tbuckley/cabot-search huggingface dataset:
Joseph Goldberger: Unsung Hero
Authors: Bradley K. Evans
Journal: Annals of Internal Medicine (1995)

Letters15 January 1995Joseph Goldberger: Unsung HeroBradley K. Evans and Alvan R. FeinsteinBradley K. EvansSearch for more papers by this author and Alvan R. FeinsteinSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-122-2-199501150-00027 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Physicians have always had dilemmas in reconciling our sometimes conflicting obligations to individual persons and society. A major role of informed consent, as used in the past and in many research projects today, is to allow individual persons to volunteer for activities that are aimed mainly at benefiting society [1]. Direct benefits for the volunteers can also come from the pardons given to prisoners many years ago for the pellagra experiments or from the money given to participants in experiments at contemporary clinical research centers [1].Nevertheless, times and customs change, as well as views about ethics. We ...References1. Levine RJ. Ethics and Regulation of Clinical Research. 2d ed. Baltimore: Urban and Schwarzenberg; 1986. Google Scholar2. Elmore JG, Feinstein AR. Joseph Goldberger: an unsung hero of American clinical epidemiology. Ann Intern Med. 1994; 121:372-5. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe history of pellagra therapyGoldberger’s war:The life and work of a public health crusaderPellagra and skin 15 January 1995Volume 122, Issue 2Page: 157 ePublished: 15 August 2000 Issue Published: 15 January 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Prevalence of Anderson-Fabry Disease in Male Patients With Late Onset Hypertrophic Cardiomyopathy
Authors: B. Sachdev, T. Takenaka, H. Teraguchi, C. Tei, P. Lee, W.J. McKenna, P.M. Elliott
Journal: Circulation (2002)

Although studies have suggested that "late-onset" hypertrophic cardiomyopathy (HCM) may be caused by sarcomeric protein gene mutations, the cause of HCM in the majority of patients is unknown. This study determined the prevalence of a potentially treatable cause of hypertrophy, Anderson-Fabry disease, in a HCM referral population.Plasma alpha-galactosidase A (alpha-Gal) was measured in 79 men with HCM who were diagnosed at > or =40 years of age (52.9+/-7.7 years; range, 40-71 years) and in 74 men who were diagnosed at <40 years (25.9+/-9.2 years; range, 8-39 years). Five patients (6.3%) with late-onset disease and 1 patient (1.4%) diagnosed at <40 years had low alpha-Gal activity. Of these 6 patients, 3 had angina, 4 were in New York Heart Association class 2, 5 had palpitations, and 2 had a history of syncope. Hypertrophy was concentric in 5 patients and asymmetric in 1 patient. One patient had left ventricular outflow tract obstruction. All patients with low alpha-Gal activity had alpha-Gal gene mutations.Anderson-Fabry disease should be considered in all cases of unexplained hypertrophy. Its recognition is important given the advent of specific replacement enzyme therapy.
Evolution of Breast Cancer Screening in the Medicare Population: Clinical and Economic Implications
Authors: Brigid K. Killelea, Jessica B. Long, Anees B. Chagpar, Xiaomei Ma, Rong Wang, Joseph S. Ross, Cary P. Gross
Journal: JNCI Journal of the National Cancer Institute (2014)

Newer approaches to mammography, including digital image acquisition and computer-aided detection (CAD), and adjunct imaging (e.g., magnetic resonance imaging [MRI]) have diffused into clinical practice. The impact of these technologies on screening-related cost and outcomes remains undefined, particularly among older women. Using the Surveillance, Epidemiology, and End Results–Medicare linked database, we constructed two cohorts of women without a history of breast cancer and followed each cohort for 2 years. We compared the use and cost of screening mammography including digital mammography and CAD, adjunct procedures including breast ultrasound, MRI, and biopsy between the period of 2001 and 2002 and the period of 2008 and 2009 using χ2 and t test. We also assessed the change in breast cancer stage and incidence rates using χ2 and Poisson regression. All statistical tests were two-sided. There were 137150 women (mean age = 76.0 years) in the early cohort (2001–2002) and 133097 women (mean age = 77.3 years) in the later cohort (2008–2009). The use of digital image acquisition for screening mammography increased from 2.0% in 2001 and 2002 to 29.8% in 2008 and 2009 (P < .001). CAD use increased from 3.2% to 33.1% (P < .001). Average screening-related cost per capita increased from $76 to $112 (P < .001), with annual national fee-for-service Medicare spending increasing from $666 million to $962 million. There was no statistically significant change in detection rates of early-stage tumors (2.45 vs 2.57 per 1000 person-years; P = .41). Although breast cancer screening–related costs increased substantially from 2001 through 2009 among Medicare beneficiaries, a clinically significant change in stage at diagnosis was not observed.
Respiratory work in relation to cardiopulmonary bypass
Authors: C. W. Deal, J. J. Osborn, E. Louis, S. Elliott, F. Gerbode
Journal: Thorax (1967)

