tbuckley/cabot-search huggingface dataset:
Efficacy and safety of oral cyclosporin A (CyA; SandimmunR) for long-term treatment of chronic severe plaque psoriasis
Authors: C. LABURTE, R. GROSSMAN, J. ABI-RACHED, K.H. ABEYWICKRAMA, L. DUBERTRET
Journal: British Journal of Dermatology (1994)

Summary The value of oral cyclosporin A (CyA: Sandimmun®) in the treatment of chronic severe plaque psoriasis has already been established. Many controlled studies have addressed the issues of efficacy and safety, mostly in studies of several months duration. Patients treated for up to several years have been reported, but never in multicentre controlled studies. Guidelines have established the maximum dose permissible to reduce the risk of side-effects. However, the efficacy and safety of therapy of longer duration remain under investigation. The results of a multicentre prospective randomized clinical study (251 patients) to evaluate the efficacy, safety and tolerability of two dose levels of CyA (2·5 or 5 mg/kg/day) for inducing remission, and for use in long-term maintenance therapy for up to 21 months, are presented. An assessment of relapse as the dose was tapered (during the last 3 months of treatment), and the reversibility of CyA-induced side-effects, is also presented (follow-up phase of 3 months). Efficacy was evaluated by means of the psoriasis area and severity index (PASI). Safety was assessed by using the results of vital signs, physical examination, laboratory tests and physician and patient evaluation of adverse events. During the induction of remission phase of therapy, a total of 184 patients (73%) were treated successfully. The percentage of patients classified as successes at the endpoint was significantly higher in the group on 5·0 mg/kg/day (92%) than in that on 2·5 mg/kg/day (52%; P≤0·001). A total of 215 (86%) patients reported at least one adverse event during the study. In 136 patients (54%) the reported adverse event was judged by the investigator as being related to CyA. Nineteen patients (8%) reported events that were judged as severe, and related to treatment with CyA. A total of 45 patients (18%) discontinued treatment due to adverse events. Hypertension was one of the reasons, or the reason, for discontinuation in 16 patients (6%). The occurrence of hypertension appeared unrelated to CyA dose. One hundred and sixteen patients (46%) experienced a maximum increase in serum creatinine >30% above baseline values on at least one occasion. This increase in serum creatinine was often transient, and was one of the reasons, or the reason, for discontinuation in 24 patients (10%). An increase in serum creatinine >30% above baseline was dose-related. The results of this study show that 5·0 mg/kg/day of CyA is significantly more effective than 2·5 mg/kg/day in the treatment of chronic plaque psoriasis. Depending on the dose group, some patients relapsed as CyA was tapered, but without rebound. Hypertension and an increase in serum creatinine were the two most frequently encountered complications of treatment.
Animal and Clinical Pharmacologic Techniques in Drug Evaluation
Authors: Eleanor Berman
Journal: JAMA (1964)

Much so-called "clinical pharmacology" is being practiced by physicians inadequately prepared for the task. The general practitioner agreeing to undertake "some drug trials on his patients" is usually in a rather poor position to assess the claims presented by pharmaceutical firms. His concept of what constitutes an acceptable experimental design in drug evaluation in either animal or human is hazy at best. The present volume resulted from a training program in clinical pharmacology organized at Hahnemann Medical College and Hospital. Basic objectives and general principles of clinical pharmacology are defined. Among the general topics presented are variability in drug response; drug screening and the evaluation of new compounds in animals; kinetics of absorption, distribution, excretion, and metabolism of drugs; statistical problems in the planning and performance of clinical trials; and general principles in experimental design in drug evaluation in man. Legal considerations in testing new drugs in humans are also
Demographics and correlates of five-year change in echocardiographic left ventricular mass in young black and white adult men and women: the Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Julius M Gardin, Debra Brunner, Pamela J Schreiner, Xiaoyuan Xie, Cheryl L Reid, Karen Ruth, Diane E Bild, Samuel S Gidding
Journal: Journal of the American College of Cardiology (2002)
Bioluminescent Monitoring of Islet Graft Survival after Transplantation
Authors: Yuxin Lu, Hoa Dang, Blake Middleton, Zesong Zhang, Lorraine Washburn, Martha Campbell-Thompson, Mark A Atkinson, Sanjiv Sam Gambhir, Jide Tian, Daniel L Kaufman
Journal: Molecular Therapy (2004)

