tbuckley/cabot-search huggingface dataset:
Smallpox in Central Province, Nyasaland
Authors: J. M. Sword
Journal: BMJ (1961)

Smailpox has always bwn endemic in Nyasaland, with occasional outbreaks of such proportions that they can be termed epidemics.Vaccination campaigns are continually under way, and the year 1960 was no exception.In the middle of the year, however, and especially in the Central Province, much political opposition was encountered.As a result the vaccination programme was greatly restricted, and in some villages was brought to a standstill.This opposition was withdrawn in October and the vaccina- tion campaign was reintroduced, though by this time it was too late to prevent outbreaks of the disease.
The Construct of Minor and Major Depression in Alzheimer’s Disease
Authors: Sergio E Starkstein, Ricardo Jorge, Romina Mizrahi, Robert G Robinson
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: This study examined the frequency of major and minor depression in Alzheimer’s disease and determined whether these types of depression have a different functional and psychopathological impact and whether there is a change in the prevalence of major and minor depression throughout the stages of Alzheimer’s disease. METHOD: A consecutive series of 670 patients with probable Alzheimer’s disease were assessed with the Structured Clinical Interview for DSM-IV; specific instruments to rate the presence and severity of depression, anxiety, apathy, irritability, delusions, pathological affective crying, performance of activities of daily living, and social functioning; and a standardized neuropsychological evaluation. Diagnoses of major and minor depression were generated from DSM-IV criteria. RESULTS: Twenty-six percent of the patients had major depression, 26% had minor depression, and 48% were not depressed. Major depression was significantly associated with sad mood in all three stages of the illness, although this association dropped significantly for minor depression in severe Alzheimer’s disease. Both major and minor depression were significantly associated with more severe psychopathology, functional impairments, and social dysfunction. Depressive symptoms that most strongly discriminated between Alzheimer’s disease patients with and without sad mood were guilty ideation, suicidal ideation, loss of energy, insomnia, weight loss, psychomotor retardation/agitation, poor concentration, and loss of interest. CONCLUSIONS: Our study demonstrates that DSM-IV criteria for major and minor depression identify clinically relevant syndromes of depression in Alzheimer’s disease, mild levels of depression can produce significant functional impairment, and the severity of psychopathological and neurological impairments increases with increasing severity of depression.
UTILIZATION OF DIAGNOSTIC TRANSTEMPORAL GUIDED HIGH MECHANICAL INDEX ULTRASOUND AND A SYSTEMIC MICROBUBBLE INFUSION TO TREAT ISCHEMIC STROKE WITHOUT FIBRINOLYTIC AGENTS
Authors: Thomas Richard Porter, Shunji Gao, William Shi, Francois Vignon, Jeffry Powers, John Lof, Shelby Kutty, Feng Xie
Journal: Journal of the American College of Cardiology (2011)
Multipotent Progenitor Cells Are Present in Human Peripheral Blood
Authors: Daniela Cesselli, Antonio Paolo Beltrami, Silvia Rigo, Natascha Bergamin, Federica D'Aurizio, Roberto Verardo, Silvano Piazza, Enio Klaric, Renato Fanin, Barbara Toffoletto, Stefania Marzinotto, Laura Mariuzzi, Nicoletta Finato, Maura Pandolfi, Annarosa Leri, Claudio Schneider, Carlo Alberto Beltrami, Piero Anversa
Journal: Circulation Research (2009)

To determine whether the peripheral blood in humans contains a population of multipotent progenitor cells (MPCs), products of leukapheresis were obtained from healthy donor volunteers following the administration of granulocyte colony-stimulating factor. Small clusters of adherent proliferating cells were collected, and these cells continued to divide up to 40 population doublings without reaching replicative senescence and growth arrest. MPCs were positive for the transcription factors Nanog, Oct3/4, Sox2, c-Myc, and Klf4 and expressed several antigens characteristic of mesenchymal stem cells. However, they were negative for markers of hematopoietic stem/progenitor cells and bone marrow cell lineages. MPCs had a cloning efficiency of ≈3%, and following their expansion, retained a highly immature phenotype. Under permissive culture conditions, MPCs differentiated into neurons, glial cells, hepatocytes, cardiomyocytes, endothelial cells, and osteoblasts. Moreover, the gene expression profile of MPCs partially overlapped with that of neural and embryonic stem cells, further demonstrating their primitive, uncommitted phenotype. Following subcutaneous transplantation in nonimmunosuppressed mice, MPCs migrated to distant organs and integrated structurally and functionally within the new tissue, acquiring the identity of resident parenchymal cells. In conclusion, undifferentiated cells with properties of embryonic stem cells can be isolated and expanded from human peripheral blood after granulocyte colony-stimulating factor administration. This cell pool may constitute a unique source of autologous cells with critical clinical import.
Hepatic uptake of a modified low molecular weight heparin in rats.
Authors: G Stehle, E A Friedrich, H Sinn, A Wunder, J Harenberg, C E Dempfle, W Maier-Borst, D L Heene
Journal: Journal of Clinical Investigation (1992)

