tbuckley/cabot-search huggingface dataset:
Levamisole-induced arthritis.
Authors: P Siklos
Journal: BMJ (1977)

two separate analyses2 3 we concluded that from 1956 to 1973 age-specific mortality from ischaemic heart disease increased in both sexes, but the increase was greater in women than in men, except in age groups above 55 years, and in young men this increase was less marked during the 1960s than it was in earlier years.The reasons for the different conclusions arise from the inclusion by Clayton et al of deaths due to hypertensive disease in their analyses of ischaemic heart disease trends.It is not, however, clear why they did this.With the introduction of effective treatment for hypertension there are reasonable grounds for believing that the reduction in mortality from hypertensive disease in recent years is real and not simply due to transfer of cases from hypertensive categories into ischaemic heart disease categories.4If such transfer did occur one would expect it to have affected men and women to the same extent, but this did not happen.If deaths attributable to hypertensive disease are excluded from analyses of ischaemic heart disease trends the conclusions of Clayton et al are consistent with ours and together they indicate the need to explain the recent increase in ischaemic heart disease among women.
Pathogenesis of calcium-containing gallstones. Canine ductular bile, but not gallbladder bile, is supersaturated with calcium carbonate.
Authors: R V Rege, E W Moore
Journal: Journal of Clinical Investigation (1986)

Calcium precipitation in bile is a requisite event in the initiation and growth of all pigment gallstones. Calcium solubility in bile is thus of great importance. This is the first attempt to define the ion-product of CaCO3 in bile in any species. If the ion-product: [Ca++] X [CO = 3] exceeds solubility product (K'sp), the sample is supersaturated and CaCO3 precipitation is thermodynamically possible. We have recently determined K'sp of calcite to be 3.76 X 10(-8) mol/liter at 37 degrees C and total ionic strength = 0.16 M. Gallbladder (GB) bile was obtained from 15 anesthetized dogs after 12-24-h fasts. Duct bile was obtained from three dogs (n = 12) during variable taurocholate infusion. Samples were assayed for pH, partial pressure of carbon dioxide (PCO2), total bile salt concentration ([TBS]), total calcium concentration ([Ca]), and free calcium ion concentration ([Ca++]). With increasing [TBS] in both GB and duct bile, there was a linear decline in pH, a curvilinear decline in [HCO-3] and [CO = 3], and linear increase in [Ca++] and [Ca]. All ductular samples were supersaturated with CaCO3, with saturation indices (SI) as high as 17.5 and a mean of 8.36 +/- 1.43 (SE). In sharp contrast, none of the GB samples were supersaturated, due to the marked decline in [CO = 3] upon concentration and acidification of bile. In GB bile, the SI ranged from 0.006 to 0.126, with a mean of 0.039 +/- 0.011. The gallbladder thus produced a change in the SI from a value as high as 17.5 to a value as low as 0.006 in concentrated GB bile, which is a nearly 3,000-fold change. The average change in the SI was approximately 215-fold. Since all duct samples were supersaturated, and since the dog does not normally form gallstones, the data support our previous hypotheses that: (a) in canine bile, as in canine pancreatic juice, a nucleating factor is necessary for CaCO3 precipitation; (b) bile salts are important buffers for Ca++ in bile; and (c) normal GB mucosal function (concentration and acidification of bile) plays an important role in reducing CaCO3 lithogenicity in GB bile.
Bronchial Hyperresponsiveness in Children and Adolescents with Crohn's Disease
Authors: ANTONIO MANSI, SALVATORE CUCCHIARA, LUIGI GRECO, PAOLA SARNELLI, CHIARA PISANTI, MARIA TERESA FRANCO, FRANCESCA SANTAMARIA
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Pulmonary manifestations have been described in Crohn's disease (CD). Bronchial responsiveness to methacholine (MCh) was evaluated in 14 children with CD with no evidence of airway disease, 10 asthmatics, and 10 healthy subjects. In patients with CD total blood eosinophils and serum IgE were 0.20 x 10(9) x L(-1) (95% CI -1.68 to 2.08) and 138.4 kU x L(-)(1) (95% CI 18.84 to 257.96), respectively. Three patients with CD had positive prick tests. Bronchial hyperresponsiveness (BHR) was demonstrated in 10 patients with CD (71%) and in the asthmatics, but not in control subjects. In patients with CD PD(20) appeared significantly greater than in asthmatics (699 microg [95% CI 238 to 1,115] versus 104 microg [95% CI 37.35 to 293]; p < 0.05), and was not related either to baseline FEV(1) or IgE or eosinophils (r = 0.32; r = -0.5; r = -0.15, p = NS, respectively). Neither activity nor treatment or duration of CD affected BHR. Five nonatopic CD patients underwent a second MCh challenge over a 25-mo period: the PD(20) appeared significantly greater than basal PD(20) (1,941 microg versus 575 microg, p < 0.05, respectively), in the absence of significant changes of disease activity. BHR might be the expression of subclinical airway inflammation, a phenomenon which can be responsible for the development of various pulmonary manifestations in CD.
P08.07 * LEPTOMENINGEAL GLIOMATOSIS: A SINGLE INSTITUTION RETROSPECTIVE STUDY OF 31 PATIENTS
Authors: D. Autran, E. Tabouret, M. Barrie, C. Boucard, A. Terciolo, A. Loundou, P. Metellus, H. Dufour, D. Figarella-Branger, O. L. Chinot
Journal: Neuro-Oncology (2014)

