tbuckley/cabot-search huggingface dataset:
Transposition of the Great Vessels
Authors: CHARLOTTE FERENCZ
Journal: Circulation (1966)

A microscopic study of the lungs of 106 patients with transposition of the great vessels has revealed early and severe hypertensive alterations in the pulmonary arteries. These striking changes, associated in almost all instances with normal pulmonary veins, indicate a state of high resistance of the arterial bed. Pulmonary arterial damage was, in general, most advanced in the patients with a large ventricular septal defect, but in spite of this these were the patients who lived longest. It seemed obvious, therefore, that their relatively favorable course was due to a greater beneficial than damaging effect of the ventricular septal defect. Consideration of these findings in the light of known physiologic data has led to a clarification of the physiologic variations of the transposition circulation. Using the recognized physiologic definitions of flows and shunts the transposition circulation is characterized by a diminished effective flow and a bidirectional but predominantly left-to-right shunt. The effect of a large intracardiac communication is to increase the effective flow and to lessen the shunts. With increasing size of the intracardiac communication the spectrum is completed when the circulatory characteristics of a single ventricle are reached in which the anatomic position of the great vessels becomes physiologically insignificant. The effect of a common systolic ejectile force in patients with a large ventricular septal defect will be similar in the transposition circulation and in the normal circulation. Three physiologic states are possible which depend upon the relative magnitude of the systemic and pulmonary resistances. The early appearance and malignant nature of the hypertensive alterations in the pulmonary arteries of patients with transposition of the great vessels suggest that the impact upon the lungs of high blood flow and pressure is aggravated by arterial vasoconstriction. This may be initiated by anoxia and a lowered blood pH. Elevation of pulmonary venous pressure and the increased viscosity of the blood due to polycythemia may add to the damage. Prominence of the bronchial arteries noted in the lung sections suggests that an expanded bronchial circulation augments the effective flow in these patients. If the bronchial venous drainage leads to systemic veins, the bronchial circulation could act as an accessory pulmonary circulation and could improve the effective flow without having to cross the already overloaded intracardiac communications. The anatomic findings and physiologic considerations reported in this study reveal several aspects of the early and severely damaging cardiopulmonary effect of transposition of the great vessels and indicate an urgent necessity of surgical therapy in early life.
Sequel of a Case of Puncture through the Abdominal Parietes in Impassable Obstruction of the Bowels
Authors: H. Cooper
Journal: BMJ (1857)

BuTmU MIDICAL JOUaZALj ORIGINAL (MMUNIOATIONS.[ (AGUST 8,1857.were then brouligt together in the usual way; a long stight splint,reahing from the foot nearly to the axilla, was applied to the outside of the limb, having a deficiency opposite to the wound, where itb place was supplied by an iron bar.There was still some inclination of the limb inwards.Water dre g was applied to the wound.JuJy 10th.He lhas been doing well; the limb is brought into a better position.July 14th.The wound is looking healthy.The child's heAlth is very good.Jutly 23rd.He has been progressing most favourably since
Comparative Pharmacokinetics and Insulin Action for Three Rapid-Acting Insulin Analogs Injected Subcutaneously With and Without Hyaluronidase
Authors: Linda Morrow, Douglas B. Muchmore, Marcus Hompesch, Elizabeth A. Ludington, Daniel E. Vaughn
Journal: Diabetes Care (2012)

To compare the pharmacokinetics and glucodynamics of three rapid-acting insulin analogs (aspart, glulisine, and lispro) injected subcutaneously with or without recombinant human hyaluronidase (rHuPH20).This double-blind six-way crossover euglycemic glucose clamp study was conducted in 14 healthy volunteers. Each analog was injected subcutaneously (0.15 units/kg) with or without rHuPH20.The commercial formulations had comparable insulin time-exposure and time-action profiles as follows: 50% exposure at 123-131 min and 50% total glucose infused at 183-186 min. With rHuPH20, the analogs had faster yet still comparable profiles: 50% exposure at 71-79 min and 50% glucose infused at 127-140 min. The accelerated absorption with rHuPH20 led to twice the exposure in the first hour and half the exposure beyond 2 h, which resulted in 13- to 25-min faster onset and 40- to 49-min shorter mean duration of insulin action.Coinjection of rHuPH20 with rapid-acting analogs accelerated insulin exposure, producing an ultra-rapid time-action profile with a faster onset and shorter duration of insulin action.
Environmental Influence on Implantable Pacemakers
Authors: Richard A. Carleton
Journal: JAMA (1965)