Fractionated and unfractionated heparins are widely used as antithrombotic agents. Because of their heterogeneous composition, it is difficult to study the pharmacokinetics of these drugs. We now report on a new method for labeling low molecular weight heparins with 131I by binding tyramine to the anhydromannose end of the molecules. We examined the pharmacokinetics of the compound by intravenous injection of 131I-tyramine-heparin into Wistar rats. About 18% of the activity was found in the liver, whereas 33% was detected in urine. Biological activity in terms of Factor Xa inhibition was measurable. Since evidence from cell culture experiments implies that reticuloendothelial cell system receptors might be involved in heparin metabolism, maleylated BSA, a substance known to block scavenger receptors, was injected before the radiolabeled heparin compound. The liver uptake was reduced from 17.4 to 4.8%. Injection of unfractionated heparin before tracer application caused a considerable increase in urine excretion of the tracer substance. To our knowledge, this is the first report that liver uptake of heparins is linked to scavenger receptor mediated mechanisms in vivo. This interaction of heparins with scavenger receptors might play an important role in the biology of the vessel wall.
C-stage in Colon Cancer: Implications of Carcinoembryonic Antigen Biomarker in Staging, Prognosis, and Management
Authors: Pragatheeshwar Thirunavukarasu, Shyamsunder Sukumar, Magesh Sathaiah, Meredith Mahan, Kothai Divya Pragatheeshwar, James F. Pingpank, Herbert Zeh, Christopher J. Bartels, Kenneth K.W. Lee, David L. Bartlett
Journal: JNCI Journal of the National Cancer Institute (2011)

The American Joint Committee on Cancer (AJCC) has proposed the inclusion of pretreatment serum carcinoembryonic antigen (CEA) level (C-stage) into the conventional TNM staging system of colon cancer. We assessed the prognosis of various stages of colon cancer after such an inclusion.Data for all patients (N = 17 910) diagnosed with colonic adenocarcinoma (AJCC stages I, IIA, IIB, IIC, IIIA, IIIB, IIIC, and IV, based on TNM staging system) between January 1, 2004, and December 31, 2004, with a median follow-up of 27 months (range 0-35 months), were collected from the Surveillance, Epidemiology, and End Results database. C-stage (C0-stage = normal CEA level; C1-stage = elevated CEA level) was assigned to all patients with available CEA information (n = 9083). Multivariable analyses using Cox proportional hazards models were used to identify independent factors associated with prognosis. Prognosis of overall stages (AJCC stages I-IV and C0 or C1) was analyzed using Kaplan-Meier survival curves. All statistical tests were two-sided.C1-stage was independently associated with a 60% increased risk of overall mortality (hazard ratio of death = 1.60, 95% confidence interval = 1.46 to 1.76, P < .001). Overall survival was decreased in patients with C1-stage cancer compared with C0-stage cancer of the respective overall stages (P < .05). Similarly, decreased overall survival was noted in patients with stage I C1 cancer compared with stage IIA C0 or stage IIIA C0 cancer (P < .001), in patients with stage IIA C1 cancer compared with stage IIIA C0 (P < .001), and in patients with stage IIB C1 or stage IIC C1 cancer compared with stage IIIB C0 cancer (P < .001).C-stage was an independent prognostic factor for colon cancer. The results support routine preoperative CEA testing and C-staging upon diagnosis of colon cancer and the inclusion of C-stage in the conventional TNM staging of colon cancer.
Automobile Injury—Selected Risk Factors and Prevention in the Health Care Setting
Authors: Michael R. Polen
Journal: JAMA (1988)

