tbuckley/cabot-search huggingface dataset:
Adenosine and adenosine analogues stimulate adenosine cyclic 3', 5'-monophosphate-dependent chloride secretion in the mammalian ileum.
Authors: J W Dobbins, J P Laurenson, J N Forrest
Journal: Journal of Clinical Investigation (1984)

Adenosine receptors that modulate adenylate cyclase activity have been identified recently in a number of tissues. The purpose of these investigations was to determine the effect of adenosine on ion transport in rabbit ileum in vitro. Adenosine and some of its analogues were found to increase the short circuit current (Isc) and the order of potency was N-ethylcarboxamide-adenosine greater than or equal to 2-chloroadenosine greater than phenylisopropyladenosine greater than adenosine. Purine-intact adenosine analogues had no effect on Isc. The effect of adenosine on Isc was enhanced by deoxycoformycin, an adenosine deaminase inhibitor, and by dipyridamole, an adenosine uptake inhibitor. The increase in Isc induced by 2-chloroadenosine was partially reversed in a dose-dependent manner by 8-phenyltheophylline but not by theophylline or isobutylmethylxanthine. 2-Chloroadenosine increased cyclic AMP content, and stimulated net Cl secretion; these effects were partially blocked by 8-phenyltheophylline. These results suggest that there is an adenosine receptor on rabbit ileal mucosal cells that stimulates adenylate cyclase, which results in secondary active Cl secretion.
DYNAMICS OF KIDNEY FUNCTION FOLLOWING AORTIC VALVE REPLACEMENT USING CKD-EPI BASED GFR ESTIMATION
Authors: Marc Najjar, Halit Yerebakan, Robert Sorabella, Maliha Hossain, Catherine Wang, Hiroo Takayama, Yoshifumi Naka, Mathew Williams, Michael Argenziano, Craig Smith, Isaac George
Journal: Journal of the American College of Cardiology (2014)
Loffler's syndrome.
Authors: A Sakula
Journal: BMJ (1973)

Pre-admission Investigations SIR,-I presume that hospital case summar- ies are frequently used for research purposes and should therefore be as accurate as possible.During 20 years in general practice it has struck me as very odd that according to these summaries the patient's investigations and specific treatment nearly always start on his admission to hospital or attendance at the outpatient department.There is rarely any reference to investigations done by the gen- eral practitioner before the patient came under the care of the hospital.Yet with open access to x-ray and laboratory facilities con- siderable information may have been obtain- ed concerning the patient's illness before referral to a hospital consultant.The case summaries also give the impression that a considerable time has elapsed between the patient presenting his symptoms to the G.P. and his subsequent referral to hospital, with- out the G.P. doing anything positive.
In vivo effects of orally administered prednisolone on prostaglandin and leucotriene production in ulcerative colitis.
Authors: K Lauritsen, L S Laursen, K Bukhave, J Rask-Madsen
Journal: Gut (1987)

<h3>Abstract</h3> A tacrolimus population pharmacokinetic (PK) study with 440 subjects was performed using real world data extracted from electronic heath records (EHRs) to identify patient factors affecting variability in tacrolimus PK parameters. Using last-dose times extracted by our own natural language processing system, <i>medExtractR</i>, we assessed the effects of incorporating last-dose times in the data on tacrolimus PK parameter estimates. The estimates of population level PK parameters were Cl = 24.9 L/h [23.5, 26.3] and V = 6310 L [5461, 7159]. There was no appreciable difference in parameters estimates with <i>vs</i>. without last-dose time incorporated in the data. We also investigated the effects of absorption rate constants that are often fixed at a published value in tacrolimus population PK analysis. Our sensitivity analysis revealed little difference between parameters estimated assuming a range of absorption rate constants.
Strict product liability arrives: implications for doctors
Authors: C. Dyer
Journal: BMJ (1988)

