tbuckley/cabot-search huggingface dataset:
Acetyl-<scp>l</scp>-Carnitine Improves Pain, Nerve Regeneration, and Vibratory Perception in Patients With Chronic Diabetic Neuropathy
Authors: Anders A.F. Sima, Menotti Calvani, Munish Mehra, Antonino Amato
Journal: Diabetes Care (2005)

We evaluated frozen databases from two 52-week randomized placebo-controlled clinical diabetic neuropathy trials testing two doses of acetyl-L-carnitine (ALC): 500 and 1,000 mg/day t.i.d.Intention-to-treat patients amounted to 1,257 or 93% of enrolled patients. Efficacy end points were sural nerve morphometry, nerve conduction velocities, vibration perception thresholds, clinical symptom scores, and a visual analogue scale for most bothersome symptom, most notably pain. The two studies were evaluated separately and combined.Data showed significant improvements in sural nerve fiber numbers and regenerating nerve fiber clusters. Nerve conduction velocities and amplitudes did not improve, whereas vibration perception improved in both studies. Pain as the most bothersome symptom showed significant improvement in one study and in the combined cohort taking 1,000 mg ALC.These studies demonstrate that ALC treatment is efficacious in alleviating symptoms, particularly pain, and improves nerve fiber regeneration and vibration perception in patients with established diabetic neuropathy.
Limitation of combination therapy of interferon and ribavirin for older patients with chronic hepatitis C
Authors: Yoshiaki Iwasaki, Hiroshi Ikeda, Yasuyuki Araki, Toshiya Osawa, Keiji Kita, Masaharu Ando, Toshinari Shimoe, Kouichi Takaguchi, Noriaki Hashimoto, Toshitsugu Kobatake, Minoru Tomita, Mitsuhiko Kawaguchi, Haruhiko Kobashi, Kohsaku Sakaguchi, Yasushi Shiratori
Journal: Hepatology (2005)

In contrast to the United States, Japanese patients with chronic hepatitis C currently treated with interferon are generally 10 to 15 years older. Older patients, however, tend to experience more frequent adverse events. This study was conducted to clarify the effect of patient age on the efficacy and safety of combination therapy. We consecutively enrolled 208 patients with naïve chronic hepatitis C. Patients were classified into three groups according to age: younger than 50 years of age (n = 52); 50 to 59 years old (n = 83); and 60 years of age or older (n = 73). Interferon alpha-2b therapy was administered daily for 2 weeks, followed by 3 times per week for 22 weeks, while ribavirin was administered daily. Of the 208 study patients, discontinuation of therapy or dose reduction was required in 116 (56%) and was more frequent in older patient groups: 38%, 48%, and 77% for the <50, 50–59, and ≥60-year-old patient groups, respectively (P < .001). Multivariate analysis showed patient age to be independently associated with adherence to therapy. A sustained virological response was achieved in 77 (37%) patients, with genotype, viral load, and adherence to therapy associated with this achievement. A tendency toward a lower sustained virological response rate was seen in the older patients. In conclusion, patient age is an important factor contributing to the safety of combination therapy. Thus, treatment schedule should be modified, or other therapeutic modalities should be considered for older patients with chronic hepatitis C. (HEPATOLOGY 2006;43:54–63.)
Simultaneous targeting of Aurora kinases and Bcr-Abl kinase by the small molecule inhibitor PHA-739358 is effective against imatinib-resistant BCR-ABL mutations including T315I
Authors: Artur Gontarewicz, Stefan Balabanov, Gunhild Keller, Riccardo Colombo, Alessio Graziano, Enrico Pesenti, Daniel Benten, Carsten Bokemeyer, Walter Fiedler, Jürgen Moll, Tim H. Brümmendorf
Journal: Blood (2008)
Management of Hyperkinetic And Handicapped Children
Authors: Samuel Livingston
Journal: JAMA (1969)

