tbuckley/cabot-search huggingface dataset:
Distinct Tumor Stage–Specific Inhibitory Effects of 2-Methoxyestradiol in a Breast Cancer Mouse Model Associated with Id-1 Expression
Authors: Jung-Im Huh, Alfonso Calvo, Rhonda Charles, Jeffrey E. Green
Journal: Cancer Research (2006)

Abstract 2-Methoxyestradiol (2ME2), a metabolite of 17-β-estradiol, inhibits angiogenesis and has additional antitumor activities. We have analyzed the tumor stage–specific effects of 2ME2 in the C3(1)/Tag transgenic mouse model for breast cancer, which spontaneously develops estrogen receptor–negative mammary tumors following a predictable progression of lesion formation. When given either as a therapeutic agent in established tumors (late intervention study) or in mice with pre-invasive mammary lesions (early intervention study), tumor growth was reduced by 60% compared with untreated controls and was associated with an induction of apoptosis. In a prevention study, a significant reduction in mammary intraepithelial neoplasia (MIN) lesions was observed in animals beginning treatment at 6 weeks of age, before the appearance of histopathologic abnormalities. However, although 2ME2 reduced the number of MIN lesions in the prevention study, a paradoxical increase in tumor multiplicity and growth rate was observed. This was associated with unusual cystic tumor formation, in which significant central necrosis was observed, surrounded by an outer region of proliferative tumor cell growth. The characteristics of the cystic tumor formation in mice treated with 2ME2 at early ages are consistent with an impaired angiogenic response as observed in mice deficient for inhibitor of differentiation (Id-1). We further show that Id-1 expression is negatively regulated by 2ME2, which may be an additional mechanism for the antiangiogenic effect of 2ME2. Although 2ME2 significantly reduced tumor growth at late stages, these results also suggest that altered tumor morphology and accelerated tumor growth may occur if 2ME2 is administered in a prevention setting for prolonged periods. (Cancer Res 2006; 66(7): 3495-503)
Difficulties in the diagnosis and management of unsuspected tuberculous enteritis and colitis
Authors: E. J. M. Campbell
Journal: Gut (1961)

Five patients with tuberculous enteritis and one with possible tuberculous colitis are described, all of whom presented difficult problems of diagnosis and management. Chest radiographs were normal in three cases, and radiology of the bowel was misleading in five. Two developed intestinal malabsorption with megaloblastic anaemia. The finding of tubercle bacilli in the faeces presented an important diagnostic problem in one of the cases with a normal chest radiograph. All the patients required both medical and surgical treatment, and the outcome in five has been very good and relatively satisfactory in the sixth. The last case particularly illustrates the difficulty of ultimate diagnosis in some patients with granulomatous or ulcerative entero-colitis.
Is age-related decline in lean mass and physical function accelerated by obstructive lung disease or smoking?
Authors: B. van den Borst, A. Koster, B. Yu, H. R. Gosker, B. Meibohm, D. C. Bauer, S. B. Kritchevsky, Y. Liu, A. B. Newman, T. B. Harris, A. M. W. J. Schols
Journal: Thorax (2011)

