tbuckley/cabot-search huggingface dataset:
Screening for Gestational Diabetes Mellitus: A Systematic Review for the U.S. Preventive Services Task Force
Authors: Teresa A. Hillier, Kimberly K. Vesco, Kathryn L. Pedula, Tracy L. Beil, Evelyn P. Whitlock, David J. Pettitt
Journal: Annals of Internal Medicine (2008)

Background: In 2003, the U.S. Preventive Services Task Force concluded that evidence was insufficient to advise for or against routinely screening all pregnant women for gestational diabetes mellitus. Purpose: To review evidence about the benefits and harms of screening for gestational diabetes. Data Sources: Databases (MEDLINE, Database of Abstracts of Reviews of Effects, Health Technology Assessment Database, National Institute for Health and Clinical Effectiveness, and Cochrane Library) were searched for reports published from January 2000 to 15 November 2007 (and from 1966 to 1999 for additional studies on screening at less than 24 weeks' gestation), citations in the 2003 evidence report, and studies identified through consultation of experts and searches of bibliographies. Study Selection: English-language studies that used standard 1- or 2-step testing for gestational diabetes and that evaluated at least 1 of the following outcomes: neonatal mortality; brachial plexus injury; clavicular fracture; admission to a neonatal intensive care unit for hypoglycemia, hyperbilirubinemia, or the respiratory distress syndrome; maternal mortality; and preeclampsia or pregnancy-induced hypertension. Data Extraction: 2 reviewers evaluated 1607 abstracts, critically appraised 288 articles, and qualitatively synthesized 13 studies. Data Synthesis: No randomized, controlled trials that directly evaluated the risks and benefits of gestational diabetes screening were found. One good-quality randomized, controlled trial of treatment of mild gestational diabetes in a screening-detected population supported a reduction in serious neonatal complications and showed that gestational diabetes treatment also reduced the risk for gestational hypertension. Very limited evidence was found to evaluate early screening for gestational diabetes (before 24 weeks' gestation). Limited evidence suggests that serious maternal hypoglycemia is rare with treatment and that overall quality of life is not worse among women receiving gestational diabetes treatment compared with women not receiving treatment. Limitation: The literature is limited by lack of a consistent standard for screening or diagnosis of gestational diabetes. Conclusion: Limited evidence suggests that gestational diabetes treatment after 24 weeks improves some maternal and neonatal outcomes. Evidence is even more sparse for screening before 24 weeks' gestation.
Burden of Invasive<i>Staphylococcus aureus</i>Infections in Hospitalized Infants
Authors: Jessica E. Ericson, Victor O. Popoola, P. Brian Smith, Daniel K. Benjamin, Vance G. Fowler, Daniel K. Benjamin, Reese H. Clark, Aaron M. Milstone
Journal: JAMA Pediatrics (2015)

<h3>Importance</h3> <i>Staphylococcus aureus</i>is a frequent cause of infection in hospitalized infants. These infections are associated with increased mortality and morbidity and longer hospital stays, but data on the burden of<i>S aureus</i>disease in hospitalized infants are limited. <h3>Objectives</h3> To compare demographics and mortality of infants with invasive methicillin-resistant<i>S aureus</i>(MRSA) and methicillin-susceptible<i>S aureus</i>(MSSA), to determine the annual proportion of<i>S aureus</i>infections that were MRSA, and to contrast the risk of death after an invasive MRSA infection with the risk after an invasive MSSA infection. <h3>Design, Setting, and Participants</h3> Multicenter retrospective study of a large, nationally representative cohort at 348 neonatal intensive care units managed by the Pediatrix Medical Group. Participants were 3888 infants with an invasive<i>S aureus</i>infection who were discharged from calendar year 1997 through calendar year 2012. <h3>Exposure</h3> Invasive<i>S aureus</i>infection. <h3>Main Outcomes and Measures</h3> The incidence of invasive<i>S aureus</i>infections, as well as infant characteristics and mortality after MRSA or MSSA infection. <h3>Results</h3> The 3888 infants had 3978 invasive<i>S aureus</i>infections (2868 MSSA and 1110 MRSA). The incidence of invasive<i>S aureus</i>infection was 44.8 infections per 10 000 infants. The yearly proportion of invasive infections caused by MRSA increased from calendar year 1997 through calendar year 2006 and has moderately decreased since then. Infants with invasive MRSA or MSSA infections had similar gestational ages and birth weights. Invasive MRSA infections occurred more often at a younger postnatal age. For infants with available mortality data, more infants with invasive MSSA infections (n = 237) died before hospital discharge than infants with invasive MRSA infections (n = 110). The proportions of infants who died after invasive MSSA and MRSA infections were similar at 237 of 2474 (9.6%) and 110 of 926 (11.9%), respectively (<i>P</i> = .05). The adjusted risk of death before hospital discharge was similar after invasive MSSA and MRSA infections (risk ratio, 1.19; 95% CI, 0.96-1.49). The risks of death at 7 and 30 days after invasive infection were similar between infants with invasive MSSA infection and infants with invasive MRSA infection. <h3>Conclusions and Relevance</h3> Infant mortality after invasive MRSA and MSSA infections is similar, but MSSA causes more infections and more deaths in infants than MRSA. Measures to prevent<i>S aureus</i>infection should include MSSA in addition to MRSA.
Functional and Structural Changes in the Kidney in the Early Stages of Obesity
Authors: JEFFREY R. HENEGAR, STEVEN A. BIGLER, LISA K. HENEGAR, SURESH C. TYAGI, JOHN E. HALL
Journal: Journal of the American Society of Nephrology (2001)

