tbuckley/cabot-search huggingface dataset:
Role of P53 and MDM2 in Treatment Response of Human Germ Cell Tumors
Authors: Anne-Marie F. Kersemaekers, Frank Mayer, Michel Molier, Pascale C. van Weeren, J. Wolter Oosterhuis, Carsten Bokemeyer, Leendert H.J. Looijenga
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Testicular germ cell tumors (TGCTs) of adolescents and adults are very sensitive to systemic treatment. The exquisite chemosensitivity of these cancers has been attributed to a high level of wild-type P53. MATERIALS AND METHODS: To clarify the role of P53 in treatment sensitivity and resistance of TGCTs, we performed immunohistochemistry and Western blotting analysis on a series of 39 fresh-frozen primary TGCTs before therapy (unselected series). In a series of formalin-fixed paraffin-embedded TGCTs of patients with fully documented clinical course, including treatment-sensitive (n = 17) and -resistant (n = 18) tumors, P53 status was assessed by immunohistochemistry and mutation analysis. In addition, the involvement of MDM2, a P53 antagonist, was investigated by immunohistochemistry, reverse transcriptase polymerase chain reaction, and in situ hybridization. RESULTS: Immunohistochemistry demonstrated absence of staining for P53 in 36%, 41%, and 17% of the unselected, responding, and nonresponding TGCTs, respectively. Of the positive TGCTs, most tumors, ie, 49%, 41%, and 33%, showed 1% to 10% positive nuclei. This overall low level of P53 was confirmed by Western blotting. Mutation analysis revealed only one silent P53 mutation in one of the responding patients. All embryonal carcinomas were homogeneously positive for MDM2, encoded by the full length mRNA, while a heterogeneous pattern was found for the other histologic components. Amplification of MDM2 was detected in one out of 12 embryonal carcinomas. CONCLUSION: Although our results are in line with previous findings of the presence of wild-type P53 in TGCTs, they show that a high level of P53 does not relate directly to treatment sensitivity of these tumors, and inactivation of P53 is not a common event in the development of cisplatin resistance.
The Role of Intestinal Gas in Functional Abdominal Pain
Authors: Robert B. Lasser, John H. Bond, Michael D. Levitt
Journal: New England Journal of Medicine (1975)

A washout technic with intestinal infusion of an inert gas mixture was used to study the relation of gas to functional abdominal symptoms. The volume of gas in the intestinal tract (176 plus or minus 28 ml S.E.M.) of 12 fasting patients with chronic complaints of excess gas did not differ significantly (P greater than 0.10) from that of 10 controls (199 plus or minus 31 ml). Similarly, there was no difference in the composition or accumulation rate of intestinal gas. However, more gas tended to reflux back into the stomach in patients who complained of abdominal pain during infusion of volumes of gas well tolerated by controls. Six patients with severe pain during the study had intestinal transit times of gas (40 plus or minus 6 minutes S.E.M.) that were significantly (P less than 0.05) longer than those of the control group (22 plus or minus 3 minutes). Thus, complaints of bloating, pain and gas may result from disordered intestinal motility in combination with an abnormal pain response to gut distention rather than from increased volumes of gas.
‘Autoimmunity’ is not always associated with prolonged survival in melanoma patients
Authors: C. Pföhler, R. Schmaltz, S. Graeber, W. Tilgen
Journal: British Journal of Dermatology (2008)

Journal Article ‘Autoimmunity’ is not always associated with prolonged survival in melanoma patients Get access C. Pföhler, C. Pföhler Department of Dermatology Search for other works by this author on: Oxford Academic Google Scholar R. Schmaltz, R. Schmaltz Department of Dermatology Search for other works by this author on: Oxford Academic Google Scholar S. Graeber, S. Graeber Institute for Medical Biometry, Epidemiology and Medical Informatics, The Saarland University Hospital, 66421 Homburg/Saar, Germany E‐mail: hacpfo@uniklinik‐saarland.de Search for other works by this author on: Oxford Academic Google Scholar W. Tilgen W. Tilgen Department of Dermatology Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 159, Issue 3, 1 September 2008, Pages 735–736, https://doi.org/10.1111/j.1365-2133.2008.08675.x Published: 01 September 2008
Evidence for defect of complement-mediated phagocytosis by monocytes from patients with rheumatoid arthritis and cutaneous vasculitis.
Authors: N P Hurst, G Nuki
Journal: BMJ (1981)

