tbuckley/cabot-search huggingface dataset:
Reversal of Benztropine Toxicity by Physostigmine
Authors: M. Khaled El-Yousef
Journal: JAMA (1972)

<h3>To the Editor.—</h3> Duvoisin and Katz (<b>206</b>:1963-1965, 1968) indicated that the anticholinergic drugs, including scopolamine, atropine, and various antiparkinsonian agents, can cause a toxic confusional state, and that physostigmine, a compound which antagonizes anticholinergic effects, is effective in reversing this "central anticholinergic syndrome." Certain patients experience a worsening of psychotic symptoms on high doses of phenothiazines given in combination with antiparkinsonian agents or tricyclic antidepressants. All of these medications theoretically possess anticholinergic properties, so that additive anticholinergic activity might be expected to occur, producing what is essentially an atropine psychosis. This report describes three female schizophrenic patients who had episodes of clinical worsening after receiving a combination of psychotropic and antiparkinsonian agents, and whose symptoms reversed with physostigmine administration. The first patient received daily doses of benztropine mesylate, 12 mg; perphenazine, 72 mg; and imipramine, 150 mg; the second patient received benztropine mesylate, 6.0 mg; and thioridazine, 150 mg,
Mediterranean diet and telomere length
Authors: P. M. Nilsson
Journal: BMJ (2014)

Genetic factors may contribute to the link between Mediterranean diet and longer telomeres

Interest in telomere biology has increased in recent years, both because of the quest for a reliable marker of biological ageing and because shorter telomeres in leucocytes have been shown to predict coronary heart disease (CHD).1 2 The methodological challenges of measuring telomere length have caused some delays in the progress of telomere research,3 but strong genetic arguments exist in favour of a more causal association between abnormalities in telomere biology and CHD.4 Most studies on the link between telomere length and disease remain cross sectional in design, so considerations of cause and effect are difficult. Observational research using repeated measurement of telomere length is needed to calculate the telomere attrition rate. The rate at which telomeres shorten is thought to be an even better biomarker of the ageing process than just measuring telomere length once.

Genetic factors are important to our understanding of telomere biology and its role in risk of CHD, but we also know from many studies that lifestyle components are associated with both CHD risk and telomere length. …
ANGIOSCOPIC ASSESSMENT OF ARTERIAL REPAIR FOUR TO EIGHT MONTHS AFTER ZOTAROLIMUS-ELUTING STENT IMPLANTATION: IMPLICATIONS FOR LATE STENT THROMBOSIS
Authors: Takayuki Ishihara, Masaki Awata, Masaaki Uematsu, Fusako Sera, Tetsuya Watanabe, Masashi Fujita, Osamu Iida, Shin Okamoto, Nobuaki Tanaka, Tomoharu Dohi, Tsuyoshi Mishima, Kiyonori Nanto, Yukika Mizukami, Yoshio Ishida, Shinsuke Nanto, Seiki Nagata
Journal: Journal of the American College of Cardiology (2011)
Nephritogenic Potential of Anti-DNA Antibodies against Necrotic Nucleosomes
Authors: Elin Synnøve Mortensen, Ole Petter Rekvig
Journal: Journal of the American Society of Nephrology (2009)

Systemic lupus erythematosus is an inflammatory autoimmune syndrome of unknown cause. Kidney disease is a central and serious complication in this syndrome. Deposition of chromatin-containing immune complexes within glomerular membranes is considered a key event in the pathogenesis of lupus nephritis. One set of autoantibodies that participate in these complexes is directed against components of chromatin, particularly against double-stranded DNA (dsDNA). Matzinger's danger model implicates chromatin fragments as both inducers and glomerular targets for nephritogenic anti-dsDNA and anti-nucleosome antibodies. In context of this model, apoptosis, secondary necrosis, and exposure of chromatin fragments may causally trigger autoimmunity and subsequent lupus nephritis. The exposure of glomerular basement membrane-associated extracellular chromatin depends on an observed acquired downregulation of renal DNase1 transcription and loss of nuclease activity preceding development of severe nephritis; this downregulation would result in reduced fragmentation and clearance of chromatin fragments. These fragments bind glomerular basement membrane structures with high affinity. In addition, exposed chromatin fragments contain structures that stimulate the innate immune system through Toll-like receptors and the adaptive immune system to produce affinity-maturated pathogenic anti-chromatin and anti-dsDNA antibodies that are central to the development of lupus nephritis.
Systematic Review and Meta-analysis of the Clinical Effectiveness of Shock Wave Lithotripsy, Retrograde Intrarenal Surgery, and Percutaneous Nephrolithotomy for Lower-pole Renal Stones
Authors: James F. Donaldson, Michael Lardas, Duncan Scrimgeour, Fiona Stewart, Steven MacLennan, Thomas B.L. Lam, Samuel McClinton
Journal: European Urology (2014)
Abstract P6-07-34: Disease-related outcomes with adjuvant chemotherapy in HER2 positive or triple negative T1a/bN0 breast cancers
Authors: T Shao, AJ Olszewski, SK Boolbol, Y Migdady, K Boachie-Adjei, BJ Sakr, P Klein, W Sikov
Journal: Cancer Research (2012)

