tbuckley/cabot-search huggingface dataset:
Importance of identifying Mycobacterium bovis as a causative agent of human tuberculosis
Authors: C. Allix-Béguec, M. Fauville-Dufaux, K. Stoffels, D. Ommeslag, K. Walravens, C. Saegerman, P. Supply
Journal: European Respiratory Journal (2010)

To the Editors: 

The case study described hereafter emphasises the potentially vital importance of Mycobacterium bovis identification for appropriate tuberculosis patient management.

M. bovis , the classical causative agent of bovine tuberculosis, can be responsible for human TB, which makes this bacterium an important zoonotic species. In developed countries, the introduction of pasteurisation, preventing contamination from milk of infected cows, and eradication programmes for infected herds have considerably reduced the prevalence of human disease due to the bovine TB bacillus, but have not completely eradicated it 1–3. Nevertheless, in many developed countries, the possibility of TB due to M. bovis infection, instead of Mycobacterium tuberculosis , is considered unlikely or even disregarded by microbiologists and clinicians.

Distinction of M. bovis from M. tuberculosis has significant relevance to patient management. In contrast to the other members of the M. tuberculosis complex, M. bovis is intrinsically resistant to pyrazinamide 4. Beyond its use for specific M. bovis identification, this natural resistance is particularly important to consider. Pyrazinamide is usually given in the classical first-line TB treatment, as it is an effective sterilising drug that helps to shorten TB therapy due to its synergistic effect with rifampicin 5. Thus, in case of M. bovis infection, pyrazinamide would be ineffective if implemented in a patient's anti-TB regimen. Unfortunately, results of in vitro susceptibility assays to pyrazinamide by conventional methods are not systematically correlated to in vivo activity. Susceptibility is, therefore, not often routinely assayed in laboratories. In addition, TB due to M. bovis is clinically, radiologically and microscopically indistinguishable from disease caused by M. tuberculosis . After culture on solid media, M. bovis displays specific characteristics like dysgonic colonies, and negative biochemical test results for nitrate …
DNMT3B Expression Might Contribute to CpG Island Methylator Phenotype in Colorectal Cancer
Authors: Katsuhiko Nosho, Kaori Shima, Natsumi Irahara, Shoko Kure, Yoshifumi Baba, Gregory J. Kirkner, Li Chen, Sumita Gokhale, Aditi Hazra, Donna Spiegelman, Edward L. Giovannucci, Rudolf Jaenisch, Charles S. Fuchs, Shuji Ogino
Journal: Clinical Cancer Research (2009)

DNA methyltransferase-3B (DNMT3B) plays an important role in de novo CpG island methylation. Dnmt3b can induce colon tumor in mice with methylation in specific CpG islands. We hypothesized that cellular DNMT3B level might influence the occurrence of widespread CpG island methylation (i.e., the CpG island methylator phenotype, CIMP) in colon cancer.Utilizing 765 colorectal cancers in two cohort studies, we detected DNMT3B expression in 116 (15%) tumors by immunohistochemistry. We assessed microsatellite instability, quantified DNA methylation in repetitive long interspersed nucleotide element-1 (LINE-1) by Pyrosequencing, eight CIMP-specific promoters [CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1], and eight other CpG islands (CHFR, HIC1, IGFBP3, MGMT, MINT1, MINT31, p14, and WRN) by real-time PCR (MethyLight).Tumoral DNMT3B overexpression was significantly associated with CIMP-high [> or =6/8 methylated CIMP-specific promoters; odds ratio (OR), 3.34; 95% confidence interval, 2.11-5.29; P < 0.0001]. The relations between DNMT3B and methylation in 16 individual CpG islands varied substantially (OR, 0.80-2.96), suggesting variable locus-to-locus specificities of DNMT3B activity. DNMT3B expression was not significantly related with LINE-1 hypomethylation. In multivariate logistic regression, the significant relation between DNMT3B and CIMP-high persisted (OR, 2.39; 95% confidence interval, 1.11-5.14; P = 0.026) after adjusting for clinical and other molecular features, including p53, beta-catenin, LINE-1, microsatellite instability, KRAS, PIK3CA, and BRAF. DNMT3B expression was unrelated with patient outcome, survival, or prognosis.Tumoral DNMT3B overexpression is associated with CIMP-high in colorectal cancer. Our data support a possible role of DNMT3B in nonrandom de novo CpG island methylation leading to colorectal cancer.
Randomized Multicenter Phase II Trial of a Biweekly Regimen of Fluorouracil and Leucovorin (LV5FU2), LV5FU2 Plus Cisplatin, or LV5FU2 Plus Irinotecan in Patients With Previously Untreated Metastatic Gastric Cancer: A Fédération Francophone de Cancérologie Digestive Group Study—FFCD 9803
Authors: Olivier Bouché, Jean Luc Raoul, Franck Bonnetain, Marc Giovannini, Pierre Luc Etienne, Gérard Lledo, Dominique Arsène, Jean Francois Paitel, Véronique Guérin-Meyer, Emmanuel Mitry, Bruno Buecher, Marie Christine Kaminsky, Jean François Seitz, Philippe Rougier, Laurent Bedenne, Chantal Milan
Journal: Journal of Clinical Oncology (2004)