<h3>Background and aims</h3> Cross-sectional studies suggest that obstructive lung disease (OLD) and smoking affect lean mass and mobility. A study was undertaken to investigate whether OLD and smoking accelerate the ageing-related decline in lean mass and physical functioning. <h3>Methods</h3> 260 patients with OLD (mean±SD forced expiratory volume in 1 s (FEV<sub>1</sub>) 63±18% predicted), 157 smoking controls (FEV<sub>1</sub> 95±16% predicted), 866 former-smoking controls (FEV<sub>1</sub> 100±16% predicted) and 891 never-smoking controls (FEV<sub>1</sub> 104±17% predicted) participating in the Health, Aging and Body Composition (ABC) Study were studied. At baseline the mean age was 74±3 years and participants reported no functional limitations. Baseline and 7-year longitudinal data of body composition (by dual-energy x-ray absorptiometry), muscle strength (by hand and leg dynamometry) and Short Physical Performance Battery (SPPB) were investigated. <h3>Results</h3> Compared with never-smoking controls, patients with OLD and smoking controls had a significantly lower weight, fat mass, lean mass and bone mineral content (BMC) at baseline (p&lt;0.05). While the loss of weight, fat mass, lean mass and strength was comparable between patients with OLD and never-smoking controls, the SPPB declined 0.12 points/year faster in men with OLD (p=0.01) and BMC declined 4 g/year faster in women with OLD (p=0.02). In smoking controls only lean mass declined 0.1 kg/year faster in women (p=0.03) and BMC 8 g/year faster in men (p=0.02) compared with never-smoking controls. <h3>Conclusions</h3> Initially well-functioning older adults with mild-to-moderate OLD and smokers without OLD have a comparable compromised baseline profile of body composition and physical functioning, while 7-year longitudinal trajectories are to a large extent comparable to those observed in never-smokers without OLD. This suggests a common insult earlier in life related to smoking.
Weight-Loss Therapy in Type 2 Diabetes: Effects of Phentermine and Topiramate Extended Release
Authors: W. Timothy Garvey, Donna H. Ryan, Nancy J.V. Bohannon, Robert F. Kushner, Miriam Rueger, Roman V. Dvorak, Barbara Troupin
Journal: Diabetes Care (2014)

Treatment algorithms for type 2 diabetes recommend weight loss for disease management. The safety and efficacy of treatment with phentermine (PHEN)/topiramate (TPM) extended release (ER) plus lifestyle modification for weight loss and glycemic benefits were assessed in two randomized, double-blind, placebo-controlled 56-week studies of obese/overweight adults with type 2 diabetes.The OB-202/DM-230 Study was a 56-week phase 2 trial that randomized subjects to receive once-daily placebo or PHEN/TPM ER 15 mg/92 mg (15/92). The primary end point was change in HbA₁c level. A post hoc analysis of a subpopulation with type 2 diabetes from a second study, CONQUER, is also presented. All subjects made lifestyle modifications, and comorbidities were managed to the standard of care.The study groups comprised 130 subjects with type 2 diabetes enrolled in the OB-202/DM-230 Study (mean baseline HbA₁c 8.7% [72 mmol/mol]) and 388 subjects with type 2 diabetes in the CONQUER Study (mean baseline HbA1c 6.8% [51 mmol/mol]). At week 56 in the OB-202/DM-230, change in weight (from intent-to-treat sample with last observation carried forward [ITT-LOCF]) was -2.7% for placebo and -9.4% for PHEN/TPM ER 15/92 (P < 0.0001 vs. placebo). Change in HbA1c level (from ITT-LOCF) was -1.2% (-13.1 mmol/mol) for placebo and -1.6% (-17.5 mmol/mol) for PHEN/TPM ER 15/92 (P = 0.0381). In both the OB-202/DM-230 and CONQUER, greater numbers of patients randomized to receive PHEN/TPM ER treatment achieved HbA₁c targets with reduced need for diabetic medications when compared with the placebo group. Common adverse events included paraesthesia, constipation, and insomnia.PHEN/TPM ER plus lifestyle modification can effectively promote weight loss and improve glycemic control as a treatment approach in obese/overweight patients with type 2 diabetes.
Latent tuberculosis infection in patients with chronic plaque psoriasis who are candidates for biological therapy
Authors: P. Gisondi, E. Pezzolo, G. Lo Cascio, G. Girolomoni
Journal: British Journal of Dermatology (2014)

