tbuckley/cabot-search huggingface dataset:
TREATMENT OF THE PATHOLOGICALLY FLEXED KNEE
Authors: CHARLES A. PARKER
Journal: JAMA (1923)

The pathologically flexed knee, unless firmly ankylosed, is a weak knee, and, if the deforming process continues inflammatory, is usually painful in walking. The flexion shortens the functional length of the limb and increases the limp. All of these are undesirable complications and should be avoided or corrected.  The extended knee, even in complete paralysis of the limb, will support the body weight, standing or walking; in arthritis it reduces the movement, and thus the pain, to a minimum; and the extended position gives the greatest length of the limb with the least amount of limping. These are the conditions of comfort, and should be secured and maintained.  Neglect of these simple principles is so common and the results are so distressing that one feels fully justified in emphasizing their consideration.  While the instability of the flexed knee in poliomyelitis furnishes a constant plea for more general dissemination of the
Writing and speaking in medicine
Authors: R E Smith
Journal: BMJ (1976)

Advice centre for postgraduate medical educationThe three Councils for Postgraduate Medical Education (in England and Wales, Scotland, and Northern Ireland) are setting up a National Advice Centre to advise doctors on opportunities for postgraduate medical edu- cation and training in the United Kingdom.The centre will bring together several separate agencies at present helping doctors (part- icularly those from overseas).The service will incorporate that provided by the BMA for non-members and that run by the British Postgraduate Medical Federation for overseas doctors.The BMA will continue to advise its own members and those of affiliated organ- isations.The centre,
Abstract IA13: Niches and pathways of latent and overt metastasis
Authors: Joan Massagué
Journal: Cancer Research (2013)

Abstract The signals and niches that allow disseminated tumor cells (DTCs) to stay viable as metastasis seeds are largely unknown. An understanding of these mechanisms is needed for the development of treatments to eradicate DTCs and prevent metastasis. We have identified molecular mechanisms that prime breast cancer DTCs for survival and stem cell fitness in distant organs. For survival, SRC primes DTCs for a robust PI3K-Akt response to CXCL12 and IGF1 in the bone marrow, and the leukocyte-tethering receptor VCAM-1 primes DTCs for PI3K-Akt activation by leukocyte contacts in the lungs. For stem cell fitness, the extracellular matrix protein tenascin-C (TNC) forms micrometastatic niches that promote WNT and NOTCH signaling. Additionally, a CXCL1-S100A8 paracrine loop protects DTCs from the stresses of metastasis and chemotherapy, providing a basis for these two clinically linked phenomena. In some cases, the pathways driving carcinoma formation additionally mediate metastasis. VHL inactivation leads to HIF signaling as a tumor-initiating event in clear cell renal carcinoma (ccRCC). However, VHL mutation status in ccRCC is not correlated with clinical outcome. We found that during ccRCC progression, cancer cells exploit diverse epigenetic alterations to empower a branch of the VHL-HIF pathway for metastasis through CXCR4 and CYTIP. The strength of this activation is associated with poor clinical outcome. Thus, metastasis can be driven by an epigenetically expanded output of the tumor-initiating pathway as well as by events that are mechanistically uncoupled from the tumor-initiating pathway. In preclinical models, SRC kinase inhibitors, VCAM-1 blocking antibodies, and CXCL1 receptor inhibitors suppress metastasis and augment the efficacy of chemotherapy, providing new avenues for targeting DTCs in the adjuvant setting. Citation Format: Joan Massagué. Niches and pathways of latent and overt metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr IA13.
Pleural Effusion in Hodgkin's Disease
Authors: Frank W. Ellis
Journal: JAMA (1963)

<h3>To the Editor:—</h3> In the Questions and Answers section of the June 15 issue ofThe Journal(<b>184</b>:908 ) there is a question regarding management of pleural effusion in Hodgkin's disease. The reply to the query mentions the use of systemic treatment, as well as local (intrapleural) chemotherapeutic and radioactive agents, quite acceptably. However, I consider it a surprising omission that externally delivered radiation therapy is not even mentioned. In my experience as an internist interested in cancer chemotherapy, I have found that my radiation-therapy colleagues have been able to control effusions in Hodgkin's disease by judicious irradiation to the mediastinum and/or pleura in cases where systemic and local agents have failed. I feel that by and large, where technically feasible, radiation therapy in Hodgkin's disease still holds the most prominent place—a simple fact that sometimes seems to be overlooked in this age of enthusiasm for cancer chemotherapy.
Prediction of cardiovascular events in clinically selected high-risk NIDDM patients. Prognostic value of exercise stress test and thallium-201 single-photon emission computed tomography.
Authors: G Vanzetto, S Halimi, T Hammoud, D Fagret, P Y Benhamou, D Cordonnier, B Denis, J Machecourt
Journal: Diabetes Care (1999)

