tbuckley/cabot-search huggingface dataset:
QUANTITATIVE STUDIES OF PROSTATIC SECRETION
Authors: Charles Huggins, Philip Johnson Clark
Journal: The Journal of Experimental Medicine (1940)

Cystic hyperplasia of the prostate occurs spontaneously in senile dogs only when they possess physiologically effective amounts of androgenic hormone. The cysts are closely grouped and radially arranged in a conical manner with the base of the cone at the periphery of the gland. Flattened and columnar epithelium, varying from about 5 to 25micro are seen in each cyst. The cysts communicate with the urethra by way of ducts. Both normal and cystic prostates undergo marked atrophy when the testes are removed, the chief difference 3 months after orchiectomy being the persistence of slightly dilated clefts and spaces at the site of the former cysts in the senile state. In the castrate dog whose prostate gland is being reconstructed as result of the influence of daily injections of androgen, certain doses of estrogen prevent increase of secretion and still larger doses greatly depress the output of the gland. In dogs so treated by daily injections of testosterone propionate, 10 mg., the amount of secretion is maintained from day to day at a level by daily injections of stilbestrol, 0.4 to 0.6 mg. and greatly depressed by doses of 1 to 1.5 mg. When the larger amounts of estrogen are used, together with androgen, squamous metaplasia occurs in the posterior lobe of the prostate while the epithelium of the acini decreases in height to cuboidal or low columnar form; these histological signs of activity of both androgen and estrogen on the prostate show that inhibition of the male hormone by stilbestrol is incomplete at these ratios. In dogs with either normal or cystic prostate glands, the prostate decreases in size when estrogen is injected in amounts to depress prostatic secretion profoundly. The gland is maintained in an atrophic state and overdosage avoided by controlled periodic injections of stilbestrol until secretion is reduced to the minimum, followed by free intervals, the estrogen being again administered when secretion measurably increases. The shrinkage is related to depression of male hormone production. Overdosage of estrogen causes the prostate gland of dogs to enlarge, and structures of the posterior lobe and utriculus respond first and most markedly with metaplasia caused by this material. The prostatic enlargement does not resemble the common cystic hyperplasia of senile dogs. Metaplasia rapidly disappears from the prostate, and the epithelial structures quickly return to normal when estrogen is discontinued and androgen is administered.
Functional magnetic resonance imaging reveals brain regions mediating the response to resistive expiratory loads in humans.
Authors: D Gozal, O Omidvar, K A Kirlew, G M Hathout, R B Lufkin, R M Harper
Journal: Journal of Clinical Investigation (1996)

Obstructive lung disease is the most common form of respiratory disturbance. However, the location of brain structures underlying the ventilatory response to resistive expiratory loads is unknown in humans. To study this issue, midsagittal magnetic resonance images were acquired in eight healthy volunteers before and after application of a moderate resistive expiratory load (30 cmH2O/liter/s), using functional magnetic resonance imaging (fMRI) strategies (1.5-T magnetic resonance; repetition time: 72 ms; echo time: 45 ms; flip angle: 30 degrees; field of view: 26 cm; slice thickness: 5 mm; 128 x 256 x 1 number of excitations). Digital image subtractions and region of interest analyses revealed significant increases in fMRI signal intensity in discrete areas of the ventral medulla, ventral and dorsal pontomedullary structures, basal forebrain, and cerebellum. Upon load withdrawal, a rapid fMRI signal off-transient occurred in all activated sites. Application of an identical load immediately after recovery from the initial stimulus resulted in smaller signal increases (P < 0.02). Prolongation of load duration was associated with progressive fMRI signal decrease across activated regions. In three additional subjects, the threshold for significant MRI signal increases was established at expiratory loads > or = 15 cmH2O/liter/s and was dose dependent with increasing loads. We conclude that resistive expiratory loads > or = 15 cmH2O/liter/s elicit regional activation of discrete brain locations in humans.
The Kidney in Cyanotic Congenital Heart Disease.
Authors: I. D. B. Rennie
Journal: Annals of Internal Medicine (1968)

