tbuckley/cabot-search huggingface dataset:
<i>In Utero p</i> , <i>p</i> ′-DDE Exposure and Infant Neurodevelopment: A Perinatal Cohort in Mexico
Authors: Luisa Torres-Sánchez, Stephen J. Rothenberg, Lourdes Schnaas, Mariano E. Cebrián, Erika Osorio, Maria del Carmen Hernández, Rosa M. García-Hernández, Constanza del Rio-Garcia, Mary S. Wolff, Lizbeth López-Carrillo
Journal: Environmental Health Perspectives (2007)

BackgroundEvidence suggests that p,p′-dichlorodiphenyldichloroethene (DDE) affects neurodevelopment in infants, although a critical exposure window has not yet been identified.ObjectivesOur goal was to assess the prenatal DDE exposure window and its effect on the psychomotor development index (PDI) and mental development index (MDI) during the first year of life.MethodsWe recruited 244 children whose pregnancies and deliveries were uncomplicated, and whose mothers were monitored throughout the pregnancy. Participating mothers were not occupationally exposed to DDT (dichlorodiphenyltrichloroethane) but were residents of a zone in Mexico with endemic malaria. We measured serum levels of DDE before pregnancy and during each trimester of the pregnancy. We evaluated PDI and MDI of the Bayley Scales for Infant Development (BSID-II), at 1, 3, 6, and 12 months of age. We adjusted for quality of the home environment and maternal intellectual coefficient (IQ). We used generalized mixed-effects models for statistical analysis.ResultsThird-trimester DDE level (7.8 ± 2.8 ppb) was significantly higher than the level at baseline, first, and second trimesters, but the differences never exceeded 20%. Only DDE levels during the first trimester of pregnancy were associated with a significant reduction in PDI (every doubled increase of DDE level reduced the PDI 0.5 points). DDE was not associated with MDI.ConclusionsA critical window of exposure to DDE in utero may be the first trimester of the pregnancy, and psychomotor development is a target of this compound. Residues of DDT metabolites may present a risk of developmental delay for years after termination of DDT use.
Making sense of rising caesarean section rates: Reducing caesarean section rates should not be the primary objective
Authors: Michael R Odent
Journal: BMJ (2004)

Promoting walking and cycling as an alternative to using cars Vested interests doom puny healthcare interventionsEditor-Ogilvy et al's systematic review on promoting walking and cycling as an alternative to using cars treats motoring as if it were a disease that can be cured, without examining the social forces that lead to car use. 1 The effects they find in their review are hardly surprising, given the social currents opposing them: car advertising, predict and provide road planning, the giant car "park," and other horrors of surburbia.Big business and big government alike have a vested interest in its continued growth.Those who have bought into this motor dependent lifestyle can be trusted to extend the infliction of motor tyranny on everyone else: motorists object to being taxed, although they are major polluters, or confined by speed limits, although they killed 3508 people in Britain last year.I try to undermine this metal carapaced horde.Any driver suffering from a condition in which lack of exercise is a factor: hypertension, obesity, stress, depression-much of the general practice caseload in fact-is told to sell their car and get a bike instead.I do have my successesfor example, a man in his 50s who came back to his follow up appointment, saying he wished he lived further from work so he had more time on his bike every day.But when I look at the vested interests lined up against me-not least George W Bush's latest oil grab-I wonder why I bother.Urban doctors who continue to drive are particularly depressing.Since when do you need a car to carry a briefcase?
Failure of Phenothiazines in Sickle Cell Anemia
Authors: Howard A. Pearson
Journal: JAMA (1967)

