tbuckley/cabot-search huggingface dataset:
Role of arginine vasopressin and angiotensin II in cardiovascular responses to combined acute hypoxemia and hypercapnic acidosis in conscious dogs.
Authors: C E Rose, R L Godine, K Y Rose, R J Anderson, R M Carey
Journal: Journal of Clinical Investigation (1984)

The physiological relationship of increased circulating angiotensin II and vasopressin to circulatory changes during combined hypoxemia and hypercapnic acidosis is unclear. To evaluate the role(s) of angiotensin II and vasopressin, seven unanesthetized female mongrel dogs with controlled sodium intake (80 meq/24 h X 4 d) were studied during 40 min of combined acute hypoxemia and hypercapnic acidosis (PaO2, 36 +/- 1 mmHg; PaCO2, 55 +/- 2 mmHg; pH = 7.16 +/- 0.04) under the following conditions: (a) intact state with infusion of vehicles alone; (b) beta-adrenergic blockade with infusion of d,l-propranolol (1.0 mg/kg bolus, 0.5 mg/kg per h); of the vasopressin pressor antagonist d-(CH2)5Tyr(methyl)arginine-vasopressin (10 micrograms/kg); and (d) simultaneous vasopressin pressor and angiotensin II inhibition with the additional infusion of 1-sarcosine, 8-alanine angiotensin II (2.0 micrograms/kg per min). The rise in mean arterial pressure during the combined blood-gas derangement with vehicles appeared to be related to increased cardiac output, since total peripheral resistance fell. Beta-adrenergic blockade abolished the fall in total peripheral resistance and diminished the rise in cardiac output during combined hypoxemia and hypercapnic acidosis, but the systemic pressor response was unchanged. In addition, the rise in mean arterial pressure during the combined blood-gas derangement was unaltered with vasopressin pressor antagonism alone. In contrast, the simultaneous administration of the vasopressin pressor and angiotensin II inhibitors during combined hypoxemia and hypercapnic acidosis resulted in the abrogation of the overall systemic pressor response despite increased cardiac output, owing to a more pronounced fall in total peripheral resistance. Circulating catecholamines were increased during the combined blood-gas derangement with vasopressin pressor and angiotensin II blockade, suggesting that the abolition of the systemic pressor response in the last 30 min of combined hypoxemia and hypercapnic acidosis was not related to diminished activity of the sympathetic nervous system. These studies show that vasopressin and angiotensin II are major contributors to the systemic pressor response during combined acute hypoxemia and hypercapnic acidosis.
Correction: Reserpine Dosage
Authors: LAWRENCE Z. FEIGENBAUM
Journal: Annals of Internal Medicine (1988)

Letters and Corrections1 May 1988Correction: Reserpine DosageLAWRENCE Z. FEIGENBAUM, M.D.LAWRENCE Z. FEIGENBAUM, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-108-5-777_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptI was pleased that my response (1) to Dr. Moser's editorial (2) on cost containment and hypertension was published. Unfortunately, the proper dosage of reserpine should have been "0.25 mg/d," not 2.5 mg/d....References1. FEIGENBAUM L. Cost containment and hypertension [Letter]. Ann Intern Med. 1988;108:148-9. LinkGoogle Scholar2. MOSER M. "Cost containment" in the management of hypertension. Ann Intern Med. 1987;107:107-9. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: LAWRENCE Z. FEIGENBAUM, M.D.Affiliations: University of California, San Francisco San Francisco Institute on Aging San Francisco, CA 94120 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1988Volume 108, Issue 5Page: 777-777KeywordsHypertensionReserpine ePublished: 1 December 2008 Issue Published: 1 May 1988 PDF downloadLoading ...
Lords support animal experiments but call for alternatives
Authors: R. Dobson
Journal: BMJ (2002)

Animal experiments are necessary, but more needs to be done to develop and promote alternative methods, says the House of Lords Select Committee on Animals in Scientific Procedures.

In a new report the committee recommends the setting up of research units to find ways of reducing the need for animals and replacing them.

“There is scope for the scientific community to give a greater priority to the development of non-animal methods,” it says. “The UK Government should use their influence to urge the EU to make the development and validation of replacements for animal experiments a priority, particularly in toxicology.”