Strict product liability becomes a reality in the United Kingdom next week, when part I of the Consumer Protection Act 1987 comes into force on 1 March. Yet little guidance has so far emerged on what the new r?gime will mean for doctors, and most doctors probably assume it will have little effect on their practices. Representatives of the BMA's General Medical Services Committee and the department of health are discussing the matter with a view to issuing guidance to general practitioners, and the Central Committee for Hospital Medical Services is pursuing the question of guidance for hospital doctors. In fact, the act will impose a considerable burden of record keeping on doctors if they are not to find themselves legally liable for the supply of a defective drug or other medical product. The act makes producers of defective products liable without the need to prove negligence, but suppliers will also become liable unless they can identify the producer. Not only dispensing general practitioners will become suppliers but also any doctors who give patients drugs or appliances from their bags or consulting rooms. In the case of items supplied by doctors in hospitals the health authority will be the supplier. Doctors and health authorities will therefore need to keep full records identifying the source of every item supplied, and records will need to be preserved for 10 years, the cut off point for taking legal action; draft guidelines from the BMA suggest that this may well have to include the cat gut used in operations. Doctors fitting  contraceptive devices, for instance, must keep a note of the brand fitted. The litigation over the Dalkon Shield has shown that in the 1970s when the shield was popular, many doctors simply wrote intrauterine contraceptive  without identifying the type. Doctors who cannot identify the supplier of a device fitted after 1 March could be liable in subsequent litigation. Doctors could also become strictly liable as producers if they mix their own medicines or modify drugs or appliances before supplying them to the patient. The Pharmaceutical Society of Great Britain has issued guidelines for pharmacists that dispensing doctors would also do well to follow. The society suggests that when making bulk quantities of medicine for sale as a nostrum or for subsequent dispensing records should be kept of the suppliers, batch numbers, dates received, and dates issued. A BMA internal memorandum has raised the question of doctors who introduce additives into intravenous fusions, which is common practice in operating theatres and intensive care units. Under the act it seems that they could be considered producers.
Abstract 1510: Improving replication kinetics by using a single shRNA p21/Waf-1 construct in backbone of prostate specific CRAd
Authors: Naser U. Hoti, Sadaf Mustafa, Wasim Chowdhury, Tamara Johnson, Shawn E. Lupold, Ronald Rodriguez
Journal: Cancer Research (2010)

Abstract Conditionally replicating adenoviruses (CRAds) represent a promising modality for the treatment of neoplastic diseases, including Prostate Cancer. Selectively replicative viruses can be generated by placing a tissue or cancer-specific promoter upstream of one or more of the viral genes required for replication (e.g., E1A, E1B). We have previously reported the attenuated replication of these viruses by multiple cellular mechanisms. In this study we investigated the importance of p21/Waf-1, a cdk inhibitor on viral replication and tumor growth. Using RNA interference against p21/Waf-1 in prostate cancer cells we demonstrated an increase viral replication and viral oncolysis of the prostate cancer cells. Similarly CRAd viruses that carry p21/Waf-1 shRNA (Ad5-RV004.21) were able to prevent tumor outgrowth by inhibiting growth of established tumor xenografts that resulted in a marked increase in the mean survival time of tumor-bearing mice compared to CRAd with out p21/Waf-1shRNA (Ad5-RV004) or mock treated control groups. Furthermore in combinatory studies of Ad5-RV004.21 with Adriamycin a supra-additive effect was observed only in CRAds viruses that harbor shRNA against p21/Waf-1. Taken together these findings of enhance viral replication in prostate cancer cells by using RNA interference against the cdk inhibitor (p21/Waf-1) have significant implications in the development of prostate-specific CRAd therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1510.
Bone changes and their significance in children with ichthyosis on long-term etretinate therapy
Authors: D.G. PAIGE, M.R. JUDGE, D.G. SHAW, D.J. ATHERTON, J.I. HARPER
Journal: British Journal of Dermatology (1992)

