tbuckley/cabot-search huggingface dataset:
Expenditures on health research in sub-Saharan African countries: results of a questionnaire-based survey
Authors: Derege Kebede, Chris Zielinski, Peter Ebongue Mbondji, Issa Sanou, Wenceslas Kouvividila, Paul-Samson Lusamba-Dikassa
Journal: Journal of the Royal Society of Medicine (2014)

To estimate the sources of funds for health research (revenue) and the uses of these funds (expenditure).A structured questionnaire was used to solicit financial information from health research institutions.Forty-two sub-Saharan African countries.Key informants in 847 health research institutions in the 42 sub-Saharan African countries.Expenditure on health research by institutions, funders and subject areas.An estimated total of US$ 302 million was spent on health research by institutions that responded to the survey in the World Health Organization (WHO) African Region for the biennium 2005-2006. The most notable funders for health research activities were external funding, ministries of health, other government ministries, own funds and non-profit institutions. Most types of health research performers spent significant portions of their resources on in-house research, with medical schools spending 82% and government agencies 62%. Hospitals spent 38% of their resources on management, and other institutions (universities, firms, etc.) spent 87% of their resources on capital investment. Research on human immunodeficiency virus/tuberculosis and malaria accounted for 30% of funds, followed by research on other communicable diseases and maternal, perinatal and nutritional conditions (23%).Research on major health problems of the Region, such as communicable diseases, accounts for most of the research expenditures. However, the total expenditure is very low compared with other WHO regions.
What Is the Best Chemotherapy Treatment Option for Anthracycline and Taxane Pretreated Metastatic Breast Cancer?
Authors: Sunil Verma, Maureen Trudeau, George Dranitsaris, Mark Clemons, Anil A. Joy, John R. MacKey
Journal: Journal of Clinical Oncology (2005)

We commend Keller et al for their study evaluating pegylated liposomal doxorubicin (PLD) versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer. 1 With the increasing use of anthracyclines and taxanes in the adjuvant and first-line metastatic settings, there is a need for effective therapeutic agents for this patient population on disease progression.Commonly used agents include capecitabine, vinorelbine, gemcitabine, and PLD.Unfortunately, there are few randomized trials in the literature comparing the efficacy of these agents against one another in patients with disease that would be considered anthracycline and taxane refractory.Keller et al have performed a well-designed clinical trial to help answer the question as to which chemotherapy treatment option is the most appropriate for this particular patient population.They conclude that PLD is comparable in efficacy to vinorelbine or mitomycin C plus vinblastine, with a superior toxicity profile.However, overall survival remains poor with no statistical difference between PLD and the comparator arms (10.4 months v Ͻ 9.0 months respectively, p Ͻ ϭ NS).The Keller study has limited practical application as it fails to incorporate another effective agent, capecitabine, a current standard option for this anthracycline and taxane refractory population.Capecitabine, an oral fluorouracil prodrug, has significant activity in metastatic breast cancer (MBC) with reported response rates in taxane-refractory metastatic breast cancer of 20%. 2 There are also two small, phase IIB studies in the first-line setting (intravenous cyclophosphamide, methotrexate, fluorouracil v Ͻ capecitabine, and paclitaxel v Ͻ capecitabine); both favor capecitabine. 3,4 Given the lack of trials comparing vinorelbine with capecitabine, we conducted a retrospective review at two large Canadian cancer centers to evaluate the efficacy of capecitabine, vinorelbine, or both agents sequentially in anthracycline and taxane refractory MBC. 5 One hundred forty-one patients met study inclusion criteria: 45 patients received single agent vinorelbine, 68 patients received single agent capecitabine, and 28 patients received combined sequential therapy.The mean duration of therapy was 2.3 months with vinorelbine and 4.6 months with the capecit-
Ventricular Fibrillation During Hypothermia Successfully Treated by Rewarming and Electroshock
Authors: E. Husfeldt, O. Secher
Journal: Thorax (1956)