Background Screening for latent tuberculosis infection (LTBI) is mandatory in patients with psoriasis prior to biological therapy. Objectives To investigate the prevalence of LTBI in patients with psoriasis who are candidates for biological therapy. Methods LTBI was investigated in patients with moderate-to-severe psoriasis (n = 243), Crohn disease (n = 64) or rheumatoid arthritis (RA) (n = 56) and in healthcare workers (n = 1683). LTBI diagnosis was based on positive QuantiFERON-B Gold In-Tube (QFT-GIT) in vitro assay without any clinical, radiological or microbiological evidence of active tuberculosis. Results LTBI was diagnosed in 8·2% of patients with psoriasis, 7% with Crohn disease and 9% with RA, and in 8·8% of healthcare workers (P = 0·9). Patients with psoriasis who also had LTBI (n = 20) received a 9-month prophylaxis with isoniazid (5 mg kg−1 daily). None of these patients developed active tuberculosis infection after receiving biological therapy (etanercept, adalimumab, infliximab or ustekinumab) for 37 ± 32 weeks (mean ± SD). All patients with psoriasis were retested for LTBI after 31 ± 1·7 months. Five of the 20 patients with LTBI presented QFT-GIT reversion and two patients out of 243 (0·8%) had QFT-GIT conversion and received antibiotic prophylaxis. Conclusions The prevalence of LTBI in patients with psoriasis is similar to that in patients with Crohn disease or RA and in healthcare workers. Prophylaxis with isoniazid is effective in preventing tuberculosis reactivation in patients with LTBI receiving biological therapy.
Sickle Cell Disease, Vasculopathy, and Therapeutics
Authors: Adetola A. Kassim, Michael R. DeBaun
Journal: Annual Review of Medicine (2012)

Sickle cell disease (SCD) is caused by a mutation in both beta globin genes, resulting in chronic hemolysis and multiorgan disease that ultimately leads to premature death. Although hemoglobin S (HbS) polymerization and vaso-occlusion are central to the pathogenesis of SCD, overlapping pathways implicated in SCD-related endothelial dysfunction include hemolysis, defects in nitric oxide metabolism, ischemia-reperfusion injury, oxidative stress, increased cell-to-cell adhesion, and proinflammatory and coagulation mediators. Progression of organ-specific vasculopathy often precedes organ dysfunction and may provide targets for therapeutic intervention. SCD-related vasculopathies include, but are not limited to, moyamoya that often precedes cerebral infarcts or hemorrhage, proliferative retinopathy prior to loss of eyesight, pulmonary vasculopathy associated with pulmonary hypertension, and renal vasculopathy prior to the onset of chronic renal disease. This review evaluates evidence that SCD vasculopathy is a harbinger for organ dysfunction and reviews the potential for targeted antivasculopathy therapies.
Phase II Study of Neoadjuvant Docetaxel, Vinorelbine, and Trastuzumab Followed by Surgery and Adjuvant Doxorubicin Plus Cyclophosphamide in Women With Human Epidermal Growth Factor Receptor 2–Overexpressing Locally Advanced Breast Cancer
Authors: Steven A. Limentani, Adam M. Brufsky, John K. Erban, Mohammed Jahanzeb, Deborah Lewis
Journal: Journal of Clinical Oncology (2007)

