tbuckley/cabot-search huggingface dataset:
Cancer-Associated Hypercalcemia: Morbidity and Mortality
Authors: Stuart H. Ralston
Journal: Annals of Internal Medicine (1990)

Study Objective: To review the effects of antihypercalcemic treatment on morbidity and mortality in cancer-associated hypercalcemia. Design: Retrospective study of 126 consecutive patients with cancer-associated hypercalcemia. Setting: Inpatient referrals from a teaching hospital in the United Kingdom. Intervention: Medical antihypercalcemic therapy supplemented by specific anticancer therapy where possible. Measurements and Main Results: Median survival was 30 days. Survival did not differ in patients treated with different antihypercalcemic regimens but was longer (median, 135 days; P < 0.001) in a subgroup of 26 patients for whom specific anticancer therapy was available. Polyuria and polydipsia improved after therapy in 83% of cases, central nervous system symptoms in 71%, constipation in 70%, nausea and vomiting in 56%, anorexia in 50%, and malaise and fatigue in 47% (all significant, P < 0.001, pre-treatment compared with post-treatment). Pain control improved in only 23% of cases (not significant). Only 7% of patients with post-treatment serum calcium values above 3.50 mmol/L improved clinically compared with 80% whose calcium values fell below 2.80 mmol/L ( P < 0.001). Corresponding figures for the proportion of patients discharged from the hospital were 0% and 68% (P < 0.001). Conclusions: Life expectancy is poor in cancer-associated hypercalcemia even in patients who are actively treated. Antihypercalcemic therapy has an important palliative role, however, because symptoms are usually improved and, in many cases, patients may be made well enough to be discharged from the hospital during the terminal stages of their illness.
Mental Health Aspects of Shoplifting
Authors: T. C. N. Gibbens, C. Palmer, J. Prince
Journal: BMJ (1971)

A ten-year follow-up of 886 shoplifters showed clear differences between women and men. Men tended to have previous convictions and to steal books (unknown in women). Of the 532 women nearly one third were foreign-born, and this group comprised 46% of offenders aged 17-30. The peak age among British women was 51-60.First offenders accounted for 80% of the women, and their reconviction rate was 11%; among those with any kind of previous conviction the rate was 50%. The rate of admission to hospital for women shoplifters is three times higher than average.
Phytosterols Promote Liver Injury and Kupffer Cell Activation in Parenteral Nutrition–Associated Liver Disease
Authors: Karim C. El Kasmi, Aimee L. Anderson, Michael W. Devereaux, Padade M. Vue, Wujuan Zhang, Kenneth D. R. Setchell, Saul J. Karpen, Ronald J. Sokol
Journal: Science Translational Medicine (2013)

Parenteral nutrition-associated liver disease (PNALD) is a serious complication of PN in infants who do not tolerate enteral feedings, especially those with acquired or congenital intestinal diseases. Yet, the mechanisms underlying PNALD are poorly understood. It has been suggested that a component of soy oil (SO) lipid emulsions in PN solutions, such as plant sterols (phytosterols), may be responsible for PNALD, and that use of fish oil (FO)-based lipid emulsions may be protective. We used a mouse model of PNALD combining PN infusion with intestinal injury to demonstrate that SO-based PN solution causes liver damage and hepatic macrophage activation and that PN solutions that are FO-based or devoid of all lipids prevent these processes. We have furthermore demonstrated that a factor in the SO lipid emulsions, stigmasterol, promotes cholestasis, liver injury, and liver macrophage activation in this model and that this effect may be mediated through suppression of canalicular bile transporter expression (Abcb11/BSEP, Abcc2/MRP2) via antagonism of the nuclear receptors Fxr and Lxr, and failure of up-regulation of the hepatic sterol exporters (Abcg5/g8/ABCG5/8). This study provides experimental evidence that plant sterols in lipid emulsions are a major factor responsible for PNALD and that the absence or reduction of plant sterols is one of the mechanisms for hepatic protection in infants receiving FO-based PN or lipid minimization PN treatment. Modification of lipid constituents in PN solutions is thus a promising strategy to reduce incidence and severity of PNALD.
Axioms for governing health systems
Authors: Jeffrey Braithwaite
Journal: BMJ (2005)

M any important human endeavours crystallise their wisdom into one or more, and usually several, axioms. Why are there no axioms for governing the health system? Axioms are the fundamental underpinnings of social movements, academic disciplines, or intellectual pursuits. They postulate self evident principles within a logic that everyone accepts.

