tbuckley/cabot-search huggingface dataset:
Glutathione redox pathway and reperfusion injury. Effect of N-acetylcysteine on infarct size and ventricular function.
Authors: M B Forman, D W Puett, C U Cates, D E McCroskey, J K Beckman, H L Greene, R Virmani
Journal: Circulation (1988)

Glutathione peroxidase is an important enzyme in the degradative cascade of reactive oxygen free radicals. N-Acetylcysteine (NAC) is a low molecular weight compound that has been used clinically to replenish glutathione. To assess the role of the glutathione redox pathway on reperfusion injury, 23 animals underwent 90 minutes of proximal left anterior descending coronary artery occlusion followed by 24 hours of reperfusion with the administration of NAC (n = 11) or saline (n = 12) beginning 30 minutes into occlusion and continuing for 3 hours after reperfusion. Regional ventricular function was measured with contrast ventriculography, and regional myocardial blood flow was determined with microspheres. At 24 hours, the area at risk was defined in vivo with Monastral Blue, and the area of necrosis was defined by incubation in triphenyltetrazolium. Biopsies were taken from the ischemic and nonischemic zones to determine levels of total glutathione, superoxide dismutase and glutathione peroxidase activity, and reactivity to thiobarbituric acid, an index of lipid peroxidation. The rate-pressure product and myocardial blood flow were similar in the two groups throughout the study. No significant differences were noted in infarct size expressed as a percentage of the area at risk (28.6 +/- 5.3% vs. 36.6 +/- 6.0%) and of the total left ventricle (14.4 +/- 3.2% vs. 16.5 +/- 3.1%), and no differences were noted between the two groups on examination of the ischemic subendocardium by light and electron microscopy. Both groups exhibited similar degrees of dyskinesis during occlusion; however, treated animals showed significant improvement in regional radial shortening at 3 hours (3.4 +/- 2.4% vs. -2.4 +/- 2.1%, p less than 0.02) and 24 hours (9.2 +/- 2.2% vs. -2.5 +/- 6.3%, p less than 0.001) after reperfusion. No differences were present in total glutathione, thiobarbituric acid reactivity, or superoxide dismutase and glutathione peroxidase activity in the ischemic zones of the two groups. This study suggests that N-acetylcysteine treatment before reperfusion may reduce myocardial stunning but does not limit myocyte death after reperfusion.
Acute hemodynamic effects of pacing therapy on left ventricular function in patients with heart failure and atrial fibrillation: Comparison of left ventricular pacing and biventricular pacing
Authors: Taro Okada, Yukihiko Yoshida, Makoto Kondo, Kosuke Watanabe, Masahiro Mutoh, Takumi Yamada, Tomomitsu Tani, Shoji Yamakami, Kazuki Iwata, Yoshimasa Murakami, Toyoaki Matsushita, Mitsuhiro Okamoto, Naoya Tsuboi, Haruo Hirayama, Teruo Itoh, Junji Toyama
Journal: Journal of the American College of Cardiology (2003)
Brazil's Family Health Programme
Authors: M. Harris, A. Haines
Journal: BMJ (2010)

A cost effective success that higher income countries could learn from

Healthcare reforms in Brazil began in 1988 as part of a broader sociopolitical movement at the end of nearly 20 years of military rule. The new constitution was underpinned by principles of budgetary and political decentralisation, community participation in local budget setting, and the acknowledgment that health and access to health care is a universal human right. This laid the foundation for the Sistema Unico de Saude , or Unified Health System, and began a nationwide shift from tertiary centre based health care to comprehensive primary health care, free at the point of use, funded by the taxpayer, and inspired by the Alma-Ata Declaration of 1978.

