tbuckley/cabot-search huggingface dataset:
Hypomagnesemia in Type II Diabetes: Effect of a 3-Month Replacement Therapy
Authors: Nicole L Eibl, Hans-Peter Kopp, Helga R Nowak, Christoph J Schnack, Pierre G Hopmeier, Guntram Schernthaner
Journal: Diabetes Care (1995)

OBJECTIVE To investigate the effects of long-term high-dose oral magnesium (Mg) therapy (30 mmol/day) in patients with type II diabetes. Low plasma magnesium levels have been reported in type II diabetes and are associated with insulin resistance and diabetic late complications. RESEARCH DESIGN AND METHODS Forty patients with type II diabetes and hypomagnesemia were observed in a randomized double-blind placebo-controlled trial for 3 months (body mass index: 28 ± 4 kg/m2; HbA1c: 7.4 ± 0.8%). Plasma and urine magnesium and metabolic control parameters were determined, and side effects were considered, especially with regard to patients' compliance. RESULTS A significant increase in plasma magnesium levels was observed after 3 months of treatment (Mg: 0.73 ± 0.8 vs. 0.81 ±0.1 mmol/1), reaching magnesium levels of the control group (0.88 ± 0.8 mmol/1; NS); metabolic control, however, was not altered (HbA1c: 7.2 ± 0.7 vs. 7.4 ± 0.9%). Six months after the end of the trial, plasma magnesium declined to pretreatment levels (Mg: 0.73 ± 0.07 mmol/1). The prevalence of side effects was high at the beginning and was reduced significantly during treatment. CONCLUSIONS We conclude that oral magnesium replacement therapy corrects hypomagnesemia after a minimum treatment period of 3 months. These observations might be important for the prevention of diabetic late complications.
Familial Chronic Mononucleosis
Authors: MARK BALLOW
Journal: Annals of Internal Medicine (1982)

A syndrome of chronic mononucleosis occurred in two members of a family. Symptoms were chronic malaise and fatigue; recurrent upper respiratory tract infections; and mild, variable immune abnormalities. Intermittently positive heterophil titers were present for more than 2 years after acute infectious mononucleosis. Epstein-Barr-virus-specific antibodies were persistently abnormal. In the proband, the R component of the early antigen complex was present for 3 years and she never developed normal antibodies to Epstein-Barr nuclear antigen. Her brother had low to absent Epstein-Barr nuclear antigen titers, and antibodies to both the R and D component of the early antigen complex. Primary and acquired immunodeficiency states can show abnormal Epstein-Barr-virus-specific serologic findings that may reflect an attempt by the host to limit virus spread in the presence of deficient immune responses. This action may result in alterations of the Epstein-Barr virus-latent state, and lead to a chronic active infection and a syndrome of chronic mononucleosis.
Relationships between Responsiveness of the Bronchi to Acetylcholine and Cyclic AMP Response of Lymphocytes to Beta<sub>1</sub>‐ and Beta2‐Adrenergic Receptor Stimulation in Patients with Asthma
Authors: Sohei Makino, Ryosuke Ikemori, Takiishi Fukuda, Shinji Motojima
Journal: Allergy (1983)

Decreased response of beta‐adrenergic receptor has been considered to he one of the causes of increased responsiveness of the bronchi in asthma. Since beta‐adrenergic receptor has two subtypes, beta 1 and beta 2 , and the bronchodilating effect of beta stimulants is mediated by beta 2 ‐receptor, responsiveness of the bronchi is expected to correlate to the cyclic AMP response of lymphocytes to a beta 2 ‐stimulant. Responsiveness of the bronchi was expressed as respiratory threshold to acetylcholine (RT‐Ach), which was the minimal concentration of acetylcholine solution to cause an initial decrease of FEV 1 of more than 20% of the baseline value. Beta 1 and heta 2 ‐responses were expressed as the increments of cyclic AMP content of 10 6 lymphocytes incubated with norepinephrine (beta 1 ‐stimulant) and salbutamol (beta 2 ‐stimulant). RT‐Ach showed a significant correlation with the beta 2 ‐cyclic AMP response of lymphocytes, but not with the beta 1 ‐response among patients with asthma. Sixteen symptomatic patients on continuous beta‐stimulants showed lower RT‐Ach value and diminished beta 2 ‐receptor activity of lymphocytes compared with 14 patients in remission. These results suggest that selective beta 2 ‐adrenergic blockade may he one of the causes of bronchial hypersensitivity in asthma, though it should be noted that in this study beta‐adrenergic responses were examined in lymphocytes and were compared with the responsiveneness of the bronchi. Possible beta‐receptor subsensitivity induced by administration of beta‐stimulants is discussed.
Genomic Incidental Findings: Reducing the Burden to Be Fair
Authors: Velizara Anastasova, Alessandro Blasimme, Sophie Julia, Anne Cambon-Thomsen
Journal: The American Journal of Bioethics (2013)