<h3>Background</h3> Tobacco displays at the point of sale (PoS) are an important means for the tobacco industry to communicate with consumers. With regulations prohibiting PoS displays recently having come into force in Ireland, passed into law in England, Wales and Northern Ireland and some Australian states, and being considered in New Zealand, Finland and Brazil, this is an increasingly important issue. This study explores the nature of displays, the extent to which they are tobacco industry funded, and the relation between the tobacco companies and retailers. <h3>Methods</h3> Three areas were chosen to gain a snapshot of PoS displays in England. Over 100 retailers were visited, with interviews taking place on site. Information was gathered on the type and size of tobacco display, who was paying for the display, requirements and incentives, and visits by industry representatives. <h3>Results</h3> The majority of retailers had gantries provided by tobacco companies. A minority of these were fitted with automated dispensers called retail vending machines. Attractive lighting and colour were often used to highlight particular products. Most retailers were being visited by industry representatives who checked displays. Some retailers also reported incentives offered to them for displaying products. <h3>Conclusions</h3> The results suggest that the tobacco industry presence and control in the retail environment is significant. Tobacco companies overwhelmingly provided tobacco gantries in the shops surveyed and influenced displays through a combination of requirements and incentives. The extensive involvement of tobacco companies in providing and monitoring retail displays suggests the importance of implementing policies to end this form of advertising.
Germline <i>PTEN</i> Mutations As a Cause of Early-Onset Endometrial Cancer
Authors: Gideon M. Blumenthal, Phillip A. Dennis
Journal: Journal of Clinical Oncology (2008)

TO THE EDITOR: In the article by Lu et al, 1 the investigators conducted a prospective assessment of the prevalence of Lynch syndrome in women diagnosed with endometrial cancer before age 50 years. Although they identified germline Lynch syndrome–associated mutations in 9% of their patient population, their data also suggest that for 91% of patients with early-onset endometrial cancer, the genetic basis is unclear. One genetic condition that could contribute is Cowden syndrome (CS), which is another inherited cancer susceptibility syndrome in which early endometrial cancer can occur. CS is characterized by germline mutations in the tumor suppressor PTEN that is located on chromosome 10q23.3. Loss of PTEN increases activation of the Akt/mTOR pathway, increases tumorigenesis in many organs in preclinical studies (including the uterus), and is a poor prognostic factor for many types of cancer. Germline mutations in PTEN are associated with a number of hamartomatous syndromes, of which CS is the prototype. CS patients develop thyroid, breast, and endometrial cancers at an earlier age than the general population, and have an overall increased incidence of these cancers compared with the general population. In a young woman diagnosed with endometrial cancer, a thorough history and physical examination evaluating signs of CS such as macrocephaly, mucocutaneous lesions (ie, facial trichilemmomas, acral keratoses, papillomatous lesions, or mucosal lesions) should be performed. If a patient meets established clinical criteria for CS, 2 or has a family member diagnosed with CS, referral for genetic testing and sequencing for germline mutation of PTEN should be considered. Although Lynch syndrome and CS can independently contribute to early-onset endometrial cancer, defects in mismatch repair (MMR), microsatellite instability (MSI), and PTEN mutations might be etiologically related. For example, in a population-based study of patients with sporadic endometrial cancer, 3 tumors with MSI had a higher frequency of PTEN mutations. Patients whose tumors harbored MSI and PTEN mutations were more likely to be diagnosed at an advanced stage and exhibited a worse prognosis. Zhou et al 4 demonstrated that a high frequency of somaticPTEN mutations, especially
Emergency portacaval anastomosis (EPCA): The long-awaited trial
Authors: Harold O. Conn
Journal: Hepatology (1986)

