tbuckley/cabot-search huggingface dataset:
Role of Vitamins in Embryonic Development
Authors: D. H. M. Woollam, J. W. Millen
Journal: BMJ (1956)

MYASTHENIA GRAVIS MEDICAJORNAL15 are in complete remission and not taking neostigmine at the time of writing, and 9 others (a total of 24, or 55%) have transient or minimal ocular symptoms only.TABLE III.-Contemporary Assessment of the SeriesGroup 1 (minimal or no disability) .24 2 (slight disability) .13 3 (moderate ,, ).7 4 (severe ,, ).0 Dead.9 Not traced.7 60 Group 1=Normal activity with minimal, transient, or no ocular symptoms.Group 2=Slight tiredness or more prolonged ocular symptoms.Group 3= Unable to work or do housework but still ambulant.Group 4=Bedridden, in hospital, or unable to walk. SummaryMyasthenia gravis is an uncommon disease, but its incidence is at least 1 in 40,000 of the population, and there are probably at least 2,000 examples in Great Britain at any one time.The records of 60 patients (25 males and 35 females) personally observed over the period 1934-55 have been analysed.The age of onset of symptoms varied from 6 to 75 years, being between 21 and 50 in 65%.The diagnosis is frequently overlooked in the early stages, especially when there is a monosymptomatic onset.Twelve patients had purely ocular symptoms through- out; conversely, in only five was there no history of ocular symptoms.The disease is characterized by daily fluctuations as well as by partial and complete remissions, sometimes for long periods.In this series 50% at no time had had a complete remission.The shortest history in a fatal example was one year.The longest history of continuing symptoms was 28 years.The discovery of neostigmine has revolutionized the treatment and prognosis of the disease; very large doses can apparently be taken for an indefinite period, the highest dosage in this series being 600 mg. a day for 20 years.Personal experience of other methods of treat- ment (including thymic irradiation, thymectomy, and the use of pyridostigmine) is too small from which to draw conclusions.The mortality in medically treated patients is still probably not less than 20%.
Brain Electrolytes and Fluid Metabolism
Authors: Robert L. McLaurin
Journal: JAMA (1973)

This volume, by a clinical neurologist and a neurochemist, provides an up-to-date review of current knowledge concerning fluid and electrolytes in the nervous system. This work cuts across several subspecialties and, therefore, may appeal to a variety of individuals: physiologists, chemists, and clinical neurologists and neurosurgeons. The first half of the book is devoted to basic concepts and data. The current knowledge of blood-brain barrier and cerebrospinal fluid physiology is presented in detail, followed by several chapters dealing with electrolytes in the cerebrospinal fluid (CSF), in the brain substance, and within the cells. Each ion is treated separately as far as possible, and the relations between the ions are then presented. The electrophysiological implications of the ion concentrations and movements are reviewed extensively. The second half is concerned primarily with clinical matters based on the preceding fundamental knowledge. An excellent chapter deals with acid-base balance of the CSF. The chapters
High Incidence of Allograft Cirrhosis in Hepatitis C Virus Genotype 1B Infection Following Transplantation: Relationship With Rejection Episodes
Authors: Martín Prieto, Marina Berenguer, José Miguel Rayón, Juan Córdoba, Lidia Argüello, Domingo Carrasco, Antonio García-Herola, Vicente Olaso, Manuel De Juan, Miguel Gobernado, José Mir, Joaquín Berenguer
Journal: Hepatology (1999)

The natural history of hepatitis C virus (HCV) infection following liver transplantation and predictors of disease severity remain controversial. The aims of the study were to assess in a homogeneous population of 81 cyclosporine–based HCV–infected liver transplant recipients mostly infected with genotype 1b and undergoing strict protocol annual biopsies: 1) the histological progression of posttransplantation HCV disease and, in particular, the incidence of HCV–related graft cirrhosis within the first 5 years after surgery; and 2) the relationship between progression to cirrhosis and i) rejection episodes and ii) first–year liver biopsy findings. We studied 81 consecutive HCV–RNA-positive patients (96% genotype 1b) undergoing liver transplantation between 1991 and 1996 with a minimum histological follow–up of 1 year. All patients received cyclosporine–based immunosuppression and underwent protocol yearly liver biopsies for the first 5 years. The mean histological follow–up was 32 months (range, 12–60 months). Biopsies were scored according to the histological activity index (HAI), with separate evaluation of grade (activity) and stage (fibrosis). Histological hepatitis, present in 97% of patients in the most recent biopsy, was moderate or severe in 64%. Twelve patients developed HCV–related cirrhosis at a median time of 24 months (range, 12–48 months), with an actuarial rate of HCV–cirrhosis of 3.7%, 8.5%, 16%, 28%, and 28% at 1, 2, 3, 4, and 5 years, respectively. Rejection was significantly more common among patients with cirrhosis versus those without (83% vs. 48%; P = .02), with an association between the incidence of cirrhosis and the number of rejection episodes: 5%, 15%, and 50% in patients without rejection, one and two episodes, respectively ( P = .001). The degree of activity and fibrosis score in the first–year biopsy were higher in patients who developed cirrhosis than in those who did not ( P = .008 and .18, respectively). In conclusion, HCV genotype 1b-infected liver recipients are at a high risk of developing graft cirrhosis in the first 4 to 5 years following transplantation, especially those with previous rejection episodes. First–year liver biopsies may help to sooner identify patients at the highest risk, improving further patient management.
Effects of ACTH on Induced Malaria in Man
Authors: Edward H. Kass, Quentin M. Geiman, Maxwell Finland
Journal: New England Journal of Medicine (1951)