In-vitro measurements of the rate of monocyte phagocytosis of heat-killed yeast preopsonised in human AB serum from 14 patients with rheumatoid arthritis and 14 normal controls showed a significant reduction in five patients with active vasculitis but no change in nine with active arthritis alone. Further studies of complement- and Fc-mediated monocyte phagocytosis in which the rate constants (Kc and KFc respectively) were determined using complement-coated Saccharomyces cerevisiae and Candida albicans opsonised with IgG in monocytes from nine patients with rheumatoid vasculitis and 12 controls showed a significant reduction in Kc (p less than 0.01) but normal KFc. Kc was normal in three patients with inactive vasculitis. Low Kc was correlated with low serum C3 concentrations but not with Clq binding or anticomplementary activity, and no evidence of intracytoplasmic or membrane-bound immune complexes was detected in monocytes from patients with active vasculitis. These results show that cutaneous vasculitis in rheumatoid arthritis is associated with selective impairment of complement-mediated monocyte phagocytosis, which does not appear to result from receptor blockade by immune complexes.
POINTS OF VALUE IN ROENTGENOSCOPY OF THE GASTRO-INTESTINAL TRACT
Authors: R. WALTER MILLS
Journal: JAMA (1913)

The ordinary methods of physical examinations have never been satisfactory when employed to determine the normal and pathologic topography, conditions and activities of the gastro-intestinal tract. Percussion, on account of the abdominal gases and solids, furnishes only the crudest information and is often actually misleading. Auscultation rarely furnishes evidence indicative of specific conditions; there are no normal sounds of constancy that may act as a means of comparison. Inspection furnishes no information not better elicited by palpation, with the exception of the observation of visible peristalsis. Palpation is of much value when suitable conditions exist. Into this situation is now introduced a method approaching precision for the purposes mentioned—the visualization of the gastro-intestinal tract by the Roentgen ray through the ingestion of an opaque substance, usually bismuth—a method which appeals to the most accurate of the senses, sight, and at once accomplishes much that we have been attempting to force
Acute graft pyelonephritis and long-term kidney allograft outcome
Authors: Magali Giral, Giovani Pascuariello, Georges Karam, Maryvonne Hourmant, Diego Cantarovich, Jacques Dantal, Gilles Blancho, Stephanie Coupel, Regis Josien, Pascal Daguin, Sandra Méchineau, Jean Paul Soulillou
Journal: Kidney International (2002)
15. Genetically Targeted Adenovirus Vector Carrying Reovirus σ1-Based Attachment Protein for Improved Systemic Gene Delivery
Authors: Frederik H.E. Schagen, Harm C.A. Graat, Jan E. Carette, Terence S. Dermody, Michael A. vanGeer, Victor W. van Beusechem
Journal: Molecular Therapy (2006)