s1 May 1968The Kidney in Cyanotic Congenital Heart Disease.I. D. B. Rennie, M.R.C.P.I. D. B. Rennie, M.R.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-5-1183_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThere is an increased prevalence of proteinuria in patients with cyanotic congenital heart disease (CCHD), independent of the exact cardiac lesion and unrelated to cardiac operations. In 194 such patients, both screening tests for total urine protein and albumin excretion rates measured by immunoassay showed abnormally high levels when compared with controls.A description was given of the methods used to quantitate blood values in CCHD. It was shown that the rate of protein excretion correlated directly with the mean height of the hemoglobin, the length of time it had been raised, and with the hematocrit and inversely with the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Chicago, Illinois PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1968Volume 68, Issue 5Page: 1183-1183KeywordsCongenital heart diseaseExcretionHeart diseasesImmunoassaysLesionsPatientsProteinsProteinuriaRenal diseasesUrine Issue Published: 1 May 1968 PDF downloadLoading ...
PTU-103 Audit into the Management of Acute Variceal Bleeds and the Role of Tips
Authors: V Chhaya, A Bevan, F Stanley, M Pollard, S Clark
Journal: Gut (2013)

<h3>Introduction</h3> The mortality associated with acute variceal bleeding is significant with a 70% risk of recurrent haemorrhage in survivors. Our aim was to assess the outcome from variceal bleeding at St George’s Hospital over a one year period, to determine whether current clinical guidelines in the management of variceal bleeding are being adhered to, and to assess whether we are utilising the role for early TIPS (transjugular intrahepatic portosystemic shunt) in patients with variceal bleeding. <h3>Methods</h3> A dataset of all adult patients admitted from 1/4/11 for a period of 12 months was obtained with a primary diagnosis code of K922 Gastrointestinal haemorrhage, unspecified (n = 378). Genuine cases were confirmed by reference to the Micromed endoscopy reporting tool, CEPOD emergency theatre lists, bereavement records and old inpatient lists for the Hepatology firm. Case notes were obtained for the final sample of 23 patients. <h3>Results</h3> The main cause of variceal bleeding (65%) was alcoholic liver disease (ALD). 78% were rebleeds of which 83% were within the last 6 months. 61% of patients had features of decompensation (ascites 86%, renal dysfunction 29%). Only 4% of cases were Childs-Pugh A, with 61% of cases being Childs-Pugh B and 35% Childs-Pugh C. The predicted 3 month mortality according to the MELD (model for end stage liver disease) score was 6–19.6%. An average of 2 to 3 units of blood was transfused to 78% of patients and 60% of patients required either FPP, platelets or both. All patient received an endoscopy during their admission, of which 74% were carried out within 12 hours. Only 52% were intubated for procedure and 39% were admitted to ITU post procedure. 96% received antibiotics, 87% received terlipressin and 79% were discharged on propranolol. Only 35% of patients received sucralfate post banding. Only 13% of patients had a TIPS procedure. A further 48% of our sample could have been considered for TIPS where no contra-indication was found (i.e hepatic encephalopathy not secondary to UGI bleeding or renal dysfunction). The average length of stay was 14 days and the 30 day mortality rate was 13%. <h3>Conclusion</h3> The pharmacological management was generally good and our mortality rate of 13% was better than the quoted figures of 30% in the literature. However, we identified a possible 48% of the sample could have been considered for TIPS which is no longer considered rescue therapy alone with good evidence for its early use, with subsequent prevention of readmission from a variceal bleed. We recommend early pharmacotherapy with terlipressin and antibiotics as soon as varices are suspected with early ITU involvement, airway protection at endoscopy and early TIPS in selected patients. <h3>Disclosure of Interest</h3> None Declared.
Specialty Board Examinations: Credentials vs Competence
Authors: Stewart Wolf
Journal: JAMA (1976)

Dr Aring's commentary on page 1849 brings to mind a sobering thought for the Bicentennial. In recent times, the traditional American values, namely, self-reliance, self-assessment, and emphasis on individual standards of excellence, appear to have given way to a greater and greater concern for appearances, for the opinions of others, and the approval of peers. A psychologist might say that America, once largely inner-directed, has become more and more outer-directed. Moreover, there are indications that our preoccupation with credentials, with setting standards for everyone, may have blunted the aspirations of the few. Alan Gregg pointed out many years ago that credentials do not necessarily equate with competence. In his address to the American College of Physicians, he reminded his colleagues that the board examinations were not finding out what the candidates could do. They were not really ascertaining what the candidates knew, but only whether or not they knew the
Reply to Rodrigues et al.
Authors: G. Karamanolis, K. Triantafyllou, D. Polymeros, S. Ladas
Journal: Endoscopy (2010)

