tbuckley/cabot-search huggingface dataset:
T cell activation-associated hepatic injury: mediation by tumor necrosis factors and protection by interleukin 6.
Authors: H Mizuhara, E O'Neill, N Seki, T Ogawa, C Kusunoki, K Otsuka, S Satoh, M Niwa, H Senoh, H Fujiwara
Journal: The Journal of Experimental Medicine (1994)

This study investigates the molecular mechanisms underlying the induction of and protection from T cell activation-associated hepatic injury. When BALB/c mice were given a single intravenous injection of concanavalin A (Con A) (> or = 0.3 mg/mouse), they developed acute hepatic injury as assessed by a striking increase in plasma transaminase levels within 24 h. Histopathologically, only the liver was injured while moderate infiltration of T cells and polymorphonuclear cells occurred in the portal areas and around the central veins. The induction of hepatic injury was dependent on the existence as well as the activation of T cells, as untreated BALB/c nu/nu mice or BALB/c mice pretreated with a T cell-specific immunosuppressive drug, FK506, failed to develop disease. Significant increases in the levels of various cytokines in the plasma were detected before an increase in plasma transaminase levels. Within 1 h after Con A injection, tumor necrosis factor (TNF) levels peaked, this being followed by production of two other inflammatory cytokines, interleukin 6 (IL-6) and IL-1. Passive immunization with anti-TNF but not with anti-IL-1 or anti-IL-6 antibody, conferred significant levels of protection. Moreover, administration of rIL-6 before Con A injection resulted in an IL-6 dose-dependent protection. A single administration of a given dose of rIL-6 completely inhibited the release of transaminases, whereas the same regimen induced only 40-50% inhibition of TNF production. More than 80% inhibition of TNF production required four consecutive rIL-6 injections. These results indicate that: (a) TNFs are critical cytokines for inducing T cell activation-associated (Con A-induced) hepatitis; (b) the induction of hepatitis is almost completely controlled by rIL-6; and (c) rIL-6 exerts its protective effect through multiple mechanisms including the reduction of TNF production.
Serum Uric Acid Levels Correlate with the Severity and the Mortality of Primary Pulmonary Hypertension
Authors: NORITOSHI NAGAYA, MASAAKI UEMATSU, TORU SATOH, SHINGO KYOTANI, FUMIO SAKAMAKI, NORIFUMI NAKANISHI, MASAKAZU YAMAGISHI, TAKEYOSHI KUNIEDA, KUNIO MIYATAKE
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Serum uric acid (UA), the final product of purine degradation, has been proposed to be a marker for impaired oxidative metabolism and a possible predictor of mortality in patients with chronic heart failure. To elucidate whether serum UA correlates with the severity and the mortality of primary pulmonary hypertension (PPH), serum UA was assessed in 90 patients with PPH together with other clinical variables. Right heart catheterization was performed in all patients. Serum UA was significantly elevated in patients with PPH compared with age-matched control subjects (7.5 +/- 2.5 versus 4.9 +/- 1.2 mg/ml, p < 0.001). Serum UA negatively correlated with cardiac output (r = -0.52, p < 0.001) and positively correlated with total pulmonary resistance (r = 0.57, p < 0.001). Serum UA significantly decreased from 7.1 +/- 1.9 to 5.9 +/- 1.6 mg/dl with vasodilator therapy, associated with a reduction in total pulmonary resistance from 22 +/- 6 to 17 +/- 7 Wood units. During a mean follow-up period of 31 mo, 53 patients died of cardiopulmonary causes. Among noninvasive variables, serum UA was independently related to mortality by a multivariate Cox proportional-hazards analysis. The Kaplan-Meier survival curves according to the median value of serum UA demonstrated that patients with high serum UA had a significantly higher mortality rate than did those with low serum UA (log-rank test, p < 0.01). These results suggest that serum UA increases in proportion to the clinical severity of PPH and has independent association with long-term mortality of patients with PPH.
Establishment of a new Epstein‐Barr virus nuclear antigen‐positive B‐cell line, BALL‐2, with t(8;14)(q24;q32) chromosome abnormality from B‐cell acute lymphoblastic leukemia, L2
Authors: Ichiro Kubonishi, Masanori Daibata, Shoki Yano, Masaharu Isobe, Nobuyuki Kurosawa, Hideki Nagumo, Zen‐Ichi Ogita, Junko H. Ohyashiki, Keisuke Toyama, Isao Miyoshi
Journal: American Journal of Hematology (1991)

