tbuckley/cabot-search huggingface dataset:
Reduced Gene Expression of Vascular Endothelial NO Synthase and Cyclooxygenase-1 in Heart Failure
Authors: Carolyn J. Smith, Dong Sun, Carl Hoegler, Barrie S. Roth, Xiaoping Zhang, Gong Zhao, Xiao-Bin Xu, Yukage Kobari, Kirkwood Pritchard, William C. Sessa, Thomas H. Hintze
Journal: Circulation Research (1996)

Abstract Endothelium-dependent responses are depressed in coronary and peripheral blood vessels after the onset of pacing-induced heart failure in dogs and heart failure of various etiologies in humans. The present study was designed to examine whether these responses were due to decreases in the expression of endothelial cell NO synthase (ecNOS) and cyclooxygenase-1 (COX-1). After 1 month of left ventricular pacing, 8 mongrel dogs were monitored for heart failure as defined by clinical signs and left ventricular end diastolic pressures &gt;25 mm Hg. Total RNA and protein were isolated from endothelial cells scraped from the thoracic aorta and analyzed by Northern and Western blotting, respectively. Blots probed with 32 P-labeled cDNAs for ecNOS and COX-1 were quantified densitometrically, and results were normalized against GAPDH or von Willebrand factor (vWF). In arbitrary units, the ratios of ecNOS to GAPDH were 2.66±0.77 (mean±SEM, n=17) and 1.12±0.37 (n=6), and the ratios of COX-1 to GAPDH were 1.52±0.52 and 0.56±0.15 before and after heart failure, respectively. These represent 56% to 64% ( P &lt;.05) reductions in ecNOS and COX-1 gene expression. There was no change in the ratios of either COX-1 or ecNOS to vWF. There was also a marked reduction in ecNOS protein after heart failure, estimated at 70%. A marked reduction in nitrite production, a measure of enzyme activity, from thoracic aortas in response to stimulation by either acetylcholine or bradykinin also occurred. To determine whether ecNOS and COX-1 could be independently regulated, an orally active NO-releasing agent, CAS 936, was given to 7 normal dogs for 7 days, and aortic ecNOS and COX-1 mRNAs were analyzed. The ratio of ecNOS to GAPDH was depressed by 52% ( P &lt;.05) in aortas from these dogs, whereas the ratio of COX-1 to GAPDH was unchanged. Similar results were found when data were normalized to vWF. These results suggest that at least two endothelial vasodilator gene products are reduced in heart failure, as opposed to a selective defect in NO synthase gene expression.
Delayed Rupture of the Spleen After Cardiac Massage
Authors: Rubin Berlinerblau
Journal: JAMA (1980)

THE widespread practice of external cardiac massage has drawn growing attention to the complications of this vigorous and often traumatic treatment. Although most of these complications are detected early and their mechanisms easily understood, others may become evident only after a marked delay and when their time relationship to the cardiac massage is no longer clear. Such a case of late and life-threatening complication is presented here. <h3>Report of a Case</h3> A 57-year-old woman was admitted to the emergency room of the Maimonides Medical Center, Brooklyn, NY, because of chest pain of several hours' duration, radiating into the left arm and associated with nausea and diaphoresis and syncope. She had two episodes of ventricular fibrillation, during which she received external cardiac massage. The ECG showed a pattern of inferior wall myocardial infarction, and her enzyme levels were elevated. On the 13th hospital day, the patient complained of pain in the
Teaching Rounds: Third-Party Rounds
Authors: Hugh H. Hussey
Journal: JAMA (1974)

At the 1973 Annual Convention, the Nebraska delegation presented a resolution (No. 14) calling for "a thorough study of third-party rounds" with a report on the subject to be delivered at the 1973 Clinical Convention. ("Rounds" was intended to mean the visiting of patients by physicians.) Reference committee hearings on the subject were extensive and complex. Terms such as third-party rounds, business rounds, teaching rounds, and working rounds were bandied about, adding confusion to complexity. In any event, the reference committee requested "further study of this important subject by appropriate AMA councils or committees." So it was that at the 1973 Clinical Convention, the Council on Medical Education, and the Council on Medical Service jointly reported that "third-party rounds" is a term subject to interpretive confusion but seemingly meant to refer to teaching rounds conducted by physicians who are not actively involved in management of patients' care. The councils deemed
Medicine a la mode
Authors: D. Spence
Journal: BMJ (2008)

