tbuckley/cabot-search huggingface dataset:
Antibody Patterns to Herpesvirus saimiri-Induced Antigens in Owl Monkeys2
Authors: Gary R. Pearson, Thomas Orr, Harvey Rabin, John Cicmanec, Dharam Ablashi, Gary Armstrong
Journal: JNCI Journal of the National Cancer Institute (1973)

Antibody-response patterns to 3 major groups of Herpesvirus saimiri (HVS)-associated antigens [early antigens (EA), late antigens (LA), membrane antigens (MA)] in 10 owl monkeys infected with HVS were related to the clinical course of HVS-induced disease. Results are also presented which show that EA is produced 4–8 hours earlier than LA in HVS-infected cells providing further evidence that these were 2 distinct groups of antigens. In animals that developed neoplasms, antibodies against all 3 groups of antigens were found; however, the antibody response to EA was delayed, in general, 2–4 weeks compared with the responses to LA and MA. Two owl monke,s inoculated with HVS and one inoculated with HVS-induced tumor cells did not develop gross or clinical signs of disease; antibodies to LA and MA, but not EA, were detected in serum samples from these monkeys. These results provide additional evidence that the antibody response to EA may indicate lymphoproliferation (or cell transformation).
Induction of Differentiation in Acute Promyelocytic Leukemia Cells by 9-cis Retinoic Acid α-Tocopherol Ester (9-cisTretinoin Tocoferil)
Authors: Makoto Makishima, Kazuhiko Umesono, Koichi Shudo, Tomoki Naoe, Kenji Kishi, Yoshio Honma
Journal: Blood (1998)
Identifying and managing common childhood language and speech impairments
Authors: Sheena Reilly, Cristina McKean, Angela Morgan, Melissa Wake
Journal: BMJ (2015)

Learning to speak is one of life's most important accomplishments.Language, usually acquired so effortlessly, underpins every child's learning and ability to interact with others and to establish relationships.Poor communication has profound implications for employment, health, literacy, parenting the next generation, and social inequalities.It is therefore of great societal concern that language, speech, and fluency disorders are among the most common developmental disorders.The aim of this clinical review is to summarise the current information on language and speech impairments to help general practitioners, universal well child services, and paediatricians to identify the most common problems, understand their clinical course, decide when to refer and for what services, and understand what improvements can be expected. Which are the most common language and speech problems?This review focuses on the three most common preschool problems: language impairment, speech impairment, and disorders of fluency known as stuttering or stammering.Prevalence estimates vary by diagnostic criteria, sampling frame, and age (table 1⇓).Table 2⇓ summarises the long term impacts of these conditions based on findings from longitudinal studies.
Outcome and risk factor of very elderly patients over 90 years admitted to intensive care unit
Authors: Yun Su Sim, Tae Rim Shin, Sang Myeon Park, Dong Gyu Kim
Journal: European Respiratory Journal (2013)

Backgrounds:Population worldwide is aging due to declines of both fertility and mortality rates. Consequently, demands for critical care and admission to intensive care unit (ICU) in very elderly patients are increasing. The evaluation of outcome and risk factor of very elderly patients admitted to ICU is important as implications on health resources in terms of triage. Methods:Clinical records of 183 patients (1.08 % of total 16939 ICU patients ≥ 18 years) over 90 years admitted to ICU were analyzed retrospectively from January 2003 to July 2012. Results:Causes of ICU admission were pneumonia(16%), heart failure(12%), cerebral infarction(11%). ICU mortality of patients over 90 years was 27% while ICU mortality of total patient ≥ 18 years was 14%. Risk factors of ICU mortality were analyzed in 155 patients except 33 patients transferred other healthcare center in state of hopeless. In univariate analysis, patients of chronic renal failure( p =0.023), pneumoni ( p =0.006), lymphocyte≤1000 /m3( p =0.035), creatinine≥1.0 mg/dL( p <0.001), albumin≤3.0 g/dL( p =0.012), cholesterol≤130 mg/dL( p =0.010), CRP≥66 mg/dL( p =0.012), SAPS II≥37( p <0.001), APACHE II ≥14( p <0.001), Mechanical ventilation( p <0.001), and vasopressor( p <0.001) showed higher mortality. In multivariate analysis by Cox hazard model, risk factors of ICU patients≥18 years were CRP≥66 mg/dL(HR=3.118, p =0.019), SAPS II≥37(HR=5.813, p =0.015), and vasopressor(HR=2.851, p =0.024). Conclusion:Mortality of very elderly patients over 90 years admitted to ICU is high. Furthermore, a requirement of vasopressor, a high CRP and a high SAPS II score had poor prognosis in very elderly patients over 90 years admitted to the ICU.
A novel, selective, orally active, potent small molecule inhibitor of Hsp90
Authors: P. M. Steed, P. Fadden, S. Hall
Journal: Journal of Clinical Oncology (2006)

