tbuckley/cabot-search huggingface dataset:
Studies of the proliferation and differentiation of immature myeloid cells in vitro. I. chronic myelogenous leukemia
Authors: Zique Wang, Xue Zhi Gao, Harvey D. Preisler
Journal: American Journal of Hematology (1989)

Abstract Immature cells prepared from chronic myelogenous leukemic patients in the chronic or blastic phase of their disease were placed into suspension culture in vitro and studied over a 2‐week period. Regardless of the status of the disease, the immature cells proliferated and maintained good viability. In contrast, evolution of the disease toward blastic crisis was associated with a progressive loss in the ability of the immature cells to differentiate. Cell proliferation and differentiation were independent of added growth factors.
Thrombopoietin expands hematopoietic stem cells after transplantation
Authors: Norma Fox, Greg Priestley, Thalia Papayannopoulou, Kenneth Kaushansky
Journal: Journal of Clinical Investigation (2002)

Multiple lines of evidence indicate that thrombopoietin (TPO) contributes to the development of hematopoietic stem cells (HSC), supporting their survival and proliferation in vitro. To determine whether TPO supports the impressive expansion of HSC observed following transplantation, we transplanted normal marrow cells into lethally irradiated Tpo–/– and Tpo+/+ mice and quantified HSC self-renewal and expansion and hematopoietic progenitor cell homing. Although essentially identical numbers of marrow-associated colony forming unit–culture (a surrogate measure of stem cell homing) were observed in each type of recipient 24 hours following transplantation, we found that a minimum of fourfold greater numbers of marrow cells were required to radioprotect Tpo-null mice than to radioprotect controls. To assess whether long-term repopulating (LTR) HSCs self-renew and expand in Tpo–/– recipients or controls, we performed limiting-dilution secondary transplants using donor cells from the Tpo–/– or Tpo+/+ recipients 5–7.5 weeks following primary transplantation. We found that LTR HSCs expand to levels 10–20 times greater within this time period in normal recipients than in Tpo-null mice and that physiologically relevant amounts of TPO administered to the Tpo–/– recipients could substantially correct this defect. Our results establish that TPO greatly promotes the self-renewal and expansion of HSCs in vivo following marrow transplantation.
Comparison of three inhaled non-steroidal anti-inflammatory drugs on the airway response to sodium metabisulphite and adenosine 5'-monophosphate challenge in asthma.
Authors: M. Wang, A. Wisniewski, I. Pavord, A. Knox, A. Tattersfield
Journal: Thorax (1996)

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are used to assess the role of prostaglandins in asthma but their effects on bronchoconstrictor challenges have been inconsistent. The effects of three nebulised nonsteroidal anti-inflammatory drugs on the airway response to inhaled sodium metabisulphite (MBS) and adenosine 59-monophosphate (AMP) were compared in the same asthmatic subjects to see whether contractile prostaglandins were involved in MBS or AMP induced bronchoconstriction. A possible protective effect of the osmolarity or pH of the inhaled solutions was also assessed. METHODS: Two double blind placebo controlled studies were carried out. In study 1, 15 non-aspirin sensitive patients with mild asthma attended on four occasions and inhaled 5 ml of lysine aspirin (L-aspirin) 900 mg, indomethacin 50 mg, sodium salicylate 800 mg, or saline 20 minutes before an inhaled MBS challenge. On four further occasions 14 of the patients inhaled the same solutions followed by an inhaled AMP challenge. In study 2, 10 of the patients attended on four additional occasions and inhaled 5 ml of 0.9%, 3%, 10%, or 9.5% saline with indomethacin 50 mg 20 minutes before an inhaled MBS challenge. RESULTS: In study 1 inhaled lysine aspirin had a similar effect on MBS and AMP induced bronchoconstriction, increasing the provocative dose causing a 20% fall in FEV1 (PD20) by 1.29 (95% CI 0.54 to 2.03) and 1.23 (95% CI 0.53 to 1.93) doubling doses, respectively. Indomethacin increased the MBS PD20 and AMP PD20 by 0.64 (95% CI -0.1 to 1.38) and 0.99 (95% CI 0.29 to 1.69) doubling doses, respectively. Sodium salicylate had no significant effect on either challenge. The two solutions causing most inhibition were the most acidic and the most alkaline. In study 2 inhaled 9.5% saline with indomethacin (osmolarity 3005 mOsm/kg) increased the MBS PD20 by 1.1 doubling doses (95% CI 0.2 to 2.0) compared with only 0.09 (95% CI -0.83 to 1.0) and 0.04 (95% CI -0.88 to 0.95) doubling doses with 3% saline (918 mOsm/kg) and 10% saline (2994 mOsm/ kg), respectively. CONCLUSIONS: Inhaled L-aspirin and indomethacin have broadly similar protective effects against MBS and AMP induced bronchoconstriction in the doses given, although the effect of indomethacin on MBS was not quite statistically significant. The osmolarity and pH of the solutions did not appear to be important determinants of the response. The effect of L-aspirin and indomethacin is likely to be the result of cyclooxygenase inhibition reducing the production of contractile prostaglandins during MBS and AMP challenge.
Non-variceal upper gastrointestinal haemorrhage: guidelines
Journal: Gut (2002)

