Calcium intake has been consistently, modestly inversely associated with colorectal neoplasms, and supplemental calcium reduced adenoma recurrence in clinical trials. Milk products are the major ...source of dietary calcium in the United States, but their associations with colorectal neoplasms are unclear. Data pooled from three colonoscopy-based case-control studies of incident, sporadic colorectal adenoma (n = 807 cases, 2,185 controls) were analyzed using multivariable unconditional logistic regression. Residuals from linear regression models of milk with dietary calcium were estimated as the noncalcium, insulin-like growth factor 1-containing component of milk. For total, dietary, and supplemental calcium intakes, the adjusted odds ratios (ORs) comparing the highest to the lowest intake quintiles were 0.94 (95% confidence interval CI 0.69-1.30), 0.86 (CI 0.62-1.20), and 0.99 (CI 0.77-1.27), respectively. The corresponding ORs for consumption of total milk products, total milk, nonfat milk, total milk product residuals, and nonfat milk residuals were, respectively, 0.99, 0.90, 0.92, 0.94, and 0.95; all CIs included 1.0. For those who consumed any whole milk relative to those who consumed none, the OR was 1.15 (CI 0.89-1.49). These results are consistent with previous findings of modest inverse associations of calcium intakes with colorectal adenoma, but suggest that milk products may not be associated with adenoma.
Pigmented villonodular synovitis (PVNS) is an uncommon proliferative lesion of synovial tissue. In diffuse PVNS, recurrence rates are high after resection alone. Adjuvant external beam radiation ...therapy contributes to improved local control. Limited data exist for intra-articular radioisotope therapy after surgical resection. We report institutional experience with intra-articular chromic phosphate ((32)P).
Records were reviewed from the Department of Radiation Oncology at Indiana University. Nine cases of PVNS treated with (32)P were identified (mean age=40). Seven patients were treated at time of recurrence and 2 patients were treated prophylactically. Intra-articular injections were performed by accessing the joint space, aspirating joint fluid, reinjecting 1-2 mCi of (32)P, and barbitaging to ensure good distribution in the joint space. No external beam radiation therapy was delivered. One patient was lost to followup. Mean followup of remaining patients was 20 months (range, 2-48).
Eleven injections were performed in 9 patients. Eight had PVNS in the knee(s) and 1 patient had involvement of the hip. Two patients were treated more than once, one for a recurrence in the same joint at 13 months and another for PVNS of a contralateral joint. Three clinical recurrences (2, 13, and 28 months) were noted. Two of three recurrences were in patients who had bulky diffuse PVNS at the time of injection. Overall local control was 70%. In patients without bulky diffuse PVNS at the time of injection, local control was 88%.
We report success using intra-articular injections of (32)P after synovectomy in patients with PVNS.
Depletion or dysfunction of CD4+ T lymphocytes profoundly perturbs host defenses and impairs immunogenicity of vaccines. Here, we show that plasmid DNA vaccination with a cassette encoding antigen ...(OVA) and a second cassette encoding full-length CD40 ligand (CD40L), a molecule expressed on activated CD4+ T lymphocytes and critical for T cell helper function, can elicit significant titers of antigen-specific immunoglobulins in serum and Tc1 CD8+ T cell responses in CD4-deficient mice. To investigate whether this approach leads to CD4+ T cell-independent vaccine protection against a prototypic AIDS-defining infection, Pneumocystis (PC) pneumonia, we used serum from mice vaccinated with PC-pulsed, CD40L-modified DCs to immunoprecipitate PC antigens. Kexin, a PC antigen identified by this approach, was used in a similar DNA vaccine strategy with or without CD40L. CD4-deficient mice receiving DNA vaccines encoding Kexin and CD40L showed significantly higher anti-PC IgG titers as well as opsonic killing of PC compared with those vaccinated with Kexin alone. Moreover, CD4-depleted, Kexin-vaccinated mice showed a 3-log greater protection in a PC challenge model. Adoptive transfer of CD19+ cells or IgG to SCID mice conferred protection against PC challenge, indicating a role of humoral immunity in the protection. The results of these studies show promise for CD4-independent vaccination against HIV-related or other opportunistic pathogens.
Electron-rich aryl ethers and phenols react with isoprene (2-methylbuta-1,3-diene) in the presence of catalytic Bi(OTf)(3) at 40 °C to afford the corresponding prenylated or 2,2-dimethylchroman ...products, respectively, in moderate to good yields. This transformation offers a convenient and expedient entry to prenylated derivatives of electron-rich aromatics that often display enhanced biological activities. The methodology has been employed in the efficient synthesis of a biologically active natural product and related compounds.
Given temporal changes in diabetes prevalence and stroke incidence, this study investigated age, race, and sex differences in the diabetes-stroke association in a contemporary prospective cohort, the ...REasons for Geographic and Racial Differences in Stroke (REGARDS) Study.
We included 23,002 non-Hispanic black and white U.S. adults aged ≥45 years without prevalent stroke at baseline (2003-2007). Diabetes was defined as fasting glucose ≥126 mg/dL, random glucose ≥200 mg/dL, or use of glucose-lowering medication. Incident stroke events were expert adjudicated and available through September 2017.
The prevalence of diabetes was 19.1% at baseline. During follow-up, 1,018 stroke events occurred. Among adults aged <65 years, comparing those with diabetes to those without diabetes, the risk of stroke was increased for white women (hazard ratio HR 3.72 95% CI 2.10-6.57), black women (HR 1.88 95% CI 1.22-2.90), and white men (HR 2.01 95% CI 1.27-3.27) but not black men (HR 1.27 95% CI 0.77-2.10) after multivariable adjustment. Among those aged ≥65 years, diabetes increased the risk of stroke for white women and black men, but not black women (HR 1.05 95% CI 0.74-1.48) or white men (HR 0.86 95% CI 0.62-1.21).
