tbuckley/cabot-search huggingface dataset:
Take a Look at Me Now
Authors: Quinn Leslie
Journal: JAMA (2015)

The somber holiday weekend ended with an early-morning ambulance ride down sleepy city streets toward an imposing concrete building. As the vehicle jostled my body to and fro, I tried to summon the energy to curse the psychiatrist whose signature ultimately sealed my fate—a hospital admission to protect me from myself—but was exhausted from the mixed episode in which I had been drowning for the last three days. I had been speaking much too rapidly (even for my normally quick tongue) and sleeping far too little to explain my body’s unrelenting state of hyperarousal. I was so agitated and irritable that even my parents avoided me lest I snap at them for no good reason. As my mood shattered into a thousand pieces, leaving me numb and questioning life, I begrudgingly accepted that I needed help. For ten days of intense cognitive behavioral group therapy, I avoided the dilemma posed by simultaneously being a young health care professional and a person with bipolar disorder by pretending to be someone else entirely. However, upon my release, I could no longer hide—returning to my everyday world would mean constantly being judged as two diametrically opposed forces.
CTLA4Ig inhibits T cell–dependent B-cell maturation in murine systemic lupus erythematosus
Authors: Masahiko Mihara, Irene Tan, Yelena Chuzhin, Bhoompally Reddy, Lalbachan Budhai, Aton Holzer, Yun Gu, Anne Davidson
Journal: Journal of Clinical Investigation (2000)

Long-term administration of CTLA4Ig prevents the onset of disease in systemic lupus erythematosus–prone (SLE-prone) NZB/NZW F1 mice. To determine the mechanism of this effect, we engineered an adenovirus that expresses murine CTLA4Ig. Administration of a single high dose of this virus results in long-term expression of CTLA4Ig in the serum and absence of an immune response to the adenoviral vector. We administered Ad-CTLA4Ig to 19- to 22-week-old NZB/NZW F1 mice and evaluated the effect on anti-DNA antibody–producing B cells. We show that CTLA4Ig has a beneficial effect on murine SLE for as long as it is present in the serum. This effect is associated with decreased expansion of both the IgM and IgG autoreactive B-cell population, inhibition of immunoglobulin class switching, decreased frequency and altered pattern of somatic mutation, and a marked decrease in the numbers of activated CD4-positive T cells. In contrast, intrinsic B-cell hyperreactivity and the survival of plasma cells in the bone marrow, both of which are less dependent on T-cell help, appear to be unaffected by CTLA4Ig. High-dose CTLA4Ig did not induce permanent tolerance in this autoimmune disease model. Furthermore, although the mice survived in a conventional housing facility, treatment with Ad-CTLA4Ig was immunosuppressive.
Production of B cell stimulatory factor-2 and interferon gamma in the central nervous system during viral meningitis and encephalitis. Evaluation in a murine model infection and in patients.
Authors: K Frei, T P Leist, A Meager, P Gallo, D Leppert, R M Zinkernagel, A Fontana
Journal: The Journal of Experimental Medicine (1988)

Synthesis of B cell-stimulating factor-2 (BSF-2) and IFN-gamma was shown in cerebrospinal fluids (CSF) collected from mice with experimental viral meningitis. In the CSF, the level of BSF-2 started to increase 24 h after intracerebral infection with lymphocytic choriomeningitis virus (LCMV) with rapid increase after day 4. IFN-gamma was not detected in the CSF before day 5 or 6 after infection, but increased sharply thereafter. In athymic nude mice, LCMV infection did not result in meningitis, and both BSF-2 and IFN-gamma levels were only slightly and transiently elevated. These findings suggest that activated mature T cells are required for development of disease and production of both BSF-2 and IFN-gamma. As observed in mice, BSF-2 was also detected in 16 out of 19 CSF samples collected from patients with acute viral infections of the central nervous system (CNS). Intrathecal production of BSF-2 and IFN-gamma may be instrumental in local production of antiviral antibodies by B lymphocytes/plasma cells invading the CNS during viral CNS disease.
Complete Mesocolic Excision With Central Vascular Ligation Produces an Oncologically Superior Specimen Compared With Standard Surgery for Carcinoma of the Colon
Authors: Nicholas P. West, Werner Hohenberger, Klaus Weber, Aristoteles Perrakis, Paul J. Finan, Philip Quirke
Journal: Journal of Clinical Oncology (2009)

