tbuckley/cabot-search huggingface dataset:
Differential effect of isotype on efficacy of anti-tumor necrosis factor alpha chimeric antibodies in experimental septic shock.
Authors: A J Suitters, R Foulkes, S M Opal, J E Palardy, J S Emtage, M Rolfe, S Stephens, A Morgan, A R Holt, L C Chaplin
Journal: The Journal of Experimental Medicine (1994)

Immune complexes containing human gamma (g)1 or murine g2a antibodies generate secondary effector mechanisms via Fc receptor binding or complement activation, whereas those containing human g4 or murine g1 antibodies generally do not. Therefore, isotype selection of therapeutic antibodies may have important clinical consequences. In a rabbit model of human tumor necrosis factor (rhuTNF)-induced pyrexia, a murine/human chimeric g4 anti-human TNF-alpha monoclonal antibody (mAb) (cCB0011) showed a dose-dependent inhibition of pyrexia, whereas a g1 isotype variant of the same mAb gave a marked pyrexia that was seen at all doses indicative of an immune complex-mediated response. To investigate whether isotype difference could influence mAb efficacy in pathological disease states, hamster/murine chimeric g1 and g2a anti-murine TNF-alpha mAbs (TN3g1, TN3g2a) were studied in experimental shock in mice and rats. In lipopolysaccharide-induced shock in mice, treatment with TN3g1 mAb at 30 and 3 mg/kg resulted in 90% survival by 72 h (p &amp;lt; or = 0.004), and prolonged survival to 45 h (p &amp;lt; or = 0.05), respectively, compared with 100% mortality by 27 h in controls. In contrast, a g2a isotype variant of the same mAb (30 mg/kg) resulted in only 10% survival by 72 h (p &amp;lt; or = 0.05). In a neutropenic sepsis model in rats there was greater survival in animals receiving the g1 isotype of TN3 compared with g2a isotype variant (70 vs. 27%; p &amp;lt; or = 0.005) with 100% mortality in the controls. These differences were not due to the pharmacokinetic profiles of the mAbs. In models of experimental shock antibody isotype can affect outcome with inactive isotypes (human g4 and murine g1) being more efficacious than active isotypes (human g1 and murine g2a).
Prevalence of Kidney Damage in Australian Adults
Authors: Steven J. Chadban, Esther M. Briganti, Peter G. Kerr, David W. Dunstan, Timothy A. Welborn, Paul Z. Zimmet, Robert C. Atkins
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. The incidence of ESRD is increasing dramatically. Progression to end-stage may be halted or slowed when kidney damage is detected at an early stage. Kidney damage is frequently asymptomatic but is indicated by the presence of proteinuria, hematuria, or reduced GFR. Population-based studies relating to the prevalence of kidney damage in the community are limited, particularly outside of the United States. Therefore, the prevalence of proteinuria, hematuria, and reduced GFR in the Australian adult population was determined using a cross-sectional study of 11,247 noninstitutionalized Australians aged 25 yr or over, randomly selected using a stratified, cluster method. Subjects were interviewed and tested for proteinuria—spot urine protein to creatinine ratio (abnormal: ≥0.20 mg/mg); hematuria—spot urine dipstick (abnormal: 1+ or greater) confirmed by urine microscopy (abnormal: >10,000 red blood cells per milliliter) or dipstick (abnormal: 1+ or greater) on midstream urine sample; and reduced GFR—Cockcroft-Gault estimated GFR (abnormal: <60 ml/min per 1.73 m2). The associations between age, gender, diabetes mellitus, and hypertension, and indicators of kidney damage were examined. Proteinuria was detected in 2.4% of cases (95% CI: 1.6%, 3.1%), hematuria in 4.6% (95% CI: 3.8%, 5.4%), and reduced GFR in 11.2% (95% CI: 8.6%, 13.8%). Approximately 16% had at least one indicator of kidney damage. Age, diabetes mellitus, and hypertension were independently associated with proteinuria; age, gender, and hypertension with hematuria; and age, gender, and hypertension with reduced GFR. Approximately 16% of the Australian adult population has either proteinuria, hematuria, and/or reduced GFR, indicating the presence of kidney damage. Identifying and targeting this section of the population may provide a means to reduce the burden of ESRD. E-mail: [email protected] edu.au
Aspirin modifies nitric oxide synthase activity in platelets: effects of acute versus chronic aspirin treatment
Authors: P O'Kane
Journal: Cardiovascular Research (2003)