Such propositions are typically used to remind members of obligatory values, to teach a lesson, or perhaps to prove a point. Although they have various commandments, the world's religions, for example, profess to the multitude something like, “Attend to matters spiritual, learn the sacred ways, and apply their principles in your life.” Environmentalists hold to their own indispensable tenets about the stewardship of nature, the core of which approximates to “The earth is all we have, and its resources must be sustainably nurtured.” Medicine's prime axiom is short, piercing, and famous: “First, do no harm.”

The idea of the axiom originated in mathematics. Axioms in mathematicians' hands are very strictly expressed, typically as formulas encoding unimpeachable truths without the need for further proof. This type of Euclidean rigour is relaxed in other disciplines, but the force behind it—that specificity in axioms is vital—is retained.

Thomas …
Familial atrial septal defect with prolonged atrioventricular conduction.
Authors: W E Pease, A Nordenberg, R L Ladda
Journal: Circulation (1976)

This report describes a family with frequent recurrence of congenital heart disease in multiple generations. Eight members had atrial septal defect (ASD) of the fossa ovalis type and seven members had other forms of congenital heart disease. One branch of the pedigree showed a predominance of ASD with prolonged atrioventricular (A-V) conduction and initially suggested an autosomal dominant gene effect. A variety of other forms of congenital heart disease were found in several first degree relatives of those with ASD as well as in more distant relatives. The variability of congenital heart disease in this pedigree is compatible with the polygenic mode of inheritance. Definition of the inheritability of congenital heart disease in a specific family has important consequences in the determination of the recurrence risks for all family members.
Obesity, Heart Failure Due to
Authors: Howard N. Simpson
Journal: New England Journal of Medicine (1958)

WHEN it comes to a matter such as establishing a new eponym, "letting the fish and chips fall where they may"1 is excellent advice from the learned Dickensian scholars on the editorial board of the Journal. When the symptom complex under consideration, obesity associated with a reversible form of cardiopulmonary failure, has been recognized in the American literature for twenty-one years and interest has recently revived,2 the situation becomes one of general concern.Unfortunately, in any discussions of all-important priority, there are bound to be some hurt feelings, especially when, as in the present subject, the original description of . . .
The Arab World
Authors: HAROLD W. GLIDDEN
Journal: American Journal of Psychiatry (1972)

The hostility of the Arab collectivity toward Israel is governed by two key emotions inherent in the Arab culture. Their defeat by Israel brought them shame, which can only be eliminated by revenge. Arabs fear domination and thus a strong Israel, but their fear of domination by other Arab factions prevents them from forming a joint offensive. The Arab-Israeli hostility is a classic case of culture conflict, which is a major reason why it has been so prolonged and intractable.
Abstract 72: Amino terminus of SEPT9_i1 impacts cellular localization: Implications for mammary tumorigenesis
Authors: Laura Stanbery, Elizabeth M. Petty, Sofia D. Merajver
Journal: Cancer Research (2012)