A prospective randomized trial was conducted in all comers with cirrhosis and bleeding varices comparing 1) emergency portacaval shunt (EPCS) performed within 8 hr of admission, with 2) emergency medical therapy (EMT) followed in 2-6 wks by elective portacaval shunt in survivors. All patients received identical supportive therapy initially, and the EMT group received vasopressin in continuous infusion and, if necessary, esophageal balloon tamponade to control varix bleeding. No patients refused to participate in the trial, and there were no escape or cross-over provisions in the protocol. Randomization resulted in 21 patients receiving EPCS and 22 patients receiving EMT. All patients were followed up for at least 3 yrs. Mean age was 48 yrs in each group. Cirrhosis was caused by alcoholism in 95% of each group. On admission, there were similar incidences in the 2 groups of ascites (EPCS-52%, EMT-50%), jaundice (EPCS-48%, EMT-50%), encephalopathy (EPCS-33%, EMT-14%), severe muscle wasting (EPCS-48%, EMT-59%), hyperdynamic state (82% in both groups), SGOT ≥ 100 u (EPCS-33%, EMT-36%), ICG retention ≥ 50% (EPCS-24%, EMT-23%), and ingestion of alcohol within 7 d of bleeding (EPCS-62%, EMT-59%). Child's risk classes in the EPCS group were A-10%, B-38%, and C-52%, while in the EMT group they were A-41%, B-32%, and C-27%, suggesting that the EPCS group had somewhat more severe liver disease. There were highly significant differences (p &lt; 0.01) in the results obtained by the 2 forms of treatment. Bleeding was permanently controlled in 100% of patients who underwent EPCS, but in 45% who received EMT. Mean requirement for blood transfusion was 5.8 u in the EPCS group and 15.5 u in the EMT group. 81% of the EPCS patients survived to leave the hospital compared to 45% of the EMT group. The 3-yr survival rate was 67% following EPCS compared to 27% following the combination of EMT and elective shunt. It is concluded that EPCS is significantly more effective than EMT followed by elective shunt in the treatment of bleeding varices in alcoholic cirrhosis.
Effects of brief coronary occlusion and reperfusion on porcine coronary artery reactivity.
Authors: J P Headrick, D A Angello, R M Berne
Journal: Circulation (1990)

The loss of coronary vasodilator reserve after ischemia-reperfusion may be due to endothelial injury, and this vascular dysfunction may contribute to functional alterations observed after ischemia. To determine whether endothelial dysfunction occurs after relatively brief periods of moderate low-flow ischemia in vivo, open-chest swine were subjected to 15 minutes of critical, subtotal left anterior descending coronary artery occlusion (80%) followed by 60 minutes of reperfusion. Serial measurements of regional coronary flow were made with the radiolabeled microsphere technique. After 60 minutes of reperfusion, the left anterior descending coronary artery was excised together with a section of the normally perfused left circumflex coronary artery to examine in vitro the relaxations to the endothelium-dependent dilators ADP and bradykinin and to the endothelial-independent dilators sodium nitroprusside and adenosine. Contractions to serotonin in quiescent rings were also examined. Endocardial and transmural blood flows recovered to preocclusion levels within 60 minutes of reperfusion, as did the epicardial-to-endocardial ratio. Vascular responses in isolated, reperfused left anterior descending coronary artery rings were significantly different from responses in control left circumflex coronary artery rings. Endothelium-dependent relaxations to adenosine diphosphate and bradykinin were significantly depressed in the left anterior descending coronary artery rings compared with left circumflex coronary artery rings (p less than 0.05). Serotonin-induced contractions were significantly greater in occluded-reperfused left anterior descending than in left circumflex coronary arteries (p less than 0.05). Relaxations to adenosine and sodium nitroprusside were not significantly different between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Dietary Sugar, Glycemic Load, and Pancreatic Cancer Risk in a Prospective Study
Authors: D. S. Michaud
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Evidence from both animal and human studies suggests that abnormal glucose metabolism plays an important role in pancreatic carcinogenesis. We investigated whether diets high in foods that increase postprandial glucose levels are associated with an increased risk of pancreatic cancer. Methods: In a cohort of U.S. women (n = 88 802) participating in the Nurses' Health Study, 180 case subjects with pancreatic cancer were diagnosed during 18 years of follow-up. We used frequency of intake of individual foods as reported on a food-frequency questionnaire in 1980 to calculate sucrose, fructose, and carbohydrate intakes; glycemic index (postprandial blood glucose response as compared with a reference food); and glycemic load (glycemic index multiplied by carbohydrate content). Analyses of relative risk (RR) were performed by using multivariable Cox proportional hazards models to adjust for potential confounders. All statistical tests were two-sided. Results: Carbohydrate and sucrose intake were not associated with overall pancreatic cancer risk in this cohort. A statistically nonsignificant 53% increase in risk of pancreatic cancer (RR = 1.53, 95% confidence interval [CI] = 0.96 to 2.45) was observed among women with a high glycemic load intake, and a similar association was observed for fructose intake (RR = 1.57, 95% CI = 0.95 to 2.57). The associations of glycemic load and fructose intakes with pancreatic cancer risk were most apparent among women with elevated body mass index (≥25 kg/m2) or with low physical activity. Among women who were both overweight and sedentary, a high glycemic load was associated with an RR of 2.67 (95% CI = 1.02 to 6.99; highest versus lowest quartile of intake; P for trend = .03), and high fructose was associated with an RR of 3.17 (95% CI = 1.13 to 8.91; P for trend = .04). Conclusion: Our data support other findings that impaired glucose metabolism may play a role in pancreatic cancer etiology. A diet high in glycemic load may increase the risk of pancreatic cancer in women who already have an underlying degree of insulin resistance.
Mindreading underlies metacognition
Authors: Peter Carruthers
Journal: Behavioral and Brain Sciences (2009)

