tbuckley/cabot-search huggingface dataset:
Antitumour necrosis factor-alpha antibodies (infliximab) in the treatment of a patient with toxic epidermal necrolysis
Authors: M. Fischer, E. Fiedler, W.C. Marsch, J. Wohlrab
Journal: British Journal of Dermatology (2002)

Journal Article Antitumour necrosis factor‐α antibodies (infliximab) in the treatment of a patient with toxic epidermal necrolysis Get access M. Fischer, M. Fischer Department of Dermatology and Venereology, Martin‐Luther‐University Halle‐Wittenberg, Ernst‐Kromayer‐Straβe 5–8, D‐06097 Halle (Saale), Germany E‐mail: matthias.fischer@medizin.uni‐halle.de Search for other works by this author on: Oxford Academic Google Scholar E. Fiedler, E. Fiedler Department of Dermatology and Venereology, Martin‐Luther‐University Halle‐Wittenberg, Ernst‐Kromayer‐Straβe 5–8, D‐06097 Halle (Saale), Germany E‐mail: matthias.fischer@medizin.uni‐halle.de Search for other works by this author on: Oxford Academic Google Scholar W.C. Marsch, W.C. Marsch Department of Dermatology and Venereology, Martin‐Luther‐University Halle‐Wittenberg, Ernst‐Kromayer‐Straβe 5–8, D‐06097 Halle (Saale), Germany E‐mail: matthias.fischer@medizin.uni‐halle.de Search for other works by this author on: Oxford Academic Google Scholar J. Wohlrab J. Wohlrab Department of Dermatology and Venereology, Martin‐Luther‐University Halle‐Wittenberg, Ernst‐Kromayer‐Straβe 5–8, D‐06097 Halle (Saale), Germany E‐mail: matthias.fischer@medizin.uni‐halle.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 146, Issue 4, 1 April 2002, Pages 707–709, https://doi.org/10.1046/j.1365-2133.2002.46833.x Published: 01 April 2002
Treatment of the nephrotic syndrome.
Authors: G Rose
Journal: BMJ (1970)

in this case begins with the weaker dose of 10 mg.working up to the larger one of 50 mg., whoch dosage was continued at weekly intervals after routine investigation of the urine for proteinuria.In the far-off days before 1945 various clinicians at the Charterhouse Rheumatism Clinic who had been using gold injections for over 12 years (aurocalcium) found that after testing for sensitivity to gold the best results were obtained by giving the highest dose of 50 mg.initially, the second dose 25 mg., and the subsequent weekly doses of 10 mg. until a remission occurred and if there was no evidence of toxicity by blood, urine, and clinical tests.It was considered unwise to continue the gold injections when the patient went into remission.The course was repeated if a relapse occurred, and very often two courses only were given, and then usually for a period of several months only.I am aware of the disfavour with which gold injections were regarded soon after 1945 owing to reports of severe toxic reactions.Only in the past 10 years has its popularity in therapy reappeared.However, a survey of its uses for over 12 years at the Charterhouse Clinic revealed no severe gold reactions.A reminder of the good results of gold therapy may not be out of place.-Iam, etc.,
A Phase I Clinical Trial of CHT-25 a 131I-Labeled Chimeric Anti-CD25 Antibody Showing Efficacy in Patients with Refractory Lymphoma
Authors: Gairin Dancey, John Violet, Alessandra Malaroda, Alan J. Green, Surinder K. Sharma, Roslyn Francis, Shokri Othman, Sweta Parker, John Buscombe, Natalie Griffin, Pei-San Chan, Anmol Malhotra, Nicholas Woodward, Alan Ramsay, Philip Ross, T. Andrew Lister, Peter Amlot, Richard Begent, Christopher McNamara
Journal: Clinical Cancer Research (2009)