Abstract A new Epstein‐Barr virus nuclear antigen (EBNA)‐positive B‐cell line, designated BALL‐2, was spontaneously established from the peripheral blood of a 14‐year‐old boy with an EBNA‐negative B‐cell acute lymphoblastic leukemia (B‐ALL), L2 in the French‐American‐British classification. The BALL‐2 cell line grew in suspension with or without forming clumps of cells. The cultured cells exhibited lymphoid morphology with indented or tabulated nuclei, prominent nucleoli, and relatively abundant cytoplasm. Immunologic and cytogenetic studies showed that the BALL‐2 cell line expressed the B‐cell phenotype, Cplg+, Smlg+, CD19+, CD20+, CD38+, la+, and had chromosome translocation, t(8;14)(q24;q32). The same phenotypic and chromosome markers were present in original leukemia cells. These results indicated that the cell line was derived from the patient's leukemia cells. Unexpectedly, however, BALL‐2 cells were positive for EBNA and EB virus DMA. Gene analysis of the BALL‐2 cell line showed biallelic rearrangements in the JH locus. One of the JH rearrangement comigrated with a rearranged c‐ myc gene, indicating the translocation had occurred between JH and c‐ myc loci. The t(8;14) abnormality is a known chromosome marker of Burkitt lymphoma and L3 type ALL. Our studies revealed that this translocation and myc gene rearrangement can also be found in L2 type B‐ALL.
Absolute asthenozoospermia and ICSI: what are the options?
Authors: C. Ortega, G. Verheyen, D. Raick, M. Camus, P. Devroey, H. Tournaye
Journal: Human Reproduction Update (2011)

Complete asthenozoospermia, i.e. 100% immotile spermatozoa in the ejaculate, is reported at a frequency of 1 of 5000 men. Its diagnosis implies a poor fertility prognosis even with ICSI. It is extremely important to distinguish between two different groups of patients with complete asthenozoospermia, i.e. virtual or absolute asthenozoospermia. With the former group having some motile spermatozoa after extensive processing of the semen, absolute asthenozoospermia can be associated with metabolic deficiencies, ultrastructural abnormalities of the sperm flagellum, necrozoospermia otherwise it can be idiopathic. In the management of persistent absolute asthenozoospermia, it is very important to elucidate its nature and whenever possible to correct the potential causes. We reported data published in the literature on the aetiology of absolute asthenozoospermia and the different techniques to improve ICSI outcome. We propose an algorithm for diagnosis and treatment of this condition. Different results regarding fertilization, cleavage and pregnancy rate have been published in patients with absolute asthenozoospermia undergoing ICSI. However, the results vary widely depending on the sperm origin and the technique applied for immotile sperm selection. The percentage of viable spermatozoa varies between 0 and 100%. Absolute immotile spermatozoa is one of the most important causes of reduced fertilization and pregnancy rates after ICSI and different techniques are used to improve ICSI outcomes. However, it still remains unclear which is the best technique to improve the pregnancy outcomes in these couples.
Pharmacokinetics-Based Integration of Multiple Doses of Intravenous Pegaspargase in a Pediatric Regimen for Adults With Newly Diagnosed Acute Lymphoblastic Leukemia
Authors: Dan Douer, Ibrahim Aldoss, Matthew A. Lunning, Patrick W. Burke, Laleh Ramezani, Lisa Mark, Janice Vrona, Jae H. Park, Martin S. Tallman, Vassilios I. Avramis, Vinod Pullarkat, Ann M. Mohrbacher
Journal: Journal of Clinical Oncology (2014)

Asparaginase treatment is standard in all pediatric acute lymphoblastic leukemia (ALL) regimens, whereas in adults, it is either excluded or administered for a shorter duration. Several adult ALL protocols are adapting pediatric regimens, but the optimal implementation of asparaginase is not well studied, considering its potential higher toxicity. We studied a pegaspargase dosing strategy based on its pharmacokinetic characteristics in adults.Between 2004 and 2009, 51 adults age 18 to 57 years with newly diagnosed ALL were treated with a regimen adapted from a pediatric trial that included six doses of intravenous pegaspargase at 2,000 IU/m(2) per dose. Intervals between doses were longer than 4 weeks and rationally synchronized with other chemotherapy drugs to prevent overlapping toxicities. Pegaspargase was administered with steroids to reduce hypersensitivity. Asparaginase-related toxicities were monitored after 173 pegaspargase doses.The most common grade 3/4 asparaginase-related toxicities were lengthy hyperbilirubinemia and transaminitis, occasionally resulting in subsequent treatment delays. All toxicities resolved spontaneously. Forty-five percent of patients were able to receive all six doses of pegaspargase, and 61% received ≥ three doses. In only 20% of patients, the drug was discontinued after pegaspargase-related serious toxicity. Ninety-six percent achieved complete remission, almost all within 4 weeks, and a low induction death rate was seen. Seven-year disease-free and overall survival were 58% and 51%, respectively.Our dose and schedule of pegaspargase, based on its pharmacokinetics, and our detailed toxicity profile could be applied for safer adaptation of pediatric ALL protocols in adults.
Impaired acetaldehyde oxidation in alcoholics
Authors: K R Palmer, W J Jenkins
Journal: Gut (1982)

