tbuckley/cabot-search huggingface dataset:
The Efficacy of Acarbose in the Treatment of Patients with Non–Insulin-Dependent Diabetes Mellitus: A Multicenter, Controlled Clinical Trial
Authors: Jean-Louis Chiasson
Journal: Annals of Internal Medicine (1994)

Objective: To evaluate the long-term efficacy of acarbose, an α-glucosidase inhibitor, in improving glycemic control in patients with non–insulin-dependent diabetes mellitus. Design: A 1-year, multicenter, randomized, double-blind, placebo-controlled study. Setting: Seven university-affiliated, community-based, tertiary care diabetes clinics. Patients: 354 patients with non–insulin-dependent diabetes mellitus were recruited; 77 were being treated with diet alone, 83 with diet and metformin, 103 with diet and sulfonylurea, and 91 with diet and insulin. Patients in each treatment group were randomly assigned to either acarbose or placebo for 1 year. Eighty-seven percent of patients receiving acarbose and 92% of those receiving placebo were included in the efficacy analysis (n = 316). Measurements: At baseline and at 3-month intervals, levels of hemoglobin A1c (HbA1c), fasting and postprandial plasma glucose, fasting and postprandial serum C-peptide, and fasting serum lipids were measured. Results: Compared with placebo, acarbose treatment caused a significant decrease in the mean postprandial plasma glucose peak (90 minutes) in all four groups (19.0 ±0.4 mmol/L to 15.5 ±0.4 mmol/L; P < 0.001). Analysis of the postprandial plasma glucose incremental area under the curve showed that the change from baseline to the end of the treatment period differed for placebo and acarbose recipients by 4.73 mmol x h/L in the diet alone group (P < 0.001), 2.06 mmol x h/L in the metformin group (P = 0.01), 2.65 mmol x h/L in the sulfonylurea group (P < 0.001), and 3.13 mmol x h/L in the insulin group (P = 0.001). Corresponding decreases in HbA1c levels occurred; these were 0.9% in the diet alone group (P = 0.005), 0.8% in the metformin group (P = 0.011), 0.9% in the sulfonylurea group (P = 0.002), and 0.4% in the insulin group (P = 0.077). Acarbose did not significantly affect mean serum C-peptide or mean serum lipid levels. Conclusions: Acarbose improved long-term glycemic control in patients with non–insulin-dependent diabetes mellitus regardless of concomitant antidiabetic medication. *For author affiliations, current author addresses, and a listing of collaborators, see end of text.
Hypotension (Shock) in Dogs Produced by <i>Escherichia coli</i> Endotoxin
Authors: LLOYD D. MACLEAN, MAX H. WEIL
Journal: Circulation Research (1956)

Intravenous injection of endotoxin from Escherichia coli in dogs is characterized by an immediate and precipitous decline in blood pressure with a simultaneous elevation of portal vein pressure. This reaction is abolished by hepatectomy or exclusion of the liver from the circulation and is believed due to trapping of blood in the liver. The reactions observed suggest that the profound biological effects of endotoxin are at least partially the result of anaphylaxis. The lethal effects of endotoxin are enhanced by removal of the liver.
Abstract 5563: Targeting the PH domain of TIAM1 to inhibit prostate cancer metastasis.
Authors: Emmanuelle J. Meuillet, Sylvestor A. Moses, Jana Jandova, Eugene A. Mash, Shuxing Zhang
Journal: Cancer Research (2013)

