tbuckley/cabot-search huggingface dataset:
Biodistribution of rAAV Vectors Following Intraocular Administration: Evidence for the Presence and Persistence of Vector DNA in the Optic Nerve and in the Brain
Authors: Nathalie Provost, Guylène Le Meur, Michel Weber, Alexandra Mendes-Madeira, Guillaume Podevin, Yan Cherel, Marie-Anne Colle, Jack-Yves Deschamps, Philippe Moullier, Fabienne Rolling
Journal: Molecular Therapy (2004)

The purpose of our study was to evaluate the biodistribution of rAAV vectors following subretinal or intravitreal injection. In rats, we performed subretinal or intravitreal injections of rAAV-2/2.CMV.gfp. In large animals, rAAV-2/4.CMV.gfp or rAAV-2/5.CMV.gfp was delivered into the subretinal space while rAAV-2/2.CMV.gfp was delivered either to the subretinal space or to the vitreous. In euthanized animals, we undertook a complete necropsy. In animals maintained alive, we collected blood and tissue samples from the submandibular lymph node, liver, and gonads. We analyzed total DNA, extracted from various tissue samples and peripheral blood mononuclear cells (PBMC), by PCR. Following subretinal or intravitreal injections in rats and in large animals, vector sequences were not detected in the liver or in the gonads but were occasionally found in PBMC. An unexpected result was the detection of rAAV sequences in the optic nerve following subretinal injection. The most striking finding was the detection of vector sequences in the brain, along the visual pathway, in rAAV-2/2 intravitreally injected dogs. These findings raise safety concerns regarding intraocular administration of rAAV vectors and will have an impact on the development of future gene therapy trials for retinal diseases.
The Surgery an insider's view
Authors: M. Gabbay
Journal: BMJ (1997)

“So what's it like being filmed?” That's what I kept hearing from fellow professionals during my brief spell in the limelight as one of the doctors featured in The Surgery , a three part documentary shown on Channel 4's Cutting Edge series in April.

It all began early last year, when we were approached by Touch Productions, which had been commissioned to make a documentary about general practice. They wanted to focus on the pressures on general practice, including the recruitment crisis, out of hours stresses, and the ways that the locus of control of health funding is shifting into primary care. They thought that the stress would be most acute in an inner city, and our practice fitted the bill.

Once they arrived, and the researcher and production team got to know a bit more about us they …
Endothelium-mediated and direct actions of acetylcholine on rabbit aortic baroreceptors.
Authors: P A Munch
Journal: Circulation Research (1994)

Effects of exogenous acetylcholine on single-unit aortic baroreceptors were studied using a rabbit in vitro aortic arch/aortic nerve preparation. The arch was perfused with Krebs-Henseleit solution at constant pressure while simultaneously recording arch diameter and baroreceptor discharge frequency. Administration of acetylcholine over a wide range of concentrations (10(-9) to 10(-4) mol/L) evoked multiple dose-dependent changes in baroreceptor activity. "Low" concentrations (&lt; 10(-6) mol/L) consistently dilated arch and increased baroreceptor discharge (n = 11). These responses were prevented by prerelaxing smooth muscle with sodium nitroprusside (10(-7) mol/L, n = 6) and were augmented by precontracting smooth muscle with norepinephrine (0.5 x 10(-7) mol/L, n = 11). Thus, the baroreceptor responses were dependent quantitatively on the level of preexisting vasoactive tone. The responses also were antagonized by atropine (10(-7) mol/L, n = 6), which inhibits release of endothelium-derived relaxing factor (EDRF), and by N-monomethyl-L-arginine (10(-5) mol/L, n = 6), a specific blocker of nitric oxide formation (primary relaxing factor responsible for acetylcholine vasorelaxation). Hexamethonium was ineffective (n = 6). These results indicate that "low-dose" responses to acetylcholine were mediated solely by release of EDRF. In contrast, "high" concentrations of acetylcholine (&gt; 10(-6) mol/L) constricted arch and reduced baroreceptor discharge in most units (66%). These responses were blocked by atropine, but not by hexamethonium, and were attributed to direct contraction of the smooth muscle. In the remaining baroreceptors (33%), discharge increased irrespective of changes in diameter or preexisting vasoactive tone, but not in the presence of hexamethonium. Therefore, some baroreceptors were stimulated chemically by acetylcholine (or an intermediary substance), probably through activation of nicotinic receptors on the sensory endings. The effects of acetylcholine on the baroreceptor pressure-frequency curve also were examined by injecting slow pressure ramps before and during acetylcholine treatment. Low concentrations that relaxed smooth muscle shifted the curve to lower pressures; high concentrations that contracted smooth muscle shifted the curve to higher pressures. Last, when acetylcholine was given with the diameter rather than the pressure held constant, the baroreceptor reciprocal responses to smooth muscle relaxation and contraction were directionally reversed but remained consistent with the changes in wall tension.(ABSTRACT TRUNCATED AT 400 WORDS)
Firearm Design and Firearm Violence-Reply
Authors: Garen Wintemute
Journal: JAMA (1996)

