Showing papers by "University of Tennessee Health Science Center published in 2006"
Oak Ridge National Laboratory1, University of Tennessee2, West Virginia University3, Umeå University4, University of British Columbia5, United States Department of Energy6, Ghent University7, Swedish University of Agricultural Sciences8, Institut national de la recherche agronomique9, Virginia Tech10, Michigan Technological University11, University of Toronto12, Pennsylvania State University13, University of Provence14, University of Georgia15, University of Florida16, University of California, Berkeley17, Lawrence Berkeley National Laboratory18, University of Arizona19, Purdue University20, Stanford University21, United States Department of Agriculture22, University of Helsinki23, University of Turku24, Massachusetts Institute of Technology25, University of Tennessee Health Science Center26, University of Tübingen27
TL;DR: The draft genome of the black cottonwood tree, Populus trichocarpa, has been reported in this paper, with more than 45,000 putative protein-coding genes identified.
Abstract: We report the draft genome of the black cottonwood tree, Populus trichocarpa. Integration of shotgun sequence assembly with genetic mapping enabled chromosome-scale reconstruction of the genome. More than 45,000 putative protein-coding genes were identified. Analysis of the assembled genome revealed a whole-genome duplication event; about 8000 pairs of duplicated genes from that event survived in the Populus genome. A second, older duplication event is indistinguishably coincident with the divergence of the Populus and Arabidopsis lineages. Nucleotide substitution, tandem gene duplication, and gross chromosomal rearrangement appear to proceed substantially more slowly in Populus than in Arabidopsis. Populus has more protein-coding genes than Arabidopsis, ranging on average from 1.4 to 1.6 putative Populus homologs for each Arabidopsis gene. However, the relative frequency of protein domains in the two genomes is similar. Overrepresented exceptions in Populus include genes associated with lignocellulosic wall biosynthesis, meristem development, disease resistance, and metabolite transport.
4,025 citations
TL;DR: Although the loss of muscle mass is associated with the decline in strength in older adults, this strength decline is much more rapid than the concomitant loss of Muscle mass, suggesting a decline in muscle quality.
Abstract: BACKGROUND: The loss of muscle mass is considered to be a major determinant of strength loss in aging. However, large-scale longitudinal studies examining the association between the loss of mass and strength in older adults are lacking. METHODS: Three-year changes in muscle mass and strength were determined in 1880 older adults in the Health, Aging and Body Composition Study. Knee extensor strength was measured by isokinetic dynamometry. Whole body and appendicular lean and fat mass were assessed by dual-energy x-ray absorptiometry and computed tomography. RESULTS: Both men and women lost strength, with men losing almost twice as much strength as women. Blacks lost about 28% more strength than did whites. Annualized rates of leg strength decline (3.4% in white men, 4.1% in black men, 2.6% in white women, and 3.0% in black women) were about three times greater than the rates of loss of leg lean mass ( approximately 1% per year). The loss of lean mass, as well as higher baseline strength, lower baseline leg lean mass, and older age, was independently associated with strength decline in both men and women. However, gain of lean mass was not accompanied by strength maintenance or gain (ss coefficients; men, -0.48 +/- 4.61, p =.92, women, -1.68 +/- 3.57, p =.64). CONCLUSIONS: Although the loss of muscle mass is associated with the decline in strength in older adults, this strength decline is much more rapid than the concomitant loss of muscle mass, suggesting a decline in muscle quality. Moreover, maintaining or gaining muscle mass does not prevent aging-associated declines in muscle strength.
2,266 citations
Ohio State University1, Fred Hutchinson Cancer Research Center2, University of Cincinnati3, University of Iowa4, University of California, Davis5, University of Alabama at Birmingham6, University of Arizona7, University of Washington8, Rush University Medical Center9, Wake Forest University10, University of Nevada, Reno11, University of Texas at San Antonio12, Kaiser Permanente13, University of Pittsburgh14, University of California, Los Angeles15, Stony Brook University16, Baylor College of Medicine17, University of North Carolina at Chapel Hill18, Wayne State University19, Howard University20, George Washington University21, University of California, Irvine22, University of Tennessee Health Science Center23, Medical College of Wisconsin24, University of California, San Diego25, Rutgers University26, University of Florida27, National Institutes of Health28, Harvard University29, University of Minnesota30, University of Massachusetts Boston31, University of Miami32, Emory University33, University of Wisconsin-Madison34, Stanford University35, Northwestern University36, University at Buffalo37, Brown University38, Yeshiva University39
TL;DR: Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones.
Abstract: Background The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal. Methods We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers. Results Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P<0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with...
1,765 citations
TL;DR: Low muscle mass did not explain the strong association of strength with mortality, demonstrating that muscle strength as a marker of muscle quality is more important than quantity in estimating mortality risk.
Abstract: Background. Although muscle strength and mass are highly correlated, the relationship between direct measures of low muscle mass (sarcopenia) and strength in association with mortality has not been examined. Methods. Total mortality rates were examined in the Health, Aging and Body Composition (Health ABC) Study in 2292 participants (aged 70–79 years, 51.6% women, and 38.8% black). Knee extension strength was measured with isokinetic dynamometry, grip strength with isometric dynamometry. Thigh muscle area was measured by computed tomography (CT) scan, and leg and arm lean soft tissue mass were determined by dual energy x-ray absorptiometry (DXA). Both strength and muscle size were assessed as in gender-specific Cox proportional hazards models, with age, race, comorbidities, smoking status, level of physical activity, fat area by CT or fat mass by DXA, height, and markers of inflammation, including interleukin-6, C-reactive protein, and tumor necrosis factor-a considered as potential confounders. Results. There were 286 deaths over an average of 4.9 (standard deviation ¼ 0.9) years of follow-up. Both quadriceps and grip strength were strongly related to mortality. For quadriceps strength (per standard deviation of 38 Nm), the crude hazard ratio for men was 1.51 (95% confidence interval, 1.28–1.79) and 1.65 (95% confidence interval, 1.19–2.30) for women. Muscle size, determined by either CT area or DXA regional lean mass, was not strongly related to mortality. In the models of quadriceps strength and mortality, adjustment for muscle area or regional lean mass only slightly attenuated the associations. Further adjustment for other factors also had minimal effect on the association of quadriceps strength with mortality. Associations of grip strength with mortality were similar. Conclusion. Low muscle mass did not explain the strong association of strength with mortality, demonstrating that muscle strength as a marker of muscle quality is more important than quantity in estimating mortality risk. Grip strength provided risk estimates similar to those of quadriceps strength.
