tbuckley/cabot-search huggingface dataset:
Differences in Chromosome Constitution of Twins with Acute Leukemia
Authors: Avery A. Sandberg, Jean Cortner, Nobuo Takagi, M. Amini Moghadam, Lois H. Crosswhite
Journal: New England Journal of Medicine (1966)

THE interpretation of chromosomal changes in human acute leukemia and the origin of such changes is complicated by two salient karyotypic findings in this disease: the remarkable diversity of the chromosomal changes, when present, in the (acute) leukemic cells; and the absence of observable chromosomal aberrations in a substantial number of cases of this disease.1 The reasons for such chromosomal diversity have remained obscure; however, studies of twins with acute leukemia might shed considerable light on the genesis of these chromosomal changes. Thus, the development of acute leukemia in a pair of infant fraternal twins offers an unusual opportunity for . . .
Glucocorticoids modulate macrophage surface oligosaccharides and their bone binding activity.
Authors: Z Bar-Shavit, A J Kahn, L E Pegg, K R Stone, S L Teitelbaum
Journal: Journal of Clinical Investigation (1984)

The circumstantial evidence that indicates that glucocorticoids (GC) may stimulate osteoclastic resorption in vivo has recently found support in observations that demonstrate that these compounds effectively increase the activity of isolated resorptive cells (osteoclasts, macrophage polykaryons, and elicited macrophages [MO] ) in vitro. Data are presented here that indicate that this stimulation by GC is due to an enhancement of the initial stage of the resorption process, the attachment of cells to bone, and that this is caused by alterations of cell surface oligosaccharides. Specifically, dexamethasone and cortisol enhance by 80% the attachment of MO to bone surfaces in a dose dependent manner but do not alter or reduce the binding of these cells to other surfaces (plastic, collagen, and hydroxyapatite crystals). The effect of GC on cell-bone attachment is blocked by the glycosylation inhibitor, tunicamycin, and the glycosylation modifier, swainsonine; this demonstrates that asparagine-linked oligosaccharides are involved in the stimulatory process. Flow cytometric analysis of GC-treated cells using a panel of fluoresceinated lectins confirms this by indicating a selective, enhanced exposure of plasma membrane-associated N-acetylglucosamine and N-acetylgalactosamine residues, sugars we have previously shown to be pivotal in MO-bone binding. Finally, progesterone, a known GC antagonist, blocks GC-stimulated resorption, macrophage-bone binding, and membrane oligosaccharide modification, presumably by competing for the GC receptor. Progesterone alone alters none of these processes. Thus, GC stimulates the resorptive activity of macrophages by enhancing the initial events in the degradative process (cell-bone binding) and does so, apparently, via receptor-mediator alteration of cell surface glycoproteins.
The functional and mechanistic relatedness of EZH2 and menin in hepatocellular carcinoma
Authors: Shu-Bin Gao, Bin Xu, Li-Hong Ding, Qi-Lin Zheng, Li Zhang, Qi-Fan Zheng, Shan-Hua Li, Zi-Jie Feng, Jie Wei, Zhen-Yu Yin, Xianxin Hua, Guang-Hui Jin
Journal: Journal of Hepatology (2014)
South African foundation is accused of “compromising” care of people with HIV and AIDS
Authors: Pat Sidley
Journal: BMJ (2005)

Hundreds of healthcare professionals involved in the care of HIV and AIDS patients in the Western Cape province of South Africa have written to the provincial administration, voicing their concern about the activities of a foundation that promotes “micronutrients”—combinations of vitamins, minerals, and other trace elements—as a treatment for AIDS and that discourages the use of antiretroviral drugs.

They may soon be joined by doctors belonging to the South African Medical Association, who are considering joining the AIDS activist group, the Treatment Action Campaign, in legal action against the South African government for not controlling the Dr Rath Health Foundation's activities. The activists and the doctors are critical of the health minister, not only for failing to put a stop to the foundation's activities …
Selective Molecular Potassium Channel Blockade Prevents Atrial Fibrillation
Authors: Guy Amit, Kan Kikuchi, Ian D. Greener, Lizhu Yang, Victor Novack, J. Kevin Donahue
Journal: Circulation (2010)

