tbuckley/cabot-search huggingface dataset:
Family size, fertility preferences, and sex ratio in China in the era of the one child family policy: results from national family planning and reproductive health survey
Authors: Qu Jian Ding, Therese Hesketh
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objectives</b> To examine the impact of the one child family policy in China on fertility, preferred family size, and sex ratio. <b>Design</b> Secondary analysis of data from the Chinese cross sectional national family planning and reproductive health survey, 2001. Interviews of representative sample of women aged 15-49. <b>Results</b> Data were obtained from 39 585 women, with a total of 73 202 pregnancies and 56 830 live births. The average fertility rate in women over 35 (n = 17 078) was 1.94 (2.1 in rural areas and 1.4 in urban areas) and for women under 35 (n = 11 543) 1.73 (1.25 and 1.79). Smaller families were associated with younger age, higher level of education, and living in an urban area. The male to female ratio was 1.15 and rose from 1.11 in 1980-9 to 1.23 for 1996-2001. Most women wanted small families: 35% preferred one child and 57% preferred two. <b>Conclusion</b> Since the one child family policy began, the total birth rate and preferred family size have decreased, and a gross imbalance in the sex ratio has emerged.
Do Organohalogen Contaminants Contribute to Histopathology in Liver from East Greenland Polar Bears ( <i>Ursus maritimus</i> )?
Authors: Christian Sonne, Rune Dietz, Pall S. Leifsson, Erik W. Born, Robert J. Letcher, Maja Kirkegaard, Derek C. G. Muir, Frank F. Riget, Lars Hyldstrup
Journal: Environmental Health Perspectives (2005)

In East Greenland polar bears (Ursus maritimus), anthropogenic organohalogen compounds (OHCs) (e.g., polychlorinated biphenyls, dichlorodiphenyltrichloroethane, and polybrominated diphenyl ethers) contributed to renal lesions and are believed to reduce bone mineral density. Because OHCs are also hepatotoxic, we investigated liver histology of 32 subadult, 24 adult female, and 23 adult male East Greenland polar bears sampled during 1999-2002. Light microscopic changes consisted of nuclear displacement from the normal central cytoplasmic location in parenchymal cells, mononuclear cell infiltrations (mainly portally and as lipid granulomas), mild bile duct proliferation accompanied by fibrosis, and fat accumulation in hepatocytes and pluripotent Ito cells. Lipid accumulation in Ito cells and bile duct hyperplasia accompanied by portal fibrosis were correlated to age, whereas no changes were associated with either sex or season (summer vs. winter). For adult females, hepatocytic intracellular fat increased significantly with concentrations of the sum of hexachlorocyclohexanes, as was the case for lipid granulomas and hexachlorobenzene in adult males. Based on these relationships and the nature of the chronic inflammation, we suggest that these findings were caused by aging and long-term exposure to OHCs. Therefore, these changes may be used as biomarkers for OHC exposure in wildlife and humans. To our knowledge, this is the first time liver histology has been evaluated in relation to OHC concentrations in a mammalian wildlife species, and the information is important to future polar bear conservation strategies and health assessments of humans relying on OHC-contaminated food resources.
The Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors Vatalanib and Pazopanib Potently Induce Apoptosis in Chronic Lymphocytic Leukemia Cells <i>In vitro</i> and <i>In vivo</i>
Authors: Julian Paesler, Iris Gehrke, Rajesh Kumar Gandhirajan, Alexandra Filipovich, Magdalena Hertweck, Felix Erdfelder, Sabrina Uhrmacher, Simon Jonas Poll-Wolbeck, Michael Hallek, Karl-Anton Kreuzer
Journal: Clinical Cancer Research (2010)

