tbuckley/cabot-search huggingface dataset:
Relation between steady-state force and intracellular [Ca2+] in intact human myocardium. Index of myofibrillar responsiveness to Ca2+.
Authors: J K Gwathmey, R J Hajjar
Journal: Circulation (1990)

A novel approach was developed allowing the measurement of steady-state force and intracellular calcium concentration ([Ca2+]i) in tetanized human ventricular trabeculae carneae without pharmacological intervention. We compared and contrasted three methods of assessing calcium sensitivity of the myofilaments: 1) force-[Ca2+] relations in skinned fiber preparations, 2) peak twitch force-peak [Ca2+]i relations, and 3) steady-state force-[Ca2+]i relations in intact muscles. Steady-state contractile activation was achieved rapidly by tetanizing intact human trabeculae, loaded with aequorin, a Ca2(+)-sensitive bioluminescent protein, at a stimulation frequency of 15-20 Hz. Steady-state force and [Ca2+]i were measured during tetani, and the force versus [Ca2+]i relation was obtained by varying the extracellular calcium concentration ([Ca2+]o). Force-[Ca2+]i relations obtained from control and myopathic hearts were fitted to the Hill equation: %Force = [Ca2+]inh/([Ca2+]inh50% + [Ca2+]inh), where nh is the Hill coefficient, and [Ca2+]50% is the [Ca2+] required for 50% activation. The curves of tetani had Hill coefficients of 5.21 +/- 0.20 (n = 6) and 5.61 +/- 0.60 (n = 10) and [Ca2+]50% of 0.56 +/- 0.05 microM (n = 6) and 0.54 +/- 0.09 microM (n = 10) in control and myopathic muscles, respectively. We also constructed peak force-peak [Ca2+]i relations using isometric twitches from the same muscles. These curves were shifted toward higher [Ca2+]i compared with the steady-state force-[Ca2+]i curve derived from tetani. Ryanodine (1 microM), which increased the time course of the Ca2+ and force transients, shifted the peak force-peak [Ca2+]i relation to the left, without affecting the steady-state force-[Ca2+]i relation. Exposure to 10 mM caffeine shifted the steady-state force-[Ca2+]i relation to the left, whereas exposure to 3 microM isoproterenol shifted this relation to the right. Experiments using skinned fiber preparations were performed in parallel with experiments on intact muscles from the same hearts. The force-pCa (-log[Ca2+]) relations in saponin-skinned trabeculae from control and myopathic tissue were superimposable. Ryanodine (1 microM) had no effect on the force-pCa relation in skinned fibers. Maximal tension was evoked by the posttetanic twitch, which was larger than the tetanus. This potentiation was abolished in the presence of ryanodine, a sarcoplasmic reticulum inhibitor. We propose that the changes in the steady-state force-[Ca2+]i relations are correlated with alterations in the sensitivity of the myofilaments to Ca2+, whereas changes in the peak force-peak [Ca2+]i relations represent temporal changes in the twitch transient.(ABSTRACT TRUNCATED AT 400 WORDS)
Carbon Dioxide and Obstructed Cerebral Blood Flow
Authors: Stephen A. Hegedus
Journal: JAMA (1965)

The effect of carbon dioxide on cerebral blood flow was studied in ten patients with unilateral internal carotid obstruction. Inhalation of 5% carbon dioxide increased the cerebral blood flow significantly from 28.8 to 40.5 ml/100 gm of brain weight per minute (a 40% increase). A significant correlation was established between cerebral blood flow, neurological defects, and angiographic crossfilling. Increased cerebrovascular resistance in carotid obstruction is attributed to increased cerebrovascular tonus, which tends to preserve pressure gradients all along the cerebral arterial tree in the presence of a decreased volume of inflow. Carbon dioxide inhalation increased the cerebral blood flow by virtue of reduction of this cerebrovascular resistance, thereby serving to reduce stasis in less efficiently perfused arteries. Intermittent inhalation of 5% carbon dioxide in air is recommended as an adjunct to vascular surgery in treatment of unilateral carotid obstructions.
How to make a compelling submission to NICE: tips for sponsoring organisations
Authors: A. Burls
Journal: BMJ (2003)

