tbuckley/cabot-search huggingface dataset:
Aspirin, Acetaminophen, and Bleeding
Authors: Emily E. Czapek
Journal: JAMA (1976)

The relationship between aspirin and increased bleeding in hemophiliacs was described many years ago.<sup>1</sup>This was later found to be secondary to interference with platelet function. It has since become apparent that many drugs other than aspirin, including antihistamines, thorazine derivatives, and probably guaifenesin (glyceryl guiacolate), interfere with platelet function.<sup>2</sup>As such, these compounds render anyone with a bleeding diathesis more likely to have problems with hemostasis. Although the safest measure from the standpoint of bleeding is to avoid all such medication in patients with bleeding problems, this often becomes impractical. For example, an antipyretic is frequently needed in the pediatric age group, where high fevers may predispose to febrile convulsions. Antihistamines and guaifenesin are contained in many "overthe-counter" remedies, and both of these, as well as thorazine derivatives, are commonly prescribed. Therefore, suitable alternatives to such medications have been sought. Acetaminophen has been used with increasing frequency
Recurrent Urinary Tract Infections in Men
Authors: JAMES W. SMITH
Journal: Annals of Internal Medicine (1979)

All men with recurrent urinary tract infections entered into a study had a positive antibody-coated bacteria test, and 52% had evidence for prostate infection. Escherichia coli infection was present in 74% and urinary tract symptoms in 57% of those randomized. Thirty-eight patients were randomized in a double-blind clinical trial to receive either 10 d of treatment with trimethoprim/sulfamethoxazole or a 12-week course of the drug. The cure rate in patients receiving 12 weeks of therapy (nine of 15) was higher than that in patients receiving a single 10-d course (three of 15); difference was marginally significant (P = 0.06). Recurrences were usually with the same organism, and most (78%) occurred within 4 weeks of discontinuing therapy. This study indicates that a standard 10-d course of therapy usually fails to cure men with recurrent urinary tract infections with a positive antibody-coated bacteria test.
Safeguards needed now to prevent unethical genetic selection in future
Authors: Sally Hargreaves
Journal: BMJ (2002)

Embryos should not be selected for behavioural traits such as sexual orientation, antisocial behaviour, and intelligence on the basis of genetic information, according to a report out this week from the Nuffield Council on Bioethics.

Although the report's authors acknowledge that research into links between genes and behaviour is in its early stages, they stress the need to examine ethical and social issues raised by potential developments now, in order to put safeguards in place for the future. “This is a potentially explosive area,” said Professor Bob Hepple, of Clare College, …
Observer Agreement and Variability in Measuring Gastric Mucosal Blood Flow by Laser Doppler Flowmetry in Humans
Authors: T. Iwao, A. Toyonaga, M. Ikegami, K. Oho, M. Sumino, M. Sakaki, H. Harada, K. Tanikawa
Journal: Endoscopy (1993)

We evaluated the reliability (i.e. reproducibility and variability) in measuring regional gastric mucosal blood flow by laser Doppler flowmetry in a total of 32 subjects (12 normal subjects and 20 patients with cirrhosis). The measurements were performed in quadruplicate within 10 min by observer A (A1, A2) and B (B1, B2) using blind techniques. The intraclass correlation coefficient (Ri) was used to assess observer agreement. Overall, the level of intra- (Ri, 0.87 for A1 vs. A2 and 0.87 for B1 vs. B2) and interobserver agreement (0.86 for A vs. B) was excellent. In contrast, there was a higher observer variability assessed by coefficient of variation. Overall, the mean value of coefficient of variation was 12% (max. 35%) for A1 vs. A2, 12% (max. 35%) for B1 vs. B2, and 13% (max. 33%) for A vs. B. These results suggest that laser Doppler flowmetry, although the reproducibility may be clinically acceptable, seems to still be a subjective method for quantitation of gastric mucosal blood flow in humans. Therefore, studies using this method can only be acceptable when the changes that investigators intend to measure are significantly higher than the variability.
The road to reform
Authors: Josep Figueras, Nata Menabde, Reinhard Busse
Journal: BMJ (2005)