Safety and efficacy limit currently available atrial fibrillation (AF) therapies. We hypothesized that atrial gene transfer would allow focal manipulation of atrial electrophysiology and, by eliminating reentry, would prevent AF.In a porcine AF model, we compared control animals to animals receiving adenovirus that encoded KCNH2-G628S, a dominant negative mutant of the I(Kr) potassium channel alpha-subunit (G628S animals). After epicardial atrial gene transfer and pacemaker implantation for burst atrial pacing, animals were evaluated daily for cardiac rhythm. Electrophysiological and molecular studies were performed at baseline and when animals were euthanized on either postoperative day 7 or 21. By day 10, none of the control animals and all of the G628S animals were in sinus rhythm. After day 10, the percentage of G628S animals in sinus rhythm gradually declined until all animals were in AF by day 21. The relative risk of AF throughout the study was 0.44 (95% confidence interval 0.33 to 0.59, P<0.01) among the G628S group versus controls. Atrial monophasic action potential was considerably longer in G628S animals than in controls at day 7, and KCNH2 protein levels were 61% higher in the G628S group than in control animals (P<0.01). Loss of gene expression at day 21 correlated with loss of action potential prolongation and therapeutic efficacy.Gene therapy with KCNH2-G628S eliminated AF by prolonging atrial action potential duration. The effect duration correlated with transgene expression.
Possible Role of T-Strain Mycoplasma in Nongonococcal Urethritis
Authors: Maurice C. Shepard, Charles E. Alexander, Carl D. Lunceford, Paul E. Campbell
Journal: JAMA (1964)

A study of urethritis patients at a US Naval Base in Luzon, Republic of the Philippines, was conducted by a naval research team to determine the nature of a urethritis problem there. Of 203 men in the study, 117 had uncomplicated gonorrhea and 22 had gonorrhea additionally associated with<i>Mycoplasma</i>(PPLO) and "L" organisms—a total of 139 gonorrhea cases. Urethritis among the remaining 64 men was nongonococcal. However, 33 of the 64 men had nongonococcal urethritis associated with a recently reported organism—the T-strain<i>Mycoplasma</i>. In 30 of these 33 men, this organism was the only<i>Mycoplasma</i>recovered in culture. We suggest that a distinct form of venereal urethritis has emerged which is associated with the T-strain<i>Mycoplasma</i>organism and which is completely unresponsive to penicillin.
Early Surgery in Patients With Mitral Regurgitation Due to Flail Leaflets
Authors: Lieng H. Ling, Maurice Enriquez-Sarano, James B. Seward, Thomas A. Orszulak, Hartzell V. Schaff, Kent R. Bailey, A. Jamil Tajik, Robert L. Frye
Journal: Circulation (1997)

Background The optimal timing for surgery in patients with mitral regurgitation is disputed. Because of the frequency of left ventricular dysfunction, which is difficult to predict, early surgery has been recommended, but its potential benefits have not been demonstrated. Methods and Results The outcomes of 221 patients (mean age, 65±13 years; 71% males) with flail leaflets diagnosed with two-dimensional echocardiography between 1980 and 1989 who were eligible for operation were analyzed. Group I comprised 63 patients who had early mitral valve surgery (within 1 month after diagnosis). Group II comprised 158 patients initially treated conservatively (80 of whom were operated on later). Group I patients were younger ( P =.009), had more symptoms ( P &lt;.0001), and were more frequently in atrial fibrillation ( P =.023) than group II patients. There was no difference in ejection fraction between the groups. The early surgery strategy was followed by an improved overall survival rate ( P= .028) and a lower incidence of cardiovascular deaths ( P =.025), congestive heart failure ( P =.046), and new chronic atrial fibrillation ( P =.032), as confirmed by multivariate analysis (adjusted risk ratios of 0.31, 0.18, 0.38, and 0.05, respectively; all P&lt; .02). Conclusions In patients with mitral regurgitation due to flail leaflets, the strategy of early surgery versus conservative management is associated with an improved long-term survival rate, decreased cardiac mortality, and decreased morbidity after diagnosis. This outcome advantage suggests that early surgery is a reasonable treatment option to be considered in low-risk candidates with repairable valves and severe mitral regurgitation.
Recombinant factor VIII products and inhibitor development in previously untreated boys with severe hemophilia A
Authors: Thierry Calvez, Hervé Chambost, Ségolène Claeyssens-Donadel, Roseline d’Oiron, Véronique Goulet, Benoît Guillet, Virginie Héritier, Vanessa Milien, Chantal Rothschild, Valérie Roussel-Robert, Christine Vinciguerra, Jenny Goudemand
Journal: Blood (2014)
'Melanoma? It Can't Be Melanoma!' A Subset of Melanomas That Defies Clinical Recognition
Authors: William K. Andersen
Journal: JAMA (1991)

