tbuckley/cabot-search huggingface dataset:
Statistical Issues in Toxicokinetic Modeling: A Bayesian Perspective
Authors: Pascale Bernillon, Frédéric Y Bois
Journal: Environmental Health Perspectives (2000)

Determining the relationship between an exposure and the resulting target tissue dose is a critical issue encountered in quantitative risk assessment (QRA). Classical or physiologically based toxicokinetic (PBTK) models can be useful in performing that task. Interest in using these models to improve extrapolations between species, routes, and exposure levels in QRA has therefore grown considerably in recent years. In parallel, PBTK models have become increasingly sophisticated. However, development of a strong statistical foundation to support PBTK model calibration and use has received little attention. There is a critical need for methods that address the uncertainties inherent in toxicokinetic data and the variability in the human populations for which risk predictions are made and to take advantage of a priori information on parameters during the calibration process. Natural solutions to these problems can be found in a Bayesian statistical framework with the help of computational techniques such as Markov chain Monte Carlo methods. Within such a framework, we have developed an approach to toxicokinetic modeling that can be applied to heterogeneous human or animal populations. This approach also expands the possibilities for uncertainty analysis. We present a review of these efforts and other developments in these areas. Appropriate statistical treatment of uncertainty and variability within the modeling process will increase confidence in model results and ultimately contribute to an improved scientific basis for the estimation of occupational and environmental health risks.
Photosensitizer-conjugated silica-coated gold nanoclusters for fluorescence imaging-guided photodynamic therapy
Authors: Peng Huang, Jing Lin, Shouju Wang, Zhijun Zhou, Zhiming Li, Zhe Wang, Chunlei Zhang, Xuyi Yue, Gang Niu, Min Yang, Daxiang Cui, Xiaoyuan Chen
Journal: Biomaterials (2013)
Tissue Typing, Antilymphocyte Globulin, and Prophylactic Graft Irradiation in Cadaver Kidney Transplantation
Authors: J. A. Myburgh, B. Goldberg, A. M. Meyers, P. J. P. Van Blerk, L. Gecelter, C. J. Mieny, S. Browde, M. Shapiro, A. Zoutendyk, C. G. Anderson
Journal: BMJ (1970)

In a series of 27 recipients of cadaver kidney grafts, 26 were at the time of writing alive, 3 to 25 months after transplantation, and 25 patients were alive with functioning first grafts. The one-year patient survival in 18 patients was 94% and the one-year graft survival was 89%. There was no beneficial correlation between tissue matching and the frequency of major early rejection episodes or graft function 12 or more months after transplantation. Antilymphocyte globulin administration was associated with a lower incidence of early rejection episodes, but this was not statistically significant. A combination of prophylactic graft irradiation and antilymphocyte globulin administration for at least the first two weeks was associated with a significantly reduced frequency of major early rejection episodes and appreciably better graft function at 12 months. This effect could not be ascribed to better tissue matching.
South Africa's Health: Restructuring South Africa's health care: dilemmas for planners
Authors: R. Kale
Journal: BMJ (1995)

Restructuring South Africa's health care involves providing care to the majority who have so far been deprived of it without destroying the excellent tertiary health care facilities and the high standards of academic medicine that exist in the country. South Africa spends 6.4% of its gross domestic product on health, which is more than the goal—5% by the year 2000—set by the World Health Organisation. But 46% of this amount is spent on the private sector, which serves 19% of the population, as was explained by Dr Nkosazana Zuma, South Africa's health minister, in her health budget speech to the parliament on 20 October 1994. Moreover, 75% of the health budget, which was 14 billion Rand for 1994-5, is spent on hospitals and academic institutions. In effect, the amount spent on health care for most of the population is much less than the 5% recommended by the World Health Organisation.



This is the last in a series of articles reporting on health care in South Africa



Dr Zuma said in her speech that the cornerstone on which the future health care system will be built would be a district health system offering a package of primary health care provided by a district health authority. She clarified that primary health care was not synonymous with preventive health care and that the proposed system would achieve a balance between promotion, prevention, rehabilitation, and curative services. She also outlined definite goals that the government was committed to achieve: these focused on the control of infectious diseases, an obvious priority for any developing country (box).

Finding the money for primary health care is difficult. Much of it will have to come from the academic institutions. Dr Zuma said that the government and the deans of the academic institutions had agreed to cut their expenditure …
Pfizer pays record fine for off-label promotion of four drugs
Authors: J. H. Tanne
Journal: BMJ (2009)

Pfizer, the world’s largest drug company, has agreed to pay $2.3bn (£1.4bn; €1.6bn) to settle charges of fraud and civil and criminal liability over its promotion of off-label use of four drugs.

