tbuckley/cabot-search huggingface dataset:
Helmet legislation and admissions to hospital for cycling related head injuries in Canadian provinces and territories: interrupted time series analysis
Authors: J. Dennis, T. Ramsay, A. F. Turgeon, R. Zarychanski
Journal: BMJ (2013)

<b>Objective</b> To investigate the association between helmet legislation and admissions to hospital for cycling related head injuries among young people and adults in Canada. <b>Design</b> Interrupted time series analysis using data from the National Trauma Registry Minimum Data Set. <b>Setting</b> Canadian provinces and territories; between 1994 and 2003, six of 10 provinces implemented helmet legislation. <b>Participants</b> All admissions (n=66 716) to acute care hospitals in Canada owing to cycling related injury between 1994 and 2008. <b>Main outcome measure</b> Rate of admissions to hospital for cycling related head injuries before and after the implementation of provincial helmet legislation. <b>Results</b> Between 1994 and 2008, 66 716 hospital admissions were for cycling related injuries in Canada. Between 1994 and 2003, the rate of head injuries among young people decreased by 54.0% (95% confidence interval 48.2% to 59.8%) in provinces with helmet legislation compared with 33.1% (23.3% to 42.9%) in provinces and territories without legislation. Among adults, the rate of head injuries decreased by 26.0% (16.0% to 36.3%) in provinces with legislation but remained constant in provinces and territories without legislation. After taking baseline trends into consideration, however, we were unable to detect an independent effect of legislation on the rate of hospital admissions for cycling related head injuries. <b>Conclusions</b> Reductions in the rates of admissions to hospital for cycling related head injuries were greater in provinces with helmet legislation, but injury rates were already decreasing before the implementation of legislation and the rate of decline was not appreciably altered on introduction of legislation. While helmets reduce the risk of head injuries and we encourage their use, in the Canadian context of existing safety campaigns, improvements to the cycling infrastructure, and the passive uptake of helmets, the incremental contribution of provincial helmet legislation to reduce hospital admissions for head injuries seems to have been minimal.
The Estrogen Receptor Cofactor SPEN Functions as a Tumor Suppressor and Candidate Biomarker of Drug Responsiveness in Hormone-Dependent Breast Cancers
Authors: Stéphanie Légaré, Luca Cavallone, Aline Mamo, Catherine Chabot, Isabelle Sirois, Anthony Magliocco, Alexander Klimowicz, Patricia N. Tonin, Marguerite Buchanan, Dana Keilty, Saima Hassan, David Laperrière, Sylvie Mader, Olga Aleynikova, Mark Basik
Journal: Cancer Research (2015)

The treatment of breast cancer has benefitted tremendously from the generation of estrogen receptor-α (ERα)-targeted therapies, but disease relapse continues to pose a challenge due to intrinsic or acquired drug resistance. In an effort to delineate potential predictive biomarkers of therapy responsiveness, multiple groups have identified several uncharacterized cofactors and interacting partners of ERα, including Split Ends (SPEN), a transcriptional corepressor. Here, we demonstrate a role for SPEN in ERα-expressing breast cancers. SPEN nonsense mutations were detectable in the ERα-expressing breast cancer cell line T47D and corresponded to undetectable protein levels. Further analysis of 101 primary breast tumors revealed that 23% displayed loss of heterozygosity at the SPEN locus and that 3% to 4% harbored somatically acquired mutations. A combination of in vitro and in vivo functional assays with microarray-based pathway analyses showed that SPEN functions as a tumor suppressor to regulate cell proliferation, tumor growth, and survival. We also found that SPEN binds ERα in a ligand-independent manner and negatively regulates the transcription of ERα targets. Moreover, we demonstrate that SPEN overexpression sensitizes hormone receptor-positive breast cancer cells to the apoptotic effects of tamoxifen, but has no effect on responsiveness to fulvestrant. Consistent with these findings, two independent datasets revealed that high SPEN protein and RNA expression in ERα-positive breast tumors predicted favorable outcome in patients treated with tamoxifen alone. Together, our data suggest that SPEN is a novel tumor-suppressor gene that may be clinically useful as a predictive biomarker of tamoxifen response in ERα-positive breast cancers.
A rare cause of "cellulitis"
Authors: R J Van Wensen, J P Ruurda, H J Van Geffen, K Bosscha
Journal: Gut (2008)

A 74-year-old man presented to the emergency department with lower back pain and left lower quadrant pain. His medical history included Parkinson’s disease and left inguinal hernia repair. He was dyspnoeic and coughing.

