tbuckley/cabot-search huggingface dataset:
Robust systemic transduction with AAV9 vectors in mice: efficient global cardiac gene transfer superior to that of AAV8
Authors: Katsuya Inagaki, Sally Fuess, Theresa A. Storm, Gregory A. Gibson, Charles F. Mctiernan, Mark A. Kay, Hiroyuki Nakai
Journal: Molecular Therapy (2006)

It has been recently shown that recombinant adeno-associated virus serotype 8 (rAAV8) is a robust alternative serotype vector that overcomes many of the limitations of rAAV2 and transduces various tissues efficiently and globally through systemic vector administration. AAV9 is a serotype newly isolated from human tissues, but our knowledge of the biology of rAAV9 in vivo is currently limited. Here, we demonstrate by a series of comprehensive side-by-side experiments with rAAV8 and 9 vectors delivered via different routes or at various doses in mice that rAAV9 vectors share the robustness of rAAV8, i.e., (1) very high liver transduction efficiency irrespective of whether vectors are administered intravascularly or extravascularly and (2) substantial transduction in the heart, skeletal muscle, and pancreas by peripheral vein injection. Importantly, rAAV9 transduced myocardium 5- to 10-fold higher than rAAV8, resulting in over 80% cardiomyocyte transduction following tail vein injection of as low as 1.0 × 1011 particles per mouse. Thus rAAV9, as well as rAAV8, is a robust vector for gene therapy applications and rAAV9 is superior to rAAV8 specifically for cardiac gene delivery by systemic vector administration.
A COMPARATIVE STUDY OF FLAXEDIL AND SYNCURINE COMBINED WITH PENTOTHAL ANESTHESIA IN MODIFYING ELECTROCONVULSIVE THERAPY
Authors: WILLIAM L. HOLT, DONALD NISWANDER, DEWEY K. ZIEGLER, RICHARD TURK
Journal: American Journal of Psychiatry (1953)

The authors have treated over 200 patients with electroconvulsive therapy modified by Sodium Pentothal anesthesia and curarization with Syncurine or Flaxedil or both. Sodium Pentothal was the usual cause for the infrequently occurring cough, bronchospasm, and rash. No case of Flaxedil allergy was encountered in 111 patients. The availability of several intravenous anesthetics and several types of curarizing drugs supplemented by antihistaminics helps the therapist to avoid or control allergic respiratory reactions, but intubation should be available. After maximal softening of the seizure with Flaxedil, the time required for return of self-sustaining respiratory movement can be greatly shortened with the use of prostigmine or Tensilon. This cuts the time of oxygen administration after the seizure in half as compared with Syncurine-treated cases, as for the latter drug no antidote is available. Tensilon, 5 to 10 mg., must be given only intravenously after the seizure. Its use permits avoidance of atropine, needed when prostigmine is employed. As we believe atropinization is needed to prevent seizure-induced salivation and cardiac arrest, we prefer to give 2 to 2.5 mg. of prostigmine intramuscularly, conserving available veins for the more essential curarizing injection. After Flaxedil injection, pulse rates rose 10 to 40 beats per minute, whereas Syncurine produced no change. Blood pressure changes with Flaxedil are essentially the same as with Syncurine. Hypertensive patients may show a fall of 40 to 60 mm. systolic and 10 to 20 mm. diastolic, attributed to Pentothal anesthesia. Of 21 "Flaxedil" cases tested, two-thirds (including 2 markedly hypertensive patients) showed less than 10 mm. change in blood pressure before their seizure. During and immediately after the seizure blood pressure rose 40 to 60 mm. systolic and 10 to 30 mm. diastolic even when the seizure was externally perceptible only in the face. We believe that complete abolition of seizure muscle rigor decreases but does not remove the element of danger in the giving of ECT to patients with cardiovascular disease, as changes in blood pressure and cardiac rate and rhythm, probably of central origin, nonetheless occur. This produced coronary occlusion in one of our cases. Within the limitations outlined above, Flaxedil joins Syncurine as a valuable addition to available synthetic curarizing drugs employed in modification of the electroconvulsion.
Which Fractures Are Associated with Low Appendicular Bone Mass in Elderly Women?
Authors: Dana G. Seeley, Warren S. Browner, Michael C. Nevitt, Harry K. Genant, Jean C. Scott, Steven R. Cummings
Journal: Annals of Internal Medicine (1991)

