tbuckley/cabot-search huggingface dataset:
Aetiology of Acute Hemiplegia in Childhood
Authors: E. R. Bickerstaff
Journal: BMJ (1964)

Paterson-Kelly Syndrome-jacobs and Kilpatrick MEDICTJSHOUNAL appear to fall into the transitional state, the early stage of which has been described as pre-pernicious anaemia and the later stage as latent pernicious anaemia (Wood, Cowling, Ungar, and Gray, 1960).The evolution of gastric atrophy to latent pernicious anaemia has been described by Wood et al. (1960), but it is not known whether gastric atrophy invariably progresses to this stage.The transformation of latent into clinical pernicious anaemia is believed to depend on the individual's body stores of vitamin B and on external precipitating factors, such as infection.The fact that achlorhydria was so often found in those of our patients whose absorption of vitamin B 12 was normal suggests that the patients with latent pernicious anaemia may have had a pre-existing simple atrophic gastritis.The significance of gastric atrophy in iron-deficiency anaemia is not certain.It has been held that the gastric mucosal changes are the result of iron deficiency (Davidson and Markson, 1955 ; Badenoch et al., 1957).Against this view is the rarity of achlorhydria in the chronic iron-deficiency anaemia of hookworm infestation (Foy and Kondi, 1960; Ball, personal communication) and the finding that gastric atrophy, when it does occur, is not reversed by the administration of iron (Lees and Rosenthal, 1958).Coghill (1960) has shown that atrophic gastritis is more common in those patients with iron-deficiency anaemia in whom there is no evidence either of blood loss or of excep- tionally deficient iron intake.This " idiopathic " gastric atrophy appears to be genetically determined.It is most com- mon in the Northern European races and rare in equatorial Africa.It is often a prelude to the development of pernicious anaemia.The combination of iron deficiency and the Paterson- Kelly syndrome is not found in a population unaffected by gastric atrophy.In patients with gastric atrophy, however, the Paterson-Kelly syndrome may appear either before there is any anaemia or after the gastric atrophy has led to the development of latent pernicious anaemia or iron-deficiency anaemia.Dysphagia may occur in patients with uncomplicated pernicious anaemia, so that iron deficiency does not appear to be essential to its development. SummaryAn investigation of 55 cases of the Paterson-Kelly syndrome showed a high incidence of iron deficiency, achlorhydria, and subnormal vitamin-B,21 absorption.It is suggested that this syndrome is associated with the genetically determined gastric atrophy found in patients with pernicious anaemia and that iron deficiency is a secondary feature.We are indebted to the staff of the Cardiff Royal Infirmary, who have allowed us to investigate patients under their care, and to Professor H. Scarborough for his helpful criticism.
Studies on the mode of action of non-steroid anti-inflammatory drugs.
Authors: D A Willoughby, M DiRosa
Journal: Annals of the Rheumatic Diseases (1972)

Annals of the Rheumatic Diseases we usually use penicillin, and the choice of drugs is really between penicillin and cloxacillin.When we are dealing with a septic arthritis, we usually think it is due to staphylococci.Is there any information you can give us about the protein binding of penicillin G? DR.HOWELL Benzyl penicillin is much less highly bound than cloxacillin.Obviously it would diffuse into the joint very much better and would be the best drug to use against a penicillin-sensitive staphylococcus.
Autonomous growth of a human neuroblastoma cell line is mediated by insulin-like growth factor II.
Authors: O M El-Badry, J A Romanus, L J Helman, M J Cooper, M M Rechler, M A Israel
Journal: Journal of Clinical Investigation (1989)

