tbuckley/cabot-search huggingface dataset:
Risk assessment for neurobehavioral toxicity.
Authors: D E McMillan
Journal: Environmental Health Perspectives (1987)

A study by the National Academy of Sciences/National Research Council (NAS/NRC) found neurobehavioral toxicity to be one of the areas where almost no data are available for the assessment of toxicity. Using the NAS/NRC report and a data base from the American Conference of Government Industrial Hygienists (ACGIH), an estimate of the number of neurobehavioral toxins in commercial chemicals can be made. Although the assumption made in making such a calculation may be invalid, the exercise suggests that the number of neurobehavioral toxins may be quite large. There does seem to be general agreement as to what type of neurobehavioral test procedures are appropriate for regulatory purposes. Select committees have consistently recommended the use of test batteries that include schedule-controlled behavior, motor activity, and neuropathological examination following in vivo perfusion, for regulatory purposes. Alkyltin data developed from such a battery were applied to the risk assessment model employed by the United States Environmental Protection Agency (EPA) in their calculations of acceptable daily intake. Using this test battery and the EPA risk assessment model, the acceptable daily intake calculated is of the same order of magnitude as the total limit values established by the ACGIH. A number of special issues in neurobehavioral toxicity also are discussed, including the definition of adverse neurobehavioral toxic effects, species extrapolation, correlation of behavior and neuropathology, alternative methods, and quality of life issues.
Cost-Effectiveness of the Interventions in the Primary Prevention of Diabetes Among Asian Indians
Authors: Ambady Ramachandran, Chamukuttan Snehalatha, Annasami Yamuna, Simon Mary, Zhang Ping
Journal: Diabetes Care (2007)

OBJECTIVE—In the Indian Diabetes Prevention Programme (IDPP), a 3-year randomized, controlled trial, lifestyle modification (LSM) and metformin helped to prevent type 2 diabetes in subjects with impaired glucose tolerance (IGT). The direct medical costs and cost-effectiveness of the interventions relative to the control group are reported here. RESEARCH DESIGN AND METHODS—Relative effectiveness and costs of interventions (LSM, metformin, and LSM and metformin) in the IDPP were estimated from the health care system perspective. Costs of intervention considered were only the direct medical costs. Direct nonmedical, indirect, and research costs were excluded. The cost-effectiveness of interventions was measured as the amount spent to prevent one case of diabetes within the 3-year trial period. RESULTS—The direct medical cost to identify one subject with IGT was Indian rupees (INR) 5,278 ($117). Direct medical costs of interventions over the 3-year trial period were INR 2,739 ($61) per subject in the control group, INR 10,136 ($225) with LSM, INR 9,881 ($220) with metformin, and INR 12,144 ($270) with LSM and metformin. The number of individuals needed to treat to prevent a case of diabetes was 6.4 with LSM, 6.9 with metformin, and 6.5 with LSM and metformin. Cost-effectiveness to prevent one case of diabetes with LSM was INR 47,341 ($1,052), with metformin INR 49,280 ($1,095), and with LSM and metformin INR 61,133 ($1,359). CONCLUSIONS—Both LSM and metformin were cost-effective interventions for preventing diabetes among high risk-individuals in India and perhaps may be useful in other developing countries as well. The long-term cost-effectiveness of the interventions needs to be assessed.
The cyclotron saga continues: Author's reply
Authors: R D Errington
Journal: BMJ (1991)

needlestick injuries that has not been assessed in a trial.'Should not their dogmatic approach follow, rather than precede, publication of data that support non-recapping?There is no published evidence to show that non-recapping reduces the incidence of needlestick injury.As Professor D C Anderson and colleagues rightly point out, the Needle Guard significantly reduces the rate of needlestick injury associated with venepuncture.'It is a matter of concern that people working in a clinical trials centre choose to ignore published data and fail to present new data to corroborate their views.
Frequency of nocturnal symptoms in asthmatic children attending a hospital out-patient clinic
Authors: GG Meijer, DS Postma, JB Wempe, J Gerritsen, K Knol, WM van Aalderen
Journal: European Respiratory Journal (1995)

