tbuckley/cabot-search huggingface dataset:
Effects of Carnitine in Ischemic and Fatty Acid Supplemented Swine Hearts
Authors: A. James Liedtke, Stephen H. Nellis, Gary Copenhaver
Journal: Journal of Clinical Investigation (1979)

Free fatty acids (FFA) in excess FFA: albumin molar ratios have been determined to additionally compromise mechanical performance in ischemic hearts. Carnitine, an intracellular carrier of FFA and an agent which is lost to the heart during ischemia, has been postulated to in part restore function with its replacement. To test whether its benefits are also operative in a setting of excess FFA, these studies were performed. In the main protocol, four groups of perfused swine hearts (n = 45) were compared during 50 min of control flow (179.7 ml/min) and 40 min of global ischemia (106.1 ml/min). Initial base-line serum FFA:albumin molar ratios and carnitine levels in all groups were 1.3:1 and 8.5 nmol/ml, respectively. In two of these groups FFA:albumin ratios were increased to 5.9:1 with constant infusions of Intralipid. In two alternate groups (one with and one without extra FFA supplements) dl-carnitine was supplied, sufficient to increase serum levels nearly 200-fold. Ischemia per se in 14 hearts significantly decreased several parameters of global and regional mechanical function including left ventricular (LV) and mean aortic pressures, LV isovolumetric pressure development (max dp/dt), LV epicardial motion, and LV work, together with concomitant decreases in myocardial oxygen consumption. Elevated FFA in 12 hearts rendered similarly ischemic further decreased mechanical function (LV pressure: −20.8%, P < 0.05; mean aortic pressure −26.9%, P < 0.05; LV max dp/dt: −39%, P < 0.05; regional LV shortening: −51.1%, P < 0.05; and LV work: −50.3%, P < 0.05) as compared with nonsupplemented hearts. dl-Carnitine treatments in nine hearts, not supplemented with extra FFA were without apparent effect in improving overall hemodynamic performance. However, dl-carnitine in 10 high FFA-ischemic hearts effected several improvements as compared with the untreated group: LV pressure was increased 25.6%, P < 0.025; mean aortic pressure: +43.5%, P < 0.05; LV max dp/dt: +41.5%, P < 0.05; regional LV shortening: +241.3%, P < 0.001; and LV work: +76.2%, P < 0.05 at comparable levels of myocardial oxygen consumption. In a separate protocol, the effects of stereospecificity were also studied by comparing l- with dl-carnitine in globally perfused, palmitate-supplemented hearts (five hearts in each treatment group). At similar conditions of flow and serum FFA, changes in mechanical function were comparable, except for a tendency to perform greater LV work at reduced flows in the l-carnitine-treated hearts. Thus, it was demonstrated that carnitine in ischemic hearts is capable of preserving mechanical function under conditions of excess FFA, presumably by modifying the toxic effects of FFA intermediates. The major therapeutic actions appeared to derive from the l-isomer of carnitine.
Effect of heparin on platelet aggregation
Authors: H. I. Saba, S. R. Saba, G. A. Morelli
Journal: American Journal of Hematology (1984)

Abstract The effect of heparin on platelet aggregation was systematically examined on platelets in plasma (PRP), as well as on gel‐filtered, washed, and formaldehyde‐fixed platelets. Results indicate that, although heparin causes a mild potentiation of platelet aggregation in the PRP systems, a significant inhibitory activity is observed when heparin is added to isolated platelets. This inhibitory activity appears to be specific and not related to the impurities in the heparin preparations, as heparinase, as well as protamine, effectively neutralizes the heparin‐mediated inhibitory activity on platelet aggregation. Although heparin‐mediated inhibitory activity can be demonstrated in the presence of a number of different agonists (ADP, arachidonic acid, thrombin, Ionophore A23187, epinephrine, and ristocetin), the most pronounced inhibition is seen in the presence of ristocetin. Further studies show that heparin enhances thrombox‐ane generation in isolated platelets. Platelets pretreated with heparin, however, fail to respond to preformed thromboxane. These findings suggest that, in addition to the potentiation of thromboxane production in platelets, heparin may also attribute some change(s) to the platelet(s)/platelet membrane, which interferes with their ability to respond to the agonists of platelet aggregation. This antiaggregatory activity of heparin was found to be inhibited by a factor(s) present in plasma but not in serum.
INTESTINAL OBSTRUCTION
Authors: G. H. Whipple, H. B. Stone, B. M. Bernheim
Journal: The Journal of Experimental Medicine (1914)