Abstract TIAM1 (T-lymphoma invasion and metastasis-inducing protein-1) is a highly conserved guanine nucleotide exchange factor and contains an Dbl Homology (DH)/C-terminal Pleckstrin Homology (PH) domain. The crystal structure of DH-PH of TIAM1 in complex with Rac-1 has been reported. TIAM1 has been found to be over-expressed cancers such as breast, colon and prostate cancers. An increase in TIAM1 expression has been shown to be associated with increased metastatic potential of breast cancer cell lines and is also correlated with poor prognosis of patients with prostate cancer. TIAM1 is thus a novel PH domain-containing drug target directly related to cancer progression, metastasis and patient survival. We have identified and characterized novel small molecule inhibitors targeting the phosphoinositide lipid binding PH domain of TIAM1 in order to selectively inhibit cell migration, invasion and survival. An In Silico screen of our internal and Maybridge library using the crystal structure of TIAM1 has identified 11 compounds that bind to the PH domain. In vitro assays revealed that compounds TPH-3 and TPH-15 significantly reduced the amount of active Rac1 in PC-3 prostate cancer cells (EC50 of 2.73±0.13 and 2.38±0.98 μM) by binding to PH-TIAM1 with high affinity (KD in the micromolar range) using surface plasmon resonance (SPR) spectrometry. Both compounds displaced PtdIns-3,4,5-P3 in a SPR competitive binding assay. TPH-3 and TPH-15 inhibited cell proliferation with EC50 of 19.8±3.2 and 28.7±1.7 μM in prostate cancer cells LnCaP and EC50 of 18.6±1.8 and 33.3±6.7 μM in PC-3. Wound healing assays and lamellipodia formation were both inhibited by the compounds. TPH-15 inhibited ≈70% of PC-3 invasion using a matrigel invasion assay. Finally, TPH-15 exhibits anti-tumor properties in a PC-3 mouse xenograft study (%T/C≈38.8) with good pharmacokinetic properties (T1/2≈5 hours). Cardio-injection of prostate PC-3 cells in SCID mice was used to test the effects of TPH-15 in the prevention of bone metastasis. Mice were treated with 50mg/kg ip of TPH-15 once a day for 5 days. TPH-15-treated mice developed significantly less pelvic bone lesions than the untreated group and TPH-15 treated mice lived longer, on average, than the untreated group. Overall, we have identified novel compounds which exhibit the ability to reduce prostate cancer bone metastasis by binding to the PH domain of TIAM1, an important GEF in the process of metastasis. Citation Format: Emmanuelle J. Meuillet, Sylvestor A. Moses, Jana Jandova, Eugene A. Mash, Shuxing Zhang. Targeting the PH domain of TIAM1 to inhibit prostate cancer metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5563. doi:10.1158/1538-7445.AM2013-5563
PREDICTION OF LONG-TERM OUTCOMES IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION UNDERGOING PERCUTANEOUS CORONARY INTERVENTION BY MEHRAN'S RISK SCORE OF CONTRAST-INDUCED NEPHROPATHY
Authors: Jin Wi, Young-Guk Ko, Jung-Sun Kim, Byeong-Keuk Kim, Donghoon Choi, Jong-Won Ha, Myeong-Ki Hong, Won-Heum Shim, Seung-Yun Cho, Yangsoo Jang
Journal: Journal of the American College of Cardiology (2011)
A novel <i>ABCA12</i> mutation 3270delT causes harlequin ichthyosis
Authors: M. Akiyama, K. Sakai, G. Wolff, I. Hausser, J.R. McMillan, D. Sawamura, H. Shimizu
Journal: British Journal of Dermatology (2006)

Conflicts of interest: None declared. Harlequin ichthyosis (HI) is a severe and often fatal congenital ichthyosis with an autosomal recessive inheritance pattern.1 The clinical features include thick, plate‐like scales with ectropion, eclabium, and flattened ears. The skin development is altered in utero.2,ABCA12 mutations have been reported to underlie HI3, 4 and it was clarified that HI is caused by severe functional defects in the keratinocyte lipid transporter ABCA12.3 The pathomechanism of HI lies in the defective function of the lipid transporter ABCA12 which causes abnormal lipid lamellar granule transport in the keratinocytes, and results in a malformation of the epidermal lipid barrier.3 Until the 1980s, newborns affected with HI rarely survived beyond the neonatal period. However, recently, HI babies have often had a better prognosis.5–7 It is still unclear whether the good prognosis in HI is due to some remnant ABCA12 protein transporter function in the patients or not. Here, we report a girl with HI with a novel homozygous ABCA12 deletion mutation leading to a complete loss of function of ABCA12, who has survived despite having severe ichthyosis showing the clinical features of nonbullous congenital ichthyosiform erythroderma (NBCIE).
The Interaction Mode of Premalignant Schwann and Immune Effector Cells during Chemically Induced Carcinogenesis in the Rat Peripheral Nervous System Is Strongly Influenced by Genetic Background
Authors: Katharina M. Gering, Judith A.M. Marx, Klaus Lennartz, Christine Fischer, Manfred F. Rajewsky, Andrea Kindler-Röhrborn
Journal: Cancer Research (2006)

