Sunitinib

Sunitinib and its active metabolite (SU012662) are selective inhibitors of multiple receptor tyrosine kinases associated with tumour growth and angiogenesis. The clinical efficacy of oral sunitinib has been demonstrated in patients with advanced gastrointestinal stromal tumours (GIST). In a phase III, randomised, double-blind, placebo-controlled, multicentre trial in patients with metastatic and/or unresectable GIST following unsuccessful imatinib therapy, the median time to tumour progression and median progression-free survival time were > or =4-fold longer in patients receiving sunitinib 50 mg/day than in those receiving placebo, in 6-week cycles consisting of 4 weeks of treatment followed by a 2-week rest period. Sunitinib also exhibited antitumour activity in patients with advanced renal cell carcinoma (RCC) following unsuccessful cytokine therapy. In two multicentre, single-arm, phase II clinical trials in patients with cytokine-refractory metastatic RCC, partial responses were reported in 40% and 43% of patients receiving sunitinib 50 mg/day for 4 weeks followed by 2 weeks without treatment in 6-week cycles; 27% and 22% of patients achieved stable disease for > or =3 months. Sunitinib was more effective than interferon-alpha as a first-line therapy in patients with metastatic RCC. In a large, well designed, phase III trial in previously untreated patients, progression-free survival was significantly longer in patients receiving sunitinib 50 mg/day in 6-week cycles (4 weeks of treatment followed by a 2-week rest period) compared with those receiving interferon-alpha 9MU three times weekly (47.3 vs 24.9 weeks). In general, sunitinib was well tolerated in patients with GIST and RCC, with adverse events usually being of mild or moderate severity.     

Self-perception of body weight among high school students in Taipei, Taiwan

Self-perception of body weight and other weight-related factors were assessed among 2665 Taipei, Taiwan high school students. A high percent of the girls (70.7%) and boys (42.2%) reported that they were too fat and these percentages were much higher than those reported by U.S. students in a recent Youth Risk Behavior Survey. In addition, only 13.2% of girls and 22.0% of boys reported being completely satisfied with their weight and the level of dissatisfaction with weight appeared to be greater than among U.S. students. Yet, in comparison to U.S. students, the Taiwanese students were considerably less likely than their U.S. counterparts to engage in weight management practices (e.g., dieting, eating less food, using diet pills). Taiwanese students with a self-perception of being too fat were more likely than those with perceptions of being just right or too thin to engage in weight management practices, to be dissatisfied with their weight, feel that they were unattractive, estimate that their same-sex peers were trying to lose weight, and have a higher body mass index. The findings from this study showed a relationship between self-perception of body size and engaging in weight control behaviors was consistent with other research. It suggested that self-perception of body weight, more so than objective weight status, was predictive of weight loss behavior and also negative psychological outcomes associated with poor body weight image. As a result, self-perception of weight may be an important point of focus for the design and implementation of clinical and public health initiatives targeted at this adolescent population as well as others.     

Quality of life, symptomatology and healthcare utilization in HIV/HCV co-infected drug users in Miami

HIV/HCV co-infection is becoming one of the main causes of death in HIV+ persons. We determined quality of life, clinical symptoms and health care utilization in HIV mono-infected and HIV/HCV co-infected chronic drug users. After consenting 218 HIV+ drug users, a physical examination and questionnaires on demographics, quality of life, drugs of abuse, and healthcare utilization were completed. Blood was drawn for HCV status, CD4 cell count, HIV viral load, CBC and chemistry. HIV/HCV co-infected participants had significantly higher risk of having poorer perceived outlook and health, presented significantly more frequent depression and physical symptoms, and used significantly more healthcare services than those infected with HIV only, after adjusting for age, gender, ethnicity, CD4 cell count, and viral load. Diminished quality of life in the HIV/HCV co-infected group was explained by increased frequency of depression, physical symptoms, healthcare utilization, and poor access to HCV treatment in this population.     