Twenty-four patients undergoing cardiopulmonary bypass have been studied and the work of respiration was measured (1) before the incision, (2) before bypass with the thorax open, (3) after bypass, and (4) after suturing of the incision. Our results indicate that moving the thoracic wall requires 10 to 14% of the respiratory work and that little change occurs as a consequence of cardiopulmonary bypass.
Validation of Peptide Immunotherapy as a New Approach in the Treatment of Allergic Rhinoconjunctivitis: The Clinical Benefits of Treatment with Amb a 1 Derived T cell Epitopes
Authors: R.P. Hafner, A. Salapatek, D. Patel, M. Larché, P. Laidler
Journal: Journal of Allergy and Clinical Immunology (2012)

A series of T-cell epitopes from cat allergen, Fel d1, formulated into a short-course peptide vaccine (ToleroMune Cat) was previously shown to significantly reduce allergic rhinoconjunctivitis symptoms shortly after vaccine therapy ended and persistently, one year after dosing start (tolerance). In this study, we evaluated the efficacy of a vaccine from a newly identified series of T-cell epitopes from ragweed allergen Amb a1 (ToleroMune Ragweed) on allergic rhinoconjunctivitis symptoms. Screened ragweed allergic subjects attended four consecutive 3-hour Baseline Challenges in an Environmental Exposure Chamber (EEC) where airborne ragweed pollen levels were controlled at 3500±500 grains/m3 . Total Rhinoconjunctivitis Symptom Score (TRSS) was scored every 30 minutes on a scale of 0-24. 275 subjects were randomised to placebo, or one of four ToleroMune Ragweed treatment arms. Subjects returned to a series of 4 consecutive, 3-hour Post-Treatment EEC Challenges 18-22weeks after the start of treatment. Treatment with ToleroMune Ragweed resulted in the largest changes in TRSS in the most symptomatic subjects who had the highest scores at Baseline. In this group, treatment with the highest dose of ToleroMune Ragweed showed a mean change in the TRSS score at the post treatment EEC visit of -5.77±5.31 versus a change of -2.93±5.31 on placebo (p <0.05). The product was safe and well tolerated. The efficacy of T cell epitope-based peptide immunotherapy has been demonstrated for cat and ragweed allergies. This new treatment modality offers an exciting alternative short-course immunotherapy with an enhanced safety profile that is potentially applicable across multiple allergens.
OBSERVATIONS CONCERNING A PERSISTING INFECTION OF HELA CELLS WITH POLIOMYELITIS VIRUS
Authors: W. Wilbur Ackermann, Hilda Kurtz
Journal: The Journal of Experimental Medicine (1955)

A culture of HeLa cells has been subjected to prolonged observation with the finding that periodically Type III poliomyelitis virus could be isolated from it. A requirement of the culture for survival was the presence in it of serum of certain individuals who had had previous experience with poliomyelitis virus. In the presence of serum containing no antibodies to poliomyelitis virus, the culture demonstrated spontaneous cytopathology. From certain series of passages virus could be isolated while attempts were unsuccessful from others also showing cellular disintegration. The conclusion is reached that the virus does not persist in the culture always in a state exhibiting the infectious property, rather what persists is the potentiality of the culture to give rise to fully active virus. The immune serum could inhibit the cytopathogenic effect of the virus without eliminating the infection.
Erythrocyte detergent-resistant membrane proteins: their characterization and selective uptake during malarial infection
Authors: Sean C. Murphy, Benjamin U. Samuel, Travis Harrison, Kaye D. Speicher, David W. Speicher, Marion E. Reid, Rainer Prohaska, Philip S. Low, Michael J. Tanner, Narla Mohandas, Kasturi Haldar
Journal: Blood (2003)
Intravenous Pulse Administration of Cyclophosphamide Is an Effective and Safe Treatment for Sensitized Cardiac Allograft Recipients
Authors: Silviu Itescu, Elizabeth Burke, Katherine Lietz, Ranjit John, Donna Mancini, Robert Michler, Eric Rose, Mehmet Oz, Niloo Edwards
Journal: Circulation (2002)

