tbuckley/cabot-search huggingface dataset:
CHANGES IN HUMORAL IMMUNITY OCCURRING DURING THE EARLY STAGES OF EXPERIMENTAL PNEUMOCOCCUS INFECTION
Authors: Edward E. Terrell
Journal: The Journal of Experimental Medicine (1930)

A study was made of the changes in humoral immunity occurring during the early phases of experimental pneumococcus infection in the dog and cat. The methods devised by Robertson and Sia were employed to demonstrate the presence of anti-pneumococcus properties in the serum of animals naturally resistant to this micro-organism. It was found that with a generalized and overwhelming infection accompanied by early blood invasion, there was a prompt and rapid decrease in the concentration of natural humoral immune bodies which frequently disappeared entirely by the time of death. This same early diminution of humoral immune substances, opsonins, agglutinins, and pneumococcidal-promoting bodies was observed in animals that survived a moderately severe generalized infection but the concentration of immune bodies rose again with the onset of recovery. The decrease in concentration of humoral immune substances during a severe generalized infection appeared to be due to the combination of "S" substance with the normal immune bodies. When the pneumococcus infection was more localized as in the case of true lobar pneumonia a quite different sequence of events was observed to occur. Several animals, in which extensive lobar pneumonia was produced, showed the presence in quantity of humoral immune bodies in the blood throughout the course of an infection terminating fatally. These findings suggest that after the inception of pneumococcus infection in the dog and cat the chief function of natural anti-pneurnococcus substances in the blood is to limit or prevent blood invasion. When pneumococcic infection is localized these circulating antibodies appear to have little effect either in preventing the spread of the process or determining the outcome of the disease.
The 10 remaining mysteries of inflammatory bowel disease
Authors: J.-F. Colombel, A. J M Watson, M. F Neurath
Journal: Gut (2007)

Tremendous progress has been made in our understanding of the pathobiology of inflammatory bowel disease (IBD: Crohn's disease (CD) and ulcerative colitis (UC)) through research on mouse models of gut inflammation, human population genetics studies and immunological research.1–4 However, despite these important advances, many of the primary features of human IBD remain unexplained. In this article we pose a series of 10 fundamental questions about the epidemiology and clinical course of IBD that remain unanswered to this day. In order to obtain "best guess" answers to these questions, we have interviewed experts who are leaders in the field of each question. This article is a distillation of their opinions which we hope will refocus future research onto these remaining mysteries (Box 1) which are essential for improving the clinical management of IBD. The incidence of IBD has risen sharply in the last 50 years in the USA and western European countries; with the increase occurring in higher social classes before lower social classes.5 6 The increase in incidence is too rapid to be accounted for by genetic changes and strongly points to changes in environmental risk factors, especially changes in diet and intestinal microflora.7 In Japan, a correlation between incidence of IBD and fat and meat intake has been reported.8 Changes in diet and food preparation could influence intestinal microflora. Large variations in the range of bacterial lineages within the intestines of different individuals have been reported.9 However, the relationship between the microbial community structure within the gut and IBD is unknown. New concepts that intestinal microbiota exist in a finely balanced ecosystem in which changes to one microbial species influences other species suggest that ideas that IBD is caused by a single microbial species may be oversimplistic.10 #### Box 1 The 10 remaining mysteries of inflammatory bowel disease
Integrating Health Status and Survival Data
Authors: Roberto Benzo, Max H. Farrell, Chung-Chou H. Chang, Fernando J. Martinez, Robert Kaplan, John Reilly, Gerard Criner, Robert Wise, Barry Make, James Luketich, Alfred P. Fishman, Frank C. Sciurba
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

