tbuckley/cabot-search huggingface dataset:
Placental Transfer of Radioactive Digitoxin in Pregnant Women and its Fetal Distribution
Authors: GEORGE T. OKITA, ERNEST J. PLOTZ, M. EDWARDS DAVIS, John H. Curry, Frederick D. Smith
Journal: Circulation Research (1956)

Placental transfer of radioactive C 14 -digitoxin was investigated in four pregnant women. The concentration of the labeled drug and its metabolic products in the various fetal organs was determined. Less than 1 per cent of the administered glycoside was detected in the fetus as unchanged digitoxin and less than 3.5 per cent as its metabolites. The fetal heart and kidney of 11 to 12 weeks gestation had the highest concentrations. However, at near term the fetal liver, gallbladder and intestine had somewhat similar concentrations. Metabolic conversion of the cardiac glycoside by fetal liver as well as biliary excretion is indicated from the tissue distribution data.
Incidence of Galactorrhea-Reply
Authors: Maire T. Buckman
Journal: JAMA (1976)

Dr Kemmann refers to several studies in which the incidence of galactorrhea among women of childbearing age was low. A similar number of studies can be cited in which the incidence of galactorrhea was substantially higher, ranging from 12% to 46%.<sup>1-4</sup>The striking differences in the reported incidences of galactorrhea can be attributed to two factors. The technique of the breast examination is crucial to the detection of occult galactorrhea. A systematic examination, using both hands to exert pressure from the periphery (where the alveolar cells are synthesizing milk) toward the nipple in a perimetric fashion, will yield a higher incidence of galactorrhea than a casual squeeze of the subareolar tissue. The second factor yielding contrasting results is the definition of galactorrhea. All studies exclude bloody or purulent secretions, but the definition of "milk-like" is tenuous. Some investigators exclude cloudy or opalescent secretions, which are not obviously
A multicenter, placebo-controlled, double-blind study of intermittent therapy with itraconazole for the treatment of onychomycosis of the fingernail☆, ☆☆
Authors: R ODOM, R ALY, R SCHER, C DANIELIII, B ELEWSKI, N ZAIAS, R DEVILLEZ, M JACKO, N OLEKAG, B MOSKOVITZ
Journal: Journal of the American Academy of Dermatology (1997)
Selective depletion of fibroblasts preserves morphology and the functional integrity of peritoneum in transgenic mice with peritoneal fibrosing syndrome
Authors: Hirokazu Okada, Tsutomu Inoue, Yoshihiko Kanno, Tatsuya Kobayashi, Yusuke Watanabe, Shinichi Ban, Eric G. Neilson, Hiromichi Suzuki
Journal: Kidney International (2003)
Measles immunisation: results of a local programme to increase vaccine uptake.
Authors: H Carter, I G Jones
Journal: BMJ (1985)

Investigations showed that the measles immunisation programme in our health board was a failure. Surveys of health care staff and parents to determine the cause of the problem identified several aspects of concern: the immunisation of children was often left to parental initiative, with only 29% of general practitioners playing an active part in recalling children by the 15th month of age; general practitioners, clinical medical officers, paediatricians, and health visitors all required education on several aspects of measles immunisation; parents also required more information about the importance of preventing this disease. A coordinated effort to remedy these problems was introduced which achieved an increase of 13% in vaccine uptake during 1984. These findings may have implications beyond our own area.
Changes in antibiotic sensitivity in strains of Staphylococcus aureus, 1952-78.
Authors: Z A Hassam, E J Shaw, R A Shooter, D B Caro
Journal: BMJ (1978)

Two hundred strains of Staphylococcus aureus isolated from outpatients with infections of the skin and subcutaneous tissues were tested for sensitivity to penicillin, erythromycin, tetracycline, sodium fusidate, methicillin, clindamycin, chloramphenicol, and gentamicin. One hundred and sixty-three (81.5%) of the strains were resistant to penicillin and 16 (8%) resistant to tetracycline. Incidence of resistance to other antibiotics was low. No strain was resistant to chloramphenicol, gentamicin, or methicillin. When compared with results of earlier studies, there was an increase in the incidence of resistance to penicillin and tetracycline, but no appreciable increase in resistance to other antibiotics.
Lung Perfusion
Authors: Howard Pierpont
Journal: JAMA (1962)