I limped home with my bike, blood seeping through the knee of my jeans. I still have the scar. My flares had got caught up in the chain, and I was sent sprawling from my chopper. Enormous flared collars, cuffs, and trouser bottoms were all the rage then but would be far too dangerous to be allowed on children today for fear of tripping, entanglement, and the real risk of Bri-Nylon static electrocution. But fashion changes, and a few years later I risked sterility by squeezing into drainpipe …
Unemployment rates: an alternative to the Jarman index?
Authors: B Jarman
Journal: BMJ (1991)

on tattooing.Those who decide to have a tattoo should do so with full knowledge of the conse- quences.In addition, voung people need both the opportunity to reflect on their knowledge and the skills to make and sustain decisions against tattooing if this is their choice.These, and related tasks, should be the prime responsibility of health educators working with and through teachers and others with a responsibility for the education and development of young people.School health educators, however, are a beleaguered group with insufficient resources and support, and no core curriculum time is allocated to their subject.Smith may disagree with our view that doctors are not the most appropriate people to provide education on tattoos for youngsters but, we are sure, will join with us in calling for greater emphasis on health education in schools.
The Effect of Nebulized Epinephrine on Respiratory Mechanics and Gas Exchange in Bronchiolitis
Authors: ANDREW H. NUMA, GARY D. WILLIAMS, CAROLYN J. DAKIN
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Nebulized epinephrine has been advocated as a treatment for airway obstruction in infants with bronchiolitis; however, its effect on respiratory mechanics and gas exchange has been poorly documented to date. We performed a preinterventional and postinterventional study with primary outcome measures of mechanics (measured by single-breath occlusion passive deflation) and oxygenation and ventilation indices in order to measure the effects of nebulized epinephrine in infants requiring mechanical ventilation for RSV-positive bronchiolitis. A two-compartment model was used to describe respiratory mechanics in patients with nonlinear flow-volume curves. Nebulized epinephrine (0.5 mg/kg) was administered to 15 patients (median age, 0.19 yr; weight, 4.4 kg). Resistance decreased significantly in slow and fast compartments in 87 and 70% of patients, respectively. Median resistance in the slow compartment decreased from 0.427 to 0.198 cm H2O/ml/s (p = 0.0015) and in the fast compartment from 0.167 to 0.116 cm H2O/ ml/s (p = 0.018). Compliance, oxygenation index, and ventilation index were not significantly changed after administration of epinephrine. We conclude that nebulized epinephrine substantially improves respiratory system resistance but not oxygenation or ventilation indices. This may be because of the effects of epinephrine on oxygen consumption or ventilation-perfusion matching.
STRADα deficiency results in aberrant mTORC1 signaling during corticogenesis in humans and mice
Authors: Ksenia A. Orlova, Whitney E. Parker, Gregory G. Heuer, Victoria Tsai, Jason Yoon, Marianna Baybis, Robert S. Fenning, Kevin Strauss, Peter B. Crino
Journal: Journal of Clinical Investigation (2010)

Polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome (PMSE) is a rare human autosomal-recessive disorder characterized by abnormal brain development, cognitive disability, and intractable epilepsy. It is caused by homozygous deletions of STE20-related kinase adaptor α (STRADA). The underlying pathogenic mechanisms of PMSE and the role of STRADA in cortical development remain unknown. Here, we found that a human PMSE brain exhibits cytomegaly, neuronal heterotopia, and aberrant activation of mammalian target of rapamycin complex 1 (mTORC1) signaling. STRADα normally binds and exports the protein kinase LKB1 out of the nucleus, leading to suppression of the mTORC1 pathway. We found that neurons in human PMSE cortex exhibited abnormal nuclear localization of LKB1. To investigate this further, we modeled PMSE in mouse neural progenitor cells (mNPCs) in vitro and in developing mouse cortex in vivo by knocking down STRADα expression. STRADα-deficient mNPCs were cytomegalic and showed aberrant rapamycin-dependent activation of mTORC1 in association with abnormal nuclear localization of LKB1. Consistent with the observations in human PMSE brain, knockdown of STRADα in vivo resulted in cortical malformation, enhanced mTORC1 activation, and abnormal nuclear localization of LKB1. Thus, we suggest that the aberrant nuclear accumulation of LKB1 caused by STRADα deficiency contributes to hyperactivation of mTORC1 signaling and disruption of neuronal lamination during corticogenesis, and thereby the neurological features associated with PMSE.
Letter: Further application of the nitroblue tetrazolium test.
Authors: R M Rowan, A M Gordon, A K Chaudhuri, F Moran
Journal: BMJ (1974)

