tbuckley/cabot-search huggingface dataset:
The US perspective: lessons learned from the Racial and Ethnic Approaches to Community Health (REACH) Program
Authors: Wayne H Giles
Journal: Journal of the Royal Society of Medicine (2010)

In 2002, the US Institute of Medicine (IOM) reached the conclusion ‘Disparities in health care are one of the nation's most serious health care problems. Research has extensively documented the pervasiveness of racial and ethnic disparities.’1

The disparities noted by the IOM are widespread. In the US, deaths from heart disease are 30% higher among African-Americans than Caucasians, and deaths from stroke are 40% higher among African-Americans than Caucasians. The incidence of diabetes is 2.3 times higher among American-Indian Alaska Natives, 1.6 times higher among African-Americans, and 1.5 times higher among Hispanics when compared with Caucasians. The rate of cervical cancer is five times higher in Vietnamese women than Caucasian women. Finally, the rate of infant mortality (death within the first 12 months of age) is 2.5 times higher in African-Americans than in Caucasians.

While these statistics may seem disturbing, the fact that these disparities are not new is even more disturbing. In fact, WEB Dubois documented alarming disparities between African-Americans and Caucasians in 1899 when he wrote The Philadelphia Negro. Dubois noted alarmingly high rates of cancer, heart disease and stroke among African-Americans residing in Philadelphia. In 1899, Dubois called for the elimination of health disparities with the statement: ‘We must endeavor to eliminate, so far as possible, the problem elements which make a difference in health among people’.2

In 1999, the US Federal Government launched the REACH (Racial and Ethnic Approaches to Community Health) Program.3 This program, while headed by the Centers for Disease Control and Prevention (CDC), had a number of federal and private sector partners who were instrumental in guiding it. These partners included the Offices of Minority Health, Public Health Science, and the Assistance Secretary for Program Planning and Evaluation from the Department of Health and Human Services. Other partners included the Office of Minority Health and Health Disparities at the National Institutes of Health, the Administration on Aging, the California Endowment, and the Society for Public Health Education. Without the advice, guidance, and partnership of these influential organizations, the REACH program would not have been as successful as it has been.
Phase I Trial of G3139, a bcl-2 Antisense Oligonucleotide, Combined With Doxorubicin and Cyclophosphamide in Children With Relapsed Solid Tumors: A Children's Oncology Group Study
Authors: Susan R. Rheingold, Michael D. Hogarty, Susan M. Blaney, James A. Zwiebel, Calies Sauk-Schubert, Reddy Chandula, Mark D. Krailo, Peter C. Adamson
Journal: Journal of Clinical Oncology (2007)

To determine the maximum-tolerated dose, toxicity, pharmacokinetics, and biologic effects of G3139 when administered with doxorubicin and cyclophosphamide to children with relapsed solid tumors.Patients received a 7-day continuous infusion of 3, 5, or 7 mg/kg/d of G3139 every 21 days. Doxorubicin, cyclophosphamide, and dexrazoxane were administered on days 5 and 6 of the infusion. Pharmacokinetics and biology studies were performed during the first course.Thirty-seven patients, median age 14 years (range, 1 to 19 years), were enrolled, of whom 29 were fully assessable for toxicity. Because of dose-limiting neutropenia, doses of doxorubicin 30 mg/m2/d for 2 days, dexrazoxane 300 mg/m2/d for 2 days, and cyclophosphamide 500 mg/m2/d for 2 days were reduced initially, but with the addition of granulocyte colony-stimulating factor (GCSF), could be re-escalated to starting doses. At the 7 mg/kg/d dose level, only one of six patients experienced DLT (neutropenia > 7 days). At this dose, the average (+/- standard deviation) steady-state G3139 concentration was 2.04 +/- 1 microg/mL, a concentration associated with biologic activity. Eleven of 15 patients had reduced bcl-2 expression in peripheral-blood mononuclear cells at the first assessable time point of G3139 exposure, and in eight of 14 patients with serial specimens this reduction persisted through day 6.The recommended phase II dose of G3139 is 7 mg/kg/d as a 7-day continuous infusion, with cyclophosphamide 500 mg/m2/d and doxorubicin 30 mg/m2/d on days 5 and 6, followed by GCSF. G3139 may accentuate the myelosuppressive effects of doxorubicin and cyclophosphamide. Evidence for biologic effects of G3139 was demonstrated.
Pulse steroid therapy in rheumatoid arthritis.
Authors: J Webb
Journal: Annals of the Rheumatic Diseases (1988)

