tbuckley/cabot-search huggingface dataset:
The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis
Authors: Mustafa S. Ascha, Ibrahim A. Hanouneh, Rocio Lopez, Tarek Abu-Rajab Tamimi, Ariel F. Feldstein, Nizar N. Zein
Journal: Hepatology (2010)

Nonalcoholic steatohepatitis (NASH) is a well-recognized cause of cirrhosis and has been increasingly associated with the development of hepatocellular carcinoma (HCC). The aims of this study were to (1) estimate the incidence of HCC in patients with NASH-related cirrhosis, (2) compare incidence in NASH-related cirrhosis with hepatitis C virus (HCV)-related cirrhosis, and (3) identify risk factors of HCC in patients with NASH-related cirrhosis compared with HCV-related cirrhosis. Adult patients with cirrhosis secondary to chronic HCV (n = 315) or NASH (n = 195) were evaluated at our hepatobiliary clinic between 2003 and 2007. To assess for HCC development, all patients were monitored using serial abdominal computed tomography and serum alpha-fetoprotein every 6 months. Kaplan-Meier analysis was performed to estimate the cumulative incidence of HCC. Descriptive statistics were computed for all factors. Univariate and multivariate Cox regression analysis were used to assess associations between HCC and factors of interest. The median follow-up was 3.2 years (25th percentile [P25], 75th percentile [P75]: 1.7, 5.7) during which 25/195 (12.8%) of NASH-cirrhotic and 64/315 (20.3 %) of HCV-cirrhotic patients developed HCC ( P = 0.03). Yearly cumulative incidence of HCC was found to be 2.6% in patients with NASH-cirrhosis, compared with 4.0% in patients with HCV cirrhosis ( P = 0.09). Multivariate regression analysis revealed that older age ( P = 0.006) and alcohol consumption ( P = 0.002) were independent variables associated with development of HCC in patients with NASH-cirrhosis. Compared with nondrinkers, patients who reported any regular alcohol consumption were at greater risk for HCC development (hazard ratio: 3.6; P25, P75: 1.5, 8.3). Conclusion: Patients with NASH cirrhosis have a greatly increased risk of liver cancer. Alcohol consumption, a modifiable risk factor, appears to be the most significant factor associated with risk of HCC development in our study population. (Hepatology 2010;)
Treatment of Hodgkin's Disease: With What and By Whom?
Authors: JOHN R. DURANT
Journal: Annals of Internal Medicine (1970)

Editorials1 December 1970Treatment of Hodgkin's Disease: With What and By Whom?JOHN R. DURANT, M.D., F.A.C.P.JOHN R. DURANT, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-73-6-1033 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptUntil recently Hodgkin's disease has been considered a malignant disorder of multifocal origin which, although running a variable course, eventually terminated in the death of the patient. This view resulted in what Easson ( 1 ) has called a therapeutic attitude of "pessimism, procrastination, and pills." Despite overwhelming evidence favoring curability, the palliative attitude toward Hodgkin's disease has been very difficult to change. Nevertheless the concept that this disorder is curable has gradually gained acceptance primarily through the work of such radiotherapists as Gilbert, Easson, Peters, Kaplan, and Johnson. These investigators have shown indisputably that aggressive radiation therapy can cure...References1. EASSON E: The possibilities for the cure of Hodgkin's Disease. Cancer 19:345-350, 1966 CrossrefGoogle Scholar2. JOHNSONTHOMASSCHNEIDERMAN RLM: Preliminary experience with total nodal irradiation in Hodgkin's Disease. Radiology 96:603-608, 1970 CrossrefMedlineGoogle Scholar3. LACHER M: Chemotherapy of Hodgkin's disease. In press. Google Scholar4. CURRANJOHNSON RR: Tolerance to chemotherapy after prior irradiation for Hodgkin's disease. Ann Intern Med 72: 505-509, 1970 LinkGoogle Scholar5. MOORES R: Comparison of combination therapy vs. nitrogen mustard in Hodgkin's disease. Proc Amer Ass Cancer Res 11: 58, 1970 Google Scholar6. : Unpublished data Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: JOHN R. DURANT, M.D., F.A.C.P.Affiliations: Cancer Research and Training Program University of Alabama in Birmingham Birmingham, Ala. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byImproved survival in the treatment of advanced hodgkin's disease at a nonuniversity institution (1970–1979)Hodgkin’s Disease 1 December 1970Volume 73, Issue 6Page: 1033-1035KeywordsHodgkin lymphomaRadiation therapyRunning ePublished: 1 December 2008 Issue Published: 1 December 1970 PDF downloadLoading ...
Bias in Phylogenetic Reconstruction of Vertebrate Rhodopsin Sequences
Authors: Belinda S. W. Chang, Dana L. Campbell
Journal: Molecular Biology and Evolution (2000)

