tbuckley/cabot-search huggingface dataset:
Inhibition of Angiotensin-Converting Enzyme in Renal-Transplant Recipients with Hypertension
Authors: John J. Curtis, Robert G. Luke, John D. Whelchel, Arnold G. Diethelm, Patricia Jones, Harriet P. Dustan
Journal: New England Journal of Medicine (1983)

HYPERTENSION has a high prevalence among recipients of renal allografts.1 , 2 Such post-transplantation hypertension may contribute3 , 4 to the high mortality from atherosclerotic vascular disease observed in this relatively young population.5 , 6 Although the cause of persistent post-transplantation hypertension is not well understood, it is believed to be multifactorial in nature,7 , 8 and several investigators have suggested that the renin–angiotensin system plays an important part.9 , 10 Captopril, an oral angiotensin-converting-enzyme inhibitor, has been reported to be an especially effective agent for hypertensive states mediated by the renin–angiotensin system.11 , 12 In cases in which the renin–angiotensin system is important in post-transplantation hypertension, captopril should be an ideal . . .
Epinephrine-induced reversal of verapamil's electrophysiologic and therapeutic effects in patients with paroxysmal supraventricular tachycardia.
Authors: F Morady, W H Kou, A H Kadish, L K Toivonen, J A Kushner, S Schmaltz
Journal: Circulation (1989)

The purpose of our study was to determine whether an infusion of epinephrine reverses the electrophysiologic effects of verapamil and whether reversal of verapamil's effects on the induction of paroxysmal supraventricular tachycardia (PSVT) by epinephrine during electropharmacologic testing is predictive of stress-related recurrences of PSVT during long-term treatment with verapamil. The infusion rates of epinephrine used in this study were 25 and 50 ng/kg/min, which previously have been demonstrated to result in plasma epinephrine concentrations in the range that occurs during a variety of stresses in humans. The subjects of this study were 17 patients with recurrent PSVT who underwent an electrophysiologic study in the control state and after at least 2 days of treatment with 240-480 mg/day verapamil. After assessing the response to verapamil, epinephrine was infused and testing was repeated. Verapamil significantly slowed atrioventricular conduction and prolonged refractoriness in the atrium and atrioventricular node. The effects of the two infusion rates of epinephrine were generally similar in magnitude and, therefore, the results were pooled. Epinephrine partially or completely reversed all of verapamil's electrophysiologic effects. Verapamil suppressed the induction of sustained PSVT in 15 patients. Epinephrine facilitated the induction of PSVT in seven of these 15 patients. All 15 patients were treated on a long-term basis with verapamil. The eight patients in whom epinephrine did not facilitate the induction of PSVT had no recurrences of PSVT during 9-18 months of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)
Physiological anticoagulation. Resistance to activated protein C and venous thromboembolism.
Authors: B Dahlbäck
Journal: Journal of Clinical Investigation (1994)

Venous thromboembolism is a serious, potentially lethal health problem affecting 1 per 1,000 people annually (1-3).Major surgery, fractures, complicated pregnancy, the use of oral con- traceptives, and immobilization increase the risk of thrombosis.In addition, thrombosis is often familial, suggesting that genetic risk factors are involved (3)(4)(5)(6).Until recently, the major genetic defects known to predispose for thrombosis were deficiencies of antithrombin III, protein C, and protein S. Together these did not account for more than 5-10% of the cases (3-5, 7).In the last year, hereditary activated protein C (APC)' resistance, has been identified as a basis for a majority of cases of familial thrombosis (8-13).In contrast to other genetic de- fects associated with thrombosis, APC resistance is highly prev- alent in the general population (8, 10).It afflicts affected individuals with a life-long increased risk of thrombosis.APC resistance, its molecular basis, and a short description of the protein C anticoagulant system will be presented. Balance between pro-and anticoagulant forcesA number of plasma proteins function in harmony with cellular components to provide efficient and localized hemostasis (14, 15).Proteolytic events arranged in a cascade fashion lead to the explosive, but yet controlled formation of thrombin.Thrombin generated at sites of vascular injury activates factors V and VII (to Va and Villa) in a positive feedback reaction, activates and aggregates platelets and converts fibrinogen into insoluble fibrin (Fig. 1).Factors Va and Villa bind to negatively charged phos- pholipids exposed on activated platelets and serve as receptor sites for the proteolytic enzymes, factors IXa and Xa, respec- tively ( 15, 16).In contrast, at sites of intact vasculature, binding of thrombin to the endothelial membrane protein thrombo- modulin converts thrombin from a procoagulant into an antico- agulant protease, which activates protein C ( 17-19).APC inactivates the membrane bound factors Va and VIIIa by limited proteolysis in a reaction which is potentiated by a cofactor protein designated protein S. APC is highly specific in its action.It cleaves and inactivates cell surface bound factors Va and VIlla, but has no effect on circulating factors V and VI.Pro- and anticoagulant mechanisms are under physiological condi-
Modulation of cholinergic neural bronchoconstriction by endogenous nitric oxide and vasoactive intestinal peptide in human airways in vitro.
Authors: J K Ward, M G Belvisi, A J Fox, M Miura, S Tadjkarimi, M H Yacoub, P J Barnes
Journal: Journal of Clinical Investigation (1993)