In Reply.  —I agree with Mr Feldman's point that a reactive, uninformed gun control policy may have unintended negative consequences. I disagree with his contention (not a surprising one, coming as it does from an industry representative) that we should therefore abandon the product-oriented approach. Mr Feldman sets up a straw man by arguing that any attention given to firearms per se ignores the user  he cites. I am not aware that anyone, whatever their position on firearms policy may be, suggests that these human factors should be ignored: I certainly do not.  Rather, we have largely ignored any possible effect on firearm violence that is attributable to firearms themselves—a head-in-the-sand approach that we have forsworn in recent decades, with highly beneficial results, in the case of both motor vehicles and cigarettes.  Consider, as just 1 example, the hundreds of thousands of inexpensive handguns produced each year by the southern California
Ethacrynic Acid
Authors: PAUL J. CANNON, HENRY O. HEINEMANN, WILLIAM B. STASON, JOHN H. LARAGH
Journal: Circulation (1965)

Ethacrynic acid, a chemically different diuretic, has been evaluated in 82 patients. The drug was remarkably potent when administered intravenously (0.5 to 1 mg./Kg.) or by mouth (doses to 50 mg. four times per day). It proved particularly effective in patients with refractory edema, and in edematous states accompanied by azotemia or electrolyte disturbances. Its natriuretic effects added to those of other diuretics and potentiation actually appeared to occur when it was combined with a carbonic-anhydrase inhibitor. Renal clearance data indicated that ethacrynic acid has a unique mode of action. There was little effect on glomerular filtration or renal plasma flow and its major action was to block sodium and chloride reabsorption probably in both proximal and distal portions of the renal tubules. Ion exchange mechanisms seemed little affected by the drug because it characteristically increased both hydrogen and potassium ion excretion. In general the degree of induced potassium loss correlated well with the rate of endogenous aldosterone secretion. Furthermore, ethacrynic acid did not cause potassium loss in one adrenalectomized subject nor in another subject pretreated with an aldosterone antagonist. Diuresis induced by ethacrynic acid was often accompanied by the development of systemic metabolic alkalosis. Factors in the development of this alkalosis were (1) urinary K + loss with hypokalemia, (2) urinary H + loss, and (3) in edematous patients the rapid large loss of relatively HCO 3 - -free fluid from the extracellular fluid space. The systemic alkalosis was found to be accompanied by compensatory alveolar hypoventilation. These studies of the mechanisms of the alkalosis point to the occasional importance of the administration of chloride, of potassium, or of saline as corrective measures. Diuresis with ethacrynic acid, like other diuretic agents, produced marked increases in the rate of aldosterone secretion of normal subjects. More variable effects were observed in patients with heart disease, possibly because improvement in their circulatory status operated to lower hormone secretion activity. Ethacrynic acid had effects on urate excretion that resembled thiazide diuretics. Higher blood levels of intravenous administration were uricosuric. Lower blood levels of oral therapy caused renal urate retention and hyperuricemia. Most of the problems associated with the use of ethacrynic acid appeared to be related more to its pharmacologic potency than to any truly toxic effect. Because of this it is suggested that the sensitivity and response pattern of each patient be determined in stepwise fashion. In most patients with edema an intermittent dosage schedule provides a more efficient diuretic response and allows time intervals for correction of any electrolyte imbalance. If used with a thorough understanding of its pharmacologic effects ethacrynic acid promises to be a most useful agent in the therapy of patients with difficult or refractory edema.
Ascorbic Acid Deficiency Associated with Gastric Lesions
Authors: Charles C. Lund
Journal: New England Journal of Medicine (1942)

