tbuckley/cabot-search huggingface dataset:
Canine Mammary Neoplasms and Progestogens
Authors: Laurnie W. Nelson
Journal: JAMA (1972)

The mixed mammary tumor is a distinct entity in dogs, with only rare reports of similar neoplasms in man. From data now available, megestrol acetate, chlormadinone acetate, and progesterone may have a promotional effect on the occurence of canine mixed mammary tumors. These compounds—progesterone and progesterone derivatives—have marked species difference, with dogs unusually responsive. Species variability in drug metabolism and drug sensitivity and individual specific variation in target organ pathology are all important in the safety evaluation of products for human use. The facts presented herein support the contention that an increased incidence of the progestogen-dependent canine mixed mammary tumor is, in itself, of little relevance in projecting potential tumorigenesis in women.
Abscess Formation in a Pheochromocytoma
Authors: Charles P. Giel
Journal: New England Journal of Medicine (1954)

THIS report presents the first case, to my knowledge, in which a salmonella infection localized in a pheochromocytoma. No other reported case of necrosis and abscess formation in a pheochromocytoma, or salmonella abscess of the adrenal gland, is available, and only 1 previous case of salmonella abscess of any tumor. Indeed, a review of the literature discloses little attention to infection or abscess in internal tumors.Case ReportA 29-year-old married hardware salesman was admitted to the hospital on October 28, 1953, with complaints of shaking chills and fever of 3 weeks' duration. The fever had suddenly appeared 1 week . . .
Rat liver sinusoidal endothelial cells (LSECs) express functional low density lipoprotein receptor-related protein-1 (LRP-1)
Authors: Cristina Ionica Øie, Rupa Shree Appa, Ida Hilden, Helle Heibroch Petersen, Albrecht Gruhler, Bård Smedsrød, John-Bjarne Hansen
Journal: Journal of Hepatology (2011)
Educational Programs in US Medical Schools, 1994-1995
Authors: Barbara Barzansky
Journal: JAMA (1995)

THE PURPOSE of this article is to review the current status of educational programs leading to the doctor of medicine degree in US medical schools. However, it is important to remember that such programs do not exist in isolation. They are part of institutions—medical schools and associated clinical facilities, such as teaching hospitals—that are sensitive to external environmental factors. For example, since medical schools derive a significant percentage of their income from the medical practice activities of clinical faculty members,<sup>1</sup>changes in the health care system, such as the growth of managed care, have great potential to affect medical schools. There is already evidence that increased managed care penetration can cause a decrease in school revenues from faculty practice.<sup>2</sup>Such decreases in revenue can, in turn, affect the ability of the medical school to implement its educational program. Medical schools have begun to cope with the challenge raised
Selection of Patients for Clinical Trials
Authors: R. N. Herrington
Journal: BMJ (1973)

ing genetic effects where pooling of genes will occur, but it is not acceptable in assessing radiation carcinoma and leukaemia risk.However, perhaps the worst anomaly lies in the collection of radiation records.Radia- tion workers in establishments subject to the Factories Actl 2 must, by law, have correct and accurate radiation records which are transferred with them when they change jobs.Other establishments such as univer- sities and hospitals generally adopt the same procedure for their radiation workers,3 and recently the National Radiological Protection Board has set up a computerized record system which represents the first attempt to institute some form of central register.The irony of the situation is that a large proportion of radiation workers will receive doses of less than 0.25 rem per year, this being the limit of measurement, and such doses will be carefully recorded.Doses ob- tained from medical and dental exposures for particular individuals on the other hand, which will in many cases considerably ex- ceed these figures, will in general not be precisely known and will not be recorded.Such a situation is palpably absurd and it is obviously time that all radiation doses received by any individual from any source, whether it be occupational or from medical or dental diagnosis, should be accurately known and centrally recorded.Only when this is done can any reasonable evaluation of radiation risk be made.-Iam, etc.,
Altered cardiac hormone and contractile protein messenger RNA levels following left ventricular myocardial infarction in the rat: an in situ hybridization histochemical study
Authors: R Young
Journal: Cardiovascular Research (1998)