There is evidence that vascular endothelial growth factor (VEGF) is a critical microenvironmental factor that exerts angiogenesis-independent effects on the survival of chronic lymphocytic leukemia (CLL) cells. Vatalanib and pazopanib are potent orally available VEGF receptor tyrosine kinase inhibitors. We investigated the efficacy and selectivity of both compounds in CLL cells, simulated potential combination with conventional cytostatics, and tested the effect of both substances on CLL-like tumor xenografts.Primary CLL and normal peripheral blood cells were tested for viability after incubation with varying concentrations of both inhibitors. Further, phosphorylation status of VEGF receptor on treatment, caspase activation, and poly(ADP-ribose) polymerase cleavage were assessed. Combinations of each inhibitor with fludarabine, vincristine, and doxorubicin were analyzed for possible synergistic effects in vitro. For in vivo testing, mice grafted with the CLL-like cell line JVM-3 were treated orally with each inhibitor.Vatalanib and pazopanib decreased phosphorylation of the VEGF receptor, along with induction of apoptosis in CLL cells in clinically achievable concentrations. Healthy B cells were only mildly affected. Immunoblots showed downregulation of the antiapoptotic proteins XIAP and MCL1, whereas poly(ADP-ribose) polymerase cleavage was increased. Combinations with conventional cytostatic agents resulted in synergistic effects. Treatment of xenografted mice with 100 mg/kg of body weight for 21 days resulted in tumor inhibition rates of 76% (vatalanib) and 77% (pazopanib). In two mice, a total tumor eradication could be observed. No gross systemic toxicity occurred.We conclude that VEGF inhibition is a promising new therapeutic approach in CLL. Vatalanib and pazopanib seem to be effective and safe candidates to be further evaluated for this purpose.
Hepatic Carcinogenesis of Aflatoxin M1 in Rainbow Trout (Salmo gairdneri) and Its Enchancement by Cyclopropene Fatty Acids23
Authors: R. O. Sinnhuber, D.J Lee, J. H. Wales, M. K. Landers, A. C. Keyl
Journal: JNCI Journal of the National Cancer Institute (1974)

Aflatoxin M1, a hydroxylated metabolite of aflatoxin B1, has been found in the milk, urine, and tissues of animals which have consumed aflatoxin B1. Aflatoxin M1, isolated from cultures of Aspergillus f1avus and fed to rainbow trout, was a potent liver carcinogen but less carcinogenic than aflatoxin B1. Levels of 4 and 16 parts per billion (ppb) aflatoxin M1 in a purified test diet produced a 13 and 60% incidence, respectively, of hepatoma in 12 months. Cyclopropenoid fatty acids (CPFA), which promote the carcinogenicity of aflatoxin B1 in trout, behave similarly with M1. Dietary levels of 4 ppb aflatoxin M1 with CPFA gave a 70% incidence of liver cancer in 8 months. Trout that received 20 ppb aflatoxin M1 in their diet for 5–30 days developed a 3–12% incidence of hepatoma in 12 months. A significant number of mortalities occurred amongfemale trout with aflatoxin M1-induced hepatomas at time of maturation (16–20 months) in contrast to no mortality in males.
Treatment of Non-puerperal Galactorrhoea with an Ergot Alkaloid
Authors: P. M. Lutterbeck, J. S. Pryor, L. Varga, R. Wenner
Journal: BMJ (1971)

Three patients suffering from non-puerperal galactorrhoea over periods ranging from two months to six years were treated with an ergot alkaloid, 2-Br-alpha-ergocryptine (CB 154). In all three cases the galactorrhoea was terminated. The apparent prolactin antagonism exhibited by this compound is discussed.
Cyclin-Dependent Kinase Inhibitor AT7519 as a Potential Drug for MYCN-Dependent Neuroblastoma
Authors: M. Emmy M. Dolman, Evon Poon, Marli E. Ebus, Ilona J.M. den Hartog, Carel J.M. van Noesel, Yann Jamin, Albert Hallsworth, Simon P. Robinson, Kevin Petrie, Rolf W. Sparidans, Robbert J. Kok, Rogier Versteeg, Huib N. Caron, Louis Chesler, Jan J. Molenaar
Journal: Clinical Cancer Research (2015)