Evidence in support of products being assessed by the National Institute for Clinical Excellence can be presented in various ways to make products seem more attractive than they really are During health technology appraisals the National Institute for Clinical Excellence (NICE) invites sponsors of the technology to make a submission in support of their product. These submissions can be of variable quality. We examine some of the more dubious techniques that can be used by sponsoring organisations to make their products seem attractive to those making reimbursement decisions. Although the following "advice" is based on real examples of submissions to NICE, it should be remembered that similar biases can be found in academic, peer reviewed publications and that such practices are not the preserve of industry. ### Generating the evidence
Pfizer Australia faces scrutiny over atorvastatin advertising campaign
Authors: M. Sweet
Journal: BMJ (2012)

Pfizer Australia has been accused of breaching regulations banning advertisements aimed directly at consumers by placing in the media what it calls “community service announcements” about its cholesterol lowering drug atorvastatin (which it markets as Lipitor).

Ken Harvey, adjunct associate professor in the School of Public Health at La Trobe University, Melbourne, has lodged a complaint about the notices with the code of conduct committee of the industry body Medicines Australia. The notices appeared in newspapers and were broadcast on radio earlier this month.

Harvey alleges that the campaign amounts to promotion of a prescription product to the general public and is part of a strategy to maintain market share in the face of competition from generic products.

However, Pfizer says that the notices are …
Lichen Planus, Wickham;s Striae and Blood Vessels
Authors: T. J. Ryan
Journal: British Journal of Dermatology (1971)

Journal Article Lichen Planus, Wickham;s Striae and Blood Vessels Get access T. J. Ryan T. J. Ryan United Oxford Hospitals Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 85, Issue 5, 1 November 1971, Pages 497–498, https://doi.org/10.1111/j.1365-2133.1971.tb14068.x Published: 01 November 1971
Efficacy of Curosurf in a rat model of acute respiratory distress syndrome
Authors: HP van Helden, WC Kuijpers, PE Langerwerf, RC Langen, HP Haagsman, PL Bruijnzeel
Journal: European Respiratory Journal (1998)

Curosurf, a natural lung surfactant, is considered a potential candidate for improving the treatment of acute respiratory distress syndrome (ARDS). To investigate this in a rat model of early-stage ARDS, Curosurf (62.5, 125 or 250 mg x kg(-1)) was administered by intratracheal bolus at 10 or 24 h following an intratracheal lipopolysaccharide (LPS; 1.6 mg x kg(-1)) challenge. Survival, respiratory frequency (fR), lung wet weight (LWW), total protein and cell differentiation in bronchoalveolar lavage fluid (BALF) were assessed. Curosurf treatment at 10 h after LPS challenge resulted in 100% survival at both 62.5 and 125 mg x kg(-1); at a dose of 250 mg x kg(-1) administered at 10 h after LPS, 1 out of 6 animals died. At a dose of 125 mg x kg(-1) Curosurf administered at 24 h after LPS, 1 out of 6 animals died. In contrast, only 35% of animals survived when not treated with Curosurf. Curosurf treatment resulted in an improved fR and in a significantly decreased LWW, total protein and number of polymorphonuclear cells in BALF. In conclusion, Curosurf treatment improved respiratory frequency and decreased mortality, pulmonary oedema and inflammation. As the decreased mortality was observed in spontaneously breathing nonoxygenated animals, the results cannot be extrapolated to human artificially ventilated acute respiratory distress syndrome patients with the expectation of a decreased mortality. The results suggest, however, that Curosurf may be an important therapeutic measure in early-stage acute respiratory distress syndrome.
Abstract 3969: A novel statistical method for detecting association of copy number variations in genome-wide association studies of cancers
Authors: Jianxin Shi, Peng Li
Journal: Cancer Research (2012)

Abstract Copy number variations (CNVs) are one of the major genetic resources in human populations. In large scale genome-wide association studies (GWAS), CNVs are usually detected from intensity data, quantified as Log R Ratio (LRR) and B-allele Frequency (BAF), generated by single nucleotide polymorphism (SNP) genotyping arrays. The standard approach for detecting CNV associations is based on two-step procedures: CNVs are first detected using intensity data and then association is tested based on the detected CNVs. Because the accuracy of CNV calling depends on the number of probes covered in the CNV region, short CNVs are generally detected with low sensitivity. Consequently, the statistical power of detecting short CNVs associated with diseases is low. We develop a novel method, variable thresholding exact statistic (VTES) implemented in a package SegCNV, for identifying genomic regions within which the frequency of CNVs is significantly higher in cases than in controls. VTES optimally summarizes the LRR and BAF of the probes to maximize the power. Extensive simulation studies demonstrated that VTES had a much better power for detecting rare, short CNVs associated with common diseases compared to standard two-step procedures, while maintaining correct type-I error rates. Particularly, the power of VTES is close to the ideal power when CNVs can be called perfectly. VTES is flexible to detect both recurrent CNVs and non-overlapping CNVs associated with diseases. VTES is computationally efficient and can analyze a GWAS of 2000 subjects within 20 hours using a single core. We applied VTES to a GWAS of testicular cancer and lung cancer, and identified regions that show strong evidences of CNV associations. We expect that VTES will prove useful for CNV association analysis in existing large scale GWAS of cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3969. doi:1538-7445.AM2012-3969
Baclofen and Tricyclic Antidepressants: Possible Interaction
Authors: Michael J. Silverglat
Journal: JAMA (1981)