Purpose To determine the efficacy and safety of a biweekly regimen of leucovorin (LV) plus fluorouracil (FU) alone or in combination with cisplatin or irinotecan in patients with previously untreated metastatic gastric adenocarcinoma and to select the best arm for a phase III study. Patients and Methods One hundred thirty-six patients (two were ineligible) were enrolled onto the randomized multicenter phase II trial. Patients received LV 200 mg/m 2 (2-hour infusion) followed by FU 400 mg/m 2 (bolus) and FU 600 mg/m 2 (22-hour continuous infusion) on days 1 and 2 every 14 days (LV5FU2; arm A), LV5FU2 plus cisplatin 50 mg/m 2 (1-hour infusion) on day 1 or 2 (arm B), or LV5FU2 plus irinotecan 180 mg/m 2 (2-hour infusion) on day 1 (arm C). Results The overall response rates, which were confirmed by an independent expert panel, were 13% (95% CI, 3.4% to 23.3%), 27% (95% CI, 14.1% to 40.4%), and 40% (95% CI, 25.7% to 54.3%) for arms A, B, and C, respectively. Median progression-free survival and overall survival times were 3.2 months (95% CI, 1.8 to 4.6 months) and 6.8 months (95% CI, 2.6 to 11.1 months) with LV5FU2, respectively; 4.9 months (95% CI, 3.5 to 6.3 months) and 9.5 months (95% CI, 6.9 to 12.2 months) with LV5FU2-cisplatin, respectively; and 6.9 months (95% CI, 5.5 to 8.3 months) and 11.3 months (95% CI, 9.3 to 13.3 months) with LV5FU2-irinotecan, respectively. Conclusion Of the three regimens tested, the combination of LV5FU2-irinotecan is the most promising and will be assessed in a phase III trial.
Fusobacterium nucleatum Potentiates Intestinal Tumorigenesis and Modulates the Tumor-Immune Microenvironment
Authors: Aleksandar D. Kostic, Eunyoung Chun, Lauren Robertson, Jonathan N. Glickman, Carey Ann Gallini, Monia Michaud, Thomas E. Clancy, Daniel C. Chung, Paul Lochhead, Georgina L. Hold, Emad M. El-Omar, Dean Brenner, Charles S. Fuchs, Matthew Meyerson, Wendy S. Garrett
Journal: Cell Host & Microbe (2013)
METABOLIC INTERACTIONS OF DIABETES AND PREGNANCY
Authors: Thomas A. Buchanan, M.D, John L. Kitzmiller, M.D
Journal: Annual Review of Medicine (1994)

▪ Abstract Many of the embryonic and fetal abnormalities that occur in pregnancies complicated by maternal diabetes are the result of development in a metabolically abnormal environment. Diabetic embryopathy (birth defects and spontaneous abortions) results from maternal metabolic abnormalities during the first 6–7 weeks of gestation. The embryopathy appears to be multifactorial in origin, and the resulting defects remain important causes of morbidity and mortality in diabetic pregnancies. Diabetic fetopathy (predominantly macrosomia and neonatal hypoglycemia) results from fetal overnutrition and hyper-insulinemia during the second and third trimesters. Fetopathy may cause significant morbidity not only in the perinatal period, but also in later life as overweight infants grow up to be overweight children and young adults. Careful regulation of maternal metabolism from the preconceptional period onward can reduce greatly or even eliminate the excess risks that have been incurred by infants of diabetic mothers in the past. Successful management of maternal diabetes requires knowledge of the alterations in intermediary metabolism that normally occur during pregnancy, as discussed in this chapter.
Mapatumumab, a Fully Human Agonistic Monoclonal Antibody That Targets TRAIL-R1, in Combination with Gemcitabine and Cisplatin: a Phase I Study
Authors: Constantijne H. Mom, Jaap Verweij, Corina N.A.M. Oldenhuis, Jourik A. Gietema, Norma Lynn Fox, Renée Miceli, Ferry A.L.M. Eskens, Walter J. Loos, Elisabeth G.E. de Vries, Stefan Sleijfer
Journal: Clinical Cancer Research (2009)

To evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of mapatumumab, a fully human monoclonal antibody targeting tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1), in combination with gemcitabine and cisplatin.Patients with advanced solid tumors received gemcitabine 1,250 mg/m(2) i.v. on days 1 and 8 and cisplatin 80 mg/m(2) i.v. on day 1 of each 21-day cycle. Escalating mapatumumab doses were administered i.v. every 21 days. Toxicity was evaluated and pharmacokinetic analysis of plasma mapatumumab, gemcitabine, 2-difluoro-2-deoxyuridine, and unbound and total platinum was done. TRAIL-R1 tumor expression was determined immunohistochemically.Forty-nine patients received mapatumumab (1 mg/kg, n = 4; 3 mg/kg, n = 7; 10 mg/kg, n = 12; 20 mg/kg, n = 13; or 30 mg/kg, n = 13). A median of six cycles (range, 1-48) was administered. The adverse events most commonly observed reflect the toxicity profile of gemcitabine and cisplatin. Dose-limiting toxicities were seen in 3 of 12 patients at 10 mg/kg, consisting of grade 3 transaminitis, neutropenic fever, and grade 4 thrombocytopenia. At 20 mg/kg, 2 of 12 patients had dose-limiting toxicities, including grade 4 thrombocytopenia and grade 4 fatigue. The maximum tolerated dose was not reached. Pharmacokinetic interactions have not been observed. Twelve patients had a partial response, and 25 patients showed stable disease with a median duration of 6 months.Mapatumumab in combination with gemcitabine and cisplatin is safe and well tolerated at doses up to 30 mg/kg. Further studies on this combination are warranted.
Protecting adolescents from harm. Findings from the National Longitudinal Study on Adolescent Health
Authors: Michael D Resnick, Peter S. Bearman, Robert Wm Blum, Karl E. Bauman, Kathleen M. Harris, Jo Jones, Joyce Tabor, Trisha Beuhring, Renee E Sieving, Marcia Shew, Marjorie Ireland, Linda H Bearinger, J. Richard Udry
Journal: JAMA (1997)

The main threats to adolescents' health are the risk behaviors they choose. How their social context shapes their behaviors is poorly understood.To identify risk and protective factors at the family, school, and individual levels as they relate to 4 domains of adolescent health and morbidity: emotional health, violence, substance use, and sexuality.Cross-sectional analysis of interview data from the National Longitudinal Study of Adolescent Health.A total of 12118 adolescents in grades 7 through 12 drawn from an initial national school survey of 90118 adolescents from 80 high schools plus their feeder middle schools.The interview was completed in the subject's home.Eight areas were assessed: emotional distress; suicidal thoughts and behaviors; violence; use of 3 substances (cigarettes, alcohol, marijuana); and 2 types of sexual behaviors (age of sexual debut and pregnancy history). Independent variables included measures of family context, school context, and individual characteristics.Parent-family connectedness and perceived school connectedness were protective against every health risk behavior measure except history of pregnancy. Conversely, ease of access to guns at home was associated with suicidality (grades 9-12: P<.001) and violence (grades 7-8: P<.001; grades 9-12: P<.001). Access to substances in the home was associated with use of cigarettes (P<.001), alcohol (P<.001), and marijuana (P<.001) among all students. Working 20 or more hours a week was associated with emotional distress of high school students (P<.01), cigarette use (P<.001), alcohol use (P<.001), and marijuana use (P<.001). Appearing "older than most" in class was associated with emotional distress and suicidal thoughts and behaviors among high school students (P<.001); it was also associated with substance use and an earlier age of sexual debut among both junior and senior high students. Repeating a grade in school was associated with emotional distress among students in junior high (P<.001) and high school (P<.01) and with tobacco use among junior high students (P<.001). On the other hand, parental expectations regarding school achievement were associated with lower levels of health risk behaviors; parental disapproval of early sexual debut was associated with a later age of onset of intercourse (P<.001).Family and school contexts as well as individual characteristics are associated with health and risky behaviors in adolescents. The results should assist health and social service providers, educators, and others in taking the first steps to diminish risk factors and enhance protective factors for our young people.
The mouse gut T lymphocyte, a novel type of T cell. Nature, origin, and traffic in mice in normal and graft-versus-host conditions.
Authors: D Guy-Grand, C Griscelli, P Vassalli
Journal: The Journal of Experimental Medicine (1978)

