tbuckley/cabot-search huggingface dataset:
Utility of ultrasonography in the diagnosis of autosomal dominant polycystic kidney disease in children.
Authors: P A Gabow, W J Kimberling, J D Strain, M L Manco-Johnson, A M Johnson
Journal: Journal of the American Society of Nephrology (1997)

To determine the utility of ultrasonography (US) in diagnosing autosomal dominant polycystic kidney disease (ADPKD) in children, this study examined 106 children who were at 50% risk for the disease. The children underwent a history, physical examination, abdominal US, and gene linkage analysis (GLA) with tightly linked markers for ADPKD1 and ADPKD2 genes. Only ADPKD1 children were studied. A child was considered affected by US if any cysts were detected and affected by GLA if he or she shared the same haplotype as the affected parent. Forty-two children (40%) were considered to be unaffected by both GLA and US. Forty-eight children (45%) were considered affected by both modalities. Only two of these children had a single cyst. Fourteen children (13%) were considered affected by GLA with normal initial US. These children tended to have larger kidneys than children who were unaffected by GLA. Eight of these 14 children had subsequent positive ultrasonograms. Two children had a positive ultrasonogram with GLA showing them to be unaffected; in one of these children, a subsequent ultrasonogram was interpreted to be normal with a medullary pyramid. Thus, overall the false negative rate was 25%, and the false positive rate was 2%. The false negative rate was highest in the children who were 3 months to 5 years of age (38%). Clinicians must understand the utility of US in diagnosing ADPKD in at-risk children and must not interpret a normal study as absence of disease in this population.
Antitumor Activity of ZD6474, a Vascular Endothelial Growth Factor-2 and Epidermal Growth Factor Receptor Small Molecule Tyrosine Kinase Inhibitor, in Combination with SC-236, a Cyclooxygenase-2 Inhibitor
Authors: Concetta Tuccillo, Marco Romano, Teresa Troiani, Erika Martinelli, Floriana Morgillo, Ferdinando De Vita, Roberto Bianco, Gabriella Fontanini, Raffaele A. Bianco, Giampaolo Tortora, Fortunato Ciardiello
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The epidermal growth factor receptor (EGFR) autocrine pathway plays an important role in cancer cell growth. Vascular endothelial growth factor (VEGF) is a key regulator of tumor-induced endothelial cell proliferation and vascular permeability. Enhanced cyclooxygenase-2 (COX-2) expression has been linked to cancer cell proliferation, EGFR activation, VEGF secretion, and tumor-induced angiogenesis. ZD6474 is an orally available, small molecule, dual VEGF receptor-2 (VEGFR-2) and EGFR tyrosine kinase inhibitor. We investigated the activity of ZD6474 in combination with SC-236, a selective COX-2 inhibitor, to determine the antitumor activity of the simultaneous blockade of EGFR, COX-2, and VEGF functions. Experimental Design: The antitumor activity in vitro and in vivo of ZD6474 and/or SC-236 was tested in human cancer cell lines with a functional EGFR autocrine pathway. Results: The combination of ZD6474 and SC-236 determined supra-additive growth inhibition in all cancer cell lines tested. In nude mice bearing established human colon (GEO) or lung adenocarcinoma (A549) cancer xenografts and treated with ZD6474 and/or SC-236 for 3 weeks, a reversible tumor growth inhibition was seen with each agent, whereas a more prolonged growth inhibition that lasted for 3 to 5 weeks following the end of treatment resulted from the combination of the two agents. A long-term, 10-week treatment with ZD6474 plus SC-236 resulted in sustained tumor growth inhibition in all mice with tumor eradication in 3 of 10 GEO tumor–bearing mice and in 4 of 10 A549 tumor–bearing mice. Conclusions: This study provides a rationale for evaluating the simultaneous blockade of EGFR, COX-2, and VEGF signaling as cancer therapy in a clinical setting.
Effect of Aminoacetonitrile on the Metabolism of Diethylnitrosamine During Liver Carcinogenesis2
Authors: D. Mundt, D. Hadjiolov
Journal: JNCI Journal of the National Cancer Institute (1974)