The US Department of Justice said it was the largest healthcare fraud settlement in the department’s history and the largest criminal fine ever.

The New York Times noted that $2.3bn amounted to less than three weeks of Pfizer sales (www.nytimes.com, 3 Sep, “Pfizer to pay $2.3 billion to settle inquiry over marketing”).

Unlike in previous settlements by drug companies, the announcement of the settlement was made at a Washington press conference by …
THE ROLE OF THE MYOCARDIUM IN PERICARDITIS.
Authors: ALFRED STENGEL
Journal: JAMA (1901)

Pericarditis is a condition of danger in any one or all of the following ways: 1, as a focus of infection; 2, as a cause of mechanical or reflex disturbance of the heart action; 3, as a starting point for a spreading inflammatory lesion. As a focus of infection its danger is greater than is that of pleurisy or possibly even of peritonitis. The exudations of the pericardium are habitually more hemorrhagic or purulent than are those of the pleura in similar or the same infection and the clinical indications of general infection are also significant of a more virulent process. The mechanical dangers are usually of little consequence, and, as has been found in the case of endocarditis, wider knowledge gives evidence that the circulatory disturbances of pericarditis are occasioned by changes in the heart muscle to a much greater extent than by mechanical or reflex disorders of the
"Safety of medical electrical equipment".
Authors: D E Oliver
Journal: BMJ (1979)

although haemolysis is to be expected if copper is indeed involved in the aetiology of Indian childhood cirrhosis, its presence has yet to be adequately documented and we are grateful to Professor Ozsoylu for the opportunity of discussing this point.Neither caeruloplasmin nor reduced glutathione was measured in our patient, although the former (as copper oxidase) was elevated in the patients of Kapoor et al.2
ADDRESS OF THE CHAIRMAN OF THE SECTIO N ON SURGERY AND ANATOMY—READ TO THE MEETING OF THE AMERICAN MEDICAL ASSOCIATION, JUNE, 1883.
Authors: W. F. PECK
Journal: JAMA (1883)

In performing the duties of Chairman of the Surgical Section, it is not deemed practicable to encompass all that the organic law of the Association may contemplate. For, in reporting upon the progress made in surgical science, it is recognized that many theories are, at present, announced as facts, which, when experience and demonstration shall have thoroughly tested them, may be eliminated, to perhaps reappear when the cycle of professional experience again completes its revolution. The greatest progress has been made in operative surgery, although other departments have been constantly receiving new light and attaining results that add to our already extensive accumulations. It is not claimed that large numbers of new operations have been originated and performed, but it is evident, that the better understanding of pathological conditions, has stimulated surgeons to establish a standard for operations hitherto ventured upon in rare and extreme instances only. In pathology the
Abstract 5206: Systems biology identification of processes/pathways facilitating the development of high-grade serous ovarian cancer
Authors: Curt Balch, Rohit Jadhav, Fang Fang, Jay Pilrose, Meng Li, Changyu Shen, Lang Li, Tim H-M Huang, Kenneth P. Nephew
Journal: Cancer Research (2012)