Abstract Background: Previous studies reported higher relapse rates in T1a/bN0 breast cancers characterized by high-risk biology (HER2 positive or triple negative). The benefits of adjuvant chemotherapy in this group have not been evaluated. The purpose of our study was to determine potential impact of chemotherapy on incidence of relapses and to define the population appropriate for treatment based on observational data. Methods: We pooled data from two multi-institutional databases spanning the period of 1996–2008 (Beth Israel Medical Center) and 2000–2010 (Brown University). We fitted a propensity score model to adjust for unbalanced confounders between the groups treated or untreated with adjuvant chemotherapy and, in case of HER2+ disease, with trastuzumab. Competing risk analysis was employed to study the effect of chemotherapy on cancer relapses in the matched population. Results: The study included 321 patients (160 from Beth Israel and 161 from Brown) with a median age of 57 years (range 28–88). 111 (35%) cases were triple negative (TN) and 210 (65%) were HER2+ (of which 64% were ER+). 41% patients received adjuvant chemotherapy and 22% of HER2+ cases received trastuzumab. The treated group differed from untreated with regards to distribution of age, menopausal status, year of diagnosis, histological subtype and grade, tumor size, rates of mastectomy, and adjuvant endocrine therapy. All confounders were successfully balanced with the propensity score analysis. With a median follow-up of 56 months, 20 relapses (12 locoregional and 8 distant) and 10 unrelated deaths occurred. The cumulative incidence of relapse at 5 years was 7.3% (95% CI, 4.3–11.4) and relapse-free survival was 90.2% (95% CI, 85.2–93.6). Age less then 35 years (46.4% vs. 6.1%, p = 0.0004) and TN status (12.9% for TN versus 4.8% for HER2+, p = 0.03) were associated with higher risk of relapse. No significant differences with regards to tumor size (T1a or T1b), surgery type and other variables were observed. There was no significant effect of chemotherapy on incidence of relapse (Hazard ratio 1.2, 95% CI 0.34–4.23, p = 0.78), relapse-free survival or distant recurrence-free interval after propensity score adjustment. Additionally in the HER2+ patients, no benefit of trastuzumab was detected (hazard ratio 0.78, 95% CI 0.06–9.85, p = 0.85). Adjuvant endocrine therapy was associated with lower risk of relapse in the ER+ subgroup (p = 0.04). Conclusion: Survival outcomes in very early stage breast cancer are excellent with current therapy even in biologically aggressive subtypes. Triple negative status and very young age correlate with higher incidence of relapse. While adjuvant endocrine therapy may be effective in ER positive subset, the risk/benefit ratio of chemotherapy with or without trastuzumab remains uncertain. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-07-34.
Gonadotroph Cell Adenomas of the Pituitary*
Authors: PETER J. SNYDER
Journal: Endocrine Reviews (1985)