<h3>To the Editor:—</h3> Both the Council on Drugs and J.G. Millichap, MD, are to be commended for the article, "Drugs in Management of Hyperkinetic and Perceptually Handicapped Children" (<b>206</b>:1527, 1968), the former for the invitation and the latter for his presentation of the diagnostic and therapeutic considerations affecting hyperactivity in children. Behavioral disorders constitute an ever-increasing problem for physicians who will find this article invaluable for the useful information it provides. We note that Dr. Millichap selects the central nervous system stimulants as the agents of choice while admitting that "... controlled studies are limited and there is no satisfactory explanation of the mechanism by which these drugs act." A comparable statement could also be made of the antianxiety and antipsychotic agents which are recommended as alternative agents in patients who fail to respond to the central nervous system stimulants. Our purpose in writing is to draw attention to one
Impaired left ventricular diastolic filling in patients with coronary artery disease: assessment with radionuclide angiography.
Authors: R O Bonow, S L Bacharach, M V Green, K M Kent, D R Rosing, L C Lipson, M B Leon, S E Epstein
Journal: Circulation (1981)

To assess left ventricular (LV) diastolic filling at rest in patients with coronary artery disease (CAD), we analyzed high-resolution time-activity curves (10-20 msec/frame) obtained from gated radionuclide angiograms in 231 patients. Peak LV filling rate (PFR), expressed in end-diastolic volumes per second (EDV/sec), was subnormal in CAD patients (1.8 +/- 0.6 [+/- SD] vs normal mean of 3.3 +/- 0.6, p les than 0.001) and time to PFR (TPFR), measured from end-systole to PFR, was prolonged (171 +/- 41 msec vs normal mean of 136 +/- 23 msec, p less than 0.001). These indexes were also abnormal in the 141 patients with normal resting LV ejection fraction (PFR = 2.1 +/- 0.5 EDV/sec; TPFR = 175 +/- 36 msec) and in 123 patients without Q waves on the ECG (PFR = 2.1 +/- 0.5 EDV/sec; TPFR = 168 +/- 38 msec). Abnormal LV filling at rest (PFR less than 2.5 EDV/sec or TPFR greater than 180 msec) was found in 91% of all patients with CAD, 86% of patients with normal resting LV ejection fractions, 85% of patients without Q waves, and 82% of patients with normal resting LV ejection fraction, no resting regional wall motion abnormalities and no Q waves. Thus, LV diastolic filling, evaluated noninvasively by radionuclide angiography, is abnormal in a high percentage of patients with CAD at rest independent of LV systolic function or previous myocardial infarction.
Biologic activity of purified cotton bract extracts in man and guinea pig.
Authors: M G Buck, E N Schachter, R B Fick, W W Merrill, J A Cooper, J J Keirns, J Oliver, J H Wall
Journal: Environmental Health Perspectives (1986)

Purified aqueous extracts of cotton bract induce acute airway constriction in healthy volunteers never before exposed to cotton bract. The response is similar to that of textile workers who inhale cotton dust. Approximately 60% of volunteers respond to bract extract with significant decreases in lung function, and these volunteers show an increased number of lymphocytes present in their lungs. Following inhalation of bract, the percent of polymorphonuclear leukocytes increases. Macrophages obtained by bronchoalveolar lavage from volunteers pre-challenged with bract extract release increased amounts of chemotactic factor and superoxide anion. Efforts to detect release of histamine and leukotrienes in volunteers following challenge with bract show no increase in urinary histamine and no significant release of leukotrienes in lung lavage fluid. Purified extracts exhibit chemotactic activity in vitro. They also contract guinea pig ileal longitudinal muscle in vitro. This preparation contains mast cells but no basophils, and the H-1 blocker, mepyramine blocks the contraction. Purified bract extracts contain no histamine or endotoxin but other contractors of smooth muscle may be present. The purified extract exhibits spectral, fluorescent, and radioimmune assay properties similar to a leukotriene B-like component. Cotton bract appears to have direct as well as cell-mediated activities.
Same-day endoscopic retrograde cholangiopancreatography after transduodenal endoscopic ultrasound-guided needle aspiration: do we need to be cautious?
Authors: F. Di Matteo, L. Shimpi, A. Gabbrielli, M. Martino, M. Caricato, A. Esposito, M. De Cicco, R. Coppola, G. Costamagna
Journal: Endoscopy (2006)

Patients who are undergoing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for suspected pancreatic tumors frequently undergo endoscopic retrograde cholangiopancreatography (ERCP) for palliation of their symptoms. Performing EUS-FNA and ERCP in tandem may be cost-effective and may reduce procedure time, but the potential risks associated with this approach have not been clearly defined in the literature. We report two patients who underwent same-day therapeutic ERCP after transduodenal EUS-FNA for pancreatic tumors. Endoscopic biliary manipulation during ERCP aggravated an inadvertent and subclinical needle puncture injury to the bile duct sustained during the preceding EUS-FNA. This resulted in leakage of bile into the retroperitoneal space, and both patients required laparotomy and surgical drainage. Additional clinical evidence is needed to clarify these issues and to determine whether it would be prudent to perform therapeutic ERCP prior to diagnostic transduodenal EUS-FNA when these two procedures are planned as sequential or same-day procedures.
Acute brain stem stroke during neck manipulation
Authors: T K Daneshmend
Journal: BMJ (1984)