The effect of chronic administration of aminoacetonitrile (AAN) on the metabolism of 14C-diethylnitrosamine (DEN) was measured as a function of the ethylation of liver RNA and 14CO2 exhalation in rats continuously fed unlabeled carcinogen. The results were compared with those of acute experiments in which a single application of 14C-DEN led to 14CO2 exhalation and ethylation of liver RNA, whereas both effects were significantly lower after a single injection of AAN. After continuous feeding with DEN followed by a dose of BC-DEN, the exhalation of 14CO2 was reduced in those rats which had also been continuously treated with AAN. In rats fed DEN continuously but given no further treatment, no inhibition in the output of 14CO2 was recorded, compared with that of the acute experiment. However, the exhalation was prolonged. Chronic administration of AAN and DEN together also significantly decreased the ethylation rate of liver RNA in rats. The influence of AAN treatment during DEN carcinogenesis in rats was investigated. A change of organotropy with development of esophageal tumors was established. The possible function of carcinogen metabolism in induction of esophageal and liver tumors was discussed.
Nasal Epithelium Potential Difference at High Altitude (4,559 m)
Authors: Heimo Mairbäurl, Jörn Weymann, Andreas Möhrlein, Erik R. Swenson, Marco Maggiorini, J. Simon R. Gibbs, Peter Bärtsch
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Hypoxia inhibits activity and expression of ion transport proteins of cultured lung alveolar epithelial cells. Here we tested, whether in vivo hypoxia at high altitude (4,559 m) also inhibits lung ion transport. Transepithelial nasal potentials (NP) were determined as a surrogate measure of lung ion transport activity before and during the stay at altitude. In normoxia, total NP was approximately 20% higher in control subjects than in susceptibles to high-altitude pulmonary edema, but there was no difference between groups in amiloride-inhibitable NPs. At high altitude total NP increased 250% in both groups, whereas amiloride-sensitive NP decreased in control subjects only (−80%), and the chloride ion (Cl−)–sensitive portion of NP almost doubled. Because many mountaineers suffer from nasal dryness at high altitude, a control study was performed in normobaric hypoxia (12% oxygen, 6 hours) at a controlled humidity of 50%. In this study, no change in total NP or its amiloride- and Cl-sensitive portions was observed. The increased Cl− secretion at high altitude but no such change in normobaric hypoxia suggests that nasal dryness may stimulate local active Cl− and fluid secretion in the upper respiratory tract. It is therefore uncertain whether similar changes also occur at the alveolar epithelium.
Evolution of transmitted HIV-1 drug resistance in HIV-1-infected patients in Italy from 2000 to 2010
Authors: M. Colafigli, C. Torti, E.M. Trecarichi, L. Albini, A. Rosi, V. Micheli, N. Manca, G. Penco, B. Bruzzone, G. Punzi, P. Corsi, G. Parruti, P. Bagnarelli, L. Monno, A. Gonnelli, R. Cauda, S. Di Giambenedetto
Journal: Clinical Microbiology and Infection (2012)
50 years for the Netherlands Association of Sports Medicine (VSG) and counting!
Authors: Edwin A Goedhart, Babette M Pluim
Journal: British Journal of Sports Medicine (2015)

On 8th May 1965, a small group of pioneers founded the Netherlands Association of Sports Medicine (VSG) in Amsterdam. As we celebrate our 50-year anniversary, our blossoming professional organisation has almost 150 sports medicine specialists and 250 other doctors with an interest in sports medicine.