In this contemporary cohort, the diabetes-stroke association varied by age, race, and sex together, with a more pronounced effect observed among adults aged <65 years. With the recent increase in the burden of diabetes complications at younger ages in the U.S., additional efforts are needed earlier in life for stroke prevention among adults with diabetes.
Background: The United States implemented mandatory folic acid fortification of enriched cereal grains in 1998. Although several studies have documented the resulting decrease in anemia and folate ...deficiency, to our knowledge, no one has determined the prevalence of folate-deficiency anemia after fortification.Objective: We determined the prevalence of folate deficiency and folate-deficiency anemia within a sample of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort.Design: The REGARDS cohort is a prospective cohort of 30,239 black and white participants living in the contiguous United States. We measured serum folate concentrations in a random sample of 1546 REGARDS participants aged ≥50 y with baseline hemoglobin and red blood cell mean corpuscular volume measurements. Folate deficiency was defined as a serum folate concentration <6.6 nmol/L (<3.0 ng/mL), and anemia was defined as a hemoglobin concentration <13 g/dL in men and <12 g/dL in nonpregnant women (WHO criteria). Folate-deficiency anemia was defined as the presence of both folate deficiency and anemia.Results: The mean hemoglobin concentration was 13.6 g/dL, and 15.9% of subjects had anemia. The median serum folate concentration was 34.2 nmol/L (15.1 ng/mL), and only 2 of 1546 participants 0.1%) were folate deficient. Both subjects were African American women with markedly elevated C-reactive protein concentrations, macrocytosis, and normal serum cobalamin concentrations; only one subject was anemic. Overall, the prevalence of folate-deficiency anemia was <0.1% (1 of 1546 subjects).Conclusion: Our data suggest that, after mandatory folic acid fortification, the prevalence of folate-deficiency anemia is nearly nonexistent in a community-dwelling population in the United States.
Serum albumin concentration is a commonly available biomarker with prognostic value in many disease states. It is uncertain whether serum albumin concentrations are associated with incident end-stage ...renal disease (ESRD) independently of urine albumin-to-creatinine ratio (ACR).
A longitudinal evaluation was performed of a population-based community-living cohort from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. Participants were ≥45 years of age at study entry and had serum albumin, creatinine, cystatin C and spot urine ACR measured at the baseline visit (n = 19 633). Estimated glomerular filtration rate (eGFR) was from the Chronic Kidney Disease Epidemiology Collaboration combined creatinine-cystatin C equation. Baseline serum albumin concentration was the predictor variable, and hazard ratios (HRs) for incident ESRD (from US Renal Data System linkage) were calculated in sequentially adjusted models.
Age at study entry was 63.9 ± 9.7 years, 62% of the participants were female and 40% were black. Mean eGFR at baseline was 83.3 ± 20.8 mL/min/1.73 m2. Over a median 8-year follow-up, 1.2% (n = 236) developed ESRD. In models adjusted for baseline eGFR, ACR and other ESRD risk factors, the HR for incident ESRD was 1.16 95% confidence interval (CI) 1.01-1.33 for each standard deviation (0.33 g/dL) lower serum albumin concentration. The HR comparing the lowest (<4 g/dL) and highest quartiles (≥4.4 g/dL) of serum albumin was 1.61 (95% CI 0.98-2.63). Results were qualitatively similar among participants with eGFR <60 and ≥60 mL/min/1.73 m2, and those with and without diabetes.
In community-dwelling US adults, lower serum albumin concentration is associated with higher risk of incident ESRD independently of baseline urine ACR, eGFR and other ESRD risk factors.
To determine the efficacy and safety of commonly prescribed regimens for the treatment of vitamin D insufficiency.
We performed a retrospective analysis of 306 consecutive patients who were ...prescribed ergocalciferol (vitamin D2) for correction of vitamin D insufficiency at the Atlanta Veterans Affairs Medical Center between February 2003 and May 2006. Serum levels of parathyroid hormone, 25-hydroxyvitamin D (25-OHD), and calcium were compared before and after treatment with ergocalciferol. Patients who did not have a 25-OHD determination (n = 41) were excluded from analysis. Vitamin D deficiency, insufficiency, and sufficiency were defined as a serum 25-OHD level of <20 ng/mL, 21 to 29 ng/mL, and > or =30 ng/mL, respectively.
We identified 36 discrete prescribing regimens. The 3 most common regimens were ergocalciferol 50,000 IU once weekly for 4 weeks followed by 50,000 IU once monthly for 5 months (n = 48); ergocalciferol 50,000 IU once monthly for 6 months (n = 80); and ergocalciferol 50,000 IU 3 times weekly for 6 weeks (n = 27). Each of these 3 treatments significantly increased serum 25-OHD (P<.01), but vitamin D sufficiency was achieved in only 38%, 42%, and 82% of study subjects, respectively. Regimens with >600,000 IU of ergocalciferol given for a mean of 60 +/- 40 days achieved sufficiency in 64% of cases, without vitamin D toxicity.
In this study, regimens that contained at least 600,000 IU of ergocalciferol appeared to be the most effective in achieving vitamin D sufficiency. Guidelines for the treatment of vitamin D insufficiency in healthy adults should be developed.
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