tbuckley/cabot-search huggingface dataset:
Simulation studies of the electrocardiogram. II. Ischemia and infarction.
Authors: W T Miller, D B Geselowitz
Journal: Circulation Research (1978)

Experimental studies of the myocardial action potentials following coronary artery occlusion have shown that the resulting regional ischemia is reflected by characteristics changes in the shapes of the action potentials in the ischemic region. The principal changes are decreases in the magnitude of the resting potential and in the action potential duration. Action potentials with prolonged durations have been observed in the infarcted regions of experimental animals after the development of inverted T waves in the surface electrocardiogram (ECG). We use such abnormal action potentials in our digital computer model to study the effects of acute myocardial ischemia and infarction on the surface ECG. The heart is represented in sufficient detail to allow variations in the location and size of the ischemic injury and in the distribution of the severity of injury within the injured region. The evolution of acute infarctions is simulated by progressively modifying the abnormal action potentials assigned to the injured region. Calculated standard 12 lead ECGs and torso isopotential surface maps for simulated acute ischemia and infarction are in good agreement with patient data reported in the literature. Typical simulations include anterior and inferior transmural ischemia and infarction and anterior subendocardial ischemia. The model is used to examine relationships between torso surface potentials during ventricular activation and recovery and the site and size of the ischemic injury.
Remission in Goodpasture's syndrome: report of two patients treated by immunosuppression and review of the literature
Authors: A. Seaton, J. M. Meland, N. L. Lapp
Journal: Thorax (1971)

Two patients with Goodpasture9s syndrome are reported. One showed an apparently spontaneous remission and has survived in good health for over five years since the onset of his illness; he was treated for part of this time with steroids and chlorambucil. The second patient failed to respond to steroids but appeared to improve rapidly from a moribund state on administration of azathioprine; he remains well, although in mild renal failure, over a year later. The management of 35 other patients reported to have survived this illness is reviewed. It appears that both the renal and pulmonary features of Goodpasture9s syndrome may undergo spontaneous remission, and that the latter can sometimes be suppressed with steroid or immunosuppressant therapy. On four occasions the pulmonary manifestations of the disease have been arrested by nephrectomy.
Phase II Study of Etoposide and Cisplatin With Concurrent Twice-Daily Thoracic Radiotherapy Followed by Irinotecan and Cisplatin in Patients With Limited-Disease Small-Cell Lung Cancer: West Japan Thoracic Oncology Group 9902
Authors: Hiroshi Saito, Yoshiki Takada, Yukito Ichinose, Kenji Eguchi, Shinzoh Kudoh, Kaoru Matsui, Kazuhiko Nakagawa, Minoru Takada, Shunichi Negoro, Kenji Tamura, Masahiko Ando, Takuhito Tada, Masahiro Fukuoka
Journal: Journal of Clinical Oncology (2006)

We initially conducted a randomized phase II study to compare irinotecan and cisplatin (IP) versus irinotecan, cisplatin, and etoposide (IPE) after etoposide and cisplatin (EP) with concurrent twice-daily thoracic radiotherapy (TRT) in limited-disease small-cell lung cancer (LD-SCLC). We amended the protocol to evaluate IP after EP with concurrent twice-daily TRT in a single-arm phase II study because of an unacceptable toxicity in IPE.Previously untreated patients with LD-SCLC were treated intravenously with etoposide 100 mg/m2 on days 1 through 3 and cisplatin 80 mg/m2 on day 1 with concurrent twice-daily TRT (1.5 Gy per fraction, a total dose of 45 Gy) beginning on day 2 followed by three cycles of irinotecan 60 mg/m2 on days 1, 8, and 15 and cisplatin 60 mg/m2 on day 1 of a 4-week cycle.Of the 51 patients enrolled, 49 patients were assessable for response and toxicity. The overall response rate and complete response rate were 88% and 41%, respectively. The median survival time for all patients was 23 months. The 2-year and 3-year survival rates were 49% and 29.7%, respectively. The median progression-free survival was 11.8 months. The major toxicities observed were neutropenia (grade 4, 84%), febrile neutropenia (grade 3, 31%), infection (grade 3 to 4, 33%), electrolytes imbalance (grade 3 to 4, 20%), and diarrhea (grade 3 to 4, 14%).EP with concurrent twice-daily TRT followed by the consolidation of IP appears to be an active regimen which deserves further phase III testing in patients with LD-SCLC.
Utero-ovarian interaction in the regulation of reproductive function
Authors: H Alexander, G Zimmermann, G W Wolkersdörfer, C Biesold, M Lehmann, J Einenkel, G Pretzsch, D Baier
Journal: Human Reproduction Update (1998)