Over the past 15 years progress in Brazilian public health has been remarkable. Infant mortality has dropped from 48 per 1000 to 17 per 1000. In just the past five years, hospital admissions due to diabetes or stroke have decreased by 25%, the proportion of children under 5 years old who are underweight has fallen by 67%, over 75% of women now receive seven or more antenatal consultations, and diphtheria, tetanus, and pertussis (DTP) vaccine coverage in children less than 1 year old is greater than 95% in most municipalities. …
Proton beam therapy: more than a leap of faith?
Authors: J. Gornall
Journal: BMJ (2012)

Excess deposition of proteoglycans (PGs) has been described in the subepithelial layer of the asthmatic airway wall. However, less is known about deposition in the airway smooth muscle (ASM) layer, and whether the pattern of deposition is altered depending upon disease severity. Endobronchial biopsies were performed in patients with severe or moderate asthma (defined using American Thoracic Society criteria) and in control subjects. Biopsies were immunostained for the PGs biglycan, lumican, versican and decorin. PG deposition was measured in the subepithelial and ASM layers, the former by calculating the area of positive staining, and the latter by determining the percentage area stained using point counting. Immunostaining for PGs was prominent in biopsies from both moderate and severe asthmatics, compared with control subjects. While there was no difference in the amount of PG in the subepithelial layer between the two asthmatic groups, the percentage area of biglycan and lumican staining in the ASM layer was significantly greater in moderate <i>versus</i> severe asthmatics. Differences in the deposition of proteoglycans within the airway smooth muscle layer of moderate <i>versus</i> severe asthmatics potentially impact on the functional behaviour of the airway smooth muscle in these two groups of patients.
UK operating theatre practitioners seek regulation
Authors: R. Dobson
Journal: BMJ (1999)

Measures to increase the regulation of the United Kingdom's 8000 operating theatre practitioners were introduced in a 10 minute rule bill due to be read in the House of Commons as the BMJ went to press.

The bill highlighted what were described as “the on-going risks to patients created by the lack of statutory registration and regulation.” The Association of Operating Department Practitioners, which currently operates a voluntary register, has been trying for more than 10 years to get formal regulation introduced …
OTITIS MEDIA COMPLICATING OPERATIONS ON THE GASSERIAN GANGLION
Authors: HORACE R. LYONS
Journal: JAMA (1923)

Otitis media complicating operations on the gasserian ganglion was first observed in the Mayo Clinic about three years ago, in a patient who complained of a sense of fulness and deafness following section of the posterior root of the gasserian ganglion for trifacial neuralgia. Since then, such observations have been made several times. This type of otitis media occurs from a few days to several weeks after operation on the gasserian ganglion. The chief complaint is a sense of fulness and deafness on the side on which the operation is performed. Otalgia is never severe, and is not a common complaint. Examination of the ears discloses a fulness in the inferior quadrants of the tympanic membrane, with more or less obliteration of the common landmarks. There is usually a fluid level, and a bubbling sound is heard with inflation of the eustachian tube. Two patients said that they had "water
Efficacy and Safety of Alirocumab in Reducing Lipids and Cardiovascular Events
Authors: Jennifer G. Robinson, Michel Farnier, Michel Krempf, Jean Bergeron, Gérald Luc, Maurizio Averna, Erik S. Stroes, Gisle Langslet, Frederick J. Raal, Mahfouz El Shahawy, Michael J. Koren, Norman E. Lepor, Christelle Lorenzato, Robert Pordy, Umesh Chaudhari, John J.P. Kastelein
Journal: New England Journal of Medicine (2015)

Alirocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9), has been shown to reduce low-density lipoprotein (LDL) cholesterol levels in patients who are receiving statin therapy. Larger and longer-term studies are needed to establish safety and efficacy.We conducted a randomized trial involving 2341 patients at high risk for cardiovascular events who had LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or more and were receiving treatment with statins at the maximum tolerated dose (the highest dose associated with an acceptable side-effect profile), with or without other lipid-lowering therapy. Patients were randomly assigned in a 2:1 ratio to receive alirocumab (150 mg) or placebo as a 1-ml subcutaneous injection every 2 weeks for 78 weeks. The primary efficacy end point was the percentage change in calculated LDL cholesterol level from baseline to week 24.At week 24, the difference between the alirocumab and placebo groups in the mean percentage change from baseline in calculated LDL cholesterol level was -62 percentage points (P<0.001); the treatment effect remained consistent over a period of 78 weeks. The alirocumab group, as compared with the placebo group, had higher rates of injection-site reactions (5.9% vs. 4.2%), myalgia (5.4% vs. 2.9%), neurocognitive events (1.2% vs. 0.5%), and ophthalmologic events (2.9% vs. 1.9%). In a post hoc analysis, the rate of major adverse cardiovascular events (death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization) was lower with alirocumab than with placebo (1.7% vs. 3.3%; hazard ratio, 0.52; 95% confidence interval, 0.31 to 0.90; nominal P=0.02).Over a period of 78 weeks, alirocumab, when added to statin therapy at the maximum tolerated dose, significantly reduced LDL cholesterol levels. In a post hoc analysis, there was evidence of a reduction in the rate of cardiovascular events with alirocumab. (Funded by Sanofi and Regeneron Pharmaceuticals; ODYSSEY LONG TERM ClinicalTrials.gov number, NCT01507831.).
Abstract 5376: Systematic analysis of peptide linker length and liposomal polyethylene glycol coating on cellular uptake of peptide-targeted liposomal nanoparticles
Authors: Jared Stefanick, Jonathan Ashley, Tanyel Kiziltepe, Basar Bilgicer
Journal: Cancer Research (2014)