Objectives: Cardiac remodeling secondary to myocardial infarction is associated with hypertrophy of surviving myocardium and altered cardiac gene expression. The present study examined the spatiotemporal expression of cardiac contractile protein and peptide hormone mRNA following left ventricular myocardial infarction (LVMI) in the rat heart. Methods: LVMI was produced in Wistar rats by ligation of the left anterior descending coronary artery and mRNA levels of cardiac α-actin (cACT), skeletal α-actin (sACT), ventricular myosin light chain-2 (MLC-2v), β-myosin heavy chain (β-MHC) and pre-proatrial natriuretic peptide (ppANP) were examined at 24 h, 1 and 4 weeks) post-LVMI by in situ hybridization histochemistry with 35S-labeled oligonucleotide probes. Results: Infarct size, determined at 1 week post-LVMI, was 44.5±2.7% of the combined left ventricular epi- and endocardial surface area. Myocyte fiber width, reflecting cellular hypertrophy, was increased in left ventricular, mid-septal and mid-right ventricular muscle fibers by 11–20% at 1 week post-LVMI (P<0.05) and by 24–29% at 4 weeks (P<0.05). At 24 h, 1 and 4 weeks post-LVMI, heart- and lung/body weight ratios were significantly elevated compared to sham-operated rats (1.3–1.8-fold, P<0.01 and 1.6–2.9-fold, P<0.005, respectively). PpANP mRNA levels in the left ventricle were increased 3.8- and 3.3-fold at 1 and 4 weeks (P<0.05), with highest levels in the epicardium, papillary muscle, infundibulum and apex of the chamber. Septal and right ventricular ppANP mRNA levels were highest at 24 h post-LVMI (2.1- and 2.6-fold increase, P<0.05) and remained elevated at 4 weeks, with maximum levels at the left endocardial surface of the septum and apex of the chambers. Atrial levels of cACT mRNA were increased 1.9-fold at 1 week post-LVMI (P<0.05) and remained elevated at 4 weeks. Skeletal ACT mRNA, not normally expressed in the adult rat heart, was induced as early as 24 h post-LVMI in both atria, the septum and right ventricle, with discrete hybridization signal detected at the apex of the chambers and in the right ventricular free-wall, and later (1 week) in the left ventricular epicardium. MLC-2v mRNA levels were unaltered post-LVMI, except for a transitory loss of expression at 24 h in the left atria, ventricle and apical septum. In contrast, ventricular β-MHC mRNA was markedly induced in regions containing increased ppANP mRNA, with a maximal 3.0- and 4.0-fold induction (P<0.05) seen at 1 and 4 weeks in the left ventricle and a 3.7-fold induction at 4 weeks in the septum and right ventricle (P<0.05). Conclusion: The regional increases in induced cardiac hormone and contractile protein mRNA in similar subchamber regions of the rat heart post-LVMI implies mutual activation by mechanical and/or neuroendocrine stimuli in the transcriptional response to myocardial overload.
Infertility specialist reported to the General Medical Council.
Authors: Owen Dyer
Journal: BMJ (2001)

One of Britain's most famous infertility specialists faces charges of serious professional misconduct for allegedly botching a patient's treatment and flouting treatment guidelines.

Ian Craft, aged 64, director of the London Gynaecology and Fertility Centre, is due to appear before the General Medical Council's professional conduct committee in March.