The plane of surgery in colonic cancer has been linked to patient outcome although the optimal extent of mesenteric resection is still unclear. Surgeons in Erlangen, Germany, routinely perform complete mesocolic excision (CME) with central vascular ligation (CVL) and report 5-year survivals of higher than 89%. We aimed to further investigate the importance of CME and CVL surgery for colonic cancer by comparison with a series of standard specimens.The fresh photographs of 49 CME and CVL specimens from Erlangen and 40 standard specimens from Leeds, United Kingdom, for primary colonic adenocarcinoma were collected. Precise tissue morphometry and grading of the plane of surgery were performed before comparison to histopathologic variables.CME and CVL surgery removed more tissue compared with standard surgery in terms of the distance between the tumor and the high vascular tie (median, 131 v 90 mm; P < .0001), the length of large bowel (median, 314 v 206 mm; P < .0001), and ileum removed (median, 83 v 63 mm; P = .003), and the area of mesentery (19,657 v 11,829 mm(2); P < .0001). In addition, CME and CVL surgery was associated with more mesocolic plane resections (92% v 40%; P < .0001) and a greater lymph node yield (median, 30 v 18; P < .0001).Surgeons in Erlangen routinely practicing CME and CVL surgery remove more mesocolon and are more likely to resect in the mesocolic plane when compared with standard excisions. This, along with the associated greater lymph node yield, may partially explain the high 5-year survival rates reported in Erlangen.
A 30-Week Randomized Controlled Trial of High-Dose Tacrine in Patients With Alzheimer's Disease
Authors: Margaret J. Knapp
Journal: JAMA (1994)

To evaluate the efficacy and safety of high-dose tacrine hydrochloride over 30 weeks in patients with probable Alzheimer's disease.A 30-week randomized, double-blind, placebo-controlled, parallel-group trial.Outpatients at 33 US centers.Men and women at least 50 years of age with mild to moderate Alzheimer's disease and otherwise in good health.Group 1 received placebo; group 2 received 40 mg/d of tacrine for 6 weeks, then 80 mg/d for 24 weeks; groups 3 and 4 received 40 mg/d of tacrine for 6 weeks, 80 mg/d for 6 weeks, and 120 mg/d for 6 weeks. Group 3 remained on a dosage of 120 mg/d for a total of 18 weeks; after 6 weeks at 120 mg/d, group 4 titrated to 160 mg/d for the last 12 weeks.Clinician Interview-Based Impression (CIBI), Alzheimer's Disease Assessment Scale--Cognitive subscale (ADAS-Cog), and Final Comprehensive Consensus Assessment (FCCA).A total of 663 patients entered the study; 653 patients were included in an intent-to-treat (ITT) analysis; 263 had evaluable data at 30 weeks. The results of the ITT analysis revealed significant (P < or = .05) dose-response trends and between-group comparisons on CIBI and ADAS-Cog. In evaluable patients, significant dose-response trends were observed for all three primary measures (P < or = .001). Significant differences in favor of 160 mg/d of tacrine vs placebo were observed on the CIBI (P < or = .002) and ADAS-Cog and FCCA (P < or = .001), as well as caregiver-global and quality-of-life assessments (P < or = .05). On the CIBI, 23% and 42% of tacrine-treated patients in the ITT and evaluable-patient populations, respectively, were rated improved compared with 17% and 18% of placebo patients, respectively. The primary reasons for withdrawal of tacrine-treated patients were asymptomatic liver transaminase elevations (28%) and gastrointestinal complaints (16%). These adverse events were reversible on discontinuation of treatment, and many patients were able to restart tacrine.Tacrine produced statistically significant, dose-related improvements on objective performance-based tests, clinician- and caregiver-rated global evaluations, and measures of quality of life. There was no evidence that the large number of patient withdrawals biased the overall conclusions of the study.
The Quality of Survival in Response to Treatment
Authors: W. Bradford Patterson
Journal: JAMA (1975)