Abstract In an effort to improve tumor targeting and cellular uptake of nanoparticle-based drug carriers, nanoparticles are functionalized with active targeting molecules such as antibodies, antibody fragments, small ligands, and peptides. However, active targeting approaches have not consistently shown successful outcomes. Nanoparticle design factors including: traditional methods of generating active targeting nanoparticles, PEG coatings, linkers used to conjugate targeting ligands, and various types of targeting ligands used further contribute to the inconsistencies observed with targeted nanoparticle therapies. In order to dissect the individual effects of these parameters, we employed a multifaceted synthetic strategy to prepare peptide-targeted liposomal nanoparticles with high purity, reproducibility, and precisely controlled stoichiometry of functionalities to evaluate the role of liposomal PEG coating, peptide EG-linker length, and peptide valency on cellular uptake in a systematic manner. We analyzed these parameters in two distinct disease models where the liposomes were functionalized with either HER2- or VLA-4-antagonistic peptides to target HER2-overexpressing breast cancer cells or VLA-4-overexpressing myeloma cells, respectively. When targeting peptides were tethered to nanoparticles with an EG45 (∼PEG2000) linker in a manner similar to a more traditional formulation, their cellular uptake was not enhanced compared to non-targeted versions regardless of the liposomal PEG coating used. Conversely, reduction of the liposomal PEG to PEG350 and the peptide linker to EG12 dramatically enhanced cellular uptake by ∼9-fold in breast cancer cells, while an EG6 peptide linker enhanced cellular uptake by ∼150-fold in multiple myeloma cells. Uptake efficiency is highly dependent on peptide valency, reaching a maximum and a plateau with ∼2% peptide density in the breast cancer model. Taken together, these results demonstrate the significance of using the right design elements such as the appropriate peptide EG-linker length in coordination with the appropriate liposomal PEG coating and optimal ligand density in efficient cellular uptake of liposomal nanoparticles. Citation Format: Jared Stefanick, Jonathan Ashley, Tanyel Kiziltepe, Basar Bilgicer. Systematic analysis of peptide linker length and liposomal polyethylene glycol coating on cellular uptake of peptide-targeted liposomal nanoparticles. [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 5376. doi:10.1158/1538-7445.AM2014-5376
Age based discrimination in health and social care services
Authors: D. Oliver
Journal: BMJ (2009)

