tbuckley/cabot-search huggingface dataset:
HER2,<i>TOP2A</i>, and TIMP-1 and Responsiveness to Adjuvant Anthracycline-Containing Chemotherapy in High-Risk Breast Cancer Patients
Authors: Bent Ejlertsen, Maj-Britt Jensen, Kirsten V. Nielsen, Eva Balslev, Birgitte B. Rasmussen, Gro L. Willemoe, Pernille B. Hertel, Ann S. Knoop, Henning T. Mouridsen, Nils Brünner
Journal: Journal of Clinical Oncology (2009)

Purpose To evaluate whether the combination of HER2 with TIMP-1 (HT) or TOP2A with TIMP-1 (2T) more accurately identifies patients who benefit from cyclophosphamide, epirubicin, and fluorouracil (CEF) compared with cyclophosphamide, methotrexate, and fluorouracil (CMF) than these markers do when analyzed individually. Patients and Methods The Danish Breast Cancer Cooperative Group (DBCG) 89D trial randomly assigned 980 high-risk Danish breast cancer patients to CMF or CEF. Archival tumor tissue was analyzed TIMP-1, and HER2-negative and TIMP-1 immunoreactive tumors were classified as HT nonresponsive and otherwise HT responsive. Similarly, the 2T panel was constructed by combining TOP2A and TIMP-1; tumors with normal TOP2A status and TIMP-1 immunoreactivity were classified as 2T-nonresponsive and otherwise 2T-responsive. Results In total, 623 tumors were available for analysis, of which 154 lacked TIMP-1 immunoreactivity, 188 were HER2 positive, and 139 had a TOP2A aberration. HT status was a statistically significant predictor of benefit from CEF compared with CMF (P interaction = .036 for invasive disease–free survival [IDFS] and .047 for overall survival [OS]). The 269 (43%) patients with a 2T-responsive profile had a significant reduction in IDFS events (adjusted hazard ratio, 0.48; 95% CI, 0.34 to 0.69; P &lt; .001) and OS events (adjusted hazard ratio, 0.54; 95% CI, 0.38 to 0.77; P &lt; .001). 2T status was a highly significant predictor of benefit from CEF compared with CMF (P interaction &lt; .0001 for IDFS and .004 for OS). Conclusion The 2T profile is a more accurate predictor of incremental benefit from anthracycline-containing chemotherapy than HER2, TIMP-1, or TOP2A individually, and compared with these, 2T classifies a larger proportion of patients as sensitive to anthracyclines.
Endothelium dependent vasodilatation following brief ischaemia and reperfusion in anaesthetised swine
Authors: E. O McFalls, D. J Duncker, R. Krams, H. Ward, C. Gornick, P. D Verdouw
Journal: Cardiovascular Research (1991)

Journal Article Endothelium dependent vasodilatation following brief ischaemia and reperfusion in anaesthetised swine Get access Edward O McFalls, Edward O McFalls Correspondence to: Dr McFalls Search for other works by this author on: Oxford Academic PubMed Google Scholar Dirk J Duncker, Dirk J Duncker Search for other works by this author on: Oxford Academic PubMed Google Scholar Rob Krams, Rob Krams Search for other works by this author on: Oxford Academic PubMed Google Scholar Herb Ward, Herb Ward Search for other works by this author on: Oxford Academic PubMed Google Scholar Charles Gornick, Charles Gornick Search for other works by this author on: Oxford Academic PubMed Google Scholar Pieter D Verdouw Pieter D Verdouw Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 25, Issue 8, August 1991, Pages 659–665, https://doi.org/10.1093/cvr/25.8.659 Published: 01 August 1991 Article history Received: 31 January 1991 Accepted: 25 March 1991 Published: 01 August 1991
Octreotide in gastrointestinal motility disorders.
Authors: C Owyang
Journal: Gut (1994)