Abstract Purpose: MYCN-dependent neuroblastomas have low cure rates with current multimodal treatment regimens and novel therapeutic drugs are therefore urgently needed. In previous preclinical studies, we have shown that targeted inhibition of cyclin-dependent kinase 2 (CDK2) resulted in specific killing of MYCN-amplified neuroblastoma cells. This study describes the in vivo preclinical evaluation of the CDK inhibitor AT7519. Experimental Design: Preclinical drug testing was performed using a panel of MYCN-amplified and MYCN single copy neuroblastoma cell lines and different MYCN-dependent mouse models of neuroblastoma. Results: AT7519 killed MYCN-amplified neuroblastoma cell lines more potently than MYCN single copy cell lines with a median LC50 value of 1.7 compared to 8.1 μmol/L (P = 0.0053) and a significantly stronger induction of apoptosis. Preclinical studies in female NMRI homozygous (nu/nu) mice with neuroblastoma patient-derived MYCN-amplified AMC711T xenografts revealed dose-dependent growth inhibition, which correlated with intratumoral AT7519 levels. CDK2 target inhibition by AT7519 was confirmed by significant reductions in levels of phosphorylated retinoblastoma (p-Rb) and nucleophosmin (p-NPM). AT7519 treatment of Th-MYCN transgenic mice resulted in improved survival and clinically significant tumor regression (average tumor size reduction of 86% at day 7 after treatment initiation). The improved efficacy of AT7519 observed in Th-MYCN mice correlated with higher tumor exposure to the drug. Conclusions: This study strongly suggests that AT7519 is a promising drug for the treatment of high-risk neuroblastoma patients with MYCN amplification. Clin Cancer Res; 21(22); 5100–9. ©2015 AACR.
S179D Prolactin Increases Vitamin D Receptor and p21 through Up-regulation of Short 1b Prolactin Receptor in Human Prostate Cancer Cells
Authors: Wei Wu, Erika Ginsburg, Barbara K. Vonderhaar, Ameae M. Walker
Journal: Cancer Research (2005)

Abstract In this study, we further investigated the mechanisms by which pseudophosphorylated prolactin (S179D PRL) inhibits the growth of human prostate cancer cells. When treated with S179D PRL for 3 days, LnCAP cells responded by increasing expression of the vitamin D receptor (VDR) and the cell cycle regulatory molecule, p21, whereas PC3 and DU145 cells did not. After 5 days of treatment, both PC3 and DU145 cells responded. Untreated LnCAP cells express the short 1b form (SF1b) of the human prolactin receptor, but DU145 and PC3 cells express only low amounts of this receptor until elevated by treatment with S179D PRL. DU145 and PC3 cells become sensitive to the negative effects of S179D PRL on cell number after induction of the SF1b. Transfection of either SF1b or SF1a into PC3 or DU145 cells made them sensitive to S179D PRL in the 3-day time frame, a finding that was not duplicated by transfection with the long form of the receptor. Treatment of LnCAP cells with S179D PRL increased long-term activation of extracellular signal-regulated kinase 1/2 (ERK1/2). This did not occur in PC3 and DU145 cells until transfection with SF1a/SF1b. Blockade of ERK signaling eliminated S179D PRL-stimulated expression of the VDR and p21 in LnCAP cells and transfected PC3 and DU145 cells. We conclude that initiation of alternative splicing to produce SF1b, and subsequent altered signaling, contribute to the growth inhibitory mechanisms of S179D PRL. This is the first indication of a role for short prolactin receptors in the regulation of cell proliferation.
Allergy to ingested cereals in atopic children
Authors: L. Räsänen, M. Lehto, K. Turjanmaa, J. Savolainen, T. Reunala
Journal: Allergy (1994)

