tbuckley/cabot-search huggingface dataset:
Cost of management of patients with haemophilia.
Authors: F Carter, C D Forbes, J D MacFarlane, C R Prentice
Journal: BMJ (1976)

The cost of managing 114 adult haemophiliacs in the west of Scotland was assessed for the period 1 March 1971 to 28 February 1974. Altogether 23 of them (20%) accounted for 80% of the resources used. The cost of hospital treatment of these patients during the period was compared with the predicted cost of home treatment, given the availability of freeze-dried factor VIII concentrate in sufficient amounts. We calculate that adequate on-demand home treatment would cost only 16% more than the present treatment, which is substantially less efficient.
Occurrence of renal scars in children after their first referral for urinary tract infection
Authors: M. G Coulthard, H. J Lambert, M. J Keir
Journal: BMJ (1997)

Urinary tract infections in childhood may cause renal scars, which can lead to hypertension and renal failure: diagnostic imaging is therefore important to detect children with scarring so that they can be monitored. A multidisciplinary group that produced imaging guidelines1 broadly agreed that younger children should have a dimercaptosuccinic acid (DMSA) scan to detect scarring and an ultrasonography to identify structural lesions after one infection, but most thought that children over 7 years should be investigated only after recurrent infections, using ultrasound only, perhaps because of their low risk of new scar formation.2 Others have suggested imaging only children who have a fever.3 In Newcastle we have performed ultrasound and dimercaptosuccinic acid scans (after two months free of infection) on every child when first referred after a urinary tract infection. Here we describe …
The direct electrophysiologic effects of disopyramide phosphate in the transplanted human heart.
Authors: R S Bexton, K J Hellestrand, R Cory-Pearce, R A Spurrell, T A English, A J Camm
Journal: Circulation (1983)

To evaluate the direct electrophysiologic effects of i.v. disopyramide phosphate and to differentiate these effects from its autonomically mediated actions, we administered the drug (2 mg/kg over 5 minutes) during electrophysiologic study to eight cardiac transplant recipients who had documented functional cardiac denervation. After disopyramide, the cycle length of the denervated donor right atrium increased from 626 +/- 129 to 716 +/- 148 msec (mean +/- SD, p less than 0.001), whereas that of the innervated recipient atrium decreased from 846 +/- 195 to 659 +/- 99 msec (p less than 0.02). There were small increases in both the sinus node recovery time (1128 +/- 616 to 1198 +/- 592 msec, p less than 0.05) and corrected sinus node recovery time (440 +/- 418 to 489 +/- 409 msec, p less than 0.02) of the donor atrium, whereas the recovery times of the recipient atrium shortened (sinus node recovery time, 1298 +/- 218 to 1218 +/- 196 msec; corrected sinus node recovery time, 464 +/- 108 to 410 +/- 115 msec). Disopyramide markedly prolonged all conduction intervals. The PA interval increased from 47 +/- 16 to 54 +/- 17 msec (p less than 0.01), the AH interval from 55 +/- 12 to 78 +/- 12 msec (p less than 0.001), the HV interval from 38 +/- 9 to 58 +/- 13 msec (p less than 0.001), the QRS duration from 93 +/- 18 to 129 +/- 34 msec (p less than 0.001) and the QT interval from 339 +/- 23 to 403 +/- 39 msec (p less than 0.001). There was no significant change in the effective refractory period of the atrium, ventricular or atrioventricular node. The functional refractory period of the atrioventricular node increased from 369 +/- 34 to 395 +/- 31 msec (p less than 0.001). The electrophysiologic effects of disopyramide in the denervated heart are markedly depressant. In the innervated normal heart, the majority of these effects are counteracted by the drug's autonomically mediated anticholinergic actions.
Elevated E2F1 Inhibits Transcription of the Androgen Receptor in Metastatic Hormone-Resistant Prostate Cancer
Authors: Joanne N. Davis, Kirk J. Wojno, Stephanie Daignault, Matthias D. Hofer, Rainer Kuefer, Mark A. Rubin, Mark L. Day
Journal: Cancer Research (2006)