The disclosure of incidental findings to genomic research participants is a hotly debated issue in bioethics. Gliwa and Berkman (2013) added a provocative twist to this debate by arguing that, prov...
Then There Were None
Authors: Thomas C. Coniglione
Journal: Annals of Internal Medicine (1995)

On Being a Doctor15 October 1995Then There Were NoneThomas C. Coniglione, MD and J. Arden Blough, MDThomas C. Coniglione, MDSt. Anthony Hospital Oklahoma City, OK 73101Search for more papers by this author and J. Arden Blough, MDSt. Anthony Hospital Oklahoma City, OK 73101Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-8-199510150-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail On 19 April 1995 at 9:02 a.m., a terrorist bomb destroyed the Alfred P. Murrah Federal Office Building in Oklahoma City, Oklahoma. Within minutes, the disaster plan was activated at St. Anthony Hospital, the closest medical facility. At 9:08 a.m., the first victims arrived at the emergency room in pickup trucks, cars, and vans. A red Corvette with a blown-out windshield made several trips from the blast site to the emergency room, each time leaving a bleeding victim, then speeding off to pick up another. These initial victims were treated in the emergency room for various superficial injuries caused by ... Author, Article, and Disclosure InformationAffiliations: St. Anthony Hospital Oklahoma City, OK 73101Corresponding Author: Thomas C. Coniglione, MD, St. Anthony Hospital, 1000 North Lee Street, #3129, PO Box 205, Oklahoma City, OK 73101.Current Author Addresses: Drs. Coniglione and Blough: St. Anthony Hospital, 1000 North Lee Street, #3129, PO Box 205, Oklahoma City, OK 73101. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByBlast Injuries: From Triage to Critical CareEmergency Department Impact of the Oklahoma City Terrorist Bombing 15 October 1995Volume 123, Issue 8Page: 630-632KeywordsAmbulancesArmed forcesBloodEmergency departmentLacerationsResearch laboratoriesSurgeonsSurgeryTraumatic injuryTriage Issue Published: 15 October 1995 CopyrightCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Topical Tretinoin for Photoaged Skin
Authors: Bert G. Tavelli
Journal: JAMA (1988)

To the Editor.  —The report by Weiss et al 1 as well as the accompanying editorial 2 engender vast medical, economic, and social considerations. Pronouncements such as these should be founded on extensive and scientifically sound data and conclusions, which we found lacking in this study.  The conclusions of the study are based on a combination of clinical and histopathologic findings in 30 patients (only 15 patients were treated on their faces) after only four months of treatment with topical tretinoin cream. All clinical findings are based on the subjective observations of a single observer. Clearly, any conclusions suggesting reversal of 35 to 70 years (range of patient ages) of photoaging are tenuous and premature.  The main difficulty, however, is that the study is not, as stated in the subtitle, double-blind. Fully 92% of patients treated with tretinoin experienced an irritant dermatitis. This required administration of potent topical steroids to
Paroxysmal Cold Hemoglobinuria
Authors: Charles H. Banov
Journal: JAMA (1960)

