tbuckley/cabot-search huggingface dataset:
Hereditary Factors in Atrial Septal Defect
Authors: JAMES J. NORA, DAN G. MCNAMARA, F. CLARKE FRASER
Journal: Circulation (1967)

One hundred families ascertained through a proband's having atrial septal defect (ostium secundum) were studied. Selection of certain pedigrees from the overall data could lead to the conclusion that atrial septal defect is inherited as a Mendelian dominant or a Mendelian recessive, depending on the pedigrees selected. Analysis of the overall data from this study and from the literature suggests multifactorial inheritance of atrial septal defect as the explanation most consistent with available observations. The distinction between inheritance of a defect through single factor or multifactorial modes is of more than academic interest. From the point of view of genetic counseling, the risk to the newborn is not fixed in multifactorial inheritance but increases with the number of affected relatives. From the point of view of prevention, environmental hazards such as drugs and illnesses may play an important role in the production of defects showing multifactorial inheritance.
The American Medical Association
Authors: Norman A. Welch
Journal: New England Journal of Medicine (1964)

ONE hundred and sixteen years have passed since May 5, 1847, when a handful of physicians attended the live birth of the American Medical Association. In this interim of time, the A.M.A. has achieved an impressive and enduring record in devoting its efforts to a singular, simply stated dedication written indelibly into its Constitution: "To promote the science and art of medicine and the betterment of public health."The A.M.A. has pursued its twin goals vigorously over these many years and has demonstrated a distinct and desirable virility for accomplishment. Its leadership and guidance have been eagerly sought and earnestly . . .
Tumor cell-free autologous marrow fights leukemia
Authors: Terra Ziporyn
Journal: JAMA (1983)

Several methods for purging tumor cells from the marrow of leukemic patients continue to make autologous bone marrow transplants a viable treatment alternative to the more common allogeneic transplants for such patients (<i>JAMA</i>[MEDICAL NEWS] 1982; 248:2213-2215). The transplants are carried out with curative intent in patients in second remission who have undergone chemotherapy and total body irradiation. In fact, according to George W. Santos, MD, professor of oncology and medicine and director of the bone marrow transplantation program at the Johns Hopkins University Oncology Center, Baltimore, autologous transplants may be possible in patients as old as 55 years. Santos presented his group's work at the recent International Symposium of the International Association for Comparative Research on Leukemia and Related Diseases in Cambridge, England. In many ways the problem of getting tumor cells out of autologous marrow resembles the problem of getting T cells that cause graft-<i>v</i>-host disease
Mahir Shakir Mahir
Authors: Ragheed Al Mufti
Journal: BMJ (2005)

​ConsultantConsultant surgeon London (b Baghdad 1954; q Baghdad 1977; PhD, BSc, FRCS Ed), died from stomach cancer on 15 April 2005




Figure 1




Mahir Shakir Mahir graduated with first class honours in Baghdad and did his PhD in London. He worked at hospitals throughout England before being appointed as a consultant surgeon at Newham University Hospital in 1995, where he was also lead clinician and associate clinical tutor. He moved to St Bartholomew's and Homerton University hospitals in 2000 as a consultant in general and breast surgery. He was also a clinical tutor and the lead surgeon at the Homerton. He leaves a wife, Dr Hameed-Nasrat, and two children.
Serum Cholesterol-Reply
Authors: Irving S. Wright
Journal: JAMA (1976)

The statement quoted in Dr Barach's letter was obtained from Dr William B. Kannel and confirmed by the Atherosclerosis Committees of the American Heart Association and the Inter-Society Commission for Heart Disease Resources. Dr Frederickson's position in this matter is well known. While the evidence is not conclusive beyond any question, the statement in my article does represent the opinion of many authorities in this field based on the total information available as of this time.
Use of Twice-Daily Exenatide in Basal Insulin–Treated Patients With Type 2 Diabetes
Authors: John B. Buse, Richard M. Bergenstal, Leonard C. Glass, Cory R. Heilmann, Michelle S. Lewis, Anita Y.M. Kwan, Byron J. Hoogwerf, Julio Rosenstock
Journal: Annals of Internal Medicine (2011)