We sincerely thank Rodrigues et al. for their comments on our article regarding the long-lasting effect of argon plasma coagulation (APC) therapy in patients with chronic radiation proctitis [1]. Indeed, rectal bleeding due to radiation proctitis represents a challenging condition for physicians, as its management is still under consideration.
Commentary: Heading for a therapeutic stalemate
Authors: T. Groves
Journal: BMJ (2011)

In late May I went with an open mind to the sixth Invest in ME conference in London to listen to research presentations and take part, on behalf of the BMJ , in a concluding panel discussion. Although I was aware of Invest in ME’s stance against the recent PACE trial1 and other research on non-biological approaches, I was heartened by the conference theme: “The Way Forward for ME—A Case for Clinical Trials.” I knew that laboratory science had not yet yielded biological evidence that would lead to large scale clinical trials, so I hoped to hear about trials of health services and supportive interventions to improve patients’ experiences and lives.

I heard about just one clinical trial at the conference, however. Oncologists Oystein Fluge and Olav Mella, from the University of Bergen, talked about their recent placebo controlled trial of the monoclonal antibody rituximab in 30 patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). They had found positive results for some secondary outcomes, but not for the primary outcome (self reported symptoms and quality of life at three months2), so …
Phase I and Pharmacokinetic Study of the Cytotoxic Ether Lipid Ilmofosine Administered by Weekly Two-Hour Infusion in Patients with Advanced Solid Tumors
Authors: Bruce J. Giantonio, Christine Derry, Cecilia McAleer, Joseph J. McPhillips, Peter J. O’Dwyer
Journal: Clinical Cancer Research (2004)

Abstract Purpose: A Phase I trial was performed to determine the dose-limiting toxicity and maximum tolerated dose, and to describe the pharmacokinetics of the alkyl-lysophospholipid, ilmofosine, when administered as a weekly 2-h infusion in patients with solid tumors. Experimental Design: Thirty-nine patients were entered into a trial of ilmofosine administered weekly for 4 weeks followed by a 2-week rest period. Dose escalation occurred in 10 levels from 12 to 650 mg/m2. Results: Thirty-six patients were evaluable for toxicity. The median number of cycles per patient was 1 (range, 1–4). Dose-limiting gastrointestinal toxicity occurred at 650 mg/m2 with grade 3 nausea in two patients and grade 3 vomiting and diarrhea in one patient. Grade 2 diarrhea was observed in four of six patients treated at 550 mg/m2. In addition, two patients treated at 550 mg/m2 and two patients treated at 650 mg/m2 experienced a decline in performance status of two or more levels that was determined to be due to treatment. There were no tumor responses. Stabilization of disease for at least 8 weeks occurred in six patients. Plasma concentrations of ilmofosine and its sulfoxide metabolite were evaluated by high-pressure liquid chromatography. The elimination of both compounds was biexponential with terminal half-lives of ∼40 h for ilmofosine and 48 h for the sulfoxide. The area under the concentration-time curve was dose-proportional for each compound, and there was no evidence of saturable kinetics. Conclusions: The dose-limiting toxicity of ilmofosine is gastrointestinal and the recommended dose for Phase II trials is 450 mg/m2 as a 2-h weekly infusion. The relatively long half-life of ilmofosine and its active metabolite support the use of this intermittent schedule.
A Case for Ribavirin to Treat Chronic Hepatitis E
Authors: David L. Thomas
Journal: New England Journal of Medicine (2014)

More than 30 years ago, hepatitis E virus (HEV) was shown to be the primary cause of hepatitis acquired enterically but not attributable to hepatitis A virus.1 Classified in the family Hepeviridae, HEV is an RNA virus with at least four distinct genotypes that infect humans.2 Genotypes 3 and 4 also infect animals such as swine and deer and can be acquired by ingestion of undercooked meat.3 HEV infections occur worldwide but are more common in South Asia and sub-Saharan Africa.HEV infection is usually self-limited, with viral RNA detectable in blood just before and for 1 to 3 weeks . . .
Bacillus licheniformis Sepsis
Authors: Alan M. Sugar
Journal: JAMA (1977)