Acute upper gastrointestinal bleeding is the commonest emergency managed by gastroenterologists. It has an incidence ranging from approximately 50 to 150 per 100 000 of the population each year, the incidence being highest in areas of the lowest socioeconomic status. An audit of patients admitted to hospital in the UK published in 1995 reported 11% mortality in patients admitted to hospital because of bleeding and 33% mortality in those who developed gastrointestinal bleeding while hospitalised for other reasons.1 Most deaths occur in elderly patients who have significant comorbidity and the majority are inevitable, despite improvements in medical and surgical expertise. Mortality is reported to be lower in specialist units2,3 and this is probably not related to technical developments but because of adherence to protocols and guidelines. Thus guidelines do have the potential to improve prognosis and in addition may be of value in making the best use of resources by fast tracking low risk patients, thereby optimising duration of hospital stay. “Medline” and “EMBASE” were searched to identify the evidence used in formulating these guidelines. The term “gastrointestinal hemorrhage” was used to identify general reviews, leading articles, meta-analyses, and randomised clinical trials. Not all of the recommendations have been subjected to clinical trial but represent what, in the view of the British Society of Gastroenterology (BSG) endoscopy committee, defines best clinical practice. Guidelines cannot replace clinical judgment in the management of any specific patient. Best management depends on close cooperation between medical and surgical gastroenterologists and “combined care” is essential in managing the critically ill bleeding patient. The specific management of acute variceal haemorrhage is a special subject and is not considered in detail. ### 1.1 Grading of recommendations #### Grade A #### Grade B #### Grade C
Cigarette Smoking and Pancreas Cancer: a Case--Control Study Based on Direct Interviews
Authors: D. T. Silverman, J. A. Dunn, R. N. Hoover, M. Schiffiman, K. D. Lillemoe, J. B. Schoenberg, L. M. Brown, R. S. Greenberg, R. B. Hayes, G. M. Swanson, S. Wacholder, A. G. Schwartz, J. M. Liff, L. M. Pottern
Journal: JNCI Journal of the National Cancer Institute (1994)