OBJECTIVE: We evaluated the prognostic value of an exercise stress test and thallium-201 scintigraphy for the prediction of cardiac events in selected high-risk NIDDM patients. RESEARCH DESIGN AND METHODS: NIDDM patients (n = 158, 105 men, aged 63 +/- 9 years) with two or more of the following criteria were prospectively included: age &amp;gt; or = 65 years, active smoking, hypertension &amp;gt; 160/95 mmHg, hypercholesterolemia (cholesterol &amp;gt; 5.70 mmol/l or LDL &amp;gt; 3.10 mmol/l), peripheral artery disease, abnormal rest electrocardiogram, or microalbuminuria (20-200 micrograms/min). An exercise-stress scintigraphy was performed in 77 patients able to exercise, while a dipyridamole scintigraphy was performed in 80 patients unable to exercise. Follow-up was 23 +/- 17 months. Major end points were cardiac deaths or nonfatal myocardial infarction. RESULTS: The annual event rate was 7.31% (deaths: 8, myocardial infarction: 14). Independent predictors of events were as follows: an age &amp;gt; 60 (P = 0.02), an abnormal rest electrocardiogram (P = 0.02), microalbuminuria (P = 0.001), the inability to exercise (P = 0.009), and the presence of more than two defects on scintigraphy (P = 0.001). A cardiac death occurred in 1.3% of patients able to exercise versus 8.8% of patients unable to exercise (odds ratio = 6.8, P = 0.001). Among patients unable to exercise, large perfusion defects corresponded to an annual mortality rate of 22.3%. Conversely, the negative predictive value of a normal scintigraphy for the occurrence of death was 97%. CONCLUSIONS: Inability to exercise and large perfusion defects on thallium-201 scan are major predictors of future death and myocardial infarction in high-risk NIDDM patients.
Renal Allograft Recovery Subsequent to Apparent "Hyperacute" Rejection Based on Clinical, Scintigraphic, and Pathologic Criteria
Authors: GLYNIS A. SACKS, MARTIN P. SANDLER, C LEON PARTAIN
Journal: Clinical Nuclear Medicine (1983)

An unusual case is described in which in spite of clinical, scintigraphic and histologic findings strongly supportive of a diagnosis of “hyperacute rejection,” recovery of renal function occurred. These findings are in contrast to the current literature in which it is generally accepted that a renal allograft showing neither pertechnetate transit nor hippurate concentration warrants allograft nephrectomy irrespective of the etiology. Scintigraphic evaluation included both dynamic studies after a bolus administration of Tc-99m pertechnetate and serial renogram collections after the intravenous administration of I-131 Hippuran.
SCORBUTUS IN INFANCY.
Authors: I. N. LOVE
Journal: JAMA (1895)

Prior to 1891, when the report of eleven cases of scorbutus in infancy was made by Dr. Northrup to the American Pediatric Society, I had never observed a case; at least I had never recognized it. Going back over an experience of sixteen years, the first five of which were spent in the eleemosynary institutions of St. Louis, including one year's service at the General Dispensary under the control of the Health Department, which was the receiving station for the distribution of all patients to the various hospitals of the city and where a very large number of outdoor patients were constantly treated, ranging from one hundred to one hundred and fifty cases a day (the medical colleges of St. Louis not having at that time established their private clinics), a number of cases come to mind with their various symptoms suggesting scorbutus, but such cases were invariably found in
Insulin-Dependent Diabetes Mellitus Called 'Epidemiologist's Dream'
Authors: Chris Anne Raymond
Journal: JAMA (1988)

ONCE CALLED the geneticist's nightmare, insulin-dependent diabetes mellitus (IDDM) is now yielding, at least temporarily, to modulation of the immune system. While it long has been thought that IDDM arises from a genetic susceptibility coupled with a toxic or infectious agent that initiates damage to beta cells, the recent emphasis has been on the genetic vulnerabilities. However, according to data gathered in the last few years by an international team, diabetologists may be well advised to renew their interest in the environmental triggers. In fact, says Ronald E. LaPorte, PhD, associate professor of epidemiology at the University of Pittsburgh, IDDM is the "epidemiologist's dream": a disorder that is easily diagnosed and hence well reported and whose prevalence varies widely around the world. Next on the tracking agenda for LaPorte.and colleagues is to document the prevalence of IDDM in South America, Africa, and mainland China. To date, the international team, known
Hemorrhagic Pancreatitis
Authors: Nicholas L. Tilney, John J. Collins, Richard E. Wilson
Journal: New England Journal of Medicine (1966)