Characteristics of human large granular lymphocytes and relationship to naturalPulse steroid therapy in rheumatoid arthritis SIR, After a decade of the use of intravenous 'pulse' megadose corticosteroids in rheumatoid arthritis we now have a controlled study that shows there is no difference in effect from a similar 'pulse' given orally.'Although the authors pointed out that this obviates the need for hospital admission and thus makes fewer demands on medical and copyright.
THE EFFECT OF BACTERIAL CONSTITUENTS ON THE RESISTANCE OF MICE TO HETEROLOGOUS INFECTION AND ON THE ACTIVITY OF THEIR RETICULO-ENDOTHELIAL SYSTEM
Authors: Diethelm Boehme, René J. Dubos
Journal: The Journal of Experimental Medicine (1958)

Administration of small amounts of salmonella endotoxin (20 microg.) or of acetone-extracted BCG cells (100 microg.) increases the resistance of mice to infection with Myco. fortuitum as well as their ability to clear carbon particles from their blood stream. Whereas the increased resistance to infection persists for many weeks, the clearing power returns to a normal level within a few days. When normal mice are infected with Myco. fortuitum, there occurs during the first phase of the infectious process a rise in clearing power for carbon particles followed by a fall during the terminal phase of the disease. The rise occurs more rapidly and is more pronounced in animals previously treated with salmonella endotoxin or with killed BCG cells. This acceleration and intensification of the phagocytic response to infection can be detected even in animals which exhibit a normal phagocytic index when tested several weeks after administration of endotoxin or of BCG. Although increase in resistance to infection is correlated with activation of the so called reticulo-endothelial system, there is no evidence of any direct causal relationship between the two phenomena.
Targeted electrode-based modulation of neural circuits for depression
Authors: Helen S. Mayberg
Journal: Journal of Clinical Investigation (2009)

During the last 20 years of neuroscience research, we have witnessed a fundamental shift in the conceptualization of psychiatric disorders, with the dominant psychological and neurochemical theories of the past now complemented by a growing emphasis on developmental, genetic, molecular, and brain circuit models. Facilitating this evolving paradigm shift has been the growing contribution of functional neuroimaging, which provides a versatile platform to characterize brain circuit dysfunction underlying specific syndromes as well as changes associated with their successful treatment. Discussed here are converging imaging findings that established a rationale for testing a targeted neuromodulation strategy, deep brain stimulation, for treatment-resistant major depression.
Meditation and Marijuana
Authors: MOHAMMED SHAFIL, RICHARD LAVELY, ROBERT JAFE
Journal: American Journal of Psychiatry (1974)

Using a questionnaire survey, the authors sought to discover the effect of meditation on their subjects' use of marijuana. While only' 15 percent of a nonmeditating control group had decreased or stopped their use of marijuana during the preceding three months, among the meditators proportions ranging from half to three-quartens (depending on the length of time since their initiation) had decreased or stopped their use during the first three months after initiation into meditation. The authors found that the longer a person had practiced meditation, the more likely it was that he had decreased or stopped his use of marijuana.
Risk of Epithelial Ovarian Cancer Recurrence in Patients With Rising Serum CA-125 Levels Within the Normal Range
Authors: Antonio Santillan, Ruchi Garg, Marianna L. Zahurak, Ginger J. Gardner, Robert L. Giuntoli, Deborah K. Armstrong, Robert E. Bristow
Journal: Journal of Clinical Oncology (2005)

To evaluate the risk of epithelial ovarian cancer (EOC) recurrence in patients with rising serum cancer antigen 125 (CA-125) levels that remain below the upper limit of normal (< 35 U/mL).All patients treated for EOC between September 1997 and March 2003 were identified and screened retrospectively for the following: (1) elevated serum CA-125 at time of diagnosis, (2) complete clinical and radiographic response (CR) to initial treatment with normalization of serum CA-125, (3) at least three serial serum CA-125 determinations that remained within the normal range, and (4) clinical and/or radiographic determination of disease status at the time of last follow-up or recurrence. For statistical analyses, univariate regression models were used to compare absolute and relative changes in CA-125 levels among patients with recurrent disease and those without EOC recurrence.A total of 39 patients satisfied study inclusion criteria; 22 patients manifested EOC recurrence at a median interval from complete response of 11 months. The median follow-up time from complete response to last contact was 32 months for the 17 patients in the no recurrence group. A relative increase in CA-125 of 100% (odds ratio [OR] = 23.7; 95% CI, 2.9 to 192.5; P = .003) was significantly predictive of recurrence. From baseline CA-125 nadir levels, an absolute increase in CA-125 of 5 U/mL (OR = 8.4; 95% CI, 2.2 to 32.6; P = .002) and 10 U/mL (OR = 71.2; 95% CI, 4.8 to > 999.9; P = .002) were also significantly associated with the likelihood of concurrent disease recurrence.Among patients with EOC in complete clinical remission, a progressive low-level increase in serum CA-125 levels is strongly predictive of disease recurrence.
Platelet-derived growth factor activity and mRNA expression in healing vascular grafts in baboons. Association in vivo of platelet-derived growth factor mRNA and protein with cellular proliferation.
Authors: M A Golden, Y P Au, T R Kirkman, J N Wilcox, E W Raines, R Ross, A W Clowes
Journal: Journal of Clinical Investigation (1991)