<h3>To the Editor.—</h3> Depression is not uncommon in patients with multiple sclerosis, occurring in 6% to 27% of cases.<sup>1</sup>This depression is generally secondary (reactive) and may be managed without drugs,<sup>2</sup>but tricyclic antidepressant therapy might be considered in some cases. A patient receiving baclofen experienced increased muscle relaxant effect when given two different tricyclic drugs. <h3>Report of a Case.—</h3> A 54-year-old man with a 12-year history of multiple sclerosis had spastic paraplegia, marked weakness of his left arm, and neurogenic bladder. He disclosed a two-year history of "depressions," which he described as periods of withdrawal, insomnia, and loss of interest lasting four to five days and occurring about once per month. He had been treated continuously with baclofen for 18 months and at the time of admission was taking 10 mg four times a day. This dose produced good relief of spasticity but left him with sufficient
A Placebo-Controlled, Double-Blind, Randomized Trial of Cyclosporine Therapy in Active Chronic Crohn's Disease
Authors: J Brynskov, L Freund, S N Rasmussen, K Lauritsen, O S de Muckadell, N Williams, A S MacDonald, R Tanton, F Molina, M C Campanini
Journal: New England Journal of Medicine (1989)

We randomly assigned 71 patients with active chronic Crohn's disease who were resistant to or intolerant of corticosteroids to treatment with oral cyclosporine (5 to 7.5 mg per kilogram of body weight per day) or placebo for three months. Disease activity was assessed on a clinical grading scale without knowledge of the treatment given. At the end of the treatment period, 22 of the 37 cyclosporine-treated patients (59 percent) had improvement, as compared with 11 of the 34 placebo-treated patients (32 percent) (P = 0.032). During cyclosporine treatment, there was significant improvement in plasma orosomucoid levels (P = 0.0025) and the Crohn's Disease Activity Index (P = 0.00012). The effect of treatment became evident after two weeks. In the subsequent three months, during which the patients were gradually withdrawn from treatment, the improvement continued in 14 of the 37 patients (38 percent) in the cyclosporine group and in 5 of the 34 (15 percent) in the placebo group (P = 0.034). No serious adverse events were observed. We conclude that cyclosporine has a beneficial therapeutic effect in patients with active chronic Crohn's disease and resistance to or intolerance of corticosteroids.
Involvement of Epstein-Barr virus latent membrane protein 1 in disease progression in patients with idiopathic pulmonary fibrosis
Authors: K Tsukamoto
Journal: Thorax (2000)

The role of Epstein-Barr virus (EBV) in idiopathic pulmonary fibrosis (IPF) is uncertain. A study was undertaken to detect the virus in IPF as well as to clarify the influence of EBV on the clinical features of the disease.Twenty nine lung specimens were obtained from patients with IPF, as well as five specimens from patients with systemic sclerosis with pulmonary fibrosis (SSc) and 15 specimens from controls. EBV DNA and EBV latent membrane protein 1 (LMP1) were detected using the PCR method and immunohistochemical analysis, respectively.EBV DNA was detected in 24 of 25 patients with IPF (96%), in all five patients with SSc (100%), and in 10 of 14 controls (71%). The detection ratio was significantly higher in patients with IPF than in controls (p = 0.047, odds ratio (OR) = 9.60, 95% confidence interval (CI) 0.9 to 96.9). Immunohistochemical analysis revealed that cuboidal epithelial cells were positively stained with anti-LMP1 antibody in nine of the 29 lung specimens from IPF patients. In contrast, neither the patients with SSc nor the control subjects showed positive staining. In the follow up periods LMP1 positive patients with IPF died more frequently from respiratory failure than LMP1 negative patients (4/9 versus 1/20; p = 0.022, OR = 15.20, 95% CI 1. 3 to 168.0).EBV LMP1 positivity may be associated with more rapid disease progression in IPF.
The Education of American Physicians: Historical Essays
Authors: Edgar Lee
Journal: JAMA (1980)