Abstract Previously, based on well-known stem cell phenotypes (sphere formation, potent tumorigenicity, embryonic gene expression, and chemoresistance), we used patient tumors to isolate high-grade serous (HGS) ovarian cancer-initiating cells (OCICs) that express the cell surface markers CD44 (a hyaluronate receptor) and CD117 (c-kit) (Zhang et al., 2008, Cancer Res 68:4311). Here, to identify biological pathways that underlie HGS ovarian tumorigenesis, including the specific role of OCICs in that process, we performed integrated analyses of global gene expression, DNA copy number, and DNA methylation patterns. To that end, OCICs and “bulk” (i.e., disaggregated but unsorted) tumor cells were compared to primary human normal ovarian surface epithelial (nOSE) cells that, along with fallopian tube epithelial (FTE) cells, represent hypothesized cells-of-origin for HGS pelvic cancers. Principle components analysis and unsupervised hierarchical clustering revealed distinct DNA methylation and gene expression profiles for replicate (n=3) samples of each cell type (i.e., OCIC, bulk tumor, and nOSE). Gene ontology and additional unsupervised analyses of “gene expression signatures” corresponding to the epithelial-to-mesenchymal transition (82 of 159 signature genes), TGF-beta (47 of 86 genes), and Wnt (75 of 151 genes) pathways demonstrated well-defined segregation of the three cell types, with mesenchymal and Wnt signaling hierarchies being nOSE &amp;gt; OCIC &amp;gt; bulk tumor cells. To examine early events in HGS ovarian tumorigenesis, previously published (Tone et al., 2008, Clin Cancer Res 14:4067) gene expression datasets were employed to show that nOSE, OCIC, and bulk ovarian tumor cell transcriptomes distinctly segregate from normal (FTE) and malignant fallopian epithelial transcriptomes. Interestingly, the largest divergence was between the nOSE and FTE gene expression profiles. Finally, DNA methylation and gene expression patterns were integrated, implicating specific networks/circuits in ovarian carcinogenesis. Taken together, these results support a mesenchymal-to-epithelial transition during ovarian tumorigenesis, reveal legitimate therapeutic targets (at the pathway level), and raise uncertainty that surface epithelial cells of the fallopian tube and ovary are reciprocal cells-of-origin for HGS pelvic carcinomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5206. doi:1538-7445.AM2012-5206
Genetic Diagnosis With the Denaturing Gradient Gel Electrophoresis Technique Improves Diagnostic Precision in Familial Hypercholesterolemia
Authors: Henrik Nissen, Annebirthe Bo Hansen, Per Guldberg, Niels Erik Petersen, Mogens Lytken Larsen, Torben Haghfelt, Karsten Kristiansen, Mogens Hørder
Journal: Circulation (1995)

Background Familial hypercholesterolemia (FH) is an autosomal dominant inherited disorder of lipid metabolism caused by mutations in the LDL receptor gene. FH is characterized clinically by elevated LDL cholesterol level and premature coronary disease. Diagnosing FH on clinical grounds may be difficult, and previous genetic methods are too cumbersome for routine use except in the few populations with FH-founder mutations. A simple mutation screening technique based on denaturing gradient gel electrophoresis (DGGE) has been highly useful in detecting mutations in other genes, and in the present study we evaluated the diagnostic potential of this method for the diagnosis of FH. Methods and Results Conditions for screening exon 3 of the LDL receptor gene using the DGGE technique were established and 14 Danish FH families were examined. An index patient from 1 family had an abnormal DGGE pattern; consequently, an examination of exon 3 of the LDL receptor gene in 21 members of this patient’s family was done. The DGGE pattern was seen only in patients with a definite clinical diagnosis of FH. Subsequent sequencing of exon 3 of the LDL receptor gene in these individuals revealed the presence of the French-Canadian type 4 Trp 66 -Gly mutation. However, in 4 of 11 cases in which a definite clinical diagnosis of FH had been made, the inheritance of the French-Canadian type 4 mutation could be rejected on the basis of genetic analysis. Conclusions Introduction of a simple genetic analysis based on DGGE may improve the precision of diagnosis in FH families.
Moses Maimonides' Aphorisms Regarding Analysis of Urine
Authors: FRED ROSNER
Journal: Annals of Internal Medicine (1969)

The Literature of Medicine1 July 1969Moses Maimonides' Aphorisms Regarding Analysis of UrineFRED ROSNER, M.D., SUSSMAN MUNTNER, M.D.FRED ROSNER, M.D.Search for more papers by this author, SUSSMAN MUNTNER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-71-1-217 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA rich collection of approximately 1,500 aphorisms, Medical Aphorisms of Moses Maimonides, has never been published in a modern western language. Only Hebrew and Latin editions are available in addition to Arabic and Hebrew manuscripts. The aphorisms are presented in 25 chapters or treatises based mainly on the works of Galen. Each treatise deals with a different subspecialty in medicine. The fifth treatise contains aphorisms with lessons pertaining to the urine and its examination. This treatise, which is presented below in its entirety and translated into English, is based mainly on Paris Hebrew Mss #1173.Maimonides emphasizes the necessity and... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Brooklyn, New York Jerusalem, IsraelFrom the Division of Hematology, Department of Medicine, Maimonides Medical Center, Brooklyn, N. Y.; and the History of Medicine Section, Hebrew University, Jerusalem, Israel.Requests for reprints should be addressed to Fred Rosner, M.D., 4802 Tenth Ave., Brooklyn, N. Y. 11219 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByRedacted reflections on the kidney from the Sumerians to Moses Maimonides: lessons for 21st-century clinicians and researchersPsychological Science and Religious Education in a Devout University: The Case of Pain Overlap Theory and the TalmudMaximising medicine through aphorismsDIAGNOSTIC PROCEDURES FOR THE UROGENITAL SYSTEMMoses Maimonides and Diseases of the Chest 1 July 1969Volume 71, Issue 1Page: 217-220KeywordsHematology and oncologyHistory of medicineSub-specialty careUrine Issue Published: 1 July 1969 PDF DownloadLoading ...
Safer use of traditional remedies
Authors: J. Howell, P. James, S. Ramaiah
Journal: BMJ (1994)