ACUTE hemorrhagic pancreatitis has proved fatal to 2 patients after renal homotransplantation at the Peter Bent Brigham Hospital. They had received substantiell immunosuppressive therapy for nine and eleven months respectively. This lethal complication of transplantation and immunosuppression has not previously been described. The relation of pancreatitis to various aspects in the care of these patients will be considered.Case ReportsD.P. (P.B.B.H. 0–92–44) was discovered to have congenital bladder-neck obstruction and a nonfunctioning left kidney when he was 5 years old, and surgical correction was attempted. At the age of 22 retrograde pyelography demonstrated severe hydronephrosis and hydroureter on the . . .
US government report recommends a "principle of regulatory parsimony" for synthetic biology
Authors: B. Roehr
Journal: BMJ (2010)

The US Presidential Commission for the Study of Bioethical Issues “chose a middle course to maximise public benefits while also safeguarding against risks” in making its recommendations on the regulation of synthetic biology, said the commission’s chairwoman, Amy Gutmann, president of the University of Pennsylvania. Its report was released on 16 December.

Synthetic biology goes a step beyond genetically modifying organisms—where a gene might be transferred from one organism to another or even to a different species—to digitising that genetic information. It holds the potential to use that digital database to assemble a genome one base pair at a time to create an organism from scratch.

Potential applications range from creating new drugs …
Successful Femoral Embolectomy
Authors: E. K. Althorp, J. K. N. Yearsley
Journal: BMJ (1955)

MEDICAL MEMORANDAMmIC"oHUaNs and divided, only the mesentery remaining to be dealt with.A drainage tube to the gall-bladder bed was brought out through the upper part of the wound, which was then closed in layers.The patient's general condition remained satis- factory during and after the operation.Her general con- dition improved considerably during the next twenty-four hours; she continued to make good progress until her dis- charge from hospital on the fourteenth post-operative day.COMMENT One very interesting clinical sign in this case was the distinct zone of acute tenderness over a small area.This had previously been noted by Case (1951).The gall-bladder was relatively free and mobile, but when torsion occurred it became relatively fixed and firmly abutted against the anterior parietal peritoneum.The small zone of maximal tenderness therefore corresponds fairly accurately to the area in contact with the gangrenous gall-bladder.The patient's convalescence was without incident, which is not only gratifying but interesting; Arthur (1937) esti- mated the mortality to be 16%.
Environmental and demographic risk factors for egg allergy in a population‐based study of infants
Authors: J. J. Koplin, S. C. Dharmage, A.‐L. Ponsonby, M. L. K. Tang, A. J. Lowe, L. C. Gurrin, N. J. Osborne, P. E. Martin, M. N. Robinson, M. Wake, D. J. Hill, K. J. Allen
Journal: Allergy (2012)

Although egg allergy is the most common food allergy in infants and young children, risk factors for egg allergy remain largely unknown. This study examined the relationship between environmental and demographic factors and egg allergy in a population-based infant cohort.In a study of 5276 infants (HealthNuts), infants underwent skin prick testing (SPT) to egg white at 12 months of age. Questionnaire data on relevant exposures were obtained. 699/873 (80%) infants eligible for oral food challenge (detectable wheal on SPT) attended for formal assessment of egg allergy status; 453 had confirmed egg allergy (positive challenge and SPT ≥ 2 mm). Associations between environmental and demographic factors and egg allergy were investigated using multivariable logistic regression.Children with older siblings and those with a pet dog at home were less likely to develop egg allergy by 1 year of age (adjusted OR [aOR], 0.72; 95% CI, 0.62, 0.83 per sibling; and aOR, 0.72; 95% CI, 0.52, 0.99, respectively). Caesarean section delivery, antibiotic use in infancy, childcare attendance and maternal age were not associated with egg allergy. History of allergic disease in an immediate family member and having parents born in East Asia were strong risk factors for infantile egg allergy (aOR, 1.82; 95% CI, 1.40, 2.36; and aOR, 3.30; 95% CI, 2.45, 4.45, respectively).Exposure in the first year of life to siblings and dogs may decrease the risk of subsequent egg allergy. Infants with a family history of allergy and those with parents born in East Asia are at increased risk of egg allergy.
Role of endoscopic ultrasound and multidimensional comptued tomography in predicting need for mesenteric vein resection in pancreaticoduodenectomy specimens – A histopathological correlation
Authors: Ronan Kelly, Tom Gallagher, Kevin Conlon, Emir Hoti, Donal Maguire, Justin Geoghegan, Oscar Traynor
Journal: International Journal of Surgery (2013)
Tumours of the Testicle
Authors: Bernard R. Sears
Journal: JAMA (1971)

