tbuckley/cabot-search huggingface dataset:
Effect of sex hormones on bone in primary osteoporosis
Authors: B. Lawrence Riggs, Jenifer Jowsey, Patrick J. Kelly, James D. Jones, Frank T. Maher
Journal: Journal of Clinical Investigation (1969)

The effect of sex hormones on bone tissue was studied in 12 osteoporotic patients. Surfaces of bone undergoing formation and resorption were determined by quantitative microradiography of iliac crest biopsy samples before and after treatment with estrogens in 11 postmenopausal women and with testosterone in one gonadally competent man. Before treatment, bone resorption was greater than normal in all but one patient and bone formation was normal. After treatment, bone resorption decreased to within the normal range in all patients, and bone formation did not change significantly. Biochemical studies showed significant decreases in serum calcium, phosphorus, and alkaline phosphatase levels and in urinary excretion of calcium and hydroxyproline. These changes are believed to be the consequence of the effect of the hormones on bone. The data indicate that the major effect of sex hormones in osteoporosis is an inhibition of bone resorption.
mTORC1 activation in podocytes is a critical step in the development of diabetic nephropathy in mice
Authors: Ken Inoki, Hiroyuki Mori, Junying Wang, Tsukasa Suzuki, SungKi Hong, Sei Yoshida, Simone M. Blattner, Tsuneo Ikenoue, Markus A. Rüegg, Michael N. Hall, David J. Kwiatkowski, Maria P. Rastaldi, Tobias B. Huber, Matthias Kretzler, Lawrence B. Holzman, Roger C. Wiggins, Kun-Liang Guan
Journal: Journal of Clinical Investigation (2011)

Diabetic nephropathy (DN) is among the most lethal complications that occur in type 1 and type 2 diabetics. Podocyte dysfunction is postulated to be a critical event associated with proteinuria and glomerulosclerosis in glomerular diseases including DN. However, molecular mechanisms of podocyte dysfunction in the development of DN are not well understood. Here we have shown that activity of mTOR complex 1 (mTORC1), a kinase that senses nutrient availability, was enhanced in the podocytes of diabetic animals. Further, podocyte-specific mTORC1 activation induced by ablation of an upstream negative regulator (PcKOTsc1) recapitulated many DN features, including podocyte loss, glomerular basement membrane thickening, mesangial expansion, and proteinuria in nondiabetic young and adult mice. Abnormal mTORC1 activation caused mislocalization of slit diaphragm proteins and induced an epithelial-mesenchymal transition-like phenotypic switch with enhanced ER stress in podocytes. Conversely, reduction of ER stress with a chemical chaperone significantly protected against both the podocyte phenotypic switch and podocyte loss in PcKOTsc1 mice. Finally, genetic reduction of podocyte-specific mTORC1 in diabetic animals suppressed the development of DN. These results indicate that mTORC1 activation in podocytes is a critical event in inducing DN and suggest that reduction of podocyte mTORC1 activity is a potential therapeutic strategy to prevent DN.
Dual Roles of Notch in Regulation of Apically Restricted Mitosis and Apicobasal Polarity of Neuroepithelial Cells
Authors: Shinya Ohata, Ryo Aoki, Shigeharu Kinoshita, Masahiro Yamaguchi, Sachiko Tsuruoka-Kinoshita, Hideomi Tanaka, Hironori Wada, Shugo Watabe, Takashi Tsuboi, Ichiro Masai, Hitoshi Okamoto
Journal: Neuron (2011)
Gram-Positive Infections and Quinolones in Neutropenia
Authors: Eric J. Bow
Journal: Annals of Internal Medicine (1997)