A beneficial effect of phenothiazine therapy on clinical symptomatology and red cell survival in patients with sickle cell anemia (hemoglobin SS) has been described by Lewis and Hathorn from Ghana.<sup>1-3</sup>The rationale for this treatment was based on their observations of an apparently higher than expected incidence of red cell (RBC) glucose-6-phosphate dehydrogenase (G<sub>6</sub>PD) deficiency in patients with hemoglobin SS disease when compared to normal individuals. They suggested that the enzyme deficiency might have a beneficial effect on the course of hemoglobin SS disease, thus leading to a preferential survival of those individuals with the combination. Because genetically determined G<sub>6</sub>PD deficiency was postulated to be advantageous, they then undertook treatment with pharmacologic agents which were known to inhibit the enzyme. The phenothiazine promazine (Sparine) hydrochloride inhibits G<sub>6</sub>PD<sup>4</sup>and, in high levels, interferes with in vitro sickling.<sup>1</sup> When promazine hydrochloride, in a
Noninvasive Monitoring of Cardiac Output in Critically Ill Patients Using Transesophageal Doppler
Authors: BRUNO VALTIER, BERNARD P. CHOLLEY, JEAN-PIERRE BELOT, JEAN-EMMANUEL de la COUSSAYE, JOAQUIM MATEO, DIDIER M. PAYEN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Measurement of cardiac output using thermodilution technique in mechanically ventilated patients is associated with significant morbidity. The goal of the present study was to assess the validity of cardiac output measurement using transesophageal Doppler in critically ill patients. Forty-six patients from three different intensive care units underwent 136 paired cardiac output measurements using thermodilution (COTH) and transesophageal Doppler (COTED). In addition, simultaneous suprasternal Doppler and indirect calorimetry (Fick principle) were used to measure cardiac output in 26 patients from one center. A good correlation was found between COTH and COTED (r = 0.95), with a small systematic underestimation (bias = 0.24 L/min) using transesophageal Doppler. The limits of agreement between COTH and COTED were + 2 L/min and − 1.5 L/min. Variations in cardiac output between two consecutive measures using either transesophageal Doppler or thermodilution techniques were similar in direction and magnitude (bias = 0 L/min; limits of agreement = ± 1.7 L/min). Suprasternal Doppler and indirect calorimetry yielded similar correlations and agreements in the subset of patients in whom they were used. These results confirm that transesophageal Doppler can provide a noninvasive, clinically useful estimate of cardiac output and detect hemodynamic changes in mechanically ventilated, critically ill patients.
EPICARDIAL ADIPOSE TISSUE VOLUME AND CORONARY ARTERY CALCIUM TO PREDICT MYOCARDIAL ISCHEMIA ON POSITRON EMISSION TOMOGRAPHY-COMPUTED TOMOGRAPHY STUDIES
Authors: Matthew James Janik, Gregory Hartlage, Nikolaos Alexopoulos, Zaur Mirzoyev, Dalton S. McLean, Chesnal Arepalli, Arthur E. Stillman, Paolo Raggi
Journal: Journal of the American College of Cardiology (2010)
CENTRIFUGE EXPERIMENTS WITH THE VIRUS OF VACCINIA
Authors: F. F. Tang
Journal: The Journal of Experimental Medicine (1930)

Centrifuge experiments have been carried out with cell-free, active filtrates of vaccinia virus. The experiments have shown that the virus can be concentrated by this method, even in filtrates which have been subjected to prolonged preliminary centrifugation to throw down any inert particles which may have been present in the original filtrate. This fact, together with the knowledge that the virus can be almost completely held back by the Berkefeld N filter, as reported previously (5) indicates that the virus may be of considerable size.
Corrigendum to “The transport of non-surfactant based paclitaxel loaded magnetic nanoparticles across the blood brain barrier in a rat model” [Biomaterials 33 (2012) 2936–2951]
Authors: Fahima Dilnawaz, Abhalaxmi Singh, Sujeet Mewar, Uma Sharma, N.R. Jagannathan, Sanjeeb Kumar Sahoo
Journal: Biomaterials (2012)
Targeting Chk1 in p53-deficient triple-negative breast cancer is therapeutically beneficial in human-in-mouse tumor models
Authors: Cynthia X. Ma, Shirong Cai, Shunqiang Li, Christine E. Ryan, Zhanfang Guo, W. Timothy Schaiff, Li Lin, Jeremy Hoog, Reece J. Goiffon, Aleix Prat, Rebecca L. Aft, Matthew J. Ellis, Helen Piwnica-Worms
Journal: Journal of Clinical Investigation (2012)

