tbuckley/cabot-search huggingface dataset:
HIV Infection, Hepatitis C Infection, and HAART
Authors: Shyam Kottilil, Michael A. Polis, Joseph A. Kovacs
Journal: JAMA (2004)

Abnormalities in hepatic function have become one of the most common complications occurring among human immunodeficiency virus (HIV)–infected individuals receiving highly active antiretroviral therapy (HAART), and liver disease has become an increasingly important cause of morbidity and mortality in HIV-infected patients. We present a case of a patient with HIV infection and hepatotoxicity that exemplifies the complications currently observed during the treatment of such patients. Hepatotoxicity can be a result of several factors, including a direct effect of HAART, substance abuse, and coinfection with either hepatitis C virus (HCV) or hepatitis B virus. Imaging studies may be helpful in determining the etiology; however, a liver biopsy is often necessary to be able to more accurately determine the relative contributions of different processes. Although coinfection with HCV and HIV has become a common clinical problem, optimal treatment of such patients remains to be defined and must be individualized to maximize benefit and tolerance.
Natural Selection and the Form of the Human Female Breast-Reply
Authors: Ashley Montagu
Journal: JAMA (1962)

<h3>To the Editor:—</h3> The evidence for the statement that the widespread belief that suckling a baby will deform the breast is erroneous is provided by the innumerable women who have suckled babies and have never developed anything resembling a deformed breast. Controlled studies so far as I know are, unfortunately, not available. There is a tremendous variability in the form of the female breast within the human species, and from individual to individual within each ethnic group. Lack of proper support and of care of the breast and aging will, in many cases, result in changes in the female breast which are often erroneously attributed to suckling. The fact is that precisely similar changes may be observed in the breasts of women who have never given birth to or suckled a child. Why, if the human type of female breast has such high selective value did not the anthropoids develop
Transnasal Percutaneous Endoscopic Gastrostomy Using a Standard-Diameter Gastroscope (9.8 mm)
Authors: D. Desai, A. Joshi, P. Abraham, M. Chawla, A. Sonsale
Journal: Endoscopy (2005)

Transoral percutaneous endoscopic gastrostomy (PEG) is not possible in some patients due to difficulty in opening the mouth (e. g., in patients with head and neck cancers, oral submucous fibrosis, dental misalignment, and intermaxillary fixation). Transnasal endoscopy has been used for diagnostic upper gastrointestinal endoscopy and for placement of enteral feeding tubes [1] [2]. However, the small diameter of the accessory channel in transnasal instruments (2 mm) limits their use for therapeutic interventions [3]. A study of transnasal percutaneous endoscopic gastrostomy (TN-PEG) using pediatric scopes (with an outer diameter of 7.9 mm) reported failure of the method in three of six patients [4]. TN-PEG using standard-diameter endoscopes has been reported [5].
Impairment of endothelium-dependent vasorelaxation in experimental atherosclerosis is dependent on gender
Authors: G Kojda
Journal: Cardiovascular Research (1998)

Objective: Nitric oxide (NO) has been suggested to have antiatherosclerotic effects. It has also been demonstrated that there is a greater basal release of endothelium derived relaxing factor (EDRF) in female as compared to male rabbit aorta, which also might have beneficial effects in atherosclerosis. We thus sought to determine if gender influences the severity of atherosclerosis. Methods: We studied 18 female and 18 male New Zealand White rabbits that were randomly divided in two groups of 9 animals each and fed either a standard or a cholesterol diet (0.75%) for 15 weeks. Results: In cholesterol-fed rabbits the percentage of atherosclerotic lesions in the aorta was identical in females and males and was inversely correlated with the maximal aortic relaxation to acetylcholine as assessed in organ chamber experiments (females: P<0.0008, males: P<0.0002). Importantly, the cholesterol diet induced a significantly (P<0.025) more severe impairment of maximal vasorelaxation to acetylcholine in males from 78.4±1.2% to 29.4±10.2%) compared to females (from 84.4±1.2% to 60.7±8.5%). Both male gender (P<0.0001) and the extent of impairment of endothelium-dependent relaxation (P<0.0002) were associated with a reduced aortic sensitivity to S-nitroso-N-acetyl-d,l-penicillamine, which releases NO into the organ bath. In contrast, the aortic sensitivity to the organic nitrates pentaerythritol tetranitrate and isosorbide 5-nitrate, which release NO after enzymatic metabolization within the smooth muscle, was not reduced. Conclusions: These results suggest that the impairment of endothelium-dependent vasorelaxation induced by atherosclerosis is dependent on gender. This may be due to a greater degradation of extracellular NO in the vessel wall of males.
Elsewhere in This Issue
Authors: Samuel Vaisrub
Journal: JAMA (1977)