BACKGROUND: Secondary leptomeningeal gliomatosis (LMG) is a rare and severe progression pattern of glioma. Prognostic factors and therapeutic management of this pattern remains unclear. Our objective was to evaluate characteristics and outcome of LMG patients (pts). METHODS: We retrospectively reviewed pts diagnosed with secondary LMG referred to our institution between 2004 and 2013. Diagnosis was obtained by clinical, imaging and cerebrospinal fluid (CSF) data. RESULTS: The identification and diagnosis of 31 pts with LMG was based on CSF cytology (n = 12), on MRI data (n = 16) with hyperproteinarrachia (>1.2 gr/l) (n = 9) or without (n = 7), or on meningism with hyperproteinarrachia (n = 3). At LMG diagnosis (LMGD), median age was 45 years and Karnofsky Performance Status (KPS) was <70 in 71% of pts; histological grade was IV in 20 pts and II-III in 11 pts. Median interval from initial glioma diagnosis (IGD) to LMGD was 13.5 months (glioblastoma: 8.1; grades II-III: 28.9). As first line therapy for LMG, 22 pts received an oncological treatment: BCNU-temozolomide (TMZ), n = 15; other chemotherapy, n = 7; craniospinal radiotherapy: n = 0; no further trt, n = 9. From LMGD, median PFS and median OS were 1.8 months (95% confidence interval [CI]: 0.9-2.7) and 2.1 months (CI95%: 1.3-3) respectively. Clinical improvement was observed in 6/22 treated patients, of which 3 showed concomitant imaging improvement; 13/22 pts exhibit a rapid decline. Univariate analyses showed an improved OS with age <45 years old (p < 0.001), prolonged interval from IGD to LMGD (p = 0.003) and KPS ≥70 (p = 0.012). Remained significant in the multivariate analysis: age (HR: 4.533) and interval since IGD (HR: 4.803). Among the 22 treated patients, median OS was significantly higher with BCNU-TMZ trt: 5.7 months (CI95%: 4.2-7.1) vs 2 months (CI95%: 1.1-2.9) for other trt (p = 0.008). Initial proteinorrachia and its changes during LMG treatment were not correlated to response and did not influence outcome. CONCLUSION: We identify age and time interval from IGD to LMGD as potential prognostic factors for LMGD. BCNU-TMZ combination could be an interesting therapeutic option for these patients.
The Use of Imipramine in Depressed Patients With Congestive Heart Failure
Authors: Alexander H. Glassman
Journal: JAMA (1983)

Previous studies of left ventricular performance (LVP) in depressed patients receiving tricyclic antidepressants have been performed on patients without severe heart disease. This study reports the effect of imipramine hydrochloride on LVP, assessed by radionuclide angiography, in a group of depressed patients with notable preexisting left ventricular dysfunction. Ejection fraction was measured at rest by first-pass radionuclide angiography before and after treatment with imipramine. Ejection fraction was unchanged during treatment, but seven of 15 patients experienced orthostatic hypotension of such severity that administration of the drug had to be discontinued. Plasma concentrations of the drug were essentially twice those usually seen. It is important to appreciate that although imipramine does not further impair resting LVP, this does not mean it is without risk. The physician must watch carefully for orthostatic hypotension when using imipramine in depressed patients with impaired LVP. (<i>JAMA</i>1983;250:1997-2001)
Abstract 2219: Mechanism of trancriptional repression by EWS/FLI in Ewing's sarcoma
Authors: Savita Sankar, Stephen L. Lessnick
Journal: Cancer Research (2012)