series studied, ascorbic acid deficiency caused fewer failures of healing than technical factors did. As a result of a similar study of cases with disrupted wounds, Hartzell, Winfield and Irwin4 have taken the same conservative position, placing ascorbic acid deficiency among other factors as a possible cause of delayed or poor healing. Holman,'' who studied routine surgical admissions, found that many patients had low blood plasma levels of ascorbic acid, but he did not state that disruption occurred in any of the particular cases studied. Bartlett, Jones and Ryan6 showed that, in addition to low plasma ascorbic acid levels, many patients had abnormally low clearance curves in the plasma and low excretion in the urine after the administration of test doses. A recent paper by the same authors7 presents experi-
Bacterial entombment by intratubular mineralization following orthograde mineral trioxide aggregate obturation: a scanning electron microscopy study
Authors: Jun Sang Yoo, Seok-Woo Chang, So Ram Oh, Hiran Perinpanayagam, Sang-Min Lim, Yeon-Jee Yoo, Yeo-Rok Oh, Sang-Bin Woo, Seung-Hyun Han, Qiang Zhu, Kee-Yeon Kum
Journal: International Journal of Oral Science (2014)

The time domain entombment of bacteria by intratubular mineralization following orthograde canal obturation with mineral trioxide aggregate (MTA) was studied by scanning electron microscopy (SEM). Single-rooted human premolars (n=60) were instrumented to an apical size #50/0.06 using ProFile and treated as follows: Group 1 (n=10) was filled with phosphate buffered saline (PBS); Group 2 (n=10) was incubated with Enterococcus faecalis for 3 weeks, and then filled with PBS; Group 3 (n=20) was obturated orthograde with a paste of OrthoMTA (BioMTA, Seoul, Korea) and PBS; and Group 4 (n=20) was incubated with E. faecalis for 3 weeks and then obturated with OrthoMTA–PBS paste. Following their treatments, the coronal openings were sealed with PBS-soaked cotton and intermediate restorative material (IRM), and the roots were then stored in PBS for 1, 2, 4, 8 or 16 weeks. After each incubation period, the roots were split and their dentin/MTA interfaces examined in both longitudinal and horizontal directions by SEM. There appeared to be an increase in intratubular mineralization over time in the OrthoMTA-filled roots (Groups 3 and 4). Furthermore, there was a gradual entombment of bacteria within the dentinal tubules in the E. faecalis inoculated MTA-filled roots (Group 4). Therefore, the orthograde obturation of root canals with OrthoMTA mixed with PBS may create a favorable environment for bacterial entombment by intratubular mineralization. Root canal surgeries performed with a new kind of material could successfully entrap problematic bacteria and prevent tooth abscesses. A team led by Kee-Yeon Kum from the Seoul National University School of Dentistry, South Korea, prepared roots from 60 extracted human premolar teeth. They exposed half of the teeth to Enterococcus faecalis, a bacterium commonly found in infections in root-canal treated teeth, the remaining teeth acting as controls. The roots were then filled with either a phosphate-buffered saline (PBS) solution or OrthoMTA, a newly developed type of mineral trioxide aggregate (MTA) cement composed mainly of tricalcium silicate. After incubation periods ranging from one to 16 weeks, the researchers examined the teeth using scanning electron microscopy. They found that OrthoMTA-filled roots had higher rates of mineralization and could seal or ‘entomb’ the bacteria dentinal tubules.
Norepinephrine-induced human platelet activation in vivo is only partly counteracted by aspirin.
Authors: P T Larsson, N H Wallén, P Hjemdahl
Journal: Circulation (1994)

BACKGROUND Epinephrine and mental stress may, via platelet stimulation, enhance the risk of thrombus formation. Norepinephrine is more likely than epinephrine to activate platelets in vivo because of higher levels in plasma but is less well studied in this respect. The antiplatelet drug of choice for patients with coronary artery disease, aspirin, may be less effective during sympathoadrenal activation. We therefore investigated platelet responses in vivo to exogenous norepinephrine with and without aspirin pretreatment. METHODS AND RESULTS Platelet aggregability in vivo was assessed in 11 healthy male subjects, by filtragometry ex vivo (which reflects platelet aggregability in vivo) and by measurements of plasma beta-thromboglobulin (beta-TG, which reflects platelet secretion). Norepinephrine infusions elevated venous plasma norepinephrine from 1.5 to 4 and 15 nmol/L, respectively, and enhanced platelet aggregability (filtragometry) concentration dependently (P &lt; .001). Platelet secretion (beta-TG levels) increased during high-dose infusion (P &lt; .01). Aspirin pretreatment (500 mg orally 12 hours earlier) reduced the excretion of 11-dehydrothromboxane B2 by 62 +/- 5% (P &lt; .001) and attenuated platelet aggregability at rest (P &lt; .05) but not the effect of norepinephrine infusion on platelet aggregability. Conversely, resting plasma beta-TG levels and the urinary excretion of high-molecular-weight beta-TG were not altered by aspirin pretreatment, whereas the norepinephrine-induced increase in plasma beta-TG was abolished. CONCLUSIONS Norepinephrine, at plasma levels easily attained during exercise, enhances platelet aggregability and platelet secretion in vivo in healthy humans. Aspirin may be less effective as an antithrombotic drug during sympathoadrenal activation in humans.
NOTES ON THE INTRACELLULAR OCCURRENCE OF DIPLOCOCCUS PNEUMONIÆ IN CEREBROSPINAL MENINGITIS.
Authors: LOUIS BLANCHARD WILSON
Journal: JAMA (1901)

