tbuckley/cabot-search huggingface dataset:
Controlled trial of budesonide given by the nebuhaler in preschool children with asthma.
Authors: J. G. Gleeson, J. F. Price
Journal: BMJ (1988)

OBJECTIVE--To determine whether the inhaled corticosteroid budesonide, given by a Nebuhaler spacing device, was effective in prophylaxis of asthma in preschool children. DESIGN--Double blind, placebo controlled, random order crossover trial with two week practice run in period. SETTING--Outpatient clinic referrals in secondary referral centre. PATIENTS--39 children aged 2-6 years selected for the following: able to use Nebuhaler; parents able to complete record card; poorly controlled asthma (defined); not already on systemic or inhaled steroids. Eleven withdrew for various reasons not connected with intolerance to budesonide. Age, sex, other atopies, and symptoms during run in period were similar in the 28 children who completed the trial and in the 11 who withdrew. INTERVENTIONS--Budesonide 200 micrograms or placebo (both one puff) given twice daily during 6-week treatment or control periods, using Nebuhaler after prior training. Three week "washout" at crossover. Compliance monitored by weighing canisters. Patients withdrawn if their acute attacks required treatment with systemic steroids. END POINT--Control of asthma. MEASUREMENTS AND MAIN RESULTS--Peak expiratory flow rate measured twice daily where cooperation allowed. Diary of symptoms and concomitant drug use kept daily. Results showed mean peak flow significantly higher (12% in mornings, 14% in evenings) in second three weeks of intervention compared with control period (95% confidence intervals 6.3-17.3% and 7.2-21.0%). Supplementary bronchodilator drugs reduced by 50% during intervention periods. CONCLUSIONS--Budesonide given by Nebuhaler is effective prophylaxis for preschool children with frequent asthma.
Abstract OT1-1-01: Optimizing neoadjuvant systemic treatment in HER2 positive breast cancer - The TRAIN-2 study
Authors: MS van Ramshorst, JV van Thienen, JM Stouthard, S Rodenhuis, SC Linn, GS Sonke
Journal: Cancer Research (2013)

Abstract Background Anthracycline-based regimens are still commonly used in HER2 positive (HER2+) breast cancer (BC), despite added toxicity compared to non-anthracycline containing regimens. The benefit of antracyclines in the era of trastuzumab containing regimens is controversial. Moreover, the value of anthracyclines in combination with dual-HER2 blockade is uncertain. We recently showed high pathologic complete response (pCR) rates with a weekly neoadjuvant paclitaxel-trastuzumab-carboplatin (PTC) regimen. We now aim to evaluate the effect of replacing 3 PTC cycles in this regimen with 3 FE90C-trastuzumab cycles, while adding pertuzumab to all cycles in both arms. Secondly, combined blockade of the estrogen-receptor (ER) pathway and the HER2-pathway in the presence of chemotherapy has not previously been investigated in HER2+/ER+ tumors. Trial design This is a randomized comparative trial evaluating pCR rate (ypT0/is ypN0) at surgery as primary endpoint after neoadjuvant systemic therapy with 9 cycles PTC plus pertuzumab q3w (paclitaxel 80mg/m2 day 1, 8 – trastuzumab 6mg/kg (loading dose 8mg/kg) day 1 – carboplatin AUC = 6 day 1 – pertuzumab 420mg (loading dose 840mg) day 1) versus 3 cycles FE90C-T plus pertuzumab q3w followed by 6 cycles PTC plus pertuzumab q3w. An optional second randomization (2×2 factorial design) will compare concurrent endocrine treatment with an aromatase inhibitor (and ovarian function suppression in premenopausal women and men) during neoadjuvant chemotherapy in combination with dual HER2-blockade, in patients with HER2+/ER+ tumors. Eligibility criteria Patients aged ≥18 year with histologically confirmed invasive HER2+ BC, stage II or III. Eligible patients have a performance status of 0 to 1 and adequate cardiac and organ function. Specific aims The primary objective is to compare the efficacy of 6 cycles neoadjuvant PTC plus pertuzumab preceded by either 3 cycles FE90C-T plus pertuzumab or 3 cycles PTC plus pertuzumab in stage II and III HER2+ BC. Secondary objectives are to describe the efficacy of combined HER2 and ER pathway blockade in HER2+/ER+ BC, to describe the safety of the various regimens and to identify prognostic and predictive biomarkers for pCR. Statistical methods The sample size of the study will be based on the primary objective. To detect an increase in pCR rate from 44% in the PTC arm to 58% in the FE90C-T arm at the 5% (2-sided) level of significance with an 80% power 437 patients need to be randomized (assuming ∼10% of patients will be not evaluable). Target accrual Recruitment will start in the summer of 2013 across ∼30 sites in the Netherlands. Unrestricted research support and pertuzumab are kindly provided by Roche Netherlands. The trial is sponsored by the Dutch Breast Cancer Trialists’ Group (BOOG). Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT1-1-01.
Costimulation of CD3/TcR complex with either integrin or nonintegrin ligands protects CD4<sup>+</sup> allergen‐specific T‐cell clones from programmed cell death
Authors: E. Agea, O. Bistoni, P. Bini, G. Migliorati, I. Nicoletti, G. Bassotti, C. Riccardi, A. Bertotto, F. Spinozzi
Journal: Allergy (1995)

