tbuckley/cabot-search huggingface dataset:
Try It—You'll Like It!
Authors: Rose Tracy
Journal: JAMA (1973)

Try it!... You'll like it! That's the persuasive message of an often-repeated TV commercial. That encouragement might be given to directors of programs in graduate medical education who have looked on the new requirements for internships as a bitter pill to swallow. Instead, if they digest the contents of the new policy slowly, and do not allow their digestion to be upset by emotional reaction, they should be pleasantly surprised—contrary to the result in the TV commercial—to find that the results are salutary in the long run, rather than harmful. The change by July 1, 1975, from the familiar rotating and straight internships to the flexible and categorical programs for the first year of graduate training is described elsewhere in this issue. The intent is not to eliminate or to abolish this period of training, but rather to upgrade the experience given the candidate. If the required changes are made
Randomised controlled trial of supported discharge in patients with exacerbations of chronic obstructive pulmonary disease
Authors: E Skwarska
Journal: Thorax (2000)

A randomised trial was performed on patients presenting to hospital with an exacerbation of chronic obstructive pulmonary disease (COPD) to compare outcomes in those managed at home with support with those admitted to hospital in the standard manner.Over an 18 month period all patients presenting to the Royal Infirmary of Edinburgh on weekdays (n=718) with a diagnosis of an exacerbation of COPD were assessed for inclusion in the trial. Patients with impaired level of consciousness, acute confusion, acute changes on radiography, or an arterial pH of <7.35 or with other serious medical or social reasons for admission were excluded. Patients randomised to home support were discharged with an appropriate treatment package (antibiotics, corticosteroids, nebulised bronchodilators and, if necessary, home oxygen). They were visited by a nurse the following day and thereafter at intervals of 2-3 days until recovery when they were discharged from follow up. Parallel observations were made on patients allocated to normal hospital admission up to the point of discharge. Patients in both groups were assessed at home eight weeks after the initial assessment.Among weekday patients 353 (50%) were considered obligatory admissions, 140 (19%) were admitted because of co-morbidity, 17 (2%) because of poor social circumstances, and 24 (3%) did not consent to the trial. The remaining 184 (26%) were randomised (2:1) either to home support or to a standard hospital admission. The median time to discharge was 7 days for the home support group and 5 days for the admitted group (p<0.01); 25% of the home support group and 34% of the admitted group were readmitted before the final assessment at eight weeks (p>0.05). There were no significant differences between the groups in attendances by GPs and carers or in health status measured eight weeks after the initial assessment. Satisfaction with the service was good. The mean total health service cost per patient was estimated as 877 pounds sterling for the home support group and 1753 pounds sterling for the admitted group.This study shows that home supported discharge is a well tolerated, safe, and economic alternative to hospital admission for a proportion of patients referred to hospital for admission for an exacerbation of COPD.
Trimethobenzamide Antiemetic in Immediate Postoperative Period
Authors: Carl A. Coppolino
Journal: JAMA (1962)

THE INCIDENCE OF VOMITING in the immediate postoperative period has decreased markedly with the advent of newer anesthetic agents and techniques. However, there is still a definitive incidence of this troublesome sequela as shown by the multiplicity of drugs which are available for its therapy. Many of these medications are relatively effective, but the high incidence of unpleasant side-effects sometimes prohibits their use. The exact mechanisms involved in vomiting are fairly well delineated though contributing factors are still somewhat nebulous. Borison and Wang have shown that the vomiting center is located in the medulla, and that the chemoreceptor trigger zone is located in the floor of the fourth ventricle. Schallek et al. have reported that trimethobenzamide exerts its pharmacologie activity primarily upon the chemoreceptor zone located in the floor of the fourth ventricle. Since the 2 previously mentioned facts are apparently consistent, it would appear that the use of trimethobenzamide
Oestrogen receptor alpha in pulmonary hypertension
Authors: Audrey F. Wright, Marie-Ann Ewart, Kirsty Mair, Margaret Nilsen, Yvonne Dempsie, Lynn Loughlin, Margaret R. Maclean
Journal: Cardiovascular Research (2015)