It also says that the Home Office should give urgent attention to simplifying licences, with the …
Multiphasic Health Testing in Medicine
Authors: E. G. Shelley
Journal: JAMA (1972)

To the Editor.—  Dr. Howe's Application of Automated Multiphasic Health Testing in Clinical Medicine ( 219 :885, 1972) fails to note that the Judicial Council in March 1971 and the Council on Medical Service in December 1971 issued guidelines for Automated Multiphasic Health Testing (AMHT) facilities. These two guidelines not only complement Dr. Howe's article but emphasize that the Association, itsJournal, and its committees and councils help the physician through MEDICINE IN METAMORPHOSIS.
680. Non-Viral Transposon Mediated Gene Transfer of Human Factor VIII to Hemophilia A Mice
Authors: Litao Xie, Yubin Kang, Stephen Yant, Mark Kay, Paul McCray
Journal: Molecular Therapy (2006)

Top of pageAbstract
Hemophilia A is an X-linked genetic disorder disease resulting in quantitative or qualitative deficiencies in coagulation Factor VIII and the risk for sustained bleeding after trauma or injury. The disorder is an attractive candidate for treatment by gene transfer because only partial correction is required for clinically relevant effects. We are investigating the Sleeping Beauty transposon vector system to express FVIII, using a liver-specific mouse albumin enhancer and human alpha-1-antitrypsin promoter (Alb/HAAT) to direct human FVIII cDNA expression. Transgenes under investigation include B-domain deleted human FVIII (BDD-FVIII) and a FVIII cDNA engineered to include several asparagine-linked oligosaccharides within a short B-domain spacer (F226aa/N6, Pipe et al). Using E16 hemophilia A mice on a congenic C57/BL6 background, we are contrasting expression from these constructs following hydrodynamic tail vein injection. Transposon pT3-Alb/HAAT-BDD-FVIII resulted in plasma FVIII levels of 14 ng/ml 1 week post-injection which gradually declined to |[sim]|4 ng/ml by 3 months. Preliminary results with transposon pT3-Alb/HAAT-F226aa/N6 demonstrate plasma FVIII levels of |[sim]|15 ng/ml 1 month post-injection. No antibodies to hFVIII were detected in either group. These results indicate that a Sleeping Beauty transposon with a liver-specific promoter can direct human factor VIII expression in a mouse model of FVIII and attain partial correction of the deficient protein.
Outpatient Treatment of Recent-Onset Atrial Fibrillation with the “Pill-in-the-Pocket” Approach
Authors: Paolo Alboni, Giovanni L. Botto, Nicola Baldi, Mario Luzi, Vitantonio Russo, Lorella Gianfranchi, Paola Marchi, Massimo Calzolari, Alberto Solano, Raffaele Baroffio, Germano Gaggioli
Journal: New England Journal of Medicine (2004)

In-hospital administration of flecainide and propafenone in a single oral loading dose has been shown to be effective and superior to placebo in terminating atrial fibrillation. We evaluated the feasibility and the safety of self-administered oral loading of flecainide and propafenone in terminating atrial fibrillation of recent onset outside the hospital.We administered either flecainide or propafenone orally to restore sinus rhythm in 268 patients with mild heart disease or none who came to the emergency room with atrial fibrillation of recent onset that was hemodynamically well tolerated. Of these patients, 58 (22 percent) were excluded from the study because of treatment failure or side effects. Out-of-hospital self-administration of flecainide or propafenone--the "pill-in-the-pocket" approach--after the onset of heart palpitations was evaluated in the remaining 210 patients (mean age [+/-SD], 59+/-11 years).During a mean follow-up of 15+/-5 months, 165 patients (79 percent) had a total of 618 episodes of arrhythmia; of those episodes, 569 (92 percent) were treated 36+/-93 minutes after the onset of symptoms. Treatment was successful in 534 episodes (94 percent); the time to resolution of symptoms was 113+/-84 minutes. Among the 165 patients with recurrences, the drug was effective during all the arrhythmic episodes in 139 patients (84 percent). Adverse effects were reported during one or more arrhythmic episodes by 12 patients (7 percent), including atrial flutter at a rapid ventricular rate in 1 patient and noncardiac side effects in 11 patients. The numbers of monthly visits to the emergency room and hospitalizations were significantly lower during follow-up than during the year before the target episode (P<0.001 for both comparisons).In a selected, risk-stratified population of patients with recurrent atrial fibrillation, pill-in-the-pocket treatment is feasible and safe, with a high rate of compliance by patients, a low rate of adverse events, and a marked reduction in emergency room visits and hospital admissions.
Tacrine for Alzheimer's disease
Authors: D. Riesenberg
Journal: JAMA (1994)

