A phase III clinical trial of alpha, beta-arteether injection 150 mg/ml in patients of P falciparum malaria

The aim of study was to evaluate efficacy and safety of alpha, beta-arteether injection 150 mg/ml by performing a phase III, multicentre, open label, and single treatment study in patients with P falciparum malaria. A total of 145 patients with P falciparum malaria were screened to achieve patient pool of 101 subjects based on inclusion and exclusion criteria, from which 100 patients completed the study successfully. Mean cure rate was calculated as primary efficacy parameter, while mean parasite clearance time (hours) and mean fever clearance time (hours) were calculated as secondary efficacy parameters, to evaluate efficacy of alpha, beta-arteether injection 150 mg/ml. Safety evaluation was measured by observing and monitoring adverse events, clinical examination, assessment of vitals and haematology laboratory parameters. Statistical analysis was performed with 5% level of significance. Mean cure rate, mean parasite clearance time (hours) and mean fever clearance time (hours) were 99.01%, 24.72 +/- 0.41 hours and 46.86 +/- 0.97 hours respectively. A total of 6 patients were observed with pain at injection site out of 101 enrolled patients. There were no clinically significant vitals and haematology changes. There were no abnormal posttreatment values observed. The study confirmed that alpha, gamma-arteether injection 150 mg/ml is highly effective in treatment of P falciparum malaria.     

Circulating 25-hydroxyvitamin D concentrations are correlated with cardiometabolic risk among American black and white adolescents living in a year-round sunny climate

OBJECTIVE

Low vitamin D status is common among healthy black and white adolescents residing at southern U.S. latitudes with a year-round sunny climate. Thus we aimed to study the relationships between circulating 25-hydroxyvitamin D [25(OH)D] and cardiometabolic risk factors in this population.

RESEARCH DESIGN AND METHODS

25(OH)D concentrations were measured with liquid chromatography tandem mass spectroscopy in 701 girls and boys (14–18 years old, 54% blacks, 49% females). Cardiometabolic risk was indexed by adipokines, inflammatory markers, fasting glucose, homeostatic model assessment-insulin resistance (HOMA-IR), lipid profile, and blood pressure (BP).

RESULTS

Controlling for age, sex, race, sexual maturation, season, physical activity, and percent body fat, 25(OH)D concentrations were significantly correlated with adiponectin (r = 0.06, P = 0.05), leptin (r = −0.32, P < 0.01), fibrinogen (r = −0.05, P = 0.03), glucose (r = −0.16, P = 0.02), HOMA-IR (r = −0.17, P < 0.01), HDL cholesterol (r = 0.14, P = 0.02), systolic BP (r = −0.10, P = 0.02), and diastolic BP (r = −0.21, P < 0.01). When 25(OH)D concentrations were stratified into increasing tertiles, there were significant linear upward trends for adiponectin (P = 0.01) and HDL cholesterol (P = 0.04), but significant linear down trends for glucose (P < 0.01), HOMA-IR (P < 0.01), and systolic BP (P < 0.01), after adjusting for the above covariates.

CONCLUSIONS

Circulating 25(OH)D concentrations are associated with various adverse cardiometabolic risk factors, independent of adiposity. Clinical trials addressing the effects of vitamin D supplementation on cardiometabolic risk are warranted in adolescents irrespective of their geographical regions.Low vitamin D status as indicated by circulating 25-hydroxyvitamin D [25(OH)D] is linked to cardiometabolic risk factors such as inflammation, insulin resistance, abnormal lipid profile, and high blood pressure (BP) in adults (1–4). However, few studies have evaluated the relationship between 25(OH)D concentrations and these cardiometabolic risk factors in children and adolescents. In this regard, there are at least three studies using the nationally representative sample of children and adolescents from the National Health and Nutrition Examination Survey (NHANES) (5–7). First, in 2009, Reis et al. (5) conducted a cross-sectional analysis of 3,577 fasting nondiabetic youth aged 12 to 19 years (65% whites, 14% blacks, and 11% Mexicans) who participated in the 2001–2004 NHANES. After adjustment for age, sex, race, BMI, and physical activity by self-report, 25(OH)D concentrations were found to be inversely associated with systolic BP and plasma glucose concentrations. Second, Kumar et al. (6) demonstrated that in 6,257 children and adolescents aged 1 to 21 years from the 2001–2004 NHANES sample, vitamin D deficiency (<15 ng/mL) compared with 25(OH)D sufficiency (>30 ng/mL) was associated with increased systolic BP, and lower HDL cholesterol, after multivariable adjustment. Third, in 2011, using the newly updated serum 25(OH)D data released by the National Center for Health Statistics, Ganji et al. (7) studied 5,867 adolescents aged 12–19 years from three cycles of NHANES (2001 to 2002, 2003 to 2004, and 2005 to 2006). They found that serum 25(OH)D was related to homeostatic model assessment–insulin resistance index (HOMA-IR), systolic BP, and HDL cholesterol, but not to C-reactive protein (CRP).Although the aforementioned NHANES studies in children and adolescents have been valuable, there are still questions unaddressed. First, data collection from the south U.S. regions by the study design were limited to the winter season (5–7). Second, most of the data were collected in the geographical regions with relatively high latitudes, such that it is unclear whether low vitamin D status affects cardiometabolic factors in adolescents residing in low latitudes (5–7). Finally, CRP has been the only inflammatory factor used in the analyses in relation to 25(OH)D (7). Other inflammatory factors and, perhaps more noteworthy, adipokines are not yet included.The southeastern region of the U.S. has a sunny climate and relative proximity to the equator, which should favor plentiful cutaneous production of vitamin D. However, we have recently reported that low vitamin D status is common in black and white adolescents (14–18 years of age) residing in Augusta, GA (33° North latitude) (8). Furthermore, plasma 25(OH)D concentrations were consistently and inversely related to the degree of adiposity. Thus the current study aimed to evaluate whether 25(OH)D concentrations were correlated with cardiometabolic risk factors including adipokines, inflammatory markers, fasting glucose, HOMA-IR, lipid profile, and BP independent of adiposity in this adolescent population.     