Dogs may be immunized against lethal doses of the duodenal loop poison by means of small doses of the loop fluid from dog or cat and by material obtained from human cases of intestinal obstruction. The immunity is transient and may disappear within a few weeks. Dogs immunized by repeated doses of loop fluid show a definite resistance against the intoxication of a closed duodenal loop and may survive twice the usual period. A dog that recovers from simple intestinal obstruction may possess a strong resistance to the intoxication of a closed duodenal loop, thus indicating a similar type of intoxication in the two conditions. The sera of immune dogs are inactive when incubated with duodenal loop fluid. The organ extracts and emulsions (liver, spleen, lung) of immune dogs rapidly destroy the loop poison during incubation in vitro. This destructive property is possessed by a clear filtrate of the digested immune organs, excluding adsorption, and is lost after long periods of incubation (twelve weeks). We are investigating the action of this immune organ extract to determine whether it can destroy the closed-loop poison in vivo and perhaps be of value in treatment.
Organization of Psychosocial Care in a Teaching Hospital
Authors: John M. Cleghorn
Journal: Psychotherapy and Psychosomatics (1974)

This paper describes a method of organizing the psychosocial aspects of medical care in a new teaching hospital. An attempt is made to prevent some of the problems in care identified by the Duff and Hollingshead study (8). In order to be effective, however, psychiatrists must take major steps to overcome their marginal position in the medical profession. In addition, education of medical students to comprehend and manage psychosocial problems must begin at the outset of their medical educational experience and continue throughout. These are the prerequisites for a program of psychosocial care which then faces a major organizational challenge: to transfer aspects of psychosocial care from psychiatrists to others. Ordinary problems of living as distinct from psychiatric problems should not be referred to psychiatrists. In order to accomplish this aim, stable organizational structures ramifying throughout the health care system will be required. Such structures must support informal relationships based on personal respect and the achievements of good education. Psychosocial care in teaching hospitals is not likely to improve until it has representation in the power structure of the institution. Specific goals and methods of organizing psychosocial aspects of medical care are outlined.
Hypersensitivity Factors in Ulcerative Colitis
Authors: J. Alfred Rider, Hugo C. Moeller
Journal: JAMA (1963)

ALTHOUGH in the past many factors have been implicated in the etiology of ulcerative colitis, accumulating evidence indicates that ulcerative colitis may belong to the group of hypersensitivity diseases. Severe ulcerative, local inflammatory changes in the colon may at times occur in a sudden, explosive manner implying an acute hypersensitivity reaction. Numerous systemic changes may occur producing associated conditions such as hepatitis, cirrhosis, alteration in serum proteins, iritis, uveitis, arteritis, pyoderma gangraenosum, thrombophlebitis, erythema nodosum, arthritis, or amyloidosis; these also indicate a hypersensitivity state. Furthermore, it has been shown clinically that the most effective therapy for the quick control of ulcerative colitis is based on the use of adrenocorticosteroids. The results of this kind of treatment may be just as dramatic as those in the treatment of acute asthma or other acute allergic reactions. Although allergy or sensitivity to various foodstuffs has been suggested since the early work of
Book Review Interventional Cardiovascular Medicine: Principles and Practice Edited by Gary S. Roubin, Robert M. Califf, William W. O'Neill, Harry R. Phillips III, and Richard S. Stack. 989 pp., illustrated. New York, Churchill Livingstone, 1994. $179.95. 0-443-08834-9
Authors: John A. Bittl
Journal: New England Journal of Medicine (1994)
A specific p47phox -serine phosphorylated by convergent MAPKs mediates neutrophil NADPH oxidase priming at inflammatory sites
Authors: P. M.-C. Dang
Journal: Journal of Clinical Investigation (2006)

