tbuckley/cabot-search huggingface dataset:
Myocardial biochemical, contractile, and electrical performance after imposition of hypertension in young and old rats.
Authors: J M Capasso, A Malhotra, J Scheuer, E H Sonnenblick
Journal: Circulation Research (1986)

The effects of renovascular hypertension on the biochemical, contractile, and electrical performance of myocardial tissue from rats of various ages has been examined. Male Fischer rats, 2, 7, 12, and 17 months old, were made hypertensive by constriction of the left renal artery. Ten weeks after the onset of hypertension, left ventricular papillary muscles were isolated from those four groups when 5, 10, 15, and 20 months old, respectively. Mechanical performance and transmembrane electrical events were recorded simultaneously. Contractile protein enzyme activity was determined in the same hearts from which papillary muscles were used for acquisition of mechanical and electrical information. There was a slight increase in blood pressure in control groups as a function of age while blood pressure maintained a range of approximately 179-188 mm Hg for all hypertensive groups. Heart weight of control animals increased significantly from 5 months to 20 months of age from 539 +/- 26 to 1088 +/- 56 mg, representing an increase of 101%. In hypertensive animals, heart weight increased 50% in 5-month-, 15% in 10-month-, 50% in 15-month-, and 11.7% in 20-month-old animals. Although control groups revealed alterations in mechanical, electrical, and biochemical parameters that increased as a function of age, the magnitude of the biochemical, contractile, and electrical response to hypertension varied monotonically with the extent of myocardial hypertrophy, rather than age per se. Adaptation to the stress of hypertension was observed in each age group, and was revealed as prolongation of mechanical and electrical timing parameters, depression of the load-velocity relation, and contractile protein enzyme activity. Thus, the stress of hypertension, which was tolerated by the 10- and 20-month-old animals with lesser relative hypertrophy and lesser changes in measured parameters, may represent a differential adaptation to the stress of hypertension.
Amoxapine and Neurologic Deficits
Authors: Ken Kulig, Barry H. Rumack, John A. Marx
Journal: Annals of Internal Medicine (1982)

Letters and Corrections1 August 1982Amoxapine and Neurologic DeficitsKEN KULIG, M.D., BARRY H. RUMACK, M.D., JOHN A. MARX, M.D.KEN KULIG, M.D.Search for more papers by this author, BARRY H. RUMACK, M.D.Search for more papers by this author, JOHN A. MARX, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-97-2-286_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In the cases reported by Goldberg and Spector (1), the development of permanent neurologic deficits in two patients was attributed to the toxic effects of amoxapine. We question this conclusion, and feel that a more reasonable cause for the neurologic sequellae was cerebral anoxia or severe metabolic acidosis.Both patients presented with coma, multiple seizures, and metabolic acidosis after large overdoses of amoxapine. The neurologic damage in these two patients may have had several responsible mechanisms. Central nervous system morbidity and mortality are not uncommon after status epilepticus and are felt to reflect the duration of the...References1. GOLDBERGSPECTOR MR. Amoxapine overdose: report of two patients with severe neurologic damage. Ann Intern Med. 1982;96:463-4. LinkGoogle Scholar2. AMINOFFSIMON MR. Status epilepticus: causes, clinical features and consequences in 98 patients. Am J Med. 1980;69:657-66. CrossrefMedlineGoogle Scholar3. MELDRUMHORTON BR. Physiology of status epilepticus in primates. Arch Neurol. 1973;28:1-9. CrossrefMedlineGoogle Scholar4. POSNERPLUM JF. Spinal-fluid pH and neurologic symptoms in systemic acidosis. N Engl J Med. 1967;277:605-13. CrossrefMedlineGoogle Scholar5. MATTARWEILSHUBINSTEIN JMHL. Cardiac arrest in the critically ill. II. Hyperosmolal states following cardiac arrest. Am J Med. 1974;56:162-8. CrossrefMedlineGoogle Scholar6. BROWNETSUANGPERRY JMP. Amoxapine neurotoxicity: a case report with long term follow-up. Drug Int Clin Pharm. 1982;16:404. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: KEN KULIG, M.D.; BARRY H. RUMACK, M.D.; JOHN A. MARX, M.D.Affiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1982Volume 97, Issue 2Page: 286-286KeywordsAcidosisCentral nervous systemComaEpileptic seizuresMorbidityMortalityStatus epilepticus ePublished: 1 December 2008 Issue Published: 1 August 1982 PDF downloadLoading ...
S55 Pulmonary fibrosis with and without co-existing connective tissue disease: does it affect survival?
Authors: V. Navaratnam, N. Ali, C. Smith, A. Fogarty, R. B. Hubbard
Journal: Thorax (2010)

