No benefits from combining chloroquine with artesunate for three days for treatment of Plasmodium falciparum in Guinea-Bissau

The use of a combination of chloroquine and artesunate has been suggested for treatment of malaria in Africa. We used concomitant as well as sequential medication with these 2 drugs in relation to each drug separately for children infected with Plasmodium falciparum in Guinea-Bissau from March 2000 to November 2001. By block-randomization, 474 children with symptomatic malaria were divided into 4 groups and given either a total of 8 mg artesunate per kg bodyweight for 3 d, a total of 25 mg chloroquine base per kg bodyweight for 3 d, both drugs concomitantly for 3 d, or both drugs in sequence. All children were followed weekly for 5 weeks. On day 28, parasites had been detected in 40% of the children who were treated with artesunate only compared with 21% treated with chloroquine, 20% treated with artesunate in combination with chloroquine, and 16% treated with artesunate and chloroquine in sequence; on day 35 the corresponding percentages were 48%, 29%, 27%, and 24%, respectively. The outcome of the combination of chloroquine and artesunate in the doses studied was similar to the outcome of chloroquine monotherapy regardless of whether the 2 drugs are given concomitantly (relative risk [RR] = 0.93, 95% CI 0.56-1.53, P = 0.76) or in sequence (RR = 0.78, 95% CI 0.47-1.28, P = 0.32). Thus, neither an antagonistic, an additive, or a synergistic effect of the 2 drugs was indicated.     

Vitamin D and vitamin D analogs as cancer chemopreventive agents

Epidemiologic studies have associated vitamin D, attained through nutrition and sun exposure, with reduced cancer risk. Although dose-limiting hypercalcemia has limited the use of natural vitamin D in cancer prevention, several promising new synthetic vitamin D analogs (deltanoids) are under development. Examples are KH-1060, EB-1089, 1alpha-hydroxyvitamin D5, vitamin D2, and QW-1624F2-2. Clinical targets for deltanoids include colon, prostate, and breast. Studies to elucidate the molecular mechanisms underlying the observed efficacy of deltanoids are ongoing. The vitamin D receptor, a steroid/thyroid receptor superfamily member, appears to control most deltanoid effects on proliferation, apoptosis, differentiation, and angiogenesis.     

The bioconcentration and metabolism of chlorpyrifos by the eastern oyster,Crassostrea virginica

Eastern oysters (Crassostrea virginica) were exposed to [14C]chlorpyrifos (O,O-diethyl-O-[3,5,6-trichloro-2-pyridyl] phosphorothioate) at an average measured seawater concentration of 0.6 microg/L under flow-through conditions for 28 d. The compound O,O-diethyl-O-(3,5-dichloro-6-methylthio-2-pyridyl)phosphorothioate (DMP) was extracted and identified as the single metabolite observed, and this metabolite constituted the majority of the total [14C] activity in the oyster at all sampling times. Once oysters were exposed to clean water, both chlorpyrifos and DMP residues cleared rapidly from whole oysters, with elimination half-lives of <3 d. A simple two-compartment uptake/elimination model was adequate to describe total [14C] activity in whole oysters, edible tissue, and oyster liquor. The average bioconcentration factors (BCFs) for total [14C] activity in whole oysters, edible tissue, and oyster liquor were 565, 1,400, and 35 ml/g, respectively. The parent [14C]chlorpyrifos accumulated to a peak residue concentration of 135 microg/kg in whole oyster tissue, representing an empirical [14C]chlorpyrifos BCF value in the oyster of approximately 225 ml/ g; the BCF value for [14C]chlorpyrifos was lower than the BCF for total [14C] activity in whole oysters and edible tissue because of extensive metabolism to DMP and oyster elimination processes.     

Risk factors for femicide in abusive relationships: results from a multisite case control study

OBJECTIVES: This 11-city study sought to identify risk factors for femicide in abusive relationships. METHODS: Proxies of 220 intimate partner femicide victims identified from police or medical examiner records were interviewed, along with 343 abused control women. RESULTS: Preincident risk factors associated in multivariate analyses with increased risk of intimate partner femicide included perpetrator's access to a gun and previous threat with a weapon, perpetrator's stepchild in the home, and estrangement, especially from a controlling partner. Never living together and prior domestic violence arrest were associated with lowered risks. Significant incident factors included the victim having left for another partner and the perpetrator's use of a gun. Other significant bivariate-level risks included stalking, forced sex, and abuse during pregnancy. CONCLUSIONS: There are identifiable risk factors for intimate partner femicides.     

Clinical management where medicine meets management. Get out, stay out

The project uses techniques common in substance misuse treatment to help prevent mental illness relapses. Cognitive behavioural training helps patients and carers better manage their care. Audit shows a reduction in admissions and length of stay.     

