tbuckley/cabot-search huggingface dataset:
Prognostic significance of Ki-67 immunostaining in nonmetastatic renal cell carcinoma.
Authors: W T de Riese, W N Crabtree, E P Allhoff, M Werner, S Liedke, G Lenis, J Atzpodien, H Kirchner
Journal: Journal of Clinical Oncology (1993)

PURPOSE Fresh tissue samples from nonmetastatic renal cell carcinoma (RCC) patients were analyzed by Ki-67 immunostaining to determine the prognostic significance of this tumor-biologic parameter. MATERIALS AND METHODS In a prospective study, Ki-67 immunostaining was performed on frozen sections of histologically proven node-negative RCC from 58 patients operated on between 1986 and 1988 to examine the method's prognostic value and its association with other clinicopathologic parameters such as tumor stage (pT) and grade (G). RESULTS The percentage of Ki-67-positive cells (ie, the proliferation rate [PR]) of all 58 RCC tumors ranged between 1% and 23%, while normal renal tissue exhibited PRs up to 2% only. In almost all cases, the highest PRs were observed in the peripheral zone of malignant tissue close to the normal renal tissue. PR did not correlate with pT, whereas a strongly significant correlation was observed between PR and G, as well as recurrence rate. Twenty-three of 58 patients (39.6%) developed tumor recurrence. Disease-free survival was strongly associated with PR. In a multivariate analysis, G and PR were independent prognostic markers. CONCLUSION The tumor-specific PR obtained by Ki-67 labeling seems to be an independent marker to describe the proliferative activity and aggressiveness of individual tumors. This new tumor-biologic marker detects RCC patients at high risk for recurrent disease, especially in those cases with identical pT and G.
Rebound of overdose mortality in the European Union 2003-2005: findings from the 2008 EMCDDA Annual Report
Authors: J Vicente, I Giraudon, J Matias, D Hedrich, L Wiessing
Journal: Eurosurveillance (2009)

Drug overdose is an important cause of death among young adults in Europe. According to data reported by Member States to the EMCDDA, many of the European Union countries reported a rebound in the numbers of overdose deaths in 2003-2005, following decreases in almost all reporting countries in previous years (2000 to 2003). Further investigations are needed in order to clarify the factor driving these increases and inform policies and interventions aimed at reducing these deaths.
Risks From Radon Progeny Exposure: What We Know, and What We Need to Know
Authors: R A Guilmette, N F Johnson, G J Newton, D G Thomassen, H C Yeh
Journal: The Annual Review of Pharmacology and Toxicology (1991)

Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin (IX), into equimolar amounts of Fe2+, carbon monoxide (CO), and biliverdin. The stress-responsive HO-1 isoenzyme affords protection against programmed cell death. The mechanism ...Read More
The STAR Trial: Evidence for Raloxifene as a Breast Cancer Risk Reduction Agent for Postmenopausal Women
Authors: Therese B. Bevers
Journal: Journal of the National Comprehensive Cancer Network (2007)

The 1998 approval of tamoxifen for breast cancer risk reduction opened the era of breast cancer chemoprevention. Women at increased risk for breast cancer now had an option other than healthy lifestyle and prophylactic surgery to reduce risk. However, women and their physicians were reluctant to use tamoxifen because of associated risks. Several trials investigating raloxifene suggested it may reduce breast cancer risk without having an apparent effect on the endometrium. The Study of Tamoxifen and Raloxifene (STAR) for the Prevention of Breast Cancer trial opened in 1999 to directly compare raloxifene to tamoxifen for breast cancer risk reduction. Since the unblinding of the STAR trial in 2006, raloxifene has emerged as an option for reducing breast cancer risk for postmenopausal women at increased risk for the disease.
Inflammation and Specific Symptoms of Depression
Authors: Markus Jokela, Marianna Virtanen, G. David Batty, Mika Kivimäki
Journal: JAMA Psychiatry (2015)

This cross-sectional survey tested the hypothesis that the association between C-reactive protein and depression is symptom-specific using 3 cross-sectional studies: the NHANES of 2005-2006, 2007-2008, and 2009-2010.
PSYCHIATRIC REACTION PATTERNS TO IMIPRAMINE
Authors: DONALD F. KLEIN, MAX FINK
Journal: American Journal of Psychiatry (1962)