Une observation d'ictus par occlusion traumatique de l'artere vertebrale gauche au cours d'une manipulation du cou. Ischemie aigue du tronc cerebral et du cervelet. Le traumatisme semble avoir porte au niveau de l'articulation atlas-axis. Sequelles: nystagmus, legere ataxie de la jambe et du bras droits, paralysie faciale gauche marquee. Ces troubles s'estompent au bout de 6 mois
Aspirin reduced risk of cancer in large US study
Authors: Janice Hopkins Tanne
Journal: BMJ (2007)

A new prospective cohort study adds to the evidence that regularly taking aspirin reduces the incidence of cancers and cancer mortality. But the study, in postmenopausal women in the US Midwest, found that use of non-steroidal anti-inflammatory drugs did not protect against cancer.

Researchers from the Mayo Clinic College of Medicine in Rochester, Minnesota, and the University of Minnesota in Minneapolis studied 22 507 postmenopausal women who had no history of cancer or heart disease and who took part in the Iowa women's health study. They presented their …
Leukemia-Inhibitory Factor—Neuroimmune Modulator of Endocrine Function*
Authors: C. J. Auernhammer, S. Melmed
Journal: Endocrine Reviews (2000)

Leukemia-inhibitory factor (LIF) is a pleiotropic cytokine expressed by multiple tissue types. The LIF receptor shares a common gp130 receptor subunit with the IL-6 cytokine superfamily. LIF signaling is mediated mainly by JAK-STAT (janus-kinase-signal transducer and activator of transcription) pathways and is abrogated by the SOCS (suppressor-of cytokine signaling) and PIAS (protein inhibitors of activated STAT) proteins. In addition to classic hematopoietic and neuronal actions, LIF plays a critical role in several endocrine functions including the utero-placental unit, the hypothalamo-pituitary-adrenal axis, bone cell metabolism, energy homeostasis, and hormonally responsive tumors. This paper reviews recent advances in our understanding of molecular mechanisms regulating LIF expression and action and also provides a systemic overview of LIF-mediated endocrine regulation. Local and systemic LIF serve to integrate multiple developmental and functional cell signals, culminating in maintaining appropriate hormonal and metabolic homeostasis. LIF thus functions as a critical molecular interface between the neuroimmune and endocrine systems.
Diabetes Care in Rural Area: Clinical and Metabolic Evaluation
Authors: K Derfler, W Waldhäusl, H J Zyman, K Howorka, C Holler, H Freyler
Journal: Diabetes Care (1986)

To evaluate the efficacy of conventional diabetes care in a rural area, metabolic control and the presence of late complications were studied in 622 diabetic patients treated by general practitioners beyond the reach of diabetic centers. Seventy-three (12%) of the patients were classified as type I diabetics (age, 38.0 ± 16.1 yr; duration of diabetes, 12.8 ± 9.3 yr) and 549 as type II diabetics (age, 67.0 ± 10.8 yr; duration of diabetes, 7.3 ± 5.8 yr). Fifty-eight percent of type I diabetic patients administered insulin once daily and 42% twice daily, whereas most (83%) type II diabetics on insulin received only one insulin injection per day. Treatment of type II diabetic patients consisted of sulfonylureas (58%), diet alone (22%), insulin (18%), and biguanides or a combination of sulfonylurea with biguanides (2%). Poor therapeutic efficacy was observed in all patients, and postprandial hyperglycemia (blood glucose &amp;gt;160 mg/dl) was predominant both in type I diabetics (86%) and in type II diabetics on insulin (80%) as well as off insulin (55%). HbA1c above normal (&amp;gt;5.8%) was seen in 96% of type I and in 90 and 73% of type II diabetics with or without insulin therapy, respectively. Accompanying glucosuria was present in type I (73%) and in type II diabetics (on insulin, 71%; off insulin, 33%). Mean prevalence of late diabetic complications was greatest for insulin-treated patients (type I, type II with, and type II without insulin treatment: retinopathy, 41, 56, 22%; proteinuria, 13, 14, 3%; peripheral neuropathy, 21, 51, 12%), whereas macroangiopathy (16, 53, 31%) predominated in type II diabetic patients. The cumulative hospitalization period per patient increased from 33 days during the first 5 yr to 98 days for &amp;gt;20 yr of type I diabetes but was smaller in type II diabetics on and off insulin. We conclude that considerable effort is required to improve the course of diabetes in patients on routine treatment.
Museum
Authors: John D. Stoeckle
Journal: JAMA (2003)