A "go-with" editorial generally attempts to highlight, clarify, amplify, or put into perspective the message of an important article published in the same issue. The attempt becomes an exercise in diffusion when the article bears not one but a dozen messages. Focusing then presents a problem. Such a multi-messaged paper is the case report by Crosby (p 2627). The patient, a former movie and television actress, has acute leukemia of recent onset and chronic severe lead poisoning caused by a prescribed calcium supplement made from horse bone. Despite symptoms typical of lead intoxication, the diagnosis eluded more than a score of physicians over a period of years. It was ultimately made by the patient herself. Clearly, the report has important implications for epidemiologists, toxicologists, clinicians, psychiatrists, oncologists, health-food manufacturers, and the Food and Drug Administration. It is also meaningful to a student of human nature. Where, then, should the editorial
Reliability of self reported form of female genital mutilation and WHO classification: cross sectional study
Authors: Susan Elmusharaf, Nagla Elhadi, Lars Almroth
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objective</b> To assess the reliability of self reported form of female genital mutilation (FGM) and to compare the extent of cutting verified by clinical examination with the corresponding World Health Organization classification. <b>Design</b> Cross sectional study. <b>Settings</b> One paediatric hospital and one gynaecological outpatient clinic in Khartoum, Sudan, 2003-4. <b>Participants</b> 255 girls aged 4-9 and 282 women aged 17-35. <b>Main outcome measures</b> The women9s reports of FGMthe actual anatomical extent of the mutilation, and the corresponding types according to the WHO classification. <b>Results</b> All girls and women reported to have undergone FGM had this verified by genital inspection. None of those who said they had not undergone FGM were found to have it. Many said to have undergone “sunna circumcision” (excision of prepuce and part or all of clitoris, equivalent to WHO type I) had a form of FGM extending beyond the clitoris (10/23 (43%) girls and 20/35 (57%) women). Of those who said they had undergone this form, nine girls (39%) and 19 women (54%) actually had WHO type III (infibulation and excision of part or all of external genitalia). The anatomical extent of forms classified as WHO type III varies widely. In 12/32 girls (38%) and 27/245 women (11%) classified as having WHO type III, the labia majora were not involved. Thus there is a substantial overlap, in an anatomical sense, between WHO types II and III. <b>Conclusion</b> The reliability of reported form of FGM is low. There is considerable under-reporting of the extent. The WHO classification fails to relate the defined forms to the severity of the operation. It is important to be aware of these aspects in the conduct and interpretation of epidemiological and clinical studies. WHO should revise its classification.
Early Detection, Diagnosis, and Management of Oral and Oropharyngeal Cancer
Authors: A. Mashberg, A. M. Samit
Journal: CA A Cancer Journal for Clinicians (1989)

1. Drinkers and cigarette smokers are at very high risk for the development of upper aerodigestive tract and lung squamous carcinomas. 2. The floor of the mouth, the ventrolateral tongue, and the soft palate are high-risk sites within the oral cavity and oropharynx. 3. Mucosal erythroplasia rather than leukoplakia is the earliest visual sign of oral and pharyngeal carcinomas. 4. Areas of mucosal abnormality, especially redness or inflammation in high-risk sites, that persist for more than 14 days without obvious etiology or resolution should be biopsied. 5. Asymptomatic, erythroplastic lesions should not be regarded merely as precancerous changes. The evidence indicates that these lesions in high-risk sites should be considered to be invasive carcinoma or at the very least carcinoma in situ, unless proven otherwise by biopsy. 6. Toluidine blue staining is a useful diagnostic adjunct, particularly as a method of ruling out false-negative clinical impressions. It may also be used as a screening rinse in high-risk patients to encompass the entire oral mucosa after a negative clinical examination and as a guide to improve biopsy yields. 7. If oral or pharyngeal cancer is identified, evaluations of the larynx, hypopharynx, esophagus, and lungs should be performed to rule out second primary cancers. Yearly aerodigestive surveillance should be continued after satisfactory treatment of the index cancer.
Abstract B48: Targeting SETD2 knockout cells: A synthetic lethal approach to treating ccRCC
Authors: Catherine C. Fahey, Kathryn E. Hacker, Jian Jin, Ian J. Davis, W. Kimryn Rathmell
Journal: Cancer Research (2013)

