tbuckley/cabot-search huggingface dataset:
Drug treatment for attention-deficit/hyperactivity disorder and suicidal behaviour: register based study
Authors: Q. Chen, A. Sjolander, B. Runeson, B. M. D'Onofrio, P. Lichtenstein, H. Larsson
Journal: BMJ (2014)

<b>Objective</b> To investigate the association between drug treatment for attention-deficit/hyperactivity disorder (ADHD) and risk of concomitant suicidal behaviour among patients with ADHD. <b>Design</b> Register based longitudinal study using within patient design. <b>Setting</b> Linkage of multiple national registers in Sweden. <b>Participants</b> 37 936 patients with ADHD born between 1960 and 1996 and followed from 2006 to 2009 for treatment status by ADHD drug treatment and suicide related events (suicide attempt and completed suicide). <b>Main outcome measure</b> Incidence rate of suicide related events during ADHD drug treatment periods compared with that during non-treatment periods. <b>Results</b> Among 37 936 patients with ADHD, 7019 suicide related events occurred during 150 721 person years of follow-up. At the population level, drug treatment of ADHD was associated with an increased rate of suicide related events (hazard ratio 1.31, 95% confidence interval 1.19 to 1.44). However, the within patient comparison showed a reverse association between ADHD drug treatment and rate of suicide related events (0.89, 0.79 to 1.00). Among stimulant users, a reduced within patient rate of suicide related events was seen during treatment periods (0.81, 0.70 to 0.94). Among non-stimulant/mixed users, no significantly increased within patient rate of suicide related events during non-stimulant treatment periods was seen (0.96, 0.72 to 1.30). <b>Conclusions</b> This study found no evidence for a positive association between the use of drug treatments for ADHD and the risk of concomitant suicidal behaviour among patients with ADHD. If anything, the results pointed to a potential protective effect of drugs for ADHD on suicidal behaviour, particularly for stimulant drugs. The study highlights the importance of using within patient designs to control for confounding in future pharmacoepidemiological studies.
Electrocardiographic QRS Axis Shift With Left Anterior Hemiblock
Authors: Angelo A. Deliyannis
Journal: JAMA (1971)

<h3>To the Editor.—</h3> In response to the paper of Ewy et al (<b>215</b>:429-432, 1971), we wish to report a case of intermittent left anterior hemiblock that seems to be related to metabolic factors other than hyperkalemia. <h3>Report of a Case.—</h3> A 19-year-old boy was admitted to the hospital with severe renal failure secondary to chronic glomerulonephritis. He had been receiving lanatoside C intravenously in doses of 0.4 mg every other day. On admission he was confused, oliguric (300 mg/24 hr), and was vomiting. The blood pressure was 140 mm Hg systolic and 80 mm Hg diastolic, and remained within normal limits during his hospitalization. The ocular fundi were normal. An ejection systolic murmur was heard over the base and the apex of the heart. Examination of the roentgenogram revealed the cardiac silhouette to be within normal limits. The blood urea nitrogen (BUN) level was 660 mg/100 ml; hemoglobin level,
A paradigm shift is needed to move biomedical research forward
Authors: B. Cochrane, K. Byatt
Journal: BMJ (2014)

Pound and Bracken’s article clearly and concisely captures the current status of, and key issues associated with, basic research using animals.1 In particular, and as identified by Godlee,2 one of the most relevant questions the paper raises is: “what can we do differently?”

The Dr Hadwen Trust maintains that basic biomedical research needs to be more relevant to humans and has funded a diverse portfolio of projects using …
Doctor referred to GMC after inquiry into epilepsy diagnoses
Authors: C. White
Journal: BMJ (2001)

An independent review of the management of childhood epilepsy at Leicester Royal Infirmary has confirmed allegations of misdiagnosis and overtreatment against consultant paediatrician Dr Andrew Holton. The hospital has now referred the matter to the General Medical Council.

Since his appointment in 1990, Dr Holton has cared for just over 10000 children, almost 2000 of whom he diagnosed as having epilepsy. So far, the case notes of 214 children have been examined in the three stage review, carried out by the Royal College of Paediatrics and Child Health Specialty Advisory Committee in Paediatric Neurology. Sixteen hundred cases remain to be reviewed.

Of the 214 cases, 171 gave definite or possible “cause for concern.” Just over a third of the children were not thought to have had epilepsy, and just under a third were thought to have been overtreated. To date, the investigating team have managed to review in greater depth the diagnosis and treatment of only 45 of these children, but it has concluded that there is “some level of concern in approximately 80%.”