In studies that address health-related quality of life (QoL) and survival, subjects who die are usually censored from QoL assessments. This practice tends to inflate the apparent benefits of interventions with a high risk of mortality. Assessing a composite QoL-death outcome is a potential solution to this problem.To determine the effect of lung volume reduction surgery (LVRS) on a composite endpoint consisting of the occurrence of death or a clinically meaningful decline in QoL defined as an increase of at least eight points in the St. George's Respiratory Questionnaire total score from the National Emphysema Treatment Trial.In patients with chronic obstructive pulmonary disease and emphysema randomized to receive medical treatment (n = 610) or LVRS (n = 608), we analyzed the survival to the composite endpoint, the hazard functions and constructed prediction models of the slope of QoL decline.The time to the composite endpoint was longer in the LVRS group (2 years) than the medical treatment group (1 year) (P < 0.0001). It was even longer in the subsets of patients undergoing LVRS without a high risk for perioperative death and with upper-lobe-predominant emphysema. The hazard for the composite event significantly favored the LVRS group, although it was most significant in patients with predominantly upper-lobe emphysema. The beneficial impact of LVRS on QoL decline was most significant during the 2 years after LVRS.LVRS has a significant effect on the composite QoL-survival endpoint tested, indicating its meaningful palliative role, particularly in patients with upper-lobe-predominant emphysema.
Adverse Late Effects of Childhood Cancer and Its Treatment on Health and Performance
Authors: Kirsten K. Ness, James G. Gurney
Journal: Annual Review of Public Health (2007)

More than 12,000 newly diagnosed cases of cancer occur each year in the United States among children ages 20 years or younger, and the current 5-year survival rate is near 80%. An estimated 228,000 among adults 47 years or younger and currently living in the United States had a diagnosis of cancer during childhood or adolescence. Here, we review long-term adverse effects of childhood cancer and its treatment with an emphasis on physical performance and health. We also briefly review existing guidelines that may be used to develop appropriate exercise and diet interventions for childhood cancer survivors. We suggest that there is a need for development of evidence-based, risk-based guidelines and interventions for health promotion among long-term childhood cancer survivors, particularly for those whose physical activity limitations interfere with chances for optimizing their bodies' potential in today's society.
Age-Dependent Impairment of Angiogenesis
Authors: Alain Rivard, Jean-Etienne Fabre, Marcy Silver, Dongfen Chen, Toyoaki Murohara, Marianne Kearney, Meredith Magner, Takayuki Asahara, Jeffrey M. Isner
Journal: Circulation (1999)

The effect of aging on angiogenesis in ischemic vascular disease has not been studied. Accordingly, we investigated the hypothesis that angiogenesis is impaired as a function of age.Forty days after the resection of 1 femoral artery, collateral vessel development was significantly impaired in old (aged 4 to 5 years; n=7) versus young (aged 6 to 8 months; n=6) New Zealand White (NZW) rabbits on the basis of reduced hindlimb perfusion (ischemic: normal blood pressure ratio=0.58+/-0.05 versus 0.77+/-0.06; P<0.005), reduced number of angiographically visible vessels (angiographic score=0.48+/-0.05 versus 0.70+/-0.05; P<0.01), and lower capillary density in the ischemic limb (130.3+/-5.8/mm2 versus 171.4+/-9.5/mm2; P<0.001). Angiogenesis was also impaired in old (aged 2 years) versus young (aged 12 weeks) mice as shown by reduced hindlimb perfusion (measured by laser Doppler imaging) and lower capillary density (353.0+/-14.3/mm2 versus 713.3+/-63.4/mm2; P<0.01). Impaired angiogenesis in old animals was the result of impaired endothelial function (lower basal NO release and decreased vasodilation in response to acetylcholine) and a lower expression of vascular endothelial growth factor (VEGF) in ischemic tissues (by Northern blot, Western blot, and immunohistochemistry). When recombinant VEGF protein was administered to young and old rabbits, both groups exhibited a significant and similar increase in blood pressure ratio, angiographic score, and capillary density.Angiogenesis responsible for collateral development in limb ischemia is impaired with aging; responsible mechanisms include age-related endothelial dysfunction and reduced VEGF expression. Advanced age, however, does not preclude augmentation of collateral vessel development in response to exogenous angiogenic cytokines.
Measurement of relaxation in isolated rat ventricular myocardium during hypoxia and reoxygenation
Authors: Yasuyuki Nakamura, Allen W Wiegner, Oscar H L Bing
Journal: Cardiovascular Research (1986)