1,386 citations
TL;DR: The results suggest that for many women, discontinuation of alendronate for up to 5 years does not appear to significantly increase fracture risk, however, women at very high risk of clinical vertebral fractures may benefit by continuing beyond 5 years.
Abstract: ContextThe optimal duration of treatment of women with postmenopausal osteoporosis is uncertain.ObjectiveTo compare the effects of discontinuing alendronate treatment after 5 years vs continuing for 10 years.Design and SettingRandomized, double-blind trial conducted at 10 US clinical centers that participated in the Fracture Intervention Trial (FIT).ParticipantsOne thousand ninety-nine postmenopausal women who had been randomized to alendronate in FIT, with a mean of 5 years of prior alendronate treatment.InterventionRandomization to alendronate, 5 mg/d (n = 329) or 10 mg/d (n = 333), or placebo (n = 437) for 5 years (1998-2003).Main Outcome MeasuresThe primary outcome measure was total hip bone mineral density (BMD); secondary measures were BMD at other sites and biochemical markers of bone remodeling. An exploratory outcome measure was fracture incidence.ResultsCompared with continuing alendronate, switching to placebo for 5 years resulted in declines in BMD at the total hip (−2.4%; 95% confidence interval [CI], −2.9% to −1.8%; P<.001) and spine (−3.7%; 95% CI, −4.5% to −3.0%; P<.001), but mean levels remained at or above pretreatment levels 10 years earlier. Similarly, those discontinuing alendronate had increased serum markers of bone turnover compared with continuing alendronate: 55.6% (P<.001) for C-telopeptide of type 1 collagen, 59.5% (P < .001) for serum N = propeptide of type 1 collagen, and 28.1% (P<.001) for bone-specific alkaline phosphatase, but after 5 years without therapy, bone marker levels remained somewhat below pretreatment levels 10 years earlier. After 5 years, the cumulative risk of nonvertebral fractures (RR, 1.00; 95% CI, 0.76-1.32) was not significantly different between those continuing (19%) and discontinuing (18.9%) alendronate. Among those who continued, there was a significantly lower risk of clinically recognized vertebral fractures (5.3% for placebo and 2.4% for alendronate; RR, 0.45; 95% CI, 0.24-0.85) but no significant reduction in morphometric vertebral fractures (11.3% for placebo and 9.8% for alendronate; RR, 0.86; 95% CI, 0.60-1.22). A small sample of 18 transilial bone biopsies did not show any qualitative abnormalities, with bone turnover (double labeling) seen in all specimens.ConclusionsWomen who discontinued alendronate after 5 years showed a moderate decline in BMD and a gradual rise in biochemical markers but no higher fracture risk other than for clinical vertebral fractures compared with those who continued alendronate. These results suggest that for many women, discontinuation of alendronate for up to 5 years does not appear to significantly increase fracture risk. However, women at very high risk of clinical vertebral fractures may benefit by continuing beyond 5 years.Trial Registrationclinicaltrials.gov Identifier: NCT 00398931
1,295 citations
TL;DR: A delay in the initiation of fluconazole therapy in hospitalized patients with candidemia significantly impacted mortality, and new methods to avoid delays in appropriate antifungal therapy are needed.
Abstract: BACKGROUND Inadequate antimicrobial treatment is an independent determinant of hospital mortality, and fungal bloodstream infections are among the types of infection with the highest rates of inappropriate initial treatment. Because of significant potential for reducing high mortality rates, we sought to assess the impact of delayed treatment across multiple study sites. The goals our analyses were to establish the frequency and duration of delayed antifungal treatment and to evaluate the relationship between treatment delay and mortality. METHODS We conducted a retrospective cohort study of patients with candidemia from 4 medical centers who were prescribed fluconazole. Time to initiation of fluconazole therapy was calculated by subtracting the date on which fluconazole therapy was initiated from the culture date of the first blood sample positive for yeast. RESULTS A total of 230 patients (51% male; mean age +/- standard deviation, 56 +/- 17 years) were identified; 192 of these had not been given prior treatment with fluconazole. Patients most commonly had nonsurgical hospital admission (162 patients [70%]) with a central line catheter (193 [84%]), diabetes (68 [30%]), or cancer (54 [24%]). Candida species causing infection included Candida albicans (129 patients [56%]), Candida glabrata (38 [16%]), Candida parapsilosis (25 [11%]), or Candida tropicalis (15 [7%]). The number of days to the initiation of antifungal treatment was 0 (92 patients [40%]), 1 (38 [17%]), 2 (33 [14%]) or > or = 3 (29 [12%]). Mortality rates were lowest for patients who began therapy on day 0 (14 patients [15%]) followed by patients who began on day 1 (9 [24%]), day 2 (12 [37%]), or day > or = 3 (12 [41%]) (P = .0009 for trend). Multivariate logistic regression was used to calculate independent predictors of mortality, which include increased time until fluconazole initiation (odds ratio, 1.42; P < .05) and Acute Physiology and Chronic Health Evaluation II score (1-point increments; odds ratio, 1.13; P < .05). CONCLUSION A delay in the initiation of fluconazole therapy in hospitalized patients with candidemia significantly impacted mortality. New methods to avoid delays in appropriate antifungal therapy, such as rapid diagnostic tests or identification of unique risk factors, are needed.
1,072 citations
Memorial Hospital of South Bend1, Howard University2, Northwestern University3, George Washington University4, Harvard University5, Stanford University6, Yeshiva University7, University of Pittsburgh8, Fred Hutchinson Cancer Research Center9, University of California, San Diego10, Rutgers University11, University of Alabama at Birmingham12, University of Florida13, University of Minnesota14, Ohio State University15, University of Massachusetts Medical School16, University of Miami17, Emory University18, University of California, Davis19, National Institutes of Health20, University of Wisconsin-Madison21, University of Iowa22, Kaiser Permanente23, University at Buffalo24, Wake Forest University25, Pfizer26, Brown University27, University of Arizona28, Rush University Medical Center29, University of Nevada, Reno30, University of Texas at San Antonio31, University of California, Los Angeles32, University of Cincinnati33, Stony Brook University34, Baylor College of Medicine35, University of North Carolina at Chapel Hill36, Wayne State University37, University of California, Irvine38, University of Tennessee Health Science Center39, Medical College of Wisconsin40
TL;DR: A dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women and achieved only modest effects on CVD risk factors, suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVDrisk.