Anxiety about the use of etretinate in children has been provoked by several reports describing skeletal abnormalities during long-term therapy. However, we have observed no evidence of skeletal toxicity in 42 children treated over an 11-year period. Radiological screening before and during treatment has failed to reveal abnormalities that would influence our decision to commence or to continue etretinate administration. We recommend that children who are to be treated with etretinate should have a baseline selective skeletal survey, with follow-up radiology restricted to those with pretreatment radiological abnormalities and those who develop musculo-skeletal symptoms. In addition we advise that dosage should not exceed 1 mg/kg/day. If these guidelines are followed, we believe that long-term therapy with etretinate can be given to children, with an acceptable margin of safety.
Chronic vitamin C supplementation improves endothelial function in diabetic patients with coronary artery disease
Authors: Charalambos Antoniades, Dimitris Tousoulis, Costas Tentolouris, Kyriakoula Marinou, Athanasios Trikas, Stella Brilli, Christos Pitsavos, Christodoulos Stefanadis, Pavlos Toutouzas
Journal: Journal of the American College of Cardiology (2002)
Air Pollution and Incidence of Hypertension and Diabetes Mellitus in Black Women Living in Los Angeles
Authors: Patricia F. Coogan, Laura F. White, Michael Jerrett, Robert D. Brook, Jason G. Su, Edmund Seto, Richard Burnett, Julie R. Palmer, Lynn Rosenberg
Journal: Circulation (2012)

Background— Evidence suggests that longer-term exposure to air pollutants over years confers higher risks of cardiovascular morbidity and mortality than shorter-term exposure. One explanation is that the cumulative adverse effects that develop over longer durations lead to the genesis of chronic disease. Preliminary epidemiological and clinical evidence suggests that air pollution may contribute to the development of hypertension and type 2 diabetes mellitus. Methods and Results— We used Cox proportional hazards models to assess incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for incident hypertension and diabetes mellitus associated with exposure to fine particulate matter (PM 2.5 ) and nitrogen oxides in a cohort of black women living in Los Angeles. Pollutant levels were estimated at participants' residential addresses with land use regression models (nitrogen oxides) and interpolation from monitoring station measurements (PM 2.5 ). Over follow-up from 1995 to 2005, 531 incident cases of hypertension and 183 incident cases of diabetes mellitus occurred. When pollutants were analyzed separately, the IRR for hypertension for a 10-μg/m 3 increase in PM 2.5 was 1.48 (95% CI, 0.95–2.31), and the IRR for the interquartile range (12.4 parts per billion) of nitrogen oxides was 1.14 (95% CI, 1.03–1.25). The corresponding IRRs for diabetes mellitus were 1.63 (95% CI, 0.78–3.44) and 1.25 (95% CI, 1.07–1.46). When both pollutants were included in the same model, the IRRs for PM 2.5 were attenuated and the IRRs for nitrogen oxides were essentially unchanged for both outcomes. Conclusion— Our results suggest that exposure to air pollutants, especially traffic-related pollutants, may increase the risk of type 2 diabetes mellitus and possibly of hypertension.
Preliminary observations of chondral abrasion in a canine model.
Authors: R D Altman, J Kates, L E Chun, D D Dean, D Eyre
Journal: Annals of the Rheumatic Diseases (1992)

Articular cartilage repair was followed for one year in skeletally mature dogs after destabilisation by anterior cruciate ligament transection of the stifle joint (CT), abrasion of the inferior medial condyle (ABR) to bleeding bone, or anterior cruciate transection followed by chondral abrasion (CT/ABR). ABR animals formed repair cartilage at the abrasion site (ABR and CT/ABR) at six months as determined by arthroscopy and at necropsy. CT and CT/ABR animals had an additional cartilage ulcer on the superior aspect of the medial condyle. The abraded site extended in CT/ABR condyles. Repair cartilage (ABR and CT/ABR) contained reduced amounts of proteoglycan as seen by histological loss of safranin O staining and reduced uronic acid content. Fibrocartilage was suggested by histological appearance, hypocellularity, and a higher hydroxyproline content. In contrast with ABR animals, the repair cartilage in the CT/ABR animals contained near normal amounts of hydroxyproline. Collagen profiles of abrasion site repair cartilage in ABR animals had more types I and V collagens, similar amounts of type VI collagen, and decreased amounts of types II, IX, and XI collagens than CT/ABR animals. The results of this study are consistent with abrasion chondroplasty leading to a repair cartilage. Despite extended ulcers, repair cartilage from the destabilised joint (CT/ABR) animals was more hyaline-like in its hydroxyproline content and collagen composition than repair cartilage from the stable joint (ABR animals). In these models additional measures appear to be needed as the defects induced by abrasion chondroplasty did not form a functional hyaline cartilage.
Reversible Complete Heart Block following Cardiac Surgery
Authors: PAGE A. W. ANDERSON, MARK C. ROGERS, RAMON V. CANENT, JAY M. M. JARMAKANI, PAUL H. JEWETT, MADISON S. SPACH
Journal: Circulation (1972)