Sports and exercise medicine has developed into a specialty that encompasses prevention, treatment and rehabilitation, with performance enhancement at any level.1 It is a very broad field, and the sports medicine physician is a facilitator, connecting all the professionals who are involved in supporting the athlete: physiotherapists, nutritionists, exercise physiologists, psychologists, orthopaedic surgeons, cardiologists, etc. The curriculum of the sports medicine trainee contains fellowships in all these areas, and the sports medicine doctor is therefore well equipped to coordinate the care delivered by the various specialists and advise the athlete. Their role is to ensure healthy performance of the elite athlete at one end of the spectrum, and the health and safety of patients with any medical condition that may profit from exercise, at the other end of the spectrum.

The breadth of the …
Serial morphometric analysis of sclerotic lesions in primary "focal" segmental glomerulosclerosis.
Authors: G Fuiano, N Comi, P Magri, V Sepe, M M Balletta, C Esposito, F Uccello, A Dal Canton, G Conte
Journal: Journal of the American Society of Nephrology (1996)

The possibility of missing the diagnosis of focal segmental glomerulosclerosis (FSGS) has been primarily attributed to the focal distribution of the sclerotic lesions, but this assumption has not been verified by any serial morphometric analysis of renal biopsy specimens. The aim of this study is to assess the size and the distribution of sclerotic lesions in primary FSGS and to establish the minimum number of glomeruli and sections necessary for the diagnosis. Fourteen biopsies from adult nephrotic patients with primary FSGS were carefully selected from a group of 41 biopsies, to minimize the possibility of finding and misinterpreting nonspecific glomerular scars, and were serially cut to obtain 1485 consecutive 2 microns-thick sections that, after PAS staining, showed 182 glomeruli. Fifty-seven glomeruli were "complete", i.e., they emerged after the first section and disappeared before the last section. The percentage of glomeruli with sclerotic lesions was 31.5% in the starting section, 71.8% after the observation of all serial sections, and 81.7% when only the complete glomeruli were considered. The morphometric analysis on complete glomeruli revealed that the volume of the sclerotic lesions averaged just 12.5% +/- 2.2 SE of the entire glomerular volume, and the statistical analysis revealed that the minimum number of glomeruli needed in the starting section to exclude sclerotic lesions is eight (P < 0.01) or nine (P < 0.001). If fewer glomeruli are seen, it is necessary to cut 2 microns-thick serial sections, but to examine just one of every 11 (P < 0.001), the number of sections to examine being proportional to the number of glomeruli found. In conclusion, this study shows that the distribution of sclerotic lesions in primary FSGS is not focal, but diffuse; however, because of the small size of the sclerotic lesions, the probability of missing the diagnosis is statistically relevant when fewer than eight glomeruli are found in the starting section, unless a serial morphological analysis, even on a reduced number of sections, is made.
Abstract 2386: Growth-Differentiation Factor-15 is a Strong Predictor of Adverse Outcomes in Heart Failure: Results from Val-HeFT.
Authors: Inder S Anand, Tibor Kempf, Heike Tapken, Tim Allhoff, Michael Kuskowski, Marjorie Carlson, Jay N Cohn, Helmut Drexler, Kai C Wollert
Journal: Circulation (2007)