Background: Insulin replacement in diabetes often requires prandial intervention to reach hemoglobin A1c (HbA1c) targets. Objective: To test whether twice-daily exenatide injections reduce HbA1c levels more than placebo in people receiving insulin glargine. Design: Parallel, randomized, placebo-controlled trial, blocked and stratified by HbA1c level at site, performed from October 2008 to January 2010. Participants, investigators, and personnel conducting the study were masked to treatment assignments. (ClinicalTrials.gov registration number: NCT00765817) Setting: 59 centers in 5 countries. Patients: Adults with type 2 diabetes and an HbA1c level of 7.1% to 10.5% who were receiving insulin glargine alone or in combination with metformin or pioglitazone (or both agents). Intervention: Assignment by a centralized, computer-generated, random-sequence interactive voice-response system to exenatide, 10 µg twice daily, or placebo for 30 weeks. Measurements: The primary outcome was change in HbA1c level. Secondary outcomes included the percentage of participants with HbA1c values of 7.0% or less and 6.5% or less, 7-point self-monitored glucose profiles, body weight, waist circumference, insulin dose, hypoglycemia, and adverse events. Results: 112 of 138 exenatide recipients and 101 of 123 placebo recipients completed the study. The HbA1c level decreased by 1.74% with exenatide and 1.04% with placebo (between-group difference, −0.69% [95% CI, −0.93% to −0.46%]; P < 0.001). Weight decreased by 1.8 kg with exenatide and increased by 1.0 kg with placebo (between-group difference, −2.7 kg [CI, −3.7 to −1.7]). Average increases in insulin dosage with exenatide and placebo were 13 U/d and 20 U/d. The estimated rate of minor hypoglycemia was similar between groups. Thirteen exenatide recipients and 1 placebo recipient discontinued the study because of adverse events (P < 0.010); rates of nausea (41% vs. 8%), diarrhea (18% vs. 8%), vomiting (18% vs. 4%), headache (14% vs. 4%), and constipation (10% vs. 2%) were higher with exenatide than with placebo. Limitations: The study was of short duration. There were slight imbalances between groups at baseline in terms of sex, use of concomitant glucose-lowering medications, and HbA1c levels, and more exenatide recipients than placebo recipients withdrew because of adverse events. Conclusion: Adding twice-daily exenatide injections improved glycemic control without increased hypoglycemia or weight gain in participants with uncontrolled type 2 diabetes who were receiving insulin glargine treatment. Adverse events of exenatide included nausea, diarrhea, vomiting, headache, and constipation. Primary Funding Source: Alliance of Eli Lilly and Company and Amylin Pharmaceuticals.
Rocky Mountain Labs: NIAID’s Montana campus
Authors: Karen Honey
Journal: Journal of Clinical Investigation (2009)

