tbuckley/cabot-search huggingface dataset:
Letter: Drugs and "dementia" in the elderly.
Authors: B Russell
Journal: BMJ (1973)

Pyrimethamine PoisoningSIR,-In their extremely interesting article (20 October, p. 147) Dr. Olu Akinyanju and his colleagues reported two cases of pyrimethamine poisoning in children, in one of which the manifestations included convul- sions.Convulsions may also occur when pyrimethamine is given in therapeutic doses.'-:'Geils et al.' have shown that pyrimethamine mav be of valut in the treatment of leukaemia of the central nervous system; others2:3 have confirmed this but have shown that the drug is highly toxic.Th.re are known to be better and well- tried methods for the prophylaxis and treat- ment of C.N.S. leukaemia' and the use of pyrimethamine in this condition should therefore be limited to those cases in which other types of theraty are contra'ndicated or rJfused either by the Datient cr, in the case of a child, his oar7nls.In our exo2ri- ence,2 in thu' treatment of meningeal leukaemia pyrimethamine should not be used directly after mrthowrexate and its daily dosage should not exceed 2-3 mg/kg body weigh+.--Iam, etc.,
Targeted cutaneous delivery of ciclosporin A using micellar nanocarriers and the possible role of inter-cluster regions as molecular transport pathways
Authors: Maria Lapteva, Verena Santer, Karine Mondon, Ilias Patmanidis, Gianpaolo Chiriano, Leonardo Scapozza, Robert Gurny, Michael Möller, Yogeshvar N. Kalia
Journal: Journal of Controlled Release (2014)
Ten providers bid to run 800m contract for Cambridgeshire older people's services
Authors: G. Iacobucci
Journal: BMJ (2013)

Several private healthcare providers are in the running to win the largest contract to provide NHS services since the government’s reorganisation of healthcare came into force in England.

Ten organisations, including UnitedHealth UK, Serco, and Virgin Care, have been shortlisted in the bidding process to provide integrated adult and older people’s services in Cambridgeshire in a contract worth up to £800m (€950m; $1.27bn) over five years.1

Care UK, Circle Partnership, Interserve, and Capita are also shortlisted as part of joint bids with NHS providers and other partners. Other NHS organisations and community service providers are also included on the shortlist.

Cambridgeshire and Peterborough Clinical Commissioning Group, which is leading the procurement, is seeking one or more providers for the contract, which will bundle together a range …
Detection of human T-cell lymphotropic virus type-1 proviral DNA in the saliva of an adult T-cell leukaemia/lymphoma patient using the polymerase chain reaction
Authors: S. TANIGUCHI, N. MAEKAWA, N. YASHIRO, T. HAMADA
Journal: British Journal of Dermatology (1993)

Journal Article Detection of human T‐cell lymphotropic virus type‐1 proviral DNA in the saliva of an adult T‐cell leukaemia/lymphoma patient using the polymerase chain reaction Get access S. TANIGUCHI, S. TANIGUCHI Department of Dermatology, Osaka City University Medical School, 1‐5‐7, Asahimachi, Abeno‐ku. Osaka 545, Japan Search for other works by this author on: Oxford Academic Google Scholar N. MAEKAWA, N. MAEKAWA Department of Dermatology, Osaka City University Medical School, 1‐5‐7, Asahimachi, Abeno‐ku. Osaka 545, Japan Search for other works by this author on: Oxford Academic Google Scholar N. YASHIRO, N. YASHIRO Department of Dermatology, Osaka City University Medical School, 1‐5‐7, Asahimachi, Abeno‐ku. Osaka 545, Japan Search for other works by this author on: Oxford Academic Google Scholar T. HAMADA T. HAMADA Department of Dermatology, Osaka City University Medical School, 1‐5‐7, Asahimachi, Abeno‐ku. Osaka 545, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 129, Issue 5, 1 November 1993, Pages 637–641, https://doi.org/10.1111/j.1365-2133.1993.tb00503.x Published: 01 November 1993 Article history Accepted: 11 February 1993 Published: 01 November 1993
Randomized study comparing 4′‐epi‐doxorubicin (Epirubicin) versus doxorubicin as a part of induction treatment in adult acute lymphoblastic leukemia
Authors: Manisha Bhutani, Lalit Kumar, Amish Vora, Narendra Bhardwaj, Ashutosh Kumar Pathak, Rajvir Singh, Vinod Kochupillai
Journal: American Journal of Hematology (2002)

