tbuckley/cabot-search huggingface dataset:
Hazards in Antihypertension Therapy
Authors: RUSSELL L. BERDOFF
Journal: Annals of Internal Medicine (1977)

Comments1 January 1977Hazards in Antihypertension TherapyRUSSELL L. BERDOFF, M.D., RICHARD L. CHALAL, M.D., MICHAEL MADDENRUSSELL L. BERDOFF, M.D., RICHARD L. CHALAL, M.D., MICHAEL MADDENAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-86-1-111_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: A letter from Cohen and colleagues (1) in your August issue discussed the danger of antihypertension therapy with nitroprusside and clonidine. We have recently treated a patient with nitroprusside and methyldopa and met similar difficulty.A 71-year old black woman came to the emergency room complaining of mild ankle trauma. She gave a 30-year history of hypertension controlled by "one pill daily," but had taken no medications for 3 months. She had no symptoms of hypertension. Blood pressure was 250/150 mmHg and pulse, 102 beats/min. Fundi showed severe arteriolar narrowing with no hemorrhages or exudates, and flat...Reference1. COHEN I, MOTTET M, and FRANCIS G: Dangers in nitroprusside therapy. Ann Intern Med 85:205-206, 1976 LinkGoogle Scholar1. KANADA S, KANADA D, and HUTCHINSON R: Angina-like syndrome with diazoxide therapy for hypertensive crisis. Ann Intern Med 84:696-699, 1976 LinkGoogle Scholar2. MROCZEK W and LEE W: Diazoxide therapy: use and risks (letter). Ann Intern Med 85:529, 1976 LinkGoogle Scholar3. KUMAR G, DASTOOR F, and ROBAYO J: Side effects of diazoxide. JAMA 235:275-276, 1976 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: RUSSELL L. BERDOFF, M.D.; RICHARD L. CHALAL, M.D.; MICHAEL MADDENAffiliations: The Georgetown University Medical Division District of Columbia General Hospital Washington, DC 20003 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited bySodium nitroprussidePathophysiology, clinical aspects, and treatment of hypertensive crisesFatal hypotension in normal-dose nitroprusside therapyHypotensive drugs 1 January 1977Volume 86, Issue 1Page: 111-112KeywordsAnklesBlood pressureEmergency departmentHeart rateHemorrhageHypertension ePublished: 1 December 2008 Issue Published: 1 January 1977 PDF downloadLoading ...
On the cardiovascular activity of apelin
Authors: G LOSANO
Journal: Cardiovascular Research (2004)

See article by Ashley et al.  [8]  (pages 73–82) in this issue. 

Apelin, a peptide recently isolated from bovine stomach extracts, has been seen to act as an endogenous ligand of the orphan G-protein-coupled APJ receptor [1]. The structure of apelin preproteins was deduced from the sequences of the relevant cDNAs. The preproteins consist of 77 amino acid residues, with the apelin active sequence in the C-terminal regions [1]. Apelin mRNA expression was also found in the gastrointestinal tract, adipose tissue, brain, lung, kidney, liver, skeletal muscle, and cardiovascular system. In the cardiovascular system, it has been detected in endothelial cells of large conduit arteries, coronary vessels, and endocardium of the right atrium [2].

Apelin displays several activities on various systems. It has been seen to stimulate the proliferation of gastric cells in vitro and to increase the secretion of cholecystokinin in vivo [3]. A diuretic effect is consistent with its presence in the supraoptic nucleus of the hypothalamus, where it seems to inhibit the electrical activity of vasopressin-releasing neurons [4].

On the cardiovascular system, apelin exerts potent vasodilator and positive inotropic activities. Studies on mice revealed that apelin-induced hypotension is abolished by inhibition of nitric oxide (NO) synthase and that the angiotensin II hypertensive response is enhanced in APJ-deficient animals [5]. These results suggest not only that apelin vasodilatation is mediated by NO, but also that APJ receptors counteract the pressor effect of angiotensin II, possibly in response to a basal release of apelin from the … 

*Tel.: +39 11 6707785; fax: +39 11 670 7708. Email address: gianni.losano{at}unito.it
Alterations of atrial Ca2+ handling as cause and consequence of atrial fibrillation
Authors: M. Greiser, W. J. Lederer, U. Schotten
Journal: Cardiovascular Research (2010)

