tbuckley/cabot-search huggingface dataset:
Binding Kinetics of Tetrachloro-1,2-diaminocyclohexaneplatinum(IV) (Tetraplatin) and cis-Diamminedichloroplatinum(II) at 37 C With Human Plasma Proteins and With Bovine Serum Albumin. Does Aquation Precede Protein Binding?
Authors: A. F. LeRoy, W. C. Thompson
Journal: JNCI Journal of the National Cancer Institute (1989)

Experiments were conducted at 37 degrees C to study the kinetics of (a) binding of cis-diamminedichloroplatinum (II) (CDDP) and of a racemic mixture of d- and l-isomers of trans-tetrachloro-1,2-diaminocyclohexaneplatinum (IV) [or tetraplatin (TP)] to protein [human plasma proteins or bovine serum albumin (BSA)]; (b) aquation (acid hydrolysis) of CDDP and of TP; and (c) binding of charged (aquated) CDDP species to BSA. The experiments were performed at clinically relevant concentrations for CDDP, so that the proportional concentrations of platinum complexes relative to the concentrations of other chemical species in blood plasma were similar to those obtaining in the clinical use of the drug. "Free" (unbound) platinum complexes were separated from the protein-bound complexes were separated from the protein-bound complexes by gel filtration chromatography. By use of ion-exchange chromatography, charged platinum species were separated from the uncharged species and free charged platinum species of CDDP were separated from those bound to BSA. Platinum in various fractions was quantitated by atomic absorption spectrophotometry with electrothermal atomization; proteins were quantitated by te Bradford method with Coomassie blue dye. The kinetic data obtained by the application of these methods for CDDP are in good agreement with those obtained by other methods, e.g., binding rates based on separations by centrigugal ultrafiltration. The overall protein-binding reaction of CDDP was consistent with a binding process comprising two consecutive first-order reaction steps: the rate-controlling aquation reaction [half-life (t 1/2), approximately 2 hr] followed by a more rapid binding reaction of the charged (aquated) CDDP species to the protein (t 1/2, approximately 23 min). However, the results for TP indicated that prior aquation was not required for protein binding, and we could surmise that binding of TP to protein proceeds via a direct nucleophilic attack. An unexpected finding was the marked, reproducible difference in rates of aquation between the two lots of TP that we used; this finding suggests the need for cautions evaluation of pharmacokinetic data describing the behavior of TP.
Metastatic Prostate Cancer Proven by 18F-FCH PET/CT Staging Scan in Patient With Normal PSA but High PSA Doubling Time
Authors: Marina Hodolič, Anna Margherita Maffione, Jure Fettich, Borut Gubina, Marino Cimitan, Domenico Rubello
Journal: Clinical Nuclear Medicine (2013)

A 59-year-old man presented with frequent urination. Six months ago, his prostate-specific antigen (PSA) was 1.56 ng/mL; currently it is 3.5 ng/mL (PSA doubling time = 6 months; PSA velocity = 0.19 ng/mL/mo). Biopsy revealed aggressive prostate cancer (Gleason score 5 + 5). Staging with (18)F-fluorocholine PET/CT ((18)F-FCH PET/CT) demonstrated lymph node metastasis. After 6 months of hormonal therapy with goserelin, PSA decreased to 0.38 ng/mL. A (18)F-FCH PET/CT restaging scan demonstrated a global reduction of (18)F-FCH lesion uptake with disappearance of some mediastinal and iliac pelvic lymph node activity.
Eosinophilic Fasciitis Evolving into Scleroderma
Authors: A. URBANO-MARQUEZ
Journal: Annals of Internal Medicine (1983)