Pulmonary arterial hypertension (PAH) occurs more frequently in women with mutations in bone morphogenetic protein receptor type 2 (BMPR2) and dysfunctional BMPR2 signalling underpinning heritable PAH. We have previously shown that serotonin can uncover a pulmonary hypertensive phenotype in BMPR2+/− mice and that oestrogen can increase serotinergic signalling in human pulmonary arterial smooth muscle cells (hPASMCs). Hence, here we wished to characterize the expression of oestrogen receptors (ERs) in male and female human pulmonary arteries and have examined the influence of oestrogen and serotonin on BMPR2 and ERα expression. By immunohistochemistry, we showed that ERα, ERβ, and G-protein-coupled receptors are expressed in human pulmonary arteries localizing mainly to the smooth muscle layer which also expresses the serotonin transporter (SERT). Protein expression of ERα protein was higher in female PAH patient hPASMCs compared with male and serotonin also increased the expression of ERα. 17β-estradiol induced proliferation of hPASMCs via ERα activation and this engaged mitogen-activated protein kinase and Akt signalling. Female mice over-expressing SERT (SERT+ mice) develop PH and the ERα antagonist MPP attenuated the development of PH in normoxic and hypoxic female SERT+ mice. The therapeutic effects of MPP were accompanied by increased expression of BMPR2 in mouse lung. ERα is highly expressed in female hPASMCs from PAH patients and mediates oestrogen-induced proliferation of hPASMCs via mitogen-activated protein kinase and Akt signalling. Serotonin can increase ERα expression in hPASMCs and antagonism of ERα reverses serotonin-dependent PH in the mouse and increases BMPR2 expression.
Urea cycle enzyme activities are normal and inducible by a high-protein diet in CCl4 cirrhosis of rats
Authors: Philip J. Snodgrass
Journal: Hepatology (1989)

We produced moderately severe, inactive micronodular cirrhosis in rats using CCl 4 and measured the urea cycle enzyme activities in liver after feeding a 15% casein diet for 1 week and again after a 60% casein diet for 1 week. There was no deficiency of any of the five urea cycle enzymes in cirrhotic livers of rats pair-fed the 15% casein diet. Argininosuccinate synthetase and carbamyl phosphate synthetase activities were lower than in non-pair-fed controls by some baselines. All five enzymes in cirrhotic livers were induced 1.5- to 3-fold by the high-protein diet expressed as units per 100 gm of rat. The level of carbamyl phosphate synthetase activity was lower in the livers of rats pair-fed the 60% casein diet than in control livers based on wet weight, collagen-free protein and DNA, but the activities were equal expressed as units per 100 gm of rat. This example of CCl 4 -induced cirrhosis in the rat does not serve as a good model for human cirrhosis, in which the urea cycle enzymes are reported to be decreased in activity.
321 ANTI-HDV-IGM TESTING IN HEPATITIS DELTA REVISITED: CORRELATIONS WITH DISEASE ACTIVITY AND RESPONSE TO PEGYLATED INTERFERON ALFA-2A TREATMENT
Authors: I. Mederacke, C. Yurdaydin, B. Bremer, Y. Çakaloğlu, A. Erhardt, K. Yalcin, K. Zachou, S. Gürel, B. Heidrich, G. Dalekos, H.P. Dienes, M.P. Manns, H. Wedemeyer
Journal: Journal of Hepatology (2010)
Agencies condemn new Nigerian law that may deny gay people access to HIV services
Authors: Z. Kmietowicz
Journal: BMJ (2014)

Two leading international aid agencies have called for an urgent review of a new law in Nigeria that they say could lead to the arrest and imprisonment of lesbian, gay, bisexual, and transgender (LGBT) people who access health services and those who help them.

UNAIDS and the Global Fund to Fight AIDS, Tuberculosis and Malaria said that the new law has potentially far reaching implications for health, development, and human rights. They urged the Nigerian government to …
Allergy and its mechanisms
Authors: M. Lessof
Journal: BMJ (1986)

Scientific approaches to allergy have followed a kind of Popper's progress?a series of imaginative leaps that are regarded as flashes of genius if they prove right but dangerous nonsense if they are shown to be wrong. This was perhaps justified as long as we were dealing with untestable hypotheses, but things have changed in recent years. We can now detect and measure both the immunological and non-immunological events that are triggered by an allergic reaction and also measure the release of inflammatory mediators. There is sufficient basic knowledge to allow the development of pharmaco? logical agents that will provoke or antagonise the allergic sequence and sufficient clinical skill to allow new products to be evaluated objectively.
Prominent Proptosis in Childhood Thyroid Eye Disease
Authors: Grant T. Liu, Katrinka L. Heher, James A. Katowitz, Michael Kazim, Golnaz Moazami, Thomas Moshang, James W. Teener, John Sladky, Nicholas J. Volpe, Steven L. Galetta
Journal: Ophthalmology (1996)

