tbuckley/cabot-search huggingface dataset:
Effect of vitamin A supplementation on morbidity due to Plasmodium falciparum in young children in Papua New Guinea: a randomised trial
Authors: Anuraj H Shankar, Blaise Genton, Richard D Semba, Moses Baisor, Joseph Paino, Steven Tamja, Thomas Adiguma, Lee Wu, Lawrence Rare, James M Tielsch, Michael P Alpers, Keith P West
Journal: The Lancet (1999)

Background Many individuals at risk of malaria also have micronutrient deficiencies that may hamper protective immunity. Vitamin A is central to normal immune function, and supplementation has been shown to lower the morbidity of some infectious diseases. We investigated the effect of vitamin A supplementation on malaria morbidity. Methods This randomised double-blind placebo-controlled trial of vitamin A supplementation took place in a P falciparum endemic area of Papua New Guinea. Of 520 potentially eligible children aged 6–60 months, 480 were randomly assigned high-dose vitamin A (n=239) or placebo (n=241), every 3 months for 13 months. Malaria morbidity was assessed through weekly community-based case detection and surveillance of patients who self-reported to the health centre. Cross-sectional surveys were also done at the beginning, middle, and end of the study to assess malariometric indicators. Analyses were by intention to treat. Findings The number of P falciparum febrile episodes (temperature ≥37 5°C with a parasite count of at least 8000/μL) was 30% lower in the vitamin A group than in the placebo group (178 vs 249 episodes; relative risk 0·70 [95% Cl 0·57–0·87], p=0·0013). At the end of the study P falciparum geometric mean density was lower in the vitamin A than the placebo group (1300 [907–1863] vs 2039 [1408–2951]) as was the proportion with spleen enlargement (125/196 [64%] vs 148/207 [71%]); neither difference was significant (p=0·093 and p=0·075). Children aged 12–36 months benefited most, having 35% fewer febrile episodes (89 vs 141; relative risk 0·65 [14–50], p=0·0023), 26% fewer enlarged spleens (46/79 [58%] vs 67/90 [74%], p=0·0045), and a 68% lower parasite density (1160 [95% Cl 665–2022] vs 3569 [2080–6124], p=0·0054). Vitamin A had no consistent effect on cross-sectional indices of proportion infected or with anaemia. Interpretation Vitamin A supplementation may be an effective low-cost strategy to lower morbidity due to P falciparum in young children. The findings suggest that clinical episodes, spleen enlargement, and parasite density are influenced by different immunological mechanisms from infection and anaemia.
Meropenem in cystic fibrosis patients infected with resistant Pseudomonas aeruginosa or Burkholderia cepacia and with hypersensitivity to β-lactam antibiotics
Authors: Oana Ciofu, Tim Jensen, Tacjana Pressler, Helle Krogh Johansen, Christian Koch, Niels H⊘iby
Journal: Clinical Microbiology and Infection (1996)
Literacy and Misunderstanding Prescription Drug Labels
Authors: Terry C. Davis, Michael S. Wolf, Pat F. Bass, Jason A. Thompson, Hugh H. Tilson, Marolee Neuberger, Ruth M. Parker
Journal: Annals of Internal Medicine (2006)