1. One hundred and eighty voluntary inpatients (102 schizophrenic subjects, 67 subjects with affective disorders, and 11 "other" diagnoses) were studied during treatment with imipramine. 2. Seven imipramine induced behavioral reaction patterns and their relationships to diagnosis, age, sex, patterns of medication use, and hospital discharge evaluation are presented. These include mood elevation, explicit verbal denial, manic, reduction of episodic anxiety, agitated disorganization, anhedonic socialization, and non-response. 3. Imipramine was favorably evaluated in 79% of subjects with affective disorders and 51% of schizophrenic patients. 4. The use of psychiatric reaction patterns to psychotropic drugs for categorizing patients and providing a basis for a more rational pharmacotherapy are emphasized.
The Neurobiology of Infantile Autism
Authors: A L Ciaranello, R D Ciaranello
Journal: Annual Review of Neuroscience (1995)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Safety of human immunisation with a live-attenuated Mycobacterium tuberculosis vaccine: a randomised, double-blind, controlled phase I trial
Authors: François Spertini, Régine Audran, Reza Chakour, Olfa Karoui, Viviane Steiner-Monard, Anne-Christine Thierry, Carole E Mayor, Nils Rettby, Katia Jaton, Laure Vallotton, Catherine Lazor-Blanchet, Juana Doce, Eugenia Puentes, Dessislava Marinova, Nacho Aguilo, Carlos Martin
Journal: The Lancet Respiratory Medicine (2015)
Red Cell Enzyme Deficiencies as a Cause of Hemolytic Disorders
Authors: W N Valentine
Journal: Annual Review of Medicine (1972)

The human red cell, biologically speaking, is intriguingly but deceptively simplistic. Freely floating, separable from contaminating cell types, devoid of a nucleus and cellular organelles, restricted in its energy needs and in the mechanisms for meeting them, it can be biopsied repeatedly with safety and offers many lures to the investigator. In recent years its enzymatic machinery has been explored with increasing intensity, and a variety of genetically determined inborn errors have been demonstrated (Valentine, 1, 2; Jaffe, 3). Some have been associated etiologically with hereditary hemolytic disease, and some have clarified mechanisms of what formerly were regarded as idiosyncratic reactions to drugs. Some have provided a convenient diagnostic tool for defining diseases not characterized by he­ matopoietic abnormalities. In still others, the definition of genetically de­ termined enzymopathy has been a curiosity with no counterpart in clinical disease.
NNK-induced DNA damage as measured by the comet assay is a marker of lung cancer risk
Authors: Maosheng Huang, Margaret Spitz, Yimin Zhu, Xifeng Wu
Journal: Cancer Research (2008)

1887    Purposes:  Reduced capacity to repair mutagen-induced DNA damage is implicated in susceptibility to cancer development. The nicotine-derived nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induced lung adenocarcinogen through formation of DNA adducts.  Methods:  We used the comet assay to assess whether susceptibility to NNK-induced DNA damage was associated with increased risk of lung cancer in a hospital-based case-control study. We measured baseline and NNK-induced DNA damage in peripheral blood lymphocyte assays from 401 previously untreated Caucasian lung cancer cases and 388 matched healthy controls. DNA damage using NNK as the mutagen challenge was visualized with the comet assay and quantified by the Olive tail moment parameter. Multivariable analysis was used to assess risks for lung cancer associated with level of DNA damage.  Results:  The baseline levels of DNA damage were statistically significantly higher in cases than in controls (tail moments: 1.22±0.57 vs. 1.14±0.50, P =0.025), as were NNK-induced DNA damage (2.42±1.15 vs. 2.16±1.07, P =0.001). The net NNK-induced DNA damage (NNK-induced subtracted by baseline) was also significantly higher in cases compared with controls (1.20 vs. 1.03, P = 0.018). When data were dichotomized at the median value of olive tail moments in the controls and adjusted for age, sex, and smoking status, higher levels of net NNK-induced DNA damage were associated with a significantly increased lung cancer risk (odds ratio [OR] = 1.45, 95% CI = 1.09 to 1.94). In addition, there was also a significant dose effect. Compared to individuals in the lowest quartile of damage, the ORs for individuals in the second, third and fourth quartiles were 1.32 (95% CI: 0.86-2.03), 1.59 (95% CI: 1.04-2.43), and 1.78 (95% CI: 1.17-2.70), respectively (P-for trend =0.005). In stratified analysis, the elevated risk appeared to be higher in adenocarcinoma (OR=1.50, 95% CI: 1.05-2.13) than in other histologies (OR=1.38, 95% CI, 0.95-2.00), and higher in heavy smokers (OR=1.64, 95% CI: 1.09-2.47) than in light smokers (OR=1.49, 95% CI, 0.79-2.79).  Conclusions:  This is the first study to use NNK as a challenge mutagen in the comet assay. The results suggest that NNK-induced DNA damage is associated with an increased risk of lung adenocarcinoma and the net NNK-induced olive tail moment measure may serve as a useful predictor of lung cancer risk.  Supported by NCI grants CA 55769, CA 70907 and CA 86390.
Abstract 5549: Anti-proliferative effect of Oman's medicinal plants derived active principles on breast cancer cells (MDA MB 231)
Authors: Lukmanul Hakkim
Journal: Cancer Research (2015)