Abstract: ContextMultiple epidemiologic studies and some trials have linked diet with cardiovascular disease (CVD) prevention, but long-term intervention data are needed.ObjectiveTo test the hypothesis that a dietary intervention, intended to be low in fat and high in vegetables, fruits, and grains to reduce cancer, would reduce CVD risk.Design, Setting, and ParticipantsRandomized controlled trial of 48 835 postmenopausal women aged 50 to 79 years, of diverse backgrounds and ethnicities, who participated in the Women's Health Initiative Dietary Modification Trial. Women were randomly assigned to an intervention (19 541 [40%]) or comparison group (29 294 [60%]) in a free-living setting. Study enrollment occurred between 1993 and 1998 in 40 US clinical centers; mean follow-up in this analysis was 8.1 years.InterventionIntensive behavior modification in group and individual sessions designed to reduce total fat intake to 20% of calories and increase intakes of vegetables/fruits to 5 servings/d and grains to at least 6 servings/d. The comparison group received diet-related education materials.Main Outcome MeasuresFatal and nonfatal coronary heart disease (CHD), fatal and nonfatal stroke, and CVD (composite of CHD and stroke).ResultsBy year 6, mean fat intake decreased by 8.2% of energy intake in the intervention vs the comparison group, with small decreases in saturated (2.9%), monounsaturated (3.3%), and polyunsaturated (1.5%) fat; increases occurred in intakes of vegetables/fruits (1.1 servings/d) and grains (0.5 serving/d). Low-density lipoprotein cholesterol levels, diastolic blood pressure, and factor VIIc levels were significantly reduced by 3.55 mg/dL, 0.31 mm Hg, and 4.29%, respectively; levels of high-density lipoprotein cholesterol, triglycerides, glucose, and insulin did not significantly differ in the intervention vs comparison groups. The numbers who developed CHD, stroke, and CVD (annualized incidence rates) were 1000 (0.63%), 434 (0.28%), and 1357 (0.86%) in the intervention and 1549 (0.65%), 642 (0.27%), and 2088 (0.88%) in the comparison group. The diet had no significant effects on incidence of CHD (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.90-1.06), stroke (HR, 1.02; 95% CI, 0.90-1.15), or CVD (HR, 0.98; 95% CI, 0.92-1.05). Excluding participants with baseline CVD (3.4%), the HRs (95% CIs) for CHD and stroke were 0.94 (0.86-1.02) and 1.02 (0.90-1.17), respectively. Trends toward greater reductions in CHD risk were observed in those with lower intakes of saturated fat or trans fat or higher intakes of vegetables/fruits.ConclusionsOver a mean of 8.1 years, a dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women and achieved only modest effects on CVD risk factors, suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVD risk.Clinical Trials RegistrationClinicalTrials.gov Identifier: NCT00000611
1,000 citations
University at Buffalo1, Medical College of Wisconsin2, Fred Hutchinson Cancer Research Center3, Pfizer4, Memorial Hospital of Rhode Island5, University of Nevada, Reno6, University of Miami7, University of Minnesota8, University of Massachusetts Medical School9, Emory University10, National Institutes of Health11, University of California, Davis12, Yeshiva University13, University of Wisconsin-Madison14, Stanford University15, Northwestern University16, University of Iowa17, Kaiser Permanente18, University of Arizona19, University of Washington20, Rush University Medical Center21, Wake Forest University22, University of Texas at San Antonio23, University of California, Los Angeles24, University of California, San Diego25, University of Cincinnati26, Baylor College of Medicine27, University of North Carolina at Chapel Hill28, Wayne State University29, Howard University30, George Washington University31, University of California, Irvine32, Ohio State University33, University of Tennessee Health Science Center34, University of Pittsburgh35, Stony Brook University36, Rutgers University37, University of Alabama at Birmingham38, University of Florida39, Harvard University40
TL;DR: Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women, and the long latency associated with the development of colorescopy cancer, along with the seven-year duration of the trial, may have contributed to this null finding.
Abstract: Background Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials. However, randomized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking. Methods We conducted a randomized, double-blind, placebo-controlled trial involving 36,282 postmenopausal women from 40 Women’s Health Initiative centers: 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 twice daily (1000 mg of elemental calcium and 400 IU of vitamin D3) and 18,106 received a matching placebo for an average of 7.0 years. The incidence of pathologically confirmed colorectal cancer was the designated secondary outcome. Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case–control study. Results The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo (168 and 154 cases; hazard ratio, 1.08; 95 percent confidence interval, 0.86 to 1.34; P = 0.51), and the tumor characteristics were similar in the two groups. The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups. There were no significant treatment interactions with baseline characteristics. Conclusions Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women. The long latency associated with the development of colorectal cancer, along with the seven-year duration of the trial, may have contributed to this null finding. Ongoing follow-up will assess the longer-term effect of this intervention. (ClinicalTrials.gov number, NCT00000611.)
970 citations
Fred Hutchinson Cancer Research Center1, Kaiser Permanente2, University of California, Los Angeles3, University of Pittsburgh4, University of Massachusetts Medical School5, University of Minnesota6, University of Florida7, Harvard University8, University of Miami9, Ohio State University10, Emory University11, University of California, Davis12, National Institutes of Health13, University of Wisconsin-Madison14, University of Alabama at Birmingham15, Stanford University16, University of Arizona17, Northwestern University18, Wake Forest University19, University at Buffalo20, University of Iowa21, Yeshiva University22, Howard University23, Pfizer24, Brown University25, University of Washington26, Rush University Medical Center27, University of Nevada, Reno28, University of Texas at San Antonio29, University of Cincinnati30, Baylor College of Medicine31, University of North Carolina at Chapel Hill32, Wayne State University33, George Washington University34, University of California, Irvine35, University of Tennessee Health Science Center36, Medical College of Wisconsin37, Stony Brook University38, University of California, San Diego39, Rutgers University40
TL;DR: Among postmenopausal women, a low-fat dietary pattern did not result in a statistically significant reduction in invasive breast cancer risk over an 8.1-year average follow-up period, and the nonsignificant trends observed indicate that longer, planned, nonintervention follow- up may yield a more definitive comparison.