Insulin-like growth factor II (IGF-II) mRNA was increased in two of eight neuroblastomas and in eight of eight pheochromocytomas, tumors of the adrenal medulla that occur in childhood and adulthood, respectively. RNA encoding the type I IGF receptor, the receptor thought to mediate the mitogenic effects of IGF-I and IGF-II, also was uniformly expressed in these cells. To assess the role of IGF-II in the growth of these tumor cells, we have used the SK-N-AS cultured neuroblastoma cell line, which can be continuously propagated in mitogen-free medium, as a model system. Our results strongly suggest that IGF-II, synthesized by SK-N-AS cells and acting through type I IGF receptors, contributes to the autonomous growth of this tumor cell line. (a) SK-N-AS cells synthesized large amounts of IGF-II RNA and secreted greater than 50 ng/ml of IGF-II (as determined by specific radioimmuno- and radioreceptor assays). Little, if any, IGF-I RNA or immunoreactive IGF-I were detected. (b) SK-N-AS cells possess type I IGF receptors. (c) Exogenous IGF-I and IGF-II stimulated DNA synthesis in SK-N-AS cells, and this stimulation was abolished by a blocking antibody to the type I IGF receptor. (d) This anti-receptor antibody also abolished the multiplication of SK-N-AS cells in the absence of added mitogens. We conclude that IGF-II is an autocrine growth factor for SK-N-AS cells and suggest that this mechanism may contribute to the growth of some adrenal medullary tumors.
1083 HEPATIC NK AND NKT CELLS COOPERATIVELY REGULATE LIVER REGENERATION AFTER PARTIAL HEPATECTOMY IN MICE
Authors: S. Hosoya, K. Ikejima, K. Arai, T. Aoyama, K. Kon, S. Ishikawa, H. Yamagata, S. Yamashina, K. Takeda, S. Watanabe
Journal: Journal of Hepatology (2011)
How to Use an Article Reporting a Multiple Treatment Comparison Meta-analysis
Authors: Edward J. Mills, John P. A. Ioannidis, Kristian Thorlund, Holger J. Schünemann, Milo A. Puhan, Gordon H. Guyatt
Journal: JAMA (2012)

Multiple treatment comparison (MTC) meta-analysis uses both direct (head-to-head) randomized clinical trial (RCT) evidence as well as indirect evidence from RCTs to compare the relative effectiveness of all included interventions. The methodological quality of MTCs may be difficult for clinicians to interpret because the number of interventions evaluated may be large and the methodological approaches may be complex. Clinicians and others evaluating an MTC should be aware of the potential biases that can affect the interpretation of these analyses. Readers should consider whether the primary studies are sufficiently homogeneous to combine; whether the different interventions are sufficiently similar in their populations, study designs, and outcomes; and whether the direct evidence is sufficiently similar to the indirect evidence to consider combining. This article uses the existing Users' Guides format to address study validity, interpretation of results, and application to a patient scenario.
1004. c-Jun NH2-Terminal Kinase (JNK)1 and JNK2 Have Distinct Roles in Adenovirus-Mediated Transgene Expression
Authors: Fuminori Teraishi, Bingliang Fang, Annin Liu, Futoshi Uno, Shunsuke Kagawa, Toshiyoshi Fujiwara, Noriaki Tanaka
Journal: Molecular Therapy (2006)

The c-Jun NH2-terminal kinase (JNK) signaling pathway is induced by various stress stimuli and is implicated in cell death and differentiation. However, the specific function of this pathway depends on the cell type, and the underlying mechanistic basis remains unclear. In the current study, we examined the role of JNK1 and JNK2 in adenovirus-mediated transgene expression. Using mouse embryonic fibroblasts (MEFs) deficient in either Jnk1 (Jnk1-/-) or Jnk2 (Jnk2-/-), we found that adenovirus encoding green fluorescence protein (Ad/GFP) induced much more GFP expression in Jnk2-/- MEFs than that in wild-type cells, while Jnk1-/- MEFs showed less GFP expression. We also confirmed that more GFP protein expression was observed in Ad/GFP-infected Jnk2-/- MEFs than that in wild-type or Jnk1-/- MEFs by immunoblotting. In addition, we demonstrated that adenovirus vector Ad/RGD-GFP that contains an RGD motif in the HI loop of the fiber knob expressing GFP had similar effect on GFP expression in MEFs, indicating that coxsackievirus and adenovirus receptor was not correlated with the difference between Jnk2-/- MEFs and others. Moreover, transfection of human cancer cells with the plasmid dnJNK2 encoding dominan- negative JNK2 mutant resulted in increase of GFP expression induced by Ad/GFP infection. Similarly, transfection with CMV/GFP plasmid that contains CMV promoter resulted in an increase of GFP expression in Jnk2-/- fibroblasts and dnJNK2 transfectant. These results were consitent with previous report showing that activation of stress-activated MAP protein kinases up-regulates expression of transgenes driven by the CMV promoter. Furthermore, we demonstrated that adenovirus vector Ad/RSV-Luc containing the RSV promoter expressing luciferase had similar effect on transgene expression in Jnk2-/- fibroblasts and dnJNK2 transfectant, indicating that adenovirus-mediated gene expression was regulated promoter independently in our cell system. Thus, JNK1 and JNK2 play different roles in adenovirus-mediated transgene expression in MEFs and human cancer cells, and it might be useful finding for future direction of adenovirus gene therapy. Further studies will be needed to clarify the exact molecular mechanisms by which they do so.
Rapid dendritic cell recruitment is a hallmark of the acute inflammatory response at mucosal surfaces.
Authors: A S McWilliam, D Nelson, J A Thomas, P G Holt
Journal: The Journal of Experimental Medicine (1994)