Abstract Breast cancer (BC) is leading cause of death among females in United States and it is one of the emerging threats in Oman. Heavy doses of current clinical drugs are too toxic to patient and often failed to abort the recurrence after therapy. Despite huge number of reports on development of breast cancer chemotherapeutic drugs, median survival of BC patients not improved due to extreme ongoing and post treatment toxicity. Searching of drugs which can kill BC cells in a low dose by sparing normal cells is life time goal of many cancer researchers. Keeping the above fact in mind, we searched for potential natural products from Oman's medicinal plants which can kill BC cells potentially. We tested different doses (25, 50, 75 and 100 μg/ml) of sixty crude extracts and seventeen pure compounds obtained from Omani medicinal plants along with different dilutions (1:1000, 1:1500 and 1:2000 - prepared in medium) of Omani frankincense derived heavy oil for their ability to induce the cell death in MDA MB 231 cells with normal skin fibroblast as control. Doxorubicin used as positive drug control. After 24 hrs cells were checked for cell viability by MTT assay. We set the criteria to select the potent anti-cancer active principle out of tested extracts and compounds that it should induce more than 50% cell death in ≤ 50 μg/ml drug concentration. As per this end point, fifteen extracts induced cell death in the range of 60%-90% and five pure compounds killed MDA MB 231 cells in the range of 75%-90%. Noticeably heavy oils can induce 90% cell death in very low dose (1:2000 dil.) of treatment by sparing normal skin fibroblast. Although it is primitive data, but this forms rationale for us to test this oil and other compounds and extracts in in vivo BC xenograft model and subsequently on BC heterogeneity, recurrence and metastasis. Citation Format: Lukmanul Hakkim. Anti-proliferative effect of Oman's medicinal plants derived active principles on breast cancer cells (MDA MB 231). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5549. doi:10.1158/1538-7445.AM2015-5549
Scale-up of HIV Viral Load Monitoring — Seven Sub-Saharan African Countries
Authors: Shirley Lecher, Dennis Ellenberger, Andrea A. Kim, Peter N. Fonjungo, Simon Agolory, Marie Yolande Borget, Laura Broyles, Sergio Carmona, Geoffrey Chipungu, Kevin M. De Cock, Varough Deyde, Marie Downer, Sundeep Gupta, Jonathan E. Kaplan, Charles Kiyaga, Nancy Knight, William MacLeod, Boniface Makumbi, Hellen Muttai, Christina Mwangi, Jane W. Mwangi, Michael Mwasekaga, Lucy W. Ng'Ang'A, Yogan Pillay, Abdoulaye Sarr, Souleymane Sawadogo, Daniel Singer, Wendy Stevens, Christiane Adje Toure, John Nkengasong
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