KNOWLEDGE of the distribution and metabolism of cancer chemotherapeutic agents is essential in estimating their ability to reach the target in a biochemically active form. Isolated lung perfusion provides a dynamic physiological system for such an evaluation in pulmonary tissue. Cancer chemotherapeutic agents at the present time are divided into 3 general categories: alkylating, antimetabolite, and a smaller miscellaneous group. This investigation, performed in dogs, compares the distribution, metabolism, and tissue fixation of β, β-dichloroethyl sulfide (sulfur mustard) and 5-fluorouracil, representatives of the first 2 categories respectively. Criteria for selection of drugs in such a lung perfusion are described. Perfusion Technique The method of perfusing one lung in the dog has been previously described in detail. Briefly this consists of the intrapericardial cannulation of the (left) pulmonary artery and an isolated segment of the atrial chamber draining the (left) lung. The only escape from this circuit is via a potential
The Biologic and Clinical Basis of Infectious Diseases
Authors: Jerry D. Smilack
Journal: JAMA (1976)

The mission: to present to today's medical student—in an easily readable form—the vast spectrum of microbiologic, epidemiologic, and clinical knowledge that encompasses the multidisciplinary subspecialty of infectious diseases. Impossible? Probably. But in this textbook, the editors have come closer to this ideal than any previous effort. They and their colleagueauthors at Northwestern University Medical School have assembled a volume that links the output of the laboratory to an understanding of the patient and his illness. The authors address themselves first to general interactions of host vs microbial parasite, then to specific infections of organ systems. Each chapter is well organized and timely and filled with clear diagrams, charts, and graphs. The discussion of infectious diarrhea is particularly illustrative. At its outset, the chapter differentiates the invasive from the toxigenic infections. From there, the discussion turns to<i>Salmonella</i>infection; there is judicious emphasis on the epidemiology of salmonellosis. Shigellosis and cholera
Welsh health minister plans to make the NHS more accountable
Authors: R. Dobson
Journal: BMJ (2011)

Major changes are being planned for the NHS in Wales over the next five years. Services have to be safe, sustainable, effective, and fair, the Welsh Assembly Health minister, Lesley Griffiths, said in her first major speech.

“Bringing about these changes will not be easy,” she said. “They will not be easy for the dedicated staff that work in the NHS. The changes, in some instances, won’t be easy for some patients to accept either. Change is necessary and in some cases long overdue.”

Ms Griffiths, who has also set out plans to improve maternity care in Wales, outlined her vision for the NHS at the …
STUDIES ON LEUKEMIA IN MICE
Authors: Maurice N. Richter, E. C. MacDowell
Journal: The Journal of Experimental Medicine (1930)

Lymphatic leukemia has occurred with great frequency in a particular strain of mice which have been inbred by brother-sister matings since 1921. In addition to typical cases of leukemia are others which, because of the absence of leukemic changes in the blood, correspond to "pseudoleukemia" and others which, by the presence of unusually great enlargement of certain lymph node groups resemble the "leukosarcomatoses" as observed in man. Examinations of the blood of leukemic mice have shown that leukemic blood pictures are not necessarily early in their appearance, nor are they constant. The blood picture may not, therefore, be used as a criterion for the separation of the two diseases (leukemia and pseudoleukemia) but merely indicates different phases of the same condition. Likewise, cases with lesions intermediate between the local growths of "leukosarcomatosis" and the more general lymphatic enlargements of leukemia suggest that these conditions differ only in the distribution of lesions but not in their nature. Lymphatic leukemia occurring spontaneously in this strain may be transmitted to other mice of the same strain, and carried, apparently, for an unlimited number of transfers in animals at an earlier age than that at which leukemia occurs spontaneously. In each of 10 such experiments transmissions were obtained. The lesions produced by inoculation correspond to those of spontaneous cases, in that they consist of growths of abnormal lymphoid cells which infiltrate tissues and organs and often appear in the circulating blood. Only minor differences have occurred, some of which are characteristic of certain experimental lines. After repeated transfers, the disease tends to run a more acute course. Among the cases in which transmissions occurred, are some without leukemic changes in the blood, and many with local growths at the site of inoculation or in certain node groups. The differences in the blood pictures and distribution of lesions (which latter may be influenced to some extent by the method of inoculation) correspond to similar differences which are sometimes observed in the spontaneous cases.
Cannes and Torquay as Winter Health-Resorts
Authors: S. Thomson
Journal: BMJ (1868)