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Optimizing DC Vaccination by Combination With Oncolytic Adenovirus Coexpressing IL-12 and GM-CSF
Authors: Song-Nan Zhang, Il-Kyu Choi, Jing-Hua Huang, Ji-Young Yoo, Kyung-Ju Choi, Chae-Ok Yun
Journal: Molecular Therapy (2011)

Dendritic cell (DC)-based vaccination is a promising strategy for cancer immunotherapy. However, clinical trials have indicated that immunosuppressive microenvironments induced by tumors profoundly suppress antitumor immunity and inhibit vaccine efficacy, resulting in insufficient reduction of tumor burdens. To overcome these obstacles and enhance the efficiency of DC vaccination, we generated interleukin (IL)-12- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-coexpressing oncolytic adenovirus (Ad-ΔB7/IL12/GMCSF) as suitable therapeutic adjuvant to eliminate immune suppression and promote DC function. By treating tumors with Ad-ΔB7/IL12/GMCSF prior to DC vaccination, DCs elicited greater antitumor effects than in response to either treatment alone. DC migration to draining lymph nodes (DLNs) dramatically increased in mice treated with the combination therapy. This result was associated with upregulation of CC-chemokine ligand 21 (CCL21(+)) lymphatics in tumors treated with Ad-ΔB7/IL12/GMCSF. Moreover, the proportion of CD4(+)CD25(+) T-cells and vascular endothelial growth factor (VEGF) expression was decreased in mice treated with the combination therapy. Furthermore, combination therapy using immature DCs also showed effective antitumor effects when combined with Ad-ΔB7/IL12/GMCSF. The combination therapy had a remarkable therapeutic efficacy on large tumors. Taken together, oncolytic adenovirus coexpressing IL-12 and GM-CSF in combination with DC vaccination has synergistic antitumor effects and can act as a potent adjuvant for promoting and optimizing DC vaccination.
Lymphotoxin α/β and Tumor Necrosis Factor Are Required for Stromal Cell Expression of Homing Chemokines in B and T Cell Areas of the Spleen
Authors: Vu N. Ngo, Heinrich Korner, Michael D. Gunn, Kerstin N. Schmidt, D. Sean Riminton, Max D. Cooper, Jeffrey L. Browning, Jonathon D. Sedgwick, Jason G. Cyster
Journal: The Journal of Experimental Medicine (1999)

Mice deficient in the cytokines tumor necrosis factor (TNF) or lymphotoxin (LT) alpha/beta lack polarized B cell follicles in the spleen. Deficiency in CXC chemokine receptor 5 (CXCR5), a receptor for B lymphocyte chemoattractant (BLC), also causes loss of splenic follicles. Here we report that BLC expression by follicular stromal cells is defective in TNF-, TNF receptor 1 (TNFR1)-, LTalpha- and LTbeta-deficient mice. Treatment of adult mice with antagonists of LTalpha1beta2 also leads to decreased BLC expression. These findings indicate that LTalpha1beta2 and TNF have a role upstream of BLC/CXCR5 in the process of follicle formation. In addition to disrupted follicles, LT-deficient animals have disorganized T zones. Expression of the T cell attractant, secondary lymphoid tissue chemokine (SLC), by T zone stromal cells is found to be markedly depressed in LTalpha-, and LTbeta-deficient mice. Expression of the SLC-related chemokine, Epstein Barr virus-induced molecule 1 ligand chemokine (ELC), is also reduced. Exploring the basis for the reduced SLC expression led to identification of further disruptions in T zone stromal cells. Together these findings indicate that LTalpha1beta2 and TNF are required for the development and function of B and T zone stromal cells that make chemokines necessary for lymphocyte compartmentalization in the spleen.
[43] SUBTYPE CLASSIFICATION OF HEPATOCELLULAR ADENOMAS BY MOLECULAR MARKERS AND IMMUNOHISTOCHEMISTRY
Authors: P. Bioulac-Sage, S. Rebouissou, C. Thomas, J.F. Blanc, J. Saric, E. Jeannot, A. Sa Cunha, G. Couchy, S. Imbeaud, C. Balabaud, J. Zucman-Rossi
Journal: Journal of Hepatology (2007)
Salmonella typhimurium initiates murine infection by penetrating and destroying the specialized epithelial M cells of the Peyer's patches.
Authors: B D Jones, N Ghori, S Falkow
Journal: The Journal of Experimental Medicine (1994)

