tbuckley/cabot-search huggingface dataset:
Long-term response to hydroxychloroquine in patients with discoid lupus erythematosus
Authors: S. Wahie, S.J. Meggitt
Journal: British Journal of Dermatology (2013)

The recommended first‐line oral therapy for discoid lupus erythematosus (DLE) is the antimalarial hydroxychloroquine. To the best of our knowledge, there is no published information regarding the long‐term (i.e. > 6 months) response of DLE to hydroxychloroquine in clinical practice. To describe the long‐term clinical response of DLE to hydroxychloroquine after 6 months of use. A multicentre retrospective cohort study was conducted in patients with DLE who had received treatment with hydroxychloroquine. All patients were recruited and interviewed by a single investigator and response to hydroxychloroquine assessed by the same individual through a retrospective review of case notes using a specified protocol. A total of 200 patients with DLE were recruited (F:M = 4 : 1) with a median age at diagnosis of 40 years (range 16–81) and median follow‐up of 8 years (range 0·5–37). An adequate clinical response to hydroxychloroquine was recorded in 91 patients (45·5%) but nonresponse occurred in 85 patients (42·5%). The remainder of patients either had partial response or withdrew from therapy due to toxicity or were unclassifiable. Importantly, of those individuals that did respond to hydroxychloroquine within the first 6 months of use, almost one in five eventually lost their response, despite continued administration, after a median interval of 2 years. These patients often regained disease control if treated with a combination of hydroxychloroquine and mepacrine. Of those that did not respond to hydroxychloroquine within the first 6 months of use, almost one in 10 became eventual responders either after continued administration for up to 2 years or when rechallenged on hydroxychloroquine. The remaining nonresponders relied frequently on oral corticosteroid. In this cohort of patients with DLE, long‐term clinical response to hydroxychloroquine occurred in less than 50% of patients. Nonresponders to hydroxychloroquine frequently required oral steroid to achieve disease control. These findings merit further investigation through a multicentre prospective study using a validated disease activity measure.
Surgeon is struck off for second time
Authors: Owen Dyer
Journal: BMJ (2005)

A consultant general surgeon has been struck off by the General Medical Council for a second time, three years after successfully appealing to the Privy Council against his first erasure.

Steven Walker, who worked at Blackpool Victoria Hospital from 1995 to 1998, was struck off for a series of botched operations in 2001 but then in 2003 was reinstated with conditions after appealing.

But a lengthy police inquiry led to a manslaughter conviction last year over the death of one of his patients, and the inquiry revealed that he had removed and kept a theatre register that was sought by investigators. The …
Aerosolized Surfactant in Sepsis-Induced Adult Respiratory Distress Syndrome-Reply
Authors: John G. Weg
Journal: JAMA (1995)

In Reply.  —We thank Dr Doig for his comments and queries. Enrollment in this study was from November 4,1989, through December 19, 1990. Only 18 of the 20 centers entered patients, and some sites joined the study late in 1990. The mean±SD number of entries per site was 2.8±1.5 (range, 1 to 6). A systematic record was not maintained for the number of patients screened, the number eligible for enrollment, or any reasons for exclusion other than those stated under Methods. Intermittent random evaluations at various centers did not identify any biases. Patient enrollment was limited by the strict enrollment criteria, in particular, entry within 18 hours of the onset of sepsis or sepsis syndrome (see Methods). Refusal was rare. Therefore, we believe the subjects entered into this study were representative of our general ICU populations.  Doig appropriately notes that administration of Exosurf is usually evident in the endotracheal tube
Vitamin E: Interactions with Free Radicals and Ascorbate
Authors: P B McCay
Journal: Annual Review of Nutrition (1985)

The association of the tocopherols with lipid peroxidation in biological systems began in the early days of investigations on the chemical nature of these substances (25). Since then a great deal of work has attempted to relate the symptoms of vitamin E deficiency with peroxidative degradation of lipids, primarily those associated with membranous organelles. The signs of vitamin E deficiency in various species of animals are diverse, involving different tissues with different manifestations and different degrees of severity. Thus, it seems clear that the biological function of this vitamin is not specific in the sense of its being a cofactor for an enzymic reaction (as is the case for the B-complex vitamins). Given the appropriate species and certain dietary and environmental conditions, essentially any tissue can be made to develop characteristic signs as a result of a deficiency of this vitamin. In some human disease states, supple­ mentation of vitamin E at levels far exceeding those normally required amelio­ rates or improves the condition. Because of this multiplicity of effects, a common denominator that might explain the effects of a deficiency or excess of this vitamin is not obvious. A common denominator to consider, however, is
613 THE ANTIFIBROTIC PENTOXYPHILLINE/A-TOCOPHEROL ASSOCIATION DOES NOT LIMIT LIVER FIBROSIS PROGRESSION IN PATIENTS WITH CHRONIC HEPATITIS C – ANRS HC 10
Authors: H. Fontaine, S. Fernandes, B. Nalpas, P. Bedossa, J.-D. Grangé, A. Tran, J. Guéchot, S. Candon, F. Imbert-Bismut, S. Pol
Journal: Journal of Hepatology (2009)
Accidental strangulation with a Venetian blind cord--a near miss
Authors: M. Masand
Journal: BMJ (2010)