Background: Orbital signs and symptoms occur in approximately one half of children with Graves disease, but the symptoms are usually minor and limited to the eyelids. Prominent proptosis is uncommon in children with this disorder. Methods: Review of eight children with prominent proptosis associated with thyroid eye disease. Four patients were treated at the Children's Hospital of Philadelphia, the other four at the Columbia Presbyterian Medical Center. Results: At initial presentation, children ranged in age from 3 to 16 years. There were five girls and three boys. Seven of eight children had hyperthyroidism at ophthalmic presentation. Four patients had restrictive myopathy, and all of the seven patients who underwent neuroimaging had extraocular muscle enlargement. Five patients were treated with lubrication. Two underwent orbital fat decompression. One patient had thyroid eye disease and myasthenia gravis. Conclusions: Proptosis in childhood thyroid eye disease usually is associated with a hyperthyroid state. The proptosis may be dramatic, but corneal exposure and restrictive myopathy are seen in only some of the patients. Neuroimaging shows enlarged extra-ocular muscles. Most children with this complication can be treated conservatively with topical lubrication, but orbital fat decompression may be considered in patients with more advanced conditions.
SANITARY REGULATIONS GOVERNING RAILWAYS.
Authors: L. E. LEMEN
Journal: JAMA (1896)

It is not often that a railroad surgeon is called upon to speak before you upon matters pertaining to public health. Yet, in this particular, we are not to judge the future by the past. This is truly the era of preventive medicine, because we find not only all branches of medicine battling against every scourge, but the public in general has its thoughts set on the laws which are apt to conduce to good health. It would seem that, at last, the laity has commenced to appreciate the meaning of the old adage: "Public Health is Public Wealth." In the revolution that is now taking place in scientific and social circles to promote the health of the people it behooves the railway surgeons, and railway officials to pause for a moment as to their duties and capabilities. To remain inactive in matters of this kind will be considered criminal
Antinuclear antibodies in patients receiving non-practolol beta-blockers.
Authors: J D Wilson, J Y Bullock, D C Sutherland, C Main, K P O'Brien
Journal: BMJ (1978)

Antinuclear antibodies (ANA) were found in 54 (7.0%) out of 767 treated hypertensive patients compared with 59 (2.4%) out of 2470 healthy controls. Inclusion of a non-practolol beta-blocker in the treatment regimen did not significantly affect the incidence of ANA. ANA was found in significantly more patients being treated with methyldopa (13.0%) than patients receiving other hypotensive agents (3.8%). Non-practolol beta-blockers in combination with methyldopa did not increase the incidence of ANA further.
Asymmetric dimethylarginine accumulates in the kidney during ischemia/reperfusion injury
Authors: Yosuke Nakayama, Seiji Ueda, Sho-ichi Yamagishi, Nana Obara, Kensei Taguchi, Ryotaro Ando, Yusuke Kaida, Ryuji Iwatani, Kumiko Kaifu, Miyuki Yokoro, Maki Toyonaga, Takuo Kusumoto, Kei Fukami, Seiya Okuda
Journal: Kidney International (2013)

Ischemia/reperfusion injury is the leading cause of acute tubular necrosis. Nitric oxide has a protective role against ischemia/reperfusion injury; however, the role of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in ischemia/reperfusion injury remains unclear. ADMA is produced by protein arginine methyltransferase (PRMT) and is mainly degraded by dimethylarginine dimethylaminohydrolase (DDAH). Here we examined the kinetics of ADMA and PRMT and DDAH expression in the kidneys of ischemia/reperfusion-injured mice. After the injury, DDAH-1 levels were decreased and renal and plasma ADMA values were increased in association with renal dysfunction. Renal ADMA was correlated with 8-hydroxy-2'-deoxyguanosine, a marker of oxidative stress. An antioxidant, N-acetylcysteine, or a proteasomal inhibitor, MG-132, restored these alterations. Infusion of subpressor dose of ADMA exacerbated renal dysfunction, capillary loss, and tubular necrosis in the kidneys of ischemia/reperfusion-injured wild mice, while damage was attenuated in DDAH transgenic mice. Thus, ischemia/reperfusion injury-induced oxidative stress may reduce DDAH expression and cause ADMA accumulation, which may contribute to capillary loss and tubular necrosis in the kidney.
On Intemperance in Women, with Special Reference to its Effects on the Reproductive System
Authors: J. Haddon
Journal: BMJ (1876)