<h3>Introduction</h3> The impact of co-existing connective tissue disease on the survival of patients with pulmonary fibrosis remains unclear, since studies into the subject have so far yielded varying results. This study compares the survival of individuals with idiopathic pulmonary fibrosis (IPF) to those with connective tissue disease associated pulmonary fibrosis (CTD-PF) using data from The Health Improvement Network (THIN), a large general practice database in the UK. <h3>Methods</h3> Incident cases of individuals with IPF and CTD-PF between the years 2000 and 2008 were identified. Survival analysis was performed on this dataset using Kaplan–Meier methods and Cox regression was used to compare mortality rates between patients with IPF and CTD-PF, adjusting for age and gender. <h3>Results</h3> During the study period, there were 2208 incident cases of IPF, who were predominantly male (64%) and had a mean age at time of diagnosis of 73.9 years (95% CI 73.5 to 74.4 years). In comparison there were 318 incident cases of CTD-PF, of which the majority were female (56%) and the mean age at time of diagnosis was 67.8 years (95% CI 66.6 to 68.9). The commonest connective tissue disease associated with pulmonary fibrosis was rheumatoid arthritis (211 cases), followed by systemic sclerosis (39 cases). The mean follow-up period after diagnosis for our cohort was 2.4 person years and during this period 1117 (51%) patients with IPF and 116 (36%) patients with CTD-PF had died. The mortality rates for patients with IPF and CTD-PF were 221 (95% CI 208 to 234) and 121 (95% CI 101 to 146) deaths per 1000 person years respectively. The median survival for patients with CTD-PF was significantly higher at 6.5 years compared to 3.2 years in patients with IPF (p=0.0033) (See Abstract S55 Figure 1). After adjusting for age and gender, patients with IPF had a worse prognosis compared to those with CTD-PF (HR 1.32, 95% CI 1.08 to 1.60). <h3>Conclusion</h3> Individuals who have CTD-PF have a better prognosis after diagnosis when compared to those with IPF. This may relate to the differing natural histories of the diseases and needs further investigation.
A Physician's Guide to Adoption
Authors: Andrew M. Kaunitz
Journal: JAMA (1987)

The growing number of couples seeking to adopt may have outstripped the number of babies in the United States available for adoption. Although increased availability and use of abortion have resulted in fewer single women continuing their pregnancies, the increased tendency of unmarried mothers to raise rather than relinquish their children has, in particular, limited the number of babies available for adoption. Despite the unpopularity of adoption among women with unintended pregnancies, addressing this option remains an important part of pregnancy counseling. Appropriate obstetric care of women placing their babies for adoption includes acknowledgment of the loss these women experience. Knowledge of adoption resources and willingness to discuss adoption can help physicians provide better care of unintentionally pregnant as well as infertile patients.
SCHISTOSOMA HÆMATOBIUM IN THE CANAL ZONE.
Authors: M. EARLE HIGGINS
Journal: JAMA (1906)

The following cases of infection, with the blood fluke,<i>Schistosoma h</i>æmatobium (bilharzia), occurring in routine stool examinations, would indicate that this parasite is not an uncommon one in the Canal Zone, particularly among the negro laborers from Martinique: <h3>Case 1.</h3> —Martinique negro; male. On Isthmus one month (Culebra). Admitted Dec. 2, 1905, with lobar pneumonia. Stool: Ova of bilharzia and uncinaria. Blood: On admission this was negative for malaria; nine days after crisis leucocytes were 9,500; hemoglobin, 40 per cent. Urine: During the height of fever there was a slight trace of albumin, with a few hyaline and granular casts. Albumin and casts disappeared before discharge. Sedimented specimens showed no blood or ova. There were no bladder symptoms. <h3>Case 2.</h3> —Martinique negro; male. On Isthmus one and one-half months (Panama). Admitted Dec. 10, 1905, with malaria and bronchitis. Stool: Ova of bilharzia and uncinaria;<i>Tricomonas intestinalis.</i> Urine: Negative; sedimented
Carcinogenesis studies in rodents for evaluating risks associated with chemical carcinogens in aquatic food animals.
Authors: J Huff, J Bucher, R Yang
Journal: Environmental Health Perspectives (1991)