The nitroblue tetrazolium (N.B.T.) test was performed on patients in whom a differential diagnosis of pulmonary thromboembolism or lobar pneumonia existed. The mean N.B.T. score in healthy subjects was 6.4% (range 1%-15%). Patients with uncomplicated pulmonary thromboembolism showed a mean N.B.T. value of 7.5% (range 3%-12%). In patients with lobar pneumonia the mean N.B.T. score was 42.4% (range 21%-85%). These results suggest that the N.B.T. test is of value in the differential diagnosis of pulmonary thromboembolism and lobar pneumonia.
Understanding the symptoms of “schizophrenia” in evolutionary terms
Authors: Martin Brüne
Journal: Behavioral and Brain Sciences (2004)

An evolutionary theory of schizophrenia needs to address all symptoms associated with the condition. Burns' framework could be extended in a way embracing behavioural signs such as catatonia. Burns' theory is, however, not specific to schizophrenia. Since no one single symptom exists that is pathognomonic for “schizophrenia,” an evolutionary proposal of psychiatric disorders raises the question whether our anachronistic psychiatric nosology warrants revision.
Abstract 2148: Novel therapy of liver metastases of cancer using Abraxane loaded into Multi-Stage Nanovector.
Authors: Tomonori Tanei, Mauro Ferrari, Biana Godin, Kenji Yokoi
Journal: Cancer Research (2013)

Abstract Purpose; To investigate whether the Abraxane loaded within Multi-Stage Nanovector (MSV) system (MSV-ABX) is more effective in therapy of liver metastases of breast and colorectal cancer as compared to Abraxane (ABX). Experimental Design; MTT assay was performed to evaluate sensitivity of 4T1, murine breast cancer cells and CT26, murine colon cancer cells to ABX or MSV-ABX in vitro. Experimental liver metastases were produced by intra-splenic injection of 4T1 or CT26 cells in Balb/C mice. The mice bearing liver metastases were treated with intravenous injection of (1) control (PBS), (2) ABX or (3) MSV-ABX. Then the mice were sacrificed and liver weight was measured to evaluate the therapeutic efficacy. To evaluate the biological the effects of therapeutics, we performed histological and immunohistochemical analysis of the tumor specimens. Apoptosis of 4T1 and CT26 tumor cells were evaluated by TUNEL staining, and proliferation of the tumor cells were stained using antibody to Ki67. Tumor diameter was measured in H&amp;E stained sections. Results; There was no significant difference in the sensitivity of 4T1 and CT26 cancer cells to ABX and MSV-ABX, in vitro. All the mice injected with 4T1 or CT26 cells developed multiple liver metastases. The liver weight was significantly lower in the mice treated with MSV-ABX as compared to those in the other groups. The tumor diameters in the liver were significantly smaller in the mice treated with MSV-ABX as compared to those in the other two groups. Immunofluorescent analysis revealed that MSV-ABX inhibited proliferation and increased apoptosis of 4T1 and CT26 tumor cells in the liver significantly more than ABX. Conclusions; These studies demonstrate that MSV-ABX is more effective than ABX in therapy of the liver metastasis of breast and colorectal cancer in our mouse models. These data can be translated into the clinic for planning novel clinical trials using MSV-ABX. Citation Format: Tomonori Tanei, Mauro Ferrari, Biana Godin, Kenji Yokoi. Novel therapy of liver metastases of cancer using Abraxane loaded into Multi-Stage Nanovector. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2148. doi:10.1158/1538-7445.AM2013-2148
Fatal Acute Disseminated Nocardiosis in a Child
Authors: William K. Carlile
Journal: JAMA (1963)

The 17th known instance of nocardiosis occurring in a child is reported in the case of a 7-yr-old boy from a small Midwest community. Clinically, the course was acute and fulminating rather than chronic, as is usually the case. Initial symptoms were fever, cough, malaise, and thoracic pain. The leukocytes numbered from 18,000 to 20,000; about 80% were neutrophils, which is characteristic of nocardiosis. Etiologic diagnosis was made from cultures of purulent secretion obtained at the time of bronchoscopy. Meningitis developed subsequently and the boy died. Necropsy disclosed even more widespread evidence of the disease than had been determined earlier. The use of sulfadiazine, which is almost specific for this type of infection, was begun only after the cause was established. The disease was apparently too far advanced for effective treatment. Prior use of many antibiotics was of no benefit.
'Radiopaque' Foreign Bodies
Authors: Stephen D. Boren
Journal: JAMA (1977)