Health literacy has increasingly been viewed as a patient safety issue and may contribute to medication errors.To examine patients' abilities to understand and demonstrate instructions found on container labels of common prescription medications.Cross-sectional study using in-person, structured interviews.3 primary care clinics serving mostly indigent populations in Shreveport, Louisiana; Jackson, Michigan; and Chicago, Illinois.395 English-speaking adults waiting to see their providers.Correct understanding of instructions on 5 container labels; demonstration of 1 label's dosage instructions.Correct understanding of the 5 labels ranged from 67.1% to 91.1%. Patients reading at or below the sixth-grade level (low literacy) were less able to understand all 5 label instructions. Although 70.7% of patients with low literacy correctly stated the instructions, "Take two tablets by mouth twice daily," only 34.7% could demonstrate the number of pills to be taken daily. After potential confounding variables were controlled for, low (adjusted relative risk, 2.32 [95% CI, 1.26 to 4.28]) and marginal (adjusted relative risk, 1.94 [CI, 1.14 to 3.27]) literacy were significantly associated with misunderstanding. Taking a greater number of prescription medications was also statistically significantly associated with misunderstanding (adjusted relative risk, 2.98 [CI, 1.40 to 6.34] for > or =5 medications).The study sample was at high risk for poor health literacy and outcomes. Most participants were women, and all spoke English. The authors did not examine the association between misunderstanding and medication error or evaluate patients' actual prescription drug-taking behaviors.Lower literacy and a greater number of prescription medications were independently associated with misunderstanding the instructions on prescription medication labels.
Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene
Authors: Xueping Qu, Jie Yu, Govind Bhagat, Norihiko Furuya, Hanina Hibshoosh, Andrea Troxel, Jeffrey Rosen, Eeva-Liisa Eskelinen, Noboru Mizushima, Yoshinori Ohsumi, Giorgio Cattoretti, Beth Levine
Journal: Journal of Clinical Investigation (2003)

Malignant cells often display defects in autophagy, an evolutionarily conserved pathway for degrading long-lived proteins and cytoplasmic organelles. However, as yet, there is no genetic evidence for a role of autophagy genes in tumor suppression. The beclin 1 autophagy gene is monoallelically deleted in 40–75% of cases of human sporadic breast, ovarian, and prostate cancer. Therefore, we used a targeted mutant mouse model to test the hypothesis that monoallelic deletion of beclin 1 promotes tumorigenesis. Here we show that heterozygous disruption of beclin 1 increases the frequency of spontaneous malignancies and accelerates the development of hepatitis B virus–induced premalignant lesions. Molecular analyses of tumors in beclin 1 heterozygous mice show that the remaining wild-type allele is neither mutated nor silenced. Furthermore, beclin 1 heterozygous disruption results in increased cellular proliferation and reduced autophagy in vivo. These findings demonstrate that beclin 1 is a haplo-insufficient tumor-suppressor gene and provide genetic evidence that autophagy is a novel mechanism of cell-growth control and tumor suppression. Thus, mutation of beclin 1 or other autophagy genes may contribute to the pathogenesis of human cancers.
Wall stress-induced arrhythmias in the working rat heart as left ventricular hypertrophy regresses during captopril treatment
Authors: G DALTON, J JONES, S EVANS, A LEVI
Journal: Cardiovascular Research (1997)

Objectives: (1) To determine whether regression of left ventricular hypertrophy (LVH) leads to a reduction in wall stress induced arrhythmia. (2) To determine the relationship between the time course of LVH regression and changes in arrhythmias in the spontaneously hypertensive rat heart. Methods: 67 male spontaneously hypertensive rats (SHR) and 67 normotensive Wistar Kyoto rats (WKY) rats were studied at 100 days of age. 39 of each were treated with the ACE inhibitor captopril 2 mg/ml in drinking water, and the remaining 28 were controls. At 0, 2, 4, 8 and 16 weeks hearts were removed and perfused in the working heart mode. Control afterload was 80 mm Hg and perfusate K + was 2.4 mM. Step increases in afterload (20, 40 and 80 mm Hg rises; 20 s duration; 2 min between each) were applied in random order to increase ventricular wall stress and induce arrhythmias. Results: Total number of ventricular premature beats (VPBs) elicited by each afterload step were counted. The ratio of left ventricular weight to body weight in the SHR (an index of LVH) showed a rapid and marked decline with captopril treatment (2.65 ± s.e.m. 0.07 mg/g after 2 weeks treatment compared to 3.38 ± 0.08 before treatment; P < 0.01), indicating that captopril produced rapid regression of LVH. In contrast, the number of wall stress-induced arrhythmias in SHR did not show a significant decline over the 16 week treatment period. However, when the effect of regression of LVH on wall thickness was taken into account, and compensation was made for differences in wall stress applied, there did appear to be a slow reduction in arrhythmias in SHR. This decline in VPBs was significant after 16 weeks treatment for 40 and 80 mm Hg rises in afterload ( P < 0.05). Conclusions: Treatment with captopril produced a rapid regression of LVH in the SHR. In contrast, arrhythmias declined more slowly over the 16 week period. There did not appear to be a direct relationship between the degree of regression of LVH and wall stress-induced arrhythmias in this model.
ANEMIA IN BACTERIAL ENDOCARDITIS
Authors: William B. Parsons
Journal: JAMA (1953)