Abstract This response defends the view that human metacognition results from us turning our mindreading capacities upon ourselves, and that our access to our own propositional attitudes is through interpretation rather than introspection. Relevant evidence is considered, including that deriving from studies of childhood development and other animal species. Also discussed are data suggesting dissociations between metacognitive and mindreading capacities, especially in autism and schizophrenia.
Characterization of telaprevir treatment outcomes and resistance in patients with prior treatment failure: Results from the REALIZE trial
Authors: Sandra De Meyer, Inge Dierynck, Anne Ghys, Maria Beumont, Bjorn Daems, Ben Van Baelen, James C. Sullivan, Douglas J. Bartels, Tara L. Kieffer, Stefan Zeuzem, Gaston Picchio
Journal: Hepatology (2012)

In the Phase 3 REALIZE study, 662 genotype 1 hepatitis C virus (HCV)-infected patients with prior peginterferon/ribavirin treatment failure (including relapsers, partial, and null responders) were randomized to 12 weeks of telaprevir given immediately (T12/PR48) or following 4 weeks of peginterferon/ribavirin (lead-in T12/PR48), or 12 weeks of placebo (PR48), combined with a total of 48 weeks of peginterferon alfa-2a/ribavirin. Sustained virologic response (SVR) rates were 64% (T12/PR48), 66% (lead-in T12/PR48), and 17% (PR48). This analysis aimed to characterize treatment outcomes and viral variants emerging in telaprevir-treated patients not achieving SVR. HCV NS3·4A population sequencing was performed at baseline, during treatment, and follow-up. Telaprevir-resistant variants were classified into lower-level (3- to 25-fold 50% inhibitory concentration [IC(50) ] increase: V36A/M, T54A/S, R155I/K/M/T, and A156S) and higher-level (>25-fold IC(50) increase: V36M+R155K and A156T/V) resistance. Resistant variants were uncommon at baseline. Overall, 18% (52%, 19%, and 1% of prior null and partial responders and relapsers, respectively) of telaprevir-treated patients had on-treatment virologic failure, with no significant difference with or without a lead-in. Virologic failure during the telaprevir-treatment phase was predominantly associated with higher-level resistance; virologic failure during the peginterferon/ribavirin-treatment phase was associated with higher- or lower-level, or wildtype variants, depending on genotype. Relapse occurred in 9% of patients completing assigned treatment and was generally associated with lower-level resistant variants or wildtype. Resistant variants were no longer detectable by study end (median follow-up of 11 months) in 58% of non-SVR patients.In REALIZE, variants emerging in non-SVR, telaprevir-treated patients were similar irrespective of the use of a lead-in and were consistent with those previously reported. In most patients, resistant variants became undetectable over time.
Effect of Clinical Doses of Fluoxetine on Psychological Variables in Healthy Volunteers
Authors: Y Gelfin, M Gorfine, B Lerer
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: The authors sought to determine the effect of clinically equivalent doses of fluoxetine on mood and other psychological variables in normal subjects. METHOD: Fifteen healthy volunteers received placebo for 2 weeks; fluoxetine, 10 mg/day, for 1 week; fluoxetine, 20 mg/day, for 5 weeks; and then an additional 2 weeks of placebo in the context of a single-blind study. The subjects were evaluated with a series of self- and observer-rated instruments. RESULTS: No significant effects attributable to fluoxetine were observed on any of the psychological variables examined. Minimal adverse effects were reported. CONCLUSIONS: Significant mood-elevating and other psychological effects of fluoxetine would appear to be induced only when symptomatic targets exist. (Am J Psychiatry 1998; 155:290–292)
Honokiol Induces a Necrotic Cell Death through the Mitochondrial Permeability Transition Pore
Authors: Ling Li, Weidong Han, Ying Gu, Shuang Qiu, Qinghua Lu, Jie Jin, Jianhong Luo, Xun Hu
Journal: Cancer Research (2007)

