Christopher Jensen

Role of water-soluble dietary fiber in the management of elevated plasma cholesterol in healthy subjects.

Guidelines for the use of water-soluble dietary fibers (WSDF) in the dietary management of elevated plasma cholesterol are not well-established. Consequently, 4 studies were conducted to explore the plasma lipid-lowering effects of a variety of WSDF. Studies were randomized, double-blind, placebo-controlled trials involving healthy men and women (plasma cholesterol greater than 5.17 mmol/liter; greater than 200 mg/dl). Study duration ranged from 4 to 12 weeks. The WSDF acacia gum yields a low viscosity, palatable beverage when mixed in water. However, despite its WSDF classification, acacia gum consumed for 4 weeks as the sole WSDF source (15 g of WSDF/day) or primary source in a WSDF mixture (17.2 g of WSDF/day; 56% derived from acacia gum) did not produce a significant lipid-lowering effect versus placebo. When 15 g of WSDF/day consisting of psyllium hust, pectin, and guar and locust bean gums (medium viscosity) was consumed for 4 weeks, significant reductions in cholesterol resulted (total cholesterol 8.3%, low-density lipoprotein cholesterol 12.4%; p less than 0.001) that were comparable to changes achieved with 10 g of WSDF/day from high-viscosity guar gum. The magnitude of the lipid-lowering effect was related to intake of WSDF ranging from 5 to 15 g/day (low-density lipoprotein cholesterol +0.8% [placebo], -5.6% [5 g/day], -6.8% [10 g/day], -14.9% [15 g/day]; p less than 0.01 for trend). The effects of WSDF on plasma lipids were similar for men and women. A diet rich in selected WSDF may be a useful adjunct to the dietary management of elevated plasma cholesterol.

Intraindividual variability of plasma antioxidants, markers of oxidative stress, C-reactive protein, cotinine, and other biomarkers

Background: Within-person variability in biomarkers results in random error that can attenuate estimates of association. Little information on such variability is available for a number of nutrition-related biomarkers. Methods: Blood samples obtained 2 to 4 weeks apart were analyzed for tocopherols, carotenoids, ascorbate, lipids, cotinine, C-reactive protein, and oxidative stress. Subjects (n = 206 men and women, mean age 45.4 years) were either smokers or passively exposed to smoke. We calculated intraindividual and interindividual variability and the number of measurements required to reduce attenuation. Results: For most biomarkers, 2 measurements would be required to limit the attenuation of correlation coefficients to no lower than 90% of the true correlation. If only one measurement were obtained, observed correlations would be approximately 80–88% of true correlations. For regression coefficients, 3 or 4 measures would be required. Exceptions were ascorbic acid and malondialdehyde, for which a single measure resulted in little attenuation. Conclusions: For most serum markers, collection of 2 or more measurements per person is desirable to increase the ability to detect associations between biomarkers and health-related variables. If only one measure is possible, sample sizes should be planned to permit detection of associations that are likely to be observed, not the theoretical true associations. The results of this study, in which measurements were obtained 2 to 4 weeks apart, are relevant for epidemiologic research in which the exposure of interest is the subject’s baseline or current status. It is likely that within-person variability would be greater over a period of months or years.

Long-term effects of water-soluble dietary fiber in the management of hypercholesterolemia in healthy men and women

Fifty-one healthy, moderately hypercholesterolemic men and women consuming their usual fat-modified diets completed a 6-month, randomized, double-blind, placebo-controlled, parallel comparison of 15 g/day supplemental water-soluble dietary fiber (WSDF; a mixture of psyllium, pectin, guar gum, and locust bean gum) and an inactive WSDF control (acacia gum). Compliance with the treatments was > 95%, adverse effects were minimal, and body weights remained constant. The WSDF mixture yielded 6.4% and 10.5% reductions in mean plasma total and low-density lipoprotein cholesterol concentrations, respectively, after 8 weeks, which were sustained at 16 and 24 weeks. Mean plasma high-density lipoprotein cholesterol and triglyceride concentrations were unchanged. No significant changes in mean plasma lipid or lipoprotein concentrations were observed in the control group. These data demonstrate that a WSDF approach to cholesterol management is effective as an adjunct to a fat-modified diet in healthy, moderately hypercholesterolemic men and women.

Maternal diet and risk of childhood acute lymphoblastic leukemia.

Objective. Intrauterine environmental factors, including maternal diet, may play an etiologic role in acute lymphoblastic leukemia (ALL), a common childhood cancer. Expanding on previous findings from phase 1 of the Northern California Childhood Leukemia Study (NCCLS), a population-based case-control study, we sought to further elucidate and replicate the relationships between maternal diet and ALL risk. Methods. We matched 282 case-control sets of children (205 pairs and 77 triplets) from phases 1 and 2 of the NCCLS on sex, date of birth, mothers race, Hispanic racial/ethnic status, and county of residence at birth. We used an interviewer-administered food frequency questionnaire to obtain information on maternal dietary intake in the 12 months prior to pregnancy. Results. Risk of ALL was inversely associated with maternal consumption of vegetable (adjusted odds ratio [AOR] = 0.65, 95% confidence interval [CI] 0.50, 0.84); protein sources (AOR=0.55, 95% CI 0.32, 0.96); fruit (AOR=0.81, 95% CI 0.65, 1.00); and legume food groups (AOR=0.75, 95% CI 0.59, 0.95). The risk reduction was strongest for consumption of the protein sources and vegetable food groups, independent of the childs diet up to age 2 years, and consistent across phases 1 and 2 of data collection for vegetable consumption. Conclusions. These data suggest that it may be prudent for women to consume a diet rich in vegetables and adequate in protein prior to and during pregnancy as a possible means of reducing childhood ALL risk in their offspring.