Since nocturnal symptoms indicate more severe asthma, we investigated their frequency in a hospital-based population of asthmatic children. Recognition of these symptoms offers the possibility to introduce appropriate treatment. We studied 796 consecutive children with asthma (mean (SD) age 9 (4) yrs) attending a hospital clinic, to determine whether these nocturnal symptoms predicted that daytime activities would be affected, and also the patients' perception of disease severity. At the end of a regular out-patient clinic visit, the answers to seven different questions concerning nocturnal symptoms in the previous 3 weeks were recorded. The forced expiratory volume in one second (FEV1) was &gt; or = 90% predicted in 98% of the population that was able to perform lung function measurements (72% of the total population). In 38% of the patients with nocturnal symptoms, these symptoms were reported spontaneously. When asked for, nocturnal symptoms were reported by 47% of the children; 6% every night and 34% at least once a week. Cough was the most frequently reported symptom (31%). Children with nocturnal symptoms had a lower FEV1, scored their perception of asthma as more severe, and had their daytime activities affected more than those without nocturnal symptoms. Doctors should specifically ask about nocturnal symptoms, as not all patients with nocturnal symptoms report them spontaneously and they predict more severe disease.
Nuclear Retinoid Acid Receptor Beta in Bronchial Epithelium of Smokers Before and During Chemoprevention
Authors: X.-C. Xu, J. S. Lee, J. J. Lee, R. C. Morice, X. Liu, S. M. Lippman, W. K. Hong, R. Lotan
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Retinoids can reverse neoplastic lesions and prevent second primary tumors in the aerodigestive tract. These effects are thought to be mediated by nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs), each receptor group including three subtypes (α, β , and γ). Previously, we found that RARβ expression was suppressed in lung cancer. In this study, we investigated whether expression of RARβ is modulated by chemopreventive intervention. METHODS: Using in situ hybridization, we analyzed RARβ messenger RNA (mRNA) expression in bronchial biopsy specimens from heavy smokers, at baseline and after 6 months of treatment with 13- cis -retinoic acid (13- cis -RA) or placebo. Since we had previously detected RARβ expression in 90% of bronchial specimens from nonsmokers, we considered loss of RARβ mRNA expression in at least one of six biopsy specimens at baseline in this study to be aberrant. RESULTS: RARβ mRNA expression was aberrant in 30 (85.7%) of 35 subjects in the 13- cis -RA group and in 24 (72.7%) of 33 subjects in the placebo group. After 6 months of 13- cis -RA treatment, the number of subjects who were RARβ positive in all six biopsy specimens increased from five of 35 to 13 of 35 (2.6-fold), so that the percentage of individuals with aberrant RARβ expression decreased to 62.9% (22 of 35), which represents a statistically significant difference from baseline expression (two-sided P = .01). In the placebo group, no statistically significant difference in RARβ expression was observed between baseline and 6 months. RARβ expression was not related to current smoking status or reversal of squamous metaplasia. CONCLUSIONS: These results indicate that RARβ is an independent marker of response to 13- cis -RA and may serve as an intermediate biomarker in chemoprevention trials of upper aerodigestive tract cancers.
MMPs are regulatory enzymes in pathways of inflammatory disorders, tissue injury, malignancies and remodelling of the lung
Authors: J. Muller-Quernheim
Journal: European Respiratory Journal (2011)

Members of the matrix metalloproteinase (MMP) family of zinc-dependent proteolytic enzymes regulate physiological and pathophysiological events in development, injury and repair, such as morphogenesis, vasculogenesis, remodelling of the extracellular matrix, cell migration, cleavage of cytokines, and activation of mediators and defensins. They are synthesised as secreted or transmembrane proenzymes and processed to their active forms by the removal of amino-terminal propeptides. Their activation by the cleavage of the prodomain from the latent proenzyme and the presence of natural inhibitors, such as tissue inhibitors of metalloproteinases (TIMPs), are important mechanisms that restrict the action of secreted MMPs to the micromilieu of their origin. This tight control of activation and the redundant design of the MMP system, points to their importance in the named processes. In most tissues, their constitutive expression is low and their overexpression at sites of inflammation or other pathogenic events was thought to be due the classical role of extracellular matrix degradation.

