Fetal Alcohol Spectrum Disorders (FASD): an Approach to Effective Prevention.

PURPOSE OF REVIEW: The objective of the current contribution is to propose an evidence-based, six-step approach to develop effective programs for prevention of fetal alcohol spectrum disorders. RECENT FINDINGS: Despite widespread campaigns aimed to reduce prenatal alcohol exposure, the number of affected children continues to be high. Current strategies to reduce prenatal alcohol exposure may be ineffective or counterproductive. However, proven principles of health promotion could be applied to reduce drinking in pregnancy. One such approach is Intervention Mapping (IM), a six-step procedure based on proven principles to change behaviors. SUMMARY: FASD affects all communities and is an underestimated problem worldwide. Programs based on proven principles of behavior change are warranted. Program developers can use pre-existing protocols and strategies from evidence-based practice, such as Intervention Mapping. Developers who plan their preventive programs in a systematic and evidence-based manner increase the chances of success in reducing prenatal alcohol exposure and FASD.

Ageing with an intellectual disability: the impact of personal resources on well-being.

BACKGROUND: The population of ageing people with mild and moderate intellectual disabilities (ID) is growing rapidly. This study examines how personal resources (physical health, mental health and social networks) impact the well-being of ageing people with ID. METHODS: Longitudinal survey data on 667 people with a mild or moderate ID were acquired via interviews in 2006 and 2010. Indicators of personal resources (physical health, mental health and social networks) were assessed, as were indicators of well-being (satisfaction with life, happiness and loneliness). Additionally, data on background characteristics and autonomy were gathered. RESULTS: The results show that age is positively related to decreased mobility and auditory disabilities and negatively related to independent living, autonomy in how one spends one's leisure time and autonomy in decision-making. Longitudinal analyses demonstrated that, with the exception of health that deteriorated, and social satisfaction that improved, almost all variables remained stable over the 4-year period. Further, good physical health in 2006 predicted happiness in 2010. CONCLUSION: Despite the fact that age is associated with poorer physical and mental health and a smaller social network, this study showed that older people with ID have relatively high levels of well-being. Findings are discussed in the light of coping with ageing and impact of life events.

Biotransformation of 6-thioguanine in inflammatory bowel disease patients: a comparison of oral and intravenous administration of 6-thioguanine.

BACKGROUND AND PURPOSE: Although 6-mercaptopurine and azathioprine are effective treatments in inflammatory bowel disease (IBD), many patients discontinue treatment because of side effects. 6-Thioguanine (6-TG) may be an alternative rescue therapy in these intolerant patients but the pharmacokinetics of 6-TG are not fully described. Here we have measured the pharmacokinetics of the biotransformation of 6-TG into the pharmacologically active metabolites, 6-thioguanine nucleotides (6-TGN), in IBD patients. EXPERIMENTAL APPROACH: In 12 patients with IBD, levels of 6-TGN and activities of thiopurine S-methyltransferase, xanthine oxidase and hypoxanthine guanine-phosphoribosyl-transferase were measured in a two-stage (i.v. and p.o. administration of 0.3 mg·kg(-1) 6-TG), prospective study. Median exposure of 6-TGN in red blood cells (RBC) was expressed as the ratio of the area under the curve (AUC) per mg 6-TG after i.v. dosing and that after p.o. dosing. KEY RESULTS: The median AUC per mg 6-TG was 1068 (p.o.) and 7184 (i.v.) pmol·h (8 × 10(8) RBC)(-1) . Median exposure of 6-TGN in RBC was 15% (9-28). Hypoxanthine guanine-phosphoribosyl-transferase activity correlated with peak 6-TGN and with AUC per mg (r= 0.7, P= 0.02 and r= 0.6, P= 0.03 respectively). Thiopurine S-methyltransferase activity was inversely related to AUC per mg (r=-0.8, P= 0.001), whereas that of xanthine oxidase was correlated with a lower peak 6-TGN (r=-0.7, P= 0.02). CONCLUSIONS AND IMPLICATIONS: The great variability of the AUC per mg for 6-TG observed after p.o. and i.v. administration of 6-TG, was partly explained by variability in activities of metabolizing enzymes. Exposure of 6-TGN was low in all patients.

Gemcitabine: Future Prospects of Single-Agent and Combination Studies.

Gemcitabine (2'2'-difluorodeoxycytidine, Gemzar) is a deoxycytidine analog with excellent antitumor activity against a number of solid tumors. Gemcitabine needs to be activated by deoxycytidine kinase and other kinases to its triphosphate, gemcitabine triphosphate, which can be incorporated into RNA and DNA. The latter effect is considered to be responsible for its antitumor effect and causes masked chain termination and inhibition of DNA repair. This effect may be of importance for combination with DNA interacting agents. In phase I trials daily, twice weekly, weekly and every two weeks schedules have been evaluated. At the weekly schedule of 1,000-1,250 mg/m² significant antitumor activity was observed in bladder, breast, ovary, and pancreatic cancer, non-small cell lung cancer (NSCLC), and small cell lung cancer of 31%, 33%, 22%, 11%, 22% and 27% total response rates, respectively. Gemcitabine also showed considerable improvement in clinical symptoms, while toxicity was not severe with mild myelosuppression. Due to its ability to inhibit DNA replication, combination studies were initiated with DNA damaging agents. For the various combinations with cisplatin in phase II studies on NSCLC, response rates varied from 42%-54%, with a median survival of generally more than 12 months. Also, combinations with taxanes, etoposide, doxorubicin and vindesin seem promising. Gemcitabine is an important agent for the management of several relatively chemoresistant cancer types, both with respect to anti-tumor activity and clinical benefit. Future research on combination studies deserves high priority considering the high response rates in NSCLC and bladder cancer.