tbuckley/cabot-search huggingface dataset:
False-Positive Hepatic Blood Pool Scintigraphy in Metastatic Colon Carcinoma
Authors: LAWRENCE C. SWAYNE, WILLIAM L DIEHL, THOMAS D. BROWN, NANCY J. HUNTER
Journal: Clinical Nuclear Medicine (1991)

A rare false-positive red blood cell scintigram occurred in a 49-year-old woman with two metastases from a primary adenocarcinoma of the sigmoid colon. Although the blood flow and static planar images were unremarkable, a 1-hour postinjection SPECT study showed a focus of increased activity in the inferior right lobe and a second photopenic focus in the dome. Following a trisegmentec-tomy, pathologic examination revealed the two metastases with no evidence of a hepatic hemangioma. Microscopy, however, showed a discrete area of nonspecific reactive changes (focal sinusoidal dilation and congestion) immediately adjacent to the metastasis in the inferior right lobe. It is postulated that the SPECT focus of increased activity occurred secondary to the labeled blood pool within the area of sinusoidal dilation, rather than within the adjacent metastasis.
Hypotonic-induced stretch counteracts the efficacy of the class III antiarrhythmic agent E-4031 in guinea pig myocytes
Authors: W. J. Groh, K. J. Gibson, J. G. Maylie
Journal: Cardiovascular Research (1996)

The aim was to determine the effect and mechanisms by which myocyte stretch interacts with the prolongation of action potential duration (APD) by the class III antiarrhythmic agent E-4031.Action potentials and whole-cell currents were measured in isolated guinea pig ventricular myocytes with a patch clamp procedure during perfusion of normotonic, normotonic with addition of E-4031, and hypotonic plus E-4031 solutions.Cell swelling leading to membrane stretch of myocytes in the whole-cell recording configuration occurred with hypotonic solution perfusion. APD, prolonged by E-4031, was reduced to less than control value with hypotonic-induced stretch. Evaluation of whole-cell currents after hypotonic-induced stretch revealed no significant changes in the L-type Ca2+ current, inward rectifier K+ current or the rapid component of the delayed rectifier K+ current. The slow component of the delayed rectifier K+ current (IKs) was upregulated and a stretch-induced CI- current was activated in hypotonic solutions. The hypotonic-induced modulation of these currents was not effected by protein kinase A or C inhibition.Hypotonic-induced stretch shortens APD and counteracts the effects of E-4031. This APD shortening is secondary to upregulation of IKs and activation of a stretch-induced Cl- current.
Overcoming Cancer Immune Tolerance and Escape
Authors: Guy T. Clifton, George E. Peoples
Journal: Clinical Cancer Research (2009)

Abstract Although HER2/neu–targeted cancer vaccines have shown initial promise in the adjuvant setting, a therapeutic vaccine remains elusive due to the tumor escape mechanisms of established cancer. As described by Seavey et al. in this issue of CCR, a Listeria-delivered vaccine may help overcome immune tolerance, leading to an effective therapeutic vaccine.
Do Opiates Affect the Clinical Evaluation of Patients With Acute Abdominal Pain?
Authors: Sumant R. Ranji, L. Elizabeth Goldman, David L. Simel, Kaveh G. Shojania
Journal: JAMA (2006)