To evaluate the combination of docetaxel, vinorelbine, and trastuzumab as neoadjuvant therapy for human epidermal growth factor receptor 2 (HER2)--overexpressing breast cancer.Patients with stage IIB or III breast cancer, including inflammatory disease, and HER2 overexpression (determined by fluorescent in situ hybridization) were treated with six cycles of docetaxel 60 mg/m2 and vinorelbine 45 mg/m2 administered every 14 days with granulocyte colony-stimulating factor and quinolone prophylaxis. Trastuzumab was administered as a 4 mg/kg loading dose followed by 2 mg/kg weekly for 12 weeks. The primary efficacy end point was pathologic complete response (pCR) in the breast.Of 31 enrolled patients, 68% had T3 or T4 tumors and 90% were clinically node positive. Twelve patients (39%; 95% CI, 21.6% to 55.9%) achieved pCR in the breast and lymph nodes and 14 patients (45%; 95% CI, 27.6% to 62.7%) achieved pCR in the breast alone, and 19 patients (61%; 95% CI, 44.1% to 78.4%) were node negative after neoadjuvant therapy. Clinical response was documented in 29 patients (94%; 95% CI, 78.6% to 99.2%) with 26 complete responses (84%; 95% CI, 70.9% to 96.8%). The most commonly reported grade 3/4 toxicities were neutropenia (97%), febrile neutropenia (22%), anemia (6%), mucositis/stomatitis (6%), constipation (6%), and skin rash (6%).With clinical response and pCR rates of 94% and 39%, respectively, docetaxel, vinorelbine, and trastuzumab is a highly active neoadjuvant therapy for HER2-overexpressing locally advanced breast cancer. Although well tolerated overall, significant febrile neutropenia was observed despite prophylactic measures; therefore, evaluating a similar regimen using lower docetaxel and/or vinorelbine doses is warranted.
Effective Relief of Malignant Ascites in Patients with Advanced Ovarian Cancer by a Trifunctional Anti-EpCAM × Anti-CD3 Antibody: A Phase I/II Study
Authors: Alexander Burges, Pauline Wimberger, Carolin Kümper, Vera Gorbounova, Harald Sommer, Barbara Schmalfeldt, Jacobus Pfisterer, Michail Lichinitser, Anatoliy Makhson, Vladimir Moiseyenko, Angelika Lahr, Elisabeth Schulze, Michael Jäger, Michael A. Ströhlein, Markus Maria Heiss, Thomas Gottwald, Horst Lindhofer, Rainer Kimmig
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Malignant ascites in ovarian carcinoma patients is associated with poor prognosis and reduced quality of life. The trifunctional antibody catumaxomab (anti-EpCAM × anti-CD3) enhances the antitumor activity by redirecting T cells and Fcγ receptor I/III–positive accessory cells to the tumor. This multicenter phase I/II dose-escalating study investigated tolerability and efficacy of i.p. catumaxomab application in ovarian cancer patients with malignant ascites containing epithelial cell adhesion molecule (EpCAM)–positive tumor cells. Experimental Design: Twenty-three women with recurrent ascites due to pretreated refractory ovarian cancer were treated with four to five i.p. infusions of catumaxomab in doses of 5 to 200 μg within 9 to 13 days. Results: The maximum tolerated dose was defined at 10, 20, 50, 200, and 200 μg for the first through fifth doses. Side effects included transient fever (83%), nausea (61%), and vomiting (57%), mostly CTCAE (Common Terminology Criteria for Adverse Events) grade 1 or 2. A total of 39 grade 3 and 2 grade 4 treatment-related adverse events (AE), 9 of them after the highest dose level (200 μg), were observed in 16 patients. Most AEs were reversible without sequelae. Treatment with catumaxomab resulted in significant and sustained reduction of ascites flow rate. A total of 22/23 patients did not require paracentesis between the last infusion and the end of study at day 37. Tumor cell monitoring revealed a reduction of EpCAM-positive malignant cells in ascites by up to 5 log. Conclusion: I.p. immunotherapy with catumaxomab prevented the accumulation of ascites and efficiently eliminated tumor cells with an acceptable safety profile. This suggests that catumaxomab is a promising treatment option in ovarian cancer patients with malignant ascites.
Morphology of Particles Associated With Murine Leukemia as Revealed by Negative Staining: Preliminary Report
Authors: Albert J. Dalton, Frangoise Haguenau, John B. Moloney
Journal: JNCI Journal of the National Cancer Institute (1962)

The use of the negative-staining method has revealed that the mature particles associated with murine lymphoid leukemia induced with the Moloney agent possess characteristic hexagonal heads and well-formed tails, features not previously described for animal viruses. The smallest diameter of the heads varied between 100 and 150 mμ while the tails measured approximately 250 mµ in length.
Abstract 97: Analysis of Emergency Medical Service-initiated CPR Effectiveness in Out-of Hospital Cardiac Arrest (OHCA) Cases Without Bystander-CPR: From all-Japan OHCA Utstein Registry
Authors: Hiroyuki Hanada, Hiromi Seo, Yoshihiko Seino, Hiroshi Nonogi, Ken Nagao, Takeshi Kimura
Journal: Circulation (2013)

