tbuckley/cabot-search huggingface dataset:
Early Diagnosis of Complex Diseases by Molecular Biomarkers, Network Biomarkers, and Dynamical Network Biomarkers
Authors: Rui Liu, Xiangdong Wang, Kazuyuki Aihara, Luonan Chen
Journal: Medicinal Research Reviews (2013)

Abstract Many studies have been carried out for early diagnosis of complex diseases by finding accurate and robust biomarkers specific to respective diseases. In particular, recent rapid advance of high‐throughput technologies provides unprecedented rich information to characterize various disease genotypes and phenotypes in a global and also dynamical manner, which significantly accelerates the study of biomarkers from both theoretical and clinical perspectives. Traditionally, molecular biomarkers that distinguish disease samples from normal samples are widely adopted in clinical practices due to their ease of data measurement. However, many of them suffer from low coverage and high false‐positive rates or high false‐negative rates, which seriously limit their further clinical applications. To overcome those difficulties, network biomarkers (or module biomarkers) attract much attention and also achieve better performance because a network (or subnetwork) is considered to be a more robust form to characterize diseases than individual molecules. But, both molecular biomarkers and network biomarkers mainly distinguish disease samples from normal samples, and they generally cannot ensure to identify predisease samples due to their static nature, thereby lacking ability to early diagnosis. Based on nonlinear dynamical theory and complex network theory, a new concept of dynamical network biomarkers (DNBs, or a dynamical network of biomarkers) has been developed, which is different from traditional static approaches, and the DNB is able to distinguish a predisease state from normal and disease states by even a small number of samples, and therefore has great potential to achieve “real” early diagnosis of complex diseases. In this paper, we comprehensively review the recent advances and developments on molecular biomarkers, network biomarkers, and DNBs in particular, focusing on the biomarkers for early diagnosis of complex diseases considering a small number of samples and high‐throughput data (or big data). Detailed comparisons of various types of biomarkers as well as their applications are also discussed.
Etoposide achieves potentially cytotoxic concentrations in CSF of children with acute lymphoblastic leukemia.
Authors: M V Relling, H H Mahmoud, C H Pui, J T Sandlund, G K Rivera, R C Ribeiro, W M Crist, W E Evans
Journal: Journal of Clinical Oncology (1996)

PURPOSE Although epipodophyllotoxins are commonly used in contemporary treatment regimens for acute lymphoblastic leukemia (ALL), their potential role in CNS-directed therapy has received little attention. We prospectively studied 20 children during initial remission of ALL and 16 children at relapse to assess CSF penetration of etoposide. METHODS Simultaneous plasma and CSF concentrations were assessed at a median of 2.8 hours (range, 0.4 to 5.3) after an intravenous (i.v.) or oral dose in 41 paired samples. RESULTS Etoposide given at 300 mg/m2 i.v. to patients during first remission and at 50 or 25 mg/m2 orally to those in relapse resulted in median CSF levels of 0.175 mumol/L (range, .066 to 2.12), 0.011 mumol/L (range, .004 to .032), and 0.007 mumol/L (range, .003 to .014), respectively. The CSF etoposide concentration was &gt; or = 10 nmol/L in 20 of 20, five of 10, and two of 11 courses following 300 mg/m2 i.v., 50 mg/m2 orally, and 25 mg/m2 orally, respectively, and was positively related to both the concurrent etoposide plasma concentration (R2 = .64) and to dose (R2 = .73). The median ratio of CSF to plasma concentration was 0.30% (range, 0.09% to 3.12%), which was not related to dose, plasma concentration, or time postdose at which samples were obtained, but was positively correlated with the CSF protein concentration (R2 = 0.43, P = .006). Both the absolute etoposide CSF concentrations (P = .008) and the ratio of CSF to plasma concentrations (P = .023) were higher among first-remission patients who had CSF leukemic blasts at diagnosis compared with those without CSF blasts. CONCLUSION Because etoposide concentrations as low as 10 nmol/L may be cytotoxic in vitro, prolonged daily oral low-dose (50 mg/m2) or conventional i.v. doses of etoposide may contribute to successful CNS-directed therapy in children with ALL.
Acute undifferentiated human diarrhea in the tropics
Authors: S. L. Gorbach, J. G. Banwell, B. D. Chatterjee, B. Jacobs, R. B. Sack
Journal: Journal of Clinical Investigation (1971)