In a baboon graft model of arterial intimal thickening, smooth muscle cells (SMC) have been observed to proliferate underneath an intact monolayer of endothelium and in the absence of platelet adherence. Because platelets are not present and therefore cannot be a major source of growth stimulus, we have proposed that the vascular wall cells in the graft intima express mitogens and regulate SMC proliferation. To test this hypothesis, we assayed the grafts for mitogenic activity and expression of growth factor genes. Segments of healing graft and of normal artery, when perfused ex vivo, released mitogenic activity into the perfusate. The graft released more mitogen than the normal arterial segment, and some of the activity was inhibitable with an antibody to human platelet-derived growth factor (PDGF). In addition, Northern analysis of total RNA demonstrated higher expression of PDGF-A chain mRNA in the graft intima compared to normal artery. PDGF-B chain mRNA was barely detectable in both tissues. PDGF mRNA levels within the graft interstices were not measured. In situ hybridization of 7.5- or 12-wk grafts indicated that some luminal endothelial cells and adjacent intimal SMC contained PDGF-A chain mRNA. By thymidine autoradiography, intimal SMC were observed to be proliferating in the inner third of the intima. These data demonstrate a difference in the pattern of PDGF transcript expression and luminal perfusate activity in graft as compared with control arteries. The association of intimal smooth muscle cell proliferation with intimal PDGF mRNA expression and release of PDGF-like protein supports the hypothesis that factors from cells that have grown into the graft or populated its surface rather than platelets may regulate intimal smooth muscle cell proliferation in this model.
Water for ADPKD? Probably, Yes
Authors: Vicente E. Torres
Journal: Journal of the American Society of Nephrology (2006)

“On systemic inquiry among the patients it was astonishing to find how frequently they reported having suffered from thirst, polydipsia and polyuria already at an early stage of the disease.”

—Dalgaard, 1957

Since its early descriptions, an impaired urine-concentrating capacity has been a
Nevirapine- Versus Lopinavir/Ritonavir-Based Initial Therapy for HIV-1 Infection among Women in Africa: A Randomized Trial
Authors: Shahin Lockman, Michael Hughes, Fred Sawe, Yu Zheng, James McIntyre, Tsungai Chipato, Aida Asmelash, Mohammed Rassool, Sylvester Kimaiyo, Douglas Shaffer, Mina Hosseinipour, Lerato Mohapi, Francis Ssali, Margret Chibowa, Farida Amod, Elias Halvas, Evelyn Hogg, Beverly Alston-Smith, Laura Smith, Robert Schooley, John Mellors, Judith Currier
Journal: PLoS Medicine (2012)

