tbuckley/cabot-search huggingface dataset:
Meta-Analyses of Chemotherapy for Locally Advanced and Metastatic Pancreatic Cancer
Authors: Asma Sultana, Catrin Tudur Smith, David Cunningham, Naureen Starling, John P. Neoptolemos, Paula Ghaneh
Journal: Journal of Clinical Oncology (2007)

Purpose There are a large number of randomized controlled trials involving chemotherapy in the management of advanced pancreatic cancer. Several chemotherapeutic agents, either alone or in combination with other chemotherapy or novel agents, have been used. The aim of these meta-analyses was to examine the different therapeutic approaches, and the comparisons examined were as follows: chemotherapy versus best supportive care; fluorouracil (FU) versus FU combination chemotherapy; gemcitabine versus FU; and gemcitabine versus gemcitabine combination chemotherapy. Methods Relevant trials were identified by searching databases, trial registers, and conference proceedings. The primary end point was overall survival. Results One hundred thirteen randomized controlled trials were identified, of which 51 trials involving 9,970 patients met the inclusion criteria. Chemotherapy improved survival compared with best supportive care (hazard ratio [HR] = 0.64; 95% CI, 0.42 to 0.98). FU-based combination chemotherapy did not result in better overall survival compared with FU alone (HR = 0.94; 95% CI, 0.82 to 1.08). There was insufficient evidence of a survival difference between gemcitabine and FU, but the wide CI includes clinically important differences in both directions, making a clear conclusion difficult (HR = 0.75; 95% CI, 0.42 to 1.31). Survival was improved after gemcitabine combination chemotherapy compared with gemcitabine alone (HR = 0.91; 95% CI, 0.85 to 0.97). Conclusion There was a significant survival benefit for chemotherapy over best supportive care and gemcitabine combinations over gemcitabine alone. This supports the use of gemcitabine-based combination chemotherapy in the treatment of advanced pancreatic cancer.
External Squint; Varieties; Operations for Internal and External Squint
Authors: H. Walton
Journal: BMJ (1862)

cide with those of Hutchinson and others as to the ab- sence of any fungous growth about the hairs.The disease is an atrophy, pinet simple; and a very interesting example it certainly affords.It is remarkable how purely local the change is; all the other tissues may be in full vigour of nutrition and development, except the follicles in the affected patches.There the scalp be- comes smootb, pale, thinned, and devoid of reactive vitality.In one well-marked case, croton-oil liniment, which I prescribed, produced considerable irritation of the hair-covered part of the scalp, but inone on the bald patches.Von Barensprung ascribes the atrophy to a paralysis of trophic nerves.I do not see any grouind for this assumption, and prefer to regard it as a simple loss of nutrient power in a tissue-a trtie degeneration.Local stimulation is the only treatment that is of any avail, and this must be very long continued.[To be continued.
Personality Dimensions in First-Episode Psychoses
Authors: Matcheri S. Keshavan, Harpreet S. Duggal, Gautami Veeragandham, Nancy M. McLaughlin, Debra M. Montrose, Gretchen L. Haas, Nina R. Schooler
Journal: American Journal of Psychiatry (2004)

The authors compared the patterns and specificity of premorbid personality dimensions in first-episode schizophrenia patients with those in patients with first-episode nonschizophrenia psychoses and healthy comparison subjects.A series of 63 patients with first-episode schizophrenia and related psychotic disorders, 34 patients with first-episode nonschizophrenia psychoses, and 77 healthy comparison subjects were assessed with the Personality Disorder Evaluation, a semistructured interview schedule that measures personality dimensions.Cluster A as well as cluster C dimensional scores-in particular, the avoidant personality score-were higher for the schizophrenia patients, and cluster B dimensional scores were higher for the patients with nonschizophrenia psychoses. Cluster C dimensional scores, particularly the avoidant personality score, were highly intercorrelated with all cluster A dimensional scores.The observed association between avoidant personality and schizophrenia supports the recent literature on the comorbidity of nonspectrum personality disorders in schizophrenia. This association may be related to shared neurodevelopmentally mediated impairments in social cognition in schizophrenia and some cluster C personality dimensions.
PULMONARY FUNCTION IN HYPERTHYROIDISM*
Authors: Myron Stein, Philip Kimbel, Robert L. Johnson
Journal: Journal of Clinical Investigation (1961)

