Biodistribution and radiation dosimetry of [11C]choline: a comparison between rat and human data

Purpose  

Methyl-¹¹C-choline ([¹¹C]choline) is a radiopharmaceutical used for oncological PET studies. We investigated the biodistribution and biokinetics of [¹¹C]choline and provide estimates of radiation doses in humans.     

Colorectal cancer incidence in <Emphasis Type="Italic">path_MLH1</Emphasis> carriers subjected to different follow-up protocols: a Prospective Lynch Syndrome Database report

Background

We have previously reported a high incidence of colorectal cancer (CRC) in carriers of pathogenic MLH1 variants (path_MLH1) despite follow-up with colonoscopy including polypectomy.

Methods

The cohort included Finnish carriers enrolled in 3-yearly colonoscopy (n?=?505; 4625 observation years) and carriers from other countries enrolled in colonoscopy 2-yearly or more frequently (n?=?439; 3299 observation years). We examined whether the longer interval between colonoscopies in Finland could explain the high incidence of CRC and whether disease expression correlated with differences in population CRC incidence.

Results

Cumulative CRC incidences in carriers of path_MLH1 at 70-years of age were 41% for males and 36% for females in the Finnish series and 58% and 55% in the non-Finnish series, respectively (p?>?0.05). Mean time from last colonoscopy to CRC was 32.7 months in the Finnish compared to 31.0 months in the non-Finnish (p?>?0.05) and was therefore unaffected by the recommended colonoscopy interval. Differences in population incidence of CRC could not explain the lower point estimates for CRC in the Finnish series. Ten-year overall survival after CRC was similar for the Finnish and non-Finnish series (88% and 91%, respectively; p?>?0.05).

Conclusions

The hypothesis that the high incidence of CRC in path_MLH1 carriers was caused by a higher incidence in the Finnish series was not valid. We discuss whether the results were influenced by methodological shortcomings in our study or whether the assumption that a shorter interval between colonoscopies leads to a lower CRC incidence may be wrong. This second possibility is intriguing, because it suggests the dogma that CRC in path_MLH1 carriers develops from polyps that can be detected at colonoscopy and removed to prevent CRC may be erroneous. In view of the excellent 10-year overall survival in the Finnish and non-Finnish series we remain strong advocates of current surveillance practices for those with LS pending studies that will inform new recommendations on the best surveillance interval.

     

Falls and injurious falls late in home-dwelling life

Of the Finnish persons aged 85 years or older, living at home, 555 (67% of this age class) were monitored for two years to describe the circumstances and the frequency of falls and injury-causing falls. The incidence rates of falls, major soft tissue injuries and fractures were 1039 (95% confidence interval = CI: 974-1093), 74 (58-92) and 89 (72-108), respectively. The incidence of falls was higher among women 1127 (1055-1199) than among men 755 (651-870), but only among those younger than 90 years. The probability of getting injured in a fall was higher in the morning (p = 0.010) and in the evening (p = 0.007) as compared to the daytime. More injury-causing falls than other falls were non-defined as regards ongoing activity at the time of fall (p < 0.001) and type of falling (p < 0.001). Ongoing activity and type of falling did not discriminate injury-causing falls from other falls after exclusion of the non-defined falls. We conclude that incidence of falls among the home-dwelling elderly increases up to the oldest ages, especially among the men. Time of day affects the occurrence of injuries in falls. Ongoing activity and type of falling play a minor role in falls causing injuries among the most elderly.     

Associations of body size at birth with late-life cortisol concentrations and glucose tolerance are modified by haplotypes of the glucocorticoid receptor gene

CONTEXT: Small body size at birth is associated with cardiovascular disease and type 2 diabetes in adult life. This link may be in part mediated by early-life programming of the hypothalamic-pituitary-adrenal axis (HPAA) function. OBJECTIVE: Our objective was to assess whether haplotypes of the glucocorticoid receptor (GR) gene modify this link. DESIGN AND PARTICIPANTS: We conducted a birth cohort study that included 437 men and women born in Helsinki, Finland, during 1924-1933, whose birth measurements were recorded. MAIN OUTCOME MEASURES: We studied how the oral glucose tolerance test and fasting plasma total and free cortisol concentrations and, in a subset of 162 women, a more detailed HPAA evaluation, are predicted by body size at birth and haplotypes of the GR locus. We also measured the haplotype-specific relative mRNA expression level for the haplotype of interest. RESULTS: One of the haplotypes was associated with lower birth weight and length and higher fasting plasma and mean 24-h salivary cortisol. Moreover, this haplotype modified the association of length at birth with adult phenotypes; in carriers, short length at birth was associated with increased fasting plasma cortisol, cortisol/corticosteroid-binding globulin ratio, impaired glucose tolerance or diabetes [1 cm decrease corresponded to 1.36-fold odds ratio; 95% confidence interval (CI), 1.09-1.70; P = 0.007], and higher 120-min glucose (5.8%; 95% CI, 2.5-9.1%; P = 0.0007), but no association was seen in noncarriers (P for interaction was 0.06, 0.01, 0.02, and 0.01, respectively). The mRNA expression level of this haplotype was 93.7% (95% CI, 90.5-96.8%; P = 2.2 x 10(-4)) of the expression level of the other haplotypes. CONCLUSIONS: A common GR haplotype may contribute to and modify the association of short length at birth with adult glucose tolerance and HPAA function by a mechanism that affects regulation of GR expression.