Abstract Contrary to rats of the highly sensitive inbred strain BDIX, BDIV rats are resistant to the induction of malignant schwannomas by N-ethyl-N-nitrosourea, arising predominantly in the trigeminal nerves. A point mutation of the neu/erbB-2 gene diagnostic of N-ethyl-N-nitrosourea–induced rat schwannomas is an early marker of Schwann precursor cells at high risk of subsequent malignant transformation. Neu-mutant cells initially arise at a similar frequency in sensitive and resistant animals. However, these cells disappear from the trigeminal nerves of resistant rats while giving rise to highly malignant schwannomas in susceptible animals. The resistance of BDIV rats obviously includes mechanisms to recognize and eliminate premalignant cells. The involvement of a cellular immune response was investigated in trigeminal nerves of both strains at different times after neonatal carcinogen exposure. An inflammatory reaction involving sequentially CD4+ macrophages and T helper cells, CD8+ cytotoxic T cells, and ED1+ and ED2+ macrophages was detected as a consequence of N-ethyl-N-nitrosourea treatment as early as postnatal day 40, briefly after the emergence of premalignant neu-mutant Schwann cells. It persisted throughout the observation period (40-250 days). However, there were no gross differences in immune cell counts between tumor-susceptible and tumor-resistant rats, except for a moderate increase of ED2+ macrophages in N-ethyl-N-nitrosourea–treated BDIX rats only. Differential interactions of immune effector cells with premalignant Schwann cells may thus be involved in genetically determined tumor susceptibility or resistance, which could include functional differences of immune effector cells and/or a differential capability of premalignant Schwann cells to escape or counteract the cellular immune response. (Cancer Res 2006; 66(9): 4708-14)
Health Economic Changes as a Result of Implementation of Targeted Therapy for Metastatic Renal Cell Carcinoma: National Results from DARENCA Study 2
Authors: Anne V. Soerensen, Frede Donskov, Jakob Kjellberg, Rikke Ibsen, Gregers G. Hermann, Niels V. Jensen, Kirsten Fode, Poul F. Geertsen
Journal: European Urology (2014)

Limited data exist on the economic consequences of implementing targeted therapy (TT) for metastatic renal cell carcinoma (RCC) in a real-world setting. To analyze health care and productivity costs for TT implementation in a national cohort of patients. Costs were measured per patient per year during a 2-yr follow-up during 2002–2005 (immunotherapy only) and 2006–2009 (TT implementation). All Danish patients with a diagnosis code for RCC and a procedure code for TT or immunotherapy were linked to the Danish National Patient Registry (contains information on all contacts with primary and secondary health sector). Health care and productivity costs were retrieved from the Danish case-mix system and Coherent Social Statistics, respectively. Drug costs were calculated separately from procedure codes and retail prices. Generalized linear models were used to analyze costs adjusted for age, gender, and civil status. A total of 439 patients were included for 2006–2009 and 192 for 2002–2005. Comparison of the health care cost per patient per year between 2006–2009 and 2002–2005 revealed lower inpatient costs (€11 899 vs €19 944, adjusted relative risk [RR] 0.64), higher outpatient costs (€14 308 vs €6209, RR 2.39), lower radiotherapy costs (€194 vs €633, RR 0.31), higher radiology costs (€676 vs €191, RR 3.73), and higher separately calculated drug costs (€12 040 vs €3103, RR 3.82, all p < 0.001) for the former. Total health care costs per patient per year did not significantly differ (€27 676 vs €27 856, RR 1.05, p = 0.5) between the two periods. Income from employment did not significantly differ between 2006–2009 and 2002–2005 (RR 1.11, p = 0.11) and costs associated with loss of productivity were €7852 and €8265, respectively. A different pattern of health care costs were observed but total health care costs per patient per year did not significantly differ after implementation of TT for patients with mRCC. In this nationwide study, we found changes in the pattern of health care costs for patients with metastatic kidney cancer after implementation of targeted therapy compared to an immunotherapy control period; however, total health care costs and income from employment were without significant changes.
Mortality in two radom samples of women aged 55-64 followed up for 20 years.
Authors: A L Cochrane, F Moore, I A Baker, T J Haley
Journal: BMJ (1980)