<h3>To the Editor.—</h3> Foreign bodies are a common emergency room problem. Diagnosis and treatment frequently are relatively simple, especially if the object is radiopaque. We recently had a case that demonstrates a possible diagnostic hazard. <h3>Report of a Case.—</h3> After an altercation, with a classmate, a 13-year-old boy arrived at the Clinton Primary Care Center with a ball-point pen embedded in his palate. His vital signs were stable, and results of physical examination showed only a blue pen projecting approximately 15 cm from his palate. X-ray films were taken (Fig 1 and 2). The area was anesthetized with 1% lidocaine with epinephrine, and the pen was extracted. It was noted that the pen had a plastic cap and was thus several centimeters longer than shown in the X-ray films (Fig 3 and 4). The patient was given 0.5 ml of tetanus toxoid, and therapy with phenoxymethyl penicillin, 250 mg four
Progression of Barrett’s esophagus to adenocarcinoma despite antireflux surgery
Authors: D. von Conrady, M. Smith, M. Khan, S. Tan, G. Mortimer, O. McAnena
Journal: Endoscopy (2008)

In 2004, a 63-year-old patient was diagnosed with Barrett’s esophagitis. A laparoscopic Nissen fundoplication was carried out as previously described, using a five port technique [1].
Ethnicity, Sex, and the NBME Part I Examination
Authors: James Michael Bestler
Journal: JAMA (1995)

<h3>To the Editor.</h3> —After reading the Editorial entitled "Examining the Examinations for Licensure and Certification in Medicine" by Dr Norcini,<sup>1</sup>I was left with the discomforting impression that Norcini is recommending that if candidates fail the examination it may be the examination's fault rather than the preparation of the candidate. I think that he is also suggesting that the candidate's ethnic background should be taken into account when difficulty with an examination is found. Can't a candidate just plain flunk? Then he or she can study harder, take it again next year, and hopefully do better.
TCT-99 The Vancouver Computed Tomography Sizing Guidelines for Transcatheter Aortic Valve Replacement with Balloon Expandable Valves
Authors: Alex Willson, Webb John, Melanie Freeman, David Wood, Ronen Gurvitch, Chris Thompson, Robert Moss, Stefan Toggweiler, Ronald Binder, Brad Munt, Anson Cheung, Cameron Hague, Jian Ye, Jonathon Leipsic
Journal: Journal of the American College of Cardiology (2012)
Noncirrhotic Portal Hypertension in Congenital Cytomegalovirus Infection
Authors: Fayez K. Ghishan, Harry L. Greene, Susan Halter, John A. Barnard, Roberto J. Moran
Journal: Hepatology (1984)

The majority of infants with cytomegalovirus hepatitis have resolution of the disease with little evidence of fibrosis; there are only rare instances of cirrhosis. We report an infant with cytomegalovirus hepatitis who developed portal hypertension and hematemesis at 3 months of age. Liver biopsy showed resolution of the hepatitis but the presence of noncirrhotic sinusoidal fibrosis. Because of recurrent hematemesis in spite of sclerosing therapy on two occasions, the beta antagonist propranolol was begun. Hepatic wedge pressures before and after treatment with propranolol were 13 and 7 mm Hg, respectively. The findings emphasize: (i) that cytomegalovirus hepatitis may result in noncirrhotic sinusoidal fibrosis and (ii) that propranolol may be beneficial in the management of portal hypertension secondary to noncirrhotic sinusoidal fibrosis.
Tuning This Curious Harp
Authors: Dana W. Atchley
Journal: JAMA (1964)

Francis BACON in 1605 wrote... "the office of medicine is but to tune this curious harp of man's body and to reduce it to harmony." This poetic concept of the physician displays the fundamental insight that poetry achieves repeatedly as it holds the mirror to human affairs. There is today a growing awareness of the many strings in the fine instrument of man, and of the necessity for tuning them all to produce the harmony that is health. Bacon recognized his era's sad lack of knowledge concerning people and disease, but he made some amazingly prescient suggestions. Long before Thomas Sydenham was born, Bacon urged a return to the long discarded Hippocratic "diligence which used to set down a narrative... of his patients, and how they were judged by recovery or death"; he found "medicinal histories deficient." With pathology not even in its infancy, Bacon urges that the "footsteps of
Brunette to Blonde
Authors: J. D. Spillane
Journal: BMJ (1963)

