tbuckley/cabot-search huggingface dataset:
EXPERIMENTAL INOCULATION OF MALARIA BY MEANS OF ANOPHELES LUDLOWI
Authors: Samuel T. Darling
Journal: The Journal of Experimental Medicine (1920)

Three persons were experimentally inoculated with malaria by means of Anopheles ludlowi reared from larvae and infected with a pure strain of subtertian plasmodium (Plasmodium falciparum), thus proving that there exists no mechanical impediment or obstacle to the free exit of sporozoites from the salivary ducts or proboscis. In the dissection of infected mosquitoes there were no evidences of degenerated zygotes. Sporozoites appeared promptly in the salivary glands (9 to 12 days). Inoculation occurred with ease either in an interrupted feeding or after mosquitoes had been fed twice previously. The period of incubation was 14 and 18 days. The clinical manifestations were more severe in the subject that had never been infected with malaria previously, while the splenic enlargement was most pronounced in the subject infected after a long interval of freedom from malaria. In a third subject already suffering from tertian malaria there was only the slightest evidence of physical illness elicited by the superimposed subtertian infection; his temperature, however, became duly elevated. The type of febrile reaction in the two uncomplicated cases was at first tertian, becoming quotidian later, and this phenomenon in a pure strain leads strongly to the supposition that Plasmodium falciparum possesses inherently both tertian (or subtertian) and quotidian tendencies, as well as its well known tendencies to cause fever of the irregularly remittent or continued type. The creation of a specific plasmodium to account for clinical forms of aestivo-autumnal or subtertian malaria having a quotidian periodidty is probably unwarranted. In consideration of the facility with which this species can be infected and man inoculated experimentally, the occurrence of naturally infected wild specimens, and the positive epidemiological evidence, there should no longer exist in the minds of sanitarians any doubt as to its being a malarial carrier. Operations against this species can therefore be recommended without reservation and should be carried out without delay.
VERY LOW RATES OF STENT THROMBOSIS UP TO 10 YEARS FOLLOWING DRUG-ELUTING STENT IMPLANTATION IN THE REAL WORLD CLINICAL PRACTICE
Authors: Ricardo A. Costa, Amanda Sousa, J. Ribamar Costa, Adriana Moreira, Galo Maldonado, Manuel Cano, Bruno Palmieri, Fausto Feres, Lucas Damiani, Cantidio Campos, J. Eduardo Sousa
Journal: Journal of the American College of Cardiology (2012)
Compliance With Antidepressant Medication in the Treatment of Major Depressive Disorder in Primary Care: A Randomized Comparison of Fluoxetine and a Tricyclic Antidepressant
Authors: Christopher Thompson, Robert C. Peveler, Deborah Stephenson, Jan McKendrick
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Many claims have been made for superior compliance with selective serotonin reuptake inhibitors (SSRIs) compared with tricyclic antidepressants, but to date meta-analyses have not confirmed reduced dropouts in randomized controlled trials. The authors used a randomized study design to evaluate differential compliance with antidepressant medications in a primary care setting. METHOD: A total of 152 patients treated in 10 primary care practices in the United Kingdom were included in a randomized, open-label, parallel-group study of fluoxetine and dothiepin at therapeutic doses for 12 weeks. Compliance was assessed by using pill count, patient questionnaires, and the Medication Event Monitoring System. RESULTS: The level of compliance with fluoxetine was numerically higher than the level of compliance with dothiepin on all three primary outcome measures, although the differences were not significant. In a secondary analysis using data from the Medication Event Monitoring System, both a survival analysis for length of time without a gap in medicine taking and a derived compliance index showed a significant advantage to fluoxetine. Patients in the fluoxetine group reported superior response on the health transition scale of the 36-item Short-Form Health Survey Questionnaire and numerically greater improvement on the Hamilton Depression Rating Scale. In both treatment arms patients with a superior compliance index were more likely to have improved in Hamilton depression scale scores by the last study visit. CONCLUSIONS: This study supports recent meta-analyses of SSRIs versus tricyclic antidepressants in finding no significant differences in crude indices of compliance between fluoxetine and dothiepin, despite marked differences in side effect profile and dose regimen. However, both a survival analysis and a new measure that takes account of prolonged periods of noncompliance distinguished between the treatments and was associated with improvement in both groups.
Hereditary pancreatitis: new insights into acute and chronic pancreatitis
Authors: D C WHITCOMB
Journal: Gut (1999)