We diagnosed histologically 178 cases of malignant melanoma in 1990. Thirteen cases were recorded in which the diagnosis of malignant melanoma was not considered by the clinician prior to biopsy or, in retrospect, following pathologic diagnosis. Eight of the 13 lesions were amelanotic. The majority were deeply invasive at the time of biopsy, implying poor prognosis. Despite improvements in early detection of malignant melanoma, a significant subcategory of melanomas escapes clinical diagnosis.
Man with locked-in syndrome who fought for doctors to end his life has died
Authors: Z. Kmietowicz
Journal: BMJ (2012)

Tony Nicklinson, who recently lost his case in the High Court for the right to ask a doctor to end his life, has died.

A statement from his solicitor issued on 22 August, the day of his death, said that Nicklinson had died peacefully at home with his family around him.

Nickinson, 58, had locked-in syndrome after a stroke in 2005. He had described his life as a “living nightmare.”

Nicklinson was too disabled to kill himself even with help and wanted …
National “twin study”
Authors: Ulf R Dahle
Journal: BMJ (2008)

tackling alcohol misuse Needs in adolescentsParker et al's review of alcohol misuse did not deal with the problems and needs of adolescent drinkers, who often present to emergency departments when drunk. 1 Alcohol misuse is common in this age group and its incidence is rising, at great cost to individuals, families, and wider society.It is significantly associated with risk of suicide, violence, and accidents-the most common causes of death for young people. 2 It is also an important marker of serious social problems, which should be explored with all those who present to health services. 3 Despite this, emergency department doctors often don't screen for alcohol misuse in young people and are poor at recognising it without formalised screening tools.AUDIT and its derivatives can be used in adolescents, although lower cut-off scores than for adults are probably wise.Just asking, "How often do you get drunk?"identifies young people at risk of traumatic injury through drinking, 4 and the Paddington alcohol test identifies "binge" drinkers. 5 Testing blood alcohol levels at presentation is no substitute for formally investigating drinking habits and risk behaviour because young people are drunk at lower blood alcohol concentrations than adults and binge drinking is intermittent.Although it has been reported that young people are more prone than adults to hypoglycaemia when drunk, this is rare.Other pathologies must be considered in intoxicated adolescents with hypoglycaemia, including infection or additional toxic and metabolic insults.
The Symbol of Modern Medicine
Authors: Michael E. Toedt, Dominique M. Gooby Toedt
Journal: Annals of Internal Medicine (2004)

Letters17 February 2004The Symbol of Modern MedicineMichael E. Toedt, MD and Dominique M. Gooby Toedt, MDMichael E. Toedt, MDFrom Jackson General Hospital, Millcreek Family Medicine; Ripley, WV 25271.Search for more papers by this author and Dominique M. Gooby Toedt, MDFrom Jackson General Hospital, Millcreek Family Medicine; Ripley, WV 25271.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-140-4-200402170-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Drs. Wilcox and Whitham missed several important points of history in their article about serpentine symbols of medicine (1). Regarding the Asklepian, their article makes no mention of the healing staff of Moses: “And Moses made a serpent of brass, and put it upon a pole, and it came to pass, that if a serpent had bitten any man, when he beheld the serpent of brass, he lived” (2). The Book of Numbers dates from 1444 to 1405 BC (3), while the cult of Asklepios is said to date from the sixth century BC (4).Wilcox and ...References1. Wilcox RA, Whitham EM. The symbol of modern medicine: why one snake is more than two. Ann Intern Med. 2003;138:673-7. [PMID: 12693891] LinkGoogle Scholar2. Numbers 21:9 (KJV). Google Scholar3. Christian Apologetics and Research Ministry. When Was the Bible Written and Who Wrote It? Accessed at www.carm.org/bible/biblewhen.htm on 11 April 2003. Google Scholar4. Hellenic Ministry of Culture. Sanctuary of Asklepios at Ancient Epidaurus. Accessed at www.culture.gr/2/21/211/21104a/e211da03.html on 11 April 2003. Google Scholar5. Williams R. The United States Public Health Service, 1798-1950. Washington, DC: Commissioned Officers Association of the Public Health Service; 1951. Google Scholar Author, Article, and Disclosure InformationAuthors: Michael E. Toedt, MD; Dominique M. Gooby Toedt, MDAffiliations: From Jackson General Hospital, Millcreek Family Medicine; Ripley, WV 25271. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Symbol of Modern Medicine: Why One Snake Is More Than Two* Robert A. Wilcox and Emma M. Whitham The Symbol of Modern Medicine Neni Prasad The Symbol of Modern Medicine Adrian G. Letz The Symbol of Modern Medicine Drew Hause The Symbol of Modern Medicine Meyer D. Lifschitz The Symbol of Modern Medicine Sarkis J. Chobanian The Symbol of Modern Medicine David P. Steensma The Symbol of Modern Medicine Konstantinos Paparounas The Symbol of Modern Medicine Jamie Newman The Symbol of Modern Medicine Robert A. Wilcox and Emma M. Whitham Metrics 17 February 2004Volume 140, Issue 4Page: 309KeywordsArmed forcesHistory of medicineMedical servicesSurgeons ePublished: 17 February 2004 Issue Published: 17 February 2004 Copyright & PermissionsCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The two tier syndrome behind waiting lists
Authors: D. Light
Journal: BMJ (2000)