Abstract: ContextThe hypothesis that a low-fat dietary pattern can reduce breast cancer risk has existed for decades but has never been tested in a controlled intervention trial.ObjectiveTo assess the effects of undertaking a low-fat dietary pattern on breast cancer incidence.Design and SettingA randomized, controlled, primary prevention trial conducted at 40 US clinical centers from 1993 to 2005.ParticipantsA total of 48 835 postmenopausal women, aged 50 to 79 years, without prior breast cancer, including 18.6% of minority race/ethnicity, were enrolled.InterventionsWomen were randomly assigned to the dietary modification intervention group (40% [n = 19 541]) or the comparison group (60% [n = 29 294]). The intervention was designed to promote dietary change with the goals of reducing intake of total fat to 20% of energy and increasing consumption of vegetables and fruit to at least 5 servings daily and grains to at least 6 servings daily. Comparison group participants were not asked to make dietary changes.Main Outcome MeasureInvasive breast cancer incidence.ResultsDietary fat intake was significantly lower in the dietary modification intervention group compared with the comparison group. The difference between groups in change from baseline for percentage of energy from fat varied from 10.7% at year 1 to 8.1% at year 6. Vegetable and fruit consumption was higher in the intervention group by at least 1 serving per day and a smaller, more transient difference was found for grain consumption. The number of women who developed invasive breast cancer (annualized incidence rate) over the 8.1-year average follow-up period was 655 (0.42%) in the intervention group and 1072 (0.45%) in the comparison group (hazard ratio, 0.91; 95% confidence interval, 0.83-1.01 for the comparison between the 2 groups). Secondary analyses suggest a lower hazard ratio among adherent women, provide greater evidence of risk reduction among women having a high-fat diet at baseline, and suggest a dietary effect that varies by hormone receptor characteristics of the tumor.ConclusionsAmong postmenopausal women, a low-fat dietary pattern did not result in a statistically significant reduction in invasive breast cancer risk over an 8.1-year average follow-up period. However, the nonsignificant trends observed suggesting reduced risk associated with a low-fat dietary pattern indicate that longer, planned, nonintervention follow-up may yield a more definitive comparison.Clinical Trials RegistrationClinicalTrials.gov Identifier: NCT00000611
740 citations
TL;DR: There is an increasing recognition that adipose tissue is an endocrine organ that secretes leptin and adiponectin along with a host of other paracrine and endocrine factors in addition to free fatty acids.
Abstract: The white adipose tissue, especially of humans, is now recognized as the central player in the mild inflammatory state that is characteristic of obesity. The question is how the increased accumulation of lipid seen in obesity causes an inflammatory state and how this is linked to the hypertension and type 2 diabetes that accompanies obesity. Once it was thought that adipose tissue was primarily a reservoir for excess calories that were stored in the adipocytes as triacylglycerols. In times of caloric deprivation these stored lipids were mobilized as free fatty acids and the insulin resistance of obesity was attributed to free fatty acids. It is now clear that in humans the expansion of adipose tissue seen in obesity results in more blood vessels, more connective tissue fibroblasts, and especially more macrophages. There is an enhanced secretion of some interleukins and inflammatory cytokines in adipose tissue of the obese as well as increased circulating levels of many cytokines. The central theme of this chapter is that human adipose tissue is a potent source of inflammatory interleukins plus other cytokines and that the majority of this release is due to the nonfat cells in the adipose tissue except for leptin and adiponectin that are primarily secreted by adipocytes. Human adipocytes secrete at least as much plasminogen activator inhibitor-1 (PAI-1), MCP-1, interleukin-8 (IL-8), and IL-6 in vitro as they do leptin but the nonfat cells of adipose tissue secrete even more of these proteins. The secretion of leptin, on the other hand, by the nonfat cells is negligible. The amount of serum amyloid A proteins 1 & 2 (SAA 1 & 2), haptoglobin, nerve growth factor (NGF), macrophage migration inhibitory factor (MIF), and PAI-1 secreted by the adipocytes derived from a gram of adipose tissue is 144%, 75%, 72%, 37%, and 23%, respectively, of that by the nonfat cells derived from the same amount of human adipose tissue. However, the release of IL-8, MCP-1, vascular endothelial growth factor (VEGF), TGF-beta1, IL-6, PGE(2), TNF-alpha, cathepsin S, hepatocyte growth factor (HGF), IL-1beta, IL-10, resistin, C-reactive protein (CRP), and interleukin-1 receptor antagonist (IL-1Ra) by adipocytes is less than 12% of that by the nonfat cells present in human adipose tissue. Obesity markedly elevates the total release of TNF-alpha, IL-6, and IL-8 by adipose tissue but only that of TNF-alpha is enhanced in adipocytes. However, on a quantitative basis the vast majority of the TNF-alpha comes from the nonfat cells. Visceral adipose tissue also releases more VEGF, resistin, IL-6, PAI-1, TGF-beta1, IL-8, and IL-10 per gram of tissue than does abdominal subcutaneous adipose tissue. In conclusion, there is an increasing recognition that adipose tissue is an endocrine organ that secretes leptin and adiponectin along with a host of other paracrine and endocrine factors in addition to free fatty acids.
679 citations
University of Washington1, University of Tennessee Health Science Center2, University of Arizona3, Rutgers University4, University of Iowa5, Rush University Medical Center6, Fred Hutchinson Cancer Research Center7, Brown University8, Pfizer9, University of Nevada, Reno10, University of Texas at San Antonio11, Kaiser Permanente12, University of California, Los Angeles13, University of Cincinnati14, Baylor College of Medicine15, University of North Carolina at Chapel Hill16, Wayne State University17, Howard University18, George Washington University19, University of California, Irvine20, Ohio State University21, Medical College of Wisconsin22, University of Pittsburgh23, Stony Brook University24, University of California, San Diego25, University of Alabama at Birmingham26, Harvard University27, University of Minnesota28, Yeshiva University29, University of Massachusetts Medical School30, University of Miami31, University of Florida32, Emory University33, University of California, Davis34, National Institutes of Health35, University of Wisconsin-Madison36, Stanford University37, Northwestern University38, Wake Forest University39, University at Buffalo40
TL;DR: A low-fat dietary pattern intervention did not reduce the risk of colorectal cancer in postmenopausal women during 8.1 years of follow-up, and secondary analyses suggested potential interactions with baseline aspirin use and combined estrogen-progestin use status.
