tbuckley/cabot-search huggingface dataset:
Soft Drink Consumption and Risk of Developing Cardiometabolic Risk Factors and the Metabolic Syndrome in Middle-Aged Adults in the Community
Authors: Ravi Dhingra, Lisa Sullivan, Paul F. Jacques, Thomas J. Wang, Caroline S. Fox, James B. Meigs, Ralph B. D’Agostino, J. Michael Gaziano, Ramachandran S. Vasan
Journal: Circulation (2007)

Consumption of soft drinks has been linked to obesity in children and adolescents, but it is unclear whether it increases metabolic risk in middle-aged individuals.We related the incidence of metabolic syndrome and its components to soft drink consumption in participants in the Framingham Heart Study (6039 person-observations, 3470 in women; mean age 52.9 years) who were free of baseline metabolic syndrome. Metabolic syndrome was defined as the presence of > or = 3 of the following: waist circumference > or = 35 inches (women) or > or = 40 inches (men); fasting blood glucose > or = 100 mg/dL; serum triglycerides > or = 150 mg/dL; blood pressure > or = 135/85 mm Hg; and high-density lipoprotein cholesterol < 40 mg/dL (men) or < 50 mg/dL (women). Multivariable models included adjustments for age, sex, physical activity, smoking, dietary intake of saturated fat, trans fat, fiber, magnesium, total calories, and glycemic index. Cross-sectionally, individuals consuming > or = 1 soft drink per day had a higher prevalence of metabolic syndrome (odds ratio [OR], 1.48; 95% CI, 1.30 to 1.69) than those consuming < 1 drink per day. On follow-up (mean of 4 years), new-onset metabolic syndrome developed in 717 of 4033 participants (17.8%) consuming < 1 drink/day and in 433 of 2006 persons (21.6%) [corrected] consuming > or = 1 soft drink/day [corrected] Consumption of > or = 1 soft drink per day was associated with increased odds of developing metabolic syndrome (OR, 1.44; 95% CI, 1.20 to 1.74), obesity (OR, 1.31; 95% CI, 1.02 to 1.68), increased waist circumference (OR, 1.30; 95% CI, 1.09 to 1.56), impaired fasting glucose (OR, 1.25; 95% CI, 1.05 to 1.48), higher blood pressure (OR, 1.18; 95% CI, 0.96 to 1.44), hypertriglyceridemia (OR, 1.25; 95% CI, 1.04 to 1.51), and low high-density lipoprotein cholesterol (OR, 1.32; 95% CI 1.06 to 1.64).In middle-aged adults, soft drink consumption is associated with a higher prevalence and incidence of multiple metabolic risk factors.
Evaluation of a 7-Day Continuous Intravenous Infusion of Decitabine: Inhibition of Promoter-Specific and Global Genomic DNA Methylation
Authors: Wolfram E. Samlowski, Sancy A. Leachman, Mark Wade, Pamela Cassidy, Patricia Porter-Gill, Leslie Busby, Richard Wheeler, Kenneth Boucher, Frank Fitzpatrick, David A. Jones, Adam R. Karpf
Journal: Journal of Clinical Oncology (2005)

Purpose The nucleoside analog 5-aza-2′-deoxycytidine (5-aza-CdR, decitabine) is a potent inhibitor of DNA methylation in vitro. Cellular treatment with this agent induces the re-expression of methylation-silenced genes. It remains unclear to what extent this compound inhibits DNA methylation in vivo. A clinical study was designed to examine the molecular effects and toxicity of a continuous 1-week intravenous infusion of decitabine in solid tumor patients. Methods Ten patients with refractory solid tumors were included in this study. Decitabine was administered at 2 mg/m 2 /d via continuous infusion for 168 hours. Quantitative polymerase chain reaction and high performance liquid chromatography were utilized to measure promoter-specific and global DNA methylation in peripheral-blood cells before and after treatment. Results Transient grade III/IV neutropenia (two patients) and grade II thrombocytopenia (one patient) was observed at the lowest planned dose step (2 mg/m 2 /d for 7 days). Nonhematologic toxicities were not observed. Quantitative polymerase chain reaction demonstrated significant MAGE-1 promoter hypomethylation by 14 days after the start of treatment in all 13 treatment cycles examined. Significant genomic DNA hypomethylation was also seen by day 14 in 11 of 13 treatment cycles analyzed. Genomic DNA methylation reverted to baseline levels by 28 to 35 days after the start of treatment, demonstrating that inhibition of DNA methylation by decitabine is transient. Conclusion A 168-hour continuous infusion of decitabine is well tolerated and results in the inhibition of promoter-specific and genomic DNA methylation in vivo. This treatment schedule is suitable for evaluation of decitabine in combination with agents whose activity may be enhanced by the reversal of DNA methylation–mediated gene silencing.
Indications for Renal Arteriography at the Time of Coronary Arteriography
Authors: Christopher J. White, Michael R. Jaff, Ziv J. Haskal, Daniel J. Jones, Jeffrey W. Olin, Krishna J. Rocha-Singh, Kenneth A. Rosenfield, John H. Rundback, Stuart L. Linas
Journal: Circulation (2006)

