Comparative efficacy of three 5-HT3 antagonists (granisetron, ondansetron, and tropisetron) plus dexamethasone for the prevention of cisplatin-induced acute emesis: a randomized crossover study

The purpose of this study was to compare the antiemetic efficacy of three 5-HT3 antagonists (granisetron, ondansetron, tropisetron) plus dexamethasone for the prevention of acute emesis induced by high-dose cisplatin chemotherapy. This was a randomized, open label, crossover study. Recruited into the study were 94 chemotherapy-naive patients of whom five were excluded because chemotherapy was not given, noncisplatin regimen was used instead, or presence of anticipatory vomiting. The remaining 89 evaluable patients were mostly (86.5%) male, and were all treated for head and neck cancers. The antiemetic regimens consisted of 1) granisetron 3 mg i.v. and dexamethasone 20 mg i.v. on day 1 (GRADEX); 2) tropisetron 5 mg i.v. and dexamethasone 20 mg i.v. on day 1 (TRODEX); and 3) ondansetron 8 mg i.v. and dexamethasone 20 mg i.v. to be followed by ondansetron 8 mg p.o. x 2 on day 1 (ONDEX). Patients were randomized to receive one of the three regimens in the first cycle, and treatment was crossed over to the other two regimens in subsequent cycles. Antiemetic efficacy was assessed using self-report diaries recording the number of vomiting episodes as well as duration and severity of nausea within the first 24 hours. Complete response was defined as no vomiting with or without mild nausea, and major response was defined as one vomiting episode and/or moderate to severe nausea. Major efficacy refers to either complete or major response. A total of 219 cycles was given to 89 patients: 16 received one cycle only, 16 received two cycles, and 57 received three cycles. No carryover effects were observed between cycles. Using pooled data from all cycles, the complete response rates to GRADEX, TRODEX, and ONDEX were 81%, 68%, and 71%, respectively (p = 0.11); the corresponding major efficacy rates were 91%, 93%, and 86%, respectively (p = 0.36). When only the first cycle was considered, the complete response rates to GRADEX, TRODEX, and ONDEX were 81%, 75%, and 74%, respectively (p = 0.58); the corresponding major efficacy rates were 92%, 94%, and 84%, respectively (p = 0.38). Analysis of the crossover data showed that the majority of patients achieved complete response or major efficacy with the different pairs of regimens, and there were no significant differences between different regimens in terms of complete response or major efficacy. The only exception was GRADEX versus TRODEX, in which 15.5% of patient achieved complete response with GRADEX as compared with 1.7% with TRODEX (p = 0.025). The majority of patients (53%) did not report any preference, whereas 14% preferred GRADEX, 15% preferred TRODEX, and 18% preferred ONDEX. The three 5-HT3 antagonists, when used in combination with steroids, had similar major efficacy for prophylaxis against cisplatin-induced acute emesis. Although GRADEX was superior to TRODEX in terms of complete response, this may not be of clinical significance. The choice of antiemetic regimens should therefore depend on patient preference and drug cost.     

Potent antitumor efficacy of an E1B 55 kDa-deficient adenovirus carrying murine endostatin in hepatocellular carcinoma

Data from clinical trails have shown that the antitumoral effect of ONYX-015, an E1B 55kDa-deficient adenovirus, as monotherapy is insufficient. To enhance its efficiency, CNHK200-mE, another E1B 55kDa-deficient adenovirus armed with a mouse endostatin gene was constructed and its antitumoral activities against hepatocellular carcinoma （HCC） in vitro and in vivo were investigated. The selective replication and cytotoxicity of CNHK200-mE in Hep3B and HepGII cells independent of p53 status were confirmed via TCID50 and 3-（4,5dimetylthiazol）-2,5-diphenyltetrazolium bromide （MTT） assays. Potent tumor growth suppression on SMMC-7721 xenografts in nude mice was observed and a synergistic effect of the carrier virus and the therapeutic gene was suggested. Moreover, in comparison with the nonreplicative adenovirus carrying the same therapeutic gene, amplified transgene expression of mouse endostatin in vitro and in vivo were confirmed by Western blotting and ELISA assay. The effective angiogenesis inhibition and replication of CNHK200-mE in nude mice xenografts were demonstrated by immunohistochemistry. In conclusion, the recombinant adenovirus CNHK200-mE is a replication-competent oncolytic virus mediating high expression of therapeutic gene. Because CNHK200-mE is capable of replicating in and lysing HCC cells selectively with effective tumor growth suppression and antiangiogenic activity on HCC xenografts in nude mice, it holds good potential for the treatment of HCC.     