Nevirapine (NVP) is widely used in antiretroviral treatment (ART) of HIV-1 globally. The primary objective of the AA5208/OCTANE trial was to compare the efficacy of NVP-based versus lopinavir/ritonavir (LPV/r)-based initial ART.In seven African countries (Botswana, Kenya, Malawi, South Africa, Uganda, Zambia, and Zimbabwe), 500 antiretroviral-naïve HIV-infected women with CD4<200 cells/mm(3) were enrolled into a two-arm randomized trial to initiate open-label ART with tenofovir (TDF)/emtricitabine (FTC) once/day plus either NVP (n = 249) or LPV/r (n = 251) twice/day, and followed for ≥48 weeks. The primary endpoint was time from randomization to death or confirmed virologic failure ([VF]) (plasma HIV RNA<1 log(10) below baseline 12 weeks after treatment initiation, or ≥400 copies/ml at or after 24 weeks), with comparison between treatments based on hazard ratios (HRs) in intention-to-treat analysis. Equivalence of randomized treatments was defined as finding the 95% CI for HR for virological failure or death in the range 0.5 to 2.0. Baseline characteristics were (median): age = 34 years, CD4 = 121 cells/mm(3), HIV RNA = 5.2 log(10)copies/ml. Median follow-up = 118 weeks; 29 (6%) women were lost to follow-up. 42 women (37 VFs, five deaths; 17%) in the NVP and 50 (43 VFs, seven deaths; 20%) in the LPV/r arm reached the primary endpoint (HR 0.85, 95% CI 0.56-1.29). During initial assigned treatment, 14% and 16% of women receiving NVP and LPV/r experienced grade 3/4 signs/symptoms and 26% and 22% experienced grade 3/4 laboratory abnormalities. However, 35 (14%) women discontinued NVP because of adverse events, most in the first 8 weeks, versus none for LPV/r (p<0.001). VF, death, or permanent treatment discontinuation occurred in 80 (32%) of NVP and 54 (22%) of LPV/r arms (HR = 1.7, 95% CI 1.2-2.4), with the difference primarily due to more treatment discontinuation in the NVP arm. 13 (45%) of 29 women tested in the NVP versus six (15%) of 40 in the LPV/r arm had any drug resistance mutation at time of VF.Initial ART with NVP+TDF/FTC demonstrated equivalent virologic efficacy but higher rates of treatment discontinuation and new drug resistance compared with LPV/r+TDF/FTC in antiretroviral-naïve women with CD4<200 cells/mm(3).ClinicalTrials.gov NCT00089505.
Cognitive Function in an Elderly Population With Persistent Impaired Glucose Tolerance
Authors: Matti Vanhanen, Keijo Koivisto, Johanna Kuusisto, Leena Mykkänen, Eeva-Liisa Helkala, Tuomo Hänninen, Paavo Riekkinen, Hilkka Soininen, Markku Laakso
Journal: Diabetes Care (1998)

OBJECTIVE To study cognitive function in an elderly population with persistent impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS Fasting and postload 2-h plasma glucose and insulin levels were determined at baseline in a population-based sample of 1,300 people and repeated an average of 3.5 years later in 980 subjects. At follow-up, cognitive function was evaluated in subjects with persistent normal glucose tolerance (NGT; n = 506) and IGT (n = 80) with a brief neuropsychological test battery. RESULTS Subjects with persistent IGT scored lower in the Mini-Mental State Examination (MMSE) and in the Buschke Selective Reminding Test long-term memory scores. Multiple linear regression analysis revealed that age, education, and insulin levels (either fasting or 2-h value) were associated with the MMSE score in subjects with persistent IGT. Other potential risk factors for impaired cognitive function were not significantly associated with the MMSE score. CONCLUSIONS Our study showed that persistent IGT in the elderly is associated with mildly impaired cognitive function, and hyperinsulinemia may account for this association.
Renal tubular and vascular urea transporters
Authors: D Promeneur, L Bankir, M C Hu, M M Trinh-Trang-Tan
Journal: Journal of the American Society of Nephrology (1998)

In the kidney, facilitated urea transport in precise vascular and tubular structures is mainly involved in water conservation. Three urea transporters have been cloned: UT2-long expressed in terminal inner medullary collecting duct (IMCD), UT2-short expressed in thin descending limb, and UT11 in descending vasa recta. The effect of arginine vasopressin (AVP) administration on mRNA expression of these three transporters was examined in Brattleboro rats with diabetes insipidus. V2 effects were discriminated from combined V1 + V2 effects by comparing treatments with 1-deamino-8-D-AVP (dDAVP) (selective V2 agonism) and AVP (V1 and V2 agonism). Acute and chronic treatments were studied. Abundance of specific mRNA was assessed by quantitative Northern blot analysis of RNA extracted from two regions of inner stripe of outer medulla and from two regions of inner medulla (IM). The results show that mRNA of these urea transporters are differently regulated by AVP. (1) Long-term treatment with either AVP or dDAVP does not alter UT2-long mRNA in tip IM (terminal IMCD) except for a transient initial decrease. (2) Unlike AVP, dDAVP induces the appearance of significant expression of UT2-long mRNA in base IM (initial IMCD), indicating a major V2 effect. (3) UT2-short mRNA in deep inner stripe of outer medulla and base IM (thin descending limb of short and long loops, respectively) is progressively upregulated with duration of AVP or dDAVP treatment. (4) The much higher changes in UT2-long and UT2-short induced by dDAVP compared with AVP suggest that they are dependent mainly on V2 agonism, and likely attenuated by V1 agonism. (5) UT11 mRNA expression in tip IM is equally depressed by AVP and dDAVP, indicating that this vascular transporter is also influenced by AVP and/or urine-concentrating activity, via an indirect mechanism that remains to be determined.
Improved reliability of spirometry and diffusion measurements by pneumotachograph compared to mass-flow sensor
Authors: Herman Groepenhoff, Sandra Franken, Jerica Sinkeldam, Gwenda Commandeur, Patrick Jak
Journal: European Respiratory Journal (2014)

