Opportunities for the replacement of animals in the study of nausea and vomiting

Nausea and vomiting are among the most common symptoms encountered in medicine as either symptoms of disease or side effects of treatments. Developing novel anti-emetics and identifying emetic liability in novel chemical entities rely on models that can recreate the complexity of these multi-system reflexes. Animal models (especially the ferret and dog) are the current gold standard; however, the selection of appropriate models is still a matter of debate, especially when studying the subjective human sensation of nausea. Furthermore, these studies are associated with animal suffering. Here, following a recent workshop held to review the utility of animal models in nausea and vomiting research, we discuss the limitations of some of the current models in the context of basic research, anti-emetic development and emetic liability detection. We provide suggestions for how these limitations may be overcome using non-animal alternatives, including greater use of human volunteers, in silico and in vitro techniques and lower organisms.     

Regional radiotherapy versus an axillary lymph node dissection after lumpectomy: a safe alternative for an axillary lymph node dissection in a clinically uninvolved axilla in breast cancer. A case control study with 10 years follow up

Background

To correlate the metabolic changes with size changes for tumor response by concomitant PET-CT evaluation of lung cancers after radiotherapy.

Methods

36 patients were studied pre- and post-radiotherapy with¹⁸FDG PET-CT scans at a median interval of 71 days. All of the patients were followed clinically and radiographically after a mean period of 342 days for assessment of local control or failure rates. Change in size (sum of maximum orthogonal diameters) was correlated with that of maximum standard uptake value (SUV) of the primary lung cancer before and after conventional radiotherapy.

Results

There was a significant reduction in both SUV and size of the primary cancer after radiotherapy (p < 0.00005). Among the 20 surviving patients, the sensitivity, specificity, and accuracy using PET (SUV) were 94%, 50%, 90% respectively and the corresponding values using and CT (size criteria) were 67%, 50%, and 65% respectively. The metabolic change (SUV) was highly correlated with the change in size by a quadratic function. In addition, the mean percentage metabolic change was significantly larger than that of size change (62.3 ± 32.7% vs 47.1 ± 26.1% respectively, p = 0.03)

Conclusion

Correlating and incorporating metabolic change by PET into size change by concomitant CT is more sensitive in assessing therapeutic response than CT alone.     

Comparison of the morphological transforming activities of dibenzo[a,l]pyrene and benzo[a]pyrene in C3H10T1/2CL8 cells and characterization of the dibenzo[a,l]pyrene-DNA adducts

C3H10T1/2CL8 (C3H10T1/2) mouse embryo fibroblasts were used to study the in vitro carcinogenic activities of dibenzo[a,l]pyrene (DB[a,l]P) and benzo[a]pyrene (B[a]P). The morphological transforming activities of these rodent carcinogens were compared using replicate concentration- response studies. In concentration ranges where both polycyclic aromatic hydrocarbons (PAHs) were active, DB[a,l]P proved to be four to 12 times as potent as B[a]P based on concentration. At lower concentrations DB[a,l]P was active at 0.10 and 0.20 microM, concentrations where B[a]P was inactive. This makes DB[a,l]P the most potent non-methylated PAH evaluated to date in C3H10T1/2 cells. DNA adducts of DB[a,l]P in C3H10T1/2 cells were analyzed by both TLC and TLC/HPLC 32P-postlabeling methods using mononucleotide 3'-phosphate adduct standards derived from the reactions of anti-DB[a,l]P-11,12-diol- 13,14-epoxide (anti-DB[a,l]PDE) and syn-DB[a,l]P-11,12-diol-13,14- epoxide (syn-DB[a,l]PDE) with deoxyadenosine 3'-monophosphate and deoxyguanosine 3'-monophosphate. All of the DNA adducts observed in C3H10T1/2 cells treated with DB[a,l]P were identified as being derived from the metabolism of DB[a,l]P to its fjord region diol epoxides through DB[a,l]P-11,12-diol. The predominant adduct was identified as an anti-DB[a,l]PDE-deoxyadenosine adduct. Other major adducts were anti- DB[a,l]PDE-deoxyguanosine and syn-DB[a,l]PDE-deoxyadenosine adducts with minor amounts of syn-DB[a,l]PDE-deoxyguanosine adducts. These DNA adduct data are consistent with similar findings of DB[a,l]PDE- deoxyadenosine adducts in mouse skin studies and human mammary cells in culture.      