Atherosclerotic renal artery stenosis is commonly present in patients with clinically manifest atherosclerosis in other vascular beds and is independently associated with increased cardiovascular morbidity and mortality. Screening tests such as renal angiography should be selectively applied to patients at high risk for renal artery stenosis who are potential candidates for revascularization. This multispecialty consensus document describes the rationale for patient selection for screening renal angiography at the time of cardiac catheterization.
A novel clinical test of respiratory muscle endurance
Authors: N. Hart, P. Hawkins, C-H. Hamnegård, M. Green, J. Moxham, M.I. Polkey
Journal: European Respiratory Journal (2002)

Impaired respiratory muscle endurance (RME) could reduce exercise tolerance and contribute to ventilatory failure. The aim of the present study was to develop a clinically-feasible method to measure RME using negative-pressure inspiratory-threshold loading. It was hypothesized that endurance time ( t lim ) could be predicted by normalizing oesophageal pressure-time product (PTP) per total breath cycle (PTP oes ) for maximum oesophageal pressure ( P oes,max ); the load/capacity ratio. The corresponding mouth pressures, PTP mouth and P mouth,max were also measured. The RME test was performed on 30 healthy subjects exposed to the same target pressure (70% of P oes,max ). Eight patients with systemic sclerosis/interstitial lung disease were studied to assess the validity and acceptability of the technique. Normal subjects showed a wide intersubject variation in t lim (coefficient of variation, 69%), with a linear relationship demonstrated between log t lim and PTP oes / P oes,max (r=0.88). All patients with systemic sclerosis/interstitial lung disease had normal respiratory muscle strength, but six out of eight had a reduction in RME. In conclusion, endurance time can be predicted from the load/capacity ratio, over a range of breathing strategies; this relationship allows abnormal respiratory muscle endurance to be detected in patients. Oesophageal and mouth pressure showed a close correlation, thus suggesting that the test could be applied noninvasively.
Regulation of prostasin by aldosterone in the kidney
Authors: Takefumi Narikiyo, Kenichiro Kitamura, Masataka Adachi, Taku Miyoshi, Kozo Iwashita, Naoki Shiraishi, Hiroshi Nonoguchi, Li-Mei Chen, Karl X. Chai, Julie Chao, Kimio Tomita
Journal: Journal of Clinical Investigation (2002)

Prostasin is a serine protease present in mammalian urine that increases the activity of the epithelial sodium channel (ENaC) when the two are coexpressed in Xenopus oocytes. To determine if aldosterone, one of the principal regulators of urinary Na reabsorption by the distal nephron, affects prostasin expression, we examined prostasin mRNA and protein in a cultured mouse cortical collecting duct cell line (M-1), whole rats, and patients with primary aldosteronism. Aldosterone treatment of M-1 cells substantially increased prostasin expression and stimulated 22Na uptake. Urinary excretion of prostasin in rats that were infused with aldosterone likwise increased by ∼4-fold when compared with the vehicle-infused rats. Finally, urinary excretion of prostasin in patients with primary aldosteronism was substantially increased when compared with normal patients. Adrenalectomy reduced urinary prostasin excretion to control levels, whereas urinary prostasin levels were not altered in patients undergoing surgery for other reasons. In patients with primary aldosteronism, reduction in the urinary excretion of prostasin correlated with the increase in the urinary Na/K ratio. These findings, together with our previous report that prostasin activates the amiloride-sensitive Na currents through ENaC, demonstrate that prostasin regulates Na balance in vivo by virtue of its heightened expression in the presence of aldosterone.
Another case of breathlessness
Authors: D. A Inwald
Journal: BMJ (2001)

A fit looking young man of 30 attended the surgery complaining of a week's history of increasing breathlessness while in bed at night. He had been registered at the practice for four years and was a rare visitor. During the previous day he had noticed some dyspnoea on exertion but he had continued working. That same night he had used pillows to prop himself up in bed and had felt more comfortable.