Abstract. The purpose of this study was to examine the histologic and functional changes that occur in the kidney in the early stages of obesity caused by a high-fat diet. Lean dogs (n = 8) were fed a standard kennel ration, and obese dogs (n = 8) were fed the standard kennel ration plus a supplement of cooked beef fat each day for 7 to 9 wk or 24 wk. Body weights were 58 ± 5% greater and kidney weights were 31 ± 7% greater in obese dogs, compared with the average values for lean dogs. Plasma renin activity and insulin concentrations were both 2.3-fold greater in obese dogs, compared with lean dogs. Obesity was associated with a mean arterial pressure increase of 12 ± 3 mmHg, a 38 ± 6% greater GFR, and a 61 ± 7% higher renal plasma flow, compared with lean dogs. The glomerular Bowman's space area was significantly greater (+41 ± 7%) in dogs fed the high-fat diet, compared with lean animals, mainly because of expansion of Bowman's capsule (+22 ± 7%). There was also increased mesangial matrix and thickening of the glomerular and tubular basement membranes and the number of dividing cells (proliferating cell nuclear antigen-stained) per glomerulus was 36 ± 8% greater in obese dogs, compared with lean dogs. There was also a trend for glomerular transforming growth factor-β1 expression, as estimated by semiquantitative immunohistochemical analysis, to be elevated with the high-fat diet. Therefore, a high-fat diet caused increased arterial pressure, hyperinsulinemia, activation of the renin-angiotensin system, glomerular hyperfiltration, and structural changes in the kidney that may be the precursors of more severe glomerular injury associated with prolonged obesity.
THE SITE OF SYNTHESIS OF THE 19S γ-GLOBULINS IN DYSGAMMAGLOBULINEMIA
Authors: Andre Cruchaud, Fred S. Rosen, John M. Craig, Charles A. Janeway, David Gitlin
Journal: The Journal of Experimental Medicine (1962)

Lymph nodes and splenic tissue from patients with congenital agammaglobulinemia and dysgammaglobulinemia and from normal subjects were studied with the use of immunofluorescence and histochemical stains to determine the site of synthesis of the 19S gamma(1)-globulins. The two patients with dysgammaglobulinemia had high serum concentrations of the 19S gamma(1)-globulins and a marked deficit of the 7S gamma-globulins. These patients, as well as agammaglobulinemic children, had only rare or no plasma cells in their tissues. Cells were identified in sections of spleen from a dysgammaglobulinemic child as well as from normal individuals which exhibited specific fluorescence with an anti-19S gamma-globulin antiserum adsorbed with 7S gamma(2)-globulins and which stained positively with PAS and methyl green pyronine. These cells resembled the transitional cells described by Fagraeus.
Antiangiogenic and anti-invasive effects of sunitinib on experimental human glioblastoma
Authors: Sophie de Boüard, Paulette Herlin, James G. Christensen, Edwige Lemoisson, Pascal Gauduchon, Eric Raymond, Jean-Sébastien Guillamo
Journal: Neuro-Oncology (2007)