The Division of Intramural Research (DIR) is a branch of the National Institute of Allergy and Infectious Diseases (NIAID). A fact not widely known about the DIR is that more than 20% of its research is conducted in western Montana at the Rocky Mountain Laboratories (RML) (Figure 1). Furthermore, RML soon will house one of the very few biosafety level four (BSL4) facilities — laboratories with the strictest levels of biosafety, biocontainment, and security — in the US.
Enhanced normal short-term human myelopoiesis in mice engineered to express human-specific myeloid growth factors
Authors: Paul H. Miller, Alice M. S. Cheung, Philip A. Beer, David J. H. F. Knapp, Kiran Dhillon, Gabrielle Rabu, Shabnam Rostamirad, R. Keith Humphries, Connie J. Eaves
Journal: Blood (2012)
Post-operative Pulmonary Complications
Authors: B. N. Sircar, F. K. Boston
Journal: BMJ (1940)

~~~~~~~~~~~~~~~~~~~~~~~~~~~~MEDICAL JOURNAL has become available since the clinical study was beguin.Thus Widenba-uer and Heckler (1939) found that cows' milk varied from 13 to 57 y/ per 100 gramnmes, with an average figure of 32 y, and human milk from forty-two working-class women varied from 2 >a to 36 per 100 grammes.Morgan and Haynes (1939) similarly found that the milk of two women on very different B, intakes contained 11 and 32 y per .100grammes, and that 5 mg.daily of crystalline B1 given to both mothers for a month resulted in an increased B1 content of the milk which had previously contained 11 but no increase in the other milk.From these considerations and from the clinical resuLlts recorded it therefore appears probable that supplements of vitamin B, derived from natural sources and providing not less than 100 units daily can usefully be given to infants whose progress is unsatisfactory.Acknowledgments are made to Dr. Chodak Gregory for per- mission to publish these observations and for her advice.also to Mr. H. C. H. Graves of Vitamins Limited for supplying the vitamin B, preparation used at a much reduced rate
The old case: Thorax in the 1970s
Authors: A Seaton
Journal: Thorax (2006)

As a young consultant in Cardiff in the 1970s I inherited two things: a battered old brown bakelite case that had been carried by earlier South Wales tuberculosis doctors and the editorship of Thorax . The two fitted well together. The work was shared with the surgical editors, Ben Milstein then Hugoe Matthews, who dealt with thoracic surgery and anatomy, the rest coming to me. The BMJ agreed to buy me an electric typewriter and pay secretarial expenses. Approximately one or two papers arrived each day, to be filed in the brown case. This held about 15, and it was possible to carry a week’s work together with my stethoscope wherever I went; when it was full I knew I had to deal with it. The process was quite simple and conducted by letter. Like my predecessors, I read every paper, decided whether it was of sufficient interest and, if it was, wrote to a referee asking for his or her opinion on the science and giving my personal views, thus immediately introducing a bias. Sometimes, if I didn’t think it at all interesting, I rejected it politely but firmly without asking a referee. Occasionally this attracted some discussion with the authors and once resulted in a death threat (from an …
Static and dynamic components in the vascular myogenic response to passive changes in length as revealed by electrical and mechanical recordings from the rat portal vein.
Authors: B Johansson, S Mellander
Journal: Circulation Research (1975)

The effects of static and dynamic passive stretch and shortening on electrical activity and active force were analyzed in the isolated rat portal vein. Static stretch by 40% of muscle length evoked moderate excitatory effects with enhanced mechanical activity and an average increase in spike discharge of 12% above the control value of 55 plus or minus 2.6 spikes/min. The dynamic responses studied at various rates of length change (dL/dt) over the range between minus 12 and plus 12 mm/min, i.e., minus 3 and plus 3% muscle length/sec, were much more pronounced. Active force and spike activity showed graded increases with increasing rates of stretch. The electrical activity reached a value of 180 spikes/min (approximately equal to 325% of control) at 5 mm/min; this frequency was then maintained for stretch rates up to 12 mm/min. Mechanical activity during stretch was further reinforced by the shift along the length-tension diagram. Passive shortening at rates from minus 1 to minus 12 mm/min caused graded decreases in mechanical and electrical activity below the control levels, complete inhibition being observed at the latter dL/dt. Blockade of alpha and beta receptors indicated that the responses were myogenic in nature. The findings seem to provide direct support for the myogenic hypothesis of vascular tone and responses to stretch of the vascular wall, but they indicate that emphasis should be placed on the dynamic characteristics of the stimulus rather than its static nature. This emphasis constitutes a new concept in the myogenic control of the peripheral circulation.
Drugs Five Years Later: Naloxone
Authors: WILLIAM R. MARTIN
Journal: Annals of Internal Medicine (1976)