The political transition in central and eastern Europe has not spared the region's health systems. Almost everywhere governments have abandoned the Soviet model of health care.1 Initially, this model achieved much at first in ensuring universal access to health services and tackling common infectious diseases. Yet, by the 1970s, the cracks were appearing, and now many people in the region are dying from causes that should be preventable with timely and effective health care.2

Health systems in the region have had to respond to a variety of economic and political pressures as well as to the populations' longstanding healthcare problems. Many services were of low quality and were characterised by poorly motivated health professionals, poor responsiveness to citizens' needs, and outdated clinical practices.1

Although the range and depth of challenges has varied between countries, some are common to many of them. One of the greatest challenges has been the quest for sustainable financing. Most countries in the region were quick to reject the former model of financing from general government revenues, owing to general mistrust in governments and to the desire to follow what were perceived as superior models used in neighbouring countries.3 Some form of social health insurance, based on contributions from individuals according to their earnings, seemed to offer a solution.4
CONGENITAL AND HEREDITARY GOITRE.
Authors: CHAS. W. ROOK
Journal: JAMA (1894)

<i>Case 1</i>.—Frederick, second child of Mr. and Mrs.F.B., was delivered by me, Aug. 22, 1893. Position of child in utero, L. O. A. Because of maternal exhaustion, the labor was terminated instrumentally. For a few hours, the child was cyanosed and respiration stridulous. The right lobe of the thyroid gland was of the size of a hen's egg, while the left was one-third less in size. Although the goitrous tumors have gradually decreased in size, the child involuntarily keeps its head extended that respiration may be more easily performed. The mother, aged 23, and her sister aged 26 years, have been goitrous since the ages of 12 and 17 years respectively. The notes of Cases 2, 3 and 4, the latter being a case of hereditary goitre, were kindly furnished me by my friend, Dr. E. B. Montgomery, of Quincy, Ill. <i>Case 2</i>.—Mrs. W. H. M., aged 29 years, was
Future research directions to study genetic damage in germ cells and estimate genetic risk.
Authors: I D Adler
Journal: Environmental Health Perspectives (1996)

The late Frits Sobels developed a parallelogram model to estimate genetic risk to humans based on experimental data in somatic cells (peripheral blood) of exposed animals and humans and on data from progeny studies of exposed animals (mice). Recently, an extension to the original parallelogram model was proposed to bridge the gap of extrapolation between rodent and human germ cells by studying sperm samples. The comparison in the parallelogram of rodent/human sperm data with data from rodent progeny tests to derive at an estimate of human progeny at risk is more promising. Therefore, data on all possible end points, DNA adducts, mutations, chromosomal aberrations, and aneuploidy, should be obtained in sperm of exposed rodents and humans. The technology from somatic cell studies is available or adaptable to sperm studies. Sperm samples lend themselves to automated analyses because they are a homogeneous cell population. By flow cytometry or image analysis, large cell samples can be studied per individual. Animal experiments could be conducted in the actual range of chronic human exposure to low doses. The acceptability of extrapolation from the high acute doses so far used in animal experiments to low chronic doses of human exposure could be assessed. Proof could be obtained in human germ cells for the assumption that data from animal experiments can be extrapolated to humans. Data from transgenic rodent systems may play an important role in the extension of the parallelogram approach to genetic risk estimation by providing a link between cancer and genetic risk estimates.
Cephalosporin-induced alteration in hepatic glutathione redox state. A potential mechanism for inhibition of hepatic reduction of vitamin K1,2,3-epoxide in the rat.
Authors: M C Mitchell, A Mallat, J J Lipsky
Journal: Journal of Clinical Investigation (1990)