Clinical features, hypersensitivity mechanisms, and differential diagnosis of cereal allergy or intolerance were investigated in children with atopic dermatitis (AD). On oral provocation, 18 children exhibited a positive response to wheat, three to rye, one to barley, and one to oats. Cereal-induced symptoms were dermatologic, gastrointestinal, or oropharyngeal, and their onset after provocation was immediate (eight cases), delayed (14 cases), or both immediate and delayed (one case). A combination of type I allergy tests (prick test, RAST, and histamine-release test) detected all immediate reactors and 9/14 delayed reactors. Of the five subjects remaining negative in these tests, three were positive in the patch or lymphocyte-proliferation tests. Subjects with cereal allergy or intolerance frequently possessed IgE, IgA, and IgG antibodies against gliadin, but only one of these children was HLA-DR3-positive, and none had reticulin antibodies typical of celiac disease. Combining tests of immediate and delayed hypersensitivity can confirm allergy to cereals in a more reliable way. The coexistence of cereal allergy and celiac disease seems to be rare.
Diffuse Large B-Cell Lymphoma: Clinical and Biological Characterization and Outcome According to the Nodal or Extranodal Primary Origin
Authors: Armando López-Guillermo, Luis Colomo, Mónica Jiménez, Francesc Bosch, Neus Villamor, Leonor Arenillas, Ana Muntañola, Silvia Montoto, Eva Giné, Dolors Colomer, Silvia Beà, Elías Campo, Emili Montserrat
Journal: Journal of Clinical Oncology (2005)

Purpose To study the main clinicobiologic features, response, and outcome of patients with diffuse large B-cell lymphoma (DLBCL) according to the primary site, lymph node, or different extranodal organs of the disease. Patients and Methods We included 382 patients consecutively diagnosed with DLBCL in a single institution during a 13-year period. Morphology, immunophenotyping, proliferation index, differentiation profile, bcl-2/JH rearrangement, and clinical characteristics were analyzed according to the primary site of the lymphoma. Results Sites of the disease were: lymph node, 222 cases (58%); Waldeyer's ring (WR), 42 (11%); and extranodal sites, 118 (31%), including GI tract in 45 cases. Primary extranodal cases, particularly GI, showed a bcl-6 expression more frequently than nodal cases. Patients with primary WR or GI lymphomas presented with early-stage disease, no marrow infiltration, normal serum lactate dehydrogenase, and low- to low/intermediate-risk international prognostic index (IPI) more frequently than the remainder. Complete response (CR) rate was 63%, with WR and GI lymphomas having a higher CR rate (85% and 80%, respectively) than the other groups. In the whole series, 5-year overall survival (OS) was 52%. Patients with WR or GI lymphomas showed better OS (5-year OS: 77% and 68%, respectively) than patients with nodal or other extranodal sites. In the multivariate analysis, IPI, bulky disease, and β2-microglobulin were the main variables to predict OS; no nodal or extranodal site maintained their prognostic value. Conclusion In the present series, the primary site of disease was associated with particular clinicopathologic features and outcome, though the latter largely depended on other factors.
IL-10 administration reduces PGE-2 levels and promotes CR3-mediated clearance of <i>Escherichia coli</i> K1 by phagocytes in meningitis
Authors: Rahul Mittal, Ignacio Gonzalez-Gomez, Ashok Panigrahy, Kerstin Goth, Richard Bonnet, Nemani V. Prasadarao
Journal: The Journal of Experimental Medicine (2010)