Narcotic analgesics and related drugs act as agonists on several receptors that are responsible for their effects on pain perception, mood and feeling state, and respiration, as well as other pharmacologic actions. Naloxone is the first discovered antagonist that is devoid of agonistic activity and appears to be a competitive antagonist at several receptors. The ability of naloxone to displace or prevent the binding of agonistic narcotics is partly responsible for its antagonistic effects. The ability of naloxone to rectify narcotic-depressed homeostats and precipitate abstinence is also related to its antagonistic activity. Certain cautions and principles apply in the use of naloxone in treating narcotic overdose, reversing surgical analgesia, and the treatment of neonates and children. Unapproved uses of naloxine include reversing the psychotomimetic effects of certain agonists-antagonists, terminating narcotic-induced convulsions and coma, reversing non-narcotic depression, diagnosing physical dependence, and treating narcotic addicts.
Rifaximin reduces endotoxemia and improves liver function and disease severity in patients with decompensated cirrhosis
Authors: Georgios N. Kalambokis, Epameinondas V. Tsianos
Journal: Hepatology (2011)

We read with great interest the article by Nolan regarding the pathogenetic role of intestinal endotoxin in the development of liver injury.1 Increased circulating levels of gut-derived endotoxin2 and specific sensitivity to endotoxin have been shown in cirrhosis,3 which could worsen further hepatic impairment. However, the effects of changing gut flora on liver function in patients with cirrhosis remain unclear. Treatment with synbiotics improved the Child-Pugh class as a result of significant improvements in serum bilirubin and albumin levels and in prothrombin activity.4 Additionally, probiotics reduced endotoxemia and improved the Child-Pugh score, although not significantly, in patients with compensated cirrhosis.5 Finally, treatment with paromomycin and neomycin for 3-6 months significantly improved serum albumin levels6 and the Child-Pugh score, mainly because of a decreased incidence of ascites and encephalopathy,7 respectively. Herein, we present preliminary data on the effects of rifaximin, a virtually unabsorbable antibiotic with broad-spectrum antimicrobial activity and an excellent safety profile8 on endotoxemia and liver function and disease severity in 9 liver transplant candidates with alcoholic cirrhosis (male, n = 7; mean age = 56 ± 6 years; Child-Pugh class B/C: 5/4). All patients abstained from alcohol for at least 1 year before inclusion. Plasma endotoxin levels were detected by the Limulus amebocyte lysate chromogenic endpoint assay (Hycult Biotech, Uden, The Netherlands). Clinical infection, upper gastrointestinal bleeding, and use of antibiotics or prebiotics 6 weeks before or during the study were exclusion criteria. Patients were evaluated after an 8-week observational period and after an 8-week course of rifaximin (1,200 mg/day). All measures remained unchanged during the observational period. Rifaximin significantly reduced plasma endotoxin levels, together with a significant increase in serum albumin levels and significant decreases in serum total bilirubin levels and international normalized ratio. Child-Pugh and model for end-stage liver disease scores decreased significantly after treatment (Table 1). In conclusion, intestinal decontamination by rifaximin could be a feasible, safe approach to prevent endotoxin-induced liver injury and improve liver function and disease severity in patients with decompenstaed cirrhosis. The present findings should be confirmed in a placebo-controlled trial. Georgios N. Kalambokis M.D.*, Epameinondas V. Tsianos M.D., Ph.D., F.E.B.G., A.G.A.F.*, * 1st Division of Internal Medicine and Hepato-Gastroenterology Unit University Hospital, Ioannina, Greece.
A novel device for rapid cleaning of poorly prepared colons
Authors: M. Moshkowitz, Y. Hirsch, I. Carmel, T. Duvdevany, I. Fabian, E. Willenz, J. Cohen
Journal: Endoscopy (2010)

Background: Adequate colon preparation is essential for the quality and accuracy of colonoscopy and has a significant influence on related costs. The aim of this study was to assess the efficacy and safety of a novel attachable colon-cleaning device used during colonoscopies in porcine colon.
Development and evaluation of vinpocetine inclusion complex for brain targeting
Authors: Jiaojiao Ding, Jinfeng Li, Shirui Mao
Journal: Asian Journal of Pharmaceutical Sciences (2014)

The objective of this paper is to prepare vinpocetine (VIN) inclusion complex and evaluate its brain targeting effect after intranasal administration. In the present study, VIN inclusion complex was prepared in order to increase its solubility. Stability constant (Kc) was used for host selection. Factors influencing properties of the inclusion complex was investigated. Formation of the inclusion complex was identified by solubility study and DSC analysis. The brain targeting effect of the complex after intranasal administration was studied in rats. It was demonstrated that properties of the inclusion complex was mainly influenced by cyclodextrin type, organic acids type, system pH and host/guest molar ratio. Multiple component complexes can be formed by the addition of citric acid, with solubility improved for more than 23 times. Furthermore, In vivo study revealed that after intranasal administration, the absolute bioavailability of vinpocetine inclusion complex was 88%. Compared with intravenous injection, significant brain targeting effect was achieved after intranasal delivery, with brain targeting index 1.67. In conclusion, by intranasal administration of VIN inclusion complex, a fast onset of action and good brain targeting effect can be achieved. Intranasal route is a promising approach for the treatment of CNS diseases.
