tbuckley/cabot-search huggingface dataset:
Altruism, Self-interest, and Medical Ethics
Authors: George M. Adams
Journal: JAMA (1988)

<h3>To the Editor.</h3> —I write concerning the editorial by Dr Pellegrino<sup>1</sup>and the letter in response by Dr Tiemstra and the reply by Dr Pellegrino.<sup>2</sup> Dr Pellegrino states that the thrust of his article is paternalism. I think both he and Dr Tiemstra, however, have more fundamental contradictions in their thinking. The key contradiction is the principle of altruism. The basic principle of altruism is that man has no right to exist for his own sake, that service to others is the only justification for existence, and that self-sacrifice is the highest moral duty, virtue, and value. Do not confuse altruism with kindness, good-will, or the respect for the rights of others. These are not primaries, but consequences that, in fact, altruism makes impossible.<sup>3</sup> The most moral code is the most rational code, ie, objective. The most moral thing that any professional, including physicians, can do in
Abstract LB-224: A randomized phase 2 study of two doses of itraconazole in men with metastatic castration-resistant prostate cancer (mCRPC)
Authors: Emmanuel S. Antonarakis, Elisabeth I. Heath, David C. Smith, Dana Rathkopf, Amanda L. Blackford, Daniel C. Danila, Serina King, Anja Frost, A. Seun Ajiboye, Ming Zhao, Janet Mendonca, Sushant K. Kachhap, Michelle A. Rudek, Michael A. Carducci
Journal: Cancer Research (2012)

Abstract BACKGROUND: The antifungal drug itraconazole inhibits angiogenesis and Hedgehog signaling, and delays tumor growth in murine prostate cancer xenograft models. Unlike ketoconazole, it does not suppress androgen synthesis. METHODS: A phase 2 study of oral itraconazole in men with mCRPC was conducted at 4 sites. Men were randomized to low dose (LD) or high dose (HD) itraconazole (200 or 600 mg/day) until disease progression or unacceptable toxicity. The primary endpoint was PSA progression-free survival (PPFS) at 24 wk (PSA progression = 25% PSA rise above baseline/nadir); a 45% success rate in either arm was prespecified as constituting clinical significance. Secondary endpoints were progression-free survival (PFS) at 24 wk (progression = clinical/radiographic progression or death, but not rising PSA); median PFS; median PPFS; and max PSA decline. Exploratory outcomes included CTC enumeration, analysis of adrenal androgens (serum testosterone and DHEA), VEGF analysis, and GLI1 expression in skin biopsy samples. RESULTS: The HD arm enrolled to completion (N=29), but the LD arm closed early (N=17) due to a prespecified futility analysis. Table 1 shows efficacy results. In addition, 3/5 men (60%) in the HD arm and 2/3 men (67%) in the LD arm with unfavorable (≥5) CTCs at baseline converted to favorable (&amp;lt;5) CTC counts with treatment. Itraconazole did not reduce serum testosterone or DHEA levels. It had no effect on circulating VEGF levels. In skin biopsies, downmodulation of GLI1 was seen in 33% and 68% of men in the LD and HD arms, respectively. Median PPFS was superior in men who achieved GLI1 downmodulation compared to those who did not (P=.028). Toxicities with itraconazole included fatigue, nausea, anorexia, rash, and a syndrome of hypokalemia/hypertension/edema. CONCLUSIONS: Only the HD arm met its primary endpoint. Itraconazole 600 mg/day may have activity in men with mCRPC that is not mediated by androgen suppression, and may correlate with GLI1 downmodulation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-224. doi:1538-7445.AM2012-LB-224
Right-to-left shunt at rest and increased mobility of atrial septum identify a subgroup of PFO patients at higher risk for recurrent embolism
Authors: Stefano De Castro, Domenico Cartoni, Marco Fiorelli, Maurizia Rasura, Alexia Anzini, Sergio Beni, Giuseppina Magni, Francesco Fedele, Natesa Pandian
Journal: Journal of the American College of Cardiology (1996)
Angiogenic synergism, vascular stability and improvement of hind-limb ischemia by a combination of PDGF-BB and FGF-2
Authors: Renhai Cao, Ebba Bråkenhielm, Robert Pawliuk, David Wariaro, Mark J. Post, Eric Wahlberg, Philippe Leboulch, Yihai Cao
Journal: Nature Medicine (2003)
PERSONALITY FACTORS IN PATIENTS WITH MUSCULAR DISABILITY
Authors: HERBERT S. RIPLEY, CHARLES BOHNENGEL, ADE T. MILHORAT
Journal: American Journal of Psychiatry (1943)