To achieve global targets for universal treatment set forth by the Joint United Nations Programme on human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (UNAIDS), viral load monitoring for HIV-infected persons receiving antiretroviral therapy (ART) must become the standard of care in low- and middle-income countries (LMIC) (1). CDC and other U.S. government agencies, as part of the President's Emergency Plan for AIDS Relief, are supporting multiple countries in sub-Saharan Africa to change from the use of CD4 cell counts for monitoring of clinical response to ART to the use of viral load monitoring, which is the standard of care in developed countries. Viral load monitoring is the preferred method for immunologic monitoring because it enables earlier and more accurate detection of treatment failure before immunologic decline. This report highlights the initial successes and challenges of viral load monitoring in seven countries that have chosen to scale up viral load testing as a national monitoring strategy for patients on ART in response to World Health Organization (WHO) recommendations. Countries initiating viral load scale-up in 2014 observed increases in coverage after scale-up, and countries initiating in 2015 are anticipating similar trends. However, in six of the seven countries, viral load testing coverage in 2015 remained below target levels. Inefficient specimen transport, need for training, delays in procurement and distribution, and limited financial resources to support scale-up hindered progress. Country commitment and effective partnerships are essential to address the financial, operational, technical, and policy challenges of the rising demand for viral load monitoring.
Selection of Active Drugs for Ovarian Cancer Based on CA-125 and Standard Response Rates in Phase II Trials
Authors: Gordon J. S. Rustin, Ann E. Nelstrop, Søren M. Bentzen, Simon J. Bond, Patrick McClean
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To determine whether precise definitions of response based on serial CA-125 levels can predict the activity of drugs in phase II trials for ovarian cancer as accurately as standard criteria. PATIENTS AND METHODS: Fourteen different drugs for relapsed ovarian cancer were analyzed in 25 treatment groups in 19 clinical trials. Response rates were estimated in 1,457 assessable patients according to standard criteria and in 1,092 assessable patients according to CA-125. For each drug trial, the observed response rates acted as the input data for an evaluation of how the two criteria would perform in a hypothetical Gehan two-stage phase II trial, accepting a target drug efficacy rate of 20% and a rejection error of 5%. RESULTS: CA-125 and clinical response criteria were concordant in 20 of the 25 groups, with less than 5% chance of rejecting the drug in nine groups and greater than 5% in 11 groups. In four groups, the drug had less than 5% chance of being rejected by CA-125 but greater than 5% chance of being rejected by standard criteria. The difference in the classification of drugs by the standard and CA-125 response criteria was not statistically significant (P = .38, McNemar’s test). CA-125 response rates were slightly higher than standard response rates by a factor of 1.11. CONCLUSION: Definitions based on a 50% or 75% decrease of CA-125 levels accurately predicted which drugs in phase II trials for relapsed ovarian cancer were active and justified further investigation.
Philip E. Cryer, MD: Seminal Contributions to the Understanding of Hypoglycemia and Glucose Counterregulation and the Discovery of HAAF (Cryer Syndrome)
Authors: Samuel Dagogo-Jack
Journal: Diabetes Care (2015)

Optimized glycemic control prevents and slows the progression of long-term complications in patients with type 1 and type 2 diabetes. In healthy individuals, a decrease in plasma glucose below the physiological range triggers defensive counterregulatory responses that restore euglycemia. Many individuals with diabetes harbor defects in their defenses against hypoglycemia, making iatrogenic hypoglycemia the Achilles heel of glycemic control. This Profile in Progress focuses on the seminal contributions of Philip E. Cryer, MD, to our understanding of hypoglycemia and glucose counterregulation, particularly his discovery of the syndrome of hypoglycemia-associated autonomic failure (HAAF).
NITROUS OXIDE ANOXIA IN THE TREATMENT OF SCHIZOPHRENIA
Authors: E. J. FOGEL, L. P. GRAY
Journal: American Journal of Psychiatry (1940)

1. Nitrous oxide anoxia has given good results in the treatment of early cases of schizophrenia. 2. Chronic cases, whose illness was over 2 years in duration were unchanged. 3. It is a relatively safe method in the hands of a skilled anæsthetist. The dangers of respiratory failure and irreversible damage to the brain must be remembered. 4. Nitrous oxide anoxia is less time consuming than hypoglycemia, and therefore is available to a larger group of patients. 5. The treatment is less strenuous on the patient and most of them enjoy the daily bout. 6. No accidents or untoward effects have been experienced in our series. 7. Whereas the number of cases treated so far is too small to have much statistical validity, we feel that our results are sufficiently good to warrant treating early cases by this method first. If they fail to improve after a fair trial, they can be transferred to insulin treatment. 8. This technique might be used in general hospitals in treating early cases of schizophrenia.
LEUKOCYTE ADHESION DEFICIENCY: An Inherited Defect in the Mac-1, LFA-1, and p150,95 Glycoproteins
Authors: D C Anderson, T A Springer
Journal: Annual Review of Medicine (1987)