MEDICAL 7OURAL,. 84, gave every indication of recent peritonitis.The liver was enlarged and congested.On cutting into the part of the rectum externml to the anus, it seemed a solid mass of flesh; but, on looking closely into it, a small contracted canal could be traced irregularly through the tumour.Beyond this, there was nothing to indicate tat it was intestine.
Investigation into use of drugs preceding death from asthma.
Authors: F. E. Speizer, R. Doll, P. Heaf, L. B. Strang
Journal: BMJ (1968)

Copies of death certificates were provided by the Registrar General for all deaths attributed to asthma in persons aged 5 to 34 years which were registered in England and Wales in the last quarter of 1966 and the first quarter of 1967. Information was obtained from the relevant general practitioners about 177 of the 184 subjects, and necropsy data were obtained for 113 of the 124 cases in which a post-mortem examination was known to have been made. Ninety-eight per cent. of the subjects for whom evidence was obtained were known to have been suffering from asthma, and signs of severe asthma (overdistended lungs and small bronchi plugged with mucus) were found in 91% of necropsies (57% of all deaths). Evidence that death might have been due to any other pathological condition was rare. Death was sudden and unexpected in 81% of the subjects (137 out of 171), and 59% of all deaths were referred to coroners. In 39% of cases (67 out of 171) the practitioner had not regarded the patient as suffering from severe asthma in his terminal episode. Corticosteroids and sympathomimetic preparations were the only drugs to have been used by a large proportion of patients. Two-thirds of the patients had received corticosteroids before the terminal episode, but detailed information about their use provided no suggestion that excess use could have been responsible for any large proportion of the deaths. Eighty-four per cent. of the patients were known to have used pressurized aerosol bronchodilators, and several instances of their use in excess were described. Routine inquiries about their use in the hours immediately preceding death were not made, and further evidence is required before their effect can be assessed adequately.
Wegener's Granulomatosis
Authors: Samuel K. McIlvanie
Journal: JAMA (1966)

Regression of all lesions and relief of symptoms occurred in two patients with Wegener's granulomatosis treated with chlorambucil. One patient is living and well after 22 months of treatment and the other after 12 months. Both have shown a striking reversal of abnormal protein electrophoretic patterns. Therapy with chlorambucil has been continuous.
History and Development of Forensic Medicine
Authors: S. Smith
Journal: BMJ (1951)

Forensic medicine may be defined briefly as consisting essentially of that body of medical and paramedical scientific knowledge which may be used for the purposes of administration of the Law.In discussing its history it is obviously impossible to indicate any single date as the point at which forensic medicine emerged as a recognizable, separate scientific discipline.It is justifiable, no doubt, to contend that Medicine origi- nated in the very dawn of human history, when first a cry of pain prompted a fellow-being to experiment with simple forms of assuagement.Simi'arly, the Law may be said to have its origins in the earliest sanctions which were doubtless applied to disturbers of the peace in the most primitive communities.We cannot begin to think of forensic medicine as an entity, however, until a stage of civilization is reached in which we have, on the one hand, a recogniziable legal system, and on the other an integrated body of medical knowledge and opinion.Furthermore, we cannot know much about such matters until some means of recording them has been achieved, and our earliest records take us back only about five thousand years. Egyptian Law and MedicineWe must turn, therefore, to the records of the early l?terate civilizations of the Near East, particularly to those of the Nile Valley, where, from the ancient Egyptian inscriptions on stone and later on papyri, we can obtain some idea of the state of knowledge at that early period.I believe there is some evidence that Menes, the first Pharaoh, had a considerable know- ledge of medicinal plants, and it is quite certain that at a somewhat later period there was a knowledge of medicine which was not only extensive but also clearly systematized and showed a much more scien- tific approach to medical problems than is generally realized.This much can be gleaned from the now fairly numerous medical papyri which have been translated.These include the Ebers (medical), Edwin Smith (surgical), and Hearst Papyri, and a few others which are rather more fragmentary, such as the medi- cal papyri in the British Museum.From these, from illustrative inscriptions, and from actual mummified remains, it is possible to draw many valid conclusions regarding Egyptian law and medicine from as early as 2500 B.C. onwards.There was a definite system of law, relating not only to crime but also to property, marriage, and other civil matters.The punishments
Mizoribine Corrects Defective Nephrin Biogenesis by Restoring Intracellular Energy Balance
Authors: Aya Nakajo, Jamshid Khoshnoodi, Hitoshi Takenaka, Emi Hagiwara, Takashi Watanabe, Hayato Kawakami, Ryota Kurayama, Yuji Sekine, Fumio Bessho, Shori Takahashi, Agnieszka Swiatecka-Urban, Karl Tryggvason, Kunimasa Yan
Journal: Journal of the American Society of Nephrology (2007)