13067 Background: The preclinical and clinical data evaluating derivatives of the natural product geldanamycin, including 17-AAG and 17-DMAG, reveal that inhibition of the molecular chaperone HSP90 results in multiple anti-tumor effects. SNX-5422 and SNX-5542 are potent, novel, highly specific, water soluble and orally active small molecule inhibitors of Hsp90. Here we describe the preclinical efficacy and toxicity evaluation of these compounds. Methods: The PK profile of SNX-5422 and SNX-5542 was determined following oral and iv dosing in mice and rats. HT29 xenografts were performed oral doses of SNX-5542 on a schedule of Q2DX3,2 for 2 weeks or 17-DMAG on the previously reported regimen of bid×5,2 for 2 weeks, with tumor progression and body weight monitored. Plasma, tumor and other tissues were harvested for evaluation of HSP70 induction and levels of HSP90 client proteins. Rats were treated with varying oral doses on a schedule of Q2DX3,2 for two weeks. Clinical observations were noted and standard hematology and clinical chemistry parameters were monitored. Results: SNX-5542 exhibited 37% oral BA in rats and &gt;75% in mice, with t ½ &gt;7h in each species. SNX-5542 was well tolerated in normal and tumor-bearing mice at 300 mg/m 2 Q2DX3,2 for 2 weeks, 0.9% weight gain. 17-DMAG at 30 mg/m 2 bid×5,2 for 2 weeks caused 3.3% body weight loss. At these doses, SNX-5542 exhibited 78% median tumor growth inhibition of HT29 tumors while 17-DMAG exhibited 23% inhibition. Mechanistic indicators of HSP90 inhibition correlated with efficacy across multiple dosing levels. At 120 mg/m 2 Q2DX3,2 for 2 weeks SNX-5422 was well tolerated in rats, with no significant effect on any clinical, hematology or clinical chemistry parameter with the exception of a slight increase in blood urea nitrogen levels. Histopathological evaluation of liver, thymus, spleen and kidneys revealed no significant treatment-related effects. At 120 mg/m 2 Q2DX3,2 for 13 days SNX-5422 does not exhibit any of the toxicities reported for 17-DMAG (bidX5,2 for 8 days at 24 mg/m 2 ). Conclusions: SNX small-molecule HSP90 inhibitors have favorable pharmacokinetic profiles, oral bioavailability, tolerability and superior anti-tumor activity compared to the natural product derivative 17-DMAG. [Table: see text]
Burden of smoking in acute coronary syndrome
Authors: Edelweise Merin, Ma. Encarnita Limpin, Fernando Ayuyao, Teresita De Guia
Journal: European Respiratory Journal (2012)

The purpose of this study was to evaluate the burden of smoking among patients who had acute coronary syndrome seen at Philippine Heart Center in terms of its outcomes and expenditures.  199 patients (138 males and 61 females) participated in the study. Smoking habits were recorded including their co-morbidities, GRACE and TIMI scores. Financial data were gathered, tabulated and evaluated. Outcomes of ACS were tabulated in relation to patients9 smoking history and were evaluated.  In this study, it shows that among those patients who have acute coronary syndromes, predominantly were smokers, both direct and passive smokers comprising 72% of the patients. In a developing country like ours, the mean amount expended for each person admitted for acute coronary syndrome who smokes (direct and passive) was two hundred forty-seven thousand two hundred sixty pesos (PhP 247, 260.00 ± 276,428.00 excluding physician9s professional fee) which is already a sumptuous that drains one9s finances. And of these, for every smoker patients who had acute coronary syndrome, the mean expenses for each person with each admission were PhP 217,160.00 ± 226,791.09 for those who survived and were discharged and PhP 517,960.00 ± 448,085.23 for those who died. Therefore, smoking is still prevalent among patients who have acute coronary syndrome and with each admission, each patient expend a sumptuous amount of money for the health resources.
Transdermal clonidine for ameliorating tamoxifen-induced hot flashes.
Authors: R M Goldberg, C L Loprinzi, J R O'Fallon, M H Veeder, A W Miser, J A Mailliard, J C Michalak, A M Dose, K M Rowland, N L Burnham
Journal: Journal of Clinical Oncology (1994)