The effects of hypoxia and subsequent reoxygenation were examined in isolated left ventricular papillary muscles from the rat at 28°C and 33°C. Studies of relaxation were carried out in isometric and physiologically sequenced contractions. In studies of isometric contractions, the following variables were determined: active tension (AT), maximum rate of tension increase (+dT/dt), time to peak tension (TPT), time for tension to fall from peak to 50% of peak tension (RT½), maximum rate of tension decline (-dT/dt), isometric peak (-dT/dt/T), and isometric maximum (-dT/dt per T). Variables measured in physiologically sequenced contractions were the slopes of the relation between -dT/dtmax and end systolic length (SIM) and maximum rate of isotonic muscle lengthening (+dL/dtmax) and end systolic length (Sit). Tau, the exponential time constant for isometric relaxation, was also examined. Pronounced changes in active tension and +dT/dt were seen during hypoxia at both temperatures, whereas changes in measured relaxation variables were less prominent and inconsistent. At neither 28°C nor 33°C did TPT or RTh indicate impaired relaxation during hypoxia. Isometric peak -dT/dt declined with hypoxia at both temperatures but the normalised indices, isometric peak -dT/dt/T, peak (-dT/dt per T), and tau showed consistent impairment of relaxation only at 33°C. In physiologically sequenced contractions, SIM suggested impaired relaxation during hypoxia at 28°C but not at 33°C. SIT showed impaired relaxation at both 28°C and 33°C. These findings are consistent with data suggesting impairment of the cardiac relaxing system during hypoxia. Nevertheless, relaxation appears less affected than contraction, and impairment is best seen late in the cardiac cycle.
Iron chelation therapy in aceruloplasminaemia: study of a patient with a novel missense mutation
Authors: R Mariani
Journal: Gut (2004)

We describe a novel missense mutation of ceruloplasmin in a patient with aceruloplasminaemia causing the replacement of a neutral amino acid (phenylalanine) with a polar one (serine) at position 198, probably leading to abnormal folding and secretion of the protein. The patient showed mild microcytic anaemia, mild hepatic iron overload, and marked brain iron overload. Six months of therapy with deferiprone was ineffective in removing iron from the tissues. Deferoxamine was more efficient in removing excess iron from the liver but aggravated the disease related anaemia. After more than one year of chelation treatment, the brain magnetic resonance imaging signal did not change. Overall, these findings indicate that treatment of iron overload in aceruloplasminaemia is a difficult challenge and that new iron chelators, more efficient in crossing the blood-brain barrier, are needed.
Abatacept improves both the physical and mental health of patients with rheumatoid arthritis who have inadequate response to methotrexate treatment
Authors: A S Russell, G V Wallenstein, T Li, M C Martin, R Maclean, B Blaisdell, K Gajria, J C Cole, J-C Becker, P Emery
Journal: Annals of the Rheumatic Diseases (2006)

To examine the impact of added abatacept treatment on health related quality of life (HRQoL) in patients with rheumatoid arthritis (RA) who have inadequate response to methotrexate (MTX).
Is It Time to Stop Paying for Computer-Aided Mammography?
Authors: Joshua J. Fenton
Journal: JAMA Internal Medicine (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Successful treatment of experimental B virus (Herpesvirus simiae) infection with acyclovir.
Authors: E A Boulter, B Thornton, D J Bauer, A Bye
Journal: BMJ (1980)