Abstract Background: Kidney cancer is estimated to affect 65,150 newly diagnosed individuals in 2013. Approximately 70% of these diagnoses will be clear cell renal cell carcinoma (ccRCC). Many targeted therapies for ccRCC are currently being pursued, as ccRCC is resistant to radiation and often does not respond to chemotherapy. The most commonly mutated tumor suppressor gene in ccRCC is VHL, located on chromosome 3. The loss of chromosome 3p is a high frequency event in ccRCC, which often also encompasses the genes PBRM1, BAP1, and SETD2. Mutations in one or more of these genes represent the next most common common genetic alterations in ccRCC. In our preliminary data, we have observed that mutations in SETD2, in particular, area associated with global deficits in chromatin packaging and organization. Methods: We are pursuing the opportunity to exploit SETD2 loss as a source of cellular fragility by performing a small molecule screen on SETD2 wild type and SETD2 knockout cell lines. We will use a screening set of epigenetically targeted compounds to perform a high throughput screen with cell viability as the endpoint, as well as use a selected few compounds to compare effect on wild type and knockout cells in a more in depth manner. Results: Preliminarily, we have tested SETD2 knock-down lines to confirm that we can effectively preform all aspects of this screen. In our current studies, we are repeating testing with the selected few compounds and beginning the high throughput screen with a SETD2 knockout cell line. Conclusion: Mutations in chromatin modifying genes in ccRCC present an opportunity for synthetic therapeutic approaches to induce reduced cell viability, as well as to identify unique meaningful interactions between chromatin modifier genes. Citation Format: Catherine C. Fahey, Kathryn E. Hacker, Jian Jin, Ian J. Davis, W. Kimryn Rathmell. Targeting SETD2 knockout cells: A synthetic lethal approach to treating ccRCC. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr B48.
A rodent model of NASH with cirrhosis, oval cell proliferation and hepatocellular carcinoma
Authors: Vicência M.R. de Lima, Claudia P.M.S. Oliveira, Venancio A.F. Alves, Maria Cristina Chammas, Ellen Pierre Oliveira, José Tadeu Stefano, Evandro Sobroza de Mello, Giovanni Guido Cerri, Flair José Carrilho, Stephen H. Caldwell
Journal: Journal of Hepatology (2008)
Severe Dyspnea in a Woman With Known Tuberculosis
Authors: Leonid Calenoff
Journal: JAMA (1977)

<h3>History</h3> A 35-year-old woman presented with severe dyspnea, left shoulder pain, and a dry cough. There were dullness and decreased breath sounds over the left side of the chest posteriorly. Her illness had started one year ago with productive cough, a left lower lobe infiltrate, and positive sputum cultures for<i>Mycobacterium tuberculosis</i>. She had been receiving antituberculosis treatment. Figures 1 and 2 are recent posteroanterior and lateral teleroentgenograms. <h3>Diagnosis</h3> Atelectasis of the left lung due to complete occlusion of the left main bronchus, resulting from bronchial tuberculosis. <h3>Comment</h3> The chest roentgenograms (Fig 1 and 2) show a striking shift of the mediastinum to the left, narrowing of the left intercostal spaces, and elevation of the left hemidiaphragm. The right lung has herniated to the left, passing in front of the mediastinum. The bronchogram (Fig 3) demonstrates a totally occluded left main bronchus (arrows). The occluded bronchus is also visible on
A teenager with a cough, fever, and poor appetite
Authors: S. Turcu, S. Sonnappa
Journal: BMJ (2012)

A 14 year old girl presented to her local hospital with a three week history of progressively worsening cough, fever, and poor appetite, which had not responded to a week of oral antibiotics.

On examination she had a temperature of 38°C, was pale, not clubbed, and her oxygen saturations were 95% in air. There was a dull note on percussion, with reduced air entry on auscultation in the right upper zone of the chest, and no added sounds. The rest of the systemic examination was normal. At admission, blood tests showed haemoglobin 109 g/L (reference range 105-135), white blood cell count 12.7×106 cells/L (6.0-18), neutrophils 7.65×106 cells/L (2.0-6.0), C reactive protein 33 mg/L (0-5), erythrocyte sedimentation rate 116 mm in the first hour (10). Chest radiography and computed tomography were performed (figs 1⇓ and 2⇓). She was started on intravenous antibiotics and transferred to a tertiary centre for further management. 