THE KIND of life a patient lives is as important as the fact that he is living. Physicians seldom argue over this basic premise. The quality of life, after all, is the major reason there is a medical prefession—because pain, anxiety, and other forms of misery are not happily tolerated by mankind. Recently, as we have learned to use more aggressive therapy and to continue it with life-sustaining ancillary aids, criticism has been raised that aggressive treatment often ignores patient welfare in the interest of science. The criticism is that therapy that prolongs life at a great cost in suffering, hospitalization, and money is a failure, not a success. Therefore, it is essential that we grapple with a criterion of response to therapy that deals with quality of life, knowing in advance that such criteria do not lend themselves easily to measurement and that we will presumably end up with
Follow up of people aged 65 and over with a history of emergency admissions: analysis of routine admission data
Authors: Martin Roland, Mark Dusheiko, Hugh Gravelle, Stuart Parker
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To determine the subsequent pattern of emergency admissions in older people with a history of frequent emergency admissions. <b>Design</b> Analysis of routine admissions data from NHS hospitals using hospital episode statistics (HES) in England. <b>Subjects</b> Individual patients aged  65,  75, and  85 who had at least two emergency admissions in 1997-8. <b>Main outcome measures</b> Emergency admissions and bed use in this "high risk" cohort of patients were counted for the next five years and compared with the general population of the same age. No account was taken of mortality as the analysis was designed to estimate the future use of beds in this high risk cohort. <b>Results</b> Over four to five years, admission rates and bed use in the high risk cohorts fell to the mean rate for older people. Although patients  65 with two or more such admissions were responsible for 38% of admissions in the index year, they were responsible for fewer than 10% of admissions in the following year and just over 3% five years later. <b>Conclusion</b> Patients with multiple emergency admissions are often identified as a high risk group for subsequent admission and substantial claims are made for interventions designed to avoid emergency admission in such patients. Simply monitoring admission rates cannot assess interventions designed to reduce admission among frail older people as rates fall without any intervention. Comparison with a matched control group is necessary. Wider benefits than reduced admissions should be considered when introducing intensive case management of older people.
Phosphate-Induced Vascular Calcification
Authors: Koba A. Lomashvili, Scott Cobbs, Randolph A. Hennigar, Kenneth I. Hardcastle, W. Charles O’Neill
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Hyperphosphatemia is thought to underlie medial vascular calcification in advanced renal failure, but calcification can occur in other conditions in the absence of hyperphosphatemia, indicating that additional factors are important. To identify these factors, a model of medial calcification in rat aorta in vitro was developed. Aortic rings from rats were incubated in serum-free medium for 9 d, and calcification was measured as incorporation of 45Ca and confirmed by histology and x-ray diffraction. No calcification occurred in normal vessels despite elevated free Ca2+ and PO43− concentrations of 1.8 mM and 3.8 mM, respectively, but mechanical injury resulted in extensive calcification in the media. Co-incubation studies revealed that normal aortas produced a soluble inhibitor of calcification in injured vessels that was destroyed by alkaline phosphatase. Culture of normal aortas with alkaline phosphatase resulted in calcification of the elastic lamina identified as hydroxyapatite by x-ray diffraction. This effect of alkaline phosphatase was not due to dephosphorylation of osteopontin (OPN), and calcification was not increased in aortas from OPN-deficient mice. The inhibitor was identified as pyrophosphate on the basis of the calcification induced in aortas cultured with inorganic pyrophosphatase, the inhibition of calcification in injured aortas by pyrophosphate, and the production of inhibitory levels of pyrophosphate by normal aortas. No calcification occurred under any conditions at a normal PO43− concentration. It is concluded that elevated concentrations of Ca2+ and PO43− are not sufficient for medial vascular calcification because of inhibition by pyrophosphate. Alkaline phosphatase can promote calcification by hydrolyzing pyrophosphate, but OPN is not an endogenous inhibitor of calcification in rat aorta.
Relationship Between Multiple Forms of Childhood Maltreatment and Adult Mental Health in Community Respondents: Results From the Adverse Childhood Experiences Study
Authors: Valerie J Edwards, George W Holden, Vincent J Felitti, Robert F Anda
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: This study examined the prevalence of a history of various combinations of childhood maltreatment types (physical abuse, sexual abuse, and witnessing of maternal battering) among adult members of a health maintenance organization (HMO) and explored the relationship with adult mental health of the combinations of types of childhood maltreatment and emotional abuse in the childhood family environment. METHOD: A total of 8,667 adult members of an HMO completed measures of childhood exposure to family dysfunction, which included items on physical and sexual abuse, witnessing of maternal battering, and emotional abuse in the childhood family environment. The adults’ current mental health was assessed by using the mental health scale of the Medical Outcomes Study 36-item Short-Form Health Survey. RESULTS: The prevalences of sexual abuse, physical abuse, and witnessing of maternal violence were 21.6%, 20.6%, and 14.0%, respectively, when the maltreatment types were considered separately. Among respondents reporting any of the maltreatment types, 34.6% reported more than one type of maltreatment. Lower mean mental health scores were associated with higher numbers of abuse categories (mean=78.5, 75.5, 72.8, and 69.9 for respondents with no, one, two, and three abuse types, respectively). Both an emotionally abusive family environment and the interaction of an emotionally abusive family environment with the various maltreatment types had a significant effect on mental health scores. CONCLUSIONS: Childhood physical and sexual abuse, as well as witnessing of maternal battering, were common among the adult members of an HMO in this study. Among those reporting any maltreatment, more than one-third had experienced more than one type of maltreatment. A dose-response relation was found between the number of types of maltreatment reported and mental health scores. In addition, an emotionally abusive family environment accentuated the decrements in mental health scores. Future research examining the effects of childhood maltreatment on adult mental health should include assessments of a wide range of abusive experiences, as well as the family atmosphere in which they occur.
Pulmonary disease following intravesical BCG treatment.
Authors: S Kesten, L Title, B Mullen, R Grossman
Journal: Thorax (1990)