2,460 (67) 2,830 (77) 1,000 (67) 635 (43) 2,180 (94) 2,100 (90) 3,460 (71) 3,465 (71) FC [6] 2,700 (83) 3,400 (105) 1,190 (66) 1,370 (77) 2,400 (86) 2,630 (94) 3,890 (81) 4,470 (93) MC [4] 2,480 (77) 3,160 (97) 2,430 (135) 1,390 (77) 3,400 (121) 2,390 (85) 4,960 (104) 4,650 (97) LF [5] 2,520 (81) 3,040 (97) 1,600 (104) 1,390 (90) 2,600 (116) 2,660 (118) 4,120 (93) 4,440 (101) SC [3] 2,420 (81) 2,600 (87) 850 (51) 890 (53) 1,920 (81) 1,380 (58) 3,270 (74) 3,490 (79) AT 2,230 (63) 1,235 (75) 1,870 (76) 3,465 (71) EL 3,090 (92) 1,070 (68) 2,480 (102) 4,160 (90) AL [3] 3,220 (122) 2,940 (111) 1,990 (120) 1,750 (106) 3,280 (100) 2,700 (88) 5,040 (123) 4,360 (107) HR 2,590 (83) 1,590 (95) 2,590 (108) 4,180 (92) MB 4,625 (95) 1,945 (74) 2,685 (72) 6,570 (93) EM [3] 2,640 (100) 3,240 (123) 2,290 (129) 1,315 (74) 2,690 (80) 2,340 (69) 4,940 (118) 4,690 (112) EQ 3,080 (95) 1,330 (85) 2,460 (106) 4,410 (97) Mean 2,820 (87) 3,030 (100) 1,540 (90) 1,250 (74) 2,500 (95) 2,315 (85) 4,380 (93) 4,220 (94) * Per cent of predicted values in parentheses.Since the predicted values of Needham, Rogan and McDonald (20) were measured at ATPSand the measured values in our subjects were corrected to BTPS, 9% has been added to the predicted figures.t Number of months between studies in brackets.
Contribution of TGFβ1 and TIMP2 to clinical activity of asthma and COPD
Authors: Navid Abolfath Zade Ghalejooghi, Mostafa Ghanei, Mohammad Reza Nourani, Ali Amini Harandi, Abbas Ali Imani Fooladi
Journal: European Respiratory Journal (2011)

Introduction: The process of bronchial tissue repair and remodeling in airway diseases depends on balance between production and degradation of different cytokines, leading to the regulation of extracellular matrix turnover finally.

Objectives: This study was designed to evaluate contribution of Transforming Growth Factor β1 (TGFβ1) and Tissue Inhibitor of Metaloproteinase-2 (TIMP2) to clinical activity and reversibility of asthma and chronic obstructive pulmonary disease (COPD).

Methods: In a cross sectional study on two groups of 29 asthmatics (14 males and 15 females) and 13 male COPD patients, we evaluated TIMP2 and TGFβ1 expression using semi-quantitative PCR on induced sputum samples. The relation among TIMP2 and TGFβ1 and pulmonary function test (PFT) indices and disease free period were assessed.

Results: Higher pulmonary function test (PFT) indices and longer disease free period was seen in COPD patients with raised expression of both TGFβ1 and TIMP2. On the other hand asthmatic patients had better pulmonary function status with raised TIMP2 and decreased TGFβ1 expression (p<0.05).