Angiogenesis inhibitors appear to be promising therapies for highly vascularized tumors such as glioblastoma multiforme (GBM). Sunitinib is an oral multitargeted tyrosine kinase inhibitor with both antiangiogenic and antitumor activities due to selective inhibition of various receptor tyrosine kinases, including those important for angiogenesis (vascular endothelial growth factor receptors and platelet-derived growth factor receptors). Here we evaluated the antitumor activities of sunitinib on orthotopic models of GBM in vitro and in vivo. Sunitinib potently inhibited angiogenesis that was stimulated by implantation of U87MG and GL15 cells into organotypic brain slices at concentrations as low as 10 nM. At high dose (10 μM), sunitinib induced direct antiproliferative and proapoptotic effects on GL15 cells and decreased invasion of these cells implanted into brain slices by 49% (p < 0.001). Treatment was associated with decreases in Src (35%) and focal adhesion kinase (44%) phosphorylation. However, anti-invasive activity was not observed in vivo at the highest dose level utilized (80 mg/kg per day). Survival experiments involving athymic mice bearing intracerebral U87MG GBM demonstrated that oral administration of 80 mg/kg sunitinib (five days on, two days off) improved median survival by 36% (p < 0.0001). Sunitinib treatment caused a 74% reduction in microvessel density (p < 0.05), an increase in tumor necrosis, and a decrease in number of GBM cells positive for MIB antibody. Sunitinib exhibited potent antiangiogenic activity that was associated with a meaningful prolongation of survival of mice bearing intracerebral GBM. These data support the potential utility of sunitinib in the treatment of GBM.
Quality of Care for Diabetic Patients in a Large Urban Public Hospital
Authors: Pitiporn Suwattee, J. Christopher Lynch, Merri L. Pendergrass
Journal: Diabetes Care (2003)

OBJECTIVE—We compared diabetes quality-of-care indicators for patients receiving medical treatment in three practice settings of the same hospital. RESEARCH DESIGN AND METHODS—A cross-sectional medical record review for patients receiving care between 1 July 2000 and 30 June 2001 was conducted. Records were abstracted from three practice settings: the Diabetes Clinic (DIABETES), a general medicine clinic staffed by internal medicine residents (RESIDENT), and a general medicine clinic whose providers were medical school faculty physicians (FACULTY). Record review (n = 791) yielded data on diabetes indicators that were derived primarily from the Diabetes Quality Improvement Project. RESULTS—There were significant differences between the DIABETES, RESIDENT, and FACULTY clinics for the percentages of patients with HbA1c testing (94 vs. 92 vs. 76%, P &amp;lt; 0.001), HbA1c &amp;gt;9.5% (31 vs. 36 vs. 43%, P &amp;lt; 0.05), nephropathy assessment (79 vs. 67 vs. 58%, P &amp;lt; 0.001), lipid assessment (86 vs. 79 vs. 76%, P &amp;lt; 0.050), LDL &amp;lt;130 mg/dl (54 vs. 44 vs. 43%, P &amp;lt; 0.05), blood pressure &amp;lt;140/90 mmHg (63 vs. 55 vs. 49%, P &amp;lt; 0.025), eye examinations (64 vs. 50 vs. 31%, P &amp;lt; 0.001), foot examinations (97 vs. 55 vs. 24%, P &amp;lt; 0.001), ACE inhibitor treatment (66 vs. 69 vs. 35%, P &amp;lt; 0.001), and aspirin treatment (71 vs. 59 vs. 15%, P &amp;lt; 0.001). CONCLUSIONS—There is considerable variation in diabetes management in different primary care settings of the same hospital. Although management in all settings was suboptimal, the results attained by the patients in the Diabetes Clinic represent minimal achievable goals for all diabetic patients in this hospital.
Molecular biology techniques and their applicability to the study of diabetes and hypertension
Authors: J R Ingelfinger, F Jung, S S Tang
Journal: Journal of the American Society of Nephrology (1992)

Recently developed molecular biology techniques lend themselves to the study of both normal physiology and pathophysiology. This review discusses a number of such techniques and their applicability to the study of diabetes and hypertension with the renin-angiotensin system as an example. The demonstration of specific mRNA in tissue provides strong evidence that the protein for which it encodes is expressed there. The contribution of several methods to demonstrate mRNA expression including Northern analysis, slot blot analysis, solution hybridization, in situ hybridization, run-on assays, and polymerase chain reaction are discussed in the light of how these are used to study renin-angiotensin system mechanisms. Additionally, recent developments in the study of gene transfer and identification of genes are reviewed.
Congenital and Perinatal Sensory Deprivation: Some Studies in Early Development
Authors: DAVID A. FREEDMAN
Journal: American Journal of Psychiatry (1971)

