tbuckley/cabot-search huggingface dataset:
Stabilization of sternum using absorbable copolymer plate in the open surgery for pectus deformities
Authors: Korkut Bostanci, Hakan Ozalper, Barkin Eldem, Mustafa Yuksel
Journal: European Respiratory Journal (2012)

Minimally invasive repair of pectus deformities have become the treatment of choice in recent years yet open surgery is still being widely performed for deformities such as mixed deformities or pectus arcuatum, where minimally invasive techniques are not feasible. Various materials such as steel wires can be used for stabilizing the sternum during open surgery. Absorbabale copolymer plates have been in use for the stabilization of bony structures. The aim of this study was to investigate our results of open surgery for pectus deformities using absorbable copolymer plates for sternal stabilization.  Eighteen patients who had had open surgery for pectus deformities using absorbable copolymer plates between November 2008 and January 2012 were included in the study and they were evaluated retrospectively according to the demographics, type and form of the deformity, operation duration, perioperative and postoperative complications, and recurrence.  Twelve patients were male and the median age was 19,5 (range: 14-31). Seven patients had pectus arcuatum, 7 had pectus carinatum and 4 had mixed deformity. Deformity was symmetric in 13 patients. All patients had open surgical correction with the principals of modified Ravitch sternoplasy and the sternum was stabilized by screwing a 42x42x2mm absorbable copolymer plate on sternal osteotomy line. The median operation duration was 120 minutes (40-210). One patient had seroma in the postoperative period. No recurrence was seen.  Absorbable copolymer plates can be used for the stabilization of sternum in open surgery for pectus deformities with low morbidity rates, as it is a safe, durable and easy-to-use material.
Induction chemotherapy followed by concomitant radiotherapy and weekly cisplatin versus the same concomitant chemoradiotherapy in patients with nasopharyngeal carcinoma: a randomized phase II study conducted by the Hellenic Cooperative Oncology Group (HeCOG) with biomarker evaluation
Authors: G. Fountzilas, E. Ciuleanu, M. Bobos, A. Kalogera-Fountzila, A.G. Eleftheraki, G. Karayannopoulou, T. Zaramboukas, A. Nikolaou, K. Markou, L. Resiga, D. Dionysopoulos, E. Samantas, H. Athanassiou, D. Misailidou, D. Skarlos, T. Ciuleanu
Journal: Annals of Oncology (2011)
PI3K inhibition results in enhanced estrogen receptor function and dependence in hormone receptor–positive breast cancer
Authors: Ana Bosch, Zhiqiang Li, Anna Bergamaschi, Haley Ellis, Eneda Toska, Aleix Prat, Jessica J. Tao, Daniel E. Spratt, Nerissa T. Viola-Villegas, Pau Castel, Gerard Minuesa, Natasha Morse, Jordi Rodón, Yasir Ibrahim, Javier Cortes, Jose Perez-Garcia, Patricia Galvan, Judit Grueso, Marta Guzman, John A. Katzenellenbogen, Michael Kharas, Jason S. Lewis, Maura Dickler, Violeta Serra, Neal Rosen, Sarat Chandarlapaty, Maurizio Scaltriti, José Baselga
Journal: Science Translational Medicine (2015)

Inhibition of the PI3K/AKT pathway results in induction of ER-dependent transcriptional activity and susceptibility to anti-estrogen therapy in ER-positive breast cancer.
Osmoregulatory betaine uptake by rat renal medullary slices.
Authors: J W Lohr, M A Pochal, M Acara
Journal: Journal of the American Society of Nephrology (1991)

Betaine is an osmolyte present in high concentrations in renal medullary cells. Betaine and other organic osmolytes, such as glycerophosphorylcholine, myo-inositol, and sorbitol, have been shown to increase in concentration during antidiuresis when the inner medullary extracellular osmolality rises. Its concentration may increase in renal cells either by betaine uptake or by choline metabolism to betaine. These studies measured the uptake of (14C)betaine into cortical, outer medullary and inner medullary slices from rat kidney. The tissue-to-medium ratio of (14C) betaine increased with increasing osmolality up to 450 mosmol/kg in outer medullary and inner medullary slices, but not in cortical slices. Betaine uptake increased when the osmolality was raised with NaCl or mannitol, but not with urea. When LiCl was substituted for NaCl in a medium of 300 mosmol/kg, there was significant inhibition of betaine uptake, although the tissue-to-medium ratios remained greater then unity. Thus, increases in osmolality stimulate betaine uptake in rat renal medullary slices and this uptake occurs by both sodium-dependent and sodium-independent betaine transport.
Association Between &lt;emph type="ital"&gt;BRCA1&lt;/emph&gt; and &lt;emph type="ital"&gt;BRCA2&lt;/emph&gt; Mutations and Survival in Women With Invasive Epithelial Ovarian Cancer
Authors: Kelly L. Bolton
Journal: JAMA (2012)

