tbuckley/cabot-search huggingface dataset:
EXPERIMENTAL LIVER NECROSIS; II. ENZYMES
Authors: Richard M. Pearce, Holmes C. Jackson
Journal: The Journal of Experimental Medicine (1907)

1. The presence of blood serum has a decided inhibitory effect on autolysis. Thus in the normal unwashed organs the non-coagulable nitrogen increase was 100 to 300 per cent., while in the washed it amounted to 450 per cent. The washed necrotic livers showed an increase of from 600 to 850 per cent., while that of the unwashed necrotic was only slightly above the normal unwashed. 2. While the initial amount of non-coagulable nitrogen varies it is greater in those livers showing the more extensive forms of necrosis. The final amount of autolysis is also greatest in livers of this type. As regards the rate of autolysis fifty per cent. of the total occurs in the first day in the normal and in all types of lesions both washed and unwashed. The maximum is usually reached on the third day in the unwashed, while in the washed there is a continued increase to the eighth day. At this time in the necrotic livers about two to three times as much of the total nitrogen is in the form of non-coagulable nitrogen as in the normal. 3. In the necrotic tissue the initial controls show the content of monamino-acids, with one exception, to be practically doubled. In the washed necrotic the final amount is seventy per cent. of the total nitrogen against forty-six to fifty-seven per cent. in the washed normal. In all cases the monamino-acid nitrogen runs parallel to the nitrogen in non-coagulable form, but in relation to the total nitrogen it shows a greater increase in the washed than in the unwashed organs. 4. The ammonia production in the necrotic livers as shown by the partition experiments is greater than that in the normal and this increase corresponds to that of the non-coagulable nitrogen. In the experiments concerning the absolute production of ammonia in the presence of serum a greater amount was produced in the two and five hours' lesions than in the normal livers. On the other hand, the forty-eight hour diffuse necrosis equaled the normal and the focal fell below. 5. Arginase was obtained from normal but could not be isolated from necrotic livers. 6. No constant relation could be demonstrated between the anatomical lesion in the liver and the presence of leucin and tyrosin in the urine. Leucin was found occasionally in the urine, but none in the liver. On the other hand, tyrosin was constantly present in livers with diffuse but rarely in those with focal necrosis. In the instances of diffuse necrosis in which the liver and urine of the same animal were examined tyrosin was found in both. 7. The presence of large amounts of proteoses in the necrotic liver indicates that the elimination of these substances (colloidal nitrogen of Salkowski) under such circumstances may account for a part of the total nitrogen of the urine usually attributed to the monamino-acids.
Interpreting outcome measures and defining treatment success
Authors: J.R. Ingram
Journal: British Journal of Dermatology (2013)

ORIGINAL ARTICLE, p 1326 Outcome measures research provides one of the fundamental building blocks for clinical trials throughout medicine. What defines treatment success or failure? In the process of bringing new drugs to market, disease severity scales have often been created without an initial evidence base to demonstrate validity and reliability. A classic example of this is the Psoriasis Area and Severity Index (PASI) scale, which was developed as part of a psoriasis clinical trial.1 Ideally, an outcome measure should be simple to understand, relevant to patients and clinicians, quick to perform and sensitive to change. By anchoring Patient‐Oriented Eczema Measure (POEM) scores to five patient‐assessed eczema severity bands, Charman et al.2 have further simplified the outcome measure to improve interpretation of scores. The authors asked 1000 patients with eczema to complete both a POEM score and two global anchor questions that summarized the severity of their eczema. High external validity was ensured by the inclusion of children and adults from both primary and secondary care, in both rural and urban settings. The results permitted conversion from the 28‐point POEM numerical score to five bands ranging from clear/almost clear to very severe atopic eczema. It should be remembered that severity bands may not tell the whole story because a change from one band to another may be due to only a small change in score, for example from just below to just above a band cut‐off. Fortunately, a minimal clinically important difference score of 3.4 has been established for the POEM3 and so the two parameters can be used together to permit a full interpretation of POEM score changes.
Total Lymphocyte Count as a Predictor of Absolute CD4+ Count and CD4+ Percentage in HIV-lnfected Persons
Authors: Stephen P. Blatt
Journal: JAMA (1993)