Letters15 May 1997Gram-Positive Infections and Quinolones in NeutropeniaEric J. Bow, MDEric J. Bow, MDHealth Sciences Centre, Winnipeg, Manitoba R3A 1R9, Canada, For the National Institute of Canada Clinical Trials GroupSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-10-199705150-00028 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Altclas and colleagues and Drs. Castagnola and Viscoli have cited many of the disadvantages of selective quinolone prophylaxis, including colonization and subsequent infection by opportunistic yeasts; reduction in prophylactic efficacy associated with the increasing prevalence of quinolone-resistant microorganisms in many centers; and lack of consistent effect on such outcomes as febrile morbidity, infection-related mortality, and the pattern of prescribing parenteral antimicrobial agents. Despite these criticisms, a reduction in the incidence of infection with aerobic gram-negative bacilli has been the outcome most consistently shown in clinical trials. However, differences in mortality rates related to gram-negative infection have been harder ...References1. de Marie S, van den Broek PJ, Willemze R, van Furth R. Strategy for antibiotic therapy in febrile neutropenic patients on selective antibiotic decontamination. Eur J Clin Microbiol Infect Dis. 1993; 12:897-906. Google Scholar2. Bow EJ, Loewen R, Vaughan D. Reduced requirement for gram-negative antibiotic therapy in febrile neutropenic patients with cancer who are receiving antibacterial chemoprophylaxis with oral quinolones. Clin Infect Dis. 1995; 20:907-12. Google Scholar3. Fegan C, Poynton CH, Whittaker JA. The gut mucosal barrier in bone marrow transplantation. Bone Marrow Transplant. 1990; 5:373-7. Google Scholar4. Santolaya ME, Cofre J, Villarrocl M. C-reactive protein for the management of febrile neutropenic children with cancer: a prospective study [Abstract]. Program and Abstracts of the First International Pediatric Infectious Diseases Conference. Monterey, California; 1995:149. Google Scholar Author, Article, and Disclosure InformationAffiliations: Health Sciences Centre, Winnipeg, Manitoba R3A 1R9, Canada, For the National Institute of Canada Clinical Trials Group PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 May 1997Volume 126, Issue 10Page: 831KeywordsAntibacterial therapyAntimicrobialsClinical trialsFeversMorbidityOpportunistic infectionsPathogenesisProphylaxisStem cell transplantationYeast infections Issue Published: 15 May 1997 CopyrightCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Inhibition by colchicine of biliary secretion of diethylmaleate in the rat: Evidence for microtubule-dependent vesicular transport
Authors: Micheline Dumont, Scorinnem D’Hont, Anne-Marie Durand-Schneider, Véronique Legrand-Defretin, Gérard Feldmann, Serge Erlinger
Journal: Hepatology (1991)

It has been proposed that a microtubule-dependent transport of vesicles derived from the Golgi apparatus may play a role in biliary secretion of bile salts and other cholephilic anions. To test this hypothesis, we examined the influence of colchicine and vinblastine, two microtubule inhibitors, on diethylmaleate-induced bile flow and on the biliary secretion of diethylmaleate, an organic anion whose glutathione conjugates may be secreted into bile through the Golgi apparatus and Golgi-derived vesicles. Rats were pretreated with colchicine or vinblastine, and diethylmaleate was injected intraperitoneally at doses of 28 to 400 mumol/100 gm body wt. Basal bile flow was unaffected by colchicine or vinblastine. In contrast, diethylmaleate-induced bile flow and the secretion into bile of diethylmaleate conjugates (estimated by the cation-anion gap in bile) were significantly lower in colchicine-treated and vinblastine-treated animals than in controls. Diethylmaleate-induced bile flow was reduced in proportion to diethylmaleate conjugate secretion. A linear relationship was seen between bile flow and biliary output of diethylmaleate conjugates: this relationship was similar in colchicine-treated or vinblastine-treated animals and in controls. At electron microscopy, diethylmaleate had induced distension of the Golgi saccules of the hepatocytes. In conclusion, colchicine and vinblastine inhibited the secretion into bile of diethylmaleate conjugates and diethylmaleate-induced bile flow. These results support the view that microtubule-dependent transport of Golgi-derived vesicles is involved in the biliary secretion of diethylmaleate and, perhaps, other cholephilic organic anions.
Increasing Pneumococcal Immunizations Among People With Diabetes Using Patient Reminders
Authors: Deb K. Bjorsness, Katherine M. Pellett, JoAnne Unruh, Debora R. Snipes, Susan L. Hannula, Janet M. McDowall, Jeanine A. Ford, Dorothy Gohdes, Steven D. Helgerson, Todd S. Harwell
Journal: Diabetes Care (2003)

