Milk drinking, ischaemic heart disease and ischaemic stroke II. Evidence from cohort studies

OBJECTIVE: Milk consumption is considered a risk factor for vascular disease on the basis of relevant biological mechanisms and data from ecological studies. The aim was to identify published prospective studies of milk drinking and vascular disease, and conduct an overview. DESIGN: The literature was searched for cohort studies, in which an estimate of the consumption of milk, or the intake of calcium from dairy sources, has been related to incident vascular disease. MAIN OUTCOME MEASURES: Ischaemic heart disease and ischaemic stroke. RESULTS: In total, 10 studies were identified. Their results show a high degree of consistency in the reported risk for heart disease and stroke, all but one study suggesting a relative risk of less than one in subjects with the highest intakes of milk. A pooled estimate of relative odds in these subjects, relative to the risk in subjects with the lowest consumption, is 0.87 (95% CI 0.74-1.03) for ischaemic heart disease and 0.83 (0.77-0.90) for ischaemic stroke. The odds ratio for any vascular event is 0.84 (0.78-0.90). CONCLUSIONS: Cohort studies provide no convincing evidence that milk is harmful. While there still could be residual confounding from unidentified factors, the studies, taken together, suggest that milk drinking may be associated with a small but worthwhile reduction in heart disease and stroke risk. SPONSORSHIP: The University of Wales College of Medicine and Bristol University. Current support is from the Food Standards Agency.     

A decrease in physical activity affects appetite, energy, and nutrient balance in lean men feeding ad libitum

BACKGROUND: It is not clear how decreased activity quantitatively affects energy balance (EB) in subjects feeding ad libitum. OBJECTIVE: We assessed the effect of an imposed sedentary routine on appetite, energy intake (EI), EB, and nutrient balance in lean men for 7 d. DESIGN: Six men with a mean (+/-SD) age of 23.0 +/- 2.3 y, weight of 69.2 +/- 11.4 kg, and height of 1.76 +/- 0.07 m were each studied twice during a sedentary [1.4 x resting metabolic rate (RMR)] and a moderately active (1.8 x RMR) regimen. During each treatment, they resided in the whole-body indirect calorimeter for the 7 d and had ad libitum access to a medium-fat diet of constant, measurable composition. Meal size, frequency, and composition were continually monitored. Motivation to eat was recorded during waking hours. Subjects were weighed in light clothing each morning, and their weight was corrected to nude. RESULTS: Energy expenditure was 9.7 and 12.8 MJ/d [P < 0.01; SE of the difference between means (SED) = 0.41] during the sedentary and active regimens, respectively. EI was 13.5 and 14.4 MJ/d (P = 0.463, SED = 1.06), respectively. There was no regimen effect on hunger, appetite, or body weight. By day 7, cumulative EB was 26.3 and 11.1 MJ, respectively. CONCLUSIONS: Reducing a level of physical activity from 1.8 to 1.4 x RMR can markedly affect EB. A sedentary routine does not induce a compensatory reduction of EI and leads to a significantly positive EB, most of which is stored as fat.     

Testing for prostate and colorectal cancer: comparison of self-report and medical record audit

BACKGROUND: Self-reported data are often used to determine cancer screening test utilization, but self-report may be inaccurate. METHODS: We interviewed members of three health maintenance organizations and reviewed their medical records for information on digital rectal exam (DRE), prostate-specific antigen (PSA) test, fecal occult blood test (FOBT), sigmoidoscopy, and colonoscopy (response rate 65%). We calculated the sensitivity, specificity, concordance, and kappa statistic to compare the two sources for black men (n = 363), white and other men (n = 847), and women (n = 920) by study location. RESULTS: For DRE, FOBT, sigmoidoscopy, and colonoscopy, testing rates determined by self-report were higher than those in medical records. Kappa statistics showed fair to good agreement (0.40-0.80) for PSA, sigmoidoscopy, and colonoscopy among most subgroups. For DRE and FOBT, the agreement was poor except among participants from one HMO. Sensitivity was > or = 80% for sigmoidoscopy among most subgroups, and > or = 85% for endoscopy (sigmoidoscopy and colonoscopy), >75% for DRE, and > or = 63% for PSA among all subgroups. Specificity exceeded 80% for FOBT and colonoscopy among all subgroups. Agreement was lower among older age groups. For all tests, agreement was poor between the reasons for testing. CONCLUSION: Overreporting for some cancer tests should be considered when using self-reported data to evaluate progress towards reaching national goals for prevention behaviors.     