ContextClinicians have traditionally withheld opiate analgesia from patients with acute abdominal pain until after evaluation by a surgeon, out of concern that analgesia may alter the physical findings and interfere with diagnosis.ObjectiveTo determine the impact of opiate analgesics on the rational clinical examination and operative decision for patients with acute abdominal pain.Data Sources and Study SelectionMEDLINE (through May 2006), EMBASE, and hand searches of article bibliographies to identify placebo-controlled randomized trials of opiate analgesia reporting changes in the history, physical examination findings, or diagnostic errors (those resulting in “management errors,” defined as the performance of unnecessary surgery or failure to perform necessary surgery in a timely fashion).Data ExtractionTwo authors independently reviewed each study, abstracted data, and classified study quality. A third reviewer independently resolved discrepancies.Data SynthesisStudies both in adults (9 trials) and in children (3 trials) showed trends toward increased risks of altered findings on the abdominal examination due to opiate administration, with risk ratios for changes in the examination of 1.51 (95% confidence interval [CI], 0.85 to 2.69) and 2.11 (95% CI, 0.60 to 7.35), respectively. When the analysis was restricted to the 8 adult and pediatric trials that reported significantly greater analgesia for patients who received opiates compared with those who received placebo, the risk of physical examination changes became significant (risk ratio, 2.13; 95% CI, 1.14 to 3.98). These trials exhibited significant heterogeneity (I2 = 68.6%; P = .002), and only 2 trials distinguished clinically significant changes such as loss of peritoneal signs from all other changes; consequently, we analyzed risk of management errors as a marker for important changes in the physical examination. Opiate administration had no significant association with management errors (+0.3% absolute increase; 95% CI, −4.1% to +4.7%). The 3 pediatric trials showed a nonsignificant absolute decrease in management errors (−0.8%; 95% CI, −8.6% to +6.9%). Across adult and pediatric trials with adequate analgesia, opiate administration was associated with a nonsignificant absolute decrease in the risk of management errors (−0.2%; 95% CI, −4.0% to +3.6%).ConclusionsOpiate administration may alter the physical examination findings, but these changes result in no significant increase in management errors. The existing literature does not rule out a small increase in errors, but this error rate reflects a conservative definition in which surgeries labeled as either delayed or unnecessary may have met appropriate standards of care. In published research reports, no patient experienced major morbidity or mortality attributable to opiate administration.
Doctors' communication of trust, care, and respect
Authors: Lesley Fallowfield
Journal: BMJ (2004)

EDITOR—Burkitt Wright et al have not attended one of my group's communication skills courses; yet that doesn't stop them from saying that patients valued forms of communication that are currently not emphasised in training and research, and did not intrinsically value others that are currently thought important, including provision of information and choice.1 Apart from the breathtakingly absurd suggestion that a qualitative analysis of …
Myosin isoenzyme changes in several models of rat cardiac hypertrophy.
Authors: J J Mercadier, A M Lompré, C Wisnewsky, J L Samuel, J Bercovici, B Swynghedauw, K Schwartz
Journal: Circulation Research (1981)

We studied the effect of chronic mechanical overloading on the isoenzyme composition of rat cardiac myosin in several experimental models: aortic stenosis (AS), aortic incompetence (AI), aortocaval fistula (ACF), overload of the non-infarcted area after left coronary ligation (INF), and overload of the spontaneously hypertensive rats (SHR). Samples of the left and right ventricles were isolated from these hearts, and myosins were analyzed by electrophoresis in non-dissociating conditions. The myosin isoenzymes were called V1, V2, and V3 in order of decreasing mobility, according to the nomenclature of Hoh et al. Controls of the Wistar and Wistar Kyoto (WKY) strains were almost exclusively V1, A slow age-dependent shift toward V3 was observed in the left ventricles of adult Wistar rats, which at 30 weeks of age (body weight 600 g) contained approximately 15% of this form. In all models of cardiac hypertrophy, an isoenzymic redistribution was observed with a significant increase in V3. The level of V3 was statistically correlated with the degree of hypertrophy in the AS, (n = 11, r - 0.6, P less than 0.05), the AI (n = 14, 4 = 0.88, P less than 0.001), and the AS + AI(n = 14, 4 = 0.69, P less than 0.01) but not in the ACF (n = 16, r = 0.46). The isoenzymic changes could account for the decreases in both myosin ATPase activity and cardiac contractility described previously in our laboratory and by others. They also demonstrate that changes in myosin isoenzymes represent a general response of the rat heart, to chronic mechanical overloading.
Serum peptidome for cancer detection: spinning biologic trash into diagnostic gold
Authors: L. A. Liotta
Journal: Journal of Clinical Investigation (2005)

The low molecular weight region of the serum peptidome contains protein fragments derived from 2 sources: (a) high-abundance endogenous circulating proteins and (b) cell and tissue proteins. While some researchers have dismissed the serum peptidome as biological trash, recent work using mass spectrometry–based (MS-based) profiling has indicated that the peptidome may reflect biological events and contain diagnostic biomarkers. In this issue of the JCI, Villanueva et al. report on MS-based peptide profiling of serum samples from patients with advanced prostate, bladder, or breast cancer as well as from healthy controls. Surprisingly, the peptides identified as cancer-type–specific markers proved to be products of enzymatic breakdown generated after patient blood collection. The impact of these results on cancer biomarker discovery efforts is significant because it is widely believed that proteolysis occurring ex vivo should be suppressed because it destroys endogenous biomarkers. Villanueva et al. now suggest that this suppression may in fact be preventing biomarker generation.
Jet and ultrasonic nebuliser output: use of a new method for direct measurement of aerosol output.
Authors: R D Hamilton, A Guz
Journal: Thorax (1991)

