tbuckley/cabot-search huggingface dataset:
Exciting New Advances in Neuro-Oncology: The Avenue to a Cure for Malignant Glioma
Authors: E. G. Van Meir, C. G. Hadjipanayis, A. D. Norden, H. K. Shu, P. Y. Wen, J. J. Olson
Journal: CA A Cancer Journal for Clinicians (2010)

Malignant gliomas are the most common and deadly brain tumors. Nevertheless, survival for patients with glioblastoma, the most aggressive glioma, although individually variable, has improved from an average of 10 months to 14 months after diagnosis in the last 5 years due to improvements in the standard of care. Radiotherapy has been of key importance to the treatment of these lesions for decades, and the ability to focus the beam and tailor it to the irregular contours of brain tumors and minimize the dose to nearby critical structures with intensity-modulated or image-guided techniques has improved greatly. Temozolomide, an alkylating agent with simple oral administration and a favorable toxicity profile, is used in conjunction with and after radiotherapy. Newer surgical techniques, such as fluorescence-guided resection and neuroendoscopic approaches, have become important in the management of malignant gliomas. Furthermore, new discoveries are being made in basic and translational research, which are likely to improve this situation further in the next 10 years. These include agents that block 1 or more of the disordered tumor proliferation signaling pathways, and that overcome resistance to already existing treatments. Targeted therapies such as antiangiogenic therapy with antivascular endothelial growth factor antibodies (bevacizumab) are finding their way into clinical practice. Large-scale research efforts are ongoing to provide a comprehensive understanding of all the genetic alterations and gene expression changes underlying glioma formation. These have already refined the classification of glioblastoma into 4 distinct molecular entities that may lead to different treatment regimens. The role of cancer stem-like cells is another area of active investigation. There is definite hope that by 2020, new cocktails of drugs will be available to target the key molecular pathways involved in gliomas and reduce their mortality and morbidity, a positive development for patients, their families, and medical professionals alike.
Pseudoseptic arthritis: an unusual presentation of neuropathic arthropathy.
Authors: W Louthrenoo, B E Ostrov, Y S Park, S Rothfuss, H R Schumacher
Journal: Annals of the Rheumatic Diseases (1991)

A 49 year old black man with scoliosis presented with bilateral shoulder swelling eventually shown to be due to neuropathic arthropathy related to underlying syringomyelia. The synovial fluid was highly inflammatory, but cultures from synovial fluid and synovial tissue were all sterile. Profuse fat droplets were noted and considered as a possible cause of the inflammation. This is an unusual presentation of neuropathic arthropathy in a patient who was also harbouring an adenocarcinoma that was undetected until later.
Highly potent human hematopoietic stem cells first emerge in the intraembryonic aorta-gonad-mesonephros region
Authors: Andrejs Ivanovs, Stanislav Rybtsov, Lindsey Welch, Richard A. Anderson, Marc L. Turner, Alexander Medvinsky
Journal: The Journal of Experimental Medicine (2011)

Hematopoietic stem cells (HSCs) emerge during embryogenesis and maintain hematopoiesis in the adult organism. Little is known about the embryonic development of human HSCs. We demonstrate that human HSCs emerge first in the aorta-gonad-mesonephros (AGM) region, specifically in the dorsal aorta, and only later appear in the yolk sac, liver, and placenta. AGM region cells transplanted into immunodeficient mice provide long-term high level multilineage hematopoietic repopulation. Human AGM region HSCs, although present in low numbers, exhibit a very high self-renewal potential. A single HSC derived from the AGM region generates at least 300 daughter HSCs in primary recipients, which disseminate throughout the entire recipient bone marrow and are retransplantable. These findings highlight the vast regenerative potential of the earliest human HSCs and set a new standard for in vitro generation of HSCs from pluripotent stem cells for the purpose of regenerative medicine.
Adenoviral Expression of Vascular Endothelial Growth Factor-C Induces Lymphangiogenesis in the Skin
Authors: Berndt Enholm, Terhi Karpanen, Michael Jeltsch, Hajime Kubo, Frej Stenback, Remko Prevo, David G. Jackson, Seppo Yla-Herttuala, Kari Alitalo
Journal: Circulation Research (2001)