Leukocyte adhesion deficiency (LAD) is a recently recognized autosomal-recessive trait characterized by recurrent bacterial infections, impaired pus formation and wound healing, and abnormalities in a wide spectrum of adherence-dependent functions of granulocytes, monocytes, and lymphoid cells. Features of this disease are attributable to deficiency (or absence) of cell surface expression of a family of functionally and structurally related glycoproteins. These include Mac-1 (complement receptor type 3), lymphocyte function-associated antigen-1 (LFA-1), and p150,95. Defective biosynthesis of the beta chain shared by each molecule (comprised of alpha 1 beta 1 complexes) represents the fundamental molecular basis of this disease. Recognition of the molecular pathogenesis of this disorder has allowed rich insights into the role of cellular adherence reactions in inflammation and host defense.
Infection with Virus of Herpes Simplex
Authors: R. H. Kipping, A. W. Downie
Journal: BMJ (1948)

MEDiBCRTLISOURNA 247 responded to a period of rest in bed and sanatorium regime now failed to show such response, collapse therapy being required on an ever-increasing scale.The records for the years 1940 to 1946 were inspected and the amount of collapse therapy carried out during those years calculated, with the results shown in the Table.The figures suggest that the impression of less satisfactory pulmonary healing is correct, and it would appear reason- able to regard the stringent dietetic restrictions to which the patient has been subjected as an important causal factor in the absence of clear-cut evidence pointing to any other cause operating on a general basis throughout the sana- torium.It is much more difficult to assess the degree to which the curtailment of a specific element in the diet has been responsible; for experimental evidence of the part 'played by protein, carbohydrate, or fat in influencing resis- tance to tuberculosis is scanty and inconclusive.It is worth mentioning, however, that one of the most interesting and best-documented studies of nutrition and tuberculosis (Faber, 1938) adduces evidence to show that the rise in tuberculosis mortality in Denmark during the First World War was associated particularly with a deficiency of pro- tein in the diet.In Britain it has been possible to maintain the total calorie intake by the use of carbohydrates, but the protein and fat content of the rationed diet has suffered severely, and the weight graphs suggest that the fluctuations 'in the meat and cheese rations are of significance.The importance of adequate protein for the tuberculous patient was recognized in America, where Ration Boards were em- powered to grant extra meat allocations to patients suffering from the disease (Pottenger and Pottenger, 1946).Summary Observations on the weight records of sanatorium patients during the years of rationing show that from 1943 onwards the average patient failed to show a gain in weight comparable with the gains recorded in pre-rationing years.This failure to gain weight satisfactorily was accompanied by a diminution in the powers of natural healing of the disease.It is impossible on the evidence to indicate definitely the specific elements lacking in the rationed diet, but there is a suggestion that the curtailment of protein and fat (meat and 'cheese) may be of significance.
Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer.
Authors: P A Greenberg, G N Hortobagyi, T L Smith, L D Ziegler, D K Frye, A U Buzdar
Journal: Journal of Clinical Oncology (1996)

To determine the long-term clinical course of patients with metastatic breast cancer (MBC) who achieved a complete remission with doxorubicin-alkylating agent-containing combination chemotherapy programs.To assess the long-term prognosis of MBC, we reviewed our experience with 1,581 patients treated on consecutive doxorubicin and alkylating agent-containing front-line treatment protocols between 1973 and 1982. Treatment was administered for a maximum duration of 2 years. Characteristics of long-term survivors were evaluated, and hazard rates for progression were calculated.From this group, 263 (16.6%) achieved complete responses (CR) and 49 (3.1%) remained in CR for more than 5 years. After a median duration of 191 months, 26 patients remain in first CR, four patients died in CR at times ranging from 118 to 234 months, 18 patients died of breast cancer, and one is alive with metastatic disease. Compared with the overall CR and total patient populations, the long-term CR group had more premenopausal patients, a younger median age, a lower tumor burden, and better performance status. The hazard function shows a substantial drop in risk of progression after approximately 3 years from initiation of therapy. Ten long-term CR patients developed second primary cancers: breast (3), ovary (2), pancreas (1), endometrium (1), colon (1), head and neck (1), and lung (1).Most patients with MBC treated with systemic therapies have only temporary responses to treatment, but some patients continue in CR following initial treatment. These data show that a small percentage of patients achieve long-term remissions with standard chemotherapy regimens. Remission consolidation strategies are needed.