His bundle electrograms were recorded before and throughout the postoperative course in two children who developed temporary complete heart block after surgical correction for tetralogy of Fallot. In one the complete heart block was associated with prolonged duration of the QRS complex, and in the other there was no prolongation of the QRS complex. His bundle electrograms in the patient with widened QRS identified the site of block to be between the low atrium and the His bundle, and in the patient with a QRS of normal duration the block was distal to the His bundle. Complete heart block disappeared within 3 weeks in both patients. Subsequent His bundle studies showed normal A-V conduction in the first patient except for the presence of persistent complete right bundle-branch block. In the other, prolongation of the P-R interval was persistent, and atrial pacing at high rates produced a Wenckebach type of block distal to the His bundle. These studies indicate that electrophysiologically the site of complete heart block following definitive intracardiac surgery can occur at multiple sites. Furthermore, in complete heart block the site of the pacemaker may not be accurately predicted from routine electrocardiograms alone, and His bundle recordings may be necessary to clarify this site.
Vasoactive Drugs in Circulatory Shock
Authors: Steven M. Hollenberg
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Shock occurs when failure of the cardiovascular system compromises tissue perfusion. When fluid administration fails to restore adequate arterial pressure and organ perfusion in patients with shock, therapy with vasoactive agents should be initiated. The key to selecting among vasoactive agents is to make the choice in the context of the goals of therapy. The ultimate goals of hemodynamic therapy in shock are to restore effective tissue perfusion and to normalize cellular metabolism. The clinician needs to consider ways of achieving those goals and the mechanisms of action of potential therapies. Armed with this knowledge, it becomes easier to match the mechanism of action of a particular agent to the goals of therapy. When this is done, differences among various agents are seen primarily as differences in mechanisms of action, and discussions about which agent is "best" are transformed into consideration of which agent is best suited to implement the therapeutic strategy that has been selected in a given clinical context. Despite the complex pathophysiology of shock, use of vasoactive agents for hemodynamic support of patients with shock can be guided by an underlying approach in which clinicians define specific goals and end points, titrate therapies to those end points, and evaluate the results of their interventions on an ongoing basis.
Diflunisal. A new oral analgesic with an unusually long duration of action
Authors: J. A. Forbes
Journal: JAMA (1982)

The analgesic efficacy of single 500- and 1,000-mg doses of diflunisal (Dolobid), a new nonsteroidal anti-inflammatory analgesic, was compared in a double-blind study with that of acetaminophen, 600 mg, the combination of acetaminophen, 600 mg, with codeine phosphate, 60 mg, and placebo in 159 oral surgery outpatients. Using a self-rating record, patients rated their pain and its relief hourly for 12 hours after medication. Both doses of diflunisal were significantly more effective than acetaminophen alone and produced peak analgesia comparable to that of the acetaminophen-codeine combination. Diflunisal proved to have an unusually long duration of analgesic action. Acetaminophen and the combination were significantly superior to placebo through hours 2 and 5, respectively; both doses of diflunisal were significantly superior through the end of the 12-hour observation period. None of the active treatments produced more side effects than the placebo.
Pharmaceutical Desktop References
Authors: Mark A. LaPorta
Journal: Annals of Internal Medicine (1994)

Letters1 May 1994Pharmaceutical Desktop ReferencesMark A. LaPorta, MDMark A. LaPorta, MDGateway Healthcare; Miami Beach, FL 33141Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-120-9-199405010-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Several compendia can be added to the six pharmaceutical desktop references described by Dr. Day [1]. Widely available and distributed for free through drug company mailing lists is the Physician's Compendium of Drug Therapy (Compendium Publications Group, Secaucus, New Jersey). Its organization and general usefulness are most similar to Facts and Comparisons, but the drug descriptions are short.For physicians who frequently examine and treat travellers from abroad, two books besides Martindale: The Extra Pharmacopoeia are useful. The Index Nomina is also known as the International Drug Directory (Medpharm Publishers, Stutgart, Germany, 1990, available through Drug Intelligence, ...REFERENCE1. Day RP. Desktop drug information. Ann Intern Med. 1993; 119:936-8. Google Scholar Author, Article, and Disclosure InformationAffiliations: Gateway Healthcare; Miami Beach, FL 33141 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1994Volume 120, Issue 9Page: 813-814KeywordsDrug therapyDrugsIntelligenceLibraries Issue Published: 1 May 1994 CopyrightCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Quantifying the Need for Hospital Beds
Authors: Errol C. Schneer, Jonathan E. Fielding
Journal: New England Journal of Medicine (1977)