Although the frequency of gonadotroph cell adenomas among all unselected pituitary adenomas is not yet known, it is probably much higher than previously suspected. The true incidence is probably somewhere between the 3-4% found in surgical and autopsy series, which is probably an underestimate because of its reliance on tissue content, and the 17% (24% when alpha-secreting adenomas are included) of 139 patients from this institution, which may be an overestimate of the incidence among all adenomas, because it is heavily weighted to very large adenomas in men only. Most patients who have been reported to have gonadotroph cell adenomas have similar clinical characteristics. Most are middle-aged men who have a history of normal pubertal development and a normal fertility history, and by examination are normally virilized and have testes of normal size. They are brought to medical attention because of visual impairment, which is the result of the enormous size of the adenoma. The most common hormonal characteristic of gonadotroph cell adenomas in vivo is hypersecretion of FSH, which is often accompanied by hypersecretion of FSH beta and alpha-subunit and less often by hypersecretion of LH beta or intact LH. Another common characteristic is secretion of FSH and/or LH in response to TRH. A few patients with gonadotroph cell adenomas hypersecrete intact LH and, therefore, have supranormal serum testosterone concentrations. A larger number have secondary hypogonadism because the adenomas are not secreting intact LH, but are compressing the normal gonadotroph cells and impairing LH secretion. These patients have concentrations of intact LH that are not elevated in spite of subnormal testosterone concentrations. Testosterone levels increase markedly in response to hCG. The hormonal characteristics of gonadotroph adenomas in dispersed cell culture are similar to their characteristics in vivo, including hypersecretion of FSH and LH subunits and responsiveness to TRH. Both the clinical and hormonal characteristics of gonadotroph cell adenomas usually make them readily distinguishable from pituitary enlargement due to long-standing primary hypogonadism. Pituitary adenomas that hypersecrete only alpha-subunit in vivo may also be adenomas of gonadotroph cells, because some of them secrete large amounts of FSH as well as alpha-subunit in culture. Most gonadotroph cell adenomas are now treated first by transsphenoidal surgery, to attempt to restore vision as quickly as possible, and then by supervoltage radiation to prevent regrowth of the remaining adenomatous tissue.(ABSTRACT TRUNCATED AT 400 WORDS)
Detection of IgE antibodies to larvae and adults of chironomids by enzyme‐linked immunosorbent assay
Authors: H. Matsuoka, A. Ishii, S. Noono
Journal: Allergy (1988)

Using the ELISA method, IgE antibodies to chironomid midges; Tokunagayusurika akamusi larva (TAL), T. akamusi adult (TAA), Chironomus yoshimatsui larva (CYL), C. yoshimatsui adult (CYA) and Chironomus plumosus adult (CPA), were measured in the sera of 36 children with bronchial asthma who visited Tamano City Hospital near Lake Kojiima in the Okayama prefecture. IgE antibodies to adult midges (TAA, CYA and CPA) were widely detected, but only few IgE antibodies to larvae (TAL and CYL). The amount of IgE antibody to CYA and to CPA correlated ( P &lt; 0.001), but the amount of IgE antibody to TAA and to CYA or CPA did not. This suggests that the allergenicity of CYA and CPA is similar, but the allergenicity of TAA is independent of that of CYA or CPA. On the other hand, the ELISA inhibition test showed that TAA allergenicity was independent of that of TAL, CYL, CYA, CPA and the house‐dust mite, Dermatophagoides farinae (Df), The inhibition test also showed that CYA and CPA had similar allergenicity, but differed from TAL, TAA, CYL and Df. This indicates that the allergenicities of chironomid midges change during the metamorphosis from larva to adult, and are not common among all species.
Cerivastatin preserved eNOS expression in the vascular wall and mononuclear cells and improved endothelial dysfunction in cholesterol‐fed rabbits
Authors: A.M. Jiménez, M.M. Arriero, R. García, A. López‐Blaya, S. Velasco, L. Sánchez de Miguel, L. Rico, J. Farré, S. Casado, A. López‐Farré
Journal: European Journal of Heart Failure (2000)
Hepcidin regulation by innate immune and infectious stimuli
Authors: Andrew E. Armitage, Lucy A. Eddowes, Uzi Gileadi, Suzanne Cole, Natasha Spottiswoode, Tharini Ashtalakshmi Selvakumar, Ling-Pei Ho, Alain R. M. Townsend, Hal Drakesmith
Journal: Blood (2011)
miR-133a mediates TGF-β-dependent derepression of collagen synthesis in hepatic stellate cells during liver fibrosis
Authors: Christoph Roderburg, Mark Luedde, David Vargas Cardenas, Mihael Vucur, Tobias Mollnow, Henning W. Zimmermann, Alexander Koch, Claus Hellerbrand, Ralf Weiskirchen, Norbert Frey, Frank Tacke, Christian Trautwein, Tom Luedde
Journal: Journal of Hepatology (2012)
Thymic selection of CD8+ single positive cells with a class II major histocompatibility complex-restricted receptor.
Authors: J Kirberg, A Baron, S Jakob, A Rolink, K Karjalainen, H von Boehmer
Journal: The Journal of Experimental Medicine (1994)