To determine which types of fractures have an increased incidence in elderly women with low appendicular bone mass.Prospective cohort study.Four clinical centers in the United States (Baltimore, Maryland; Minneapolis, Minnesota; Portland, Oregon; Monangehela Valley, Pennsylvania); and one coordinating center in San Francisco, California.Ambulatory, nonblack women (9704) aged 65 years or more who were recruited from population-based listings.We measured bone mass at the distal and proximal radius and calcaneus using single-photon absorptiometry. Fractures were verified radiographically. Associations were calculated as age-adjusted hazard ratios (with 95% Cls) per standard deviation decrease in bone mass.During a mean follow-up of 2.23 years, 841 nonspinal fractures occurred in 753 women. The risks for fractures of the wrist, foot, humerus, hip, rib, toe, leg, pelvis, hand, and clavicle were significantly related to reduced bone mass (P less than 0.05). These fractures represented 74% of nonspinal fractures. The overall hazard ratio for the occurrence of one or more of these fractures was 1.65 (Cl, 1.49 to 1.82) at the distal radius. In a subsample of the cohort, vertebral fractures were also related to low bone mass. Fractures of the ankle, elbow, finger, and face, however, were not associated with bone mass at any measurement site; the overall hazard ratio for these fractures was 1.12 (Cl, 0.96 to 1.30) at the distal radius.Most types of fractures have an increased incidence in elderly women with low bone mass.
Comparison between Urinary Oestrogen Assay and Serial Ultrasonic Cephalometry in Assessment of Fetal Growth Retardation
Authors: S. Campbell, A. Kurjak
Journal: BMJ (1972)

Urinary oestrogen assay and serial ultrasonic cephalometry were performed on 284 patients who were considered on clinical grounds to be at risk of having a growth-retarded fetus. It was found that ultrasonic cephalometry was significantly better than oestrogens in diagnosing the small-for-dates baby, but that there was no significant difference between the two methods in predicting perinatal asphyxia. Of the 14 stillbirths, three were in the normal ultrasonic growth rate group and five had normal oestrogen excretion. Both methods were found to be of value in the diagnosis of fetal growth-retardation, although cephalometry would seem to have some advantages, especially in distinguishing between fetal growth-retardation and mistaken maturity.
A METHOD OF DETERMINING THE PATENCY OF THE FALLOPIAN TUBES BY X RAYS
Authors: E. Williams, R. Reynolds
Journal: BMJ (1925)

APtLrr 95 to make sure no fragment is left behind.The series quoted includes two cases of haemorrhage, in both of which suprapubic cystotomy had to be performed, and in one an extraperitoneal rupture was found to exist.Both these recovered.Here also the suprapubic cases are the worst and cannot be quoted for purposes of comparison.III.-Cases operated on by Mr.
Failed vaccine campaigns may lead to polio resurgence, experts warn
Authors: John Zaracostas
Journal: BMJ (2006)

Experts have said that the failure by the four remaining countries where polio is endemic to wipe out the disease could cause a resurgence of more than 250 000 cases a year. Polio remains endemic in Nigeria, India, Pakistan, and Afghanistan.

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Saudi Arabia has issued tight polio immunisation requirements for pilgrims at the Great Mosque, Mecca

Credit: AMR NABIL/AP

“It would be a humanitarian catastrophe not to complete polio eradication now that we are so close… to the finish line,” said Robert Scott, chairman of Rotary International's “Polio-Plus” committee.

“Polio eradication hinges on vaccine supply, community acceptance, funding, and political will. The first three are in place. The last will make the difference,” he …

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Sarcoidosis and Primary Biliary Cirrhosis
Authors: Willis C. Maddrey
Journal: New England Journal of Medicine (1983)

Sarcoidosis is a systemic granulomatous disorder of unknown cause that involves many organs. The most characteristic clinical presentations of sarcoidosis include pulmonary infiltrates, lymphadenopathy, fever, infiltrative skin lesions, and uveitis. In the absence of a known cause, the diagnosis of sarcoidosis is made from demonstration of granulomatous inflammation in more than one organ in a patient in whom other causes of granulomatous disease have been excluded. The Kveim-Siltzbach skin test is positive in approximately 80 per cent of patients but is not universally available or well standardized.1 Granulomas in the liver are found in most patients with sarcoidosis, and liver . . .
Psychiatric Consultation in a Coronary Care Unit
Authors: N. H. CASSEM
Journal: Annals of Internal Medicine (1971)