Context-Approximately 10 percent of women with invasive epithelial ovarian cancer (EOC) carry deleterious germline mutations in BRCA1 or BRCA2.A recent report suggested that BRCA2 related EOC was associated with an improved prognosis, but the effect of BRCA1 remains unclear.Objective-To characterize the survival of BRCA carriers with EOC compared to non-carriers and to determine whether BRCA1 and BRCA2 carriers show similar survival patterns.Design, Setting, and Participants-We pooled data from 26 studies on the survival of women with ovarian cancer.This included data on 1,213 EOC cases with pathogenic germline mutations in BRCA1 (909) or BRCA2 (304) and 2,666 non-carriers recruited and followed for variable times between 1987 and 2010; the median year of diagnosis was 1998. Main Outcome Measures-Five year overall mortality.Results-The five-year overall survival was 36 percent (95% CI: 34-38) for non-carriers, 44 percent (95% CI: 40-48) for BRCA1 carriers and 52 percent (95% CI: 46-58) for BRCA2 carriers.After adjusting for study and year of diagnosis, BRCA1 and BRCA2 carriers showed a more favorable survival than non-carriers (BRCA1, HR=0.78; 95% CI=0.68-0.89,P=2×10 -4 ; BRCA2, HR = 0.61; 95% CI=0.50-0.76,P=6×10 -6 ).These survival differences remained after additional adjustment for stage, grade, histology and age at diagnosis (BRCA1, HR=0.73, 95% CI=0.64-0.84,P=2×10 -5 ; BRCA2, HR = 0.49, 95% CI=0.39-0.61,P=3×10 -10 ).Conclusions-Among patients with invasive epithelial ovarian cancer, having a germline mutation in BRCA1 or BRCA2 was associated with improved 5-year overall survival.
Up regulation of cathepsin K expression in articular chondrocytes in a transgenic mouse model for osteoarthritis
Authors: J P Morko
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objectives:</b> To study the expression of cysteine proteinases, particularly cathepsin K, and their extracellular inhibitor cystatin C in articular cartilage of transgenic Del1 mice which harbour a short deletion mutation in a type II collagen transgene and are predisposed to early onset osteoarthritis. <b>Methods:</b> Northern analysis was used to measure mRNA levels of cathepsins B, H, K, L, and S, and cystatin C in total RNA extracted from knee joints of Del1 mice, using their non-transgenic litter mates as controls. Immunohistochemistry and morphometry was used to study the distribution of cathepsin K and cystatin C in the knee joints. <b>Results:</b> Up regulation of cathepsin K mRNA expression was seen in the knee joints of transgenic Del1 mice at the onset of cartilage degeneration. Cathepsin K was found near sites of matrix destruction in articular chondrocytes, particularly in clusters of proliferating cells, and in calcified cartilaginous matrix. In intact articular cartilage of control animals, cathepsin K was only seen in a small number of chondrocytes. Upon aging, control animals also developed osteoarthritis, which was accompanied by increased cathepsin K expression. Cystatin C was mostly localised in and around chondrocytes located in calcified cartilage, with no obvious association with the onset of cartilage degeneration. <b>Conclusion:</b> The temporospatial distribution of cathepsin K in osteoarthritic cartilage suggests a role for this enzyme in the pathogenesis of osteoarthritis. Because cathepsin K can digest cartilage matrix components it may contribute to the development of osteoarthritic lesions. These data may provide new clues for the development of treatments aimed at preventing cartilage degeneration.
Surrogate endpoints for clinical trials in primary sclerosing cholangitis: Review and results from an International PSC Study Group consensus process
Authors: Cyriel Y. Ponsioen, Roger W. Chapman, Olivier Chazouillères, Gideon M. Hirschfield, Tom H. Karlsen, Ansgar W. Lohse, Massimo Pinzani, Erik Schrumpf, Michael Trauner, Gregory J. Gores
Journal: Hepatology (2015)

Primary sclerosing cholangitis (PSC) is a rare, but serious, cholestatic disease for which, to date, no effective therapy exists to halt disease progression toward end‐stage liver disease. Clinical trial design to study drugs that improve prognosis is hampered by the relatively low event rate of clinically relevant endpoints. To overcome this shortcoming, there is an urgent need to identify appropriate surrogate endpoints. At present, there are no established surrogate endpoints. This article provides a critical review and describes the results of a consensus process initiated by the International PSC Study Group to delineate appropriate candidate surrogate endpoints at present for clinical trials in this frequently dismal disease. The consensus process resulted in a shortlist of five candidates as surrogate endpoints for measuring disease progression: alkaline phosphatase (ALP); transient elastography (TE); histology; combination of ALP+histology; and bilirubin. Of these, histology, ALP, and TE came out as the most promising. However, the expert panel concluded that no biomarker currently exceeds level 3 validation. Combining multiple endpoints is advisable. Conclusion : At present, there are insufficient data to support level 2 validation for any surrogate endpoint in PSC. Concerted efforts by all stakeholders are highly needed. Novel, promising noninvasive biomarkers are under study and should be incorporated as exploratory endpoints in clinical trials. (H epatology 2016;63:1357–1367)
Bacterial precipitins and their immunoglobulin class in atopic asthma, non-atopic asthma, and chronic bronchitis.
Authors: R J Davies, V C Holford-Strevens, I D Wells, J Pepys
Journal: Thorax (1976)