Letters and Corrections1 September 1983Eosinophilic Fasciitis Evolving into SclerodermaA. URBANO-MARQUEZ, M.D.A. URBANO-MARQUEZ, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-99-3-412_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Fasciitis with eosinophilia is a disorder characterized by thickening and inflammation of the muscular fascia (1). Many authors consider it a variety of scleroderma that mainly involves fascia and subcutaneous tissue (2). We report the case of a patient two developed clinical features of fasciitis with eosinophilia that turned into progressive scleroderma in 3 months.A 41-year-old man who had had palindromic rheumatism for 12 years was hospitalized with a 1-month history of pain and swelling of the forearms and legs. On admission, the skin affected was indurated and edematous. The erythrocyte sedimentation rate was 120 mm/h...References1. MOUTSOPOULOSWEBBERPAULIDISFOSTIROPOULOSGOULESSHULMAN HBNGDD. Diffuse fasciitis with eosinophilia: a clinicopathologic study. Am J Med. 1980;68:701-9. CrossrefMedlineGoogle Scholar2. MICHETDOYLEGINSBURG CJW. Eosinophilic fasciitis: report of 15 cases. Mayo Clin Proc. 1981;56:27-34. MedlineGoogle Scholar3. LEWKONIALENNARTATKINSON RHM. Granulomatous vasculitis in the syndrome of diffuse fasciitis with eosinophilia. Arch Intern Med. 1982;1:73-5. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Hospital Clinico Provincial de Barcelona Barcelona, Spain PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byA Woman with Limb Swelling and Pain This case was reported by Owens W, Bertorini T, Holt H Jr, Shadle M: Diffuse fasciitis with eosinophilia (Shulman syndrome). J Clin Neuromuscul Dis 6(2):99–101, 2004.Diffuse Fasciitis With Eosinophilia (Shulman Syndrome)CARPAL TUNNEL SYNDROME ASSOCIATED WITH EOSINOPHILIC FASCIITISEosinophilic fasciitis: A good response with conservative treatmentEosinophilic fasciitis in association with chronic vasculitic-like leg ulcerationsPALMAR FASCIITIS AND POLYARTHRITIS ASSOCIATED WITH A MALIGNANT NEOPLASM: A PARANEOPLASTIC SYNDROMEFasciitis, perimyositis, myositis, polymyositis, and eosinophiliaAttitude en crochet bilatérale des doigts par fasciite avec éosinophilie (syndrome de Shulman)Morphea developing in patients previously affected with eosinophilic fasciitisEosinophilic fasciitis: Clinical spectrum and therapeutic response in 52 casesSeltenere Immundermatosen mit Gelenkbeteiligung (Dermatomyositis, Sjögren-Syndrom, Sharp-Syndrom u.a.)Toxic oil syndrome, scleroderma, and eosinophilic fasciitis 1 September 1983Volume 99, Issue 3Page: 412-412KeywordsEosinophiliaErythrocyte sedimentation rateInflammationPainRheumatic painScleroderma Issue Published: 1 September 1983 PDF downloadLoading ...
Protecting Patient Privacy Redux: Response to Open Peer Commentaries on “‘You Don't Know Me, But …’: Access to Patient Data and Subject Recruitment in Human Subjects Research”
Authors: Toby Schonfeld, Joseph S. Brown, N. Jean Amoura, Bruce Gordon
Journal: The American Journal of Bioethics (2012)

Click to increase image sizeClick to decrease image size Acknowledgments This response piece refers to the article “You Don't Know Me, But …”: Access to Patient Data and Subject Recruitment in Human Subjects Research (2011) which appeared in The American Journal of Bioethics 11(11): 32–38.
A novel risk score to predict cardiovascular disease risk in national populations (Globorisk): a pooled analysis of prospective cohorts and health examination surveys
Authors: Kaveh Hajifathalian, Peter Ueda, Yuan Lu, Mark Woodward, Alireza Ahmadvand, Carlos A Aguilar-Salinas, Fereidoun Azizi, Renata Cifkova, Mariachiara Di Cesare, Louise Eriksen, Farshad Farzadfar, Nayu Ikeda, Davood Khalili, Young-Ho Khang, Vera Lanska, Luz León-Muñoz, Dianna Magliano, Kelias P Msyamboza, Kyungwon Oh, Fernando Rodríguez-Artalejo, Rosalba Rojas-Martinez, Jonathan E Shaw, Gretchen A Stevens, Janne Tolstrup, Bin Zhou, Joshua A Salomon, Majid Ezzati, Goodarz Danaei
Journal: The Lancet Diabetes & Endocrinology (2015)
Double-Blind, Fixed-Dose, Placebo-Controlled Study of Paroxetine in the Treatment of Panic Disorder
Authors: James C. Ballenger, David E. Wheadon, Martin Steiner, William Bushnell, Ivan P. Gergel
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: This study was designed to determine the minimum paroxetine dose effective for treating panic disorder. METHOD: Of 425 patients with DSM-III-R panic disorder with or without agoraphobia who underwent a 2-week drug-free screening period, 278 patients were randomly assigned to double-blind treatment with a 10-week course of placebo or paroxetine at a dose of 10, 20, or 40 mg/day. RESULTS: At 40 mg/day, paroxetine was superior to placebo across the majority of outcome measures. Despite a mean of 9.5 to 11.6 full panic attacks during the screening period, 86.0% of the patients taking 40 mg of paroxetine, 65.2% of those taking 20 mg, 67.4% of those taking 10 mg, and 50.0% of the placebo-treated patients were free of full panic attacks during the 2 weeks ending at week 10. The 40-mg paroxetine group experienced significantly greater global improvement than the placebo group and significantly greater improvement in frequency of full and limited-symptom panic attacks, intensity of full panic attacks, phobic fear, anxiety, and depressive symptoms, usually evident by week 4. All doses of paroxetine were well tolerated, and adverse effects were consistent with those associated with selective serotonin reuptake inhibitors. CONCLUSIONS: Paroxetine is an effective and well-tolerated short-term treatment of panic disorder. The minimum dose demonstrated to be significantly superior to placebo was 40 mg/day, although some patients did respond at lower doses. (Am J Psychiatry 1998; 155:36–42)
715. Noninvasive Bioluminescence Imaging of Gene Expression Following Intracerebral Gene Delivery of AAV and Adenovirus into the Mouse Brain
Authors: Perry Liu, Hideyuki Migita, Heather Gibson, Harald Petry, Linda Cashion, Terry Hermiston, Katalin Kauser, Rick Harkins, Gabor M. Rubanyi, Ron Vergona, Hu Sheng Qian
Journal: Molecular Therapy (2005)
On the Past and Present Treatment of Insanity
Authors: G. F. Bodington
Journal: BMJ (1876)