SERIOUS infection caused by aerobic, spore-forming, Gram-positive<i>Bacillus</i>species is rare. When it occurs, the patient usually is immunologically incompetent, traumatized, or suffering from a serious underlying disorder. We report a unique case of life-threatening<i>Bacillus licheniformis</i>bacteremia and peritonitis. Other than volvulus and perforation of the upper small bowel, no co-morbid immunosuppressive disease was found. <h3>Report of a Case</h3> A 57-year-old male longshoreman, formerly alcoholic, was admitted to the hospital with abdominal pain and vomiting of eight hours' duration. He noticed the sudden onset of acute epigastric pain with radiation to the back and both flanks. Within minutes, he began vomiting bilious material that did not contain blood. There was no relief of the pain with analgesics or change of position. The patient denied having fever, chills, diarrhea, melena, hematochezia, dysuria, hematuria, cough, or chest pain. He had stopped drinking alcoholic beverages ten years earlier. He had not had
Antibiotic Prophylaxis of Infective Endocarditis During Digestive Endoscopy: Over- and Underuse in Switzerland Despite Professed Adherence to Guidelines
Authors: J. Roduit, P. Jornod, N. Dorta, A. L. Blum, G. Dorta
Journal: Endoscopy (2002)

Background and Study Aims: Guidelines for antibiotic prophylaxis of infective endocarditis associated with gastrointestinal endoscopy are not uniform. Though based on weak scientific evidence, they do represent an attempt to unify the management of antibiotic prophylaxis. We investigated whether physicians who profess to adhere to these guidelines actually do apply them correctly. Materials and Methods: A questionnaire was sent to all 195 Swiss gastroenterologists asking whether they adhered to antibiotic prophylaxis guidelines and under what conditions did they apply antibiotic prophylaxis in gastrointestinal endoscopy. We analysed whether the Swiss gastroenterologists who claim to adhere to these guidelines actually do so in practice.
Abstract 1212: Studying cancer drug resistance in patient derived xenograft tumor models
Authors: Tengfei Yu, Ying Yan, Wei Du, Yuefei Yang, Tingting Tan, Xuqin Yang, Jiali Gu, Liang Hua, Xin K. Ye, Zhenyu Gu
Journal: Cancer Research (2014)

Abstract Anti-cancer drugs, either targeted therapies or cytotoxic chemotherapies, have proven to be effective in treating certain cancer patients. However, in most cases, tumors recur and become resistant to the treatment after a period of time. There are urgent needs to understand the underlying drug resistance mechanisms, to discover drug resistance targets and drug resistance biomarkers and to develop new therapies or combination therapies to tackle this widely occurring clinical problem. Currently the main approaches to study cancer drug resistance include analyzing clinical samples and developing drug resistance models in vitro. Numerous potential resistance mechanisms have been revealed. However, validation of these findings in a clinical-like setting and to test therapies in preclinical studies requires in vivo tumor models of drug resistance. At GenenDesign, we have developed cancer drug resistance PDX tumor models through short term drug testing or long term treatment of xenograft tumor mice. Cancer drugs investigated in our studies include major classes of targeted therapeutic modalities such as Her2 inhibitors, EGFR inhibitors, FGFR inhibitors and cMet/ALK inhibitors, as well as several standard of care (SoC) chemotherapies. From these studies, we have identified de novo resistance models, acquired resistance models and reversible resistance models in multiple cancer types including lung cancer and gastric cancer. In analyzing more than a dozen of Her2 positive but Herceptin resistance PDX models, we have uncovered molecular abnormalities such as Pten deletion, PI3K mutation, amplification of EGFR, cMet and cyclin E, which have been reported previously to be associated with Herceptin resistance in early studies. Studies are on-going to test whether combination therapies will be effective in overcoming Herceptin resistance. In drug response profiling of our PDX models, we also found wide spread phenotypical and functional heterogeneity in individual tumors. The heterogeneity within each tumor, in some cases, contributed to evolving of drug resistance from initially responsive tumors. Citation Format: Tengfei Yu, Ying Yan, Wei Du, Yuefei Yang, Tingting Tan, Xuqin Yang, Jiali Gu, Liang Hua, Xin K. Ye, Zhenyu Gu. Studying cancer drug resistance in patient derived xenograft tumor models. [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 1212. doi:10.1158/1538-7445.AM2014-1212
Improved Computer-Assisted Digoxin Therapy
Authors: LEWIS B. SHEINER
Journal: Annals of Internal Medicine (1975)