Abstract Objective: Ewing's sarcoma is a highly aggressive bone-associated malignancy affecting children and young adults with most cases harboring a somatic translocation that encodes the EWS/FLI oncoprotein. EWS/FLI is an aberrant transcription factor. Most studies indicate that EWS/FLI functions as a transcriptional activator. However, recent genome-wide transcriptional studies have raised the possibility that EWS/FLI may also repress target genes, although the mechanistic basis for this repression is unknown. We sought to test the hypothesis that EWS/FLI functions as a direct transcriptional repressor at some genetic loci, and that transcriptional repression is required for the oncogenic function of EWS/FLI. Furthermore, we sought to define relevant domains and corepressors that are involved in this activity. Methods: RNAi based microarray combined with genome-wide ChIP-Chip analyses were used to identify direct repressed target genes of EWS/FLI. Soft agar and xenograft tumor formation assays were performed to assess oncogenic transformation. Deletion mutants of EWS/FLI were constructed and used to map the repression domain. Co-immunoprecipitations were performed to validate the interaction of EWS/FLI with transcriptional co-repressors. Luciferase reporter assays and gel shift assays were utilized to characterize the binding site for EWS/FLI at repressed gene promoters. Results: We identified a subset of EWS/FLI-repressed target genes that are directly bound by the protein. Using these target genes, we identified domains in EWS/FLI necessary and sufficient for repression. Interestingly, these repression domains are also necessary for oncogenic transformation. We identified two HDACs that are involved in this repression, and identified a likely candidate transcriptional repression complex that binds EWS/FLI and contributes to its repressive function. Finally, we found that transcriptional repression is absolutely required for the oncogenic function of EWS/FLI, as two downregulated targets function as suppressors of Ewing's sarcoma oncogenesis. Conclusion: Transcriptional deregulation by EWS/FLI is a key oncogenic event in Ewing's sarcoma pathogenesis. Our data demonstrated that, in addition to transcriptional activation, EWS/FLI mediated transcriptional repression is also critical in Ewing's sarcoma oncogenesis. This is the first time that a detailed molecular mechanism of EWS/FLI mediated direct repression is reported, and has important implications for therapeutic targeting of EWS/FLI in Ewing's sarcoma. 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 2219. doi:1538-7445.AM2012-2219
Differential response of seven subjects with autistic disorder to clomipramine and desipramine
Authors: C T Gordon, J L Rapoport, S D Hamburger, R C State, G B Mannheim
Journal: American Journal of Psychiatry (1992)

Clomipramine, a serotonin reuptake blocker that has unique antiobsessional properties, was hypothesized to have a different effect from that of desipramine, a tricyclic antidepressant with selective adrenergic effects, for the stereotyped, repetitive behaviors in autism.Seven subjects, ages 6-18 years, with autistic disorder completed a 10-week double-blind, crossover trial of clomipramine and desipramine following a 2-week single-blind, placebo phase.Clomipramine was superior to desipramine and placebo, as indicated by standardized ratings of autism and anger as well as ratings of repetitive and compulsive behaviors. Clomipramine and desipramine were equally superior to placebo for ratings of hyperactivity. Parents of all seven subjects elected to have their children continue to take clomipramine after the study.Clomipramine and desipramine are differentially effective in treating the obsessive-compulsive and core symptoms in autistic disorder. Biological links between compulsions and stereotyped, repetitive behaviors in autistic disorder should be explored.
Amphiregulin Promotes BAX Inhibition and Resistance to Gefitinib in Non-small-cell Lung Cancers
Authors: Benoît Busser, Lucie Sancey, Véronique Josserand, Carole Niang, Marie C Favrot, Jean-Luc Coll, Amandine Hurbin
Journal: Molecular Therapy (2009)

