tbuckley/cabot-search huggingface dataset:
Hormonal Therapy Use for Prostate Cancer and Mortality in Men With Coronary Artery Disease–Induced Congestive Heart Failure or Myocardial Infarction
Authors: Akash Nanda
Journal: JAMA (2009)

Hormonal therapy (HT) when added to radiation therapy (RT) for treating unfavorable-risk prostate cancer leads to an increase in survival except possibly in men with moderate to severe comorbidity. However, it is unknown which comorbid conditions eliminate this survival benefit.To assess whether neoadjuvant HT use affects the risk of all-cause mortality in men with prostate cancer and coronary artery disease (CAD)-induced congestive heart failure (CHF) or myocardial infarction (MI), CAD risk factors, or no comorbidity.A total of 5077 men (median age, 69.5 years) with localized or locally advanced prostate cancer were consecutively treated with or without a median of 4 months of neoadjuvant HT followed by RT at a suburban cancer center between 1997 and 2006 and were followed up until July 1, 2008. Cox regression multivariable analyses were performed assessing whether neoadjuvant HT use affected the risk of all-cause mortality, adjusting for age, year and type of RT, treatment propensity score, and known prostate cancer prognostic factors in each comorbidity group.Risk of all-cause mortality.Neoadjuvant HT use was not associated with an increased risk of all-cause mortality in men with no comorbidity (9.6% vs 6.7%, adjusted hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.72-1.32; P = .86) or a single CAD risk factor (10.7% vs 7.0%, adjusted HR, 1.04; 95% CI, 0.75-1.43; P = .82) after median follow-ups of 5.0 and 4.4 years, respectively. However, for men with CAD-induced CHF or MI, after a median follow-up of 5.1 years, neoadjuvant HT use was significantly associated with an increased risk of all-cause mortality (26.3% vs 11.2%, adjusted HR, 1.96; 95% CI, 1.04-3.71; P = .04).Neoadjuvant HT use is significantly associated with an increased risk of all-cause mortality among men with a history of CAD-induced CHF or MI but not among men with no comorbidity or a single CAD risk factor.
S144 Cigarette smoke dysregulates pro-inflammatory cytokine release from airway epithelial cells and macrophages in response to haemophilus influenzae
Authors: E. J. Moisey, L. A. Borthwick, J. Perry, A. De Soyza, A. J. Fisher
Journal: Thorax (2010)

<h3>Background</h3> Chronic obstructive pulmonary disease (COPD) is characterised by repeated viral or bacterial exacerbations which increase morbidity, mortality and accelerate lung function decline. Chronic bacterial colonisation, frequently recognised in stable COPD patients, may contribute to airway inflammation and promote disease progression. Cigarette smoke has previously been shown to alter responses to LPS via the TLR-4 receptor in cell lines. We hypothesised that cigarette smoke would suppress the innate immune responses of airway epithelial cells and macrophages to <i>Haemophilus influenzae</i> (HI) favouring persistence. <h3>Methods</h3> Primary bronchial epithelial cells (PBEC) and macrophage-like cells (THP-1) were incubated with varying concentrations of cigarette smoke extract (CSE) before stimulation with whole cell lysates of HI prepared from clinical isolates. Cell viability was assessed by flow cytometry and PBEC proliferation was analysed using an XTT assay. Pro-inflammatory cytokine release (IL-8, TNFα, IL-1β) was assessed in PBEC and PMA-differentiated THP-1 cells by ELISA. <h3>Results</h3> CSE concentrations ≤10% had no significant effect on PBEC or THP-1 cell viability, however CSE concentrations &gt;5% inhibited PBEC proliferation (p&lt;0.05, n=9). PBEC demonstrated increased release of IL-8 in response to treatment with 5% CSE and increasing doses of HI (n=3, p&lt;0.05). Co-treatment with HI + CSE accentuated IL-8 release from PBEC even at CSE concentrations of 1–2.5% which had no effect alone (p&lt;0.05, n=6). TNFα and IL-1β release from PBEC were below the detection limit of the ELISA. THP-1 cells increased the release of IL-8, TNF-α and IL-1β in response to treatment with HI (n=3, p&lt;0.05) however CSE alone had no effect on cytokine production (n=3, p&gt;0.05). Co-treatment of THP-1 cells with HI + CSE increased IL-8 release (61%), but reduced TNF-α (40%) and IL-1β (24%) release compared to treatment with HI alone (n=3, p&lt;0.05). <h3>Conclusions</h3> CSE alters epithelial cell and macrophage responses to bacterial pathogens by promoting release of the neutrophil chemokine IL-8 whilst at the same time suppressing TNFα and IL-1 β release. This dysregulation may promote continued neutrophil inflammation in the airway whilst insufficiently clearing pathogens and could be an important mechanism in COPD.
Fish oil and plasma fibrinogen.
Authors: A. T. Hostmark, T. Bjerkedal, P. Kierulf, H. Flaten, K. Ulshagen
Journal: BMJ (1988)