The Labour government is making a serious effort to shorten the waiting times for specialist assessment and treatment. But if real progress is to be made it must tackle the two tier syndrome.

Past governments have formally sponsored private practice as a second tier by assuring long waits for NHS services and by writing contracts that provide consultants with incentives and ample time to induce patients to pay high fees for the treatments they should receive free.

Waiting lists have been attacked piecemeal and it is a pointless effort. Charges that lists are artificially reduced by pressurising general practitioners not to refer, or removing people from the lists, or by making more serious cases wait longer, are shuffling exercises that leave underlying causes untouched.

> This is a blatant conflict of interest, an invitation to mischief 

The two tier syndrome has six elements that have reinforced each other so well that the public and doctors think that long waits are as much a fact of life as waiting nine months for a …
The Spectrum of Pathogenetic Mechanisms of Anemia in Patients with Chronic Myelocytic Leukemia.
Authors: M. J. Cline
Journal: Annals of Internal Medicine (1962)

s1 April 1962The Spectrum of Pathogenetic Mechanisms of Anemia in Patients with Chronic Myelocytic Leukemia.M. J. Cline, M.D., N. I. Berlin, M.D.M. J. Cline, M.D.Search for more papers by this author, N. I. Berlin, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-56-4-684_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe pathogenetic mechanisms of anemia in 11 patients with chronic myelocytic leukemia were studied using radioactive iron to measure the rate of erythropoiesis and patterns of ferro-kinetics, glycine-2-C14 and diisopropylfluorophosphate-P32 to measure red cell survival, and radioactive sodium chromate to measure total red cell volume, apparent red cell survival, and fecal blood loss.Six of the patients had normal total red cell volumes despite a low peripheral hemoglobin concentration; this discrepancy probably reflects an increased splenic erythrocyte content.Evidence for iron deficiency was found in six of the patients. Seven patients had increased plasma cell iron turnover rates as a... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Bethesda, Md. (CI) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1962Volume 56, Issue 4Page: 684-684KeywordsAnemiaBlood cellsBlood volumeChronic myelocytic leukemiaErythropoiesisHemoglobinIron deficiencyPathogensPlasma cellsSodium Issue Published: 1 April 1962 PDF DownloadLoading ...
Illuminating HDL — Is It Still a Viable Therapeutic Target?
Authors: Daniel J. Rader
Journal: New England Journal of Medicine (2007)

Raising plasma levels of high-density lipoprotein (HDL) cholesterol has been a therapeutic goal ever since the strong inverse association between HDL levels and the risk of coronary heart disease was first observed.1 Nearly two decades ago, the discovery that persons in Japan had extremely high levels of HDL cholesterol because of a genetic deficiency involving the cholesteryl ester transfer protein (CETP) led to the concept that pharmacologic inhibition of CETP could raise HDL cholesterol levels. When this theory proved to be true in humans, it led to great anticipation that CETP inhibition would permit the ultimate test of the "HDL . . .
Loss of PIP5KIγ, unlike other PIP5KI isoforms, impairs the integrity of the membrane cytoskeleton in murine megakaryocytes
Authors: Yanfeng Wang, Rustem I. Litvinov, Xinsheng Chen, Tami L. Bach, Lurong Lian, Brian G. Petrich, Susan J. Monkley, David R. Critchley, Takehiko Sasaki, Morris J. Birnbaum, John W. Weisel, John Hartwig, Charles S. Abrams
Journal: Journal of Clinical Investigation (2008)