Backgrounds: Bystander cardiopulmonary resuscitation (CPR) is essential for good neurological survival (GNS) in out-of-hospital cardiac arrest (OHCA). However previous reports from the All-Japan prospective, population-based OHCA Utstein registry of the Fire and Disaster Management Agency(J-OHCAUR) revealed that around 50% of OHCA did not receive bystander-initiated CPR and treated by the emergency medical service (EMS). The present study examined relationship among the time interval from the witnessed cardiac arrest to EMS-initiated CPR and shock, and GNS one month after the event. Methods and Results: From January 2005 through December 2011, we identified 140,363 witnessed OHCA cases from the J-OHCAUR. Among them, 74,541 cases (53.1%) did not receive bystander-CPR, and 14,911 cases had the initial rhythm of VF or VT. These EMS-initiated CPR cases were classified according to the time-interval from cardiac arrest to CPR and shock; 1,106 in the time-interval of 0 minute (shock first approach), 2.707 in 1 minute, 4.131 in 2 minutes, 2,304 in 3 minutes, 985 in 4 minutes, and 1,047 in 5 to 10 minutes. Rate of GNR (cerebral performance category scale 1 or 2) in each time-intervals were shown in the figure. Effectiveness of CPR was clearly time-dependent, and the earlier shock brought about the better GNS in any time-intervals. Conclusion: Even in OHCA cases without bystander-CPR, time-dependent effectiveness of EMS-initiated CPR and importance of the earlier shock were documented.
Renal responses to sodium restriction in patients with early diabetes mellitus.
Authors: J A Miller
Journal: Journal of the American Society of Nephrology (1997)

Increased GFR and decreased renal vascular resistance are common renal hemodynamic changes in persons with early, uncomplicated, insulin-dependent diabetes mellitus. It has been hypothesized that excess total-body sodium in patients with diabetes contributes to the renal vasodilation, possibly by suppressing vasoconstricting neurohormonal systems. This study was undertaken to examine whether sodium restriction could normalize these renal abnormalities. Subjects were 12 male patients with uncomplicated insulin-dependent diabetes mellitus (duration, < 5 yr). Results were compared with those of an age- and gender-matched control group. All subjects received either a high-sodium diet (200 mmol/day) or a sodium-restricted diet (20 mmol/day) for 7 days, according to a randomized crossover protocol. GFR and RPF were measured using inulin and para-aminohippurate clearance techniques, respectively. Subjects with diabetes were maintained euglycemic during the clearance measurements. GFR was significantly higher in the diabetic group than in the control group with sodium repletion (124 +/- 4 versus 107 +/- 8 mL/min/1.73 m2; P = 0.03), and renal vascular resistance was significantly reduced (94 +/- 6 versus 107 +/- 17 mm Hg/L/min; P = 0.05). In response to sodium restriction, the hematocrit increased significantly in both groups, as did PRA and aldosterone, although responses in the diabetic group were somewhat blunted, indicating persisting volume expansion. Despite this humoral activation, sodium restriction had little effect on renal hemodynamic function in control subjects. In the diabetic subjects, this maneuver appeared to exacerbate the underlying renal abnormalities, with the GFR increasing to 131 +/- 4 mL/min/1.73 m2 (P = 0.05) and the renal vascular resistance declining to 73 +/- 5 mm Hg/L/min (P = 0.001). These data indicate that, rather than correcting renal hyperperfusion, sodium restriction exacerbates these characteristic abnormalities, suggesting that mechanisms other than suppression of vasoconstrictor activity are operative in the underlying renal hemodynamic abnormalities of early, uncomplicated, insulin-dependent diabetes mellitus.
A CASE OF AGRANULOCYTIC ANGINA
Authors: A. D. Briscoe
Journal: BMJ (1934)