A 22 month old girl was brought to our emergency department after accidental strangulation with the looped cord of a Venetian blind. The mother had walked into the girl’s bedroom and found her hanging from the cord. The parents quickly dialled 999 and gave mouth to mouth breathing until the ambulance crew arrived.

On arrival in the emergency department the girl had an inspiratory stridor and oxygen saturation going down to 80%, and she was agitated. She had a petechial rash on her face and beaded marks (from the beaded cord of the blind) round her neck anteriorly. She was immediately intubated and stabilised before transfer to our regional paediatric intensive care unit, where she was ventilated for three days. Discharged home on day 7, she has had no neurological complications or any other abnormalities. Magnetic resonance imaging of her head and spine showed no abnormalities.

The child had been standing on the window sill trying to look out when she probably lost her footing. She was lucky that her mother had walked into the room in time, maybe within seconds of strangulation. 

It had never crossed my mind that a looped …
Characterisation of Kv4.3 in HEK293 cells: comparison with the rat ventricular transient outward potassium current
Authors: J Faivre
Journal: Cardiovascular Research (1999)

Objective: The Shal (or Kv4) gene family has been proposed to be responsible for primary subunits of the transient outward potassium current (Ito). More precisely, Kv4.2 and Kv4.3 have been suggested to be the most likely molecular correlates for Ito in rat cells. The purpose of the present study was to compare the properties of the rat Kv4.3 gene product when expressed in a human cell line (HEK293 cells) with that of Ito recorded from rat ventricular cells. Methods: The cDNA encoding the rat Kv4.3 potassium channel was cloned into the pHook2 mammalian expression vector and expressed into HEK293. Patch clamp experiments using the whole cell configuration were used to characterise the electrophysiological parameters of the current induced by Kv4.3 in comparison with the rat ventricular myocyte Ito current. Results: The transfection of HEK293 cells with rat Kv4.3 resulted in the expression of a time- and voltage-dependent outward potassium current. The current activated for potentials positive to −40 mV and the steady-state inactivation curve had a midpoint of −47.4±0.3 mV and a slope of 5.9±0.2 mV. Rat ventricular Ito current was activated at potentials positive to −20 mV and inactivated with a half-inactivation potential and a Boltzmann factor of −29.1±0.7 mV and 4.5±0.5 mV, respectively. The time course of recovery from inactivation of rat Kv4.3 expressed in HEK293 cells and of Ito recorded from native rat ventricular cells were exponentials with time constants of 213.2±4.1 msec and 23.±1.5 msec, respectively. Pharmacologically, Ito of rat myocytes showed a greater sensitivity to 4-aminopyridine than Kv4.3 since half-maximal effects were obtained with 1.54±0.13 mM and 0.14±0.02 mM on Kv4.3 and Ito, respectively. In both Kv4.3 and Ito, 4-aminopyridine appears to bind to the closed state of the channel. Finally, although a higher level of expression was observed in the atria compared to the ventricle, the distribution of the Kv4.3 gene across the ventricles appeared to be homogenous. Conclusion: The results of the present study show that Kv4.3 channel may play a major role in the molecular structure of the rat cardiac Ito current. Furthermore, because the distribution of Kv4.3 across the ventricle is homogenous, the blockade of this channel by specific drugs may not alter the normal heterogeneity of Ito current.
Research bureaucracy in the United Kingdom: Good governance is needed
Authors: Woody Caan
Journal: BMJ (2004)

EDITOR—Transparent ethical scrutiny should come sufficiently early in the “life” of a research project that the design can incorporate the management of any risks to the public. A feeding frenzy for funding opportunities can make it difficult to organise such early scrutiny. The BMJ shows examples of a new problem: the paralysis of research by bureaucracy associated with ethics committees.1 Even …
Endoscopic Sphincter of Oddi Manometry with a Portable Electronic Microtransducer System: Comparison with the Perfusion Manometry Method and Routine Clinical Application
Authors: T. Wehrmann, T. Schmitt, A. Schönfeld, W. F. Caspary, H. Seifert
Journal: Endoscopy (2000)