Atrial fibrillation (AF) is the most prevalent sustained arrhythmia. As the most important risk factor for embolic stroke, AF is associated with a high morbidity and mortality. Despite decades of research, successful (pharmacological and interventional) 'ablation' of the arrhythmia remains challenging. AF is characterized by a diverse aetiology, including heart failure, hypertension, and valvular disease. Based on this understanding, new treatment strategies that are specifically tailored to the underlying pathophysiology of a certain 'type' of AF are being developed. One important aspect of AF pathophysiology is altered intracellular Ca(2+) handling. Due to the increase in the atrial activation rate and the subsequent initial [Ca(2+)](i) overload, AF induces 'remodelling' of intracellular Ca(2+) handling. Current research focuses on unravelling the contribution of altered intracellular Ca(2+) handling to different types of AF. More specifically, changes in intracellular Ca(2+) homeostasis preceding the onset of AF, in conditions which predispose to AF (e.g. heart failure), appear to be different from changes in Ca(2+) handling developing after the onset of AF. Here we review and critique altered intracellular Ca(2+) handling and its contribution to three specific aspects of AF pathophysiology, (i) excitation-transcription coupling and Ca(2+)-dependent signalling pathways, (ii) atrial contractile dysfunction, and (iii) arrhythmogenicity.
A Factual Study of Male Homosexuality
Authors: R. E. Hemphill, A. Leitch, J. R. Stuart
Journal: BMJ (1958)

Brrm 1317 among British Forces in the Middle East in the second world war.So far 91.6% of the men have been contacted.The mortality rate of the acute attack was 0.28%, while the recurrence rate over the succeeding six years was 8.3%.The clinical features of the acute attack are briefly discussed and an account is given of the symptoms which complicated recovery.In only 3.2% of cases did subsequent ill-health last as long as seven years.No examples of subacute necrosis leading to cirrhosis occurred in this series, and to date no cases of later developing cirrhosis have been discovered.A follow-up of this size was made possible only by the co- operation of many people.In particular, we wish to mention successive Directors-General of the Army Medical Services and the consultant physicians to the Army, the Statistical Branch of the Army Medical Department, many Army records offices, the Ministry of Pensions, the Registrar-General for England and Wales, the Registrar-General for Scotland, the National Health Service Central Register Headquarters and Local Executive Councils, a large number of general practitioners, and the patients who wrote to us.We thank these and many others for their generous help.The secretarial expenses of the first part of the inquiry in 1949 were paid for by the Medical Research Council.One of us (R.
Clinical Experience With Intravenous Administration of Ethacrynic Acid
Authors: George V. Irons
Journal: JAMA (1965)

The diuretic response to a single intravenous injection of ethacrynic acid was observed on 61 occasions in 31 edematous subjects. Maximal water, sodium, chloride, and potassium diuresis occurred within the first hour, and potassium diuresis continued into the following day. The average urine volume was 1,164 cc over the first three hours and 2,378 cc over 24 hours. Average urinary electrolyte losses for the first three hours were sodium, 114 mEq; chloride, 128 mEq; potassium, 25 mEq. For the subsequent 21 hours they were sodium, 49 mEq; chloride, 44 mEq; and potassium 43 mEq. No significant electrolyte alterations occurred after a single intravenous injection. An effective diuresis was achieved in spite of azotemia, hypochloremia, hyponatremia, and hypokalemia. The drug was particularly effective when administered to eight patients manifesting pulmonary edema on 12 occasions. No significant side effects were encountered.
Abstract LB-168: Perivascular, CXCR4-expressing macrophages in tumors promote relapse following chemotherapy
Authors: Claire E. Lewis
Journal: Cancer Research (2014)