Background: Growth-Differentiation Factor-15 (GDF-15) is a member of the TGF-β family that is induced in the heart after myocardial injury. In patients with non-ST segment elevation ACS, GDF-15 is increased and provides prognostic information. Its role in heart failure is unknown. Methods &amp; Results: GDF-15 was measured in 1125 Val-HeFT patients at baseline. Baseline median GDF-15 was 2027 ng/L (IQ range 1447 to 2942) and was abnormal (&gt;1200 ng/L) in 86% of patients. Patients with GDF-15 above the median had higher NYHA class, greater volume load, lower LVEF and eGFR, higher hsCRP, norepinephrine, BNP and aldosterone, lower use of beta-blockers and higher use of diuretics (all p&lt;0.01). In a multivariate COX model including all baseline variables, GDF-15 was a significant independent predictor of death (HR, 1.5, 95% CI, 1.06–2.14), first morbid event (HR 1.56, 95% CI, 1.19–2.04), and hospitalizations for HF (HR, 1.93, 95% CI, 1.33–2.80), as was BNP for all the three endpoints (HR, 1.7, 95% CI, 1.27–2.3), (HR 1.84, 95% CI, 1.45–2.35), and (HR, 1.98, 95% CI, 1.43–2.7). Spearman correlation of BNP with GDF-15 was 0.33 p&lt;0.001. To test whether GDF-15 adds prognostic information over that provided by BNP, patients were sub-grouped using the median BNP (96 pg/mL) and GDF-15 (2027 ng/L). Figure shows survival curves for the four subgroups. In a multivariate COX analysis when both GDF-15 and BNP were above the median, the risk of death was nearly three times as great (HR 2.75, 95% CI 1.75–4.30, p&lt;0.001) compared to those with both below the median. Conclusion: GDF-15 is an important prognostic marker in HF, independent of other markers and adds prognostic information to that provided by BNP alone.
Methylated HBHA produced in M. smegmatis discriminates between active and non-active TB disease among the QFT-IT-responders
Authors: Giovanni Delogu, Teresa Chiacchio, Valentina Vanini, Ornella Butera, Gilda Cuzzi, Alessandra Bua, Paola Molicotti, Stefania Zanetti, Francesco Lauria, Susanna Grisetti, Nicola Magnavita, Giovanni Fadda, Enrico Girardi, Delia Goletti
Journal: European Respiratory Journal (2011)

Background:  Challenge in tuberculosis (TB) research is to develop a test to distinguish, among the responders to an IFN-γ release assay (IGRA), those who control  M. tuberculosis  (Mtb) replication from those that cannot. IFN-γ response to the Heparin-binding-hemagglutinin (HBHA) of Mtb has been associated with latent TB infection (LTBI), but the cumbersome procedures to purify the methylated and immunological active form of the protein from Mtb or  M. bovis  BCG have prevented the implementation of a diagnostic test. Aim of this study was to evaluate the IFN-γ response to methylated HBHA of Mtb produced in  M. smegmatis  (rHBHAms) in subjects at different stages of TB who scored positive to QuantiFERON-TB Gold in-tube (QFT-IT).   Methodology/Principal findings:  87 subjects at different stages of TB who scored positive to QFT-IT were selected. IFN-γ response to  in vitro  whole blood stimulation with rHBHAms was evaluated by short-term and long-term tests and detected by ELISA or flow cytometry. We demonstrated that the IFN-γ response to rHBHAms is mediated by CD4 +  T-cells with an effector-memory phenotype. This response, evaluated also by short-term-tests is significantly lower in active TB than in remote LTBI (p=0.0010), past TB (p=0.0152) and recent infection (p=0.05). These results were confirmed by long-term tests and by qualitative analysis using ROC analysis.   Conclusions:  For the first time to our knowledge, we showed that the T-cell response to a recombinant and methylated HBHA of Mtb produced in  M. smegmatis  in a whole blood system is immunogenic and potentially useful to discriminate between active and non-active TB disease among those responsive to QFT-IT.
Validity of 6 activity monitors during standard physical activities in COPD – Comparison with indirect calorimetry
Authors: Yogini Raste, Daniel Langer, Chris Burtin, Zafiris Louvaris, Santiago Giavedoni, Francesco Costa, Frederick Wilson, Roberto Rabinovich, Nicholas Hopkinson, Ioannis Vogiatzis, Barry Peterson, Thierry Troosters
Journal: European Respiratory Journal (2011)