Of 441 consecutive patients admitted to a coronary care unit, 145 (32.7%) were referred for psychiatric consultation. The three most frequent reasons for referral were anxiety (47), depression (44), and management of behavior (30). The focus of anxiety was impending death or death's heralds: pain, breathlessness, weakness, and new complications. Depression followed injuries to self-esteem caused by the heart attack. Most management problems stemmed from excessive denial of illness, inappropriate euphoric or sexual behavior, and hostile-dependent conflicts with the staff. Consultation requests for each problem followed different time distributions, with an early peak for anxiety on days 1 and 2, a later peak for depression on days 3 and 4, and a bimodal distribution for management referrals. The data suggest a sequence of normal emotional reactions to myocardial infarction. Psychiatric intervention included medication, explanatory clarification, environmental changes, bolstering optimism, anticipation, confrontation, and hypnosis. The mortality of the referral group (4%) was three times less than expected for this coronary care unit.
Injury to the first rib synchondrosis in a rugby footballer.
Authors: S P Kemp, S G Targett
Journal: British Journal of Sports Medicine (1999)

Injuries to the first rib synchondrosis are uncommon in sport. The potential for serious complications following posterior displacement is similar to that seen with posterior sternoclavicular joint dislocation. Clinical examination and plain radiography may not provide a definitive diagnosis. Computerised tomography is the most appropriate imaging modality if this injury is suspected. Posterior dislocation of the first rib costal cartilage with an associated fracture of the posterior sternal aspect of the synchondrosis has not been previously reported.
Tumours in Children
Authors: A. C. P. Campbell, W. Gaisford, E. Paterson, J. K. Steward
Journal: BMJ (1961)

None of the many changes in medicine during the past 25 years has been more striking than the alteration in the pattern of children's diseases.Tumours, which before the introduction of antibiotics accounted for only a small proportion of the total number of deaths in children, have been brought into sharper relief; in 1958 they were the second commonest cause of death between the ages of 1 and 15 years (Registrar-General, 1960).The fact that children with tumours are treated in many different centres makes it difficult for large series of cases to be collected.To try to overcome this difficulty, information about these patients has been recorded in the Manchester Children's Tumour Registert since September, 1953.Inclusion of a child in the Register has depended on notification of the case to the tumour registrar by the clinician or pathologist concerned.When a case was notified the registrar made a copy of the hospital notes and obtained whatever pathological material was available.In addition, he interviewed the parents to obtain a fresh clinical history and other information, which is detailed below.Sections of non-leukaemic tumours were submitted to a panel of seven pathologists.: The cases were followed up after six months and then at yearly intervals.A diagnosis was assigned on the basis of the panel's histological reports, the clinical picture, the subsequent progress of the case, and the necropsy findings, except for leukaemia, the diagnosis of which was based on the reports of the hospital pathologists.Children were included in the Register only if the following conditions were fulfilled: (1) They were first seen by a consultant because of their tumour after September 1, 1953; (2) They lived in the Manchester Hospital Region, which consists of considerable portions of Lancashire, Cheshire, Derbyshire, and Westmorland, and contains approximately one million children; (3) They were under 15 years of age.
Short chain fatty acids stimulate epithelial mucin 2 expression through differential effects on prostaglandin E1 and E2 production by intestinal myofibroblasts
Authors: L E M Willemsen
Journal: Gut (2003)

