tbuckley/cabot-search huggingface dataset:
When I use a word . . .: Monthly injections
Authors: J. Aronson
Journal: BMJ (2000)

If you want to extend the duration of action of a drug you can give it in a so called modified release formulation, from which it will slowly enter the blood and find its way to the site of action. The modern term modified release was first used, as a blanket term for all such formulations, in 1982, as far as I can discover. And before it came into currency in the 1990s (it was first used in the British National Formulary in the 22nd issue, September 1991), formulations of this kind were described as extended release (1982), delayed release (1970), prolonged release (1965), timed release (1964), controlled release (1963), long release (1962), slow release (1961), or sustained release (1956). The MESH heading “Delayed action preparations” did not enter Index Medicus until 1963. But the concept dates back at least to the 1940s, when the term menstruum was coined to describe a matrix on which such formulations could be based.

Because vaginal discharge of blood occurs monthly, the Romans called the discharge itself the menstrua (Latin mensis, a month, see BMJ 1997; 314:973). Menstrua was the plural of menstruum, which meant a monthly payment or term of office—nothing to do with your monthlies. Now medieval alchemists thought that the fetus was compounded of two parts, the spermatic and the menstrual, and they compared the base metal that they intended to transmute into gold to the spermatic part, and the solvent with which they would bring this miracle about to the menstrual. And so, forgetting their classical Latin, they called the solvent the menstruum. A menstruum thus became any liquid that would dissolve a solid, including drugs. The word was also used figuratively: “Death,” wrote Richard Whitlock in his Zootomia (1654), “is a preparing Deliquium, or melting us down into a Menstruum, fit for the Chymistry of the Resurrection to work on.”

Later the word was turned upside down, when in the 1940s Dr George P Pitkin created a solid formulation that would act as a vehicle for a solution of a water soluble drug. And, forgetting his alchemy, he called it a menstruum, Pitkin's menstruum to be exact. The idea was that after intramuscular or subcutaneous administration the menstruum would retard the rate of absorption of the drug and thus prolong its duration of action. It was used, for instance, for the subcutaneous administration of heparin (Am J Med Sci 1944; 208:54-63).

Pitkin's menstruum took about six days to make, from gelatin, dextrose, and acetic acid. The viscosity of the menstruum depended on the amounts of gelatin and dextrose it contained, and the more viscous it was the slower the rate of drug absorption. The effect of a single injection of heparin would last 24 to 72 hours or even longer. Unfortunately, not long enough for a monthly injection, which would perhaps have justified the use of the term menstruum.
Abstract 541: TGF-β signaling in the tumor microenvironment promotes tumor formation and tumor progression
Authors: Lakisha D. Moore, Tatyana Isayeva, Jessica Gurley, Selvarangan Ponnazhagan
Journal: Cancer Research (2010)

Abstract Recent studies indicated that the tumor microenvironment plays an important role in tumor growth. Both tumor cells and stromal cells produce TGF-β1, which contributes to autocrine and paracrine functions in the tumor microenvironment. During cell transformation, TGF-β induces angiogenesis, produces reactive stroma, and tumor invasiveness suggesting that crosstalk between the tumor and the stroma is very important in the progression of metastatic disease. The present study examined the effects of TGF-β1 crosstalk in the tumor microenvironment and its role in mediating tumor formation and tumor development by targeted abrogation of TGF-β expression in the tumor cells in situ. Athymic female mice were injected subcutaneously with either normal or tumor derived fibroblast, unmodified MDA-MB 435 breast cancer cells, MDA-MB 435 clones containing TGF-β siRNA either alone or in combination with fibroblasts. Implantation of the cells subcutaneously showed significant difference in tumor formation between the groups. Control animals injected with fibroblast only developed no tumors. In animals injected with TGF-β-silenced MDA-MB 435 clones there was 12.5% tumor incidence. When these same cells were injected in combination with fibroblast the tumor incidence increased to 57%. Unmodified MDA-MB 435 cells showed a tumor incidence of 85% when injected alone and 100% in the presence of fibroblasts. This data suggests that when TGF-β is inhibited in the tumor cells the surrounding stroma can provide growth factors that continue to support tumor formation. In addition to measuring the tumor incidence, tumor growth was assessed every two days over the course of 6 weeks or until tumor was removed due to necrosis. Control animals injected with fibroblasts alone showed no tumor growth. The tumors formed from TGF-β-silenced MDA-MB 435 clones display an average tumor volume of 11.2 mm3. When these cells were co-injected with fibroblasts, the average tumor volume increased to 76 mm3. Unmodified MDA-MB 435 cells produced an average tumor volume of 164.3 mm3 but when injected with fibroblast the volume increased to 229.1 mm3. This data suggests that signaling from the tumor microenvironment can promote tumor progression through TGF-β signaling pathway. Thus, understanding the role of TGF-β1 expression in the tumor microenvironment will help to develop targeted therapies for cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 541.
Abstract 1281: MALDI imaging mass spectrometry of three-dimensional cell culture systems
Authors: Amanda B. Hummon, Haohang Li, Eric Weaver
Journal: Cancer Research (2012)