Conclusion: It seems that different effect of cytokines like TGFβ1 and TIMP2 in both diseases is depended on underlying inflammatory process in airways epithelium. We supposed that TGFβ1 bidirectionally affects activity of disease in asthma and COPD. Furthermore TGFβ1 as a biomarker in sputum may have a role for evidence-based drug prescribing like corticosteroids in patients with COPD and asthma.
Induction of transgene-specific immunological tolerance in myeloablated nonhuman primates using lentivirally transduced CD34+ progenitor cells
Authors: Sam K.P Kung, Dong-Sung An, Aylin Bonifacino, Mark E Metzger, Gene-Errol Ringpis, Si-Hua Mao, Irvin S.Y Chen, Robert E Donahue
Journal: Molecular Therapy (2003)

Modeling human hematopoietic progenitor cell gene therapy in nonhuman primates allows long-term evaluation of safety, maintenance of gene expression, and potential immune response against transgene products. We transplanted autologous G-CSF/SCF-mobilized CD34+ cells transduced with lentiviral vectors expressing EGFP into myeloablated rhesus macaques. To date, more than 4 years posttransplantation, 0.5–8% EGFP expression is maintained in multiple cell lineages. The animals remain healthy with no evidence of hematopoietic abnormalities or malignancies. To assess immune functions, we actively immunized two of our transplanted animals with purified rEGFP proteins and CpG adjuvant and demonstrated stable levels of EGFP+ cell populations maintained for over 29 months despite four active immunizations. We did not detect a persistent anti-EGFP antibody response or anti-EGFP T cell response in these immunized animals. Immune response to an irrelevant antigen was normal. Taken together, our data provide formal support that transplantation of lentivirally transduced CD34+ progenitor cells in myeloablated rhesus macaques induces specific immunological tolerance toward a foreign transgene.
Considerations on the role of environmental toxins in idiopathic Parkinson’s disease pathophysiology
Authors: Francisco Pan-Montojo, Heinz Reichmann
Journal: Translational Neurodegeneration (2014)

Neurodegenerative diseases are characterized by a progressive dysfunction of the nervous system. Often associated with atrophy of the affected central or peripheral nervous structures, they include diseases such as Parkinson’s Disease (PD), Alzheimer’s Disease and other dementias, Genetic Brain Disorders, Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig’s Disease), Huntington’s Disease, Prion Diseases, and others. The prevalence of neurodegenerative diseases has increased over the last years. This has had a major impact both on patients and their families and has exponentially increased the medical bill by hundreds of billions of Euros. Therefore, understanding the role of environmental and genetic factors in the pathogenesis of PD is crucial to develop preventive strategies. While some authors believe that PD is mainly genetic and that the aging of the society is the principal cause for this increase, different studies suggest that PD may be due to an increased exposure to environmental toxins. In this article we review epidemiological, sociological and experimental studies to determine which hypothesis is more plausible. Our conclusion is that, at least in idiopathic PD (iPD), the exposure to toxic environmental substances could play an important role in its aetiology.
Hyperinsulinemia and insulin resistance in non-alcoholic steatohepatitis
Authors: Ethem Tankurt, Sevinç Biberoglu, Ender Ellidokuz, Zeliha Hekimsoy, Hale Akpinar, Abdurrahman çömlekçi, Abdullah Okan, Özgül Sagol
Journal: Journal of Hepatology (1999)
Phase I Clinical Trial of the CYP17 Inhibitor Abiraterone Acetate Demonstrating Clinical Activity in Patients With Castration-Resistant Prostate Cancer Who Received Prior Ketoconazole Therapy
Authors: Charles J. Ryan, Matthew R. Smith, Lawrence Fong, Jonathan E. Rosenberg, Philip Kantoff, Florence Raynaud, Vanessa Martins, Gloria Lee, Thian Kheoh, Jennifer Kim, Arturo Molina, Eric J. Small
Journal: Journal of Clinical Oncology (2010)