Molecular resistance mechanisms affecting the efficiency of receptor tyrosine kinase inhibitors such as gefitinib in non-small-cell lung cancer (NSCLC) cells are not fully understood. Amphiregulin (Areg) overexpression has been proposed to predict NSCLC resistance to gefitinib and we have established that Areg-overexpressing H358 NSCLC cells resist apoptosis. Here, we demonstrate that Areg prevents gefitinib-induced apoptosis in NSCLC cells. We show that H358 cells are resistant to gefitinib in contrast to H322 cells, which do not overexpress Areg. Inhibition of Areg expression by small-interfering RNAs (siRNAs) restores gefitinib sensitivity in H358 cells, whereas addition of recombinant Areg confers resistance in H322 cells. Areg knockdown overcomes resistance to gefitinib and induced apoptosis in NSCLC H358 cells in vitro and in vivo. Under gefitinib treatment, Areg decreases the expression of the proapoptotic protein BAX, inhibits its conformational change and its mitochondrial translocation. Thus, in the presence of Areg, gefitinib-mediated apoptosis is reduced because BAX is sequestered in the cytoplasm. This suggests that treatments using epidermal growth factor receptor (EGFR) inhibitors may be poorly efficient in patients with elevated levels of Areg. These findings indicate the need for inhibition of Areg to enhance the efficiency of the EGFR inhibitors in patients suffering NSCLC.
Structural and functional evolution of jejunal allograft rejection in rats and the ameliorating effects of cyclosporine therapy.
Authors: J L Madara, R L Kirkman
Journal: Journal of Clinical Investigation (1985)

We assessed the structural and functional evolution of small intestinal transplant rejection in a rat model by use of 1-micron section, electron microscopic, and in vitro electrophysiologic techniques to study jejunal mucosa 3, 6, and 9 d posttransplantation. The earliest structural abnormalities detected in jejunal loops transplanted from Lewis X Brown Norway F1 hybrids into Lewis rats occurred within 3 d posttransplantation and consisted of focal endothelial cell injury of the microvasculature and focal injury of crypt epithelial cells. Both alterations were associated with adjacent infiltration of large lymphoid cells, and both markedly progressed and became rather diffuse over the following 6 d. In contrast, villus absorptive cells were not markedly altered in structure until the 9th postoperative day. As compared with host jejuna, allograft jejunal epithelium demonstrated multiple functional abnormalities. Transepithelial resistance declined progressively by days 6 and 9 (both P less than 0.05), although baseline transepithelial spontaneous potential difference was only affected at day 9 (P less than 0.01). Stimulated absorption by allograft jejuna, as assessed by measuring electrical response to mucosal glucose, was not significantly diminished until day 9 (P less than 0.05). In contrast, stimulated secretion assessed by measurement of electrical response to serosal theophylline was diminished by day 6 (P less than .01). These data suggest that the earliest epithelial injury during rejection, as judged both structurally and functionally, occurs in the crypt and is paralleled by endothelial injury at the level of the microvasculature. Thus, the primary targets for rejection are most likely endothelial cells and crypt epithelial cells. In contrast, structural and functional impairment of villus epithelium is detectable only at substantially later times during rejection and are most likely secondary processes related to either ischemia produced by microvascular injury or decreased epithelial regenerative ability secondary to crypt injury. Last, we show that the detrimental structural and functional sequellae of jejunal transplantation across the major histocompatibility complex in this model is strikingly ameliorated with cyclosporine therapy.
Vacuum Extraction and Symphysiotomy
Authors: D. A. M. Gebbie
Journal: BMJ (1967)

ejaculate radio-opaque.One wonders whether sodium iodide, which is radio-opaque, could be used in primate experiments ?We feel that the position adopted during coitus may be important for sperm entry.Primates adopt a variation of the knee-chest position (that is, a position of rear entry with the female bending forward until the head is lower than the buttocks).If. the human female were to adopt this position, the normally ante- verted uterus would be in a nearly vertical plane, with the cervix uppermost, inviting the sperm to drop in.In Masters and Johnson's radiographic experiment, we do not know the position of the subjects.However, if they were either recum- bent or standing, this might explain how in none of the three radiographs was there the slightest sign of radio-opaque fluid in the uterus.
Prostaglandin E2 activates clusters of apical Cl- channels in principal cells via a cyclic adenosine monophosphate-dependent pathway.
Authors: B N Ling, K E Kokko, D C Eaton
Journal: Journal of Clinical Investigation (1994)