Human airway smooth muscle possesses an inhibitory nonadrenergic noncholinergic neural bronchodilator response mediated by nitric oxide (NO). In guinea pig trachea both endogenous NO and vasoactive intestinal peptide (VIP) modulate cholinergic neural contractile responses. To identify whether endogenous NO or VIP can modulate cholinergic contractile responses in human airways in vitro, we studied the effects of specific NO synthase inhibitors and the peptidase alpha-chymotrypsin on contractile responses evoked by electrical field stimulation (EFS) at three airway levels. Endogenous NO, but not VIP, was shown to inhibit cholinergic contractile responses at all airway levels but this inhibition was predominantly in trachea and main bronchus and less marked in segmental and subsegmental bronchi. To elucidate the mechanism of this modulation we then studied the effects of endogenous NO on acetylcholine (ACh) release evoked by EFS from tracheal smooth muscle strips. We confirmed that release was neural in origin, frequency dependent, and that endogenous NO did not affect ACh release. These findings show that endogenous NO, but not VIP, evoked by EFS can inhibit cholinergic neural responses via functional antagonism of ACh at the airway smooth muscle and that the contribution of this modulation is less marked in lower airways.
The Autonomic Nervous System: An Introduction to Basic and Clinical Concept
Authors: Robert E. McMasters
Journal: JAMA (1971)

For many years a readable and clinically applicable text on the autonomic nervous system has been lacking from the neurologic armamentarium, and this book appears to have met this need. Although designed for the student and practitioner, this monograph will assuredly meet the needs of many neurologists and neurosurgeons, as well as endocrinologists, for it contains succinct and well annotated discussions of almost every clinical problem concerning an area which, in the past decade or two, has become vast and difficult to assimilate for all but the most devoted students. An historical introduction and a brief review of anatomy and histology precede 12 chapters concerned with individualized clinical entities. Physiologic, pharmacologic, and biochemical concepts are considered in each of the chapters as related to the central clinical theme. Classical methodology which describes function as either sympathetic or parasympathetic is not incorporated for it is not particularly applicable to central functions;
Letter by Brook et al Regarding Article “Diesel Exhaust Inhalation Causes Vascular Dysfunction and Impaired Endogenous Fibrinolysis”
Authors: Robert D. Brook, Marie S. O’Neill, Sanjay Rajagopalan
Journal: Circulation (2006)