To determine whether the total lymphocyte count (TLC) accurately predicts a low absolute CD4+ T-cell count and CD4+ percentage in persons infected with human immunodeficiency virus (HIV).Retrospective analysis of data collected in the US Air Force HIV Natural History Study.Military medical center that performs annual medical evaluation of all HIV-infected US Air Force personnel.A total of 828 consecutive patients with no prior history of zidovudine use, evaluated from January 1985 through July 1991. For patients with multiple observations over time, a single data point within each 6-month interval was included in the analysis (N = 2866).The sensitivity, specificity, and likelihood ratio (LR) of the TLC, in the range of 1.00 x 10(9)/L to 2.00 x 10(9)/L, in predicting an absolute CD4+ T-cell count less than 0.20 x 10(9)/L or a CD4+ percentage less than 20% were calculated. In addition, the LR and pretest probability of significant immunosuppression were used to calculate posttest probabilities of a low CD4+ count for a given TLC value. The LR of the TLC in predicting an absolute CD4+ count < 0.20 x 10(9)/L increased from 2.4 (95% confidence interval, 2.2 to 2.5) for all TLCs less than 2.00 x 10(9)/L, to 33.2 (95% confidence interval, 24.1 to 45.7) for all TLCs less than 1.00 x 10(9)/L. The specificity for this prediction increased from 57% to 97% over this range. The LR also increased from 1.4 (95% confidence interval, 1.3 to 1.6) for all TLCs less than 2.00 x 10(9)/L to 9.7 (95% confidence interval, 7.1 to 13.1) for all TLCs less than 1.00 x 10(9)/L in predicting a CD4+ percentage less than 20%.The TLC, between 1.00 x 10(9)/L and 2.00 x 10(9)/L, appears to be a useful predictor of significant immunosuppression as measured by a CD4+ T-cell count less than 0.20 x 10(9)/L in HIV-infected persons. The LR for a given TLC value and the pretest probability of immunosuppression can be used to determine the posttest probability of significant immunosuppression in individual patients. For example, in a patient with a TLC less than 1.50 x 10(9)/L and a pretest probability of 16%, the posttest probability of a low CD4+ T-cell count increases to 53%. In contrast, a TLC greater than 2.00 x 10(9)/L in an individual with a pretest probability of 30% will decrease the posttest probability of a low CD4+ T-cell count to less than 4%. Physicians should find these data useful to help predict the risk for opportunistic infection among HIV-infected persons who present with syndromes that are potentially compatible with opportunistic infection but who have not had recent or prior CD4+ T-cell analysis.
Induction of p27KIP1 after unilateral ureteral obstruction is independent of angiotensin II
Authors: Jens H. Gerth, Jörg Kriegsmann, T. Tong Trinh, Rolf A.K. Stahl, Thoralf Wendt, Manfred Sommer, Günter Stein, Gunter Wolf
Journal: Kidney International (2002)
Evidence for Tuberculosis in a Prehistoric Population
Authors: Anthony J. Perzigian
Journal: JAMA (1979)

COMMENCING several thousand years before Christ and continuing to the time of European contact, the prehistory of eastern North America portrays a series of cultural adaptations. In the earliest periods, hunting and gathering were the exclusive economic pursuits; in the latest periods, agriculture was the primary pursuit. In a review of the paleopathologic literature, Buikstra<sup>1</sup>demonstrated that cases of prehistoric skeletal lesions, thought to be tuberculous, were more frequently reported for the later agriculturally based groups when compared with the earlier hunting and gathering groups. We think that this association between paleopathology and culture history is more than coincidental; indeed, the paleopathologic and paleoepidemiologic record of eastern North America closely mirrors human culture history. We report on skeletal lesions in six late prehistoric American Indians recovered from a burial mound at the Turpin Farm near Cincinnati. The site, excavated by the Cincinnati Museum of Natural History, yielded the remains
THE FUNDAMENTAL REQUIREMENTS OF ENERGY FOR PROPER NUTRITION
Authors: GRAHAM LUSK
Journal: JAMA (1918)