Simple and efficient system for fast interchange of low-energy collimators.

The inconvenience and time required for changing collimators on a scinticamera are major problems in the efficient use of the apparatus. A system is described, based on the lightweight, reversible DIVCON collimator made by Searle Radiographics for the Pho/Gamma camera that solves this problem. The core of a straight-bore, low-energy collimator is adapted to fit the DIVCON outer ring and a low-energy pinhole collimator is constructed to fit the same mounting system. Finally, an adapter using a bayonet-mount slot system is added to make collimator changing by hand possible in a minute or less.     

THY1 is a candidate tumour suppressor gene with decreased expression in metastatic nasopharyngeal carcinoma

Using oligonucleotide microarray analysis, THY1, mapping close to a previously defined 11q22-23 nasopharyngeal carcinoma (NPC) critical region was identified as showing consistent downregulated expression in the tumour segregants, as compared to their parental tumour-suppressing microcell hybrids (MCHs). Gene expression and protein analyses show that THY1 was not expressed in the NPC HONE1 recipient cells, tumour segregants, and other NPC cell lines; THY1 was exclusively expressed in the non-tumourigenic MCHs. The mechanism of THY1 gene inactivation in these cell lines was attributed to hypermethylation. Clinical study showed that in 65% of NPC specimens there was either downregulation or loss of THY1 gene expression. Using a tissue microarray and immunohistochemical staining, 44% of the NPC cases showed downregulated expression of THY1 and 9% lost THY1 expression. The frequency of THY1 downregulated expression in lymph node metastatic NPC was 63%, which was significantly higher than in the primary tumour (33%). After transfection of THY1 gene into HONE1 cells, a dramatic reduction of colony formation ability was observed. These findings suggest that THY1 is a good candidate tumour suppressor gene in NPC, which is significantly associated with lymph node metastases.     

Low staffing level is associated with malnutrition in long-term residential care homes

OBJECTIVE: To determine if staffing level is associated with poor nutrition in the long-term residential care setting, adjusting for other confounding factors. DESIGN: Cross-sectional survey. SETTING: In total, 14 residential care facilities in Hong Kong, stratified by nature (government subvention or for-profit) to reflect the overall proportion in Hong Kong. SUBJECTS: A total of 1914 subjects were assessed, using the Resident Assessment Instrument (RAI) 2.0. The response rate was 95% (1820 subjects), of which 1699 subjects had complete nutritional information. INTERVENTION: Body mass index (BMI) was calculated by weighing and height measurement, and arm span was used if the subject could not stand. Subjects who were receiving parenteral or enteral nutrition via nasogastric of enterostomy tubes were excluded. A history of weight loss of 5% in the past month or 10% in the past 6 months, leaving 25% of food uneaten, and BMI < 18.5 kg/m(2) were examined as nutritional indicators. Association with age, gender, functional disability, oral problems, taste problems, presence of physical diseases and psychological well-being was examined using chi(2)-test, and multiple logistic regression. RESULTS: In all, 26% of residents had a BMI < 18.5 kg/m(2), with a higher prevalence in the for-profit homes. History of weight loss and the record that 25% of food was left uneaten were poor indicators of low BMI. Multivariate analysis showed that having chronic obstructive airways disease, requiring help with feeding, being female, older age, were factors associated with an increased risk of poor nutrition, while being independent in activities of daily living and higher staff levels were associated with a reduced risk. CONCLUSION: Poor nutrition is a persistent problem in the long-term care setting, and inadequate staffing levels may be a reversible cause. However, resource limitations may render efforts at improvement difficult. SPONSORSHIP: SK Yee Memorial Fund.     

A behavioural genomic analysis of DNA markers associated with general cognitive ability in 7-year-olds

BACKGROUND: Five DNA markers (single-nucleotide polymorphisms, SNPs) have recently been found to be associated with general cognitive ability ('g') in a sample of 7414 7-year-old twins. These children have also been studied at 2, 3, 4, and 7 years of age on measures of cognitive and language development and behaviour problems; family environment was also assessed. METHODS: We used these data to conduct a behavioural genomic analysis of the five SNPs and a composite of them ('SNP set') that explored developmental, multivariate, and genotype-environment (GE) issues. RESULTS: The 'g' SNP set identified at 7 years yielded significant associations with 'g' as early as 2 years. In multivariate analyses at 7 years, the 'g' SNP set was more strongly associated with verbal than nonverbal ability and with reading more than mathematics performance. GE correlations were found between the SNP set for 'g' at 7 years and preschool proximal measures of the family environment (chaos and discipline) rather than distal measures (maternal education and father's occupational class), suggesting evocative rather than passive GE correlation. Significant GE interactions were found for discipline, education and occupation in which the association between the SNP set and 'g' at 7 years is stronger in low-risk environments. CONCLUSIONS: Although the effect sizes of the five SNP associations are very small, behavioural genomic analyses using a 'g' SNP set illustrate how developmental, multivariate and GE questions can be addressed as more DNA associations are identified for complex traits such as 'g'.     