On examination, he …
Plasmin(ogen) Promotes Renal Interstitial Fibrosis by Promoting Epithelial-to-Mesenchymal Transition
Authors: Guoqiang Zhang, Kelly A. Kernan, Sarah J. Collins, Xiaohe Cai, Jesús M. López-Guisa, Jay L. Degen, Yigal Shvil, Allison A. Eddy
Journal: Journal of the American Society of Nephrology (2007)

Plasminogen (Plg) activator inhibitor-1 (PAI-1) is an important fibrosis-promoting molecule. Whether this effect can be attributed to PAI-1’s activity as an inhibitor of plasmin generation is debated. This study was designed to investigate the role of Plg in renal fibrosis using in vivo and in vitro approaches. Plg-deficient (Plg−/−) and wild-type (Plg+/+) C57BL/6 mice were subjected to unilateral ureteral obstruction or sham surgery (n = 8/group; sham, days 3, 7, 14, and 21). Plg deficiency was confirmed by the absence of Plg mRNA, protein, and plasmin activity. After 21 d of unilateral ureteral obstruction, total kidney collagen was significantly reduced by 35% in the Plg−/− mice. Epithelial-to-mesenchymal transition (EMT), as typified by tubular loss of E-cadherin and acquisition of α-smooth muscle actin, was also significantly reduced in Plg−/− mice, 76% and 50%, respectively. Attenuation of EMT and fibrosis severity in the Plg−/− mice was associated with significantly lower levels of phosphorylated extracellular signal–regulated kinase (ERK) and active TGF-β. In vitro, addition of plasmin (20 μg/ml) to cultures of murine tubular epithelial cells initiated ERK phosphorylation within minutes, followed by phenotypic transition to fibroblast-specific protein-1+, α-smooth muscle actin+, fibronectin-producing fibroblast-like cells. Both plasmin-induced ERK activation and EMT were significantly blocked in vitro by the protease-activated receptor-1 (PAR-1) silencing RNA; by pepducin, a specific anti–PAR-1 signaling peptide; and by the ERK kinase inhibitor UO126. Plasmin-induced ERK phosphorylation was enhanced in PAR-1–overexpressing tubular cells. These findings support important profibrotic roles for plasmin that include PAR-1–dependent ERK signaling and EMT induction.
Gonadotropin, Steroid, and Thyroid Hormone Milieu of Young SWR Mice Bearing Spontaneous Granulosa Cell Tumors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: W G Beamer
Journal: JNCI Journal of the National Cancer Institute (1986)

Young SWR mice possessing spontaneous ovarian granulosa cell (GC) tumors were examined for evidence of endocrine dysfunction associated with tumorigenesis. Tissue levels of hormones in tumor host and normal control females were measured by radioimmunoassays, ovarian luteinizing hormone (LH) receptors by uptake of 125I-labeled human chorionic gonadotropin (hCG) administered iv, and ovarian 3-beta-hydroxysteroid dehydrogenase (3-beta-OH) activity by histochemical techniques. When data from tumor host mice were compared with control data, hypothalamic gonadotropin releasing hormone content was not significantly different. Pituitary LH and follicle-stimulating hormone (FSH) contents were significantly decreased. Serum FSH, but not LH, levels were significantly reduced. No specific uptake of 125I-labeled hCG by tumor tissue was detected, whereas uptake by nontumorous contralateral ovaries was identified and found to be similar to that of control ovaries. With respect to serum steroids in tumor host mice, progesterone, dihydrotestosterone, and testosterone were significantly reduced, whereas androstenedione, dehydroepiandrosterone, corticosterone, estrone, and estradiol were normal. Frozen sections of tumor tissue failed to show any 3-beta-OH activity, whereas prominent activity was observed in non-tumorous contralateral and control ovaries. Serum thyroxine levels, evaluated because of the known depressive effects of hypothyroidism on reproductive function, were found to be significantly elevated in tumor host mice. The above results suggest that in SWR mice with spontaneous GC tumors, gonadotropins are moderately suppressed; the granulosa tumor cells do not have LH-hCG receptors; steroidogenesis by tumor tissue is reduced, whereas peripheral conversion of adrenal androgen precursors to estrogens is normal; and elevated serum thyroxine levels have a secondary role in established GC tumors.
The pathology of lymphangioma circumscriptum
Authors: I.W. WHIMSTER
Journal: British Journal of Dermatology (1976)