Abstract Previous reports have shown that honokiol induces apoptosis in numerous cancer cell lines and showed preclinical efficacies against apoptosis-resistant B-cell chronic lymphocytic leukemia and multiple myeloma cells from relapse-refractory patients. Here, we show that honokiol can induce a cell death distinct from apoptosis in HL60, MCF-7, and HEK293 cell lines. The death was characterized by a rapid loss of integrity of plasma membrane without externalization of phosphatidyl serine. The broad caspase inhibitor z-VAD-fmk failed to prevent this cell death. Consistently, caspase activation and DNA laddering were not observed. The death was paralleled by a rapid loss of mitochondrial membrane potential, which was mechanistically associated with the mitochondrial permeability transition pore regulated by cyclophilin D (CypD) based on the following evidence: (a) cyclosporin A, an inhibitor of CypD (an essential component of the mitochondrial permeability transition pore), effectively prevented honokiol-induced cell death and loss of mitochondrial membrane potential; (b) inhibition of CypD by RNA interference blocked honokiol-induced cell death; (c) CypD up-regulated by honokiol was correlated with the death rates in HL60, but not in K562 cells, which underwent apoptosis after being exposed to honokiol. We further showed that honokiol induced a CypD-regulated death in primary human acute myelogenous leukemia cells, overcame Bcl-2 and Bcl-XL–mediated apoptotic resistance, and was effective against HL60 cells in a pilot in vivo study. To the best of our knowledge, this is the first report to document an induction of mitochondrial permeability transition pore–associated cell death by honokiol. [Cancer Res 2007;67(10):4894–903]
Erythrocyte function and marrow regulation in hemoglobin Bethesda (β145 histidine)
Authors: John W. Adamson, Akira Hayashi, George Stamatoyannopoulos, Wilbur F. Burger
Journal: Journal of Clinical Investigation (1972)

Hemoglobin Bethesda (β145 histidine) is one of the two mutants known to affect the penultimate hemoglobin tyrosines. The result of this substitution is extreme disorganization of the oxygenation function of the molecule. Red cells containing 45% Hb Bethesda and 55% Hb A have increased oxygen affinity but, paradoxically, a normal Bohr effect. As is usually seen with other hemoglobins with increased oxygen affinity, Hb Bethesda clinically is manifest in heterozygotes by erythrocytosis. Red cell production in affected individuals is erythropoietin dependent. The reciprocal interdependence of oxygen delivery and effective erythropoiesis was documented by alterations in erythropoietin excretion, quantitative iron kinetics, and reticulocyte production in response to phlebotomy-induced reduction in the oxygen-carrying capacity.
Maternal smoking in pregnancy and birth defects: a systematic review based on 173 687 malformed cases and 11.7 million controls
Authors: A. Hackshaw, C. Rodeck, S. Boniface
Journal: Human Reproduction Update (2011)

BACKGROUNDThere is uncertainty over whether maternal smoking is associated with birth defects. We conducted the first ever comprehensive systematic review to establish which specific malformations are associated with smoking.
Acute Renal Failure and Myalgia in a Transplant Patient
Authors: Behzad Najafian, Donald B. Franklin, Agnes B. Fogo
Journal: Journal of the American Society of Nephrology (2007)

A 64-yr-old man with kidney transplant for ESRD as a result of diabetic nephropathy presented with acute renal failure, weakness, myalgia, and pigmented urine. His medications included mycophenolate, cyclosporine, prednisone, furosemide, diltiazem, aspirin, simvastatin, an angiotensin receptor blocker, and insulin. A renal biopsy was performed. Pathologic findings and differential diagnosis are discussed, and the literature is reviewed.
ICUD-EAU International Consultation on Kidney Cancer 2010: Treatment of Metastatic Disease
Authors: Jean-Jacques Patard, Geraldine Pignot, Bernard Escudier, Tim Eisen, Axel Bex, Cora Sternberg, Brian Rini, Jan Roigas, Toni Choueiri, Ronald Bukowski, Robert Motzer, Ziya Kirkali, Peter Mulders, Joaquim Bellmunt
Journal: European Urology (2011)