Background: Cigarette smoking is the most consistently reported risk factor for pancreas cancer, yet the dose-response relationship in many pancreas cancer studies is weak. Because of the poor prognosis for pancreas cancer, many case-control studies have been based largely on interviews with proxy respondents, who are known to report less reliable information on detailed smoking habits than original subjects. Purpose : Our purpose was to evaluate cigarette smoking as a risk factor for pancreas cancer based on data obtained only from direct interviews and to estimate the effects of quitting smoking and of switching from nonfiltered to filtered cigarettes on risk. Our objective also was to estimate the contribution of cigarette smoking toward explaining the higher pancreas cancer incidence experienced by black Americans compared with white Americans. Methods: A population-based, case-control study of pancreas cancer was conducted during 1986-1989 in Atlanta, Ga., Detroit, Mich., and 10 counties in New Jersey. Direct interviews were successfully completed with 526 case patients and 2153 control subjects aged 30-79 years, making this the largest population-based, case-control study of pancreas cancer to date based only on direct interviews. Results : Cigarette smokers had a significant, 70% increased risk of pancreas cancer compared with the risk in non smokers. A significant, positive trend in risk with increasing duration smoked was apparent ( P <.0001), with long-term (≥40 years) smokers experiencing a modest 2.1-fold risk. We also observed a negative trend in risk with increasing years quit smoking. Smokers who quit for more than 10 years experienced about a 30% reduction in risk relative to current smokers; quitters of 10 years or less experienced no risk reduction. Switching from nonfiltered to filtered cigarettes did not appear to decrease risk. Compared with non-smokers, subjects who smoked only filtered cigarettes had a 50% elevated risk and those who smoked only nonfiltered cigarettes had a 40% elevated risk. The proportion of pancreas cancer attributable to cigarette smoking was 29% in blacks and 26% in whites. Conclusions : The relationship between cigarette smoking and pancreas cancer risk is likely to be causal, despite the weakness of the dose-response data. Long-term smoking cessation clearly reduces risk, whereas switching from nonfiltered to filtered cigarettes may not be beneficial. Cigarette smoking appears to explain little of the excess pancreas cancer risk experienced by blacks. Implications : Elimination of cigarette smoking would eventually prevent approximately 27% of pancreas cancer, saving 6750 lives in the United States annually.
GP commissioners must help improve care of emergency surgery patients, say surgeons
Authors: A. O'Dowd
Journal: BMJ (2011)

Care of patients who need emergency surgery must improve and gain a more prominent role in NHS hospitals, a new report from the Royal College of Surgeons of England says. The report claims that pressure on trusts to meet targets on elective surgery has led to the neglect of emergency surgery. Rates of mortality and complications among patients undergoing emergency surgery, which accounts for about half of NHS surgery, vary widely among hospitals in England and Wales, it says. Problems in this area include:
Dietary Fat Intake as Risk Factor for the Development of Diabetes
Authors: Anastasia C. Thanopoulou, Basil G. Karamanos, Francesco V. Angelico, Samir H. Assaad-Khalil, Alfredo F. Barbato, Maria P. Del Ben, Predrag B. Djordjevic, Vesna S. Dimitrijevic-Sreckovic, Cristina A. Gallotti, Nikolaos L. Katsilambros, Ilias N. Migdalis, Mansouria M. Mrabet, Malina K. Petkova, Demetra P. Roussi, Maria-Teresa P. Tenconi
Journal: Diabetes Care (2003)