PURPOSE To determine the efficacy of transdermal clonidine for alleviating tamoxifen-induced hot flashes in women with a history of breast cancer. PATIENTS AND METHODS A randomized, double-blind, crossover design was used in this prospective study. Women with a history of breast cancer who were receiving tamoxifen and suffering from hot flashes were potentially eligible for this protocol study. RESULTS Clonidine did reduce hot-flash frequency to a degree that was statistically impressive (P &lt; .0001), but clinically moderate (20% reduction from baseline). It also decreased hot-flash severity (P = .02, 10% reduction from baseline). Clonidine was related to increased mouth dryness (P &lt; .001), constipation (P &lt; .02), itchiness under the patch (P &lt; .01), and drowsiness (P &lt; .05). CONCLUSION Better means are needed to alleviate hot flashes among patients in whom estrogen therapy is contraindicated.
Type 1 Diabetes at a Crossroads!
Authors: William T. Cefalu, William V. Tamborlane, Jay S. Skyler
Journal: Diabetes Care (2015)

“Be at a crossroads”: to be at a stage in your life when you have to make a very important decision (1). Type 1 diabetes at a crossroads? What does that really mean? It cannot mean that progress has not been made! Indeed, in the field of diabetes, reporting of new information is clearly outpacing our ability to incorporate new findings into clinical treatment options and recommendations. Over the recent past, important new information regarding the burden of diabetes, prevention, and screening and comprehensive discussions on new therapies have been reported (2–7). However, on closer inspection, the most impressive changes in treatment and preventive strategies have been focused on type 2 diabetes. What then are the major advances in type 1 diabetes? How close are we to realizing an intervention that can delay or prevent type 1 diabetes? Are we any closer to a cure today than we were 10 years ago? What progress has been made toward the “holy grail” of offering a fully functioning artificial pancreas (AP)? To address these questions, our editorial team has elected to feature these topics in a series of articles in this issue of Diabetes Care . Specifically, articles in this issue describe research related to the present status of treatment methods and clinical outcomes in type 1 diabetes in the U.S.; discuss current concepts on the pathogenesis, prediction, and prevention of the disease; review the successes and ongoing challenges of islet transplantation; and describe a pathway for the translation of advances in diabetes technology into an AP suitable for home use by large numbers of patients (8–15).

The limitations of current treatment of type 1 diabetes are addressed in the report by Miller et al. (8), which summarizes the most recent data collected on 16,601 individuals participating …
Inequity of access to healthcare is still a problem in the NHS
Authors: S Michael Crawford
Journal: BMJ (2015)

Hawkes argues that, so long after the inception of the NHS, inequalities of access to healthcare over the socioeconomic spectrum must make a trivial contribution to disparities in outcomes.1 The evidence is clear that this is not the case.

The economic status of a patient’s immediate area of residence has a bearing on whether any treatment for …
Actin Changes in Normal Human and Rat Leukocytes and in Transformed Human Leukocytic Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN4"&gt;4&lt;/xref&gt;
Authors: J. Varani, J. A. Wass, K. M K Rao
Journal: JNCI Journal of the National Cancer Institute (1983)

The DNase I inhibition assay was used for the determination of the relative amounts of monomeric and total actin in normal human peripheral blood lymphocytes, normal Sprague-Dawley rat peritoneal leukocytes, and 6 transformed human cell lines of lymphoid and myeloid origins. In the normal lymphocytes and leukocytes, greater than 50% of the total actin was monomeric. In contrast, only 1 of the 6 transformed lines had greater than 50% of its actin in the monomeric form. In the other 5 lines, the percentage of actin in the monomeric form ranged from 23 to 39%. The normal lymphocytes, peritoneal leukocytes, and 2 of the transformed cell lines (CEM and K562) were examined in greater detail. The total actin (as a percentage of the total protein) was found to be much lower in the transformed cell lines than it was in the normal lymphocytes. The total amount of actin in the normal rat leukocytes was very similar to the amount in the normal human lymphocytes. In addition to these differences between the normal and transformed human cells, treatment of the normal lymphocytes with mitogenic doses of concanavalin A was found to significantly reduce the amount of monomeric actin in the cells. Similar treatment of the transformed cells produced no significant reduction in the monomeric actin.
Frequency of risk factors for multi-drug resistant tuberculosis among the patients enrolled at multi-drug resistant clinic in a tertiary care hospital, Pakistan
Authors: Abdul Rauf, Muqarrab Hussain Kamran, Muhammad Imran Shahzad, Humayoun Ghulam Muratza, Muhammad Zubair Shaheen
Journal: European Respiratory Journal (2014)