Abiraterone acetate is a prodrug of abiraterone, a selective inhibitor of CYP17, the enzyme catalyst for two essential steps in androgen biosynthesis. In castration-resistant prostate cancers (CRPCs), extragonadal androgen sources may sustain tumor growth despite a castrate environment. This phase I dose-escalation study of abiraterone acetate evaluated safety, pharmacokinetics, and effects on steroidogenesis and prostate-specific antigen (PSA) levels in men with CPRC with or without prior ketoconazole therapy.Thirty-three men with chemotherapy-naïve progressive CRPC were enrolled. Nineteen patients (58%) had previously received ketoconazole for CRPC. Bone metastases were present in 70% of patients, and visceral involvement was present in 18%. Three patients (9%) had locally advanced disease without distant metastases. Fasted or fed cohorts received abiraterone acetate doses of 250, 500, 750, or 1,000 mg daily. Single-dose pharmacokinetic analyses were performed before continuous daily dosing.Adverse events were predominantly grade 1 or 2. No dose-limiting toxicities were observed. Hypertension (grade 3, 12%) and hypokalemia (grade 3, 6%; grade 4, 3%) were the most frequent serious toxicities and responded to medical management. Confirmed > or = 50% PSA declines at week 12 were seen in 18 (55%) of 33 patients, including nine (47%) of 19 patients with prior ketoconazole therapy and nine (64%) of 14 patients without prior ketoconazole therapy. Substantial declines in circulating androgens and increases in mineralocorticoids were seen with all doses.Abiraterone acetate was well tolerated and demonstrated activity in CRPC, including in patients previously treated with ketoconazole. Continued clinical study is warranted.
Reducing the Burden of Cardiovascular Calcification in Patients with Chronic Kidney Disease
Authors: Wajeh Y. Qunibi
Journal: Journal of the American Society of Nephrology (2005)

Patients with chronic kidney disease (CKD) have a higher burden of atherosclerotic coronary artery disease compared with age- and gender-matched individuals with normal renal function. Cardiovascular calcification (CVC), a marker of atherosclerosis, is also more prevalent in these patients and is associated with serious clinical consequences. The pathogenesis of CVC is complex and includes factors that promote calcification and others that inhibit calcification. Thus, multiple therapeutic interventions should be used simultaneously to reduce the burden of calcification in patients with CKD. Thus far, interventional attempts have focused on curtailing the effects of factors that promote calcification such as management of known traditional factors for atherosclerotic coronary artery disease and on adopting specific approaches to normalize mineral metabolism, deliver adequate dialysis, and control serum cholesterol level. By contrast, interventions that may bolster the effects of inhibitors of calcification have not yet been studied well but are beginning to attract attention. Ideally, the goal of interventions is not only to slow or halt progression of calcification but also to reverse pre-existing calcification. Whether this goal is achievable is not currently known. This review examines the potential of various therapeutic interventions in reducing the CVC burden in patients with CKD. Moreover, the review is intended to stimulate more research in this area because the efficacy of these interventions has not been examined in controlled clinical trials.
Serum Adipocyte Fatty Acid–Binding Protein as a New Biomarker Predicting the Development of Type 2 Diabetes
Authors: Annette W.K. Tso, Aimin Xu, Pak C. Sham, Nelson M.S. Wat, Yu Wang, Carol H.Y. Fong, Bernard M.Y. Cheung, Edward D. Janus, Karen S.L. Lam
Journal: Diabetes Care (2007)