Abstract: ContextObservational studies and polyp recurrence trials are not conclusive regarding the effects of a low-fat dietary pattern on risk of colorectal cancer, necessitating a primary prevention trial.ObjectiveTo evaluate the effects of a low-fat eating pattern on risk of colorectal cancer in postmenopausal women.Design, Setting, and ParticipantsThe Women’s Health Initiative Dietary Modification Trial, a randomized controlled trial conducted in 48 835 postmenopausal women aged 50 to 79 years recruited between 1993 and 1998 from 40 clinical centers throughout the United States.InterventionsParticipants were randomly assigned to the dietary modification intervention (n = 19 541; 40%) or the comparison group (n = 29 294; 60%).The intensive behavioral modification program aimed to motivate and support reductions in dietary fat, to increase consumption of vegetables and fruits, and to increase grain servings by using group sessions, self-monitoring techniques, and other tailored and targeted strategies. Women in the comparison group continued their usual eating pattern.Main Outcome MeasureInvasive colorectal cancer incidence.ResultsA total of 480 incident cases of invasive colorectal cancer occurred during a mean follow-up of 8.1 (SD, 1.7) years. Intervention group participants significantly reduced their percentage of energy from fat by 10.7% more than did the comparison group at 1 year, and this difference between groups was mostly maintained (8.1% at year 6). Statistically significant increases in vegetable, fruit, and grain servings were also made. Despite these dietary changes, there was no evidence that the intervention reduced the risk of invasive colorectal cancer during the follow-up period. There were 201 women with invasive colorectal cancer (0.13% per year) in the intervention group and 279 (0.12% per year) in the comparison group (hazard ratio, 1.08; 95% confidence interval, 0.90-1.29). Secondary analyses suggested potential interactions with baseline aspirin use and combined estrogen-progestin use status (P = .01 for each). Colorectal examination rates, although not protocol defined, were comparable between the intervention and comparison groups. Similar results were seen in analyses adjusting for adherence to the intervention.ConclusionIn this study, a low-fat dietary pattern intervention did not reduce the risk of colorectal cancer in postmenopausal women during 8.1 years of follow-up.Clinical Trials RegistrationClinicalTrials.gov Identifier: NCT00000611
TL;DR: The Resources for Enhancing Alzheimer's Caregiver Health (REACH) study as discussed by the authors found that the intervention had no detectable effect on the number of care recipients who were institutionalized.
Abstract: Caring for a family member with dementia is extremely stressful, contributes to psychiatric and physical illness, and increases the risk for death (1, 2). The accumulating evidence on the personal, social, and health effects of dementia caregiving has generated a broad range of intervention studies, including randomized trials aimed at decreasing the burden and stress of caregiving. Several studies have demonstrated statistically significant effects in reducing caregiver burden, lowering caregiver depression, and delaying institutionalization of care recipients (1, 3, 4) through either targeted interventions that treat a specific caregiver problem, such as depression, or broad-based multicomponent interventions that include counseling, case management, and telephone support. Persistent limitations of caregiver intervention research are the paucity of well-controlled randomized trials, the limited range of outcomes examined, small sample sizes and insufficient power, geographic limitations, inadequate racial or ethnic variation, and a scarcity of comprehensive multicomponent interventions (4). Indeed, none of the 41 randomized clinical trials published in the last 5 years met Consolidated Standards of Reporting Trials (CONSORT) recommendations for reporting randomized trials (5), and many have serious methodologic problems that call into question the reported findings (4).
To address these limitations, the National Institute on Aging and the National Institute of Nursing Research funded a multisite research program designed to develop and test an effective caregiver intervention: the Resources for Enhancing Alzheimer's Caregiver Health (REACH) study. We performed the study in 2 phases. In the first phase (REACH I), we tested several different interventions at 6 U.S. sites to identify the most promising approaches to decreasing caregiver burden and depression (6). Results from the study showed that active treatments were superior to control conditions in reducing caregiver burden and that active engagement in skills training statistically significantly reduced caregiver depression (7, 8). The existing literature and findings from REACH I helped guide the design of the REACH II intervention (7, 8). We based the REACH II study on the premise that caregivers can have problems in several areas at varying levels of intensity, and thus, interventions must be responsive to variations in needs among caregivers. The findings from REACH I also suggest that interventions that use active techniques, such as role-playing and interactive practice, are more effective at improving outcomes, such as depression symptoms, compared with more passive methods, such as providing information (7). We based the REACH II intervention on these assumptions and designed the intervention to maximize outcomes by systematically targeting several problem areas, tailored the intervention to respond to the needs of each individual, and actively engaged the caregiver in the intervention process. We hypothesized that participants assigned to the intervention would do better than those in the control group on several indicators of caregiver quality of life, including depression, burden, self-care, and social support and care recipient problem behaviors, and that these differences would be largest among Hispanic or Latino persons because they have lower access to support services (8). In additional analyses, we assessed the effects of treatment on rates of caregiver clinical depression and care recipient institutional placement, as well as the benefits derived from study participation.
Context
Providing care for patients with dementia can pose enormous burdens that may be eased with assistance and support. Needs may differ by race or ethnicity.
Contributions
The investigators randomly assigned Hispanic, black, and white dementia caregivers to receive written educational materials or an intensive intervention to improve caregiver quality of life. The specific interventions were determined by caregivers, were delivered via trained personnel and telephone support groups, and targeted several dimensions of need. The study found that quality of life improved for Hispanic and white caregivers and for black spousal caregivers in the intervention group but not in the control group. The intervention had no detectable effect on the number of care recipients who were institutionalized.
Cautions
The study used only a single 6-month follow-up assessment, combined heterogeneous cultures and ethnicities into 3 groups, and excluded some ethnicities.
Implications
An intensive intervention targeting several dimensions of caregiver need improved caregiver quality of life without an apparent effect on care recipient institutionalization. The effect did not differ by caregiver race or ethnicity.
—The Editors
TL;DR: A preliminary analysis of the first large-scale sequencing of AIVs, including 2196 AIV genes and 169 complete genomes, is reported here to identify new gene alleles, persistent genotypes, compensatory mutations, and a potential virulence determinant.
Abstract: The spread of H5N1 avian influenza viruses (AIVs) from China to Europe has raised global concern about their potential to infect humans and cause a pandemic. In spite of their substantial threat to human health, remarkably little AIV whole-genome information is available. We report here a preliminary analysis of the first large-scale sequencing of AIVs, including 2196 AIV genes and 169 complete genomes. We combine this new information with public AIV data to identify new gene alleles, persistent genotypes, compensatory mutations, and a potential virulence determinant.
George Washington University1, University of California, San Diego2, Harvard University3, University of Pittsburgh4, University of Tennessee Health Science Center5, Wayne State University6, Fred Hutchinson Cancer Research Center7, University of Washington8, University of California, Irvine9, University of Massachusetts Medical School10, Brown University11, Rutgers University12, University of Miami13
TL;DR: Conjugated equine estrogens provided no overall protection against myocardial infarction or coronary death in generally healthy postmenopausal women during a 7-year period of use.
