Late-Life Body Mass Index, Rapid Weight Loss, Apolipoprotein E ε4 and the Risk of Cognitive Decline and Incident Dementia.

OBJECTIVES: To examine the effect of late-life body mass index (BMI) and rapid weight loss on incident mild cognitive impairment (MCI) and Alzheimer's disease (AD). DESIGN: Prospective longitudinal cohort study. SETTING: National Alzheimer's Coordinating Center (NACC) Uniform Data Set, including 34 past and current National Institute on Aging-funded AD Centers across the United States. PARTICIPANTS: 6940 older adults (n=5061 normal cognition [NC]; n=1879 MCI). MEASUREMENTS: BMI (kg/m2) and modified Framingham Stroke Risk Profile (FSRP) score (sex, age, systolic blood pressure, anti-hypertension medication, diabetes mellitus, cigarette smoking, prevalent cardiovascular disease, atrial fibrillation) were assessed at baseline. Cognition and weight were assessed annually. RESULTS: Multivariable binary logistic regression, adjusting for age, sex, race, education, length of follow-up, and modified FSRP related late-life BMI to risk of diagnostic conversion from NC to MCI or AD and from MCI to AD. Secondary analyses related late-life BMI to diagnostic conversion in the presence of rapid weight loss (>5% decrease in 12 months) and apolipoprotein E (APOE) ε4. During a mean 3.8-year follow-up period, 12% of NC participants converted to MCI or AD and 49% of MCI participants converted to AD. Higher baseline BMI was associated with a reduced probability of diagnostic conversion, such that for each one-unit increase in baseline BMI there was a reduction in diagnostic conversion for both NC (OR=0.977, 95%CI 0.958-0.996, p=0.015) and MCI participants (OR=0.962, 95%CI 0.942-0.983, p<0.001). The protective effect of higher baseline BMI did not persist in the setting of rapid weight loss but did persist when adjusting for APOE ε4. CONCLUSIONS: Higher late-life BMI is associated with a lower risk of incident MCI and AD but is not protective in the presence of rapid weight loss.

PROviding Better ACcess To ORgans: A comprehensive overview of organ-access initiatives from the ASTS PROACTOR Task Force.

The American Society of Transplant Surgeons (ASTS) PROviding better Access To Organs (PROACTOR) Task Force was created to inform ongoing ASTS organ access efforts. Task force members were charged with comprehensively cataloguing current organ access activities and organizing them according to stakeholder type. This white paper summarizes the task force findings and makes recommendations for future ASTS organ access initiatives.

Quality assurance evaluation of spot scanning beam proton therapy with an anthropomorphic prostate phantom.

OBJECTIVE: The purpose of this study was to evaluate spot scanning proton therapy with an anthropomorphic prostate phantom at the Proton Therapy Center of The University of Texas MD Anderson Cancer Center at Houston, TX (PTCH). METHODS: An anthropomorphic prostate phantom from the Radiological Physics Center (RPC), The University of Texas MD Anderson Cancer Center, Houston, TX, was used, which contained thermoluminescent dosemeters and GAFCHROMIC(®) EBT2 film (ISP Technologies, Wayne, NJ). The phantom was irradiated by the Hitachi synchrotron (Hitachi America, Ltd, Tarrytown, NY), and the results were compared between the treatment planning system (TPS) and RPC measurements. RESULTS: RPC results show that the right/left, inferior/superior and posterior/anterior aspects of the coronal/sagittal and EBT2 film measurements were within ±7%/±4 mm of the TPS. The RPC thermoluminescent dosemeter measurements of the prostate and femoral heads were within 3% of the TPS. CONCLUSION: The RPC prostate phantom is a useful mechanism to evaluate spot scanning beam proton therapy within certain confidence levels. ADVANCES IN KNOWLEDGE: The RPC anthropomorphic prostate phantom could be used to establish quality assurance of spot scanning proton beam for patients with prostate cancer.

The effect of calcium supplements on rectal mucosal proliferation.

Seventy-nine patients with colorectal adenomata were randomised to receive calcium carbonate (3,000 mg) or placebo in a double-blind randomised trial to assess the short- and long-term effects on rectal mucosal proliferation measured by the in vitro metaphase arrest technique crypt cell production rate (CCPR). There was no significant difference in mean CCPR between the groups before treatment or after 3 or 12 months. In those patients randomised to calcium, CCPR fell at both 3 months [9.0 (2.8) cc c-1 h-1, t = 3.15, d.f = 76, P = 0.002] and 12 months [9.2 (3.3) cc c-1 h-1 t = 2.7, d.f. = 74, P = 0.009] compared with pretreatment CCPR [12.2 (5.5) cc c-1 h-1]. We have demonstrated that calcium had no effect on mucosal proliferation compared with placebo. The results on adenoma formation are awaited.