From time to time, inquiries have come to this laboratory as to the fundamental requirements of energy for the proper nutrition of different individuals. It must be understood at the outset that portions of the data here presented are matters of established fact, repeatedly confirmed; others are based on unconfirmed observations of individual authorities, but probably correct; while still others are based on estimates as close to the actual state of affairs as one can now attain. The data may thus be classified: Absolutely accurate. Basal metabolism of all ages and sexes, and the increase in metabolism due to (a) standing; (b) walking; (c) carrying a load. Approximately accurate. Metabolism in industrial pursuits. Hypothetic. Metabolism of children during exercise. The four charts which accompany this paper show the food requirements (1) of boys from birth to 16 years of age; (2) of soldiers at hard work; (3) of men in
Baseline Left Ventricular (LV) performance and functional recovery after revascularisation: Predictive value of absolute 18F Fluorodeoxyglucose (FDG) uptake
Authors: Farzin Fath-Ordoubadi, Norma V.S. Marinho, Bruce E. Keogh, Domenico Pagano, Durval C. Costa, Paolo G. Camici
Journal: Journal of the American College of Cardiology (1996)
Targeted next-generation sequencing: A novel diagnostic tool for primary immunodeficiencies
Authors: Isaac J. Nijman, Joris M. van Montfrans, Marlous Hoogstraat, Marianne L. Boes, Lisette van de Corput, Ellen D. Renner, Patrick van Zon, Stef van Lieshout, Martin G. Elferink, Mirjam van der Burg, Clementien L. Vermont, Bert van der Zwaag, Esther Janson, Edwin Cuppen, Johannes K. Ploos van Amstel, Marielle E. van Gijn
Journal: Journal of Allergy and Clinical Immunology (2013)
Letter by Weber et al Regarding Article, “Arterial Stiffness and Cardiovascular Events: The Framingham Heart Study”
Authors: Thomas Weber, Bernd Eber, Azra Mahmud
Journal: Circulation (2010)

We read with great interest the recent report from the Framingham Heart Study investigating the prognostic impact of measures of arterial stiffness and wave reflections in the community. 1The authors confirmed that higher aortic stiffness (carotid-femoral pulsewave velocity) improves risk prediction when added to standard risk factors.However, their finding that measures of pulsatile arterial function (central pulse pressure, augmentation index, pulse pressure amplification) are not related to cardiovascular outcomes is unexpected, contradicts previous studies, 2 and deserves further reflection.First, even for population studies, the number of end points observed is relatively small, with a large proportion comprising clinically diagnosed heart failure, despite the well-documented superiority of natriuretic peptides (which were not measured in the study).It would be important to see the prognostic value of central pulse pressure, augmentation index, and pulse pressure amplification on the individual components of the combined end point.Second, as suggested by the authors, the lack of prognostic value of central pulse pressure, augmentation index, and pulse pressure amplification may be explained by the largely elderly (mean age, 63 years) and female (58%) population free of cardiovascular disease (100%).Accordingly, we have shown that the association between augmentation index and coronary artery disease was best in younger and middle-aged male patients. 3Subsequent studies revealed that central waveform characteristics are associated with cardiovascular events and mortality in patients with coronary artery disease independently of age but with stronger evidence in men.Given the inverse relationship between coronary blood flow and pulsatile hemodynamics, 4 it seems logical that the prognostic impact of pulsatile arterial function is higher in the presence of coronary atherosclerosis, being the other major limiting factor of coronary perfusion.Finally, event rates were much higher in studies that included patients with coronary artery disease, suggesting that the predictive value of central waveform characteristics may be a function of absolute cardiovascular risk.A prolonged follow-up and/or a hard clinical end point (mortality) may be important in an epidemiological study to reveal the prognostic impact of wave reflection parameters in the general population.
Mechanisms for atrial arrhythmias associated with cardiomyopathy: a study of feline hearts with primary myocardial disease.
Authors: P A Boyden, L P Tilley, A Albala, S K Liu, J J Fenoglio, A L Wit
Journal: Circulation (1984)

The cellular electrophysiologic and structural characteristics of arrhythmic and non-arrhythmic atria isolated from feline hearts with spontaneously occurring cardiomyopathy were studied. The animals were divided into three groups according to the degree of left atrial enlargement: mild (group I), moderate (group II), and severe (group III). The right atria were of relatively normal size. Microelectrode recordings showed that inexcitable cells were present in both left and right atria of all groups but were most numerous in the left atria of group III animals. Most inexcitable cells had low resting membrane potentials. There was also a significant reduction in resting membrane potentials, maximum rate of phase 0 depolarization, and action potential amplitude of excitable cells in left atria of animals in groups II and III, whereas action potentials of excitable cells in the right atria were normal. Acetylcholine or norepinephrine often restored excitability to cells that originally did not generate action potentials. Norepinephrine also caused slow-response action potentials as well as abnormal automaticity and triggered activity due to delayed afterpotentials. The diseased atria showed marked structural abnormalities, which were most pronounced in group III cats, including large amounts of interstitial fibrosis, cellular hypertrophy and degeneration, and thickened basement membranes. Therefore electrophysiologic abnormalities and concurrent changes in cell structure may be involved in the genesis of atrial tachyarrhythmias caused by cardiomyopathy.
Helmets for Child Bicyclists
Authors: Max Bader
Journal: JAMA (1990)