Systematic review of reporting rates of adverse events following immunization: An international comparison of post-marketing surveillance programs with reference to China

Background

China is the most populous country in the world, with an annual birth cohort of approximately 16 million, requiring an average of 500 million vaccine doses administered annually. In China, over 30 domestic and less than 10 overseas vaccine manufacturers supply over 60 licensed vaccine products, representing a growing vaccine market mainly due to recent additions to the national immunization schedule, but data on post-marketing surveillance for adverse events following immunization (AEFI) are sparse.

Objectives

To compare reporting rates for various categories of AEFI from China with other routine post-marketing surveillance programs internationally.

Methods

Systematic review of published studies reporting rates of AEFI by vaccine, category of reaction and age from post-marketing surveillance systems in English and Chinese languages.

Results

Overall AEFI reporting rates (all vaccines, all ages) in Chinese studies were consistent with those from similar international studies elsewhere, but there was substantial heterogeneity in regional reporting rates in China (range 2.3–37.8/100,000 doses). The highest AEFI reporting rates were for diphtheria–tetanus–pertussis whole-cell (DTwP) and acellular (DTaP) vaccines (range 3.3–181.1/100,000 doses for DTwP; range 3.5–92.6/100,000 doses for DTaP), with higher median rates for DTwP than DTaP, and higher than expected rates for DTaP vaccine. Similar higher rates for DTwP and DTaP containing vaccines, and relatively lower rates for vaccines against hepatitis B virus, poliovirus, and Japanese encephalitis virus were found in China and elsewhere in the world.

Conclusions

Overall AEFI reporting rates in China were consistent with similar post-marketing surveillance systems in other countries. Sources of regional heterogeneity in AEFI reporting rates, and their relationships to differing vaccine manufacturers versus differing surveillance practices, require further exploration.     

Abnormalities of the cadherin-catenin complex in chemically-induced colo-rectal carcinogenesis

Beta-Catenin is a multifunctional protein originally identified as a component of the cadherin cell-cell adhesion complex. It also binds the adenomatous polyposis coli (APC) tumour suppressor which controls beta-catenin cellular levels through its degradation. (beta-Catenin and/or APC mutations result in increased cytoplasmic Beta-catenin and nuclear translocation. The aim of the present study was to examine the expression and cellular localisation of alpha and beta-catenin, p120 and E-cadherin in a chemically-induced mouse model of colo-rectal cancer using 1,2-dimethylhydrazine (DMH). Female Balb/C mice were injected subcutaneously with a solution providing 25 mg DMH base/kg body weight for 17 weeks. Animals were killed and tumours identified in the intestine with a dissecting microscope. Formalin-fixed paraffin-embedded sections of normal and dysplastic colonic mucosa were stained by an indirect avidin-biotin immunohistochemical technique using mouse monoclonal antibodies, and membranous, cytoplasmic and nuclear cellular localisation was assessed by light microscopy. Staining distribution scored as follows: 3, > 90 % positive epithelial cells; 2, >50 % positive epithelial cells; 1, <50 % positive epithelial cells. Non-dysplastic colonic epithelial cells revealed beta-catenin expression at the membrane (33/41 scored 3),areas of cytoplasmic expression (24/41 scored 1) and no nuclear staining. Dysplastic colonic epithelium revealed increased membranous and cytoplasmic, beta-catenin immunoreactivity (39/41 and 38/41 both scored 3) with focal nuclear staining (14/41). Expression patterns for ac-catenin, p120, and E-cadherin were similar to beta-catenin with increased membranous and cytoplasmic immunoreactivity in dysplastic mucosa, although no nuclear staining was observed. Increased cytoplasmic expression and nuclear localisation of beta-catenin are consistent with a possible mutation in its gene, and this finding was in keeping with the mutational analysis of exon 3 by single-strand conformational polymorphism. Increased immunoreactivity of the other catenins also suggests further disruption in catenin regulation. In summary, alterations in the beta-catenin expression and cellular localisation in the DMH-induced tumours are similar to those seen inhuman sporadic colorectal tumours. The DMH is therefore a useful model for studying the abnormalities of the E-cadherin-catenin pathway in colorectal carcinogenesis.     