Objective: We examined the effects of aspirin on basal and β-adrenoceptor (β-AR)-mediated nitric oxide synthase (NOS) activity in normal platelets. Methods: NOS activity was determined from the conversion of l-[3H]arginine to l-[3H]citrulline, both basally and following β-AR stimulation, in platelets from healthy human subjects following both short- and long-term aspirin administration. Results: Basal l-[3H]citrulline increased following aspirin 800 mg administered intravenously in vivo, from 0.31±0.12 to 0.76±0.14 pmol/108 platelets (P<0.01). Isoproterenol at 1 μmol/l increased platelet NOS activity before but not following intravenous aspirin. After short-term in vitro treatment with aspirin 10 μmol/l, 400 μmol/l or 4 mmol/l, basal platelet l-[3H]citrulline increased similarly, an effect not seen with indomethacin 100 μmol/l or ibuprofen 10 μmol/l. Platelet NOS activity was not increased by albuterol 1 μmol/l, in the presence of indomethacin, ibuprofen or aspirin in vitro. By contrast, oral aspirin 75 mg daily for 14 days did not affect basal platelet NOS activity, but abolished β-adrenergic NOS activation. Conclusions: Aspirin activates basal platelet NOS acutely, but not chronically, through a mechanism independent of cyclooxygenase (COX) inhibition. By contrast, both short- and long-term aspirin treatment inhibit platelet β-adrenergic NOS activation by a COX-dependent mechanism. This indicates that aspirin exerts divergent effects on basal and β-AR-stimulated platelet NOS activity, which are likely to be of clinical relevance.
Presence and Number of Lymph Node Metastases Are Associated With Compromised Survival for Patients Younger Than Age 45 Years With Papillary Thyroid Cancer
Authors: Mohamed Abdelgadir Adam, John Pura, Paolo Goffredo, Michaela A. Dinan, Shelby D. Reed, Randall P. Scheri, Terry Hyslop, Sanziana A. Roman, Julie A. Sosa
Journal: Journal of Clinical Oncology (2015)

Cervical lymph node metastases are recognized as a prognostic indicator only in patients age 45 years or older with papillary thyroid cancer (PTC); patients younger than age 45 years are perceived to have low-risk disease. The current American Joint Committee on Cancer staging for PTC in patients younger than age 45 years does not include cervical lymph node metastases. Our objective was to test the hypothesis that the presence and number of cervical lymph node metastases have an adverse impact on overall survival (OS) in patients younger than age 45 years with PTC.Adult patients younger than age 45 years undergoing surgery for stage I PTC (no distant metastases) were identified from the National Cancer Data Base (NCDB; 1998-2006) and from SEER 1988-2006 data. Multivariable models were used to examine the association of OS with the presence of lymph node metastases and number of metastatic nodes.In all, 47,902 patients in NCDB (11,740 with and 36,162 without nodal metastases) and 21,855 in the SEER database (5,188 with and 16,667 without nodal metastases) were included. After adjustment, OS was compromised for patients with nodal metastases compared with patients who did not have them (NCDB: hazard ratio (HR), 1.32; 95% CI, 1.04 to 1.67; P = .021; SEER: HR, 1.29; 95% CI, 1.08 to 1.56; P = .006). After adjustment, increasing number of metastatic lymph nodes was associated with decreasing OS up to six metastatic nodes (HR, 1.12; 95% CI, 1.01 to 1.25; P = .03), after which more positive nodes conferred no additional mortality risk (HR, 0.99; 95% CI, 0.99 to 1.05; P = .75).Our results suggest that cervical lymph node metastases are associated with compromised survival in young patients, warranting consideration of revised American Joint Committee on Cancer staging. A change point of six or fewer metastatic lymph nodes seems to carry prognostic significance, thus advocating for rigorous preoperative screening for nodal metastases.
Nitric oxide enhances the anti-inflammatory and anti-atherogenic activity of atorvastatin in a mouse model of accelerated atherosclerosis
Authors: Stefania Momi, Angela Monopoli, Paolo Francesco Alberti, Emanuela Falcinelli, Teresa Corazzi, Valentina Conti, Daniela Miglietta, Ennio Ongini, Pietro Minuz, Paolo Gresele
Journal: Cardiovascular Research (2012)