Abstract Purpose: There is a need for new treatments for Hodgkin and T-cell lymphoma due to the development of drug resistance in a proportion of patients. This phase I study of radioimmunotherapy used CHT-25, a chimeric antibody to the α-chain of the interleukin-2 receptor, CD25, conjugated to iodine-131 (131I) in patients with refractory CD25-positive lymphomas. Experimental Design: Fifteen patients were treated (Hodgkin lymphoma, 12; angioimmunoblastic T-cell lymphoma, 1; adult T-cell leukemia/lymphoma, 2). Tumor was monitored by computed tomography and in all but two patients by 18F-fluorodeoxyglucose positron emission tomography. Results: There were no grade 3 or 4 infusion reactions. At the maximum tolerated dose of 1,200 MBq/m2, the major side effect was delayed myelotoxicity with the nadir for platelets at 38 days and for neutrophils at 53 days. One patient treated with 2,960 MBq/m2 developed prolonged grade 4 neutropenia and thrombocytopenia and died of Pneumocystis jiroveci pneumonia. Nonhematologic toxicity was mild. Single photon emission computer tomography imaging showed tumor-specific uptake and retention of 131I and no excessive retention in normal organs. Of nine patients receiving ≥1,200 MBq/m2, six responded (three complete response and three partial response); one of six patients with administered radioactivity of ≤740 MBq/m2 had a complete response. Conclusions: CHT-25 is well tolerated with 1,200 MBq/m2 administered radioactivity and shows clinical activity in patients who are refractory to conventional therapies. Phase II studies are justified to determine efficacy and toxicity in a broader range of clinical scenarios. (Clin Cancer Res 2009;15(24):7701–10)
Annona muricata leaves accelerate wound healing in rats via involvement of Hsp70 and antioxidant defence
Authors: Soheil Zorofchian Moghadamtousi, Elham Rouhollahi, Maryam Hajrezaie, Hamed Karimian, Mahmood Ameen Abdulla, Habsah Abdul Kadir
Journal: International Journal of Surgery (2015)
Cancer-Specific and Other-Cause Mortality After Radical Prostatectomy Versus Observation in Patients with Prostate Cancer: Competing-Risks Analysis of a Large North American Population-Based Cohort
Authors: Firas Abdollah, Maxine Sun, Jan Schmitges, Zhe Tian, Claudio Jeldres, Alberto Briganti, Shahrohk F. Shariat, Paul Perrotte, Francesco Montorsi, Pierre I. Karakiewicz
Journal: European Urology (2011)
NT-35 * SAFER AND MORE COMPLETE RESECTION OF INTRINSIC TUMOURS FOLLOWING INTRODUCTION OF 3D NEURO-NAVIGATIONAL ULTRASOUND CONTROLLED RESECTION: A SINGLE CENTRE STUDY
Authors: B. Vaqas, S. Epton, C. Harrison, M. Awad, K. O'Neill
Journal: Neuro-Oncology (2014)

The aim of intrinsic tumour resection is to improve survival by maximising tumour resection and minimising any new post operative neurological deficit. The aim of this study was to demonstrate if neuronavigational 3D ultrasound guided resection resulted in improved tumour resection in terms of percentage resection and clinical outcome. A retrospective consecutive case series of 50 patients who underwent resection of intrinsic tumour was collected, comprising 25 cases using neuronavigational intraoperative 3D ultrasound and 25 with standard neuronavigation without intraoperative ultrasound. The volume of the tumour was calculated both pre- and post-operatively using volumetric analysis software based on T1 contrast sequences from MRI scans. Neurological outcome was measured as the presence of new neurological deficits at discharge from the ward. The ultrasound group had 97.7% tumour resection (95% CI 96.9%- 98.5%) and the non-ultrasound group having 93.5% resection (95% CI of 92.1%-94.9%), this difference was statistically significant (p < 0.0005). There was no significant difference in the pre-op volume or tumour location between the two groups. One patient suffered new neurological deficit in the ultrasound group (4%) compared with 3 patients (12%) in the non-ultrasound group. The experience in our unit is that neuronavigational ultrasound controlled resection allows tailor made resection of the reducing tumour mass allowing safer and more complete resection. The fine control over tumour resection probably results in reduced collateral damage to adjacent structures thus reducing new post operative neurological deficit. Further studies within a larger patient sample size are required to show if this results in reduced time to recurrence and improved survival in patients with intrinsic brain tumours.
Healed Plaque Ruptures and Sudden Coronary Death
Authors: Allen P. Burke, Frank D. Kolodgie, Andrew Farb, Deena K. Weber, Gray T. Malcom, John Smialek, Renu Virmani
Journal: Circulation (2001)

