tbuckley/cabot-search huggingface dataset:
The Surgical Attack in Invasive Bladder Cancer
Authors: David M. Wallace
Journal: JAMA (1969)

The role of surgical treatment of infiltrating tumors will be affected by two factors: (1) the depth of infiltration<sup>22</sup>and (2) the extent of surface spread. Although it may well be that they represent merely the two extremes of the same disease, it is necessary, for practical purposes, to consider them as two separate forms of neoplasia—the single, infiltrating, localized lesion with which the problem may be one of lymphatic spread, or the lesion associated with widespread mucosal changes in the bladder, prostatic ducts, urethra, renal pelvis, or ureter. Localized but infiltrating lesions can be treated by endoscopic resection, by open resection with or without supplementary radioactive implant, by segmental resection, and by radical cystectomy. <h3>The Endoscopic Approach</h3> The endoscopic approach depends for its success on the capability and experience of the surgeon. There are few resectionists capable of completely resecting a tumor more than 6 cm in diameter,
The office practice of internists. IV. Professional activities other than care of private patients
Authors: D. A. Clark
Journal: JAMA (1965)

This paper reports on some elements of a study which was developed in cooperation with the New York State Society of Internal Medicine. This organization was interested in the development of methodology for evaluating the quality of medical care being rendered by their members in their own offices. As a preliminary to the methodological study itself, information on the background and characteristics of the practice of the members of the society was obtained by means of a questionnaire mailed to each member. At the time of the study, the society had 960 members, of whom 505 returned a completed questionnaire to the study group. The nature of the society and the methodology of this study were described in the first paper of this series.<sup>1</sup> In the course of many discussions with the society's advisory committee, frequent mention was made of the fact that most internists take part in many
Deregulating emergency contraception.
Authors: J B Sharma, M R Newman, R J Smith
Journal: BMJ (1993)

areas.5The programme was cost effective for Medicare and may well be cost saving.As a result of the demonstration, influenza vaccine is now a benefit covered for all beneficiaries of Medicare part B.5Unless we are serious about preventing influenza among vulnerable elderly people and emulate such initiatives, the chief medical officer's annual letter is merely a ritual.
Electrical Aspects of Human Cardiac Activity: A Clinical-Physiological Approach to Excitation and Stimulation 
Authors: D. Durrer
Journal: Cardiovascular Research (1968)

Journal Article Electrical Aspects of Human Cardiac Activity: A Clinical-Physiological Approach to Excitation and Stimulation† Get access Dirk Durrer Dirk Durrer From the University Department of Cardiology and Clinical Physiology, Wilhelmina-Gasthuis, Amsterdam, the Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 2, Issue 1, January 1968, Pages 1–18, https://doi.org/10.1093/cvr/2.1.1 Published: 01 January 1968 Article history Received: 02 November 1967 Published: 01 January 1968
Number of people infected with HIV worldwide reaches 40m
Authors: John Zarocostas
Journal: BMJ (2005)

Getting the upper hand in the fight against the spread of HIV/AIDS requires a much faster expansion in HIV prevention efforts, says a joint UNAIDS/World Health Organization report on the epidemic. In sub-Saharan Africa alone, a comprehensive prevention and treatment package “would avert 55% of new infections that otherwise would be expected to occur until 2020,” it says.

“It is clear that a rapid increase in the scale and scope of HIV prevention programmes is …
Abstract 1020: VRC2, a novel bortezomib re-sensitizing compound for the treatment of multiple myeloma.
Authors: Amriti Lulla, Holly Stessman, David Dicker, Brian Van Ness, Wafik El-Deiry, Nathan G. Dolloff
Journal: Cancer Research (2013)