Phosphatidylinositol-4,5-bisphosphate (PIP(2)) is an abundant phospholipid that contributes to second messenger formation and has also been shown to contribute to the regulation of cytoskeletal dynamics in all eukaryotic cells. Although the alpha, beta, and gamma isoforms of phosphatidylinositol-4-phosphate-5-kinase I (PIP5KI) all synthesize PIP2, mammalian cells usually contain more than one PIP5KI isoform. This raises the question of whether different isoforms of PIP5KI fulfill different functions. Given the speculated role of PIP(2) in platelet and megakaryocyte actin dynamics, we analyzed murine megakaryocytes lacking individual PIP5KI isoforms. PIP5KIgamma(-/-) megakaryocytes exhibited plasma membrane blebbing accompanied by a decreased association of the membrane with the cytoskeleton. This membrane defect was rescued by adding back wild-type PIP5KIgamma, but not by adding a catalytically inactive mutant or a splice variant lacking the talin-binding motif. Notably, both PIP5KIbeta- and PIP5KIgamma(-/-) cells had impaired PIP(2) synthesis. However, PIP5KIbeta-null cells lacked the membrane-cytoskeleton defect. Furthermore, overexpressing PIP5KIbeta in PIP5KIgamma(-/-) cells failed to revert this defect. Megakaryocytes lacking the PIP5KIgamma-binding partner, talin1, mimicked the membrane-cytoskeleton defect phenotype seen in PIP5KIgamma(-/-) cells. These findings demonstrate a unique role for PIP5KIgamma in the anchoring of the cell membrane to the cytoskeleton in megakaryocytes, probably through a pathway involving talin. These observations further demonstrate that individual PIP5KI isoforms fulfill distinct functions within cells.
Aspirin enhances the induction of type I allergic symptoms when combined with food and exercise in patients with food-dependent exercise-induced anaphylaxis.
Authors: S. Harada, T. Horikawa, M. Ashida, T. Kamo, E. Nishioka, M. Ichihashi
Journal: British Journal of Dermatology (2001)

We examined the effect of aspirin as a substitute for exercise in inducing urticaria/anaphylaxis in three patients with food‐dependent exercise‐induced anaphylaxis (FDEIA). Two of the patients had specific IgE antibodies to wheat and the other had antibodies to shrimp. Administration of aspirin before ingestion of food allergens induced urticaria in one patient and urticaria and hypotension in another, while aspirin alone or food alone elicited no response. The third patient developed urticaria only when he took all three items, i.e. aspirin, food and additional exercise, whereas provocation with any one or or two of these did not induce any symptoms. These findings suggest that aspirin upregulates type I allergic responses to food in patients with FDEIA, and further shows that aspirin synergizes with exercise to provoke symptoms of FDEIA. This is the first report of a synergistic effect of aspirin in inducing urticaria/anaphylaxis, which was confirmed using challenge tests in patients with FDEIA.
Mechanism and specificity of increased amylase/creatinine clearance ratio in pancreatitis
Authors: A. Marten, D. Beales, E. Elias
Journal: Gut (1977)

The amylase/creatinine clearance ratio (Cam/Ccr ratio) was determined in 239 subjects. In 87 hospitalised patients without pancreatic disease (controls) the Cam/Ccr ratio was 3·02 ± 0·69 (mean ± ISD). The ratio was above the normal range in all patients with acute pancreatitis but was normal in those with chronic pancreatitis and carcinoma of the pancreas. In 18 patients with choledocholithiasis a raised ratio distinguished those with pancreatitis as assessed independently by the surgeon at laparotomy from those with a macroscopically normal pancreas. Raised Cam/Ccr ratios were also found in diabetics with ketoacidosis and in three patients with fulminant alcoholic liver disease. Though a positive correlation was found between the Cam/Ccr ratio and serum creatinine concentration, abnormally high ratios did not occur in 30 patients with chronic renal failure. A significant increase in Cam/Ccr ratios was produced in six healthy volunteers by intravenous injection of glucagon. However, it is unlikely that hyperglucagonaemia alone accounts for the increased Cam/Ccr ratio seen in acute pancreatitis, as no correlation was found between the clearance ratio and the plasma glucagon concentration in a series of patients. In two other patients in whom excess circulating pancreatic polypeptide was detected the Cam/Ccr ratio was normal. It is concluded that, in view of the sensitivity and relative specificity of finding an increased Cam/Ccr ratio in acute pancreatitis, its determination should be valuable clinically, especially in those cases of hyperamylasaemia where the cause is in doubt. The mechanism whereby the ratio is increased is unknown, and it is unlikely that either glucagon or pancreatic polypeptide is a major factor in its production.