Abstract Doxorubicin or daunorubicin are routinely used to induce remission in acute lymphoblastic leukemia (ALL). Efficacy of epirubicin (an analog of doxorubicin), however, has not been adequately evaluated in ALL management. This randomized study was undertaken to compare the relative efficacy of epirubicin vs. doxorubicin as part of induction chemotherapy in adult ALL. Between January 1990 and June 1998, 79 previously untreated adult ALL patients (age 11–55 years, median 20 years) were randomized to receive either doxorubicin (Group A, n = 39) or epirubicin (Group B, n = 40) as a part of induction therapy. Vincristine and prednisolone were common in each group. The induction treatment was followed by identical consolidation and maintenance therapy. The two groups were compared as regards pretherapy clinical and laboratory parameters, dose intensity of therapy, therapeutic efficacy, myelotoxicity, and survival. Epirubicin was as effective as doxorubicin in terms of complete remission rate (80% vs. 78.3%; P = 0.87) and relapse rate (57.1% vs. 51.7%; P = 0.68). Five‐year overall survival (30% vs. 30%, P = 0.98) and disease‐free survival (40% vs. 39%, P = 0.92) at median follow‐up of 68 months was also similar in the two groups. The incidence of Grade 4 myelotoxicity was comparable in the two groups. Patients 20 years of age or less had better CR rates (90% vs. 65%; P = 0.011) and median overall survival (39 vs. 11 months; P = 0.008) compared to those who were older. From this study epirubicin appears as effective as doxorubicin as part of induction therapy for adult ALL. However, the results need to be validated on the basis of immunophenotype and cytogenetic prognostic characterization. Am. J. Hematol. 71:241–247, 2002. © 2002 Wiley‐Liss, Inc.
Significant prolongation of atrial monophasic action potential duration: short-term reverse electrophysiological changes after internal cardioversion of atrial fibrillation
Authors: T Korte
Journal: Cardiovascular Research (2002)

Since short action potentials and short refractory periods facilitate the induction of atrial reentry, this maladaptation has been proposed as the pathophysiological basis of the frequent immediate recurrences of atrial fibrillation (IRAF) after internal cardioversion. However, short-term reverse electrophysiological changes of the atria after cardioversion have not been studied in humans.Thirty-seven patients with chronic atrial fibrillation of 16+/-19 months and ten patients with an atrial fibrillation duration < or =48 h underwent internal cardioversion. Antiarrhythmic medication was only continued in 10 patients (21%), who were on amiodarone before cardioversion. Atrial monophasic action potential duration at 90% repolarization (APD(90)), sinus rate, P wave duration and interatrial conduction times between high right atrium and coronary sinus were recorded at min 0, 1, 3, 5, 10, 15 and 20 after cardioversion.Internal cardioversion was successful in all patients, but twelve of the patients with chronic AF (32%) and three of the patients with intermittent AF (30%) had one to four episodes of IRAF after 16+/-28 s. There was a significant 52+/-30 ms APD(90) prolongation, 83% of which occurred in min 0-3 (P<0.0001) and 17% in min 3-20 (P<0.05) after internal cardioversion. There was no significant temporal change in sinus rate, P-wave and interatrial conduction time during the time studied. APD(90) prolongation and its time dependence did not show a detectable difference in subgroups with chronic AF, IRAF, left atrial size >40 mm and treatment with amiodarone.There is a significant prolongation of action potential duration in min 0-3 after internal cardioversion of atrial fibrillation, whereas sinus rate and intra- and interatrial conduction time remain unchanged. APD(90) prolongation in min 0-3 shows a temporal relationship to the high rate of immediate recurrences of atrial fibrillation during this time interval. The data imply that there is a transient recovery of atrial refractoriness after cardioversion and suggest a mechanism of the high rate of early recurrences of atrial fibrillation.
Periostin as a Novel Factor Responsible for Ventricular Dilation
Authors: Naruto Katsuragi, Ryuichi Morishita, Noriko Nakamura, Tayehito Ochiai, Yoshiaki Taniyama, Yasuhiro Hasegawa, Kayoko Kawashima, Yasufumi Kaneda, Toshio Ogihara, Keijiro Sugimura
Journal: Circulation (2004)