Paroxysmal cold hemoglobinuria is not a common disease. In more than 500,000 patients over a 20-year period at the University of Chicago Clinics, Becker<sup>1</sup>reported only one case of this disease. Mackenzie<sup>2</sup>reviewed the history of the disorder and noted that it was partially observed as early as 1794. Dressler differentiated hemoglobinuria from hematuria in 1854. In 1880, Rosenback noted that hemoglobinuria could be produced in affected individuals by placing the hands and feet in ice water. In 1904, Donath and Landsteiner developed in vitro tests to demonstrate the cold hemolysin, and Mackenzie modified this by a test in which no complement is added. In 1885, Murri<sup>3</sup>was the first to point out the relationship between cold hemoglobinuria and syphilis. Becker reviewed 37 cases of syphilitic paroxysmal cold hemoglobinuria found in the literature since 1930 and attempted to differentiate between the syphilitic and the nonsyphilitic types, stating
RELATION OF PULSE WAVE VELOCITY MEASURED BY COMPUTED TOMOGRAPHY ANGIOGRAPHY WITH VULNERABLE CHARACTERISTICS OF CORONARY PLAQUE COMPOSITION AMONG PATIENTS WITH AND WITHOUT RHEUMATOID ARTHRITIS
Authors: Naser Ahmadi, Fereshteh Hajsadeghi, Tae-Young Choi, Ferdinand Flores, Silvia Munoz, Ramin Ebrahimi, Matthew Budoff, George Karpouzas
Journal: Journal of the American College of Cardiology (2011)
Abstract 2487: Mechanism of action KX01 (KX2-391), a novel tubulin polymerization and Src signaling inhibitor proceeding to Phase II clinical trials
Authors: YAHAO BU, Michael Smolinski, Jun Qu, Latif Kazim, Irwin Gelman, Lyn Dyster, David Hangauer
Journal: Cancer Research (2010)

Abstract KXO1 (KX2-391) has completed Phase I clinical trials in cancer patients and is now proceeding to Phase II. KXO1 was first characterized as a Src signaling inhibitor that exhibits potent anti-proliferative activity against a broad range of solid and liquid human cancers in vitro and in mouse models, including synergistic activity with other drugs. Using photo-affinity labeling technology, we have discovered that KXO1 also binds to tubulin at a novel binding site, and inhibits tubulin polymerization. KXO1 leads to cell cycle arrest at M phase with subsequent cell death mediated by canonical apoptosis pathways including phosphorylation of Bcl-2, loss of mitochondrial membrane permeability, and activation of caspases. Interestingly, inhibition of caspase activity by Z-VAD-FMK abrogates KXO1 induced cell death of HT29 and LNCaP cells but not in PC3-LN4 cells, suggesting the existence of caspase independent pathways capable of executing KXO1-induced cell death in certain cell types. In multi-drug resistant cancer cell lines, which overexpress p-glycoprotein, KXO1 still has equally potent anti-proliferative activity with GI50's in the low nanomolar range. KXO1 also exhibits strong anti-angiogenesis and vascular disrupting activities as revealed by an in vitro vasculature tube formation assay. KXO1 demonstrates robust activity in prostate cancer mouse xenograft models. The safety, tolerability and MTD were determined for KXO1 in a Phase 1 clinical study in patients with advanced malignancies refractory to conventional therapies. KXO1 was well tolerated at the MTD of 40 mg BID; only 1 out of 17 SAE's reported at or below the MTD was assessed as possibly KXO1-treatment related. Phase II clinical trial in prostate cancer patients will commence in early 2010. 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 2487.
ANTHRAX AT CAMP HANCOCK, GA.
Authors: JOHN B. LUDY
Journal: JAMA (1918)

The possibility of the appearance of the skin manifestations of anthrax from time to time is admitted, and the necessity of having a clear idea of the classic picture of an anthrax pustule is therefore apparent. In reporting three cases of anthrax occurring in this camp within four weeks, we hope to impress on the reader the distinguishing points in diagnosis, and the necessity for early treatment. Anthrax is definable as a specific and highly contagious disease due to<i>Bacillus anthracis</i>. Fortunately the organism never enters the unbroken skin, but gains entrance at the site of an abrasion. Any commercial animal product—hide, hair or wool— and the articles manufactured therefrom afford the source of contagion. <h3>SYMPTOMS</h3> The usual appearance of the skin manifestations of anthrax is as follows: Following a period of incubation varying from one to five days, a small red papule appears at the site of abrasion, with
Deleterious effects of oxygen radicals in ischemia/reperfusion. Resolved and unresolved issues.
Authors: R A Kloner, K Przyklenk, P Whittaker
Journal: Circulation (1989)