Two random samples of women aged 55-64 living in the Vale of Glamorgan and the Rhondda Fach were followed up for 20 years. In each sample heights, weights, serum cholesterol concentrations, and specific causes of death were noted and the Quetelet index (weight/height2) calculated. The two samples were combined for analysis of total mortality. In the combined sample there was a strong positive association between Quetlet index and both total mortality and mortality from ischaemic heart disease. Multiple logistic regression analysis showed that both of these associations were significant, as was the strong positive association between Quetelet index and mortailty from ischaemic heart disease in the samples considered separately. There was no significant association between cholesterol concentration and mortality from ischaemic heart disease in each sample. There was a small negative association between cholesterol concentration and both total mortaility in the combined sample and ischaemic heart disease in the Rhondda Fach sample. These results suggest that the Quetelet index is important for prognosis, whereas the serum cholesterol concentration is not.
Group Therapy for Asthma Patients: A Concept for the Psychosomatic Treatment of Patients in a Medical Clinic – A Controlled Study
Authors: H.-C. Deter, G. Allert
Journal: Psychotherapy and Psychosomatics (1983)

Asthma patients pose special problems as far as the medical supervision, danger of symptoms and the course of the disease are concerned. Some 90 asthma patients were registered for the treatment in the Heidelberg Medical Clinic. 31 patients who were interested in taking part were randomized into 3 groups: two treatment groups consisted of the exchange of information, discussion sessions on the illness as well as 'autogenic training' or 'functional relaxation'. The third group was the control group. Before and after treatment the patients were submitted to a thorough examination both of lungs and other internal organs as well as from the psychodiagnostical point of view. The average age of the patients was 43.5 years and the average duration of illness 16.8 years. Nevertheless, the treatment group's sympathomimetics use was significantly reduced by 1 year of treatment (p < 0.05); the use of steroids decreased as well. The number of visits of the general practitioner also decreased. These results support the conclusion that psychosomatic group therapy can make an important contribution to the treatment of asthma patients. Body therapy practised in 'autogenic training' and 'functional relaxation' seems to be another important healing factor for the treatment in addition to the discussion sessions and the exchange of information.
THE TREATMENT OF PULMONARY TUBERCULOSIS.
Authors: GEORGE WILLIAM NORRIS
Journal: JAMA (1905)

It would be entirely impossible in the short space allotted to cover comprehensively the entire treatment of a disease on which volumes have been written. I shall therefore not even endeavor to mention a large number of means and measures of undoubted utility which in the hands of various practitioners have proved of unquestionable benefit; but shall confine my remarks to a single method which has successfully stood the test of trial. I shall try to point out a series of simple and practical procedures such as are available in any climate or locality, attempting at the same time to lay emphasis on certain simple details, the oversight of which has often proved the stumbling block of the general practitioner, and I shall of necessity be forced to pass perfunctorily over certain subjects, in order to be sufficiently brief.  The only treatment which has satisfactorily stood the test of time and of investigation, is that which with various modifications, is now in vogue in the various sanatoria throughout the world.
Comparison of radio-opaque pellets and chromium sesquioxide as inert markers in studies requiring accurate faecal collections.
Authors: W J Branch, J H Cummings
Journal: Gut (1978)

Radio-opaque pellets (ROP) similar to those currently used to measure gastrointestinal transit time have been compared with chromium sesquioxide to assess their suitability for use as inert markers in the gut. Five healthy subjects took both markers with every meal for two separate three week periods while taking metabolically controlled diets. Overall recovery of both markers was satisfactory; ROP 99.7 +/- 0.3% (SD) and chromium 97.8 +/- 1.6% (SD). A comparison of the amount for each marker recovered in 69 separate faecal collection periods of various lengths showed close agreement (R = 0.99) and the tail-off in marker excretion after cessation of ROP and chromium intake was similar, although slightly more prolonged for chromium. The amount of marker retained in the gut was 13.5% greater for chromium at the end of the three week study periods. Both markers proved satisfactory for correcting variations in faecal calcium output. The ROP, however, offer clear advantages over chromium in that they are considerably easier and quicker to measure, the method of measurement using x-rays does not alter the stools and faecal handling is minimised. The precision of ROP measurement is greater and, because of the variety of ROP available, they offer more flexibility for metabolic studies. In addition, stool by stool analysis is possible enabling simultaneous measurement of mean transit time to be made in experimental subjects.
Detection of latent pernicious anaemia in iron-deficiency anaemia.
Authors: J. H. Dagg, A. Goldberg, W. N. Gibbs, J. R. Anderson
Journal: BMJ (1966)