An optimal stimulation of CD4 + cells in an immune response requires not only signals transduced via the TcR/CD3 complex, but also costimulatory signals delivered as a consequence of interactions between T‐cell surface‐associated costimulatory receptors and their counterparts on antigen‐presenting cells ‘APC). The intercellular adhesion molecule‐1 ‘ICAM‐1, CD54) efficiently costimulates proliferation of resting, but not antigen‐specific, T cells. In contrast, CD28 and CD2 support interleukin ‘IL)‐2 synthesis and proliferation of antigen‐specific T cells more efficiently than those of resting T cells. The molecular basis for this differential costimulation of T cells is poorly understood. Cypress‐specific T‐cell clones ‘TCC) were generated from four allergic subjects during in vivo seasonal exposure to the allergen. Purified cypress extract was produced directly from fresh collected pollen and incubated with the patients' mononuclear cells. Repeated allergen stimulation was performed in T‐cell cultures supplemented with purified extract and autologous APC. The limiting‐dilution technique was then adopted to generate allergen‐specific TCC, which were also characterized by their cytokine secretion pattern as ThO ‘IL‐4 plus interferon‐gamma) or Th2 ‘IL‐4). Costimulation‐induced proliferation or apoptosis was measured by propidium iodide cytofluorometric assay. By cross‐linking cypress‐specific CD4 + and CD8 + T‐cell clones with either anti‐CD3 or anti‐CD2, anti‐CD28, and anti‐CD54 monoclonal antibodies, we demonstrated that CD4+ clones ‘with ThO‐ or Th2‐type cytokine production pattern) undergo programmed cell death only after anti‐CD3 stimulation, whereas costimulation with either anti‐CD54 or anti‐CD28 protects target cells from apoptosis. The costimulation‐induced protection from apoptotic death was associated with a significant rise in IL‐4 secretion in both Th0 and Th2‐type clones. In contrast, cypress‐specific Th0 CD8 + clones were more susceptible to stimulation‐induced apoptosis via either anti‐CD3 or anti‐CD2, alone or in combination with anti‐CD54 or anti‐CD28, thus displaying only slight but nonsignificant modifications in the pattern of IL‐4 secretion. The death‐promoting costimulatory effects were not observed with highly purified normal resting CD4 + or CD8 + lymphocytes. Taken together, these results suggest that TcR engagement by an allergen in the context of functionally active APC induces activation‐dependent cell death of some, perhaps less specific, cells, and this may be an important homeostatic mechanism through which functional expansion of allergen‐specific T cells is regulated during an ongoing immune response.
A REPORT OF BACTERIAL VACCINE THERAPY IN A SERIES OF PROSTATIC CASES
Authors: H. C. BUMPUS
Journal: JAMA (1918)

Following the appearance of the paper by Cabot and Crabtree,1 setting forth the favorable results obtained from the administration of colon vaccine in a series of eight prostatic cases, the procedure was adopted from time to time in the Mayo Clinic; but not until May, 1917, was it systematically carried out.
Mathematics and medicine. Test reduction: III-Practical applications.
Authors: W I Card, P A Emerson
Journal: BMJ (1980)

While there is no generally applicable method of test reduction, ways in which the problem can be tackled can usually be suggested. These include the examination of error rates of tests and the use of current statistical methods. When the cost-effectiveness of some more expensive test has to be measured, a model of the decision problem needs to be developed, with an attempted estimation of the values or utilities of the states of health that result from treatment.
Abstract 2560: Cyclin-dependent kinase inhibitor SU9516 enhances sensitivity to methotrexate in human T-cell Jurkat cells
Authors: Hitoji Uchiyama, Yoshihiro Sowa, Miki Wakada, Mayumi Yogosawa, Ryoko Nakanishi, Mano Horinaka, Chihiro Shimazaki, Masafumi Taniwaki, Toshiyuki Sakai
Journal: Cancer Research (2010)