We describe mice that express a transgenic T cell receptor alpha/beta (TCR-alpha/beta) specific for peptide 111-119 from influenza hemagglutinin presented by I-Ed class II major histocompatibility complex (MHC) molecules. The transgenic TCR is expressed on CD4+8- as well as CD4-8+ mature T cells even in mice that are deficient in rearrangement or do not express endogenous TCR-alpha genes. The CD4-8+ T cells require I-Ed class II MHC molecules for positive selection and can be activated to proliferate and to kill by I-Ed molecules presenting the relevant peptide. Full maturation of these cells, however, also requires the presence of class I MHC molecules. The results are compatible with the notion that T cell maturation requires multiple receptor-ligand interactions and establish an exception to the rule that class II-restricted TCRs are exclusively expressed by mature CD4+8- cells.
Concentrations of interleukin 6 and tumour necrosis factor in serum and stools of children with Shigella dysenteriae 1 infection.
Authors: D G de Silva, L N Mendis, N Sheron, G J Alexander, D C Candy, H Chart, B Rowe
Journal: Gut (1993)

Serum interleukin 6 (IL-6) and tumour necrosis factor (TNF) were measured in children with dysentery during an epidemic caused by Shigella dysenteriae 1. IL-6 and TNF were also measured in fresh stool filtrates from children with acute gastroenteritis. The median serum IL-6 concentration was raised significantly in the children with complications (haemolytic uraemic syndrome, leukemoid reaction, thrombocytopenia, thrombocytosis, and severe colitis lasting more than one week) during the first week (n = 18, 9-7728 pg/ml; median 107) and in the second week (n = 13, 5-312 pg/ml; median 77), compared with convalescent sera (n = 10, &lt; 3-85 pg/ml; median 39; p &lt; 0.02 and &lt; 0.05 respectively). The median IL-6 concentration during the first week was significantly higher in the group with complicated disease than in those with no complications (n = 8, &lt; 3-37 pg/ml; median 5; p &lt; 0.001). Although serum TNF concentrations were significantly raised in the complicated group during the first and second weeks of the illness and in the uncomplicated group compared with convalescence, there was no significant difference in the TNF concentrations between the complicated and uncomplicated groups. IL-6 was detectable in stool filtrates from eight of 13 children with S dysenteriae 1 infection and four of eight children with S flexneri infection. It was not detectable in Cryptosporidia, rotavirus, or adenovirus infections, those with pathogen-negative acute diarrhoea or controls. Seven of 13 children with S dysenteriae 1 and three of nine children with S flexneri infections had TNF detectable in stools. None of the children with Salmonella, Cryptosporidia, rotavirus of children with pathogen-negative diarrhoea and controls had detectable TNF in stool filtrates. It is postulated that the local and generalised vasculitis observed in shigellosis may be related to a direct effect of Shiga toxin on endothelial cells or caused by cytokine production stimulated by endotoxin, or both.
Apes and language: Human uniqueness again?
Authors: Robert W. Mitchell, H. Lyn Miles
Journal: Behavioral and Brain Sciences (1995)

Abstract Wilkins &amp; Wakefield's intriguing model of language evolution is deficient in evidence of human uniqueness in metaphorical matching, amodal representation, reference, conceptual structure, hierarchical organization, linguistic comprehension, sign use, laterality, and handedness. Primates show communicative reference, laterality, and handedness, and apes in particular show hierarchical organization, conceptual structure, cross-modal abilities, sign use, and displaced reference.
Rehabilitation in the Royal Air Force
Authors: R. Watson-Jones
Journal: BMJ (1942)

