tbuckley/cabot-search huggingface dataset:
Severe Insulin-Induced Hypoglycemia Associated with Deficiencies in the Release of Counterregulatory Hormones
Authors: Guenther Boden, George A. Reichard, Robert D. Hoeldtke, Iraj Rezvani, Oliver E. Owen
Journal: New England Journal of Medicine (1981)

A FALL in blood glucose to hypoglycemic levels usually triggers a prompt release of catecholamines, glucagon, growth hormone, and cortisol. These so-called counterregulatory hormones are believed to restore blood glucose to normal concentrations by increasing hepatic glucose production (in the cases of glucagon, epinephrine, and cortisol) or by decreasing peripheral use of glucose (in the cases of epinephrine and growth hormone). The relative contributions of the individual hormones in counteracting insulin-induced hypoglycemia, however, have not been established.In this paper, we report the case of an insulin-dependent diabetic patient who was capable of synthesizing and releasing all the counterregulatory hormones . . .
AT-24 * PHASE 1/2 TRIAL OF BEVACIZUMAB PLUS TPI 287, A NOVEL BRAIN PENETRABLE ANTI-MICROTUBULE AGENT, FOR THE TREATMENT OF RECURRENT GLIOBLASTOMA
Authors: S. Goldlust, L. B. Nabors, J. P. Duic, C. Conrad, S. Silberman, S. Singer, G. Farmer
Journal: Neuro-Oncology (2014)

BACKGROUND: TPI 287, a novel anti-microtubule agent of the taxoid class that readily penetrates the blood-brain barrier, is under investigation for the treatment of recurrent glioblastoma (GBM). A dose-escalation Phase 1/2 trial was designed to determine the maximum tolerated dose (MTD) and efficacy of TPI 287 in combination with bevacizumab. Initial results from the dose escalation stage of the trial are reported here. METHODS: Patients with GBM at first relapse after standard therapy without prior exposure to anti-angiogenic agents are eligible for enrollment. Bevacizumab is administered at 10 mg/kg as an IV infusion once every 2 weeks. TPI 287 is administered as a 1-hour IV infusion every 3 weeks. Employing a standard 3 + 3 design, dose escalation of TPI 287 is planned until a dose-limiting toxicity (DLT) is observed in order to select the recommended Phase 2 dose. MRIs are obtained at the end of every six-week cycle with response assessment via RANO criteria. RESULTS: As of June 2014, a total of 9 subjects have been enrolled in the first 3 dose-escalation cohorts (140, 150, and 160 mg/m2). No DLTs have been observed to date, and no drug-related grade 3/4 adverse events have been reported. Among the 7 patients evaluable for response, 3 achieved a partial response, and 2 had stable disease (1 confirmed, 1 unconfirmed). Four of these first 9 patients remain on study 39 weeks after start of the trial. TPI 287 dose escalation continues. CONCLUSIONS: Preliminary data to date indicate that TPI 287 is safe in combination with bevacizumab for the treatment of recurrent GBM. Evolving safety and efficacy results will be presented.
Cutaneous Medicine and Surgery: An Integrated Program in Dermatology
Authors: Jeffrey B. Smith
Journal: JAMA (1996)

<b>Atlas of Cutaneous Surgery</b>, edited by June K. Robinson, Kenneth A. Arndt, Philip E. LeBoit, and Bruce U. Wintroub, 390 pp, with illus, $150, ISBN 0-7216-5404-5, Philadelphia, Pa, WB Saunders Co, 1996. <b>Cutaneous Medicine and Surgery: Self Assessment and Review</b>, edited by Jeffrey S. Dover, 324 pp, with illus, paper, $40, ISBN 0-7216-5408-8, Philadelphia, Pa, WB Saunders Co, 1996. <b>Cutaneous Medicine and Surgery: Pocket Guide</b>, edited by Jeffrey S. Dover, 763 pp, with illus, paper, $37.50, ISBN 0-7216-5409-6, Philadelphia, Pa, WB Saunders Co, 1996. In editing the new dermatology reference text<i>Cutaneous Medicine and Surgery</i>, Drs Arndt, LeBoit, Robinson, and Wintroub have delivered what is in our opinion a dermatological slam dunk. With over 280 contributing authors, most of whom are recognized authorities, this two-volume, 1900-page text is remarkably concise yet thorough in its coverage of the ever-expanding scope of dermatologic diseases. What we found most appealing is the consistent
Antithrombotic Therapy With Fondaparinux in Relation to Interventional Management Strategy in Patients With ST- and Non–ST-Segment Elevation Acute Coronary Syndromes
Authors: Shamir R. Mehta, William E. Boden, John W. Eikelboom, Marcus Flather, P. Gabriel Steg, Alvaro Avezum, Rizwan Afzal, Leopoldo S. Piegas, David P. Faxon, Petr Widimsky, Andrzej Budaj, Susan Chrolavicius, Hans-Jurgen Rupprecht, Sanjit Jolly, Christopher B. Granger, Keith A.A. Fox, Jean-Pierre Bassand, Salim Yusuf
Journal: Circulation (2008)