Abstract Methotrexate (MTX), a classical anti-folate drug, has been used to treat various hematological malignancies. Since MTX prevents tumor cells from proliferating by inhibiting dihydrofolate reductase (DHFR), DHFR expression is a key determinant of resistance to MTX in malignant hematological tumor cells. In fact, it is well known that elevated expression of DHFR is a direct factor in clinical therapeutic resistance to MTX. First of all, we demonstrated that the sensitivity to MTX was enhanced by the knockdown of the DHFR gene in human T-cell leukemia cell. Concretely, the anti-proliferative effect of MTX was significantly enhanced by the knockdown of DHFR expression by siRNA in Jurkat cells. Therefore, a novel strategy down-regulating DHFR expression seems promising for enhancing sensitivity to MTX. On the other hand, the expression of DHFR is controlled by the transcription factor E2F. Unphosphorylated retinoblastoma (RB) protein is known to bind and inhibit the E2F. Cyclin-dependent kinase (CDK) inhibitors activate RB function and inhibit E2F function. Then we tested whether CDK inhibitor acted as a suppressor of DHFR through the E2F site of the promoter. We found that SU9516, a cyclin-dependent kinase inhibitor, decreased phospho-RB (Ser780) and reduced the expression of both DHFR mRNA and protein, and the DHFR promoter activity was attenuated by SU9516 dependent on the E2F site. Furthermore, pretreatment with SU9516 significantly enhanced sensitivity to MTX in a colony formation assay. To expand these results in Jurkat cells, we have also examined other leukemic cell lines (human T cell leukemia CCRF-CEM cells and human erythroleukemia K562 cells) and confirmed that SU9516 also repressed the levels of DHFR protein and phopho-RB (Ser780), and enhanced the cytotoxicity of MTX in a colony formation assay in both of cell lines. To expand these results by SU9516, we have examined other CDK inhibitors (Purvalanol A and Cdk4/6 Inhibitor IV) and confirmed that these agents also decreased DHFR protein and phospho-RB (Ser780), and enhanced the cytotoxicity of MTX in a colony formation assay in Jurkat cells as similar as SU9516. Based on these findings, we conclude that a combination of cyclin-dependent kinase inhibitors and MTX may be useful for overcoming resistance to MTX. 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 2560.
Syndrome of inappropriate antidiuretic hormone secretion due to treatment of lung cancer with cisplatin.
Authors: T J Littlewood, A P Smith
Journal: Thorax (1984)

Cisplatin (cisdichlorodiammineplatinum 11) is used increasingly in the chemotherapy of malignant tumours, including carcinoma of the bronchus.We report here two cases of dilutional hyponatraemia secondary to the inappropriate secretion of antidiuretic hormone that developed in two patients with bronchial carcinoma receiving treat- ment with cisplatin. Ca repof CASE 1A 61 year old woman presented with a two day history of pleuritic chest pain and a productive cough.Material obtained by biopsy of an endoscopically visible bronchial tumour showed appearances of small cell undifferentiated carcinoma.Staging procedures suggested that this was confined to the thorax.Haematological and biochemical indices were normal.She commenced treatment with two cycles of intravenous vincristine 1*2 mg/m2, adriamycin 40
A Good-Looking Cast
Authors: George A. Filinger
Journal: JAMA (1966)

<h3>To the Editor:—</h3> About 50 years ago my father suffered a broken leg in a horse-and-carriage runaway. A local country doctor, using a local anesthetic, set the broken bone and applied a heavy "gosh awful" looking cast. The whole operation took about an hour and a half and my father rode home with us in what was left of the carriage. This week (1965) my wife slipped on a rug and cracked a bone in her wrist. A trained local doctor set the bone and applied a heavy "gosh awful" looking cast enclosing the forearm. This took 21/2 hours in a clinic, and 18 hours in a hospital following a general anesthetic. Why haven't the plastic experts, chemists, textile workers, physicists, or someone developed a light, strong, good-looking cast?
Teratological research using in vitro systems. II. Rodent limb bud culture system.
Authors: L Friedman
Journal: Environmental Health Perspectives (1987)