The frequent occurrence of anemia in bacterial endocarditis has not been sufficiently emphasized. Recognition of this association is particularly important in cases in which the use of antibiotic therapy for an undiagnosed febrile illness may have masked some of the usual symptoms and signs of the disease. Anemia and other hematological disturbances may occasionally even overshadow the more familiar manifestations of bacterial endocarditis to such a degree that the disease may be mistaken for a primary hematological disorder. Since antibiotic therapy cures most cases of subacute bacterial endocarditis, it is important that the diagnosis of anemia be made correctly and as early as possible. The occurrence of anemia along with bacterial endocarditis is usually mentioned in descriptions of the disease. In 1927 Pepper<sup>1</sup>reported anemia in 19 of 20 cases of subacute bacterial endocarditis caused by nonhemolytic Streptococcus viridans. In 1939 Middleton and Burke<sup>2</sup>reported anemia, usually of
Nebulised colistimethate sodium improves quality of life in patients with bronchiectasis colonised by pseudomonas aeruginosa
Authors: Charles Haworth, Diana Bilton, Robert Kenyon
Journal: European Respiratory Journal (2013)

Pseudomonas aeruginosa ( P. aeruginosa ) colonisation has a negative quality of life (QoL) impact in patients with bronchiectasis. 1 To date there is little published work on the long term effects of inhaled antibiotics on QoL in this population.

We conducted a randomised, double-blind, controlled study to investigate the efficacy of ≤6 months nebulised CMS in patients with non-cystic fibrosis bronchiectasis colonised by susceptible P. aeruginosa [[ISRCTN49790596][1]]. Patients self-administered CMS (Promixin; 1 MIU/mL) or placebo (0.45% saline), twice daily via an I-neb AAD System. Here we report QoL results, measured with St. George’s Respiratory Questionnaire (SGRQ). SGRQ assesses QoL across 3 domains (symptoms, activity, impact) and was administered at weeks 0, 12, and 26.

Patients with <80% compliance were excluded from analysis, leaving: n=54 (weeks 0 & 12); n=31 (week 26), for each arm. Total mean % SGRQ (Table 1), and mean changes from baseline per SGRQ domain (Table 2) are reported.

View this table:

Table 1. Mean SGRQ (%).





View this table:

Table 2. Mean Δ baseline (%).





The significant QoL improvement with CMS, compared with placebo (p=0.018), was primarily due to significant improvements in symptoms (p=0.001) and impact (p=0.008) domains.

These results indicate that patients with bronchiectasis colonised by P. aeruginosa benefit from dramatic improvements in QoL when treated with CMS delivered via the I-neb AAD System.