The physiological regulation of fertile reproductive cycle in mammals depends on interactions between hypothalamus-pituitary, ovarian and uterine stimuli. Over the past 20 years, much has been learned about the interrelation between the affluent and effluent lymph and vascular drainage in and around both ovarian and uterine tissues. An essential feature in the regulation of the fertile cycle is the functional status of the ovary, particularly the corpus luteum. During the time of implantation and the early pregnancy, an active corpus luteum is essential. As human chorionic gonadotrophin (HCG) is important in the maintenance of the corpus luteum, we investigated if it was produced by the cyclic endometrium. Immunohistochemical and in-situ hybridization reactions were performed but neither identified the presence of HCG during the proliferative phase. Positive staining and β-human chorionic gonadotrophin (β-HCG) mRNA were observed during the secretory phase in the glandular cells of the endometrium. The results were confirmed by Western blotting of secretory phase endometrium extracts and assessment of the functional secretory capacity of primary endometrial cultures. Polymerase chain reaction (PCR) investigations showed a positive result in the secretory phase. We postulate that, based on the very close morphological interrelation between the uterus and the ovary, the β-HCG of the endometrium is the primary factor for the maintenance of the corpus luteum and early pregnancy. Keywords:chorionic gonadotrophin β-subunit/cyclic endometrium/human/in-situ hybridization/utero-ovarian interaction
Association Between Brain Functional Failure and Dementia Severity in Alzheimer’s Disease: Resting Versus Stimulation PET Study
Authors: P Pietrini, M L Furey, G E Alexander, M J Mentis, A Dani, M Guazzelli, S I Rapoport, M B Schapiro
Journal: American Journal of Psychiatry (1999)

This study tested the hypothesis that regional cerebral glucose metabolism during neuronal activation is a more sensitive index of neuronal dysfunction and clinical severity in Alzheimer's disease than is glucose metabolism at rest.The subjects were 15 Alzheimer's disease patients with a wide range of Mattis Dementia Rating Scale scores (23-128). By using positron emission tomography, absolute glucose metabolism was measured in the parietal, occipital (visual areas), and temporal (auditory areas) cortical regions during rest (eyes/ears covered) and audiovisual stimulation.In the parietal cortex, glucose metabolism correlated with dementia severity in both conditions. In contrast, in the relatively preserved visual and auditory cortical regions, glucose metabolism predicted dementia severity during stimulation but not at rest.These findings suggest that regional cerebral glucose metabolism during stimulation is a more sensitive index of the functional/metabolic failure of neuronal systems than is metabolism at rest.
Efficacy and Safety of Ezetimibe Coadministered With Atorvastatin or Simvastatin in Patients With Homozygous Familial Hypercholesterolemia
Authors: Claude Gagné, Daniel Gaudet, Eric Bruckert
Journal: Circulation (2002)