The ability of hospitals to renovate and expand physical capacity and to develop new services is subject to state-conducted certificate-of-need programs as mandated by the National Health Planning and Resources Development Act of 1974 (P.L. 93–641). In Massachusetts, the Determination of Need statute of 1971 placed responsibility for this program in the Department of Public Health and granted it approval power over capital expenditures of $100,000 or more for a new structure or for an addition to, or alteration of, an existing health-care facility, the addition of four or more beds and any major change in services of all health . . .
Off-label marketing: free speech or illegal promotion?
Authors: E. Silverman
Journal: BMJ (2013)

A recent study showed that p11 expressed in cholinergic interneurons (CINs) of the nucleus accumbens (NAc) is a key regulator of depression-like behaviors. Dopaminergic neurons projecting to the NAc are responsible for reward-related behaviors, and their function is impaired in depression. The present study investigated the role of p11 in NAc CINs in dopamine responses to rewarding stimuli. The extracellular dopamine and acetylcholine (ACh) levels in the NAc were determined in freely moving male mice using <i>in vivo</i> microdialysis. Rewarding stimuli (cocaine, palatable food, and female mouse encounter) induced an increase in dopamine efflux in the NAc of wild-type (WT) mice. The dopamine responses were attenuated (cocaine) or abolished (food and female mouse encounter) in constitutive p11 knock-out (KO) mice. The dopamine response to cocaine was accompanied by an increase in ACh NAc efflux, whereas the attenuated dopamine response to cocaine in p11 KO mice was restored by activation of nicotinic or muscarinic ACh receptors in the NAc. Dopamine responses to rewarding stimuli and ACh release in the NAc were attenuated in mice with deletion of p11 from cholinergic neurons (ChAT-p11 cKO mice), whereas gene delivery of p11 to CINs restored the dopamine responses. Furthermore, chemogenetic studies revealed that p11 is required for activation of CINs in response to rewarding stimuli. Thus, p11 in NAc CINs plays a critical role in activating these neurons to mediate dopamine responses to rewarding stimuli. The dysregulation of mesolimbic dopamine system by dysfunction of p11 in NAc CINs may be involved in pathogenesis of depressive states.
Use of a Long-acting Inhaled β<sub>2</sub>-Adrenergic Agonist, Salmeterol Xinafoate, in Patients with Chronic Obstructive Pulmonary Disease
Authors: STEPHEN I. RENNARD, WAYNE ANDERSON, RICHARD ZuWALLACK, JOSEPH BROUGHTON, WILLIAM BAILEY, MITCHELL FRIEDMAN, MICHAEL WISNIEWSKI, KATHLEEN RICKARD
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Chronic obstructive pulmonary disease (COPD) is a condition in which continuous bronchodilation may have clinical advantages. This study evaluated salmeterol, a β -agonist bronchodilator with a duration of action substantially longer than that of short-acting β -agonists, compared with ipratropium, an anticholinergic bronchodilator, and placebo in patients with COPD. Four hundred and five patients with COPD received either salmeterol 42 μ g twice daily, ipratropium bromide 36 μ g four times daily, or placebo for 12 wk in this randomized, double-blind, parallel-group study. Patients were stratified on the basis of bronchodilator response to albuterol ( > 12% and > 200-ml improvement) and were randomized within each stratum. Bronchodilator response was measured over 12 h four times during the treatment period. Salmeterol provided similar maximal bronchodilatation to ipratropium but had a longer duration of action and a more constant bronchodilatory effect with no evidence of bronchodilator tolerance. Both active treatments were well tolerated. Salmeterol was an effective bronchodilator with a consistent effect over this 12-wk study in patients with COPD, including those “unresponsive” to albuterol. The long duration of action of salmeterol offers the advantage of twice daily dosing compared with the required four times a day dosing with ipratropium.