AimsThe aim of the present study was to assess whether the addition of a nitric oxide (NO)-donating moiety to atorvastatin enhances anti-inflammatory and anti-atherogenic effects in an animal model of endothelial dysfunction, systemic peroxidation and inflammation, and accelerated atherosclerosis.
Synthesis of the second component of complement by long-term primary cultures of human monocytes.
Authors: L P Einstein, E E Schneeberger, H R Colten
Journal: The Journal of Experimental Medicine (1976)

A method has been developed for preparation of confluent monolayers of human monocytes from small volumes of blood and for maintenance of these pure monocyte cultures for up to 16 wk in vitro. These cells phagocytosed 5.7 mum diameter latex beads, rosetted with erythrocytes coated with IgG or with C3, killed Listeria monocytogenes, and synthesized both lysozyme and the second component of complement. Lysozyme was secreted at a rate of approximately 50,000 mol/min per cell for at least 12 wk in cultures. The maximal rate of C2 synthesis and secretion was considerably less; i.e., approximately 30 mol/min per cell between the 2nd and 12th wk in culture. Monocytes produced little C2 during the first 6 days in culture after which a marked increase in the rate of C2 production was noted. This increase was coincident with morphologic evidence of monocyte maturation.
Impact of A1C Screening Criterion on the Diagnosis of Pre-Diabetes Among U.S. Adults
Authors: Devin M. Mann, April P. Carson, Daichi Shimbo, Vivian Fonseca, Caroline S. Fox, Paul Muntner
Journal: Diabetes Care (2010)

OBJECTIVE New clinical practice recommendations include A1C as an alternative to fasting glucose as a diagnostic test for identifying pre-diabetes. The impact of these new recommendations on the diagnosis of pre-diabetes is unknown. RESEARCH DESIGN AND METHODS Data from the National Health and Nutrition Examination Survey 1999–2006 (n = 7,029) were analyzed to determine the percentage and number of U.S. adults without diabetes classified as having pre-diabetes by the elevated A1C (5.7–6.4%) and by the impaired fasting glucose (IFG) (fasting glucose 100–125 mg/dl) criterion separately. Test characteristics (sensitivity, specificity, and positive and negative predictive values) using IFG as the reference standard were calculated. RESULTS The prevalence of pre-diabetes among U.S. adults was 12.6% by the A1C criterion and 28.2% by the fasting glucose criterion. Only 7.7% of U.S. adults, reflecting 61 and 27% of those with pre-diabetes by A1C and fasting glucose, respectively, had pre-diabetes according to both definitions. A1C used alone would reclassify 37.6 million Americans with IFG to not having pre-diabetes and 8.9 million without IFG to having pre-diabetes (46.5 million reclassified). Using IFG as the reference standard, pre-diabetes by the A1C criterion has 27% sensitivity, 93% specificity, 61% positive predictive value, and 77% negative predictive value. CONCLUSIONS Using A1C as the pre-diabetes criterion would reclassify the pre-diabetes diagnosis of nearly 50 million Americans. It is imperative that clinicians and health systems understand the differences and similarities in using A1C or IFG in diagnosis of pre-diabetes.
DSM-IV field trials for attention deficit hyperactivity disorder in children and adolescents
Authors: B B Lahey, B Applegate, K McBurnett, J Biederman, L Greenhill, G W Hynd, R A Barkley, J Newcorn, P Jensen, J Richters
Journal: American Journal of Psychiatry (1994)

Optimal diagnostic thresholds were determined for DSM-IV attention deficit hyperactivity disorder, and the psychometric properties were compared to alternative definitions.Structured diagnostic interviews of multiple informants for 380 clinic-referred youths aged 4-17 years were conducted. In addition, standardized clinicians' validation diagnoses of attention deficit disorder were obtained to assess agreement with clinical judgment. Measures of impairment were obtained to assess the accuracy of identifying youth with an impairing condition.Three subtypes of attention deficit hyperactivity disorder (predominantly inattentive, predominantly hyperactive-impulsive, and combined types) were distinguished on the basis of the degree of deviance on separate dimensions of inattention and hyperactivity-impulsivity. These three subtypes were found to differ in terms of types of impairment, age, and sex ratio, but not ethnicity. In terms of case identification of attention deficit hyperactivity disorder, DSM-IV was found to be very similar to DSM-III-R, except that DSM-IV identified more impaired girls and preschool children.These results support the decision to subdivide the heterogeneous category of DSM-III-R attention deficit hyperactivity disorder into three subtypes. The resulting DSM-IV definition appears to be somewhat less biased toward the symptom pattern typical of elementary school boys.
Patients who fast in Ramadan need better advice
Authors: Z. Ismail Panju
Journal: BMJ (2012)