In vivo applicability of adenoviral vectors (AdV) for cancer gene therapy is limited by sequestration of AdV by the liver and lack of adenovirus receptor CAR on many primary tumors. To circumvent these limitations we developed prototype genetically targeted AdV that lack all known adenovirus interaction sites with cellular receptors (CAR, HSG and integrins) and carry a unique target-binding moiety. The adenovirus fiber protein was replaced with a chimeric molecule comprising the capsid-anchoring tail domain of fiber, the oligomerization T(ii) domain of reovirus attachment protein |[sigma]|1 and a His-tag as model targeting moiety. Furthermore, the RGD motif in the penton base protein was mutated. The chimeric |[sigma]|1-based molecule was incorporated into AdV capsids and allowed efficient propagation of AdV without requirement for complementing fiber. Importantly, the His-tag conferred targeted tropism to the AdV, resulting in up to 50-fold greater transduction efficiency on cells expressing a His-tag binding receptor than on parental cells lacking this receptor. Targeting was mediated through binding of the chimeric molecule, as transduction was strongly inhibited by a His-tag specific antibody. In focus of the important issue of liver de-targeting, we studied transduction of HepG2 cells and mouse liver cells in explanted liver slices with intact tissue architecture. In comparison to control AdV with native tropism, genetically targeted AdV exhibited 3-log reduction in HepG2 transduction and 3-4-log reduction in the stringent liver slice model. We also studied in vivo persistence and biodistribution of genetically targeted AdV after systemic delivery by tail vein injection into C57bl/6 mice. Blood samples collected during the first 2 hours after injection revealed rapid clearance of the control vector with native tropism, leaving less than 1% of the administered dose after 10 minutes, which declined further to less than 0.1% after 30 minutes. In contrast, the targeted AdV declined to 1% of the administered dose only after 1 hour, and this level remained stable for at least the next hour. Analysis of all tested tissues, i.e., liver, heart, spleen, lungs and kidney revealed a significant reduction of transduction by the targeted AdV in comparison to the control vector. In fact, transduction of lung and kidney by the targeted AdV was undetectable. Finally, in contrast to AdV with native tropism, the targeted AdV did not agglutinate human red blood cells. This suggests that the targeted AdV would be less susceptible to sequestration by red blood cells in the human circulation. Together, our findings suggest that the reovirus |[sigma]|1-based chimeric attachment molecule provides a promising platform for generation of targeted AdV with improved characteristics for systemic in vivo gene delivery.
The Search for the "Coronary" Archetype and the Damocles Test
Authors: HOWARD B. SPRAGUE
Journal: Circulation (1966)

The Search for the "Coronary" Archetype and the Damocles Test A BABY born in 1901 had one chance in three of dying of an acute disease dur- ing his lifetime; by 1945 this chance was only one in ten.In four out of five cases he will now live to die of a chronic disease.Civilization usually preserves its members for more lingering and partial deaths, save in some instances, when sudden vascular occlusions or ruptures occur.This is not a new observation.Emer- son, in his studies of the medical statistics of Philadelphia in 1827 wrote "among barbarous nations and the poor of civilized ones, acute diseases produce the mortality.Among the better classes of civilized nations, chronic maladies abound."Western man, faced with this prospect, and having been so notably successful in abolishing acute diseases, is trying desperate- ly to find out why he is not immortal.Partic- ularly is he seeking to discover why some approach immortality more nearly than do others, or at least attain 110 years of age, the probable biological limit of man's life.True, Old Parr is said to have lived to 152 years and 9 months, and to have married a widow when he was 120 years old.Even at this age prosperity overcame him.The autop- sy report by Dr. Harvey November 16, 1635, says, "In short, all his inward parts appeared so Healthy, that if he had not changed his Dyet and Air, he might perhaps have Lived a good while longer.But coming out of a Clear, Thin and Free Air, into the Thick Air of London, and after a Constant, Plain and Homely Country diet, being taken into a Splendid Family [of the Earl of Arundel], where he fed High and Drank plentifully of the best Wines; whereupon the natural Functions of the Parts of his Body were over- charged, his Lungs obstructed, and the Habit of the whole Body quite Disordered, upon
Colloid Goiter and Atherosclerosis
Authors: RONALD A. WELSH, JACK P. STRONG, HENRY C. MCGILL
Journal: Circulation (1961)