Periostin is highly expressed in the myocardium in patients with heart failure. However, no report has documented the function of periostin. To identify the function of periostin in the pathophysiology of heart failure, overexpression or loss of function of the periostin gene was examined by direct transfection into the rat heart.Rats transfected with the periostin gene by the HVJ-liposome method showed left ventricular (LV) dilation as assessed by echocardiography, accompanied by an increase in periostin expression. Consistently significant differences were observed in LV pressure, LV end-diastolic pressure, LV dP/dt(max), and LV dP/dt(min) at 6 and 12 weeks after transfection in rats transfected with the periostin gene, accompanied by a decrease in cardiac myocytes and an increase in collagen deposition. Importantly, periostin has the ability to inhibit the spreading of myocytes and the adhesion of cardiac fibroblasts with or without fibronectin. Markers of cardiac dysfunction such as brain natriuretic peptide and endothelin-1 gene expression were significantly increased after transfection in the LV of rats transfected with the periostin gene. These data demonstrate that overexpression of the periostin gene led to cardiac dysfunction. Thus, we examined the inhibition of periostin in Dahl salt-sensitive rats by an antisense strategy because periostin is highly expressed in heart failure. Importantly, inhibition of periostin gene expression resulted in a significant increase in survival rate, accompanied by an improvement of LV function.The present study demonstrates the contribution of the periostin gene to cardiac dilation in animal models. Inhibition of periostin might become a new therapeutic target for the treatment of heart failure.
Mapping the Gene for Hereditary Cutaneous Malignant Melanoma–Dysplastic Nevus to Chromosome Lp
Authors: Sherri J. Bale, Nicholas C. Dracopoli, Margaret A. Tucker, Wallace H. Clark, Mary C. Fraser, Ben Z. Stanger, Philip Green, Helen Donis-Keller, David E. Housman, Mark H. Greene
Journal: New England Journal of Medicine (1989)

We used molecular genetic techniques and multipoint linkage analyses to locate the gene responsible for cutaneous malignant melanoma-dysplastic nevus. We evaluated 99 relatives and 26 spouses in six families with a predisposition to melanoma. Thirty-four family members had cutaneous malignant melanoma, and 31 of these 34 also had histologically confirmed dysplastic nevi. Twenty-four family members had dysplastic nevi alone. An analysis of the cosegregation of the cutaneous malignant melanoma–dysplastic nevus trait with 26 polymorphic DNA markers on the short arm of chromosome 1 demonstrated the presence of a gene for susceptibility to melanoma. The gene was located between an anonymous DNA marker (D1S47) and the gene locus for pronatrodilatin, a commonly used reference gene (PND), in chromosome band 1p36. The odds were greater than 260,000:1 in favor of linkage at this location. (N Engl J Med 1989;320:1367–72.)
Characterization of animal models for primary sclerosing cholangitis (PSC)
Authors: Peter Fickert, Marion J. Pollheimer, Ulrich Beuers, Carolin Lackner, Gideon Hirschfield, Chantal Housset, Verena Keitel, Christoph Schramm, Hanns-Ulrich Marschall, Tom H. Karlsen, Espen Melum, Arthur Kaser, Bertus Eksteen, Mario Strazzabosco, Michael Manns, Michael Trauner
Journal: Journal of Hepatology (2014)

Primary sclerosing cholangitis (PSC) is a chronic cholangiopathy characterized by biliary fibrosis, development of cholestasis and end stage liver disease, high risk of malignancy, and frequent need for liver transplantation. The poor understanding of its pathogenesis is also reflected in the lack of effective medical treatment. Well-characterized animal models are utterly needed to develop novel pathogenetic concepts and study new treatment strategies. Currently there is no consensus on how to evaluate and characterize potential PSC models, which makes direct comparison of experimental results and effective exchange of study material between research groups difficult. The International Primary Sclerosing Cholangitis Study Group (IPSCSG) has therefore summarized these key issues in a position paper proposing standard requirements for the study of animal models of PSC.
79 MONOCISTRONIC HEPATITIS C REPORTER VIRUS RECOMBINANTS OF ALL MAJOR GENOTYPES EXPRESSING ENHANCED GREEN FLUORESCENT PROTEIN TAGGED NS5A PROTEIN
Authors: J.M. Gottwein, J.B. Lademann, T.K.H. Scheel, T.B. Jensen, J.C. Prentoe, J. Bukh
Journal: Journal of Hepatology (2009)
Secondary Screening System for Preclinical Testing of Human Lung Cancer Therapies
Authors: David W. Mulvin, Randy B. Howard, Dawn H. Mitchell, Patricia E. Noker, Carol A. Kruse, Henry D. Chu, Paul A. Bunn, Michael R. Johnston
Journal: JNCI Journal of the National Cancer Institute (1992)