The Fifth and Sixth Organization to Assess Strategies in Ischemic Syndromes (OASIS 5 and 6) trials evaluated fondaparinux, a synthetic factor Xa inhibitor, in patients with non-ST- and ST-segment elevation acute coronary syndromes, respectively. Combined results for these 2 trials on major efficacy and safety outcomes and data on the effects of fondaparinux in relation to interventional management strategy have not been previously reported.We performed an individual patient-level combined analysis of 26 512 patients from the OASIS 5 and 6 trials who were randomized in a double-blind fashion to fondaparinux 2.5 mg daily or a heparin-based strategy (dose-adjusted unfractionated heparin or enoxaparin). Results were stratified according to whether an early invasive, a delayed invasive, or an initial conservative management strategy was performed. Fondaparinux was superior to heparin in reducing the composite of death, myocardial infarction, or stroke (8.0% versus 7.2%; hazard ratio [HR], 0.91; P=0.03) and death alone (4.3% versus 3.8%; HR, 0.89; P=0.05). Fondaparinux reduced major bleeding by 41% (3.4% versus 2.1%; HR, 0.59; P<0.00001) and had a more favorable net clinical outcome than heparin (11.1% versus 9.3%; HR, 0.83; P<0.0001). In 19 085 patients treated with an invasive strategy, fondaparinux suppressed ischemic events to an extent similar to heparin and reduced major bleeding by more than one-half, resulting in a superior net clinical outcome (10.8% versus 9.4%; HR, 0.87; P=0.008). A similar benefit also was observed in those treated with a conservative strategy (HR, 0.74; 95% confidence interval, 0.64 to 0.85; P<0.001).Compared with a heparin-based strategy, fondaparinux reduced mortality, ischemic events, and major bleeding across the full spectrum of acute coronary syndromes and was associated with a more favorable net clinical outcome in patients undergoing either an invasive or a conservative management strategy.
Intravenous Delivery of PTH/PTHrP Type 1 Receptor cDNA to Rats Decreases Heart Rate, Blood Pressure, Renal Tone, Renin Angiotensin System, and Stress-Induced Cardiovascular Responses
Authors: Samuel Fritsch, Veronique Lindner, Sandra Welsch, Thierry Massfelder, Michele Grima, Sylvie Rothhut, Mariette Barthelmebs, Jean-Jacques Helwig
Journal: Journal of the American Society of Nephrology (2004)

While parathyroid hormone type 1 receptor (PTH1R)-mediated vasodilatory, cardiac stimulatory, and renin-activating effects of exogenous PTH/PTH-related protein (PTHrP) are acknowledged, interactions of endogenous PTHrP with these systems remain unclear, mainly because the unavailability of viable PTHrP/PTH1R knockout mice. Transgenic mice overexpressing PTH1R in smooth muscle strongly have supported the PTHrP/PTH1R system as a cardiovascular system (CVS) regulator, but the consequences on renovascular (RVS) and renin-angiotensin systems (RAS) have not been explored in these studies. The aim was to develop a model in which one could study the consequences on CVS, RVS, and RAS of generalized PTH1R overexpression. Systemic PTH1R cDNA plasmid delivery was used in adult rats, a system that is amenable to studies in isolated perfused kidneys and that minimizes development-induced compensatory mechanisms. Intravenous administration of hPTH1R or green fluorescence protein–tagged hPTH1R in pcDNA3 resulted 3 wk later, in generalized expression of hPTH1R (mRNA and protein), especially in vessels, liver, heart, kidney, and central nervous system, where it is expressed physiologically. As expected, PTH1R overexpression decreased BP and renal tone. Unexpected, however, PTH1R overexpression decreased heart rate. These studies also revealed that endogenous PTHrP actually inhibits renin release and that hPTH1R overexpression tends to increase that effect. Striking, liver production and circulatory level of angiotensinogen and hence plasma renin activity were markedly reduced. Thus, abrupt PTH1R overexpression in adult rats profoundly alters the CVS, RVS, and RAS, strongly supporting the PTH/PTHrP/PTH1R system as crucial for heart and vascular tone regulation. In addition, these results revealed that PTH1R-mediated mechanisms might have protective effects against cardiovascular stress–induced responses, including stimulations in heart rate and RAS.
Evidence that a hemoglobin adduct used for dosimetry of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone is a carboxylic ester.
Authors: S G Carmella, S S Kagan, S S Hecht
Journal: Environmental Health Perspectives (1993)