People with diabetes are at high risk for morbidity and mortality from influenza and pneumonia (1). Both the Centers for Disease Control and Prevention and the American Diabetes Association recommend that individuals with diabetes receive a pneumococcal and an annual influenza immunization regardless of age (2,3). Although the prevalence of pneumococcal immunizations among people with diabetes has increased, the level is still suboptimal, particularly among those aged <65 years (4). Efforts to increase the coverage level of immunizations in adults have largely been directed toward those ≥65 years of age who are Medicare beneficiaries (5,6). Thus clinicians and younger individuals with diabetes may be less likely to consider pneumococcal immunization. Several interventions have been shown to increase adult immunizations, including provider and patient reminder/recall, assessment and feedback to physicians, and standing orders for immunization (7). This report describes a quality improvement effort to increase pneumococcal immunizations in people with diabetes using a simple computerized diabetes monitoring system to facilitate patient reminders.

The Montana Department of Public Health and Human Services began to work in collaboration with three practices in Great Falls, MT, to monitor and improve diabetes care. The settings included a multispecialty practice, a community health center, and an Indian health center. Each of these practices used the Diabetes Care Monitoring System (DCMS), an electronic data system developed for primary care practices to …
Breast screening saves lives
Authors: N. J Wald, M. R Law, S. W Duffy
Journal: BMJ (2009)

Godlee concludes incorrectly that our silence implies assent to Gotzsche and colleagues’ views on the magnitude of the effect of mammographic screening in reducing breast cancer mortality.1 2 3 4

In 1993 a meta-analysis of randomised trials showed a 24% reduction in breast cancer mortality among all women aged 50-74 invited for screening,5 a result that has been generally accepted. This intention …
Acute renal failure after punishment beatings
Authors: D. M G Bowley, C. Buchan, L. Khulu, K. D Boffard
Journal: Journal of the Royal Society of Medicine (2002)

In the face of soaring crime rates, South Africa has seen the growth of vigilante groups that seek to mete out summary justice. Punishment, described as ‘African medicine’, often involves beating of the suspect with a whip (or sjambok). Victims of sjambokking have characteristic patterns of injury.
Notch induces human T-cell receptor γδ+ thymocytes to differentiate along a parallel, highly proliferative and bipotent CD4 CD8 double-positive pathway
Authors: S Van Coppernolle, S Vanhee, G Verstichel, S Snauwaert, A van der Spek, I Velghe, M Sinnesael, M H Heemskerk, T Taghon, G Leclercq, J Plum, A W Langerak, T Kerre, B Vandekerckhove
Journal: Leukemia (2011)
Reply to D. Przepiorka et al and M.K. Jensen
Authors: Alan K. Burnett, Robert K. Hills
Journal: Journal of Clinical Oncology (2013)

1 recently published the first results of the Medical Research Council (MRC) acute myeloid leukemia (AML) trial AML16 that comprised patients older than 60 years with high-risk myelodysplastic syndrome or AML, a trial that suggested a modest increase in 3-year cumulative survival for patients receiving gemtuzumab ozogamicin (GO) on day 1 of the first induction course.Apparently, there was "no interaction with other treatment interventions." 1(p3924) The results of the random assignment between standard MRC induction chemotherapy (daunorubicin/cytarabine) versus the experimental daunorubicin/clofarabine arm were not presented, although these data were bound to be available concomitant with the GO results.The supplementary data section does indeed suggest that there was a clinically meaningful interaction, albeit not statistically significant, with other treatment interventions.Thus, the cumulative 3-year survival was only significantly improved among patients receiving the experimental daunorubicin/clofarabine induction courses, whereas there was no evidence of a significant survival benefit for patients receiving the standard MRC induction chemotherapy (randomized daunorubicin/cytarabine: odds ratio, 0.9; 95% CI, 0.71 to 1.16; and nonrandomized daunorubicin/ cytarabine: odds ratio, 0.96; 95% CI, 0.75 to 1.22).The study does not merit reconsideration of GO as a component of therapy for older patients with AML treated with standard MRC induction chemotherapy, as suggested. 2
Overdose of Tetanus Toxoid
Authors: Sidney Lerner
Journal: JAMA (1974)