In 67 patients with diseases involving the muscles the anatomical involvement, bio-chemical findings and personality factors were investigated. Many cases presented problems in diagnosis between structural disease of the nervous or muscular systems and psychoneurotic reactions. Emotional changes often were accompanied by altered performance of the muscles. When the symptomatology was more severe than could be explained satisfactorily by the physical studies, the psychopathological findings were demonstrated to be of importance in the development of the clinical picture. In some instances an original diagnosis of muscle disease was shown to be erroneous by proof that a psychoneurosis existed and the symptoms could be improved by psychotherapy. The type of adjustment in those with muscle disease depended on a complexity of factors, such as the personality prior to the illness, the age of onset and the type and the course of the disability. Suggestion played an important part in the symptomatic change after administration of various medications. Study of both the physical and personality factors was found to be of value in the diagnosis and treatment of muscle disease.
Study of urinary tract infection in children in one health district
Authors: L Pead, R Maskell
Journal: BMJ (1994)

To determine the number of children who had urine specimens sent for culture, who had infections or sterile pyuria, and who were investigated further. To relate the laboratory findings to the results of imaging.One year survey of urine specimens submitted to a laboratory; review of previous and subsequent laboratory reports; review of the findings of imaging of the urinary tract.Portsmouth and South East Hampshire health district.An estimated population of 89,086 children aged 12 years or under.Urine bacterial count and results of imaging.12,551 urine specimens were submitted from 7450 children, 3138 boys and 4312 girls. 2238 children had infection or sterile pyuria at least once during the study (13.9/1000 boys, 37/1000 girls). 996 (45%) of the children with infection or sterile pyuria underwent some form of imaging. 128 children who had infection or sterile pyuria were already known to have urinary tract abnormalities and 114 children had newly identified abnormalities (1.0/1000 boys, 1.5/1000 girls). 50 (44%) of the children with newly detected abnormalities had no pyuria and 48 (42%) had bacterial counts below 10(8)/l. Eight children who had sterile pyuria on presentation were found to have abnormalities on imaging.Urinary tract infection is much commoner in children than is widely believed. Low bacterial counts, the absence of pyuria, or a finding of sterile pyuria should not be disregarded.
Reproductive toxicology of disinfection by-products.
Authors: M K Smith, H Zenick, E L George
Journal: Environmental Health Perspectives (1986)

The chronic exposure of large segments of the population to disinfected drinking water has necessitated an evaluation of the health effects of the by-products of the chlorination process. This paper reviews the available information concerning the reproductive consequences associated with exposure to disinfection by-products. Four groups of compounds are discussed: the trihalomethanes, in particular chloroform; the chlorinated phenols; chlorinated humic substances; and the haloacetonitriles. In the pregnant female, chloroform and the 2- and 2,4-chlorophenols produced low levels of embryo- and fetotoxicity. Chloroform induced terata when administered by inhalation. The chlorinated humic substances and 2,4,6-trichlorophenol were without significant reproductive effects. The haloacetonitriles showed in utero toxicity, becoming more severe with increasing halogen substitution.
Standardization of nomenclature and causality assessment in drug-induced liver injury: Summary of a clinical research workshop
Authors: Robert J. Fontana, Leonard B. Seeff, Raúl J. Andrade, Einar Björnsson, Christopher P. Day, Jose Serrano, Jay H. Hoofnagle
Journal: Hepatology (2010)