The growth of blood and lymphatic vasculature is mediated in part by secreted polypeptides of the vascular endothelial growth factor (VEGF) family. The prototype VEGF binds VEGF receptor (VEGFR)-1 and VEGFR-2 and is angiogenic, whereas VEGF-C, which binds to VEGFR-2 and VEGFR-3, is either angiogenic or lymphangiogenic in different assays. We used an adenoviral gene transfer approach to compare the effects of these growth factors in adult mice. Recombinant adenoviruses encoding human VEGF-C or VEGF were injected subcutaneously into C57Bl6 mice or into the ears of nude mice. Immunohistochemical analysis showed that VEGF-C upregulated VEGFR-2 and VEGFR-3 expression and VEGF upregulated VEGFR-2 expression at 4 days after injection. After 2 weeks, histochemical and immunohistochemical analysis, including staining for the lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), the vascular endothelial marker platelet-endothelial cell adhesion molecule-1 (PECAM-1), and the proliferating cell nuclear antigen (PCNA) revealed that VEGF-C induced mainly lymphangiogenesis in contrast to VEGF, which induced only angiogenesis. These results have significant implications in the planning of gene therapy using these growth factors.
Effect of Recombinant Human Platelet-activating Factor-Acetylhydrolase on Allergen-induced Asthmatic Responses
Authors: NOREEN R. HENIG, MOIRA L. AITKEN, MARK C. LIU, ALBERT S. YU, WILLIAM R. HENDERSON
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Platelet-activating factor (PAF) is a potent lipid mediator associated with key features of asthma such as airway constriction, eosinophil infiltration, edema, and mucus accumulation. Regulation of PAF occurs primarily through degradation to biologically inactive lyso-PAF by cellular and secreted PAF-acetylhydrolase (PAF-AH). We evaluated the effect of human recombinant PAF-AH (rPAF-AH) on the dual phase asthmatic response in atopic subjects with mild asthma. Effects on induced sputum cell counts and differentials, eosinophilic cationic protein (ECP), and tryptase were evaluated. Enrolled subjects demonstrated a positive skin test and a dual asthmatic response to allergen inhalation challenge. Fourteen subjects received rPAF-AH (1 mg/kg) or placebo intravenously in a randomized, double blind, placebo-controlled, two-period crossover study. Treatment with rPAF-AH did not significantly reduce either the early- or late-asthmatic response. Sputum eosinophil cell counts were not affected by treatment, but there was a trend toward a reduction in sputum neutrophils. No significant change in sputum ECP and tryptase was observed between rPAF-AH and placebo. Thus, at the dose studied, the unique anti-PAF agent rPAF-AH demonstrated no significant effect on the allergen-induced dual-phase asthmatic response.
Chronic Cigarette Smoking
Authors: Joseph R. Tucci
Journal: JAMA (1972)

The effect of chronic cigarette smoking upon adrenocortical and sympathoadrenomedullary activity was studied in 94 normal males. Plasma cortisol levels at 8 AM and 4 PM obtained in six habitual smokers of one to two packs per day and in six nonsmokers were comparable and showed a normal circadian variation. Twenty-four hour urinary 17-hydroxycorticosteroid, 11-hydroxycorticosteroid, cortisol, and catecholamine excretion were assayed in 25 habitual smokers of one-half to one pack per day, 23 smokers of one to two packs per day, and in 34 nonsmokers. No significant differences were noted. Ordinary cigarette smoking does not appear to interfere with clinical assessment of pituitary-adrenocortical and sympathoadrenomedullary activity. Also, these data fail to implicate overactivity of these systems in the pathogenesis of cardiovascular and other disorders found in the habitual cigarette smoker of less than two packs per day.
Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer
Authors: James J Farrell, Lei Zhang, Hui Zhou, David Chia, David Elashoff, David Akin, Bruce J Paster, Kaumudi Joshipura, David T W Wong
Journal: Gut (2011)