<h3>To the Editor:—</h3> Following the publication of our paper "Environmental Influence on Implantable Cardiac Pacemakers" (<i>JAMA</i><b>190</b>:938-940 [Dec 7] 1964), we received a most thought-provoking letter from a physician which pointed out a deficiency in our study. Although a wide variety of commonplace and exotic devices and environments were tested, the device which daily is closest to a man's bosom was overlooked by three investigators who happen to be brush-and-safety-razor advocates. Pacemakers have now been tested in immediate `contact with eight models (four manufacturers) of electric razors. None of these shaving devices interrupted or interfered with pacemaker activity.
Association between molecular lesions and specific B-cell receptor subsets in chronic lymphocytic leukemia
Authors: Davide Rossi, Valeria Spina, Riccardo Bomben, Silvia Rasi, Michele Dal-Bo, Alessio Bruscaggin, Francesca Maria Rossi, Sara Monti, Massimo Degan, Carmela Ciardullo, Roberto Serra, Antonella Zucchetto, Josep Nomdedeu, Pietro Bulian, Alberto Grossi, Francesco Zaja, Gabriele Pozzato, Luca Laurenti, Dimitar G. Efremov, Francesco Di-Raimondo, Roberto Marasca, Francesco Forconi, Giovanni Del Poeta, Gianluca Gaidano, Valter Gattei
Journal: Blood (2013)
Lysine Demethylase LSD1 Coordinates Glycolytic and Mitochondrial Metabolism in Hepatocellular Carcinoma Cells
Authors: Akihisa Sakamoto, Shinjiro Hino, Katsuya Nagaoka, Kotaro Anan, Ryuta Takase, Haruka Matsumori, Hidenori Ojima, Yae Kanai, Kazunori Arita, Mitsuyoshi Nakao
Journal: Cancer Research (2015)

The hallmark of most cancer cells is the metabolic shift from mitochondrial to glycolytic metabolism for adapting to the surrounding environment. Although epigenetic modification is intimately linked to cancer, the molecular mechanism, by which epigenetic factors regulate cancer metabolism, is poorly understood. Here, we show that lysine-specific demethylase-1 (LSD1, KDM1A) has an essential role in maintaining the metabolic shift in human hepatocellular carcinoma cells. Inhibition of LSD1 reduced glucose uptake and glycolytic activity, with a concurrent activation of mitochondrial respiration. These metabolic changes coexisted with the inactivation of the hypoxia-inducible factor HIF1α, resulting in a decreased expression of GLUT1 and glycolytic enzymes. In contrast, during LSD1 inhibition, a set of mitochondrial metabolism genes was activated with the concomitant increase of methylated histone H3 at lysine 4 in the promoter regions. Consistently, both LSD1 and GLUT1 were significantly overexpressed in carcinoma tissues. These findings demonstrate the epigenetic plasticity of cancer cell metabolism, which involves an LSD1-mediated mechanism.
Incidence and recurrence rates of colorectal adenomas estimated by annually repeated colonoscopies on asymptomatic Japanese
Authors: Y Yamaji
Journal: Gut (2004)

Whereas high recurrence rates of colorectal adenomas after polypectomy are widely recognised, little is known of the natural incidence in those with no neoplastic lesions initially. It is also known that single colonoscopy has a significant miss rate.To elucidate the incidence and recurrence rates of colorectal neoplasms from a large cohort of asymptomatic Japanese patients on the basis of annually repeated colonoscopies.A total of 6225 subjects (4659 men and 1566 women) participating in an annual colonoscopic screening programme and completing three or more colonoscopies were analysed during the 14 year period between 1988 and 2002. Patients were divided into three groups according to the findings of the initial two colonoscopies: 4084 subjects with no neoplasm, 1818 with small adenomas <10 mm, and 323 with advanced lesions, including carcinoma in situ, severe dysplasia, or large adenomas > or =10 mm. Mean age at the second colonoscopy was 48.8 years.For all types of colorectal neoplasms, the incidence rate in those with no initial neoplasm was 7.2%/year whereas recurrence rates in those with small adenomas and advanced lesions were 19.3% and 22.9%/year, respectively. For advanced colorectal lesions, the incidence rate was 0.21%/year whereas recurrence rates in those with small adenomas and advanced lesions were 0.64% and 1.88%/year, respectively. Colorectal neoplasms were in general more likely to develop in males and older subjects.Although recurrence rates after polypectomy were elevated, the incidence rates in subjects with no neoplastic lesions initially were quite high.
Vitamin D: An innate antiviral agent suppressing hepatitis C virus in human hepatocytes
Authors: Meital Gal-Tanamy, Larisa Bachmetov, Amiram Ravid, Ruth Koren, Arie Erman, Ran Tur-Kaspa, Romy Zemel
Journal: Hepatology (2011)