Hereditary pancreatitis: new insights into acute and chronic pancreatitisHereditary pancreatitis has recently emerged as an important pancreatic disease.Although relatively rare, this genetic disorder has provided major breakthroughs in our understanding of acute and chronic pancreatitis and pancreatic cancer.Furthermore, study of this disorder promises additional insights into the pathophysiology of human pancreatitis, new strategies for developing animal models of disease, and new therapies to treat or prevent acute and chronic pancreatitis.A review of recent findings and mechanisms of disease should benefit scientists who study the pancreas and physicians who care for individuals with pancreatitis.This report will focus on acute and chronic pancreatitis. Clinical featuresThe first family with hereditary pancreatitis was described by Comfort and Steinberg in 1952. 1 Careful evaluation of four definite and two probably aVected family members revealed an autosomal dominant inheritance pattern, onset of symptoms between five and 23 years, but no other ". ..earmarks which distinguish it from non-hereditary chronic relapsing pancreatitis".These observations remain accurate with the caveat that penetrance, the fraction of patients with the mutation that eventually express the disease, is 80%. 2-6Attacks of acute pancreatitis usually begin in childhood, 7 but age of onset can range from infancy to the fifth or sixth decade of life.The acute attacks may vary from mild abdominal discomfort to severe life-threatening episodes with pancreatic necrosis, splenic vein thrombosis, 8 pseudocysts, 9 and death. 3 10Chronic pancreatitis follows recurrent attacks of acute pancreatitis with all of its common complications-unrelenting pain, parenchymal and ductal calcifications, duct distortion, fibrosis, maldigestion and diabetes mellitus. 3-6 10 11 These features make hereditary pancreatitis indistinguishable from other causes of acute and chronic pancreatitis, save the relatively early age of onset, the autosomal dominant inheritance pattern and lack of other identifiable aetiologies. Why do cationic trypsinogen mutations cause hereditary pancreatitis?To date, the genetic studies on hereditary pancreatitis families reveal only two specific mutations in the cationic trypsinogen gene.No other disease associated mutations have been identified in any pancreatic digestive enzyme genes, including anionic trypsinogen or mesotryspinogen.However, this should not be a great surprise because
Toll-like receptors in cardiovascular diseases
Authors: D DEKLEIJN, G PASTERKAMP
Journal: Cardiovascular Research (2003)

The Toll-like receptor family recognizes mostly exogenous ligands like bacterial lipopolysaccharides or DNA and activates the inflammatory cell. Evidence is accumulating that these Toll-like receptors are important in cardiovascular pathologies. Recently, expression of Toll-like receptors in arterial and myocardial cells has been shown and mouse knockout and human studies on polymorphisms point to a role of Toll-like receptor 4 in neointima formation and atherosclerosis. It is now becoming clear that these receptors not only serve as receptors for pathogen-associated molecular patterns but are also involved in the initiation and progression of cardiovascular pathologies.
CD40/CD40 Ligand Signaling in Mouse Cerebral Microvasculature After Focal Ischemia/Reperfusion
Authors: Mami Ishikawa, Thorsten Vowinkel, Karen Y. Stokes, Thiruma V. Arumugam, Gokhan Yilmaz, Anil Nanda, D. Neil Granger
Journal: Circulation (2005)

CD40/CD40 ligand (CD40L) signaling contributes to proinflammatory and prothrombogenic responses in the vasculature. CD40/CD40L expression is elevated in patients after a transient ischemic attack or stroke. The purpose of this study was to investigate the role of CD40/CD40L signaling in cerebral microvascular dysfunction and tissue injury response to middle cerebral artery occlusion (MCAO) and reperfusion.Intravital fluorescence microscopy was used to visualize the cerebral microcirculation of wild-type (WT), CD40-deficient, and CD40L-deficient mice subjected to 1-hour MCAO and 4-hour reperfusion. The adhesion of platelets and of leukocytes and vascular permeability were measured in postcapillary venules after 4-hour and 1-hour reperfusions, respectively. Cerebral infarct volume was analyzed 24 hours after reperfusion. Platelet and leukocyte adhesion was elevated and blood/brain barrier function was compromised by MCAO in WT mice. Blood cell recruitment and increased permeability were blunted in both CD40-deficient and CD40L-deficient mice. Infarct volume was also reduced in CD40- and CD40L-deficient mice compared with WT mice.Our findings indicate that CD40/CD40L signaling contributes to inflammatory and prothrombogenic responses and brain infarction induced by MCAO and reperfusion. The CD40/CD40L dyad may play a significant pathogenic role in the acute phase of ischemic stroke.
Economic downturn threatens to derail millennium development goals
Authors: P. Moszynski
Journal: BMJ (2009)

The global financial crisis could undermine progress on fulfilling the millennium development goals unless new ways are found to secure additional funding and deliver aid more effectively. This is a warning from a symposium held this week at the Royal Society in London. 