Abstract Activation of E2F transcription factors, through disruption of the retinoblastoma (Rb) tumor-suppressor gene, is a key event in the development of many human cancers. Previously, we showed that homozygous deletion of Rb in a prostate tissue recombination model exhibits increased E2F activity, activation of E2F-target genes, and increased susceptibility to hormonal carcinogenesis. In this study, we examined the expression of E2F1 in 667 prostate tissue cores and compared it with the expression of the androgen receptor (AR), a marker of prostate epithelial differentiation, using tissue microarray analysis. We show that E2F1 expression is low in benign and localized prostate cancer, modestly elevated in metastatic lymph nodes from hormone-naïve patients, and significantly elevated in metastatic tissues from hormone-resistant prostate cancer patients (P = 0.0006). In contrast, strong AR expression was detected in benign prostate (83%), localized prostate cancer (100%), and lymph node metastasis (80%), but decreased to 40% in metastatic hormone-resistant prostate cancer (P = 0.004). Semiquantitative reverse transcription-PCR analysis showed elevated E2F1 mRNA levels and increased levels of the E2F-target genes dihyrofolate reductase and proliferating cell nuclear antigen in metastatic hormone–independent prostate cancer cases compared with benign tissues. To identify a role of E2F1 in hormone-independent prostate cancer, we examined whether E2F1 can regulate AR expression. We show that exogenous expression of E2F1 significantly inhibited AR mRNA and AR protein levels in prostate epithelial cells. E2F1 also inhibited an AR promoter-luciferase construct that was dependent on the transactivation domain of E2F1. Furthermore, using chromatin immunoprecipitation assays, we show that E2F1 and the pocket protein family members p107 and p130 bind to the AR promoter in vivo. Taken together, these results show that elevated E2F1, through its ability to repress AR transcription, may contribute to the progression of hormone-independent prostate cancer. (Cancer Res 2006; 66(24): 11897-906)
Sustained Expression of Therapeutic Level of Factor IX in Hemophilia B Dogs by AAV-Mediated Gene Therapy in Liver
Authors: Lili Wang, Timothy C. Nichols, Marjorie S. Read, Dwight A. Bellinger, Inder M. Verma
Journal: Molecular Therapy (2000)

We demonstrate that a single intraportal vein injection of a recombinant adeno-associated virus (rAAV) vector encoding canine factor IX (cFIX) cDNA under the control of a liver-specific enhancer/promoter leads to a long-term correction of the bleeding disorder in hemophilia B dogs. Stable expression of the therapeutic level of cFIX (5% of normal level) was detected in the plasma of a dog injected with an AAV vector at a dose of 4.6 × 1012 particles/kg for over 7 months. Both whole-blood clotting time (WBCT) and activated partial thromboplastin time (aPTT) of the treated dogs have been greatly decreased since the treatment. No anti-canine factor IX antibodies have been detected in the treated animals. Importantly, no bleeding has been observed in the dog that expresses a therapeutic level of cFIX for 7 months following vector administration. Moreover, no persistent significant hepatic enzyme abnormalities were detected in the treated dogs. Thus, a single intraportal injection of a rAAV vector expressing cFIX successfully corrected the bleeding disorder of hemophilia B dogs, supporting the feasibility of using AAV-based vectors for liver-targeted gene therapy of genetic diseases.
Mrs Bottomley asks for more integrity for NHS
Authors: J Warden
Journal: BMJ (1994)

Directors of NHS boards must declare private interests that could affect their NHS work and publish the pay of chief executives and the chairpersons and members of the boards in annual reports, said Virginia Bottomley, the health secretary, last week. These requirements are laid down in a new draft code of conduct, which sets out “public service values” of integrity, openness, and accountability. Mrs Bottomley warned that she would sack anyone …
Reactive Oxygen Species Regulate Caspase Activation in Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Resistant Human Colon Carcinoma Cell Lines
Authors: Kamel Izeradjene, Leslie Douglas, David M. Tillman, Addison B. Delaney, Janet A. Houghton
Journal: Cancer Research (2005)

Abstract The effects of reactive oxygen species (ROS) on tumor necrosis factor–related apoptosis–inducing ligand (TRAIL)–induced apoptosis in solid cancers have yet to be clearly defined. In this study, we found that the classic uncoupler of oxidative phosphorylation, carbonyl cyanide m-chlorophenylhydrazone (CCCP), induced a reduction in ΔΨm and generation of ROS. This uncoupling effect enhanced TRAIL-induced apoptosis in TRAIL-resistant human colon carcinoma cell lines (RKO, HT29, and HCT8). Sensitization was inhibited by benzyloxycarbonyl-valine-alanine-aspartate fluoromethylketone, indicating the requirement for caspase activation. CCCP per se did not induce apoptosis or release of proapoptotic factors from mitochondria. Generation of ROS by CCCP was responsible for TRAIL-induced Bax and caspase activation because scavenging ROS completely abrogated apical caspase-8 activation and further downstream events leading to cell death. Overexpression of Bcl-2 did not prevent the initial loss of ΔΨm and ROS generation following CCCP treatment, but did prevent cell death following TRAIL and CCCP exposure. Uncoupling of mitochondria also facilitated TRAIL-induced release of proapoptotic factors. X-linked inhibitor of apoptosis overexpression abrogated TRAIL-induced apoptosis in the presence of CCCP and decreased initiator procaspase-8 processing, indicating that additional processing of caspase-8 required initiation of a mitochondrial amplification loop via effector caspases. Of interest, depletion of caspase-9 in RKO cells did not protect cells from TRAIL/CCCP-induced apoptosis, indicating that apoptosis occurred via a caspase-9–independent pathway. Data suggest that in the presence of mitochondrial-derived ROS, TRAIL induced mitochondrial release of Smac/DIABLO and inactivation of X-linked inhibitor of apoptosis through caspase-9–independent activation of caspase 3.
Brain abscess complicating cervical traction.
Authors: A. T. Reece, N. V. Todd
Journal: BMJ (1988)