Vitamin D supplementation was reported to improve the probability of achieving a sustained virological response when combined with antiviral treatment against hepatitis C virus (HCV). Our aim was to determine the in vitro potential of vitamin D to inhibit HCV infectious virus production and explore the mechanism(s) of inhibition. Here we show that vitamin D(3) remarkably inhibits HCV production in Huh7.5 hepatoma cells. These cells express CYP27B1, the gene encoding for the enzyme responsible for the synthesis of the vitamin D hormonally active metabolite, calcitriol. Treatment with vitamin D(3) resulted in calcitriol production and induction of calcitriol target gene CYP24A1, indicating that these cells contain the full machinery for vitamin D metabolism and activity. Notably, treatment with calcitriol resulted in HCV inhibition. Collectively, these findings suggest that vitamin D(3) has an antiviral activity which is mediated by its active metabolite. This antiviral activity involves the induction of the interferon signaling pathway, resulting in expression of interferon-β and the interferon-stimulated gene, MxA. Intriguingly, HCV infection increased calcitriol production by inhibiting CYP24A1 induction, the enzyme responsible for the first step in calcitriol catabolism. Importantly, the combination of vitamin D(3) or calcitriol and interferon-α synergistically inhibited viral production.This study demonstrates for the first time a direct antiviral effect of vitamin D in an in vitro infectious virus production system. It proposes an interplay between the hepatic vitamin D endocrine system and HCV, suggesting that vitamin D has a role as a natural antiviral mediator. Importantly, our study implies that vitamin D might have an interferon-sparing effect, thus improving antiviral treatment of HCV-infected patients.
Ubiquitous high-level gene expression in hematopoietic lineages provides effective lentiviral gene therapy of murine Wiskott-Aldrich syndrome
Authors: Alexander Astrakhan, Blythe D. Sather, Byoung Y. Ryu, Socheath Khim, Swati Singh, Stephanie Humblet-Baron, Hans D. Ochs, Carol H. Miao, David J. Rawlings
Journal: Blood (2012)
Points: Polyunsaturated fatty acids and colchicine in multiple sclerosis
Authors: L Mervyn
Journal: BMJ (1979)

This would perhaps bring home to the DHSS the extent to which the consultants are financ- ing the Health Service by running their own cars.I personally as a consultant manage to run one mini.My wife wonders why I spend all this money running a car for the sake of the NHS when she never has the use of it.I feel that the time has come now for my wife to have the use of our car and to insist that the hospital provides transport when it is needed.
A Case-Control Study of Caffeine and Methylxanthines in Benign Breast Disease
Authors: Flora Lubin
Journal: JAMA (1985)

A dietary case-control study of 854 histologically diagnosed cases of benign breast disease (BBD), 755 matched surgical controls, and 723 matched neighborhood controls was conducted in Israel between 1977 and 1980. No association between coffee consumption and BBD was found. Analyses by histological type, degree of ductal atypia, age, sex, and ethnic origin, controlling for several confounding factors, confirmed the lack of association. The estimated mean intake of methylxanthines was also similar for cases and controls (302, 312, and 313 mg for cases, surgical controls, and neighborhood controls, respectively). No evidence of a dose-response was noted. Our results suggest that there is no association between coffee or methylxanthine consumption and BBD, although we had a 70% chance of finding a risk ratio of 1.5 with an error of 5%. (<i>JAMA</i>1985;253:2388-2392)
Permission for Autopsies
Authors: Milton G. Bohrod
Journal: JAMA (1961)