The view from two sides: a qualitative study of community and medical perspectives on screening for colorectal cancer using FOBT

BACKGROUND: Population-wide screening for people at average risk of colorectal cancer (CRC) by faecal occult blood test (FOBT) is under consideration in Australia. METHODS: Qualitative methods were used to examine the views of community members who did (n = 18) or did not (n = 12) participate in a pilot program of FOBT screening. In addition, views were obtained from general practitioners (GPs) and specialist gastroenterologists directly involved in the implementation of the program. Two focus group sessions were conducted with screening participants and interviews were conducted with nonparticipants, GPs and gastroenterologists. RESULTS: The findings suggest that CRC screening by FOBT distributed to households by mail was well accepted by the community and by the medical practitioners involved in its implementation. The trial had little negative effect on general practice. Both medical practitioners and consumers raised concerns about the efficacy of FOBT screening. Medical practitioners were also concerned about the potential burden mass screening could place on the public (government-funded) health care sector. CONCLUSIONS: It would seem that CRC screening using FOBT will not enjoy unqualified support from the community or from medical practitioners involved in the continuum of screening. Information about the objectives of screening programs, in general, and the efficacy of FOBT screening in particular, needs to be provided to the community to ensure informed individual choice.     

Benzoxepin-derived estrogen receptor modulators: a novel molecular scaffold for the estrogen receptor

We present and examine the efficacy of a novel benzoxepin-based scaffold for modulation of the human estrogen receptor. Receptor tolerance of this new molecular scaffold is examined through presentation of experimentally determined antiproliferative effects on human MCF-7 breast tumor cells and measured binding affinities. The effect of functional group substitution on the benzoxepin scaffold is explored through a brief computational structure-activity relationship investigation with molecular simulation.     

6-azapyrimidine-2'-deoxy-4'-thionucleosides: antiviral agents against TK+ and TK- HSV and VZV strains

The synthesis of a series of novel 1-(2-deoxy-4-thio-beta-D-erythro-pentofuranosyl)-(6-azapyrimidine) nucleosides is described. X-ray crystallographic data of the thymidine derivative allowed conformational analysis, which indicated a twist (3T2) sugar conformation. Hydrogen-bonded assemblies for the crystal structure were determined using PLATON software to allow further interpretation of the crystal packing and base interactions. The 6-azapyrimidine nucleosides described were evaluated against a range of viral strains. The thymidine analogue showed pronounced activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), varicella-zoster virus (VZV), and vaccinia virus. This compound lost only 5- to 10-fold of its antiviral activity against thymidine kinase (TK)-deficient HSV-1 and VZV strains. These observations suggest that the compounds may not entirely depend on viral TK-catalyzed phosphorylation for antiviral activity and/or use an alternative metabolic activation pathway, and/or display a unique mechanism of antiviral action by the unmetabolized nucleoside analogue.     

A GC-MS method for the determination of isoxsuprine in biological fluids of the horse utilizing electron impact ionization

Isoxsuprine is used to treat navicular disease and other lower-limb problems in the horse. Isoxsuprine is regulated as a class 4 compound by the Association of Racing Commissioners, International (ARCI) and, thus, requires regulatory monitoring. A gas chromatography-mass spectrometry method utilizing electron impact ionization was developed and validated for the quantitation of isoxsuprine in equine plasma or equine urine. The method utilized robotic solid-phase extraction and tri-methyl silyl ether products of derivatization. Products were bis-trimethylsilyl (TMS) isoxsuprine and tris-TMS ritodrine, which released intense quantifier ions m/z 178 for isoxsuprine and m/z 236 for ritodrine that were products of C-C cleavage. To our knowledge, this procedure is faster and more sensitive than other methods in the literature. Concentrations in urine and plasma of isoxsuprine were determined from a calibrator curve that was generated along with unknowns. Ritodrine was used as an internal standard and was, therefore, present in all samples, standards, and blanks. Validation data was also collected. The limit of detection of isoxsuprine in plasma was determined to be 2 ng/mL, the limit of quantitation of isoxsuprine in plasma was determined to be < 5 ng/mL. The mean coefficient of determination for the calibrator curves for plasma was 0.9925 +/- 0.0052 and for calibrator curves for urine 0.9904 +/- 0.0075. The recovery efficiencies at concentrations of 50, 200, and 300 ng/mL were 76%, 73%, and 76%, respectively, in plasma and 92%, 89%, and 91% in urine.     