Very early deficiency of coenesthetic (i.e., nonspecific) sensory experience results in gross, apparently irreversible, personality disturbances. The author presents evidence indicating that the high incidence of autistic disturbances in the congenitally blind is also due to coenesthetic deprivation. The congenitally deaf child, who tends to be very active and responsive during the early months of postpartal life, does not show the kinds of characterologic deviations regularly observed in the environmentally deprived and very frequently observed in the congenitally blind.
Genetic and Neurochemical Modulation of Prefrontal Cognitive Functions in Children
Authors: Adele Diamond, Lisa Briand, John Fossella, Lorrie Gehlbach
Journal: American Journal of Psychiatry (2004)

The catechol O-methyltransferase (COMT) gene affects how long dopamine acts in the prefrontal cortex. The Methionine polymorphism, which results in a slower breakdown of prefrontal dopamine, is associated with better adult prefrontal cortex function. The authors investigated the relation between the COMT gene polymorphism and cognitive performance in children.Children were tested on cognitive tasks that depend on the dorsolateral prefrontal cortex and seem to be sensitive to the level of dopamine there (dots-mixed task), depend on that neural region but appear insensitive to its dopamine content (self-ordered pointing), and depend on other neural systems (recall memory and mental rotation). After data collection, cheek swabs were obtained from all children. DNA was extracted and genotyped for the COMT gene with polymerase chain reaction.Children who were homozygous for the Methionine polymorphism performed significantly better on the dots-mixed task but not on others.The findings provide an existence proof that genotypic differences can relate to differences in cognitive performance in typically developing children. The authors achieved a level of specificity never previously attempted; the COMT polymorphism was found to be differentially related to performance on tasks linked to the same prefrontal region by whether cognitive requirements of the tasks were sensitive to the level of dopamine found. These results challenge accepted notions that since dopamine is important for some cognitive functions dependent on the prefrontal cortex, it is important for all. The differential sensitivity of distinct cognitive abilities to specific neurotransmitters may make possible targeted pharmacological interventions.
Modifiable practices associated with sudden death among hemodialysis (HD) patients: the Dialysis Outcomes and Practice Patterns Study (DOPPS)
Authors: Michel Jadoul, Yang Li, J. Thumma, F. Tentori, H. Morgenstern, D. Mendelssohn, T. Tomo, F. Port, B.M. Robinson
Journal: Journal of the American Society of Nephrology (2009)
496 GENOTYPIC RESISTANCE REDUCED TO VERY LOW LEVELS IN CHRONIC HEPATITIS B (CHB) PATIENTS TREATED OVER 2-YEARS WITH TELBIVUDINE (LDT) WHEN CONSIDERING BASELINE CHARACTERISTICS AND ROADMAP
Authors: F. Zoulim, S. Zeuzem, T. Piratvisuth, H.L. Chan, J. Hou, J. Jia, S. Bosset, A. Uddin, Y. Dong, A. Trylesinski
Journal: Journal of Hepatology (2012)
MicroRNA-21 targets the vitamin D–dependent antimicrobial pathway in leprosy
Authors: Philip T Liu, Matthew Wheelwright, Rosane Teles, Evangelia Komisopoulou, Kristina Edfeldt, Benjamin Ferguson, Manali D Mehta, Aria Vazirnia, Thomas H Rea, Euzenir N Sarno, Thomas G Graeber, Robert L Modlin
Journal: Nature Medicine (2012)
Chronic ataluren (PTC124) treatment of nonsense mutation cystic fibrosis
Authors: M. Wilschanski, L.L. Miller, D. Shoseyov, H. Blau, J. Rivlin, M. Aviram, M. Cohen, S. Armoni, Y. Yaakov, T. Pugatch, M. Cohen-Cymberknoh, N.L. Miller, A. Reha, V.J. Northcutt, S. Hirawat, K. Donnelly, G.L. Elfring, T. Ajayi, E. Kerem
Journal: European Respiratory Journal (2011)