UUIyY 2% Ad- organism of the fever-excitant, the pyrogenic matter (be this conttaitn Zizvum or what it may), and the onset of the characteristic phenomena,has not yet been demonstrated; in other words, the proximate cause of fever remains undetermined.Several minor lacrtnce and unsettled questions we have had occasion to notice.The work we have passed in review, as before observed, is almost
Therapeutic Efficacy of Bone Marrow Transplant, Intracranial AAV-mediated Gene Therapy, or Both in the Mouse Model of MPS IIIB
Authors: Coy D Heldermon, Kevin K Ohlemiller, Erik D Herzog, Carole Vogler, Elizabeth Qin, David F Wozniak, Yun Tan, John L Orrock, Mark S Sands
Journal: Molecular Therapy (2010)

Sanfilippo syndrome type B (MPS IIIB) is a lysosomal storage disease resulting from a deficiency of N-acetyl-glucosaminidase (NAGLU) activity. In an attempt to correct the disease in the murine model of MPS IIIB, neonatal mice were treated with intracranial AAV2/5-NAGLU (AAV), syngeneic bone marrow transplant (BMT), or both (AAV/BMT). All treatments resulted in some improvement in clinical phenotype. Adeno-associated viral (AAV) treatment resulted in improvements in lifespan, motor function, hearing, time to activity onset, and daytime activity level, but no reduction of lysosomal storage. BMT resulted in improved hearing by 9 months, and improved circadian measures, but had no effect on lifespan, motor function, or central nervous system (CNS) lysosomal storage. AAV/BMT treatment resulted in improvements in hearing, time to activity onset, motor function, and reduced CNS lysosomal storage, but had no effect on lifespan. Combination therapy compared to either therapy alone resulted in synergistic effects on hearing and CNS lysosomal inclusions but antagonistic effects on motor function and lifespan. AAV alone is more efficacious than BMT or AAV/BMT treatment for lifespan. BMT was the least efficacious treatment by all measures. CNS-directed AAV treatment alone appears to be the preferred treatment, combining the most efficacy with the least toxicity of the approaches assessed. Sanfilippo syndrome type B (MPS IIIB) is a lysosomal storage disease resulting from a deficiency of N-acetyl-glucosaminidase (NAGLU) activity. In an attempt to correct the disease in the murine model of MPS IIIB, neonatal mice were treated with intracranial AAV2/5-NAGLU (AAV), syngeneic bone marrow transplant (BMT), or both (AAV/BMT). All treatments resulted in some improvement in clinical phenotype. Adeno-associated viral (AAV) treatment resulted in improvements in lifespan, motor function, hearing, time to activity onset, and daytime activity level, but no reduction of lysosomal storage. BMT resulted in improved hearing by 9 months, and improved circadian measures, but had no effect on lifespan, motor function, or central nervous system (CNS) lysosomal storage. AAV/BMT treatment resulted in improvements in hearing, time to activity onset, motor function, and reduced CNS lysosomal storage, but had no effect on lifespan. Combination therapy compared to either therapy alone resulted in synergistic effects on hearing and CNS lysosomal inclusions but antagonistic effects on motor function and lifespan. AAV alone is more efficacious than BMT or AAV/BMT treatment for lifespan. BMT was the least efficacious treatment by all measures. CNS-directed AAV treatment alone appears to be the preferred treatment, combining the most efficacy with the least toxicity of the approaches assessed.
Kinetics of lymphocyte subpopulation in intestinal mucosa of protein deficient Giardia lamblia infected mice.
Authors: P Upadhyay, N K Ganguly, B N Walia, R C Mahajan
Journal: Gut (1986)