quently giddy, and unable to exert his mind, he can walk fairly, and usually does six miles a-day.His appetite is good.His pulse is de- liberate, sixty in the minute.There can, I think, be little doubt that some central disease of his .nervoussystem in the left side is present, by which the various right- sided symptoms are to be explained.The retraction of iris and activity of pupil, with such a considerable degree of tension, are, I think, very exceptional.
Influence of beta-2 adrenergic receptor gene polymorphism on the hemodynamic response to propranolol in patients with cirrhosis
Authors: Juan Turnes, Manuel Hernández‐Guerra, Juan G. Abraldes, Pau Bellot, Rafael Oliva, Juan Carlos García‐Pagán, Jaime Bosch
Journal: Hepatology (2005)

The beta-2-adrenergic receptor (β2--AR) has several single-nucleotide polymorphisms. These influence the functional response to adrenergic stimulation; genotypes homozygous for Gly16-Glu27 or Gly16-Gln27 alleles (Gly16-Glu/Gln27 haplotypes) are associated with enhanced response, whereas genotypes homozygous for Arg16-Gln27 alleles (Arg16-Gln27) show a decreased response. We hypothesized that gene polymorphisms at the β2-AR may influence the hemodynamic response to propranolol in patients with cirrhosis. The β2-AR gene polymorphisms were determined by direct sequencing of the polymerase chain reaction (PCR) products in 48 patients with cirrhosis. All patients also had hepatic and systemic hemodynamic studies before and after propranolol administration. Prevalence of Gly16-Glu/Gln27 haplotypes was 29.1%, Arg16-Gln27 haplotype was 16.7%, and 54.2% were compound heterozygotes. Patients with cirrhosis with Gly16-Glu/Gln27 haplotypes had a greater decrease in heart rate, cardiac index, and hepatic blood flow after propranolol administration than those with Arg16-Gln27 haplotype. However, the HVPG response to propranolol was similar in both groups, whereas estimated hepatic sinusoidal resistance increased significantly in Gly16-Glu/Gln27 haplotypes but not in Arg16-Gln27 (+27.1 ± 17.8% vs -17.9 ± 13.9%, P = .042), suggesting that unopposed vasoconstrictive activity at the intrahepatic circulation hinders the fall in HVPG despite enhanced hemodynamic response to propranolol in Gly16-Glu/Gln27 haplotypes. In conclusion, β2-AR gene polymorphisms influence the response to beta-blockade. However, HVPG reduction cannot be predicted from polymorphism analysis. Patients with the Gly16-Glu/Gln27 haplotypes may benefit from the association of hepatic vasodilators to propranolol therapy. (HEPATOLOGY 2005;43:34–41.)
Transplanted Hepatocytes Over-expressing FoxM1B Efficiently Repopulate Chronically Injured Mouse Liver Independent of Donor Age
Authors: Nicolas Brezillon, Martine Lambert-Blot, Serban Morosan, Dominique Couton, Claudia Mitchell, Dina Kremsdorf, Robert H Costa, Helene Gilgenkrantz, Jacques-Emmanuel Guidotti
Journal: Molecular Therapy (2007)