Background :Multidrug Resistant TB is a major infectious health problem.Despite its high prevalence in Pakistan,its various risk factors are not being addressed properly.   Objective :The objective of this study was to determine the frequency of various risk factors for MDR-TB among the patients enrolled at MDR-Clinic.   Methods :A descriptive cross sectional study was conducted at MDR clinic Nishtar Hospital Multan from 01 May 2012 to 31 Jan 2014.Those patients were enrolled whose culture and DST of MTB were positive for MDR-TB.   Results :Of the total(n=110) MDR-TB patients,60 were males and 50 were females.Mean age of patients was 36.65± 7.92 years,94(85.4%)patients have an age range 15-50years and 12(10.9%)were above 50 years.Ninty eight (89.09%) patients have monthly income below Rs.10,000 and 71(64.5%)patients belong to rural areas.Thirty five (31.8%) were Illiterate and 43(39.09%)had primary education.Of the total,108(89.09%) had a previous h/o TB and only 2(1.8%) were new cases.Forty two(38.2%)were defaultor and 65(59.09%)had treatment failure.74(67.27%) have a greater distance from TB treatment center and were not under DOTS and 36(32.73%)were under DOTS.Thirteen(13.8%)patients have family h/o TB and 5(4.5%) have h/o contact with MDR-TB patients.Four(3.6%)were health care workers and 1(0.9%)was HIV positive.   Conclusion :Previous TB treatment,poverty,illiteracy,rural population,greater distance from TB treatment center,Non DOTS and poor compliance have been observed in majority of the cases in this study.These factors should be particularly addressed in high burden MDR-TB country like Pakistan in order to reduce its burden.
Validation of treatment failure criteria of nosocomial pneumonia in ICU
Authors: Mariano Esperatti, Miquel Ferrer, Lina Maria Saucedo, Valeria Giunta, Antoni Torres
Journal: European Respiratory Journal (2011)

Rationale:  Nosocomial pneumonia (NP) is the most important infection acquired in ICU. There is no clear and validated definition to evaluate treatment failure (TF).   Objective:  To validate a previously established definition of TF of NP in ICU.   Methods:  We prospectively collected data of NP in ICU, evaluated the rate of TF at 72 hours after beginning antibiotic treatment and compared the groups with or without TF. TF was defined as the presence of any of the following: failure to improve the PaO 2 /FiO 2  ratio or need for intubation because of pneumonia, persistence of fever or hypothermia plus purulent respiratory secretions, worsening of the pulmonary infiltrate by >50%, or occurrence of septic shock or multiple organ dysfunction not present on day 1.   Results:  We evaluated 297 cases; 178 with ventilator-associated pneumonia (VAP) and 119 with non-VAP. 165 patients (55%) fulfilled TF criteria. There was no difference between groups in demographics, severity scores (APACHE-II, SOFA), or inflammatory response assessed by CRP (TF vs. non-TF). Treatment failure was related with increased mortality in the ICU (45%  vs.  18%, p vs . 16±21 days, p=0.035), but with similar hospital stay. Failure to improve the PaO 2 /FiO 2  was the only individual component of TF definition associated with the evaluated clinical outcomes.   Conclusion:  The definition of TF appears to correlate well with relevant clinical outcomes, mainly due to the respiratory parameters.
A systematic review of endurance, resistance and combined exercise training in COPD
Authors: Ulrik Winning Iepsen, Karsten Juhl Jørgensen, Thomas Jørgen Ringbæk, Peter Lange
Journal: European Respiratory Journal (2014)

Background  Endurance training (ET) in pulmonary rehabilitation of COPD is known to improve exercise capacity and health related quality of life (HRQoL), but dyspnea limits the training intensity. Therefore, resistance training (RT) may be a feasible alternative in COPD.  Aims  To compare the effects of 1) RT versus ET, and 2) ET plus RT versus ET alone on HRQoL, walking distance, harms, muscle strength and exercise capacity in COPD.  Methods  We identified randomized controlled trials (RCT) from a systematic search. Two review authors independently extracted data, assessed risk of bias and quality of evidence. Meta-analyses were performed if possible. All decisions were made by consensus.  Results  We included 14 RCTs (592 participants). Intervention length was tree to twelve weeks. We found moderate-quality evidence of significant improvements of leg muscle strength (194 participants) in the ET plus RT group versus the ET group (figure 1), but there was very low to moderate-quality evidence of no significant difference in HRQoL, walking distance and exercise capacity. A non-significant trend favoring RT in leg muscle strength was found in the comparison of RT versus ET group (121 participants), standardized mean difference was 0.55 (CI:-0.15 to 1.25), but no difference for all other outcomes.  Conclusion  Adding RT to ET improves leg muscle strength, but does not improve exercise capacity or HRQoL when compared to ET alone.
Bronchoprotective activity and safety assessment of two novel dual-acting MABA compounds (LAS190792 and LAS191351) in dogs
Authors: Amadeu Gavaldà, Mònica Aparici, Jose Luis Montero, Carlos Puig, Christopher Doe, Montserrat Miralpeix
Journal: European Respiratory Journal (2014)