He strode into the surgery briskly with no obvious breathlessness; he looked the picture of health. On examination the only abnormality …
Fracture Prevention With Vitamin D Supplementation
Authors: Heike A Bischoff-Ferrari, Walter C Willett, John B Wong, Edward Giovannucci, Thomas Dietrich, Bess Dawson-Hughes
Journal: JAMA (2005)

The role and dose of oral vitamin D supplementation in nonvertebral fracture prevention have not been well established.To estimate the effectiveness of vitamin D supplementation in preventing hip and nonvertebral fractures in older persons.A systematic review of English and non-English articles using MEDLINE and the Cochrane Controlled Trials Register (1960-2005), and EMBASE (1991-2005). Additional studies were identified by contacting clinical experts and searching bibliographies and abstracts presented at the American Society for Bone and Mineral Research (1995-2004). Search terms included randomized controlled trial (RCT), controlled clinical trial, random allocation, double-blind method, cholecalciferol, ergocalciferol, 25-hydroxyvitamin D, fractures, humans, elderly, falls, and bone density.Only double-blind RCTs of oral vitamin D supplementation (cholecalciferol, ergocalciferol) with or without calcium supplementation vs calcium supplementation or placebo in older persons (> or =60 years) that examined hip or nonvertebral fractures were included.Independent extraction of articles by 2 authors using predefined data fields, including study quality indicators.All pooled analyses were based on random-effects models. Five RCTs for hip fracture (n = 9294) and 7 RCTs for nonvertebral fracture risk (n = 9820) met our inclusion criteria. All trials used cholecalciferol. Heterogeneity among studies for both hip and nonvertebral fracture prevention was observed, which disappeared after pooling RCTs with low-dose (400 IU/d) and higher-dose vitamin D (700-800 IU/d), separately. A vitamin D dose of 700 to 800 IU/d reduced the relative risk (RR) of hip fracture by 26% (3 RCTs with 5572 persons; pooled RR, 0.74; 95% confidence interval [CI], 0.61-0.88) and any nonvertebral fracture by 23% (5 RCTs with 6098 persons; pooled RR, 0.77; 95% CI, 0.68-0.87) vs calcium or placebo. No significant benefit was observed for RCTs with 400 IU/d vitamin D (2 RCTs with 3722 persons; pooled RR for hip fracture, 1.15; 95% CI, 0.88-1.50; and pooled RR for any nonvertebral fracture, 1.03; 95% CI, 0.86-1.24).Oral vitamin D supplementation between 700 to 800 IU/d appears to reduce the risk of hip and any nonvertebral fractures in ambulatory or institutionalized elderly persons. An oral vitamin D dose of 400 IU/d is not sufficient for fracture prevention.
MACROPHAGE-LYMPHOCYTE CLUSTERS IN THE IMMUNE RESPONSE TO SOLUBLE PROTEIN ANTIGEN IN VITRO
Authors: Ole Werdelin, Otto Brændstrup, Eskild Pedersen
Journal: The Journal of Experimental Medicine (1974)

We have studied the physical interaction between macrophages and lymphocytes during the immune response to purified protein derivative of tuberculin (PPD) in vitro. Mixtures of peritoneal macrophages and lymph node lymphocytes from guinea pigs immunized with tubercle bacilli formed cell clusters during 20 h of culture with PPD. The number of clusters produced was correlated to the number of immune lymphocytes in the cultures. Peritoneal macrophages which had been pulsed with PPD and untreated lymph node lymphocytes produced cell clusters in the absence of free PPD in numbers equivalent to those produced by the same cells in the presence of free PPD. In cultures containing a mixture of PPD-pulsed macrophages, not-pulsed macrophages, and immune lymphocytes with no free PPD, cell clusters developed mainly between the antigen-pulsed macrophages and lymphocytes. Cluster formation was antigen-specific with the specificity residing in the lymphocytes, mainly or exclusively in the T lymphocytes. These data indicate that in the process of cell cluster formation macrophages serve as antigen-binding (or -processing) cells, while a subpopulation of lymphocytes interact physically and specifically with the macrophages.
Determination of Genes Related to Gastrointestinal Tract Origin Cancer Cells Using a cDNA Microarray
Authors: Tae Moon Kim, Ha Jin Jeong, Min Young Seo, Sang Chul Kim, Gabee Cho, Chan Hee Park, Tae Soo Kim, Kyu Hyun Park, Hyun Cheol Chung, Sun Young Rha
Journal: Clinical Cancer Research (2005)