Bacillus Calmette-Guérin (BCG) is an attenuated strain of Mycobacterium bovis that has been used in the treatment of malignant disease for over 20 years and for the treatment of bladder cancer since 1976. Major complications of this treatment are infrequent. We report two cases of systemic illness with pulmonary manifestations after treatment with intravesical BCG.
STUDIES ON THE SUPRARENAL CORTEX
Authors: George A. Harrop, Louis J. Soffer, William M. Nicholson, Margaret Strauss
Journal: The Journal of Experimental Medicine (1935)

1. A group of experiments is reported in which bilaterally suprarenalectomized adult male dogs have been maintained in apparently normal condition over prolonged periods, up to 5 months, without the use of any suprarenal gland preparation or extract and by the administration of sodium chloride and sodium bicarbonate alone. Withdrawal of the salts then produced typical suprarenal insufficiency. 2. The relation of the absence of free hydrochloric acid in the gastric juice of suprarenalectomized animals, in addition to, or independent of the factor of dehydration, for the production of anorexia and hypoglycemia, is discussed. 3. Further evidence is presented in these experiments in support of the view that the suprarenal cortical hormone in the adult male dog is concerned with the regulation of sodium excretion by the kidney, and thus eventually with the proper maintenance of water balance in the organism. It has no direct influence on carbohydrate metabolism. 4. The reciprocal changes in the plasma concentrations of urea and of potassium which take place as the concentrations of plasma sodium and chlorides vary, are pointed out as furnishing a mechanism whereby abrupt alterations in osmotic pressure are dampened, and the volumes of fluids in extracellular and intracellular compartments more efficiently stabilized.
Rate and predictors of treatment prescription for hepatitis C
Authors: A. A Butt, A. C Justice, M. Skanderson, M. O Rigsby, C. B Good, C K. Kwoh
Journal: Gut (2006)

<b>Background:</b> The true treatment rate for hepatitis C virus (HCV) in veterans is unknown. <b>Aim:</b> To determine the treatment prescription rates and predictors of treatment prescription for HCV in a large national population. <b>Methods:</b> The Department of Veterans Affairs National Patient Care Database (NPCD) was used to identify all HCV-infected people between the fiscal years 1999 and 2003 using the <i>International classification of diseases</i>, 9th revision codes. Demographic information, medical and psychiatric comorbidities, and drug and alcohol use diagnoses were retrieved. Pharmacy data were retrieved from the Department of Veterans Affairs Pharmacy Benefits Management (PBM) database. Logistic regression analysis was used to determine the predictors of treatment for HCV in HCV. <b>Results:</b> 113 927 veterans in the Department of Veterans Affairs care with a diagnosis of HCV were identified. The treatment prescription rate for HCV was 11.8%. Patients not prescribed treatment were older, more likely to be from minority races, have more alcohol and drug misuse, and have medical and psychiatric comorbid conditions. In a multivariate logistic regression model, the following factors were predictive of non-treatment for HCV: increasing age (odds ratio (OR) 0.77 for each 5-year increase in age; 95% confidence interval (CI) 0.76 to 0.78); black race (OR 0.64; 95% CI 0.6 to 0.68); Hispanic race (OR 0.88; 95% CI 0.8 to 0.96); alcohol abuse and dependence (OR 0.62; 95% CI 0.59 to 0.65); drug abuse and dependence (OR 0.78; 95% CI 0.74 to 0.82); anaemia (OR 0.18; 95% CI 0.16 to 0.21); hepatitis B infection (OR 0.72; 95% CI 0.62 to 0.83); coronary artery disease (OR 0.9; 95% CI 0.85 to 0.97); stroke (OR 0.75; 95% CI 0.67 to 0.85); bipolar disorder (OR 0.64; 95% CI 0.58 to 0.70); major depression (OR 0.72; 95% CI 0.67 to 0.77); mild depression (OR 0.56; 95% CI 0.53 to 0.59); and schizophrenia (OR 0.71; 95% CI 0.65 to 0.77). The following factors were associated with a higher likelihood of treatment prescription for HCV: liver cirrhosis (OR 1.6; 95% CI 1.5 to 1.7); and diabetes (OR 1.07; 95% CI 1.02 to 1.12). <b>Conclusions:</b> A small number of HCV-infected veterans were prescribed treatment for HCV. Non-treatment is associated with increasing age, non-white race, drug and alcohol abuse, and dependence and comorbid illnesses. Reasons for non-treatment need further study.
Is Leptin a Mediator of Adverse Prognostic Effects of Obesity in Breast Cancer?
Authors: Pamela J. Goodwin, Marguerite Ennis, I. George Fantus, Kathleen I. Pritchard, Maureen E. Trudeau, Jarley Koo, Nicky Hood
Journal: Journal of Clinical Oncology (2005)