The findings have prompted the regional director of public health …
Tanycytes of the hypothalamic median eminence form a diet-responsive neurogenic niche
Authors: Daniel A Lee, Joseph L Bedont, Thomas Pak, Hong Wang, Juan Song, Ana Miranda-Angulo, Vani Takiar, Vanessa Charubhumi, Francesca Balordi, Hirohide Takebayashi, Susan Aja, Eric Ford, Gordon Fishell, Seth Blackshaw
Journal: Nature Neuroscience (2012)
Lower Plasma Adiponectin Levels Are Associated with Larger Tumor Size and Metastasis in Clear-Cell Carcinoma of the Kidney
Authors: Jehonathan H. Pinthus, Nir Kleinmann, Britton Tisdale, Suman Chatterjee, Jian-Ping Lu, Aubrey Gillis, Tamika Hamlet, Gurmit Singh, Forough Farrokhyar, Anil Kapoor
Journal: European Urology (2008)
Evolution of Surgical Treatment of Coronary Artery Occlusive Disease
Authors: George P. Noon
Journal: JAMA (2009)

A 42-year-old man had extensive occlusive disease of the coronary artery and angina pectoris. An autogenous saphenous vein bypass from the ascending aorta to the anterior descending coronary artery was performed on Nov 23, 1964. The patient suffered an asymptomatic anterior myocardial infarction during operation but made an uncomplicated recovery. Seven years after the operation, the graft functions with normal left ventricular hemodynamics, while the occlusive process has produced obstruction of the left main coronary artery and almost complete occlusion of the right coronary artery. To our knowledge, this is the first successful case of a saphenous vein-coronary artery bypass with the longest follow-up of a functioning coronary vein bypass graft. See PDF for full text of the original JAMA article .
Interaction of Bile Salts With Calcium Hydroxyapatite: Inhibitors of Apatite Formation Exhibit High-Affinity Premicellar Binding
Authors: Sui-Min Qiu, Roger D. Soloway, Roger S. Crowther
Journal: Hepatology (1992)

Of the major human bile salts, only the glycine-conjugated dihydroxy species prevent the transformation of amorphous calcium phosphate to calcium hydroxyapatite, a component of gallstones; we have proposed that this inhibition occurs by competition between the bile salt and HPO4(2-) anions for binding site on the apatite crystal embryo. Now we show that the binding affinity of bile salts to fully mature hydroxyapatite has the following order: glycine-conjugated dihydroxy salts > taurine-conjugated dihydroxy salts > glycocholate approximately taurocholate. Glycine-conjugated dihydroxy bile salts bound with high affinity as "premicellar" aggregates, but the remaining species appeared to bind as a wider range of aggregate sizes. Glycochenodeoxycholate binding was decreased as the pH increased from 6.6 to 9.8 and the apatite surface charge reversed from net positive to net negative. Binding was competitively inhibited by HPO4(2-), but not by H2PO4-. Ca2+ promoted the binding of glycochenodeoxycholate, taurochenodeoxycholate and glycocholate, and for the latter two bile salts the increase was associated with enhanced "premicellar" binding. The binding of taurocholate was not influenced by Ca2+. When either glycocholate or taurocholate was mixed with glycochenodeoxycholate, mixed aggregates were formed that had a lower affinity for apatite than had pure glycochenodeoxycholate aggregates. Because only glycine-conjugated dihydroxy bile salts inhibit apatite formation, these results suggest that inhibition depends on high-affinity "premicellar" bile salt-apatite binding.
High Plasma Level of Remnant-Like Particle Cholesterol in the Metabolic Syndrome
Authors: Akira Satoh, Hisashi Adachi, Makoto Tsuruta, Yuji Hirai, Akiko Hiratsuka, Mika Enomoto, Kumiko Furuki, Asuka Hino, Tomohiro Takeuchi, Tsutomu Imaizumi
Journal: Diabetes Care (2005)

The metabolic syndrome is associated with a high incidence of cardiovascular disease even when the abnormalities present in the syndrome are mild. The underlying mechanism of the metabolic syndrome has not been elucidated. We investigated whether a strong atherogenic lipoprotein, remnant-like particle (RLP) lipoprotein cholesterol, is elevated in the metabolic syndrome.We performed a health examination among the residents of a rural community in Japan. Complete datasets, including fasting RLP cholesterol levels, were obtained in 1,261 subjects (509 men and 752 women) without diabetes and who were not taking lipid-lowering drugs. The subjects' medical history, use of alcohol, and smoking habits were ascertained by a questionnaire.All of the components of the metabolic syndrome were significantly related to RLP cholesterol by univariate analysis. Total cholesterol and smoking habits were also positively associated with RLP cholesterol. The subjects with the metabolic syndrome showed only mild abnormalities of each component. When RLP cholesterol levels were stratified by the number of the components of the metabolic syndrome, there was a strong association between RLP cholesterol levels and the number of components (P < 0.001 and F = 72.7).RLP cholesterol levels are elevated in the metabolic syndrome, and this elevation may underlie the high incidence of cardiovascular disease in the metabolic syndrome.
Emergency psychiatric services in England and Wales
Authors: S. Johnson, G. Thornicroft
Journal: BMJ (1995)