Oxygen free radicals are known to be generated during periods of ischemia followed by reperfusion. There is still some controversy, however, concerning the use of electron paramagnetic resonance spectroscopy to accurately detect and identify the free radical species that are formed. There is no doubt that oxygen radicals are deleterious to the myocardium; free radicals cause left ventricular dysfunction and structural damage to myocytes and endothelial cells in both in vitro and in vivo preparations. Potential sources of these cytotoxic oxygen species include the xanthine oxidase pathway, activated neutrophils, mitochondria, and arachidonate metabolism, yet the crucial source of free radicals in the setting of ischemia and reperfusion is unresolved. There is little doubt that oxygen radicals play a role in the phenomenon of stunned myocardium induced by brief periods of ischemia followed by reperfusion; numerous studies have consistently observed that pretreatment with free radical scavengers and antioxidants enhances contractile function of stunned, postischemic tissue. Whether oxygen free radical scavengers administered only during reperfusion enhance recovery of stunned myocardium in models of brief ischemia remains to be determined. In models of prolonged ischemia (2 hours) followed by reperfusion, we have not observed a beneficial effect of scavengers on stunned myocardium. The issue of whether oxygen free radical scavengers are capable of reducing so-called irreversible or lethal reperfusion injury remains, in our opinion, unresolved. Although some studies have observed that agents such as superoxide dismutase and catalase reduce infarct size in ischemia and reperfusion models, many others have reported negative results. Additional studies will be needed to resolve this ongoing controversy. Oxygen free radicals may also contribute to reperfusion-induced arrhythmias in rodent heart preparations; however, less data are available in other animal models. The concept of reperfusion injury should not be considered a deterrent to reperfusion for the treatment of acute myocardial infarcts in the clinical setting. Thrombolytic therapy reduces myocardial infarct size, enhances recovery of left ventricular function, and improves survival. Whether incremental beneficial effects on these parameters will be obtained when oxygen radical-scavenging agents are used as adjuvant therapy to thrombolysis in patients remains to be determined.
Westminster primary care trust introduces programme to prevent heart disease
Authors: O. Mashta
Journal: BMJ (2009)

The health minister Ara Darzi has unveiled an innovative community based programme to prevent cardiovascular disease, which he hopes will be replicated throughout the United Kingdom.

The programme, called Healthy Hearts and Minds is the most comprehensive cardiovascular disease prevention programme in England, according to the commissioning body, NHS Westminster, and will cost it about £7m (€8m;$10m) over three years. 

The trust says that the programme offers unique benefits, by saving lives, saving money by preventing expensive hospitalisation, and tackling health inequities.

The programme includes three initiatives—checks to assess vascular risk to be carried out at general practices and extended to pharmacies from April; a programme to prevent vascular disease; and a new community …
Ultra-rapid delayed rectifier channels: molecular basis and therapeutic implications
Authors: U. Ravens, E. Wettwer
Journal: Cardiovascular Research (2010)

The ultrarapid delayed rectifier channels have attracted considerable interest as targets for 'atrial-selective' antiarrhythmic drugs because they contribute to atrial but not to ventricular repolarization. Thus, IKur channel blockers are expected to prolong selectively the atrial effective refractory period without inducing proarrhythmic effects due to excessive ventricular action potential prolongation. Here we provide an overview of the properties of IKur channels in expression systems and native cardiomyocytes. The ion conducting pore of the channel is formed by four Kv1.5 α-subunits, whereas the ancillary β-subunits Kvβ1.2, Kvβ1.3, and Kvβ2.1 control channel trafficking and plasma membrane integration as well as activation and inactivation kinetics. Investigation of IKur channel blockers in cardiomyocytes is complicated (i) by substantial overlap of IKur with other currents, notably the transient outward current Ito, (ii) by lack of drug selectivity, and (iii) by disease-induced regulation of IKur. Some new compounds developed as IKur blockers are described and their efficacy in treatment of atrial fibrillation (AF) is discussed. Current evidence suggests that pure IKur channel block may not be sufficient to suppress AF.
Is There a Good MAP for Septic Shock?
Authors: James A. Russell
Journal: New England Journal of Medicine (2014)

As fundamental as the issue is, there is no clear, high-level evidence to determine the most effective mean arterial pressure (MAP) for resuscitation of patients with septic shock. During hypotension, three salient aspects of cardiovascular physiology are important. First, the autoregulation of cerebral blood flow maintains an adequate level over a wide range of pressures until a critical pressure (about 50 mm Hg) is reached; below this level, as the pressure falls, so does cerebral blood flow. Second, chronic hypertension shifts the autoregulatory curve of the relationship between pressure and perfusion so that perfusion is decreased at a higher critical . . .
Broken Thermometer in Child's Rectum.
Authors: H. Speier
Journal: JAMA (1906)