We read with interest the results of the article by Mills et al 1 demonstrating an acute impairment in microvascular endothelial function after the controlled inhalation of diesel exhaust particles by healthy men.As discussed, their observations complement our findings regarding exposure to both concentrated 2 and ambient levels 3 of particulate matter.The sum of evidence thus suggests that the acute triggering of systemic vascular dysfunction is likely a central mechanism linking air pollution to increased short-term cardiovascular risk.However, we believe that an important observation in the study by Mills et al 1 was not adequately addressed.When blood pressure was measured in the 15 subjects 2 hours after exposure, they observed a very pronounced, although marginally statistically nonsignificant, elevation of 8 mm Hg (Pϭ0.13) for systolic and 6 mm Hg (Pϭ0.08) for diastolic pressure.No discussion of this trend toward a clinically meaningful pro-hypertensive response was provided.In 23 healthy adults, we previously demonstrated that diastolic blood pressure rapidly increased by 6 mm Hg after the inhalation of concentrated ambient particles mixed with ozone. 4Zanobetti et al 5 also found blood pressure to be increased in direct relation to ambient levels of particulate matter in 62 Boston area residents with heart disease.The lack of statistical significance of the blood pressure elevation in the article by Mills et al 1 is most probably explained simply by an inadequate sample size.If more subjects had been tested, it is likely that a significant pressor response would have been found in their study as well.We believe it is crucial to highlight this important vascular response to pollution.The findings of Mills et al 1 actually serve to bolster the evidence that an acute increase in blood pressure, 4,5 probably mediated by vasoconstriction 2 in resistance arterioles within susceptible individuals, is a factor contributing to the increased risk for myocardial infarction/ischemia and stroke after air pollution exposure.The results also suggest that basal arteriole tone and not just agonist-stimulated vasodilatation is altered in a manner favoring vasoconstriction.Their study 1 was likely similarly underpowered and not specifically designed to observe air pollution-mediated alterations in resting arterial tone.More detailed studies should be performed to corroborate this hypothesis.
Action zones will modernise the NHS
Authors: L. Beecham
Journal: BMJ (1997)

The British government has earmarked over £30m ($48m) to establish up to 10 health action zones in England to break down barriers between health and social care (5 July, p 7).

Health authorities will be encouraged to work more closely with social services departments and to form partnerships with local businesses, community groups, and voluntary organisations. Once set …
Immunization Against Tetanus
Authors: G. M. Bailey
Journal: BMJ (1954)

I am grateful to Dr. Whitelaw for the following histological report." Ovarian tissue shows a follicular cyst filled with blood clot.Section of appendix is cyst-like in character with diameter of lumen 1.0 cm.In the specimen there is no occluding stricture.The wall is composed of a lining of high mucus-secreting columnar cells.There are no remains of cysts, and lumen is filled with mucin material with a few scattered cells.The submucosa is narrowed, fibrous, and has a few scattered lymphoid follicles.The muscular coat is of considerable thickness (1.7 mm.) and in two places is ruptured or deficient, and the mucous contents pour through and infiltrate the peritoneal coat.The cells associated with the 'mucin' are plasma cells and round cells and a few foreign body giant cells.There are no cells of epithelial origin in this over-spill."The patient had an uneventful convalescence, and subsequent questioning failed to elicit any history that could have been con- strued as appendicitis.The muscle hypertrophy and the perfora- tion would conform with Wilson's theory of appendiceal diverticula,l which in the absence of a constriction must represent the continuous efforts of the appendix to expel its unusually pro- fuse and viscous secretions.
The Effect of Weight Loss on Endothelial Functions in Obesity
Authors: Katherine Esposito, Carmen Di Palo, Raffaele Marfella, Dario Giugliano
Journal: Diabetes Care (2003)

We read with interest the article by Sciacqua et al. (1) showing improvement of endothelial function in healthy obese subjects (no sex specified) after short-term (12–16 weeks) weight loss. By adopting a low-calorie diet associated with exercise, only two-thirds of the subjects enrolled in the study were able to achieve a reduction of at least 10% of initial weight (due to a high drop-out rate). In these subjects, maximal vasodilator response to the highest dose of acetylcholine increased from 211 to 358% of baseline, indicating improved endothelium-dependent vasodilation. The choice of obese subjects …
Abstract 86: DNA methylation of tumor suppressor and metastasis suppressor genes in circulating tumor cells
Authors: Maria Chimonidou, Areti D. Strati, Alexandra Tzitzira, Georgia Sotiropoulou, Nikos Malamos, Vassilis Georgoulias, Evi Lianidou
Journal: Cancer Research (2011)