Background and Study Aims: Endoscopic perfusion manometry (PM) of the sphincter of Oddi (SO) requires expensive equipment which is relatively large and uncomfortable to handle in the endoscopic retrograde cholangiopancreatography (ERCP) setting. Furthermore, the volume load of the biliopancreatic system may contribute to the increased risk of pancreatitis after SO manometry.
Natural History of Benign Solid and Cystic Thyroid Nodules
Authors: Erik K. Alexander, Shelley Hurwitz, Jenny P. Heering, Carol B. Benson, Mary C. Frates, Peter M. Doubilet, Edmund S. Cibas, P Reed Larsen, Ellen Marqusee
Journal: Annals of Internal Medicine (2003)

Background: Thyroid nodules are common and most often benign. The natural history of benign thyroid nodules, however, is unclear. Objective: To determine the natural history of cytologically benign thyroid nodules using ultrasonography. Design: Retrospective case series. Setting: Single tertiary care clinic. Participants: All patients referred to the Brigham and Women's Hospital Thyroid Nodule Clinic, Boston, Massachusetts, who had benign cytologic results on ultrasonography-guided fine-needle aspiration of a thyroid nodule between 1995 and 2000 and returned for a requested follow-up examination 1 month to 5 years later. Measurements: Nodule dimensions were measured at both visits, and growth was defined as an increase in calculated volume of 15% or greater. These results were correlated with the time between examinations, age, sex, baseline serum thyroid-stimulating hormone concentration, and cystic content of each nodule. Results: Nodule volume increased over time (P < 0.001). The estimated proportion of nodules with an increase in volume of 15% or greater after 5 years was 89%. Nodules with greater cystic content were less likely to grow than solid nodules (P = 0.01). Seventy-four of the 330 nodules were reaspirated on the second visit. Despite an average increase in volume of 69%, only 1 of 74 reaspirated nodules was malignant. Conclusion: Most solid, benign thyroid nodules grow. Therefore, an increase in nodule volume alone is not a reliable predictor of malignancy.
Dermatologic problems of musicians
Authors: James R. Nethercott, D. Linn Holness
Journal: Journal of the American Academy of Dermatology (1991)

To the Editor: We were interested to read the original article by Rimmer andSpielvogel (J AM ACAD DERMATOl 1990;22:657-63) and the letters of Signore, and Kanwar and Kaur (J AM ACAD DERMATOL 1991;24:321-2) regarding dermatologic problems in musicians. We have seen two musicians in whom allergic contactdermatitis developed. Onewas a63-year-oldmale violinist. He hada 5-year history ofan eczematous eruptionon the leftside ofhisneck. Patch testingrevealed a 2+ reaction tocolophony, both20% and 60%inpetrolatum.Despitehisattempts touseaslittlerosinas possible, theeruption continued. The otherperson was a 25-yearold harpist. Shehada 5-month history ofan eczematous eruption onthetipsofher fingers onher right hand. She Journal of the American Academy of Dermatology
Comparative analysis of portal cell infiltrates in antimitochondrial autoantibody–positive versus antimitochondrial autoantibody–negative primary biliary cirrhosis
Authors: Qinglong Jin, Yuki Moritoki, Ana Lleo, Koichi Tsuneyama, Pietro Invernizzi, Hitoshi Moritoki, Kentaro Kikuchi, Zhe-Xiong Lian, Gideon M. Hirschfield, Aftab A. Ansari, Ross L. Coppel, Eric M. Gershwin, Junqi Niu
Journal: Hepatology (2011)