1. Wilson et al. Eur Respir J. 1997;10:1754-1760.

 [1]: /external-ref?link_type=ISRCTN&access_num=ISRCTN49790596
Stool DNA and Occult Blood Testing for Screen Detection of Colorectal Neoplasia
Authors: David A. Ahlquist, Daniel J. Sargent, Charles L. Loprinzi, Theodore R. Levin, Douglas K. Rex, Dennis J. Ahnen, Kandice Knigge, M. Peter Lance, Lawrence J. Burgart, Stanley R. Hamilton, James E. Allison, Michael J. Lawson, Mary E. Devens, Jonathan J. Harrington, Shauna L. Hillman
Journal: Annals of Internal Medicine (2008)

Stool DNA testing is a new approach to colorectal cancer detection. Few data are available from the screening setting.To compare stool DNA and fecal blood testing for detection of screen-relevant neoplasia (curable-stage cancer, high-grade dysplasia, or adenomas >1 cm).Blinded, multicenter, cross-sectional study.Communities surrounding 22 participating academic and regional health care systems in the United States.4482 average-risk adults.Fecal blood and DNA markers. Participants collected 3 stools, smeared fecal blood test cards and used same-day shipment to a central facility. Fecal blood cards (Hemoccult and HemoccultSensa, Beckman Coulter, Fullerton, California) were tested on 3 stools and DNA assays on 1 stool per patient. Stool DNA test 1 (SDT-1) was a precommercial 23-marker assay, and a novel test (SDT-2) targeted 3 broadly informative markers. The criterion standard was colonoscopy.Sensitivity for screen-relevant neoplasms was 20% by SDT-1, 11% by Hemoccult (P = 0.020), 21% by HemoccultSensa (P = 0.80); sensitivity for cancer plus high-grade dysplasia did not differ among tests. Specificity was 96% by SDT-1, compared with 98% by Hemoccult (P < 0.001) and 97% by HemoccultSensa (P = 0.20). Stool DNA test 2 detected 46% of screen-relevant neoplasms, compared with 16% by Hemoccult (P < 0.001) and 24% by HemoccultSensa (P < 0.001). Stool DNA test 2 detected 46% of adenomas 1 cm or larger, compared with 10% by Hemoccult (P < 0.001) and 17% by HemoccultSensa (P < 0.001). Among colonoscopically normal patients, the positivity rate was 16% with SDT-2, compared with 4% with Hemoccult (P = 0.010) and 5% with HemoccultSensa (P = 0.030).Stool DNA test 2 was not performed on all subsets of patients without screen-relevant neoplasms. Stools were collected without preservative, which reduced detection of some DNA markers.Stool DNA test 1 provides no improvement over HemoccultSensa for detection of screen-relevant neoplasms. Stool DNA test 2 detects significantly more neoplasms than does Hemoccult or HemoccultSensa, but with more positive results in colonoscopically normal patients. Higher sensitivity of SDT-2 was particularly apparent for adenomas.
The Placental Transport, Synthesis and Metabolism of Hormones and Drugs which Affect Thyroid Function*
Authors: ELIO ROTI, ANGELO GNUDI, LEWIS E. BRAVERMAN
Journal: Endocrine Reviews (1983)

FETAL DEVELOPMENT is dependent upon the presence of the placenta. This organ, which interfaces the maternal and fetal vascular systems, not only regulates the transfer of various substrates from mother to fetus but also produces polypeptide hormones important for the maintenance of pregnancy, the induction of labor (1) and the synthesis and metabolism of steroid hormones necessary for the development of the fetus (2). In this review we will examine the role of the placenta on various aspects of maternal and fetal thyroid function including the transport, synthesis, and metabolism of hormones and compounds related to thyroid function. In this section we will review the available information on the transport of thyroid and related hormones and compounds known to affect thyroid function. The role of the placenta in the transport of the iodothyronines has been studied in many species. In the rat, Hoskins et al. (3) demonstrated that the administration of large doses of thyroxine (T4) to prophylthiouracil (PTU) treated pregnant rats prevented fetal goiter.
Viral Myocarditis
Authors: Decheng Yang, Jen Yu, Zongshu Luo, Christopher M. Carthy, Janet E. Wilson, Zhewei Liu, Bruce M. McManus
Journal: Circulation Research (1999)