Introduction : The standard error of measurement (SEM) is recommended as most appropriate to express error of a single measurement. Consequently, SEM is important in assessing pulmonary function instruments. Therefore we measured the SEM of spirometry and diffusion variables of our, to be replaced, mass flow sensor systems and to purchase pneumotachogtraph systems.

Method: Four healthy pulmonary function technicians measured ten times their spirometry and diffusion parameters on two pulmonary function systems equipped with a pneumotachograph sensor (SentrySuite, Carefusion) in random sequence within a time period of two weeks. This procedure was repeated on two systems equipped with a mass flow sensor (Vmax, Carefusion). The variance components were estimated by analysis of variation. SEM was calculated by taking the sum of the square root of error variance components. The smallest detectable change (SDC), calculated by 1.96\*SEM\*√2, was considered a true minimal significant change between two single measurements.

Results: 

![Figure][1] 



SEM: standard error of the measurement, SDC: smallest detectable change, VC: vital capacity,FEV1: forced volume in one second, DLCO: single breath diffusion capacity for carbon monoxide and VA: alveolar volume. 

Conclusion: Reliability of spirometry and diffusion measurements is improved when measured by pneumotachograph - compared to mass-flow sensor pulmonary function systems.

 [1]: pending:yes
Environmental effects and aquatic organisms: investigations of molecular mechanisms of carcinogenesis.
Authors: R J Van Beneden
Journal: Environmental Health Perspectives (1997)

Cancers of the reproductive system are among the leading causes of mortality in women in the United States. While both genetic and environmental factors have been implicated in their etiology, the extent of the contribution of environmental factors to human diseases remains controversial. To better address the role of environmental exposures in cancer etiology, there has been an increasing focus on the development of nontraditional, environmentally relevant models. Our research involves the development of one such model. Gonadal tumors have been described in the softshell clam (Mya arenaria) in Maine and the hardshell clam (Mercenaria spp.) from Florida. Prevalence of these tumors is as high as 40% in some populations in eastern Maine and 60% in some areas along the Indian River in Florida. The average tumor prevalence in Maine and Florida is approximately 20 and 11%, respectively. An association has been suggested between the use of herbicides and the incidence of gonadal tumors in the softshell clam in Maine. The role of environmental exposures in the development of the tumors in Mercenaria in Florida is unknown; however, there is evidence that genetic factors may contribute to its etiology. Epidemiologic studies of human populations in these same areas show a higher than average mortality rate due to cancers of the reproductive system in women, including both ovarian and breast cancer. The relationship, if any, among these observations is unknown. Our studies on the molecular basis of this disease in clams may provide additional information on environmental exposures and their possible link to cancer in clams and other organisms, including humans.
International Union of Pharmacology. XLVI. G Protein-Coupled Receptor List
Authors: Steven M. Foord, Tom I. Bonner, Richard R. Neubig, Edward M. Rosser, Jean-Phillipe Pin, Anthony P. Davenport, Michael Spedding, Anthony J. Harmar
Journal: Pharmacological Reviews (2005)

NC-IUPHAR (International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification) and its subcommittees provide authoritative reports on the nomenclature and pharmacology of G protein-coupled receptors (GPCRs) that summarize their structure, pharmacology, and roles in physiology and pathology. These reports are published in Pharmacological Reviews (http://www.iuphar.org/nciuphar_arti.html) and through the International Union of Pharmacology (IUPHAR) Receptor Database web site (http://www.iuphar-db.org/iuphar-rd). The essentially complete sequencing of the human genome has allowed the cataloging of all of the human gene sequences potentially encoding GPCRs. The IUPHAR Receptor List (http://www.iuphar-db.org/iuphar-rd/list/index.htm) presents this catalog giving IUPHAR-approved nomenclature (where available), known ligands, and gene names for all of these potential receptors (excluding sensory receptors and pseudogenes) together with links to curated sequence, descriptive information, and additional links in the Entrez Gene database (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene). This list is a major new initiative of NC-IUPHAR that, through continuing curation, defines the target of our ongoing receptor classification and invites further input from the scientific community.