Background:  Reduced physical activity is an important feature of COPD. A range of monitors are available, but the validity of their various output parameters is not well established for patients with chronic diseases. The IMI PROactive project evaluated 6 activity monitors: SenseWear (SW); RT3; Actiwatch (AW); Actigraph (AG); Dynaport Minimod (MM) and Lifecorder Kenz (KZ).   Methods:  40 patients (GOLD stage 1-4; Age 67±7, FEV1 56±18%pred, 6MWD 430±127) were recruited in 4 centres. Patients wore all activity monitors and a portable metabolic system and performed a 1 hour standard activity set (including walking, standing, stair climbing and upper limb tasks). Activity intensity (METs), assessed by indirect calorimetry, was compared to activity monitor outcomes. Average VO 2  during the protocol was also calculated (8.78±1.72 ml min -1  kg -1 ) and compared to activity monitor outputs; METs (SW, MM); activity counts or Vector Magnitude Units, VMU (AW, AG, RT3); or a general activity outcome (KZ).   Results:  Table 1 gives median (IQR) for Pearson correlation between VO 2  and activity monitor outcomes and that between mean METS over the study and mean activity monitor output.   Conclusion:  The MM, SW, RT3 and AG give acceptable estimates of minute-by-minute variation in metabolic activity during physical activity. SW, MM, AW and KZ show acceptable correlations between overall metabolic activity and monitor output. These findings could guide users in choosing valid activity monitors for research or clinical questions.
Differential effects of chemotherapy regimens and menopausal status on IL-6 levels in breast cancer (BC) patients during two cycles of treatment: Implications for “chemo brain.”
Authors: M. C. Janelsins, O. Palesh, J. A. Roscoe, K. M. Mustian, C. E. Heckler, L. J. Peppone, L. Sprod, G. R. Morrow
Journal: Journal of Clinical Oncology (2010)

e19556 Background: The etiology of chemotherapy-related cognitive impairment (e.g. frequent bouts of forgetfulness; difficulties with attention), commonly referred to as “chemo brain,” is not well understood. Alterations in cytokine (e.g. IL-6) and hormone levels are hypothesized to play a role in “chemo brain” because abnormal concentrations of these molecules alter neuronal integrity, leading to cognitive impairments in other diseases. Understanding factors that contribute to “chemo brain” is important because this information could identify patients at risk and inform treatment. Patients receiving doxorubicin-based (with cyclophosphamide, or cyclophosphamide and fluorouracil; AC/CAF) chemotherapy or a combination of cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy report experiencing cognitive difficulties but it is unclear what causes these cognitive difficulties. Cytokine responses and menopausal status may be involved. Methods: This secondary analysis examined relationships between IL-6, menopausal status prior to chemotherapy, and type of chemotherapy among BC patients (N = 50) receiving combinations of AC/CAF or CMF. Levels of IL-6 were assessed at baseline (T1) and after 2 chemotherapy cycles (T2). T-tests were used to compare between group and within group differences on IL-6. Means and change scores (T2-T1) are reported. Results: Paired t-tests showed a significant increase in IL-6 over time in the AC/CAF group (4.95 pg/mL;p = 0.04) while values in the CMF group decreased (−1.46 pg/mL;p = 0.05). At T2, there was a significant difference in IL-6 (7.78 pg/mL;p = 0.03) between AC/CAF and CMF groups, but not at T1. IL-6 levels were not different between AC/CAF and CMF groups among premenopausal women at T2; there was a marginally significant difference in IL-6 between these groups among post-menopausal women (8.69 pg/mL;p = 0.09). Conclusions: These results suggest that chemotherapy regimen and menopausal status can influence levels of IL-6. Research is warranted on the importance of menopausal status, chemotherapy regimens and subsequent alterations in cytokines on “chemo brain.” No significant financial relationships to disclose.
Asthma control and demographic, nutritional, functional and quality of life
Authors: Carmen Centeno, Carlos Martinez, Zoran Stojanovic, Nuria Bruguera, Jorge Abad, Ignasi Garcia, Marisol Prats, Juan Ruiz-Manzano, Josep Morera
Journal: European Respiratory Journal (2012)

We studied if the Asthma Control Test (ACT) is related to nutritional and inflammation status, symptoms, lung function and quality of life (QOL).

METHODS

Prospective cross-sectional study with 3 groups: ACT 20; assesing: demographic data, nutritional and inflammation status, lung function, no of exacerbations, hyperventilation syndrome (Nijmegen Questionnaire, NQ) and QOL (St. George's Respiratory Questionnaire, SGRQ).