<h3>To the Editor.—</h3> I would like to report a patient who received an overdose of "tetanus toxoid, fluid." A total dose of 3.8 ml (2.0 ml intramuscularly in one buttock, 1.6 ml in the other, and 0.2 ml subcutaneously in the left deltoid region) was inadvertently administered to a 32-year-old female employee. The patient was to have received prophylactic γ-globulin (0.02 ml/lb of body weight) because of a puncture wound of her little finger by a hypodermic needle in a contaminated disposal box. Based on her report of localized reactions to tetanus toxoid in the past, the 0.2-ml dose rather than the standard 0.5 ml of tetanus toxoid, fluid was ordered. There was no immediate local or systemic response. The patient refused hospitalization for observation. Fifty milligrams of diphenhydramine hydrochloride (Benadryl) orally every four hours was prescribed for three days. A local reaction manifested by mild erythema, heat, induration, slight
Suppression of intractable cough.
Authors: C J Stewart, T J Coady
Journal: BMJ (1977)

Pyorala et al4 suggested the possibility that this decreased anticoagulant tolerance was not due to a retardation of the metabolism of the anticoagulant drugs.Their results suggested that C17-alkylated steroids affect the turnover of vitamin-K-dependent clotting factors, an impairment of synthesis being a likely mechanism.It was thought possible that C17alkylated steroids might diminish the stores of this vitamin available for metabolic competition with anticoagulant agents.
Hospital volume, hospital teaching status, patient socioeconomic status, and outcomes in patients hospitalized with sickle cell disease
Authors: Timothy L. McCavit, Hua Lin, Song Zhang, Chul Ahn, Charles T. Quinn, Glenn Flores
Journal: American Journal of Hematology (2011)

Sickle cell disease (SCD) accounts for ~100,000 hospitalizations in the US annually. Quality of care for hospitalized SCD patients has been insufficiently studied. Therefore, we aimed to examine whether four potential determinants of quality care, [1] hospital volume, [2] hospital teaching status, [3] patient socioeconomic status (SES), and [4] patient insurance status, are associated with three quality indicators for patients with SCD: [1] mortality, [2] length of stay (LOS), and [3] hospitalization costs. We conducted an analysis of the 2003–2005 Nationwide Inpatient Sample (NIS) datasets. We identified cases using all ICD-9CM codes for SCD. Both overall and SCD-specific hospital volumes were examined. Multivariable analyses included mixed linear models to examine LOS and costs, and logistic regression to examine mortality. About 71,481 SCD discharges occurred from 2003 to 2005. Four hundred and twenty five patients died, yielding a mortality rate of 0.6%. Multivariable analyses revealed that SCD patients admitted to lower SCD-specific volume hospitals had [1] increased adjusted odds of mortality (quintiles 1–4 vs. quintile 5: OR, 1.36; 95% CI, 1.05, 1.76) and [2] decreased LOS (quintiles 1–4 vs. quintile 5, effect estimate 20.08; 95%CI, 20.12, 20.04). These are the first data describing associations between lower SCD-specific hospital volumes and poorer outcomes.
RESEARCH WORK AT THE HARVARD MEDICAL SCHOOL.
Authors: HAROLD C. ERNST
Journal: JAMA (1904)

The data for this summary of research work done in connection with the Harvard Medical School, were obtained from answers to the following questions: As to how many individuals are connected with the department—both as teachers and engaged in research; as to how many places for research workers—in addition to the regular teaching force—exist in each department; as to whether there are any funds that can be drawn on for the assistance of research work independently of the money contributed by the school; as to what the facilities for research are; and as to what researches are now being carried on in each department. Questions of this nature were addressed to all the departments in the school having laboratories attached to them, or having influence over laboratories not directly under the control of the school. In making up such a summary as this, at this time, the present condition of
Data quality in predictive toxicology: reproducibility of rodent carcinogenicity experiments.
Authors: E Gottmann, S Kramer, B Pfahringer, C Helma
Journal: Environmental Health Perspectives (2001)