The National Cancer Institute has instituted a primary screening system for testing new agents against cultured cancer cell lines. The purpose of this study was to determine the feasibility of using a nude rat orthotopic (organ-specific) human lung cancer model system as an in vivo secondary screen for general evaluation of new anticancer agents and therapies active against lung cancer. To make this determination, we tested whether this system allows measurement of uptake and tumoricidal activity of anticancer therapies. Tumor-bearing lungs from 53 Rowett nude rats with orthotopically implanted human large-cell undifferentiated lung carcinoma (NCI-H460) were perfused ex vivo for 1 hour with or without each of two anticancer modalities. Lungs were perfused with blood-free perfusate alone (untreated control), perfusate with 100 μg/mL doxorubicin (treated positive control), or perfusate with lymphokine-ac-tivated killer cells plus human recombinant interleukin-2 (LAK/rIL-2). Weight gain during perfusion was the criterion used to quantitate lung injury. Treatment efficacy was measured by clonogenic assay after enzymatic disaggregation of the perfused tumors. Doxorubicin levels in the tumor and in the uninvolved lung were measured by high-performance liquid chromatography. Both treatment groups showed only slight increases in lung weight compared with that in the untreated control group, suggesting good lung tolerance of the procedure. Lung and tumor levels of doxorubicin were 320± 21 ng/mg of tissue and 32± 5 ng/mg of tissue (means ± SE), respectively. Clonogenic assay demonstrated a fivefold to 10-fold reduction in the surviving fraction of tumor cells with doxorubicin but no change with LAK/rIL-2. We conclude that this system allows demonstration of tumor uptake and tumoricidal activity of doxorubicin but that it does not demonstrate LAK/rIL-2 cytotoxicity. The system may be useful for general secondary preclinical assessment of experimental lung cancer therapies. Further testing is needed before general use could be considered. The ability of the system to allow detection of a dose-response relationship as well as synergism in combined therapies is under investigation. [J Natl Cancer Inst 84: 31–37, 1992]
Reduced Secondary Disease Mortality in Mouse Radiation Chimeras&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C. C. Congdon, D. A. Gardiner, M. A. Kastenbaum
Journal: JNCI Journal of the National Cancer Institute (1967)

A program was undertaken to ascertain the role of donor marrow age, cell dose, day of injection after irradiation, and sex as single or interacting factors in determining the 90-day cumulative mortality from secondary disease in mouse radiation chimeras. It was found that 40 million 3-day-old donor marrow cells gave the fewest deaths (∼5%). An experimental design approach was used, and the present report concerns a 2 × 33factorial design (Design 4). Extrabinomial variation in deaths among mice in different cages was absent from Design 4, and no animals in the experiments reported here died earlier than 12 days after 950 r X irradiation.
RADIOFREQUENCY ABLATION IMPROVES QUALITY OF LIFE SCORES NOT ONLY IN PATIENTS WITH ATRIAL FIBRILLATION BUT THEIR SIGNIFICANT OTHERS TOO!
Authors: Subba Reddy Vanga, Mazda Biria, Jayasree Pillarisetti, Donita Atkins, Caroline Murray, Warren Chen, Loren Berenbom, Martin Emert, Rhea Pimentel, Raghu Dendi, Sudharani Bommana, James Vacek, Buddhadeb Dawn, Luigi Di Biase, Andrea Natale, Dhanunjaya Lakkireddy
Journal: Journal of the American College of Cardiology (2011)
Intracranial Tumors in Childhood
Authors: J. Gordon Millichap
Journal: JAMA (1962)

In 2 children, presented because of involuntary movements, the diagnoses of rheumatic chorea, dystonia musculorum deformans, and encephalitis were entertained before roentgenologic signs of expanding cerebral lesions were demonstrated. A 6-year-old boy developed chorea in the left arm 4 months after an attack of scarlet fever. The movement disorder progressed and later involved the left leg and right arm. The diagnosis of an astrocytoma in the right thalamus was made at craniotomy performed 14 months after the onset of symptoms. A 12-year-old girl began to limp shortly after recovery from a respiratory infection. The dystonia progressed, and signs of focal involvement of cranial nerves and corticospinal tracts appeared. A franctional pneumoencephalogram ultimately revealed a mass in the upper part of the pons and midbrain.
Fibre types in skeletal muscles of chronic obstructive pulmonary disease patients related to respiratory function and exercise tolerance
Authors: A Satta, GB Migliori, A Spanevello, M Neri, R Bottinelli, M Canepari, MA Pellegrino, C Reggiani
Journal: European Respiratory Journal (1997)