Abstract Septins were first discovered in Saccharomyces cerevisiae as proteins essential for faithful cell division. They are highly conserved and found in all eukaryotes with the exception of plants. One septin, SEPT9, was cloned from a region of allelic imbalance in breast and ovarian cancers on chromosome 17q25. Further analysis showed that SEPT9 encoded multiple protein isoforms. Retroviral expression of one isoform, SEPT9_i1, promoted oncogenic phenotypes including, increased cell proliferation, invasion, motility, and genomic instability in mammary epithelial cells. In addition, abnormal nuclear localization of SEPT9_i1 was observed. SEPT9_i1 is highly expressed in many cancers including, breast, ovarian, prostate, and head and neck. SEPT9_i1 differs from other SEPT9 isoforms by 25 unique amino acids at the N terminus. SEPT9_i3, which lacks these 25 amino acids, does not exhibit the same pro-oncogenic phenotypes associated with SEPT9_i1. The goal of this study is to determine the functional relevance of these amino acids with respect to cellular localization as well as phenotypes related to mammary tumorigenesis and metastasis. First, bioinformatic analysis revealed a bipartite nuclear localization signal within the 25 unique amino acids but no other recognized functional domains. To determine the effects of these 25 amino acids on nuclear localization, FLAG-tagged deletion (ΔN)-SEPT9_i1, full-length (FL) -SEPT9_i1, and empty vector control constructs were transiently transfected into two immortalized human mammary epithelial cell lines, HME and MCF-10a. Immunofluorescence analyses of FL-SEPT9_i1 and ΔN-SEPT9_i1 localization revealed a dramatic decrease in the amount of SEPT9_i1 localized to the nucleus in the ΔN-SEPT9_i1 versus FL- SEPT9_i1 lines. Stably expressing FL-SEPT9_i1 and ΔN-SEPT9_i1 HS578t cell lines were also generated using nucleofection for examination of the effects of ΔN-SEPT9_i1 on cellular phenotypes including cell proliferation, cell motility and invasion. We present data indicating that the deletion of the N terminal 25 amino acids decreases cell motility and invasion as compared to SEPT9_i1 in HS578t cells. In addition, we show increased cell proliferation in cells expressing ΔN-SEPT9_i1 as compared to both EV and SEPT9_i1. To date our results implicate an oncogenic role for high SEPT9_i1 in mammary tumorigenesis where the unique 25 amino acids of SEPT9_i1 may impact tumorigenesis. Further investigation could provide valuable insight into developing targeted chemotherapeutic agents. 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 72. doi:1538-7445.AM2012-72
Epidemiology of Long-Term Survival with Acute Leukemia
Authors: Robert W. Gibson, Saxon Graham
Journal: New England Journal of Medicine (1974)

To define factors distinguishing long-term from short-term survivors among children with acute leukemia, 59 who survived for at least five years were compared with 59 who survived for two years or less. The two groups were matched for age, sex, histology and time and physician of treatment. Seven traits characterized the patient with the highest likelihood of short-term survival. Short-term survivors differed from the long-term in having had a high initial white-cell count; their mothers were less likely to have had complications during their pregnancies with the subjects, were more likely to have had a history of disease, viral and other, in the five-year period before the subject's birth, were more likely to have had irradiation when pregnant with the subject, and were more apt to have been older at their first live birth; the subject was more likely to have been a product of a third or later pregnancy. Thus, of the characteristics examined, those relating to the mother's pregnancy and disease history appeared most cogent. (N Engl J Med 290:583–587, 1974)
Use of Misoprostol during Pregnancy and Möbius' Syndrome in Infants
Authors: A L Pastuszak, L Schüler, C E Speck-Martins, K E Coelho, S M Cordello, F Vargas, D Brunoni, I V Schwarz, M Larrandaburu, H Safattle, V F Meloni, G Koren
Journal: New England Journal of Medicine (1998)

Patients with upper gastrointestinal ulceration may be treated with misoprostol, but it is not recommended for pregnant women because it may stimulate uterine contractions and cause vaginal bleeding and miscarriage. Recent data from Brazil, where misoprostol is used orally and vaginally as an abortifacient, have suggested a relation between the use of misoprostol by women in an unsuccessful attempt to terminate pregnancy and Möbius' syndrome (congenital facial paralysis) in their infants.
Paternalism, Family Duties, and My Aunt Maude
Authors: Alan Silver
Journal: JAMA (1988)

<h3>To the Editor.—</h3> Dr Miles'<sup>1</sup>plea to "accommodate<i>family</i>initiatives into decision making" so as to temper the "sudden injunction proscribing professional benevolence" and "the<i>physician's</i>duties honor[ing] the boundary of bodily integrity" is compelling. In Maude's case, the family's presumption was that authorization for the cataract surgery was blocked by irrationality and false belief. The willingness, however, was there. Her "true" self would assent to the procedure. Such a presumption requires a deep understanding of Maude—in this instance, better than Maude has herself. It assumes sufficient knowledge to conclude that her irrationality is a form of "external control" and that therefore she is not able to authorize informed consent relative to her real desires (the "sense<sub>1</sub>" informed consent of Faden and Beauchamp<sup>2</sup>). Dr Miles argues that the family has such knowledge and knows Maude sufficiently to understand the state of her psychological autonomy, including the limitations
Plasmacytic Leukemia
Authors: Norman P. Hill, Clinton Van Zandt Hawn
Journal: New England Journal of Medicine (1950)