Only five cases (all in females and four fatal) of agranulo- cytic angina have been-reported in this country.In- America and on the Continent, however, many cases have been investigated, and' much has been written on the subject.By far the majority of patients have been females, and the mortality has been very high.Batten' was the first to record a case in England, and subsequent cases have been reported by Garrod and Williamws,2 Pilkington,3 Leys,4 and Abrahams.5It 'appeared, there- fore, that a case occurring in a man of 71, with subsequent recovery, was sufficiently unusual to be worth putting on record. History of CaseThe patient, a small, spare man, aged 71 years, had not felt well since June, 1933.He complained of feeling easily tired, of being irritable, and of having a poor appetite.The only previous history of any 'importance was an attack c;f renal colic six years before, which wxas folloxved by the passage per urethram of a small calculus.He was first seen on August 31st, 1933.In addition to the symptoms mentioned above he had some difficulty and pain in swallowing, owing to an ulcer which was situated on the left
The Impact of Culture on Food-Related Behavior
Authors: M L Axelson
Journal: Annual Review of Nutrition (1986)

Some of the sociodemographic and psychosocial determinants of individuals' food-related behaviors were examined in this chapter. The empirical research indicates that individuals do participate differentially in their culture. But, the reasons for why people eat what they eat are still incompletely understood, as evidenced by the inadequate predictive ability of the determinants examined.
Efficacy of high-dose alkylating chemotherapy in HER2/neu-negative breast cancer
Authors: S. Rodenhuis, M. Bontenbal, Q.G.C.M. van Hoesel, W.M. Smit, M.A. Nooij, E.E. Voest, E. van der Wall, P. Hupperets, H. van Tinteren, J.L. Peterse, M.J. van de Vijver, E.G.E. de Vries
Journal: Annals of Oncology (2006)
Phospholipase A <sub>2</sub> in Vascular Disease
Authors: Eva Hurt-Camejo, Germán Camejo, Helena Peilot, Katarina Öörni, Petri Kovanen
Journal: Circulation Research (2001)

Secretory phospholipase A 2 (PLA 2 ) can be proatherogenic both in the circulation and in the arterial wall. In blood plasma, PLA 2 can modify the circulating lipoproteins and so induce formation of small dense LDL particles, which are associated with increased risk for cardiovascular disease. In the arterial wall, PLA 2 can hydrolyze lipoproteins. The PLA 2 -modified lipoproteins bind tightly to extracellular proteoglycans, which may lead to their enhanced retention in the arterial wall. The modified lipoproteins may also aggregate and fuse, which can lead to accumulation of their lipids within the extracellular matrix. The PLA 2 -modified particles are more susceptible to further modifications by other enzymes and agents and can be taken up by macrophages, leading to accumulation of intracellular lipids. In addition, lysophospholipids and free fatty acids, the hydrolysis products of PLA 2 , promote atherogenesis. Thus, these lipid mediators can be carried, either by the PLA 2 -modified lipoproteins themselves or by albumin, into the arterial cells, which then undergo functional alterations. This may, in turn, lead to specific changes in the extracellular matrix, which increase the retention and accumulation of lipoproteins within the matrix. In the present article, we discuss the possible actions of PLA 2 enzymes, especially PLA 2 -IIA, in the arterial wall during atherogenesis.
NECROPSY FINDINGS IN HTLV-I ASSOCIATED MYELOPATHY
Authors: Shin'Ichiro Akizuki, Okifumi Nakazato, Yasunori Higuchi, Katsuhiko Tanabe, Mihoko Setoguchi, Seiji Yoshida, Yoshitaka Miyazaki, Shunsuke Yamamoto, Shinji Sudou, Kunihiro Sannomiya, Toru Okajima
Journal: The Lancet (1987)