<h3>Objective</h3> The associations between oral diseases and increased risk of pancreatic cancer have been reported in several prospective cohort studies. In this study, we measured variations of salivary microbiota and evaluated their potential associations with pancreatic cancer and chronic pancreatitis. <h3>Methods</h3> This study was divided into three phases: (1) microbial profiling using the Human Oral Microbe Identification Microarray to investigate salivary microbiota variation between 10 resectable patients with pancreatic cancer and 10 matched healthy controls, (2) identification and verification of bacterial candidates by real-time quantitative PCR (qPCR) and (3) validation of bacterial candidates by qPCR on an independent cohort of 28 resectable pancreatic cancer, 28 matched healthy control and 27 chronic pancreatitis samples. <h3>Results</h3> Comprehensive comparison of the salivary microbiota between patients with pancreatic cancer and healthy control subjects revealed a significant variation of salivary microflora. Thirty-one bacterial species/clusters were increased in the saliva of patients with pancreatic cancer (n=10) in comparison to those of the healthy controls (n=10), whereas 25 bacterial species/clusters were decreased. Two out of six bacterial candidates (<i>Neisseria elongata</i> and <i>Streptococcus mitis</i>) were validated using the independent samples, showing significant variation (p&lt;0.05, qPCR) between patients with pancreatic cancer and controls (n=56). Additionally, two bacteria (<i>Granulicatella adiacens</i> and <i>S mitis</i>) showed significant variation (p&lt;0.05, qPCR) between chronic pancreatitis samples and controls (n=55). The combination of two bacterial biomarkers (<i>N elongata</i> and <i>S mitis</i>) yielded a receiver operating characteristic plot area under the curve value of 0.90 (95% CI 0.78 to 0.96, p&lt;0.0001) with a 96.4% sensitivity and 82.1% specificity in distinguishing patients with pancreatic cancer from healthy subjects. <h3>Conclusions</h3> The authors observed associations between variations of patients9 salivary microbiota with pancreatic cancer and chronic pancreatitis. This report also provides proof of salivary microbiota as an informative source for discovering non-invasive biomarkers of systemic diseases.
Association of Violence With Emergence of Persecutory Delusions in Untreated Schizophrenia
Authors: Robert Keers, Simone Ullrich, Bianca L. DeStavola, Jeremy W. Coid
Journal: American Journal of Psychiatry (2013)

Psychosis is considered an important risk factor for violence, but studies show inconsistent results. The mechanism through which psychotic disorders influence violence also remains uncertain. The authors investigated whether psychosis increased the risk of violent behavior among released prisoners and whether treatment reduced this risk. They also explored whether active symptoms of psychosis at the time of violent behavior explained associations between untreated psychosis and violence.The U.K. Prisoner Cohort Study is a prospective longitudinal study of prisoners followed up in the community after release. Adult male and female offenders serving sentences of 2 or more years for a sexual or violent offense were classified into four groups: no psychosis (N=742), schizophrenia (N=94), delusional disorder (N=29), and drug-induced psychosis (N=102). Symptoms of psychosis, including hallucinations, thought insertion, strange experiences, and delusions of persecution, were measured before and after release. Information on violence between release and follow-up was collected through self-report and police records.Schizophrenia was associated with violence but only in the absence of treatment (odds ratio=3.76, 95% CI=1.39-10.19). Untreated schizophrenia was associated with the emergence of persecutory delusions at follow-up (odds ratio=3.52, 95% CI=1.18-10.52), which were associated with violence (odds ratio=3.68, 95% CI=2.44-5.55). The mediating effects of persecutory delusions were confirmed in mediation analyses (β=0.02, 95% CI=0.01-0.04).The results indicate that the emergence of persecutory delusions in untreated schizophrenia explains violent behavior. Maintaining psychiatric treatment after release can substantially reduce violent recidivism among prisoners with schizophrenia. Better screening and treatment of prisoners is therefore essential to prevent violence.
Green Tea Constituent Epigallocatechin-3-Gallate and Induction of Apoptosis and Cell Cycle Arrest in Human Carcinoma Cells
Authors: N. Ahmad, D. K. Feyes, R. Agarwal, H. Mukhtar, A.-L. Nieminen
Journal: JNCI Journal of the National Cancer Institute (1997)