Immunohistochemical analysis of challenge sites such as skin and the peritoneal cavity has identified neutrophils as virtually the sole cellular participants in acute bacterial inflammation, peak influx occurring 24-48 h in advance of mononuclear cell populations associated with adaptive immunity. This study challenges the general applicability of this paradigm. We demonstrate here that the earliest detectable cellular response after inhalation of Moraxella catarrhalis organisms is the recruitment of putative class II major histocompatibility complex-bearing dendritic cell (DC) precursors into the airway epithelium, the initial wave arriving in advance of the neutrophil influx. Unlike the neutrophils which rapidly transit into the airway lumen, the DC precursors remain within the epithelium during the acute inflammatory response where they differentiate, and develop the dendriform morphology typical of resident DC found in the normal epithelium. During the ensuing 48-h period, these cells then migrate to the regional lymph nodes. No comparable DC response was observed after epidermal or intraperitoneal challenge, and it may be that mucosal surfaces are unique in their requirement for rapid DC responses during acute inflammation. We hypothesize that the role of the DC influx during acute inflammation may be surveillance for opportunistic viruses, and that this covert protective mechanism is operative at a restricted number of mucosal tissue sites.
Implications of applying widely accepted cholesterol screening and management guidelines to a British adult population: cross sectional study of cardiovascular disease and risk factors
Authors: N. Unwin, R. Thomson, A. M. O'Byrne, M. Laker, H. Armstrong
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective:</b> To compare the implications of four widely used cholesterol screening and treatment guidelines by applying them to a population in the United Kingdom. <b>Design:</b> Guidelines were applied to population based data from a cross sectional study of cardiovascular disease and risk factors. <b>Setting:</b> Newcastle upon Tyne,United Kingdom. <b>Subjects:</b> General population sample (predominantly of European origin) of 322&nbsp;men and 319&nbsp;women aged 25-64 years. <b>Main outcome measures:</b> Proportions recommended for screening and treatment. <b>Methods:</b>Criteria from the British Hyperlipidaemia Association, the <i>British Drugs and Therapeutics Bulletin</i> (which used the Sheffield table), the European Atherosclerosis Society, and the American national cholesterol education programme were applied to the population. <b>Results:</b> Proportions recommended for treatment varied appreciably. Based on the <i>British Drugs and Therapeutics Bulletin</i> guidelines, treatment was recommended for 5.3% (95% confidence interval 2.9% to 7.7%) of men and 3.3% (1.5% to 5.3%) of women, while equivalent respective values were 4.6&nbsp;(2.3&nbsp;to 6.9) and 2.8 (1.0&nbsp;to 4.6) for the British Hyperlipidaemia Association, 23% (18.4% to 27.6%) and 10.6% (7.3% to 14.0%) for the European Atherosclerosis Society, and 37.2% (31.9% to 42.5%) and 22.2% (17.6% to 26.8%) for the national cholesterol education programme. Only the British Hyperlipidaemia Association and <i>Drugs and Therapeutics Bulletin</i> guidelines recommend selective screening. Applying British Hyperlipidaemia Association guidelines,from 7.1% (4.3% to 9.9%) of men in level one to 56.7% (51.3% to 62.1%) of men in level three, and from 4.4% (2.1% to 6.7%) of women in level one to 54.4% (48.9% to 59.9%) of women in level three would have been recommended for cholesterol screening. Had the <i>Drugs andTherapeutics Bulletin</i> guidelines been applied, 22.2% (16.5% to27.9%) of men and 12.2% (8.6% to 15.8%) of women would have been screened. <b>Conclusions:</b> Without evidence based guidelines, there are problems of variation. A consistent approach needs to be developed and agreed across the United Kingdom.
Sporadic Urban Leptospirosis
Authors: Joseph M. Vinetz
Journal: Annals of Internal Medicine (1996)