The proportion of cardiac transplant recipients with preexisting sensitization to HLA alloantigens has been increasing. Sensitization prolongs duration to obtaining a donor and predicts poorer long-term allograft survival because of increased risk of cellular rejections. We investigated the effect of cyclophosphamide pulse therapy in sensitized cardiac allograft recipients.Pretransplant and posttransplant outcomes were compared between 88 cardiac allograft recipients at risk for sensitization and 26 sensitized recipients treated with intravenous cyclophosphamide pulse therapy together with intravenous immune globulin before transplant and as part of a cyclosporine-based triple immunosuppressive regimen after transplant. Preformed IgG anti-HLA antibodies predicted longer duration to transplantation, earlier cellular rejection, and 2.7-fold higher cumulative rejection frequency (P=0.002). Before transplant, cyclophosphamide reduced waiting time and mortality to levels in nonsensitized patients. After transplant, cyclophosphamide prevented induction of IgG anti-HLA class II antibodies and interleukin-2 receptor--positive T-cell outgrowth from biopsy sites (both P<0.01), prolonged the rejection-free interval (P=0.009), and reduced cumulative rejections to levels in nonsensitized patients (P=0.003). By multivariable analysis, the risk of rejection was 3.7-fold higher in patients treated with mycophenolate mofetil than patients treated with cyclophosphamide (P=0.019). There were no differences in infectious or other significant complications.Immunosuppression incorporating intravenous cyclophosphamide before and after transplantation is safe and highly effective in sensitized cardiac transplant recipients. When used after transplantation as part of triple immunosuppression, cyclophosphamide is superior to mycophenolate mofetil in reducing rejection. The mechanism may involve prevention of diversification of the recipient immune response to donor HLA class II molecules.
Effects of bezafibrate on dyslipidemia with cholestasis in children with familial intrahepatic cholestasis–1 deficiency manifesting progressive familial intrahepatic cholestasis
Authors: Hironori Nagasaka, Tohru Yorifuji, Kenichi Hirano, Akemi Ota, Yumiko Toyama-Nakagawa, Tomozumi Takatani, Hirokazu Tsukahara, Kunihiko Kobayashi, Masaki Takayanagi, Yukihiro Inomata, Shinji Uemoto, Takashi Miida
Journal: Metabolism (2008)
Combination Treatment with Mirabegron and Solifenacin in Patients with Overactive Bladder: Efficacy and Safety Results from a Randomised, Double-blind, Dose-ranging, Phase 2 Study (Symphony)
Authors: Paul Abrams, Con Kelleher, David Staskin, Tomasz Rechberger, Richard Kay, Reynaldo Martina, Donald Newgreen, Asha Paireddy, Rob van Maanen, Arwin Ridder
Journal: European Urology (2014)
Effects of oxygen on exertional dyspnea and exercise performance in patients with COPD
Authors: Keisuke Miki, Ryoji Maekura, Toru Hiraga, Hisako Hashimoto, Seigo Kitada, Mari Miki, Kenji Yoshimura, Yoshitaka Tateish
Journal: European Respiratory Journal (2011)

Background: Accumulation of studying the oxygen (O2) response in chronic obstructive pulmonary disease (COPD) should provide important clues to the pathophysiology of exertional dyspnea.  We investigated the exercise responses of hyperoxia on the dyspnea profile, as well as cardio-pulmonary, acidotic and sympathetic parameters in 35 patients with stable COPD.  Methods: The patients breathed 24% O2 or compressed air (CA) in random order during two incremental cycle exercise tests.  Results: The PaO2 and PaCO2 values were higher (P   Conclusion: Regardless of breathing CA or hyperoxia, COPD patients did not develop ventilatory compensation for the exertional acidosis to stop exercise, resulting in reaching a similar pH. During a standardized exercise phase, hyperoxia did not change the pattern of exertional dyspnea while breathing CA in these patients, although hyperoxia exerted miscellaneous effects.
Cross-cultural differences in rating hyperactive-disruptive behaviors in children
Authors: E M Mann, Y Ikeda, C W Mueller, A Takahashi, K T Tao, E Humris, B L Li, D Chin
Journal: American Journal of Psychiatry (1992)