Every year, highway crashes cause tens of thousands of deaths and millions of nonfatal injuries, many of which can be prevented. Following a mandate from the US Preventive Services Task Force, in this article we describe the magnitude of the automobile injury problem, identify injury risk factors that might be reduced by clinically based preventive programs, and review reports of interventions by health professionals to promote the use of child restraint devices, the only area in which we found published evaluations. We conclude that despite the lack of experimental evidence of the long-term effectiveness of clinically based efforts to promote occupant restraint use, such efforts may be warranted because of the enormous social and economic costs of automobile injury. In addition, physicians and other health professionals are urged to consider promoting nonclinical automobile injury prevention measures. (<i>JAMA</i>1988;259:76-80)
Novel Biological Functions of High-Density Lipoprotein Cholesterol
Authors: Chieko Mineo, Philip W. Shaul
Journal: Circulation Research (2012)

In addition to its role in reverse cholesterol transport, high-density lipoprotein (HDL) cholesterol has direct action on numerous cell types that influence cardiovascular and metabolic health. Cellular responses to HDL entail its capacity to invoke cholesterol efflux that causes signal initiation via scavenger receptor class B, type I, and plasma membrane receptor activation by HDL cargo molecules. In endothelial cells and their progenitors, HDL attenuates apoptosis and stimulates proliferation and migration. HDL also has diverse anti-inflammatory actions in both endothelial cells and leukocytes. In vascular smooth muscles, HDL tempers proinflammatory, promigratory, and degradative processes, and through actions on endothelium and platelets HDL is antithrombotic. There are additional actions of HDL of potential cardiovascular consequence that are indirect, including the capacities to promote pancreatic β-cell insulin secretion, to protect pancreatic β cells from apoptosis, and to enhance glucose uptake by skeletal muscle myocytes. Furthermore, HDL decreases white adipose tissue mass, increases energy expenditure, and promotes the production of adipose-derived cytokine adiponectin that has its own vascular-protective properties. Many of these numerous actions of HDL have been observed not only in cell culture and animal models but also in human studies, and assessments of these functions are now being applied to patient populations to better-elucidate which actions of HDL may contribute to its cardioprotective potential and how they can be quantified and targeted. Further work on the many mechanisms of HDL action promises to reveal new prophylactic and therapeutic strategies to optimize both cardiovascular and metabolic health.
Hand osteoarthritis in older women is associated with carotid and coronary atherosclerosis: the AGES Reykjavik study
Authors: H Jonsson, G P Helgadottir, T Aspelund, G Eiriksdottir, S Sigurdsson, T Ingvarsson, T B Harris, L Launer, V Gudnason
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> There is evidence that atherosclerosis may contribute to the initiation or progression of osteoarthritis. To test this hypothesis, the presence and severity of hand osteoarthritis (HOA) was compared with markers of atherosclerotic vascular disease in an elderly population. <h3>Patients and Methods:</h3> The AGES Reykjavik Study is a population-based multidisciplinary study of ageing in the elderly population of Reykjavik. In a study of 2264 men (mean age 76 years; SD 6) and 3078 women (mean age 76 years; SD 6) the severity of HOA, scored from photographs, was compared with measures of atherosclerosis. These included carotid intimal thickness and plaque severity, coronary calcifications (CAC) and aortic calcifications and reported cardiac and cerebrovascular events. <h3>Results:</h3> After adjustment for confounders, both carotid plaque severity and CAC were significantly associated with HOA in women, with an odds ratio of 1.42 (95% CI 1.14 to 1.76, p = 0.002) for having CAC and 1.25 (95% CI 1.04 to 1.49, p = 0.016) for having moderate or severe carotid plaques. Both carotid plaques and CAC also exhibited significant linear trends in relation to HOA severity in women in the whole AGES Reykjavik cohort (p&lt;0.001 and p = 0.027, respectively, for trend). No significant associations were seen in men. Despite this evidence of increased atherosclerosis, women with HOA did not report proportionally more previous cardiovascular or cerebrovascular events. <h3>Conclusions:</h3> The results indicate a linear association between the severity of HOA and atherosclerosis in older women. The pathological process of HOA seems to have some components in common with atherosclerosis. Prospective studies may help elucidate the possible mechanisms of this relationship.
The poor man's capillary microscope. A novel technique for the assessment of capillary morphology
Authors: R. M Bauersachs
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVES</h3> To evaluate a new method for rapid and efficient assessment of capillary morphology. <h3>METHODS</h3> Nailfold capillary morphology in 18 patients with Raynaud's phenomenon was investigated with a new bedside test, based on a modified dermatoscope using a novel gel-immersion technique. These findings were compared with those obtained by standard capillary microscopy. <h3>RESULTS</h3> With the standard microscope, six patients had dilated capillaries, six had mega-capillaries, seven had avascular fields, eight had ramified capillaries, six had contorted capillaries, and seven patients showed micro-haemorrhages, respectively. The dermatoscope identified exactly the same patients to have the same capillary abnormalities. One hundred and thirty six fingers were available for pairwise comparison: The κ statistic was 0.93 for dilated capillaries, 0.97 for mega-capillaries, 0.93 for avascular areas, 0.78 for ramified capillaries, 0.81 for contorted capillaries, and 0.94 for micro-haemorrhages, respectively. The average examination time was 18 (range 8–30) minutes with the standard microscope and 4 (3–8) minutes with the dermatoscope. <h3>CONCLUSION</h3> A new diagnostic tool for rapid and efficient examination of nailfold capillaries is described for circumstances when a standard microscope is not available. This study shows that the hand held device can be used in clinical routine with sufficient diagnostic efficacy and little expenditure, both timewise and financially.
Genome-Wide DNA Methylation Patterns in Wild Samples of Two Morphotypes of Threespine Stickleback (Gasterosteus aculeatus)
Authors: Gilbert Smith, Carl Smith, John G. Kenny, Roy R. Chaudhuri, Michael G. Ritchie
Journal: Molecular Biology and Evolution (2014)