Fish and shellfish caught in polluted waters contain potentially dangerous amounts of toxic and carcinogenic chemicals. Public concern was heightened when a large percentage of winter flounder taken from Boston Harbor was found to have visible cancer of the liver; winter flounder outside the estuary area had no liver lesions. Long-term chemical carcinogenesis studies could be easily and feasibly designed using laboratory rodents offered diets containing fish caught in polluted waters. Induced cancers in rodents would corroborate field observations in fish; positive results from these studies would provide further evidence about potential human health hazards from eating substantial amounts of chemically contaminated fish. Nonetheless, fish and aquatic organisms should be viewed as environmental biological monitors of pollution or of potential human health hazards, and authorities responsible for assuring clean and safe rivers, bodies of water, and biota should give more attention to these valid biological indicators or sentinels of environmental pollution. Consequently, fish and other sea creatures alone should serve as alarms regarding whether water areas constitute public health hazards.
Phase I/II and Pharmacodynamic Study of Dovitinib (TKI258), an Inhibitor of Fibroblast Growth Factor Receptors and VEGF Receptors, in Patients with Advanced Melanoma
Authors: Kevin B. Kim, Jason Chesney, Douglas Robinson, Humphrey Gardner, Michael M. Shi, John M. Kirkwood
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Dovitinib (TKI258) is an orally available inhibitor of fibroblast growth factor (FGF), VEGF, and platelet-derived growth factor receptors. This phase I/II dose–escalation study was conducted to evaluate the safety, pharmacodynamics, and preliminary efficacy of dovitinib in the treatment of advanced melanoma. Experimental Design: Patients with advanced melanoma resistant or refractory to standard therapies or for whom no standard therapy was available were enrolled. Dovitinib was administered at doses ranging from 200 to 500 mg/d. Results: Forty-seven patients were enrolled. The most frequently reported adverse events were fatigue (77%; grade ≥3, 28%), diarrhea (77%; grade ≥3, 11%), and nausea (77%; grade ≥3, 9%). Six dose-limiting toxicities were observed in the 400-mg and 500-mg dose cohorts, which consisted of grade 3 nausea, fatigue, and diarrhea and grade 4 fatigue events. The maximum tolerated dose was 400 mg/d. The best tumor response was stable disease, which was observed in 12 patients. Increases in plasma FGF23, VEGF, and placental growth factor and decreases in soluble VEGF receptor 2 were noted during the first cycle of treatment, consistent with FGF receptor (FGFR) and VEGF receptor (VEGFR) inhibition. Dynamic contrast-enhanced MRI analysis showed a dose-dependent decrease in tumor blood flow and vascular permeability with dovitinib therapy. A decrease in FGFR phosphorylation was observed in paired tumor biopsy samples from a patient treated with dovitinib at a dose of 400 mg/d. Conclusions: At a dose of 400 mg/d, dovitinib showed an acceptable safety profile and limited clinical benefit and inhibited FGFR and VEGFR. Clin Cancer Res; 17(23); 7451–61. ©2011 AACR.
Histomorphometric and Biochemical Correlates of Arterial Procollagen Gene Expression During Vascular Repair After Experimental Angioplasty
Authors: M. Asad Karim, D. Douglas Miller, Melody A. Farrar, Elias Eleftheriades, Bouyella H. Reddy, Clyniece M. Breland, Allen M. Samarel
Journal: Circulation (1995)