Abstract Substantial evidence supports dysregulated B-cell immune responses in patients with primary biliary cirrhosis (PBC), including the presence of serum antimitochondrial antibodies (AMAs). However, recent reports from murine models of PBC suggest that B cells may also provide regulatory function, and indeed the absence of B cells in such models leads to exacerbation of disease. The vast majority of patients with PBC have readily detectable AMAs, but a minority (&lt;5%) are AMA negative (AMA−), even with recombinant diagnostic technology. This issue prompted us to examine the nature of B-cell infiltrates surrounding the portal areas in AMA-positive (AMA+) and AMA− patients, because they display indistinguishable clinical features. Of importance was the finding that the degree of bile duct damage around the portal areas was significantly milder in AMA+ PBC than those observed in AMA− PBC patients. The portal areas from AMA− patients had a significant increase of cluster of differentiation (CD)5+ cells infiltrating the ductal regions, and the levels of B-cell infiltrates were worse in the early phase of bile duct damage. The frequency of positive portal areas and the magnitude of CD5+ and CD20+ cellular infiltrates within areas of ductal invasion is associated with the first evidence of damage of biliary duct epithelia, but becomes reduced in the ductopenia stage, with the exception of CD5+ cells, which remain sustained and predominate over CD20+ cells. Conclusion: Our data suggest a putative role of B-cell autoimmunity in regulating the portal destruction characteristic of PBC. (Hepatology 2012)
Evidence for structural sympathetic reinnervation after orthotopic cardiac transplantation in humans.
Authors: R F Wilson, B V Christensen, M T Olivari, A Simon, C W White, D D Laxson
Journal: Circulation (1991)

Cardiac transplantation (CT) causes total cardiac denervation.To test directly for sympathetic reinnervation in humans, we measured the cardiac release of norepinephrine (NE) in response to tyramine (an agent that causes NE release from intact sympathetic nerve terminals) and sustained handgrip exercise (a reflex sympathetic stimulus) in 12 patients less than 5 months after CT, in 50 patients 1 year or more after CT, and in eight patients without CT. Plasma [NE] was measured in the aorta [( NE]Ao) and coronary sinus [( NE]CS) at rest, after tyramine administration (55 micrograms/kg, i.v.), and during sustained handgrip exercise. Cardiac NE release was determined by subtracting [NE]Ao from [NE]CS [( NE]CS-Ao). NE release was defined as [NE]CS-Ao during the intervention-[NE]CS-Ao at rest (delta [NE]CS-Ao). In patients studied within 5 months of CT, no significant NE release occurred after tyramine administration (delta [NE]CS-Ao, 33 +/- 18 pg/ml; range, -98 to 117 pg/ml) or handgrip exercise (delta [NE]CS-Ao, -34 +/- 10 pg/ml; range, -46 to 8 pg/ml; n = 10). Conversely, in 39 of 50 patients studied 1 year or more after CT, tyramine administration caused a significant cardiac NE release (delta [NE]CS-Ao, 500 +/- 59 pg/ml; range, -11 to 1,918 pg/ml), and handgrip exercise caused a significant NE release in 17 of 41 patients (delta [NE]CS-Ao, 189 +/- 34 pg/ml; range, -211 to 949 pg/ml). In normally innervated patients, tyramine caused an even larger NE release (delta [NE]Ao-CS, 1,943 +/- 210 pg/ml; range, 1,152 to 2,977 pg/ml), and handgrip exercise caused a significant NE release in two of seven patients (delta [NE]CS-Ao, 143 +/- 51 pg/ml; range, -15 to 338 pg/ml).Early after CT, neither tyramine nor handgrip exercise caused a significant cardiac release of NE, suggesting sympathetic denervation. Late after CT, most patients had a significant, but subnormal, NE release in response to pharmacological or reflex stimuli, suggesting that limited sympathetic reinnervation occurs in most patients after orthotopic CT.
304 METABOLIC SYNDROME (MS) IS A NEGATIVE PREDICTOR OF TREATMENT OUTCOME IN PATIENTS WITH CHRONIC HEPATITIS C: RESULTS FROM THE IDEAL STUDY
Authors: M.S. Sulkowski, J.W. King, S.A. Harrison, L. Rossaro, K.-Q. Hu, E.J. Lawitz, M.L. Schiffman, A.J. Muir, G.W. Galler, J. McCone, L.M. Nyberg, W.M. Lee, R. Ghalib, J.G. McHutchison, S. Noviello, V.S. Goteti, J.K. Albrecht, C.A. Brass
Journal: Journal of Hepatology (2010)
Hematuria and Proteinuria Associated with Methicillin Administration
Authors: Ralph D. Feigin, Arnold Fiascone
Journal: New England Journal of Medicine (1965)