Background —Subclinical episodes of plaque disruption followed by healing are considered a mechanism of increased plaque burden. Detailed pathological studies of healed ruptures, however, are lacking. Methods and Results —We identified acute and healed ruptures from 142 men who died of sudden coronary death and performed morphometric measurements of plaque burden, luminal stenosis, and smooth muscle cell phenotype. Healed ruptures were found in 61% of hearts and were associated with healed myocardial infarction, increased heart weight, dyslipidemia, and diabetes. Multiple healed rupture sites with layering were frequently found in segments with acute and healed rupture; the percent area luminal narrowing increased with increased numbers of healed sites of previous rupture. The underlying percent luminal narrowing for acute ruptures (mean 79±15%) exceeded that for healed ruptures (mean 66±14%, P =0.0001), and the area within the internal elastic lamina was significantly less in healed ruptures than in acute ruptures, when segments were grouped by distance from the ostium. Healed ruptures favored the accumulation of immature smooth muscle cells at repair sites, with a cellular proliferation index of 0.40±0.09%, significantly higher than the index at the sites of rupture ( P =0.008). Conclusions —These data provide evidence that silent plaque rupture is a form of wound healing that results in increased percent stenosis. Healed ruptures occur in arteries with less cross-sectional area luminal narrowing than acute ruptures and are a frequent finding in men who die suddenly with severe coronary atherosclerosis.
Genome‐Wide Mapping of DNA Hydroxymethylation in Osteoarthritic Chondrocytes
Authors: Sarah E. B. Taylor, Ye Henry Li, Wing H. Wong, Nidhi Bhutani
Journal: Arthritis & Rheumatology (2015)

Objective To examine the genome‐wide distribution of hydroxymethylated cytosine (5hmC) in osteoarthritic (OA) and normal chondrocytes in order to investigate the effect on OA‐specific gene expression. Methods Cartilage was obtained from OA patients undergoing total knee arthroplasty or from control patients undergoing anterior cruciate ligament reconstruction. Genome‐wide sequencing of 5hmC‐enriched DNA was performed in a small cohort of normal and OA chondrocytes to identify differentially hydroxymethylated regions (DhMRs) in OA chondrocytes. Data from the genome‐wide sequencing of 5hmC‐enriched DNA were intersected with global OA gene expression data to define subsets of genes and pathways potentially affected by increased 5hmC levels in OA chondrocytes. Results A total of 70,591 DhMRs were identified in OA chondrocytes as compared to normal chondrocytes, 44,288 (63%) of which were increased in OA chondrocytes. The majority of DhMRs (66%) were gained in gene bodies. Increased DhMRs were observed in ∼50% of genes previously implicated in OA pathology including MMP3, LRP5, GDF5, and COL11A1. Furthermore, analyses of gene expression data revealed gene body gain of 5hmC appears to be preferentially associated with activated, but not repressed, genes in OA chondrocytes. Conclusion This study provides the first genome‐wide profiling of 5hmC distribution in OA chondrocytes. We had previously reported a global increase in 5hmC levels in OA chondrocytes. Gain of 5hmC in the gene body is found to be characteristic of activated genes in OA chondrocytes, highlighting the influence of 5hmC as an epigenetic mark in OA. In addition, this study identifies multiple OA‐associated genes that are potentially regulated either singularly by gain of DNA hydroxymethylation or in combination with loss of DNA methylation.
The Heat Is on
Authors: Georg Wick
Journal: Circulation (2006)

t is common knowledge that atherosclerosis is a multifactorial disease, and the disease-promoting role of classic risk factors for atherosclerosis, such as high serum cholesterol levels, diabetes, hypertension, smoking, and various types of infections, has been proven in innumerable clinical studies.Despite the fact that we are dealing with a chronic disease, however, there is a surprising scarcity of reports dealing with the very first stages of atherogenesis, ie, those that are not yet leading to clinical symptoms.It is now evident that inflammatory/immunologic processes play a major role in the development of atherosclerosis.The correlation between the presence and amount of inflammatory surrogate markers and the occurrence of sonographically demonstrable early arterial changes becomes more significant the earlier in the course of the disease that these analyses are performed.Although complicated atherosclerotic lesions, as the name implies, are composed of many different cellular and extracellular constituents, the earliest lesions are characterized by intimal infiltration by mononuclear cells often still without the presence of foam cells, especially in those instances in which risk factors other than high serum cholesterol levels are operative.In this context, it is important to remember that the first intima-infiltrating cells in early, clinically nonapparent lesions are lymphoid cells, followed by blood-borne monocytes, and finally smooth muscle cells immigrating from the media. 1 Later, both the scavenger receptor-expressing macrophages and smooth muscle cells may transform into foam cells accompanied by fibroblast and myofibroblast proliferation with collagenous and noncollagenous extracellular matrix protein deposition leading to the paradigmatic hardening of the arterial wall.The antigenic specificity of early intima-infiltrating lymphoid cells is still to be determined.
Recommendations for Physical Activity and Recreational Sports Participation for Young Patients With Genetic Cardiovascular Diseases
Authors: Barry J. Maron, Bernard R. Chaitman, Michael J. Ackerman, Antonio Bayés de Luna, Domenico Corrado, Jane E. Crosson, Barbara J. Deal, David J. Driscoll, N.A. Mark Estes, Claudio Gil S. Araújo, David H. Liang, Matthew J. Mitten, Robert J. Myerburg, Antonio Pelliccia, Paul D. Thompson, Jeffrey A. Towbin, Steven P. Van Camp
Journal: Circulation (2004)

