tbuckley/cabot-search huggingface dataset:
Ensuring the health of future populations
Authors: H. Graham
Journal: BMJ (2012)

Patients on dialysis require phosphorus binders to prevent hyperphosphatemia and are iron deficient. We studied ferric citrate as a phosphorus binder and iron source. In this sequential, randomized trial, 441 subjects on dialysis were randomized to ferric citrate or active control in a 52-week active control period followed by a 4-week placebo control period, in which subjects on ferric citrate who completed the active control period were rerandomized to ferric citrate or placebo. The primary analysis compared the mean change in phosphorus between ferric citrate and placebo during the placebo control period. A sequential gatekeeping strategy controlled study-wise type 1 error for serum ferritin, transferrin saturation, and intravenous iron and erythropoietin-stimulating agent usage as prespecified secondary outcomes in the active control period. Ferric citrate controlled phosphorus compared with placebo, with a mean treatment difference of −2.2±0.2 mg/dl (mean±SEM) (<i>P</i>&lt;0.001). Active control period phosphorus was similar between ferric citrate and active control, with comparable safety profiles. Subjects on ferric citrate achieved higher mean iron parameters (ferritin=899±488 ng/ml [mean±SD]; transferrin saturation=39%±17%) versus subjects on active control (ferritin=628±367 ng/ml [mean±SD]; transferrin saturation=30%±12%; <i>P</i>&lt;0.001 for both). Subjects on ferric citrate received less intravenous elemental iron (median=12.95 mg/wk ferric citrate; 26.88 mg/wk active control; <i>P</i>&lt;0.001) and less erythropoietin-stimulating agent (median epoetin-equivalent units per week: 5306 units/wk ferric citrate; 6951 units/wk active control; <i>P</i>=0.04). Hemoglobin levels were statistically higher on ferric citrate. Thus, ferric citrate is an efficacious and safe phosphate binder that increases iron stores and reduces intravenous iron and erythropoietin-stimulating agent use while maintaining hemoglobin.
Consultants need flexibility in their careers
Authors: Z. Kmietowicz
Journal: BMJ (2002)

Hospital consultants need to be offered the flexibility to develop their career in line with their interests to prevent them from leaving the profession early, burning out, or getting bored, says a report out this week.

The report has called on the NHS, royal colleges, and faculties to provide careers advice for consultants, many of whom are dissatisfied with their workload, pressures, and increasing responsibilities.

With better career structure and possibilities of retraining, consultants will be able to avoid becoming overstressed or bored by taking breaks from clinical practice to concentrate …
NUTRITIONAL CYTOPENIA (VITAMIN M DEFICIENCY) IN THE MONKEY
Authors: William C. Langston, William J. Darby, Carroll F. Shukers, Paul L. Day
Journal: The Journal of Experimental Medicine (1938)

Young rhesus monkeys (Macaca mulatta) were given a diet containing casein, polished rice, whole wheat, salt mixture, sodium chloride, cod liver oil, and ascorbic acid. They developed a syndrome characterized by anemia, leukopenia, and loss of weight. Ulceration of the gums and diarrhea were common, and death occurred between the 26th and 100th day. 4 monkeys were given the deficient diet supplemented with 1 mg. of riboflavin daily, and these developed the characteristic signs and died. in periods of time similar to the survival of monkeys receiving the deficient diet alone. Nicotinic acid, either alone or in combination with riboflavin and thiamin chloride, failed to alter appreciably the course of the deficiency manifestations. Thus, it is evident that this nutritional cytopenia is not the result of a deficiency of vitamin B, riboflavin, or nicotinic acid. The deficient diet supplemented with either 10 gm. of dried brewers' yeast or 2 gm. of liver extract (Cohn fraction G) daily supported good growth, permitted normal body development, and maintained a normal blood picture over long periods. It is obvious that yeast and liver extract contain a substance essential to the nutrition of the monkey which is not identical with any of those factors of the vitamin B complex that have been chemically identified. We have proposed the term vitamin M for this factor which prevents nutritional cytopenia in the monkey.
Human Hematopoietic PGD2 Synthase: Inhibition by 15-deoxy–12,14-PGJ2 and Sulindac Sulfide, and Localization to Mast Cells
Authors: G.M. Greig, F. Masse, F. Nantel, A. Chateauneuf, G. O'Neill, G. O'Neill
Journal: Journal of Allergy and Clinical Immunology (2006)
Immunology in Medicine: A Comprehensive Guide to Clinical Immunology
Authors: Noel R. Rose
Journal: JAMA (1978)