Neutrophil NADPH oxidase plays a key role in host defense and in inflammation by releasing large amounts of superoxide and other ROSs. Proinflammatory cytokines such as GM-CSF and TNF-alpha prime ROS production by neutrophils through unknown mechanisms. Here we used peptide sequencing by tandem mass spectrometry to show that GM-CSF and TNF-alpha induce phosphorylation of Ser345 on p47phox, a cytosolic component of NADPH oxidase, in human neutrophils. As Ser345 is located in the MAPK consensus sequence, we tested the effects of MAPK inhibitors. Inhibitors of the ERK1/2 pathway abrogated GM-CSF-induced phosphorylation of Ser345, while p38 MAPK inhibitor abrogated TNF-alpha-induced phosphorylation of Ser345. Transfection of HL-60 cells with a mutated p47phox (S345A) inhibited GM-CSF- and TNF-alpha-induced priming of ROS production. This event was also inhibited in neutrophils by a cell-permeable peptide containing a TAT-p47phox-Ser345 sequence. Furthermore, ROS generation, p47phox-Ser345 phosphorylation, and ERK1/2 and p38 MAPK phosphorylation were increased in synovial neutrophils from rheumatoid arthritis (RA) patients, and TAT-Ser345 peptide inhibited ROS production by these primed neutrophils. This study therefore identifies convergent MAPK pathways on Ser345 that are involved in GM-CSF- and TNF-alpha-induced priming of neutrophils and are activated in RA. Inhibition of the point of convergence of these pathways might serve as a novel antiinflammatory strategy.
Lichenoid skin lesions as a sign of β2-microglobulin-induced amyloidosis in a long-term haemodialysis patient
Authors: K.C. SATO, M. KUMAKIRI, H. KOIZUMI, M. ANDO, A. OHKAWARA, Y. FUJIOKA, T. KON
Journal: British Journal of Dermatology (1993)

We report a case of β2‐microglobulin‐induced amyloidosis. The patient was a 40‐year‐old man suffering from non‐amyloid nephropathy, who had been treated by haemodialysis for 20 years. Lichenoid skin lesions, consisting of groups of pin‐head‐sized shiny papules, were present on the arms and trunk. On histological examination, amyloid deposits were present, principally in the dermal papillae, hut also around the sweat ducts and hair follicles. The amyloid displayed potassium‐permanganate‐resistant Congo red affinity, and green birefringence under polarized light, Immuno‐histochemically, β2‐microglobulin was demonstrated in the lesions, confirming that they were a manifestation of β2‐microglobulin‐associated amyloidosis. Skin lesions of this type have not been reported previously in β2‐microglobulin‐associated amyloidosis.
Stimulus to Gastric Acid Secretion Arising Outside the Stomach, Duodenum, and Pancreas
Authors: Ward D. O'Sullivan, Richard D. Sweeney, Mary Austin Jung
Journal: JAMA (1963)

THE ROLE of the vagus nerves and the gastric antrum in stimulating gastric acid secretion is well known. The pancreas and duodenum also are considered to have a functional effect on gastric acidity. The experimental work presented in this paper indicates that a hormone effectively stimulating gastric acid secretion, is produced elsewhere than the stomach, pancreas, and duodenum.  Method  Two experimental preparations were made. In one, a Heidenhain pouch was constructed and the rest of the stomach save for a 1 cm cuff was removed. Intestinal continuity was restored by gastroenterostomy and entero-enterostomy. In the second preparation, the Heindenhain pouch was again constructed, the remainder of the stomach removed, and the esophagus directly anastomosed to the duodenum.  The secretions of the Heidenhain pouch were collected daily and analyzed for volume, pH, free acidity, and total acidity. After a minimum of a month, a portacaval transposition was made. The inferior
ST Segment Elevation Myocardial Infarction
Authors: Toby Rogers, Rafal Dworakowski, Habib Khan, Ranjit Deshpande, Jatin Desai, Emma Alcock, Philip MacCarthy
Journal: Circulation (2013)