A template for change and response to work hour restrictions

Surgical program directors are seeking how to best meet the work hour restrictions recently mandated by the American College of Graduate Medical Education. Implementation of an 80-hour work week forces major change to graduate medical education, especially surgical education. Creative restructuring of surgical training is necessary to ensure compliance. Developing an innovative solution to meet these requirements must consider programmatic needs, requiring commitment to a change process. The Department of Surgery at Eastern Virginia Medical School experienced a 5-month strategic planning process that generated the Mendoza plan. This plan uses an every third night call model and a night float model to meet site-specific needs. The specifics of the Mendoza plan protect the cornerstone of surgical education, which is continuity of patient care and resident education. The Mendoza plan, and the process leading to its development, may provide insightful information for other surgical residency programs planning to meet work hour guidelines.     

Can a practicing surgeon detect early lymphedema reliably?

BACKGROUND: Lymphedema may be identified by simpler circumference changes as compared with changes in limb volume. METHODS: Ninety breast cancer patients were prospectively enrolled in an academic trial, and seven upper extremity circumferences were measured quarterly for 3 years. A 10% volume increase or greater than 1 cm increase in arm circumference identified lymphedema with verification by a lymphedema specialist. Sensitivity and specificity of several different criteria for detecting lymphedema were compared using the academic trial as the standard. RESULTS: Thirty-nine cases of lymphedema were identified by the academic trial. Using a 10% increase in circumference at two sites as the criterion, half the lymphedema cases were detected (sensitivity 37%). When using a 10% increase in circumference at any site, 74.4% of cases were detected (sensitivity 49%). Detection by a 5% increase in circumference at any site was 91% sensitive. CONCLUSIONS: An increase of 5% in circumference measurements identified the most potential lymphedema cases compared with an academic trial.     

Inhibition of mitochondrial Na+-Ca2+ exchanger increases mitochondrial metabolism and potentiates glucose-stimulated insulin secretion in rat pancreatic islets

The mitochondrial Na(+)-Ca(2+) exchanger (mNCE) mediates efflux of Ca(2+) from mitochondria in exchange for influx of Na(+). We show that inhibition of the mNCE enhances mitochondrial oxidative metabolism and increases glucose-stimulated insulin secretion in rat islets and INS-1 cells. The benzothiazepine CGP37157 inhibited mNCE activity in INS-1 cells (50% inhibition at IC(50) = 1.5 micro mol/l) and increased the glucose-induced rise in mitochondrial Ca(2+) ([Ca(2+)](m)) 2.1 times. Cellular ATP content was increased by 13% in INS-1 cells and by 49% in rat islets by CGP37157 (1 micro mol/l). Krebs cycle flux was also stimulated by CGP37157 when glucose was present. Insulin secretion was increased in a glucose-dependent manner by CGP37157 in both INS-1 cells and islets. In islets, CGP37157 increased insulin secretion dose dependently (half-maximal efficacy at EC(50) = 0.06 micro mol/l) at 8 mmol/l glucose and shifted the glucose dose response curve to the left. In perifused islets, mNCE inhibition had no effect on insulin secretion at 2.8 mmol/l glucose but increased insulin secretion by 46% at 11 mmol/l glucose. The effects of CGP37157 could not be attributed to interactions with the plasma membrane sodium calcium exchanger, L-type calcium channels, ATP-sensitive K(+) channels, or [Ca(2+)](m) uniporter. In hyperglycemic clamp studies of Wistar rats, CGP37157 increased plasma insulin and C-peptide levels only during the hyperglycemic phase of the study. These results illustrate the potential utility of agents that affect mitochondrial metabolism as novel insulin secretagogues.     

The effect of the bovine hemoglobin oxygen therapeutic HBOC-201 on human neutrophil activation in vitro

BACKGROUND: We previously demonstrated that HBOC-201 is an efficient resuscitation fluid. However, little is known about its immunomodulatory effects. The goal of this study was to investigate human neutrophil activation after exposure to HBOC-201 and other low-volume resuscitation fluids. METHODS: Whole blood from 10 healthy volunteers was serially diluted with HBOC-201, 7.5% hypertonic saline (HTS), 7.5% hypertonic saline-6% dextran 70 (HSD), Hextend, or PentaLyte. After an incubation period, samples were analyzed for oxidative burst and CD11b expression using flow cytometry. RESULTS: Increases in both CD11b and oxidative burst activity were noted in samples diluted with HBOC-201, Hextend, PentaLyte, and lactated Ringer's solution. Samples maximally diluted with HBOC-201 demonstrated increased CD11b expression when compared with lactated Ringer's solution and Hextend (196.11% vs. 22.68% and 33.97%; p = 0.018 and p = 0.033). CONCLUSION: Although differences were noted only at the highest dilutions, further studies investigating the effects of HBOC-201 are warranted.