Abstract 3D cell cultures have increased complexity compared to simple monolayer and suspension cultures, recapitulating the cellular architecture in the body. For example, many colon cancer cell lines form rounded heterogeneous spheroid structures that mimic the pathophysiological properties of tumors when grown under appropriate cell culture conditions. Classical imaging methodologies, like immunohistochemistry, are commonly used to examine the distribution of specific species within the spheroids. However, there is a need for an unbiased discovery-based methodology that would allow examination of protein/peptide distributions in 3D culture systems, without a need for prior knowledge of the analytes. We have developed MALDI imaging mass spectrometry protocols to examine protein distributions in 3D cultures models. Using the HCT 116 colon carcinoma cell line, we have grown spheroids measuring 1 mm in diameter for MALDI IMS imaging. We detect changes in the spatial distribution of proteins across the spheroids by IMS. While most proteins are distributed across the structures, some are localized to either the proliferative outer rim of the spheroids or to the central necrotic core. We are now expanding our studies to map the changes in protein distribution that accompany knockdown of E-cadherin (CDH1). We are inserting inducible shRNAs targeting CDH1 into HCT 116 cells. Once our cells stably express the shRNAs, we will grow spheroids and then trigger knockdown of CDH1 expression. We will map changes in protein expression over a time course using the MALDI imaging mass spectrometry protocols we have developed. As CDH1 is a critical component of cell-cell junctions, we anticipate that its reduction will trigger phenotypic changes in the spheroid structures. In addition, we expect to see a shift in transcriptional activity that correlates with activation of the Epithelial-Mesenchymal Transition. Our unbiased protein mapping technology enables us to examine previously observed protein changes that result from CDH1 reduction. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1281. doi:1538-7445.AM2012-1281
Therapeutic Measures in Rheumatic Fever
Authors: Richard Gubner, Murrill Szucs
Journal: New England Journal of Medicine (1945)

IT IS not encouraging to reflect that the cause of rheumatic fever is unknown, that its symptoms are often obscure and its recognition is accordingly difficult, and that effective treatment is lacking. Still, much has been learned concerning this disease, and recent demonstrations of the effectiveness of sulfonamide prophylaxis constitute a notable advance in its control. Neither sulfonamides1 2 3 nor penicillin4 , 5 has proved of any value in the actual treatment of rheumatic fever.The present report comprises an analysis of various therapeutic measures in 150 cases of acute rheumatic fever in young men treated during 1944. The types of therapy employed . . .
The coexistence of parkinsonism-like symptoms and tardive dyskinesia
Authors: M A Richardson, T J Craig
Journal: American Journal of Psychiatry (1982)