Patients with triple-negative breast cancer (TNBC) - defined by lack of estrogen receptor and progesterone receptor expression as well as lack of human epidermal growth factor receptor 2 (HER2) amplification - have a poor prognosis. There is a need for targeted therapies to treat this condition. TNBCs frequently harbor mutations in TP53, resulting in loss of the G1 checkpoint and reliance on checkpoint kinase 1 (Chk1) to arrest cells in response to DNA damage. Previous studies have shown that inhibition of Chk1 in a p53-deficient background results in apoptosis [corrected] in response to DNA damage. We therefore tested whether inhibition of Chk1 could potentiate the cytotoxicity of the DNA damaging agent irinotecan in TNBC using xenotransplant tumor models. Tumor specimens from patients with TNBC were engrafted into humanized mammary fat pads of immunodeficient mice to create 3 independent human-in-mouse TNBC lines: 1 WT (WU-BC3) and 2 mutant for TP53 (WU-BC4 and WU-BC5). These lines were tested for their response to irinotecan and a Chk1 inhibitor (either UCN-01 or AZD7762), either as single agents or in combination. The combination therapy induced checkpoint bypass and apoptosis in WU-BC4 and WU-BC5, but not WU-BC3, tumors. Moreover, combination therapy inhibited tumor growth and prolonged survival of mice bearing the WU-BC4 line, but not the WU-BC3 line. In addition, knockdown of p53 sensitized WU-BC3 tumors to the combination therapy. These results demonstrate that p53 is a major determinant of how TNBCs respond to therapies that combine DNA damage with Chk1 inhibition.
Technique, complications, and clinical value of endomyocardial biopsy in patients with heterotopic heart transplants.
Authors: D K Cooper, R C Fraser, A G Rose, O Ayzenberg, G S Oldfield, J Hassoulas, D Novitzky, C J Uys, C N Barnard
Journal: Thorax (1982)

A review of 157 consecutive biopsies of donor endomyocardium in patients with heterotopic heart transplants is reported. The technique of percutaneous transvenous endomyocardial biopsy after this operation is described; manipulation of the catheter and bioptome into the junction of the donor superior vena cava and right atrium can be difficult when this anastomotic junction is small, as a result either of operative surgical technique or of subsequent contraction. The complication rate was 4%, but one patient may have died from infection resulting from biopsy when the bioptome had to be introduced at the groin. The histopathological changes seen in the biopsy specimens have been graded according to a scoring system to give the clinician a guide to the severity of rejection. Histopathological assessment was of clinical value in 96% of cases, but was inaccurate on two occasions, once because an opinion was given on what was in retrospect an inadequate sample. In patients undergoing persistent low-grade acute or chronic rejection there was difficulty in detecting or appreciating the true extent of myocardial fibrosis; this led to inadequate immunosuppressive treatment in two patients. Attention is drawn to the fact that ischaemic fibrosis resulting from the vascular changes of chronic rejection may spare the endomyocardium, which is kept viable by intracavitary blood, and that this may lead to a misleading histopathological report.
Concurrent Chemoradiotherapy for Limited-Stage Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type
Authors: Kazuyuki Shimada, Ritsuro Suzuki
Journal: Journal of Clinical Oncology (2010)

We read with great interest the two recent articles regarding the phase II trial of concurrent chemoradiotherapy for newly diagnosed patients with limited-stage extranodal natural killer/T-cell lymphoma, nasal type (nasal ENKL). 1,2These two studies employed a similar treatment design, but the radiation dose (median, 50 v 40 Gy) and chemotherapeutic regimen used were considerably different.The Japanese study used multidrug chemotherapy DeVIC (dexamethasone, etoposide, ifosfamide, and carboplatin) concurrently with radiotherapy. 1 In contrast, the Korean study employed cisplatin alone in combination with radiotherapy. 2The latter study used the VIPD (etoposide, ifosfamide, cisplatin, and dexamethasone) regimen as a postchemoradiotherapy therapy.Both studies were provoked by the currently unsatisfactory results of using chemotherapy followed by radiotherapy, 3,4 and have concluded that concurrent chemoradiotherapy is the better option for this particular lymphoma subtype, which expresses multidrug resistance associated p-glycoprotein. 5However, the conceptual view of the two studies are different to a certain degree; the former elected to use multidrug resistance-unrestricted agents to induce an antitumor effect, but the latter used cisplatin as a radiation sensitizer.Regarding the analytic method and interpretation of results for the study by Kim et al, there appear to be several serious issues which should be clarified.The authors reported an overall response rate of 83.3% (95% CI, 65.3 to 94.4) and complete response rate (CR) of 80.0% (95% CI, 65.7 to 94.3) as a result of the intention-to-treat analysis.According to the statistical methods employed in this article, the authors calculated sample size to detect the difference in superiority of the control (70% CR rate) to the target 90% CR rate.Considering that the lower limit of the 95% CI was below 70%, the authors failed to verify their hypothesis and could not conclude the efficacy of this regimen.Furthermore, in this study, two patients withdrew from the study during treatment (after radiotherapy and after first course of VIPD) and five patients died as a result of disease progression, infection, or relapse (disease progression, n ϭ 1; infection, n ϭ 2; relapse, n ϭ 2).In addition, another patient was described to experience relapse.Considering the five deaths and six progression/death events, the authors may not be able to obtain 3-year overall survival rate of 86.3% and progression-free survival rate of 85.2% because these values cannot exceed the simple division of 23 of 28 ϭ 82.1% and 22 of 28 ϭ 78.6%, respectively.As such, the survival rates presented appear to be obtained by including four failure events in the calculation.Moreover, in this study, the authors did not describe the median
AD 1040, 1940, or 2080?
Authors: C. Rollins Hanlon
Journal: JAMA (1969)