Background To determine the transcriptional, biochemical, and histomorphometric correlates of neointimal procollagen accumulation during arterial repair after balloon angioplasty of atherogenic vessels, rabbit iliac artery collagen content and the induction of α 1 (I) and α 1 (III) procollagen mRNA were assessed in normal vessels and at 2, 7, and 30 days after angioplasty. Methods and Results Quantitative iliac artery histomorphometric neointimal collagen analysis was performed using a specific picrosirius red stain under polarized light. Arterial cross-sectional area reduction, total cellularity, and vascular smooth muscle cell density (per 10 4 μ 2 of neointima) were quantified in routine and immunohistochemically stained sections (α-actin and RAM-11), from which biochemical concentrations of tissue protein, RNA, and DNA were also measured. Collagen comprised 0.23±0.1 mg/mg of total protein in the normal vessel wall and did not increase in vessels studied 2 and 7 days after angioplasty (0.26±0.06, 0.28±0.05 mg/mg of protein, P =NS). By 30 days after angioplasty, &gt;50% of the protein concentration was collagen (0.55±0.11 mg/mg of protein, P =.02). Collagen-positive histological staining also increased significantly from 17±2% of the neointima at day 2 to 32±5% by day 30 ( P =.01). The transcript regulatory signal for α 1 (I) procollagen mRNA was induced 2 days after angioplasty, peaking at 7 days for both α 1 (I) and α 1 (III), and returning to control levels 30 days after angioplasty. A significant luminal cross-sectional area reduction of the arterial wall was confirmed both by angiography and histomorphometry ( P =.01). This was not associated with a significant change in α-actin (+) vascular smooth muscle cell density (38±7 nuclei per 10 4 μ 2 at day 2 and at day 30) or tissue DNA concentration ( P =NS). Conclusions We conclude that procollagen genes are transcriptionally activated early (2 to 7 days) after angioplasty vessel injury and that collagen subsequently constitutes a major biochemical and histological component of the proliferative neointima by 30 days after angioplasty. Alterations in pathways regulating procollagen metabolism may also contribute to the accumulation of extracellular matrix and growth of the neointima in the late repair phase after vessel wall injury.
Distinct roles of L-selectin and integrins α4β7 and LFA-1 in lymphocyte homing to Peyer's patch-HEV in situ: The multistep model confirmed and refined
Authors: Robert F. Bargatze, Mark A. Jutila, Eugene C. Butcher
Journal: Immunity (1995)

Circulating lymphocytes home to the mucosal lymphoid organs, Peyer's patches (PP), through high endothelial venules (HEV). In situ analyses revealed that transfused lymph node cells (LNCs) interact with PP-HEV in a series of overlapping adhesion events: L-selectin (CD62L) > alpha 4 beta 7 initiates interaction, L-selectin and alpha 4 beta 7 both participate in rolling, and G alpha i-linked activation triggers arrest that requires both alpha 4 beta 7 and LFA-1. alpha 4 beta 7 dramatically reduces rolling velocity, and appears to be required for engagement of LFA-1. In contrast with resting LNC, preactivated LNC or alpha 4 beta 7hi lymphoma cells require only alpha 4 beta 7 for arrest in PP-HEV. The predominant PP-HEV ligand for alpha 4 beta 7 but also apparently for L-selectin is the mucosal addressin MAd-CAM-1. These results validate the concept of multimolecular adhesion/decision cascades in physiologic lymphocyte-endothelial recognition, define a novel role for alpha 4 integrins as a "bridge" between selectin and beta 2 integrin-dependent events, and reemphasize the potential for direct adhesion through preactivated alpha 4 integrins alone.
Breast cancer screening is to be reviewed, cancer tsar announces
Authors: N. Hawkes
Journal: BMJ (2011)

The leaflet sent to women in England who are called for breast cancer screening is to be rewritten for the second time, and the effectiveness of screening is to be reviewed by an independent panel, as the Department of Health moves to resolve growing doubts over the programme.

The undertakings are announced today in the BMJ by the national cancer director, Mike Richards ( BMJ 2011;343:d6843, doi:10.1136/bmj.d6894). Although he backs the advice of the Advisory Committee on Breast Cancer Screening that the programme saves lives and does more good than harm, he says that he will have no hesitation in putting a contrary view before ministers if the review should reach a different conclusion.

He has also promised a new approach …
RELATIONS OF DISEASE, CRIME AND VICE.
Authors: W. O. HENRY
Journal: JAMA (1895)

I would define these terms by saying that disease is the violation of any physiologic law or any abnormal activity in living tissue. Crime is the violation of any human law, or any abnormal activity in the civil world. Vice is the violation of any moral law, or any abnormal activity in the moral world. We have to-day in the United States more than one hundred thousand tramps who find it easier to get a living by begging from door to door than by labor, and hence take to this sort of life. There are more than five hundred thousand criminals in this land to-day and only one-fifth of them are behind the bars. It is estimated that two women out of every one hundred in this country are fallen women. The percentage of divorces to marriages is alarmingly great so that in some States there is one divorce granted
Successful External Cardiac Resuscitation in Myocardial Infarction
Authors: Louis Gillespie
Journal: JAMA (1963)