Hypoprothrombinemia is a serious adverse effect of antimicrobial therapy that occurs after administration of some second- and third-generation cephalosporins which contain the methyltetrazole-thiol (MTT) group. Previous studies have shown that in vitro MTT directly inhibits microsomal gamma-carboxylation of a synthetic pentapeptide. Since MTT is a thiocarbamide, a type of compound that can increase oxidation of glutathione, the present studies were carried out to determine whether alterations in hepatic glutathione redox state might interfere with vitamin K metabolism. Dose-related increases in biliary efflux and hepatic concentration of oxidized glutathione (GSSG) occurred after intravenous administration of MTT or MTT-containing antibiotics to rats. This finding suggested that these compounds could alter the hepatic glutathione redox state in vivo. Microsomal reduction of vitamin K epoxide occurred in the presence of 100 microM dithiothreitol (DTT), but was inhibited by preincubation with GSSG at concentrations as low as 10 microM. At higher concentrations of DTT (1.0 mM) inhibition by GSSG persisted, but higher concentrations were required, suggesting that the thiol/disulfide ratio, rather than the absolute concentration of GSSG was important. By contrast, GSSG did not effect microsomal gamma-carboxylation of a pentapeptide, using either vitamin K1 or its hydroquinone as a cofactor. These findings suggest a novel mechanism for the hypoprothrombinemia occurring after administration of MTT-containing antibiotics.
Mortality in North Korea rises by 40% in seven years
Authors: J. Lamar
Journal: BMJ (2001)

Famine, floods, and a healthcare system on the brink of collapse have pushed North Korea's death rate up by almost 40% in the past seven years, Gro Harlem Brundtland, director general of the World Health Organization, has said.

Ms Brundtland, who was speaking on her return from a four day visit to Pyongyang, appealed for aid to rebuild a healthcare system that she said was …
RNA Aptamer Blockade of Osteopontin Inhibits Growth and Metastasis of MDA-MB231 Breast Cancer Cells
Authors: Zhiyong Mi, Hongtao Guo, M Benjamin Russell, Yingmiao Liu, Bruce A Sullenger, Paul C Kuo
Journal: Molecular Therapy (2008)

Osteopontin (OPN) is a secreted phosphoprotein which mediates tumorigenesis, local growth, and metastasis in a variety of cancers. It is a potential therapeutic target for the regulation of cancer metastasis. RNA aptamer technology targeting OPN may represent a clinically viable therapy. In this study, we characterize the critical sequence of an RNA aptamer, termed OPN-R3, directed against human OPN. It has a Kd of 18 nmol/l and binds specifically to human OPN as determined by RNA electrophoretic mobility assays. In MDA-MB231 human breast cancer cells examined under fluorescence microscopy, OPN-R3 ablates cell surface binding of OPN to its cell surface CD44 and αvβ3 integrin receptors. Critical enzymatic components of the OPN signal transduction pathways, PI3K, JNK1/2, Src and Akt, and mediators of extracellular matrix degradation, matrix metalloproteinase 2 (MMP2) and uroplasminogen activator (uPA), are significantly decreased following exposure to OPN-R3. OPN-R3 inhibits MDA-MB231 in vitro adhesion, migration, and invasion characteristics by 60, 50, and 65%, respectively. In an in vivo xenograft model of breast cancer, OPN-R3 significantly decreases local progression and distant metastases. On the basis of this “proof-of-concept” study, we conclude that RNA aptamer targeting of OPN has biologically relevance for modifying tumor growth and metastasis. Osteopontin (OPN) is a secreted phosphoprotein which mediates tumorigenesis, local growth, and metastasis in a variety of cancers. It is a potential therapeutic target for the regulation of cancer metastasis. RNA aptamer technology targeting OPN may represent a clinically viable therapy. In this study, we characterize the critical sequence of an RNA aptamer, termed OPN-R3, directed against human OPN. It has a Kd of 18 nmol/l and binds specifically to human OPN as determined by RNA electrophoretic mobility assays. In MDA-MB231 human breast cancer cells examined under fluorescence microscopy, OPN-R3 ablates cell surface binding of OPN to its cell surface CD44 and αvβ3 integrin receptors. Critical enzymatic components of the OPN signal transduction pathways, PI3K, JNK1/2, Src and Akt, and mediators of extracellular matrix degradation, matrix metalloproteinase 2 (MMP2) and uroplasminogen activator (uPA), are significantly decreased following exposure to OPN-R3. OPN-R3 inhibits MDA-MB231 in vitro adhesion, migration, and invasion characteristics by 60, 50, and 65%, respectively. In an in vivo xenograft model of breast cancer, OPN-R3 significantly decreases local progression and distant metastases. On the basis of this “proof-of-concept” study, we conclude that RNA aptamer targeting of OPN has biologically relevance for modifying tumor growth and metastasis.
Heterogeneity of follicle stimulating hormone: control and physiological function
Authors: S. Chappel
Journal: Human Reproduction Update (1995)