Barely 25 years have passed since the demonstration of induced immunologic tolerance to neonatally injected antigens and the simulation of human autoimmune disease by experimental immunization. These experimental benchmarks have greatly broadened the scope of immunology from a medical specialty concerned primarily with the diagnosis and prevention of infectious disease to a natural science whose major concern is the recognition and distinction of self from nonself. The growth of immunology as a natural science has had impact on virtually all phases of medicine.<i>Immunology in Medicine</i>, edited by Holborow and Reeves, is designed primarily to help the practicing clinician to understand the fundamental principles and applications of immunology in order better to solve day-to-day clinical problems. The book accomplishes its goal admirably. The first chapters describe in depth the biology of the immune system, especially the cells that are responsible for specific recognition and for the production of antibodies. The
Breaks and Other Bad Breaks for Breakers
Authors: Gary R. Hansen
Journal: JAMA (1985)

<h3>To the Editor.—</h3> Recent letters have documented multiple hazards of break dancing,<sup>1-4</sup>which include masking of testicular torsion, cervical subluxation and dislocation, flank hematoma, clavicle and forearm fractures, torn or sprained ligaments, and alopecia. Two 14-year-old male adolescents were seen in the emergency department on the same day for an uncommon Salter type I fracture of the proximal humerus incurred while break dancing (Figure). Fractures of the proximal humeral epiphyseal plate represent only 3% of all physeal fractures.<sup>5</sup>These humeral fractures may occur at any age until epiphyseal closure,<sup>5,6</sup>and causes include a direct blow to the arm or a fall onto an outstretched arm.<sup>5</sup>Both our patients sustained a fracture while performing a maneuver that involved supporting all or most of the body weight on one hand for a short time during a rapid series of maneuvers. A shearing force on a relatively weak epiphyseal plate
THE TREATMENT OF CHRONIC OOPHORITIS AND ASSOCIATED CONDITIONS
Authors: T. Cameron
Journal: BMJ (1910)

CHRONIC 0 5PHORITIS.[E THE BLOURNL 69 NobleI in 1,118 collected cases found carcinoma of the body in 29 (2.4 per cent.),epithelioma of the cervix uteri in 12 (1 per cent.),sarcoma in 22 (1.8 per cent.),chorion- -epithelioma in 2 (0.16 per cent.).Another American writer who has very recently discussed this subject, Ellice MacDonald, found in 700 cases of fibromyomata malignant disease present in 35 (5 per cent.)-namely,adeno-carcinoma in 20 (2.9 per cent.),sarcoma in 7 <1 per cent.),carcinoma in 6 (0.5 per cent.),chorion- epithelioma in 2 (0.29 per cent.).Kelly and Cullen2 state that " in an examination of over 1,400 cases of myomatous ,uteri adeno-carcinoma was detected in the body of the uterus in about 1.7 per cent."Haultain,8 in a series of 120 cases, found malignant disease in 5.8 per cent.; adeno.-carcinoma in 5, and sarcoma in 2. Scharlieb,' in a series of 100 cases, found 3 cases of malignancy (1 sarcoma, 2 adeno-carcinoma).Very similar figures could be given
Substance Use and Abuse-Reply
Authors: Joseph Westermeyer
Journal: JAMA (1991)

In Reply.  —Ms Thomson raises the issue that substance use cannot be distinguished from substance abuse merely on the basis of the drug or its dose. She is correct. A pilot or surgeon might consume an amount of alcohol that might be appropriate at a dinner party, yet dangerous before a flight or an operation. Likewise, the same applies to individuals taking certain medications, or persons with certain brain conditions or who are at an age that may cause impairment by amounts that would be benign for others. These and other complexities have contributed to the development of special training and specialty status in the field. Interested persons can contact the American Society of Addiction Medicine and the American Association of Psychiatrists in Alcoholism and the Addictions.  I concur with Dr Ireland that on the basis of lifetime risk, alcohol abuse remains the major substance abuse within our profession. By
THE FAILURE OF INTRACRANIAL PRESSURE-VOLUME CHANGE TO INFLUENCE RENAL FUNCTION 1
Authors: Robert A. Fishman, Roman J. Halla
Journal: Journal of Clinical Investigation (1953)