Abstract The relapse of cancer after frontline therapies like chemotherapy is a major clinical problem as tumors often grow back at the site of surgical removal and/or as metastases. Tumor-associated macrophages (TAMs) are a major cellular component of both primary and metastatic tumors, and promote such key processes in tumor progression as angiogenesis, immunosuppression, invasion, and metastasis. Gene expression profiling and immunostaining studies have identified both classically (M1) and alternatively (M2) activated TAMs in human and mouse tumors. Heavily M2-skewed TAMs - those expressing the angiopoietin receptor, TIE2 - have been shown to be important for angiogenesis and immunosuppression in mouse tumors. Moreover, high levels of TAMs expressing another M2 marker, CD163, correlate with poor prognosis in various forms of human cancer. TAMs have been shown recently to reduce the sensitivity of mouse mammary tumors to cytotoxic agents like paclitaxel (PTX) and doxorubicin. Here, we report on our use of various mouse tumor models to investigate the role of TAMs in tumor relapse after chemotherapy. Our studies show that a distinct subset of M2-skewed, CXCR4hi VEGF+ TAMs cluster around blood vessels after administration of various cytotoxic agents. This correlated with increased tumor CXCL12 levels - and the selective depletion of this perivascular TAM subset, using the CXCR4 antagonist, AMD3100 (Plerixafor), revealed an important role for these cells in driving revascularisation and regrowth in post-chemotherapy tumors. Additionally, adoptive transfer of this TAM subset into tumor-bearing mice after chemotherapy accelerated tumor regrowth. No such effect was seen with non-M2 skewed TAMs isolated from the same tumors. These studies suggest that combining chemotherapy with inhibitors of the CXCL12-CXCR4 axis could delay tumor relapse in cancer patients. Citation Format: Claire E. Lewis. Perivascular, CXCR4-expressing macrophages in tumors promote relapse following chemotherapy. [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 LB-168. doi:10.1158/1538-7445.AM2014-LB-168
Studies on the Renal Concentrating and Diluting Mechanisms in the Premature Infant12
Authors: Philip L. Calcagno, Mitchell I. Rubin, David H. Weintraub
Journal: Journal of Clinical Investigation (1954)

It is known that young premature infants are unable to concentrate urine to the same degree as adults.The following hypotheses have been advanced to explain this difference: (a) A lowered production of antidiuretic hormone (1); (b) a re- ,duced response of the distal renal tubule (end- organ) to antidiuretic hormone (2); (c) a de- creased rate of solute excretion secondary to a lower rate of glomerular filtration (3).Heller and Zaimis found that there is a lower concentration of antidiuretic hormone in the pitui- tary body of newborn infants than in adults, when compared on a body weight basis (1).Yet these authors believe that in spite of this smaller amount of hormone in the pituitary of the newborn in- fant, there is still a sufficient quantity of the hor- mone to produce a maximally concentrated urine, if the hormone is released and if the renal tubule of the newborn infant is responsive.Heller (2) also showed that amounts of pituitary extract, which produced a pronounced inhibition of water diuresis in adults, had only a slight and fleeting ef- fect on the kidney of newborn infants.In com- paring the response of three premature infants with that of two adults to intravenously adminis- tered pitressin during water diuresis, it was found (4) that the extent and duration of the anti- diuretic response was less in the premature infant.The third hypothesis, the effect of solute excre- tion, can be tested by noting the changes in urine osmolarity in response to solute loading.If the lower concentrating capacity during hydropenia were solely a reflection of the lower solute load in the premature infant, then a rise in the osmolar concentration should occur with loading.
Acute monoarthritis associated with lipid liquid crystals.
Authors: A J Reginato, H R Schumacher, D A Allan, J L Rabinowitz
Journal: Annals of the Rheumatic Diseases (1985)

We describe three women with unexplained acute monoarthritis and birefringent lipid spherules or lipid liquid crystals in their synovial fluid. Synovial fluid aspirated within 24 hours of onset showed leucocyte counts ranging from 10 X 10(9) to 46 X 10(9)/1 with 91-95% polymorphonuclear cells. Numerous positively birefringent 2-6 micron microspherules were seen inside and outside polymorphonuclear cells. These were dissolved in alcohol-ether but were not digested by uricase. Other non-birefringent globules of similar size that stained with Sudan black B were also seen. Transmission electron microscopy identified osmiophilic homogeneous or multilamellated material in phagocytic vacuoles. Serum lipids, lipase, and repeated joint radiographs were normal. Arthritis subsided completely after treatment with colchicine in one patient and nonsteroidal anti-inflammatory agents in two. Thus birefringent microspherules can be found in association with acute, otherwise unexplained, arthritis. It seems possible that certain lipid liquid crystals may induce synovial inflammation similar to inflammation seen in other crystal induced arthritides.
Survival after Orthotopic Liver Transplantation: A Follow-up Report of Two Patients
Authors: R. Y. Calne, R. Williams
Journal: BMJ (1970)