Two spurious nodes were found in phylogenetic analyses of vertebrate rhodopsin sequences in comparison with well-established vertebrate relationships. These spurious reconstructions were well supported in bootstrap analyses and occurred independently of the method of phylogenetic analysis used (parsimony, distance, or likelihood). Use of this data set of vertebrate rhodopsin sequences allowed us to exploit established vertebrate relationships, as well as the considerable amount known about the molecular evolution of this gene, in order to identify important factors contributing to the spurious reconstructions. Simulation studies using parametric bootstrapping indicate that it is unlikely that the spurious nodes in the parsimony analyses are due to long branches or other topological effects. Rather, they appear to be due to base compositional bias at third positions, codon bias, and convergent evolution at nucleotide positions encoding the hydrophobic residues isoleucine, leucine, and valine. LogDet distance methods, as well as maximum-likelihood methods which allow for nonstationary changes in base composition, reduce but do not entirely eliminate support for the spurious resolutions. Inclusion of five additional rhodopsin sequences in the phylogenetic analyses largely corrected one of the spurious reconstructions while leaving the other unaffected. The additional sequences not only were more proximal to the corrected node, but were also found to have intermediate levels of base composition and codon bias as compared with neighboring sequences on the tree. This study shows that the spurious reconstructions can be corrected either by excluding third positions, as well as those encoding the amino acids Ile, Val, and Leu (which may not be ideal, as these sites can contain useful phylogenetic signal for other parts of the tree), or by the addition of sequences that reduce problems associated with convergent evolution.
A randomized controlled trial of lamivudine to treat acute hepatitis B
Authors: M. Kumar, S. Satapathy, R. Monga, K. Das, S. Hissar, C. Pande, B. C. Sharma, S. K. Sarin
Journal: Hepatology (2006)

The role of antivirals in patients with acute viral hepatitis B (AVH-B) has not been evaluated in controlled trials. The aim of this study was to evaluate the efficacy of lamivudine in patients with AVH-B. AVH-B patients with serum bilirubin of more than 5 mg/dL were randomized to receive either 100 mg of lamivudine daily for 3 months (group 1, n = 31) or placebo (group 2, n = 40). Patients were considered to have severe AVH-B if they fulfilled 2 of 3 criteria: (1) hepatic encephalopathy; (2) serum bilirubin ≥ 10.0 mg/dL; and (3) international normalized ratio (INR) ≥ 1.6. At week 4, HBV DNA levels were significantly lower ( P = 0.037) in group 1 (median: 3.6721 log copies/mL) than group 2 (median: 4.2721 log copies/mL). Thereafter, HBV DNA levels were comparable in the 2 groups. The improvement in serum bilirubin, ALT, and INR values was similar in the 2 groups. Twenty-two patients (71%) in group 1 and 25 patients (62.5%) in group 2 had severe AVH-B. Results were similar when patients with severe AVH-B were analyzed separately. After 12 and 18 months, 93.5% and 92.5%, respectively, of patients in the lamivudine group and 96.7% and 97.5%, respectively, of patients in the placebo group lost HBsAg. There were no deaths in either group. After 1 year, 21 patients (67.7%) in group 1 and 34 patients (85%) in group 2 developed protective anti-HBs titers ( P = 0.096). All HBeAg-positive patients in both groups lost e antigen and anti-HBe developed in 71% and 87.5% of patients in groups 1 and 2, respectively ( P = 0.132). Conclusion: Though lamivudine causes a greater decrease in levels of HBV DNA, it does not cause significantly greater biochemical and clinical improvement as compared to placebo in patients with acute hepatitis B. Hepatology 2007;45:97–101.)
Effect of caspase inhibitors on myocardial infarct size and myocyte DNA fragmentation in the ischemia–reperfused rat heart
Authors: T Okamura
Journal: Cardiovascular Research (2000)