The authors used the Simpson-Angus Neurological Rating Scale and the Simpson Abbreviated Dyskinesia Rating Scale to evaluate 132 psychiatric inpatients for the presence of parkinsonism-like symptoms and tardive dyskinesia, respectively. Ninety-four percent of these patients had been on a stable drug regimen for a minimum of 2 weeks before assessment; 91% were being treated with neuroleptics, 42% with antiparkinson agents, and 7% with tricyclic antidepressants. Tardive dyskinesia and parkinsonism-like symptoms coexisted in 17.4% of the 132 patients. Such coexistence poses a therapeutic dilemma for the clinician because drug treatment of improve one neurological condition may exacerbate the other.
AB0536 Prevalence of inflammatory back pain among workers of a university health sciences campus
Authors: F. Onen, D. Solmaz, P. Cetin, S. Akar, N. Akkoc
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The early identification of IBP may provide early diagnosis of axial spondyloarthritis. However the exact prevalence of inflammatory back pain (IBP) in the general population is not well documented. <h3>Objectives</h3> The aim of this study was to determine the prevalence of IBP in the workers of a university campus in Izmir, Turkey. <h3>Methods</h3> The study was conducted in the Health Sciences Campus with a population of 2894 workers who aged between 20 years and 67 years, at Dokuz Eylul University in Izmir. A sample size of 395 subjects was calculated by assuming that the IBP prevalence of 5% in the general population using OpenEpi (version 2.3 Atlanta, GA, USA), based on a confidence interval of ±2%. Six trained medical students using a standard questionnaire performed a face-to-face interview with participants. The subjects were classified as having IBP using various criteria including Calin criteria, Berlin criteria and ASAS Experts’ criteria. <h3>Results</h3> A total of 381 subjects (131 male, 250 female; mean age: 38.0 ± 9.4) were contacted with an acceptance rate of 96.5%. Among them, 299 (78.5 %; CI 95% 74-82) had experienced back pain at least one time in their life. A total of 172 subjects (45.1 %; CI 95% 40-50) had chronic back pain lasting more than a month. Among 381 subjects, 82 (21.5 %; CI 95% 17-25) were classified as having IBP according to Calin Criteria. The prevalence of IBP according to Berlin and ASAS Experts’ criteria was found to be 7.0% (CI 95% 4-10) and 6.5% (CI 95% 4-9), respectively (Table). Among subjects with chronic back pain, the prevalence of IBP was estimated as 43.4 % (CI 95% 36-51), 15.1 % (CI 95% 10-21) and 14.8 % (CI 95% 10-20), based on Calin, Berlin and ASAS Experts’ criteria, respectively. Two patients had a previous diagnosis of axial spondyloarthritis. A previous diagnosis of lumbar disc hernia (LDH) was more frequent in subjects classified as having IBP (35.4%) than those classified as not having IBP (p&lt;0.05). <h3>Conclusions</h3> This study is still in progression to investigate the prevalence of axial spondyloarthritis in the same population. The present results suggest that IBP is more common than expected in the general adult population. <h3>Disclosure of Interest</h3> None Declared
Endoscopic vacuum-assisted therapy of an infected pancreatic pseudocyst
Authors: I. Wallstabe, A. Tiedemann, I. Schiefke
Journal: Endoscopy (2011)

Infected pancreatic pseudocysts are serious complications of acute and chronic pancreatitis [1] [2] [3]. Endoscopic vacuum-assisted therapy (EVAT) is a reliable treatment for abscesses that are accessible endoscopically [4] [5]. We report the first case in which EVAT was used in the treatment of an infected pancreatic pseudocyst.
CB-04 * EPIGENETIC REGULATION OF GLIOBLASTOMA TUMORIGENICITY: A HYBRID MODEL
Authors: C. Chen, D. Kozono, J. Li, M. Nitta, O. Sampetrean, D. Gonda, D. Kushwaha, S. Vandenberg, V. Ramakrishnan, S. Zhu, F. Furnari, H. Matsui, O. Harismendy, W. Cavenee, Y. Mao, O. Becher, C.-H. Kwon, K. Ligon, H. Saya, B. Carter
Journal: Neuro-Oncology (2014)