Although few policies guide the local planning of emergency psychiatric services in Britain, service users and their carers frequently express a preference for local teams that can respond quickly to crises.1 Acute psychiatric services are now usually provided by sector teams for defined geographical catchment areas.2 The provision of emergency response as part of an integrated range of local services has substantial advantages in terms of continuity of care and service accessibility,3 but such care may be difficult to sustain at night and at weekends for a small sector.4 We describe how emergency services in England and Wales are currently organised and staffed, comparing patterns of provision outside office hours with those during the day.

### and results

We sent questionnaires to the general …
Prostate specific antigen test must be repeated before biopsy
Authors: S. Gottlieb
Journal: BMJ (2003)

The ability of indirect dopamine agonists to induce gnawing in male C57Bl/6J mice was compared to that of direct dopamine agonists acting at dopamine D1 or D2 receptor subtypes. Holes left by the mice on the corrugations of packing cardboard were used as an objective index of gnawing. Indirect dopamine agonists, including dopamine releasers such as fencamfamine, (+)-amphetamine and amfenolic acid and dopamine uptake inhibitors such as cocaine, GBR 12909 (1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-[3- phenylpropyl]piperazine diHCl) and nomifensine produced dose-dependent increases in gnawing. None of the direct agonists (e.g., apomorphine, quinpirole or SKF 82958 [(+/-)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro- 1H-3-benzazepine]) increased gnawing. Although these compounds varied in potency and efficacy, 18 structurally diverse compounds induced gnawing in 100% of the mice tested. Four weak indirect agonists (3,4-methyl-enedioxymethamphetamine, amantadine, 2-phenylethylamine and benztropine) failed to induce gnawing. The lack of efficacy of postsynaptic dopamine agonists was not changed by various combinations of postsynaptic agonists (e.g., dopamine D1 and D2 agonists in combination). Nonetheless, the dopaminergic nature of the gnawing response was confirmed in experiments in which a host of compounds with primary actions at nondopaminergic sites did not induce gnawing; compounds included nicotine, caffeine, dizocilpine, lidocaine, fluoxetine and nisoxetine. In addition, both the dopamine D1 antagonist SCH 23390 [R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro- 1H-3-benzazepine], the D2 antagonist eticlopride and the dopamine D1/D2 antagonist flupenthixol produced dose-dependent blockade of gnawing induced by either cocaine or methylphenidate.(ABSTRACT TRUNCATED AT 250 WORDS)
Influence of Antibiotic Treatment on Breast Carcinoma Development in Proto-<i>neu</i> Transgenic Mice
Authors: Anna Rossini, Cristiano Rumio, Lucia Sfondrini, Elda Tagliabue, Daniele Morelli, Rosalba Miceli, Luigi Mariani, Marco Palazzo, Sylvie Ménard, Andrea Balsari
Journal: Cancer Research (2006)

Abstract The effect of prolonged antibiotic treatments on tumor development was evaluated in proto-neu transgenic mice, which spontaneously develop mammary carcinomas. Virgin transgenic mice were treated with metronidazole/ciprofloxacin or gentamicin through the drinking water. The hazard ratio [HR; 95% confidence interval (95% CI)] of breast cancer occurrence in metronidazole/ciprofloxacin-treated mice was more than triple that for controls [3.11 (1.13-8.53); P = 0.028], whereas only a slight increase in HR (95% CI) was observed in gentamicin-treated mice [1.39 (0.56-3.47); P = 0.481]. Tumor growth rate in gentamicin-treated mice was significantly faster than in untreated control mice (P = 0.043). Moreover, mammary glands from mice treated with either antibiotic regimen showed increased lobulization, with more numerous and more developed terminal ductal lobular units than in controls. These results indicate that prolonged exposure to relevant doses of antibiotics affects the mammary glands in this particular model of HER-2/neu transgenic mice; further studies to understand the precise mechanism by which antibiotic treatments influence mammary gland differentiation are critical. (Cancer Res 2006; (12): 6219-24)
Phospholipid source and molecular species composition of 1,2-diacylglycerol in agonist-stimulated rat cardiomyocytes
Authors: Y Eskildsen-Helmond
Journal: Cardiovascular Research (1998)