In a subset of patients with cystic fibrosis (CF), nonsense mutations (premature stop codons) disrupt production of full-length, functional CF transmembrane conductance regulator (CFTR). Ataluren (PTC124) allows ribosomal readthrough of premature stop codons in mRNA. We evaluated drug activity and safety in patients with nonsense mutation CF who took ataluren three times daily (morning, midday and evening) for 12 weeks at either a lower dose (4, 4 and 8 mg·kg −1 ) or higher dose (10, 10 and 20 mg·kg −1 ). The study enrolled 19 patients (10 males and nine females aged 19–57 yrs; dose: lower 12, higher seven) with a classic CF phenotype, at least one CFTR nonsense mutation allele, and an abnormal nasal total chloride transport. Both ataluren doses were similarly active, improving total chloride transport with a combined mean change of -5.4 mV (p&lt;0.001), and on-treatment responses (at least -5 mV improvement) and hyperpolarisations (values more electrically negative than -5 mV) in 61% (p&lt;0.001) and 56% (p = 0.002) of patients. CFTR function was greater with time and was accompanied by trends toward improvements in pulmonary function and CF-related coughing. Adverse clinical and laboratory findings were uncommon and usually mild. Chronic ataluren administration produced time-dependent improvements in CFTR activity and clinical parameters with generally good tolerability.
The Hyperglycemia: Intensive Insulin Infusion In Infarction (HI-5) Study
Authors: N. Wah Cheung, Vincent W. Wong, Mark McLean
Journal: Diabetes Care (2006)

OBJECTIVE—There is conflicting evidence regarding the benefit of intravenous insulin therapy on mortality following acute myocardial infarction (AMI). The goal of the current study was to determine whether improved glycemic control, achieved through an insulin/dextrose infusion with a variable rate of insulin, reduces mortality among hyperglycemic patients with AMI. RESEARCH DESIGN AND METHODS—Subjects suffering AMI with either known diabetes or without diabetes but blood glucose level (BGL) ≥7.8 mmol/l were randomized to receive insulin/dextrose infusion therapy for at least 24 h to maintain a BGL &amp;lt;10 mmol/l or conventional therapy. RESULTS—A total of 240 subjects were recruited. Insulin/dextrose infusion did not reduce mortality at the inpatient stage (4.8 vs. conventional 3.5%, P = 0.75), 3 months (7.1 vs 4.4%, P = 0.42), or 6 months (7.9 vs. 6.1%, P = 0.62). There was, however, a lower incidence of cardiac failure (12.7 vs. 22.8%, P = 0.04) and reinfarction within 3 months (2.4 vs. 6.1%, P = 0.05). When analyzed by mean BGL achieved during the first 24 h, mortality was lower among subjects with a mean BGL ≤8 mmol/l, compared with subjects with a mean BGL &amp;gt;8 mmol/l (2 vs. 11% at 6 months, P = 0.02). CONCLUSIONS—We did not find a reduction in mortality among patients who received insulin/dextrose infusion therapy. However, it remains possible that tight glycemic control with insulin therapy following AMI improves outcomes.
Chemokines, Chemokine Receptors, and Renal Disease
Authors: STEPHAN SEGERER, PETER J. NELSON, DETLEF SCHLO[Combining Diaeresis]NDORFF
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Leukocyte trafficking from peripheral blood into affected tissues is an essential component of the inflammatory reaction to virtually all forms of injury and is an important factor in the development of many kidney diseases. Advances in the past few years have highlighted the central role of a family of chemotactic cytokines called chemokines in this process. Chemokines help to control the selective migration and activation of inflammatory cells into injured renal tissue. Chemokines and their receptors are expressed by intrinsic renal cells as well as by infiltrating cells during renal inflammation. This study summarizes the in vitro and in vivo data on chemokines and chemokine receptors in renal diseases with a special focus on potential therapeutic effects on inflammatory processes.
Resistance to Anti-EGFR Therapy in Colorectal Cancer: From Heterogeneity to Convergent Evolution
Authors: Sandra Misale, Federica Di Nicolantonio, Andrea Sartore-Bianchi, Salvatore Siena, Alberto Bardelli
Journal: Cancer Discovery (2014)

Abstract The EGFR-targeted antibodies cetuximab and panitumumab are used to treat metastatic colorectal cancers. Mutations in KRAS, NRAS, and BRAF and amplification of ERBB2 and MET drive primary (de novo) resistance to anti-EGFR treatment. Recently, the emergence of alterations in the same genes was detected in patients who responded to EGFR blockade and then relapsed. These results illuminate a striking overlap between genes that, when mutated, drive primary and secondary resistance to anti-EGFR antibodies. Remarkably, although the mechanisms of resistance are genetically heterogeneous, they biochemically converge on key signaling pathways. This knowledge is being translated in the rational design of additional lines of therapy. Significance: Anti–EGFR-targeted therapies are used for the treatment of metastatic colorectal cancer. Molecular heterogeneity impairs their efficacy by fuelling de novo and acquired resistance. In this review, we highlight how genetically distinct resistance mechanisms biochemically converge on a limited number of signaling pathways that can be therapeutically intercepted. Cancer Discov; 4(11); 1269–80. ©2014 AACR.