Cause and outcome of atypical chest pain in patients admitted to hospital

In patients with acute chest pain the prime need, usually, is to diagnose and treat myocardial infarction or ischaemia. When a cardiac origin for the pain has been excluded, patients are commonly discharged without either a diagnosis or a plan for follow-up. We studied a group of such patients to see how far causation was pursued and how their mortality compared with that of patients with a proven cardiac cause for their symptoms. The study population was 250 patients admitted over five weeks with chest pain suspected of being cardiac in origin. Initial assessment included an electrocardiogram and measurement of troponin T. If neither of these indicated a cardiac event, the patient was deemed to have 'atypical' chest pain and the cause, where defined, was recorded. Outcomes at one year were determined by questionnaire and by assessment of medical notes. Of the 250 patients, 142 had cardiac pain (mean age 79 years, 58% male) and 108 atypical chest pain (mean age 60 years, 55% male). Of those with atypical pain, 40 were discharged without a diagnosis; in the remaining 68 the pain was thought to be musculoskeletal (25), cardiac (21), gastrointestinal (12) or respiratory (10) in origin. 41 patients were given a follow-up appointment on discharge. At one year, data were available on 103 (96%) patients. The mortality rate was 2.9% (3 patients) compared with 18.3% in those with an original cardiac event. Half of the patients with atypical pain had undergone further investigations and 14% had been readmitted. The yield of investigative procedures was generally low (20%) but at the end of the year only 27 patients remained undiagnosed. Patients with atypical chest pain form a substantial proportion of emergency admissions. The symptoms often persist or recur. The commonest causation is musculoskeletal, but a sizeable minority remain undiagnosed even after follow-up.     

Capsaicinoids and capsinoids. A potential role for weight management? A systematic review of the evidence

Capsaicinoids are a group of chemicals found in chilli peppers, with bioactive properties. The purpose of this study is to systematically review research investigating the potential benefits capsaicinoid compounds may have in relation to weight management. Medical databases were searched and 90 trials found, 20 of which were selected for inclusion, involving 563 participants. Three main areas of potential benefit for weight management were found: (1) increased energy expenditure; (2) increased lipid oxidation and (3) reduced appetite. Trial duration, dosage and sized varied, though trials were generally of high quality with a low risk of bias. It was observed that consumption of capsaicinoids increases energy expenditure by approximately 50kcal/day, and that this would produce clinically significant levels of weight loss in 1-2years. It was also observed that regular consumption significantly reduced abdominal adipose tissue levels and reduced appetite and energy intake. The mechanism of action is not presently fully understood, although it is well accepted much of the effects are caused by stimulation of the TRPV1 receptor. While capsaicinoids are not a magic bullet for weight loss, the evidence is that they could play a beneficial role, as part of a weight management program.     

Differential associations between the food environment near schools and childhood overweight across race/ethnicity, gender, and grade

Epidemiologic studies have observed influences of the food environment near schools on children's overweight status but have not systematically assessed the associations by race, sex, and grade. The authors examined whether the associations between franchised fast food restaurant or convenience store density near schools and overweight varied by these factors using data for 926,018 children (31.3% white, 55.1% Hispanic, 5.7% black, and 8% Asian) in fifth, seventh, or ninth grade, nested in 6,362 schools. Cross-sectional data were from the 2007 California physical fitness test (also known as "Fitnessgram"), InfoUSA, the California Department of Education, and the 2000 US Census. In adjusted models, the overweight prevalence ratio comparing children in schools with 1 or more versus 0 fast food restaurants was 1.02 (95% confidence interval (CI): 1.01, 1.03), with a higher prevalence ratio among girls compared with boys. The association varied by student's race/ethnicity (P = 0.003): Among Hispanics, the prevalence ratio = 1.02 (95% CI: 1.01, 1.03); among blacks, the prevalence ratio = 1.03 (95% CI: 1.00, 1.06), but among Asians the prevalence ratio = 0.94 (95% CI: 0.91, 0.97). For each additional convenience store, the prevalence ratio was 1.01 (95% CI: 1.00, 1.01), with a higher prevalence ratio among fifth grade children. Nuanced understanding of the impact of food environments near schools by race/ethnicity, sex, and grade may help to elucidate the etiology of childhood overweight and related race/ethnic disparities.