Epigenetic marks such as DNA methylation play important biological roles in gene expression regulation and cellular differentiation during development. To examine whether DNA methylation patterns are potentially associated with naturally occurring phenotypic differences, we examined genome-wide DNA methylation within Gasterosteus aculeatus, using reduced representation bisulfite sequencing. First, we identified highly methylated regions of the stickleback genome, finding such regions to be located predominantly within genes, and associated with genes functioning in metabolism and biosynthetic processes, cell adhesion, signaling pathways, and blood vessel development. Next, we identified putative differentially methylated regions (DMRs) of the genome between complete and low lateral plate morphs of G. aculeatus. We detected 77 DMRs that were mainly located in intergenic regions. Annotations of genes associated with these DMRs revealed potential functions in a number of known divergent adaptive phenotypes between G. aculeatus ecotypes, including cardiovascular development, growth, and neuromuscular development.
Loss of secretion in mouse-human hybrids need not be due to the loss of a structural gene.
Authors: R L Raison, K Z Walker, C R Halnan, D Briscoe, A Basten
Journal: The Journal of Experimental Medicine (1982)

Three cloned mouse-human lines (B1-29, E2-42, and A2-31) secreting human immunoglobulin (Ig) were obtained from a fusion between the mouse myeloma line NS-1 and human tonsillar lymphocytes stimulated in vitro with pokeweed mitogen. One line, B1-29, has continued to secrete human IgG for a period of 2 yr in culture. This line was recloned three times to give a panel of secreting and nonsecreting subclones. Most of the nonsecreting subclones had also lost surface Ig. The structural genes for human Ig heavy chains have been provisionally assigned to chromosome 14, which also encodes the enzyme nucleoside phosphorylase. Human nucleoside phosphorylase was detected in all secreting and nonsecreting B1-29 subclones, indicating the presence of human chromosome 14. The retention of chromosome 14 in nonsecreting clones implied that the structural genes for human Ig were A2-31 and E2-42, which had stopped secreting, an attempt was made to restimulate the secreting of human Ig with mitogens A2-31 was unique among the cell lines examined, in that chromosome 14 could not be detected by an isoenzyme marker. Lipopolysaccharide, at an optimum dose of 10 micrograms/ml, restimulated these nonsecreting hybrid lines to secrete human IgG in levels up to 0.7 micrograms/ml. Loss of Ig secretion may not therefore be caused by loss of Ig structural genes.
Comparison of a low dose polyethylene glycol electrolyte solution with lactulose for treatment of chronic constipation
Authors: A Attar, M Lémann, A Ferguson, M Halphen, M-C Boutron, B Flourié, E Alix, M Salmeron, F Guillemot, S Chaussade, A-M Ménard, J Moreau, G Naudin, M Barthet
Journal: Gut (1999)

