tbuckley/cabot-search huggingface dataset:
Skeletal Muscle Metastases on FDG PET/CT Imaging
Authors: Alok R. Khandelwal, Amol M. Takalkar, David L. Lilien, Ajay Ravi
Journal: Clinical Nuclear Medicine (2012)

To define the radiological imaging features and clinical findings of the patients with skeletal muscle metastasis.4454 computed tomography (CT), 1802 magnetic resonance imaging (MRI) and 2569 positron emission tomography/computed tomography (PET/CT) imaging studies of the oncology patients performed between March 2009 and July 2012 in the Radiology and Nuclear Medicine Departments of our hospital were retrospectively reviewed.Fifty-two patients had 91 different metastatic skeletal muscle masses. Twenty-one patients (40%) were diagnosed with lung carcinoma as being the most common primary source. Forty-seven patients (90%) had metastatic disease somewhere else at the time of detection of skeletal muscle metastasis. Thirty-three patients (63%) had lymph node metastasis which was the most common site. Muscles mostly affected by metastatic disease were gluteals (15%), psoas (8.7%), erector spinae (8.7%), rectus abdominis (7.6%), latissimus dorsi (6.5%). The mean size of the lesions was 30 mm (range, 10-120 mm). The most common appearance on contrast-enhanced CT was a rim-enhancing intramuscular mass with central hypoattenuation. On MRI, skeletal muscle metastases mostly revealed isointense signal on T1-weighted images, heterogeneous high signal with peritumoral edema on T2-weighted images and extensive enhancement with central necrosis on gadolinium-DTPA (diethylene triamine pentaacetic acid) enhanced images.Skeletal muscle metastasis may be an incidental finding on CT. The most common CT appearance is a rim-enhancing intramuscular mass with central hypoattenuation. On MRI, extensive tumoral enhancement, central necrosis and peritumoral edema are highly acceptable features of skeletal muscle metastasis.
Abstract A31: Regulation of ErbB4 receptor tyrosine kinase by the SUMO system
Authors: Anna Korhonen, Maria Sundvall, Katri Vaparanta, Klaus Elenius
Journal: Cancer Research (2013)

Abstract The members of the ErbB family (EGFR/ErbB1, ErbB2, ErbB3, and ErbB4) of receptor tyrosine kinases (RTK) regulate key cellular processes including proliferation, differentiation, and survival, and play critical roles in several human malignancies. The alternatively spliced ErbB4 JM-a isoform was the first RTK found to signal by a mechanism involving proteolytic release of an intracellular receptor domain (ErbB4 ICD). The released ErbB4 ICD can translocate into the nucleus, where it functions as a transcriptional coregulator. ErbB4 ICD has been shown to regulate mammary epithelial development in vivo. Furthermore, nuclear ErbB4 immunoreactivity is frequently observed in clinical breast cancer samples. Although these findings suggest that ErbB4 signaling via ICD is biologically significant, little is known about the regulation of ErbB4 ICD functions or cellular localization. We hypothesized that the soluble ErbB4 ICD is likely to be regulated by different mechanisms than the ones controlling conventional RTK signaling. One regulatory mechanism that is often employed by nuclear proteins is the small ubiquitin-like modifier (SUMO) system. SUMO proteins modify protein substrates covalently, and alter their function through changes in activity, stability, or cellular localization. Here, we demonstrate that ErbB4 ICD is modified by SUMO-1 and SUMO-3. Full-length ErbB4 was not sumoylated, indicating that SUMO is a specific regulatory modification for the soluble ICD. By using site-directed mutagenesis followed by sumoylation assays, we mapped the major SUMO acceptor site in ErbB4. No differences were found between wild type and sumoylation deficient mutant of ErbB4 in biochemical assays measuring the tyrosine kinase activity of ErbB4, or activation of canonical RTK signaling pathways downstream of ErbB4. However, we showed that protein inhibitor of activated STAT3 (PIAS3), a SUMO E3 ligase that could stimulate the sumoylation, modulated the transcriptional coregulatory activity of ErbB4 ICD in luciferase reporter assays, as well as the function of ErbB4 ICD in mammary epithelial cell differentiation. Based on these findings we propose that the SUMO system regulates the nuclear signaling of ErbB4 ICD. Citation Format: Anna Korhonen, Maria Sundvall, Katri Vaparanta, Klaus Elenius. Regulation of ErbB4 receptor tyrosine kinase by the SUMO system. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A31.
The Effect of Metoclopramide Treatment on Diabetic Cystoparesis
Authors: Dennis D. Venable
Journal: JAMA (1988)