Ramadan is the lunar calendar month in which Muslims spiritually and physically “cleanse,” which includes abstaining from food and drink between dawn and dusk. This year Ramadan will be observed between 19 July and 18 August. Being Muslim, this was a tradition I grew up with, and aside from new diagnoses of diabetes presenting during this time, resulting from dehydration or blood glucose derangements exacerbated by fasting, I had never considered the medical implications.1 2

In my more youthful years, Ramadan fell in winter, and late sunrise and early sundown meant that you really only missed lunch. Islam prioritises health above all else so it always seemed clear that you fasted if you could, and if you couldn’t then you didn’t. It was only when I began a general practice rotation last year that I saw that the situation is often less clear cut, and religious fasting has the potential to adversely affect health.

The …
Lacrosse stick entrapment injury to the thumb
Authors: L A Livingston, S L Forbes
Journal: British Journal of Sports Medicine (2003)

A case of injury to the left thumb following an errant stick check, and subsequent entrapment of the digit in the open sidewall of a lacrosse stick, is presented. A circumferential laceration, severe swelling, and bruising to the proximal phalanx resulted. This case report emphasises the need to limit the dimensions of openings in the sidewalls of lacrosse sticks to prevent the occurrence of this and other preventable injuries.
The 21-gene recurrence score assay impacts adjuvant therapy recommendations for ER-positive, node-negative and node-positive early breast cancer resulting in a risk-adapted change in chemotherapy use
Authors: W. Eiermann, M. Rezai, S. Kümmel, T. Kühn, M. Warm, K. Friedrichs, A. Schneeweiss, S. Markmann, H. Eggemann, J. Hilfrich, C. Jackisch, I. Witzel, H. Eidtmann, A. Bachinger, S. Hell, J. Blohmer
Journal: Annals of Oncology (2012)

BackgroundWe carried out a prospective clinical study to evaluate the impact of the Recurrence Score (RS) on treatment decisions in early breast cancer (EBC).Patients and methodsA total of 379 eligible women with estrogen receptor positive (ER+), HER2-negative EBC and 0–3 positive lymph nodes were enrolled. Treatment recommendations, patients' decisional conflict, physicians' confidence before and after knowledge of the RS and actual treatment data were recorded.ResultsOf the 366 assessable patients 244 were node negative (N0) and 122 node positive (N+). Treatment recommendations changed in 33% of all patients (N0 30%, N+ 39%). In 38% of all patients (N0 39%, N+ 37%) with an initial recommendation for chemoendocrine therapy, the post-RS recommendation changed to endocrine therapy, in 25% (N0 22%, N+ 39%) with an initial recommendation for endocrine therapy only to combined chemoendocrine therapy, respectively. A patients' decisional conflict score improved by 6% (P = 0.028) and physicians' confidence increased in 45% (P < 0.001) of all cases. Overall, 33% (N0 29%, N+ 38%) of fewer patients actually received chemotherapy as compared with patients recommended chemotherapy pre-test. Using the test was cost-saving versus current clinical practice.ConclusionRS-guided chemotherapy decision-making resulted in a substantial modification of adjuvant chemotherapy usage in node-negative and node-positive ER+ EBC.
Persistent Neurological Deficit Precipitated by Hot Bath Test in Multiple Sclerosis
Authors: Joseph R. Berger
Journal: JAMA (1983)

For a half century, the hot bath test has been used as a "diagnostic test" in multiple sclerosis. The appearance of new neurological signs or aggravation of preexisting signs generally is transient, with resolution on return of body temperature to normal. We have observed four patients, however, with considerable and prolonged neurological debilitation after hot bath testing. We suggest caution in the application of such testing. (<i>JAMA</i>1983;249:1751-1753)
Transmural myocardial deformation in the ischemic canine left ventricle.
Authors: F J Villarreal, W Y Lew, L K Waldman, J W Covell
Journal: Circulation Research (1991)