Idiosyncratic drug-induced liver injury (DILI) is an important but relatively infrequent cause of potentially severe acute and chronic liver injury. The aim of this clinical research workshop was to review and attempt to standardize the current nomenclature and terminology used in DILI research. Because DILI is a diagnosis of exclusion, selected elements of the medical history, laboratory tests, and previous reports were proposed to improve causality assessment. Definitions and diagnostic criteria regarding the onset of DILI, evolution of liver injury, risk factors, and mandatory testing versus optional testing for competing causes were reviewed. In addition, the role of intentional and inadvertent rechallenge, liver histology, and host genetic polymorphisms in establishing the diagnosis and prognosis of DILI were reviewed. Consensus was established regarding the need to develop a web-of-knowledge database that provides concise, reliable, and updated information on cases of liver injury due to drugs and herbal and dietary supplements. In addition, the need to develop drug-specific computerized causality assessment methods that are derived from prospectively phenotyped cases was a high priority. Proposed scales for grading DILI severity and assessing the likelihood of an agent causing DILI and written criteria for improving the reliability, accuracy, and reproducibility of expert opinion were reviewed. Finally, the unique challenges of assessing causality in children, patients with underlying liver disease, and subjects taking herbal and dietary supplements were discussed. Conclusion: Workshop participants concluded that multicenter referral networks enrolling patients with suspected DILI according to standardized methodologies are needed. These networks should also collect biological samples that may provide crucial insights into the mechanism(s) of DILI with the ultimate aim of preventing future cases of DILI. (HEPATOLOGY 2010)
A phase I, open-label dose-escalation study of continuous treatment with BIBF 1120 in combination with paclitaxel and carboplatin as first-line treatment in patients with advanced non-small-cell lung cancer
Authors: R.C. Doebele, P. Conkling, A.M. Traynor, G.A. Otterson, Y. Zhao, S. Wind, P. Stopfer, R. Kaiser, D.R. Camidge
Journal: Annals of Oncology (2012)
Molecular characterisation of red cell glucose‐6‐phosphate dehydrogenase deficiency in Singapore Chinese
Authors: S. Saha, N. Saha, J. S. H. Tay, K. Jeyaseelan, J. B. Basair, S. E. Chew
Journal: American Journal of Hematology (1994)

Abstract Sixty‐two G6PD deficient Chinese males have been investigated for the presence of seven mutations of the coding region of the G6PD gene by natural and artifically created amplified restriction sites. The results show that the G to T substitution at nucleotide (nt) 1376 and G to A substitution at nt 1388 represent 24% and 21% of G6PD deficiency, respectively, in the Singapore Chinese; 37% of the sample could not be characterised. The remaining samples were identified as follows: 10% C→T at nt 563, 5% A→G at nt 95, and 3% C→T at nt 1024. The G to A substitution (nt 487) and the substitution A→G (nt 493) were not present in this sample. None of the subjects with the Mediterranean mutation (563 C→T) had the silent mutation at 1311 (C→T). This study confirms the extreme molecular heterogeneity of the G6PD gene in the Chinese. © 1994 Wiley‐Liss, Inc.
Low Bone Mineral Density and Risk of Fracture in White Female Nursing Home Residents
Authors: Julie M. Chandler
Journal: JAMA (2000)

Low bone mineral density (BMD) is a strong risk factor for fracture in community-dwelling white women, but the relationship in white female nursing home residents, for whom fracture rates are highest, is less clear.To assess the relative contribution of low BMD to fracture risk in nursing home residents.Prospective cohort study with baseline data collected April 1995 to June 1997, with 18 months of follow-up.Forty-seven randomly selected nursing homes in Maryland.A total of 1427 white female nursing home residents aged 65 years or older.Documented osteoporotic fracture occurring during follow-up as a function of baseline BMD measurements higher vs lower than the median, and after controlling for demographic, functional, cognitive, psychosocial, and medical factors.A total of 223 osteoporotic fractures occurred among 180 women. Low BMD and transfer independence were significant independent risk factors for fracture in this nursing home sample (P<.001) and the 2 factors acted synergistically (P =.06) to further increase fracture risk. Compared with women whose BMD was higher than the median (0. 296 g/cm(2)), those whose BMD was lower than the median had an unadjusted hazard ratio for risk of fracture of 2.1 (95% confidence interval [CI], 1.5-2.8); women who were independent in transfer had a hazard ratio of 1.6 (95% CI, 1.2-2.2) compared with women dependent in transfer. Among residents independent in transfer, those with BMD below the median had a more than 3-fold increase in fracture risk compared with those with higher BMD (unadjusted hazard ratio, 3.1; 95% CI, 2.2-4.4). Among residents dependent in transfer, those with BMD below the median had a 60% increase in fracture risk (unadjusted hazard ratio, 1.6; 95% CI, 1.1-2.3). Adjustment for covariates did not alter the BMD-fracture relationship.Our data indicate that low BMD and independence in transfer are significant predictors of osteoporotic fracture in white female nursing home residents. JAMA. 2000;284:972-977
Immunoleukopenia as an Aspect of Hypersensitivity to Propylthiouracil
Authors: Richard A. Walzer
Journal: JAMA (1963)