We compared 121 replicate rodent carcinogenicity assays from the two parts (National Cancer Institute/National Toxicology Program and literature) of the Carcinogenic Potency Database (CPDB) to estimate the reliability of these experiments. We estimated a concordance of 57% between the overall rodent carcinogenicity classifications from both sources. This value did not improve substantially when additional biologic information (species, sex, strain, target organs) was considered. These results indicate that rodent carcinogenicity assays are much less reproducible than previously expected, an effect that should be considered in the development of structure-activity relationship models and the risk assessment process.
Risks of Postmenopausal Hormone Replacement
Authors: Sean I. Savitz, Lou Caplan
Journal: JAMA (2002)

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The "athletic heart". Prevalence and physiological significance of left ventricular enlargement in distance runners
Authors: W. J. Raskoff
Journal: JAMA (1976)

To evaluate the prevalence and importance of "physiological" left ventricular hypertrophy (LVH) in athletes, 30 marathon runners were studied. Electrocardiographic evidence of LVH, present in 24 subjects, was associated with concomitant echocardiographic evidence of a thickened left ventricular (LV) posterior wall in five, with an enlarged end-diastolic LV diameter in three, as well as with roentgenographic evidence of cardiomegaly in three subjects. Echocardiographic evidence of superior LV function was noted in six. Maximal treadmill stress provoked no ischemic change. Cardiac hypertrophy and dilatation commonly develop in well-conditioned athletes, but the changes in LV size are slight. This "physiological" type of LVH does not lead to an ischemic response during exercise, in contrast to that which is seen in pathological forms of LVH. Physiological LVH may, however, contribute to superior ventricular function.
Abstract 5161: The development of therapeutic inhibitors of the KDM5 histone demethylases
Authors: Heidi R. Hudlebusch, Bo Heinemann, Jesper M. Nielsen, Daniela Kleine-Kohlbrecher, Camilla Hauge, Thomas Boesen, Marc Labelle, Lars-Ole Gerlach, Peter Staller, Peter Birk
Journal: Cancer Research (2014)

Abstract Histone methyl marks contribute to the regulation of chromatin architecture and of DNA-based processes such as replication, repair and gene transcription. There is increasing evidence for alterations in histone methylation patterns in cancer and other human diseases. Importantly, aberrant methylation can contribute to deregulated gene expression and thereby to excessive proliferation, survival and metastasis of cancer cells. Histone methyl transferases and demethylases establish a dynamic equilibrium of histone modifications, and the expression and activity of several members of these enzyme families are deregulated in human cancer. The jumonji C-domain histone H3K4me3/2 demethylase KDM5B/PLU1/JARID1B as well as its close relative KDM5A/JARID1A are potential oncogenes. Both proteins are overexpressed in human tumors and the gene encoding KDM5B is e.g. amplified in invasive breast cancer cells. Results obtained with RNA interference and targeted deletions in mice have provided additional support for a critical role of KDM5 demethylases in cancer cells. EpiTherapeutics is developing novel cancer drugs targeting the enzymatic activity of histone demethylases. Here we present our recent progress in obtaining selective, potent, and cell-permeable inhibitors of the KDM5 demethylases. Biochemical and cellular activities, pharmacological data, and in vivo antitumor activity will be discussed. Citation Format: Heidi R. Hudlebusch, Bo Heinemann, Jesper M. Nielsen, Daniela Kleine-Kohlbrecher, Camilla Hauge, Thomas Boesen, Marc Labelle, Lars-Ole Gerlach, Peter Staller, Peter Birk. The development of therapeutic inhibitors of the KDM5 histone demethylases. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5161. doi:10.1158/1538-7445.AM2014-5161
Queensland report on deaths recommends sweeping changes
Authors: Bob Burton
Journal: BMJ (2005)

A review into the clinical services at Queensland's Bundaberg Hospital triggered by the deaths and injuries attributed to Jayant Patel ( BMJ 2005;330:1468) has recommended sweeping procedural changes at the hospital and at Queensland Health, the responsible government department.

Dr Patel operated on about 1000 patients while he was at the hospital between April 2003 and April 2005. The department had informed the commission of inquiry into Patel's service, headed by Tony Norris QC, that 88 of Dr Patel's patients had died.

A clinical case review by Peter Woodruff, an associate professor, found …