The challenge of organizing a history of medical education is not unlike the challenge of medical education itself. Which way and how thick does one slice the vast loaf to provide nourishing, palatable, and attractive substance for further growth? What should be included and what must be trimmed away? This requires a good understanding of the subject, sound judgment, and a set of values, which give overall shape and character to the whole. Professor Numbers and his colleagues have demonstrated these qualities admirably in putting together this fine collection of historical essays. Martin Kaufman's excellent overview at the beginning provides a sensitive, integrative framework for the individual parts as represented by 12 significant disciplines. The subjects are well balanced between the basic sciences, the clinical specialties, and broader sociomedical fields, including public health and medical ethics. All are interesting as well as informative, with an index and appropriate footnotes, which
Protection against group B meningococcal disease. III. Immunogenicity of serotype 2 vaccines and specificity of protection in a guinea pig model.
Authors: C E Frasch, J D Robbins
Journal: The Journal of Experimental Medicine (1978)

Protein vaccines were prepared from the serotype antigen of group B Neisseria meningitidis strain M986. The detergents Triton X-100, Emulphogene BC-720, and deoxycholate were used to removed the toxic lipopolysaccharide (LPS) portion of the serotype antigen. The LPS was most preferentially solubilized by Emulphogene. Guinea pigs were immunized with one or two doses of vaccine given intramuscularly without adjuvants and the antibody response quantitated by an enzyme-linked immunosorbant assay. Immunization with graded doses of vaccine between 25 to 200 microgram protein indicated a wide range of effective dosage and that a two-dose immunization schedule was superior to a single immunization. The vaccines elicited peak mean serum antibody levels of approximately 30 microgram/ml with bactericidal titers of 1:1,600-1:6,400. The peak antibody levels occurred 5-6 wk after immunization and persisted above preimmune levels for several months. To evaluate the protective effects of immunization, stainless steel springs were implanted subcutaneously into the guinea pigs. The resulting chambers, in unimmunized animals, could be infected with less than 100 type 2 organisms. A single 25-50 microgram dose of vaccine protected 50% of animals from challenge by 5 X 10(5) type 2 meningococci, and as little as 1 microgram vaccine significantly reduced the severity of infection. A two-dose immunization schedule was best and provided nearly complete protection for at least 4 mo against type 2 strains of meningococcal groups B, C, and Y.
An Address ON THE PAST, PRESENT, AND FUTURE OF MIDWIFERY
Authors: B. P. Watson
Journal: BMJ (1922)

E~~~~~~~~~~~~~~IKDICAL JOUR'(LL bedside to gather facts and make observations.In this he was true to tlle inductive methiod: a collector of facts from wlhich to induce general principles.Puritani m in the seventeenith century produced its Crom- well, the embodiment of relentless energy and resistless brain force; its Milton, who showed to whlat lieights of grandeur and majesty our own dear language can attain; and its Bunyan, wlho, all unlettered as lhe was, in the simplest and sweetest vernacular penned tlle finest allegory the world will ever read.To tllese great productions of Puritanism may we not witlh justice add thle natne of Tlhomnas Sydenham, the great Puritan physician, wlio founided for all time and for all countries tlle art of clinical medicine.CONCLUSION.
Hepatic iron and zinc concentrations after portacaval shunting for nonalcoholic cirrhosis
Authors: Paul C. Adams, Colin Bradley, Jaroslav V. Frei
Journal: Hepatology (1994)