Abstract Purpose: We evaluated the genome-wide gene expression profiles of various cancer cell lines to identify the gastrointestinal tract cancer cell–related genes. Experimental Design: Gene expression profilings of 27 cancer cell lines and 9 tissues using 7.5K human cDNA microarrays in indirect design with Yonsei reference RNA composed of 11 cancer cell line RNAs were done. The significant genes were selected using significant analysis of microarray in various sets of data. The selected genes were validated using real-time PCR analysis. Results: After intensity-dependent, within-print-tip normalization by loess method, we observed that expression patterns of cell lines and tissues were substantially different, divided in two discrete clusters. Next, we selected 115 genes that discriminate gastrointestinal cancer cell lines from others using significant analysis of microarray. Among the expression profiles of five gastric cancer cell lines, 66 genes were identified as differentially expressed genes related to metastatic phenotype. YCC-16, which was established from the peripheral blood of one advanced gastric cancer patient, produced a unique gene expression pattern resembling the profiles of lymphoid cell lines. Quantitative real-time reverse transcription-PCR results of selected genes, including PXN, KRT8, and ITGB5, were correlated to microarray data and successfully discriminate the gastrointestinal tract cancer cell lines from hematologic malignant cell lines. Conclusions: A gene expression database could serve as a useful source for the further investigation of cancer biology using the cell lines.
A Recent Illustration of Some Essentials of Circadian Chronotherapy Study Design
Authors: William Hrushesky, Patricia Wood, Francis Levi, Reinhard von Roemeling, Georg Bjarnason, Christian Focan, Klaus Meier, Germaine Cornélissen, Franz Halberg
Journal: Journal of Clinical Oncology (2004)

TO THE EDITOR: In 1985, a comparison of the circadian timing of doxorubicin 60 mg/m 2 and cisplatin 60 mg/m 2 given every 28 days to patients with large-volume stage III and stage IV ovarian cancer was published. 1 This comparison of morning doxorubicin and evening cisplatin with evening doxorubicin and morning cisplatin was based on studies in a rat model that predicted that morning doxorubicin followed by evening cisplatin would be less toxic and more effective. 2 The two circadian schedules, compared with one another, kept the order of the drugs constant and the interval between them constant, because other studies had shown that the sequence of and intervals between cytotoxic drugs are also temporal sources of potential relevance to both cytotoxic drug toxicity and efficacy. Patients treated with the morning doxorubicin and evening cisplatin schedule had fewer infections and fewer bleeding episodes; required fewer RBC transfusions; had less nausea, fewer vomiting episodes, and less emesis; had less severe renal damage; and experienced less frequent and less severe peripheral neuropathy. The WBC and platelet counts in patients treated with this schedule recovered by day 21, while the opposite circadian schedule resulted in cumulative marrow toxicity. This resulted in diminished dose intensity. At the same time, the patients treated with the least toxic schedule had a four-fold greater 5-year rate of survival. 3 These findings were confirmed with related drugs in European ovarian cancer patients. 4 A presentation of these data to the members of the Gynecologic Oncology Group (GOG) followed. The ovarian cancer committee had other priorities, but the endometrial cancer committee expressed interest, even though no chronotherapeutic data were available for that cancer. A single-arm study of 6 AM doxorubicin, followed by cisplatin 12 hours later, resulted in an unexpectedly high objective response rate in advanced endometrial cancer. 5 GOG investigators subsequently wished to determine whether circadian doxorubicin and cisplatin timing was relevant to toxicity and outcome in patients with advanced endometrial cancer, and insisted that the control arm not specify drug timing. The ultimate study design specified the order of drugs for both regimens, doxorubicin first and cisplatin second, and required that in the control arm, both drugs be given together, while in the circadian arm, these agents were to be given 12 hours apart.
Cross-Sectional and Prospective Study of Lung Function in Adults With Type 2 Diabetes
Authors: Hsin-Chieh Yeh, Naresh M. Punjabi, Nae-Yuh Wang, James S. Pankow, Bruce B. Duncan, Christopher E. Cox, Elizabeth Selvin, Frederick L. Brancati
Journal: Diabetes Care (2008)