<h3>To the Editor:—</h3> Those of us who have considered the reasons why families deny permission for autopsies have long felt that love and consideration have little or nothing to do with refusals. We have pointed out that the highest autopsy rates in our general hospitals have frequently been in the pediatric departments. No matter how low one's estimate of humankind, one is forced to admit that most men love their children; it seems unlikely, therefore, that love is the motive for refusing necropsy permission. Recently, you have published data inThe Journalwhich demonstrate this argument very clearly. In Table 13 (<i>JAMA</i><b>177</b>:629 [Sept. 2] 1961), in the article on graduate medical education, you list the 20 nonfederal hospitals with the highest autopsy rates. Of these, 13 (65%) are children's hospitals, located in many parts of the country. Since pediatric hospitals make up only a small fraction of the
Clinical outcome and monitoring of minimal residual disease in patients with acute lymphoblastic leukemia expressing the <i>MLL/ENL</i> fusion gene
Authors: Loredana Elia, Sara Grammatico, Francesca Paoloni, Marco Vignetti, Angela Rago, Natalia Cenfra, Sergio Mecarocci, Marco Mancini, Matteo Luciani, Francesco Di Raimondo, Giovanni Cazzaniga, Mabel Matarazzo, Maria Luisa Moleti, Lidia Santoro, Gianluca Gaidano, Robin Foà, Franco Mandelli, Giuseppe Cimino
Journal: American Journal of Hematology (2011)

We analyzed 12 MLL/ENL positive ALL patients consecutively diagnosed between 1999 and 2009. The MLL/ENL fusion was identified in 4/150 (2.6%), 8/993 (0.8%), and 0/70 of pediatric, adult, and elderly patients, respectively. Eight patients had a WBC count >50 × 10(9) /L. Ten cases had an evaluable immunophenotyping. A B or T precursor ALL occurred in 7 and 3 patients, respectively. Eleven/12 patients (92%) achieved CR. At 48 months, overall survival and event-free survival rates were 73.3% and 67%, respectively. At CR, a parallel RT-PCR evaluation of the MLL/ENL expression was available in 5 cases. Of these latter, 2 tested MLL/ENL-negative and 3 positive. The minimal residual disease molecular monitoring showed that MLL/ENL status did not correlate with outcome. In fact, all the 2 PCR-negative and 1 of the 3 PCR-positive cases relapsed. Further, a MLL/ENL expression, not preceding a relapse, was detected several times during the follow-up of five long-survivors. In conclusion, also in adults, the MLL/ENL fusion identifies a rare leukemic entity with a favorable prognosis. The observed inconsistency between the clinical cure and the presence of detectable MLL/ENL transcript suggests the existence of a MLL/ENL-expressing "preleukemia" stem cells, similar to what demonstrated for the AML1/ETO-positive leukemia setting.
Arise, Sir Lancelot
Authors: J. O. Drife
Journal: BMJ (1999)

Greying beard, dark suit, middle age spread, consultant status. Coincidence, or have I been subconsciously working on my image? Anyone over 50 feels like a youngster in an ageing body, but for a few of us, Simon Sparrow is trapped inside Lancelot Spratt.

Doctor in the House was published in 1952, when I was 4 years old. The film was produced in 1954 by Betty Box, who died recently. Sir Lancelot was played by James …
Indirect arterial pulse tracings in children with coarctation of the aorta before and after operation.
Authors: M Oyonarte, D F Dickinson, D Medici, D I Hamilton
Journal: Thorax (1980)

Eleven children with coarctation of the aorta were investigated before and after surgical treatment, using simultaneous indirect carotid and femoral pulse wave tracing. The timing of the onset of the femoral pulse in the children with coarctation, both before and after operation, did not differ significantly from normal. However, the time interval between the peak of the femoral pulse and the dicrotic notch of the carotid pulse was significantly shorter than normal in the children with coarctation before operation. After operation, the peak femoral to carotid dicrotic notch time interval was restored to normal. It is suggested that this simple non-invasive test might be of value in the long-term follow-up of patients after operation for coarctation of the aorta, particularly in those undergoing operation early in childhood, to detect residual or recurrent coarctation.
Prevalence and Risk Factors for Micro- and Macroalbuminuria in an Italian Population-Based Cohort of NIDDM Subjects
Authors: Graziella Bruno, Paolo Cavallo-Perin, Giuseppe Bargero, Milena Borra, Valentina Calvi, Nicola D'Errico, Piercarlo Deambrogio, Gianfranco Pagano
Journal: Diabetes Care (1996)