The efficacy of the new nucleoside analogue acyclovir against B virus (Herpesvirus simiae) was investigated in rabbits and Vero cells infected with 2-136 and 0.3-1.0 TCD50 of the virus respectively. In the Vero cells 1 mg of acyclovir/1 reduced the yield of virus by 90%, which was slightly less than the effect on herpes simplex virus. Results in the rabbits varied with the interval between doses, duration of treatment, and delay before starting treatment. Acyclovir controlled an otherwise lethal infection when given not less than eight-hourly for 14 days. Withdrawing treatment after 9-10 days resulted in late-onset fatal disease in some rabbits. Treatment begun within 24 hours after infection gave complete protection, and rabbits first treated up to five days after infection showed a significant reduction in mortality (p less than 0.001). The plasma half life of acyclovir is twice as long in man as in rabbits and progression of the disease is much slower. Hence acyclovir may be useful for post-exposure prophylaxis against B virus infection in man and possibly also for treatment of the disease.
Cardioprotective Effect of Beta-3 Adrenergic Receptor Agonism
Authors: Xiaolin Niu, Vabren L. Watts, Oscar H. Cingolani, Vidhya Sivakumaran, Jordan S. Leyton-Mange, Carla L. Ellis, Karen L. Miller, Konrad Vandegaer, Djahida Bedja, Kathleen L. Gabrielson, Nazareno Paolocci, David A. Kass, Lili A. Barouch
Journal: Journal of the American College of Cardiology (2012)
C-fms expression correlates with monocytic differentiation in PML-RARα+ acute promyelocytic leukemia
Authors: R Riccioni, E Saulle, S Militi, N M Sposi, M Gualtiero, N Mauro, M Mancini, D Diverio, F Lo Coco, C Peschle, U Testa
Journal: Leukemia (2003)
Letter: An easy death--an uneasy argument.
Authors: S L Smith
Journal: BMJ (1975)

It seems clear that the only spastic infant in our series would have been equally likely to be handicapped had it been delivered by caesarean section and, in our hands, prolonged resuscitation did not keep alive spastics caused by the mode of delivery, so depressing our perinatal loss rate.I thank Mr. E. 0.
Intrapatient Cetuximab Dose Escalation in Metastatic Colorectal Cancer According to the Grade of Early Skin Reactions: The Randomized EVEREST Study
Authors: Eric Van Cutsem, Sabine Tejpar, Dirk Vanbeckevoort, Marc Peeters, Yves Humblet, Hans Gelderblom, Jan B. Vermorken, Frederic Viret, Bengt Glimelius, Elisa Gallerani, Alain Hendlisz, Annemieke Cats, Markus Moehler, Xavier Sagaert, Soetkin Vlassak, Michael Schlichting, Fortunato Ciardiello
Journal: Journal of Clinical Oncology (2012)

Purpose Skin toxicity in patients receiving cetuximab has been associated positively with clinical outcome in several tumor types. This study investigated the effect of cetuximab dose escalation in patients with irinotecan-refractory metastatic colorectal cancer who had developed no or mild skin reactions after 21 days of treatment at the standard dose. This article reports clinical and pharmacokinetic (PK) data. Patients and Methods After 21 days of standard-dose cetuximab (400 mg/m 2 initial dose, then 250 mg/m 2 per week) plus irinotecan, patients with ≤ grade 1 skin reactions were randomly assigned to standard-dose (group A) or dose-escalated (to 500 mg/m 2 per week; group B) cetuximab. Patients with ≥ grade 2 skin reactions continued on standard-dose cetuximab plus irinotecan (group C). Results The intent-to-treat population comprised 157 patients. PK profiles reflected the dose increase and were predictable across the dose range investigated. Weekly cetuximab doses of up to 500 mg/m 2 were well tolerated, and grade 3 and 4 adverse events were generally comparable between treatment groups. Dose escalation (n = 44) was associated with an increase in skin reactions ≥ grade 2 compared with standard (n = 45) dosing (59% v 38%, respectively). Dose escalation, compared with standard dosing, showed some evidence for improved response rate (30% v 16%, respectively) and disease control rate (70% v 58%, respectively) but no indication of benefit in relation to overall survival. In an exploratory analysis, dose escalation seemed to increase response rate compared with standard dosing in patients with KRAS wild-type but not KRAS mutant tumors. Conclusion Cetuximab serum concentrations increased predictably with dose. Higher dose levels were well tolerated. The possible indication for improved efficacy in the dose-escalation group warrants further investigation.
Prognostic Role of Minimal Residual Disease in Mature B-Cell Acute Lymphoblastic Leukemia of Childhood
Authors: Lara Mussolin, Marta Pillon, Valentino Conter, Matilde Piglione, Luca Lo Nigro, Paolo Pierani, Concetta Micalizzi, Salvatore Buffardi, Giuseppe Basso, Luigi Zanesco, Angelo Rosolen
Journal: Journal of Clinical Oncology (2007)