Islet transplantation offers a potential therapy to restore glucose homeostasis in type 1 diabetes patients. A method to image transplanted islets noninvasively and repeatedly would greatly assist studies of islet transplantation. Using recombinant adenovirus, we show that isolated rodent and human islets can be genetically engineered to express luciferase and then imaged after implantation into NOD-scid mice using a cooled charge-coupled device. The magnitude of the signal was dependent on the islet dose. Adenovirus-directed luciferase expression, however, rapidly attenuated. We next tested lentivirus vectors that should direct the long-term expression of reporter genes in transduced islets. Transplanted lentivirus-transduced islets restored euglycemia long term in streptozotocin-treated NOD-scid mice. The signal from implanted lentivirus-transduced islets was related directly to the implanted islet mass, and the signal did not attenuate over the observation period. Viral transduction, luciferase expression, and repeated imaging had no apparent long-term deleterious effects on islet function after implantation. These data demonstrate that the introduction of reporter genes into an isolated tissue allows the long-term monitoring of its survival following implantation. Such imaging technologies may allow earlier detection of graft rejection and the adjustment of therapies to prolong graft survival posttransplantation.
A genome-wide association study identifies two new risk loci for Graves' disease
Authors: Xun Chu, Chun-Ming Pan, Shuang-Xia Zhao, Jun Liang, Guan-Qi Gao, Xiao-Mei Zhang, Guo-Yue Yuan, Chang-Gui Li, Li-Qiong Xue, Min Shen, Wei Liu, Fang Xie, Shao-Ying Yang, Hai-Feng Wang, Jing-Yi Shi, Wei-Wei Sun, Wen-Hua Du, Chun-Lin Zuo, Jin-Xiu Shi, Bing-Li Liu, Cui-Cui Guo, Ming Zhan, Zhao-Hui Gu, Xiao-Na Zhang, Fei Sun, Zhi-Quan Wang, Zhi-Yi Song, Cai-Yan Zou, Wei-Hua Sun, Ting Guo, Huang-Ming Cao, Jun-Hua Ma, Bing Han, Ping Li, He Jiang, Qiu-Hua Huang, Liming Liang, Li-Bin Liu, Gang Chen, Qing Su, Yong-De Peng, Jia-Jun Zhao, Guang Ning, Zhu Chen, Jia-Lun Chen, Sai-Juan Chen, Wei Huang, Huai-Dong Song
Journal: Nature Genetics (2011)
Patients are denied operations to cut costs, surgeons say
Authors: J. Wise
Journal: BMJ (2010)

Surgeons in England have decried “stealth cuts” that restrict access to a number of operations so as to save money.

ENT-UK, the specialty association for ear, nose, and throat surgeons, says that it has received reports from members that primary care trusts across the country have drawn up and distributed lists of hospital services that will no longer be funded, regardless of clinical opinion. It says that this has been done without public consultation or debate and without discussion with the relevant hospital specialists.

The association says that operations at risk include gallstone removal, tonsillectomy, operations for chronic glue ear, inguinal hernia operations, and orthopaedic procedures such as operations for back pain. ENT-UK says there is clear evidence and established guidance from the National Institute for Health and Clinical Excellence on who benefits from …
Endocrine Function after Spontaneous Infarction of the Human Pituitary: Report, Review, and Reappraisal*
Authors: JOHANNES D. VELDHUIS, JAMES M. HAMMOND
Journal: Endocrine Reviews (1980)

NO COMPREHENSIVE review has been available to define preservation or loss of pituitary function after acute hemorrhagic infarction of the hypophysis in man. Published experience is limited to individual reports emphasizing unusual features of pituitary apoplexy, such as "autohypophysectomy" in acromegaly (1–4), atypical presentations such as pituitary "pseudotumor" (5), or the occurrence of "hypothalamic hypopituitarism" (6–8). In the following work, we have collated data from the gynecological, neurological, neurosurgical, radiological, and internal medicine literature, to permit systematic examination of residual endocrine function after pituitary apoplexy. These data are supported by detailed hormonal evaluations of four additional patients with pathologically proven pituitary apoplexy. Collectively, our observations document a high prevalence of multiple adenohypophyseal deficits, and illustrate the diversity of etiological settings in which pituitary apoplexy has been described. Our studies with the administration of hypothalamic releasing factors have prompted critical reappraisal of the precise mechanisms causing hypopituitarism after pituitary infarction.
Clinical Application of Thyrotropin-Releasing Hormone
Authors: Jerome M. Hershman
Journal: New England Journal of Medicine (1974)