A consortium of the Action for Global Health advocacy network of European health and development charities warns that development funding, particularly for the health related goals, remains seriously off-track. The goals aim to reduce child mortality, improve maternal health, and combat HIV/AIDS, malaria, and other diseases.

Last week the Word Health Organization’s director …
The effect of steroid and dithranol therapy on cyclic nucleotides in psoriatic epidermis
Authors: E. M. SAIHAN, JANET ALBANO, J. L. BURTON
Journal: British Journal of Dermatology (1980)

Absolute values of both cAMP and cGMP leves were measured in the involved and uninvolved skin of psoriatic patients, and also the effect of topical therapy on these levels in the involved skin was studied. The mean cGMP level in the untreated psoriatic plaque was increased by 300% compared to the non-involved skin (which did not differ from normal skin), but no significant difference in cAMP levels was found. Epidermal stripping of uninvolved skin, which stimulates cell proliferation, did not change the cGMP level. Treatment of the psoriasis with dithranol caused the cGMP levels to return to normal, but a potent topical glucocorticoid, in contrast, produced no such decrease. This may imply that the two drugs act at different levels in suppressing cell replication, and dithranol may be a useful tool for the further investigation of cyclic nucleotide metabolism.
Fewer colon cancer patients have surgery but survival is increasing, US study shows
Authors: J. Wise
Journal: BMJ (2015)

The number of patients with stage IV colorectal cancer who undergo primary tumour resection in the United States has decreased significantly over time, a retrospective cohort study has shown. However, patient survival rates have improved, and the researchers wrote in the journal JAMA Surgery that surgery may still be overused.

The study included data from the National Cancer Institute’s registry of 64 157 patients in …
Evaluation of a Screening Test for Hyperlipidemia
Authors: Eduardo Zorrilla
Journal: JAMA (1974)

A simple test that requires only minutes and is designed to indicate whether triglyceride or cholesterol levels or both are elevated in serum was applied to 502 fresh serum specimens. Quantitative determinations of total cholesterol and triglycerides were also obtained. Using arbitrary criteria to define hypertriglyceridemia (triglyceride level &gt; 150 mg/100 ml) and hypercholesterolemia (cholesterol level &gt; 300 mg/100 ml) the test yields a rate of 3.1% false-negative results and a 20.7% rate of false-positive results. This degree of accuracy could reduce the number of quantitative lipid analyses done for screening purposes in a proportion much greater than the inherent error of the test. (<i>JAMA</i>228:589-592, 1974)
Meta-analysis of efficacy of quinine for treatment of nocturnal leg cramps in elderly people
Authors: M. Man-Son-Hing, G. Wells
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To assess quantitatively the efficacy of quinine (as quinine sulphate) compared with placebo in the treatment of nocturnal leg cramps. <b>Design</b>: A meta-analysis of six randomised, double blind, crossover trials. <b>Setting</b>: Randomised trials that were available as of April 1994. <b>Subjects</b>: A total of 107 general ambulatory patients who suffered from regular nocturnal leg cramps from six clinical trials. <b>Results</b>: Data from individual patients were used to calculate point estimates and 95% confidence intervals for each of the outcome measures reported by these studies. Treatment with quinine resulted in a significant reduction in the number of cramps for a four week period compared with placebo (8.83 fewer cramps; 95% confidence interval 4.16 to 13.49). Treatment with quinine reduced the number of nights with cramps by 27.4% (24.0% to 30.8%) compared with placebo. Treatment did not produce a significant change in the severity or duration of individual nocturnal leg cramps. Side effects were uncommon. <b>Conclusions</b>: The results indicate that quinine can prevent nocturnal leg cramps in general ambulatory populations. Given the possible serious side effects of treatment with quinine, the benefits and risks in patients taking this drug should be closely monitored. <h3>Key messages</h3> Key messages The results of this meta-analysis show that quinine sulphate is more effective than placebo in reducing the number of cramps experienced by patients This analysis also suggests that dosing is cumulative, therefore a trial of at least four weeks of quinine may be necessary to show a beneficial effect Quinine should be taken on a regular as opposed to as needed basis as it could not be shown definitively to reduce the severity or duration of an individual cramp
Cooperation between FGF8b Overexpression and PTEN Deficiency in Prostate Tumorigenesis
Authors: Chen Zhong, Gohar Saribekyan, Chun-Peng Liao, Michael B. Cohen, Pradip Roy-Burman
Journal: Cancer Research (2006)