IT HAS BEEN estimated that 10% of the patients sustaining acute myocardial infarction will develop sudden cessation of the circulation due to asystole or ventricular fibrillation.<sup>1</sup>The incidence of this complication is far greater when myocardial infarction occurs in the younger age group.<sup>2</sup>Thoracotomy and internal cardiac massage has been, until recently, the only method available for resuscitation of the circulation. This procedure has been rewarding on many occasions when cardiac arrest has occurred during surgery, but attempts to apply this technique to the cardiac arrest of acute myocardial infarction have met with much less success. Since 1947, when Beck and others first applied openchest resuscitation and defibrillation to the human heart,<sup>3</sup>only nine cases of successful cardiac resuscitation in myocardial infarction by this method have been reported.<sup>4</sup>The paucity of good results may be ascribed to the less adaptable environment of the medical ward, the
Workshop on human health impacts of halogenated biphenyls and related compounds.
Authors: M A Kamrin, L J Fischer
Journal: Environmental Health Perspectives (1991)

A workshop on the Human Health Impacts of Halogenated Biphenyls and Related Compounds was held to assess the state of current research on these chemicals and to make recommendations for future studies. Participants discussed results from laboratory animal experiments on PCBs, PBBs, dioxins, and dibenzofurans which demonstrate a common mode of toxicological action while also revealing large variations in toxicological potency both within and between these chemical families. These variations demonstrate the importance of congener-specific analyses in future studies of effects of exposure to these compounds. Results from epidemiological studies of environmentally exposed adult and pediatric populations from the U.S., Japan, and Taiwan and occupationally exposed cohorts from around the world were considered. It was concluded that available evidence did not demonstrate serious adverse effects such as cancer, in exposed adult cohorts but did provide indications of possible neurobehavioral effects in children exposed in utero. In addition, workshop participants described newly developed markers of exposure and techniques for assessing endocrinological, immunological, and neurological effects and suggested these be applied to epidemiological studies of the effects of polyhalogenated compounds. Other recommendations included identification of other cohorts and development of a large registry of exposed individuals; performance of detailed studies of reproductive function and outcomes in exposed populations; and follow up of neurobehavioral effects in offspring of exposed women.
Chenotherapy for Gallstone Dissolution
Authors: Johnson L. Thistle
Journal: JAMA (1978)

Clinical experience with chenodeoxycholic acid therapy for dissolving gallstones is reported, with particular attention to determinants of response. Of 12 patients receiving 15 mg/kg/day or more, ten responded (83%); only 15 of 40 patients (38%) receiving less than 15 mg/kg/day responded. Large solitary stones and stones in gallbladders that visualized poorly after oral cholecystography had a lower response rate. Radiopaque stones did not respond in 18 patients. Five of ten patients with stones in the common bile duct responded. Small, dose-related elevations in SGOT were the only biochemical abnormality observed. Liver biopsy specimens showed no notable abnormality. Diarrhea was an infrequent problem. Stones recurred in three of 15 patients during six to 48 months of observation without treatment. Chenodeoxycholic acid, when given in adequate dosage, continues to appear promising as medical therapy for asymptomatic radiolucent gallstones in radiologically visualizing gallbladders. (<i>JAMA</i>239:1041-1046, 1978)
Production of Chronic Atrioventricular Block in Dogs Without Thoracotomy
Authors: M. Turina, I. Babotai, W. Wegmann
Journal: Cardiovascular Research (1968)

Total heart block was produced in dogs without thoracotomy by means of a formaldehyde injection into the bundle of His. The method was successful in 22 out of 24 experiments. It is a useful model for haemodynamic studies in the intact animal.
Abstract IA4-1: Gene-based trial matching
Authors: Timothy J. Yeatman
Journal: Clinical Cancer Research (2010)

Abstract In 2006, the Moffitt Cancer Center initiated an ambitious initiative in personalized medicine called Total Cancer Care. One goal of the project was to develop a protocol and informed consent, a biorepository and a clinical and molecular database that would support the next generation of clinical trials. To date, the single protocol has accrued more than 57,000 patients and over 17,000 tumor samples, of which more than 12,000 have been molecularly profiled on a global gene expression microarray. Sequencing analyses now suggest there are a finite number (~12) of cancer pathways activated by specific driver genes. Emerging data suggest gene expression profiles may provide more inclusive portraits of pathway activation than simple canonical gene mutation analysis. The resultant clinical and molecular database we are developing holds promise for developing new trial approaches that may be faster, require fewer patients, and may increase response rates by finding the right patients for the right trials through gene based trial matching. New approaches to trial development and design that leverage a database, and the associated technical and regulatory challenges, will be discussed. Citation Information: Clin Cancer Res 2010;16(14 Suppl):IA4-1.