He is accused of ignoring medical guidelines in treating a woman in her 40s and mistakenly implanting gametes in a faulty …
Epidermal Growth Factor Receptor Mutation and Pathologic-Radiologic Correlation Between Multiple Lung Nodules with Ground-Glass Opacity Differentiates Multicentric Origin from Intrapulmonary Spread
Authors: Jin-Haeng Chung, Gheeyoung Choe, Sanghoon Jheon, Sook-Whan Sung, Tae Jung Kim, Kyung Won Lee, Jae Ho Lee, Choon-Taek Lee
Journal: Journal of Thoracic Oncology (2009)
S66 Is hospital readmission an appropriate outcome measure for community-acquired pneumonia?
Authors: J. Brettell, M. A. Woodhead
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> There is no ideal outcome measure for studies in community-acquired pneumonia (CAP). Readmission to hospital within 30 days is one proposed measure which coincidentally the NHS now imposes financial penalties on Trusts for. We sought to investigate the frequency and validity of this measure for CAP and to examine factors predictive of readmission in CAP. <h3>Methods</h3> All adult cases (ICD10 J10–J18) admitted in 2010 were identified from Trust Information records. Those readmitted within 30 days of discharge were regarded as cases and reason for readmission was ascertained. The two consecutive admissions after each readmission case were used as controls to identify features predictive of readmission. All were validated as CAP by inspection of radiographs and case records. <h3>Results</h3> 562 cases were identified. 93 were excluded. 96 (20%) of the remaining 469 died. 55 (12%) were readmitted. Eight of these were excluded and six case notes were lost leaving 41 cases who were compared with 72 controls who had not been readmitted. Of these 113, mean age was 61 (95% CIs 57–65), 59% were male, 85% had one or more comorbid disease, 83% were admitted from their own home, 54% were CURB65 0–1, 26% CURB65 2, 23% CURB65 3–5. Readmission was considered by the admitting physician to be CAP-related in only 16 (39%), but even in these CRP was raised at readmission in only 81%. Non-CAP reasons for readmission were varied and were distributed across at least 8 disease areas. Only 13 (32)% of all readmissions were considered to have been preventable at the first admission. Age (OR 0.995; 95%CI 0.959 to 1.033), presence of comorbid disease (2.045; 0.415 to 10.089), Charlson comorbidity index (1.082; 0.785 to 1.491), initial length of stay (1.009; 0.984 to 1.034), CURB65&gt;0 (2.003; 0.551 to 7.282) and initial treatment with tazocin (2.502; 0.804 to 7.784) were significantly related to readmission, but CIs all included unity. <h3>Conclusion</h3> The low frequency, lack of relationship to CAP in the majority and lack of preventability at the index admission suggest that readmission within 30 days of discharge is not a valid outcome marker for CAP. Age and markers of biological unfitness predict readmission.
CLINICAL AND ELECTROENCEPHALOGRAPHIC STUDIES IN PYKNOLEPSY
Authors: JOSEPH W. OWEN, LOUIS BERLINROOD
Journal: American Journal of Psychiatry (1942)

Eight cases of typical pyknolepsy are presented. Four of these ceased spontaneously during the period of observation. Clinically they were similar to petit mal epilepsy except for the mildness of their symptoms, the fairly monotonous course, their lack of deterioration and the tendency to spontaneous cure. Electroencephalographic studies were made on three of these cases after they had ceased, four during their still active phase, and one before and after cessation of the attacks. Normal brain potentials were found in the spontaneously recovered cases whereas in the active ones typical petit mal electrical patterns were observed. From the study of these eight cases it appears that pyknolepsy is a form of petit mal epilepsy because of: 1. The similarity in the clinical picture; 2. The electroencephalographic pattern in the active phase showing a wave and spike formation found in petit mal epilepsy; 3. The lack of evidence of definite psychogenic factors; 4. The high incidence of epilepsy in families of patients with pyknolepsy as revealed by a study of the literature.
Circulatory Status and Response to Cardiac Rehabilitation in Patients With Heart Failure
Authors: John R. Wilson, Jay Groves, Glenn Rayos
Journal: Circulation (1996)

Background We recently reported that some patients with heart failure and exercise intolerance exhibit severe hemodynamic dysfunction during exercise, whereas others have normal cardiac output responses to exercise. We postulated that patients with preserved cardiac output responses to exercise are limited by deconditioning and would respond to exercise training, whereas patients with reduced cardiac output responses are limited by skeletal muscle underperfusion and would not improve with exercise training. The present study was undertaken to test this hypothesis. Methods and Results Thirty-two patients with heart failure were studied. Hemodynamic response to maximal treadmill exercise was measured; then patients were enrolled in a standard 3-month cardiac rehabilitation program. Peak exercise V o 2 , lactate threshold, and quality-of-life questionnaires were assessed at 1, 2, and 3 months. Twenty-one patients had normal cardiac output responses to exercise. All 21 patients participated in the rehabilitation program without difficulty, and 9 (43%) responded to rehabilitation, defined as a &gt;10% increase in both peak exercise V o 2 and the anaerobic threshold. Of the 11 patients with reduced cardiac output responses to exercise, 3 discontinued rehabilitation because of severe exhaustion, and only 1 qualified as a responder (9%; P &lt;.04 versus preserved cardiac output). Conclusions Patients with heart failure and normal cardiac output responses to exercise frequently improve with exercise training. Patients with severe hemodynamic dysfunction during exercise usually do not improve with training, which suggests that they are limited primarily by circulatory factors.
Lovastatin-Induced Phosphatidylinositol-4-Phosphate 5-Kinase Diffusion from Microvilli Stimulates ROMK Channels
Authors: Bing-Chen Liu, Li-Li Yang, Xiao-Yu Lu, Xiang Song, Xue-Chen Li, Guangping Chen, Yichao Li, Xincheng Yao, Donald R. Humphrey, Douglas C. Eaton, Bao-Zhong Shen, He-Ping Ma
Journal: Journal of the American Society of Nephrology (2014)