Abstract Two commonly occurring genetic aberrations of human prostate cancer [i.e., overexpression of a mitogenic polypeptide (fibroblast growth factor 8, isoform b or FGF8b) and loss of function of PTEN tumor suppressor] were recapitulated into a new combinatorial mouse model. This model harboring the Fgf8b transgene and haploinsufficiency in Pten, both in a prostate epithelium–specific manner, yielded prostatic adenocarcinoma with readily detectable lymph node metastases, whereas single models with each of the defects were shown earlier to progress generally only up to prostatic intraepithelial neoplasia (PIN). In addition to late age-related development of typical adenocarcinoma, the model also displayed a low incidence of mucinous adenocarcinoma, a rare variant type of human prostatic adenocarcinoma. The cooperation between FGF8b activation and PTEN deficiency must be linked to acquisition of additional genetic alterations for the progression of the lesions to primary adenocarcinoma. Here, we identified loss of heterozygosity at the Pten gene leading to bialleic loss, as a necessary secondary event, indicating that a complete loss of PTEN function is required in the development of invasive cancer in the model. Analyses of expression of downstream mediators phospho-AKT (p-AKT) and p27KIP1, in various types of lesions, however, revealed a complex picture. Although PIN lesions displayed relatively strong expression of p-AKT and p27KIP1, there was a notable heterogeneity with variable decrease in their immunostaining in adenocarcinomas. Together, the results further underscore the notion that besides activation of AKT by loss of PTEN function, other PTEN-regulated pathways must be operative for progression of lesions from PIN to adenocarcinoma. (Cancer Res 2006; 66(4): 2188-94)
Urocortin induces positive inotropic effect in rat heart
Authors: Eva Calderón-Sanchez, Carmen Delgado, Gema Ruiz-Hurtado, Alejandro Domínguez-Rodríguez, Victoria Cachofeiro, María Rodríguez-Moyano, Ana María Gomez, Antonio Ordóñez, Tarik Smani
Journal: Cardiovascular Research (2009)

The aim of this study is to evaluate the positive inotropic effect of urocortin (Ucn) and to characterize its signalling pathways. Contractility was measured in ex vivo Langendorff-perfused hearts isolated from Wistar rats. Isolated ventricular cardiomyocytes were used to analyse intracellular calcium ([Ca2+]i) transients evoked by electrical stimulation and L-type Ca2+ current by confocal microscopy and whole-cell patch-clamping, respectively. The application of Ucn to perfused hearts induced progressive, sustained, and potent inotropic and lusitropic effects that were dose-dependent with an EC50 of approximately 8 nM. Ucn effects were independent of protein kinase A (PKA) activation but were significantly reduced by protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) inhibitors and by brefeldin A, an antagonist of guanine nucleotide exchange factor, suggested to be an inhibitor of exchange protein activated by cAMP (Epac). These whole-organ effects were correlated with the inotropic effects observed in isolated cells: Ucn increased ICaL density, [Ca2+]i transients, cell shortening and Ca2+ content of sarcoplasmic reticulum. Our results show that Ucn evokes potent positive inotropic and lusitropic effects mediated, at least in part, by an increase in ICaL and [Ca2+]i transient amplitude. These effects may involve the activation of Epac, PKC, and MAPK signalling pathways.
OnabotulinumtoxinA 100 U Significantly Improves All Idiopathic Overactive Bladder Symptoms and Quality of Life in Patients with Overactive Bladder and Urinary Incontinence: A Randomised, Double-Blind, Placebo-Controlled Trial
Authors: Christopher Chapple, Karl-Dietrich Sievert, Scott MacDiarmid, Vik Khullar, Piotr Radziszewski, Christopher Nardo, Catherine Thompson, Jihao Zhou, Cornelia Haag-Molkenteller
Journal: European Urology (2013)
Organization of Health Services in the Soviet Union: Overview and Trends
Authors: MIKE GORMAN
Journal: American Journal of Psychiatry (1968)