Background and Purpose: The polyphenolic compounds present in green tea show cancer chemopreventive effects in many animal tumor models. Epidemiologic studies have also suggested that green tea consumption might be effective in the prevention of certain human cancers. We investigated the effect of green tea polyphenols and the major constituent, epigallocatechin-3-gallate, on the induction of apoptosis (programmed cell death) and regulation of cell cycle in human and mouse carcinoma cells. Methods: Human epidermoid carcinoma cells (cell line A431), human carcinoma keratinocyte (cell line HaCaT), human prostate carcinoma cells (cell line DU145), mouse lymphoma cells (cell line L5178Y), and normal human epidermal keratinocytes (NHEKs) were used. Apoptosis was assessed by 1) the formation of internucleosomal DNA fragments by agarose gel electrophoresis, 2) confocal microscopy, and 3) flow cytometry after tagging the DNA fragments by fluorescence label. The distribution of cells in different phases of the cell cycle was analyzed by flow cytometry. Results: Treatment of A431 cells with green tea polyphenols and its components, epigallocatechin-3-gallate, epigallocatechin, and epicatechin-3-gallate, resulted in the formation of internucleosomal DNA fragments, characteristic of apoptosis. Treatment with epigallocatechin- 3-gallate also resulted in apoptosis in HaCaT, L5178Y, and DU145 cells, but not in NHEK. Confocal microscopy and flow cytometry confirmed the findings. The DNA cell cycle analysis showed that in A431 cells, epigallocatechin- 3-gallate treatment resulted in arrest in the G 0 −G 1 phase of the cell cycle and a dose-dependent apoptosis. Conclusions: Green tea may protect against cancer by causing cell cycle arrest and inducing apoptosis. It needs to be evaluated in human trials.
The effects of antihypertensive therapy on carotid vascular structure in man
Authors: J. Mayet, A. V. Stanton, A.-M. Sinclair, J. MacKay, M. Shahi, R. A. Foale, A. Nicolaides, N. R. Poulter, P. S. Sever, S. A.McG. Thom, A. D. Hughes
Journal: Cardiovascular Research (1995)

An increased carotid intima-media thickness (IMT) has been found to be associated with a number of cardiovascular risk factors such as age, hypertension, cigarette smoking, hypercholesterolaemia and left ventricular hypertrophy. Our objective was to assess whether carotid intima-media thickness in hypertensive patients could be reduced by antihypertensive therapy.13 hypertensive patients, 10 previously untreated, were examined using carotid ultrasonography and echocardiography at baseline and then at 8 weeks and 39 weeks after commencement of antihypertensive therapy with ramipril and the second-line addition of felodipine.By the end of the study significant regression of IMT (0.1(0.05-0.16) mm, F-value 10.2, P < 0.01) and left ventricular mass index had occurred (25(10.7-39.3) g/m2, F-value 9.7, P < 0.01). The reduction in IMT was significantly related to the reduction in mean arterial pressure, r = 0.55, P = 0.05).Antihypertensive therapy with ramipril and felodipine causes regression of IMT in hypertensive patients, probably chiefly through blood pressure reduction. Large prospective studies are required to assess whether a reduction in IMT results in a reduction in morbidity and mortality.
Diagnostic Orphans: Adolescents With Alcohol Symptoms Who Do Not Qualify for DSM-IV Abuse or Dependence Diagnoses
Authors: Nancy Kaczynski Pollock, Christopher S. Martin
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: Little is known about the validity of the DSM-IV criteria for alcohol use disorders when applied to adolescents. This report describes a group of "diagnostic orphans," adolescents with one or two DSM-IV alcohol dependence symptoms who do not meet the DSM-IV criteria for alcohol abuse or alcohol dependence. METHOD: The study included 199 male and 173 female subjects aged 13–19 years. All subjects were regular drinkers, recruited from community sources and alcohol treatment programs. At baseline and at 1-year follow-up, DSM-IV alcohol use disorders were assessed with a version of the Structured Clinical Interview for DSM-III-R, modified for DSM-IV criteria. RESULTS: Diagnostic orphans represented 31% of the drinkers without an alcohol use disorder. The orphans were similar to the alcohol abusers and dissimilar to the other drinkers in alcohol and substance use patterns and in the course of alcohol problems over 1 year. CONCLUSIONS: The results indicate limitations of the DSM-IV criteria for alcohol use disorders when applied to adolescents. Diagnostic orphans should be considered separately from other drinkers in research and treatment efforts.
A new delivery system of clobetasol-17-propionate (lipid-loaded microspheres 0.025%) compared with a conventional formulation (lipophilic ointment in a hydrophilic phase 0.025%) in topical treatment of atrophic/erosive oral lichen planus. A Phase IV, randomized, observer-blinded, parallel group clinical trial
Authors: G. Campisi, G. Giandalia, V. De Caro, C. Di Liberto, P. Arico, L.I. Giannola
Journal: British Journal of Dermatology (2004)