Background   Beagle dogs were used to assess the bronchoprotective potency, duration of action and the effect on heart rate of two M 3 -antagonist/β 2 -agonist (MABA) compounds in development for chronic respiratory diseases with airflow limitation.   Methods   Airway resistance response to acetylcholine challenges (10 µg/kg i.v.) were assessed prior to and at 10, 20 and 30 minutes, and 1, 3, 6 and 24 hours after administration of nebulized LAS190792 (0.3–30 µg/kg) and LAS191351 (0.1–10 µg/kg) (n=3–9). Heart rate (HR), plasma glucose and potassium concentrations were assessed. Washout was ≥6 days between treatments. Comparators were olodaterol and tiotropium.   Results   The dose needed to inhibit bronchoconstriction by 40% was: LAS190792 0.03 µg/kg, tiotropium 0.04 µg/kg, olodaterol 0.18 µg/kg and LAS191351 0.40 µg/kg. At the highest dose devoid of HR effects the half-life was g24 hours for LAS191351 (10 µg/kg) and tiotropium (0.3 µg/kg), 13.3±3.8 hours for LAS190792 (10 µg/kg) and 5.4±1.6 hours for olodaterol (1 µg/kg). The safety margin of LAS190792 and LAS191351 was 333 and g25, respectively, higher than that of olodaterol (4.9). No plasma potassium concentration changes were observed for any drug. Changes in plasma glucose concentration were transient and observed only at the highest dose tested of LAS190792 and olodaterol.   Conclusion   LAS190792 and LAS191351 exhibited potent bronchoprotection and had a long duration of action. HR effects were reduced and a wide safety margin was seen. Both compounds may provide sustained bronchodilation and a reduced potential for cardiac effects in humans.
Low risk of secondary leukemias after chemotherapy without mechlorethamine in childhood Hodgkin's disease. German-Austrian Pediatric Hodgkin's Disease Group.
Authors: G Schellong, M Riepenhausen, U Creutzig, J Ritter, J Harbott, G Mann, H Gadner
Journal: Journal of Clinical Oncology (1997)

BACKGROUND In the last two decades, it has become evident that secondary leukemias after Hodgkin's disease (HD) are mainly caused by the treatment with alkylating agents, especially mechlorethamine. Since 1978, the German-Austrian trials for childhood HD have used combined chemoradiotherapy without mechlorethamine. PATIENTS AND METHODS The risk of secondary hematologic malignancies (SHM) was assessed in the total cohort of 667 children treated in four consecutive German-Austrian trials between 1978 and 1990. Primary chemotherapy for stages IA/B and IIA consisted of two cycles of vincristine, procarbazine, prednisone, and doxorubicin (OPPA) or OPA (without procarbazine) and, for more advanced stages, of two cycles of OPPA or OPA plus two, four, or six cycles of COPP or COMP (C, cyclophosphamide; M, methotrexate). Radiotherapy was given in the first study to extended fields, and in later trials to involved fields only. In 591 patients, only primary therapy was given; 76 patients (11%) needed additional salvage therapy. The actuarial survival rate at 15 years is 94%. RESULTS SHM developed in 5 of 667 patients: four acute myeloid leukemias (AMLs) and one myelodysplastic syndrome (MDS). The estimated cumulative risk for SHM at 15 years is 1.1% (95% CI, 0.0% to 2.2%). Salvage therapy was a significant risk factor for SHM (relative risk, 7.25; P = .03), whereas age, sex, stage of HD, splenectomy, and amount of alkylating agents were not. CONCLUSION The observed risk of SHM is smaller than in other studies (adults and children) in which chemotherapy with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) was given. This difference can be attributed to the lower cumulative doses of alkylating agents, the absence of mechlorethamine in the chemotherapy, and the small number of patients who needed salvage therapy in the presented cohort. In general, differences in the incidence of SHM after HD reflect complex differences between treatment strategies.