<b>Background:</b> The mucus layer protects the gastrointestinal mucosa from mechanical, chemical, and microbial challenge. Mucin 2 (MUC-2) is the most prominent mucin secreted by intestinal epithelial cells. There is accumulating evidence that subepithelial myofibroblasts regulate intestinal epithelial cell function and are an important source of prostaglandins (PG). PG enhance mucin secretion and are key players in mucoprotection. The role of bacterial fermentation products in these processes deserves further attention. <b>Aims:</b> We therefore determined whether the effect of short chain fatty acids (SCFA) on MUC-2 expression involves intermediate PG production. <b>Methods:</b> Both mono- and cocultures of epithelial cells and myofibroblasts were used to study the effects of SCFA on MUC-2 expression and PG synthesis. Cell culture supernatants were used to determine the role of myofibroblast derived prostaglandins in increasing MUC-2 expression in epithelial cells. <b>Results:</b> Prostaglandin E<sub>1</sub> (PGE<sub>1</sub>) was found to be far more potent than PGE<sub>2</sub> in stimulating MUC-2 expression. SCFA supported a mucoprotective PG profile, reflected by an increased PGE<sub>1</sub>/PGE<sub>2</sub> ratio in myofibroblast supernatants and increased MUC-2 expression in mono- and cocultures. Incubation with indomethacin revealed the latter to be mediated by PG. <b>Conclusions:</b> SCFA can differentially regulate PG production, thus stimulating MUC-2 expression in intestinal epithelial cells. This mechanism involving functional interaction between myofibroblasts and epithelial cells may play an important role in the mucoprotective effect of bacterial fermentation products.
Practitioner's Poetry
Authors: William Butterfield
Journal: JAMA (1967)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Usefulness of Angioscopy in Stenotic Processes of the Carotid - A Comparison with Morphological Findings
Authors: A. Schwartz, K.-F. Bürrig, A. Aulich
Journal: Endoscopy (1988)

The development of a new generation of ultrathin flexible fiberscopes permitted direct in-vivo intravascular visualization of pathological changes. But not until the construction of a double-lumen balloon catheter for simultaneous obstruction of the blood flow and rinsing of the vessel did an accurate percutaneous transluminal examination become possible. For testing the usefulness of angioscopic intraluminal diagnosis, 48 carotid arteries from 32 autopsies were examined independently by angioscopy and morphologically. There was a high degree of correspondence between the two methods, especially in cases with low-degree stenosis or complicated plaques, in which other examination methods often fail. Problems of underestimating fibrous plaques and optical projection upstream of the stenosis are discussed.
Host programmed death ligand 1 is dominant over programmed death ligand 2 expression in regulating graft-versus-host disease lethality
Authors: Asim Saha, Kazutoshi Aoyama, Patricia A. Taylor, Brent H. Koehn, Rachelle G. Veenstra, Angela Panoskaltsis-Mortari, David H. Munn, William J. Murphy, Miyuki Azuma, Hideo Yagita, Brian T. Fife, Mohammed H. Sayegh, Nader Najafian, Gerard Socie, Rafi Ahmed, Gordon J. Freeman, Arlene H. Sharpe, Bruce R. Blazar
Journal: Blood (2013)
A Phase 1 clinical trial of Hantaan virus and Puumala virus M-segment DNA vaccines for haemorrhagic fever with renal syndrome delivered by intramuscular electroporation
Authors: J.W. Hooper, J.E. Moon, K.M. Paolino, R. Newcomer, D.E. McLain, M. Josleyn, D. Hannaman, C. Schmaljohn
Journal: Clinical Microbiology and Infection (2014)

Haemorrhagic fever with renal syndrome (HFRS) is endemic in Asia, Europe and Scandinavia, and is caused by infection with the hantaviruses Hantaan (HTNV), Seoul (SEOV), Puumala (PUUV), or Dobrava (DOBV) viruses. We developed candidate DNA vaccines for HFRS expressing the Gn and Gc genes of HTNV or PUUV and evaluated them in an open-label, single-centre Phase 1 study. Three groups of nine participants each were vaccinated on days 0, 28 and 56 with the DNA vaccines for HTNV, PUUV, or a mixture of both vaccines using the Ichor Medical Systems TriGrid Intramuscular Delivery System. All vaccinations consisted of a total dose of 2.0 mg DNA in an injected volume of 1 mL saline. For the combined vaccine, the mixture contained equal amounts (1.0 mg) of each DNA vaccine. There were no study-related serious adverse events. Neutralizing antibody responses were measured by a plaque reduction neutralization test. Neutralizing antibody responses were detected in five of nine and seven of nine individuals who completed all three vaccinations with the HTNV or PUUV DNA vaccines, respectively. In the combined vaccine group, seven of the nine volunteers receiving all three vaccinations developed neutralizing antibodies to PUUV. The three strongest responders to the PUUV vaccine also had strong neutralizing antibody responses to HTNV. These results demonstrate that the HTNV and PUUV DNA vaccines delivered by electroporation separately or as a mixture are safe. In addition, both vaccines were immunogenic, although when mixed together, more participants responded to the PUUV than to the HTNV DNA vaccine.
All the Madmen
Authors: D. Ingle
Journal: BMJ (2010)

“All the Madmen” was inspired by the mental health problems of David Bowie’s brother and was released 39 years ago (before Bowie achieved major fame), on the album The Man Who Sold the World . It recognises the separation from society of mentally ill people, who are sent to “mansions cold and grey.” In a lucid interval, spoken instead of sung, the national shame of mental illness and policies of alienation and institution are questioned with sadness: “Where can the horizon lie / When a nation hides / Its organic minds in a cellar.”