The thyroid glands from 453 patients 20 to 79 years of age from the New Orleans area were classified according to the presence of colloid goiter, and the coronary arteries and aortas from these same patients were independently graded for atherosclerotic lesions. There was no correlation between colloid goiter and atherosclerosis; nor was there any difference in the percentages of deaths from atherosclerosis in goitrous patients as compared to nongoitrous patients. Because goiter may differ in its functional manifestations from one geographic area to another, and because one group of investigators in Finland has reported a strong association between the two diseases, similar studies should be conducted in other areas. The subject of increased severity of atherosclerosis in human hypothyroidism was reviewed, and it was concluded that the presently recorded data are not adequate to establish a positive relationship.
Systematic review of misdiagnosis of conversion symptoms and “hysteria”
Authors: Jon Stone, Roger Smyth, Alan Carson, Steff Lewis, Robin Prescott, Charles Warlow, Michael Sharpe
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> Paralysis, seizures, and sensory symptoms that are unexplained by organic disease are commonly referred to as “conversion” symptoms. Some patients who receive this diagnosis subsequently turn out to have a disease that explains their initial presentation. We aimed to determine how frequently this misdiagnosis occurs, and whether it has become less common since the widespread availability of brain imaging. <b>Design</b> Systematic review. <b>Data sources</b> Medline, Embase, PsycINFO, Cinahl databases, and searches of reference lists. <b>Review methods</b> We included studies published since 1965 on the diagnostic outcome of adults with motor and sensory symptoms unexplained by disease. We critically appraised these papers, and carried out a multivariate, random effect, meta-analysis of the data. <b>Results</b> Twenty seven studies including a total of 1466 patients and a median duration of follow-up of five years were eligible for inclusion. Early studies were of poor quality. There was a significant (P &lt; 0.02) decline in the mean rate of misdiagnosis from the 1950s to the present day; 29% (95% confidence interval 23% to 36%) in the 1950s; 17% (12% to 24%) in the 1960s; 4% (2% to 7%) in the 1970s; 4% (2% to 6%) in the 1980s; and 4% (2% to 6%) in the 1990s. This decline was independent of age, sex, and duration of symptom in people included in the studies. <b>Conclusions</b> A high rate of misdiagnosis of conversion symptoms was reported in early studies but this rate has been only 4% on average in studies of this diagnosis since 1970. This decline is probably due to improvements in study quality rather than improved diagnostic accuracy arising from the introduction of computed tomography of the brain.
Thirty-Month Follow-Up of Resting and Postexercise Apexcardiogram in Asymptomatic Subjects
Authors: WILBERT S. ARONOW
Journal: Circulation (1973)

Ninety-eight asmptomatic subjects who had a resting and postexercise apexcardiogram and maximal treadmill stress test (MTST) were clinically evaluated 30 months later. Two of six subjects (33%) with an initially abnormal resting apexcardiogram and two of 92 subjects (2.2%) with an initially normal resting apexcardiogram developed coronary heart disease within 30 months. Three of 15 subjects (20%) with an initially abnormal postexercise apexcardiogram and one of 83 subjects (1.2%) with an initially normal postexercise apexcardiogram developed coronary heart disease within 30 months. Two of four subjects (50%) with an initially abnormal resting apexcardiogram and MTST and two of 94 subjects (2.1%) without both an initially abnormal resting apexcardiogram and MTST developed coronary heart disease within 30 months. Three of seven subjects (43%) with an initially abnormal postexercise apexcardiogram and MTST and one of 91 subjects (1.1%) without both an initially abnormal postexercise apexcardiogram and MTST developed coronary heart disease within 30 months. An abnormal resting apexcardiogram, postexercise apexcardiogram, or MTST correlated with an increased incidence of subsequent coronary heart disease. An abnormal postexercise apexcardiogram plus an abnormal MTST correlated best with an increased incidence of subsequent coronary heart disease.
Tardive Dyskinesia
Authors: BURTRUM C. SCHIELE
Journal: Annals of Internal Medicine (1973)

Tardive dyskinesia, a syndrome characterized by rhythmical, involuntary movements of the tongue, face, mouth, or jaw, is a persistent neurological disorder associated with antipsychotic drug use. The syndrome may have to be distinguished from other drug-induced neurological disorders. Advice on management is offered.
Gaps in information are impeding progress in cancer care in England
Authors: S. Mayor
Journal: BMJ (2010)

Wide variations in the care provided by different primary care trusts and a lack of high quality information are blocking further improvements in the care of patients in England with cancer, warns a new report.

Improving the care of patients with cancer has been a priority for the NHS for the past decade, in recognition of the fact that mortality rates in England for several cancers are higher than in other European countries. The NHS cancer plan was published in 2000 to improve cancer services, and this was followed by the cancer reform strategy in 2007, when figures showed that although improvements had been made, the gap in survival rates had not closed.