A 51-year-old man collapsed in an Internet café while eat- ing a sandwich.He received bystander cardiopulmonary resuscitation and was in ventricular fibrillation on arrival of the emergency services.He was cardioverted at the scene and brought intubated to the cardiac catheter laboratory, bypassing the emergency room.This is now standard practice for all outof-hospital ventricular fibrillation arrests in our hospital.His electrocardiogram on arrival exhibited first-degree atrioventricular block (PR interval, 285 ms), incomplete left bundle branch block (QRS interval, 120 ms), with anterior Q waves and ST elevation (Figure 1).His bedside echocardiogram showed a mild anterior wall motion abnormality with normal left ventricular function.We elected to perform immediate coronary angiography with a view to primary percutaneous coronary intervention.Coronary angiography revealed atheromatous but unobstructed coronary arteries, but a foreign body was noted in the right main bronchus (Figure 2).Our cardiothoracic surgical colleagues retrieved the foreign body in the cardiac catheter laboratory under fluoroscopic guidance using a rigid bronchoscope, forceps, and finally an intravascular snare catheter.The foreign body was confirmed to be a dental bridge.He was extubated on day 2 and was discharged from the hospital on day 5 with no neurological deficit.The cause of his collapse was in all probability primary respiratory arrest leading to hypoxiainduced ST segment elevation and ventricular fibrillation.His peak troponin I level was 0.93 mcg/L (normal range, <0.05 mcg/L) and creatine kinase was 154 U/L.This remarkable case illustrates that not every out-of-hospital ventricular fibrillation arrest with ST segment elevation presenting to a primary percutaneous coronary intervention center is attributable to coronary artery occlusion.This case also highlights the importance of the multidisciplinary team in the management of patients who present after out-of-hospital cardiac arrest.
Transatlantic agreement signed on health care and emergency measures
Authors: Charles Marwick
Journal: BMJ (2001)

The United Kingdom and the United States have agreed to collaborate on improving the quality of health care and to exchange data to facilitate responses to health emergencies. This is the essence of an agreement signed last week in Washington by Tommy Thompson, the US secretary for health and human services, and Alan Milburn, UK secretary of state for health.

The foundations for the agreement were laid in England in 1998 at a meeting held jointly by two private foundations, the US Commonwealth Fund and the UK Nuffield Trust. A basis …
Postoperative Correction of Scoliosis
Authors: J. William Fielding
Journal: JAMA (1962)

The purpose of this paper is to study the effect of applying a postoperative rather than a preoperative correctional plaster in cases of scoliosis. This has advantages in that it shortens the period of hospitalization, the patient is more comfortable, and surgery is easier without the jacket. Seventy patients were so studied. In 68 of these, a preoperative test correction was compared with the final immediate postoperative correction in plaster. This was done to compare the correction that would have been obtained with the actual correction obtained. They were found to be essentially the same. Forty-four of these patients were followed from 1 to 3 years and the end-result was evaluated. The average initial correction was 45% of their preoperative erect curve. The average maintained correction, however, was 30%.
Safety of Recombinant Adeno-Associated Virus Type 2–RPE65 Vector Delivered by Ocular Subretinal Injection
Authors: Samuel G. Jacobson, Gregory M. Acland, Gustavo D. Aguirre, Tomas S. Aleman, Sharon B. Schwartz, Artur V. Cideciyan, Caroline J. Zeiss, Andras M. Komaromy, Shalesh Kaushal, Alejandro J. Roman, Elizabeth A.M. Windsor, Alexander Sumaroka, Susan E. Pearce-Kelling, Thomas J. Conlon, Vincent A. Chiodo, Sanford L. Boye, Terence R. Flotte, Albert M. Maguire, Jean Bennett, William W. Hauswirth
Journal: Molecular Therapy (2006)