Objective: Caspase family proteases are recognized as key mediators of apoptosis. However, the role of caspases in the ischemia–reperfused heart remains uncertain. We evaluated the effect of caspase inhibitors on myocardial infarct size and the myocyte DNA fragmentation in the ischemia–reperfused rat hearts. Methods: Three groups of Sprague–Dawley rats (n=7, each) were subjected to 30 min of ischemia followed by 6 h of reperfusion. One of the following drugs: (1) YVAD-aldehyde, a caspase-1-like protease inhibitor (3.5 mg/kg; YVAD), (2) DEVD-aldehyde, a caspase-3-like protease inhibitor (3.5 mg/kg, DEVD), (3) vehicle (140 μl/kg) was administered intravenously 5 min prior to the ischemia in each group. Myocardial infarct size was defined by triphenyltetrazolium chloride (TTC) staining. Immunohistochemical staining by in situ nick end labeling (TUNEL) of cardiomyocytes and DNA electrophoresis were used for detecting DNA fragmentation. Ultrastructural analysis was done by electron microscopy. The caspase activity was measured in the myocardium of both groups. Results: The percentage of TUNEL-positive myocyte nuclei (%AP) was quantified by microscopy. A ladder pattern was detected by electrophoresis of DNA from the risk area and TUNEL-positive myocytes were seen in the risk area. The %AP was significantly reduced from 20±1% to 12±3% by YVAD and to 10±3% by DEVD (both P<0.01). However, caspase inhibitors did not significantly change the infarct size. Electronmicrograph showed similar salcolemmal and mitochondrial damage in both group. The caspase activity was blocked by DEVD at 4 h after reperfusion. Conclusion: Myocyte DNA fragmentation and caspase activation was inhibited by caspase inhibitors without reduction of the infarct size in ischemia–reperfused rat hearts.
Emerging Infectious Diseases
Authors: Anthony S. Fauci
Journal: JAMA (2004)

Extraordinary strides in identifying and eliminating the pathogens behind many of the major scourges of the last century prompted the US Surgeon General in 1967 to declare that the war against infectious diseases had been won. But the announcement was premature. The steady stream of emerging and reemerging infectious diseases since the 1960s has been a sobering wake-up call. Despite many accomplishments in the realm of antibiotics and vaccines such a declaration of victory was not justified. It is now clearer than ever that the human species is in the midst of a war with the microbial world—a resilient foe that will never be completely defeated. The AIDS pandemic illustrates how a new human pathogen emerged as a result of a complex series of opportunities that were presented to an unusual virus that first infected primates. After the virus crossed over to humans most likely as a result of genetic mutations together with accidental transmission human immunodeficiency virus (HIV) rapidly spread among different population groups due to profound changes in social and economic conditions in certain countries. (excerpt)
The Discovery of Drug-Induced Illness
Authors: Hershel Jick
Journal: New England Journal of Medicine (1977)

The increased use of drugs (and the concurrent increased risks of drug-induced illness) require definition of relevant research areas and strategy. For established marketed drugs, research needs depend on the magnitudes of risk of an illness from a drug and the base-line risk. With the drug risk high and the base-line risk low, the problem surfaces in premarketing studies or through the epidemic that develops after marketing. If the drug adds slightly to a high base-line risk, the effect is undetectable. When both risks are low, adverse effects can be discovered by chance, but systematic case-referent studies can speed discovery. If both risks are high, clinical trials and nonexperimental studies may be used. With both risks intermediate, systematic evaluations, especially case-referent studies are needed. Newly marketed drugs should be routinely evaluated through compulsory registration and follow-up study of the earliest users.
Responsiveness of the core set, response criteria, and utilities in early rheumatoid arthritis
Authors: A C Verhoeven
Journal: Annals of the Rheumatic Diseases (2000)