The microflora of the small and large intestine was determined in 17 adults with acute undifferentiated diarrhea in Calcutta, India. On the basis of bacteriologic findings, the patients could be divided into two groups: those with a predominant flora of Escherichia coli (eight patients) and those with a mixed coliform flora (nine patients). In the former group, E. coli were distributed throughout the small and large bowel. Broth filtrates of these isolates contained an enterotoxin which caused fluid accumulation in the rabbit intestinal loop model. Toxigenic E. coli were cleared rapidly from the small bowel during the acute period; some patients only had the "hot" strains in their fecal effluent. During convalescence, the serotypes of E. coli changed and the new strains did not elaborate enterotoxin. Only one of the eight patients had a serotype previously associated with diarrhea. Acute undifferentiated diarrhea in the remaining cases was apparently caused by untypable E. coli or by typable strains not generally considered pathogenic. Small bowel and fecal cultures from the mixed flora group revealed a heterogeneous mixture of Gram-negative enteric bacilli and a distinct pattern could not be discerned. Further study will be needed to elucidate the cause of diarrhea in these cases.
Glucose Metabolism and the Response to Insulin by Human Adipose Tissue in Spontaneous and Experimental Obesity
Authors: L. B. Salans, G. A. Bray, S. W. Cushman, E. Danforth, J. A. Glennon, E. S. Horton, E. A. H. Sims
Journal: Journal of Clinical Investigation (1974)

[1-(14)C]glucose oxidation to CO(2) and conversion into glyceride by adipose tissue from nonobese and obese subjects has been studied in vitro in the presence of varying medium glucose and insulin concentrations as functions of adipose cell size, the composition of the diet, and antecedent weight gain or loss. Increasing medium glucose concentrations enhance the incorporation of glucose carbons by human adipose tissue into CO(2) and glyceride-glycerol. Insulin further stimulates the conversion of glucose carbons into CO(2), but not into glyceride-glycerol. Incorporation of [1-(14)C]glucose into glyceride-fatty acids by these tissues could not be demonstrated under any of the conditions tested. Both adipose cell size and dietary composition influence the in vitro metabolism of glucose in, and the response to insulin by, human adipose tissue. During periods of ingestion of weight-maintenance isocaloric diets of similar carbohydrate, fat, and protein composition, increasing adipose cell size is associated with (a) unchanging rates of glucose oxidation and increasing rates of glucose carbon incorporation into glyceride-glycerol in the absence of insulin, but (b) decreasing stimulation of glucose oxidation by insulin. On the other hand, when cell size is kept constant, increasing dietary carbohydrate intake is associated with an increased basal rate of glucose metabolism and response to insulin by both small and large adipose cells. Thus, the rate of glucose oxidation and the magnitude of the insulin response of large adipose cells from individuals ingesting a high carbohydrate diet may be similar to or greater than that in smaller cells from individuals ingesting an isocaloric lower carbohydrate diet.The alterations in basal glucose metabolism and insulin response observed in adipose tissue from patients with spontaneous obesity are reproduced by weight gain induced experimentally in nonobese volunteers; these metabolic changes are reversible with weight loss. The relationships among adipose cell size, dietary composition, and the metabolism of adipose tissue are similar in spontaneous and in experimental obesity.
Sleep disordered breathing in pycnodysostosis patients
Authors: Nilay Bas Ikizoglu, Yasemin Gokdemir, Serap Turan, Zeynep Atay, Belma Haliloglu, Fazilet Karakoc, Bulent Karadag, Refika Ersu
Journal: European Respiratory Journal (2014)