Alveolar partial pressures of carbon dioxide and oxygen measured by a helium washout techniqueThe estimation of arterial carbon dioxide pressure (Paco2) by Professor J Jordanoglou and colleagues (July 1990;45:520-4) assumes the equivalence of Bohr-Enghoff deadspace' with the helium deadspace by multiple breath washout (the "ventilatory deadspace" of Cumming and Guyatt5).In a letter to Clinical Science following their previous paper' I pointed out the fallacy of this assumption.4I note that in their Thorax paper the authors mention pulmonary embolism as a cause ofdiscrepancy and took steps to exclude this in their patients.Any kind ofventilation- perfusion (V/O2) mismatch, however unless due solely to ventilation-volume (V/V) mis- match, will introduce such a discrepancy, and their patients with chronic bronchitis and asthma must be presumed liable to such I/a non-uniformity.This doubtless accounts for much of the rather wide scatter in their figure 2. The 95% confidence interval about regres- sion is about + 154 kPa (115 mm Hg).Another difficulty is that the ventilatory dead- space for helium increases, during washout, with breath number if V/V mismatching is present.The choice of first breath deadspace by Professor Jordanoglou and colleagues is quite arbitrary.This criticism is not merely about in- accuracy.The rebreathing method for oxygenated mixed venous carbon dioxide tension (Pvco2)' is inaccurate, as all methods are.But the target is the intended one.The
Abstract 5016: The human sub-ependymal zone harbors glioblastoma precursors and represents a distinct therapeutic target.
Authors: Sara Grazia Maria Piccirillo, Inma Spiteri, Andrea Sottoriva, Anestis Touloumis, Suzan Ber, Stephen J. Price, Richard Heywood, Nicola-Jane Francis, Vincent P. Collins, Ashok R. Venkitaraman, Christina Curtis, John C. Marioni, Simon Tavare’, Colin Watts
Journal: Cancer Research (2013)

Abstract Glioblastoma (GB), the most common and aggressive adult brain tumor, is characterized by phenotypic diversity and ultimately treatment failure. Using fluorescence-guided sampling we integrated copy number aberration, gene expression and molecular clock data to show that the sub-ependymal zone (SEZ) contains precursor cells of the corresponding mass. The genetically distinct tumor margin contains non self-renewing cells that retain the potential to regenerate the tumor. Functional assays confirmed that SEZ and marginal disease were less clinically aggressive compared to the mass compartment in the same tumor. However, resistance to supra-maximal chemotherapy doses and differential patterns of drug response were observed between compartments. These data provide novel insights into the basis of clinical diversity, poor treatment response and emergence of resistant disease in GB patients. Citation Format: Sara Grazia Maria Piccirillo, Inma Spiteri, Andrea Sottoriva, Anestis Touloumis, Suzan Ber, Stephen J. Price, Richard Heywood, Nicola-Jane Francis, Vincent P. Collins, Ashok R. Venkitaraman, Christina Curtis, John C. Marioni, Simon Tavare’, Colin Watts. The human sub-ependymal zone harbors glioblastoma precursors and represents a distinct therapeutic target. [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 5016. doi:10.1158/1538-7445.AM2013-5016
Cryoglobulinaemia in HCV infection: coming in from the cold
Authors: O M CROSBIE, G J M ALEXANDER
Journal: Gut (1999)

See article on page 122 

Hepatitis C virus (HCV) antibodies are detected in up to 1.5% of blood donors worldwide and HCV is estimated to infect at least 4 million people in the USA alone.1 HCV is probably the commonest cause of liver disease and hepatocellular carcinoma in the developed world and has become the leading reason for liver transplantation in many centres. HCV is thought to be the aetiological factor in the majority of cases of mixed cryoglobulinaemia in which HCV RNA is concentrated in high titre in cryoprecipitates.2Conversely, up to 54% of patients with HCV infection have detectable cryoglobulins, which are associated with symptoms in roughly 25%, most commonly including cutaneous manifestations and arthralgias but much less often glomerulonephritis and neurological abnormalities.3 Although some studies have noted a correlation between the severity of liver disease and the level of cryoglobulins in serum, this has not been a consistent observation.