A study of lymphangioma circumscriptum has been carried out over a number of years in an attempt to understand its nature and pathogenesis, with a view to improving treatment. It is postulated that the lesion consists essentially of a collection of large muscular-coated lymphatic cisterns, lying deep in the subcutaneous plane and communicating via dilated dermal lymphatics with the superficial vesicles. It seems that these cisterns do not communicate directly, if at all, with the general lymphatic system but represent a sequestrated part of it. They have been shown by cannulation to pulsate at a slow steady rate producing a rise and fall of pressure within them. It is believed that the vesicles are saccular dilatations of superficial lymphatics, secondary to raised pressure transmitted from the pulsating cisterns beneath. It is suggested that may be possible to treat these lesions more successfully and with better cosmetic results by excising the subcutaneous cisterns and leaving the overlying skin intact.
Differentiation Therapy Exerts Antitumor Effects on Stem-like Glioma Cells
Authors: Benito Campos, Feng Wan, Mohammad Farhadi, Aurélie Ernst, Felix Zeppernick, Katrin E. Tagscherer, Rezvan Ahmadi, Jennifer Lohr, Christine Dictus, Georg Gdynia, Stephanie E. Combs, Violaine Goidts, Burkhard M. Helmke, Volker Eckstein, Wilfried Roth, Philipp Beckhove, Peter Lichter, Andreas Unterberg, Bernhard Radlwimmer, Christel Herold-Mende
Journal: Clinical Cancer Research (2010)

Stem-like tumor cells comprise a highly tumorigenic and therapy-resistant tumor subpopulation, which is believed to substantially influence tumor initiation and therapy resistance in glioma. Currently, therapeutic, drug-induced differentiation is considered as a promising approach to eradicate this tumor-driving cell population; retinoic acid is well known as a potent modulator of differentiation and proliferation in normal stem cells. In glioma, knowledge about the efficacy of retinoic acid-induced differentiation to target the stem-like tumor cell pool could have therapeutic implications.Stem-like glioma cells (SLGC) were differentiated with all-trans retinoic acid-containing medium to study the effect of differentiation on angiogenesis, invasive growth, as well as radioresistance and chemoresistance of SLGCs. In vivo effects were studied using live microscopy in a cranial window model.Our data suggest that in vitro differentiation of SLGCs induces therapy-sensitizing effects, impairs the secretion of angiogenic cytokines, and disrupts SLGCs motility. Further, ex vivo differentiation reduces tumorigenicity of SLGCs. Finally, we show that all-trans retinoic acid treatment alone can induce antitumor effects in vivo.Altogether, these results highlight the potential of differentiation treatment to target the stem-like cell population in glioblastoma.
PSYCHIATRIC APPRAISALS OF PARENTS AND SIBLINGS OF SCHIZOPHRENIC CHILDREN
Authors: DONALD MEYERS, WILLIAM GOLDFARB
Journal: American Journal of Psychiatry (1962)

An attempt has been made to demonstrate the heuristic value of the concept etiological heterogeneity in investigations into the etiology of childhood schizophrenia. Emphasis has been put on the awareness possible varying mixtures of etiological factors including somatic deficit (acquired and/or genetic) and psychosocial factors. Stress has been placed on the need for techniques that adequately measure the subtler indications of neurological impairment in the children and the adequacy of the families' interaction with the children, in order to assess their relative roles in childhood schizophrenia. The division of a group of schizophrenic children into a subgroup with signs and/or history suggestive of neurological impairment and a subgroup without such signs or history has been supported in previous studies done at the Ittleson Center. The findings supporting this kind of grouping included differences in many areas of ego functioning of the children, differences in the adequacy of the families, and differences in the maternal attitudes of the mothers. The validity of this subdivision is further supported in the present study by differences in the incidence of schizophrenia in the mothers of those 2 subgroups. There are twice as many mothers of the "nonorganic" subgroup diagnosed schizophrenic as there are mothers of the "organic" subgroup. The importance of the psychosocial impact of families with schizophrenic parent(s) is underlined by the finding that families in which one or both parents are schizophrenic have a lower family adequacy rating than families without parental psychosis.
B-Type Natriuretic Peptides and Cardiovascular Risk
Authors: Emanuele Di Angelantonio, Rajiv Chowdhury, Nadeem Sarwar, Kausik K. Ray, Reeta Gobin, Danish Saleheen, Alexander Thompson, Vilmundur Gudnason, Naveed Sattar, John Danesh
Journal: Circulation (2009)