Lymphocytes of the mouse intestinal mucosa, identified in tissue sections or purified suspensions of intraepithelial lymphocytes as T cells (gut T lymphocytes [GTL]), were studied in normal mice or in beige mice (the equivalent of the Chediak-Higashi syndrome in man, characterized by giant granules in various cell types, including mast cells). Mice were studied in normal or in germ-free conditions, or during a graft versus host (GVH) reaction resulting from the injection of parental thymocytes into lethally irradiated F1 mice, a condition leading to massive accumulation of T lymphocytes of donor origin in the host gut mucosa. In normal as well as in GVH conditions, a high percentage of the gut IE lymphocytes contain granules (up to 80% in the beige mouse). These granules have ultrastructural, hostochemical and other features resembling those of mast cell granules; in beige mice, up to 50% of them can be shown to contain histamine. Granulated T cells are also found in the lamina propria. It appears that the GTL may progressively lose their surface T antigens when the granules become more developed. Kinetics of [3H]TdR labeling of the GTL, transfer experiments with T cells of various origins, selective [3H]TdR labeling and selective irradiation of the Peyer's patches (PP), and effect of thoraic duct (TD) drainage led to the conclusion that GTL are the progeny of T cells stimulated to divide in the PP microenvironment, which endows them with a gut-homing tendency. From the PP, these cells follow a cycle, migrating to the TD and to the blood to colonize the whole intestinal mucosa, the majority of them as dividing cells undergoing a single round of traffic, with some probably able to recirculate and becoming a more long-lived variety. Antigenic stimulation within the PP is necessary for the emergence of GTL progenitors, but their gut-homing property is unrelated to the antigen as shown with fetal gut grafts, notably in GVH where grafts syngeneic to the host or donor become similarly infiltrated by GTL. On the basis of their properties and of further evidence to be reported elsewhere, it is proposed that GTL belong to a special class of T lymphocytes, related to the immune defenses of the mucosal systems in general, and capable of acting as progenitors of mucosal mast cells.
Increased anaphylatoxins (C3a and C4a) in psoriatic sera
Authors: K. OHKOHCHI, H. TAKEMATSU, H. TAGAMI
Journal: British Journal of Dermatology (1985)

We measured C3a and C4a anaphylatoxins in the serum of 56 psoriatic patients and 36 healthy control subjects by radioimmunoassay in order to clarify the mechanism of complement activation occurring in psoriatic lesions. Whereas a small amount of anaphylatoxins were demonstrable even in the sera of healthy adults, the serum concentrations of C3a and C4a anaphylatoxins were significantly higher in psoriatic patients than those in non-psoriatic controls. The increased serum anaphylatoxin levels did not correlate well with either the extent or the activity of the skin lesions, but a comparison of anaphylatoxin levels in 10 patients before and after successful treatment of skin lesions showed that the serum anaphylatoxin levels decreased with improvement of the skin lesions. Our results suggest that complement activation takes place in psoriatic patients chiefly via the classical pathway.
Residential exposure to aircraft noise and hospital admissions for cardiovascular diseases: multi-airport retrospective study
Authors: A. W. Correia, J. L. Peters, J. I. Levy, S. Melly, F. Dominici
Journal: BMJ (2013)

To investigate whether exposure to aircraft noise increases the risk of hospitalization for cardiovascular diseases in older people (≥ 65 years) residing near airports.Multi-airport retrospective study of approximately 6 million older people residing near airports in the United States. We superimposed contours of aircraft noise levels (in decibels, dB) for 89 airports for 2009 provided by the US Federal Aviation Administration on census block resolution population data to construct two exposure metrics applicable to zip code resolution health insurance data: population weighted noise within each zip code, and 90th centile of noise among populated census blocks within each zip code.2218 zip codes surrounding 89 airports in the contiguous states.6 027 363 people eligible to participate in the national medical insurance (Medicare) program (aged ≥ 65 years) residing near airports in 2009.Percentage increase in the hospitalization admission rate for cardiovascular disease associated with a 10 dB increase in aircraft noise, for each airport and on average across airports adjusted by individual level characteristics (age, sex, race), zip code level socioeconomic status and demographics, zip code level air pollution (fine particulate matter and ozone), and roadway density.Averaged across all airports and using the 90th centile noise exposure metric, a zip code with 10 dB higher noise exposure had a 3.5% higher (95% confidence interval 0.2% to 7.0%) cardiovascular hospital admission rate, after controlling for covariates.Despite limitations related to potential misclassification of exposure, we found a statistically significant association between exposure to aircraft noise and risk of hospitalization for cardiovascular diseases among older people living near airports.
COMPLETE QUADRICEPS MUSCLE TEAR AT 5 YEARS FOLLOW-UP. REVIEW OF LITERATURE
Authors: Francesco Oliva, Alessio Giai Via, Nicola Maffulli
Journal: British Journal of Sports Medicine (2013)