<h3>To the Editor.—</h3> DiGuiseppi et al<sup>1</sup>note that "bicycling injuries to children account for 300 000 emergency department visits and 500 to 600 deaths each year in the United States." Yet, despite an extensive bicycle helmet campaign in Seattle, Wash, the level of bicycle helmet use by children is only 15.7%. In the control city, Portland, Ore, it was 2.9%. The effect of the campaign was meritorious, but fell far short of levels needed to make much of an impression on bicycle-related head injuries among children. More dramatic action is needed if helmet use is not to flounder at the same level as that found with automobile seat restraints prior to recent stronger measures. We need to make bicycle helmet use by younger children an expected group norm that they and their parents will recognize as sensible and accept as a routine practice. Education by physicians, police, schools,
Combination treatment strategies in early rheumatoid arthritis
Authors: E Suresh
Journal: Annals of the Rheumatic Diseases (2005)

Combinations of disease modifying antirheumatic drugs (DMARDs) are increasingly being used in patients with early rheumatoid arthritis (RA) when long term results with sequential DMARD monotherapy are disappointing. Combination DMARD therapy may be more effective than monotherapy, and has no additional short term adverse events. The evidence for using combination DMARD therapy is still weak, however, and further trials are needed.
Combination Chemotherapy in Advanced Adrenocortical Carcinoma
Authors: Martin Fassnacht, Massimo Terzolo, Bruno Allolio, Eric Baudin, Harm Haak, Alfredo Berruti, Staffan Welin, Carmen Schade-Brittinger, André Lacroix, Barbara Jarzab, Halfdan Sorbye, David J. Torpy, Vinzenz Stepan, David E. Schteingart, Wiebke Arlt, Matthias Kroiss, Sophie Leboulleux, Paola Sperone, Anders Sundin, Ilse Hermsen, Stefanie Hahner, Holger S. Willenberg, Antoine Tabarin, Marcus Quinkler, Christelle de la Fouchardière, Martin Schlumberger, Franco Mantero, Dirk Weismann, Felix Beuschlein, Hans Gelderblom, Hanneke Wilmink, Monica Sender, Maureen Edgerly, Werner Kenn, Tito Fojo, Hans-Helge Müller, Britt Skogseid
Journal: New England Journal of Medicine (2012)

Adrenocortical carcinoma is a rare cancer that has a poor response to cytotoxic treatment.We randomly assigned 304 patients with advanced adrenocortical carcinoma to receive mitotane plus either a combination of etoposide (100 mg per square meter of body-surface area on days 2 to 4), doxorubicin (40 mg per square meter on day 1), and cisplatin (40 mg per square meter on days 3 and 4) (EDP) every 4 weeks or streptozocin (streptozotocin) (1 g on days 1 to 5 in cycle 1; 2 g on day 1 in subsequent cycles) every 3 weeks. Patients with disease progression received the alternative regimen as second-line therapy. The primary end point was overall survival.For first-line therapy, patients in the EDP-mitotane group had a significantly higher response rate than those in the streptozocin-mitotane group (23.2% vs. 9.2%, P<0.001) and longer median progression-free survival (5.0 months vs. 2.1 months; hazard ratio, 0.55; 95% confidence interval [CI], 0.43 to 0.69; P<0.001); there was no significant between-group difference in overall survival (14.8 months and 12.0 months, respectively; hazard ratio, 0.79; 95% CI, 0.61 to 1.02; P=0.07). Among the 185 patients who received the alternative regimen as second-line therapy, the median duration of progression-free survival was 5.6 months in the EDP-mitotane group and 2.2 months in the streptozocin-mitotane group. Patients who did not receive the alternative second-line therapy had better overall survival with first-line EDP plus mitotane (17.1 month) than with streptozocin plus mitotane (4.7 months). Rates of serious adverse events did not differ significantly between treatments.Rates of response and progression-free survival were significantly better with EDP plus mitotane than with streptozocin plus mitotane as first-line therapy, with similar rates of toxic events, although there was no significant difference in overall survival. (Funded by the Swedish Research Council and others; FIRM-ACT ClinicalTrials.gov number, NCT00094497.).
Abstract 3721: Combination of temozolomide and O6- benzylguanine inhibits breast cancer growth
Authors: Sheila Jeudy, Kalkunte S. Srivenugopal, Santhi D. Konduri
Journal: Cancer Research (2012)