Glioblastoma is one of the most devastating of human cancers, with near-uniform fatality within two years of diagnosis. Therapeutic failure is thought to be related to small subpopulations of cells that exhibit the properties of self-renewal and tumorigenicity. Understanding how such subpopulations attain and retain these properties remains a central question in oncology. One fundamental issue is whether tumorigenicity exists within a static population of elite cells or whether the capacity is stochastically acquired. To test these models, we assayed in vitro tumor sphere formation frequencies and in vivo tumor growth of subclones of established glioblastoma lines as well as stem cell lines derived from patients and genetically engineered mouse models. Our findings were best described by a hybrid model that is largely deterministic (elite) but with opportunities for dynamic (stochastic) interchange between non-tumorigenic and tumorigenic states. To identify determinants of tumorigenicity, we performed gene expression profiling of the subclones. Analysis of the data suggested that tumorigenicity in glioblastoma is a dynamic property driven by variations in MYC expression, consistent with the effects of ectopic expression and knockdown. Transitions between tumorigenic and non-tumorigenic cell states were associated with changes in histone modifications at the MYC locus, suggesting epigenetic regulation. The role of MYC as a "tumorigenicity gene" is fundamentally distinct from those previously ascribed to oncogenes. The model suggests the need for therapeutic strategies that disrupt the dynamic transition between cell states.
Autonomic Abnormalities and Autoantibodies to Beta-Adrenergic Receptors
Authors: Claire M. Fraser, J. Craig Venter, Michael Kaliner
Journal: New England Journal of Medicine (1981)

We identified autoantibodies to β2-adrenergic receptors in the plasma of three apparently normal subjects, four patients with allergic asthma, one subject who was "preallergic" (at risk of allergy), and one patient with cystic fibrosis. Although these antibodies appeared to be heterogeneous, they shared the ability to affect binding of [125l]protein A to calf-lung membranes, to inhibit beta-adrenergic ligand binding to calf-lung beta-adrenergic receptors, and to precipitate solubilized calf-lung beta-adrenergic receptors in an indirect immunoprecipitation assay. The presence of autoantibodies to beta-adrenergic receptors in these subjects correlates with abnormal autonomic responsiveness characterized by alpha-adrenergic and cholinergic hypersensitivity and beta-adrenergic hyposensitivity. These findings suggest that autoantibodies to beta-adrenergic receptors may play a part in the development of autonomic abnormalities. (N Engl J Med. 1981; 305:1165–70.)
Enhanced Filling and Cholecystokinin-Induced Emptying of the Human Gallbladder After Glyceryl Trinitrate Administration
Authors: LÁSZLÓ MADÁCSY, ATTILA SZEPES, VIKTÓRIA BERTALAN, LÁSZLÓ PÁVICS, LÁSZLÓ CSERNAY, JÁNOS LONOVICS
Journal: Clinical Nuclear Medicine (2002)

MADÁCSY, LÁSZLÓ M.D., Ph.D.; SZEPES, ATTILA M.D.; BERTALAN, VIKTÓRIA M.D.; PÁVICS, LÁSZLÓ M.D., PhD.; CSERNAY, LÁSZLÓ M.D., D.M.Sc., AND; LONOVICS, JÁNOS M.D., D.M.Sc. Author Information
Abstract 3876: Role of Stat3 transcriptional activation in a preclinical mouse model of prostate cancer and potential as a therapeutic target
Authors: Marco A. De Velasco, Motoyoshi Tanaka, Kaori Fujimoto-Ouchi, Yoichiro Moriya, Yurie Kura, Yasuki Kobayashi, Yutaka Yamamoto, Yuji Hatanaka, Hiroyuki Kato, Kazuhiro Yoshikawa, Kazuto Nishio, Hirotsugu Uemura
Journal: Cancer Research (2012)