The effects of octreotide on six normal subjects and five patients with scleroderma were investigated. Changes in intestinal motility and in plasma motilin were examined after a single injection of octreotide. Octreotide stimulated intense intestinal motor activity in normal subjects. Motility patterns in the scleroderma patients were chaotic and non-propagative, but, after octreotide was given, became well coordinated, aborally directed, and nearly as intense as in normal volunteers. Clinical responses and changes in breath hydrogen were also evaluated in the five scleroderma patients who had further treatment with octreotide at a dose of 50 micrograms/day subcutaneously for three weeks. A reduction in symptoms of abdominal pain, nausea, vomiting, and bloating was seen. Additionally, there was an improvement in bacterial overgrowth as objectively measured by breath hydrogen testing. The effects of octreotide (100 micrograms/day subcutaneously) on the perception of rectal distension were investigated in a double blind, placebo controlled study in healthy volunteers. Octreotide was shown to reduce the perception of rectal distension without affecting motor pathways or local rectal reflexes. This enhanced tolerance to volume distension seems to result from inhibition of sensory afferent pathways as shown by electroencephalographic studies showing diminished evoked spinal and cortical potentials after octreotide. In irritable bowel syndrome patients with rectal urgency, octreotide reduces rectal pressures and perception after rectal distension to near normal values.
Duodenal ulcer healing by separate reduction of postprandial and nocturnal acid secretions have different pathophysiology.
Authors: S K Lam, C L Lai, M Ng, K H Fok, W M Hui
Journal: Gut (1985)

The endoscopic healing rates and factors related to healing of two cimetidine regimens designed to reduce respectively postprandial and nocturnal acid secretions were studied in a randomised trial of cimetidine 200 mg tds with meals, vs 600 mg at bedtime, vs 200 mg tds with meals plus 400 mg at bedtime in 246 patients with duodenal ulcer. The respective healing rates were 62.3%, 63.1%, 77.5% at four weeks and 86.6%, 83.3%, 91.2% at eight weeks. The healing rates at four weeks of both meal time and bedtime regimens were inferior (p less than 0.05) to that of the standard regimen. Analysis of 45 prospectively obtained factors showed that (i) habitual cigarette smoking adversely affected healing with the meal time regimen but not with the others, indicating that its adverse effect disappeared once nocturnal acid secretion was reduced, (ii) habitual use of analgesics impaired and their abstinence favoured healing by both meal time and bedtime regimens but these effects were lost with the standard regimen, suggesting that if analgesics cannot be withdrawn during ulcer treatment, a reduction of both meal time and night time acid secretions should be ensured, (iii) responders with the meal time and bedtime regimens had respectively significantly higher postprandial serum gastrin and higher basal acid output than the corresponding non-responders suggesting that these responders had different pathophysiology, and (iv) high maximal acid output and large ulcers healed less well by any regimen.
Lipoprotein Utilization and Cholesterol Synthesis by the Human Fetal Adrenal Gland*
Authors: BRUCE R. CARR, EVAN R. SIMPSON
Journal: Endocrine Reviews (1981)

Of all the endocrine glands in the human fetus, the adrenal has perhaps aroused the greatest interest. The human fetal adrenal (HFA) glands secrete very large quantities of steroid hormones; indeed it can be computed that the adrenals of some human fetuses near term secrete 100–200 mg steroids daily, most of which is dehydroisoandrosterone sulfate (DS). The rate of steroid secretion by the fetal adrenals may be 5 times that of the adrenals of adults at rest (1, 2). During human pregnancy the rate of estrogen production increases strikingly. In fact, the production rate of estriol in near-term pregnant women is 1000-fold greater than that in nonpregnant women (3). The site of estrogen production is the placenta, and the precursor of these large quantities of estrogen has been shown to be DS that is principally of fetal origin (4). Ryan (5) demonstrated that the aromatase activity of placental tissue was high and Cig-steroids were converted to estrogens rapidly in trophoblasts.
Antiretroviral Therapy in Adults
Authors: Charles C. J. Carpenter, David A. Cooper, Margaret A. Fischl, Jose M. Gatell, Brian G. Gazzard, Scott M. Hammer, Martin S. Hirsch, Donna M. Jacobsen, David A. Katzenstein, Julio S. G. Montaner, Douglas D. Richman, Michael S. Saag, Mauro Schechter, Robert T. Schooley, Melanie A. Thompson, Stefano Vella, Patrick G. Yeni, Paul A. Volberding
Journal: JAMA (2000)