A 15-year-old girl developed a hypersensitivity syndrome believed to be associated with administration of propylthiouracil for thyrotoxicosis. The clinical picture included leukopenia; slowly healing ulcerations of the skin; intermittent purpuric lesions of the face, hands, ankles, and feet; frequent febrile episodes; pain and swelling of joints; splenomegaly; and hyperglobulinemia. Antibodies against the autologous white blood cells were demonstrated by immunofluorescent staining techniques with the inference that these autoantibodies were destructive and antileukocytic.
How many psychiatric beds?
Authors: G Thornicroft, G Strathdee
Journal: BMJ (1994)

Forty years ago Houston wrote: “By incarceration we were aggravating the natural process of the disease. At last a new era is dawning and the doors of despair are being unlocked.”1 Since 1954 the number of psychiatric beds in Britain has fallen by almost two thirds to 50 278.2 The key issue about this trend is, how far is far enough? Do we now need more or fewer psychiatric beds? To debate this thoroughly the emphasis should be on the whole mental health service system rather than on numbers of beds alone. Four issues need to be directly addressed: the mental health services required in each local area, the needs for secure provision and the links between forensic and community services, integrated methods of efficient management of psychiatric beds, and interagency working arrangements.

Not only beds are needed. As the Health of the Nation's key area handbook on mental illness indicates, a consensus now exists about the range and scale of services required in each local area.*RF 3-5* The inquiry by the House of Commons Health Select Committee into services for seriously mentally …
Lack of progress at summit spells disaster for poor countries
Authors: Z. Kmietowicz
Journal: BMJ (2002)

Crucial talks to protect the future of the planet and to combat world poverty ended in what environmentalists called “a giant fudge,” with government ministers bowing to pressure from big business and failing to agree an action plan.

The United Nations meeting, held in Bali, Indonesia, was a preparation for the Earth Summit to be held in Johannesburg in August—the follow up to the last Earth Summit in Rio de Janeiro 10 years ago. Its aim was to draft a blueprint for …
Optimal method of dosing HER2/<i>neu</i> peptide vaccines: U.S. Military Cancer Institute Clinical Trials Group Study 1-01, 1-02, 1-03, and 1-04.
Authors: LC Benavides, JD Gates, JP Holmes, EA Mittendorf, S Ponniah, GE Peoples
Journal: Cancer Research (2009)