Abstract The development of novel agents including the proteasome inhibitor bortezomib (Btz) has significantly improved treatment outcomes in multiple myeloma (MM). Despite these advances, resistance to therapy invariably emerges and MM remains an incurable disease. The objective of this study was to identify new therapeutic agents and combinations with the ability to overcome resistance to Btz in MM cells. We developed a high throughput drug screening (HTS) assay system to discover small molecules that selectively target Btz resistant MM cells as single agents and/or re-sensitize resistant cells to Btz. For HTS we used isogenic pairs of Btz sensitive (595 P) and resistant (595 VR) cells derived from iMycCα/Bcl-xL transgenic mouse model of MM. Cell viability was the HTS assay read-out, and 3 treatment groups (595 P, 595 VR, and 595 VR + Btz) were included to identify compounds with selective activity against Btz resistant cells as single agents, and compounds that restore Btz sensitivity in the presence of Btz. Our screening of multiple publically-available compound libraries identified several chemical structures with selective activity against Btz resistant cells. One compound in particular showed modest but significant selectivity for Btz resistant cells as a single agent, and most notably, exhibited potent Btz re-sensitizing activity when the 2 drugs were combined. We named this compound Velcade Re-sensitizing Compound 2, or VRC-2 for short. The Btz re-sensitizing activity of VRC-2 was confirmed using multiple human and mouse cell lines that had been selected for Btz resistance in vitro. IC50s for VRC-2 in normal mouse and human fibroblasts were 100-fold higher than that observed in MM cells, suggesting it may have a low toxicity profile in vivo. We are currently evaluating the activity of VRC-2 in animal models of MM, alone and in combination with Btz, and conducting molecular studies to identify its precise mechanism of action. This study establishes the proof-of-principal for our HTS approach and demonstrates the potential of VRC-2 in Btz refractory MM. Citation Format: Amriti Lulla, Holly Stessman, David Dicker, Brian Van Ness, Wafik El-Deiry, Nathan G. Dolloff. VRC2, a novel bortezomib re-sensitizing compound for the treatment of multiple myeloma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1020. doi:10.1158/1538-7445.AM2013-1020
Paul Garner Large
Authors: A. Large
Journal: BMJ (2009)

Paul Garner Large was brought up in Durban, and his boyhood and upbringing were comfortably serene. His scholastic promise became evident in his early years. His secondary school education was at Michaelhouse, a distinguished Diocesan school in inland Natal, whence he matriculated well in 1937. He had by then decided that he would pursue medicine as a career, and he enrolled at Guy’s Hospital Medical School in 1938. He was one of many South Africans who, at that time, travelled to England to study medicine, many of them favouring Guy’s. Its rugby side (the oldest extant rugby club in the world) was formidable, and strong in South African players.

The second world war came in September 1939, and as it grew fiercer, and London subject to aerial bombardment, many of Guy’s patients, staff, and students were evacuated to so called sector hospitals in Kent and Sussex. Medical students, as everyone else, were inconvenienced by this decentralisation, by Home Guard and ARP (Air Raid Precautions) duties, and by uncertainty about improvised programmes of teaching. Required academic standards remained high, but distractions and a disjointed curriculum imposed extra strain on students. Any wish to join one of the armed forces was scotched, for medical students were labelled as being in a reserved occupation.

After qualifying MB BS (London) in …
Black spots concentrate oncogenic asbestos fibers in the parietal pleura. Thoracoscopic and mineralogic study.
Authors: C Boutin, P Dumortier, F Rey, J R Viallat, P De Vuyst
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Epidemiologic and pathologic data demonstrate that malignant mesothelioma occurs preferentially after exposure to long amphibole asbestos fibers. However, mineralogic studies have rarely detected such fibers in the parietal pleura. We hypothesized that the distribution of asbestos fibers in the pleura was heterogeneous and that they might concentrate in certain areas, as does coal dust in patients showing anthracotic "black spots" of the parietal pleura during thoracoscopy. We collected thoracoscopic biopsy samples from these black spots and from normal areas of the parietal pleura and lung from 14 subjects (eight with and six without asbestos exposure). Asbestos content was determined by transmission electron microscopy. In exposed subjects, mean fiber concentrations were 12.4 +/- 9.8 x 10(6) fibers/g of dry tissue in lung, 4.1 +/- 1.9 in black spots, and 0.5 +/- 0.2 in normal pleura. In unexposed patients, concentrations were 0, 0.3 +/- 0.1, and 0, respectively. Amphiboles outnumbered chrysotile in all samples. A total of 22.5% of fibers were > or = 5 microns in length in black spots. A histologic similarity of these black spots with milky spots is suggested by conventional and electron microscopy. We conclude that the distribution of asbestos fibers is heterogeneous in the parietal pleura. Indeed, the fibers concentrate in black spots, where they can reach high concentrations. These findings could explain why the parietal pleura is the target organ for mesothelioma and plaques.
Caffeine Decreases Exercise-Induced Myocardial Flow Reserve
Authors: Mehdi Namdar, Pascal Koepfli, Renate Grathwohl, Patrick T. Siegrist, Michael Klainguti, Tiziano Schepis, Raphael Delaloye, Christophe A. Wyss, Samuel P. Fleischmann, Oliver Gaemperli, Philipp A. Kaufmann
Journal: Journal of the American College of Cardiology (2005)
Electron microscopic studies of xeroderma pigmentosum: unusual changes in the keratinocyte
Authors: TAKUO TSUJI
Journal: British Journal of Dermatology (1974)