THYROTROPIN-releasing hormone (TRH) was the first of the hypothalamic regulatory factors to be purified. In 1969 its structure was shown to be the tripeptide, pyroglutamyl-histidyl-prolinamide,1 , 2 and it was synthesized by several groups.3 , 4 This molecule has been identified by immunoassay in the hypothalamus of many species. Its principal action in mammals is the release of thyroid-stimulating hormone (thyrotropin or TSH) from specific cells, the thyrotropes of the anterior pituitary gland. Synthesis of TRH occurs in several nuclei of the hypothalamus. TRH is secreted into the portal venous system traversing from hypothalamus directly to the pituitary gland. It interacts with specific receptors . . .
Estrogen Therapy in Men with Myocardial Infarction
Authors: Jessie Marmorston
Journal: JAMA (1960)

Long-term therapy with estrogens, in well-tolerated doses, was studied in men with myocardial infarction. This report indicates the feasibility of such studies. Of 109 men treated with estrogen for an aggregate of over 900 months, only 15 left the clinic for reasons other than death. Of these 15, 8 left before the appearance of any clinical manifestation of the estrogen therapy. The dosage schedule called for small initial doses and gradual increases until minor evidences were observed. Breast tenderness was the first finding in all but one patient. Long-term clinical studies of estrogen therapy in men, therefore, appear entirely feasible.
Ceftriaxone in Haemophilus influenzae Type b Meningitis
Authors: John S. Bradley
Journal: JAMA (1988)

To the Editor.  —Jacobs et al 1 report the first apparent case, to my knowledge, of a failure of ceftriaxone to sterilize cerebrospinal fluid (CSF) after three days of therapy in a child with Haemophilus influenzae type b pneumonia with sepsis. This information stands in contrast to a large body of clinical data in which ceftriaxone has been used to treat meningitis and invasive soft tissue disease. 2-8 The report is of great concern to me and, I believe, to others who use ceftriaxone and other third-generation cephalosporins preferentially as empirical therapy for meningitis. 9 Several aspects of this case report deserve comment.  Assuming that the organisms cultured from the blood and CSF were identical isolates, the minimal inhibitory concentration of H influenzae type b to ceftriaxone of these strains appears to be identical to previously reported values. 10 Unfortunately, a minimum bactericidal concentration was not reported. It is possible
Intracranial Hemorrhage Associated with Amphetamine Abuse
Authors: Stanley J. Goodman
Journal: JAMA (1970)

<h3>To the Editor.—</h3> A variety of profound personality changes have been noted in patients taking amphetamines intravenously over a period of weeks and months.<sup>1</sup>At least ten deaths have been reported due to a toxic hypermetabolic state characterized first by transient hyperactivity, then hyperpyrexia, acidosis, and cardiovascular collapse.<sup>2</sup> This report describes two patients with intracranial hemorrhage occurring shortly after they had taken amphetamines. <h3>Report of Cases.—Case 1.—</h3> An 18-year-old Negro boy was admitted to Harbor General Hospital because of peristent severe bifrontal headache and a single seizure. For several months he had been occasionally taking as many as two to three 10-mg dextroamphetamine sulfate tablets a day. Two days prior to admision, he took 50 mg dextroamphetamine sulfate orally in less than one hour. Within an hour he developed an increasingly severe bifrontal headache. One day prior to admission, he was observed by friends to have
Abstract 223: Apoptotic activity of <i>Polygonum cuspidatum</i> in KB human oral cancer cells through the downregulation of specificity protein 1
Authors: Ji-Ae Shin, Jung-Hyun Shim, Jae-Gyu Jeon, Sung-Dae Cho
Journal: Cancer Research (2010)

