-month period. MEASUREMENTS AND MAIN RESULTS: Ninety-seven patients underwent a total of 111 radiologic procedures with documented administration of intravenous contrast dye. Average time from procedure to laboratory follow-up, excluding one patient, was 2.62+/-1.56 days. Average serum creatinine levels before and after the procedure were 1.10+/-0.19 and 1.13+/-0.23 mg/dl, respectively (p>0.05). Four patients developed contrast material-associated nephropathy. An additional four patients with borderline serum creatinine levels at baseline (1.4 mg/dl) had a serum creatinine level of 1.5 mg/dl or greater after the procedure. CONCLUSION: Our results indicated that electronic consultations result in timely evaluation of serum creatinine levels in patients receiving metformin who undergo a radiologic procedure involving intravenous contrast material. Also, the study suggests that nearly 4% of patients with diabetes mellitus and normal renal function may develop contrast material-associated nephropathy [corrected] with nonionic contrast material. In addition, about 8% of patients with diabetes treated with metformin (with baseline serum creatinine levels < 1.5 mg/dl) who undergo a procedure with nonionic intravenous contrast material acquire an increased risk (serum creatinine > or = 1.5 mg/dl) of lactic acidosis. These findings support the recommendations of the Food and Drug Administration regarding metformin monitoring in patients undergoing radiologic procedures involving administration of intravenous contrast media.     

Dietary clofibrate inhibits induction of hepatic antioxidant enzymes by chronic estradiol in female ACI rats

Excess production of H₂O₂ has been implicated in oncogenesis. The object of the present study was twofold: first, to determine the influence of chronic estradiol (E₂) on the activities of selected hepatic antioxidant enzymes in female ACI rats, a strain that is highly sensitive to the induction of estrogen dependent mammary tumors; secondly, to evaluate the actions of dietary clofibrate, a peroxisome proliferator, on activities of these enzymes in control and E₂-treated ACI rats. Enzymes selected for study were: NAD(P)H quinone oxidoreductase (NQO1), glutathione S-transferase (GST) and glutathione peroxidase (GPx). Cytosolic catalase (CAT) was also measured as an index of peroxisome proferation in control and E_2- treated animals. E₂ was administered chronically over 6 and 12 week periods from cholesterol pellet implants containing either 1 or 3 mg E₂. Animals were fed AIN-76A diets with or without 0.4% clofibrate over the experimental period. NQO1 and GST but not GPx were induced to varying degrees (NQO1 about 300%, and GST about 45–97%) by chronic E₂-treatment. E₂-induced increases in these activities were completely prevented in rats exposed to dietary clofibrate. Dietary clofibrate also caused slight but significant reductions in baseline activities of NQO1, GST and GPx in control animals. Serum E₂ levels, increased approximately 540% in a dose-dependent manner, and were not altered by dietary clofibrate. It is concluded that chronic E2 treatment markedly induces several important hepatic antioxidant enzymes in female ACI rats, and induction of these activities by E2 is inhibited completely by dietary clofibrate. Both of these actions have the potential to markedly influence the profile of E₂ metabolites exported from the liver to E₂ sensitive extrahepatic tissues and influence the initiation and progression of hormone-dependent tumors.     

"I want more time with my doctor": a quantitative study of time and the consultation

BACKGROUND: Although consultations have increased in length, patients still express dissatisfaction with how much time they spend with their doctor. OBJECTIVES: This study aimed to explore aspects of consultation time and to examine the correlates of patients' desire for more time. METHODS: A quantitative cross-sectional design was used. General practice patients from eight UK practices (n = 294) completed a questionnaire following a consultation regarding their satisfaction with the consultation, their beliefs about how long the consultation lasted (perceived time) and how long they would have preferred it to last (preferred time). The actual consultation length (real time) was recorded by the doctor. RESULTS: The majority of patients underestimated how long the consultation took, and a large minority stated that they would have preferred more time. When controlling for both real time and perceived time, a preference for more time was correlated with a dissatisfaction with the emotional aspects of the consultation and a lower intention to comply with the doctors recommendations. It was unrelated to satisfaction with the information giving and examination components of the consultation. CONCLUSION: Patients' dissatisfaction with consultation length could be managed by making consultations longer. Alternatively, it could also be managed by changing how a given time is spent. In particular, a doctor who listens and tries to understand their patient may make the patient feel more satisfied with the consultation length and subsequently more motivated to follow any recommendations for change.     