Journal Article Electron microscopic studies of xeroderma pigmentosum: unusual changes in the keratinocyte Get access TAKUO TSUJI TAKUO TSUJI Department of Dermatology, Osaka City University Medical School, Abeno, Osaka 545, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 91, Issue 6, 1 December 1974, Pages 657–666, https://doi.org/10.1111/j.1365-2133.1974.tb12452.x Published: 01 December 1974 Article history Accepted: 08 April 1974 Published: 01 December 1974
Steroids in COPD: still up in the air?
Authors: D. D. Sin, S. F. P. Man
Journal: European Respiratory Journal (2010)

Inhaled corticosteroids (ICS) have had a wild and controversial rollercoaster ride in chronic obstructive pulmonary disease (COPD). With the success of ICS in asthma and with the advent of the Dutch Hypothesis, suggesting that asthma and COPD had a similar pathogenic origin, there was great hope that ICS would be the saviour for millions of patients suffering from COPD, by palliating symptoms and changing its natural history. Based on this promise, by the mid 1980s, clinicians were routinely recommending ICS therapy to their patients, even though there was an absence of compelling grade A evidence from large randomised controlled trials (RCTs) demonstrating efficacy 1.

By the late 1990s, the promise was shattered by the publication of several seminal RCTs that clearly showed that ICS did not modify the rate of decline in forced expiratory volume in 1 s (FEV1) and had only a modest effect on symptoms 2–4. These data re-inforced the notion that COPD was a steroid-resistant state and many leading experts in the field concluded that ICS had no role in COPD, except during exacerbations 5. Ostensibly, ICS were dead and buried.

However, the new millennium brought new hope for ICS. Proponents argued that while ICS may not alter the rate of decline in FEV1, it improved patient based outcomes including survival. This optimism was fuelled by several large observational studies and meta-analyses 6–9 that demonstrated a distinct survival benefit for patients who were prescribed ICS. This enthusiasm, however, was dashed in 2007 by the publication of the long-awaited TORCH (TOwards a Revolution in COPD Health) Study, which failed to show an unequivocal survival advantage for patients assigned to a steroid-containing treatment …
Phenylpropanolamine Exposure and Subsequent Hospitalization
Authors: Pamela Aselton
Journal: JAMA (1985)

To the Editor.—  We have reviewed the experience of Group Health Cooperative of Puget Sound relative to the use of cough and cold preparations containing phenylpropanolamine hydrochloride and the subsequent need for hospitalization for malignant hypertension ( International Classification of Diseases , eighth revision, 400.0, 438.3), arrhythmia (416.0-416.9), neuropsychiatric illness (300.1-300.9, 303.0-303.9, 309.1-309.9, 306.4, 306.5, 306.8, 306.9, 308.8, 308.9, 310.9, 311.5, 311.9, 318.9, and 345.1-345.9), and nonhemorrhagic stroke (433.0, 433.1, and 436.0-436.9). From 1977 through 1982, there were 253,334 prescriptions filled for phenylpropanolamine-containing products at local Group Health Cooperative pharmacies for members younger than 65 years. Assuming that each person filling a prescription for a phenylpropanolamine-containing preparation was at risk for one of the disorders studied for 30 days after the prescription was filled, this experience represents 7,600,020 person-days at risk for hospitalization among phenylpropanolamine users. Taking the whole population of Group Health Cooperative younger than 65 years (person-years), multiplying by 365,
THE FRUSTRATION THRESHOLD
Authors: MANDEL SHERMAN
Journal: American Journal of Psychiatry (1947)