OBJECTIVE—To investigate the role of dietary factors in the development of type 2 diabetes. RESEARCH DESIGN AND METHODS—In the context of the Multinational MGSD Nutrition Study, three groups of subjects were studied: 204 subjects with recently diagnosed diabetes (RDM), 42 subjects with undiagnosed diabetes (UDM) (American Diabetes Association criteria—fasting plasma glucose [FPG] ≥126 mg/dl), and 55 subjects with impaired fasting glucose (IFG) (FPG ≥110 and &amp;lt;126 mg/dl). Each group was compared with a control group of nondiabetic subjects, matched one by one for center, sex, age, and BMI. Nutritional habits were evaluated by a dietary history method, validated against the 3-day diet diary. In RDM, the questionnaire referred to the nutritional habits before the diagnosis of diabetes. Demographic data were collected, and anthropometrical and biochemical measurements were taken. RESULTS—Compared with control subjects, RDM more frequently had a family history of diabetes (49.0 vs. 14.2%; P &amp;lt; 0.001), exercised less (exercise index 53.5 vs. 64.4; P &amp;lt; 0.01), and more frequently had sedentary professions (47.5 vs. 27.4%; P &amp;lt; 0.001). Carbohydrates contributed less to their energy intake (53.5 vs. 55.1%; P &amp;lt; 0.05), whereas total fat (30.2 ± 0.5 vs. 27.8 ± 0.5%; P &amp;lt; 0.001) and animal fat (12.2 ± 0.3 vs. 10.8 ± 0.3%; P &amp;lt; 0.01) contributed more and the plant-to-animal fat ratio was lower (1.5 ± 0.1 vs. 1.8 ± 0.1; P &amp;lt; 0.01). UDM more frequently had a family history of diabetes (38.1 vs. 19.0%; P &amp;lt; 0.05) and sedentary professions (58.5 vs. 34.1%; P &amp;lt; 0.05), carbohydrates contributed less to their energy intake (47.6 ± 1.7 vs. 52.8 ± 1.4%; P &amp;lt; 0.05), total fat (34.7 ± 1.5 vs. 30.4 ± 1.2%; P &amp;lt; 0.05) and animal fat (14.2 ± 0.9 vs. 10.6 ± 0.7%; P &amp;lt; 0.05) contributed more, and the plant-to-animal fat ratio was lower (1.6 ± 0.2 vs. 2.3 ± 0.4; P &amp;lt; 0.05). IFG differed only in the prevalence of family history of diabetes (32.7 vs. 16.4%; P &amp;lt; 0.05). CONCLUSIONS—Our data support the view that increased animal fat intake is associated with the presence of diabetes.
Riociguat improves excessive exercise ventilation in patients with inoperable chronic thromboembolic pulmonary hypertension
Authors: Roberta Pulcheri Ramos, Priscila Figueiredo, Eloara V.M. Ferreira, Carolina Messina, Rudolf Oliveira, J. Alberto Neder, Luiz Eduardo Nery, Jaquelina Sonoe Ota Arakaki
Journal: European Respiratory Journal (2013)

Rationale: Excessive exercise ventilation in patients with CTEPH is thought to be mainly attributable to increased physiological dead space ventilation due to proximal obstructive thrombotic lesions. Accordingly, pulmonary endarterectomy has been shown to improve ventilatory responses during exercise. The impact of drug therapy on such alterations is still to be determined.  Objective: To evaluate the effect of riociguat on the excessive exercise ventilation in patients with inoperable CTEPH  Methods: 6 patients with inoperable CTEPH performed a symptom-limited ramp-incremental cardiopulmonary exercise testing (CPET) on a cycle ergometer before and 8-12 months after treatment with riociguat.  Results: Long term treatment with riociguat significantly improved six minute walk distance (382 ± 63 to 431 ± 75m, p 0.05).  Conclusions: Riociguat improves excessive exercise ventilation in patients with inoperable distal CTEPH.
Risk of Infection-Related Cancers after the Loss of a Child: A Follow-up Study in Sweden
Authors: Fang Fang, Katja Fall, Pär Sparén, Hans-Olov Adami, Heiddis B. Valdimarsdóttir, Mats Lambe, Unnur Valdimarsdóttir
Journal: Cancer Research (2010)