However, MMPs are no longer thought of as just matrix-degrading proteins. Rather, proteolysis should be viewed as an important post-translational principle of regulating a fast spectrum of biological processes, and the functional redundancy in combination with a wide substrate overlap underscores the pivotal roles of MMPs not only as effectors but also in regulatory mechanisms. Thus, MMPs are essential in many physiological events and the increasing interest in their function originates from their contribution to inflammatory and remodelling processes, in which they regulate physical barriers, release bioactive factors, participate in membrane shedding, modulate chemokine gradients that regulate leukocyte motility, activate cells via triggering of proteinase-activated receptors (PAR), and alter the activity status of other proteases, including other MMPs. Consequently, the majority of MMP substrates are non-matrix proteins, which underscores their critical roles in regulatory processes [1, 2]. Reports implicating MMPs in destructive pathogenic …
Adenovirus-mediated intralesional interferon-γ gene transfer induces tumor regressions in cutaneous lymphomas
Authors: Reinhard Dummer, Jessica C. Hassel, Friederike Fellenberg, Stefan Eichmüller, Tanja Maier, Philippe Slos, Bruce Acres, Pascal Bleuzen, Vincent Bataille, Patrick Squiban, Günter Burg, Mirjana Urosevic
Journal: Blood (2004)
The Molecular Basis of Sex: Linking Yeast to Human
Authors: Willie J. Swanson, Jan E. Aagaard, Victor D. Vacquier, Magnus Monné, Hamed Sadat Al Hosseini, Luca Jovine
Journal: Molecular Biology and Evolution (2011)

Species-specific recognition between egg and sperm, a crucial event that marks the beginning of fertilization in multicellular organisms, mirrors the binding between haploid cells of opposite mating type in unicellular eukaryotes such as yeast. However, as implied by the lack of sequence similarity between sperm-binding regions of invertebrate and vertebrate egg coat proteins, these interactions are thought to rely on completely different molecular entities. Here, we argue that these recognition systems are, in fact, related: despite being separated by 0.6–1 billion years of evolution, functionally essential domains of a mollusc sperm receptor and a yeast mating protein adopt the same 3D fold as egg zona pellucida proteins mediating the binding between gametes in humans.
Treatment in inflammatory bowel disease affects IGRA performance
Authors: Miguel Arias, Sabino Riestra, Ruth DeFrancisco, Ana Pando, Juan José Palacios, Patricio Escalante, José Belda, Luis Molinos, Marta García-Clemente, Begoña Palomo, Luis Rodrigo, Amador Prieto, Ana Losada, Pere Casan
Journal: European Respiratory Journal (2012)

Introduction: The detection LTBI in patients with inflammatory bowel disease (IBD) before treatment with anti-tumor necrosis factor α must be made with chest radiograph and TST. In immunocompromised patients the limitations of this strategy are well known, therefore it is advisable to use new diagnostic methods based on the release of interferon-γ (IGRA).

Material and Methods: 204 IBD patients underwent screening for detection of LTBI where T-SPOT.TB (T.SPOT) and QuantiFERON-TB Gold In Tube (QTF) determinations were performed simultaneously, also lymphogram, TST and chest X-ray were performed. ITL was defined when the TST and / or any IGRA was positive.

Results: 156 patients had Crohn disease, 42 ulcerative colitis and 6 non-specific colitis. 34 were treated with 5-aminosalicylic acid, 63 with immunomodulators, 32 anti-TNF-α, 27 corticosteroids and 47 a combination of them. 14 were positive QFT, 24 for the T-SPOT and 55 for the TST. The lymphogram showed an association between TSPOT + and QTF + and the amount of circulating CD8 (> 500 cells) while QFT- SPOT + results have the amount of CD8 reduced (<500). Moreover, their treatment modified all lymphocyte populations particularly the IMS and corticosteroids.

Conclusion: The immunomodulatory treatment of patients with IBD altered lymphocyte profile which, in turn, is related to the result of testing LTBI. A correct interpretation of the results for the study of LTBI needs to know the treatment received and requires an assessment of lymphocyte populations that verifies its normality. If the lymphocytes are low, particularly CD8, the effectiveness of IGRA (specially the QTF), is very small and require every test possible to rule out LTBI.
Loss of suppressor T cells in adult NZB/NZW mice.
Authors: R S Krakauer, T A Waldmann, W Strober
Journal: The Journal of Experimental Medicine (1976)