In a society in which the state operates all psychiatric facilities, long-range planning can be directly related to what the top health officials see as major patient needs. After reviewing the organization of health services, with particular reference to budget-making, research, and training, the author reports that the U.S. team was impressed with the self-questioning and flexibility that characterize the thinking of Soviet psychiatric planners.
Effect of priming with granulocyte–macrophage colony-stimulating factor in younger adults with newly diagnosed acute myeloid leukemia: a trial by the Acute Leukemia French Association (ALFA) Group
Authors: X Thomas, E Raffoux, S de Botton, C Pautas, P Arnaud, T de Revel, O Reman, C Terré, B Corront, C Gardin, Q-H Le, B Quesnel, C Cordonnier, J-H Bourhis, M Elhamri, P Fenaux, C Preudhomme, M Michallet, S Castaigne, H Dombret
Journal: Leukemia (2007)
Simulation of macroamylasaemia by salivary-type (`S type') hyperamylasaemia
Authors: J. E. Berk, L. Fridhandler, K. Montgomery
Journal: Gut (1973)

Hyperamylasaemia with low or normal urinary amylase excretion in the face of normal renal function has been noted to be indirect evidence for the existence of macroamylasaemia. A more refined indicator is a low ratio of renal amylase clearance to creatinine clearance. This report describes observations made in three patients, each of whom displayed the indirect features suggestive of macroamylasaemia. In none of these patients, however, could a serum macroamylase be demonstrated by chromatography. Ultracentrifugation was also done in one of the patients and likewise failed to disclose a macroamylase in the serum. When the isozyme nature of the serum amylase in each of these patients was examined, there was found to be a marked rise in activity of the salivary-type isoamylase (`S-type amylase9). The pancreatic-type isoamylase (`P-type amylase9) was normal in one patient and perhaps slightly above normal in the other two. These data indicate that (1) S-type hyperamylasaemia may exhibit the indirect criteria taken to indicate macroamylasaemia and thereby simulate the latter disorder; and (2) unequivocal identification of macroamylasaemia requires the direct demonstration of the presence in the serum of a macromolecular amylase complex.
Microsatellite instability but not thymidylate synthase is a prognostic variable in primary colon cancers from patients treated in 5-FU-based adjuvant studies
Authors: F. A. Sinicrope, R. L. Rego, K. C. Halling, N. R. Foster, D. J. Sargent, B. Laplant, A. J. French, C. J. Allegra, J. A. Laurie, R. M. Goldberg, S. N. Thibodeau
Journal: Journal of Clinical Oncology (2006)

10019 Background: Colon cancers with microsatellite instability (MSI) display resistance to 5-fluorouracil (5-FU), and in vitro resistance can be reversed by restoring DNA mismatch repair proficiency. 5-FU inhibits the thymidylate synthase (TS) enzyme and TS may predict clinical outcome after 5-FU-based chemotherapy. To define molecular predictors of prognosis, we analyzed TS, p53, chromosome 17p allelic imbalance (AI), and patient survival stratified by MSI status. Methods: Primary colon carcinomas from patients enrolled in five 5-FU-based adjuvant therapy trials were analyzed for MSI and 17p AI using 11 microsatellite markers (MSI-H: ≥ 30% of the loci demonstrating instability). For 17p AI, markers included D17S261 and TP53 at or near the p53 locus. Expression of DNA mismatch repair (hMLH1, PharMingen; hMSH2; Oncogene), TS (TS106, Zymed), and p53 (D07, Novacastra) proteins were analyzed by immunohistochemistry. Correlations between markers and associations with overall survival (OS) were determined. Patients were censored at 5 years for DFS and at 8 years post study randomization for overall survival (OS) data. Results: Of 320 Dukes’ stage B2 and C cancers studied, 60 of 320 (19%) were MSI-H. TS expression variables (intensity, extent, weighted score) were similar in MSI-H and MSI stable/low frequency (MSS/MSI-L) cancers; similar results were found using DNA mismatch repair (dMMR) proteins. MSI-H tumors had lower stage (p= 0.0007), fewer metastatic lymph nodes (p= 0.004), and improved OS (vs. MSS/MSI-L tumors; p= 0.01). Loss of dMMR proteins was also associated with better OS (p= 0.006). None of the TS variables were prognostic for OS. Histologic grade (p= 0.0008) and nodal status (p= 0.0002) were associated with OS in contrast to 17p LOH or p53. Only MSI status or dMMR, histologic grade, and tumor stage were independent markers for OS. Conclusions: MSI-H tumors show earlier stage at presentation and better stage-adjusted survival rates. MSI status and TS expression were unrelated and TS was not prognostic, suggesting that TS levels cannot explain therapeutic resistance to 5-FU reported in MSI-H colon cancers. [Table: see text]