Amplification and overexpression of epidermal growth factor receptor gene in glioblastomas of Chinese patients correlates with patient’s age but not with tumor’s clinicopathological pathway

It is believed that there are two distinct pathological pathways leading to the development of human glioblastomas (GBM) in Caucasian populations. Primary (de novo) GBM most often occurs in older individuals, and is characterized by the overexpression/amplification of epidermal growth factor receptor gene (EGFR), whereas secondary GBM, which progresses from a low-grade astrocytoma, often affects younger individuals and frequently contains the TP53 mutation. We and others have previously found that the age of onset of GBM in Chinese patients tends to be younger than that in Caucasian patients. To identify whether GBMs from Chinese patients share this common pattern of genetic alterations, expression levels of EGFR and TP53 and TP53 mutation were analyzed in 56 randomly selected Chinese GBMs (30 primary and 26 secondary), including 47 adult-onset and 9 pediatric GBMs. Consistent with other studies, overexpression/mutation of TP53 and aneuploid DNA content were more frequently detected in secondary GBMs of Chinese adult patients. In contrast to that observed in Caucasian patients, no significant difference was observed in the age distribution and the frequency of EGFR overexpression/amplification between primary and secondary GBMs in adult Chinese patients. Furthermore, the overexpression of EGFR was much higher in late-onset (age >45 years) GBMs (73%) than that in both early-onset (age 18–45 years) (17%) and pediatric (age <18 years) GBMs (11%), suggesting that overexpression of EGFR in Chinese GBMs may be associated closely with the patients age but not with the tumors pathological pathway.     

Dermatoglyphics and Schizophrenia: a meta-analysis and investigation of the impact of obstetric complications upon a-b ridge count

BACKGROUND: Patients with schizophrenia show deviances in their dermatoglyphics, in particular reductions in palmar a-b ridge counts (ABRCs), which are evidence of an early developmental deviance. However, the severity or the origin of these ABRC changes has not been established. METHOD: (i) We examined the published literature on the ABRC in patients with schizophrenia against controls with a random effects meta-analysis. (ii) We used linear regression to study the ABRC in our sample of families including 125 patients with schizophrenia, 107 of their unaffected relatives and 98 controls. (iii) The effect of obstetric complications on the patient's ABRC was examined using the Lewis Murray scale. RESULTS: The pooled standardised effect size of ABRC differences between patients and controls obtained by our meta-analysis was 0.39 (95% CI: 0.05-0.73; p=0.03). In our sample, there were no significant differences in ABRCs between those with schizophrenia, their relatives and controls. Only those patients with obstetric complications had significantly reduced ABRC compared to controls (p=0.01). CONCLUSIONS: We confirmed the presence of significant yet mild ABRC reductions in schizophrenia. These represent a subtle deviance from the norm and could be present in certain subsets of patients, possibly those who suffered early developmental insults.     

Classification of in vivo autofluorescence spectra using support vector machines

An algorithm based on support vector machines (SVM), the most recent advance in pattern recognition, is presented for use in classifying light-induced autofluorescence collected from cancerous and normal tissues. The in vivo autofluorescence spectra used for development and evaluation of SVM diagnostic algorithms were measured from 85 nasopharyngeal carcinoma (NPC) lesions and 131 normal tissue sites from 59 subjects during routine nasal endoscopy. Leave-one-out cross-validation was used to evaluate the performance of the algorithms. An overall diagnostic accuracy of 96%, a sensitivity of 94%, and a specificity of 97% for discriminating nasopharyngeal carcinomas from normal tissues were achieved using a linear SVM algorithm. A diagnostic accuracy of 98%, a sensitivity of 95%, and a specificity of 99% for detecting NPC were achieved with a nonlinear SVM algorithm. In a comparison with previously developed algorithms using the same dataset and the principal component analysis (PCA) technique, the SVM algorithms produced better diagnostic accuracy in all instances. In addition, we investigated a method combining PCA and SVM techniques for reducing the complexity of the SVM algorithms.