<h3>To the Editor:—</h3> I cannot refrain from calling to your attention a typo which appears in the St. Patrick's Day or Salvador Dali issue ofThe Journal. As March moves rapidly towards April 15th, it is apparent that there are millions of people in this country, including authors and typesetters who could easily put down 1040 in place of almost any number you might mention. A particularly amusing concatenation is the characterization of it as "the late 1040's" (<b>207</b>:2080, 1969). In C. P. Snow's book,<i>Varieties of Men</i>, he reports a conversation between the great mathematician Hardy and a visitor concerning the immense wealth of information and inter-relationships tied up in what might appear to the nonmathematician as a simple number. If I were privy to the mode of entry into the "numbers" game in St. Louis, I would certainly put 25 or 50 cents down today on either
Asymptomatic HIV-infected Individuals on Antiretroviral Therapy Exhibit Impaired Lung CD4<sup>+</sup>T-Cell Responses to Mycobacteria
Authors: Kondwani C. Jambo, Dominic H. Banda, Louise Afran, Anstead M. Kankwatira, Rose D. Malamba, Theresa J. Allain, Stephen B. Gordon, Robert S. Heyderman, David G. Russell, Henry C. Mwandumba
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

HIV-infected persons on antiretroviral therapy (ART) remain at higher risk of pulmonary tuberculosis (TB) than HIV-uninfected individuals. This increased susceptibility may be caused by impairment of alveolar macrophage (AM) function and/or mycobacteria-specific alveolar CD4(+) T-cell responses observed in HIV-infected ART-naive adults.To determine whether ART was associated with improvement in both AM function, assessed by phagosomal proteolysis, and alveolar CD4(+) T-cell responses to Mycobacterium in HIV-infected individuals.Peripheral blood was drawn and bronchoalveolar lavage (BAL) performed on healthy, 35 HIV-uninfected, 25 HIV-infected ART-naive, and 50 HIV-infected ART-treated asymptomatic adults. Phagosomal proteolysis of AM was assessed with fluorogenic beads. Mycobacteria-specific CD4(+) T-cell responses were measured by intracellular cytokine staining.HIV-infected adults on ART exhibited lower plasma HIV viral load and higher blood CD4(+) T-cell count than ART-naive adults. AM proteolysis and total mycobacteria-specific Th1 CD4(+) T-cell responses in individuals on ART for greater than or equal to 4 years were similar to HIV-uninfected control subjects but those on ART for less than 4 years had impaired responses. Total influenza-specific alveolar Th1 CD4(+) T-cell responses were intact in all individuals receiving ART. In contrast, BAL and blood mycobacteria-specific polyfunctional CD4(+) T-cell responses were impaired in adults on ART irrespective of duration.AM and mycobacteria-specific alveolar CD4(+) T-cell responses in HIV-infected adults on ART for less than 4 years are impaired and may partly explain the high risk of TB in HIV-infected individuals on ART. Strategies to augment ART to improve lung immune cell function and reduce the high incidence of TB in HIV-infected adults who initiate ART should be investigated.
The Side Population of Ovarian Cancer Cells Is a Primary Target of IFN-α Antitumor Effects
Authors: Lidia Moserle, Stefano Indraccolo, Margherita Ghisi, Chiara Frasson, Elena Fortunato, Silvana Canevari, Silvia Miotti, Valeria Tosello, Rita Zamarchi, Alberto Corradin, Sonia Minuzzo, Elisabetta Rossi, Giuseppe Basso, Alberto Amadori
Journal: Cancer Research (2008)