The experiment to determine the threshold of frustration was conducted with normal, neurotic and psychotic subjects. It was difficult to present a problem which was equally motivating, and which would always result in frustration at the point of failure. Preliminary experimentation showed that a learning situation in which each subject was psychologically prepared to consider success imperative was the best method of creating frustration. It was much easier to create frustration in the children than in the adults, and the reactions of the children were much more consistent. The difficulty of frustrating adults was probably due to two factors, the rationalization of their failures and the inability to motivate them in the task presented. Most of the children were easily motivated in a learning situation, obviously because they were accustomed to respond to learning situations in school. The adults, however, evaded the frustration crises because they tended to create many reasons why they could not complete the tasks successfully. The threshold of frustration was measured in terms of the rapidity with which frustration could be induced and the difficulty of the task which produced it. The criteria of frustration were: 1. Disruption of the integrated and planned activity. 2. Haphazard activity involving the hands, arms and body. 3. Significant changes of the physiological reactions, such as the rhythm and amplitude of the brain waves, skin resistance, respiration, blood pressure and pulse. The most consistent physiological reactions which correlated with frustration were skin resistance as measured by the photopolygraph, and respiration. Changes in the brain waves were not as significant as the other measures, although there was a marked and consistent difference between the schizophrenic and the normal. The electroencephalographic tracings in the schizophrenic individuals were unusually stable, with few changes in rhythm or amplitude as contrasted with the many variations in the normal and neurotic individuals. The threshold of frustration was significantly higher in all of the schizophrenic subjects than in the neurotic or the normal. The neurotic threshold was quite variable, and was lower than in the normal. Whether the threshold of frustration of the neurotic individual correlates with the severity of the neurosis could not be adequately ascertained because there was no way of clinically quantifying a neurotic condition. No claim can be made regarding the diagnostic value of the threshold of frustration. It is not too presumptuous, however, to claim that it can be a valuable adjunct to a clinical diagnosis. It may be especially valuable because the threshold can be determined objectively and quantitatively, although one must be aware of the inevitable difficulties involved in determining frustration in an artificial laboratory situation. The method may be especially valuable in those cases where the clinical data are not sufficiently adequate and where differentiation between individuals is necessary.
Abstract P1-05-01: Characterization of human postpartum breast involution: Implications for young women’s breast cancer
Authors: VF Borges, S Jindal, D Gao, P Bell, SM Edgerton, CB Ambrosone, AD Thor, P Schedin
Journal: Cancer Research (2013)