The existence of a heterogeneous population of follicle stimulating hormone (FSH) was described many years ago. Other pituitary glycoproteins, such as thyroid stimulating hormone (TSH) and luteinizing hormone (LH) as well as placental human chorionic gonadotrophin (HCG) also exhibit heterogeneity. Because FSH plays a significant role in a variety of ovarian activities such as follicular maturation, selection of the dominant follicle and ovulation, the possible role of subpopulations of FSH with distinct physicochemical characteristics is of great interest. After a great deal of investigation, the physiological significance of this biochemical phenomenon has yet to be fully understood. Investigators have employed immunoassays, in-vitro bioassays and radioreceptor assays to study the biological activity of the individual isoforms of FSH. As more information has accumulated, it has become clear that some of the initial assumptions used to interpret data may be incorrect. This review is provided to update the reader with available information on the topic as it relates to FSH and to point out issues that require re-evaluation in this area.
Chronic Abuse of Zolpidem
Authors: Christian A. Gericke
Journal: JAMA (1994)

<h3>To the Editor.</h3> —The imidazopyridine zolpidem has only recently been marketed as a rapid-onset, short-acting hypnotic. It has been assumed that zolpidem has a lower potential for abuse than benzodiazepines because of its unpleasant adverse effects at higher doses. However, in baboons the drug had a higher reinforcing efficacy than any benzodiazepine tested and self-injection rates were similar to those maintained by pentobarbital or secobarbital.<sup>1</sup> A 33-year-old man with known major depression since the age of 26 years was admitted to our hospital for evaluation of an unprovoked generalized tonic-clonic seizure that occurred 14 hours after the reported ingestion of 60 to 80 mg of zolpidem. The seizure was self-limited. Anterograde amnesia was present and memory returned to normal only after 4 to 5 days. An electroencephalogram showed increased photoreactivity 7 days after the acute event; another 8 days later a 24-hour recording, which included photosensitivity testing, was completely
Care for Rural Veterans
Authors: Bridget M. Kuehn
Journal: JAMA (2012)

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β-Catenin Signaling Is a Critical Event in ErbB2-Mediated Mammary Tumor Progression
Authors: Babette Schade, Robert Lesurf, Virginie Sanguin-Gendreau, Tung Bui, Geneviève Deblois, Sandra A. O'Toole, Ewan K.A. Millar, Sara J. Zardawi, Elena Lopez-Knowles, Robert L. Sutherland, Vincent Giguère, Michael Kahn, Michael Hallett, William J. Muller
Journal: Cancer Research (2013)