Abstract: Background In recent randomized trials, conjugated equine estrogens (CEE) with continuous medroxyprogesterone acetate provided no protection against coronary heart disease in postmenopausal women and may have increased cardiac risk. These trials did not address the role of unopposed estrogen for coronary protection. Methods A total of 10 739 women aged 50 to 79 years at baseline (mean age, 63.6 years) who had previously undergone hysterectomy were randomized to receive CEE, 0.625 mg/d, or placebo at 40 US clinical centers beginning in 1993. The trial was terminated early after 6.8 years of follow-up (planned duration, 8.5 years). This report includes final, centrally adjudicated results for the primary efficacy outcome (myocardial infarction or coronary death), secondary coronary outcomes, and subgroup analyses. Results During the active intervention period, 201 coronary events were confirmed among women assigned to receive CEE compared with 217 events among women assigned to receive placebo (hazard ratio, 0.95; nominal 95% confidence interval, 0.79-1.16). Among women aged 50 to 59 years at baseline, the hazard ratio for the primary outcome was 0.63 (nominal 95% confidence interval, 0.36-1.08). In that age group, coronary revascularization was less frequent among women assigned to receive CEE (hazard ratio, 0.55; nominal 95% confidence interval, 0.35-0.86), as were several composite outcomes, which included the primary outcome and coronary revascularization (hazard ratio, 0.66; nominal 95% confidence interval, 0.44-0.97). Conclusions Conjugated equine estrogens provided no overall protection against myocardial infarction or coronary death in generally healthy postmenopausal women during a 7-year period of use. There was a suggestion of lower coronary heart disease risk with CEE among women 50 to 59 years of age at baseline.
TL;DR: It is shown that the tumour surveillance pathway mediated by Arf, MDM2, MDMX and p53 is activated after loss of RB1 during retinogenesis, providing evidence that the p53 pathway is inactivated in retinoblastoma and that this cancer does not originate from intrinsically death-resistant cells as previously thought.
Abstract: Most human tumours have genetic mutations in their Rb and p53 pathways, but retinoblastoma is thought to be an exception. Studies suggest that retinoblastomas, which initiate with mutations in the gene retinoblastoma 1 (RB1), bypass the p53 pathway because they arise from intrinsically death-resistant cells during retinal development. In contrast to this prevailing theory, here we show that the tumour surveillance pathway mediated by Arf, MDM2, MDMX and p53 is activated after loss of RB1 during retinogenesis. RB1-deficient retinoblasts undergo p53-mediated apoptosis and exit the cell cycle. Subsequently, amplification of the MDMX gene and increased expression of MDMX protein are strongly selected for during tumour progression as a mechanism to suppress the p53 response in RB1-deficient retinal cells. Our data provide evidence that the p53 pathway is inactivated in retinoblastoma and that this cancer does not originate from intrinsically death-resistant cells as previously thought. In addition, they support the idea that MDMX is a specific chemotherapeutic target for treating retinoblastoma.
TL;DR: The creation of a multifunctional surface can be achieved by co-sputtering the osteoconductive HA with antibacterial Ag with no significant difference in the in vitro cytotoxicty was observed between HA and Ag-HA surfaces.
TL;DR: Women with type 2 diabetes are at increased risk for fractures, seen among black and non-Hispanic white women after adjustment for multiple risk factors including frequent falls and increased BMD (in a subset).
Abstract: Context: Some but not all studies have shown higher rates of fracture in individuals with type 2 diabetes. Objective: The objective of the study was to determine the risk of fracture in postmenopausal women with type 2 diabetes and determine whether risk varies by fracture site, ethnicity, and baseline bone density. Design, Setting, and Participants: Women with clinically diagnosed type 2 diabetes at baseline in the Women’s Health Initiative Observational Cohort, a prospective study of postmenopausal women (n = 93,676), were compared with women without diagnosed diabetes and risk of fracture overall and at specific sites determined. Main Outcome Measures: All fractures and specific sites separately (hip/pelvis/upper leg; lower leg/ankle/knee; foot; upper arm/shoulder/elbow; lower arm/wrist/hand; spine/tailbone) were measured. Bone mineral density (BMD) in a subset also was measured. Results: The overall risk of fracture after 7 yr of follow-up was higher in women with diabetes at baseline after controllin...
TL;DR: These observational results suggest that TZDs may cause bone loss in older women, and these results need to be tested in a randomized trial.
Abstract: Context: Activation of peroxisome proliferator-activated receptor-γ by thiazolidinediones (TZDs) results in lower bone mass in mice. Objective: The objective of the study was to determine whether TZD use is associated with changes in bone mineral density (BMD) in older adults with type 2 diabetes. Design: We analyzed 4-yr follow-up data from the Health, Aging, and Body Composition observational study. Setting: The study was conducted in a general community. Patients: White and black, physically able men and women, aged 70–79 yr at baseline with diabetes defined by self-report, use of hypoglycemic medication, elevated fasting glucose (≥126 mg/dl), or elevated 2-h glucose tolerance test (≥200 mg/dl) participated in the study. Main Outcome Measures: Whole-body, lumbar spine (derived from whole body), and hip BMD were measured by dual-energy x-ray absorptiometry at 2-yr intervals. Results: Of 666 diabetic participants, 69 reported TZD use at an annual visit, including troglitazone (n = 22), pioglitazone (n = ...
TL;DR: This consensus statement will outline precipitating factors and recommendations for the diagnosis, treatment, and prevention of DKA and HHS in adult subjects based on a previous technical review and more recently published peer-reviewed articles since 2001.
Abstract: Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are the two most serious acute metabolic complications of diabetes. Most patients with DKA have autoimmune type 1 diabetes; however, patients with type 2 diabetes are also at risk during the catabolic stress of acute illness such as trauma, surgery, or infection. Table 1 outlines the diagnostic criteria and electrolyte and fluid deficits for both disorders. The mortality rate in patients with DKA is <5% in experienced centers, whereas the mortality rate of patients with HHS still remains high at ∼11% (1–8). Death in these conditions is rarely due to the metabolic complications of hyperglycemia or ketoacidosis but rather relates to the underlying precipitating illness. The prognosis of both conditions is substantially worsened at the extremes of age and in the presence of coma and hypotension (7,9–11)
This consensus statement will outline precipitating factors and recommendations for the diagnosis, treatment, and prevention of DKA and HHS in adult subjects. It is based on a previous technical review and more recently published peer-reviewed articles since 2001, which should be consulted for further information.