Muscle injuries are challenging problems for surgeons. Most of muscle trauma are treated conservatively with excellent results but severe muscle injury may indicate the need for surgical repair. Repair of belly muscle laceration is technically demanding because of the sutures pull out and the likelihood of clinical failure is high. Different suture techniques have been described in literature even if the best suturing technique is debated. Moreover many biological approaches to improve muscle healing have been proposed. We present a case of complete quadriceps muscle tear treated with surgical repair at 5 years follow-up and a review of literature.
Interleukin-1 receptor antagonist decreases bone loss and bone resorption in ovariectomized rats.
Authors: R B Kimble, J L Vannice, D C Bloedow, R C Thompson, W Hopfer, V T Kung, C Brownfield, R Pacifici
Journal: Journal of Clinical Investigation (1994)

Interleukin-1 (IL-1), a cytokine produced by bone marrow cells and bone cells, has been implicated in the pathogenesis of postmenopausal osteoporosis because of its potent stimulatory effects on bone resorption in vitro and in vivo. To investigate whether IL-1 plays a direct causal role in post ovariectomy bone loss, 6-mo-old ovariectomized rats were treated with subcutaneous infusions of IL-1 receptor antagonist (IL-1ra), a specific competitor of IL-1, for 4 wk, beginning either at the time of surgery or 4 wk after ovariectomy. The bone density of the distal femur was measured non invasively by dual-energy X-ray absorptiometry. Bone turnover was assessed by bone histomorphometry and by measuring serum osteocalcin, a marker of bone formation, and the urinary excretion of pyridinoline cross-links, a marker of bone resorption. Ovariectomy caused a rapid increase in bone turnover and a marked decrease in bone density which were blocked by treatment with 17 beta estradiol. Ovariectomy also increased the production of IL-1 from cultured bone marrow cells. Ovariectomy induced-bone loss was significantly decreased by IL-1ra treatment started at the time of ovariectomy and completely blocked by IL-1ra treatment begun 4 wk after ovariectomy. In both studies IL-1ra also decreased bone resorption in a manner similar to estrogen, while it had no effect on bone formation. In contrast, treatment with IL-1ra had no effect on the bone density and the bone turnover of sham-operated rats, indicating that IL-1ra specifically blocked estrogen-dependent bone loss. In conclusion, these data indicate that IL-1, or mediators induced by IL-1, play an important causal role in the mechanism by which ovariectomy induces bone loss in rats, especially following the immediate post ovariectomy period.
Delaminid for multidrug-resistant pulmonary tuberculosis
Authors: Richard J Lessells
Journal: Thorax (2012)

Delaminid for multidrug-resistant pulmonary tuberculosisDelaminid (OPC-67683) is an investigational drug for tuberculosis from a new class (nitro-dihydro-imidazooxazole derivatives) that inhibits synthesis of mycolic acid.This multicentre phase 2 randomised clinical trial evaluated the efficacy and safety of delaminid at two doses (100 mg bd, 200 mg bd) versus placebo administered for 8 weeks in combination with a standardised background regimen for multidrug-resistant pulmonary tuberculosis.Delaminid increased the proportion achieving sputum culture conversion at 2 months (45% and 42% at 100 mg and 200 mg, respectively) compared with placebo (30%).Time to culture conversion was also significantly shorter with delaminid.In general, delaminid had an acceptable safety profile, but the one concerning finding was that prolongation of QT interval on ECG was more common in both delaminid groups (10% and 13% for 100 mg and 200 mg, respectively) compared with placebo (4%).The episodes of prolonged QT interval were not associated with any clinical events.Further surveillance for cardiotoxicity will be essential as development moves forward.Delaminid is one of a number of drugs that now offers hope for improved treatment of drug-resistant tuberculosis.It should be noted that this trial only included four HIV-infected participants and excluded those with CD4 cell count <350 cells/μl and those on antiretroviral therapy.A phase 3 trial is already underway, which will, in certain sites, include HIV co-infected participants, and which will report on longer-term outcomes.The use of delaminid alongside other investigational agents in novel regimens is also an area of particular interest for future research.