venous heparin and warfarin, which was given orally for about six months.One patient (case 1) required radiotherapy for a recurrence of a localised lymphoma but thereafter remained free of a recurrence 30 months after starting chemotherapy.Three patients showed no recurrence of lymphoma 14, 18, and 21 months after starting chemotherapy, and the last patient (case 5) was in remission, having recently completed chemo- therapy.
764 ABNORMAL SYSTEMIC BIOMOLECULAR EXPRESSION OF CALCIUM-SENSING RECEPTORS (CARS) IN CIRRHOTIC RATS: A NEW MECHANISM OF DISEASE IN PORTAL HYPERTENSION
Authors: G. Sansoe', M. Aragno, C. Tomasinelli, L. Valfre' di Bonzo, F. Rosina, A. Smedile, M. Rizzetto, M. Parola
Journal: Journal of Hepatology (2009)
Growth Factor Injections Reverse Type 2 Diabetes in Mice
Authors: Tracy Hampton
Journal: JAMA (2014)

One injection of recombinant fibroblast growth factor 1 (rFGF1) restored healthy blood glucose levels in obese diabetic mice for more than 2 days in a recent study (Suh JM et al. Nature. doi:10.1038/nature13540 [published online July 16, 2014]).
Biomimetic synthesis of active stilbenolignan derivatives by oxidative coupling and acid-catalyzed polymerization
Authors: Chunsuo Yao, Mao Lin, Qingyun Yang
Journal: Acta Pharmaceutica Sinica B (2013)

Two new stilbenolignans and one novel lactone stilbenolignan with a seven-membered ring were biomimetically synthesized by an oxidative coupling reaction and acid-catalyzed polymerization with either isorhapontigenin and ferulic acid or sinapinic acid, respectively, as the starting materials. The structures of the stilbenolignans were defined using spectral analysis and their mechanisms of formation are discussed. Anti-oxidant and anti-inflammatory activities of the novel stilbenolignans were tested, and the lactone stilbenolignan was observed to exhibit potent anti-oxidant activity.
XX. The Flexner Report of 1910
Authors: Lester S. King
Journal: JAMA (1984)

The so-called Flexner report,<sup>1</sup>published in 1910, is probably the most grossly overrated document in American medical history. Its reputation superbly illustrates the<i>post hoc ergo propter hoc</i>fallacy: medical education underwent great changes after the Flexner report appeared; therefore the credit belongs to Flexner. This reasoning has endowed the report with canonical status that has resulted in some horrendous distortion of the historical record.<sup>2</sup> Long before 1910, vast changes were gathering momentum, whose force has received all too little attention. Only recently have scholars given us a better perception. In 1959 Jarcho effectively reviewed some of the trends prior to the Flexner report and discussed relevant causal factors. Hudson emphasized that the "the tide of reform was running heavy by 1910" and that Flexner's "enduring legacy" really derived from what he accomplished later through the General Education Board. Chapman, in a cautious reappraisal, admitted that "the effect
Hepatitis B virus integration in hepatitis B virus-related hepatocellular carcinoma in childhood
Authors: Mei-Hwei Chang, Pei-Jer Chen, Jen-Yang Chen, Ming-Yang Lai, Hey-Chi Hsu, Der-Cheng Lian, Yueh-Giao Liu, Ding-Shinn Chen
Journal: Hepatology (1991)