Salmonella species are known to initiate infection of mammalian hosts by penetrating the intestinal epithelium of the small bowel. These bacteria preferentially interact with Peyer's patches which are collections of lymphoid follicles making up the gut-associated lymphoid tissue. We infected murine ligated intestinal loops with invasive and noninvasive Salmonella typhimurium strains for 30, 60, 120, and 180 min and examined the infected tissue by transmission electron microscopy. Within 30 min, we found that invasive S. typhimurium exclusively entered M cells found within the follicle-associated epithelium (FAE) of the Peyer's patches. Initially, interactions between invasive bacteria and enterocytes adjacent to the M cells were not found. Invasion of M cells was associated with the ability of the bacteria to invade tissue culture cells. S. typhimurium mutants, which were noninvasive for tissue culture cells, could not be found in ligated loops associated with M cells or enterocytes after incubations of 30, 60, 120, or 180 min. At 60 min, internalized invasive S. typhimurium were cytotoxic for the M cells. Destruction of an M cell formed a gap in the FAE which allowed organisms to invade enterocytes adjacent to the dead cell. Later in the infection process (120 and 180 min), the presence of bacteria beneath the FAE correlated with changes in the cytoarchitecture of the lymphoid follicle. In addition, replicating Salmonella began to enter both the apical and basolateral surfaces of enterocytes adjacent to infected M cells.
Homocysteine-Lowering and Cardiovascular Disease Outcomes in Kidney Transplant Recipients
Authors: Andrew G. Bostom, Myra A. Carpenter, John W. Kusek, Andrew S. Levey, Lawrence Hunsicker, Marc A. Pfeffer, Jacob Selhub, Paul F. Jacques, Edward Cole, Lisa Gravens-Mueller, Andrew A. House, Clifton Kew, Joyce L. McKenney, Alvaro Pacheco-Silva, Todd Pesavento, John Pirsch, Stephen Smith, Scott Solomon, Matthew Weir
Journal: Circulation (2011)

Background— Kidney transplant recipients, like other patients with chronic kidney disease, experience excess risk of cardiovascular disease and elevated total homocysteine concentrations. Observational studies of patients with chronic kidney disease suggest increased homocysteine is a risk factor for cardiovascular disease. The impact of lowering total homocysteine levels in kidney transplant recipients is unknown. Methods and Results— In a double-blind controlled trial, we randomized 4110 stable kidney transplant recipients to a multivitamin that included either a high dose (n=2056) or low dose (n=2054) of folic acid, vitamin B6, and vitamin B12 to determine whether decreasing total homocysteine concentrations reduced the rate of the primary composite arteriosclerotic cardiovascular disease outcome (myocardial infarction, stroke, cardiovascular disease death, resuscitated sudden death, coronary artery or renal artery revascularization, lower-extremity arterial disease, carotid endarterectomy or angioplasty, or abdominal aortic aneurysm repair). Mean follow-up was 4.0 years. Treatment with the high-dose multivitamin reduced homocysteine but did not reduce the rates of the primary outcome (n=547 total events; hazards ratio [95 confidence interval]=0.99 [0.84 to 1.17]), secondary outcomes of all-cause mortality (n=431 deaths; 1.04 [0.86 to 1.26]), or dialysis-dependent kidney failure (n=343 events; 1.15 [0.93 to 1.43]) compared to the low-dose multivitamin. Conclusions— Treatment with a high-dose folic acid, B6, and B12 multivitamin in kidney transplant recipients did not reduce a composite cardiovascular disease outcome, all-cause mortality, or dialysis-dependent kidney failure despite significant reduction in homocysteine level. Clinical Trial Registration— http://www.clinicaltrials.gov . Unique identifier: NCT00064753.