BILATERAL DUPUYTREN'S CONTRACTURE IN A BLACK PATIENT

The first case of Dupuytren's contracture in a black patient with no obvious caucasian admixture was reported in 1979. This condition is rare in the purely black population and since 1979 only 23 cases have been reported. We present the case of a black man with no history of caucasian admixture with bilateral Dupuytren's contracture. We suggest that this condition may not be as rare as the literature suggests and, that canvassing other hand societies for their experience, particularly in the continent of Africa, may help to establish the true incidence of this condition.     

Vitelliform dystrophy and pattern dystrophy of the retinal pigment epithelium: concomitant presence in a family.

We describe three siblings presenting unusual pigmented dystrophic lesions of the fovea. The first sibling showed macroreticular dystrophy associated with butterfly shaped dystrophy in one eye and associated with vitelliform cyst in the other eye. The second showed the atrophic outcome of a vitelliform cyst with development of subretinal neovascular membrane in one eye and a radial pigmented macular dystrophy in the other eye. The third sibling had bilateral macular vitelliform lesions. This vitelliform patterned dystrophy of the retinal pigment epithelium may represent a new form that should be classified near Best's disease and the pattern dystrophies.     

Electroretinographic oscillatory potentials in insulin-dependent diabetes patients: A long-term follow-up

PURPOSE: The aim of this research was to study the relevance of long-term follow-up of electroretinographic oscillatory potentials (OPs) in predicting the onset of minimal non-proliferative diabetic retinopathy in insulin-dependent diabetes patients. METHODS: A total of 80 insulin-dependent diabetics, with normal fundi and normal OPs at first examination, were followed prospectively for 10 years. Oscillatory potentials were measured and fundus examinations performed once or twice per year. RESULTS: During follow-up, 35% of patients developed diabetic retinopathy after a mean disease duration of 12 +/- 2 years. A decrease in OP amplitudes was seen in 46% of this group, but reductions were also seen in the 25% of patients whose fundi remained normal. Statistical analysis of best-fit survival curves shows a significant difference (p < 0.001) in the point of Kaplan-Meiers' curve maximal linearity (TmaxS). CONCLUSIONS: It appears that eyes with reduced OP amplitude have a greater probability of developing diabetic retinopathy. Subnormal OP amplitudes are not proof of real concomitant visible vascular damage, but may reflect a predisposition to functional neurosensorial disorder.     

Caffeine intake reduces sleep duration in adolescents

In our study, we hypothesized that higher caffeine intake would be associated with lower sleep duration among 13-year-old adolescents. In addition, we aimed to identify food sources of caffeine intake in this sample. Eligible participants were adolescents who were born in 1990 and attended school in Porto, Portugal, in 2003/2004. Self-administered questionnaires were used, and diet was evaluated using a food frequency questionnaire. From the 2160 eligible participants, only 1522 with valid information regarding their diet were included in this study. In our sample, the median intake of caffeine was 23.1 mg/d, with soft drinks being the major source. Ice tea presented the highest median (25th-75th percentiles) contribution (33.1% [14.0-52.1]), followed by cola (21.1% [6.4-37.6]). Regarding cocoa products, chocolate bars presented a median contribution of 5.1% (1.0-14.0), and snacks containing chocolate had a contribution of 3.0% (0.5-7.2). Coffee and tea presented a negligible contribution. Adolescents who reported less sleep duration and those who spent more time watching TV during the weekend had a significantly higher caffeine intake. Overall, boys had higher intakes of caffeine from soft drinks, and private school attendees, those who had parents with more education, who reported less television viewing time and had lower body mass index presented higher intakes of caffeine from chocolate. Considering sleeping more than 9.5 hours as a reference class, for each increase of 10 mg/d in caffeine intake, we found that the odds ratio of sleeping 8.5 hours or less was 1.12 (95% confidence interval, 1.06-1.19). Our results support the hypothesis that caffeine intake was inversely associated with sleep duration in adolescents.