Purpose Leptin, an adipocyte-derived cytokine that is elevated in obesity, has been associated with carcinogenesis, tumor migration and invasion, enhancement of angiogenesis, and increased aromatase activity. It has been suggested that leptin may mediate adverse prognostic effects of obesity in breast cancer. Patients and Methods Four hundred seventy-one women with surgically resected T1-3, N0-1, M0 breast cancer were studied. Leptin was assayed in stored fasting blood specimens obtained before adjuvant therapy. Women were followed prospectively for distant disease-free survival (DDFS) and overall survival (OS). Results Patients ranged from 26 to 74 years of age, and staging was as follows: T1 = 262, T2 = 151, T3 = 23, TX = 35, N0 = 323, and N1 = 148. Estrogen receptor was positive in 286 patients, and progesterone receptor was positive in 259 patients. One hundred forty-five patients received adjuvant chemotherapy, 146 received adjuvant tamoxifen, 46 received both, and 134 received neither. Mean leptin was 15.2 ± 10.1 ng/mL. Univariately, leptin was associated with OS (overall P = .049; P = .014 postmenopausal). Leptin was not associated with DDFS overall or in any menopausal subgroup (P ≥ .19). In multivariate Cox modeling, leptin was not significantly associated with DDFS or OS (P = .11 and 0.075, respectively). Adjustment for insulin or body mass index further reduced the association of leptin with outcome. Conclusion Although leptin is strongly correlated with obesity and insulin, we could not show that it is independently associated with prognosis in early-stage breast cancer. Because we cannot rule out modest prognostic effects, we recommend additional research to explore this potential association, particularly in postmenopausal women.
Micrometastases or Isolated Tumor Cells and the Outcome of Breast Cancer
Authors: Maaike de Boer, Carolien H.M. van Deurzen, Jos A.A.M. van Dijck, George F. Borm, Paul J. van Diest, Eddy M.M. Adang, Johan W.R. Nortier, Emiel J.T. Rutgers, Caroline Seynaeve, Marian B.E. Menke-Pluymers, Peter Bult, Vivianne C.G. Tjan-Heijnen
Journal: New England Journal of Medicine (2009)

The association of isolated tumor cells and micrometastases in regional lymph nodes with the clinical outcome of breast cancer is unclear.
A Novel Nanoparticulate Formulation of Arsenic Trioxide with Enhanced Therapeutic Efficacy in a Murine Model of Breast Cancer
Authors: Richard W. Ahn, Feng Chen, Haimei Chen, Stephan T. Stern, Jeffrey D. Clogston, Anil K. Patri, Meera R. Raja, Elden P. Swindell, Vamsi Parimi, Vincent L. Cryns, Thomas V. O'Halloran
Journal: Clinical Cancer Research (2010)

The clinical success of arsenic trioxide (As(2)O(3)) in hematologic malignancies has not been replicated in solid tumors due to poor pharmacokinetics and dose-limiting toxicity. We have developed a novel nanoparticulate formulation of As(2)O(3) encapsulated in liposomal vesicles or "nanobins" [(NB(Ni,As)] to overcome these hurdles. We postulated that nanobin encapsulation of As(2)O(3) would improve its therapeutic index against clinically aggressive solid tumors, such as triple-negative breast carcinomas.