We recently showed that lovastatin attenuates cyclosporin A (CsA)-induced damage of cortical collecting duct (CCD) principal cells by reducing intracellular cholesterol. Previous studies showed that, in cell expression models or artificial membranes, exogenous cholesterol directly inhibits inward rectifier potassium channels, including Kir1.1 (Kcnj1; the gene locus for renal outer medullary K(+) [ROMK1] channels). Therefore, we hypothesized that lovastatin might stimulate ROMK1 by reducing cholesterol in CCD cells. Western blots showed that mpkCCDc14 cells express ROMK1 channels with molecular masses that approximate the molecular masses of ROMK1 in renal tubules detected before and after treatment with DTT. Confocal microscopy showed that ROMK1 channels were not in the microvilli, where cholesterol-rich lipid rafts are located, but rather, the planar regions of the apical membrane of mpkCCDc14 cells. Furthermore, phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2], an activator of ROMK channels, was detected mainly in the microvilli under resting conditions along with the kinase responsible for PI(4,5)P2 synthesis, phosphatidylinositol-4-phosphate 5-kinase, type I γ [PI(4)P5K I γ], which may explain the low basal open probability and increased sensitivity to tetraethylammonium observed here for this channel. Notably, lovastatin induced PI(4)P5K I γ diffusion into planar regions and elevated PI(4,5)P2 and ROMK1 open probability in these regions through a cholesterol-associated mechanism. However, exogenous cholesterol alone did not induce these effects. These results suggest that lovastatin stimulates ROMK1 channels, at least in part, by inducing PI(4,5)P2 synthesis in planar regions of the renal CCD cell apical membrane, suggesting that lovastatin could reduce cyclosporin-induced nephropathy and associated hyperkalemia.
Structural basis of ciliary movement.
Authors: P Satir
Journal: Environmental Health Perspectives (1980)

All motile somatic cilia, including those of the human respiratory tract, are similar in ultrastructure in that they consist of an axenome of 9 + 2 microtubules surrounded by a specialized extension of the cell membrane. The axonemal elements provide the ciliary motor, which is powered by ATP hydrolysis. In respiratory cilia, mutants occur where axonemal assembly is aberrant such that the doublet attachments known as arms (Afzelius and co-workers) or spokes (Sturgess) have been shown to be missing. These mutant cilia are apparently nonmotile. In model cilia, the arms are composed of dynein, a class of ATPase isoenzymes and associated polypeptides characterized byGibbons and colleagues. In negative stain preparations of arms, three subunits can be seen. In the presence of ATP, dynein functions with a set polarity to form transient cross-bridges that cause the microtubule doublets of the axoneme to slide relative to one another. After brief trypsin treatment, the axonemal microtubules slide almost completely apart with the arms of doublet n pushing doublet n + 1 in a tipward direction. To produce ciliary beating in vivo, sliding is carefully controlled and coordinated, in part probably by the spoke system. The ciliary membrane is responsible for maintaining the appropriate levels of ATP, Mg2+, and Ca2+, and Ca2+ (ca. 10(-7) M) around the axoneme. The beat of certain cilia--e.g., L cilia of mussel gills--can be arrested by increasing axonemal Ca2+ concentration, for example, in the presence of the ionophore A23187 and high external Ca2+. Although the net results of changes in axonemal Ca2+ concentration are not always complete stoppage of beat or of sliding, this ion is also part of the general behavioral control of ciliary motility.
Multiepitope HER2 Targeting Enhances Photoimmunotherapy of HER2-Overexpressing Cancer Cells with Pyropheophorbide-a Immunoconjugates
Authors: Mark D. Savellano, Brian W. Pogue, P. Jack Hoopes, Ellen S. Vitetta, Keith D. Paulsen
Journal: Cancer Research (2005)