THE presence of plasmacytes in the peripheral blood of patients with multiple myeloma, particularly in the terminal stages of the disease, is a well known phenomenon. It is also recognized that multiple myeloma, on occasion, exists in a diffuse form throughout the bone marrow without the production of the usual nodular tumor masses causing local resorption of bone. The subject of this report is a case in which plasmacytic leukemia was the dominant form of the disease, clinically and pathologically, throughout its course.Case ReportW. S. (M.I.B.H. 40313), a 55-year-old foreign-born laborer, was admitted to the hospital on February . . .
The Canonization of a Divine Healer in Russia.
Authors: C. D. Spivak
Journal: JAMA (1902)

Denver, Colo., Sept. 22, 1902. <h3>To the Editor:</h3> —The divine healers, Christian scientists et al in the United States and elsewhere should hurry up and go to Russia for instructions in their art of divination, for it is in orthodox Russia that things are carried to their extreme limit of what sane people call absurdity, but which to the minds of the befogged should mean, logical conclusions. There, in mother Russia, once a divine healer is a healer forever; he performs the same functions after his death as when alive, a feat not yet attained by the crack-brained in the United States. The following proclamation, published in the government organ<i>Pravitelstvenni Vyestnik</i>, reads like a document of the middle ages: The memory of the holy Seraphim of the Saratov desert, who was gathered unto his fathers, Jan. 2, 1883, is kept in deep veneration by the orthodox Russian people. To
One Hundred Orthopaedic Conditions Every Doctor Should Understand
Authors: Phillip G. Spiegel
Journal: JAMA (1992)

It is a given that some scientific intelligentsia find the study of bones to be boring. In order to dispel and bury that notion forever, Dr Meals and his gaggle of 26 medical student coauthors have produced a 310-page paperback text that is not only fun to read, but instructive as well. Using a format of short-story telling for each of the 62 chapters (related conditions are grouped together to form 100 subjects), orthopedic subjects are made interesting and informative. Basic musculoskeletal principles are heavily emphasized in italics on the borders, illustrations and x-rays appropriately accompany the text but do not overwhelm it, and a terse, up-to-date bibliography finishes the chapters. For example, would you believe a chapter called "Pool Party" teaches us about diving accidents, cervical spine injuries, protocol for trauma victims, neurological and radiological evaluations, and thoracic and lumbar spinal instability... in just six pages? Cleverness and didactics
High Prevalence of RET Tyrosine Kinase Activation in Mexican Patients with Papillary Thyroid Carcinomas
Authors: Ivan Martínez, Alejandra Mantilla, María E Medrano, Rogelio Hernández, Dulce María Hernández, Minerva Lazos, Hector Santiago, Beatriz González, Alfredo Hidalgo, Mauricio Salcedo
Journal: Endocrine Pathology (2001)
GMC assessment of Fergusson case was not at fault
Authors: W. Savage
Journal: BMJ (2001)

EDITOR—As an elected member of the General Medical Council who has just become a screener but who had no involvement with the Fergusson case, I disagree with the criticism by Jarvis of those who instigated the GMC conduct procedures.1

The screener must decide whether a complaint raises a question of serious professional misconduct. If so, he or she must then refer the case to the preliminary proceedings committee, which will decide whether it should be referred to the professional conduct committee. If not, the screener's judgment must be …
Serum Cholesterol Levels In the Medical Community
Authors: W. L. Warner
Journal: JAMA (1968)

<h3>To the Editor:—</h3> Many investigators<sup>1-5</sup>have shown that the risk of a clinical episode of coronary artery disease is closely correlated with serum cholesterol levels. These epidemiologic studies show that the hypercholesterolemic population has a three to five times greater risk of coronary heart disease (CHD) than the normocholesterolemic population. Recognition of this important correlation has generated efforts to screen large population groups for elevated cholesterol levels. It is an interesting observation that physicians and their families are seldom included in local health programs. Because of this it seemed particularly appropriate to carry out a cholesterol-screening program exclusively for physicians and their guests at medical conventions. Accordingly, Flint Laboratories carried out such a program at eight medical meetings, beginning with the American Medical Association convention, 1967, and ending with the AMA convention, 1968. The screening program included 2,973 individuals, who were selected for no reason other than their presence
Glutaredoxin 5 deficiency causes sideroblastic anemia by specifically impairing heme biosynthesis and depleting cytosolic iron in human erythroblasts
Authors: Hong Ye, Suh Young Jeong, Manik C. Ghosh, Gennadiy Kovtunovych, Laura Silvestri, Danilo Ortillo, Naoya Uchida, John Tisdale, Clara Camaschella, Tracey A. Rouault
Journal: Journal of Clinical Investigation (2010)