This excellent monograph is worth an evening of anyone's time and is especially recommended to house officers. It fills the bill, fits the pocket, and, at $7, must be one of the best bargains of the year. A urologist, radiotherapist, and pathologist survey the literature and review the London Hospital cases. Scrutiny of the combined material leads them to reaffirm two standard British positions that differ from ours. They support the British pathologic nomenclature and distrust lymphadenectomy. En route to these conclusions, the authors give a full account of diagnosis, staging, and planned management. There is a chapter on history and a huge bibliography. The chapter on differential diagnosis should be read by everyone who examines males. The technique of orchiectomy is given much more space than lymphadenectomy, which the authors carefully reject. Their argument against the latter procedure is stated with the cogency of informed, sweet reasonableness. American advocacy
Abstract CT404: Phase I/II study of VAL-083 in patients with recurrent glioblastoma multiforme
Authors: Kent C. Shih, Manish R. Patel, Jeffrey Bacha, Dennis M. Brown, William J. Garner, Anne Steino, Richard S. Schwartz, Sarath Kanekal, Mike Li, Lorena M. Lopez, Howard A. Burris
Journal: Cancer Research (2014)

Abstract Median survival for patients with recurrent glioblastoma multiforme (GBM) is less than 6 months. Front-line systemic therapy is temozolomide, but chemo-resistance due to O6-methylguanine-DNA-methyltransferase (MGMT) activity has been implicated in poor outcomes. VAL-083 is a structurally unique bi-functional DNA alkylating small molecule drug that crosses the blood-brain barrier and accumulates in brain tumor tissue. Previous human clinical studies by several investigators have suggested that VAL-083 has anti-tumor activity against a broad range of tumor types including GBM. In preclinical in vitro studies, VAL-083 demonstrated activity in a wide range of cancer cell lines, including pediatric and adult GBM cell lines and GBM cancer stem cells. Notably, due to crosslink formation on N7 of guanine, VAL-083 overcomes chemo-resistance to MGMT in vitro. In light of extensive safety data from several clinical trials and promising efficacy signals in CNS tumors, DelMar initiated a new clinical study to determine the safety, tolerability, pharmacokinetics, anti-tumor activity in patients with recurrent GBM. This is an open-label, single-arm Phase I/II dose-escalation study in patients with histologically-confirmed initial diagnosis of malignant GBM. The study utilizes a 3+3 dose-escalation design. Patients receive VAL-083 i.v. on days 1, 2, and 3 of a 21 day cycle. GBM patients have previously been treated with surgery and/or radiation, if appropriate, and must have failed both bevacizumab and temozolomide, unless contraindicated. In the ongoing trial, cohorts 1 through 4 (10 mg/m2) have completed the trial successfully with no drug-related serious adverse events (SAEs), and maximum tolerated dose (MTD) was not yet reached. Enrollment for Cohort 5 (20 mg/m2) has been initiated. Pharmacokinetic analyses show dose-dependent increase in exposure with a short 1-2 hour plasma half-life and a Cmax of &amp;lt;200 ng/ml at 10 mg/m2. Historical data suggests a long half-life in the cerebrospinal fluid (CSF) (&amp;gt;20 hours) with preferential accumulation to brain tumor tissue. MGMT status of patients and drug concentration in the CSF are being evaluated when possible. ClinicalTrials.gov Identifier: NCT01478178 Citation Format: Kent C. Shih, Manish R. Patel, Jeffrey Bacha, Dennis M. Brown, William J. Garner, Anne Steino, Richard S. Schwartz, Sarath Kanekal, Mike Li, Lorena M. Lopez, Howard A. Burris. Phase I/II study of VAL-083 in patients with recurrent glioblastoma multiforme. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT404. doi:10.1158/1538-7445.AM2014-CT404
Evidence-Based Medicine: A New Paradigm for the Patient-Reply
Authors: Gordon Guyatt
Journal: JAMA (1993)