Although the pathogenesis of DKA is better understood than that of HHS, the basic underlying mechanism for both disorders is a reduction in the net effective action of circulating insulin coupled with a concomitant elevation of counterregulatory hormones, such as glucagon, catecholamines, cortisol, and growth hormone (1,3,4,8–13). DKA and HHS can fall anywhere along the disease continuum of diabetic metabolic derangements. At one extreme, pure DKA without significant hyperosmolarity typically indicates the total or relative absence of insulin (seen in type 1 diabetes). At the other extreme, HHS without ketoacidosis typically occurs with lesser degrees of insulin deficiency, as seen in type 2 diabetes. However, …
TL;DR: In alveolar macrophages the cystic fibrosis transmembrane conductance regulator Cl− channel participates in phagosomal pH control and has bacterial killing capacity, and it is hypothesized that CFTR contributes to lysosomal acidification and that in its absence phagolysosomes acidify poorly, thus providing an environment conducive to bacterial replication.
Abstract: Acidification of phagosomes has been proposed to have a key role in the microbicidal function of phagocytes. Here, we show that in alveolar macrophages the cystic fibrosis transmembrane conductance regulator Cl- channel (CFTR) participates in phagosomal pH control and has bacterial killing capacity. Alveolar macrophages from Cftr-/- mice retained the ability to phagocytose and generate an oxidative burst, but exhibited defective killing of internalized bacteria. Lysosomes from CFTR-null macrophages failed to acidify, although they retained normal fusogenic capacity with nascent phagosomes. We hypothesize that CFTR contributes to lysosomal acidification and that in its absence phagolysosomes acidify poorly, thus providing an environment conducive to bacterial replication.
TL;DR: Sketches may be a useful tool to identify overweight children when measurements are not available and recognition of physical activity limitations and physicians’ concerns may heighten the parent's level of concern.
Abstract: OBJECTIVE. This study explored parents9 perceptions about their child9s appearance and health and evaluated a tool to determine parents9 visual perception of their child9s weight. METHODS. Parents of children aged 2 to 17 years were surveyed concerning their child9s appearance and health and opinions about childhood overweight. They also selected the sketch (from 7 choices) that most closely matched the body image of their child using 1 of 8 gender–and age-range–specific panels of sketches. Children9s height and weight were measured. Respondents were grouped by child body mass index (BMI) percentile ( RESULTS. Of the 223 children, 60% were CONCLUSIONS.Few parents of overweight and AROW children recognized their child as overweight or were worried. Recognition of physical activity limitations and physicians’ concerns may heighten the parent9s level of concern. Sketches may be a useful tool to identify overweight children when measurements are not available.
TL;DR: Limited literacy is independently associated with a nearly 2-fold increase in mortality in the elderly, given the growth of the aging population and the prevalence of chronic diseases.
Abstract: BACKGROUND: While limited literacy is common and its prevalence increases with age, no prospective study has assessed whether limited literacy is associated with mortality in older adults.
TL;DR: The "brain-skin connection," which may underlie inflammatory skin diseases triggered or aggravated by stress, is reviewed, and relevant general principles of skin neuroimmunology and neuroendocrinology are summarized.
TL;DR: To determine the relationship between health literacy, demographics, and access to health care, a national survey of over-65s and over-75s is conducted in the United States.
Abstract: OBJECTIVES: To determine the relationship between health literacy, demographics, and access to health care. DESIGN: Cross-sectional study, Health, Aging and Body Composition data (1999/2000). SETTING: Memphis, Tennessee, and Pittsburgh, Pennsylvania. PARTICIPANTS: Two thousand five hundred twelve black and white community-dwelling older people who were well functioning at baseline (without functional difficulties or dementia). MEASUREMENTS: Participants’ health literacy was assessed using the Rapid Estimate of Adult Literacy in Medicine. Scores were categorized into 0 to sixth-, seventh- to eighth-, and ninth-grade and higher reading levels (limited health literacy defined as o9th grade). Participants’ demographics, socioeconomic status, comorbidities, and three indicators of healthcare access (whether they had a doctor/ regular place of medical care, an influenza vaccination within the year, or insurance for medications) were also assessed. RESULTS: Participants’ mean age was 75.6, 52% were female, 38% were black, and 24%had limited health literacy. After adjusting for sociodemographics, associations remained between limited health literacy and being male, being black, and having low income and education, diabetes mellitus, depressive symptoms, and fair/poor self-rated health (Po.02). After adjusting for sociodemographics, health status, and comorbidities, older people with a sixthgrade reading level or lower were twice as likely to have any of the three indicators of poor healthcare access (odds ratio 51.96, 95% confidence interval 51.34‐2.88). CONCLUSION: Limited health literacy was prevalent and was associated with low socioeconomic status, comorbidities, and poor access to health care, suggesting that it may be an independent risk factor for health disparities in older people. J Am Geriatr Soc 54:770–776, 2006.
Yale University1, University of Alabama at Birmingham2, Stanford University3, Cincinnati Children's Hospital Medical Center4, Children's National Medical Center5, University of Mississippi6, University of Toronto7, Children's Hospital of Wisconsin8, Boston Children's Hospital9, University of California, San Francisco10, University of Tennessee Health Science Center11, Memorial Hospital of South Bend12, University of Michigan13, Nationwide Children's Hospital14, University of Pittsburgh15
TL;DR: The type of operation performed for perforated necrotizing enterocolitis does not influence survival or other clinically important early outcomes in preterm infants.
Abstract: Background Perforated necrotizing enterocolitis is a major cause of morbidity and mortality in premature infants, and the optimal treatment is uncertain. We designed this multicenter randomized trial to compare outcomes of primary peritoneal drainage with laparotomy and bowel resection in preterm infants with perforated necrotizing enterocolitis. Methods We randomly assigned 117 preterm infants (delivered before 34 weeks of gestation) with birth weights less than 1500 g and perforated necrotizing enterocolitis at 15 pediatric centers to undergo primary peritoneal drainage or laparotomy with bowel resection. Postoperative care was standardized. The primary outcome was survival at 90 days postoperatively. Secondary outcomes included dependence on parenteral nutrition 90 days postoperatively and length of hospital stay. Results At 90 days postoperatively, 19 of 55 infants assigned to primary peritoneal drainage had died (34.5 percent), as compared with 22 of 62 infants assigned to laparotomy (35.5 percent, P...
TL;DR: It is suggested that for high virulence in mammalian species an avian H5N1 virus with a cleavable hemagglutinin requires adaptive changes in polymerase genes to overcome the species barrier, and novel antivirals targeting polymerase proteins should be developed.