Abstract Abstract #3139 Background: Our Cancer Vaccine Development Program has performed phase I and II clinical trials using immunogenic peptides from the HER2/neu protein. AE37 (aa:776-790+Ii-Key) is HLA promiscuous whereas E75 (aa:369-377) and GP2 (aa:654-662) are HLA-A2/A3+ restricted. The peptides are located on the intracellular, extracellular, and transmembrane portions of the HER2/neu protein. We evaluate patients who required dose reductions and compare them to those who did not in our three peptide vaccine trials to determine the immunologic and clinical relevance of different responses to the peptide vaccines. Methods: Three vaccine trials were performed separately with similar dose escalation design by varying the amount of AE37, GP2 or E75 peptide and GM-CSF adjuvant. Dose reductions (DR) were made in event of significant toxicity (&amp;gt;100mm local or ≥grade 2 systemic) by decreasing GM-CSF (or peptide if no GM-CSF) by 50% for subsequent inoculations. We compared patients necessitating DR and those who did not. Immune response was measured ex vivo via 3H-thymidine proliferative assays or HLA-A2:Ig dimer assays and in vivo via DTH reactions pre- and post-vaccine. Recurrence and mortality data were available for E75 treated patients at 30-month median follow-up. Results: 132 patients underwent peptide vaccination and 39 patients required DR (Table 1).&amp;#x2028; &amp;#x2028; No patient had grade 3-5 local or systemic toxicities. DR patients, particularly those reduced for robust local reactions (DR-L), had greater immune responses ex vivo and in vivo. The post-vaccine DTH in DR-L patients compared to all other vaccinated patients was significantly larger in E75 (24.5±4.1mm vs. 12.7±1.3mm; p=0.001) and trended towards significant in AE37 (69.4±10.3mm vs. 35.8±14.9mm; p=0.08) and GP2 (48.9±14.1mm vs. 24.1±3.3mm; p=0.08). No recurrences or deaths were noted in the E75 DR patients; but for patients not requiring dose reductions there were 10 (12.5%) recurrences and 1 (1.25%) death.Discussion: All three peptide vaccines are safe and well-tolerated with minimal toxicity. The safety was partly due to reducing GM-CSF (or peptide if no GM-CSF) by 50% for patients with &amp;gt;100mm local reactions or &amp;gt;grade 2 systemic toxicity. DR patients, particularly DR-L patients, immunological responses were larger. This increased immune response (noted by DTH) suggests improved clinical response as there have been no recurrences or deaths among DR patients. Our analysis indicates that the optimal method of dosing HER2/neu peptide vaccines consists of constant peptide dose with a large enough dose of adjuvant to generate robust local reactions and that when local reactions are &amp;gt;100mm performing DR of adjuvant by 50% for subsequent inoculations. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3139.
HFE mutations and chronic hepatitis C: H63D and C282Y heterozygosity are independent risk factors for liver fibrosis and cirrhosis
Authors: Andreas Erhardt, Andrea Maschner-Olberg, Claudia Mellenthin, Günther Kappert, Ortwin Adams, Andreas Donner, Reinhard Willers, Claus Niederau, Dieter Häussinger
Journal: Journal of Hepatology (2003)
<sup>31</sup> P NMR Spectroscopy Detects Metabolic Abnormalities in Asymptomatic Patients With Hypertrophic Cardiomyopathy
Authors: Wulf-Ingo Jung, Ludger Sieverding, Johannes Breuer, Thomas Hoess, Stefan Widmaier, Oliver Schmidt, Michael Bunse, Franz van Erckelens, Jürgen Apitz, Otto Lutz, Guenther J. Dietze
Journal: Circulation (1998)

Background —Hypertrophic cardiomyopathy (HCM) often causes sudden, unexpected death in adolescents and young adults. Alterations in myocardial metabolism are considered to be causes for contractile dysfunction. We examined the question of whether metabolic abnormalities antedate the manifestation of symptoms in patients with HCM. Methods and Results —Proton-decoupled 31 P NMR spectroscopy of the anterior left ventricular wall of the heart of 14 young, asymptomatic patients with HCM was performed with a 1.5-T whole-body imager. Spectra of the phosphate metabolites were compared with those of normal control subjects. The patients exhibited a significantly reduced ( P &lt;0.02) ratio of phosphocreatine (PCr) to ATP of 1.98±0.37 (mean±SD), compared with 2.46±0.53 obtained in 11 normal control subjects. In addition, the group of patients with severe hypertrophy of the interventricular septum (n=8) showed a significantly increased ( P &lt;0.05) P i -to-PCr ratio, with a P i ×100/PCr of 20.0±8.3 versus 9.7±7.2 in control subjects. Both abnormalities are similar to those found in ischemic myocardium. This view is also supported by a significantly increased ( P &lt;0.01) phosphomonoester (PME)-to-PCr ratio, with a PME×100/PCr of 20.7±11.2 compared with 8.4±6.7 in control subjects, indicating altered glucose metabolism. Conclusions — 31 P NMR spectroscopy detects alterations of myocardial metabolism in asymptomatic patients with HCM. These alterations may contribute to the understanding of the pathophysiology and natural history of the disease.
The spaces left over between REM sleep, dreaming, hippocampal formation, and episodic autobiographical memory
Authors: Hans J. Markowitsch, Angelica Staniloiu
Journal: Behavioral and Brain Sciences (2013)

Abstract It is argued that Llewellyn's hypothesis about the lack of rapid eye movement (REM)-sleep dreaming leading to loss of personal identity and deficits in episodic memory, affectivity, and prospection is insufficiently grounded because it does not integrate data from neurodevelopmental studies and makes reference to an outdated definition of episodic memory.