Abstract —Differences in host susceptibility to viral myocarditis caused by a given strain of coxsackievirus B3 (CVB3) are known to be largely related to host genetic factors. Little is known, however, about the key genes that encode determinants (mediators) of myocarditis development or the nature of injury. To identify these genes and further understand the molecular mechanisms of the disease process, we have used a murine model and the differential display technique to fingerprint mRNAs from CVB3-infected mouse hearts. Total RNA was extracted from hearts of 4- and 10-week-old A/J(H-2 a ) mice at day 4 after CVB3 infection, and mRNAs were detected by reverse transcriptase–polymerase chain reaction and subsequently analyzed on polyacrylamide DNA sequencing gels. The differentially displayed bands were confirmed by Northern hybridization using the bands as cDNA probes. Twenty-eight upregulated or downregulated bands were selected from the sequencing gels; among these, 2 upregulated and 3 downregulated cDNA fragments were confirmed by Northern hybridization. DNA sequence analysis and GenBank searching have determined that 4 of the 5 candidate genes are homologous to genes encoding Mus musculus inducible GTPase, mouse mitochondrial hydrophobic peptide (a subunit of NADH dehydrogenase), mouse β-globin, and Homo sapiens cAMP-regulated response element binding protein (CREB) binding protein (CBP), respectively. The remaining candidate gene matches an unpublished cDNA clone, M musculus Nip21 mRNA (GenBank accession number, AF035207 ), which is homologous to human Nip2, a Bcl-2 binding protein. Our data suggest preliminarily that both structural and nonstructural genes are involved in myocarditis development. For the structural gene, β-globin, we further confirmed its downregulation at the protein level by measuring the mean cell volume of red blood cells and found it was marginally reduced in the CVB3-infected group ( P &lt;0.06), with no change in hemoglobin concentration. Cardiac myoglobin concentration was also measured and found to be decreased ( P &lt;0.005), with a parallel decrease in total soluble protein in the CVB3-infected mouse myocardium ( P &lt;0.01). We also noted that the ratio of myoglobin to total protein was not significantly changed; this may be due to the downregulation of additional genes in the host heart, a number being observed on the differential display gels. The significant downregulation of β-globin major gene expression in the heart may be relevant to impaired cardiac function in both the early and late postinfection period. The other identified nonstructural genes are known to be involved in regulation of gene expression, signal transduction pathways, and apoptotic cell death. The altered expression of structural and nonstructural genes may play important roles in the mediation of myocarditis development and perhaps other pathological processes in the heart.
The Early Progenitors of Mouse Dendritic Cells and Plasmacytoid Predendritic Cells Are within the Bone Marrow Hemopoietic Precursors Expressing Flt3
Authors: Angela D'Amico, Li Wu
Journal: The Journal of Experimental Medicine (2003)

Flt3 ligand (Flt3L) is a growth factor for hemopoietic progenitors and can promote the expansion of both conventional dendritic cells (DCs) and plasmacytoid predendritic cells (p-preDCs). The cells responding to Flt3L treatment and the precursors for the DCs and p-preDCs had not been fully characterized. We examined different mouse bone marrow (BM) hemopoietic precursor populations for the surface expression of Flt3 and tested them for early DC and p-preDC precursor activity. Most DC precursor activity, other than that given by multipotent hemopoietic stem cells, was within the downstream precursors expressing Flt3. The majority of mouse BM common lymphoid precursors expressed high levels of Flt3 and these were the most efficient precursors of both DCs and p-preDCs. In contrast, only a small proportion of the common myeloid precursors (CMPs) expressed Flt3, but the precursor activity for both DCs and p-preDCs was within this minor Flt3+ CMP fraction. The granulocyte and macrophage precursors and pro-B cells did not express Flt3 and had no DC or p-preDC precursor activity. These findings demonstrate that the early precursors for all DC subtypes are within the BM Flt3+ precursor populations, regardless of their lymphoid or myeloid lineage orientation.
Atg5 Regulates Phenethyl Isothiocyanate–Induced Autophagic and Apoptotic Cell Death in Human Prostate Cancer Cells
Authors: Ajay Bommareddy, Eun-Ryeong Hahm, Dong Xiao, Anna A. Powolny, Alfred L. Fisher, Yu Jiang, Shivendra V. Singh
Journal: Cancer Research (2009)