Orthotopic liver transplantation is limited by the shortage of liver donors, leading to elderly patients being enrolled as donors with increasing frequency. Alternative strategies such as cell therapy are therefore needed. Because transplanted hepatocytes do not proliferate into a recipient liver, repopulation strategies have been developed. We have previously published a proof of concept that hepatocytes harboring a survival selective advantage can efficiently repopulate a mouse liver. We develop here an alternative approach by conferring a selective proliferative advantage on transplanted hepatocytes over resident ones. FoxM1B is a transcription factor that, when over-expressed into hepatocytes, accelerates the cell cycle and maintains the hepatocyte in vivo proliferative capacity of aged livers. We now demonstrate that transplanted hepatocytes over-expressing FoxM1B repopulate the liver of mice subjected to continuous injury far more efficiently than control hepatocytes. We show that old hepatocytes that over-express FoxM1B retain their cell division capacity and repopulate liver as well as young ones, in contrast with old non-modified hepatocytes, which lose their proliferative capacity. In conclusion, our results point to the potential use of FoxM1B expression in hepatocyte-based therapy protocols in diseases where host hepatocytes are chronically injured, especially if donor hepatocytes come from old livers.
Abstract 2522: Therapeutic synergism of cabazitaxel in combination with cisplatin in tumor-bearing mice
Authors: Patricia Vrignaud
Journal: Cancer Research (2011)

Abstract Cabazitaxel (Jevtana), a semi-synthetic taxane derived from 10-deacetyl baccatin III, is as efficient as docetaxel in promoting tubulin assembly in vitro and stabilizing microtubules against cold-induced depolymerization. Cabazitaxel was selected for clinical development based on better antiproliferative activity than docetaxel against chemotherapy resistant tumor-cell lines (Bissery M.C. et al, AACR 2000) and a broad spectrum of in vivo antitumor activity (Vrignaud P. et al, AACR 2000), not only in docetaxel-sensitive tumor models, such as the human gastric N87 xenograft, but also in tumors models in which docetaxel was either poorly active or inactive. As an example, cabazitaxel was highly active in mice bearing UISO-BCA1 tumors, a human mammary xenograft expressing Her-2, which is poorly sensitive to ixabepilone and not sensitive to docetaxel. In addition, cabazitaxel penetrates the blood brain barrier (Cisternino S. et al, British J. Pharm. 2003) and has marked antitumor activity in nude mice bearing intracranial glioblastomas (Dykes D.J. et al, AACR 2000). Cabazitaxel was recently approved by the FDA for patients with metastatic hormone-refractory prostate cancer previously treated with docetaxel-based therapy. In order to explore other therapeutic indications, the cabazitaxel-cisplatin combination was evaluated in C51 tumor-bearing mice. A 5-arm dose-response study was performed with cabazitaxel and cisplatin administered IV on days 5 and 12 after tumor implantation as single agents and in combination using 3 different sequences of administration: simultaneous in group A and sequentially separated by a 24h interval in groups B (cabazitaxel first) and C (cisplatin first). At their highest nontoxic doses (HNTD), both single agents were found active with tumor growth delays (T-C) of 15.2 days for cabazitaxel at 20 mg/kg/inj and 22.1 days for cisplatin at 4.3 mg/kg/inj. The 3 combination arms showed greater antitumor activity at their respective HNTD with T-C of 38.4 days in group A, 37.8 days in B, and 36.2 days in C. Of interest, 2 (A) and 3 (B &amp; C) dose levels were found more active than the single agents in the combination arms. In conclusion, a therapeutic synergism was achieved when cabazitaxel was combined with cisplatin in C51 tumor-bearing mice. These data are supporting the ongoing Phase I clinical study of cabazitaxel-cisplatin combination in solid tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2522. doi:10.1158/1538-7445.AM2011-2522
Hyperfunctional coagulation factor IX improves the efficacy of gene therapy in hemophilic mice
Authors: Alessio Cantore, Nisha Nair, Patrizia Della Valle, Mario Di Matteo, Janka Màtrai, Francesca Sanvito, Chiara Brombin, Clelia Di Serio, Armando D'Angelo, Marinee Chuah, Luigi Naldini, Thierry VandenDriessche
Journal: Blood (2012)
Notes on Evaluating the Quality of Medical Care
Authors: Eli Ginzberg
Journal: New England Journal of Medicine (1975)

A 1974 policy statement of the Institute of Medicine of the National Academy of Sciences, "Advancing the Quality of Health Care," presents the conclusions of a committee charged with considering the implications of mechanisms for the review of the quality of medical care. The following comments were prompted by this report and by a discussion at the fall meeting of the Institute of Medicine on the subject.The term "quality" is used when reference is made to so many discrete aspects of health care, such as access, availability, appropriateness, cost effectiveness, that it is impossible to arrive at a definition . . .