In Taiwan, hepatocellular carcinoma is one of the major malignancies in children between 5 and 14 yr of age. We studied the status of hepatitis B virus DNA in the hepatocellular carcinoma and nontumorous liver tissues of eight children with positive serum HBsAg and maternal HBsAg. The hepatocellular carcinoma tissues from five of the eight children showed integration of hepatitis B virus DNA into host cellular DNA sequences. A pattern of single-site integration in four children and a multiple-site integration pattern in one child were demonstrated. In the remaining three children, hepatitis B virus DNA could not be demonstrated in the tumor tissues. Using subgenomic fragments of the hepatitis B virus genome as probes, we found that the X gene fragment and the surface antigen gene fragment were the most conserved sequences. The single-site integration of hepatitis B virus DNA in childhood hepatocellular carcinoma may have hit the critical region, resulting in insertional mutagenesis and early development of hepatocellular carcinoma. With a short incubation period and less exposure to environmental carcinogens during early life, childhood hepatocellular carcinoma may provide a good model to study the carcinogenic potential of hepatitis B virus.
Safety and effectiveness of first line eflornithine for <i>Trypanosoma brucei gambiense</i> sleeping sickness in Sudan: cohort study
Authors: Gerardo Priotto, Loretxu Pinoges, Isaac Badi Fursa, Barbara Burke, Nathalie Nicolay, Guillaume Grillet, Cathy Hewison, Manica Balasegaram
Journal: BMJ (2008)

<b>Objective</b> To assess the safety and effectiveness of eflornithine as first line treatment for human African trypanosomiasis. <b>Design</b> Cohort study. <b>Setting</b> Control programme in Ibba, southern Sudan. <b>Participants</b> 1055 adults and children newly diagnosed with second stage disease in a 16 month period. <b>Main outcome measures</b> Deaths, severe drug reactions, and cure at 24 months. <b>Results</b> 1055 patients received eflornithine for 14 days (400 mg/kg/day in adults and 600 mg/kg/day in a subgroup of 96 children). Overall, 2824 drug reactions (2.7 per patient) occurred during hospital stay, 1219 (43.2%) after the first week. Severe reactions affected 138 (13.1%) patients (mainly seizures, fever, diarrhoea, and bacterial infections), leading to 15 deaths. Risk factors for severe reactions included cerebrospinal fluid leucocyte counts ≥100×10<sup>9</sup>/l (adults: odds ratio 2.6, 95% confidence interval 1.5 to 4.6), seizures (adults: 5.9, 2.0 to 13.3), and stupor (children: 9.3, 2.5 to 34.2). Children receiving higher doses did not experience increased toxicity. Follow-up data were obtained for 924 (87.6%) patients at any follow-up but for only 533 (50.5%) at 24 months. Of 924 cases followed, 16 (1.7%) died during treatment, 70 (7.6%) relapsed, 15 (1.6%) died of disease, 403 (43.6%) were confirmed cured, and 420 (45.5%) were probably cured. The probability of event free survival at 24 months was 0.88 (0.86 to 0.91). Most (65.8%, 52/79) relapses and disease related deaths occurred after 12 months. Risk factors for relapse included being male (incidence rate ratio 2.42, 1.47 to 3.97) and cerebrospinal fluid leucocytosis: 20-99×10<sup>9</sup>/l (2.35, 1.36 to 4.06); ≥100×10<sup>9</sup>/l (1.87, 1.07 to 3.27). Higher doses did not yield better effectiveness among children (0.87 <i>v</i> 0.85, P=0.981). Conclusions Eflornithine shows acceptable safety and effectiveness as first line treatment for human African trypanosomiasis. Relapses did occur more than 12 months after treatment. Higher doses in children were well tolerated but showed no advantage in effectiveness.
The late, but not early, asthmatic response is dependent on IL-5 and correlates with eosinophil infiltration
Authors: Grzegorz Cieslewicz, Adrian Tomkinson, Andy Adler, Catherine Duez, Jurgen Schwarze, Katsuyuki Takeda, Kirsten A. Larson, James J. Lee, Charles G. Irvin, Erwin W. Gelfand
Journal: Journal of Clinical Investigation (1999)