IN THE course of investigations of the antipyretic action of pituitary adrenocorticotrophic hormone (ACTH),1 the hormone was given to a patient with syphilis of the central nervous system who was undergoing treatment with induced malaria. It was found that the periodicity of the paroxysms and the height to which the temperature rose were apparently not affected by the hormone but that defervescence was accelerated. Routine studies of the life cycle of the malarial parasites during treatment with ACTH revealed unusually high parasite counts in the blood stream. Similar studies were therefore made on other patients; the data thus obtained indicate . . .
Plasma Normetanephrine and Metanephrine for Detecting Pheochromocytoma in von Hippel–Lindau Disease and Multiple Endocrine Neoplasia Type 2
Authors: Graeme Eisenhofer, Jacques W.M. Lenders, W. Marston Linehan, McClellan M. Walther, David S. Goldstein, Harry R. Keiser
Journal: New England Journal of Medicine (1999)

The detection of pheochromocytomas in patients at risk for these tumors, such as patients with von Hippel-Lindau disease or multiple endocrine neoplasia type 2 (MEN-2), is hindered by the inadequate sensitivity of commonly available biochemical tests. In this study we evaluated measurements of plasma normetanephrine and metanephrine for detecting pheochromocytomas in patients with von Hippel-Lindau disease or MEN-2.We studied 26 patients with von Hippel-Lindau disease and 9 patients with MEN-2 who had histologically verified pheochromocytomas and 50 patients with von Hippel-Lindau disease or MEN-2 who had no radiologic evidence of pheochromocytoma. Von Hippel-Lindau disease and MEN-2 were diagnosed on the basis of germ-line mutations of the appropriate genes. The plasma concentrations of normetanephrine and metanephrine were compared with the plasma concentrations of catecholamines (norepinephrine and epinephrine) and urinary excretion of catecholamines, metanephrines, and vanillylmandelic acid.The sensitivity of measurements of plasma normetanephrine and metanephrine for the detection of tumors was 97 percent, whereas the other biochemical tests had a sensitivity of only 47 to 74 percent. All patients with MEN-2 had high plasma concentrations of metanephrine, whereas the patients with von Hippel-Lindau disease had almost exclusively high plasma concentrations of only normetanephrine. One patient with von Hippel-Lindau disease had a normal plasma normetanephrine concentration; this patient had a very small adrenal tumor (<1 cm). The high sensitivity of measurements of plasma normetanephrine and metanephrine was accompanied by a high level of specificity (96 percent).Measurements of plasma normetanephrine and metanephrine are useful in screening for pheochromocytomas in patients with a familial predisposition to these tumors.
Cholangitis as a late complication of choledochoduodenostomy: the sump syndrome
Authors: M. Venerito, L. Fry, S. Rickes, P. Malfertheiner, K. Mönkemüller
Journal: Endoscopy (2009)