Will be against the law if the 2009 equality bill is enacted

The 2009 Equality Bill will, if enacted, make age based discrimination in the provision of health care and social care illegal for the first time in the United Kingdom. In a speech in 2008, the then health secretary, Alan Johnson, said, “Old age is the new middle age. Health and social care services need to adapt to the changing needs of today’s older people . . . to promote health in old age and help older people to maintain independence and quality of life.”1 People over 65 already account for more than 60% of hospital bed days and most expenditure on health and social care. In 2007 there were 8.2 million people aged over 65 in England and Wales, but this is projected to increase to 11.6 million by 2026—an increase of 46%—with similar projected rises in the prevalence of disability and dependency.2 Core users of health care will continue to be older people, many of whom will be frail, have long term conditions, and rely on support from social services or informal carers. A demographic shift in the ratio of retired to working people and multiple competing demands on health services and local government make …
Abnormal Pulmonary Function in Adults with Sickle Cell Anemia
Authors: Elizabeth S. Klings, Diego F. Wyszynski, Vikki G. Nolan, Martin H. Steinberg
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Pulmonary complications of sickle cell anemia (Hb-SS) commonly cause morbidity, yet few large studies of pulmonary function tests (PFTs) in this population have been reported.PFTs (spirometry, lung volumes, and diffusion capacity for carbon monoxide [DLCO]) from 310 adults with Hb-SS were analyzed to determine the pattern of pulmonary dysfunction and their association with other systemic complications of sickle cell disease.Raw PFT data were compared with predicted values. Each subject was subclassified into one of five groups: obstructive physiology, restrictive physiology, mixed obstructive/restrictive physiology, isolated low DLCO, or normal. The association between laboratory data of patients with decreased DLCO or restrictive physiology and those of normal subjects was assessed by multivariate linear regression.Normal PFTs were present in only 31 of 310 (10%) patients. Overall, adults with Hb-SS were characterized by decreased total lung capacities (70.2 +/- 14.7% predicted) and DLCO (64.5 +/- 19.9%). The most common PFT patterns were restrictive physiology (74%) and isolated low DLCO (13%). Decreased DLCO was associated with thrombocytosis (p = 0.05), with hepatic dysfunction (elevated alanine aminotransferase; p = 0.07), and a trend toward renal dysfunction (elevated blood urea nitrogen and creatinine; p = 0.05 and 0.07, respectively).Pulmonary function is abnormal in 90% of adult patients with Hb-SS. Common abnormalities include restrictive physiology and decreased DLCO. Decreased DLCO may indicate more severe sickle vasculopathy characterized by impaired hepatic and renal function.
Macrophage component gp160, a major trypsin-sensitive surface glycoprotein.
Authors: E Remold-O'Donnell
Journal: The Journal of Experimental Medicine (1980)

Macrophages secrete a large number of proteases, implying in vivo exposure of the cell surface to proteolytic conditions. Mild trypsin treatment of 125I-labeled guinea pig peritoneal macrophages preferentially cleaves one surface component of apparent 160,000 mol wt. Similar trypsin treatment of macrophages with 3H-labeled carbohydrate surface moieties also cleaves a single 3H-labeled 160,000 mol wt glycoprotein, referred to as gp160. Nonreducing sodium dodecyl sulfate (SDS)-electrophoresis established that gp160 of trypsinized cells remains assembled in the membrane as a multichain disulfide-bonded molecule. gp160 was purified by detergent extraction, L. culinaris lectin affinity chromatography and DEAE-cellulose chromatography. The corresponding molecule from trypsinized cells was purified by the same procedure. Reducing SDS-electrophoresis of purified trypsinized 125I-labeled gp160 revealed two proteolytic fragments with apparent molecular weights of 85,000 and 71,000. Thus, mild trypsin treatment of macrophages preferentially cleaves a single surface protein, possibly at a single site. Because the two fragments of gp160 are accessible to lactoperoxidase and trypsin, both must be exposed on the membrane surface. The reactive carbohydrate site was found on the 85,000 mol wt fragment, which alone contains the 3H-label introduced into intact cells by neuraminidase, galactose, oxidase, and [3H]KBH4.
Effects of angiographic contrast media on sino-atrial nodal function
Authors: C. W. WHITE, D. L. ECKBERG, T. INASAKA, F. M. ABBOUD
Journal: Cardiovascular Research (1976)

Injection of meglumine diatrizoate (Renografin-76) into the selectively perfused sinus node artery of the dog produces bradycardia which is unaltered by autonomic blockade or by changes in sinus node artery pressure. Contrast agents and other hyperosmolar substances prolong the R-R interval in proportion to their osmolarity. Selective injection of contrast media into other cannulated segments of the coronary tree produces no change in heart rate. Transfemoral arteriography, however, produces bradycardia with both right and left coronary injections. Both direct and reflex sinus node depression occur with coronary arteriography in the dog. Direct effects are mediated by hyperosmolarity.
Diagnosis and Management of Genitourinary Cancer
Authors: Hugh A. G. Fisher
Journal: JAMA (1988)