Background Polyethylene glycol (PEG) 3350 is a non-absorbable, non-metabolised osmotic agent used in lavage solutions for gut cleansing. Aims To compare the efficacy of PEG and lactulose in chronic constipation. Methods A total of 115 patients with chronic constipation entered a multicentre, randomised, comparative trial. They initially received two sachets containing either PEG (13 g/sachet) or lactulose (10 g/sachet) and were given an option to change the dose to one or three sachets/day, depending on response. Results Ninety nine patients completed the trial. After four weeks, patients in the PEG group (n=50) had a higher number of stools and a lower median daily score for straining at stool than patients in the lactulose group (n=49). Overall improvement was greater in the PEG group. Clinical tolerance was similar in the two groups, but flatus was less frequently reported in the PEG group. The mean number of liquid stools was higher in the PEG group but the difference was significant only for the first two weeks. There were no serious adverse events and no significant change in laboratory tests in either group. At the end of the study, the number of sachets used by the patients was 1.6 (0.7)/day in the PEG group and 2.1 (0.7)/day in the lactulose group. Sixty one patients completed a further two months open study of one to three sachets PEG daily; there was no loss of efficacy and no serious toxicity. Conclusion Low dose PEG 3350 was more effective than lactulose and better tolerated.
Poor management, not drug costs, is hampering implementation of NICE guidance
Authors: Adrian O'Dowd
Journal: BMJ (2005)

Poor financial management and not the cost of drugs and treatment is preventing clinicians in England from doing their jobs properly, says the Audit Commission.

The watchdog of public spending claims that much of the guidance issued by the National Institute for Health and Clinical Excellence (NICE) is not implemented because trusts do not organise their finances well enough.

Better communication between clinical and financial staff will help the situation, says the commission in its report on the financial implications of NICE guidance, which was published last week in conjunction with the institute.

Hospitals and primary care trusts could boost clinical excellence if they followed all of NICE's guidance, which is …
Evidence for caveolin-1 as a new susceptibility gene regulating tissue fibrosis in systemic sclerosis
Authors: Mirko Manetti, Yannick Allanore, Mohamad Saad, Cinzia Fatini, Vanessa Cohignac, Serena Guiducci, Eloisa Romano, Paolo Airó, Paola Caramaschi, Ilaria Tinazzi, Valeria Riccieri, Alessandra Della Rossa, Rosanna Abbate, Roberto Caporali, Giovanna Cuomo, Guido Valesini, Philippe Dieudé, Eric Hachulla, Jean-Luc Cracowski, Kiet Tiev, Luc Letenneur, Philippe Amouyel, Jean-Charles Lambert, Gilles Chiocchia, Maria Martinez, Lidia Ibba-Manneschi, Marco Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2012)

Caveolin-1 (CAV1) is an inhibitor of tissue fibrosis and has been implicated in the pathogenesis of systemic sclerosis (SSc). The aim of the study was to analyse the possible association of CAV1 gene single nucleotide polymorphisms (SNP) with SSc.A total population of 3974 individuals (1355 SSc patients, 2619 controls) was studied. Genotype data for 23 SNP spanning the CAV1-CAV2 gene locus were obtained from a genome-wide scan conducted in a French population (564 SSc patients, 1776 controls). Three CAV1 SNP (rs926198, rs959173, rs9920) displaying the most significant associations with SSc and/or clinical phenotypes were then genotyped in an Italian population (791 SSc patients, 843 controls). CAV1 protein expression in skin biopsies was investigated by immunohistochemistry and western blotting.In the French population, the CAV1 rs959173 C minor allele showed a significant protective association with susceptibility to SSc (OR 0.71, 95% CI 0.59 to 0.86, p(adjusted)=0.009), and with the subset of patients with limited cutaneous SSc (OR 0.71, 95% CI 0.56 to 0.89, p(adjusted)=0.018). The association was replicated in the Italian population and strengthened in the combined populations through Cochran-Mantel-Haenszel meta-analysis (SSc: pooled OR 0.81, 95% CI 0.71 to 0.92, p=0.0018; limited cutaneous SSc: pooled OR 0.80, 95% CI 0.69 to 0.93, p=0.0053). Genotype/protein expression correlations revealed that the rs959173 C protective allele was associated with increased CAV1 protein expression.These results add CAV1 to the list of SSc susceptibility genes and provide further evidence for the contribution of this pathway in the fibrotic process that characterises SSc pathogenesis.