Hepatic iron and zinc concentrations were determined in 26 consecutive nonalcoholic cirrhotic patients who had previously undergone portacaval shunting and then liver transplantation and 37 control patients. Stainable iron was graded on a scale of 0 to 4; 11 shunt patients and 3 control patients had grade 2 to 4 iron staining. Mean hepatic iron concentration was significantly increased (20.1 +/- 4.1 mumol/gm) in the shunt group compared with the control group (9.1 +/- 2.3 mumol/gm) (normal value, < 35 mumol/gm) (p = .015, Student's t test). Mean hepatic iron index (hepatic iron/age) was 0.5 +/- 0.10 in the shunt group and 0.19 +/- 0.04 in the control group (p = 0.002). One shunt patient had a hepatic iron index of greater than 2. Hepatic zinc was not significantly different between the shunt group (2.42 +/- 0.18 mumol/gm) and the control group (2.56 +/- 0.14 mumol/gm). Serial biopsy specimens were analyzed in 17 cases (6 shunt, 11 controls), and the mean annual rate of iron accumulation was significantly greater in shunt patients (4.75 mumol/gm/yr) than in control cases (0.93 mumol/gm/yr, p = 0.037). Although increased stainable iron was common after portacaval shunting, quantitative iron analysis demonstrated increased hepatic iron concentrations in only 6 of 26 shunt patients and 3 of 37 control patients (p = 0.14, chi 2 test). Quantitative hepatic iron analysis demonstrated in this study that portacaval shunt patients have far less accumulated iron than hemochromatosis patients and are unlikely to have tissue injury resulting from iron overload.
THE SIGNIFICANCE OF BLOODY DISCHARGES FROM THE BOWELS IN YOUNG CHILDREN.
Authors: FRANK WOODBURY
Journal: JAMA (1884)

Read in Section on Diseases of Children, American Medical Association, May, 1884. The occurrence of blood in the alvine discharges of a young child, whether in amount large enough to constitute actual intestinal hæmorrhage, or existing only as a few small clots or streaks of blood, is a symptom which naturally excites alarm in the minds of those having it in charge, and usually is the signal for prompt appeal for medical aid. Whether rightfully or not, in an individual case, it may be considered as the rule that this accident in childhood is of much more serious import than in adult life, although in some instances the pathological conditions are identical. On account of the gravity and urgency of the morbid states involved, the opportunity for the exhibition of skill in diagnosis, and the possibility of brilliant results from appropriate treatment, I would regard this class of cases as
A Little Survivor
Authors: M A Levitt, A R Hong
Journal: New England Journal of Medicine (1997)

Figure 1. The hand of an infant girl who was born at 24 weeks of gestation and weighed 540 g (1 lb 3 oz) at birth is shown. The infant was found to have jejunal atresia on the sixth day of life and underwent a small-bowel resection with primary anastomosis. She recovered from the surgical procedure, was able to tolerate feedings on the 12th postoperative day, and steadily gained weight. She appeared to have no neurologic abnormalities. The infant remained in the neonatal intensive care unit for more than three months, and at the time of discharge, she weighed 2.9 . . .
Susceptibility to "Australia Antigen Hepatitis" in Leukemia.
Authors: Alton I. Sutnick
Journal: Annals of Internal Medicine (1969)

s1 May 1969Susceptibility to "Australia Antigen Hepatitis" in Leukemia.Alton I. Sutnick, M.D., F.A.C.P., W. Thomas London, M.D., F.A.C.P., Baruch S. Blumberg, M.D., F.A.C.P.Alton I. Sutnick, M.D., F.A.C.P.Search for more papers by this author, W. Thomas London, M.D., F.A.C.P.Search for more papers by this author, Baruch S. Blumberg, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-5-1104_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn 1965 Blumberg and associates reported the finding of a new antigen (Australia antigen (Au)) in sera of patients with leukemia. Since then we have published a large body of evidence—including clinical, laboratory, and liver biopsy material—pointing to an intimate relationship of Au with both acute hepatitis and chronic anicteric hepatitis. When viewed under the electron microscope Au is a particle 200 A in diameter and has a number of characteristics that one would expect of a virus particle. The possibility that this is a casual agent of viral hepatitis is currently being investigated. The relationship to leukemia is still... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Alton I. Sutnick, M.D., F.A.C.P.; W. Thomas London, M.D., F.A.C.P.; Baruch S. Blumberg, M.D., F.A.C.P.Affiliations: Fox Chase, Philadelphia, Pennsylvania PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byViral Hepatitis: Revised Concepts as a Result of the Study of Australia AntigenAdditional Specificities of Australia Antigen and the Possible Identification of Hepatitis Carriers 1 May 1969Volume 70, Issue 5Page: 1104-1104KeywordsAntigensBiopsyChronic hepatitisClinical laboratoriesElectron microscopyHepatitisHepatitis ALiver ePublished: 1 December 2008 Issue Published: 1 May 1969 PDF downloadLoading ...