Background: Surprisingly, many inner-city residents have antibodies to Leptospira interrogans. The manner in which these persons acquire this organism in the absence of recognized occupational, recreational, or epidemic risk factors is not known. Objective: To study the epidemiology of patients with leptospirosis who acquired L. interrogans in inner-city Baltimore, Maryland. Design: Epidemiologic investigation. Setting: Inner-city university hospital. Patients: Three inner-city residents who developed leptospirosis. Measurements: Trapping rats in alleys where the patients may have acquired L. interrogans; polymerase chain reaction (PCR) analysis of patient serum and cerebrospinal fluid specimens and rat tissues to determine the presence of leptospiral DNA; and serologic testing of serum from patients and rats by microagglutination assay to confirm L. interrogans infection. Results: Three patients developed leptospirosis after probable percutaneous exposure to rat (Rattus norvegicus) urine in Baltimore alleys. A PCR assay detected L. interrogans DNA in samples of body fluid obtained from the first two patients at presentation (one in cerebrospinal fluid, the other in serum). Results of PCR done on serum drawn from the third patient after antibiotic therapy began were negative. A microagglutination test showed that all patients had high levels of antibodies to the L. interrogans serogroup lcterohaemorrhagiae. In 19 of 21 rats that were trapped in the alleys where the patients had sustained lacerations before illness developed, kidney or brain tissues were positive by PCR for the presence of L. interrogans. Conclusions: A population was discovered to be at risk for acquiring L. interrogans: urban residents who are sporadically exposed to rat urine in the inner city. Inner-city rats often carry L. interrogans. Polymerase chain reaction can quickly establish the diagnosis of leptospirosis and is useful for epidemiologic study. An endemic substrate for the transmission of the organism is present in inner-city Baltimore. Leptospirosis may become increasingly recognized in deteriorating inner cities in which rat populations are expanding.
UK economy can withstand a doubling in health spending in next 50 years, conference hears
Authors: N. Hawkes
Journal: BMJ (2012)

While the NHS is likely to face severe funding pressures in the next 50 years and absorb a growing proportion of public spending, the financial position looking forward is not hopeless, a meeting at the King’s Fund in London on 18 July was told.

John Appleby, chief economist at the fund, said that it was possible that by 2059 health spending would represent 16% of GDP, double the present 8%. “It doesn’t seem to me that will break the bank,” he said. The precise outcome was sensitive to many assumptions and would depend on political decisions and choices, but the US already spends more than 16% of its GDP on health.

The discussion was framed around the Office for Budget Responsibility’s Fiscal Sustainability Report.1 The office’s central estimate was that by 2060-1 NHS spending would …
Treating lung cancer in the NHS market
Authors: H. Pickles
Journal: BMJ (1997)

The improvement of cancer services is a high priority with the profession and the government. There now seems to be an opportunity to bring survival rates up to the best of those outside Britain and to provide the type of patient sensitive service for which lobby groups are clamouring. How will this affect the treatment of lung cancer?

Throughout Britain purchasers are working with clinicians to define cancer units and centres and outlining the types of services needed. If five year survival is the key outcome measure recognition of potentially operable cases is a top priority in lung cancer. But for the majority of people with an inoperable disease proper emphasis is needed on quality of life, the involvement of those with sensitive communication skills, the cautious use of specific treatments, and the palliative approach. Improvements are needed in the present services and these improvements will cost more.