Abstract Background: Circulating tumor cells (CTCs) are associated with prognosis in a variety of human cancers and have been proposed as a liquid biopsy for follow up examinations. We show, that established tumor suppressor and metastasis suppressor genes (CST6, BRMS1, and SOX17) are epigenetically silenced in CTCs isolated from peripheral blood of breast cancer patients. Methods: Peripheral blood was obtained from 56 patients with operable breast cancer, 27 patients with verified metastasis and 23 healthy individuals. Extraction of genomic DNA was performed in the EpCAM positive immunomagnetically selected CTC fraction of peripheral blood mononuclear cells (PBMC). DNA samples were subjected to sodium bisulphite conversion and tested for the presence of methylated and unmethylated gene promoter sequences by methylation specific PCR (MSP). All samples were also checked for CK-19 expression by RT-qPCR. Results: In CTCs of patients with operable breast cancer, CST6 promoter methylation was observed in 17.9%, BRMS1 promoter methylation in 30.4%, and SOX17 promoter methylation in 53.6%. In CTCs of patients with verified metastasis, CST6 promoter methylation was observed in 37.0%, BRMS1 promoter methylation in 44.4%, and SOX17 promoter methylation in 74.1%. Conclusions: Our results provide the first evidence that DNA methylation of tumor suppressor and metastasis suppressor genes is a hallmark feature of CTCs and confirm their heterogeneity. Our findings add a new dimension on the malignant nature of CTCs and may underlie the acquisition of malignant properties, including their stemlike phenotype. Moreover, these epigenetic markers open new possibilities for the exploitation of CTCs in monitoring cancer metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 86. doi:10.1158/1538-7445.AM2011-86
Dexamethasone Proves Deleterious in Cerebral Malaria
Authors: David A. Warrell, Sornchai Looareesuwan, Mary J. Warrell, Prakit Kasemsarn, Ravivan Intaraprasert, Danai Bunnag, Tranakchit Harinasuta
Journal: New England Journal of Medicine (1982)

High-dose dexamethasone was compared with placebo in a double-blind trial involving 100 comatose patients with strictly defined cerebral malaria. The two treatment groups, whose members were six to 70 years old, proved comparable on admission. There were eight deaths in the dexamethasone group and nine in the placebo group (no significant difference; P = 0.8); at post-mortem examination the brain showed features diagnostic of cerebral malaria in all but one patient who died. Dexamethasone prolonged coma among the survivors: the interval between the start of treatment and the full recovery of consciousness was 63.2±5.9 hours (mean ±S.E.M.) in the dexamethasone group, as compared with 47.4±3.2 hours in the placebo group (P = 0.02). Complications, including pneumonia and gastrointestinal bleeding, occurred in 26 patients given dexamethasone and 11 given placebo (P = 0.004). Only five patients had neurologic sequelae. Results were similar in a subgroup of 28 children six to 14 years old. Dexamethasone is deleterious in cerebral malaria and should no longer be used. (N Engl J Med. 1982; 306:313–9.)
Dasatinib, a small-molecule protein tyrosine kinase inhibitor, inhibits T-cell activation and proliferation
Authors: Andrew E. Schade, Gary L. Schieven, Robert Townsend, Anna M. Jankowska, Vojkan Susulic, Rosemary Zhang, Hadrian Szpurka, Jaroslaw P. Maciejewski
Journal: Blood (2007)
Lithium Maintenance Treatment of Depression and Mania in Bipolar I and Bipolar II Disorders
Authors: Leonardo Tondo, Ross J. Baldessarini, John Hennen, Gianfranco Floris
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: Effects of long-term lithium treatment for depressive and manic phases of type I and type II bipolar disorders were compared. METHOD: Clinical research records of 317 patients with DSM-IV-defined bipolar disorder (188 with type I and 129 with type II) were analyzed for frequency and duration of affective episodes and hospitalizations before (mean=8.38 years) versus during (mean=6.35 years) lithium maintenance treatment. Treatment effects were also assessed by survival analysis of interepisode intervals and by multivariate regression testing for factors associated with response to treatment. RESULTS: Bipolar I and bipolar II patients were ill before treatment a similar percentage of time, but the subtype distinction was supported descriptively. Lithium had superior benefits in type II patients, with significantly greater reduction of episodes per year and of the percentage of time ill. Reduction of depressive morbidity was similarly strong in both diagnostic types. During treatment, bipolar II patients had 5.9-fold longer interepisode intervals and were twice as likely as type I patients to have no new episodes. Starting lithium maintenance earlier predicted greater improvement. CONCLUSIONS: Lithium maintenance yielded striking long-term reductions of depressive as well as manic morbidity in both bipolar disorder subtypes, with greater overall benefits in type II patients and with earlier treatment.
Hemophilia, Antineoplastic Factor, and Immune Complexes
Authors: ROBERT P. KIMBERLY
Journal: Annals of Internal Medicine (1984)