Background:  Pycnodysostosis is an autosomal recessive disease characterized by short stature, osteosclerosis, increased bone fragility. In these patients maxillary and mandibular hypoplasia, flattening of the mandibular angle, long soft palate, narrow palate structure can lead to pharyngeal narrowing and obstructive sleep apnea syndrome (OSAS). Our aim was to evaluate sleep disordered breathing in children with pycnodysostosis.   Methods:  Demographic data, pediatric sleep questionnaire (PSQ) scores, polysomnography results and treatments of pycnodysostosis patients who were followed by Pediatric Endocrinology Department in Marmara University were evaluated.   Results:  Mean age of the eight patients (7 girls, one boy) in the study was 12.2 ± 4.2 years, mean age at diagnosis was 6.5 ± 4 years. Habituel snoring was reported in 7 (87%) and apnea during sleep was reported in 3 (37.5%) patients. Two patients had adenoidectomy and one had tonsillectomy. 4 patients (50%) received growth hormone. Mean PSQ score was 0.41 ± 0.19. Polysomnography revealed OSAS in six patients (75%). Two (25%) had severe and four (50%) had mild OSAS. OSAS was detected in 5 of 6 patients with PSQ score greater than 0.33. One of the two patients with PSQ score less than 0.33 had mild OSAS. OAHI ranged between 0-15.1 (median 2.9), central apnea index ranged between 0-2.1 (median 0.4). Mean SpO2 value was 94.5± 1.6% and lowest SpO2 value was 90.5 ± 3.5%. BPAP was started in three patients. Control PSG was planned for other patients during follow-up.   Conclusion:  Sleep related breathing disorders are frequent in pycnodysostosis and although PSQ can be used to screen, polysomnography should be offered to all patients with pycnodysostosis.
One hundred autotransplants for relapsed or refractory Hodgkin's disease and lymphoma: value of pretransplant disease status for predicting outcome.
Authors: A P Rapoport, J M Rowe, P A Kouides, R A Duerst, C N Abboud, J L Liesveld, C H Packman, S Eberly, M Sherman, M A Tanner
Journal: Journal of Clinical Oncology (1993)

PURPOSE One hundred autotransplants for Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) were examined prospectively to identify variables with prognostic significance. PATIENTS AND METHODS Ninety-six patients with relapsed or refractory HD or NHL underwent 100 autotransplants. Patients received high-dose carmustine (BCNU), etoposide, cytarabine, and cyclophosphamide (BEAC) followed by unpurged autologous stem-cell rescue. RESULTS The 3-year actuarial event-free survival (EFS) rate for the 47 HD patients is 49%, with a median followup duration of 2 years. For the 53 NHL patients, the 3-year actuarial EFS rate is 40%, with a median follow-up duration of 19 months. By multivariate analysis, minimal disease on admission (all areas &lt; or = 2 cm) is associated with improved EFS (HD, P = .003, NHL, P = .03). The projected EFS rate for HD patients entering with minimal disease is 70% versus 15% for patients with bulky disease (P = .0001). The projected EFS rate for NHL patients with minimal disease is 48% versus 25% for patients with bulky disease (P = .04). Posttransplant involved-field radiotherapy, administered to 26 of the last 61 patients, was associated with an improved EFS rate for NHL patients (P = .015). The BEAC regimen was well tolerated by patients who entered the study with minimal disease (mortality rate, &lt; 5%), but caused significant toxicity in patients with bulky disease (mortality rate, 25%). CONCLUSION Disease burden before autotransplantation is an important predictor of regimen-related toxicity and EFS. Posttransplant involved-field radiotherapy may improve outcomes in select patients with NHL. The BEAC regimen is safe and effective, particularly for patients with minimal disease.
Importance of Angina in Patients With Coronary Disease, Heart Failure, and Left Ventricular Systolic Dysfunction
Authors: E. Marc Jolicœur, Allison Dunning, Serenella Castelvecchio, Rafal Dabrowski, Myron A. Waclawiw, Mark C. Petrie, Ralph Stewart, Pardeep S. Jhund, Patrice Desvigne-Nickens, Julio A. Panza, Robert O. Bonow, Benjamin Sun, Tan Ru San, Hussein R. Al-Khalidi, Jean L. Rouleau, Eric J. Velazquez, John G.F. Cleland
Journal: Journal of the American College of Cardiology (2015)
Phase II trial of preoperative radiation therapy and chemotherapy for patients with localized, resectable adenocarcinoma of the pancreas: an Eastern Cooperative Oncology Group Study.
Authors: J P Hoffman, S Lipsitz, T Pisansky, J L Weese, L Solin, A B Benson
Journal: Journal of Clinical Oncology (1998)