This review represents a compilation of information related to the rodent limb bud culture system from approximately 80 publications after 1969 and conversations with workers in the field. Most of these papers and book chapters refer exclusively to studies with the mouse limb bud. Sections in this review include historical review, end point measurements, activating systems, types of compounds studied and dose response, reproducibility, statistical analysis, equipment and personnel requirements, mechanisms, and summary.
Routine Use of Transrectal Ultrasound in Rectal Carcinoma: Results of a Prospective Multicenter Study
Authors: F. Marusch, A. Koch, U. Schmidt, R. Zippel, R. Kuhn, S. Wolff, M. Pross, A. Wierth, I. Gastinger, H. Lippert
Journal: Endoscopy (2002)

Preoperative transrectal ultrasound (TRUS) can establish the depth of penetration of a tumor, and thus provide important information for decisions about further management. In the literature, this method is reported to have a high level of sensitivity and specificity. Our investigation aimed at establishing the quality of the diagnostic procedure and treatment of colorectal carcinoma.This investigation, which covered a 1-year period, and involved 75 hospitals, was conducted in the form of a prospective multicenter study and included a total of 3756 patients. For rectal carcinomas, all endosonographically determined uT categories were compared with histologically established T categories (pT).At 49 hospitals a total of 499 TRUS examinations in 1463 rectal carcinomas (34.1 %) were performed. A comparison of uT with pT category was possible for 422 TRUS examinations. Agreement between the preoperative endosonographic diagnosis with the histological diagnosis was found in 63.3 % (n = 267) of cases (95 % confidence interval 58.5 % - 67.9 %). The diagnostic accuracy was 50.8 % for pT1 carcinomas, 58.3 % for pT2 lesions, 73.5 % for pT3 tumors, and 44.4 % for pT4 carcinomas. Overstaging was observed in 23.9 %, overall, and understaging in 12.8 %. Understaging was significantly less common than overstaging (P < 0.05, s.).The accuracy of transrectal ultrasound used as a routine clinical examination in rectal carcinoma patients was clearly lower than that reported in the literature. We conclude that TRUS may aid decisions relevant to treatment only when used by well-trained investigators with a large case load of rectal carcinoma patients. Centralization of transrectal ultrasonography service is mandatory if a high level of quality is to be achieved with this method.
Efficient induction of apoptosis in cultured rat glomerular mesangial cells by dimeric monoclonal IgA anti-Thy-1 antibodies
Authors: Toshinobu Sato, Mieneke G.A. van Dixhoorn, Willeke E.M. Schroeijers, Leendert A. van Es, Mohamed R. Daha
Journal: Kidney International (1997)
Evaluation of Infertility-Reply
Authors: Ronald S. Swerdloff, Stephen P. Boyers
Journal: JAMA (1983)

<h3>In Reply.—</h3> Dr Schwarzstein has raised a number of interesting points in his letter in response to our article, "Evaluation of the Male Partner of an Infertile Couple: An Algorithmic Approach." We are of common mind regarding the importance of a careful history and physical examination. The article focused on laboratory testing, since it was published as part of a series inThe Journalentitled TOWARD OPTIMAL LABORATORY USE. The history should, of course, include questions regarding cryptorchidism and genital infections. Physical examination includes careful palpation of the epididymis, vas deferens, and spermatic veins with the Valsalva maneuver, as indicated in several places in the article. We have used the Doppler stethoscope in an attempt to detect subclinical varicoceles with mixed success. Spermatic venography carries considerable expense to the patient and probably should be reserved for those with a high degree of suggestion of nonpalpable varicoceles, ie, increased number of
Use of the Therapeutic Footwear Benefit Among Diabetic Medicare Beneficiaries in Three States, 1995
Authors: Jonathan R Sugarman, Gayle E Reiber, Greg Baumgardner, Cecilia M Prela, Joseph Lowery
Journal: Diabetes Care (1998)

To determine the extent to which Medicare provided reimbursement for therapeutic footwear to diabetic Medicare beneficiaries in Washington, Alaska, and Idaho in 1995.Using inpatient, outpatient, and durable medical equipment claims data, we selected a cohort of diabetic Medicare beneficiaries. Therapeutic footwear claims were identified using a set of billing codes intended only for the diabetes footwear benefit. People at "high risk" or "possibly increased risk" for foot problems who might benefit from therapeutic footwear were identified using a combination of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes in any of the databases.Among 608,804 beneficiaries, 10.2% (62,170) met the inclusion criteria for diabetes. Of the diabetic beneficiaries, 13.0% (8,079) had at least one "high risk" diagnosis, and 14.0% (8,686) had at least one "possibly increased risk" diagnosis. The percentage of diabetic beneficiaries with therapeutic footwear claims was 2.9% among those with diagnoses high risk, 0.7% among those with diagnoses indicating possibly increased risk, and 0.1% among those with no diagnosis from the list. Altogether, only 0.6% of beneficiaries meeting the diabetes case ascertainment criteria had a therapeutic footwear claim in 1995.Few diabetic Medicare beneficiaries in Washington, Alaska, and Idaho had claims for reimbursement for therapeutic footwear in 1995. The low utilization of the footwear benefit may represent an important opportunity to improve care for Medicare beneficiaries with diabetes. Further work should be done to characterize the use of the benefit in other regions and to assess whether the low level of usage reflects underutilization.
Time factor in the measurement of response to bronchodilators
Authors: G. J. Mushin
Journal: Thorax (1967)