Adipocyte fatty acid-binding protein (A-FABP) is abundantly expressed in adipocytes and plays a role in glucose homeostasis in experimental animals. We have previously shown that circulating A-FABP levels are associated with the metabolic syndrome, which confers an increased risk of type 2 diabetes. Here we investigated whether serum A-FABP levels could predict the development of diabetes in a 10-year prospective study.Baseline serum A-FABP levels were measured with an enzyme-linked immunosorbent assay in 544 nondiabetic subjects, recruited from the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort, who were followed prospectively to assess the development of type 2 diabetes. The role of A-FABP in predicting the development of type 2 diabetes over 10 years was investigated using Cox regression analysis.At baseline, serum sex-adjusted A-FABP levels were higher in subjects with impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) (P < 0.00001 versus normal glucose tolerance) and correlated positively with adverse cardiometabolic risk factors. Over 10 years, 96 subjects had developed type 2 diabetes. High baseline A-FABP was predictive of type 2 diabetes, independent of obesity, insulin resistance, or glycemic indexes (relative risk [RR] 2.25 [95% CI 1.40-3.65]; P = 0.001; above versus below sex-specific median). High A-FABP levels remained an independent predictor of type 2 diabetes in the high-risk IGT/IFG subgroup (adjusted RR 1.87 [1.12-3.15]; P = 0.018).Serum A-FABP was associated with glucose dysregulation and predicted the development of type 2 diabetes in a Chinese cohort.
Glycemic Control, Atherosclerosis, and Risk Factors for Cardiovascular Disease in Individuals With Diabetes
Authors: Elizabeth Selvin, Josef Coresh, Sherita H. Golden, Lori L. Boland, Frederick L. Brancati, Michael W. Steffes
Journal: Diabetes Care (2005)

OBJECTIVE—Glycemic control (HbA1c [A1C]) is strongly associated with microvascular disease in individuals with diabetes, but its relation to macrovascular disease and atherosclerosis is less clear. This study examines the relationship between A1C, carotid intima-media thickness (IMT), and traditional cardiovascular risk factors in individuals with diabetes. RESEARCH DESIGN AND METHODS—A cross-sectional study of 2,060 people with diagnosed and undiagnosed (unrecognized) diabetes in the Atherosclerosis Risk in Communities study was performed. RESULTS—LDL and HDL cholesterol, plasma triglycerides, and waist-to-hip ratio were significantly associated with A1C after multivariable adjustment. African Americans with undiagnosed and diagnosed diabetes had significantly elevated A1C values compared with whites, even after adjustment for potentially confounding factors. There was a graded association between A1C and carotid IMT. In a fully adjusted model in individuals with undiagnosed diabetes, the odds ratio (OR) of being in the highest quartile of IMT versus the lowest was 2.46 (95% CI 1.16–5.03, comparing the highest quartile of A1C to the lowest). In people with diagnosed diabetes, the comparable OR was 2.62 (1.36–5.06). CONCLUSIONS—This study identified several important associations between A1C and known risk factors for cardiovascular disease and suggested that A1C is independently related to carotid IMT. Chronically elevated glucose levels may contribute to the development of atherosclerosis in people with diabetes, independent of other risk factors.
Combined low-FOXP3+ and -CD3+tumor infiltrating lymphocytes: a signature of stage II MSS colorectal cancer at high-risk of recurrence
Authors: Giuseppe Di Caro, Giuseppe Celesti, Fabio Grizzi, Paolo Bianchi, Gianluca Basso, Federica Marchesi, Alberto Mantovani, Alberto Malesci, Luigi Laghi
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Low densities of tumor infiltrating lymphocytes (TILs) predict colorectal cancer (CRC) post-surgical recurrence, the likelihood of progression also depending upon tumor stage and microsatellite (MS) status. We benchmarked FoxP3+TIL and CD3+TIL densities as predictor of
Septic arthritis in rheumatoid disease causing bilateral shoulder dislocation: diagnosis and treatment assisted by grey scale ultrasonography.
Authors: B M Gompels, L G Darlington
Journal: Annals of the Rheumatic Diseases (1981)