Fig 1 Chest radiograph





Fig 2 Chest computed tomogram





### 1 What abnormality do the figures show and what is the most likely diagnosis?

#### Short answer

There is a round opacity with air fluid level in the right upper zone on the chest radiograph, which can be localised to the right upper lobe on the computed tomogram. The appearance suggests a lung abscess.

#### Long answer

A large circular mass can be seen in the right upper to mid zone on the chest radiograph with air fluid level within …
Direct pro‐arrhythmogenic effects of angiotensin II can be suppressed by AT<sub>1</sub> receptor blockade in human atrial myocardium
Authors: Dirk von Lewinski, Jens Kockskämper, Sven‐Ulrich Rübertus, Danan Zhu, Jan D. Schmitto, Friedrich A. Schöndube, Gerd Hasenfuss, Burkert Pieske
Journal: European Journal of Heart Failure (2008)
Quality Comes Home
Authors: Donald M. Berwick
Journal: Annals of Internal Medicine (1996)

Without a clear focus on the needs and experiences of individual patients, much of the financial and structural reorganization now rampant in health care will be unlikely to yield improvements that matter to the patients we serve. As we change the system of care, five principles can help guide our investment of energy: 1) Focus on integrating experiences, not just structures; 2) learn to use measurement for improvement, not measurement for judgment; 3) develop better ways to learn from each other, not just to discover “best practices”; 4) reduce total costs, not just local costs; and 5) compete against disease, not against each other.
The effects of free fatty acids on gluconeogenesis and glycogenolysis in normal subjects
Authors: Xinhua Chen, Nayyar Iqbal, Guenther Boden
Journal: Journal of Clinical Investigation (1999)

We have quantitatively determined gluconeogenesis (GNG) from all precursors, using a novel method employing 2H20 to address the question of whether changes in plasma free fatty acids (FFA) affect GNG in healthy, nonobese subjects. In the first study (n = 6), plasma FFA were lowered at 16 to 20 hours with nicotinic acid (NA) and were then allowed to rise at 20 to 24 hours (FFA rebound after administration of NA). FFA decreased from 387 μM at 16 hours to 43 μM at 20 hours, and then rebounded to 1,823 μM at 24 hours. GNG decreased from 58.1% at 16 hours to 38.6% of endogenous glucose production at 20 hours (P < 0.005) and then rebounded to 78.9% at 24 hours (P < 0.05). Conversely, glycogenolysis (GL) increased from 41.9% at 16 hours to 61.4% at 20 hours (P < 0.05), and then decreased to 21.1% at 24 hours (P < 0.05). In the second study (controls; n = 6), volunteers were analyzed between 16 and 24 hours after the last meal. FFA rose from 423 to 681 μM (P < 0.05), and GNG from 50.3% to 61.7% (P < 0.02), whereas GL decreased from 49.7% to 38.3% (P < 0.05). Endogenous glucose production decreased at the same rate in both studies, from 10.7 to 8.6 μmol/kg/min (P < 0.05). In study 3 (n = 6), in which the NA-mediated decrease of plasma FFA was prevented by infusion of lipid and heparin, neither FFA nor GNG changed significantly. In summary, our data suggest that (a) acute changes in plasma FFA produce acute changes in GNG and reciprocal changes in GL; (b) the decrease in EGP between 16 and 24 hours of fasting is due to a fall in GL; and (c) NA has no direct effect on GNG.
Response to Letter Regarding Article, “Efficacy and Safety of Dabigatran Compared With Warfarin in Relation to Baseline Renal Function in Patients With Atrial Fibrillation: A RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) Trial Analysis”
Authors: Ziad Hijazi, Stefan H. Hohnloser, Jonas Oldgren, Ulrika Andersson, Stuart J. Connolly, John W. Eikelboom, Michael D. Ezekowitz, Paul A. Reilly, Agneta Siegbahn, Salim Yusuf, Lars Wallentin
Journal: Circulation (2014)
A new approach to integrate toxicity grade and repeated treatment cycles in the analysis and reporting of phase I dose-finding trials
Authors: A. Doussau, R. Thiébaut, B. Geoerger, P. Schöffski, A. Floquet, M.C. Le Deley, S. Mathoulin-Pélissier, E. Rizzo, P. Fumoleau, C. Le Tourneau, X. Paoletti
Journal: Annals of Oncology (2014)
Obstructive sleep apnoea and driving.
Authors: J. R. Stradling
Journal: BMJ (1989)