2 observations d'abces du cerveau apres traction continue pendant quelques semaines pour le traitement de fractures-luxations du rachis cervical (C4-C5 dans 1 cas, C6-C7 dans l'autre. Traitement par drainage puis antibiotiques. Certains instruments utilises pour la traction sont dangereux parce qu'ils ne sont pas munis de moyens de limiter la penetration
Simulated Ischemia Increases the Susceptibility of Rat Cardiomyocytes to Hypercontracture
Authors: Y.V. Ladilov, B. Siegmund, C. Balser, H.M. Piper
Journal: Circulation Research (1997)

The hypothesis that rat cardiomyocytes become susceptible to hypercontracture after anoxia/reoxygenation was investigated. The cells were gradually overloaded with Ca2+ after different periods of simulated ischemia (substrate-free anoxia, medium at pH 6.4) followed by 20 minutes of reoxygenation. The cytosolic Ca2+ concentration (measured with fura 2) at which the cells developed maximal hypercontracture (Camax) was used as an index for their susceptibility to hypercontracture (SH). SH was increased in cardiomyocytes after prolonged periods of simulated ischemia; ie, these cells developed hypercontracture at significantly lower cytosolic Ca2+ levels than did normoxic cells (Camax, 0.80 +/- 0.05 mumol/L versus 1.27 +/- 0.05 mumol/L; P < .01). To find the possible cause of increased SH, the influence of Ca2+ overload, acidosis, and protein dephosphorylation were studied. Prevention of cytosolic Ca2+ overload in anoxic cardiomyocytes or imitation of ischemic acidosis in normoxic cells did not influence Camax. In contrast, use of 10 mumol/L cantharidin (inhibitor of protein phosphatases 1 and 2A) during anoxic superfusion prevented the reduction of Camax. Furthermore, treatment of normoxic cardiomyocytes with 20 mmol/L of the chemical phosphatase 2,3-butanedione monoxime reduced Camax. Therefore, prolonged simulated ischemia increases susceptibility of cardio-myocytes to hypercontracture. This seems to be due to protein dephosphorylation.
Ursula Margaret Hutchinson
Authors: M. Ions
Journal: BMJ (2004)

General practitioner Bierfield, Nelson, Lancashire (b 1957; q Galway 1981; MRCGP), died from cancer on 29 October 2003.

Ursula trained in Ireland before coming to Manchester in 1986 to complete her general practice training. She became a full time principal in 1986. In 2000 she obtained her diploma in dermatology and went on to set up an intermediate care clinic in dermatology for primary care. In 1999 she became an undergraduate tutor for the University of Manchester. She leaves a husband, Roger.
Human colonic mononuclear cells: studies of cytotoxic function.
Authors: Z M Falchuk, E Barnhard, I Machado
Journal: Gut (1981)

We isolated lymphocytes from the lamina propria of colon from 19 patients with inflammatory bowel disease, colon cancer, and certain benign conditions to determine: (1) if these lymphocytes could mediate mitogen-induced (MICC) and spontaneous cell-mediated cytotoxicity (SCMC), and (2) if there were any differences in cytotoxic effectiveness which could relate to the underlying disease. We found that lamina propria lymphocytes functioned well in MICC reactions with phytohaemagglutinin, but not concanavalin A as the inducing mitogen (specific lysis 28 5% vs 5 3%). Lamina propria lymphocytes did not mediate SCMC (specific lysis 0.3%). Neither the presence of inflammation not the underlying disease of the patient influenced the cytotoxic activity. Peripheral blood lymphocytes from normal subjects and patients performed well in MICC assay with both phytohaemagglutinin and concanvalin A as the inducing mitogen and were equally effective in SCMC reactions.
Production of chemotactic activity for polymorphonuclear leukocytes by cultured rat hepatocytes exposed to ethanol.
Authors: H D Perez, F J Roll, D M Bissell, S Shak, I M Goldstein
Journal: Journal of Clinical Investigation (1984)