Rochester, Minn., Dec. 6, 1906. <h3>To the Editor:</h3> —I was interested in the report of a broken thermometer in a child's rectum, inThe Journal, Dec. 1, 1906, page 1841, and was surprised to read that no other such case was found recorded. A similar case occurred in my practice about twelve years ago. A child about a year and a half old seemed indisposed and the mother proceeded to take the temperature by rectum. The child made a sudden movement and the instrument broke off at the upper constriction, leaving the bulb in the rectum. I reached the house about an hour afterward. The child was evidently in pain, crying and straining ineffectually. An anesthetic was given, and with the aid of a small bivalve ear speculum the bulb was extracted. It was placed somewhat obliquely; the sharp, jagged end had penetrated the mucous membrane, thus probably frustrating the
3BP2-deficient mice are osteoporotic with impaired osteoblast and osteoclast functions
Authors: Noam Levaot, Paul D. Simoncic, Ioannis D. Dimitriou, Andrew Scotter, Jose La Rose, Adeline H.M. Ng, Thomas L. Willett, Chiachien J. Wang, Salima Janmohamed, Marc Grynpas, Ernst Reichenberger, Robert Rottapel
Journal: Journal of Clinical Investigation (2011)

A fine balance between bone resorption by osteoclasts and bone formation by osteoblasts maintains bone homeostasis. In patients with cherubism, gain-of-function mutations in 3BP2, which is encoded by SH3-domain binding protein 2 (SH3BP2), cause cystic lesions with activated osteoclasts that lead to craniofacial abnormalities. However, little is known about the function of wild-type 3BP2 in regulating bone homeostasis. Here we have shown that 3BP2 is required for the normal function of both osteoblasts and osteoclasts. Initial analysis showed that Sh3bp2–/–mice developed osteoporosis as a result of reduced bone formation despite the fact that bone resorption was impaired. We demonstrated using reciprocal bone marrow chimeras, a cell-intrinsic defect of the osteoblast and osteoclast compartments in vivo. Further, Sh3bp2–/– osteoblasts failed to mature and form mineralized nodules in vitro, while Sh3bp2–/– osteoclasts spread poorly and were unable to effectively degrade dentine matrix in vitro. Finally, we showed that 3BP2 was required for Abl activation in osteoblasts and Src activation in osteoclasts, and demonstrated that the in vitro defect of each cell type was restored by the respective expression of activated forms of these kinases. These findings reveal an unanticipated role for the 3BP2 adapter protein in osteoblast function and in coordinating bone homeostatic signals in both osteoclast and osteoblast lineages.
Assessing Readiness for Medical Education
Authors: William C. McGaghie
Journal: JAMA (2002)

The attrition rate of 5% to 50% from US medical schools in the 1920s propelled the development of a test that would measure aptitude for medical studies. Since its development in 1928, the Medical College Admission Test (MCAT) has undergone 5 revisions. The first version was divided into 6 to 8 subtests that focused on memory, knowledge of scientific terminology, reading and comprehension, and logic. The second, which appeared in 1946, was reduced to 4 categories: verbal and quantitative skills, science knowledge, and added a category called understanding modern society. The major difference in the third version, launched in 1962, expanded the test's understanding modern society section to a broader test of general information. In 1977, the MCAT underwent its fourth change: its science section, reading and quantitative skill assessment sections were expanded; its general liberal arts knowledge section was eliminated; its scoring report structure and scoring range were altered; and its cultural and social bias was minimized. The current version, beginning in 1991, has undergone another significant change. Although it does not contain independent measures of either liberal arts or numeracy as separate categories, quantitative skills are needed to solve some of the problems in biological and physical sciences. However, its principal innovation is the writing sample section. Through its 74-year history, the various renditions of the MCAT demonstrate that the definition of aptitude for medical education reflects the professional and social mores and values of the time.
Fatal Relapse of Coccidioidomycosis Ten Years after Treatment with Amphotericin B
Authors: Pierce Gardner, Earl W. Fuller
Journal: New England Journal of Medicine (1969)

SINCE the introduction of amphotericin B for parenteral administration in 1957, there have been numerous reports of its success in the treatment of patients with disseminated coccidioidomycosis.1 , 2 Treatment failures have generally been due to primary drug failures or relapse within a short time of therapy.2 3 4 The effect of amphotericin B on the tendency to late relapse in patients with disseminated coccidioidomycosis is not known. This case report, documenting relapse 10 years after apparently successful therapy, emphasizes the necessity for lifelong follow-up observation of treated patients. Case Report L.D., a 53-year-old Negro, entered the hospital on December 4, 1968, because of . . .