Ineffectiveness of antibiotics in treating neonatal Escherichia coli K1 meningitis and the emergence of antibiotic-resistant strains evidently warrants new prevention strategies. We observed that administration of interleukin (IL)-10 during high-grade bacteremia clears antibiotic-sensitive and -resistant E. coli from blood of infected mice. Micro-CT studies of brains from infected animals displayed gross morphological changes similar to those observed in infected human neonates. In mice, IL-10, but not antibiotic or anti-TNF antibody treatment prevented brain damage caused by E. coli. IL-10 administration elevated CR3 expression in neutrophils and macrophages of infected mice, whereas infected and untreated mice displayed increased expression of FcγRI and TLR2. Neutrophils or macrophages pretreated with IL-10 ex vivo exhibited a significantly greater microbicidal activity against E. coli compared with cells isolated from wild-type or IL-10−/− mice. The protective effect of IL-10 was abrogated when CR3 was knocked-down in vivo by siRNA. The increased expression of CR3 in phagocytes was caused by inhibition of prostaglandin E-2 (PGE-2) levels, which were significantly increased in neutrophils and macrophages upon E. coli infection. These findings describe a novel modality of IL-10–mediated E. coli clearance by diverting the entry of bacteria via CR3 and preventing PGE-2 formation in neonatal meningitis.
The HLA-DR4 family of haplotypes consists of series of distinct DR and DS molecules.
Authors: G T Nepom, B S Nepom, P Antonelli, E Mickelson, J Silver, S M Goyert, J A Hansen
Journal: The Journal of Experimental Medicine (1984)

Among DR4-associated HLA-D antigens, distinct and consistent structural variations were found for the products of two human "Ia-like" loci, DR and DS. Analysis of neuraminidase-treated immunoprecipitated DR molecules from 15 HLA-DR4-associated HLA-D homozygous B-lymphoblastoid cell lines by two dimensional polyacrylamide gel electrophoresis identified five distinct DR beta chains. In addition, gel analysis of immunoprecipitated DS molecules identified three distinct DS beta chains. Altogether, five distinct DR4 haplotypes were defined according to the observed structural diversity of the DR and DS beta chains. These gene products presumably contribute the dominant polymorphisms recognized by T cells in mixed lymphocyte reaction (MLR). Thus, these studies indicate that the serologic specificity known as HLA-DR4 is not a single haplotype, but a determinant present on products of individual loci arrayed into distinctly different haplotypes. These findings suggest that distinct products of individual loci, rather than conventional HLA specificities defined by alloimmune sera, may represent the genetic markers relevant to HLA-D/DR associated diseases.
Statins for primary prevention: strategic options to save lives and money
Authors: J. Shepherd
Journal: Journal of the Royal Society of Medicine (2004)

Although the statins have effectively ended the debate on the benefit of cholesterol lowering, there is less agreement on how and when they should be used in the primary prevention of vascular disease. Some investigators favour aggressive intervention, on the premise that endemic diseases need fundamental action;1 others take a more conservative stance, fearful that the high prevalence of occlusive arterial disease a wholesale attempt to counter would overwhelm an already stressed healthcare system.2

Geoffrey Rose,3 the doyen of preventive cardiology, stated in 1991 that 'all policy decisions should be based on absolute measures of risk; relative risk is strictly for researchers only'. By extrapolation then, risk management for prevention of coronary heart disease should be based on absolute global risk assessment, so that scarce healthcare resources can be targeted at those patients in greatest need. Remarkably, within the space of a decade, this advice has been enshrined in two series of guidelines providing recommendations for prevention of coronary heart disease in clinical practice. In 1994, a Task Force with representation from the European Atherosclerosis Society, the European Society of Cardiology and the European Society of Hypertension emphasized the importance of overall vascular risk assessment in a report4 that unified preventive strategies for vascular disease across Europe. This document has recently been updated and modified5 to make it applicable to more than thirty European countries.6

Enlightenment in Europe has spread to the USA. The third report of the Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults—a group within the framework of the National Cholesterol Education Program that has driven national policy on cholesterol management since the 1980s—although still focusing on LDL cholesterol as the primary target of therapy, expands its horizons to include other lipid and non-lipid risk factors within a management portfolio for prevention of vascular disease based on the absolute risk of the patient.7 The principles of the European and US coronary prevention guidelines are therefore fundamentally the same, promoting the use of global risk assessment and treatment strategies that broaden choice for the clinician and expand options for the citizen.
ZD1694: A novel thymidylate synthase inhibitor with substantial activity in the treatment of patients with advanced colorectal cancer. Tomudex Colorectal Study Group.
Authors: J R Zalcberg, D Cunningham, E Van Cutsem, E Francois, J Schornagel, A Adenis, M Green, A Iveson, M Azab, I Seymour
Journal: Journal of Clinical Oncology (1996)