An 84-year-old woman was admitted for cholangitis. Her leukocyte count was 14.76 Gpt/L (normal range 4.0 – 10.0 Gpt/L), total bilirubin was 67 mmol (normal < 17 mmol), alkaline phosphatase was 6.48 mmol (normal range 0.58 – 1.74 mmol) and γ-glutamyltransferase was 7.04 (normal range 0.1 – 0.7). The past medical history was remarkable for a cholecystectomy and a choledochoduodenostomy carried out 21 and 15 years ago, respectively. An abdominal ultrasound carried out after admission to the referring hospital showed dilation of the common bile duct (CBD) and choledocholithiasis. Therapy with tazobactam/piperacillin and metronidazole was started. Endoscopic retrograde cholangiopancreatography (ERCP) was carried out twice at the same hospital but failed both times, and the patient was referred to our medical center.
Low Efficiency of the Standard Dosing of Unfractionated Heparin in Patients NSTEMI Elderly Female and Moderate Chronic Kidney Disease Hospitalized Within 12 Hours
Authors: Nikishin Aleksey, Nurbaev Timur, Jakubbekov Nodir, Hasanov Mahsud, Abdullaeva Saodat
Journal: Journal of the American College of Cardiology (2013)
G9a influences neuronal subtype specification in striatum
Authors: Ian Maze, Dipesh Chaudhury, David M Dietz, Melanie Von Schimmelmann, Pamela J Kennedy, Mary Kay Lobo, Stephanie E Daws, Michael L Miller, Rosemary C Bagot, Haosheng Sun, Gustavo Turecki, Rachael L Neve, Yasmin L Hurd, Li Shen, Ming-Hu Han, Anne Schaefer, Eric J Nestler
Journal: Nature Neuroscience (2014)
Instability of Pertussis-Vaccine Component in Quadruple Antigen Vaccine
Authors: Margaret Pittman
Journal: JAMA (1962)

The potency of pertussis antigen alone or in combination with diphtheria and tetanus toxoids is generally stable throughout its dating period of 18 months. The present investigation revealed that when poliomyelitis vaccine was added to the triple-antigen vaccine, potency of pertussis vaccine was unstable and that the rate of loss was about 6% per month. Loss was more rapid in samples exposed to the normal variable conditions on the market than in those held constantly under refrigeration. To compensate for this loss, the initial potency estimate requirement has been increased, and the dating period has been decreased to 4 months from date of issue. These factors have limited the availability of the product until the cause of deterioration has been removed.
Fats, Oil, Health
Authors: E. N. Hetherington
Journal: JAMA (1990)

To the Editor.—  Much is being written about cholesterol. The general public is as confused as we in the medical profession are. I read no convincing evidence that pure, unadulterated dietary cholesterol has a bearing on serum cholesterol, but I do read about saturated, monounsaturated, and polyunsaturated fats having an effect on serum cholesterol level.  It is known to cooks that oils are different. Peanut oil has a high flash point; olive oil smokes when it is heated; lard makes the best piecrust.  The evidence that olive oil is good for cholesterol problems grows 1 ; conversely, coconut oil is bad, 2 etc. Each oil and fat has its own profile of saturated, monounsaturated, and polyunsaturated oils.  No one is listening to the cooks, who tell us that the combinations do different things. Why does not the same thing hold true—that the effect of oil on cholesterol depends on its total
Fractures of Base of Fifth Metatarsal
Authors: J. B. Pearson
Journal: BMJ (1962)

SEPSIS IN THE HOME sBRSH from staphylococcal infections, 45% of which were frequent in children, but there was no significant difference in incidence between the sexes.The chance of recurrence of staphylococcal infection in an individual was double the incidence in the general population, while the risk of a recurrence in any members of the same family was four times the rate experienced by a family with no previous infection.Infection in one individual later spread to other members of the family in no fewer than half the cases.It was nearly always found that a single staphylococcal strain was the cause of all the lesions in a family.Comparing the staphylococcal strains found in the lesion and in the anterior nares, these were found to be identical in the individual with the lesion in two- thirds of the instances, while in half the cases another member of the patient's family was carrying the lesion strain, whether or not the patient was a nasal carrier of this strain.Evidence is presented for the belief that the axilla and the perineum must be regarded as carrier sites in addition to the nose, and that there may be an associa- tion between the position of the lesion and the site of carriage of the causative staphylococcus.I am indebted to Dr. M. T. Parker, lately Director of the Public Healtb Laboratory in Manchester.Dr. Parker was responsible for all the bacteriological services required in this study
Altitude sickness: Hyperventilatory capacity may predict altitude sickness
Authors: M. Ledochowski
Journal: BMJ (2003)

EDITOR–Barry and Pollard reviewed altitude sickness.1 Tibetans and Sherpas (of Tibetan origin) have better physical performance at high altitude than whitepeople,2 possibly because of genetic differences.3 Acute adaptation to high altitude and low oxygen supply is primarilyby hyperventilation, which both improves oxygen saturation and increases blood pH. The capacity tocorrect respiratory alkalosis is thus …
The receptor tyrosine kinase EphA2 promotes mammary adenocarcinoma tumorigenesis and metastatic progression in mice by amplifying ErbB2 signaling
Authors: Dana M. Brantley-Sieders, Guanglei Zhuang, Donna Hicks, Wei Bin Fang, Yoonha Hwang, Justin M.M. Cates, Karen Coffman, Dowdy Jackson, Elizabeth Bruckheimer, Rebecca S. Muraoka-Cook, Jin Chen
Journal: Journal of Clinical Investigation (2008)