To the Editor.  —In a recent letter, Chaudhuri et al 1 reported their anecdotal experience with a single case of presumed diabetic cystoparesis in which their patient demonstrated  bladder  after ten days of oral administration of metoclopramide hydrochloride at a daily dosage of 40 mg. The metoclopramide treatment was administered for diabetic gastroparesis, and the improved bladder function was evidenced by a decrease in an asymptomatically elevated postvoid residual urine volume.  Nestler et al 2 had earlier published a similar case report of improvement in bladder function in a diabetic man who had required intermittent catheterization and subsequently resumed spontaneous voiding after treatment with metoclopramide for accompanying diabetic gastroparesis. Other reports of possible effects of metoclopramide therapy on the urinary tract have been limited. In an uncontrolled clinical trial in ten patients with a variety of chronic neurological conditions clinically characterized by flaccid, areflexic bladders, Vaidyanathan et al
Pericardial adaptations during chronic cardiac dilation in dogs.
Authors: G L Freeman, M M LeWinter
Journal: Circulation Research (1984)

The manner in which the pericardium adapts to chronic cardiac dilation is not known. Recent work from our laboratory indirectly suggested that the size of the pericardium and/or its pressure-volume relation was altered by chronic cardiac enlargement. To examine this question further, we compared pericardial pressure-volume and stress-strain relations, surface area, mass, and average thickness in seven normal dogs and seven with chronic volume overload hypertrophy due to a systemic arteriovenous fistula. Dogs with significant cardiac hypertrophy had an increased pericardial volume at any pressure and a proportionality constant for the slope of the entire curve as determined by nonlinear regression analysis. This was associated with parallel increases in pericardial surface area and mass such that average thickness was unchanged. Stress-strain analysis of the data revealed that the mechanical properties of the pericardium were not significantly different in dogs with chronic cardiac dilation. These results indicate that during chronic cardiac dilation the pericardium enlarges in size and mass. The pericardial chamber is more compliant, although the intrinsic stiffness of the pericardium appears to be unchanged. Further, since pericardial mass is increased, the response to chronic dilation appears to also involve the addition of new pericardial tissue.
Focus: Westminster Labour finds power is heaven on earth
Authors: J. Warden
Journal: BMJ (1997)

“Small earthquake, not many dead” best sums up the British general election of 1997. Although it swept the Conservatives from power and installed a Labour government with an unassailable majority, the political landscape remains remarkably stable.

The outcome has been accepted with equanimity all round. The electorate is quietly pleased. The civil service is revitalised. And the Conservatives have taken their defeat, the worst for 165 years, with stoicism. As Virginia Bottomley, a former health secretary, put it, they are like survivors from the Titanic.

The Labour party, out of office for 18 years, is still dazed by the scale of its achievement. The new government's majority alone, at 179, is larger than the total …
International Co-operation in Postgraduate Medical Education in Malaya
Authors: E. S. Monteiro
Journal: BMJ (1959)

We have in India enormous out-patient attendances every day-perhaps this also is true of Burma and some other Eastern countries.At our hospital in Bombay the out-patient department attendance every morning is 2,400.This out-patient service is almost a specialty, distinct and different from others.The diagnosis and assessment of progress as practised here have to be seen to be believed.It is not clinical medicine alone, although it is the most "clinical" of all medical activities.The full educational potential of this phase of medical service in India has remained unexplored.I invite the clinical teachers amongst you to India for this experience, which will certainly be interesting.I would also invite public health teachers to come and get acquainted with our rural and public health projects.Perhaps your concepts regarding public health, your impressions about standards of normal health, and therefore your expectations about the practicability of solutions to rural health problems will be subjected to considerable strain, but in your first-hand acquaintance with this problem lies our hope for a more practicable approach towards a healthy world.
Abstract 2233: Rearrangement of ERG and CHD1 genes in prostate cancer as a marker of tumor heterogeneity
Authors: Irina V. Tereshchenko, Hua Zhong, Marina Chekmareva, Urmila Santanam, Whitney Petrosky, Noriko Kane-Goldsmith, Jay A. Tischfield, Robert DiPaola
Journal: Cancer Research (2014)