Kinetics of gut lymphocyte subpopulations were studied in normal and malnourished groups of mice infected with Giardia lamblia. The maximum parasite load was observed at second, third, and first week of postinfection in normal controls, moderate (8%) and severe (3%) protein deficient groups respectively. The number of G lamblia trophozoite in 3% protein deficient group was low compared with control groups. A significant increase in T cell population of intraepithelial lymphocytes and lamina propria in normal and moderate protein deficient groups was observed with the development of infection. It was less marked, however, in the severely malnourished group. Interplay of mucosal immune status with nutrition and G lamblia infection is discussed.
Keeping pace with new technologies: systems needed to identify and evaluate them
Authors: A. Stevens, R. Milne, R. Lilford, J. Gabbay
Journal: BMJ (1999)

Of the three major pressures on health services worldwide—changing demography, growing expectations, and new healthcare interventions (technologies) —the last is generating the most concern and the most dramatic responses. New healthcare technologies are becoming more numerous, more expensive, and possibly more effective than ever before. About 50 new drugs are launched each year, and the number of new devices, procedures, and ways of providing care is growing all the time. 

#### Summary points

New and changing technologies are a major pressure on health services, challenging cost control and research capacity

The NHS system to identify and evaluate new technologies and select the most important ones for assessment needs to develop a range of suitable research methods and the means to disseminate knowledge and implement the technologies

A pragmatic research solution is evolving, with rapid reviews, modelling, economic evaluation, and pragmatic trials as well as the mainstream efficacy trials and Cochrane reviews

Closer contact between research managers and the research team and new tools such as tracker trials may need to be developed too

Not only is there a challenge in relation to cost control, but, more compellingly, in relation to determining effectiveness.1 For example, it is often not clear:

Without this information there is a risk of distorted priorities as political pressure to keep a lid on budgets creates a tension between the claims of different technologies for part of the public purse.

In 1992 the Advisory Group on Health Technology Assessment suggested that the “costs of providing unevaluated new forms of care within the NHS should be met only if they are being offered within the …
Narrative Review: Protein Degradation and Human Diseases: The Ubiquitin Connection
Authors: Eyal Reinstein, Aaron Ciechanover
Journal: Annals of Internal Medicine (2006)

Between the 1950s and 1980s, many scientists focused on the process by which the genetic code is translated into proteome. However, little attention was devoted to the mechanism responsible for protein degradation. When researchers discovered the organelle lysosome, they assumed that cellular proteins were degraded within it. However, several independent lines of evidence strongly suggested that intracellular proteolysis was largely nonlysosomal. The discovery of the ubiquitin proteasome system (UPS) resolved this enigma. It is now recognized that degradation of intracellular proteins by the UPS is involved in the regulation of a broad array of cellular processes, including cell-cycle division; DNA repair, growth, and differentiation; quality control; and regulation of membrane receptors and ion channels. Not surprisingly, aberrations in thesystem have been implicated in the pathogenesis of numerous human diseases, and it seems that pharmacologic manipulation of the UPS might alter the outcome of many diseases, especially malignant conditions and possibly neurodegenerative and chronic inflammatory diseases. These findings have led to increasing efforts to develop mechanism-based drugs that modulate UPS activity, one of which is already on the market. In the near future, one can expect to see the development of new, potent, and highly specific drugs that target the degradation pathways of a single or a few proteins without affecting other proteins.
Direct Correlation of External Systolic Time Intervals with Internal Indices of Left Ventricular Function in Man
Authors: C. EDWIN MARTIN, JAMES A. SHAVER, MARK E. THOMPSON, P. SUDHAKAR REDDY, JAMES J. LEONARD
Journal: Circulation (1971)