That the diplococcus pneumoniæ, in common with other micro-organisms, may occasionally be found within leucocytes as the result of phagocytosis in inflammatory processes, has been frequently noted by numerous observers. Its extracellular position, however, in the exudate in cerebrospinal meningitis is so markedly the rule that the point is used as a differential characteristic between the organism and diplococcus intracellularis meningitidis. Consequently, the preponderatingly intracellular position of diplococcus pneumoniæ in the following four cases of cerebrospinal meningitis makes them of sufficient interest to warrant their record. <h3>Case 1.</h3> —In June, 1898, a specimen of cerebro-spinal fluid from a case of cerebrospinal meningitis, removed by lumbar puncture during the third week of the disease, showed in direct cover-slip preparations, numerous encapsulated, lanceolate, Gram-staining diplococci, most of which were intracellular. Cultures in broth, on plain and blood agar, and Löffler's blood serum developed, without admixture of other organisms, a diplococcus, which, despite
Public Hysteria and Medical Practice
Authors: Lorin Koran
Journal: JAMA (1975)

To the Editor.—  Sixty years ago, public hysteria, together with the prejudices of public officials and a few physicians, led to the abandonment of a potentially useful treatment for a serious medical illness. 1,2 Treatment of opiate addiction with maintenance doses of opiates was outlawed for 50 years, and hundreds of thousands of opiate addicts suffered needlessly as a result. 3 History is about to repeat itself. Hysteria and prejudices regarding the possible side effects of electroconvulsive therapy (ECT) are now bringing about an abandonment of this treatment for depression, schizophrenia, and other mental disorders for which it has been shown to be relatively safe and quite efficacious. 4,5 A new law (AB 4481) ensures that ECT will cease to be used in California. The law requires that ECT not be used until all other appropriate treatment modalities have been exhausted and the decision of the treating physician has been
An Unusual Case of Diffuse Large B-Cell Lymphoma Involving the Vulva Evaluated by 18F-FDG PET/CT
Authors: Giorgio Treglia, Gaetano Paone, Ulrike Perriard, Luca Ceriani, Luca Giovanella
Journal: Clinical Nuclear Medicine (2013)

We describe an unusual case of diffuse large B-cell lymphoma involving the vulva detected and staged by F-FDG PET/CT. An 83-year-old female patient with history of endometrial carcinoma underwent F-FDG PET/CT for follow-up. PET/CT detected an area of increased F-FDG uptake corresponding to a vulvar nodule; moderate and diffuse F-FDG uptake in the bone marrow was also evident. Based on these PET/CT findings, the patient underwent biopsy of the vulvar nodule. Histology demonstrated the presence of a diffuse large B-cell lymphoma of the vulva. Bone marrow biopsy was positive for lymphoid infiltration.
Pharmacological treatments in pregnant women with psoriasis in the U.S.A.
Authors: H.C. Lin, J.N. Hunnicutt, F.A. Moustafa, A.L. Rohr, K.E. Huang, R. Balkrishnan, S.R. Feldman
Journal: British Journal of Dermatology (2014)

conclusion, this study showed high rates of self-reported improvement in patients' QoL after a mean interval of 10 years following ETS for palmar hyperhidrosis.
Ethical problems in feeding patients with advanced dementia.
Authors: A Norberg, B Norberg, G Bexell
Journal: BMJ (1980)