To the Editor.  —The 30-week study of tacrine hydrochloride by Dr Knapp and colleagues 1 was the most edifying report yet published on this new treatment for Alzheimer's disease. Urinary incontinence is a major reason for institutionalization of patients with Alzheimer's disease. We were unable to find any assessment of the effect of tacrine on incontinence in the published article. However, the authors state that a clinician did develop a comprehensive impression of... behaviors and activities of daily living. 1(p986) Since the latter include toileting, we wonder if more specific information is available on changes in continence during treatment with tacrine.
THE USE OF CARBON DIOXIDE SNOW IN TREATING BLASTOMYCOSIS
Authors: HARRY MALCOME HEDGE
Journal: JAMA (1928)

I have examined the literature and various textbooks, and have made a search for reports of the use of carbon dioxide snow in the treatment of blastomycosis, but I find that little mention has been made of it. The early eruption on the skin occupies an area usually restricted in size and when thus localized it may successfully be treated with carbon dioxide snow, a substance now at hand even in most distant towns and at the command of every general practitioner. If, however, the disease is neglected, it soon assumes grave proportions; it may resist even the most active measures and result disastrously.  The diagnosis of blastomycosis is not of great difficulty nor does it require a large amount of laboratory procedure or equipment. A microscope, a glass slide, a cover glass and a bottle of 10 per cent sodium hydroxide are all that is necessary. The disease begins
Transfer of glycosylphosphatidylinositol-anchored proteins to deficient cells after erythrocyte transfusion in paroxysmal nocturnal hemoglobinuria
Authors: Elaine M. Sloand, Lori Mainwaring, Keyvan Keyvanfar, Jichun Chen, Jaroslaw Maciejewski, Harvey G. Klein, Neal S. Young
Journal: Blood (2004)
Changes in Proximal and Distal Tubular Reabsorption Produced by Rapid Expansion of Extracellular Fluid*
Authors: John P. Hayslett, Michael Kashgarian, Franklin H. Epstein
Journal: Journal of Clinical Investigation (1967)

Acute infusions of isotonic saline in the rat cause an increase in glomerular filtration rate and in the excretion of salt and water. The kidney swells, due to expansion of tubular and interstitial volume. Despite the increase in tubular diameter, transit time through the proximal tubules and loops of Henle is decreased, presumably owing to a greatly accelerated rate of tubular flow. Proximal tubular reabsorption, measured in blocked tubules, is inhibited in a way that cannot be ascribed to changes in tubular diameter. The prolongation of proximal reabsorptive half-time is not affected by the administration of aldosterone. It occurs equally in rats chronically loaded with or deprived of salt, and it is therefore not likely that it is influenced by the renal content of renin. In contrast, reabsorption from the distal convoluted tubule is enhanced by saline infusion. This change is observed in segments of tubules blocked with oil and isolated from their glomeruli and thus appears to occur independently of changes in glomerular filtration or tubular flow.
Reply to M. Buyse et al
Authors: Daniel D. Von Hoff, William Sutherland, Mitesh J. Borad, Peter Rosen, David M. Loesch
Journal: Journal of Clinical Oncology (2011)