Hemoglobin adducts of the carcinogenic tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) release 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) upon mild base or acid hydrolysis. HPB has been detected in hydrolysates of hemoglobin from smokers and snuff dippers and has been proposed as a dosimeter of exposure to and metabolic activation of NNK in people exposed to tobacco products. In this study, labeling experiments were carried out with [18O]NaOH that provide strong evidence that the globin adduct that releases HPB upon hydrolysis is a carboxylic ester. Globin was isolated from rats treated with [5-3H]NNK. This globin was reacted with NaCNBH3, followed by hydrolysis at room temperature with 0.2 N NaOH. Analysis of the products demonstrated the presence of 4-hydroxy-1-(3-pyridyl)-1-butanol, but not HPB. These results demonstrate that the adduct in globin has a free carbonyl group and is not a Schiff base. This sequence of reactions was then carried out with [18O]NaOH under conditions that were shown to result in incorporation of 18O if nucleophilic displacement at C-4 had occurred. Analysis by GC-MS of the 4-hydroxy-1-(3-pyridyl)-1-butanol formed in this experiment demonstrated that there was no incorporation of 18O. These results are consistent only with the hydrolysis of an ester by a BAC2 mechanism. Therefore, the adduct releasing HPB upon mild base hydrolysis must be a 4-(3-pyridyl)-4-oxobutyl ester of aspartate, glutamate, or a terminal carboxylate.(ABSTRACT TRUNCATED AT 250 WORDS)
Relationship of skin‐prick reactivity to aeroallergens and hyperresponsiveness to challenges with methacholine and adenosine monophosphate
Authors: Stephen J. Fowler, Brian J. Lipworth
Journal: Allergy (2003)

Background: Clarification of the relationship between atopy and bronchial hyperresponsiveness (BHR), both key features of asthma, is critical to our understanding of the disease. We therefore investigated the putative relationship between skin‐prick reactivity to aeroallergens and BHR to direct and indirect stimuli. Methods: We performed a retrospective analysis of data from 332 patients presenting with a diagnosis of asthma. Patients were characterized by skin prick tests (SPT), spirometry and bronchial challenge with methacholine and adenosine monophosphate (AMP). Results: For patients who had BHR to methacholine but not AMP, the presence of atopy was associated with a lower PD 20 (the provocative dose of methacholine producing a fall in FEV 1 of 20%), amounting to a geometric mean (95% confidence interval (CI)) of 2.3‐fold (1.4–4.0) difference. Furthermore, the number of skin‐prick positive (SPP) responses was related to methacholine reactivity: 0–1 SPP, PD 20 = 69.9 µg; 2–4 SPP, PD 20 = 47.8 µg; 5–8 SPP, PD 20 = 35.6 µg. There was a 2.0‐ fold (1.1–3.6) difference between the groups with a low (0–1 SPP) and high (5–8 SPP) degree of skin‐prick reactivity. A similar pattern was seen when data were analyzed including only perennial allergens. Spirometry was unrelated to the degree of skin‐prick reactivity. Discussion: These results suggest that skin‐prick reactivity to aeroallergens is associated with BHR to methacholine.
Associate general practitioners
Authors: L. Marshall
Journal: BMJ (1997)

The associate scheme was one positive development which came out of the controversial changes of the 1990 GP contract. It acknowledged that singlehanded practitioners in isolated areas were having difficulty in finding and affording locum cover for study leave and holidays. It also acknowledged that being on call for 24 hours a day, seven days a week for 52 weeks a year was not a satisfactory situation in the present day NHS. Advertisements for associate general practitioners are ever present in the BMJ and the rewards seem generous. So what is life really like for these associates?

The associate scheme allows the deployment of an extra doctor between two singlehanded principals, primarily in rural areas of Britain. Most of the posts are in the highlands and islands of Scotland, though there are a frew posts in the inner cities. The scheme thus allows three doctors to work for two thirds of the year each. Though this sounds comfortable, most associates work for practices where on call cover by a general practitioners' cooperative is not possible because of the isolation and distances involved: the associate and the two principals still each have a continuous on call commitment for 34 weeks of the year.

