Serum 25-hydroxy vitamin D and survival in advanced colorectal cancer: a retrospective analysis.

Higher serum 25-hydroxy vitamin D [25(OH)D] levels are associated with decreased colorectal cancer (CRC) incidence. In this retrospective study of Stage IV CRC patients, we evaluate whether 25(OH)D levels at diagnosis correlate with survival. Stored sera from carcinoembryonic antigen (CEA) measurements obtained between February 2005 and March 2006 were screened. The first 250 patients with CEA ± 30 days of Stage IV CRC diagnosis were included. Serum 25(OH)D levels were determined and categorized as adequate ≥ 30 ng/mL, or deficient <30 ng/mL. Multivariable Cox regression models controlling for albumin and Eastern Cooperative Oncology Group performance status were used to investigate whether higher 25(OH)D levels were associated with prolonged survival. A total of 207 patients (83%) were vitamin D-deficient (median = 21 ng/mL), with deficiencies significantly more likely among non-Hispanic black patients (P = 0.009). Higher levels were associated with prolonged survival in categorical variable analysis: adequate vs. deficient, hazard ratio = 0.61, 95% confidence interval = 0.38-0.98, P = 0.041. A majority of newly diagnosed Stage IV CRC patients are vitamin D-deficient. Our data suggest that higher 25(OH)D levels are associated with better overall survival. Clinical trials to determine whether aggressive vitamin D repletion would improve outcomes for vitamin D-deficient CRC patients are warranted.

Suitability of quality control materials for prostate-specific antigen (PSA) measurement: inter-method variability of common tumor marker control materials.

BACKGROUND: Quality control materials with minimal inter-assay differences and clinically relevant proportions of different molecular forms of the analyte are needed to optimize intra- and inter-laboratory accuracy and precision. METHODS: We assessed if clinically relevant total prostate-specific antigen (tPSA) levels were present in seven commercially available Multi Constituent Tumor Marker Controls (MC-TMC). Further, we determined the concentration of free PSA (fPSA) and calculated the percentage of free PSA (%fPSA) in all materials. Finally, we determined variability of TMC materials across several commonly used PSA platforms. RESULTS: All MC-TMC materials contained at least one concentration of tPSA in normal and pathologic range. Control materials varied in the amount of fPSA and %fPSA, with most controls consisting of fPSA only and only one MC-TMC containing medically relevant levels of around 35% fPSA. Only a minority of MC-TMC materials showed minimal variability across four PSA methods while the majority of PSA controls showed wide inter-method differences. CONCLUSIONS: Use of many commercially available controls for PSA could lead to biased PSA measurements because they contain medically irrelevant proportions of fPSA and show significant variation among different PSA assay platforms.

Role of nutrients in the development of neonatal immune response.

Nutrients exert unique regulatory effects in the perinatal period that mold the developing immune system. The interactions of micronutrients and microbial and environmental antigens condition the post-birth maturation of the immune system, influencing reactions to allergens, fostering tolerance towards the emerging gastrointestinal flora and ingested antigens, and defining patterns of host defense against potential pathogens. The shared molecular structures that are present on microbes or certain plants, but not expressed by human cells, are recognized by neonatal innate immune receptors. Exposure to these activators in the environment through dietary intake in early life can modify the immune response to allergens and prime the adaptive immune response towards pathogens that express the corresponding molecular structures.

Clinical events in prostate cancer lifestyle trial: results from two years of follow-up.

OBJECTIVES: Previous research has demonstrated that patients with prostate cancer participating in the Prostate Cancer Lifestyle Trial had a reduction in prostate-specific antigen (PSA) levels, inhibition of LNCaP cell growth, and fewer prostate cancer-related clinical events at the end of 1 year compared with controls. The aim of this study was to examine the clinical events in this trial during a 2-year period. METHODS: The Prostate Cancer Lifestyle Trial was a 1-year randomized controlled clinical trial of 93 patients with early-stage prostate cancer (Gleason score <7, PSA 4-10 ng/mL) undergoing active surveillance. The patients in the experimental arm were encouraged to adopt a low-fat, plant-based diet, to exercise and practice stress management, and to attend group support sessions. The control patients received the usual care. RESULTS: By 2 years of follow-up, 13 of 49 (27%) control patients and 2 of 43 (5%) experimental patients had undergone conventional prostate cancer treatment (radical prostatectomy, radiotherapy, or androgen deprivation, P < .05). No differences were found between the groups in other clinical events (eg, cardiac), and no deaths occurred. Three of the treated control patients but none of the treated experimental patients had a PSA level of >or=10 ng/mL, and 1 treated control patient but no treated experimental patients had a PSA velocity of >2 ng/mL/y before treatment. No significant differences were found between the untreated experimental and untreated control patients in PSA change or velocity at the end of 2 years. CONCLUSIONS: Patients with early-stage prostate cancer choosing active surveillance might be able to avoid or delay conventional treatment for at least 2 years by making changes in their diet and lifestyle.