Abstract It is unknown whether severe emotional stress due to loss of a child influences the risk of cancers susceptible to immune modulation such as infection-related cancers. We conducted a historic cohort study in 1990 to 2004 on the basis of the Swedish Multi-Generation Register including 4,687,073 parents. Death of a child was identified through the Causes of Death Register. Poisson regression was used to derive the relative risks (RR) and 95% confidence intervals (CI) of infection-related cancers, comparing the incidence rates of parents who lost a child with those who never lost a child. A total of 101,306 parents (2%) had lost a child during follow-up, among whom 1,608 subsequently developed infection-related cancers. After adjustment for age, sex, calendar year, educational level, and civil status, the overall RR of 14 cancers studied was 1.07 (95% CI: 1.02–1.12). Parents who lost a child were particularly at a higher risk for cancers potentially associated with human papilloma virus (HPV) infection such as cervical cancer (RR: 1.46; 95% CI: 1.17–1.80). Higher RRs for most cancers were obtained within 5 years after child loss and excess risk for liver and stomach cancers was confined to that period. No association was observed for lymphoma and nonmelanoma skin cancer at any time point after child loss. Although potential confounding by unmeasured factors cannot be ruled out, our findings lend support to the hypothesis that severe life stressors, such as child loss, may raise the risk for several, chiefly HPV-related, cancers. Cancer Res; 71(1); 116–22. ©2011 AACR.
A Lecture on TREATMENT OF MAMMARY CARCINOMA BY RADIATION
Authors: G. L. Cheatle
Journal: BMJ (1930)

<h3>Abstract</h3> <h3>Introduction</h3> Despite increased emphasis on education and training for patient safety in medical schools, there is little known about factors influencing decision making regarding patient safety behaviours. This study examined the nature and magnitude of factors which may influence opinions around patient safety related behaviours as a means of providing insights into how Australian doctors and medical students view these issues relative to members of the public. <h3>Methods</h3> A national, multicentre, prospective, on-line cross sectional survey was conducted using responses to hypothetical clinical scenarios. Three cohorts were surveyed - Australian enrolled medical students, medical doctors and members of the public. Participant responses were compared for the different contextual variables within the scenarios and the participants’ demographic characteristics – student, doctor, member of the public, gender and age (if public or doctors)/ seniority in the course (if a medical student). <h3>Results</h3> In total there were 2602 medical student participants, 809 doctors and 503 members of the Australian public. Medical doctors were more likely than other cohorts to have statistically significant differences in how they viewed the acceptability of patient safety related behaviours; doctors were more tolerant of medical students not reporting concerning behaviours. Medical students’ opinions frequently demonstrated a ‘transition effect’, bridging between the doctors and publics’ attitudes, consistent with professional identity formation. <h3>Conclusions</h3> Opinions on the acceptability of medical students’ patient safety related behaviours were influenced by the demographics of the cohort and the contextual complexity of the scenario. Although the survey used hypothetical scenarios, doctors and medical students’ opinions appear to be influenced by cognitive dissonances, biases and heuristics which may negatively affect patient safety. <i>‘Opinion is the medium between knowledge and ignorance’</i> Plato
Effects of formoterol and budesonide on GM-CSF and IL-8 secretion by triggered human bronchial epithelial cells
Authors: S.H. Korn, A. Jerre, R. Brattsand
Journal: European Respiratory Journal (2001)

The effect of formoterol, alone and in combination with budesonide, upon tumour necrosis factor-α stimulated (10 ng·mL −1 ) human bronchial epithelial cells was investigated. Addition of formoterol (≥10 −10 M) reduced granulocyte macrophage-colony stimulating factor (GM-CSF) levels, as assessed by enzyme-linked immunosorbent assay, by 40–50% and increased interleukin (IL)-8 levels by ∼50%. The effects of formoterol were long lasting (23 h). Budesonide (10 −8 M) reduced the amounts of both cytokines (GM-CSF and IL-8) by 40%. Simultaneous addition of formoterol and budesonide reduced GM-CSF levels ∼75%, while IL-8 levels were decreased ∼40%, similar to the reduction obtained with budesonide alone. The glucocorticoid receptor (GR) antagonist RU486 did not influence the effect of formoterol, suggesting no involvement of the GR. Formoterol rapidly induced an elevation in intracellular cyclic adenosine monophosphate, which was reduced in the presence of propranolol. In addition, the alterations in cytokine secretion induced by formoterol could be fully blocked by propranolol, demonstrating that these effects are β 2 -receptor mediated. In conclusion, the combination of budesonide and formoterol reduces the secretion of granulocyte macrophage-colony stimulating factor to basal levels and counteracts the capacity of formoterol alone to induce interleukin-8 production, modulations which may facilitate improved asthma control.
Bigger numbers needed!
Authors: H.F. Becker
Journal: European Respiratory Journal (2004)