Phenethyl isothiocyanate (PEITC) is a promising cancer chemopreventive agent but the mechanism of its anticancer effect is not fully understood. We now show, for the first time, that PEITC treatment triggers Atg5-dependent autophagic and apoptotic cell death in human prostate cancer cells. Exposure of PC-3 (androgen independent, p53 null) and LNCaP (androgen responsive, wild-type p53) human prostate cancer cells to PEITC resulted in several specific features characteristic of autophagy, including appearance of membranous vacuoles, formation of acidic vesicular organelles, and cleavage and recruitment of microtubule-associated protein 1 light chain 3 (LC3) to autophagosomes. A normal human prostate epithelial cell line (PrEC) was markedly more resistant toward PEITC-mediated cleavage and recruitment of LC3 compared with prostate cancer cells. Although PEITC treatment suppressed activating phosphorylations of Akt and mammalian target of rapamycin (mTOR), which are implicated in regulation of autophagy by different stimuli, processing and recruitment of LC3 was only partially/marginally reversed by ectopic expression of constitutively active Akt or overexpression of mTOR-positive regulator Rheb. The PEITC-mediated apoptotic DNA fragmentation was significantly attenuated in the presence of a pharmacologic inhibitor of autophagy (3-methyl adenine). Transient transfection of LNCaP and PC-3 cells with Atg5-specific small interfering RNA conferred significant protection against PEITC-mediated autophagy as well as apoptotic DNA fragmentation. A xenograft model using PC-3 cells and Caenorhabditis elegans expressing a lgg-1:GFP fusion protein provided evidence for occurrence of PEITC-induced autophagy in vivo. In conclusion, the present study indicates that Atg5 plays an important role in regulation of PEITC-induced autophagic and apoptotic cell death.
Population-based Incidence Estimates of Influenza-associated Respiratory Failure Hospitalizations, 2003 to 2009
Authors: Justin R. Ortiz, Kathleen M. Neuzil, Tessa C. Rue, Hong Zhou, David K. Shay, Po-Yung Cheng, Colin R. Cooke, Christopher H. Goss
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: The incidence of influenza-associated acute respiratory failure is unknown.Objectives: To estimate the population-based incidence of influenza-associated acute respiratory failure hospitalizations.Methods: This is a cohort study from January 2003 through March 2009 using hospitalization databases for Arizona, California, and Washington from the Healthcare Cost and Utilization Project and influenza surveillance data for regions encompassing these states. Acute respiratory failure requiring mechanical ventilation was defined by International Classification of Diseases-9-CM code. We used negative-binomial regression modeling to estimate the incidence of influenza-associated events.Measurements and Main Results: The incidence of influenza-associated acute respiratory failure was 2.7 per 100,000 person-years (95% confidence interval, 0.2–23.5), and during the influenza season, 3.8% of all respiratory failure hospitalizations were attributable to influenza. Compared with adults aged 18–49 years, the incidence rate ratio for influenza-associated acute respiratory failure was lower among children aged 1–4 (0.9) and 5–17 years (0.3); however, it was higher among adults aged 50–64 (4.8), 65–74 (10.4), 75–84 (19.9), and 85 years and older (33.7). Results were similar with more sensitive and specific outcome definitions and in a sensitivity analysis using only Arizona-specific outcome and surveillance data.Conclusions: Our data indicate that influenza was an important contributor to respiratory failure hospitalizations during 2003–2009. Clinicians should maintain a high index of suspicion for influenza among hospitalized patients with acute respiratory illness when influenza is circulating in a community. Influenza has a greater effect on respiratory failure in the elderly, for whom better prevention measures are needed.