Automated feedback control methods were applied to a medical problem, in a computer program that used measured serum digoxin concentrations (as feedback) to predict future concentrations and to achieve desired concentrations. The system was validated by comparing its ability with the corresponding ability of physicians to regulate digoxin dosage. The prospective, randomized study included 51 patients. In the presence of varying amounts of feedback (serum digoxin concentration) information, the computer always predicted future digoxin concentrations as accurately as did physicians. For both computer and physician, the decrease in the prediction errors when two concentrations were known against that when no concentrations were known was significant: mean absolute error decreased from 0.40 to 0.25 ng/ml for the physicians and from 0.45 to 0.27 ng/ml for the computer. Thus the computer system is capable of simulating and reproducing a sophisticated aspect of physician behavior: "learning" about individual patient responses. The computer achieved desired concentrations more accurately than did physicians, especially when two or more previous digoxin concentrations were available (mean absolute achievement error for computer, 0.28 ng/ml; for physicians, 0.50 ng/ml).
Angioscopic Predictors of Early Adverse Outcome After Coronary Angioplasty in Patients With Unstable Angina and Non–Q-Wave Myocardial Infarction
Authors: Sergio Waxman, Michael A. Sassower, Murray A. Mittleman, Stuart Zarich, Akira Miyamoto, Karen S. Manzo, James E. Muller, George S. Abela, Richard W. Nesto
Journal: Circulation (1996)

Clinical and angiographic criteria have a limited ability to predict adverse outcome in patients with unstable angina who are undergoing percutaneous transluminal coronary angioplasty (PTCA). We investigated whether the use of angioscopy can improve prediction of early adverse outcome after PTCA.Angioscopic characterization of the culprit lesion was performed before PTCA in 32 patients with unstable angina and 10 with non-Q-wave infarction. Seven patients (17%) had an adverse outcome (myocardial infarction, repeat PTCA, or need for coronary artery bypass graft surgery) within 24 hours after PTCA. Six of 18 patients with a yellow culprit lesion had an adverse outcome compared with 1 of 24 in whom the culprit lesion was white (P = .03). Six of 20 patients with plaque disruption suffered an adverse outcome compared with 1 of 22 with nondisrupted plaques (P = .04). Six of 17 patients with intraluminal thrombus had an adverse outcome, whereas only 1 of 25 patients without thrombus suffered an adverse outcome (P = .01). Yellow color, disruption, and thrombus at the culprit lesion site were associated with an eightfold increase in risk of adverse outcome after PTCA. The prediction of PTCA outcome based on characteristics of the plaque that were identifiable by angioscopy was superior to that estimated by the use of angiographic variables.In patients with unstable angina and non-Q-wave infarction, angioscopic features of disruption, yellow color, or thrombus at the culprit lesion site can identify patients at high risk of early adverse outcome after PTCA. Angioscopy was superior to angiography for prediction of PTCA outcome.
Neuroleptic Malignant Syndrome
Authors: Reuven Sandyk
Journal: JAMA (1986)

<h3>To the Editor.—</h3> We read with interest the recent article by Friedman et al entitled "A Neuroleptic Malignantlike Syndrome due to Levodopa Therapy Withdrawal."<sup>1</sup>The authors speculate that the dysfunction underlying the neuroleptic malignant syndrome (NMS) occurs at more than one level of the neuraxis, on the ground that the multiple symptoms and signs cannot be reconciled to the pathophysiology of one anatomic area. We would like to suggest, however, that the key factor to the pathophysiology of the NMS is a dysregulation in the activity of endorphins at the diencephalic level. Our hypothesis is based on the following evidence and rationale. First, it is understood that the hypothalamus regulates temperature,<sup>2</sup>level of consciousness,<sup>3</sup>and motor activity.<sup>4</sup>The hypothalamus is rich in endorphins and dopamine, the former being implicated in both hypothermia and hyperthermia. Dopaminergic pathways link the hypothalamus with the substantia nigra.<sup>5</sup> Recent studies
Molecular characterization of hepatocellular adenomas developed in patients with glycogen storage disease type I
Authors: Julien Calderaro, Philippe Labrune, Guillaume Morcrette, Sandra Rebouissou, Dominique Franco, Sophie Prévot, Alberto Quaglia, Pierre Bedossa, Louis Libbrecht, Luigi Terracciano, G. Peter A. Smit, Paulette Bioulac-Sage, Jessica Zucman-Rossi
Journal: Journal of Hepatology (2012)