Don't generalise about traditional remedies

EDITOR,--David J Atherton's article on traditional remedies makes repeated generalisations about these remedies, their practitioners, and patients.1 He states that “when people from less developed countries emigrate they continue to seek medical advice from traditional practitioners” and that “large amounts of traditional medicine are imported into Britain,” but he …
Nasal nitric oxide, the guardian of paranasal sinuses, is paradoxically increased by high doses of intravenous glucocorticoids
Authors: B. Degano, L. Têtu, E. Serrano, A. Didier, J. ‐F. Arnal
Journal: Allergy (2005)

Background: High concentrations of nitric oxide (NO) originating from a type‐2 nitric oxide synthase (NOS2) located within the paranasal sinuses are measured in nasal air in man. NO is believed to play a central role in nonspecific defense of paranasal sinuses. Glucocorticoids (GCs), a therapeutic often used for a wide range of diseases, is known to strongly downregulate NOS2. Aims of the study: To investigate the effect of very high intravenous doses of GCs on nasal NO in man. Methods: Nasal NO was measured in 15 patients without any history of allergy or chronic airway disorder who were treated for 3 days with a daily dose of 1000 mg methylprednisolone for an exacerbation of multiple sclerosis. Nasal NO was also measured in 30 matched control subjects. Results: In control subjects, the maximal value of nasal NO [mean (SE)] was 233 (8) part per billion (ppb), and did not differ from patients with multiple sclerosis [maximum value: 219 (13) ppb; left nostril: 214 (12) ppb; right nostril: 215 (12) ppb]. After GCs treatment, nasal NO increased in patients [maximum value: 250 (13) ppb ( P &lt; 0.0001); left nostril: 249 (12) ppb ( P &lt; 0.0001); right nostril: 244 (13) ppb ( P &lt; 0.0001)]. Conclusions: We conclude that GCs do not decrease but even increase nasal NO.
P390The modulation of cardiac muscle Ca2+-sensitivity by PKA phosphorylation can be uncoupled by EMD57033 and re-coupled by EGCG
Authors: A E Messer, M Papadaki, P Vikhorev, S B Marston
Journal: Cardiovascular Research (2014)

Hypertrophic cardiomyopathy (HCM)-causing mutations in sarcomeric proteins have been proposed to increase myofilament Ca2+-sensitivity. Dilated cardiomyopathy (DCM)-causing mutations may decrease myofilament Ca2+-sensitivity but recently some mutations have been found that show an unchanged Ca2+-sensitivity whilst some even showed an increase in Ca2+-sensitivity. However, a common feature of most DCM and several HCM-causing mutations is the uncoupling of the phosphorylation of Ser 22 and 23 of cardiac troponin I from the change in Ca2+-sensitivity. We studied the effects of small molecules that bind to troponin C to modulate Ca2+-sensitivity using single thin filaments containing human cardiac troponin moving on skeletal myosin in the in vitro motility assay. EMD57033 is a Ca2+-sensitiser and causes a dose dependent increase in Ca2+-sensitivity (optimum at 30μM). EMD57033 increased Ca2+-sensitivity in wild-type, in DCM mutations (TPM1 E40K and E54K) and in troponin from myectomy samples (from patients with hypertrophic obstructive cardiomyopathy). In addition, in wild-type, Ca2+-sensitivity becomes independent of troponin I phosphorylation, this uncoupling by EMD57033 mimics the effect of HCM mutations in this system. Epigallocatechin 3-Gallate (EGCG) is a Ca2+-desensitiser, 100μM reduces Ca2+-sensitivity of native human thin filaments by 1.5-fold. EGCG also decreased Ca2+-sensitivity in thin filaments with DCM mutations (TPM1 E40K and E54K) HCM mutations (TNNT2 K280N) and in troponin from myectomy samples. Uniquely, EGCG also restored the phosphorylation dependence of Ca2+-sensitivity to thin filaments containing tropomyosin DCM mutations or myectomy samples where the Ca2+-sensitivity is normally uncoupled. For thin filaments with the tropomyosin E40K mutation, Ca2+-sensitivity of phosphorylated (P) and unphosphorylated (unP) troponin is the same (EC50 0.261μM and 0.252μM respectively) whilst in the presence of EGCG, Ca2+-sensitivity dependence on phosphorylation is restored (EC50 P = 0.324μM, unP = 0.104μM). The same pattern was observed with four other DCM mutations, two HCM mutations and also in troponin from myectomy samples that are usually uncoupled. The Ca2+-sensitivity and recoupling effects were also seen in contracting myofibrils. Propranolol treatment dephosphorylates myofibrils with a corresponding increase in Ca2+-sensitivity. However, with the ACTC DCM mutation E361G, there was no difference in Ca2+-sensitivity. When EGCG was added, the Ca2+-sensitivity difference was restored. Thus, EGCG potentially can reverse the effect of mutations that cause DCM.
Platelet factor 4 binds to bacteria, inducing antibodies cross-reacting with the major antigen in heparin-induced thrombocytopenia
Authors: Krystin Krauel, Christian Pötschke, Claudia Weber, Wolfram Kessler, Birgitt Fürll, Till Ittermann, Stefan Maier, Sven Hammerschmidt, Barbara M. Bröker, Andreas Greinacher
Journal: Blood (2010)
Laparoscopic Liver Resection for Hepatocellular Carcinoma: Korean Experiences
Authors: Ho-Seong Han, Yoo-Seok Yoon, Jai Young Cho, Dae Wook Hwang
Journal: Liver Cancer (2013)