To update recommendations for antiretroviral therapy for adult human immunodeficiency virus type 1 (HIV-1) infection, based on new information and drugs that are available. A 17-member international physician panel with antiretroviral research and HIV patient care experience initially convened by the International AIDS Society-USA in December 1995. Available clinical and basic science data including phase 3 controlled trials; data on clinical, virologic, and immunologic end points; research conference reports; HIV pathogenesis data; and panel expert opinion. Recommendations were limited to therapies available (US Food and Drug Administration approved) in 1999. The panel assesses new research reports and interim results and regularly meets to consider how the new data affect therapy recommendations. Recommendations are updated via full-panel consensus. Guidelines are presented as recommendations if the supporting evidence warrants routine use in the particular situation and as considerations if data are preliminary or incomplete but suggestive. The availability of new antiretroviral drugs has expanded treatment choices. The importance of adherence, emerging long-term complications of therapy, recognition and management of antiretroviral failure, and new monitoring tools are addressed. Optimal care requires individualized management and ongoing attention to relevant scientific and clinical information in the field.
Rupatadine improves quality of life in mastocytosis: a randomized, double‐blind, placebo‐controlled trial
Authors: F. Siebenhaar, A. Förtsch, K. Krause, K. Weller, M. Metz, M. Magerl, P. Martus, M. K. Church, M. Maurer
Journal: Allergy (2013)

Abstract Background Mastocytosis is frequently associated with mast cell‐mediated symptoms which require relieving medication. While second generation antihistamines (sg AH s) are the first line therapeutic strategy to treat mast cell mediator‐related symptoms, controlled clinical trials on how they improve quality of life have not been performed. Methods This randomized, double‐blind, placebo‐controlled, cross‐over trial assessed rupatadine 20 mg daily in the treatment of mastocytosis symptoms in 30 adult patients. Symptoms were assessed by a visual analogue scale ( VAS ) and symptom specific quality of life questionnaire ( I tchy Q o L ). Results The mean I tchy Q o L total score and VAS symptom score were significantly improved in the rupatadine treatment phase compared with placebo. There were also significant reductions from placebo in the severity of itch, wheal and flare, flushing, tachycardia and headache but not gastrointestinal symptoms. Conclusions In this first comprehensive trial of a sg AH in mastocytosis, rupatadine 20 mg daily for 4 weeks significantly controlled symptoms and improved patients' quality of life.
Identification of ferroportin disease in the Indian subcontinent
Authors: D F Wallace
Journal: Gut (2005)

Haemochromatosis is a common inherited disorder of iron metabolism, characterised by excessive iron absorption and deposition in tissues. The majority of cases are associated with mutations in the HFE gene and inherited in an autosomal recessive manner.1 Autosomal dominant forms of haemochromatosis have been reported, mainly associated with mutations in the ferroportin 1 gene.2 This syndrome, termed type 4 haemochromatosis or more recently ferroportin disease,3 is usually characterised by an early increase in serum ferritin with normal transferrin saturation. Iron accumulation is most prominent in Kupffer cells and other macrophages, in addition to hepatocytes. Some patients do not tolerate venesection therapy well and can develop anaemia. Hereditary iron overload disorders appear to be uncommon in Asia. Secondary iron overload due to beta thalassaemia is relatively common in the Indian subcontinent. However, primary iron overload disorders …
BAL findings in a patient with pulmonary alveolar proteinosis successfully treated with GM-CSF
Authors: O D Schoch
Journal: Thorax (2002)

Background: Idiopathic pulmonary alveolar proteinosis (PAP) has recently been recognised as a disease of impaired alveolar macrophage function caused by neutralising anti-granulocyte-macrophage colony-stimulating (anti-GM-CSF) autoantibodies. Subcutaneous recombinant human GM-CSF is a novel treatment for PAP, but its mechanism of action is unclear. Methods: Clinical, functional, and bronchoalveolar lavage (BAL) findings were prospectively evaluated in a patient with PAP treated with daily subcutaneous GM-CSF 8 μg/kg for 12 weeks. Results: Treatment resulted in improvements in dyspnoea, lung function, and peak cycle ergometry performance. In serum and BAL fluid the titre of anti-GM-CSF autoantibodies was raised at baseline and markedly reduced on treatment. At baseline the BAL fluid cellular profile showed a decrease in the absolute number and the percentage of macrophages (50%) and an increase in lymphocytes (45%), predominantly CD4+. This cellular distribution remained unchanged after 6 and 12 weeks of treatment while macrophages became morphologically normal and functionally improved. Extracellular proteinaceous material completely disappeared. Conclusions: Clinically successful treatment of PAP with GM-CSF was associated with a profound reduction in GM-CSF neutralising autoantibodies, improvement in alveolar macrophage morphology and function, but persistent BAL lymphocytosis.
Chronic lymphocytic leukemia preceded by cold agglutinin disease: intraclonal immunoglobulin light-chain diversity inVH4-34 expressing single leukemic B cells
Authors: Sarka Ruzickova, Axel Pruss, Marcus Odendahl, Karsten Wolbart, Gerd-Rüdiger Burmester, Jürgen Scholze, Thomas Dörner, Arne Hansen
Journal: Blood (2002)
Failure of spermatogenesis in mouse lines deficient in the Na+-K+-2Cl– cotransporter
Authors: Amy J. Pace, Eddie Lee, Krairek Athirakul, Thomas M. Coffman, Deborah A. O’Brien, Beverly H. Koller
Journal: Journal of Clinical Investigation (2000)

The Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) carries 1 molecule of Na(+) and K(+) along with 2 molecules of Cl(-) across the cell membrane. It is expressed in a broad spectrum of tissues and has been implicated in cell volume regulation and in ion transport by secretory epithelial tissue. However, the specific contribution of NKCC1 to the physiology of the various organ systems is largely undefined. We have generated mouse lines carrying either of 2 mutant alleles of the Slc12a2 gene, which encodes this cotransporter: a null allele and a mutation that results in deletion of 72 amino acids of the cytoplasmic domain. Both NKCC1-deficient mouse lines show behavioral abnormalities characteristic of mice with inner ear defects. Male NKCC1-deficient mice are infertile because of defective spermatogenesis, as shown by the absence of spermatozoa in histological sections of their epididymides and the small number of spermatids in their testes. Consistent with this observation, we show that Slc12a2 is expressed in Sertoli cells, pachytene spermatocytes, and round spermatids isolated from wild-type animals. Our results indicate a critical role for NKCC1-mediated ion transport in spermatogenesis and suggest that the cytoplasmic domain of NKCC1 is essential in the normal functioning of this protein.
Risk Assessment for and Strategies To Reduce Perioperative Pulmonary Complications for Patients Undergoing Noncardiothoracic Surgery: A Guideline from the American College of Physicians
Authors: Amir Qaseem, Vincenza Snow, Nick Fitterman, E. Rodney Hornbake, Valerie A. Lawrence, Gerald W. Smetana, Kevin Weiss, Douglas K. Owens
Journal: Annals of Internal Medicine (2006)

Postoperative pulmonary complications play an important role in the risk for patients undergoing noncardiothoracic surgery. Postoperative pulmonary complications are as prevalent as cardiac complications and contribute similarly to morbidity, mortality, and length of stay. Pulmonary complications may even be more likely than cardiac complications to predict long-term mortality after surgery. The purpose of this guideline is to provide guidance to clinicians on clinical and laboratory predictors of perioperative pulmonary risk before noncardiothoracic surgery. It also evaluates strategies to reduce the perioperative pulmonary risk and focuses on atelectasis, pneumonia, and respiratory failure. The target audience for this guideline is general internists or other clinicians involved in perioperative management of surgical patients. The target patient population is all adult persons undergoing noncardiothoracic surgery. *This paper, written by Amir Qaseem, MD, PhD, MHA; Vincenza Snow, MD; Nick Fitterman, MD; E. Rodney Hornbake, MD; Valerie A. Lawrence, MD; Gerald W. Smetana, MD; Kevin Weiss, MD, MPH; and Douglas K. Owens, MD, MS, was developed for the Clinical Efficacy Assessment Subcommittee of the American College of Physicians (ACP): Douglas K. Owens, MD, MS (Chair); Mark Aronson, MD; Patricia Barry, MD, MPH; Donald E. Casey Jr., MD, MPH, MBA; J. Thomas Cross Jr., MD, MPH; Nick Fitterman, MD; E. Rodney Hornbake, MD; Katherine D. Sherif, MD; and Kevin B. Weiss, MD, MPH (Immediate Past Chair). Approved by the ACP Board of Regents on 21 January 2006.
Intraventricular administration of amphotericin B. Use of subcutaneous reservoir in four patients with mycotic meningitis
Authors: P. Witorsch
Journal: JAMA (1965)