PURPOSE Tomudex (ZD1694; Zeneca Ltd, Macclesfield, United Kingdom) appears to have a favorable toxicity profile (defined in phase I studies) and antitumor activity in a broad range of epithelial tumors. We report here the results of a large phase II study of Tomudex in advanced colorectal cancer (CRC). PATIENTS AND METHODS One hundred seventy-seven patients were entered onto the study between October 1992 and September 1993. Patients were required to have advanced CRC without prior chemotherapy (adjuvant chemotherapy was permissible) and at least one measurable lesion. Tomudex (ZD1694) was administered at a dose of 3 mg/m2 intravenously once every 3 weeks in the absence of toxicity or disease progression. Patients were assessed for objective response, progression, and survival. RESULTS Of 177 patients entered onto the study, 5% had received prior adjuvant chemotherapy and 83% had liver metastases. Objective responses were seen in 26% of patients (95% confidence interval, 19% to 33%; four complete responses [CRs] and 41 partial responses [PRs]) while median time to progression was 4.2 months and median survival 9.6 months. All sites were audited, and responses were reviewed by an independent panel. Common toxicities included mild reversible transaminitis, nausea and vomiting, and asthenia or flu-like symptoms, and World Health Organization (WHO) grade 3 and 4 leukopenia and diarrhea were seen in 6% and 9.8% of patients, respectively. Stomatitis and alopecia were common. CONCLUSION In this large multicenter phase II study of patients with advanced CRC, interesting activity was seen (objective response rate, 26%). In addition, Tomudex has an acceptable toxicity profile and a convenient dosing schedule (single intravenous injection every 3 weeks) and thus appears to offer real potential as a novel agent for the treatment of patients with advanced CRC.
Sudden onset diffuse erythema and oedema of the breast
Authors: Inês Vasconcelos, Miguel de Sousa Mendes, Jörg Linke, Winfried Schoenegg
Journal: BMJ (2015)

A 40 year old premenopausal white woman presented to a general gynaecologist with diffuse redness, swelling, and rapidly progressive pain in her left breast. She did not have a fever. Her medical history included one full term pregnancy with spontaneous delivery 19 years earlier. Her maternal grandmother had died of breast cancer at age 65 years. On physical examination, a warm and painful diffuse oedematous erythema was found in the inner quadrants of the breast (fig 1⇓), but she was otherwise in good general health.





### 1. On the basis of the history and examination findings, what are the differential diagnoses and the probable diagnosis?

#### Short answer

Non-lactational mastitis, cellulitis, abscess, and inflammatory breast cancer (IBC). Figure 1⇑ shows a classic presentation of IBC.

#### Discussion

Breast masses require triple test evaluation—physical examination, radiological examination, and needle biopsy—the results of which must all agree. IBC is diagnosed on clinical grounds, so the physical examination is key. The classic findings are diffuse erythema and oedema with bulging intradermal lymphatics enveloping more than a third of the breast, as well as the absence of systemic symptoms such as malaise and fever.

The differential diagnosis in this setting, based on the physical examination, includes non-lactational mastitis, cellulitis, abscess, and inflammatory breast cancer. Non-lactational abscesses …
Hirudin versus heparin for anticoagulation in continuous renal replacement therapy
Authors: O. Vargas Hein, C. von Heymann, M. Lipps, S. Ziemer, C. Ronco, H.H. Neumayer, S. Morgera, M. Welte, W.J. Kox, C. Spies
Journal: Intensive Care Medicine (2001)