PURPOSE A prospective, multiinstitutional trial was initiated in 1991 to examine the tolerance to and efficacy of a program of preoperative chemoradiotherapy (CTRT) and surgical resection for patients with localized adenocarcinoma of the pancreas. PATIENTS AND METHODS Fifty-three patients were assessable for analysis, with a median follow-up of 52 months for survivors. Radiation therapy (RT) totaling 5,040 cGy in 180 cGy fractions with mitomycin 10 mg/m2 day 2 and fluorouracil (5-FU) 1,000 mg/m2/d continuous infusion days 2 through 5 and 29 through 32 were given as preoperative adjuvant therapy. Twelve patients did not proceed to surgery (one death, one toxicity, three local progression, six distant metastases, one intercurrent illness), whereas 41 patients underwent surgery. Of these, 17 patients did not have resection (11, hepatic and/or peritoneal metastases and six local extension that precluded resection). Twenty-four patients had tumor resection (19 Whipple, four total pancreatectomy, one distal pancreatectomy). RESULTS Treatment toxicity was primarily hematologic, although a comparable number suffered biliary tract complications, either from obstruction or cholangitis as a result of an occluded stent or the primary tumor. There was one postoperative death. Median survival for the entire group and for the 24 patients with resection was 9.7 and 15.7 months. This survival rate reflected the advanced state of most resected cancers (positive peritoneal cytology, three patients; margins within 2 mm, 13 patients; involved lymph nodes, four patients; and need for superior mesenteric vein (SMV) resection, four patients). Tumor progression was most frequent at metastatic sites. CONCLUSION This preoperative CTRT protocol was feasible and safe in a cooperative group setting. Entry of patients with advanced tumors probably accounted for the suboptimal resectability and survival results.
Anemia in hemodialysis patients
Authors: F Madore, E G Lowrie, C Brugnara, N L Lew, J M Lazarus, K Bridges, W F Owen
Journal: Journal of the American Society of Nephrology (1997)

Despite the prevalent use of recombinant human erythropoietin (rhEPO), anemia is a frequent finding in hemodialysis patients. The goal of this study was to evaluate the impact of anemia on patient survival and characterize the determinants of hematopoiesis that may be amenable to therapeutic manipulation to enhance rhEPO responsiveness and reduce death risk. Patient characteristics and laboratory data were collected for 21,899 patients receiving hemodialysis three times per week in dialysis centers throughout the United States in 1993. Hemoglobin concentrations (Hb) < or =80 g/L were associated with a twofold increase in the odds of death (odds ratio = 2.01; P = 0.001) when compared with Hb 100 to 110 g/L. No improvement in the odds of death was afforded for Hb >110 g/L. Using multiple linear regression, variables of rhEPO administration (rhEPO dose and percentage of treatments that rhEPO was administered), variables of iron status (serum iron, transferrin saturation, and ferritin), variables of nutritional status (serum albumin and creatinine concentration), and the dose of dialysis (urea reduction ratio) were found to be significantly associated with hemoglobin concentration (P < 0.001). Age, race, and gender were also found to be significantly associated with hemoglobin concentrations (P < 0.001). From this report, the following conclusions may be made. (1) Anemia may be predictive of an increased risk of mortality in some hemodialysis patients. (2) Hemoglobin concentrations > 110 g/L are not associated with further improvements in the odds of death. (3) Laboratory surrogates of iron stores, nutritional status, and the delivered dose of dialysis are predictive of hemoglobin concentration. Whether manipulation of the factors that improve anemia will also enhance the survival of patients on hemodialysis is unknown and should be evaluated by prospective, interventional studies.
Quantitative computed tomography (QCT) measured 5th generation airways, emphysema and airflow obstruction in chronic obstructive pulmonary disease (COPD) from a COPDMAP cohort
Authors: Ruth Hartley, Bethan Barker, Mini Pakkal, Aparna Desphande, Chris Brightling, Sumit Gupta
Journal: European Respiratory Journal (2014)