Topical application of clobetasol-17-propionate has been diffusely reported as an efficacious therapy in atrophic/erosive oral lichen planus (OLP), without exposing the patient to systemic side-effects. However, prolonged contact and respective topical effects on the oral mucosa should be avoided.The aim of the present study was to evaluate efficacy and compliance of new lipid microspheres loaded with 0.025% of clobetasol propionate (formulation A) compared with a commonly used formulation (a sort of dispersion of a lipophilic ointment in a hydrophilic phase) with the same amount of drug (formulation B) in the topical treatment of OLP.Fifty patients with symptomatic OLP were enrolled in a controlled single-blind phase IV clinical trial. After a dropout of five patients, a total of 45 patients [12 males and 33 females; mean age 61.1 years (+/- 12.3 SD; range 25-82)] were treated (17 with formulation A and 28 with formulation B, matched for gender and age; P > 0.2) with the same dosage regimen. At times T0, T1 and T2 we evaluated the following parameters: (i) pain score (by linear visual analogue scale; 0-100); (ii) clinical score; (iii) clinical resolution; and (iv) patient compliance. Statistical analysis was calculated using S-Plus 4.0 and SPSS 9.0 (Student's t-test, chi(2), Kolmogorov-Smirnow, Friedman, Student-Newman-Keuls, Mann-Whitney U-test and Spearman tests).Both formulations were found to be similar for parameters ii, iii and iv, although with a better general trend for formulation A; a significant difference was registered for formulation A in terms of a reduction in painful symptoms (parameter i) at time T2 (P = 0.02).Our results suggest that the new topical drug delivery system (formulation A) may enhance, at least in terms of symptom remission and compliance, the effectiveness of clobetasol propionate at a dose of 0.025% in OLP therapy.
FRACTURES OF THE LOWER END OF THE RADIUS IN ADULTS: COLLES'S FRACTURE AND BACKFIRE FRACTURE
Authors: H. Edwards, E. B. Clayton
Journal: BMJ (1929)

MTL BJms 61 like any other remedy, act as a stimulus to those defensive powers in the human body which need to he called into play, and that different individuals cannot all be expected to respond to the same stimulus to the same extent or even in the same manner.Analogies witlh the treatnient of syphilis are suggestive in this connexioni; it is well recog- nized that over-treatment of this malady may be as bad as, ol )erhaps worse thani, no tr-eatmiient at all, and that the problem in the cure of syphilis is not to get as much of the specific remedy into the body as possible, but that amount which is capable of producing the optimum response by the tissule defences in the individual con- cernied.Such a view of the mode of the specific action, if any, of a mineral water would go far to explain certain difficulties and anomnalies which are some- times enicouintered.There is no doubt that there is a vast field for experi- meenta I research into the many problems coinnected witlh spa treatment, of whiclh only the borders ha-e as yet been exploi-ed.Further, tlherie is need for miior-e publicationi of the resuilts of tr-eatmlent of ser-ies of c ases.It is to be regr-ettecl that physicianis at spas so seldom pu-t on recor-d their experiences.For this there are probably three reasonis: first, a natural but perhaps undue, apprehension that such a proceeding lays the writer openi to the charge Of adveritisemenit; secondly, the difficulty of following up the aftei'-Iistories of patients wlho are only under direct ob)servation for a short tijne; and, thirdly, the fat that manyv of the cases met with are of a very clhron-ic clharacter and that so mlluch damnage has beeni already done that several courses of tr eatment may be niecessarv before tile complaint is broought to a standstill, and even then full functional restorationi iiay be impossible.I thiink it was Sydenham who said, " Chlronic diseases require chroniic treatmenit," and this is as true of spa therapy as of anv other-a point perhaps not sufficiently recognized and insisted upon.
THE PHARMACOLOGY OF PERCAINE
Authors: M. C. G. Israels, A. D. MacDonald
Journal: BMJ (1931)

_MEDCAL JOURNAL done in order to enable a large final dose to be given and at the same time to avoid the inconvenience which would have been caused to the patients had it been decided to work up to the maximum dose by an increased number of injections.Very few of those inoculated