Glutaredoxin 5 (GLRX5) deficiency has previously been identified as a cause of anemia in a zebrafish model and of sideroblastic anemia in a human patient. Here we report that GLRX5 is essential for iron-sulfur cluster biosynthesis and the maintenance of normal mitochondrial and cytosolic iron homeostasis in human cells. GLRX5, a mitochondrial protein that is highly expressed in erythroid cells, can homodimerize and assemble [2Fe-2S] in vitro. In GLRX5-deficient cells, [Fe-S] cluster biosynthesis was impaired, the iron-responsive element–binding (IRE-binding) activity of iron regulatory protein 1 (IRP1) was activated, and increased IRP2 levels, indicative of relative cytosolic iron depletion, were observed together with mitochondrial iron overload. Rescue of patient fibroblasts with the WT GLRX5 gene by transfection or viral transduction reversed a slow growth phenotype, reversed the mitochondrial iron overload, and increased aconitase activity. Decreased aminolevulinate δ, synthase 2 (ALAS2) levels attributable to IRP-mediated translational repression were observed in erythroid cells in which GLRX5 expression had been downregulated using siRNA along with marked reduction in ferrochelatase levels and increased ferroportin expression. Erythroblasts express both IRP-repressible ALAS2 and non-IRP–repressible ferroportin 1b. The unique combination of IRP targets likely accounts for the tissue-specific phenotype of human GLRX5 deficiency.
Massachusetts Medical Society
Authors: Earl Brewer, Robert J. Haggerty
Journal: New England Journal of Medicine (1957)

Commercially available household rat poisons may contain phosphorus, alpha-naphthathiourea, thallium, arsenic, strychnine, cyanides, squill, sodium fluoroacetate and warfarin. Warfarin accounted for 29 of the 38 cases of rodenticide ingestion reported to the Boston Poison Information Center in the past two years.Warfarin is a 4-hydroxy coumarin derivative that causes death in rodents from blood loss and shock by a twofold action: inhibition of prothrombin formation and capillary damage.1 This compound is marketed in a concentrated form with corn meal containing 0.5 per cent warfarin, and as a commercially available bait in a concentration of 0.025 to 0.054 per cent warfarin. . . .
Adaptor Protein LAPF Recruits Phosphorylated p53 to Lysosomes and Triggers Lysosomal Destabilization in Apoptosis
Authors: Nan Li, Yuanyuan Zheng, Wei Chen, Chunmei Wang, Xingguang Liu, Weigang He, Hongmei Xu, Xuetao Cao
Journal: Cancer Research (2007)

Abstract Evidence suggests a functional association between the tumor suppressor p53 and apoptosis-involved organelle lysosome; however, the detailed mechanisms remain poorly understood. We recently reported that a lysosome-targeting protein, LAPF (lysosome-associated and apoptosis-inducing protein containing PH and FYVE domains), could initiate apoptosis of L929 cells through a lysosomal-mitochondrial pathway. In this study, we show that LAPF specifically interacted with phosphorylated p53 (Ser15/18) both in vitro and in vivo, which could be enhanced by apoptotic stimuli, such as tumor necrosis factor α (TNF-α) and ionizing irradiation. The PH domain of LAPF and the transactivation domain of p53 mediated the interaction between both molecules. Phosphorylated p53 (Ser15/18) could translocate to lysosomes before lysosomal membrane permeabilization (LMP) in LAPF-initiated and TNF-induced apoptosis. Silencing of LAPF expression abrogated lysosomal translocation of phosphorylated p53 (Ser15/18), whereas silencing of p53 expression had no effect on lysosomal translocation of LAPF. Similar to that of LAPF silencing, silencing of endogenous p53 expression in L929 cells could significantly impair TNF-α–induced LMP and apoptosis. However, reexpression of wild-type p53, p53S15D (substitution of Ser15 to Asp that mimics a phosphorylated state), and p53R175H (a transcription-deficient mutant) in p53-knockdown L929 cells could rescue the decrease in TNF-induced apoptosis. The data suggest that phosphorylated p53 (Ser15/18) might translocate to lysosome via forming complexes with adaptor protein LAPF and subsequently result in LMP and apoptosis, which might be in a transcription-independent manner. [Cancer Res 2007;67(23):11176–85]