Wheat fibre, lactulose and rectal mucosal proliferation in individuals with a family history of colorectal cancer.

In a single-blind study 38 individuals at increased risk of developing colorectal cancer because of a family history of the disease were randomized to take 10.5 g wheat fibre (Trifyba) or 60 ml lactulose daily for 12 weeks. Rectal biopsies were taken before and after treatment and rectal mucosal proliferation was measured by the crypt cell production rate (CCPR). The mean(s.d.) CCPR was significantly lower in those taking wheat fibre after 12 weeks (7.2(3.4) crypt cells per crypt per h) compared both with values obtained before treatment with wheat fibre (10.2(5.1) crypt cells per crypt per h; P = 0.02) and after treatment with lactulose (9.4(3.8) crypt cells per crypt per h; P = 0.05). Proliferation in the lactulose group was not significantly different at 12 weeks compared with the value obtained before treatment. This study confirms an antiproliferative effect of wheat fibre in a group of high-risk individuals.

DNA content of rectal mucosa and rectal mucosal proliferation in individuals at high risk of colorectal cancer.

Genetic changes are important in the development of colorectal cancer. Ploidy and rectal mucosal proliferation were measured in histologically normal rectal mucosa of 85 individuals (mean age 59 years, range 29-74) who had a total colonoscopy. Fifty-one subjects had an adenoma or were undergoing adenoma surveillance. Twenty-two subjects had a strong family history of colorectal cancer and 12 individuals comprised a control group who had a normal colonoscopy without a family history of colorectal cancer. An abnormal DNA content (aneuploidy) was found in the normal mucosa of nine (10.6%) individuals. There was no significant difference in rectal mucosal proliferation with those who had aneuploidy and those who had diploidy. There was a trend towards increased proliferation in those with aneuploidy and adenomas, compared with controls. Of the 35 individuals undergoing adenoma surveillance, eight had recurrent adenomas, and three of these expressed aneuploidy. In the other 27, in whom no adenomas were found, no individual expressed aneuploidy (P = 0.01, Fisher's exact test). Aneuploidy within histologically normal mucosa is an unusual feature, which requires further investigation, particularly in patients developing adenomas.

Cell kinetics of the in vitro metaphase arrest technique and the clinical applications.

The in vitro metaphase arrest technique (crypt cell production rate-CPPR) has been used to measure human rectal mucosal proliferation. Study of preincubation times, dose response curves and lag phases suggest that a concentration of vincristine of 5 micrograms/ml and 16 hour preincubation with time point increments between 25 and 125 minutes give optimal conditions for measuring rectal mucosal proliferation. Twenty individuals had rectal CCPR repeated without intervention of any kind. Close correlation was found between the two values (r = 0.89 and P = 0.0001). The effect of polyethylene glycol bowel preparation was also studied in 35 subjects. There was good correlation (r = 0.66, P = 0.007). There was close correlation between rectal and caecal CCPR as measured in 20 patients who had colonoscopy (r = 0.72, P = 0.0003). The in vitro metaphase arrest technique is a useful parameter of rectal mucosal proliferation and may be used with confidence in a number of different clinical situations.

The identification of high and low risk groups for colorectal cancer using rectal mucosal crypt cell production rate (CCPR).

Rectal mucosal proliferation was measured in 116 individuals using the metaphase arrest technique crypt cell production rate (CCPR). CCPR was found to be significantly elevated in individuals with adenomas (n = 42, CCPR = 13 cc c-1h-1, range 7-25 Cl 10-15) compared with normals (n = 21, CCPR = 10 cc c-1h-1 range 5-24 Cl 7-11, Mann-Whitney P = 0.001 z = 3.2). Mucosal proliferation was increased among individuals who were undergoing adenoma follow up but in whom no further adenomas were found (n = 37 CCPR = 12 range 5-26 cc c-1h-1 Cl 10-14) compared to controls (Mann-Whitney P = 0.01 z = 2.4) Proliferation in vegetarians i.e. low risk (n = 16) was similar to controls. Measurement of proliferative indices in rectal mucosa by the stathmokinetic technique CCPR can discriminate between high and low risk groups for colorectal cancer.