Aged patients with dementia if not stricken by an acute disease sooner or later approach a terminal phase that is distinguished by a failure of spoon feeding. This condition induces great anxiety in the workers who care for these patients. The interaction between patient and care-worker during spoon-feeding failure is described by the psychological model of double-binding. Two serious consequences of double-binding are the distancing of the care-workers from the patient and scapegoating among the care-workers. It is essential that the pressure of double-bindings in the wards should be reduced.
The Use of Telepaque in Cholecystography
Authors: Clark F. Miller, John W. Carrier
Journal: New England Journal of Medicine (1953)

AMONG the relatively new orally administered radio-opaque mediums for cholecystography that are in common use today, Priodax (iodoalphionic acid) has enjoyed the greatest popularity since its introduction ten years ago. In recent years it has been in regular use at the Central Maine General Hospital. However, Menophen, placed on the market in 1944, is preferred by some workers. Both these mediums are satisfactory, but the incidence of side effects such as nausea and diarrhea, though small, leaves room for improvement. Moreover, every radiologist has seen a few cases in which a gall bladder failed to present the usual dense shadow . . .
Pivotal role of cardiac lineage protein-1 (CLP-1) in transcriptional elongation factor P-TEFb complex formation in cardiac hypertrophy
Authors: J ESPINOZADEROUT, M WAGNER, K SHAHMIRI, E MASCARENO, B CHAQOUR, M SIDDIQUI
Journal: Cardiovascular Research (2007)

Our aim was to determine if the expression pattern of CLP-1 in developing heart is consistent with its role in controlling RNA transcript elongation by transcriptional elongation factor b (P-TEFb) and if the inhibitory control exerted over P-TEFb by CLP-1 is released under hypertrophic conditions.We performed immunoblot and immunofluorescence analysis of CLP-1 and the P-TEFb components cdk9 and cyclin T in fetal mouse heart and 2 day post-natal mouse cardiomyocytes to determine if they are co-localized. We induced hypertrophy in rat cardiomyocytes either by mechanical stretch or treatment with hypertrophic agents such as endothelin-1 and phenylephrine to determine if CLP-1 is released from P-TEFb in response to hypertrophic stimuli. The involvement of the Jak/STAT signal transduction pathway in this process was studied by blocking this pathway with the Jak2 kinase inhibitor, AG490, and assessing the association of CLP-1 with P-TEFb complexes.We found that CLP-1 is expressed along with P-TEFb components in developing heart during the period in which knockout mice lacking the CLP-1 gene develop cardiac hypertrophy and die. Under conditions of hypertrophy induced by mechanical stretch or agonist treatment, CLP-1 dissociates from the P-TEFb complex, a finding consistent with the de-repression of P-TEFb kinase activity seen in hypertrophic cardiomyocytes. Blockage of Jak/STAT signaling by AG490 prevented release of CLP-1 from P-TEFb despite the ongoing presence of hypertrophic stimulation by mechanical stretch.CLP-1 expression in developing heart and isolated post-natal cardiomyocytes colocalizes with P-TEFb expression and therefore has the potential to regulate RNA transcript elongation by controlling P-TEFb cdk9 kinase activity in heart. We further conclude that the dissociation of CLP-1 from P-TEFb is responsive to hypertrophic stimuli transduced by cellular signal transduction pathways. This process may be part of the genomic stress response resulting in increased RNA transcript synthesis in hypertrophic cardiomyocytes.
Thin Needle Percutaneous Transhepatic Cholangiography - Historical Review
Authors: Kunio Okuda
Journal: Endoscopy (1980)

In this review, the historical background of the development of the thin needle technique for percutaneous transhepatic cholangiography is described. History goes back to 1921 when cholangiography was first attempted via the gallbladder in Germany. Despite the subsequent progress, frequent bile leakage necessitated a turn to the transhepatic technique which was vastly improved by the introduction of the TV monitoring system. Finally, the development and refinement of the technique for percutaneous transhepatic cholangiography which occurred mainly in Japan, particularly at the Chiba University Hospital, first in the hands of surgeons and then internists, is detailed with references.
Authors' reply to Pande and Soumerai
Authors: L. Silver, M. T. Bassett
Journal: BMJ (2011)

Pande and Soumerai present an overly simplistic critique, not grounded in the reality of public policy evaluations.1 We did not conclude, as they suggest, that the intervention was ineffective. The 15% of patrons who reported seeing and using calorie information purchased fewer calories. In 2009 almost 1.3 million New Yorkers reported eating fast food at least once a week, resulting …