Signs of sepsis may be obscure in patients with rheumatoid arthritis, particularly in association with long-term steroid therapy. If mortality is to be avoided, a high index of suspicion must be maintained for the diagnosis, and doubtful joints should be aspirated for culture and prompt therapy with the correct antibiotic. In this report a patients with advanced rheumatoid arthritis presented with bilateral shoulder dislocation due to septic arthritis. Ultrasonography was particularly helpful in guiding a 20 G needle to fluid collections with the debris-filled joint capsules and in facilitating successful aspiration. Ultrasound also provided a painless, noninvasive, and safe method of serial assessment of the joints after therapy.
Identification of soluble Fc receptors in mouse serum and the conditioned medium of stimulated B cells.
Authors: E Pure, C J Durie, C K Summerill, J C Unkeless
Journal: The Journal of Experimental Medicine (1984)

We have evaluated the expression of surface Fc gamma 2b/gamma 1R by lipopolysaccharide (LPS)-activated murine spleen cells, the release of soluble Fc gamma 2b/gamma 1R by activated spleen cells, and the presence of circulating Fc gamma 2b/gamma 1R in mouse serum. LPS activation of murine spleen cells and a cloned B cell line, BCL-1 CW 13.20-3B3, resulted in a 5-10-fold increase in surface Fc gamma 2b/gamma 1R and the concominant appearance in the culture medium of a soluble molecule that is antigenically related to the Fc gamma 2b/gamma 1R. The increase in cell-associated and soluble Fc gamma 2b/gamma 1R after LPS activation is attributable primarily to B cells. Circulating Fc gamma 2b/gamma 1R was also detected in normal mouse serum at a concentration of 10(-9) to 10(-8) M. Levels of circulating Fc gamma 2b/gamma 1R increase with the age of the animals, and were low in adult germ-free mice and elevated in young mice with certain autoimmune diseases. The circulating Fc gamma 2b/gamma 1R bound to IgG-Sepharose, and was partially purified by affinity chromatography on 2.4G2 Fab-Sepharose. After radiolabeling and immunoprecipitation with rabbit anti-Fc gamma 2b/gamma 1R serum, one component of Mr 48,000, was detected.
The High Prevalence of Vitamin D Insufficiency across Australian Populations Is Only Partly Explained by Season and Latitude
Authors: Ingrid A.F. van der Mei, Anne-Louise Ponsonby, Ola Engelsen, Julie A. Pasco, John J. McGrath, Daryl W. Eyles, Leigh Blizzard, Terence Dwyer, Robyn Lucas, Graeme Jones
Journal: Environmental Health Perspectives (2007)

BackgroundInadequate sun exposure and dietary vitamin D intake can result in vitamin D insufficiency. However, limited data are available on actual vitamin D status and predictors in healthy individuals in different regions and by season.MethodsWe compared vitamin D status [25-hydroxyvitamin D; 25(OH)D] in people < 60 years of age using data from cross-sectional studies of three regions across Australia: southeast Queensland (27°S; 167 females and 211 males), Geelong region (38°S; 561 females), and Tasmania (43°S; 432 females and 298 males).ResultsThe prevalence of vitamin D insufficiency (≤ 50 nmol/L) in women in winter/spring was 40.5% in southeast Queensland, 37.4% in the Geelong region, and 67.3% in Tasmania. Season, simulated maximum daily duration of vitamin D synthesis, and vitamin D effective daily dose each explained around 14% of the variation in 25(OH)D. Although latitude explained only 3.9% of the variation, a decrease in average 25(OH)D of 1.0 (95% confidence interval, 0.7–1.3) nmol/L for every degree increase in latitude may be clinically relevant. In some months, we found a high insufficiency or even deficiency when sun exposure protection would be recommended on the basis of the simulated ultraviolet index.ConclusionVitamin D insufficiency is common over a wide latitude range in Australia. Season appears to be more important than latitude, but both accounted for less than one-fifth of the variation in serum 25(OH)D levels, highlighting the importance of behavioral factors. Current sun exposure guidelines do not seem to fully prevent vitamin D insufficiency, and consideration should be given to their modification or to pursuing other means to achieve vitamin D adequacy.