Serum Vitamin B12This was reduced to less than 140 4tqug./ml. in 11 patients and to less than 100 ju/g./ml. in eight of these.Among the 22 patients there are thus three groups.
Junior doctors' confidence in their skill in minor surgery.
Authors: S Dowling
Journal: BMJ (1991)

services authority because she believed that I should provide the "morning after pill" under my agreement to provide contraceptive services to her.It was only at the informal complaints procedure that the subject was clarified, and no further action was taken.I was advised, however, that I should give patients specific instructions on where to obtain a second opinion and therefore the drugs they demand, the analogy being that I should instruct someone with an injury how
Anticytokine Strategies in the Treatment of the Systemic Inflammatory Response Syndrome
Authors: C A Dinarello, J A Gelfand, S M Wolff
Journal: JAMA (1993)

The systemic inflammatory response syndrome (SIRS) is an acute illness characterized by generalized activation of the endothelium. The most severe form of the syndrome is found in patients with shock due to gram-negative sepsis. We examined both animal and limited human data for the contribution of cytokines to this syndrome. Cytokines are endogenously produced proteins of small molecular weight and multiple biological effects. The cytokines interleukin 1 (IL-1) and tumor necrosis factor (TNF), as well as interferon-γ and interleukin 8, are discussed. Laboratory investigations suggest that these cytokines play a critical role in SIRS by promoting the biochemical and clinical characteristics of SIRS. The biochemical changes induced by TNF and IL-1 include increased synthesis of nitric oxide, prostaglandins, platelet-activating factor, and endothelial cell adhesion molecules. Specific blockade of TNF using neutralizing antibodies or soluble receptors to TNF in animal models of SIRS reduces mortality and severity of disease. Similar results have been observed blocking IL-1 using soluble IL-1 receptors or IL-1 receptor antagonists. Preliminary clinical studies suggest that blockade may be useful in treating human SIRS. The various strategies for blocking IL-1 and TNF are presented; in addition, their mechanism(s) of action and safety in humans are discussed. We conclude that based on animal studies and preliminary clinical trials, strategies to block IL-1 or TNF may benefit patients with the syndrome, although thorough clinical trials have not been completed. (<i>JAMA</i>. 1993;269:1829-1835)
RADIUM IN THE TREATMENT OF MENOPAUSAL HEMORRHAGE WITHOUT DEMONSTRABLE LESION
Authors: WILLIAM NEILL
Journal: JAMA (1927)

In women, the end of the reproductive function occurs at a more or less definite period called the menopause or climacteric, which bgeins at about 40 but varies in individuals and races. Local and general signs normally characterize this period, the local being confined to manifest retrogressive changes in the reproductive organs and the glands of internal secretion, while functional disturbances, affecting the general organism, are flushings with alternating heat and cold, increased nervousness, indigestion, and a variety of psychic disturbances, the vasomotor derangements being the most important. As a rule, the menopausal period runs its normal course from one to several years without excessive hemorrhage or any exaggerated symptoms. Most women pass through this epoch and its irregularities, needing as treatment only rest during the continuance of the bleeding. The intervals of the bleeding tend to become longer and the menstruation less profuse. Excluding the pathologic lesions that will
Tardive Dyskinesia and Informed Consent
Authors: Alan M. Weinberg
Journal: JAMA (1986)

<h3>To the Editor.—</h3> Dr Glass and Mr Arkin<sup>1</sup>provided important guidelines in their response to Dr Schnee's question regarding tardive dyskinesia and informed consent. An issue that was not addressed by any of the individuals is the inappropriateness of having a psychiatric patient discharged from a hospital, whether this be a private or state mental health facility, if he or she has never been informed of the risks of tardive dyskinesia. Indeed, the need to educate patients regarding the longterm risk of tardive dyskinesia is one that is certainly a necessity and in most instances is best performed by the psychiatrist initially treating the patient. As consultant to an adolescent day program and director of an adolescent inpatient unit, I insist that all patients be fully educated regarding the side effects of their medications. Given the age of these patients, the families are always included either separately or jointly in