A group of relatively uncommon but important genetic cardiovascular diseases (GCVDs) are associated with increased risk for sudden cardiac death during exercise, including hypertrophic cardiomyopathy, long-QT syndrome, Marfan syndrome, and arrhythmogenic right ventricular cardiomyopathy. These conditions, characterized by diverse phenotypic expression and genetic substrates, account for a substantial proportion of unexpected and usually arrhythmia-based fatal events during adolescence and young adulthood. Guidelines are in place governing eligibility and disqualification criteria for competitive athletes with these GCVDs (eg, Bethesda Conference No. 26 and its update as Bethesda Conference No. 36 in 2005). However, similar systematic recommendations for the much larger population of patients with GCVD who are not trained athletes, but nevertheless wish to participate in any of a variety of recreational physical activities and sports, have not been available. The practicing clinician is frequently confronted with the dilemma of designing noncompetitive exercise programs for athletes with GCVD after disqualification from competition, as well as for those patients with such conditions who do not aspire to organized sports. Indeed, many asymptomatic (or mildly symptomatic) patients with GCVD desire a physically active lifestyle with participation in recreational and leisure-time activities to take advantage of the many documented benefits of exercise. However, to date, no reference document has been available for ascertaining which types of physical activity could be regarded as either prudent or inadvisable in these subgroups of patients. Therefore, given this clear and present need, this American Heart Association consensus document was constituted, based largely on the experience and insights of the expert panel, to offer recommendations governing recreational exercise for patients with known GCVDs.
Massive xanthomatosis and altered composition of atherosclerotic lesions in hyperlipidemic mice lacking acyl CoA:cholesterol acyltransferase 1
Authors: Michel Accad, Steven J. Smith, Dale L. Newland, David A. Sanan, Lloyd E. King, MacRae F. Linton, Sergio Fazio, Robert V. Farese
Journal: Journal of Clinical Investigation (2000)

Inhibitors of acyl CoA:cholesterol acyltransferase (ACAT) have attracted considerable interest as a potential treatment for atherosclerosis. Currently available inhibitors probably act nonselectively against the two known ACATs. One of these enzymes, ACAT1, is highly expressed in macrophages in atherosclerotic lesions, where it contributes to foam-cell formation. In this study, we examined the effects of selective ACAT1 deficiency in two mouse models of atherosclerosis. In the setting of severe hypercholesterolemia caused by deficiency in apoE or the LDL receptor (LDLR), total ACAT1 deficiency led to marked alterations in cholesterol homeostasis and extensive deposition of unesterified cholesterol in the skin and brain. Bone marrow transplantation experiments demonstrated that ACAT1 deficiency in macrophages was sufficient to cause dermal xanthomas in hyperlipidemic LDLR-deficient mice. ACAT1 deficiency did not prevent the development of atherosclerotic lesions in either apoE-deficient or LDLR-deficient mice, despite causing relatively lower serum cholesterol levels. However, the lesions in ACAT1-deficient mice were atypical in composition, with reduced amounts of neutral lipids and a paucity of macrophages in advanced lesions. Although the latter findings may be associated with increased lesion stability, the marked alterations in cholesterol homeostasis indicate that selectively inhibiting ACAT1 in the setting of severe hyperlipidemia may have detrimental consequences.
A NEW METHOD FOR ESTIMATING SERUM ACID PHOSPHATASE OF PROSTATIC ORIGIN APPLIED TO THE CLINICAL INVESTIGATION OF CANCER OF THE PROSTATE 12
Authors: William H. Fishman, R. M. Dart, C. D. Bonner, W. F. Leadbetter, F. Lerner, F. Homburger
Journal: Journal of Clinical Investigation (1953)