Intensive lifestyle changes may affect the progression of prostate cancer.

PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.

A neuroanatomical construct for the amnesic effects of propofol.

BACKGROUND: This study was designed to identify neuroanatomical locations of propofol's effects on episodic memory by producing minimal and maximal memory impairment during conscious sedation. Drug-related changes in regional cerebral blood flow (rCBF) were located in comparison with rCBF increases during a simple word memory task. METHODS: Regional cerebral blood flow changes were assessed in 11 healthy volunteers using H215O positron emission tomography (PET) and statistical parametric mapping (SPM99) at 600 and 1,000 ng/ml propofol target concentrations. Study groups were based on final recognition scores of auditory words memorized during PET scanning. rCBF changes during propofol administration were compared with those during the word memory task at baseline. RESULTS: Nonoverlapping memory effects were evident: low (n = 4; propofol concentration 523 +/- 138 ng/ml; 44 +/- 13% decrement from baseline memory) and high (n = 7; 829 +/- 246 ng/ml; 87 +/- 6% decrement from baseline) groups differed in rCBF reductions primarily in right-sided prefrontal and parietal regions, close to areas activated in the baseline memory task, particularly R dorsolateral prefrontal cortex (Brodmann area 46; x, y, z = 51, 38, 22). The medial temporal lobe region exhibited relative rCBF increases. CONCLUSIONS: As amnesia becomes maximal, rCBF reductions induced by propofol occur in brain regions identified with working memory processes. In contrast, medial temporal lobe structures were resistant to the global CBF decrease associated with propofol sedation. The authors postulate that the episodic memory effect of propofol is produced by interference with distributed cortical processes necessary for normal memory function rather than specific effects on medial temporal lobe structures.

Development of immunocompetence: role of micronutrients and microorganisms.

Normal maturation of immune response at birth is both supported and stimulated by the gastrointestinal microenvironment, which provides both nutrients and antigenic microbial exposure to the developing child. Micronutrients, trace elements, and vitamins are present in the local environment and have important regulatory effects on adaptive immune cell function through effects on type of cytokine response. Congenital HIV infection is critically affected by both nutrient imbalance and alteration in gastrointestinal microflora, which may impair growth and development as well as immune response. Studies described here indicate that micronutrient deficiency is common in congenital HIV exposure even where infection has not occurred and that gastrointestinal recolonization may exert a restorative effect on both immune response and growth in children with HIV infection.

Ovarian cancer antigen CA125 is encoded by the MUC16 mucin gene.

Serum assays based on the CA125 antigen are widely used in the monitoring of patients with ovarian cancer; however very little is known about the molecular nature of the CA125 antigen. We recently cloned a partial cDNA (designated MUC16) that codes for a new mucin that is a strong candidate for being the CA125 antigen. This assignment has now been confirmed by transfecting a partial MUC16 cDNA into 2 CA125-negative cell lines and demonstrating the synthesis of CA125 by 3 different assays. Of the 3 antibodies (OC125, M11 and VK-8) tested on the transfected cells, only the first 2 were strongly positive, indicating the differential expression of the CA125 epitopes in these cells. The cloning and expression of CA125 antigen opens the way to an understanding of its function in normal and malignant cells.

Midazolam decreases cerebral blood flow in the left prefrontal cortex in a dose-dependent fashion.

Midazolam, a short-lived benzodiazepine producing sedation and reversible anterograde amnesia, was administered intravenously to 14 healthy male volunteers. Regional cerebral blood flow (rCBF) was measured using positron emission tomography (PET) with intravenous H2 15O at either a 'high' midazolam EEG effect (EEG signs of stage 2 sleep), or 'low' midazolam EEG effect (increase in EEG beta power only). Memory tests administered following PET scans showed significant drug-induced impairment in learning and retrieval at the same drug concentration at which PET images were acquired. Statistical parametric mapping was used to identify regions where rCBF changes after drug administration were significantly different in the high- vs. low- effect groups. Dosexcondition interactions were found in the left dorsolateral prefrontal cortex [Brodmann's areas (BA) 9 and 46], bilateral orbital-frontal cortex (BA 47), the left middle temporal gyrus (BA 22) and the right hippocampus. The predominantly left frontal rCBF decreases occur in a region associated with semantic processing, working memory, and encoding of verbal material, a process preferentially affected by midazolam. Our interpretation is that rCBF changes in the hippocampus are unlikely to mediate the anterograde amnesia produced by midazolam. Although in the present study PET images were acquired during the resting state rather than during memory processing, these results underscore the need for further investigation relating to the interaction of midazolam with specific cognitive operations in these brain regions.