To determine the extent to which the reported variations across countries in the prevalence of attention-deficit hyperactivity disorder are due to cultural differences among raters, the authors examined the degree to which mental health professionals in four countries differed in their ratings of hyperactive-disruptive behaviors in children.Mental health professionals from China (N = 8), Indonesia (N = 12), Japan (N = 9), and the United States (N = 8) rated the presence and degree of hyperactive-disruptive behaviors in standardized videotape vignettes of four 8-year-old boys participating in individual and group activities.Chinese and Indonesian clinicians gave significantly higher scores for hyperactive-disruptive behaviors than did their Japanese and American colleagues.These findings suggest that perceptions of hyperactivity vary significantly across countries even if uniform rating criteria are applied. Without correction for these perceptual differences, cross-cultural prevalence rates of hyperactivity may not be comparable.
Sustained Remission of Schizophrenia Among Community-Dwelling Older Outpatients
Authors: Lisa A. Auslander, Dilip V. Jeste
Journal: American Journal of Psychiatry (2004)

The frequency and nature of sustained remission of schizophrenia are controversial.The authors assessed the prevalence of sustained remission among 155 middle-aged and elderly outpatients living independently. They compared patients with sustained remission to symptomatic schizophrenia patients and normal comparison subjects using standardized psychopathological, cognitive, and functional measures.Eight percent of the older schizophrenia patients living independently met criteria for sustained remission. Their level of psychopathology was similar to that in normal subjects and lower than that in symptomatic patients. On cognition, quality of well-being, and everyday functioning, the group with sustained remission was intermediate between the normal and symptomatic groups and differed significantly from the normal subjects.Sustained remission can occur even in older patients with very chronic illness, but its prevalence is lower than that in several published reports. Remission may reflect a return to premorbid functioning, consistent with neurodevelopmental hypotheses of schizophrenia.
A separation of clinical from epidermal thinning effect in the topical glucocorticoid clobetasone butyrate
Authors: D.V. STEVANOVIC, LYN WILSON, C.G. SPARKES
Journal: British Journal of Dermatology (1977)

Clobetasone butyrate ointment has been shown to be more effective in treating psoriasis and eczema than flurandrenolone ointment yet to cause less epidermal thinning in a human experimental model. This is an indication that the clinical activity of topical glucocorticoids may not necessarily be inseparable from their propensity to cause atrophy of the skin.
Surgical treatment for pulmonary aspergilloma: a 28 year experience
Authors: J. C. Chen, Y. L. Chang, S. P. Luh, J. M. Lee, Y. C. Lee
Journal: Thorax (1997)

Pulmonary aspergilloma has been treated surgically for many years but the mortality rates of larger surgical series, varying from 7% to 23%, is not considered acceptable by today's standards. The authors report their experience in the surgical treatment of pulmonary aspergilloma and present a review of the literature.Sixty seven patients who underwent thoracotomy for pulmonary aspergilloma from 1968 to 1995 were studied retrospectively by reviewing their medical records.The most common clinical presentation of pulmonary aspergilloma was haemoptysis which occurred in 61 patients (91.0%). Tuberculosis was the most common pre-existing disease, occurring in 54 patients (80.6%). The plain chest radiograph showed the typical "air-crescent" sign in 36 patients (53.7%). Systemic antifungal therapy neither palliated the clinical symptoms nor eradicated the aspergilloma, and transarterial embolisation was also unsuccessful. Surgery offered the only chance of cure for both unilateral and bilateral disease. Procedures varied from segmentectomy to pneumonectomy with most (61.4%) undergoing lobectomy. There was one death following surgery from pneumonia and 15 postoperative complications occurred in 12 patients-empyema (7), massive bleeding (3), bronchopleural fistula (2), wound infection (2), and Horner's syndrome (1). Postoperatively, most of the patients were symptom-free.With appropriate preoperative evaluation and judicious surgical technique, surgery is the preferred treatment for pulmonary aspergilloma, both for eradicating the tumour and for curing the underlying disease.
Inhibition of protein phosphatase 1 by inhibitor-2 exacerbates progression of cardiac failure in a model with pressure overload
Authors: S. Grote-Wessels, H. A. Baba, P. Boknik, A. El-Armouche, L. Fabritz, H.-J. Gillmann, D. Kucerova, M. Matus, F. U. Muller, J. Neumann, M. Schmitz, F. Stumpel, G. Theilmeier, J. Wohlschlaeger, W. Schmitz, U. Kirchhefer
Journal: Cardiovascular Research (2008)