We have investigated suppressor T-cell activity in female NZB/NZW F1 mice using PWM-driven IgM biosynthesis in vitro as an indicator system. In initial we studied we observed that spleen cells from normal mice (BALB/c, C57BL/6), as well as from young (4 wk) and adult (18 wk) NZB/NZW mice, cultured in the presence of PWM synthesize 860 +/- 120 ng IgM/10(6) cells/7 days. However, when Con A (at 2 mug/ml) was added directly to the cultures (along with PWM), cells obtained from adult normal mice and young NZB/NZW mice showed a 94% suppression of IgM synthesis, whereas cells obtained from adult NZB/NZW mice were suppressed significantly less. To analyze these findings we studied the effect of Con A-induced suppressor cells (cells cultured with Con A for 24 h and washed free of Con A) on PWM-driven IgM biosynthesis. Spleen cells obtained from normal mice cultured in the presence of Con A-pulsed cells obtained from normal mice and young NZB/NZW mice showed an 83-88% suppression of PWM-driven IgM synthesis. Similarly, supernates obtained from Con A-pulsed cells of normal mice or of young NZB/NZW mice suppressed PWM-driven IgM synthesis. This suppression by Con A-pulsed cells and their supernates required T cells since T-cell fractions but not B-cell fractions eluted from anti-Fab Sephadex columns mediated suppression of co-cultured normal cells; in addition, Con A-pulsed cells treated with anti-theta and complement do not mediate suppression. These studies of Con A-induced suppressor cell activity in normal mice and young NZB/NZW mice contrast with studies of Con A-induced suppressor cell activity in adult NZB/NZW mice. We found that adult NZB/NZW Con A-pulsed cells and supernates obtained from the Con A-pulse cells had vastly decreased suppressor potential; in this case the Con A-pulse cells and supernatant fluids derived from such cells did not suppress PWM-driven IgM synthesis by normal cells. Finally, whereas spleen cells from young and adult NZB/NZW mice differ in their suppressor cell potential, cells from both sources could respond equally to suppressor signals in that Con A-pulsed normal cells or supernates derived from such cells caused equivalent suppression of PWM-driven IgM synthesis by young and adult NZB/NZW cells. These observations allow us to conclude that NZB/NZW mice lose suppressor T-cell activity as they age.
Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF: Metalloproteinase inhibitors as a new therapy
Authors: Masanori Asakura, Masafumi Kitakaze, Seiji Takashima, Yulin Liao, Fuminobu Ishikura, Tsuyoshi Yoshinaka, Hiroshi Ohmoto, Koichi Node, Kohichiro Yoshino, Hiroshi Ishiguro, Hiroshi Asanuma, Shoji Sanada, Yasushi Matsumura, Hiroshi Takeda, Shintaro Beppu, Michihiko Tada, Masatsugu Hori, Shigeki Higashiyama
Journal: Nature Medicine (2002)
Interrelation of Coronary Calcification, Myocardial Ischemia, and Outcomes in Patients With Intermediate Likelihood of Coronary Artery Disease
Authors: Matthew P. Schenker, Sharmila Dorbala, Eric Cho Tek Hong, Frank J. Rybicki, Rory Hachamovitch, Raymond Y. Kwong, Marcelo F. Di Carli
Journal: Circulation (2008)

Background— Although the value of coronary artery calcium (CAC) for atherosclerosis screening is gaining acceptance, its efficacy in predicting flow-limiting coronary artery disease remains controversial, and its incremental prognostic value over myocardial perfusion is not well established. Methods and Results— We evaluated 695 consecutive intermediate-risk patients undergoing combined rest-stress rubidium 82 positron emission tomography (PET) perfusion imaging and CAC scoring on a hybrid PET-computed tomography (CT) scanner. The frequency of abnormal scans among patients with a CAC score ≥400 was higher than that in patients with a CAC score of 1 to 399 (48.5% versus 21.7%, P &lt;0.001). Multivariate logistic regression supported the concept of a threshold CAC score ≥400 governing this relationship (odds ratio 2.91, P &lt;0.001); however, the frequency of ischemia among patients with no CAC was 16.0%, and its absence only afforded a negative predictive value of 84.0%. Risk-adjusted survival analysis demonstrated a stepwise increase in event rates (death and myocardial infarction) with increasing CAC scores in patients with and without ischemia on PET myocardial perfusion imaging. Among patients with normal PET myocardial perfusion imaging, the annualized event rate in patients with no CAC was lower than in those with a CAC score ≥1000 (2.6% versus 12.3%, respectively). Likewise, in patients with ischemia on PET myocardial perfusion imaging, the annualized event rate in those with no CAC was lower than among patients with a CAC score ≥1000 (8.2% versus 22.1%). Conclusions— Although increasing CAC content is generally predictive of a higher likelihood of ischemia, its absence does not completely eliminate the possibility of flow-limiting coronary artery disease. Importantly, a stepwise increase occurs in the risk of adverse events with increasing CAC scores in patients with and without ischemia on PET myocardial perfusion imaging.
Methodological concerns and recommendations on policy consequences of the World Health Report 2000
Authors: Celia Almeida, Paula Braveman, Marthe R Gold, Celia L Szwarcwald, Jose Mendes Ribeiro, Americo Miglionico, John S Millar, Silvia Porto, Nilson do Rosario Costa, Vincente Ortun Rubio, Malcolm Segall, Barbara Starfield, Claudia Travassos, Alicia Uga, Joaquim Valente, Francisco Viacava
Journal: The Lancet (2001)
Support for National Health Insurance among U.S. Physicians: A National Survey
Authors: Ronald T. Ackermann, Aaron E. Carroll
Journal: Annals of Internal Medicine (2003)