Background:  Airflow obstruction in COPD is due to small airway obliteration and emphysema. QCT can be used to measure airway geometry in airways bigger than 2mm diameter. Whether the absence of visible 5th generation airways is associated with airflow obstruction and emphysema is unknown.   Aims:  Use QCT to describe presence and size of 5 th  generation segmental airways and explore relationships with lung function in COPD.   Methods:  COPD MAP subjects underwent low dose thoracic CT (Siemens 16) and spirometry. Fully automated software (Apollo,VIDA Diagnostics, Iowa) was used for post processing of CT scans. Patients were divided into 2 groups according to whether or not 15 or more 5 th  generation segmental bronchi were visualised by CT. Spirometry was correlated with QCT measured emphysema (Percentile 15) and airway morphometry (mean percentage wall area [%WA]) for 5 th  generation airways).   Results:  86 patients were recruited; 67% male, 81% ex-smokers, with mean (SEM) age 69(1) years, and post-bronchodilator FEV 1  % predicted and FEV 1 /FVC ratio of 54(2)% and 52(1)% respectively. Subjects with 15 or more 5th generation airways visible had higher mean (SEM) FEV 1  % predicted (57[2]% versus 48[3]% ; p=0.024) and less severe QCT determined emphysema (-959.03[2.51] versus -972.47[3.93]; p   Discussions:  In COPD obliteration of smaller airways determined from QCT reconstructed airways is associated with more airflow obstruction and emphysema. The role of QCT in evaluating small airways disease, and the clinical implications of these observations require further investigation.
Sex Differences in Pharmacokinetics and Pharmacodynamics
Authors: Monica Gandhi, Francesca Aweeka, Ruth M. Greenblatt, Terrence F. Blaschke
Journal: The Annual Review of Pharmacology and Toxicology (2004)

The importance of reviewing and studying sex-based differences in pharmacologic parameters is demonstrated by the increasing data on gender variation in drug efficacy and toxicity profiles. Sex-based differences in the four major factors that contribute to interindividual pharmacokinetic variability—bioavailability, distribution, metabolism, and elimination—are theorized to stem from variations between men and women in factors such as body weight, plasma volume, gastric emptying time, plasma protein levels, cytochrome P450 activity, drug transporter function, and excretion activity. Sex-determined variations in pharmacodynamics have traditionally been more difficult to study, but a number of recent studies have explored these differences. This review examines the biologic basis of differences in pharmacokinetics and pharmacodynamics between the sexes and summarizes studies that have addressed these differences. As an example, sex-based variation in the efficacy and toxicity of antiretroviral therapy in human immunodeficiency virus (HIV)-infected patients is explored more thoroughly to illustrate some of the factors underlying sex-based differences in drug therapy.
Tuberculosis (TB) and depression
Authors: Neli Macharashvili, Maia Archvadze, Lamara Vashakidze
Journal: European Respiratory Journal (2013)

Data on depression among TB patients are scarce.

AIM of study was to determine frequency and forms of depression among TB patients and optimization of its management.Research was conducted at NCTL among 180 patients of 18-60 age (after written consent).I group -130 patients with resistant TB, where stress factor was newly determined presence of MDRTB: II group -50 patients “new cases”, where stress factor was newly diagnosed TB.Depression screening was done by PHR-11 questionnaire,evaluation of its stage and patient’s psycho-type was conducted by Beki 21 questionnaire test and Lusher test.

Results. Research showed presence of any form of depression among all 150 MDRTB patients.From 92 men 22 (16,9%) had mild,28 (21,5%)-moderate and 42 (32,3%) severe forms of depression.Among 58 women,14 (10,7%) had mild,16 (12,3%)-moderate and 28 (21,5%) severe forms.

Depression was also revealed in all cases of newly diagnosed TB-50 patients.Among them 17 (34,1%) mild,20 (40)%) –moderate ,13 (26%)-severe forms.The moderate and severe forms required psychiatrist and/or psychologist’s help and medicament treatment (neuroleptic,antidepressant).Mild forms needed no interference.

Conclusion: Newly determined TB,just as newly determined presence of resistant form,as a rule,causes existence of different forms of depression (as a result of stigma,fear of socio-economic problems,etc).Depression screenibg and its relevant management is necessary among all TB patients,because it’s one of the mains terms of TB patients’ compliance to anti-TB treatment and its efficiency.
Results of Species-Specific Hemagglutination Tests on “Transformed,” Nontransformed, and Primary Cell Cultures&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: K. G. Brand, J. T. Syverton
Journal: JNCI Journal of the National Cancer Institute (1962)

Experiences with and technical modifications of the hemagglutination and absorption tests for species determination of cultivated mammalian cells are described. A report is presented on experimental species determination of 17 “transformed” and 14 non transformed established cell strains. Primary cell cultures of corresponding species served as controls. The transformed cell strains tested were reportedly derived from human, monkey, rabbit, swine, calf, hamster, or duck tissues. All were found not to belong to the species of stated or assumed origin, but were either of mouse or human species. The significance of these findings in respect to the so-called cell “transformation” phenomenon is discussed.