Validation of responsiveness and discriminative power of the World Health Organisation/International League of Associations for Rheumatology (WHO/ILAR) core set, the American College of Rheumatology (ACR), and European League for Rheumatology (EULAR) criteria for improvement/response, and other single and combined measures (indices) in a trial in patients with early rheumatoid arthritis (RA).Ranking of measures by response (standardised response means and effect sizes) and between-group discrimination (unpaired t test and chi(2) values) at two time points in the COBRA study. This study included 155 patients with early RA randomly allocated to two treatment groups with distinct levels of expected response: combined treatment, high response; sulfasalazine treatment, moderate response.At week 16, standardised response means of core set measures ranged between 0.8 and 3.5 for combined treatment and between 0.4 and 1.2 for sulfasalazine treatment (95% confidence interval +/-0.25). Performance of patient oriented measures (for example, pain, global assessment) was best when the questions were focused on the disease. The most responsive single measure was the patient's assessment of change in disease activity, at 3.5. Patient utility, a generic health status measure, was moderately (rating scale) to poorly (standard gamble) responsive. Response means of most indices (combined measures) exceeded 2.0, the simple count of core set measures improved by 20% was most responsive at 4.1. Discrimination performance yielded similar but not identical results: best discrimination between treatment groups was achieved by the EULAR response and ACR improvement criteria (at 20% and other percentage levels), the pooled index, and the disease activity score (DAS), but also by the Health Assessment Questionnaire (HAQ) and grip strength.Responsiveness and discrimination between levels of response are not identical concepts, and need separate study. The WHO/ILAR core set comprises responsive measures that discriminate well between different levels of response in early RA. However, the performance of patient oriented measures is highly dependent on their format. The excellent performance of indices such as the ACR improvement and EULAR response criteria confirms that they are the preferred primary end point in RA clinical trials.
Success with infliximab in treating refractory hemophagocytic lymphohistiocytosis
Authors: Tomoko Henzan, Koji Nagafuji, Hiroshi Tsukamoto, Toshihiro Miyamoto, Hisashi Gondo, Shinsaku Imashuku, Mine Harada
Journal: American Journal of Hematology (2005)

Abstract Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder characterized by fever, pancytopenia, hepatosplenomegaly, liver dysfunction, and hemophagocytosis. A 29‐year‐old woman, diagnosed with systemic lupus erythematosus in 1996, developed HLH in early June 2002. HLH remained refractory during 1.5 months of treatment including corticosteroid, cyclosporine, plasma exchange, vincristine, and etoposide. Infliximab (5 mg/kg/day) was then administered twice. After the second administration, the patient attained remission. Because HLH itself is not a neoplasm but an uncontrolled immune reaction, blocking cytokines involved in the reaction should have therapeutic potentials. For HLH patients not responding to conventional therapy, anticytokine treatment with infliximab may represent one of promising options. Am. J. Hematol. 81:59–61, 2006. © 2005 Wiley‐Liss, Inc.
Disseminated Aspergillosis in a Presumably Immunocompetent Host
Authors: Henry D'Silva
Journal: JAMA (1982)

Disseminated aspergillosis was found in an apparently healthy man. Although he had a history of diabetes and recent alcohol ingestion, there was no pathological evidence of diabetes mellitus or cirrhosis at autopsy.  ( JAMA 1982;248:1495-1497)
Diminished inotropic responsiveness to ouabain in aged rat myocardium.
Authors: G Gerstenblith, H A Spurgeon, J P Froehlich, M L Weisfeldt, E G Lakatta
Journal: Circulation Research (1979)

We studied the effect of advanced age on the response to paired pacing and on the relationship between ouabain-induced inotropy and inhibition of (Na + K)-ATPas€ in hearts from young adult and senescent rats.In isometric trabeculae carneae, control values of developed tension (DT) and maximal rate of tension development (dT/dt) were not age-related.There was no age-related difference in the response to extrasystolic potentiation at prematurity intervals from 400 msec to the mechanical refractory period.The maximal response occurred at a prematurity interval of 200 msec and was above 200% of control.The inotropic response to ouabain occurred over a concentration range from 2 x 10~6 to 6 x 10" s M. DT and dT/dt in muscles from the young adult group exhibited a greater response than those from the senescent group; e.g., at 6 x 10" s M both parameters were approximately four times greater in the former group.There was no age-dependent difference in ouabain-induced enzyme inhibition, which occurred over the same concentration range as did ouabain-induced alterations in mechanical function.These data indicate that paired pacing, but not ouabain, results in similar increases in inotropy and therefore similar increases in myoplasmic calcium concentration in young adult and aged rat myocardium.The age-dependent difference in ouabain responsiveness appears to be related to an age-associated alteration in a step other than enzyme inhibition linking ouabain binding to increased myoplasmic calcium levels.
Particulate guanylyl cyclase and cholinergic control of cardiac excitability is site specific
Authors: N. Herring, J. A.B. Zaman, D. J. Paterson
Journal: Cardiovascular Research (2002)