The remaining 17 weeks is taken as study leave and holiday. How this time off is arranged is flexible. Some practices will decide to work in one week blocks, in which up to six weeks of on call are matched by similarly long periods of leave. Others work a system where each doctor has a few days off each week, with increasing flexibility around holiday periods.

Associate general practitioners are employed by the principals, …
Poor accuracy and interobserver reliability of knee arthroscopy measurements are improved by the use of variable angle elongated probes
Authors: S P Oakley
Journal: Annals of the Rheumatic Diseases (2002)

(a)To determine the accuracy and reliability of arthroscopic measurements of cartilage lesion diameter in an artificial right knee model; (b) to determine whether the use of a set of variable angle elongated probes improves performance; and (c) to identify other sources of variability.Ovoid "lesions" were drawn on the five cartilage surfaces of four plastic knees models. Two observers assessed these 20 lesions arthroscopically, measuring two diameters in orientations parallel and orthogonal to the probe. Observer 1 (orthopaedic surgeon) and observer 2 (arthroscopic rheumatologist) made two sets of measurements, firstly with the conventional probe and five months later with the variable angle elongated (VAE) probes. The knees were disarticulated to determine true lesion diameter.Observer 1 had negligible bias and good accuracy regardless of orientation or probe type. Observer 2 demonstrated both bias and poor accuracy using the conventional probe. Both improved using VAE probes. Poor interobserver reliability with conventional probes also improved using VAE probes. Major sources of variability could be traced to the probe type, the characteristics of the operator, and the orientation of the lesion in relation to the probe; the lesion location itself did not cause variability.Variation in accuracy and poor interobserver reliability of measurements with conventional methods of cartilage lesion diameter measurement improved when specially designed measurement probes were used. Arthroscopic measurements performed as well as most clinical and radiographic measures. These findings have important implications for the use of arthroscopy as an outcome in multicentre trials where arthroscopists have different levels of experience.
The Food and Drug Administration and Medroxyprogesterone Acetate
Authors: Allan Rosenfield
Journal: JAMA (1983)

In 1978, the Food and Drug Administration denied approval of the three-month injectable contraceptive depot medroxyprogesterone acetate for use in the United States. This decision goes against the advice of the FDA's own scientific advisory panels, as well as the rulings of the World Health Organization and the drug regulation institutions of more than 70 developed and developing countries. In response to protest from the manufacturer of depot medroxyprogesterone acetate and from many health professionals, the FDA took the unusual step of scheduling a public board of inquiry to review its decision in January 1983. Reviewing the scientific literature on the risks and benefits of depot medroxyprogesterone acetate, we find no reason to deny depot medroxyprogesterone acetate approval, provided that studies of its possible side effects are continued and that women use it only after having made an informed choice between this and other methods of contraception. (<i>JAMA</i>1983;249:2922-2928)
OBSERVATIONS ON PROTARGIN STRONG AS A PREOPERATIVE PROPHYLACTIC
Authors: B. REESE
Journal: JAMA (1924)

At the suggestion of Dr. F. H. Verhoeff, an attempt was made to determine the effectiveness of the preparation of the eye for operation at the Massachusetts Charitable Eye and Ear Infirmary. In forty cases, cultures were taken before and after preparation. The work was done merely to find out in what measure the preparations, as carried out as a routine at this hospital, were effective. As the results may be of more than local interest, they are reported here. The routine preparation of the eye at this hospital consists of the instillation of 4 per cent. protargin strong as soon as the patient is brought to the operating room. Then a wide region surrounding the eye is painted with 2 per cent. iodin, including the eye brow and lids (the eyelashes have previously been cut) up to the lid margins. The conjunctival sac is then irrigated with saturated solution
Psychiatric status of adolescents who had extreme temperaments at age 7
Authors: M Maziade, C Caron, R Côté, C Mérette, H Bernier, B Laplante, P Boutin, J Thivierge
Journal: American Journal of Psychiatry (1990)

Two temperamentally extreme (extremely easy and extremely difficult) subgroups of children were selected at the age of 7 years from a large random sample of the general population of Quebec City. The clinical status, family functioning, IQ, and academic performance of these children were reassessed at 12 and 16 years of age. Findings suggest that extreme temperament at age 7 predicts psychiatric status in preadolescence and adolescence only when family functioning is also taken into account. The adolescents who had been temperamentally difficult children and who were living in families with dysfunctional behavior control displayed more clinical disorders.
Contraction of human hepatic stellate cells activated in culture: A role for voltage-operated calcium channels
Authors: Ramón Bataller, Josep M. Nicolás, Pere Ginès, M.Nives Görbis, Eva Garcia-Ramallo, Sergio Lario, Ester Tobías, Massimo Pinzani, Andrew P. Thomas, Vicente Arroyo, Juan Rodés
Journal: Journal of Hepatology (1998)
Estimating the risk of heart attack.
Authors: A G Shaper, M Walker
Journal: BMJ (1991)