AAV2 delivery of the RPE65 gene to the retina of blind RPE65-deficient animals restores vision. This strategy is being considered for human trials in RPE65-associated Leber congenital amaurosis (LCA), but toxicity and dose efficacy have not been defined. We studied ocular delivery of AAV-2/2.RPE65 in RPE65-mutant dogs. There was no systemic toxicity. Ocular examinations showed mild or moderate inflammation that resolved over 3 months. Retinal histopathology indicated that traumatic lesions from the injection were common, but thinning within the injection region occurred only at the two highest vector doses. Biodistribution studies at 3 months postinjection showed no vector in optic nerve or visual centers in the brain and only isolated non-dose-related detection in other organs. We also performed biodistribution studies in normal rats at about 2 weeks and 2 months postinjection and vector was not widespread outside the injected eye. Dose-response results in RPE65-mutant dogs indicated that the highest 1.5-log unit range of vector doses proved efficacious. The efficacy and toxicity limits defined in this study lead to suggestions for the design of a subretinal AAV-2/2.RPE65 human trial of RPE65-associated LCA.
Hyperglycemia in Acute Illness—Reply
Authors: Victor M. Montori, M. Molly McMahon, Bruce R. Bistrian
Journal: JAMA (2003)

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Serum and urinary proteins, lysozyme (muramidase), and renal dysfunction in mono- and myelomonocytic leukemia
Authors: W. Pruzanski, M. E. Platts
Journal: Journal of Clinical Investigation (1970)

Serum levels, urinary excretion, and clearances of several proteins of different molecular weights were studied in 18 patients with mono- and myelomonocytic leukemia. Nine patients had normal renal function (group A) and nine had impaired renal function with azotemia (group B). The majority of patients in both groups had increased concentration of immunoglobulins, particularly IgG, IgA, and IgM; IgD level was normal. Serum transferrin and alpha(2)-macroglobulin were frequently reduced while the level of ceruloplasmin was often increased, especially in patients with azotemia. The activity of lysozyme in the serum was high in all patients, but was considerably higher in group B. Proteinuria was found in most patients but was more prominent in group B. Almost invariably albumin constituted less than 25% of the total protein excreted. Qualitative analysis of various urinary proteins by immunochemical techniques and clearance studies suggested the presence of glomerular as well as tubular dysfunction. Determination of urinary lysozyme frequently showed no direct correlation between the serum level of the enzyme and its concentration in the urine or its clearance by the kidney. In addition to glomerular filtration, impaired tubular reabsorption may account for the high level of lysozyme in the urine. It is postulated that the very high level of lysozyme in the glomerular filtrate and possibly hypergammaglobulinemia may play a role in the induction of tubular damage. Renal impairment has been correlated with histological changes in the kidneys. From a comparative study of various leukemias, it seems that the combined glomerular-tubular dysfunction is a manifestation unique to mono- and myelomonocytic leukemia.
Radiofrequency Ablation of Drug‐Resistant Cancer Cells Using Molecularly Targeted Carboxyl‐Functionalized Biodegradable Graphene
Authors: Abhilash Sasidharan, Amal J. Sivaram, Archana P. Retnakumari, Parwathy Chandran, Giridharan Loghanathan Malarvizhi, Shantikumar Nair, Manzoor Koyakutty
Journal: Advanced Healthcare Materials (2015)

Under ultralow radiofrequency (RF) power, transferrin-conjugated graphene nanoparticles can thermally ablate drug- or radiation-resistant cancer cells very effectively. The results suggest that graphene-based RF hyperthermia can be an efficient method to manage drug-/radiation-resistant cancers.
Abstract 4263: Angiotensin Converting Enzyme Inhibitors in Patients with Coronary Artery Disease and Preserved Left Ventricular Function: A Meta-Analysis of Randomized Controlled Trials.
Authors: Sripal Bangalore, Shruthi Pranesh, Shruthi Chandrashekhar, Sonali Mantoo, Sandeep Pulimi, Franz H Messerli
Journal: Circulation (2008)

Background: The Angiotensin Converting Enzyme Inhibitors (ACEIs) have been shown to improve outcomes in patients with heart failure and myocardial infarction. However, there is conflicting evidence...