Topical vapocoolant quickly and effectively reduces vaccine-associated pain: results of a randomized, single-blinded, placebo-controlled study

BACKGROUND: Comprehensive international travel preparation often requires several vaccines. Up to 90% of adults have some fear of injections, mostly due to injection-related pain. Pediatric studies with routine vaccines have shown topical anesthetic EMLA cream (lidocaine and prilocaine, Astra Pharmaceuticals, Inc.) and the topical vapocoolant Fluori-Methane (dichlorodifluoromethane and trichlorodifluoromethane, Gebauer Co.) to be equally effective in reducing pain from vaccinations. EMLA cream is expensive and requires a 60-min application, while Fluori-Methane (FM) is immediate in onset of action and inexpensive. Skin anesthesia begins at 10 degrees C. Fluori-Methane can briefly cool the skin to 0 degrees C. METHODS: We studied the effectiveness of topical vapocoolant on adult clients at our international travel clinic in a randomized, controlled trial of topical FM vs. cold (4 degrees C) saline placebo. Using a preset randomization table, participants served as their own controls, receiving placebo/control or active agent (participant blinded) in one arm (left or right), and a similar number of vaccines in the untreated arm. Vaccines were administered according to a set protocol per arm to minimize the risk of bias. Pain was measured using a modified McGill present pain intensity (PPI) pain index. Subjects rated their pain immediately and at 5 min on a six-level scale, noting treated and untreated arms separately. A questionnaire was completed on intervention preferences. Sample size was predetermined to achieve 90% statistical power estimating 25% efficacy (minimum n=172). RESULTS: One hundred and eighty-five participants were enrolled; 93 FM and 92 cold saline placebo. FM-treated arms had a significant reduction in immediate pain compared to untreated arms (pain scale mean 2.2 vs. 3.1; p<.0001), and compared to placebo (mean 2.2 vs. 2.8; p<.01). Delayed pain at 5 min was not affected by FM or control (mean 1.9 vs. 2.0) compared to no intervention (pain scale 1.9). The intervention preference questionnaire indicated that participants did not find FM therapy uncomfortable. They would choose FM therapy in the future, over a cream, especially if a wait was involved. CONCLUSION: The topical vapocoolant Fluori-Methane is an effective, quick, preferred, inexpensive agent for reducing vaccine-associated injection pain for international travel clients.     

Selective effects of simultaneous monoamine depletion on mood and emotional responsiveness

Monoamines play a significant role in the regulation of mood and emotion. While the selective effects of serotonin and catecholamine depletion on mood have been described, the effects of simultaneous monoamine depletion on subjective measures of mood and emotional responsiveness are yet to be examined. The current study aimed to investigate the effects of simultaneous monoamine depletion on mood and emotional responsiveness in healthy participants. Twenty female participants completed a randomized, double-blind, placebo-controlled study, under a balanced control condition (B), and a combined monoamine depletion condition (CMD; via tryptophan, tyrosine and phenylalanine depletion). Mood ratings Visual Analogue Mood Scale (VAMS) and Profile Of Mood States (POMS) and measures of emotional responsiveness (Emotional Stroop and International Affective Picture System) were examined at baseline and 5 h post-depletion. Following CMD, participants rated themselves as feeling sadder, more antagonistic, and mentally slower on three VAMS subscales. There were no significant mood changes found on the POMS or measures of emotional responsiveness. These findings suggest that simultaneous depletion of all monoamines may have selective effects on mood. The findings provide evidence that the simultaneous monoamine depletion technique may be a useful experimental method to probe central monoamine function in humans.