Acute alcoholic hepatitis is characterized by infiltration of the liver parenchyma with polymorphonuclear leukocytes. As a possible explanation for this phenomenon, we have found that ethanol stimulates cultured rat hepatocytes to generate potent chemotactic activity. Hepatocytes (greater than 99% pure), isolated from the livers of Sprague-Dawley rats, responded to incubation with ethanol (2.0-10 mM) by releasing chemotactic activity for human polymorphonuclear leukocytes into culture supernatants in a time- and concentration-dependent fashion. Chemotactic activity was maximal after incubation of hepatocytes with 10 mM ethanol for 6 h. It was undetectable in the absence of ethanol and was reduced in the presence of either the alcohol dehydrogenase inhibitor, 4-methylpyrazole, or the acetaldehyde dehydrogenase inhibitor, cyanamide. Ethanol failed to stimulate generation of chemotactic activity by either rat dermal fibroblasts, hepatic sinusoidal endothelial cells, or Kupffer cells. The chemotactic activity generated by ethanol-treated rat hepatocytes was recovered from culture supernatants in the lipid phase after extraction with chloroform/methanol. Thin-layer chromatography and high performance liquid chromatography of chloroform/methanol extracts demonstrated that the chemotactic factor probably is a polar lipid. This chemotactic lipid may account, in part, for the leukocytic infiltration of the liver parenchyma that is observed during the course of acute alcoholic hepatitis.
SUGGESTIONS FOR LESSENING THE FREQUENCY OF RELAPSES AFTER TREATMENT OF MORPHINISM.
Authors: A. J. PRESSEY
Journal: JAMA (1901)

Every physician well understands that the percentage of relapses of patients treated for morphinism is large—just how large I do not know. In many instances it has been an absolute impossibility for me to keep track of the cases I have treated. During a correspondence with a physician a few months ago in regard to my treating his son for the morphin addiction, he wrote me that he knew that statistics proved that 95 per cent. of all patients cured relapsed. I have heard it stated that one can prove almost anything, except facts, by statistics. If the physician has the statistics to corroborate his assertion, I am prepared to believe the statement correct. It has been estimated by some who have had considerable experience that 50 per cent. of cases treated relapsed. I dare say that that is a fair estimate when all classes of cases are counted, but
Abstract 1814: Perceived Cardiac Risk Underestimated Among Urban Diabetics
Authors: Jerilyn K Allen, Cheryl Dennison, Allison Purcell, Sarah Szanton, Martha Hill, Rosemarie Previte
Journal: Circulation (2007)

Cardiovascular disease (CVD) is the leading cause of death in diabetics; however, understanding among diabetics of the importance of CVD as a major health threat is unknown. We studied perceived and actual risk of developing CVD and the factors associated with perceptions of CVD risk in a sample of 82 type II diabetic patients without diagnosed CVD. Data were collected during baseline evaluation for a randomized trial to reduce total CVD risk in urban community clinics. Perceived risk was determined by the patients’ estimation of their personal likelihood of developing heart disease and objective risk was calculated using the Framingham Index. Depressive symptoms were measured by the CES-D and overall perception of health by the EuroQuol. CVD risk factors were measured directly using standardized procedures. The sample was 73% female and 93% Black. Mean age was 54 ± 11 years, 32% had not graduated from high school and 55% had annual household incomes &lt;$20,000. CVD risk factor burden was high: 70% were obese; 68% had BP≥130/80; 56% had high LDL-C; and 31% were current smokers. The Framingham 10 year CVD risk ranged from 1–33% with average risk of 11.4 ± 7.2%. In contrast, only 18% of patients perceived themselves at high risk for developing heart disease. Objective and perceived CVD risk were not significantly associated (β=−0.38; p&lt;0.31). Increased levels of perceived risk were associated with younger age (β= −0.648; p=0.007), greater depressive symptoms (β=0.87; p&lt;.000), poorer general health perception (β= −0.51; p&lt;.000); and current smoking (β=14.27; p=0.02); but there was no association with HgA1c, LDL-C, or blood pressure levels. In a multivariate model, greater depressive symptoms, poorer general health perceptions, and current smoking were independently associated with perceived risk for CVD. Urban, disadvantaged diabetics in this study of predominately Black women had many CVD risk factors and increased objective risk for developing CVD. However, there was a gap between perceived and actual risk of CVD. Attempts to improve the cardiovascular health of underserved groups should include interventions to increase awareness and control of CVD risk factors among type II diabetics, particularly aimed at racial/ethnic minority women.
Facet joints and low back pain.
Authors: A H Murley
Journal: BMJ (1978)