In this issue of the European Respiratory Journal , Roebuck et al. 1 assess the effect of Cheyne-Stokes respiration (CSR) on mortality in patients with heart failure. Of the 78 patients, the largest patient group studied so far, CSR was present in 33 (42%). After 500 days of follow-up, mortality was increased in patients with CSR, but after a median of 52 months of follow-up, this difference was no longer present.

Congestive heart failure is one of the leading causes of morbidity and mortality in developed countries and, despite advances in pharmacological therapy, incidence rates are still rising. Ever since the description of apnoeas followed by a waxing and waning breathing pattern (Cheyne 1818 and Stokes 1854), the occurrence of breathing disturbances in chronic congestive heart failure has been recognised in the medical community. However, until a couple of years ago, many may have thought that CSR was a rare condition occurring in a few patients with end-stage heart failure or severe stroke. In fact, several studies published in recent years uniformly demonstrate that CSR is a very common problem in patients with stable congestive heart failure, with prevalence rates ranging 33–40% 2, 3. CSR leads to several unfavourable consequences: hypoxia, arousal from sleep, sympathetic activation, blood pressure …
Annexin 5 overexpression increased articular chondrocyte apoptosis induced by basic calcium phosphate crystals
Authors: H K Ea, V Monceau, E Camors, M Cohen-Solal, D Charlemagne, F Liote
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objectives:</h3> Basic calcium phosphate (BCP) crystals (octacalcium phosphate (OCP), carbapatite (CA) and hydroxyapatite (HA)) are associated with severe forms of osteoarthritis. In advanced osteoarthritis, cartilage shows chondrocyte apoptosis, overexpression of annexin 5 (A5) and BCP crystal deposition within matrix vesicles. We assessed in vitro whether BCP crystals and overexpression of A5 increased chondrocyte apoptosis. <h3>Methods:</h3> Apoptosis was induced by BCP crystals, tumour necrosis factor (TNF)-α (20 ng/ml) and Fas ligand (20 ng/ml) in normal articular chondrocytes (control) and in A5 overexpressed chondrocytes, performed by adenovirus infection. Apoptosis was assessed by caspase 3 (Cas3) activity, and DNA fragmentation. <h3>Results:</h3> All BCP crystals, TNF-α and Fas ligand induced chondrocyte apoptosis as demonstrated by decreased cell viability and increased Cas3 activity and DNA fragmentation. TUNEL (terminal deoxyribonucleotide transferase-mediated dUTP nick end-labelling)-positive staining chondrocytes were increased by OCP (12.4 (5.2)%), CA (9.6 (2.6)%) and HA (9.2 (3.0)%) crystals and TNF-α (9.6 (2.4)%) stimulation compared with control (3.1 (1.9)%). BCP crystals increased Cas3 activity in a dose-dependent fashion. BCP-crystal-induced chondrocyte apoptosis was independent from TNF-α and interleukin-1β pathways but required cell-crystal contact and intralysosomal crystal dissolution. Indeed, preincubation with ammonium chloride, a lysosomal inhibitor of BCP crystal dissolution, significantly decreased BCP-crystal-induced Cas3 activity. Finally, overexpression of A5 enhanced BCP crystal- and TNF-α-induced chondrocyte apoptosis. <h3>Conclusions:</h3> Overexpression of A5 and the presence of BCP crystals observed in advanced osteoarthritis contributed to chondrocyte apoptosis. Our results suggest a new pathophysiological mechanism for calcium-containing crystal arthropathies.