AimsThe progression of human heart failure is associated with increased protein phosphatase 1 (PP1) activity, which leads to a higher dephosphorylation of cardiac regulatory proteins such as phospholamban. In this study, we tested the hypothesis whether the inhibitor-2 (I-2) of PP1 can mediate cardiac protection by inhibition of PP1 activity.
Concurrent chemoradiotherapy for N2 or N3 squamous cell carcinoma of the head and neck from an occult primary
Authors: A. Argiris, S.M. Smith, K. Stenson, B.B. Mittal, H.J. Pelzer, M.S. Kies, D.J. Haraf, E.E. Vokes
Journal: Annals of Oncology (2003)
Phase I Dose-Finding Study of Pazopanib in Hepatocellular Carcinoma: Evaluation of Early Efficacy, Pharmacokinetics, and Pharmacodynamics
Authors: Thomas Yau, Pei-Jer Chen, Pierre Chan, C. Martin Curtis, Philip S. Murphy, A. Benjamin Suttle, Jennifer Gauvin, Jeffrey P. Hodge, Mohammed M. Dar, Ronnie T. Poon
Journal: Clinical Cancer Research (2011)

A phase I dose-escalating study of pazopanib was conducted to determine the maximum tolerated dose (MTD), pharmacokinetic/pharmacodynamic relationships, and clinical activity in patients with advanced hepatocellular carcinoma (HCC).Asian patients (N = 28) were dose escalated on pazopanib (200-800 mg) once daily (QD) on 21-day cycles, with MTD as the primary endpoint using a modified 3 + 3 design. Changes in tumor vasculature were evaluated by dynamic contrast-enhanced MRI (DCE-MRI).Two of five patients at the 800-mg dose level experienced dose-limiting toxicities [grade 3 aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevations and grade 3 malaise]. The MTD in patients with HCC (Child-Pugh class A) was 600 mg QD. Diarrhea, skin hypopigmentation, and AST elevation were the most commonly reported adverse events at the MTD. Mean C(max) and area under the concentration-time curve (AUC(0-6)) of pazopanib and its metabolites did not increase dose proportionally across the 200 to 800 mg range. Reductions in IAUGC and K(trans) were shown at all pazopanib doses evaluated, with the greatest reductions at 600 and 800 mg. Although larger DCE-MRI parameter decreases were associated with larger C(24) and C(max) values, there was no constant relationship between tumor perfusion decreases measured by DCE-MRI and plasma pazopanib pharmacokinetic parameters. Overall, 19 patients (73%) had either partial response or stable disease.Pazopanib has a manageable safety profile in patients with advanced HCC, and 600 mg was chosen for further development of pazopanib in advanced HCCs. Moreover, pazopanib reduced tumor vessel leakage, as shown by DCE-MRI, indicating a direct effect on HCC vasculature that might be associated with its antitumor activity.
Differential expression of oestrogen receptor isoforms and androgen receptor in the normal vulva and vagina compared with vulval lichen sclerosus and chronic vaginitis
Authors: A.H. Taylor, M. Guzail, F. Al-Azzawi
Journal: British Journal of Dermatology (2007)

Although the expression of the oestrogen receptor (ER) alpha isoform and androgen receptor (AR) has been examined in vulval lichen sclerosus (VLS), the distribution pattern of ERalpha, ERbeta and AR has not been described in chronic atrophic vaginitis nor correlated with markers of proliferation (Ki-67) in either of these diseased tissues.To measure the levels and distribution of ERalpha, ERbeta and AR immunoreactivity in relation to Ki-67 in normal and diseased vulva and vagina.The expression of ERalpha, ERbeta and AR in relation to the proliferation marker Ki-67 in VLS, squamous hyperplasia of the vulva and chronic atrophic vaginitis was determined by immunohistomorphometric analysis and compared with that in normal vulva and vagina.VLS showed similar ERalpha and ERbeta expression in the 'epidermal' and 'dermal' tissue layers to that of normal vulvae, whereas AR expression appeared to be absent in most cases. ERbeta and Ki-67 expression was correlated with ERalpha expression but only in the 'fibrovascular' layer of the vulva. ERalpha expression was absent from the 'fibromuscular' layer of diseased vulvae, while ERbeta expression was absent in normal tissues but was highly expressed in diseased vulvae. ERalpha expression was significantly correlated with AR expression in the fibrovascular layer of the vagina and inversely correlated with Ki-67 staining in the parabasal cells of the epidermis in patients with chronic atrophic vaginitis.These data suggest that ER expression and levels may be implicated in the aetiopathology of VLS and chronic atrophic vaginitis.