The side population (SP), recently identified in several normal tissues and in a variety of tumors based on its ability to extrude some fluorescent dyes, may comprise cells endowed with stem cell features. In this study, we investigated the presence of SP in epithelial ovarian cancer and found it in 9 of 27 primary tumor samples analyzed, as well as in 4 of 6 cultures from xenotransplants. SP cells from one xenograft bearing a large SP fraction were characterized in detail. SP cells had higher proliferation rates, were much less apoptotic compared with non-SP cells, and generated tumors more rapidly than non-SP cells. We also investigated the effects of IFN-alpha, a cytokine that has widely been used to treat solid tumors, on epithelial ovarian cancer cells and observed that IFN-alpha exerted marked antiproliferative and proapoptotic effects on primary cultures containing high numbers of SP cells. In vitro, IFN-alpha treatment invariably caused a dramatic reduction in SP size in tumor cell lines of different origins; moreover, IFN-alpha treatment of purified SP cells was associated with a distinctive change in their transcriptional profile. Gene therapy with human IFN-alpha resulted in regression of established tumors bearing a large SP fraction, which was not observed when tumors bearing low SP levels were treated. These findings could have relevant clinical implications because they imply that tumors bearing large SP numbers, albeit rare, could be sensitive to IFN-alpha treatment.
THE ETIOLOGY OF INFANTILE DIARRHEA.
Authors: ROSA ENGELMAN
Journal: JAMA (1895)

In order to arrive at any just conception of the subject, attention must be directed to the entire alimentary canal, as well as to milk, the staple food of infancy and childhood. A straight almost indifferentiated tube swarms from mouth to arms, with facultative, obligate, saprophytic and pathogenic germs. Milk, particularly during the heated term, is fertile soil for various fermentations, microbic contamination, and the exogenous as well as endogenous development of toxins. An unclean mouth, a slight error in diet, constitutional taint, immature sensitive cellular metabolism invite these germs to unusual lodgment and activity. Their great number and variety exclude a specific relation to the particular disease manifestations under consideration. The question resolves itself into a discussion of the toxemic, septicemic or pyemic genesis of the several morbid gastro-intestinal disturbances, in which not one or a few, but many and various microorganisms play a part. Escherich long since proved
Systematic Review: Using Magnetic Resonance Imaging to Screen Women at High Risk for Breast Cancer
Authors: Ellen Warner, Hans Messersmith, Petrina Causer, Andrea Eisen, Rene Shumak, Donald Plewes
Journal: Annals of Internal Medicine (2008)

A sensitive and acceptable screening regimen for women at high risk for breast cancer is essential. Contrast-enhanced magnetic resonance imaging (MRI) of the breast is highly sensitive for diagnosis of breast cancer but has variable specificity.To summarize the sensitivity, specificity, likelihood ratios, and posttest probability associated with adding MRI to annual mammography screening of women at very high risk for breast cancer.English-language literature search of the MEDLINE, EMBASE, and Cochrane databases from January 1995 to September 2007, supplemented by hand searches of pertinent articles.Prospective studies published after 1994 in which MRI and mammography (with or without additional tests) were used to screen women at very high risk for breast cancer.Methods and potential biases of studies were assessed by 2 reviewers, and data were extracted and entered into 2 x 2 tables that compared American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) scores of MRI plus mammography, mammography alone, or MRI alone with results of breast tissue biopsies.Eleven relevant, prospective, nonrandomized studies that ranged from small single-center studies with only 1 round of patient screening to large multicenter studies with repeated rounds of annual screening were identified. Characteristics of women that varied across study samples included age range, history of breast cancer, and BRCA1 or BRCA2 mutation status. Studies used dynamic contrast-enhanced MRI with axial or coronal plane images (European studies) or sagittal images (North American studies) that were usually interpreted without knowledge of mammography results. The summary negative likelihood ratio and the probability of a BI-RADS-suspicious lesion (given negative test findings and assuming a 2% pretest probability of disease) were 0.70 (95% CI, 0.59 to 0.82) and 1.4% (CI, 1.2% to 1.6%) for mammography alone and 0.14 (CI, 0.05 to 0.42) and 0.3% (CI, 0.1% to 0.8%) for the combination of MRI plus mammography, using a BI-RADS score of 4 or higher as the definition of positive.Differences in patient population, center experience, and criteria for positive screening results led to between-study heterogeneity. Data on patients with nonfamilial high risk were limited, and no data were available on recurrence or survival.Screening with both MRI and mammography might rule out cancerous lesions better than mammography alone in women who are known or likely to have an inherited predisposition to breast cancer.