Direct correlation of externally measured systolic time intervals with internally measured indices was obtained using catheter-tip micromanometers in six patients who had normal coronary arteriograms. Simultaneous recordings were made of central aorta and left ventricular pressure, maximum rate of rise in left ventricular pressure (dp/dt), external carotid pulse, external and internal sound, and electrocardiogram. Acute interventions were used to vary the indices by a variety of mechanisms including changes in contractility, preload, afterload, and heart rate. The initial values and the changes in these values produced by acute interventions are identical for left ventricular ejection time (LVET) whether measured externally (range 175 to 385 msec) or internally (range 169 to 392), r = 0.99. Although the absolute values differed for internally measured isovolumic contraction time (internal ICT), externally measured ICT, and preejection time (PEP), there was good linear correlation between the changes observed in these values following the interventions. Changes in PEP and internal ICT showed excellent linear correlation (r = 0.94) and were also alike in absolute value following the interventions. The interval from the Q wave of the electrocardiogram to rise in left ventricular pressure (electrical-mechanical delay) did not change significantly during these interventions. During a period of spontaneous isorhythmic dissociation there was close tracking between beat-to-beat changes in PEP and internal ICT and between externally and internally measured LVET. Following acute interventions PEP and left ventricular dp/dt changed inversely. Externally measured systolic time intervals have therefore been shown in man to correlate well with directly measured internal indices, both in steady-state conditions and during a series of acute interventions. This convenient and atraumatic method has been shown to be a valid and sensitive measure of myocardial performance.
Predicting who develops chronic low back pain in primary care: a prospective study
Authors: E. Thomas, A. J Silman, P. R Croft, A. C Papageorgiou, M. I V Jayson, G. J Macfarlane
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objectives:</b> To quantify the relative contribution of premorbid and episode specific factors in determining the long term persistence of disabling symptoms of low back pain. <b>Design:</b>Prospective cohort study. <b>Setting:</b> Two general practices in the south Manchester area. <b>Participants:</b> 180 patients, who previously participated in a cross sectional population survey, who consulted because of low back pain during the study period. They were followed at 1 week and 3 and 12 months after consultation. <b>Main outcome measure:</b> Persistent disabling low back pain in the 12 months after the consultation. <b>Results:</b> Disabling low back pain persisted in one third of participants after consultation and was more common with increasing age, among those with a history of low back pain, and in women. Persistence of symptoms was associated with “premorbid” factors (high levels of psychological distress (odds ratio 3.3; 95% confidence interval 1.5 to 7.2), poor self rated health (3.6; 1.9 to 6.8), low levels of physical activity (2.8; 1.4 to 5.6), smoking (2.1; 1.0 to 4.3), dissatisfaction with employment (2.4; 1.3 to 4.5)) and factors related to the episode of low back pain (duration of symptoms, pain radiating to the leg (2.6; 1.3 to 5.1), widespread pain (6.4; 2.7 to 15), and restriction in spinal mobility). A multivariate model based on six factors identified groups whose likelihood of persistent symptoms ranged from 6% to 70%. <b>Conclusions:</b> The presence of persistent low back pain is determined not only by clinical factors associated with pain but also by the premorbid state
Preventive Care for HIV-Positive Adults-Reply
Authors: John Jewett
Journal: JAMA (1993)

<h3>In Reply.</h3> —Drs Olson, Wallace, Weiss, and Kennedy argue that annual testing of<i>Toxoplasma</i>IgG titers in HIV-infected patients is unnecessary. We agree that the low rate of<i>Toxoplasma</i>seroconversion documented in their recent study suggests that annual testing, which we mentioned in our article, is probably unnecessary. We believe that it may still be useful to repeat testing in patients with negative titers once a patient's CD4 cell count is below 0.20×10<sup>9</sup>/L, particularly in areas where exposure to toxoplasmosis may be more frequent than in the western United States where their study was performed. Prior to a CD4 cell count of 0.20×10<sup>9</sup>/L,<i>Toxoplasma</i>encephalitis is unlikely.<sup>1</sup>Thus, test results are unlikely to have an important role in patient management at earlier stages of HIV, further diminishing the value of serial testing. We believe Dr Bachman's suggestion that teaching patients to seek immediate medical evaluation
DECREASED RESPONSE TO CLOPIDOGREL IS A RISK FACTOR FOR CARDIOVASCULAR EVENTS AFTER STENT IMPLANTATION : CROSS VERIFY STUDY
Authors: Chi-hoon Kim, Kyung-Woo Park, Kihyun Jeon, Si-Hyck Kang, Kyung-Hee Kim, Hae-Young Lee, Hyun-Jae Kang, Bon-Kwon Koo, Dae-Won Sohn, Byung-Hee Oh, Young-Bae Park, Hyo-Soo Kim
Journal: Journal of the American College of Cardiology (2010)