This study aimed to investigate the relationship between skeletal muscle, fibre type composition, functional respiratory impairment and exercise tolerance in patients with moderate to severe chronic obstructive pulmonary disease (COPD). A group of 22 COPD patients and 10 healthy control subjects were studied. In COPD patients, vital capacity (VC) and forced expiratory volume in one second (FEV1) were reduced to 79% and 51%, respectively. Diffusion indices (transfer factor of the lung for carbon monoxide (TL,CO) and carbon monoxide transfer coefficient (KCO)) were also reduced. Arterial oxygen tension (Pa,O2) was normal or slightly altered. A maximal exercise test was performed and anaerobic threshold was calculated. Muscle samples from vastus lateralis were obtained by needle biopsy. Myosin heavy chain (MHC) and light chain (MLC) isoforms were separated by gel electrophoresis and quantified by densitometry. MHC isoforms were considered as molecular markers of fibre types. The proportion of the fast MHC-2B isoform was increased in COPD patients. TL,CO, KCO, VC and FEV1 were positively correlated with slow MHC isoform content. TL,CO and KCO were also negatively correlated with the content of the fast MHC-2B isoform. No correlation was found between exercise parameters and MHC isoform composition. The co-ordinated expression between MHC and MLC isoforms was altered in COPD patients. We conclude that reduced oxygen availability, probably in combination with muscle disuse, may determine muscle alterations in chronic obstructive pulmonary disease patients. The altered correlations between myosin heavy chain and light chain isoforms suggest that co-ordinated protein expression is lost in chronic obstructive pulmonary disease muscles.
Effect of peer led programme for asthma education in adolescents: cluster randomised controlled
Authors: S. Shah
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To determine the effect of a peer led programme for asthma education on quality of life and related morbidity in adolescents with asthma. <b>Design:</b> Cluster randomised controlled trial. <b>Setting:</b> Six high schools in rural Australia. <b>Participants:</b> 272 students with recent wheeze, recruited from a cohort of 1515 students from two school years (mean age 12.5 and 15.5 years); 251 (92.3%) completed the study. <b>Intervention:</b> A structured education programme for peers comprising three steps (the "Triple A Program"). <b>Main outcome measures:</b> Quality of life, school absenteeism, asthma attacks, and lung function. <b>Results:</b> When adjusted for year and sex, mean total quality of life scores showed significant improvement in the intervention than control group. Clinically important improvement in quality of life (&gt;0.5 units) occurred in 25% of students with asthma in the intervention group compared with 12% in the control group (P=0.01). The number needed to treat was 8 (95% confidence interval 4.5 to 35.7). The effect of the intervention was greatest in students in year 10 and in females. Significant improvements occurred in the activities domain (41% <i>v</i> 28%) and in the emotions domain (39% <i>v</i> 19%) in males in the intervention group. School absenteeism significantly decreased in the intervention group only. Asthma attacks at school increased in the control group only. <b>Conclusion:</b> The triple A programme leads to a clinically relevant improvement in quality of life and related morbidity in students with asthma. Wider dissemination of this programme in schools could play an important part in reducing the burden of asthma in adolescents
Liver cell apoptosis in chronic hepatitis C correlates with histological but not biochemical activity or serum HCV-RNA levels
Authors: Fiorella Calabrese, Patrizia Pontisso, Elena Pettenazzo, Luisa Benvegnù, Alessandro Vario, Liliana Chemello, Alfredo Alberti, Marialuisa Valente
Journal: Hepatology (2000)

In hepatitis C virus (HCV) infection, mechanisms responsible for liver cell damage are still poorly understood and both necrosis and apoptosis may be operative. By using terminal deoxynucleotydil transferase-mediated d-UTP-biotin nick-end labeling (TUNEL) we have evaluated and quantified apoptosis in liver biopsy specimens from 61 patients with chronic hepatitis C. All patients had detectable apoptotic cells in the liver. Presence of increased apoptotic activity was confirmed in selected cases by electron microscopy and by DNA gel electrophoresis. The amount of liver cell apoptosis expressed as apoptotic index, ranged between 0.01% to 0.54% and showed a positive correlation with histological activity grading ( P &lt; .0005) and with the amount of infiltrating CD8-positive cells ( P = .01). Apoptosis did not correlate with transaminase levels or with HCV load and genotype. These results support the concept that immune-mediated apoptosis may play a role in the pathogenesis of chronic hepatitis C and indicate that this type of reaction may occur in the absence of significant alanine transaminase (ALT) elevation, thus explaining the lack of correlation between biochemical activity and liver histological damage.
BMA meeting: NHS must not penalise whistleblowers, representatives say
Authors: D. Cohen
Journal: BMJ (2010)

Doctors’ contracts should include clauses entitling them to publish and speak on matters without the prior consent of the employing authority, the BMA annual conference has heard.

Demanding that the BMA should lobby for the safeguarding of whistleblowers, Paul Anderson, a respiratory medicine consultant in Sheffield, said that doctors had specific obligations to protect patients. This included raising concerns if the safety of patients has been compromised, protecting patients …