treatment is restarted and continued for a further 12 weeks.We agree with the authors that selfadministered subcutaneous heparin is safe and effective and has revolutionised the manage- ment of thromboembolism of pregnancy; we would encourage patients on long-term anticoagulants to discontinue oral warfarin and change to self-administered subcutaneous heparin well before conception takes place.
Hospitals must take lead on new care models and work better with GPs, think tank says
Authors: G. Iacobucci
Journal: BMJ (2015)

Acute care hospitals in England must avoid adopting a “fortress mentality” in the face of financial and workload pressure and instead focus on new models of care and improving relationships with general practice, a healthcare think tank has urged.

In its new report the King’s Fund acknowledged that NHS hospitals were facing mounting service and financial pressure but said that they should look beyond merely safeguarding their own organisations and focus on leading system-wide changes that improved services for all patients.1 It said that better …
Associations of Borderline and Low Normal Ankle-Brachial Index Values With Functional Decline at 5-Year Follow-Up
Authors: Mary M. McDermott, Jack M. Guralnik, Lu Tian, Kiang Liu, Luigi Ferrucci, Yihua Liao, Leena Sharma, Michael H. Criqui
Journal: Journal of the American College of Cardiology (2009)
Isolated diastolic dysfunction of right ventricle: stress-induced pulmonary hypertension
Authors: R. Faludi, A. Komócsi, J. Bozó, G. Kumánovics, L. Czirják, L. Papp, T. Simor
Journal: European Respiratory Journal (2008)

To the Editors: 

We read with great interest the article of Huez et al. 1. Their results, which were mostly noninvasive, suggest that isolated longitudinal diastolic dysfunction of the right ventricle may be a sign of stress-induced (or latent) pulmonary hypertension. The aim of our letter is to confirm this observation with the help of our results based on invasive measurements.

In total, 58 patients (mean age 54±8 yrs, 48 female) were examined. These comprised 15 healthy subjects who had no signs or symptoms of heart disease and 43 consecutive patients suffering from connective tissue disease (CTD), of whom 38 had systemic sclerosis, two had systemic lupus erythematosus, two had mixed CTD and one had polymyositis. Patients in the latter group were referred to the University of Pecs (Pecs, Hungary) on suspicion of pulmonary artery hypertension (PAH). Patients with atrial fibrillation and severe mitral or tricuspid insufficiency were excluded from the study.

The local ethics committee approved the study. All subjects had given written …
Relationship between Deoxyribonucleoprotein and Deoxyribonucleic Acid Antibodies in Systemic Lupus Erythematosus
Authors: Pierre Robitaille, Eng M. Tan
Journal: Journal of Clinical Investigation (1973)

A soluble preparation of nucleoprotein (sNP), a complex of native deoxyribonucleic acid (DNA) and histones, was isolated from calf thymus nuclei and labeled with [125I]iodide. Isotope-labeled antigen ([125I]sNP) was used in a primary binding radioimmunoassay method to detect antibodies to both sNP and native DNA. Sera with antibody to native DNA reacted with the DNA moiety of sNP and bound [125I] sNP, but this binding was completely inhibited by addition of unlabeled native DNA. Antibody to sNP which reacted with DNA-histone complex was not inhibited in the radioimmunoassay by addition of unlabeled DNA. Thus, antibodies to sNP and native DNA could be detected and differentiated by use of a single isotopically labeled antigen. In systemic lupus erythematosus (SLE), sera with binding to [125I]sNP was present in 21/36 (58%) patients. The majority (18/21) had antibodies to sNP and native DNA present simultaneously, one had antibody only to sNP and two had antibody only to DNA. In contrast, patients with other connective tissue diseases rarely showed binding to [125I]sNP. Serial studies on SLE patients showed that high serum binding to [125I]sNP paralleled renal disease activity as reflected by the degree of proteinuria. A fall in binding was observed with subsidence of renal disease and reappearance of increased binding coincided with exacerbation. In these patients, antibodies to sNP and DNA appeared or disappeared pari passu suggesting that in addition to the previously demonstrated role of antibody to native DNA, antibody to sNP might also be implicated in the pathogenesis of immunologically-mediated tissue lesions such as SLE nephritis.