Background— Measurement of B-type natriuretic peptide (BNP) concentration or its precursor (N-terminal fragment [NT-proBNP]) is recommended in patients with symptoms of left ventricular dysfunction and in other settings, but the relevance of these peptides to cardiovascular disease (CVD) in general populations or in patients with stable vascular disease is uncertain. Methods and Results— Data were collated from 40 long-term prospective studies involving a total of 87 474 participants and 10 625 incident CVD outcomes. In a comparison of individuals in the top third with those in the bottom third of baseline values of natriuretic peptides, the combined risk ratio (RR), adjusted for several conventional risk factors, was 2.82 (95% confidence interval [CI], 2.40 to 3.33) for CVD. Analysis of the 6 studies with at least 250 CVD outcomes (which should be less prone to selective reporting than are smaller studies) yielded an adjusted RR of 1.94 (95% CI, 1.57 to 2.39). RRs were broadly similar with BNP or NT-proBNP (RR, 2.89 [95% CI, 1.91 to 4.38] and 2.82 [95% CI, 2.35 to 3.38], respectively) and by different baseline vascular risk (RR, 2.68 [95% CI, 2.07 to 3.47] in approximately general populations; RR, 3.35 [95% CI, 2.38 to 4.72] in people with elevated vascular risk factors; RR, 2.60 [95% CI, 1.99 to 3.38] in patients with stable CVD). Assay of BNP or NT-proBNP in addition to measurement of conventional CVD risk factors yielded generally modest improvements in risk discrimination. Conclusions— Available prospective studies indicate strong associations between circulating concentration of natriuretic peptides and CVD risk under a range of different circumstances. Further investigation is warranted, particularly in large general population studies, to clarify any predictive utility of these markers and to better control for publication bias.
The Applicability of the Parting Tool or Angular Gouge to the Surgery of the Skull
Authors: W. A. Lane
Journal: BMJ (1893)

INov. 11, 18s3. when loss of continuity between several segments of the lower extremity was established, whether by injury or operation.What he considered necessary was that surgeons should be guided by definite and accurate scientific mecha- nical principles in the treatment they adopted.Surgeons were too often utterly devoid of principle; he did not mean
Intravenous gammaglobulin treatment in patients with hypogammaglobulinaemia.
Authors: A So, M K Brenner, I D Hill, G L Asherson, A D Webster
Journal: BMJ (1984)

Intravenous gammaglobulin was compared with the standard British intramuscular preparation in patients with hypogammaglobulinaemia and chronic bronchitis. Five patients were given six months9 treatment with the weekly intramuscular preparation and six months9 treatment with intravenous gammaglobulin given once every 18 days. During the trial they recorded symptoms of infection, absence from work, and sputum volume; lung function tests were performed during the intravenous treatment. The half life of the intravenous IgG and changes in serum IgG and C1q concentrations were also measured in seven other patients who received intravenous gammaglobulin every two weeks for 12 weeks. IgG concentrations, sputum volume, and infection scores were significantly better during intravenous treatment and there were no adverse effects from the intravenous gammaglobulin. These five patients were significantly more healthy when they received an intravenous gammaglobulin preparation, probably because the intravenous preparation increased serum IgG concentrations. Although longer studies are needed, intravenous gammaglobulin should be considered for patients with severe chest disease and those who cannot tolerate intramuscular injections.
New Approaches to Preventing, Diagnosing, and Treating Neonatal Sepsis
Authors: Karen Edmond, Anita Zaidi
Journal: PLoS Medicine (2010)