Abstract Introduction: Women diagnosed with breast cancer within 5 years postpartum have poor outcomes. In rodents, postpartum mammary gland involution promotes tumor progression and metastasis, implicating breast involution in the poor prognosis of breast cancers diagnosed in postpartum women. Rodent mammary gland involution is characterized by wound healing programs that include epithelial cell death, immune cell infiltrate, and fibrillar collagen deposition; all attributes associated with breast cancer progression. Thus, the gland remodeling of postpartum involution may provide a plausible explanation for how postpartum breast involution promotes breast cancer. Here, we characterize human breast tissue across pregnancy, lactation, and the postpartum time-period to determine if remodeling of the secretory competent breast to a quiescent state involves loss of secretory lobules, and whether involution is mediated by wound healing-like programs. Methods: Adjacent normal breast tissues from pre-menopausal women (n = 140), aged 20-45 years, were grouped by reproductive categories of never-been-pregnant (NBP), pregnant, lactating, and by time since last delivery, and evaluated histologically and by special stain for epithelial area, lobular subtype composition, apoptosis, immune cell infiltration, and collagen deposition, using computer assisted quantitative methods. Statistical comparisons between multiple categories were done using one way ANOVA. Results: Dramatic increases in breast epithelial area and lobule differentiation were observed, with 5-8 fold increases for pregnancy and 10-13 fold for lactation, over nulliparous controls. By 12 months postpartum, epithelial content and lobular differentiation were indistinguishable from nulliparous controls, consistent with complete regression of the lobular structures developed in preparation for lactation. Analyses of apoptosis, immune cell infiltration, and collagen deposition confirmed human postpartum breast involution is characterized by wound healing-like, tissue remodeling programs. Conclusion: Human postpartum breast involution is a dominant tissue-remodeling process that returns the gland to a morphological state largely indistinguishable from the never-been-pregnant gland. Further, involution occurs within a defined window of time. Our data implicate postpartum breast involution as window of risk for breast cancer progression and suggest a rational window for intervention. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-05-01.
Evaluation of Nucleolar Organizer Regions in Human Bladder Cancers by Light- and Electron-Microscopic Morphometry
Authors: Toru Shimazui, Yasuo Uchiyama, Katsunori Uchida, Kazunori Hattori, Atsushi Takahashi, Hideyuki Akaza, Kenkichi Koiso
Journal: European Urology (1998)
Phase II Trial of Biweekly Administration of Vinorelbine and Gemcitabine in Pretreated Advanced Breast Cancer
Authors: G. P. Stathopoulos
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To determine the efficacy of gemcitabine (GEM) plus vinorelbine (VRL) administered biweekly in pretreated patients with advanced breast cancer. PATIENTS AND METHODS: Advanced breast cancer patients without response, with stable disease, or with recurrence within 6 months of prior treatment were given GEM 1,000 mg/m2 and VRL 25 mg/m2, once every 2 weeks for at least six cycles. RESULTS: Of the 51 patients enrolled, 50 (median, age 58 years; range, 34 to 76 years) were assessable. All patients had prior chemotherapy with an anthracycline-related regimen that included taxanes in 50% of the cases. Four patients (8%) had a complete response (CR) and 23 (46%) had a partial response (PR), for an overall response rate of 54%; 16 (32%) had stable disease and 7 (14%) experienced disease progression. Response occurred mainly in patients with soft tissue (83.3%) and lung metastasis (66.7%). Response duration was 4 to 8+, 4 to 9+, and 4 to 9 months for those with CR, PR, and stable disease, respectively. The regimen was well tolerated, with grade 1 to 2 myelotoxicity and asthenia reported. No patient required a dose reduction. Gastrointestinal side effects were negligible. Patients received 99.7% (range, 93.0% to 100.0%) of the planned dose-intensity of each drug. CONCLUSION: GEM in combination with VRL is an active regimen for advanced breast cancer patients, and biweekly administration significantly reduces myelotoxicity.
Immunohistochemical localization of basic and acidic fibroblast growth factors in the developing rat heart.
Authors: P Spirito, Y M Fu, Z X Yu, S E Epstein, W Casscells
Journal: Circulation (1991)

We used biochemical and immunohistochemical techniques to investigate the expression and distribution of immunoreactive basic and acidic fibroblast growth factors (bFGF and aFGF, respectively) in the hearts of rat embryos (11-20 days of gestation) and of postnatal rats (1-35 days after birth). Our purpose was to assess the relation between the cellular distribution of these growth factors and histogenetic and morphogenetic events in the developing heart.Western-blot analysis of heparin-bound material from neonatal heart extracts identified a single band with a molecular weight of approximately 18 kD for both bFGF and aFGF. Five antibodies for bFGF and three for aFGF showed superimposable distribution of immunoreactive bFGF and aFGF in the heart at each stage examined. At the cellular level, these peptides were localized in the cytoplasm and extracellular matrix. In the myocytes, immunostaining was positive throughout the embryonic and neonatal periods. In the majority of the mesenchymal cells of the cushions and endothelial cells of endocardium and vessels, staining was also positive. In the smooth muscle cells of the aorta, other large arteries, and coronary arteries, immunostaining was intensely positive at early stages of development but became faint or negative with increasing cell differentiation.The wide distribution of immunoreactive bFGF and aFGF that we identified in the developing rat heart suggests that these growth factors play an important role in heart cytodifferentiation and morphogenesis. Their superimposable distribution may reflect functional interaction. The progressive changes in their distribution suggest a changing role for these peptides during organogenesis.