designed specifically to examine the efficacy of the step 1 diet in free living people and provide evidence that is relevant to current guidelines.' Thompson passes no comment on these trials, citing instead the "success" of diet in an uncon- trolled trial in 23 patients attending a lipid clinic, in which serum cholesterol concentration fell by 10% over six months.Readers must judge for themselves whether this estimate of efficacy, subject as it is to the error of small numbers and regression to the mean, should be preferred to unconfounded estimates of a reduction in cholesterol concentra- tion averaging 2% (range 0-4%) from five well designed prospective controlled trials of the step 1 diet.These trials were conducted in eight countries and studied 10 647 high risk people.We believe that Thompson, as a coauthor of a set of guidelines cited in our paper,4 is unwise to dismiss so quickly the evidence we have drawn together.We agree that it is absurd to believe that hyperlipidaemia will stop being a problem if it is ignored.It is equally absurd to expect that the problem will be resolved by guidelines that are patently flawed or by widespread implementation of dietary recommendations shown repeatedly to have little effect in sound, controlled trials.If experts who take it on themselves to provide guidance for ordinary doctors are unwilling to heed the scientific evidence available it is perhaps not surprising that the lay press takes an interest in the matter.
Hypersensitivity to Cimetidine
Authors: BALDEV S. SANDHU
Journal: Annals of Internal Medicine (1982)

Letters and Corrections1 July 1982Hypersensitivity to CimetidineBALDEV S. SANDHU, M.B., CH.B., RAMIRO REQUENA, M.D.BALDEV S. SANDHU, M.B., CH.B.Search for more papers by this author, RAMIRO REQUENA, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-97-1-138_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Cimetidine (Tagamet; Smith Kline & French, Philadelphia, Pennsylvania), a specific H2 receptor antagonist, has been widely used in medical practice with remarkably few adverse reactions (1) since its introduction in 1976. In 1981, Sawyer and associates published "Cimetidine: Adverse Reactions and Acute Toxicity" (2), containing approximately 100 reports of acute Cimetidine toxicity; there was no mention of any report of type I hypersensitivity. Our review of the literature showed one previous report (3) of a type I hypersensitivity response to Cimetidine in which a 35-year-old woman developed facial edema, laryngospasm and dyspnea related to Cimetidine administration. The...References1. MCGUIGAN J. A consideration of the side effects of Cimetidine. Gastroenterology. 1981;80:181-92. CrossrefMedlineGoogle Scholar2. SAWYERCONNORSCALLEY DCR. Cimetidine: adverse reactions and acute toxicity. Am J Hosp Pharm. 1981;38:188-97. MedlineGoogle Scholar3. DELAUNOIS L. Hypersensitivity to Cimetidine [Letter]. N Engl J Med. 1979;300:1216. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The Jewish Hospital and Medical Center of Brooklyn Brooklyn, NY 11238 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDrug-induced urticariaY a-t-il des facteurs favorisant la réaction allergique, inhérents au terrain, aux médicaments, à la technique d'utilisation ? Indication du bilan prédictifY a-t-il des facteurs favorisant la réaction allergique, inhérents au terrain, aux médicaments, à la technique dˈutilisation ?Indication du bilan prédictifDrug-associated anaphylaxis: 20 years of reporting in the Netherlands (1974-1994) and review of the literatureAngioedema and Urticaria Associated With Omeprazole Confirmed by Drug RechallengeCimetidine-Associated Adverse ReactionAdverse Reactions and Interactions with H2-Receptor AntagonistsHypersensitivity to CimetidineCimetidine-Induced EosinophiliaTHE FIRST REPORT OF CIMETIDINE-INDUCED ANAPHYLAXIS IN JAPANESECimetidine-induced cutaneous vasculitisCimetidine and HypersensitivityBALDEV S. SANDHU, M.B. CH.B., RAMIRO REQUENA, M.D.Hypersensitivity to CimetidineP. GARCÍA-ORTEGA, A. CADAHÍACimetidine HypersensitivityRUSSELL B. LEFTWICH, M.D., RONALD A. SIMON, M.D. 1 July 1982Volume 97, Issue 1Page: 138-138KeywordsAdverse reactionsDyspneaEdemaHypersensitivityToxicity Issue Published: 1 July 1982 PDF downloadLoading ...