Treatment planning for radiotherapy with very high‐energy electron beams and comparison of VHEE and VMAT plans

PURPOSE The aim of this work was to develop a treatment planning workflow for rapid radiotherapy delivered with very high-energy electron (VHEE) scanning pencil beams of 60-120 MeV and to study VHEE plans as a function of VHEE treatment parameters. Additionally, VHEE plans were compared to clinical state-of-the-art volumetric modulated arc therapy (VMAT) photon plans for three cases. METHODS VHEE radiotherapy treatment planning was performed by linking EGSnrc Monte Carlo (MC) dose calculations with inverse treatment planning in a research version of RayStation. In order to study the effect of VHEE treatment parameters on VHEE dose distributions, a matlab graphical user interface (GUI) for calculation of VHEE MC pencil beam doses was developed. Through the GUI, pediatric case MC simulations were run for a number of beam energies (60, 80, 100, and 120 MeV), number of beams (13, 17, and 36), pencil beam spot (0.1, 1.0, and 3.0 mm) and grid (2.0, 2.5, and 3.5 mm) sizes, and source-to-axis distance, SAD (40 and 50 cm). VHEE plans for the pediatric case calculated with the different treatment parameters were optimized and compared. Furthermore, 100 MeV VHEE plans for the pediatric case, a lung, and a prostate case were calculated and compared to the clinically delivered VMAT plans. All plans were normalized such that the 100% isodose line covered 95% of the target volume. RESULTS VHEE beam energy had the largest effect on the quality of dose distributions of the pediatric case. For the same target dose, the mean doses to organs at risk (OARs) decreased by 5%-16% when planned with 100 MeV compared to 60 MeV, but there was no further improvement in the 120 MeV plan. VHEE plans calculated with 36 beams outperformed plans calculated with 13 and 17 beams, but to a more modest degree (<8%). While pencil beam spacing and SAD had a small effect on VHEE dose distributions, 0.1-3 mm pencil beam sizes resulted in identical dose distributions. For the 100 MeV VHEE pediatric plan, OAR doses were up to 70% lower and the integral dose was 33% lower for VHEE compared to 6 MV VMAT. Additionally, VHEE conformity indices (CI100 = 1.09 and CI50 = 4.07) were better than VMAT conformity indices (CI100 = 1.30 and CI50 = 6.81). The 100 MeV VHEE lung plan resulted in mean dose decrease to all OARs by up to 27% for the same target coverage compared to the clinical 6 MV flattening filter-free (FFF) VMAT plan. The 100 MeV prostate plan resulted in 3% mean dose increase to the penile bulb and the urethra, but all other OAR mean doses were lower compared to the 15 MV VMAT plan. The lung case CI100 and CI50 conformity indices were 3% and 8% lower, respectively, in the VHEE plan compared to the VMAT plan. The prostate case CI100 and CI50 conformity indices were 1% higher and 8% lower, respectively, in the VHEE plan compared to the VMAT plan. CONCLUSIONS The authors have developed a treatment planning workflow for MC dose calculation of pencil beams and optimization for treatment planning of VHEE radiotherapy. The authors have demonstrated that VHEE plans resulted in similar or superior dose distributions for pediatric, lung, and prostate cases compared to clinical VMAT plans.

Black Is the New Black: Prolapsing Primary Anorectal Melanoma

A 59-year-old Caucasian male was evaluated in the emergency department for a several-month history of a prolapsing, previously reducible anorectal mass. Examination revealed a large, black mass prolapsing through the anus (Fig. 1). After manual reduction, a CT scan showed a 7.4 cm 9 5.3 cm mass that extended from the proximal rectum to the anus, with near-complete obstruction of the proximal rectum (Fig. 2). Given the risk of recurrent incarcerated prolapse and the need for tissue diagnosis, the decision was made to proceed with excisional biopsy. Operative examination demonstrated two large pedunculated black masses originating from the distal rectum that were resected. Otherwise, the rectal mucosa appeared mildly inflamed but normal. The patient was discharged home the same day. Histologic sections of the specimens showed large, pleomorphic cells with prominent cherry-red nucleoli and brown pigmentation, melanin and Sry-related HMgBox gene (SOX)-10 positive, consistent with malignant melanoma (Fig. 3). Melanoma cells invaded the stalks of both specimens. A combined positron emission/computed tomography scan showed no evidence of fluorodeoxyglucose-avid lymphadenopathy or metastatic disease. Multidisciplinary tumor board discussion of the case recommended wide local excision of the surgical sites to confirm negative margins, and sentinel lymph node biopsy with possible inguinal lymphadenectomy, followed by adjuvant radiotherapy and systemic chemotherapy. The patient, who was from out of state, elected to return home and pursue therapy for his cancer at another medical center. Consequently, he was lost to follow-up.