Proteins are modified and folded within the endoplasmic reticulum (ER). When the influx of proteins exceeds the capacity of the ER to handle the load, the ER is "stressed" and protein biogenesis is affected. We have previously shown that the induction of ER stress by ATP depletion in podocytes leads to mislocalization of nephrin and subsequent injury of podocytes. The aim of the present study was to determine whether ER stress is associated with proteinuria in vivo and whether the immunosuppressant mizoribine may exert its antiproteinuric effect by restoring normal nephrin biogenesis. Induction of nephrotic-range proteinuria with puromycin aminonucleoside in mice increased expression of the ER stress marker GRP78 in podocytes, and led to the mislocalization of nephrin to the cytoplasm. In vitro, mizoribine, through a mechanism likely dependent on the inhibition of inosine 5'-monophosphate dehydrogenase (IMPDH) activity in podocytes, restored the intracellular energy balance by increasing levels of ATP and corrected the posttranslational processing of nephrin. Therefore, we speculate that mizoribine may induce remission of proteinuria, at least in part, by restoring the biogenesis of slit diaphragm proteins in injured podocytes. Further understanding of the ER microenvironment may lead to novel approaches to treat diseases in which abnormal handling of proteins plays a role in pathogenesis.
Trends in Death Rates Among U.S. Adults With and Without Diabetes Between 1997 and 2006
Authors: Edward W. Gregg, Yiling J. Cheng, Sharon Saydah, Catherine Cowie, Sanford Garfield, Linda Geiss, Lawrence Barker
Journal: Diabetes Care (2012)

OBJECTIVE To determine whether all-cause and cardiovascular disease (CVD) death rates declined between 1997 and 2006, a period of continued advances in treatment approaches and risk factor control, among U.S. adults with and without diabetes. RESEARCH DESIGN AND METHODS We compared 3-year death rates of four consecutive nationally representative samples (1997–1998, 1999–2000, 2001–2002, and 2003–2004) of U.S. adults aged 18 years and older using data from the National Health Interview Surveys linked to National Death Index. RESULTS Among diabetic adults, the CVD death rate declined by 40% (95% CI 23–54) and all-cause mortality declined by 23% (10–35) between the earliest and latest samples. There was no difference in the rates of decline in mortality between diabetic men and women. The excess CVD mortality rate associated with diabetes (i.e., compared with nondiabetic adults) decreased by 60% (from 5.8 to 2.3 CVD deaths per 1,000) while the excess all-cause mortality rate declined by 44% (from 10.8 to 6.1 deaths per 1,000). CONCLUSIONS Death rates among both U.S. men and women with diabetes declined substantially between 1997 and 2006, reducing the absolute difference between adults with and without diabetes. These encouraging findings, however, suggest that diabetes prevalence is likely to rise in the future if diabetes incidence is not curtailed.
Abstract 4245: Preclinical study of puquitinib, a novel orally available PI3K inhibitor in phase I clinical trials
Authors: Chengying Xie, Yongping Xu, Liguang Lou
Journal: Cancer Research (2011)