Abstract: H5N1 influenza viruses transmitted from poultry to humans in Asia cause high mortality and pose a pandemic threat. Viral genes important for cell tropism and replication efficiency must be identified to elucidate and target virulence factors. We applied reverse genetics to generate H5N1 reassortants combining genes of lethal A/Vietnam/1203/04 (VN1203), a fatal human case isolate, and nonlethal A/chicken/Vietnam/C58/04 (CH58) and tested their pathogenicity in ferrets and mice. The viruses' hemagglutinins have six amino acids differences, identical cleavage sites, and avian-like α-(2,3)–linked receptor specificity. Surprisingly, exchanging hemagglutinin and neuraminidase genes did not alter pathogenicity, but substituting CH58 polymerase genes completely attenuated VN1203 virulence and reduced viral polymerase activity. CH58's NS gene partially attenuated VN1203 in ferrets but not in mice. Our findings suggest that for high virulence in mammalian species an avian H5N1 virus with a cleavable hemagglutinin requires adaptive changes in polymerase genes to overcome the species barrier. Thus, novel antivirals targeting polymerase proteins should be developed.
TL;DR: There has been an increase in the incidence and severity of acute osteoarticular infections in Memphis and patients with community-associated MRSA infections are at higher risk of subperiosteal abscess requiring surgical intervention.
Abstract: INTRODUCTION: An increase in the incidence and severity of acute osteoarticular infections in children was perceived after the emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA) in our community. This study was performed to describe changes in the epidemiology and clinical features of acute osteoarticular infections. METHODS: The records of patients discharged from Le Bonheur Children's Medical Center with a diagnosis of acute osteoarticular infection between 2000 and 2004 were reviewed. Data regarding signs and symptoms, diagnostic testing, therapeutics, surgery, and hospital course were collected. RESULTS: There were 158 cases of acute osteoarticular infection. The incidence increased from 2.6 to 6.0 per 1000 admissions between 2000 and 2004. The proportion of infections caused by methicillin-susceptible S. aureus (MSSA) remained constant (10%-13%) and that caused by MRSA rose from 4% to 40%. There was no difference between MRSA and MSSA patients in the duration of fever or pain before diagnosis. Seventy-one percent of patients with MRSA had subperiosteal abscesses compared with 38% with MSSA (P = 0.02). Ninety-one percent of MRSA patients required a surgical procedure compared with 62% of MSSA patients (P < 0.001). Median hospital stay was 7 days for MSSA patients and 10 days for MRSA patients (P = 0.0001). Three patients developed chronic osteomyelitis, 2 with MRSA. There was no association between a delay in institution of appropriate antibiotic therapy and presence of subperiosteal abscess (P = 0.8). CONCLUSIONS: There has been an increase in the incidence and severity of acute osteoarticular infections in Memphis. Patients with community-associated MRSA infections are at higher risk of subperiosteal abscess requiring surgical intervention.
Wayne State University1, Yeshiva University2, University of Tennessee Health Science Center3, Memorial Hospital of South Bend4, Fred Hutchinson Cancer Research Center5, National Institutes of Health6, University at Buffalo7, Baylor College of Medicine8, Harvard University9, University of California, San Diego10, Wake Forest University11, University of Iowa12
TL;DR: CEE increases the risk of ischemic stroke in generally healthy postmenopausal women and in women with prior or current use of statins or aspirin and there was no convincing evidence to suggest that CEE had an effect on therisk of hemorrhagic stroke.
Abstract: Background— The Women’s Health Initiative (WHI) Estrogen Alone trial assessed the balance of benefits and risks of hormone use in healthy postmenopausal women. The trial was stopped prematurely because there was no benefit for coronary heart disease and an increased risk of stroke. This report provides a thorough analysis of the stroke finding using the final results from the completed trial database. Methods and Results— The WHI Estrogen Alone hormone trial is a multicenter, double-blind, placebo-controlled, randomized clinical trial in 10 739 women aged 50 to 79 years who were given daily conjugated equine estrogen (CEE; 0.625 mg; n=5310) or placebo (n=5429). During an average follow-up of 7.1 years, there were 168 strokes in the CEE group and 127 in the placebo group; 80.3% of strokes were ischemic. For all stroke the intention-to-treat hazard ratio [HR] (95% CI) for CEE versus placebo was 1.37 (1.09 to 1.73). The HR (95% CI) was 1.55 (1.19 to 2.01) for ischemic stroke and 0.64 (0.35, 1.18) for hemorrh...
University of Mississippi1, University of Tennessee Health Science Center2, Mayo Clinic3, University of Kansas4, University of Michigan5, University of South Alabama6, Temple University7, University of Virginia8, University of Texas Medical Branch9, Saint Louis University10, Cedars-Sinai Medical Center11, Eastern Virginia Medical School12
TL;DR: To provide practical guidelines for treatment, this document covers results of published research studies in the literature and areas developed by consensus agreement where clinical research trials remain lacking in the field of gastroparesis.
Abstract: This clinical review on the treatment of patients with gastroparesis is a consensus document developed by the American Motility Society Task Force on Gastroparesis. It is a multidisciplinary effort with input from gastroenterologists and other specialists who are involved in the care of patients with gastroparesis. To provide practical guidelines for treatment, this document covers results of published research studies in the literature and areas developed by consensus agreement where clinical research trials remain lacking in the field of gastroparesis.
TL;DR: The distinct responses of different cell types to viral infection are highlighted and the need to consider this variation when interpreting studies of the interactions between respiratory cells and viral pathogens is considered.
Abstract: Secondary bacterial infections often complicate respiratory viral infections, but the mechanisms whereby viruses predispose to bacterial disease are not completely understood. We determined the effects of infection with respiratory syncytial virus (RSV), human parainfluenza virus 3 (HPIV-3), and influenza virus on the abilities of nontypeable Haemophilus influenzae and Streptococcus pneumoniae to adhere to respiratory epithelial cells and how these viruses alter the expression of known receptors for these bacteria. All viruses enhanced bacterial adhesion to primary and immortalized cell lines. RSV and HPIV-3 infection increased the expression of several known receptors for pathogenic bacteria by primary bronchial epithelial cells and A549 cells but not by primary small airway epithelial cells. Influenza virus infection did not alter receptor expression. Paramyxoviruses augmented bacterial adherence to primary bronchial epithelial cells and immortalized cell lines by up-regulating eukaryotic cell receptors for these pathogens, whereas this mechanism was less significant in primary small airway epithelial cells and in influenza virus infections. Respiratory viruses promote bacterial adhesion to respiratory epithelial cells, a process that may increase bacterial colonization and contribute to disease. These studies highlight the distinct responses of different cell types to viral infection and the need to consider this variation when interpreting studies of the interactions between respiratory cells and viral pathogens.