Since the report from the Expert Advisory Group on Cancer was not accompanied by any promise of new or earmarked funding, the …
SELF-REGULATION OF GROWTH IN THREE DIMENSIONS
Authors: Judah Folkman, Mark Hochberg
Journal: The Journal of Experimental Medicine (1973)

Multi-cell spheroids were grown in soft agar. When each spheroid was cultured in a large volume of medium, frequently renewed, all spheroids eventually reached a dormant phase at a diameter of approximately 3-4 mm and a population of approximately 10(6) cells. In the dormant spheroid, newly generated cells at the periphery balanced those lost by necrosis in the center. We propose that this dormant phase is due to a gradual reduction in the ratio of surface area to volume: a size is achieved beyond which there is insufficient surface area for the spheroid to eliminate catabolites and absorb nutrients. Thus, in the face of unlimited space and of new medium, three-dimensional cell populations become self-regulating. This phenomenon contrasts with standard tissue culture in which cell populations, living on a flat plane in two dimensions, will not stop growing in the face of unlimited space and new medium because the ratio of surface area to volume remains constant. These experiments provide a mechanism for our observations in vivo: before vascularization, solid tumors live by simple diffusion as three-dimensional spheroids or ellipsoids. They become dormant at a diameter of only a few millimeters; once vascularized, they are released from this dormant phase and begin exponential growth. Thus, tumor dormancy resulting from absence of angiogenesis in vivo, may operate by the same mechanism responsible for dormancy of spheroids in vitro.
Interpreting Cost Analyses of Clinical Interventions
Authors: E. Andrew Balas
Journal: JAMA (1998)

Objective.—In the present era of cost containment, physicians need reliable data about specific interventions. The objectives of this study were to assist practitioners in interpretation of economic analyses and estimation of their own costs of implementing recommended interventions.Data Sources.—MEDLINE search from 1966 through 1995 using the text words cost or expense and medical subject heading (MeSH) terms costs and cost analysis, cost control, cost of illness, cost savings, or cost-benefit analysis.Study Selection.—The 4 eligibility criteria were clinical trial with random assignment; health care quality improvement intervention tested; effects measured on the process or outcome of care; and cost calculation mentioned in the report.Data Extraction.—After independent abstraction and after consensus development, financial data were entered into a costing protocol to determine which costs related to the intervention were provided.Data Synthesis.—Of 181 articles, 97 (53.6%) included actual numbers on the costs of the intervention. Of 97 articles analyzed, the most frequently reported cost figures were in the category of operating expenses (direct cost, 61.9%; labor, 42.3%; and supplies, 32.0%). General overhead was not presented in 91 (93.8%) of the 97 studies. Only 14 (14.4%) of the 97 studies mentioned start-up costs. The text word $ in the abstract and the most useful MeSH index term of cost-benefit analysis appeared with nearly equal frequency in the articles that included actual cost data (37.1% vs 35.1%). Two thirds of articles indexed with the MeSH term cost control did not include cost figures.Conclusions.—Statements regarding cost without substantiating data are made habitually in reports of clinical trials. In clinical trial reports presenting data on expenditures, start-up costs and general overhead are frequently disregarded. Practitioners can detect missing information by placing cost data in a standardized protocol. The costing protocol of this study can help bridge care delivery and economic analyses.
Cytotoxic Conjugates Containing Translational Inhibitory Proteins
Authors: S Ramakrishnan, D Fryxell, D Mohanraj, M Olson, B Li
Journal: The Annual Review of Pharmacology and Toxicology (1992)

Cytotoxic drugs administered during conventional chemotherapy are taken up by sensitive nontarget organs besides the tumor cells and this often leads to unwanted side effects . These problems have initiated studies during the past decade to develop novel methods in which the therapeutic reagents could be directed to specific cell populations to widen the therapeutic window. The concept of targeting drugs was proposed nearly a hundred years ago by Paul Erlich, who envisioned the possibility of transporting toxic substances to tumor cells by carrier molecules (magic bullets). This novel approach became a reality with the advent of tumor selective monoclonal antibodies (Mabs) produced by somatic cell hybridization. Both cytotoxic drugs and toxin polypeptides have been chemically linked to Mabs. During the past decade various molecules have been produced and tested in a number of model systems (reviewed in 1-10). The range of targets includes (a) ex vivo treatment of bone marrow grafts to remove contaminating leukemic cells and alloreactive T cells , (b) administration of conjugates to inhibit tumor growth