We appreciate the thoughtful correspondence by Buyse et al with respect to this important developing area of clinical trials that use a molecular profiling approach. We have considered their remarks regarding the use of a progression-free survival (PFS) ratio in this setting. We do not consider the comments of Buyse et al to counter our conclusion, given thatwewerenotseekingtoshowthatmolecularprofilingyieldedahigher averagetimetotumorprogression.Theideawastoshowthat itworkedin some patients, more often than would have been expected, and to examine successes to help determine in which patients it was working and why. This is why we felt that it was appropriate to use the PFS ratio in this pilot trial, rather than to undertake formal comparisons of overall average treatment effect. However, to our knowledge, this is the first time that the PFS ratio end point has been used in a molecular profiling study, so discussion on this point is certainly warranted. Thedesignofourpilottrialwaschallengingbecauseourpatientshad progressed while receiving multiple other therapies and because of the nature of trying to treat individual patients with different histologic types of cancer (with potentially different natural histories of disease). To additionally address the comments by Buyse et al, in addition to PFS, other parameters such as tumor size were observed. We were encouraged that, in addition to the primary end point of the PFS ratio of 1.3, there was also shrinkage of some patients’ tumors (Fig 4, waterfall plot from the original article). Obviously, designing clinical trials to test molecular profiling is an evolving challenge. It is notable that other groups are exploring different end points for these studies; for instance, the BiomarkerIntegrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial is investigating the disease control rate at 8 weeks for patients with non–small-cell lung cancer, and in the Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis 2 (I-Spy 2), the end point is pathologic complete response. There is no doubt that molecular profiling of patients’ tumor tissue using a variety of techniques will be important from now on, given the recently reported successes of molecular targeted agents. Designs for clinical trials to evaluate the utility of increasingly sophisticated methods of molecular characterization of patients’ tumors (and the microenvironments of their tumors) is obviously an important and evolving area for clinical research and clinical trial design. The continued work of Buyse et al with respect to those clinical trial designs is much appreciated.
Nigerian president holds key to global polio eradication
Authors: Fiona Fleck
Journal: BMJ (2004)

Nigeria's President Olusegun Obasanjo is expected to intervene to persuade the Muslim states in northern Nigeria to join a second round of poliomyelitis vaccinations across West Africa between 23 and 26 March, World Health Organization officials have said.

Leaders in the Nigerian states boycotted the first round of a campaign to immunise 63 million children across west Africa, claiming that the oral vaccine caused sterility and spread AIDS and branding the WHO campaign a US plot to depopulate Africa.

The boycott is a major setback for WHO's campaign to eradicate polio globally by …
Plant based insect repellent and insecticide treated bed nets to protect against malaria in areas of early evening biting vectors: double blind randomised placebo controlled clinical trial in the Bolivian Amazon
Authors: N Hill, A Lenglet, A M Arnéz, I Carneiro
Journal: BMJ (2007)

<b>Objective</b> To determine the effectiveness in reducing malaria of combining an insect repellent with insecticide treated bed nets compared with the nets alone in an area where vector mosquitoes feed in the early evening. <b>Design</b> A double blind, placebo controlled cluster-randomised clinical study. <b>Setting</b> Rural villages and peri-urban districts in the Bolivian Amazon. <b>Participants</b> 4008 individuals in 860 households. <b>Interventions</b> All individuals slept under treated nets; one group also used a plant based insect repellent each evening, a second group used placebo. <b>Main outcome measure</b> Episodes of <i>Plasmodium falciparum</i> or <i>P vivax</i> malaria confirmed by rapid diagnostic test or blood slide, respectively. <b>Results</b> We analysed 15 174 person months at risk and found a highly significant 80% reduction in episodes of <i>P vivax</i> in the group that used treated nets and repellent (incidence rate ratio 0.20, 95% confidence interval 0.11 to 0.38, P&lt;0.001). Numbers of <i>P falciparum</i> cases during the study were small and, after adjustment for age, an 82% protective effect was observed, although this was not significant (0.18, 0.02 to 1.40, P=0.10). Reported episodes of fever with any cause were reduced by 58% in the group that used repellent (0.42, 0.31 to 0.56, P&lt;0.001). <b>Conclusions</b> Insect repellents can provide protection against malaria. In areas where vectors feed in the early evening, effectiveness of treated nets can be significantly increased by using repellent between dusk and bedtime. This has important implications in malaria vector control programmes outside Africa and shows that the combined use of treated nets and insect repellents, as advocated for most tourists travelling to high risk areas, is fully justified. <b>Registration</b> NCT 00144716.
Best books on epidemiology: a personal choice
Authors: S Wessely
Journal: BMJ (1994)

\***|Epidemiology for the Uninitiated. 3rd edn. D Coggan, G Rose, D Barker. (£6.95.) BMJ, 1993. ISBN 0-7279-0770-0.

\***|Epidemiology in Medical Practice. 4th edn. D Barker, G Rose. (pounds sterling10.50.) Churchill Livingstone, 1990. ISBN 0-443-03783.