OBJECTIVE—The aim of this study was to test the hypothesis that diabetes is independently associated with reduced lung function, both cross-sectionally and longitudinally. RESEARCH DESIGN AND METHODS—We conducted cross-sectional and prospective analyses of diabetes status and lung function decline using baseline and 3-year follow-up data on 1,100 diabetic and 10,162 nondiabetic middle-aged adults from the Atherosclerosis Risk in Communities (ARIC) Study. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were measured at baseline and at the 3-year follow-up using standard spirometry. RESULTS—At baseline, adults with diabetes had significantly lower predicted FVC (96 vs. 103%, P &amp;lt; 0.001) and predicted FEV1 (92 vs. 96%, P &amp;lt; 0.001) than those without diabetes. These differences remained significant after adjustment for demographic characteristics, adiposity, smoking, physical activity index, education, and ARIC field center. Graded, inverse associations were observed between hyperglycemia, diabetes severity (i.e., duration of diabetes and types of antidiabetes medications), and FVC and FEV1 (all Ptrend &amp;lt; 0.001). In prospective analyses, FVC declined faster in diabetic adults than in their nondiabetic counterparts (64 vs. 58 ml/year, P = 0.01). Diabetes severity as indicated by intensity of antidiabetic treatment also showed graded relationships with the rate of FVC decline (P &amp;lt; 0.01). CONCLUSIONS—These data support the notion that the lung is a target organ for diabetic injury. Additional research is required to identify pathophysiologic mechanisms and to determine clinical significance.
Folic acid-preventable spina bifida and anencephaly
Authors: G P Oakley
Journal: JAMA (1993)

One of the most exciting medical findings of the last part of the 20th century is that folic acid, a simple, widely available, water-soluble vitamin, can prevent spina bifida and anencephaly (SBA). Not since the rubella vaccine became available 30 years ago have we had a comparable opportunity for primary prevention of such common and serious birth defects. The many epidemiologic studies that resulted in the identification of the preventive effect of folic acid is a model for the kind of research that needs to be done to identify the causes of and primary prevention strategies for other birth defects, the leading cause of infant mortality in the United States. An overview of this research will let readers appreciate the contribution of the article by Werler et al,<sup>1</sup>which is published in this issue of<i>JAMA</i>. See also pp 1233 and 1257. Spina bifida and anencephaly are common, serious
Relative roles of cardiac and arterial baroreceptors in vasopressin regulation during hemorrhage in conscious dogs.
Authors: Y T Shen, A W Cowley, S F Vatner
Journal: Circulation Research (1991)

To determine the relative roles of cardiac and sinoaortic baroreceptors in mediation of arginine vasopressin (AVP) release, hemorrhage was performed in five groups of conscious splenectomized dogs: 1) all nerves intact; 2) either chronic surgical or acute pharmacological (intrapericardial lidocaine) cardiac denervation (CD); 3) chronic sinoarotic denervation (SAD); 4) combined chronic sinoartic denervation plus either chronic or acute cardiac denervation (SAD + CD); and 5) all nerves intact, but with ganglionic blockade. Hemorrhage (0.5 ml/min/kg) reduced mean arterial pressure similarly in the intact and CD groups. Decreases in mean arterial pressure were augmented in SAD, SAD + CD, and ganglion-blocked groups compared with responses in intact and CD groups. There were no differences in responses of plasma AVP to hemorrhage in the intact and CD groups, but the AVP response was significantly blunted in the SAD + CD group as compared with SAD alone. When compared during the early stage of hemorrhage, at the same reduction in mean arterial pressure, the rise in AVP was greater in the ganglion-blocked group than in the SAD + CD group, but was less than in the intact group. With a protocol to reduce mean arterial pressure by 20 mm Hg over the same period (42 +/- 0.6 minutes) in four of the groups, the blood volume required to reduce mean arterial pressure by 20 mm Hg was similar in the intact (20 +/- 1 ml/kg) and CD (21 +/- 1 ml/kg) groups, but was less in the SAD (12 +/- 1 ml/kg) and SAD + CD (12 +/- 1 ml/kg) groups. Again, similar increases were observed in AVP between the intact (50 +/- 9 pg/ml) and CD (51 +/- 9 pg/ml) groups, whereas increases in AVP were diminished in the SAD (11 +/- 3 pg/ml) and SAD + CD (7 +/- 2 pg/ml) groups. In the presence of an AVP antagonist, decreases in mean arterial pressure and increases in total peripheral resistance with hemorrhage were affected similarly in both the intact and CD groups, whereas hemodynamic impairment by AVP blockade was less marked in the SAD and SAD + CD groups. These results indicate that cardiac receptors are not the major regulators of AVP release during progressive hemorrhage in conscious dogs. However, when the complicating influences of sinoaortic reflexes were eliminated, a modest role for cardiac receptors was uncovered.