Faced with the prospect of discharge, the patient protagonist recognises his comfort in Librium, …
Radio-opaque pellets as faecal markers for faecal fat estimation in malabsorption.
Authors: F G Simpson, G P Hall, J Kelleher, M S Losowsky
Journal: Gut (1979)

Thirty-seven patients undergoing routine investigation for malabsorption were given radio-opaque pellets (ROP) which were compared with polyethylene glycol and chromic oxide as continuous faecal markers. Percentage recovery of all markers showed a wide range. The recovery of all markers was very similar, and radio-opaque pellet-corrected daily faecal fat correlated very closely with PEG-and chromic oxide-corrected fat results. Estimation of ROP is precise, simple, and minimises faecal handling. ROP are suitable for routine use in faecal fat studies and have advantages over markers used at present.
USE AND ABUSE OF CORTISONE AND CORTICOTROPIN (ACTH) IN DERMATOLOGY
Authors: Paul A. O'Leary
Journal: JAMA (1953)

Four and a half years have elapsed since we first treated patients who had lupus erythematosus and psoriasis with cortisone, and in four previous reports<sup>1</sup>our colleagues and one of us (P. A. O'L.) have recorded our experiences with and impressions of the value of cortisone and corticotropin (ACTH) in the treatment of various dermatological conditions. From the beginning, it was apparent that cortisone did not cure patients with skin diseases, although in some cases the symptoms were minimized and in other cases of fatal diseases the life expectancy may have been extended. At the present time, cortisone and corticotropin are used extensively and sometimes indiscriminately in the treatment of cutaneous diseases of all types, and patients with dermatoses that run a short and self-limited course and those with fatal skin diseases now receive these drugs uniformly. It is not a new experience for physicians to use a drug
Low-Dose Prednisone Induces Rapid Reversible Axial Bone Loss in Patients with Rheumatoid Arthritis
Authors: Roland F. J. M. Laan
Journal: Annals of Internal Medicine (1993)

Objective: To determine the effects of a short course of a low dose of a glucocorticoid agent on bone mass. Design: Double-blind, placebo-controlled, randomized study. Setting: Outpatient clinic of a university hospital. Patients: Forty patients with active rheumatoid arthritis. Intervention: All patients started receiving intramuscular gold salts. In addition, they were randomly allocated to receive either prednisone or placebo. The initial dose was 10 mg/d, which was tapered between weeks 12 and 20. Thereafter, patients were followed for an additional 24 weeks. Measurements: Lumbar bone mineral density was measured with dual-energy, quantitative computed tomography in a trabecular and a cortical region of interest. Results: Despite favorable effects on disease activity and functional capacity, trabecular bone mineral density decreased in the prednisone-treated patients between baseline and week 20 (mean change, 8.2%; 95% CI, 12.7% to 3.7%; P = 0.001). Little change was found in the placebo-treated patients (P > 0.2), and the prednisone group had a greater mean bone loss than the placebo group (9.5%; CI, 3.4% to 15.6%; P = 0.003). After discontinuation of prednisone, an increase was found in trabecular bone mineral density between weeks 20 and 44 (mean change, 5.3%; CI, 0.7% to 9.9%; P = 0.03). Little change was found after withdrawal of placebo (P > 0.2). The mean improvement in the prednisone group was 6.8% (CI, 0.8% to 12.8%; P = 0.03) greater than for placebo. In both treatment groups, cortical bone mineral density did not change markedly in either period (P 0.2). Conclusions: Low doses of glucocorticoid agents cause marked vertebral trabecular bone loss in the initial months of therapy in patients with active rheumatoid arthritis. After discontinuation of treatment, this bone loss seems to be (partially) reversible.