Abdominal cocoon: a unique presentation in an immunodeficient infant

Abdominal cocoon is a rare disorder that may pose a diagnostic conundrum in patients presenting with intermittent symptoms of small bowel obstruction. We describe the imaging findings of a unique case of abdominal cocoon that presented in infancy.     

Identification of somatic mutations in non-small cell lung carcinomas using whole-exome sequencing

Lung cancer is the leading cause of cancer-related death, with non-small cell lung cancer (NSCLC) being the predominant form of the disease. Most lung cancer is caused by the accumulation of genomic alterations due to tobacco exposure. To uncover its mutational landscape, we performed whole-exome sequencing in 31 NSCLCs and their matched normal tissue samples. We identified both common and unique mutation spectra and pathway activation in lung adenocarcinomas and squamous cell carcinomas, two major histologies in NSCLC. In addition to identifying previously known lung cancer genes (TP53, KRAS, EGFR, CDKN2A and RB1), the analysis revealed many genes not previously implicated in this malignancy. Notably, a novel gene CSMD3 was identified as the second most frequently mutated gene (next to TP53) in lung cancer. We further demonstrated that loss of CSMD3 results in increased proliferation of airway epithelial cells. The study provides unprecedented insights into mutational processes, cellular pathways and gene networks associated with lung cancer. Of potential immediate clinical relevance, several highly mutated genes identified in our study are promising druggable targets in cancer therapy including ALK, CTNNA3, DCC, MLL3, PCDHIIX, PIK3C2B, PIK3CG and ROCK2.     

Synthesis of new naphthoisoxazole amide derivatives and study of their biological evaluations

A series of naphthoisoxazole amide derivatives 4a–h have been synthesized from naphthoisoxazole acetic acid 3. 2-Acetyl-1-naphthol-1 on reaction with pulverized sodium and diethyl carbonate gave 4-hydroxy naphthopyrone 2 which on Posner reaction gave naphthoisoxazole acetic acid 3. The cytotoxic activity study for inhibiting melanoma cell survival was evaluated on a series of melanoma cell lines. The anticonvulsant activity of these compounds has been evaluated in Wistar rats. A compound called 4h has been found to have anticonvulsant activity comparable to that of the standard drug phenytoin.     

Use of a novel adjunctive kissing-balloon technique with the Trellis device to successfully prevent embolization across juxtaposed kissing aortoiliac stents

The Trellis thrombectomy system (Covidien) has been used successfully to perform isolated pharmacomechanical thrombectomy of both venous and arterial thrombi. The device is designed to provide localized treatment while preventing both systemic spread of the thrombolytic agent and also distal embolization. However, when this device is utilized to remove thrombi at bifurcation lesions, embolization into the contralateral vessel can potentially occur. We describe a novel and simple technique of adjunctive kissing balloon inflation while using the Trellis device for the management of an aortoiliac occlusion that occurred in one of two juxtaposed stents previously placed in the distal aorta into the bilateral iliac arteries. This technique prevented distal embolization into the contralateral iliac artery.     

Toward a quantitative method for estimating tumour-stroma ratio in breast cancer using polarized light microscopy

The tumour-stroma ratio (TSR) has been explored as a useful source of prognostic information in various cancers, including colorectal, breast, and gastric. Despite research showing potential prognostic utility, its uptake into the clinic has been limited, in part due to challenges associated with subjectivity, reproducibility, and quantification. We have recently proposed a simple, robust, and quantifiable high-contrast method of imaging intra- and peri-tumoural stroma based on polarized light microscopy. Here we report on its use to quantify TSR in human breast cancer using unstained slides from 40 patient samples of invasive ductal carcinoma (IDC). Polarimetric results based on a stromal abundance metric correlated well with pathology designations, showing a statistically significant difference between high- and low-stroma samples as scored by two clinical pathologists. The described polarized light imaging methodology shows promise for use as a quantitative, automatic, and standardizable tool for quantifying TSR, potentially addressing some of the challenges associated with its current estimation.