Abstract The transcription factor, Stat3, has been implicated in the growth and progression of several cancer types including lung skin, liver, ovarian, kidney, colon cancer and prostate. Stat3 has also been shown to induce the metastatic behavior of prostate cancer cells in vitro and in vivo. Activation of Stat3 occurs by the binding of various cytokines to its receptors leading to the activation of the JAK/Stat3 signaling pathway. Of these cytokines, interleukin-6 (IL-6) has been implicated in regulating growth of various malignant tumors and activated IL-6 has been shown to be elevated in the sera from patients with metastatic prostate cancer. In the present study we examined the IL6-induced Stat3 transcriptional activation in the development and progression of prostate cancer and its possible role as a target for the treatment of prostate cancer using the prostate-specific conditional targeting PTEN knockout mouse model. Homozygous PTEN-mutants develop prostate cancer in a stage-specific manner and have the ability to grow and develop castration-resistant prostate cancer after total androgen ablation by castration. ELISA assays revealed increased expression of soluble IL-6 receptor (IL-6R) in tissue lysates from prostate tumors in non-castrated and castrated mice (77.0 ± 6.17 vs 23.75 ± 5.17 ng/g of tissue, p&amp;lt;0.001, respectively) at 32 wks of age. Immunohistochemical analysis revealed correlated expression of with Stat3 transcriptional activation, proliferation and androgen receptor in tumors from castrated mice. To determine the role of IL-6R induced transcriptional activation of Stat3, non-castrated and castrated tumor bearing mice were treated with an anti-mouse IL-6R antibody (MR-16). Mice treated with MR-16 showed downregulation of phosphorylated Stat3, however, treatment failed to inhibit tumor development and cellular proliferation. However, it was discovered that therapeutic doses of MR16 treatment resulted in increased phosphorylation of Erk1/2. Our data suggests that inhibition of IL-6R-induced Stat3 activation is insufficient to suppress tumor growth; however, further studies need to be conducted to evaluate the efficacy of horizontal combination strategies targeting Stat3 and MAP kinase signaling cascades. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3876. doi:1538-7445.AM2012-3876
Abstract 4801: Hypomethylation of a LINE-1 promoter activates an alternate transcript of the MET oncogene in bladders with cancer
Authors: Gangning Liang, Erika M. Wolff, Han F. Han, Hyany-Min Byun, Shikhar Sharma, Peter Nichols, Kimberly D. Siegmund, Peter A. Jones
Journal: Cancer Research (2010)

Abstract Background: It was recently shown that a large portion of the human transcriptome can originate from within repetitive elements, leading to ectopic expression of protein-coding genes. However the mechanism of transcriptional activation of repetitive elements has not been definitively elucidated. Principal findings: For the first time, we directly demonstrate that hypomethylation of retrotransposons causes altered gene expression in humans. We also reveal that active LINE-1s switch from a tetranucleosome to dinucleosome structure, acquiring H2A.Z and nucleosome free regions upstream of TSSs, previously shown only at active single copy genes. Hypomethylation of a specific LINE-1 promoter was also found to induce an alternate transcript of the MET oncogene in bladder tumors and across the entire urothelium of tumor-bearing bladders. Conclusions: These data show that, in addition to contributing to chromosomal instability, hypomethylation of LINE-1s can alter the functional transcriptome and plays a role not only in human disease but also in disease predisposition. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4801.
FRI0557 Standardised Mortality Rates Are Increased in Patients with Severe Juvenile Idiopathic Arthritis: Table 1.
Authors: R. Davies, T.R. Southwood, L. Kearsley-Fleet, M. Lunt, K.L. Hyrich
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Mortality rates in children with juvenile idiopathic arthritis (JIA) are increased compared to the general population. Systemic arthritis, a more severe subtype of JIA, is expected to be linked to an increase in mortality compared to other subtypes although evidence is so far lacking. <h3>Objectives</h3> To calculate the standardised mortality rates (SMR) in children with severe JIA, defined as requiring biologic therapy. <h3>Methods</h3> The study population comprised JIA subjects recruited to the BSPAR Etanercept Cohort Study. Deaths were identified through follow-up via hospital questionnaires and links to the national death register. All patients were followed from registration until death, last follow-up, or 31/12/2012, whichever came first. Poisson regression calculated crude incidence rates per 1,000 person years (pyears). SMRs were calculated using age- and gender-specific mortality rates in the UK population. <h3>Results</h3> 693 patients were registered and followed over 4475 pyears (mean age 11 years, median disease duration at registration 4 years, mean follow-up per patient 6.4 years). Seven deaths were reported, with an expected rate of 0.96. Four of the deaths occurred in systemic JIA patients. The incidence rate was 1.6/1,000 pyears with an SMR of 7.3 (95% CI) 2.9, 15.0). Patients with systemic JIA had an SMR of 21.7 (95% CI 5.9, 55.4) with non-systemic SMR of 3.9 (0.8, 11.3) (Table 1) Causes of death included macrophage activation syndrome, sepsis, and 2 in association with stem-cell transplants. <h3>Conclusions</h3> In a select group of patients with severe JIA, there appears to be a high mortality rate, particularly among severe systemic JIA, compared to a healthy paediatric population. Whilst death is still a rare outcome, this study highlights the importance of the diagnosis of JIA. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3241