A variety of lesions of the central nervous sys- tem may be associated with disturbances of renal function characterized by either the increased urinary loss of sodium and chloride (1-3) or the retention of salt (3-8).It has also been postu- lated that changes in the excretion of salt, second- ary to alterations in the volume of blood or extra- cellular fluid, are mediated by a "volume receptor" located in the cranial cavity (9-12).The follow- ing experiments were therefore undertaken in order to investigate the influence of alterations in intracranial venous volume and pressure, and cerebrospinal fluid (CSF) volume and pressure on renal function. METHODSFemale dogs were anesthetized with sodium pento- barbital (30 mg. per Kg.) except for two experiments in which chloralose (75 mg. per Kg.) was used.Urine was collected through an indwelling catheter.The bladder was washed out with distilled water after each collection and emptied completely by blowing out with air.Glomerular filtration rate was measured by the clearance of exogenous creatinine (Ccr) (13) and renal plasma flow was estimated from the clearance of paraminohippurate (CPAH) (14).Urine was analyzed for sodium with a flame photometer and for chloride titrimetrically (15).Cisternal, femoral arterial, and jugular venous pressures were measured with Statham strain gauges and recorded on a Brush oscillograph.Pressure in the jugular vein was obtained by passing a polyethylene catheter up to the level of the intracranial jugular bulb.
LMP-420: a novel purine nucleoside analog with potent cytotoxic effects for CLL cells and minimal toxicity for normal hematopoietic cells
Authors: Y M Mowery, J B Weinberg, M N Kennedy, K M Bond, J O Moore, M C Lanasa, J P Gockerman, L F Diehl, S V Pizzo, G J Cianciolo, D R Friedman
Journal: Leukemia (2010)
Law as a Tool to Facilitate Healthier Lifestyles and Prevent Obesity
Authors: Lawrence O. Gostin
Journal: JAMA (2007)

FACE CONSIDERABLE CHALlenges trying to prevent overweight and obesity in society, primarily because a person's own behavior is often the root cause of the disease.Individuals make personal choices about their diet, exercise, and lifestyle, so disease is often thought of as a matter of personal, not governmental, responsibility.Obesity, one of the 10 leading US health indicators, 1 is associated with increased risk of death from type 2 diabetes, hypertension, coronary heart disease, stroke, and certain cancers. 2 Yet the proportion of overweight and obese children and adults is alarmingly high and continues to increase.In 2005, 60.5% of adults in the United States were overweight (body mass index, 25-30), 23.9% were obese (body mass index, 31-40), and 3% were extremely obese (body mass index Ͼ40).African Americans have the highest obesity prevalence at 33.9%. 3The prevalence of adult obesity increased significantly in every state during the 1990s; therefore, no state will meet the targets for reduced rates of obesity set in Healthy People 2010. 4 Similarly, 16% of children and adolescents were overweight, a prevalence that has increased nearly 50% between 1999 and 2002. 5Obesity could shorten the average lifespan of an entire generation by 2 to 5 years, which, if true, would result in the first reversal in life expectancy since data were collected in 1900. 6besity primarily affects the individual, but it also has high socioeconomic costs.The aggregate consequences of individual choices are countless preventable disabilities and deaths, affecting families and the entire community.Obesityattributable medical expenditures reached $75 billion in the United States in 2003, with substantial additional indirect costs in lost productivity. 7Critics of state regulation argue that individuals should absorb the cost of their own illness, but taxpayers finance about half of all medical costs through Medicare and Medicaid, and employers cover most of the rest.The government arguably has a legitimate interest in controlling medical and social costs of individuals' unhealthy behaviors that are borne by society at large.Moreover, nonwhite and poor individuals experience substantial disproportionate burdens from obesity, with poor diet and sedentary lifestyles contributing to socioeconomic disparities.
Effect of Gallopamil on Myocardial Ischaemia During Percutaneous Transluminal Coronary Angioplasty
Authors: B. Rauch, J. Neumann, G. Richardt, R. Kranzhöfer, R. Barth, R. Zimmermann, H.P. Koch, H. Tillmanns, A. Schömig
Journal: Drugs (1991)
LEAD POISONING IN CHILDREN
Authors: CHARLES F. McKHANN
Journal: JAMA (1933)