Abstract Efforts to develop targeted therapy based on genomic findings are complicated by the polygenic nature of drug resistance and genetic heterogeneity between separate biopsy cores. These findings have led to the conclusion that analysis of multiple biopsy cores and consideration of multiple targeted agents will be important. Because of our concern that these assessments may be missing an additional layer of heterogeneity within even a single biopsy core, which sequencing alone may not identify, we studied the genetic heterogeneity of cells in focal areas using TMA. Using confocal microscopy, we analyzed the most common and prostate cancer specific gene rearrangement (TMPRSS2-ERG fusion and CHD1 deletion) in neighboring single cells in a tumor focus without changing the stromal microenvironment. We evaluated 56 patients that underwent radical prostatectomy at CINJ with pathological assessment, grading, and ERG rearrangement status. Overall, ERG rearrangements occurred in 24/56 (42.9%) patients. The most frequent mechanism of rearrangements was deletion (58%), while a split event was confirmed in 25% of the ERG-rearranged cases. In 88% of cases the ERG rearrangement was associated with TMPRSS2-ERG gene fusion. A copy number gain of the non-rearranged ERG gene occurred in 10/56 (17.6%) cases. A heterogeneous mix of ERG deletions, translocations, and copy number changes occurred in 8/24 (33%) patients, with a combination of deletions and translocations alone occurring in 3/24 (12.5%) cases. 20/21 (95%) of analyzed cases with ERG-rearrangement were negative for CHD1 gene rearrangement (p&amp;lt; 0.01). Overall, 14/45 (31.1%) of patients had CHD1 deletion, and 13/14 (93%) CHD1- cases correlate with ERG-rearrangement negative status (p&amp;lt; 0.01). 10/45 (22.2%) cases represent CHD1 gene copy number gain. These results support the notion that additional heterogeneity may be present even in a focus of a single biopsy core. These data are extremely important and urgently require further study to understand heterogeneity of genetic changes, because clinical studies have already been launched using genetic changes such as TMPRSS2-ERG fusions found in a single core biopsy to direct a specific therapy, including a trial using ABT-888 only in patients with this fusion now ongoing at CINJ. Citation Format: Irina V. Tereshchenko, Hua Zhong, Marina Chekmareva, Urmila Santanam, Whitney Petrosky, Noriko Kane-Goldsmith, Jay A. Tischfield, Robert DiPaola. Rearrangement of ERG and CHD1 genes in prostate cancer as a marker of tumor heterogeneity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2233. doi:10.1158/1538-7445.AM2014-2233
Benefits and Risks of Corticosteroid Prophylaxis in Adult Cardiac Surgery
Authors: Kwok M. Ho, Jen Aik Tan
Journal: Circulation (2009)