Two adult patients with terminal fatal liver disease were treated by orthotopic transplantation. One survived 11 months and died as a result of recurrent biliary intra-abdominal sepsis; the other patient is alive and well in the 18th month after transplantation and has virtually normal liver function. It is concluded that liver grafting can provide valuable therapy.
Ventral Oral Mucosal Onlay Graft Urethroplasty in Nontraumatic Bulbar Urethral Strictures: Surgical Technique and Multivariable Analysis of Results in 214 Patients
Authors: Guido Barbagli, Francesco Montorsi, Giorgio Guazzoni, Alessandro Larcher, Nicola Fossati, Salvatore Sansalone, Giuseppe Romano, Nicolòmaria Buffi, Massimo Lazzeri
Journal: European Urology (2013)
Abstract 2279: Adenine nucleotide translocase-2 is a key molecule in the enhancement of TRAIL sensitivity by flavonoids
Authors: Masakatsu Oishi, Yosuke Iizumi, Takashi Ueda, Saya Ito, Terukazu Nakamura, Fumiya Hongo, Yoshio Naya, Tsuneharu Miki, Toshiyuki Sakai
Journal: Cancer Research (2014)

Abstract Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine which belongs to the tumor necrosis factor family. TRAIL binds to death receptor (DR) 4 and DR5 and selectively induces apoptosis in various malignant tumors, but not in normal cells. Therefore, TRAIL is an attractive cancer therapeutic agent. However, several malignant tumors have resistance to TRAIL and overcoming this resistance is essential for chemotherapy using the TRAIL pathway. Anticancer agents such as bortezomib, etoposide, doxorubicin, and irinotecan have been reported to upregulate DR5 and sensitize cancer cells to TRAIL in vitro and in vivo. Since these agents cause various adverse effects, we and others have screened dietary compounds inducing DR5 expression and identified several flavonoids as DR5 inducers. For instance, dietary flavonoid apigenin and quercetin enhance TRAIL sensitivity by upregulating DR5. However, the mechanisms by which these flavonoids upregulate DR5 are unknown. To elucidate the mechanisms by which these flavonoids induce DR5, we explored the proteins binding to apigenin and quercetin, but not the flavonoid genistein which did not induce DR5. We used magnetic FG beads, which recently revealed the target of thalidomide and the mechanism of thalidomide teratogenicity. We identified ANT2 as a binding protein of flavonoids, apigenin and quercetin, upregulating DR5. As with the treatment of apigenin and quercetin, knockdown of ANT2 enhanced TRAIL-induced apoptosis by upregulating DR5. Moreover, knockdown of ANT2 attenuated the enhancement of TRAIL-mediated apoptosis by apigenin and quercetin. In the present study, we show that ANT2 is a target of flavonoids which upregulate DR5 and sensitize malignant tumor cells to TRAIL. Citation Format: Masakatsu Oishi, Yosuke Iizumi, Takashi Ueda, Saya Ito, Terukazu Nakamura, Fumiya Hongo, Yoshio Naya, Tsuneharu Miki, Toshiyuki Sakai. Adenine nucleotide translocase-2 is a key molecule in the enhancement of TRAIL sensitivity by flavonoids. [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 2279. doi:10.1158/1538-7445.AM2014-2279
ALUMINOSILICATES AND SENILE PLAQUE FORMATION IN ALZHEIMER'S DISEASE
Authors: J.M. Candy, J. Klinowski, R.H. Perry, E.K. Perry, A. Fairbairn, A.E. Oakley, T.A. Carpenter, J.R. Atack, G. Blessed, J.A. Edwardson
Journal: The Lancet (1986)
THE PHYSIOLOGIC ACTION, ELIMINATION AND THERAPEUTIC APPLICATION OF SODIUM CACODYLATE, USED HYPODERMATICALLY.
Authors: SPENCER L. DAWES
Journal: JAMA (1907)

According to Burlureaux,<sup>1</sup>the credit of the introduction of sodium cacodylate as a therapeutic agent belongs to Gautier, who on June 6, 1899, reported a series of observations in which he (Burlureaux) assisted. During the succeeding four years numberless enthusiastic, not to say extravagant, articles by European observers heralded the drug as a desirable substitute for metallic arsenic. On Jan. 31, 1903, however, T. R. Fraser<sup>2</sup>gave the drug, so far as English and American clinicians and authors are concerned, its<i>coup de grâce</i>, for, with but one or two exceptions, all English and American textbooks on materia medica deny the possibility of the drug, used hypodermatically, having either physiologic action or therapeutic value. In the article alluded to Fraser says: "The... therapeutic effects of arsenic are caused by its pharmacologic action, and if it be so united with other bodies as to be incapable of producing any
Acquired Cutis Laxa Associated With Heavy Chain Deposition Disease Involving Dermal Elastic Fibers
Authors: John T. O’Malley, Vivette D. D’Agati, William H. Sherman, Marc E. Grossman
Journal: JAMA Dermatology (2014)