Abstract O6 methylguanine DNA methyltransferease (MGMT) is over expressed in breast cancer cells. A number of cytotoxic agents utilized in the treatment of cancer directly or indirectly damage DNA, thus initiating a cascade of events which finalizes in cell death. MGMT has received significant focus for its role in the repair of DNA damage caused by a number of chemotherapeutics including alkylating agents, chlorethylating and methylating agents. In the present study, we tested the administration of the MGMT inhibitor [O6-benzylguanine (BG)] at non-toxic doses in combination with MGMT alkylator (temozolomide) on breast cancer cells in cell culture and xenograft models. Here, we report that temozolomide in combination with BG effectively inhibits breast cancer cell growth in vitro and in vivo. Here, we also report that BG either alone or in combination with temozolomide inhibits gene expressions which are involved in breast tumorigenesis and cell division process (CDC20, TOP2A, AURKB, BIRC5) and induces the expression of p21cip1 cell cycle inhibitor. The combination also enhanced PARP cleavage, indicative of apoptosis. In breast cancer xenograft models, BG alone or in combination with temozolomide caused marked delay in tumor growth. These findings suggest that MGMT inhibition may provide a novel and effective approach for breast cancer growth inhibition. Furthermore, the combination of MGMT inhibitors and MGMT alkylators can provide alternative therapeutic approaches to treat breast cancer. 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 3721. doi:1538-7445.AM2012-3721
Solitary Plasmacytoma and Obstructive Jaundice
Authors: C. Jack Bark
Journal: JAMA (1967)

<h3>To the Editor:—</h3> Multiple myeloma is a disseminated or multicentric neoplasm of plasma cells or related elements with usually a rapid fatal outcome. Textbooks also describe solitary plasmacytomas, mostly in the upper respiratory tract and rarely in the kidney, lung, and mediastinum. Recently, lesions in the central nervous system<sup>1</sup>and testis<sup>2</sup>have been observed. To date, apparently no example of solitary plasmacytoma in the liver has been described. This report describes such a case associated with obstructive jaundice. <h3>Report of a Case:—</h3> A 76-year-old white man was admitted to the Cedars of Lebanon Hospital with a two-week history of jaundice, anorexia, pruritus, clay-colored stools, and dark urine. He had had hepatitis without sequelae as a youth. There was no history of gallbladder disease. Physical examination revealed a cytic mass in the right upper quadrant thought to be a distended gallbladder. Laboratory studies included numerous bilirubin determinations, giving average
Infantile Spasms and Hyperekplexia Associated With Isolated Sulfite Oxidase Deficiency
Authors: J. Lloyd Holder, Satish Agadi, William Reese, Catherine Rehder, Michael M. Quach
Journal: JAMA Neurology (2014)

Isolated sulfite oxidase deficiency (ISOD) causes severe intellectual disability, epilepsy, and shortened life expectancy. Intractable seizures are invariable in children with ISOD; however, to our knowledge, infantile spasms with a corresponding hypsarrhythmia pattern on electroencephalogram have never been reported. In addition, the nonepileptic paroxysmal movement disorder hyperekplexia has not previously been reported with ISOD.We describe an infant with ISOD who initially presented with neonatal seizures, diffusion restriction noted on magnetic resonance imaging, and elevated serum S-sulfocysteine consistent with ISOD. A homozygous mutation in the SUOX gene was identified, confirming the diagnosis. Uniquely, this patient developed a profound accentuated startle response that did not have a corresponding electrographic change on electroencephalogram consistent with hyperekplexia. This was followed by a change in the child's electroencephalogram to the chaotic pattern of hypsarrhythmia and brief tonic seizures with attenuation of the hypsarrhythmia pattern characteristic of infantile spasms.The evolution of seizures associated with ISOD is poorly characterized because of the small number of patients. We report what we believe to be the first case of a child with ISOD who developed infantile spasms and hyperekplexia. This expands the phenotypes associated with ISOD and also should caution clinicians to not assume that all abnormal movements are seizures.