Background — Patients with homozygous familial hypercholesterolemia (HoFH) have a high incidence of cardiovascular morbidity and mortality from premature atherosclerosis, and the efficacy of pharmacological therapy has been limited. We evaluated the efficacy, safety, and tolerability of ezetimibe, a novel cholesterol absorption inhibitor, in a multicenter, double-blind, randomized trial of HoFH patients receiving atorvastatin or simvastatin. Methods and Results — Fifty patients with a diagnosis of HoFH on the National Cholesterol Education Program Step 1 or stricter diet and taking open-label atorvastatin 40 mg/d or simvastatin 40 mg/d (statin-40) with (n=25) or without (n=25) concomitant LDL apheresis were randomized to 1 of 3 double-blind treatments: atorvastatin or simvastatin 80 mg/d (statin-80, n=17); ezetimibe 10 mg/d plus atorvastatin or simvastatin 40 mg/d (n=16); or ezetimibe 10 mg/d plus atorvastatin or simvastatin 80 mg/d (n=17) for 12 weeks. The primary end point was mean percentage change in LDL cholesterol (LDL-C) from statin-40 baseline to the end point for patients receiving statins alone (statin-80) versus patients receiving ezetimibe plus atorvastatin or simvastatin at either dose (ezetimibe plus statin-40/80). Ezetimibe plus statin-40/80 significantly reduced LDL-C levels compared with statin-80 (−20.7% versus −6.7%, P =0.007). In the high-dose statin cohorts, ezetimibe plus statin-80 reduced LDL-C by an additional 20.5% ( P =0.0001) versus statin-80. Similar significant reductions in LDL-C concentrations were observed for patients with genotype-confirmed HoFH (n=35). Ezetimibe was safe and well tolerated. Conclusions — Ezetimibe coadministered with atorvastatin or simvastatin in patients with HoFH produced clinically important LDL-C reductions compared with best current therapy. Ezetimibe provides a new, complementary pharmacological approach for this high-risk population.
Variable expression and treatment of PAPA syndrome
Authors: Meike A Schellevis, Monique Stoffels, Esther P A H Hoppenreijs, Evelien Bodar, Anna Simon, Jos W M van der Meer
Journal: Annals of the Rheumatic Diseases (2011)

Pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome is an autosomal dominant autoinflammatory syndrome caused by a missense mutation in the PSTPIP1 gene on the long arm of chromosome 15. So far only three families have been described.1,–,7

In this letter we would like to describe three members of a new family with PAPA syndrome with variable symptoms and the effects of different treatments, including successful treatment during pregnancy with the interleukin 1 (IL-1) receptor antagonist anakinra.

Case 1: A girl born in 1999. In 2002 she presented with an acute arthritis of the left ankle, accompanied by fever and an acute phase response (table 1). Septic arthritis was suspected, but blood and synovial fluid cultures remained negative. The symptoms persisted despite antibiotic treatment and diminished only gradually. After another episode of sterile arthritis, PAPA syndrome was suspected and genetically confirmed (c 688G>A (p.Ala 230 Thr) mutation in exon …
HLA-linked genetic control of the specicity of human cytotoxic T-cell responses to influenza virus.
Authors: S Shaw, W E Biddison
Journal: The Journal of Experimental Medicine (1979)

We have investigated elements of the genetic control of human in vitro cytotoxic T-cell responses to influenza virus-infected autologous cells by studies of a large family. The pattern of virus-immune cytotoxicity among siblings demonstrated T-cell recognition of influenza virus predominantly (greater than 90%) in association with determinants which are coded by genes linked to HLA (P less than 0.0002). Many family members consistently generated cytotoxic activity against influenza predominantly in association with antigens coded by genes of only one of their HLA haplotypes. Such haplotype preferences were consistent among HLA-identical siblings, indicating that the specificity of the T-cell response to influenza virus in association with HLA-A and -B antigens is controlled by genes linked to HLA.
Cigarette Smoke Induction of Osteopontin (SPP1) Mediates T <sub>H</sub> 17 Inflammation in Human and Experimental Emphysema
Authors: Ming Shan, Xiaoyi Yuan, Li-zhen Song, Luz Roberts, Nazanin Zarinkamar, Alexander Seryshev, Yiqun Zhang, Susan Hilsenbeck, Seon-Hee Chang, Chen Dong, David B. Corry, Farrah Kheradmand
Journal: Science Translational Medicine (2012)

The destruction of lung tissue in emphysema is orchestrated by antigen-presenting cells that have been activated by smoke.
THE PROBLEM OF RES IPSA LOQUITUR
Authors: C E WASMUTH
Journal: Annals of Internal Medicine (1960)