Efficacy and other milestones for human papillomavirus vaccine introduction

Last year, the World Health Organization (WHO) convened a gathering of experts, including scientists, national regulatory authorities, industry representatives, epidemiologists and government officials from both developed and developing countries to discuss appropriate endpoint measurements for HPV vaccine efficacy and effectiveness trials. The consultation also considered the regulatory requirements and public health issues that vaccine candidates should address before deployment, particularly in developing countries. This report summarizes the discussions and the conclusions reached over the course of the consultation. The general consensus of the consultation was that it would be desirable to have a globally-agreed, measurable efficacy endpoint for considering deployment of HPV vaccines in public health settings. After hearing from experts about virological and clinical endpoints to be considered, requirements of regulatory authorities of various countries and endpoints used to measure efficacy and effectiveness for another known cancer vaccine (hepatitis B), the experts agreed that ethical and time considerations make it necessary to use a surrogate endpoint, and not invasive cervical cancer, to define efficacy of HPV vaccines. While regulatory authorities of each country ultimately will determine the endpoints required for licensure, the consultation recommended that the endpoint for efficacy in population-based studies be, based on current knowledge, histologically-classified cervical intraepithelial neoplasias (CIN) of moderate or high-grade, as well as cancer. Since persistent infection with the same high-risk type is considered a predictor for moderate or high-grade cervical dysplasias and cancer, they might represent a useful endpoint in future vaccine efficacy studies. Indeed, if vaccines prove to be effective against transient or persistent HPV infections, it is likely that they will protect women against cervical cancer. The consultation recognized that in the context of many developing countries, efficacy alone might not provide enough information for countries to decide whether or not to adopt HPV vaccines as a public health prevention tool against cervical cancer. The consultation unanimously agreed that additional clinical bridging studies as well as studies to clarify local epidemiology should be conducted in certain developing countries to determine the potential impact of vaccination. Such countries should also undertake targeted interventions to ensure acceptability and programmatic feasibility of the vaccination. Recognizing that upon vaccine introduction it will be some years before a reduction in cervical cancer is detectable at the population level, the consultation stressed the importance of maintaining existing cervical screening programmes while such long-term studies are conducted. The following paper explains the background and rationale behind these conclusions and elaborates on specific considerations for vaccine study and introduction in developing countries.     

Predictors of rehospitalization after total weight recovery in adolescents with anorexia nervosa

OBJECTIVE: The current study analyzed the variables related to rehospitalization after total weight recovery in adolescents with anorexia nervosa. METHOD: One hundred and one patients first admitted for inpatient treatment, aged 11-19 years, were followed up for 12 months after discharge. RESULTS: Twenty-five subjects (24.8%) required readmission after complete weight recovery and 76 (75.2%) did not. Duration of disorder, weight loss, body mass index at first admission, and global body image distortion were similar in the two groups. Patients needing readmission had a lower rate of weight gain (p < .001), a lower mean age (p = . 007), a higher mean score on the Eating Attitudes Test (EAT; p = .009), and a higher percentage of hips overestimation (p = .049). In a stepwise logistic regression analysis, these three variables predicted readmission and correctly classified 77.6% of patients. Taken as discrete variables, age younger than 15 years old, EAT score above 55, and a rate of weight gain lower than 150 grams per day were associated with a higher percentage of readmissions. DISCUSSION: The variables most clearly related to readmission were young age, abnormal eating attitudes, and a low rate of weight gain.     

Geographical variations in heart deaths and diabetes: effect of climate and a possible relationship to magnesium

BACKGROUND: Geographical variations in deaths from heart disease and the prevalence of diabetes occur in the United States. METHODS: These geographical variations, by state, were compared to the tertiles of the Z-score (Z-climate) obtained from the mean annual temperature and precipitation, by state, and to the tertiles of the Z-score (Z-environment) obtained from six environmental factors, by state, in monovariant analyses of variance. RESULTS: Both Z-scores were significantly related to male heart deaths (Z-climate: p = 0.000009; Z-environment: p = 0.000043) with Z-climate being the most significant. Both Z-scores were significantly related to the 1998 prevalence of diabetes (Z-climate: p = 0.00018; Z-environment: p = 0.0059) with the climate again being the most significant. CONCLUSIONS: Increased temperature can increase magnesium sweat losses, which may not be compensated by diet or water intake. Climate relationships to these diseases need further investigation.     

Formulation, characterization, and in vitro evaluation of silymarin-loaded lipid microspheres

The objective of our study was to incorporate and evaluate Silymarin, a chemically defined natural hepatoprotective agent, in lipid microstructured systems. Various constituents of lipid microspheres—namely, internal oily core; surfactant such as soyabean lecithin; and cosurfactants such as span 20, tween 20, tween 80, and propylene glycol—were tried in different concentrations to optimize the final formulation characteristics such as globule size range, structural integrity, sustainability, and percent drug-holding capacity. The final formulation (formulation A) was characterized with respect to size and morphology using transmission electron microscopy and laser diffraction technique. The enhanced mean percent release of 56.70 ± 2.03% was observed in 36 hr from silymarin-loaded lipid microspheres (formulation A), as compared to 18.67 ± 0.192% with silymarin solution (formulation B). Thus, a stable delivery system having synergistic hepatoprotective effect of silymarin and soyabean lecithin could successively be produced for passive targeting to the liver.     