RESULTS

81 patients (19 men, 62 women, 47.4±16.1 years). Average ACT was 18.7±5 (poorly controlled group, PCG 22.2% vs well-controlled group, WCG 50.62%). There were significant differences in the 3 groups.

View this table:

Table 1





Using Bonferroni test, the differences were based on PCG and WCG. Only in dyspnea, FEV1%, NQ and SGRQ, we saw significant differences between partial and PCG. Multiple linear regression considered activity and symptoms (SGRQ) as independent variables. There were no differences in nutrition and inflammation, except for the CRP.

CONCLUSIONS

The difference between the three groups was at the expense of that between PCG and WCG. PCG presented severe course of disease, worse lung function, hyperventilation, some degree of inflammation, increased number of exacerbations and poorer QOL. There was no relationship between worse asthma control and nutrition.
Routine episiotomy in developing countries
Authors: A Maduma-Butshe, A. Dyall, P. Garner
Journal: BMJ (1998)

More women in developing countries are delivering their babies in hospitals. In Latin America institutional births account for 70% of all deliveries; in Africa, 36%; and in developing countries overall some 40%.1 What is becoming apparent is that in some countries virtually all the women delivering in hospital will be surgically cut. If they miss out on a caesarean section they will have an episiotomy. For example, Brazil has caesarean section rates of greater than 30%, and Argentina has episiotomy rates of greater than 80% for vaginal births. Questions about high caesarean sections rates have been raised in the past, but unnecessary episiotomies have not been widely debated.

Obstetricians in the tropics continue to instruct health staff to apply a policy of “avoid …
Energy Balance After Sodium–Glucose Cotransporter 2 Inhibition
Authors: Giulia Ferrannini, Thomas Hach, Susanne Crowe, Arjun Sanghvi, Kevin D. Hall, Ele Ferrannini
Journal: Diabetes Care (2015)

OBJECTIVE Sodium–glucose cotransporter 2 (SGLT2) inhibitors cause substantially less weight loss than expected from the energy excreted via glycosuria. Our aim was to analyze this phenomenon quantitatively. RESEARCH DESIGN AND METHODS Eighty-six patients with type 2 diabetes (HbA1c 7.8 ± 0.8% [62 ± 9 mmol/mol], estimated glomerular filtration rate [eGFR] 89 ± 19 mL ⋅ min−1 ⋅ 1.73 m−2) received empagliflozin (25 mg/day) for 90 weeks with frequent (n = 11) assessments of body weight, eGFR, and fasting plasma glucose (FPG). Time-dependent glucose filtration was calculated as the product of eGFR and FPG; time-dependent glycosuria was estimated from previous direct measurements. The relation of calorie-to-weight changes was estimated using a mathematical model of human energy metabolism that simulates the time course of weight change for a given change in calorie balance and calculates the corresponding energy intake changes. RESULTS At week 90, weight loss averaged −3.2 ± 4.2 kg (corresponding to a median calorie deficit of 51 kcal/day [interquartile range (IQR) 112]). However, the observed calorie loss through glycosuria (206 kcal/day [IQR 90]) was predicted to result in a weight loss of –11.3 ± 3.1 kg, assuming no compensatory changes in energy intake. Thus, patients lost only 29 ± 41% of the weight loss predicted by their glycosuria; the model indicated that this difference was accounted for by a 13% (IQR 12) increase in calorie intake (269 kcal/day [IQR 258]) coupled with a 2% (IQR 5) increase in daily energy expenditure (due to diet-induced thermogenesis). This increased calorie intake was inversely related to baseline BMI (partial r = −0.34, P &amp;lt; 0.01) and positively to baseline eGFR (partial r = 0.29, P &amp;lt; 0.01). CONCLUSIONS Chronic glycosuria elicits an adaptive increase in energy intake. Combining SGLT2 inhibition with caloric restriction is expected to be associated with major weight loss.