Objective: The aim was to investigate the consequences of simultaneous stimulation of phospholipase C and D by agonists for the molecular species composition of 1,2-diacylglycerol and phospholipids in cardiomyocytes. Methods: Serum-free cultured neonatal rat cardiomyocytes were stimulated by endothelin-1, phenylephrine or phorbolester. The molecular species of 1,2-diacylglycerol (in mol%) and those derived from phosphatidylcholine and phosphatidylinositol were analyzed by high-performance liquid chromatography and their absolute total concentration (nmol per dish) by gas–liquid chromatography. Phospholipids were labelled with [14C]glycerol or double-labelled with [14C]16:0 and [3H]20:4n6 for measurements of respectively, the amount of or relative rate of label incorporation into 1,2-diacylglycerol. Results: The major molecular species of 1,2-diacylglycerol in unstimulated cells was found to be 18:0/20:4 (57 mol%). The same species was observed predominantly in phosphatidylinositol (73 mol% compared to 11 mol% in phosphatidylcholine). A significant decrease (about 10 mol%) was found for the 18:0/20:4 species of 1,2-diacylglycerol during stimulation (10–40 min) with endothelin-1 or phorbolester, but not phenylephrine. The results of the double-labelling experiments were consistent with the latter finding: the ratio [3H]20:4 over [14C]16:0 in 1,2-diacylglycerol decreased from 1.70 in the control to 1.40 during 10-min endothelin-1 or phorbolester stimulation, but not during phenylephrine stimulation. The [14C]glycerol incorporation into 1,2-diacylglycerol remained relatively constant under agonist-stimulated conditions as did the total concentration of 1,2-diacylglycerol. Conclusions: 1,2-Diacylglycerol present in unstimulated cardiomyocytes is likely derived from phosphatidylinositol. During stimulation with endothelin-1 and phorbolester, but not phenylephrine, phosphatidylcholine becomes an increasingly important source for 1,2-diacylglycerol due to sustained activation of phospholipase D. The 1,2-diacylglycerol level remains relatively constant during agonist stimulation which strongly indicates that particular molecular species of 1,2-diacylglycerol more than its total concentration determine the activation of protein kinase C isoenzymes.
Macrophage colony-stimulating factor (rM-CSF) stimulates pinocytosis in bone marrow-derived macrophages.
Authors: E L Racoosin, J A Swanson
Journal: The Journal of Experimental Medicine (1989)

Incubation of murine bone marrow-derived macrophages (BMM) in medium containing recombinant macrophage colony-stimulating factor (rM-CSF) stimulated influx, efflux, and the net accumulation of the fluid-phase pinocytic marker, lucifer yellow (LY). Stimulation was dose dependent, occurred within 5 min of addition of the growth factor, and was sustained. Previous experiments had shown that BMM treated with PMA were stimulated to accumulate LY, but compared with rM-CSF-treated cells, the onset of stimulation in PMA-treated macrophages was slower. In further comparisons of rM-CSF- and PMA-stimulated LY accumulation, it was found that rM-CSF-stimulated pinocytosis could be abolished by pretreatment with 0.5 mg/ml trypsin, whereas neither unstimulated nor PMA-stimulated LY accumulation was affected by trypsin pretreatment. These findings indicate that the rM-CSF response was initiated at the cell surface, while the PMA response occurred via intracellular (or trypsin-resistant) receptors. However, once initiated, the pinocytic responses elicited by either agent were very similar. First, rM-CSF-treated cells, like PMA-treated cells, showed extensive ruffling and formation of large phase-bright pinosomes. Second, both rM-CSF- and PMA-stimulated LY accumulation could be inhibited by treatment of cells with the cytoskeleton destabilizing drugs nocodazole, colchicine, or cytochalasin D. Finally, rM-CSF, like PMA, was found to stimulate efflux of LY from cells preloaded with the dye. Thus, both rM-CSF and PMA stimulate the net rate of solute flow through the macrophage endocytic compartment.
Book Review Depression and Brain Dysfunction Edited by Frank G. Gilliam, Andres M. Kanner, and Yvette I. Sheline. 298 pp., illustrated. Abingdon, England, Informa Healthcare/Taylor &amp; Francis, 2006. $179.95. 1-84214-214-3
Authors: Eric D. Caine
Journal: New England Journal of Medicine (2006)
Hospitals, Heal Yourselves
Authors: Jerome P. Kassirer
Journal: New England Journal of Medicine (1999)