DIMETHOXYPHENYL-PENICILLIN has generally been regarded as of low toxicity and has been used increasingly often in the treatment of sepsis due to penicillinase-producing staphylococci.1 , 2 That methicillin is not wholly free from untoward side effects is illustrated by the following report of a child in whom gross hematuria and proteinuria developed during parenteral methicillin therapy.Case ReportD.G. (M.G.H. 129–39–24), a 2 1/2-year-old boy, was admitted to the hospital on July 2, 1964, after x-ray study of the chest revealed an abscess cavity in the right lower lobe measuring 5 cm. in greatest diameter. He had been in excellent health until . . .
Proopiomelanocortin mrna expression by small cell bladder carcinoma associated with cushing’s syndrome: diagnostic contribution of in situ hybridization
Authors: Elli Lakka-Papadodima, Yvonne Dimoula, George Kontogeorgos, Zissoula Manika, John Kiayias, Harafambos Theodorou
Journal: Endocrine Pathology (1994)
A COMPARATIVE STUDY OF ANTIDEPRESSANTS IN BALANCED THERAPY
Authors: DAVID C. ENGLISH
Journal: American Journal of Psychiatry (1961)

Isocarboxazid, an iproniazid analog, showed better results in the treatment of 195 patients with depressive and acute schizophrenic reactions than were seen in varying numbers of patients on 7 other antidepressants, including 223 treated with iproniazid. With a median improvement time of 8 days, isocarboxazid alone equals or exceeds ECT in speed and effectiveness, and shows no major side effects. Isocarboxazid appears to have the strongest "activation" effect of any amine oxidase inhibitor, is easily managed in maintenance usage, and can be combined with other antidepressants or tranquilizers, at least one of the latter having been used with it in every one of the 195 patients in this series. It is quite effective in both acute schizophrenic and depressed patients, and the fact that these diagnoses constitute 83% of private psychiatric hospital admissions indicates the potential wide range of application of isocarboxazid. The mood-elevating effect of isocarboxazid correlates with the rise of norepinephrine, but not with the earlier serotonin increase. The frequently seen early sedative effect of isocarboxazid, however, does accompany the rise in serotonin. This "double-action" of isocarboxazid is one of the basic reasons for the sharp difference in its clinical effects from those of amphetamine. Pharmacologically, "balanced therapy" is simply the outside reinforcement of the isocarboxazid tranquilization in agitated and disturbed patients. Although a good "balance" does not produce hyperactivation, under conditions of unusual stress the patient can be deliberately carried "higher." In the special case of extremely disturbed psychotics only partially controllable with high phenothiazine dosages, isocarboxazid can be used to provide a reinforcing reserpine-type tranquilization. Concern about possible hepatotoxicity seems unwarranted, not only because there were no significant liver function changes during this study, but because a suicidal risk with a mild chlorpromazine or endemic hepatitis showed clinical improvement and resolution of his jaundice while on isocarboxazid. The drug produces no obvious change in the ECT threshold and shows little clinical potentiation of alcohol but minimizes the "morning after." It "potentiates" phenothiazines sufficiently to improve the "tranquilization" of extremely disturbed patients.
Galactose ingestion increases vascular permeability and collagen solubility in normal male rats.
Authors: K Chang, M Tomlinson, J R Jeffrey, R G Tilton, W R Sherman, K E Ackermann, R A Berger, T J Cicero, C Kilo, J R Williamson
Journal: Journal of Clinical Investigation (1987)

In view of the similarity of cataracts and neuropathy in galactose-fed and diabetic rats, the present experiments were undertaken to determine whether consumption of galactose-enriched diets (10, 25, or 50% by weight) also increases collagen crosslinking and permeation of vessels by 125I-albumin analogous to that observed in diabetic rats. The observations in these experiments: demonstrate that consumption of galactose-enriched diets for 3 wk selectively increases 125I-albumin permeation of the same vascular beds affected in diabetic rats and by diabetic vascular disease in humans (i.e., the aorta and vessels in the eye, kidney, sciatic nerve, and new tissue formed in the diabetic milieu); demonstrate that the susceptibility of the vasculature to aldose reductase-linked injury (increased permeability) varies greatly in different tissues; indicate that collagen solubility (crosslinking) changes in galactose-fed rats differ sharply from those in diabetic rats; and provide new evidence that consumption of galactose-enriched diets induces a hypogonadal state in male rats.
NHS conference is warned of dangers of Transatlantic Trade and Investment Partnership
Authors: M. Limb
Journal: BMJ (2015)

The United Kingdom must revive the “spirit of 1945” to preserve the NHS as a publicly funded and publicly provided institution, the People’s Convention for the NHS has heard.

More than 100 campaigners met in central London on Saturday 11 April to call for a united, nationwide effort to halt and roll back privatisation, funding cuts, and service closures. The People’s Convention for the NHS is an umbrella organisation supported by groups such as the People’s Assembly against Austerity, Keep Our NHS Public, People’s March for the NHS, various trade unions, and community campaigns.

Sue Richards, co-chair of Keep our NHS Public, dismissed the pledge …