The myocardium is a complex three-dimensional structure consisting of myocytes interconnected by a dense collagen weave that courses in different directions. Regional ischemia can be expected to produce complex changes in ventricular deformation. In the present study, we examined the effects of ischemia on two- and three-dimensional finite strains during acute transmural myocardial ischemia in 13 open-chest anesthetized dogs. In contrast to systolic deformation observed during the control period in which circumferential shortening exceeded longitudinal shortening, our results indicate that after 5 minutes of acute ischemia, end-systolic in-plane lengthening across the left ventricular wall occurs in approximately equal amounts in the circumferential and longitudinal directions. Along with these changes in extensional strains, there were significant negative transverse shearing deformations during ischemia. Myocardial ischemia also resulted in a loss of the normal end-systolic transmural gradients of shortening and thickening. Three-dimensional end-diastolic strains indicate that the left ventricular wall undergoes a significant passive reconfiguration that varies transmurally with lengthening in the epicardial tangent plane and wall thinning increasing from the epicardium toward the endocardium. The large systolic changes in shearing deformations with ischemia could potentially influence collateral blood flow and certainly indicate that uniaxial measurements of deformation in the ischemic myocardium, which do not account for shearing deformation, are incomplete and must be interpreted with caution. Moreover, normal transmural systolic gradients in deformation, which would be anticipated on geometric grounds, are lost during ischemia, implying that the material properties of ischemic tissue or the loading conditions imposed on the ischemic region by partially impaired adjacent myocardium vary transmurally.
Helicobacter pylori and gastric cancer: correlation with gastritis, intestinal metaplasia, and tumour histology.
Authors: A Wee, J Y Kang, M Teh
Journal: Gut (1992)

This study aimed to examine the association between Helicobacter pylori, histological gastritis, and intestinal metaplasia in gastric cancers of different histological types. A total of 169 gastrectomy specimens received in one pathology department were studied. Altogether 156 were adenocarcinomas (intestinal type 87, diffuse type 50, mixed type 19). Gastritis occurred in 137 of 163 body specimens (84%) and in 126 of 131 antral specimens (96%). Its presence was unrelated to tumour histology. Atrophic gastritis was more common in both body and antral mucosa in intestinal type compared with diffuse type carcinoma. This was also true for intestinal metaplasia of the body, but not of the antral mucosa. H pylori was present in 101 of 163 (62%) body specimens and 56 of 131 (43%) antral specimens. In intestinal type carcinoma, H pylori was found in 52/84 (62%) body specimens and in 24/70 (34%) antral specimens, while the corresponding figures for diffuse type carcinoma were 29/48 (60%) and 17/38 (45%) respectively. Tumour histology therefore had no influence on the occurrence of H pylori. Tumour site had no effect on the presence or absence of gastritis, atrophic changes, intestinal metaplasia, or H pylori. While both H pylori and gastritis are associated with gastric cancer, the association is unrelated to tumour histology and may not be a causal one.
Carboplatin (CBDCA, JM-8) and VP-16-213 in previously untreated patients with small-cell lung cancer.
Authors: J F Bishop, D Raghavan, R Stuart-Harris, G Morstyn, R Aroney, R Kefford, K Yuen, J Lee, P Gianoutsos, I N Olver
Journal: Journal of Clinical Oncology (1987)

The efficacy and toxicity of carboplatin 100 mg/m2, administered intravenously (IV) daily X 3, and VP-16-213 120 mg/m2, IV daily X 3, administered every 28 days for six courses, was assessed in 94 (36 limited stage, 58 extensive stage) previously untreated patients with small-cell lung cancer. Mediastinal irradiation using 50 Gy in 25 fractions was given to all limited-stage patients with a complete (CR) or partial response (PR) after three chemotherapy courses. Cranial irradiation was administered to all patients with CR. Objective responses were seen in 77% (CR 40%, PR 37%) of patients with limited-stage and 58% (CR, 9%; PR, 49%) with extensive-stage disease. Median relapse-free survival for objective responders with limited stage was 14.6 months and 7.9 months for extensive-stage patients. Median relapse-free survival following CR was 15.4 months and 8.5 months for PR. Median survival was 15.3 months for limited-stage and 8.1 months for extensive-stage patients. The combination was well tolerated with mild nausea or less (World Health Organization [WHO] grade 0 or 1) in 62% of patients and minimal mucositis, renal, neurotoxicity, or ototoxicity. Neutropenia less than 1.0 X 10(9)/L (WHO grade 3 or 4) was seen in 63% of patients, with two deaths from infection while neutropenic. The combination of carboplatin and VP-16-213 is a new, active program with low toxicity when applied intensively in previously untreated patients with small-cell lung cancer.