in 1959, and 873 in 1960 (case-records all personally scrutinized).Allowing for a 2.8% annual increase in population, the yearly admissions per 100,000 population were 71, 81, 82, 84, 87, and 102.Since there was a disproportionate rise in admissions to Sungei Patani Hospital (136 in 1955 and 341 in 1960), we think greater use of hospitals is a more important factor than a progressive increase in snake-bite incidence in explaining these figures.Yet observers say there are more A. rhodostonia snakes than in pre-war days.This increase is ascribed to more undergrowth on the rubber estates, where less weeding has been carried out in the post-war era partly for economic reasons but also because the undergrowth prevents land erosion.The variables in age, sex, race, location, time and circumstances of bite, and site of the bite all reflect the rural and occupational nature of the snake-bite hazard.It is noteworthy that only 18 of the 1,032 Central Kedah bites occurred in the main town.The very high incidence of bites among rubber-estate weeders is another striking feature.In Malaya the pit viper A. rhodostoma is much the most common species biting human victims.Because it is confined to the north in Malaya, over two-thirds of all snake-bite cases in the
Contained Bile Leak Secondary to Falciform Ligament TEAR Demonstrated by Hepatobiliary Imaging
Authors: MORAKINYO A. OYEWOLE TONEY, ALBERT J. MORENO, ANA A. RODRIGUEZ, GOTTLIEB L TURNBULL
Journal: Clinical Nuclear Medicine (1991)

An 18-year-old man presented to the surgical service suffering multiple traumatic injuries following a motor vehicle accident. Hepatobiliary imaging was performed to study rising serum total bilirubin, right upper quadrant
French researchers join mass protest over continuing cuts
Authors: Brad Spurgeon
Journal: BMJ (2004)

Some 15 000 research scientists gathered outside Paris City Hall on 9 March where a movement called Save Research organised a mass protest in which more than 2000 of the country's 3500 scientists who lead laboratory research teams handed in “resignation” letters in which they stated that they were boycotting their administrative duties.

Save Research is protesting against the government's axing of 550 permanent research jobs and increasing budgetary restrictions. The rally kicked off a week of protests by French public sector workers on poor levels of pay.

Two days after the lobby at City Hall, the scientists marched with about 2000 hospital workers protesting at a government plan to overhaul the public hospital system by 2007, and on 12 March scientists joined nearly 100 000 …
New study increases concern over quality of healthcare and medical education in India
Authors: G. Mudur
Journal: BMJ (2012)

A study has found that healthcare professionals—doctors and non-doctors—in rural and urban India achieved low rates of diagnosis and deviated from standard treatment guidelines. It has increased concerns about the quality of healthcare services and medical education in India.

The study found only “small differences” between doctors and other healthcare providers without medical qualifications in their adherence to standard checklists during diagnosis and “no differences” in providing the correct diagnosis or appropriate treatment. The study indicated that equipment in clinics and doctors’ educational qualifications were only “weakly associated” with the quality of care.1

Jishnu Das, a senior economist at the World Bank in Washington, DC, and the study’s principal investigator, told the BMJ , “We’re questioning assumptions that a combination of qualifications and equipment can guarantee quality. We find this is not necessarily true.”

The study relied on standardised patients recruited from local communities who walked into …
Wnt Inhibitory Factor-1 Is Silenced by Promoter Hypermethylation in Human Lung Cancer
Authors: Julien Mazieres, Biao He, Liang You, Zhidong Xu, Amie Y. Lee, Iwao Mikami, Noemi Reguart, Rafael Rosell, Frank McCormick, David M. Jablons
Journal: Cancer Research (2004)

Aberrant activation of the Wingless-type (Wnt) signaling pathway is associated with a variety of human cancers, and we recently reported the importance of aberrant Wnt signaling in lung cancer. On the other hand, inhibition of Wnt signaling suppresses growth in numerous cell types. Wnt inhibitory factor-1 (WIF-1) is a secreted antagonist that can bind Wnt in the extracellular space and inhibit Wnt signaling. Recently, down-regulation of WIF-1 has been reported in several human cancers. To discover the mechanism of WIF-1 silencing in lung cancer, we first identified the human WIF-1 promoter and subsequently examined the methylation status in the CpG islands. By using methylation-specific PCR and sequence analysis after bisulfite treatment, we demonstrate here frequent CpG island hypermethylation in the functional WIF-1 promoter region. This hypermethylation correlates with its transcriptional silencing in human lung cancer cell lines. Moreover, treatment with 5-aza-2'-deoxycytidine restores WIF-1 expression. We then studied WIF-1 expression in 18 freshly resected lung cancers, and we show a down-regulation in 15 of them (83%). This silencing also correlates with WIF-1 promoter methylation. Our results suggest that methylation silencing of WIF-1 is a common and likely important mechanism of aberrant activation of the Wnt signaling pathway in lung cancer pathogenesis, raising its therapeutic interest.