Abstract Polygonum cuspidatum (Polygonaceae) has traditionally been used in folk medicine to improve oral public health. However, there are no reports related to its potential of controlling oral cancer. In this study, we evaluated the anti-tumorigenic effects and mechanisms of methanol extract and its fractions separated from Polygonum cuspidatum root in KB human oral cancer cells. The methanol extract of Polygonum cuspidatum (MEPC) inhibited the proliferation of KB cells in a dose- and time-dependent manner by inducing caspase-dependent apoptosis. Protein and mRNA expression levels and the transactivation of Specificity protein 1 (Sp1) were markedly decreased in KB cells treated with MEPC. Ethyl acetate fraction (EA) from MEPC was more potent than aqueous fraction (AQ) from MEPC to induce apoptosis. F2, F3 and F4 from EA differentially inhibited the growth of KB cells and it depends on the amount of Emodin in F2, F3 and F4. Moreover, Emodin inhibited KB cell growth and induced caspse-dependent apoptosis. Thus, the results from this study strongly suggest that MEPC, its fraction and Emodin may be potential bioactive materials to cause apoptosis mechanism via the down-regulation of Sp1 in KB human oral cancer cells. This paper was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD, Basic Research Promotion Fund, KRF-2008-331-E00260) and Bio R&amp;D program through the Korea Science and Engineering Foundation funded by the Ministry of Education, Science and Technology (M10870050003-08N7005-00311). 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 223.
Thrombocytopenia due to acute venous thromboembolism and its role in expanding the differential diagnosis of heparin‐induced thrombocytopenia
Authors: Craig S. Kitchens
Journal: American Journal of Hematology (2004)

Thrombocytopenia is an uncommon but serious consequence of heparin administration. Occasionally patients with massive acute venous thromboembolism (VTE) will develop thrombocytopenia. As heparin or some thrombin inhibitor is strongly indicated in acute VTE, it is important to distinguish this event from heparin-induced thrombocytopenia (HIT). Four patients are presented who developed thrombocytopenia so early in their course of VTE and/or therapy with heparin that HIT was considered unlikely. The mean nadir platelet count for these four patients was 60,000/microl occurring at a mean time of 18 hr after the initiation of heparin therapy. Because of strong indications to continue heparin for their acute VTE in the face of a very low likelihood that they did have HIT, heparin was continued with excellent results and resolution of the thrombocytopenia. The literature of this subject is reviewed. Thrombocytopenia following VTE is actually rather common, but it is usually milder than in these four cases. In some cases such as these four, the thrombocytopenia can be sudden and rather severe causing diagnostic confusion with HIT.
Increased Quality of Life Among Hepatocellular Carcinoma Patients Treated With Radioembolization, Compared With Chemoembolization
Authors: Riad Salem, Margaret Gilbertsen, Zeeshan Butt, Khairuddin Memon, Michael Vouche, Ryan Hickey, Talia Baker, Michael M. Abecassis, Rohi Atassi, Ahsun Riaz, David Cella, James L. Burns, Daniel Ganger, Al B. Benson, Mary F. Mulcahy, Laura Kulik, Robert Lewandowski
Journal: Clinical Gastroenterology and Hepatology (2013)
The Role of Autoimmunity at Diagnosis of Type 1 Diabetes in the Development of Thyroid and Celiac Disease and Microvascular Complications
Authors: Sarah J. Glastras, Maria E. Craig, Charles F. Verge, Albert K. Chan, Janine M. Cusumano, Kim C. Donaghue
Journal: Diabetes Care (2005)