Molecular Mechanisms of Prolactin and Its Receptor
Authors: Charles L. Brooks
Journal: Endocrine Reviews (2012)

Prolactin and the prolactin receptors are members of a family of hormone/receptor pairs which include GH, erythropoietin, and other ligand/receptor pairs. The mechanisms of these ligand/receptor pairs have broad similarities, including general structures, ligand/receptor stoichiometries, and activation of several common signaling pathways. But significant variations in the structural and mechanistic details are present among these hormones and their type 1 receptors. The prolactin receptor is particularly interesting because it can be activated by three sequence-diverse human hormones: prolactin, GH, and placental lactogen. This system offers a unique opportunity to compare the detailed molecular mechanisms of these related hormone/receptor pairs. This review critically evaluates selected literature that informs these mechanisms, compares the mechanisms of the three lactogenic hormones, compares the mechanism with those of other class 1 ligand/receptor pairs, and identifies information that will be required to resolve mechanistic ambiguities. The literature describes distinct mechanistic differences between the three lactogenic hormones and their interaction with the prolactin receptor and describes more significant differences between the mechanisms by which other related ligands interact with and activate their receptors.
Serial circulating markers of inflammation in biliary atresia—Evolution of the post-operative inflammatory process
Authors: Bommayya Narayanaswamy, Christopher Gonde, Michael J. Tredger, Munther Hussain, Diego Vergani, Mark Davenport
Journal: Hepatology (2007)

Biliary atresia (BA) may be characterized as an occlusive cholangiopathy affecting both intra- and extra-hepatic parts of the biliary tree, together with a pronounced inflammatory response consisting of hepatic infiltration of (predominantly) CD4+ lymphocytes and macrophages. Soluble cellular adhesion molecules are also known to be raised at the time of portoenterostomy, presumably reflecting intrahepatic disease. We investigated this measurable inflammatory component longitudinally by studying a panel of cellular adhesion molecules (soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule-1 [sVCAM-1]) and soluble proinflammatory mediators (T helper 1 [interleukin [IL]-2 and interferongamma] and T helper 2 [IL-4 and IL-10]) cytokines and macrophage markers (tumor necrosis factor [TNF] alpha and IL-18) in 21 consecutive infants with BA post-Kasai portoenterostomy (KP). The levels of all adhesion molecules and cytokines (except IL-10) increased progressively by 6 months post-portoenterostomy. The response was non-polarized but with 100-fold increases in IL-2, TNFalpha and IL-18 particularly but only modest elevations in IL-10. When proinflammatory profiles were related to outcome, we found poor discrimination if assessed as clearance of jaundice but markedly higher values for IL-2, interferongamma, IL-4, IL-10, TNFalpha and sICAM-1 for those who would be transplanted by 1 year. Using ROC curve analysis for sICAM-1 levels at 1 month post-KP, a cutoff level of 1,779 ng/ml was determined to predict the need for transplantation at 1 year with 92% specificity and 87% sensitivity.The early circulating inflammatory process in BA is persistent, progressive and involves a non-polarized T cell, macrophage and cell adhesion molecule response only partially ameliorated by KP.
Anoxic hepatocyte injury: Role of reversible changes in elemental content and distribution
Authors: Marc L. Berger, Rolland C. Reynolds, Herbert K. Hagler, Dennis Bellotto, Dorabeth Parsons, Kevin J. Mulligan, Maximilian L. Buja
Journal: Hepatology (1989)

Examination of anoxic isolated hepatocytes by light and electron microscopy indicated that initial morphologic changes were largely localized to the periphery of the cells. This early phase consisted of surface bleb formation but was not accompanied by alterations in parameters of plasma membrane integrity (leakage of cellular enzymes, exclusion of trypan blue). The time course of changes in structure was temporally related to alterations in the elemental distribution and content of various subcellular compartments. These studies, which employed electron probe X-ray microanalysis, demonstrated that rapid increases in the sodium and chlorine content and decreases in the potassium content of the cytoplasm, mitochondria and nucleus occurred, whereas no change in the calcium content of any subcellular compartment was detected. Concurrently, two cellular functions known to be dependent upon ion homeostasis, sodium-dependent taurocholate uptake and mitochondrial respiratory control, became markedly impaired. Reoxygenation within 30 min resulted in the restoration of both elemental distribution and the latter two functions to baseline. These data are consistent with the hypothesis that some early functional changes may be mediated by altered ion homeostasis. In contrast, additional studies indicated that sodium and water fluxes could be dissociated from the appearance of plasma membrane blebs. Thus, this study provides direct evidence that the structural and functional changes of early anoxic hepatocyte injury cannot be explained by a single mechanistic cascade, but apparently involve multiple mechanisms which may not be directly linked.