Although ERBB2 amplification and overexpression is correlated with poor outcome in breast cancer, the molecular mechanisms underlying the aggressive nature of these tumors has not been fully elucidated. To investigate this further, we have used a transgenic mouse model of ErbB2-driven tumor progression (ErbB2(KI) model) that recapitulates clinically relevant events, including selective amplification of the core erbB2 amplicon. By comparing the transcriptional profiles of ErbB2(KI) mammary tumors and human ERBB2-positive breast cancers, we show that ErbB2(KI) tumors possess molecular features of the basal subtype of ERBB2-positive human breast cancer, including activation of canonical β-catenin signaling. Inhibition of β-catenin-dependent signaling in ErbB2(KI)-derived tumor cells using RNA interference impaired tumor initiation and metastasis. Furthermore, treatment of ErbB2(KI) or human ERBB2-overexpressing tumor cells with a selective β-catenin/CBP inhibitor significantly decreased proliferation and ErbB2 expression. Collectively, our data indicate that ERBB2-mediated breast cancer progression requires β-catenin signaling and can be therapeutically targeted by selective β-catenin/CBP inhibitors.
Spina bifida and anencephaly: miscarriage as possible cause.
Authors: C Clarke, D Hobson, O M McKendrick, S C Rogers, P M Sheppard
Journal: BMJ (1975)

In two retrospective Liverpool surveys the domestic, family, dietary, and medical environments of the mothers of children affected by anencephaly or spina bifida, or both (ASB) were examined. None seemed to be of more than minor importance and the findings of others were therefore examined to see if they suggested a major factor. The most promising lead came from the hypothesis that ASB is usually due to an interaction between twin fetuses or between a fetus and residual trophoblastic material from the previous normal pregnancy, particularly when this is of the opposite sex to the propositus. The sex finding was not confirmed. It was noted that hydatidiform moles, like children with ASB, were usually female and that moles and choriocarcinomas on the one hand and children with ASB on the other occurred in mothers of similar ages, but were to some extent reciprocal in geographical incidence. This suggested that trophoblastic disease might be a factor common to all three and if so then one would expect the frequency of miscarriages to be higher immediately before than immediately after the birth of an ASB child, since mole and choriocarcinoma seldom follow a normal pregnancy. An analysis of published data confirmed that this was almost certainly so. Hence residual pathological trophoblastic material from either a previous miscarriage or a co-twin may interact unfavourably with another fetus to produce ASB and this may be the primary cause of the condition. The hypothesis is consistent with the observed lack of concordance in twins, the high incidence in females, the maternal age effect, and the greater prevalence in social classes IV and V.
Travel-Associated Health Risks for Patients With Inflammatory Bowel Disease
Authors: Shomron Ben–Horin, Yoram Bujanover, Shulamit Goldstein, Moshe Nadler, Alon Lang, Uri Kopylov, Lior Katz, Adi Lahat, Eli Schwartz, Benjamin Avidan
Journal: Clinical Gastroenterology and Hepatology (2011)
Ticlopidine-induced aplastic anemia and quick recovery with G-CSF: Case report and literature review
Authors: A. Taher, Z. Ammash, B. Dabajah, A. Nasrallah, F. H. Mourad
Journal: American Journal of Hematology (2000)

We report here a case of ticlopidine-induced aplastic anemia that responded to G-CSF and review the literature. An 83-year-old woman was started on ticlopidine for coronary artery disease after an episode of upper gastrointestinal bleeding secondary to aspirin. She developed aplastic anemia seven weeks after initiation of ticlopidine. She was hospitalised and received empiric antibiotic therapy and granulocyte colony stimulating factor (G-CSF). Her bone marrow started to recover quickly, and white blood cell and platelet counts returned to normal within three weeks. A review of medical literature revealed 20 similar cases of ticlopidine-induced aplastic anemia resulting in death in seven cases. G-CSF has been used previously with variable success. Ticlopidine is associated with serious, sometimes fatal hematological side effects. This risk should be seriously taken into consideration when prescribing ticlopidine. G-CSF may be helpful in the treatment of ticlopidine-induced aplastic anemia. Am. J. Hematol. 63:90–93, 2000. © 2000 Wiley-Liss, Inc.