We examined cell-attached patches on principal cells of primary cultured, rabbit cortical collecting tubules. Under basal conditions, apical 9-pS Cl(-)-selective channels were observed in 9% of patches (11/126), and number of channels times open probability (NP0) was 0.56 +/- 0.21. The channel had a linear current-voltage relationship, reversal potential (Erev) near resting membrane potential, a P0 (0.30-0.70) that was independent of voltage, and complicated kinetics (i.e., bursting) at hyperpolarized potentials. NP0 and channel frequency were increased after 30 min of basolateral exposure to 0.5 microM PGE2 (18/56), 10 microM forskolin (23/36), or 0.5 mM dibutyryl cyclic adenosine monophosphate (cAMP) (25/41). Increases in NP0 appeared to be mediated primarily through an increase in the number of observed channels per patch (N), not changes in P0. After these cAMP-increasing maneuvers, N was inconsistent with a uniform distribution of channels in the apical membrane (P < 0.001), but rather the channels appeared to be clustered in pairs. Apical 0.5 microM PGE2 (12/91), apical or basolateral 0.5 microM PGF2 alpha (8/110), or 0.25 microM thapsigargin (releaser of intracellular Ca2+ stores) (7/73) did not increase NP0 or channel frequency.(a) 9-pS Cl- channels provide a conductive pathway for apical membrane Cl- transport across principal cells. (b) Channel activation by basolateral PGE2 is mediated via a cAMP-, but not a Ca(2+)-dependent mechanism. (c) Apical channels are clustered in pairs. (d) With its low baseline frequency and Erev near resting membrane potential, this channel would not contribute significantly to transcellular Cl- flux under basal conditions. (e) However, cAMP-producing agonists (i.e., PGE2, arginine vasopressin) would increase apical Cl- transport with the direction determined by the apical membrane potential.
Effects of phenobarbitone, cinnarizine, and zoxazolamine on the development of right ventricular hypertrophy and hypertensive pulmonary vascular disease in rats treated with monocrotaline
Authors: J. M. KAY, P. SMITH, D. HEATH, J. A. WILL
Journal: Cardiovascular Research (1976)

The results of this experiment suggest that the addition of zoxazolamine to the diet may prolong the survival and reduce the incidence of right ventricular hypertrophy and hypertensive pulmonary vascular disease in male rats given a single subcutaneous injection of monocrotaline. Phenobarbitone and cinnarizine were ineffective.
Management of Pruritis Ani
Authors: Carlos P. Lamar
Journal: JAMA (1965)

<h3>To the Editor:—</h3> A causal mechanism of pruritus ani, particularly in men of the middle-age range included by Dr. Copland in the "psychosomatic" group, is anal leakage of minute particles of liquid or semiliquid feces which often occurs when flatus is expelled. These small amounts of fecal material spread over the perianal skin and cause annoying irritation and at times a maddening pruritus. The usual absence of hemorrhoids, fissures, and detectable dermatitis, make this condition almost impossible to diagnose unless the patient is thoroughly questioned about flatus usually preceding or accompanying the pruritus ani. The flatulence itself is rarely continuous; it occurs in recurrent episodes which often follow the ingestion of certain foods; and it may be normal or the manifestation of some degree of food allergy or of intolerance due to digestive insufficiency. After the mechanism is explained to him, the patient is asked to maintain the anal orifice
Unintended pregnancies and the use of contraception: changes from 1984 to 1989.
Authors: A Fleissig
Journal: BMJ (1991)

A researcher randomly selected 100 birth registrations in each of 20 areas in England and Wales and sent a questionnaire to the mothers 6 months after birth to determine the 1989 proportion of unplanned pregnancies and contraceptive usage. She compared them with results from a similar survey in 1984. The 1984 and 1989 response rates stood at 79% and 76% respectively. The percentage of unplanned pregnancies between the 2 years rose significantly from 26.7%-31.3% (p.01). The proportion of these mothers who were using some form of contraception at the time of conception decreased only slightly in this period (70.5%- 69.1%). In both years, the mothers who had unintended pregnancies consisted basically of young single women or women with 2 or more children. Further, women who completed full time schooling 18 years were less likely to become pregnancy unintentionally. The percentage of mothers in the 20-24 year old group who had an unplanned pregnancy increased most significantly from 27.4%-44.4% (p.001). The percentage also increased, but less significantly, in the 25-30 year old group from 19.1-26.6% (p.01). In 1984, contraceptive usage rose significantly with age among mothers who had unintended pregnancies (p.001). For example, 37.9% of the teen mothers used a contraceptive at the time of conception while 87% of mothers 35 years did. A smaller proportion of newer mothers were taking oral contraceptives (OCs) at contraception in 1989 (10.4%) than in 1984 (12.9%), but the proportion of them who experienced an unintended pregnancy increased from 47.9% to 68.2%. 81% of 20-24 years old and 68./9% of 25-29 year olds on OCs become pregnant unintentionally in 2989 whereas, in 1984, 47.8% and 44.7% respectively did so. These results demonstrate that contraceptive users often have insufficient knowledge about contraceptives.