The continued occurrence of lead poisoning in children, despite the efforts of physicians, health agencies and insurance companies to disseminate information concerning this preventable disease, warrants the presentation of a review of certain phases of the condition and a further report of the cases observed in this clinic. <h3>SOURCES OF LEAD</h3> Lead poisoning in infants may follow the prolonged use of lead nipple shields;<sup>1</sup>in Japan poisoning has occurred frequently from the use by the mother of face powder containing lead.<sup>2</sup>In infants and older children the ingestion, over a period of time, of water containing even small amounts of lead may result in intoxication. Recently there was reported an extensive series of cases of lead poisoning following the inhalation of fumes in homes where storage battery casings were used as fuel.<sup>3</sup>However, most frequently the ingestion of lead is a result of the habit observed in
Polycombs and microRNA-223 regulate human granulopoiesis by transcriptional control of target gene expression
Authors: Giuseppe Zardo, Alberto Ciolfi, Laura Vian, Linda M. Starnes, Monia Billi, Serena Racanicchi, Carmen Maresca, Francesco Fazi, Lorena Travaglini, Nelida Noguera, Marco Mancini, Mauro Nanni, Giuseppe Cimino, Francesco Lo-Coco, Francesco Grignani, Clara Nervi
Journal: Blood (2012)
Do High Proinsulin and C-Peptide Levels Play a Role in Autonomic Nervous Dysfunction?
Authors: Jari P. Töyry, Leo K. Niskanen, Matti J. Mäntysaari, Esko A. Länsimies, Steven M. Haffner, Heikki J.J. Miettinen, Matti I.J. Uusitupa
Journal: Circulation (1997)

Background Immunoreactive insulin has been shown to predict the development of parasympathetic autonomic neuropathy. It is possible that constituents of immunoreactive insulin could explain this association. In this cross-sectional study, the relationship of specific insulin, C-peptide, and proinsulin with autonomic nervous dysfunction was evaluated in 57 NIDDM patients and 108 control subjects. Methods and Results The frequency-domain analysis of heart rate variability was determined by using spectral analysis from stationary regions of registrations while the subjects breathed spontaneously in a supine position. Total power was divided into three frequency bands: low (0 to 0.07 Hz), medium (MFP, 0.07 to 0.15 Hz), and high (HFP, 0.15 Hz to 0.50 multiplied by the frequency equal to the mean RR interval). In NIDDM patients, total power, the three frequency bands ( P &lt;.001 for each), and the MFP/HFP ratio ( P =.016), which expresses sympathovagal balance, were reduced compared with control subjects. Fasting proinsulin ( r s =−.324, P =.014 for diabetics and r s =−.286, P =.003 for control subjects), C-peptide ( r s =−.492, P &lt;.001 for diabetics and r s =−.304, P =.001 for control subjects), and total immunoreactive insulin ( r s =−.291, P =.028 for diabetics and r s =−.228, P =.017 for control subjects) were inversely related to MFP/HFP. For proinsulin and C-peptide the results did not change after controlling for the effects of age, body mass index, and fasting glucose. Conclusions Both proinsulin and C-peptide levels were significantly associated with the sympathovagal balance of autonomic nervous function in NIDDM patients and control subjects, but this study cannot determine whether these compounds are directly involved in autonomic nervous dysfunction.
Abstract 3107: Novel molecular mechanisms of MDM2-induced p21Waf1 degradation
Authors: Hongxia Xu, Zhuo Zhang, Mao Li, Ruiwen Zhang
Journal: Cancer Research (2010)