Overexpression of the receptor tyrosine kinase EPH receptor A2 (EphA2) is commonly observed in aggressive breast cancer and correlates with a poor prognosis. However, while EphA2 has been reported to enhance tumorigenesis, proliferation, and MAPK activation in several model systems, other studies suggest that EphA2 activation diminishes these processes and inhibits the activity of MAPK upon ligand stimulation. In this study, we eliminated EphA2 expression in 2 transgenic mouse models of mammary carcinoma. EphA2 deficiency impaired tumor initiation and metastatic progression in mice overexpressing ErbB2 (also known as Neu) in the mammary epithelium (MMTV-Neu mice), but not in mice overexpressing the polyomavirus middle T antigen in mammary epithelium (MMTV–PyV-mT mice). Histologic and ex vivo analyses of MMTV-Neu mouse mammary epithelium indicated that EphA2 enhanced tumor proliferation and motility. Biochemical analyses revealed that EphA2 formed a complex with ErbB2 in human and murine breast carcinoma cells, resulting in enhanced activation of Ras-MAPK signaling and RhoA GTPase. Additionally, MMTV-Neu, but not MMTV–PyV-mT, tumors were sensitive to therapeutic inhibition of EphA2. These data suggest that EphA2 cooperates with ErbB2 to promote tumor progression in mice and may provide a novel therapeutic target for ErbB2-dependent tumors in humans. Moreover, EphA2 function in tumor progression appeared to depend on oncogene context, an important consideration for the application of therapies targeting EphA2.
GSK-3β at the crossroads in the signalling of heart preconditioning: implication of mTOR and Wnt pathways
Authors: François Vigneron, Pierre Dos Santos, Sandrine Lemoine, Maryline Bonnet, Liliane Tariosse, Thierry Couffinhal, Cécile Duplaà, Béatrice Jaspard-Vinassa
Journal: Cardiovascular Research (2011)

Ischaemic preconditioning (IPC) protects the heart against prolonged lethal ischaemia through a signalling cascade involving Akt, glycogen synthase kinase-3β (GSK-3β), and mitochondrial ATP-sensitive potassium channels (mitoKATP). We previously demonstrated the involvement of the Wnt pathway in IPC in vivo via GSK-3β. A downstream target might be mammalian target of rapamycin (mTOR) since Wnt can impair tuberous sclerosis complex-2 (TSC2) phosphorylation by inhibiting GSK-3β. Here, we investigate whether the mTOR pathway is involved in cardioprotection. Isolated-perfused mouse hearts were subjected to IPC via four cycles of ischaemia/reperfusion or pharmacological preconditioning (PPC) by diazoxide, a selective mitoKATP activator. IPC, like PPC, induced an inhibition/phosphorylation of GSK-3β through Akt activation. Preconditioning also induced phosphorylation of mTOR, p70S6K, and 4E-BP1 that correlated with a significant reduction in infarct size after 40-min ischaemia and 120-min reperfusion when compared with non-preconditioned controls. Preconditioning was impaired in GSK3 knock-in mice. In transgenic mice hearts overexpressing secreted frizzled protein 1 (sFRP1, a Wnt/Frz antagonist), GSK-3β phosphorylation, mTOR activation, and cardioprotection were impaired. Cardioprotection and its signalling were also inhibited by rapamycin (an mTOR inhibitor), 5-HD (a mitoKATP blocker), and N-(2-mercaptopropionyl) glycine (MPG) as a reactive oxygen species (ROS) scavenger. We propose that the preconditioning signalling pathway involving an amplification loop results in a downregulation of GSK-3β and a constant opening of mitoKATP with ROS generation to activate the mTOR pathway and induce cardioprotection. The disruption of the Wnt/Frz pathway by sFRP1 modulates this loop, inducing GSK-3β activation. This study provides evidence that cardioprotection involves both a pro-survival mTOR pathway and a developmental Wnt pathway targeting GSK-3β.
Massive Pulmonary Thromboembolism
Authors: Richard D. Sautter
Journal: JAMA (1965)