Background: Nearly 40 million persons in the United States were without health insurance for all of 2000. National health insurance would remedy this situation, and many believe the success of reform efforts in this direction may depend on physician support. Objective: To determine the general attitudes of U.S. physicians toward the financing of national health care. Design: Cross-sectional study. Setting: National mailed survey. Participants: 3188 randomly sampled physicians from the American Medical Association Physician Masterfile. Measurements: Physicians were asked whether they support or oppose 1) governmental legislation to establish national health insurance and 2) a national health insurance plan in which all health care is paid for by the federal government. Weighted multivariate logistic regression analyses were performed to identify factors that independently predicted support for each of these strategies. Results: Sixty percent of eligible participants returned a survey. Forty-nine percent of physicians supported governmental legislation to establish national health insurance, and 40% opposed it. Only 26% of all physicians supported a national health insurance plan in which all health care is paid for by the federal government. In analyses adjusting for differences in personal and practice characteristics, physicians in a primary care specialty, physicians reporting that at least 20% of their patients had Medicaid, and physicians practicing in a nonprivate setting or in an inner-city location were statistically significantly more likely to support governmental legislation to establish national health insurance. Conclusions: A plurality of U.S. physicians supports governmental legislation to establish national health insurance. This support may be relevant to the success of future efforts to reform national health care.
The frequency of chronic thromboembolic pulmonary hypertension and associated risk factors
Authors: Ahmet Korkmaz, Tevfik Ozlu, Savas Ozsu, Zeynep Kazaz, Yilmaz Bulbul
Journal: European Respiratory Journal (2011)

The incidence of chronic thromboembolic pulmonary hypertension (CTEPH) are yet to be accurately evaluated and may be significantly underestimated.  The study enrolled 325 consecutive patients with acute pulmonary thromboembolism (PTE). In all patients PTE were diagnosed objectively and the mean follow-up was 16.3 months (range, 6-50.7 months). Outpatient visits and hospitalization records of all patients were examined.Especially, data on recurrence, mortality and CTEPH were collected. Symptomatic patients were investigated for CTEPH with echocardiography, lung perfusion scintigraphy and CT angiography according to proposed algorithms in updated guidelines of pulmonary hypertension.  The frequency of symptomatic CTEPH was 4.6% after the first episode of PTE. Symptomatic CTEPH were established in 37.5% of the patients who have a history of proven PTE and in 6.2% of the patients with previous isolated DVT. The percentage of patients with residual chronic thrombus was 48% at 3 months, 27.4% at 6 months, and 18.2% at 12 months after the diagnosis of PTE. There was significant relationship between recurrence and presence of residual thrombi after 3 months. At the time of acute event; a systolic pulmonary artery pressure (sPAP) >50 mm-Hg, presence of widespread thrombus, history of previous VTE, idiopathic PTE and high uric acid levels were associated with increased risk of developing CTEPH in univariate analysis. In multivariate analysis, sPAP> 50 mm-Hg was found that 10-fold increased for CTEPH.  As a serious complication CTEPH develops in an important part of the PTE patients. Especially, closer monitoring of high risk patients is important for early diagnosis and treatment.