Abstract The MDM2 oncogene is overexpressed in many human cancers, and the tumorigenicity of MDM2 has mainly been attributed to the auto-regulatory loop it forms with p53. However, there is increasing evidence that the tumorigenicity of MDM2 is also dependent upon its p53-independent activities. One of the p53-independent functions of MDM2 is its induction of the ubiquitin-independent proteasomal degradation of p21Waf1. The present study was designed to characterize the mechanism(s) by which MDM2 induces p21Waf1 degradation in the p53-independent setting. We determined the regions of MDM2 required for p21Waf1 degradation using pull-down assays and Western blotting, and then examined the mechanisms using limited proteolysis and fluorescence resonance energy transfer (FRET). We demonstrated that the MDM2-p21Waf1 interaction depends on MDM2's central domain, and that nuclear localization of both proteins is necessary for p21Waf1 degradation. Specifically, amino acids 226-250 of MDM2 are required for p21Waf1 binding and degradation, and amino acids 251-260 are necessary for p21Waf1 degradation. The latter region induces a conformation change in p21Waf1, increasing its binding to the C8 subunit of the proteasome, leading to its degradation. When MDM2 lacked either segment (aa 226-250 or aa 251-260), it lost its capacity to promote p21Waf1 degradation and cell cycle progression. In summary, our results demonstrate a novel mechanism by which MDM2 induces the ubiquitin-independent proteasomal degradation of an intact protein. This previously unknown chaperone-like function of MDM2 induces a conformational change in p21Waf1, leading to its increased binding to the C8 subunit of the proteasome to induce its subsequent degradation. It is possible that this mechanism may also be active for other substrates. Thus, the present study provides further evidence supporting the importance of the p53-independent activities of MDM2, confirming the significance of MDM2 as a target for cancer therapy. (Supported by NIH/NCI grants R01 CA 112029 and R01CA121211.) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3107.
Biological Determinants of Cancer Progression in Men With Prostate Cancer
Authors: Thomas A. Stamey
Journal: JAMA (1999)

ContextThe recent increase in ability to diagnose prostatic adenocarcinoma has created a dilemma for treatment decisions.ObjectiveTo determine whether prostate cancer progression is associated with a modified version of the Gleason grading system together with selected morphologic and clinical variables.DesignRetrospective analysis of a cohort of patients with peripheral zone prostate cancers who underwent surgery between August 1983 and July 1992.SettingUniversity hospital.PatientsRadical prostatectomy specimens from 379 men treated only by surgical excision were prospectively studied for 8 morphologic variables using previously standardized techniques. Variables were percentage of each cancer occupied by Gleason grade 4/5 (% Gleason grade 4/5, the Stanford modified Gleason scale), cancer volume, vascular invasion, lymph node involvement, seminal vesicle invasion, capsular penetration, positive surgical margin, prostate weight, and preoperative prostate-specific antigen (PSA) level.Main Outcome MeasureBiochemical progression of prostate cancer as indicated by serum PSA level of 0.07 ng/mL and increasing.ResultsCancer grade expressed as % Gleason grade 4/5 and cancer volume were highly predictive of disease progression. In a Cox proportional hazards model that included % Gleason grade 4/5, the traditional Gleason score was not an independent predictor of treatment failure. Positive lymph node findings and intraprostatic vascular invasion were the only other variables that remained significant at the .01 level.ConclusionThe % Gleason grade 4/5, cancer volume, positive lymph node findings, and intraprostatic vascular invasion were independently associated with prostate cancer progression, defined by an increasing PSA level. Techniques to accurately measure cancer volume and % Gleason grade 4/5 are needed to better predict which patient will experience cancer progression. The commonly accepted predictors of progression—capsular penetration and positive surgical margins—were not independently predictive of failure after radical prostatectomy.
Gastrinoma syndrome in multiple endocrine neoplasia.
Authors: D Wynick, C T Dollery, S R Bloom, J M Polak, J A Lynn
Journal: BMJ (1990)

Gastrinoma syndrome in multiple endocrine neoplasia' New approaches to localisation and management Multiple endocrine neoplasia type I is associated in 60% to 70% of patients with tumours, of the pancreatic islet cells,' which, like sporadic tumours of the islet cells, often secrete hormones.Unlike the sporadic tumours, however, multiple endocrine neoplasia type I may be associated with diffuse hyperplasia of islet cells or multiple pancreatic adenomas, or both.23The adenomas may vary in size from a small nest of cells less than 100 im in diameter to an adenoma greater than 2 cm.3 Thus the localisation and management of pan- creatic endocrine tumours in patients with the multiple endocrine neoplasia type I syndrome is often difficult, as shown by the presented case. the degree of renal impairment was mild the in- appropriately raised parathyroid hormone concentra- tion was thought to represent primary rather than tertiary hyperparathyroidism.Endoscopy showed multiple gastric and duodenal erosions, and his basal acid output was increased, at 18-3 mmol/h (normal <5 mmollh).Though the hypergastrinaemia could have been explained by the renal impairment reducing the clearance of gastrin and increasing the basal acid output, the possibility of a gastrinoma could not be excluded.Abdominal computed tomography and highly selective visceral angiography showed a 2 cm lesion in the middle third of the pancreas, with no visible hepatic metastases.