Background— Cardiopulmonary bypass and cardiac surgery are associated with a significant systemic inflammatory response that may increase postoperative complications. This meta-analysis assessed whether the benefits and risks of corticosteroid use were dose dependent in adult cardiac surgery. Methods and Results— Randomized controlled trials of the use of corticosteroid prophylaxis in adult cardiac surgery (&gt;18 years of age) requiring cardiopulmonary bypass were selected from MEDLINE (1966 to August 1, 2008), EMBASE (1988 to August 1, 2008), and the Cochrane controlled trials register without any language restrictions. A total of 3323 patients from 50 randomized controlled trials were identified and subject to meta-analysis. Corticosteroid prophylaxis reduced the risk of atrial fibrillation (25.1% versus 35.1%; number needed to treat, 10; relative risk, 0.74; 95% confidence interval [CI], 0.63 to 0.86; P &lt;0.01) and length of stay in the intensive care unit (weighted mean difference, −0.37 days; 95% CI, −0.21 to −0.52; P &lt;0.01) and hospital (weighted mean difference, −0.66 days; 95% CI, −0.77 to −1.25; P =0.03) compared with placebo. The use of corticosteroid was not associated with an increased risk of all-cause infection (relative risk, 0.93; 95% CI, 0.61 to 1.41; P =0.73), but hyperglycemia requiring insulin infusion after corticosteroid prophylaxis was common (28.2%; relative risk, 1.49; 95% CI, 1.11 to 2.01; P &lt;0.01). No additional benefits were found on all outcomes beyond a total dose of 1000 mg hydrocortisone, and very high doses of corticosteroid were associated with prolonged mechanical ventilation. Conclusions— Evidence suggests that low-dose corticosteroid is as effective as high-dose corticosteroid in reducing the risk of atrial fibrillation and duration of mechanical ventilation but with fewer potential side effects in adult cardiac surgery.
Computational Model of Steroidogenesis in Human H295R Cells toPredict Biochemical Response to Endocrine-Active Chemicals: Model Developmentfor Metyrapone
Authors: Michael S. Breen, Miyuki Breen, Natsuko Terasaki, Makoto Yamazaki, Rory B. Conolly
Journal: Environmental Health Perspectives (2009)

An in vitro steroidogenesis assay using the human adrenocortical carcinoma cell line H295R is being evaluated as a possible screening assay to detect and assess the impact of endocrine-active chemicals (EACs) capable of altering steroid biosynthesis. Data interpretation and their quantitative use in human and ecological risk assessments can be enhanced with mechanistic computational models to help define mechanisms of action and improve understanding of intracellular concentration-response behavior.The goal of this study was to develop a mechanistic computational model of the metabolic network of adrenal steroidogenesis to estimate the synthesis and secretion of adrenal steroids in human H295R cells and their biochemical response to steroidogenesis-disrupting EAC.We developed a deterministic model that describes the biosynthetic pathways for the conversion of cholesterol to adrenal steroids and the kinetics for enzyme inhibition by metryrapone (MET), a model EAC. Using a nonlinear parameter estimation method, the model was fitted to the measurements from an in vitro steroidogenesis assay using H295R cells.Model-predicted steroid concentrations in cells and culture medium corresponded well to the time-course measurements from control and MET-exposed cells. A sensitivity analysis indicated the parameter uncertainties and identified transport and metabolic processes that most influenced the concentrations of primary adrenal steroids, aldosterone and cortisol.Our study demonstrates the feasibility of using a computational model of steroidogenesis to estimate steroid concentrations in vitro. This capability could be useful to help define mechanisms of action for poorly characterized chemicals and mixtures in support of predictive hazard and risk assessments with EACs.
PREDICTION OF NON-BENEFIT FROM IMPLANTABLE CARDIOVERTER DEFIBRILLATOR TREATMENT IN PRIMARY PREVENTION PATIENTS WITH ISCHEMIC HEART DISEASE
Authors: Johannes B. Van Rees, C. Jan Willem Borleffs, Guido H. van Welsenes, Enno T. van der Velde, Lieselot van Erven, Hein Putter, Johanna G. van der Bom, Martin J. Schalij
Journal: Journal of the American College of Cardiology (2011)
Scientists in the courtroom: basic pointers for the expert scientific witness.
Authors: D L Eaton, D Kalman
Journal: Environmental Health Perspectives (1994)

The need for expert and unbiased participation in legal proceedings by physicians, industrial hygienists, toxicologists, environmental scientists, regulators, and similar professionals is hampered by lack of familiarity with the requirements of expert testimony and lack of opportunities for professional training in this activity. Drawing on material developed in a continuing education course offered by the University of Washington, we describe the role and process of being an expert witness and provide basic information regarding good professional practices pertaining to the testifying expert role.
Bile salt-induced gastric mucosal damage and histamine receptor antagonists.
Authors: H J Lewi, D C Carter
Journal: Gut (1983)