Abstract Extensive evidence implicates activation of PI3K pathway in the genesis and progression of various human cancers. PI3K inhibitors thus have considerable potential as molecular cancer therapeutics. In this report, we detailed the pharmacologic properties of puquitinib, a novel orally available PI3K inhibitor structurally distinct from all those known so far. Puquitinib reduced the levels of phosphatidylinositol-3,4,5-trisphosphate (PIP3), a product of PI3K, and inhibited the phosphorylation, translocation and membrane ruffling of AKT, the signaling component downstream from PI3K. The inhibitory effects of puquitinib on PI3K signaling were correlated with its potent anti-proliferative activity in a panel of tumor cells. Puquitinib also demonstrated potent anti-angiogenic effects in the tubule formation and cell migration assays of human umbilical vein endothelial cells, and micro-vessel spouting from matrigel-embedded rat aortic rings. Oral administration of puquitinib showed strong antitumor activity in various human cancer xenograft models without any noticeable toxicity, along with the reduction of phosphorylated AKT in tumor tissues. Collectively, the preclinical data show that puquitinib is a potent PI3K inhibitor with favorable pharmaceutical properties. Puquitinib is currently being evaluated in phase I clinical trials in China. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4245. doi:10.1158/1538-7445.AM2011-4245
Abstract OT1-2-04: PAM50 HER2-enriched (HER2E) phenotype as a predictor of early-response to neoadjuvant lapatinib plus trastuzumab in stage I to IIIA HER2-positive breast cancer
Authors: M Vidal, L de la Peña, M Oliveira, J Cortés, A Llombart, A Prat
Journal: Cancer Research (2013)

Abstract Background: The efficacy of trastuzumab in different regimens and settings has been well established, including its benefit as neoadjuvant therapy for early HER2-positive disease. Combinations of two different anti-HER2 therapies without chemotherapy have generated great expectations. However, it is unclear which group of patients benefits the most from this strategy. Within HER2-positive breast cancer, the PAM50 assay identifies a HER2-Enriched (HER2-E) intrinsic subtype characterized by high activation of the EGFR/HER2 pathway and low expression of luminal-related genes, and therefore should obtain the greatest benefit from anti-HER2 therapy. Trial Design: This non-randomized, open-label, multicentric phase II translational research study will evaluate the ability of the PAM50 HER2-E subtype to predict pathological complete response (pCR) to dual HER2 blockade with lapatinib and trastuzumab for a total of 18 weeks. Patients with hormone receptor (HR)-positive disease will also receive endocrine therapy (letrozol or tamoxifen). Eligibility Criteria: Untreated, histologically confirmed invasive breast carcinoma eligible for definitive surgery (stage I-IIIA), HER2-positive invasive breast cancer by central assessment, premenopausal or postmenopausal, ECOG performance status of 0 or 1, adequate organ function and baseline LVEF &amp;gt;50% measured by echocardiography or MUGA scan. Specific Aims: The primary objective is to evaluate the ability of the PAM50 assay to predict pCR in the breast at the time of surgery. Secondary objectives are to (1) assess the correlation of HER2-E with pCR in the breast and axilla, (2) assess the correlation of HER2-E with Residual Cancer Burden (RCB) (3) evaluate the gene expression changes from Day 0 to Day 14 and the correlations with Ki67-IHC at Day 14, (4), identify additional gene expression signatures predictive of pCR, and (5) evaluate safety and tolerability. Statistical Methods: The statistical plan is based on the assumption that breast pCR rate will be 35.0% for HER2-E tumors and 8.0% for non-HER2E. The study will have a 95% power with a significance level of 5% (two-sided) and an assumed drop-out rate of 15%. Biomarker Analyses: Baseline, 14-day treated and post-treatment (surgical) formalin–fixed, paraffin–embedded tissues will be obtained. The expression of 547 genes will be explored with the nCounter platform. Subtype will be identified using the PAM50 predictor (Parker et al. J Clin Oncol 2009). Ki-67-IHC will also be evaluated on pre-treatment and Day-14 samples. Target Accrual: 150 patients with a maximum of 75 HR-positive patients across Spain and Portugal. Patient enrollment will begin in July 2013. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT1-2-04.