Editorial1 March 1960THE PROBLEM OF RES IPSA LOQUITURCARL E. WASMUTH, M.D., LL.B.CARL E. WASMUTH, M.D., LL.B.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-52-3-729 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA malpractice suit against a physician is a civil action based on allegations by the plaintiff that the physician was negligent in making the diagnosis or in prescribing or implementing the treatment. In our system of jurisprudence, in the United States, the plaintiff must prove by expert medical testimony that the defendant failed to exercise reasonable care or skill and therefore is liable for damages. Testimony of the expert witnesses, both of the plaintiff and of the defendant, is heard by the jury, which then reaches its verdict after weighing the medical opinions and other evidence.The requirement that medical... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Taken from an address presented at the Tennessee State Society of Anesthesiologists and the University of Tennessee Post-Graduate Medical Assembly, Memphis, Tennessee, October 17 and 18, 1959.From the Department of Anesthesiology, The Cleveland Clinic Foundation, and The Frank E. Bunts Educational Institute, Cleveland, Ohio. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1960Volume 52, Issue 3Page: 729-732KeywordsAnesthesiologyExercise ePublished: 1 December 2008 Issue Published: 1 March 1960 PDF downloadLoading ...
Late Toxicity Is Not Increased in <i>BRCA1/BRCA2</i> Mutation Carriers Undergoing Breast Radiotherapy in the United Kingdom
Authors: Susan Shanley, Kate McReynolds, Audrey Ardern-Jones, Roger Ahern, Indrajit Fernando, John Yarnold, Gareth Evans, Diana Eccles, Shirley Hodgson, Sue Ashley, Linda Ashcroft, Andrew Tutt, Elizabeth Bancroft, Susan Short, Gerald Gui, Lester Barr, Andrew Baildam, Anthony Howell, Gavin Royle, Lori Pierce, Douglas Easton, Rosalind Eeles
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To undertake the first substantial clinical study of breast radiotherapy toxicity in BRCA1 and BRCA2 mutation carriers in the United Kingdom. Experimental Design: Acute and late radiation effects were evaluated in a retrospective study of 55 BRCA1 and BRCA2 mutation carriers treated with radiotherapy for breast cancer at four centers between 1983 and 2002. Individual matching with controls who had sporadic breast cancer was undertaken for age at diagnosis, time since completion of radiation, and treatment variables. Detailed assessments were undertaken by one examiner. Median follow-up was 6.75 years for carriers and 7.75 years for controls. Rates of late events (rib fractures, lung fibrosis, necrosis of soft tissue/bone, and pericarditis) as well as LENT-SOMA scores and clinical photography scores of breast size, shape, and skin telangiectasia were the primary end points. Results: No increase in clinically significant late toxicity was seen in the mutation carriers. Conclusions: These data add substantial weight to the evidence that the outcomes in the treated breast from radiotherapy in women with BRCA1 or BRCA2 mutations are comparable with those in women with sporadic breast cancer.
G Protein–Coupled Receptors Revisited: Therapeutic Applications Inspired by Synthetic Biology
Authors: Boon Chin Heng, Dominique Aubel, Martin Fussenegger
Journal: The Annual Review of Pharmacology and Toxicology (2013)

G protein-coupled receptors (GPCRs) mediate the majority of cellular responses to hormones and neurotransmitters within the human body. They have much potential in the emerging field of synthetic biology, which is the rational, systematic design of biological systems with desired functionality. The responsiveness of GPCRs to a plethora of endogenous and exogenous ligands and stimuli make them ideal sensory receptor modules of synthetic gene networks. Such networks can activate target gene expression in response to a specific stimulus. Additionally, because GPCRs are important pharmacological targets of various human diseases, genes encoding their protein/peptide ligands can also be incorporated as target genes of the response output elements of synthetic gene networks. This review aims to critically examine the potential role of GPCRs in constructing therapeutic synthetic gene networks and to discuss various challenges in utilizing GPCRs for synthetic biology applications.
Hepatitis B Virus X Protein Transactivates the Inducible Nitric Oxide Synthase Promoter
Authors: Maria José Amaro, Javier Bartolomé, Vicente Carreño
Journal: Hepatology (1999)