The effects of both an H1 receptor antagonist and an H2 receptor antagonist on changes in monovalent ion flux induced by topical sodium taurocholate were studied in antrectomised dogs fashioned with a denervated fundic pouch. The magnitude of taurocholate-induced ion flux was unaffected by topical administration of H1 or H2 receptor antagonists Parenteral administration of H1 or H2 receptor antagonist given singly or in combination produced an increase in net luminal Na+ gain before taurocholate administration but failed to reduce the magnitude of taurocholate-induced ion flux. It is concluded that histamine receptors are unlikely to have a role in the induction of mucosal injury by bile salts.
Therapeutic Hypothermia for Severe Traumatic Brain Injury
Authors: Patrick M. Kochanek
Journal: JAMA (2003)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Arginine restores cholinergic relaxation of hypercholesterolemic rabbit thoracic aorta.
Authors: J P Cooke, N A Andon, X J Girerd, A T Hirsch, M A Creager
Journal: Circulation (1991)

BACKGROUND Reduced synthesis of endothelium-derived relaxing factor (EDRF) may explain impaired endothelium-dependent vasodilation in hypercholesterolemia. Accordingly, we designed studies to determine if endothelium-dependent relaxation in hypercholesterolemic rabbits may be restored by supplying L-arginine, the precursor of EDRF. METHODS AND RESULTS Normal or hypercholesterolemic rabbits received intravenous L-arginine (10 mg/kg/min) or vehicle for 70 minutes. Subsequently, animals were killed, thoracic aortas were harvested, and vascular rings were studied in vitro. Rings were contracted by norepinephrine and relaxed by acetylcholine chloride or sodium nitroprusside. Vasorelaxation was quantified by determining the maximal response (expressed as percent relaxation of the contraction) and the ED50 (dose of drug inducing 50% relaxation; expressed as -log M). In vessels from hypercholesterolemic animals receiving vehicle, there was a fivefold rightward shift in sensitivity to acetylcholine compared with normal animals (p = 0.05, n = 5 in each group). In vessels from hypercholesterolemic animals, L-arginine augmented the maximal response to acetylcholine (83 +/- 16% versus 60 +/- 15%, p = 0.04 versus vehicle) and increased the sensitivity to acetylcholine (ED50 value: 6.7 +/- 0.2 versus 6.2 +/- 0.2, p less than 0.05 versus vehicle). Arginine did not affect maximal and EC50 responses to acetylcholine in vessels from normal animals. Arginine did not potentiate endothelium-independent responses in either group. CONCLUSIONS We conclude that the endothelium-dependent relaxation is normalized in hypercholesterolemic rabbit thoracic aorta by in vivo exposure to L-arginine, the precursor for EDRF.
Histological and immunocytological changes in psoriasis after 7 days of cyclosporin therapy
Authors: J.T. Headington, K.D. Cooper, C.N. Ellis, J. Voorhees
Journal: British Journal of Dermatology (1987)

In a double-blind trial, 21 patients were randomly assigned to receive oral cyclosporin or a vehicle control. Patients were treated for 4 weeks. Skin biopsies were taken before treatment and after 3 and 7 days. Epidermal thickness was measured by optical micrometer, and mitoses per high power field (HPF) were counted in lesional epidermis. Superficial perivascular mononuclear cell infiltrates, neutrophilic exudates and intraepidermal lymphocytosis were evaluated semi-quantitatively. Using single- and double-marker immunofluorescence techniques, the ratio of monoclonal antibody-defined leukocyte subsets to total leukocytes was also quantitatively determined. In patients receiving cyclosporin, epidermal thickness decreased by 32% compared with patients receiving only vehicle (P= 0·002). The average number of mitoses per HPF in lesional epidermis decreased by 71% by the end of 3 days of therapy. At 7 days, perivascular mononuclear cells decreased and the stratum corneum generally normalized. HLA-DR (Ia)-positive intraepidermal leukocytes found in psoriatic lesions before treatment or present in vehicle-treated lesions disappeared from the epidermis after 7 days of oral cyclosporin. Intradermal monocytes, T cells and activated T cells in the dermis decreased after 7 days of cyclosporin treatment in parallel with light microscopic findings. These findings suggest that psoriasis may have an immunological basis mediated by activated T cells and/or other immune cells.