High blood acetaldehyde levels in alcoholics after ethanol ingestion are due to reduced acetaldehyde oxidation rather than to an increased rate of its formation from ethanol. This is associated with low hepatic acetaldehyde dehydrogenase activity in alcoholic subjects and may represent a specific abnormality in them.
Molecules controlling lymphocyte-endothelial interactions in lymph nodes are produced in vessels of inflamed synovium.
Authors: A J Freemont
Journal: Annals of the Rheumatic Diseases (1987)

In vitro lymphocyte adhesion to, and selective radiosulphate uptake by, endothelial cells has been demonstrated in diseased synovium of patients with rheumatoid disease, osteoarthritis, and the peripheral arthropathy associated with ankylosing spondylitis and ulcerative colitis. These characteristics have been described previously in endothelial cells functionally specialised for promoting lymphocyte traffic from blood to lymph node parenchyma. It is suggested that these observations indicate that some synovial vessels may be responsible, at least in part, for the selective accumulation of lymphocytes in the tissue. Manipulation of the development of this type of vessel may offer a novel way of influencing the progress of inflammatory arthropathies.
Association between leukocyte telomere length and glioma risk: a case-control study
Authors: S. Wang, Y. Chen, F. Qu, S. He, X. Huang, H. Jiang, T. Jin, S. Wan,, J. Xing
Journal: Neuro-Oncology (2013)

Compelling epidemiological evidence indicates that alterations of telomere length are associated with risks of many malignancies in a tumor-specific manner, such as lung cancer, breast cancer, and non-Hodgkin's lymphoma. However, the association between leukocyte telomere length and glioma risk has not been investigated. Relative telomere length (RTL) of peripheral blood leukocytes from 467 glioma patients and 467 healthy controls, matched by age and sex, was measured using the real-time PCR-based method in a case-control study. An unconditional multivariate logistic regression model was applied to estimate the association between RTL and glioma risk. Glioma patients showed notably longer RTL than controls (median, 0.555 vs 0.444; P > .04). RTL was negatively correlated with age in both cases (ρ = −0.430; P < .001) and controls (ρ = −0.388; P < .001). After adjusting for age, sex, smoking status and family history of cancer, multivariate logistic regression analysis showed that there was a U-shaped association between RTL and glioma risk (P for nonlinearity <.001). Compared with individuals in the second tertile of RTL, the odds ratios (95% CI) for participants in the first and third tertiles were 2.16 (range, 1.52–3.09) and 3.51 (range, 2.45–5.00), respectively. Stratified analysis showed that the association between RTL and glioma risk was not modulated by major host characteristics. Our study demonstrates for the first time that either shorter or longer RTL in peripheral blood leukocytes is associated with increased glioma risk, which warrants further investigation in the future.
Association of early life growth rates with childhood wheezing and overweight
Authors: Dianne de Korte-de Boer, Monique Mommers, Carel Thijs, Marielle Jaminon, Suhreta Mujakovic, Maria Jansen, Frans Feron, Onno van Schayck
Journal: European Respiratory Journal (2013)