Reduction of in vivo lung metastases by dinuclear ruthenium complexes is coupled to inhibition of in vitro tumour invasion

Mononuclear ruthenium-dmso compounds showed interesting antimetastatic properties on experimental models of solid tumours. In line with the interesting results with multinuclear platinum complexes, which proved to overcome cisplatin resistance, we thought it worthwhile to test the pharmacological properties of some dinuclear ruthenium complexes to ascertain the possible advantages due to the introduction of a second metal centre over NAMI-A and its mononuclear analogues. These compounds belong to the general formula X2[[RuCl4(dmso-S)]2(mu-L)] or [X][[RuCl4(dmso-S)](mu-L)[RuCl3(dmso-S)(dmso-O)]] where L is a nitrogen donor ligand (pyrazine; pyrimidine; 4,4'-bipyridine; 1,2-bis(4-pyridyl)ethane; 1,2-bis(4-pyridyl) ethylene; 1,3-bis(4-pyridyl)propane) and X a counterion. We focused on parameters related to metastatic ability such as gelatinase activity, detected by zymography, and invasive potential, measured by means of a transwell chamber. These activities were correlated to the ability to inhibit tumour metastases in vivo. All dinuclear complexes, except compound D8 ([NH4]2[[RuCl4(dmso-S)]2(mu-pyz]), decrease the number of tumour cells that cross a matrigel barrier, and inhibit MMP-9 gelatinolytic activity at concentrations lower than that of NAMI-A and of other mononuclear ruthenium complexes. In vivo compounds D5 (Na2[[RuCl4(dmso-S)]2(mu-ethylbipy)]) and D7 ([NH4][[RuCl4(dmso-S)](mu-pyz)[RuCl3(dmso-S) (dmso-O)]]) show anti-metastasis activity, at two dose levels, with mild or null effect on primary tumour growth; compound D8 is the weakest active. All compounds tend to accumulate in liver and kidneys, rather than in tumour and lungs. However, compound D5, the most active in vitro on invasion and gelatinases and active in vivo on metastasis, is better concentrated in the lungs than compound D8 which is less active or inactive in vitro and in vivo. Histological analysis show liver, as well as kidney toxicities that limit in vivo activity. These data thus suggest dinuclear ruthenium complexes as promising anti-invasive agents for cancer treatment.     

Enteropathogenic Escherichia coli: stimulating neutrophil migration across a cultured intestinal epithelium without altering transepithelial conductance

INTRODUCTION: Migration of neutrophils across the intestinal epithelium is the hallmark of inflammatory conditions of the bowel. In cultured intestinal epithelial monolayer models, neutrophils can be induced to migrate along a chemotactic gradient such as n-formyl-methionyl-leucyl-phenylalanine (fMLP). Physical passage of the neutrophils across the epithelium could disrupt the tight-junctions, possibly leading to a large increase in the transepithelial conductance (G(t)). The goal of this study is to determine whether transepithelial migration of neutrophils induced by enteropathogenic (EPEC) causes changes in G(t) comparable with those seen with fMLP. METHODS: The apical side of T84 monolayers were rapidly infected with EPEC E2348/69 or exposed to 1 microM fMLP. A third group of monolayers exposed to neither EPEC nor fMLP served as control. Indium-labeled neutrophils were added to the serosal side of monolayers grown on a cell culture insert membrane (12 microm pores). G(t) was measured at fixed intervals up to 4 hours. After a 150-minute incubation, radioactivity of the neutrophils that migrated to the apical side was assayed and the number of migrating neutrophils was calculated. RESULTS: At 150 minutes, EPEC induced similar neutrophil chemotactic capability compared to fMLP (231 +/- 34.10(3) and 193 +/- 48.10(3), respectively, n = 13, P > 0.05). However, EPEC-induced neutrophil migration was not associated with significant increase in G(t), 1.13 +/- 0.16 fold of baseline G(t), in distinction with fMLP groups, 13.3 +/- 0.48 fold, n = 7 (P< 0.05). G(t) changes with EPEC were seen after 4 hours of infection, but were not different in the presence or absence of neutrophil migration (1.37 +/- 0.12 fold and 1.42 +/- 0.17 fold of baseline G(t), respectively). CONCLUSIONS: The results indicate that EPEC-induced neutrophil migration can occur without significant disruption of barrier function. In addition, the chemo-attractant recruiting neutrophils during EPEC infection is unlikely to be fMLP; and, the G(t) increase seen with fMLP-driven recruitment may indicate a discretionary compromise of barrier function during neutrophil migration.