Acquired cutis laxa is a rare cutaneous manifestation of hematologic malignancy. We report a case of γ heavy chain deposition disease (HCDD) associated with acquired cutis laxa, renal involvement, and hypocomplementemia and propose a mechanism of elastic fiber degradation in the skin of this patient with HCDD.To determine the localization of immunoglobulin heavy chains and complement activation in the skin of a patient with HCDD, we examined her skin biopsy specimens under light and electron microscopy. Analysis demonstrated the deposition of γ heavy chain and complement components C1q and C3 on the surfaces of dermal elastic fibers, indicating complement fixation by the deposited heavy chains. Electron microscopy revealed finely granular electron-dense deposits coating the surfaces of frayed dermal elastic fibers.The pathogenesis of cutis laxa in this condition is poorly understood. We hypothesize a mechanism of elastic tissue destruction by complement fixation with resultant activation of the complement cascade ultimately causing elastolysis. Based on our findings and those of other reports, we propose that skin heavy chain deposition can serve as a marker of plasma cell secretory activity in HCDD, although further studies are needed.
NHS Direct backs out of contracts to run NHS 111 because of poor funding
Authors: I. Torjesen
Journal: BMJ (2013)

NHS Direct has announced that it is withdrawing from all its contracts to run the NHS 111 urgent advice telephone service in England, claiming that the contracts were not financially sustainable.

NHS Direct had already backed out of two of its NHS 111 contract in June, before the services were even launched, citing the same reason. It wrote to commissioners in North Essex and in Cornwall and the Isles of Scilly complaining that the costs of providing the service exceeded the contract price.

The latest announcement affects all its other NHS 111 services, which cover Buckinghamshire, East London and the City, South East London, Sutton and Merton, West Midlands, Lancashire and Cumbria, Greater Manchester, Merseyside and Cheshire, and Somerset.

NHS Direct won 11 of the 46 regional contracts to deliver NHS 111. The other …
A Frequency and Semiquantitative Analysis of Pathological 68Ga DOTATATE PET/CT Uptake by Primary Site–Dependent Neuroendocrine Tumor Metastasis
Authors: Jolanta Kunikowska, Dariusz Pawlak, Anna Kolasa, Renata Mikołajczak, Leszek Królicki
Journal: Clinical Nuclear Medicine (2014)

The aim of this study was to define the frequency of neuroendocrine neoplasia (NEN) metastasis sites based on the primary lesion and create a database of SUVmax as a marker of human SSTR (somatostatin receptors) expression by semiquantitative analysis in vivo Ga DOTATATE PET/CT.Two hundred forty-five patients, 89 men and 156 women (mean [SD] age, 56.1 [12.8]), were imaged 60 to 70 minutes after 120 to 200 MBq (3.2-5.4 mCi) Ga DOTATATE injection using a Siemens Medical Solutions Biograph 64 PET/CT TruePoint. Visual assessments were made using a multimodality workstation, and sites of increased uptake were recorded. Pathological Ga DOTATATE uptake was quantified using semiquantitative analysis (SUVmax).In patients with unknown primary tumors, Ga DOTATATE PET/CT revealed primary location in 92% (pancreas, 47%; intestines, 28%; and lung, 17%).Metastases, with respect to the primary sites, were predominantly in the liver (33% vs 49% vs 40%), lymph nodes (24% vs 34% vs 25%), and bone (10% vs 20% vs 30%). The SUVmax of metastases (mean [SD]) was highest in the liver (28.7 [23.5]), followed by the adrenal glands (24.7 [9.7]), bone (24.1 [36.8]), lymph nodes (22.5 [24.5]), pancreas (24.9 [28.1]), peritoneum (21.9 [24]), and the brain (4.6 [2.9]).Ga DOTATATE PET/CT is very useful in the localization of NEN primary tumors. Ga DOTATATE PET/CT allows for visualizations of bone and lymph node metastases, not detected by any other modalities, which provides better staging and changes the clinical decision in approximately one third of patients.Our study shows that pancreatic NEN presented statistically a significantly lower frequency of bone metastases in comparison to lung and intestinal NEN. No significant frequency of metastases in the liver and lymph nodes based on primary tumors was observed.