OBJECTIVE—The purpose of this study was to explore whether the presence of thyroid and endomysial autoantibodies at diagnosis of type 1 diabetes in children predicts development of thyroid and celiac disease, respectively, and whether diabetes-associated autoantibodies at diagnosis predict development of microvascular complications up to 13 years later. RESEARCH DESIGN AND METHODS—Autoantibodies were measured at diagnosis of type 1 diabetes in 173 children aged 0–15 years and included thyroperoxidase antibody (TPOA), endomysial antibody (EMA), islet cell autoantibody, GAD antibody (GADA), and insulin autoantibody. Thyroid disease was defined as thyroid stimulating hormone level ≥5 μU/ml. Celiac disease was confirmed by small-bowel biopsy. Assessment of microvascular complications included stereoscopic fundal photography, pupillometry, thermal threshold, and albumin excretion rate (AER). RESULTS—The incidence rates for thyroid and celiac disease were 0.9 and 0.7 per 100 patient-years, respectively. Within 13 years, 6 of 13 children with positive TPOA tests at diagnosis developed thyroid disease compared with 5 of 139 children with negative TPOA tests (P &amp;lt; 0.001). All four patients with positive EMA titers at diagnosis had biopsy-proven celiac disease. Five of 11 patients who developed thyroid disease and 4 of 8 who developed celiac disease had negative TPOA and EMA tests at diagnosis, respectively. Retinopathy was detected in 39% and elevated AER in 36%. The presence of diabetes-associated autoantibodies at diagnosis did not predict microvascular complications though GADA titer levels predicted pupillary abnormality. CONCLUSIONS—Elevated TPOA and EMA levels at diagnosis of type 1 diabetes predict the development of thyroid and celiac disease, respectively. In children with negative antibody titers at diagnosis, screening at 2-year intervals is recommended.
Histamine and the pathogenesis of duodenal ulcer disease.
Authors: M E Parsons
Journal: Gut (1985)

Leading articleHistamine and the pathogenesis of duodenal ulcer disease A key role for histamine in the physiological control of gastric acid secretion was established with the advent of the histamine H2-receptor antagonists which have in vivo been shown to inhibit virtually all forms of basal and stimulated secretion.'1159
Abstract A6: microRNA sequencing of AKXD recombinant inbred panel identifies miR-216b as a candidate metastasis suppressor in a murine model of breast cancer
Authors: Farhoud Faraji, Ying Hu, Natalie Goldberger, Gang Wu, Ken H. Buetow, Jinghui Zhang, Kent W. Hunter
Journal: Cancer Research (2012)

Abstract Metastatic disease continues to be the primary cause of mortality in cancer. Using a combination of complex genetics, mouse models of breast cancer, and human epidemiology, our laboratory has demonstrated that germline polymorphism contributes to an individual's susceptibility to metastasis. In the current study, we have used the AKXD recombinant inbred panel, which is derived from inbred mice of metastasis resistant, DBA, and metastasis-prone, AKR, genetic backgrounds, to identify microRNAs whose expression is associated with metastasis. microRNA sequencing of tumor tissue from the progeny of AKXD x Polyoma Middle-T mice demonstrated that the expression of the miR-216/217 cluster is significantly negatively correlated with pulmonary metastases in the AKXD panel. Linkage analysis demonstrated a significant association between the miR-216/217 locus and the DBA allele, suggesting that the difference in expression is inherited rather than somatically acquired. Finally, we show that ectopic expression of miR-216b in murine mammary tumor cells suppresses pulmonary metastasis without significantly impacting primary tumor growth in vivo. These findings suggest that miR-216b is an inherited modifier of metastasis with metastasis suppressing activity in a mouse model of breast cancer. Citation Format: Farhoud Faraji, Ying Hu, Natalie Goldberger, Gang Wu, Ken H. Buetow, Jinghui Zhang, Kent W. Hunter. microRNA sequencing of AKXD recombinant inbred panel identifies miR-216b as a candidate metastasis suppressor in a murine model of breast cancer [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr A6.
New advances in microsphere-based single-dose vaccines
Authors: Justin Hanes, Jeffrey L Cleland, Robert Langer
Journal: Advanced Drug Delivery Reviews (1997)

Polymer microspheres have shown great potential as a next generation adjuvant to replace or complement existing aluminum salts for vaccine potentiation. Microsphere-based systems can now be made to deliver subunit protein and peptide antigens in their native form in a continuous or pulsatile fashion for periods of weeks to months with reliable and reproducible kinetics, often obviating the need for booster immunizations in animal models. Microspheres have also shown potential as carriers for oral vaccine delivery due to their protective effects on encapsulated antigens and their ability to be taken up by the Peyer's patches in the intestine. The potency of these optimal depot formulations for antigen may be enhanced by the co-delivery of vaccine adjuvants, including cytokines, that are either entrapped in the polymer matrix or, alternatively, incorporated into the backbone of the polymer itself and released concomitantly with antigen as the polymer degrades. In this article we review the use of polymer microspheres for single-step immunization and discuss future applications for the improvement of vaccines and immunotherapies by utilizing encapsulation technology.