Background   An association between childhood wheezing and overweight has been proposed, but the underlying mechanism remains unclear. It has been suggested that growth rates in early life are related to both the development of overweight and wheezing.   Aim   To investigate whether growth rates are independently related to both wheezing and overweight until age 3 years.   Methods   Children from the LucKi Birth Cohort Study with complete follow-up for questionnaires and measured height and weight (at ages 0, 7, 14 months and 3 years) were included (N=566). Wheezing was parentally reported. Overweight was defined as BMI above the 85 th  percentile. Growth rates were calculated for weight, height and BMI as the difference between z-scores at successive measurements. We performed logistic Generalised Estimating Equations analyses.   Results   A higher height growth rate was associated with lower risk of wheezing until age 3 years (adjusted (a)OR: 0.65 (0.53-0.79)), but not with overweight (aOR: 1.1 (0.9-1.3)). Higher weight growth rate and higher BMI growth rate were associated with overweight until 3 years (aOR: 2.3 (2.0-2.7) and aOR: 2.5 (2.1-2.9), respectively), but not with wheezing. The association of height growth rate with wheezing did not change after including overweight in the models.   Conclusion   Reduced height growth was associated with wheezing until age 3 years, independent from overweight. Increased weight growth and increased BMI growth were associated with overweight, but not with wheezing. These results indicate that early life growth rates do not explain an association between wheezing and overweight. Future analyses should clarify the direction of the association between height growth and wheezing.
JAUNDICE CAUSED BY LARGE EXTRAVASATIONS OF BLOOD
Authors: C. E. Newman
Journal: BMJ (1928)

EXTRAVASATIONS OF BLOOD. [TM BRJiisA^Ngiven starchy food with impunitv, and it is remarkable lhow glycosuria rapidly disappears oni full carbohydrate diet, as is shown by the following case.A woman, aged 22, had had an enlarged thyroid gland since the age of 15, but without symptoms of hyperthyroidism.Six months ago the thyroid gland increased in size, and for the first time signs of hyperthyroidism made their appearance- namely, breathlessness, sweating, exophthalmos, alnl tremor.Examination revealed a large adenomatous thyroid gland, ocular signs, exophthalmos, tremor, and a high pulse pressure.At this time there was no glycosuria.The patient while in hospital developed diphtheria and had to be removed to a fever hospital.On her return a month later the general symptoms of hyperthyroidism seemed somewhat intensified and glycosuria had appeared.Thereupon a glucose tolerance test .(50grams) was made and showed a lowered tolerance for sugar, the values being as follows: resting blood sugar normal,,half an hour after glucose administration 0.18 per cent.; one hour later 0.20 per cent.; 1j hours later 0.22 per cent.; two hours later 0.135 per cent.A trace of.sugar (0.5 per cent.approximately) appeared after the second hour.The patient was put on a full carbohydlrate diet and the glycosuria disappeared thereafter.This case is of particular interest because it illustrates two facts not infrequently found in Graves's disease-
Improvement in pulmonary function following closure of a patent foramen ovale in a man with cystic fibrosis
Authors: M Belton, Km Gyi
Journal: Journal of the Royal Society of Medicine (2009)

Patent foramen ovale (PFO) is a remnant of the fetal circulation and represents a failure of fusion of the primum and secundum septa during the postnatal period.1 Persistence of the one‐way flap valve overlying the fossa ovalis allows right‐to‐left blood flow when right atrial pressure exceeds left atrial pressure. Within the general population PFOs are relatively common and are present in 27% of unselected adults.2 Little is known of the incidence of PFOs within the cystic fibrosis (CF) population and their impact on clinical outcomes.

The present case report describes an adult CF patient who presented with neurological symptoms and deteriorating pulmonary function in the setting of a PFO. Closure of his PFO resulted not only in complete resolution of his neurological symptoms, but an improvement in pulmonary function.
Estimation and repeatability of the response to inhaled histamine in a community survey.
Authors: S Chinn, J R Britton, P G Burney, A E Tattersfield, A O Papacosta
Journal: Thorax (1987)

Epidemiological problems arising from the absence of an agreed definition of asthma have led to the use of bronchial reactivity tests in community surveys of asthma prevalence. Since only a minority of the general population will develop bronchoconstriction in response to the dose of histamine considered acceptable for use in the community it is important to make maximum use of the data available. Several methods for summarising the information in the dose-response curve obtained from a histamine challenge test have been compared. A standardised histamine challenge test was administered to 797 subjects selected from two communities, and a repeat test to 106 subjects. The test was well accepted. For most subjects FEV1 rose initially after administration of histamine (median rise 100 ml), so maximum FEV1 was used as the baseline from which the 20% fall to achieve a PD20 was calculated. In order to use all the data rather than just two points on the FEV1-log dose graph, PD20 was estimated by means of curve fitting, and the values were compared with PD20 from linear interpolation. An exponential curve was found to fit the data well. Extrapolation from the maximum dose of 4 mumol up to 8 mumol was allowed in the estimation of PD20 by both methods. The curve fitting method gave slightly more reproducible PD20 values than did linear interpolation, and also gave more estimates in the range 0.03-8 mumol. The repeatability of PD20 compared well with that of asthmatic subjects tested in a clinical environment. Curve fitting has an advantage over linear interpolation in large community studies, for which analysis of data by computer is essential.
Infliximab for severe, treatment-resistant psoriasis: a prospective, open-label study
Authors: C.H. Smith, K. Jackson, S.J. Bashir, A. Perez, A.L. Chew, A.M. Powell, M. Wain, J.N.W.N. Barker
Journal: British Journal of Dermatology (2006)