OBJECTIVE To determine the prevalence of micro- and macroalbuminuria in NIDDM and their relationship with some known and putative risk factors. RESEARCH DESIGN AND METHODS Out of a population-based cohort of 1,967 NIDDM subjects, 1,574 were investigated (80%). Albumin excretion rate (AER) was evaluated on an overnight urine collection, and plasma and urine determinations were centralized. RESULTS The prevalences of microalbuminuria (AER 20–200 μg/min), macroalbuminuria (AER &amp;gt; 200 μg/min), and hypertension were 32.1% (95% CI 29.8–34.4), 17.6% (15.7–19.5), and 67% (64.6–69.3), respectively. Apart from prevalence of hypertension, which after adjustment for age, BMI, and duration of diabetes was 2.3 times higher in women, rates were higher in men (odds ratio [OR] 1.31, 95% CI 1.04–1.66 for microalbuminuria and OR 1.63, 1.22–2.17 for macroalbuminuria). In comparison with normoalbuminuric subjects, both micro- and macroalbuminuric diabetic subjects had significantly longer duration of diabetes, higher levels of systolic blood pressure, fasting plasma glucose, HbA1c, triglycerides, and uric acid; in macroalbuminuric subjects only, levels of apolipoprotein B and HDL cholesterol were, respectively, higher and lower than in normo- and microalbuminuric subjects. In logistic regression, variables independently related to both micro- and macroalbuminuria were age, HbA1c, cigarette smoking habits, plasma uric acid, and diastolic blood pressure, after adjustment for plasma creatinine and diabetic treatment. In addition, duration of diabetes and HDL cholesterol levels were associated with macroalbuminuria. CONCLUSIONS This population-based study showed high prevalence of micro- and macroalbuminuria in NIDDM subjects, who were characterized by a more adverse pattern of cardiovascular risk factors.
Treatment of Comorbid Substance Dependence and Posttraumatic Stress Disorder
Authors: Katherine Mills
Journal: JAMA (2013)

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Studies of apoptosis in breast cancer
Authors: M. Parton
Journal: BMJ (2001)

Breast cancer is the commonest malignancy in women and comprises 18% of all cancers in women. The United Kingdom has the highest age standardised incidence and mortality from breast cancer in the world.1 Since 1990, death rates from breast cancer have decreased by over 25%, and this is at least in part due to the improved use of adjuvant tamoxifen and chemotherapy. Current research is focused on a greater understanding of the response and resistance to treatment, including the role of apoptosis. Accessibility of the primary tumour makes breast cancer uniquely suitable for such studies. Here we summarise and integrate the data on apoptosis and its role in the development, prognosis, and treatment of breast cancer.

Normal breast development is controlled by a balance between cell proliferation and apoptosis, and there is strong evidence that tumour growth is not just a result of uncontrolled proliferation but also of reduced apoptosis. The balance between proliferation and apoptosis is crucial in determining the overall growth or regression of the tumour 2 3 in response to chemotherapy, radiotherapy and, more recently, hormonal treatments. All of these act in part by inducing apoptosis.4–6 Thus it is possible to delineate the biology of individual tumours at the molecular and biochemical level by examining apoptosis and its control and regulation and to exploit these to clinical advantage. Much of this work is still the subject of research. Understanding these relations could allow individually tailored treatments to maximise tumour regression and the efficacy of treatment. It could also help to answer why some tumours fail to respond and thereby indicate new routes of drug development.

#### Summary points

Increased apoptosis with increased proliferation is associated with malignant tumours

Breast tumours with increased apoptosis are more likely to be high grade and negative for oestrogen receptors

High …
Estimation of regurgitant flow volume based on centerline velocity/distance profiles using digital color M-Q Doppler: Application to orifices of different shapes
Authors: Takahiro Shiota, Dag Teien, You-Bin Deng, Shuping Ge, Robin Shandas, Scott Holcomb, David J. Sahn
Journal: Journal of the American College of Cardiology (1994)