Neonatal sepsis or septicaemia is a clinical syndrome characterized by systemic signs of circulatory compromise (e.g., poor peripheral perfusion, pallor, hypotonia, poor responsiveness) caused by invasion of the bloodstream by bacteria in the first month of life. In the pre-antibiotic era neonatal sepsis was usually fatal. Case fatality rates in antibiotic treated infants now range between 5% and 60% with the highest rates reported from the lowestincome countries [1]. The World Health Organization (WHO) estimates that 1 million deaths per year (10% of all under-five mortality) are due to neonatal sepsis and that 42% of these deaths occur in the first week of life [2]. There are wide disparities in neonatal care between highand low-income countries. In high-income countries the major concern is the increasing numbers of extremely premature infants with high nosocomial infection rates due to multiresistant organisms in intensive care units. Health facility infections are also a major problem in lowincome countries, but the more pressing issues are the high proportion of home deliveries in unclean environments predisposing to sepsis and ensuring that all neonates have access to effective interventions from health care providers in the first days of life 2 . Indeed, new strategies that can prevent, diagnose, and treat neonates with sepsis are needed in both low- and high-income settings.
Combination Chemotherapy and ALVAC-CEA/B7.1 Vaccine in Patients with Metastatic Colorectal Cancer
Authors: Howard L. Kaufman, Heinz-Josef Lenz, John Marshall, Deepti Singh, Chris Garett, Christine Cripps, Malcolm Moore, Margaret von Mehren, Richard Dalfen, William J. Heim, Robert M. Conry, Walter J. Urba, Al B. Benson, Maria Yu, Judy Caterini, Seunghee Kim-Schulze, Mark DeBenedette, Danielle Salha, Thorsten Vogel, Ileana Elias, Neil L. Berinstein
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The combination of vaccines and chemotherapy holds promise for cancer therapy, but the effect of cytotoxic chemotherapy on vaccine-induced antitumor immunity is unknown. This study was conducted to assess the effects of systemic chemotherapy on ALVAC-CEA/B7.1–induced T-cell immunity in patients with metastatic colorectal cancer. Experimental Design: Patients with metastatic colorectal cancer were treated with fluorouracil, leucovorin, and irinotecan and were also given ALVAC-CEA/B7.1 vaccine with or without tetanus toxoid adjuvant. Eligible patients were randomized to ALVAC followed by chemotherapy and booster vaccination (group 1), ALVAC and tetanus toxoid followed by chemotherapy (group 2), or chemotherapy alone followed by ALVAC in patients without disease progression (group 3). Humoral immune responses were measured by standard ELISA assay, and carcinoembryonic antigen (CEA)-specific T-cell responses were measured by IFN-γ enzyme-linked immunospot assay. Results: One hundred eighteen patients were randomized to receive either ALVAC before and concomitantly with chemotherapy (n = 39), ALVAC with tetanus adjuvant before and concomitantly with chemotherapy (n = 40), or chemotherapy followed by ALVAC (n = 39). Serious adverse events were largely gastrointestinal (n = 30) and hematologic (n = 24). Overall, 42 patients (40.4%) showed objective clinical responses. All patients developed antibody responses against ALVAC, but increased anti-CEA antibody titers were detected in only three patients. Increases in CEA-specific T cells were detected in 50%, 37%, and 30% of patients in groups 1, 2, and 3, respectively. There were no differences in clinical or immune responses between the treatment groups. Conclusion: The combination of ALVAC-CEA/B7.1 vaccine and systemic chemotherapy has an acceptable safety profile in patients with metastatic colorectal cancer. Systemic chemotherapy did not affect the generation of CEA-specific T-cell responses following vaccination.
In vivo therapy of a murine B cell tumor (BCL1) using antibody-ricin A chain immunotoxins.
Authors: K A Krolick, J W Uhr, S Slavin, E S Vitetta
Journal: The Journal of Experimental Medicine (1982)

Prolonged remissions were induced in mice bearing advanced BCL1 tumors by the combined approach of nonspecific cytoreductive therapy and administration of a tumor-reactive immunotoxin. Thus, the vast majority of the tumor cells (approximately 95%) were first killed by nonspecific cytoreductive therapy using total lymphoid irradiation (TLI) and splenectomy. The residual tumor cells were then eliminated by intravenous administration of an anti-delta immunotoxin. In three of four experiments, all animals treated in the above fashion appeared tumor free 12-16 wk later. In one experiment, blood cells from the mice in remission were transferred to normal BALB/c recipients, and the latter animals have not developed detectable tumor for the 6 mo of observation. Because 1-10 adoptively transferred BCL1 cells will cause tumor in normal BALB/c mice by 12 wk, the inability to transfer tumor to recipients might indicate that the donor animals were tumor free. In the remainder of the animals treated with the tumor-reactive immunotoxin there was a substantial remission in all animals, but the disease eventually reappeared. In contrast, all mice treated with the control immunotoxin or antibody alone relapsed significantly earlier (3-4 wk after splenectomy).