To study the prevalence of t(8;14) at diagnosis and the response kinetics to treatment of minimal residual disease (MRD) in B-cell acute lymphoblastic leukemia (B-ALL) patients and determine its impact on prognosis.A total of 68 children affected by de novo B-ALL enrolled onto the Berlin-Frankfurt-Muenster-based Italian Association of Pediatric Hematology and Oncology LNH-97 clinical protocol were studied. Bone marrow aspirate from each patient was analyzed for the presence of t(8;14)(q24;q32) by long-distance polymerase chain reaction at diagnosis, after the first chemotherapy cycle, and after subsequent cycles until negative for MRD. Morphologic and immunophenotypic analyses were reviewed centrally.A total of 47 patients (69%) were positive for t(8;14)(q24;q32). MRD response kinetics was determined in 39 patients. All of them reached clinical complete remission and most (31 of 39) became MRD negative after the first chemotherapy cycle. The 3-year relapse-free survival (RFS) was 38% (SE = 17%) in patients MRD positive after the first chemotherapy cycle compared with 84% (SE = 7%) in MRD-negative patients (P = .0005), whereas there was no difference in RFS for children who reached a clinical complete remission after the first chemotherapy cycle versus those who did not (RFS = 72% and SE = 9%; RFS = 79% and SE = 11%, respectively; P = .8). In multivariate analysis, MRD was shown to be predictive of higher risk of failure.Our study demonstrated that MRD carries a negative prognostic impact in B-ALL patients and suggests that a better risk-adapted therapy, possibly including the use of anti-CD20 monoclonal antibody, should be considered in selected patients.
Overdiagnosis in Low-Dose Computed Tomography Screening for Lung Cancer
Authors: Edward F. Patz, Paul Pinsky, Constantine Gatsonis, JoRean D. Sicks, Barnett S. Kramer, Martin C. Tammemägi, Caroline Chiles, William C. Black, Denise R. Aberle
Journal: JAMA Internal Medicine (2014)

<h3>Importance</h3> Screening for lung cancer has the potential to reduce mortality, but in addition to detecting aggressive tumors, screening will also detect indolent tumors that otherwise may not cause clinical symptoms. These overdiagnosis cases represent an important potential harm of screening because they incur additional cost, anxiety, and morbidity associated with cancer treatment. <h3>Objective</h3> To estimate overdiagnosis in the National Lung Screening Trial (NLST). <h3>Design, Setting, and Participants</h3> We used data from the NLST, a randomized trial comparing screening using low-dose computed tomography (LDCT) vs chest radiography (CXR) among 53 452 persons at high risk for lung cancer observed for 6.4 years, to estimate the excess number of lung cancers in the LDCT arm of the NLST compared with the CXR arm. <h3>Main Outcomes and Measures</h3> We calculated 2 measures of overdiagnosis: the probability that a lung cancer detected by screening with LDCT is an overdiagnosis (<i>PS</i>), defined as the excess lung cancers detected by LDCT divided by all lung cancers detected by screening in the LDCT arm; and the number of cases that were considered overdiagnosis relative to the number of persons needed to screen to prevent 1 death from lung cancer. <h3>Results</h3> During follow-up, 1089 lung cancers were reported in the LDCT arm and 969 in the CXR arm of the NLST. The probability is 18.5% (95% CI, 5.4%-30.6%) that any lung cancer detected by screening with LDCT was an overdiagnosis, 22.5% (95% CI, 9.7%-34.3%) that a non–small cell lung cancer detected by LDCT was an overdiagnosis, and 78.9% (95% CI, 62.2%-93.5%) that a bronchioalveolar lung cancer detected by LDCT was an overdiagnosis. The number of cases of overdiagnosis found among the 320 participants who would need to be screened in the NLST to prevent 1 death from lung cancer was 1.38. <h3>Conclusions and Relevance</h3> More than 18% of all lung cancers detected by LDCT in the NLST seem to be indolent, and overdiagnosis should be considered when describing the risks of LDCT screening for lung cancer.