In this issue (see page 122), Cresta and colleagues studied 87 patients with HCV related liver disease prospectively. Forty three of the patients had detectable cryoglobulins, associated with symptoms in 12 (28%). …
Forgotten Thomas Splint
Authors: R. Harrison
Journal: BMJ (1957)

A case is reported of idiopathic CD4+T lymphocytopenia with progressive multifocal leukoencephalopathy and cervical lymph node tuberculosis. A 57 year old Japanese man presented with cervical lymphadenopathy and progressive neurological deficits, and six months later he developed akinetic mutism. He had a persistent severely depressed number of circulating CD4+T lymphocytes in the absence of human immunodeficiency virus infection. T1 weighted MRI showed a diffuse decreased signal intensity limited to the white matter without mass effect. A brain biopsy specimen had a morphology similar to that of progressive multifocal leukoencephalopathy. Polyomavirus antigen was detected in the brain lesion, and viral DNA was identified in nucleated blood cells and urine. Unusually this serious medical condition has lasted for more than three years without remission. To our knowledge this is the first patient with CD4+T lymphocytopenia with progressive multifocal leukoencephalopathy, suggesting that similar opportunistic infections should be considered even in previously normal people.
The Increasing Importance of Polymicrobial Bacteremia
Authors: Daria Kiani
Journal: JAMA (1979)

Polymicrobial bacteremia increased from 6% in 1970 to 13% in 1975 in patients with bloodstream infections. This type of serious infection most commonly complicated genitourinary (27%) and gastrointestinal (26%) conditions, frequently followed invasive procedures (68%), was more common in hospitalized patients (73%), and was often associated with malignancies (25%) or immunosuppressive or cancer chemotherapy (34%). Although polymicrobial endocarditis was more commonly encountered in recent years, this infection accounted for only 4.5% of patients with multiple organism bacteremias. Gram-negative aerobic bacteria were isolated from 62% and anaerobic bacteria in 39% of patients with polymicrobial bacteremia compared with 37% and 14%, respectively, in patients with monomicrobial bacteremia. In the 88 patients with polymicrobial bacteremia, the mortality was 44.5%, compared with 18.0% in patients with monomicrobial bacteremia.
Breast-feeding and Infectious Diarrhea-Reply
Authors: A. G. Gordon
Journal: JAMA (1987)

In Reply.—  In 1981, I concluded that infantile diarrhea was not due to contaminated food or water. 1 Up to now, this conclusion has not been challenged. Dr Holland merely shows that most Third World infant food is contaminated. More relevant is the question of why most infants thrive despite this contamination. If his references are the best available to support his thesis— and I am unaware of any better 2 —then it is time the contamination/diarrhea link was critically tested, especially now that transmission of acquired immunodeficiency syndrome via breast milk has been proposed. Fear of breast-feeding may compound the acquired immunodeficiency syndrome tragedy in Africa.  Turning to his sources, in Gambia there was no control group, and neither then nor later have Rowland et al correlated dirty food and diarrhea. No references for such a link were cited. In Chile, the dirty bottles belonged to rural children, not
An Address on THE TREATMENT OF OBSTRUCTIVE LESIONS OF THE COLON
Authors: J. P. Lockhart-Mummery
Journal: BMJ (1927)