In a series of 12 pulmonary embolectomies, there were three survivors, none of whom was over 65 years of age. The principal cause of death in the patients who did not survive was cardiovascular collapse of undetermined etiology. Sustained peripheral hypotension was used as the indication for surgical intervention. Embolectomy in other than life-threatening situations is probably unwarranted. Pulmonary arteriography should confirm the diagnosis prior to embolectomy. Cardiac arrest, which occurred in over half of the patients in this series, can be prevented or adequately managed by peripheral cannulization and partial cardiopulmonary bypass prior to thoracotomy. Cardiopulmonary bypass, because it provides adequate time for a deliberate attack, is the modality of choice for the removal of the emboli. The inferior vena cava should be ligated at the time of embolectomy to prevent further embolization.
Proteases and oxidants in experimental pulmonary inflammatory injury.
Authors: I U Schraufstätter, S D Revak, C G Cochrane
Journal: Journal of Clinical Investigation (1984)

We have examined various biochemical parameters of pulmonary inflammation in experimental animals. Intrabronchial instillation of glucose oxidase-glucose (GO/G) to produce oxidants or formylated norleu-leu-phe (FNLP) or phorbol myristate acetate (PMA) as leukocytic stimuli induced severe acute pulmonary injury in New Zealand white rabbits. PMA also induced inflammation when administered intravenously. Each stimulus induced transudation of protein from the vascular space into the pulmonary tissues, and an influx of leukocytes during the 4-6 h period of the experiment. Pathophysiologic changes were measured by edema formation (transudation of 125I-bovine serum albumin), and histologic examination. Biochemical analysis was performed by measuring concentrations of potentially injurious agents in bronchoalveolar lavage (BAL) fluid. Increased acid protease and myeloperoxidase levels were found in the BAL fluid after administration of either of the stimuli. Evidence of oxidant generation in vivo was obtained in two different ways. In the first, specific activities for catalase were measured in the BAL fluid in the presence or absence of 3-amino, 1,2,4 triazole (AT), injected at intervals before obtaining BAL fluid. In the presence of AT, specific activities for catalase dropped to 0.22 after a double instillation of FNLP and to 0.15 in the presence of GO/G. In neutrophil-depleted FNLP animals, catalase was not greatly inhibited by AT (sp act 0.90). In the second, intracellular levels of total glutathione (GSH + GSSG) in whole lung tissue and alveolar macrophages decreased when stimuli of neutrophils were administered. Intrabronchially instilled PMA, e.g., caused a drop of glutathione in whole lung tissue from the control value of 2.3 mumol GSH equivalent/100 mg dry wt to 0.54 mumol GSH equivalent/100 mg dry wt at 4 h. Neutrophil depletion and superoxide dismutase protected from this effect. From these results, we conclude that O-2 or its metabolites can initiate severe pulmonary injury as shown by the effect of GO/G and that, during development of pulmonary injury, stimulated neutrophils generate oxidants and release proteolytic enzymes into the surrounding tissues.
Block of human cardiac Kv1.5 channels by loratadine: voltage-, time- and use-dependent block at concentrations above therapeutic levels
Authors: Eva Delpón, Carmen Valenzuela, Pilar Gay, Laura Franqueza, Dirk J Snyders, Juan Tamargo
Journal: Cardiovascular Research (1997)

Objective: The aim of this study was to analyze the effects of loratadine on a human cardiac K+ channel (hKv1.5) cloned from human ventricle and stably expressed in a mouse cell line. Methods: Currents were studied using the whole-cell configuration of the patch−clamp technique in Ltk− cells transfected with the gene encoding hKv1.5 channels. Results: Loratadine inhibited in a concentration-dependent manner the hKv1.5 current, the apparent affinity being 1.2±0.2 μM. The blockade increased steeply between −30 and 0 mV which corresponded with the voltage range for channel opening, thus suggesting that the drug binds preferentially to the open state of the channel. The apparent association and dissociation rate constants were (3.6±0.5)×106·M−1·s−1 and 3.7±1.6·s−1, respectively. Loratadine, 1 μM, increased the time constant of deactivation of tail currents elicited on return to −40 mV after 500 ms depolarizing pulses to +60 mV from 36.2±3.4 to 64.9±3.6 ms (n = 6, P<0.01), thus inducing a 'crossover' phenomenon. Application of trains of pulses at 1 Hz lead to a progressive increase in the blockade reaching a final value of 48.6±4.3%. Recovery from loratadine-induced block at −80 mV exhibited a time constant of 743.0±78.0 ms. Finally, the results of a mathematical simulation of the effects of loratadine, based on an open-channel block model, reproduced fairly well the main effects of the drug. Conclusions: The present results demonstrated that loratadine blocked hKv1.5 channels in a concentration-, voltage-, time- and use-dependent manner but only at concentrations much higher than therapeutic plasma levels in man.