An air gunner was admitted to a civilian orthopaedic hospital in November, 1940, for the treatment of a torn and displaced semilunar cartilage.In August, 1941, no less than ten months after admission, he was still in hospital and still totally incapacitated.Why was recovery so long delayed?What possible explanation could there be?The diagnosis had been correctly made and a skilful opera- tion performed.The wound had healed by first intention; there was no infection, arthritis, or surgical complication.Daily massage had been continued, but the muscles were still wasted and weak.Two manipulations had been per- formed under anaesthesia, but movement was only half of normal.The gait was slow and hesitant; he limped; he could not run-he had never tried to run.The medical officer blamed him because "he would not co-operate," because he was disinterested, depressed, and resentful.He was certainly depressed, for after ten months the incapacity was more complete than on the day of admission.He was disinterested because, in his own words, "nobody takes any notice, and it looks as if it is hopeless."He was resentful because he could not believe that the fault was his.Had he not been told that " the nerve to his knee was cut"?He was transferred to one of the orthopaedic rehabilita- tion centres of the R.A.F.Medical Service.He saw the sky, the sea, the open spaces.For many months he had seen only the stone walls of hospital wards, the stone walls of massage rooms, the stone walls of many corridors.In his new surroundings there was a lounge and writing- room; there were tasteful decorations and flowers, a varied menu, and an atmosphere of well-being and contentment.After a few days he smiled.There was sometimes a sparkle in his eye.He sensed a spirit of optimism and was re- assured.His difficulties were explained, and he was taught special exercises.He learned to walk and then to run.He became an enthusiast and worked in the gymnasium, played on the fields, swam in the pool, cycled on the track.In the evenings he attended lectures and concerts, or played billiards and table-tennis.Time raced past, for he was busy.He became bronzed and fit.He laughed and was full of the joy of life.In seven weeks he returned to his unit and to full duty.The "nerve in his knee " was forgotten.Ten months-total incapacity; seven weeks-full re- covery: that is the story of rehabilitation in one air gunner.But is this an isolated case from which no conclusion should be drawn?The answer lies in the records of industry, the files of insurance companies, the experiences of H. E. Moore', the investigations of the B.M.A.
Pay for Performance, Version 2.0?
Authors: Thomas H. Lee
Journal: New England Journal of Medicine (2007)

"Old wine in a new bottle." "A financial gamble." "An early glimpse of the next generation of pay for performance." All these appraisals have been applied to Geisinger Health System's new approach to elective coronary-artery bypass grafting (CABG), which has been described with words rarely invoked in health care, such as "promise" and "guarantee." Geisinger, an integrated health care delivery system in northeastern Pennsylvania, promises that 40 key processes will be completed for every patient who undergoes elective CABG — even though several of the "benchmarks" are to be reached before or after hospitalization. And although Geisinger cannot guarantee good . . .
Diagnosis of Ruptured Bladder During a 99m Tc-DTPA Renal Study: New Indications for Radionuclide Cystography?
Authors: WILLIAM RESINGER, JAMES THRALL
Journal: Clinical Nuclear Medicine (1979)

Radionuclide cystography, which is currently used to evaluate vesicoureteral reflux, has also been used to detect perirenal and perivesical urine leakage. We report a case of intraperitoneal bladder rupture and describe potential indications and advantages of cystography for detection and evaluation.
Chronic coumarin treatment is associated with increased extracoronary arterial calcification in humans
Authors: Roger J. M. W. Rennenberg, Bernard J. van Varik, Leon J. Schurgers, Karly Hamulyak, Hugo ten Cate, Tim Leiner, Cees Vermeer, Peter W. de Leeuw, Abraham A. Kroon
Journal: Blood (2010)
1010. Developing a Potential Pain Therapy Using Engineered Zinc Finger Protein Repressors of the Sodium Channel PN3
Authors: Siyuan Tan, Mohammad M. Doroudchi, Xiaohong Zhong, Julie Qiao, Steve Zhang, Philip D. Gregory
Journal: Molecular Therapy (2006)

The voltage-gated sodium channel PN3 (Nav1.8, SCN10a), expressed exclusively in sensory neurons located in dorsal root ganglia (DRG), is a key molecule in nociceptive signaling. Increased PN3activity has been implicated in chronic pain conditions such as neuropathic pain and cancer pain. Moreover, animal studies show that knocking out the PN3 gene or reducing PN3 level improves hyperalgesia. Therefore, pain therapies that target PN3 are predicted to be effective, and may have few side effects since PN3 expression is restricted to DRG neurons. However, PN3 belongs to a family with at least 10 closely related sodium channels that have diverse biological functions, confounding efforts to identify small molecules that selectively inhibit PN3 activity. Engineered zinc finger protein (ZFP) transcription factors can be designed to target any promoter and regulate the transcription of virtually any gene. More importantly, singular specificity has been demonstrated with engineered ZFPs, making it possible to selectively modulate PN3 expression without affecting the activities of other closely related sodium channels. We have engineered ZFPs repressors that target the PN3 promoter and tested their activities in cell culture models using lentiviral vectors. In DAOY (human medulloblastoma) cell line, ZFP repressors efficiently blocked both the basal level and the activated level of PN3 transcription. Moreover, ZFP repressors effectively knocked down PN3 expression in primary DRG neurons, the target cell type for PN3-based pain therapies. We are currently optimizing these ZFP TFs to maximize the potency and specificity of PN3 repression; combined with neurotropic vectors such as herpes simplex virus (HSV), the in vivo efficacy of the ZFP repressor can be tested in animal models of pain.