This well-written text is highly recommended as a valuable reference source for use by any physician involved in the clinical care of genitourinary cancer patients, including the urologic surgeon, medical oncologist, internist, pathologist, radiologist, and radiotherapist. Each chapter is concise, well organized, and readable, with minimal overlap of subject material, enabling the editors to include a wealth of information usually available only in multivolume works or separate texts. Historical perspective, current standards of care, and future research initiatives are adequately summarized for all disease sites. The text is divided into four parts: "Basic Science Concepts of Neoplasia," "Epidemiology," "Pathology," and "Diagnosis and Therapy." Although diagnosis and management of genitourinary cancers is emphasized, the sections on epidemiology and pathology are complete, informative, and well organized for quick reference. The majority of the text is devoted to the most common genitourinary neoplasms arising from bladder, kidney, testis, and prostate, but rarer tumors,
A CASE OF ANEURYSM IN A WOMAN
Authors: H. G. Frean
Journal: BMJ (1910)

Miss H., aged 36, was first brought to the Kent County Ophthalmic Hospital on October 23rd, 1909, not on her own initiative, as she regarded her case as hopeless, but by one of my old cataract patients, who had recently undergone a successful operation, and naturally took an interest in the afflicted woman.Prev,ious History.The patient's father was born blind, and was operated upon as a baby by the late Mr. Woolcott at the Kent County Oph- thalmic Hospital.She has a brother, aged 34, who was operated upon at the Moorfields Hospital when 3 years old for cataract.Another brother and three sisters, who are all younger than her-
IMPAIRED RESPONSES OF GROWTH HORMONE AND BLOOD EOSINOPHILS TO L‐DOPA IN ATOPY
Authors: ANDRZEJ SZEZKLIK, JACEK SIERADZKI, MARIA SERWOŃASKA, ZYGMUNT PODOLEC
Journal: Allergy (1977)

In order to assess whether response to the natural precursor of catecholamines in the nervous system is impaired in atopy, 500 mg L-dopa was administered to 13 atopic patients with bronchial asthma or hay fever and 13 sex-and-age-matched control subjects. The blood eosinophil count and growth hormone (GH) levels were then determined periodically over a 4-h period. The eosinophil count rose significantly 30 and 60 min after L-dopa in healthy subjects, but not in the atopic patients. The mean rise in GH 30 and 60 min after L-dopa was significantly lower in atopic patients as compared with controls. Injection of apomorphine 0.75 mg elicited increase in GH in nine of the 10 control subjects, but only in six of the 11 atopic patients. These results indicate that central dopaminergic stimulation is often impaired in patients with atopy. In testing GH release, atopy should be considered among the causes of failure to respond.
Diabetes Insipidus and Complicated Pregnancy
Authors: James W. Campbell
Journal: JAMA (1980)

DIABETES insipidus is a rare disease. Its coexistence with pregnancy has been reported rarely. In only a few previous cases has preeclampsia been added to the clinical picture. <h3>Report of a Case</h3> A 24-year-old woman, gravida 1, para 0, was admitted at 38 weeks' gestation because of impending toxemia. Her last menstrual period had begun on Jan 10, 1977, and her expected delivery date was Oct 17, 1977. She was admitted to the hospital on Oct 3, 1977. She had a history of idiopathic diabetes insipidus since age 12. She had been treated with vasopressin (Pitressin) tannate in oil until the age of 21 when the drug therapy was switched to desmopressin acetate given by nasal spray. Her condition was well controlled with 0.25 mL/day in divided doses. At initial prenatal examination on March 11, 1977, she had appeared to be normal, and uterine size agreed with her period of
THE PRODUCTION OF ANTIBODIES BY TISSUES LIVING OUTSIDE OF THE ORGANISM
Authors: Alexis Carrel, Ragnvald Ingebrigtsen
Journal: The Journal of Experimental Medicine (1912)

Since guinea pig bone marrow and lymph gland cultivated for five days with goat blood generate substances that are hemolytic for goat red blood corpuscles, it can be concluded that tissues living outside of the organism react against an antigen by the production of an antibody.