The measurement of response to bronchodilators by recording the change in forced expiratory volume in 1 second (F.E.V.<sub>1·0</sub>) can underestimate response unless the correct time for postbronchodilator tests is chosen. In 18 patients given isoprenaline, the time of peak response varied, but a 30-minute testing time gave the closest approximation to peak response. In order to test whether repeated doses would increase the response, inhalations of isoprenaline were given at 30-minute intervals, the F.E.V.<sub>1·0</sub> being measured after each dose. There was a further response after successive doses until a plateau was reached, usually after the third dose. The maximum response obtained was often considerably greater than the response after the first administration of isoprenaline, the average increase in F.E.V.<sub>1·0</sub> being 600 ml. after the first dose and 840 ml. after repeated doses. A similar response was obtained in four patients using orciprenaline spray administered with a metered aerosol, the dose being repeated at hourly intervals. Four patients were given repeated inhalations of isoprenaline until the response reached a plateau, and then 250 mg. of aminophylline was injected intravenously. None of these patients showed any further improvement with aminophylline. The significance of these findings is discussed.
Effect of functional grade and etiology onin vivo hepatic phosphorus-31 magnetic resonance spectroscopy in cirrhosis: Biochemical basis of spectral appearances
Authors: David K. Menon, Janet Sargentoni, Simon D. Taylor-Robinson, Jimmy D. Bell, Jane I. Cox, David J. Bryant, Glyn A. Coults, Keith Rolles, Andrew K. Burroughs, Marsha Y. Margan
Journal: Hepatology (1995)

Hepatic phosphorus-31 magnetic resonance spectroscopy (31P MRS) was undertaken in 85 patients with histologically proven cirrhosis of varying etiologies and functional severity. Reference data were acquired from 16 healthy volunteers who had no history or evidence of liver disease or alcohol abuse. In vivo hepatic 31P MR spectra were acquired with pulse angle 45 degrees and repetition times (TR) of 5 and 0.5 seconds. Peak area ratios of phosphomonoesters (PME), inorganic phosphate (Pi), and phosphodiesters (PDE) relative to beta ATP, and of PME relative to PDE were calculated from spectra acquired at TR 5 seconds. Estimates of saturation effects for individual resonances were obtained by dividing the peak height at TR 5 seconds by that at TR 0.5 seconds to yield a T1-related signal height ratio (SHR). When compared with reference values, the patients with liver disease showed a significantly higher PME/ATP (P < .0001), PME/PDE (P < .0001), PME SHR (P < .001), and Pi SHR (P < .02), and a lower PDE/ATP (P < .001) and PDE SHR (P < .001). The magnitude of these changes increased significantly and progressively with increasing functional impairment. In patients with compensated cirrhosis spectral appearances varied with etiology; thus, patients with postviral cirrhosis showed a significantly higher Pi/ATP; those with alcoholic cirrhosis, a significantly lower PDE/ATP; and those with cirrhosis secondary to primary sclerosing cholangitis, a significantly lower Pi/ATP than the healthy volunteers or other etiological groups. However, spectral appearances did not vary with etiology in patients with decompensated disease. In vitro 31P MRS of perchloric extracts of samples of liver tissue obtained from 10 patients with cirrhosis at transplant hepatectomy showed increases in levels of the soluble PME metabolites, phosphorylcholine and phosphorylethanolamine, and reductions in the levels of the soluble PDE metabolites, glycerophosphorylcholine and glycerophosphorylethanolamine. These changes suggest regenerative activity in cirrhotic livers. The increases in soluble phosphomonoesters in the aqueous extracts accounted for the increased PME/ATP ratio seen in the in vivo spectra, and might account for the increase in PME SHR. The reduction in soluble phosphodiesters in the aqueous extracts did not entirely account for the reduction PDE/ATP ratio seen in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)