In Reply.  —We thank our correspondents for providing us with the opportunity to reemphasize several key points in our article.  Dr Fox has supplied a thoughtful answer to a question that the scenario never asked. While Dr Fox raised the issue of therapy (in which the elements of net costs and benefits and patient utilities are key, as we and others have stressed elsewhere 1 ), our scenario focused on the issue of prognosis. This emphasizes one of the important skills that evidence-based teachers must encourage: the careful definition of the question.  We concur with Dr Fox's philosophical approach to practice that encourages patient empowerment. There is evidence to suggest that patients are better if they are empowered, 2 though the matter warrants further study.  Since several of the authors of our article previously have identified themselves as nominalists, 1 readers will quickly grasp why we do not accept the narrow,
Pneumothorax for Esophageal Bleeding?
Authors: RICHARD L. BUTLER
Journal: Annals of Internal Medicine (1973)

Letters, Comments, and Corrections1 February 1973Pneumothorax for Esophageal Bleeding?RICHARD L. BUTLER, M.D., F.A.C.S., PETER BYLES, M.D., F.R.C.S., LAWRENCE PORT, M.D., F.A.C.P.RICHARD L. BUTLER, M.D., F.A.C.S.Search for more papers by this author, PETER BYLES, M.D., F.R.C.S.Search for more papers by this author, LAWRENCE PORT, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-2-312_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: We are reporting five cases in which esophagovariceal bleeding stopped immediately after left artificial pneumothorax, and we suggest that left artificial pneumothorax not only decreases inspiratory negative pressure, which may abet such bleeding, but can tamponade bleeding esophageal varices.Normal inspiration evacuates extrathoracic veins while filling intrathoracic veins. But strong inspirations collapse intrathoracic veins transiently, closing and distending them and causing flutter flow (1). Air counter-pressure has been shown to overcome transmural bleeding pressure and stop measured bleeding in arterial and venous injuries of limbs (2). Artificial pneumothorax raises and narrows intrathoracic pressures (3). It is safe;...References1. BRECHER G: Venous Return. New York, Grune & Stratton, 1956, pp. 72-73 Google Scholar2. LUDWIGWANGENSTEEN RS: The effect of external counterpressure on venous bleeding. Surg 66:515-520, 1969 MedlineGoogle Scholar3. COURNANDBRYANRICHARDS AND: Cardiac output in relation to unilateral pneumothorax in man. J Clin Invest 14: 181-189, 1935 CrossrefMedlineGoogle Scholar4. HAROLD J: Intrapleural hemorrhage in artificial pneumothorax. Thorax 6:162-170, 1951 CrossrefMedlineGoogle Scholar5. MOORE F: Therapeutic innovation: ethical boundaries in the initial clinical trials of new drugs and surgical procedures. Daedalus 98:502-522, 1969 Google Scholar6. HILL A: The clinical trial. N Engl J Med 247:112-119, 1952 CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Departments of Surgery, Anesthiology, and Medicine SUNY, Upstate Medical Center Syracuse, N.Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1973Volume 78, Issue 2Page: 312-313KeywordsHemorrhageVeins Issue Published: 1 February 1973 PDF DownloadLoading ...
Tachyarrhythmias in Wolff-Parkinson-White Syndrome
Authors: Andrew M. Tonkin
Journal: JAMA (1976)

THE CLASSICAL form of ventricular preexcitation associated with the Wolff-Parkinson-White syndrome<sup>1</sup>is manifested on the surface electrocardiogram by a short P-R interval (0.12 seconds or less) and a wide QRS complex (more than 0.11 seconds) with a slurred initial deflection, the δ-wave, in at least some leads. This electrocardiographic abnormality may be persistent, intermittent, or phasic. Its reported incidence ranges from 0.1 to 3.1/1,000 apparently healthy adults and from 0.8 to 4.8/1,000 children.<sup>2</sup>Uncomplicated preexcitation has no subjective manifestations. Paroxysmal tachyarrhythmias, however, occur at some time in 40% to 80% of those with abnormal ECGs. Although most patients with arrhythmias have a benign course, in some life-threatening arrhythmias develop, which may result in sudden death. <h3>Mechanisms</h3> Whereas detailed consideration of electrophysiologic mechanisms is inappropriate here, an understanding of certain features of the syndrome is essential for rational therapy. Present evidence strongly suggests that, in the great majority of