“Epidemiology is the study of how often diseases occur in different groups of people and why. Epidemiological information is used to plan and evaluate strategies to prevent illness and as a guide to the management of patients in whom disease has already developed.” This succinct introduction for Epidemiology for the Uninitiated outlines both the scope and appeal of epidemiology, and also illustrates why that particular paperback is a firm favourite among texts designed for the epidemiologically illiterate. The authors also write that “our only assumption is that readers already believe that epidemiological questions are worth answering.” Sadly it is those who do not share this belief who should be forced to read the book, or its only slightly bigger brother from the same thoroughbred stable.

\***|Statistical Models in Epidemiology. D Clayton, M Hills. (pounds sterling30.) Oxford University …
Measuring quality of care with routine data: avoiding confusion between performance indicators and health outcomes
Authors: A. Giuffrida, H. Gravelle, M. Roland
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objective:</b> To investigate the impact of factors outside the control of primary care on performance indicators proposed as measures of the quality of primary care. <b>Design:</b> Multiple regression analysis relating admission rates standardised for age and sex for asthma, diabetes, and epilepsy to socioeconomic population characteristics and to the supply of secondary care resources. <b>Setting:</b> 90 family health services authorities in England, 1989-90 to 1994-5. <b>Results:</b> At health authority level socioeconomic characteristics, health status, and secondary care supply factors explained 45% of the variation in admission rates for asthma, 33% for diabetes, and 55% for epilepsy. When health authorities were ranked, only four of the 10 with the highest age-sex standardised admission rates for asthma in 1994-5 remained in the top 10 when allowance was made for socioeconomic characteristics, health status, and secondary care supply factors. There was also substantial year to year variation in the rates. <b>Conclusion:</b> Health outcomes should relate to crude rates of adverse events in the population. These give the best indication of the size of a health problem. Performance indicators, however, should relate to those aspects of care which can be altered by the staff whose performance is being measured. <h3>Key messages</h3> The NHS executive has proposed that admission rates for asthma, diabetes, and epilepsy could be used at health authority level as indicators of the quality of primary care There is considerable year to year variation in the ranking of health authorities by admission rates for these conditions, even when rates are aggregated. This makes it hard to interpret a single year9s data: a 3 year average would be more reliable Morbidity, socioeconomic characteristics, and secondary care supply are important confounding factors that explain between a third and a half of the variation in admission rates across health authority areas Performance indicators should relate to aspects of care that can be controlled by decision makers. Confounding factors have a clear impact on admission rates and must therefore be taken into account if such rates are to be used as performance indicators
Breast Augmentor's Arm
Authors: Melvin Westreich
Journal: JAMA (1978)

<h3>To the Editor.—</h3> Recently I have noticed hand and forearm injuries sustained by plastic surgeons who perform external capsulotomy for spherical contracture of the breast. This represents an unusual work-related injury. Spherical contracture of the breast can occur following augmentation mammoplasty using silicone implants when the capsule surrounding the implant contracts forcing the flat, supple prosthesis into a firm, hard sphere to attain the smallest surface area.<sup>1</sup>These contractures can be quite distressing and uncomfortable to the patient, and until the external capsulotomy was developed, they did not have an adequate treatment. External capsulotomy for spherical breast contracture has become a common office practice for the busy plastic surgeon. The technique and the complications seen in the patient have been well described.<sup>2</sup> Three well-established local plastic surgeons have noted fairly severe upper-extremity musculoskeletal injuries following repeated use of the procedure. None of these physicians have required surgical repair
Hairy cell leukemias with unmutated IGHV genes define the minor subset refractory to single-agent cladribine and with more aggressive behavior
Authors: Francesco Forconi, Elisa Sozzi, Emanuele Cencini, Francesco Zaja, Tamara Intermesoli, Caterina Stelitano, Luigi Rigacci, Filippo Gherlinzoni, Renato Cantaffa, Anna Baraldi, Andrea Gallamini, Alfonso Zaccaria, Alessandro Pulsoni, Marco Gobbi, Maristella Tassi, Donatella Raspadori, Lorenzo Leoncini, Andrea Rinaldi, Elena Sabattini, Francesco Bertoni, Stefano A. Pileri, Francesco Lauria
Journal: Blood (2009)