The capability of hepatitis B virus (HBV) to increase the transcription of the human hepatic inducible nitric oxide synthase (iNOS) by transactivating its promoter has been studied. We have observed by reverse–transcription polymerase chain reaction (RT–PCR) that although the mRNA for the iNOS was almost undetectable in the human hepatoblastoma cell line, HepG2, it was constitutively expressed in the 2.2.15 cell line (a derivative of the HepG2 that produces complete HBV particles). Transfection of HepG2 and 2.2.15 cells with the p1iNOS–CAT plasmid (containing a 1.1–kb fragment of the iNOS promoter) resulted in an increase in chloramphenicol acetyl transferase (CAT) activity in 2.2.15 cells. Similar results were observed when HepG2 and Chang liver cell lines were cotransfected with the p1iNOS–CAT plasmid and the complete HBV genome. It was shown that pX was responsible for the transactivation by cotransfection of HepG2 cells with the p1iNOS–CAT and plasmids expressing the HBV–encoded pX protein, core antigen, and e antigen. Cotransfection of HepG2 cells with the pX expression plasmids and a series of deletion mutants of the 1.1–kb iNOS promoter fragments established that transactivation by pX depends on the presence of at least one nuclear factor–κB (NF–κB) binding site. This was further confirmed by cotransfecting cells with a plasmid expressing the NF–κB inhibitor, IκB.
SNP Genotyping Identifies New Signatures of Selection in a Deep Sample of West African Plasmodium falciparum Malaria Parasites
Authors: Alfred Amambua-Ngwa, Daniel J. Park, Sarah K. Volkman, Kayla G. Barnes, Amy K. Bei, Amanda K. Lukens, Papa Sene, Daria Van Tyne, Daouda Ndiaye, Dyann F. Wirth, David J. Conway, Daniel E. Neafsey, Stephen F. Schaffner
Journal: Molecular Biology and Evolution (2012)

We used a high-density single-nucleotide polymorphism array to genotype 75 Plasmodium falciparum isolates recently collected from Senegal and The Gambia to search for signals of selection in this malaria endemic region. We found little geographic or temporal stratification of the genetic diversity among the sampled parasites. Through application of the iHS and REHH haplotype-based tests for positive selection, we found evidence of recent selective sweeps at a known drug resistance locus, at several known antigenic loci, and at several genomic regions not previously identified as sites of recent selection. We discuss the value of deep population-specific genomic analyses for identifying selection signals within sampled endemic populations of parasites, which may correspond to local selection pressures such as distinctive therapeutic regimes or mosquito vectors.
<i>BRCA1</i> and <i>BRCA2</i> Mutation Prevalence and Clinical Characteristics of a Population-Based Series of Ovarian Cancer Cases from Denmark
Authors: Marie Soegaard, Susanne Kruger Kjaer, Mark Cox, Eva Wozniak, Estrid Høgdall, Claus Høgdall, Jan Blaakaer, Ian J. Jacobs, Simon A. Gayther, Susan J. Ramus
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To evaluate the prevalence of BRCA1 and BRCA2 mutations and associations with clinical correlates of disease in a population-based series of ovarian cancer cases from Denmark. Methods: DNA sequencing and multiplex ligation-dependent probe amplification analysis were used to analyze the BRCA1 and BRCA2 genes for coding sequence mutations and large genomic rearrangements in 445 confirmed cases of ovarian cancer. We evaluated associations between mutation status and clinical characteristics, including cancer risks for first-degree relatives and clinicopathologic features of tumors. Results: Deleterious BRCA1 or BRCA2 mutations were identified in 26 cases; thus, mutations in these genes are responsible for at least 5.8% of ovarian cancer cases in this population. Five different mutations were identified in more than one individual, suggesting that they may be founder mutations in Denmark. We identified several differences between mutation carriers and noncarriers: mutation carriers were diagnosed at a significantly early age (median, 49 and 61 years, respectively; P = 0.0001); the frequency of BRCA1 mutation carriers was 23% for women diagnosed &amp;lt;40 years, 15% for 40 to 49 years, 4% for 50 to 59 years, and 2% for ≥60 years (P = 0.00002); ovarian cancer in carriers was diagnosed at a later stage (P = 0.002) and tumors were of poorer grade (P = 0.0001); and first-degree relatives of mutation carriers had greater relative risks of both ovarian cancer [10.6 (95% confidence interval, 4.2-26.6); P &amp;lt; 0.0001] and breast cancer &amp;lt;60 years [8.7 (95% confidence interval, 3.0-25.0); P &amp;lt; 0.0001]. Conclusion: These data may have a significant effect on risk assessment and clinical management of individuals from Denmark who are predisposed to ovarian cancer because they carry a BRCA1 or BRCA2 mutation.
‘Tomudex’ (ZD1694) : A novel thymidylate synthase inhibitor with clinical antitumour activity in a range of solid tumours
Authors: D Cunningham, J Zalcberg, I Smith, M Gore, R Pazdur, H Burris, N J Meropol, G Kennealey, L Seymour
Journal: Annals of Oncology (1996)