Teaching hospitals are beset by a litany of now familiar complaints. They are often described as large and impersonal. Their expert clinician-professors are said to be aloof and uncaring. House staff rotate off services just when patients are beginning to feel comfortable with them. Personnel often disregard patients' dignity. Appointments are difficult to arrange, their locations are increasingly difficult to find, and the waiting time to see doctors is often excessive.Nevertheless, there is a general assumption that the teaching hospitals provide better care than nonteaching hospitals. They have a greater concentration of clinical expertise, a focus on clinical research, . . .
Does gold concentration in the blood influence the result of patch testing to gold?
Authors: S. Ekqvist, T. Lundh, C. Svedman, J. Björk, H. Möller, L.A.F. Nilsson, M. Bruze
Journal: British Journal of Dermatology (2009)

Background We have recently found a correlation between contact allergy to gold sodium thiosulphate (GSTS) and gold concentration in the blood (B‐Au) in a stented population: the higher the B‐Au, the stronger the patch‐test reaction. Objectives To further investigate the correlation between B‐Au and patch‐test reactivity to gold. Methods In this provocation control cross‐over trial of 24 patients with dermatitis with a known contact allergy to gold, the patients were randomized into two groups where one was topically provoked to gold (15 mg GSTS) and one to the control. All patients were simultaneously patch tested with GSTS in 10 aqueous dilutions (1·1 mg GSTS). Patch‐test readings were performed and blood was drawn. After 6 weeks, the experiment was repeated and the group that had previously been provoked with gold was now provoked with the control and vice versa. Results B‐Au was higher after gold provocation whereas no treatment effect was discerned for minimal eliciting concentration (MEC) or summarized test score (STS). Instead, significant differences in period effect were observed implying higher B‐Au and STS and lower MEC on test occasion II. The most likely explanation is the increased B‐Au and/or booster effect from test occasion I. There was a correlation between B‐Au and MEC: the higher the B‐Au, the lower the MEC. Conclusions The correlation between B‐Au and MEC indicates that the B‐Au is of importance for the skin reactivity to gold.
Epidermal growth factor receptor activity mediates renal cyst formation in polycystic kidney disease.
Authors: W G Richards, W E Sweeney, B K Yoder, J E Wilkinson, R P Woychik, E D Avner
Journal: Journal of Clinical Investigation (1998)

A consistent phenotype observed in both human patients and several different mouse models of autosomal recessive polycystic kidney disease (ARPKD) is an increased activity of the epidermal growth factor receptor (EGFR) in the affected kidneys. To determine whether this increased activity of the EGFR is a functional event that is directly part of the disease pathway of renal cyst formation, we used a genetic approach to introduce a mutant EGFR with decreased tyrosine kinase activity into a murine model of ARPKD. We found that the modified form of the EGFR could block the increase in EGFR-specific tyrosine kinase activity that normally accompanies the development of renal cysts, and this correlated with an improvement in kidney function and a substantial decrease in cyst formation in the collecting ducts. These results suggest that changes in the expression of the EGFR contribute to the formation of cysts in the collecting ducts, and that drugs that target the tyrosine kinase activity of the EGFR may potentially be therapeutic in ARPKD.
Use of melanotan I and II in the general population
Authors: M. Evans-Brown, R. T Dawson, M. Chandler, J. McVeigh
Journal: BMJ (2009)

Between 10 and 12% of the 10-year-old children in the 1970 national birth cohort were prescribed a pair of spectacles. One-fifth of these children had no impairment of visual acuity and a further 15-20% had only minimal visual defects. Only two-thirds of children with spectacles could produce them when asked to do so at the survey school medical examination; this was particularly common among those in the lower social classes and among children who had no detectable impairment. The information presented in this paper combined with that from earlier national birth cohort studies suggests that overprescribing of spectacles to school children is very common. The financial implications of this overprescribing are discussed.
Corrigendum to “Tailoring width of microfabricated nanochannels to solute size can be used to control diffusion kinetics” [Journal of Control Release 102 (2005) 123–133]
Authors: Frank Martin, Robbie Walczak, Anthony Boiarski, Michael Cohen, Teri West, Carlo Cosentino, John Shapiro, Mauro Ferrari
Journal: Journal of Controlled Release (2005)
TCTAP A-030 Safety and Efficacy of a Hybrid Dual Antiplatelet Therapy Regimen for ST-elevation Myocardial Infarction Patients: A Single-centre Experience
Authors: Deanna Khoo, Yee May Wong, Hee Hwa Ho, Yau Wei Ooi, Paul Jau, Lueng Ong, Fahim Haider Jafary, Kwok Kong Loh, Julian Tan, David Foo
Journal: Journal of the American College of Cardiology (2014)