Multi-targeting strategies improve the efficacy of antibody and immunotoxin therapies but have not yet been thoroughly explored for HER2-based cancer treatments. We investigated multi-epitope HER2 targeting to boost photosensitizer immunoconjugate uptake as a way of enhancing photoimmunotherapy. Photoimmunotherapy may allow targeted photodynamic destruction of malignancies and may also potentiate anticancer antibodies. However, one obstacle preventing its clinical use is the delivery of enough photosensitizer immunoconjugates to target cells. Anti-HER2 photosensitizer immunoconjugates were constructed from two monoclonal antibodies (mAb), HER50 and HER66, using a novel method originally developed to label photosensitizer immunoconjugates with the photosensitizer, benzoporphyrin derivative verteporfin. Photosensitizer immunoconjugates were labeled instead with a promising alternative photosensitizer, pyropheophorbide-a (PPa), which required only minor changes to the conjugation procedure. Uptake and phototoxicity experiments using human cancer cells were conducted with the photosensitizer immunoconjugates and, for comparison, with free PPa. SK-BR-3 and SK-OV-3 cells served as HER2-overexpressing target cells. MDA-MB-468 cells served as HER2-nonexpressing control cells. Photosensitizer immunoconjugates with PPa/mAb molar ratios up to approximately 10 specifically targeted and photodynamically killed HER2-overexpressing cells. On a per mole basis, photosensitizer immunoconjugates were less phototoxic than free PPa, but photosensitizer immunoconjugates were selective for target cells whereas free PPa was not. Multiepitope targeted photoimmunotherapy with a HER50 and HER66 photosensitizer immunoconjugate mixture was significantly more effective than single-epitope targeted photoimmunotherapy with a single anti-HER2 photosensitizer immunoconjugate, provided photosensitizer immunoconjugate binding was saturated. This study shows that multiepitope targeting enhances HER2-targeted photoimmunotherapy and maintains a high degree of specificity. Consequently, it seems that multitargeted photoimmunotherapy should also be useful against cancers that overexpress other receptors.
How to move to a palliative approach to care for people with multimorbidity
Authors: F. Burge, B. Lawson, G. Mitchell
Journal: BMJ (2012)

Doctors must actively guide patients in decisions to scale back treatment when appropriate 

In the first editorial in this series, Mangin and Jamoulee commented on a recent Institute of Medicine report, Living Well with Chronic Illness , which called for a paradigm shift from disease based models of care to one focused on care for patients.1 Recently, Haggerty, when discussing continuity of care for patients with multimorbidity, highlighted that patients can experience chaotic care.2 As patients with multimorbidity age and healthcare providers face increased problems with delivering complex care, doctors must identify when it is appropriate to broach the subject of scaling back or stopping treatment; they must then decide in what particular order to taper or eliminate treatments. How can clinicians and patients move through the change from disease modifying treatment to a palliative approach to care with the strong continuity Haggerty suggests?

Consider an elderly woman with five illnesses who lives alone. She has heart disease, severe osteoarthritis and rheumatoid arthritis, hypertension, and a foot ulcer; she is also poor and socially isolated, with no children living nearby. The key question for the coordinating clinician to ask is: “Would I be surprised …
GENDER-SPECIFIC ASSOCIATION OF LOWER BONE MINERAL DENSITY WITH AORTIC VALVE CALCIUM: THE MULTI ETHNIC STUDY OF ATHEROSCLEROSIS (MESA) STUDY
Authors: Karman Tandon, Kelley Branch, David Owens, Matthew Budoff, Bryan Kestenbaum, Marcelo Nacif, Kevin O'Brien
Journal: Journal of the American College of Cardiology (2014)
Muzzling doctors in the name of confidentiality
Authors: J. Gilliat
Journal: BMJ (2009)

The fluidity and ubiquitousness of the internet and mass media can result in a doctor’s reputation being savaged by misguided or malicious patients’ comments published in the public arena. The General Medical Council’s recently enacted supplementary guidance on responding to criticism in the press is deeply worrying.1 2

It specifically muzzles a doctor from …
Aspirin for Primary Prevention of Coronary Events
Authors: Michael S. Lauer
Journal: New England Journal of Medicine (2002)

A 45-year-old man with a strong family history of premature heart disease has no symptoms of coronary disease and a normal electrocardiogram. His fasting level of total cholesterol is 225 mg per deciliter, the low-density lipoprotein cholesterol level is 160 mg per deciliter, and the high-density lipoprotein cholesterol level is 35 mg per deciliter. He has no history of hypertension and does not smoke cigarettes. Should he be advised to take aspirin to reduce his risk of myocardial infarction?