Early-phase reactions (EPRs) and late-phase reactions (LPRs) are characteristic features of bronchial asthma, although the pathogenetic mechanisms responsible for each of the responses are not fully defined. A murine model of EPRs and LPRs was developed to investigate the role of IL-5 and eosinophils in development of both responses. After initial intraperitoneal sensitization and airway challenge to ovalbumin (OVA), mice were provoked by additional exposure to OVA. An EPR, characterized by a transient increase in airway responsiveness, was observed 5–30 minutes after antigen provocation. This response was followed by an LPR that reached its maximum at 6 hours after challenge and was characterized by increased airway responsiveness and significant lung eosinophilia. The EPR was blocked by cromoglycate and albuterol, whereas the LPR was abolished by cromoglycate and hydrocortisone. Before provocation with allergen, administration of anti–IL-5 antibody prevented the influx of eosinophils into the lung tissue and abolished the LPR but not EPR. These results suggest that IL-5 and eosinophils are essential for development of the LPR, but not EPR, in this model.
A Comparative Study of Elastic Properties of Rat and Guinea Pig Parenchymal Strips
Authors: FRANCESCO G. SALERNO, PETER PARÉ, MARA S. LUDWIG
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Constricted guinea pig (GP) airways are much less sensitive to changes in transpulmonary pressure (Ptp) than are those of the rat. The object of this study was to investigate whether differences in the mechanical behavior of the lung parenchyma could explain differences between the two species in the interdependence of the airway and parenchyma. Subpleural lung strips from guinea pigs and rats were excised and suspended in an organ bath. One end of each strip was attached to a force transducer and the other to a servo-controlled lever arm that effected length (L) changes in the strip. Sinusoidal oscillations at varying frequencies and amplitudes were applied at different resting tensions. Measurements of L and resting tension (T) were recorded during baseline conditions and after acetylcholine (ACh) challenge. Elastance (E) and resistance (R) were calculated by fitting changes in T and L to the equation of motion. During sinusoidal oscillations, E and R in the two species were different in both the unconstricted and constricted states. The effect of T on E was significantly different in rats and GPs; E was less dependent on T in GPs. Insofar as E is a measure of the load against which airway smooth muscle (ASM) contracts, this difference may represent a potential mechanism to explain why constricted GP airways are less sensitive to changes in Ptp.
Effective arterial elastance as index of arterial vascular load in humans.
Authors: R P Kelly, C T Ting, T M Yang, C P Liu, W L Maughan, M S Chang, D A Kass
Journal: Circulation (1992)

BACKGROUND This study tested whether the simple ratio of ventricular end-systolic pressure to stroke volume, known as the effective arterial elastance (Ea), provides a valid measure of arterial load in humans with normal and aged hypertensive vasculatures. METHODS AND RESULTS Ventricular pressure-volume and invasive aortic pressure and flow were simultaneously determined in 10 subjects (four young normotensive and six older hypertensive). Measurements were obtained at rest, during mechanically reduced preload, and after pharmacological interventions. Two measures of arterial load were compared: One was derived from aortic input impedance and arterial compliance data using an algebraic expression based on a three-element Windkessel model of the arterial system [Ea(Z)], and the other was more simply measured as the ratio of ventricular end-systolic pressure to stroke volume [Ea(PV)]. Although derived from completely different data sources and despite the simplifying assumptions of Ea(PV), both Ea(Z) and Ea(PV) were virtually identical over a broad range of altered conditions: Ea(PV) = 0.97.Ea(Z) + 0.17; n = 33, r2 = 0.98, SEE = 0.09, p less than 0.0001. Whereas Ea(PV) also correlated with mean arterial resistance, it exceeded resistance by as much as 25% in older hypertensive subjects (because of reduced compliance and wave reflections), which better indexed the arterial load effects on the ventricle. Simple methods to estimate Ea (PV) from routine arterial pressures were tested and validated. CONCLUSIONS Ea(PV) provides a convenient, useful method to assess arterial load and its impact on the human ventricle. These results highlight effects of increased pulsatile load caused by aging or hypertension on the pressure-volume loop and indicate that this load and its effects on cardiac performance are often underestimated by mean arterial resistance but are better accounted for by Ea.
Reaction to Intradermally Applied Phytohaemagglutinin in Asthma Patients in Relation to Corticosteroid Therapy
Authors: Jerzy Kruszewski, Tadeusz Płusa, Cezary Szczylik, Wiesław Wiktor‐Jedrzejczak
Journal: Allergy (1983)