In four cases of fungal meningitis, three due to Cryptococcus neoformans and one due to Coccidioides immitis, repeated doses of amphotericin B were given by needle injection into a subcutaneously placed, silicone-rubber reservoir attached to a catheter which passed through a burr-hole and the brain substance into a lateral ventricle (Ommaya reservoir). One patient with cryptococcal meningitis died of overwhelming infection after receiving amphotericin B, first intravenously and later by 15 injections into the reservoir. Two patients with cryptococcal and one with coccidioidal meningitis improved after amphotericin B treatment which included 21 to 74 injections into the reservoir.
Drug Abuse,.Sexual Attitudes, Political Radicalization, and Religious Practices of College Seniors and Public School Teachers
Authors: SAMUEL JANUS, BARBARA BESS
Journal: American Journal of Psychiatry (1973)

The authors surveyed a group of 745 public school teachers and compared them with college seniors in regard to a number of topics of concern to society today. They found that the use of drugs was more widespread among teachers than expected and that there was a close similarity between college seniors and teachers under age 30 in all areas examined. The authors point out the need for more studies on the attitudes and practices of teachers and on the effects of these factors on teaching programs.
Effect of a weightlifting belt on spinal shrinkage.
Authors: N D Bourne, T Reilly
Journal: British Journal of Sports Medicine (1991)

Spinal loading during weightlifting results in a loss of stature which has been attributed to a decrease in height of the intervertebral discs--so-called 'spinal shrinkage'. Belts are often used during the lifting of heavy weights, purportedly to support, stabilize and thereby attenuate the load on the spine. The purpose of this study was to examine the effects of a standard weightlifting belt in attenuating spinal shrinkage. Eight male subjects with a mean age of 24.8 years performed two sequences of circuit weight-training, one without a belt and on a separate occasion with a belt. The circuit training regimen consisted of six common weight-training exercises. These were performed in three sets of ten with a change of exercise after each set of ten repetitions. A stadiometer sensitive to within 0.01 mm was used to record alterations in stature. Measurements of stature were taken before and after completion of the circuit. The absolute visual analogue scale (AVAS) was used to measure the discomfort and pain intensity resulting from each of the two conditions. The circuit weight-training caused stature losses of 3.59mm without the belt and 2.87 mm with the belt (P greater than 0.05). The subjects complained of significantly less discomfort when the belt was worn (P less than 0.05). The degree of shrinkage was significantly correlated (r = 0.752, P less than 0.05) with perceived discomfort but only when the belt was not worn. These results suggest the potential benefits of wearing a weightlifting belt and support the hypothesis that the belt can help in stabilizing the trunk.
Abrupt withdrawal of beta-blockade therapy in patients with myocardial infarction: effects on infarct size, left ventricular function, and hospital course.
Authors: C H Croft, R E Rude, N Gustafson, P H Stone, W K Poole, R Roberts, H W Strauss, D S Raabe, L J Thomas, A S Jaffe
Journal: Circulation (1986)

The effects of abrupt withdrawal or continuation of beta-blockade therapy during acute myocardial infarction were evaluated in 326 patients participating in the Multicenter Investigation of the Limitation of Infarct Size (MILIS). Thirty-nine patients previously receiving a beta-blocker and randomly selected for withdrawal of beta-blockers and placebo treatment during infarction (group 1) were compared with 272 patients previously untreated with beta-blockers who were also randomly assigned to placebo therapy (group 2). There were no significant differences between the two groups in MB creatine kinase isoenzyme (15.8 +/- 10.9 vs 18.2 +/- 14.4 g-eq/m2, respectively) estimates of infarct size, radionuclide-determined left ventricular ejection fractions within 18 hr of infarction (0.44 +/- 0.15 vs 0.47 +/- 0.16) or 10 days later (0.42 +/- 0.14 vs 0.47 +/- 0.16), creatine kinase-determined incidence of infarct extension (13% vs 6%), congestive heart failure (43% vs 37%), nonfatal ventricular fibrillation (5% vs 7%), or in-hospital mortality (13% vs 9%). Patients in group 1 had more recurrent ischemic chest pain (p = .002) within the first 24 hr after infarction, but not thereafter. However, this did not appear to be related to a rebound increase in systolic blood pressure, heart rate, or double product. In a separate analysis, 20 propranolol-eligible group 1 patients randomly selected for withdrawal of beta-blockade (group 3) were compared with 15 patients randomly selected for continuation of prior beta-blockade therapy (group 4). This comparison yielded similar results. These data indicate that the beta-blockade withdrawal phenomenon is not a major clinical problem in patients with acute myocardial infarction. beta-Blockade therapy can be discontinued abruptly during acute myocardial infarction if clinically indicated.