The National Audit Office, which scrutinises public spending on behalf of parliament, looked at how effectively three of the strategy’s recommendations had been in improving services to …
Effect of prednisone followed by interferon (IFN) in children with chronic hepatitis B
Authors: R. Utili, E. Sagnelli, B. Galanti, S. Nardiello, G.B. Gaeta, G. Giusti, F. Piccinino, G. Ruggiero, T. Pizzella, A. Marrone, L. Digilio, L. Aprea, G. Pasquale, G. Cesaro
Journal: Journal of Hepatology (1991)
Right ventricular systolic function and ventricular interaction during acute embolisation of the left anterior descending coronary artery in sheep
Authors: A Jerzewski
Journal: Cardiovascular Research (1999)

Regional LV ischemia involving the septum affects LV systolic function and geometry. We investigated the effects of these changes on RV function and geometry.In six closed-chest sheep end-systolic pressure-volume relationships (ESPVRs) were constructed from ventricular volumes, measured with magnetic resonance imaging (MRI) and matching intraventricular pressures, before and after selective embolisation of the left anterior descending coronary artery (LAD). The extent of myocardial ischemia was assessed post-mortem by coronary perfusion with Evans-Blue. Alterations in septal geometry were studied by measuring the curvature, segmental length and thickness of the septum in two midventricular (short-axis) MRI slices before and during ischemia. From these data, changes in LV and RV free wall segmental lengths were calculated.Selective embolisation of the LAD resulted in left ventricular ischemia (15 +/- 2.1% of the total LV) with 23% of the septum involved. Stroke volume did not change significantly, while LV systolic pressure decreased by 24 mmHg (p < 0.05). Although RV systolic function decreased to a significantly lesser extent than LV function (p < 0.01), systolic function of both ventricles diminished significantly as indicated by substantial rightward shifts of the ESPVRs: 121% for LV and 41% for RV (both p < 0.01). At mid-ventricular level and end-systole, the septum showed significant increases in its radius of curvature and segmental length (both p < 0.05), and a significant wall thinning (p < 0.01). Calculated end-systolic lengths of LV and RV free walls also increased, by 57 and 14% respectively.LAD embolisation not only results in a significantly diminished LV systolic function but also causes RV systolic function to decline significantly. Regional dysfunction by necessity entails global dysfunction as well. Analysis of ventricular geometry reveals that both the septum and the RV free wall increase their length, which plays an important role in the pathophysiology of diminished RV systolic function concomitant with reduced LV function.
Out of the wasteland
Authors: T. Groves
Journal: BMJ (2011)

“On Margate Sands/I can connect/Nothing with nothing” wrote T S Eliot, while convalescing from what was called a nervous breakdown at the time. The Waste Land ’s most famous line, however, is its first: “April is the cruellest month.” In this April week Jackie Hopson narrates her own journey through the wasteland of depression, and the cruelty she encountered along the way makes hard reading (doi:10.1136/bmj.d93). A suicide attempt in the early 1970s led to incarceration where “it seemed that I was to be punished for my illness and sedated if I made demands.” Gradually, though, marriage, motherhood, fluoxetine, and …
Local Stiffness of the Carotid and Femoral Artery Is Associated With Incident Cardiovascular Events and All-Cause Mortality
Authors: Thomas T. van Sloten, Miranda T. Schram, Katja van den Hurk, Jacqueline M. Dekker, Giel Nijpels, Ronald M.A. Henry, Coen D.A. Stehouwer
Journal: Journal of the American College of Cardiology (2014)
The Evaluation of Hematuria in Adults
Authors: Morton A. Bosniak
Journal: JAMA (1990)

To the Editor.—  The radiological portion of the article entitled Evaluation of Hematuria in Adults by Sutton 1 is quite misleading and outdated, and it is important that a more up-to-date approach to the subject be described. I am referring to the radiological workup of the patient with hematuria that is displayed in the algorithm (Fig 1) in the article. The workup shown in the algorithm concerning imaging of renal masses might have been appropriate 10 years ago but is totally inappropriate at this time.  If a renal mass is studied by renal ultrasound examination and is found to be a cyst, the algorithm suggests cyst aspiration for confirmation. The use of cyst aspiration in this regard is totally unnecessary. If the ultrasound examination indicates that a renal mass is a cyst, nothing further need be done, since sonography is virtually 100% accurate in the diagnosis of renal cysts if