Phytohaemagglutinin (PHA) skin test (diameter of induration 24 h following intradermal injection of 1.0 microgram purified PHA) was carried out on 23 patients with exacerbated atopic asthma and 28 patients with exacerbated non-atopic asthma. Preselected adult patients had either not previously been treated with systemic corticosteroids or steroid therapy had been suspended for at least 3 months. Nearly all non-atopic asthma patients and patients with atopic asthma previously treated with corticosteroids showed increased reactions to PHA. Patients with atopic asthma not earlier treated with corticosteroids demonstrated normal responses. None of the asthmatics showed a negative PHA reaction. Administration of single depot doses of corticosteroids produced decreased reactivity to PHA in nearly all patients. These results suggest that neither atopic nor non-atopic asthma is in itself associated with impaired PHA skin reactivity but that changes in this reactivity are largely due to the corticosteroid therapy administered to these patients. In relation to PHA reactivity certain effects of this therapy may persist for as long as 3 months after its cessation.
Teaching medical ethics.
Authors: M D Jewell
Journal: BMJ (1984)

At Southampton Medical School students in the third year of the course (the first clinical year) spend one morning a week in general practice. Discussion of patients' problems with students often encompasses ethical issues, and for some time we have been aware of our inability to provide any clear frame? work for an informed debate. Our students get some formal teaching in ethics, but not until the second clinical year, and we thought that this arrangement missed the opportunity of tackling the problems when they have most relevance. As in other medical schools, the students already have a full timetable so that inserting extra sessions presents problems. Nevertheless, the third year general practice programme incorporates seven sessions in seminars in the department of primary medical care, when there are eight to 12 students in a group. We thought that part of this time could be devoted to a discussion of ethical matters, intending that students should consider the implications of clinical decisions?and it is considerably easier to encourage critical thinking in an interacting group than in a set lecture. Against that background, a chance meeting between the head of our department and Ian Kennedy, professor of medical law and ethics at King's College, London, led to a plan for five experimental sessions during the academic year 1982-3. Each student was asked to read some preliminary material. One article enumerated the fundamental principles of medical ethics, showing how they are identical both to those in general ethics and to principles identified by philosophers in antiquity.1 The second was a short extract from a book on medical ethics which discussed the nature of moral argument, showing how moral statements may be rationally defended or questioned with reference to ultimate beliefs.2 Finally, there was a published case presentation concerning a 76 year old woman admitted to hospital after a stroke. She suffered from maturity onset diabetes, controlled by tablets, and mitral valve disease and atrial fibrillation, for which she took anticoagulants. The article was in the form of a students' teaching session, where the discussion dealt with which treatments should or might be withheld, and how such questions should be answered for an individual.3 We aimed at using the first seminar to discuss general principles as they exist in all social life as well as in medicine, in terms both of their application and of their exceptions. The second seminar would then be devoted to discussing clinical cases brought by students, analysing them with reference to general principles and ensuring that the conclusions could be applied generally. As this was planned as an experiment, and as another development was being planned for assessment of the third year general practice course as a whole, we undertook no formal assessment of these seminars. What follows is the collective opinion of the teachers who took part, supported by videotapes of two sessions.
The Doctor in Politics.
Authors: None Senex
Journal: JAMA (1895)

Sept. 24,1895. <h3>To the Editor:</h3> —The opinion held by some physicians that the medical profession should take a more prominent part in political affairs has received a new impetus from the recent meeting of the County Central Committee of Cook County, Illinois. The story told of the sanguinary encounters between members of that committee has led to the suggestion that hereafter a surgeon should be appointed to attend all meetings of the "business" men who control the destinies of one of the great parties in the second city of our great Republic. The story of how oneMr. Goodman, of Evanston, had his nose broken by theHonorable "Buck" McCarthy, an alderman, and the heroic deeds of this doughty champion in producing bruises on the face of theHonorable "Jo." Lammers, also an alderman, and enucleating the eye of that worthy by the effective and simple process technically known as