We read with interest the recent study by Imai et al. [7] citability is controversial.Han et al. [3] first proposed that who provide evidence that muscarinic inhibition of pre-stimulation of muscarinic receptors in sinoatrial node cells stimulated L-type calcium current (I ) may involve an increases nitric oxide (NO) production via endothelial NO CaL increase in cGMP levels via particulate guanylyl cyclase.synthase (eNOS).Stimulation of soluble guanylyl cyclase This mechanism is apparent when cAMP has been raised was essential for cholinergic inhibition of L-type calcium by inhibition of phosphodiesterase.The role of the cGMP current (I ) following adrenergic pre-stimulation, al-CaL CaN
Abstract B33: Langerhans cells prevent melanocytic nevus development and transformation in mice.
Authors: Tahseen H. Nasti, Yuko Tsuruta, Kris McKay, Mohammad Athar, Craig Elmets, Laura Timares
Journal: Cancer Research (2015)

Abstract The function of Langerhans cells (LCs) in the skin immune system is unclear, and a matter of intense debate. In different mouse models LCs have been shown to induce antitumor immunity or promote skin squamous cell carcinoma (SCC). Their role in the control or promotion of melanoma is not known. We assessed LC's role in the development of DMBA-TPA induced pigmented benign and transformed lesions in a novel mouse model. Transgenic HuLang-DTA+/- C57Bl/6 mice, which selectively ablate epidermal LCs, were crossed with C3H/HeN mice to generate F1 LC knockout (KO) and WT littermate controls. LC-KO mice developed 40% more and 2-fold larger melanocytic lesions than WT. Cell suspensions from LC-KO pigmented skin lesions contained increased CD4+ Foxp3+ regulatory T cells and CD11b-/loGr-1hi cells, consistent with an immunosuppressive microenvironment. CD11c+CD11b+Ly6C+ APCs or MHCII+ cell numbers were fewer in lesions from LC-KO as compared to WT mice. Nests of melanocytic cells were observed at a higher frequency in draining lymph nodes (dLNs) from LC-KO as compared to WT; DLN cells contained increased numbers of TRP2+ cells and routinely gave rise to proliferative melanocytic cell lines. Real-time PCR analysis of epidermal cDNA from TPA treated LC-KO, as compared to WT, demonstrated a profound loss of IL-10, IL-12p35 and IL-12p40, indicating LCs as the major source. Further, IL-23 steady state levels in the epidermis of LC-KO are increased greater than 3-fold over WT, indicating that LCs normally suppress keratinocyte production of IL-23. Thus, in contrast to SCC, LCs inhibit development of benign and metastatic pigmented tumors. This novel murine model will be useful in elucidating transformation mechanisms and identifying novel therapeutic targets that may prevent metastatic melanoma. Citation Format: Tahseen H. Nasti, Yuko Tsuruta, Kris McKay, Mohammad Athar, Craig Elmets, Laura Timares. Langerhans cells prevent melanocytic nevus development and transformation in mice.. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr B33. doi:10.1158/1538-7445.CHTME14-B33
INTRADERMAL SALT SOLUTION TEST IN SCARLET FEVER AND DIPHTHERIA PATIENTS
Authors: WILLIAM J. BAKER
Journal: JAMA (1924)

In July, 1923, McClure and Aldrich 1 reported that the elevation or wheal produced by the intradermal injection of 0.2 c.c. of an 0.8 per cent, solution of sodium chlorid disappeared much more rapidly in a group of children having edema than it did in a group of control cases. Later they 2 used the test in sixteen cases, in children, characterized by generalized edema, albuminuria, casts and in some cases red blood cells in the urine, and unassociated with nitrogen retention in the blood or evidence of cardiovascular disease. In these cases they found that, in a general way, the greater the edema the shorter was the disappearance time, and vice versa; that when tests were made in patients with developing edema, a reduction of the disappearance time preceded other clinical evidences of edema by several days. In certain improving edematous patients, they observed an increase of the disappearance