Since the studies of Gutman and Gutman (2, 3), measurements of the serum acid phosphatase have become a recognized and widely used ancillary procedure for the diagnosis of cancer of the prostate and a practical means for the evaluation of the functional status of the tumor in many patients with metastasizing cancer of the prostate. While an abnormally increased value of serum acid phosphatase is considered to be a specific index for the presence of carcinoma of the prostate, a normal serum acid phosphatase value in itself cannot be interpreted as signifying absence of this disease. According to Bodansky and Bodansky (4) in their review of the literature, only 24 per cent of unselected patients without and 81 per cent with bone metastases from cancer of the prostate show elevated serum acid phosphatase values. Thus, 20 to 75 per cent of proven cases of cancer of the prostate show equivocal or normal serum acid phosphatase levels.
Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency
Authors: Robert S. Jackson, John W.M. Creemers, I. Sadaf Farooqi, Marie-Laure Raffin-Sanson, Andrea Varro, Graham J. Dockray, Jens J. Holst, Patricia L. Brubaker, Pierre Corvol, Kenneth S. Polonsky, Diane Ostrega, Kenneth L. Becker, Xavier Bertagna, John C. Hutton, Anne White, Mehul T. Dattani, Khalid Hussain, Stephen J. Middleton, Thomasina M. Nicole, Peter J. Milla, Keith J. Lindley, Stephen O’Rahilly
Journal: Journal of Clinical Investigation (2003)

We have previously described the only reported case of human proprotein convertase 1 (PC1) deficiency, in a female (Subject A) with obesity, hypogonadism, hypoadrenalism, and reactive hypoglycemia. We now report the second case of human PC1 deficiency (Subject B), also due to compound heterozygosity for novel missense and nonsense mutations. While both subjects shared the phenotypes of obesity, hypoadrenalism, reactive hypoglycemia, and elevated circulating levels of certain prohormones, the clinical presentation of Subject B was dominated by severe refractory neonatal diarrhea, malabsorptive in type. Subsequent investigation of Subject A revealed marked small-intestinal absorptive dysfunction, which was not previously clinically suspected. We postulate that PC1, presumably in the enteroendocrine cells, is essential for the normal absorptive function of the human small intestine. The differences in the nature and severity of presentation between the two cases cannot readily be explained on the basis of allelic heterogeneity, as the nonsense and missense mutations from both subjects had comparably severe effects on the catalytic activity of PC1. Despite Subject A's negligible PC1 activity, some mature ACTH and glucagon-like peptide 17-36amide were detectable in her plasma, suggesting that the production of these hormones, at least in humans, does not have an absolute dependence on PC1. The presence of severe obesity and the absence of growth retardation in both subjects contrast markedly with the phenotype of mice lacking PC1 and suggest that the precise physiological repertoire of this enzyme may vary between mammalian species.
Myeloproliferative neoplasms can be initiated from a single hematopoietic stem cell expressing <i>JAK2</i>-V617F
Authors: Pontus Lundberg, Hitoshi Takizawa, Lucia Kubovcakova, Guoji Guo, Hui Hao-Shen, Stephan Dirnhofer, Stuart H. Orkin, Markus G. Manz, Radek C. Skoda
Journal: The Journal of Experimental Medicine (2014)

The majority of patients with myeloproliferative neoplasms (MPNs) carry a somatic JAK2-V617F mutation. Because additional mutations can precede JAK2-V617F, it is questioned whether JAK2-V617F alone can initiate MPN. Several mouse models have demonstrated that JAK2-V617F can cause MPN; however, in all these models disease was polyclonal. Conversely, cancer initiates at the single cell level, but attempts to recapitulate single-cell disease initiation in mice have thus far failed. We demonstrate by limiting dilution and single-cell transplantations that MPN disease, manifesting either as erythrocytosis or thrombocytosis, can be initiated clonally from a single cell carrying JAK2-V617F. However, only a subset of mice reconstituted from single hematopoietic stem cells (HSCs) displayed MPN phenotype. Expression of JAK2-V617F in HSCs promoted cell division and increased DNA damage. Higher JAK2-V617F expression correlated with a short-term HSC signature and increased myeloid bias in single-cell gene expression analyses. Lower JAK2-V617F expression in progenitor and stem cells was associated with the capacity to stably engraft in secondary recipients. Furthermore, long-term repopulating capacity was also present in a compartment with intermediate expression levels of lineage markers. Our studies demonstrate that MPN can be initiated from a single HSC and illustrate that JAK2-V617F has complex effects on HSC biology.
Copying letters to patients: Most patients want copies of letters from outpatient clinics and find them useful
Authors: B R. O'Driscoll
Journal: BMJ (2003)

EDITOR–Chantler and Johnson proposed action research on the proposal to send patients copies of clinical correspondence, and Essex discussed the issue of copying letters to patients in the patient issue.1 2

Since April 2002 we have offered all patients the option of receiving copies of letters to their general practitioner from a chest and cardiology clinic. Of 1717 monitored consultations, 1504 patients …