This article describes the risks to patients with obstructive sleep apnoea of falling asleep while driving. Patients with this disease often report loss of concentration while driving, particularly on motorways in the dark. Many long distance lorry drivers have the disease, as they commonly have the major risk factor, obesity. In a survey of fatal truck accidents, the American National Transportation Safety Board is now asking relatives routinely about features of obstructive sleep apnoea, as three recent reports have shown that the road traffic accident rate of patients with this condition is up to seven times greater than that of normal drivers. The proportion of crashes in which the driver was at fault and the number of traffic violations were both appreciably higher in patients with obstructive sleep apnoea than in other drivers. About one third of the patients had had car crashes in the previous 5 years. It is suggested that as regards fitness to drive, obstructive sleep apnoea should be classified with epilepsy, hypoglycaemia and adams-stokes attacks, and that further research should be done in order to ascertain its contribution to deaths on British roads. (TRRL)
Endothelial cells require miR-214 to secrete exosomes that suppress senescence and induce angiogenesis in human and mouse endothelial cells
Authors: Bas W. M. van Balkom, Olivier G. de Jong, Michiel Smits, Jolanda Brummelman, Krista den Ouden, Petra M. de Bree, Monique A. J. van Eijndhoven, D. Michiel Pegtel, Willem Stoorvogel, Thomas Würdinger, Marianne C. Verhaar
Journal: Blood (2013)
Hypokalemic Respiratory Arrest in Diabetic Ketoacidosis
Authors: Robert J. Rushakoff
Journal: JAMA (1987)

To the Editor.—  In a recent article, 1 the authors describe the care of a 22-year-old man who presented with diabetic ketoacidosis. Clinical examination disclosed the following values: glucose, 778 mg/dL (43.1 mmol/L); pH, 6.84; bicarbonate, 2.8 mEq/L (2.8 mmol/L); and potassium, 3.3 mEq/L (3.3 mmol/L). Over a five-hour period, he was treated with intravenous insulin at 8 U/h, 150 mEq (150 mmol) of sodium bicarbonate, and 64 mEq (64 mmol) of intravenous and 409 mEq (409 mmol) of oral potassium chloride. The patient then suffered a respiratory arrest thought to be secondary to hypokalemia. Several aspects of this case deserve comment.  Recently, retrospective 2 and prospective 3 studies of the use of bicarbonate in the treatment of severe (pH of 6.89 ±0.09) diabetic ketoacidosis have shown that bicarbonate therapy does not alter the time it takes serum glucose, pH, or serum bicarbonate measurements to reach normal
THE SYMPTOMATOLOGY AND TREATMENT OF TRAUMATIC INSANITY
Authors: A. B. Richardson
Journal: American Journal of Psychiatry (1903)

The forms of diseases of the mind that have their origin in the effect of injury to the brain, direct or indirect, are quite varied, and I attempt a description of them with much hesitation and a consciousness of my inability to fully, or, I fear, satisfactorily accomplish it.I shall divide the forms of traumatic insanity into two classes.To the first class to be considered belong those that result directly from the injury, where this is the direct and sufficient exciting cause, the insanity either following immediately after the injury, or being associated with symptoms developing from that date,
Structural alterations to the pulmonary circulation in fulminant hepatic failure.
Authors: A Williams, P Trewby, R Williams, L Reid
Journal: Thorax (1979)

Like patients with chronic liver disease, those with coma due to fulminant hepatic failure may show arterial hypoxaemia even in the absence of pulmonary complications, and in both it is attributed to increased intrapulmonary arteriovenous admixture. This study is concerned with the structural alterations in the pulmonary circulation of patients who have died from fulminant hepatic failure. Precise quantitative morphometric techniques applied to the injected and inflated lung have shown the major abnormality to be a diffuse dilatation of the pulmonary vascular bed affecting arteries and veins of all structural types. At an intra-acinar level the diameter of arteries accompanying respiratory bronchioles was 232.97 micron (+/-SD 46.35) compared with 177.76 micron (+/-SD 30.43) in controls (P less than 0.01). In two-thirds of the patients pleural spider naevi were seen and, throughout the lung, similar significant dilatation of precapillary vessels; but in only one patient were precapillary anastomoses shown. While intrapulmonary venous admixture undoubtedly contributes to hypoxia in fulminant hepatic failure, its exact relation to the structural changes is not yet determined.