Letters and Corrections1 June 1984Hemophilia, Antineoplastic Factor, and Immune ComplexesROBERT P. KIMBERLY, M.D., JAMES B. BUSSEL, M.D., MARGARET W. HILGARTNER, M.D.ROBERT P. KIMBERLY, M.D.Search for more papers by this author, JAMES B. BUSSEL, M.D.Search for more papers by this author, MARGARET W. HILGARTNER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-100-6-915_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: To explain immunologic abnormalities resembling the acquired immunodeficiency syndrome in patients receiving several blood transfusions and factor VIII concentrates, Gascon and associates (1) suggest that either chronic antigenic stimulation of lymphocytes or exposure to viruses with secondary T-cell activation may play a role. In patients with hemophilia, we have gathered data that show that factor VIII concentrates modulate both circulating immune complexes and Fc-related mononuclear phagocyte function (2). Each of these effects could potentially contribute to the observed immunologic abnormalities of altered T4/T8 lymphocyte ratios and decreased natural killer cell activity.After infusions of antihemophilic factor in...References1. GASCONZOUMBOSYOUNG PNN. Immunologic abnormalities in patients receiving multiple blood transfusions. Ann Intern Med. 1984;100:173-7. LinkGoogle Scholar2. KIMBERLYINMANBUSSELPOLKHILGARTNER RRJJM. Modulation of mononuclear phagocyte system function and circulating immune complexes by lyophilized concentrates in patients with classic hemophilia. Clin Immunol Immunopathol. 1984. (In press). CrossrefMedlineGoogle Scholar3. RAOBENNETTSCHENGERSONMITCHELL VJFRM. Antigen-antibody complexes generate Lyt 1 inducers of suppressor cells. J Immunol. 1980;125:63-7. MedlineGoogle Scholar4. KORENANDERSONFISCHERCOPELANDJENSEN HSDCP. Regulation of human natural killing: I. The role of monocytes, interferon and prostaglandin. J Immunol. 1981;127:2007-13. MedlineGoogle Scholar5. PERUSSIATRINCHIERI BG. Antibody 3G8, specific for the human neutrophil Fc receptor, reacts with natural killer cells. J Immunol. 1984;132:1410-5. MedlineGoogle Scholar6. YANGZUCKER-FRANKLIN JD. Modulation of natural killer activity by polymorphonuclear leukocytes and monocytes [Abstract]. Clin Res. 1983;31:486A. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The New York Hospital-Cornell Medical Center New York, NY 0021 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByCorrection: Title of Letter on Antihemophilic Factor 1 June 1984Volume 100, Issue 6Page: 915-916KeywordsAIDSAntigensBlood transfusionHemophiliaImmune complexLymphocytesNatural killer cellsPhagocytes Issue Published: 1 June 1984 PDF DownloadLoading ...
Enhancement by tetragastrin of experimental induction of gastric epithelium in the duodenum.
Authors: M Tatsuta, H Iishi, H Yamamura, R Yamamoto, H Taniguchi
Journal: Gut (1989)

The effects of tetragastrin and truncal vagotomy on the incidence of gastric type epithelium in the duodenum by intraduodenal instillation of 5% NaOH solution were investigated in Wistar rats. Prolonged administration of 1 mg tetragastrin/kg body weight in depot form starting one week after NaOH treatment resulted in a significant increase in gastric acid secretion and the incidence and number of villi with gastric epithelium in the duodenum in experimental week 10. Villi with gastric epithelium were found in five (23%) of 22 rats in control group, whereas abnormal villi were found in 13 (59%) of 22 rats in the tetragastrin treated group (p less than 0.05). The average number of villi with gastric epithelium rose from 0.6 (0.4) per 100 villi in control rats to 2.4 (0.6) per 100 villi in tetragastrin treated rats (p less than 0.01). On histological examination, gastric type epithelium was most often found on stunted or flattened villi, and was always within the boundaries of the area of Brunner9s glands. These mucosal changes reverted toward normal with time. In week 35, the incidence of gastric epithelium was significantly less than at week 10 (p less than 0.05). In contrast, no villi with gastric epithelium were found in vagotomised rats in week 10 (p less than 0.05). Vagotomy also caused a significant decrease in gastric acid secretion. These results show that exposure of the duodenal mucosa to high levels of gastric acid enhance the induction of gastric eithelium in the duodenum.