The development of laparoscopic liver resection (LLR) has been slow due to technical difficulties. Therefore, LLR has been limited to easily accessible lesions. Recently, this procedure has been well applied to hepatocellular carcinoma. However, until now, the indications for LLR have been tumors in the peripheral portion of the anterolateral segments of the liver (segments II, III, V and VI and the inferior part of IV according to the classification of Couinaud). Due to the growing interest in LLR, there have been many attempts to apply this technique in difficult locations. The lesions in the posterior or superior part of the liver (segments I, VII, VIII and the superior part of IV), which are considered to be poor indications for LLR, have been reported to be successfully operated on by laparoscopic surgery. Accordingly, this laparoscopic approach has become similar to open surgery in many ways. One of the major advancements of LLR is anatomic liver resection including major and minor resection. Laparoscopic mono- and bisegmentectomies have also become possible with growing experience. There are a variety of monosegmentectomies and bisegmentectomies. The common representatives of bisegmentectomies are left lateral sectionectomy, right anterior sectionectomy and right posterior sectionectomy. The common operative types of monosegmentectomies are S4, S5, and S6 monosegmentectomies, etc. Central bi-sectionectomy will also be discussed. The Glissonian approach has been useful for these types of anatomic liver resection. The difficulty of controlling hemorrhage has been overcome by performing meticulous surgical techniques with newly developed instruments, and intraoperative sonography has been used to locate the lesions and guide the resection plane even for deep-seated or invisible lesions. Further accumulation of experience and technical refinements will make theses challenging procedures more reproducible and safer.
alpha1-Antitrypsin deficiency panniculitis (phenotype PiZZ) precipitated postpartum and successfully treated with dapsone
Authors: P.D. Yesudian, C.M. Dobson, N.J. Wilson
Journal: British Journal of Dermatology (2004)

Journal Article α1‐Antitrypsin deficiency panniculitis (phenotype PiZZ) precipitated postpartum and successfully treated with dapsone Get access P.D. Yesudian, P.D. Yesudian Department of Dermatology, Royal Liverpool and Broadgreen University Hospitals, Thomas Lane, Liverpool L14 3LB, U.K. E‐mail: pdyesudian@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar C.M. Dobson, C.M. Dobson Department of Dermatology, Royal Liverpool and Broadgreen University Hospitals, Thomas Lane, Liverpool L14 3LB, U.K. E‐mail: pdyesudian@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar N.J. Wilson N.J. Wilson Department of Dermatology, Royal Liverpool and Broadgreen University Hospitals, Thomas Lane, Liverpool L14 3LB, U.K. E‐mail: pdyesudian@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 150, Issue 6, 1 June 2004, Pages 1222–1223, https://doi.org/10.1111/j.1365-2133.2004.05991.x Published: 01 June 2004