<h3>Aims:</h3> To investigate the relationship between lens density measured with the Pentacam Scheimpflug System and grading score using the Lens Opacities Classification System (LOCS) III as well as that between lens density and visual acuity in age-related nuclear cataract patients. <h3>Methods:</h3> Lens density and grading score were evaluated in 138 cases (180 eyes) with age-related nuclear cataract. LogMAR visual acuity was tested with the Early Treatment Diabetic Retinopathy Study chart. The correlations between lens density value and LOCS III nuclear opacity (NO) and nuclear colour (NC) grading score and that between lens density value and logMAR visual acuity were analysed. <h3>Results:</h3> There was a linear increasing relationship between lens density value and LOCS III grading score in nuclear cataract patients. Lens density value had a stronger significant correlation with LOCS III NO score than that with NC score. The correlation between the nuclear lens density value and logMAR visual acuity was stronger than that between NO score and logMAR visual acuity or between NC score and logMAR visual acuity. <h3>Conclusion:</h3> Lens density as a quantitative and objective parameter can present the degree of NO and associated visual impairment due to nuclear cataract. The LOCS III criterion as an economic cataract grading system provides data that are in satisfactory concordance with the results obtained using the Pentacam Scheimpflug system.
All-trans and 9-cis retinoic acid alter rat hepatic stellate cell phenotype differentially
Authors: K Hellemans, I Grinko, K Rombouts, D Schuppan, A Geerts
Journal: Gut (1999)

<h3>BACKGROUND</h3> Hepatic stellate cells exert specific functions in the liver: storage of large amounts of retinyl esters, synthesis and breakdown of hepatic extracellular matrix, secretion of a variety of cytokines, and control of the diameter of the sinusoids. <h3>AIMS</h3> To examine the influence of all-<i>trans</i> retinoic acid (ATRA) and 9-<i>cis</i> retinoic acid (9RA) on extracellular matrix production and proliferation of activated hepatic stellate cells. <h3>METHODS</h3> Cells were isolated using collagenase/pronase, purified by centrifugation in nycodenz, and cultured for two weeks. At this time point the cells exhibited the activated phenotype. Cells were exposed to various concentrations of ATRA and 9RA. The expression of procollagens I, III, and IV, of fibronectin and of laminin were analysed by immunoprecipitation and northern hybridisation. <h3>RESULTS</h3> ATRA exerted a significant inhibitory effect on the synthesis of procollagens type I, III, and IV, fibronectin, and laminin, but did not influence stellate cell proliferation, whereas 9RA showed a clear but late effect on proliferation. 9RA increased procollagen I mRNA 1.9-fold, but did not affect the expression of other matrix proteins. <h3>CONCLUSION</h3> Results showed that ATRA and 9RA exert different, often contrary effects on activated stellate cells. These observations may explain prior divergent results obtained following retinoid administration to cultured stellate cells or in animals subjected to fibrogenic stimuli.
A Human Antibody–Drug Conjugate Targeting EphA2 Inhibits Tumor Growth <i>In vivo</i>
Authors: Dowdy Jackson, John Gooya, Shenlan Mao, Krista Kinneer, Linda Xu, Margarita Camara, Christine Fazenbaker, Ryan Fleming, Sudha Swamynathan, Damon Meyer, Peter D. Senter, Changshou Gao, Herren Wu, Michael Kinch, Steven Coats, Peter A. Kiener, David A. Tice
Journal: Cancer Research (2008)

Abstract The EphA2 receptor tyrosine kinase is selectively expressed on the surface of many different human tumors. We have previously shown that tumor cells can be targeted by EphA2 monoclonal antibodies and that these antibodies function, in part, by inducing EphA2 internalization and degradation. In this report, we describe the isolation and characterization of a fully human monoclonal antibody (1C1) that selectively binds both the human and rodent EphA2 receptor. After cell binding, the antibody induces rapid tyrosine phosphorylation, internalization, and degradation of the EphA2 receptor. Because monoclonal antibodies that selectively bind tumor cells and internalize provide a vehicle for targeted delivery of cytotoxics, 1C1 was conjugated to the microtubule inhibitor monomethylauristatin phenylalanine using a stable maleimidocaproyl linker. The anti-EphA2 antibody-drug conjugate [1C1–maleimidocaproyl-MMAF (mcMMAF)] stimulated the activation of caspase-3/caspase-7 and the death of EphA2-expressing cells with IC50 values as low as 3 ng/mL. Similarly, the conjugate induced degradation of the EphA2 receptor and inhibited tumor growth in vivo. Administration of 1C1-mcMMAF at doses as low as 1 mg/kg once weekly resulted in significant growth inhibition of EphA2-expressing tumors without any observable adverse effects in mouse xenograft and rat syngeneic tumor models. Our data support the use of an antibody-drug conjugate approach to selectively target and inhibit the growth of EphA2-expressing tumors. [Cancer Res 2008;68(22):9367–74]