Infliximab, a mouse-human chimeric monoclonal antibody directed against tumour necrosis factor-alpha, has been shown to be effective for moderate to severe psoriasis, but there are few data published on its use in recalcitrant, treatment-resistant disease or in combination with other antipsoriatic therapies.To report our experience with infliximab in the treatment of patients attending a tertiary referral service with severe recalcitrant disease.All patients attending a tertiary referral service for severe psoriasis who were treated with infliximab between 2002 and July 2005 were entered into a prospective, open-label study. Details on disease phenotype, clinical course and adverse events were recorded together with measures of disease severity [Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index, clinical photography] at baseline, weeks 2 and 6, and then at 2-monthly intervals throughout the treatment period.Twenty-three patients were treated with infliximab during the study; one patient had pustular psoriasis and was therefore excluded from statistical analysis. All had severe disease (baseline PASI 26.5+/-6.7, mean+/-SD, n=22) and had received at least two systemic therapies for psoriasis in the past; 16 were taking one or more concomitant therapies at the time of treatment initiation. At week 10, 95% had achieved a 50% or greater improvement in baseline PASI (PASI 50), and 77% had achieved a 75% or greater improvement (PASI 75). Efficacy was sustained in the longer term, with eight of 10 patients on treatment for more than 11 months maintaining at least a PASI 50. Only one patient had treatment withdrawn due to lack of efficacy, two suffered severe systemic infections including extrapulmonary tuberculosis (splenic abscess) and cellulitis, and six have discontinued due to adverse effects including infusion reactions (two), severe thrombocytopenia (one), hepatitis (one) and malignancy (two).Data from this open-label study suggest that infliximab is a rapidly effective treatment for patients with severe, treatment-resistant disease, although approximately 25% of patients had to discontinue therapy due to the development of serious adverse effects. Long-term follow-up, continued pharmacovigilance, and further controlled comparative studies will be required to evaluate fully the risks associated with infliximab in the context of this already difficult to treat population.
Is Diabetes Treated as an Acute or Chronic Illness in Community Family Practice?
Authors: Barbara Yawn, Stephen J. Zyzanski, Meredith A. Goodwin, Robin S. Gotler, Kurt C. Stange
Journal: Diabetes Care (2001)

OBJECTIVE—Poor quality of diabetes care has been ascribed to the acute care focus of primary care practice. A better understanding of how time is spent during outpatient visits for diabetes compared with visits for acute conditions and other chronic diseases may facilitate the design of programs to enhance diabetes care. RESEARCH DESIGN AND METHODS—Research nurses directly observed consecutive outpatient visits during two separate days in 138 community family physician offices. Time use was categorized into 20 different behaviors using the Davis Observation Code (DOC). Time use was compared for visits for diabetes, other chronic conditions, and acute illnesses during 1,867 visits by patients ≥40 years of age. RESULTS—Of 20 DOC behavioral categories, 10 exhibited differences among the three groups. Discriminant analysis identified two distinct factors that distinguished visits for chronic disease from visits for acute illness and visits for diabetes from those for other chronic diseases. Compared with visits for other chronic diseases, visits for diabetes devoted a greater proportion of time to nutrition counseling, health education, and feedback on results and less time to chatting. Compared with visits for acute illness, visits for diabetes were longer and involved a higher proportion of dietary advice, negotiation, and assessment of compliance. CONCLUSIONS—Visits for diabetes are distinct from visits for other chronic diseases and acute illnesses in ways that may facilitate patient self-management. Novel quality-improvement interventions could support and expand existing differences between family physicians’ current approaches to care of diabetes and other chronic and acute illnesses.
Paclitaxel and gemcitabine in advanced non-nasopharyngeal head and neck cancer: A phase II study conducted by the Hellenic Cooperative Oncology Group
Authors: G. Fountzilas, G. Stathopoulos, C. Nicolaides, A. Kalogera-Fountzila, H. Kalofonos, A. Nikolaou, C. Bacoyiannis, E. Samantas, C. Papadimitriou, P. Kosmidis, J. Daniilidis, N. Pavlidis
Journal: Annals of Oncology (1999)