In a study of groups of patients with atopic (extrinsic) asthma, non-atopic (intrinsic) asthma, and chronic bronchitis, no difference could be detected in the numbers having precipitating antibodies against species specific antigens from Staphylococcus aureus or Streptococcus pneumoniae compared to suitably matched control subjects. Precipitating antibodies against species specific antigens from Haemophilus influenzae, demonstrated in this investigation by double diffusion in agar gel, were found much more frequently in patients with chronic mucopurulent or obstructive bronchitis (50%) than in either asthmatic subjects (6%) or normal controls (6%) (P = less than 0.0005). While the precipitating antibody demonstrated in these patients against the extracts of Str. pneumoniae and Staph. aureus was in the IgG class alone, IgM and IgA antibody were detected against the species specific but not the non-species specific antigens of H. influenzae. These results underline the importance of H. influenzae as an infecting agent in chronic bronchitis and suggest that the finding of precipitins against the species specific H1 and H2 antigens of this bacterium denotes infection either concurrently or in the recent past. There is no evidence to suggest from this study that infection with Staph. aureus, Str. pneumoniae or H. influenzae is any more common in asthmatics as a group compared to controls or between patients with the non-atopic (intrinsic) and atopic (extrinsic) form of the disease.
Evaluation of Several Geometric Models for Estimation of Left Ventricular Circumferential Wall Stress
Authors: PHILIP A. McHALE, JOSEPH C. GREENFIELD
Journal: Circulation Research (1973)

Phasic left ventricular wall force and wall thickness were monitored with appropriate transducers to provide a direct measurement of circumferential wall stress in open-chest dogs. Left ventricular pressure and measurements of chamber geometry were used to estimate the wall stress using several geometric models. During the initial control period, peak and end-ejection measured wall stresses were 207 ± 19 and 104 ± 13 g/cm 2 , respectively. The best estimates of these values were 198 ± 18 and 117 ± 11 g/cm 2 obtained from a modified thin-wall ellipse formula in which the midwall rather than the endocardial radius was used. Wide variations in hemodynamic conditions were produced with intravenous infusions of nitroglycerin, phenylephrine, and isoproterenol. Comparison of directly measured and estimated values during all control periods and during the response to these interventions showed that both the modified thin-wall ellipse and a thick-wall ellipse were generally accurate predictors of the measured wall stress. All other models tended to underestimate measured stress. The sensitivity of the estimated wall stress computed by the models to geometric measurement errors was also evaluated. A thick-wall sphere was the most sensitive to both circumferential length and wall thickness measurement errors, and a thick-wall ellipse was the least sensitive. All models examined were relatively insensitive to base-to-apex length measurement errors.
Cardiac Complications of Liquid Protein Diets
Authors: Leslie Dornfeld
Journal: JAMA (1978)

<h3>To the Editor.—</h3> Two articles in a recent issue ofThe Journalby Singh et al (240:115, 1978) and Brown et al (240:120,1978) report the deaths from refractory ventricular tachycardia and fibrillation of three young women, obese but apparently otherwise healthy, who had been given a program of weight reduction by fasting with liquid protein. Each of the three had been fasting for five or six months and had lost about 41 kg. In each case the ECG on admission was marked by gross QT<sub>c</sub>prolongation. Singh et al state: "It is not known what proportion of patients using various liquid protein diets have such ECG abnormalities and whether all such patients are at risk for the development of serious arrhythmias." In connection with the programs of supplemented fasting with protein of high biologic availability, carbohydrates, and minerals at The Mount Sinai Hospital of Cleveland and at the University
Renal Transporters in Drug Development
Authors: Kari M. Morrissey, Sophie L. Stocker, Matthias B. Wittwer, Lu Xu, Kathleen M. Giacomini
Journal: The Annual Review of Pharmacology and Toxicology (2012)

The kidney plays a vital role in the body's defense against potentially toxic xenobiotics and metabolic waste products through elimination pathways. In particular, secretory transporters in the proximal tubule are major determinants of the disposition of xenobiotics, including many prescription drugs. In the past decade, considerable progress has been made in understanding the impact of renal transporters on the disposition of many clinically used drugs. In addition, renal transporters have been implicated as sites for numerous clinically important drug-drug interactions. This review begins with a description of renal drug handling and presents relevant equations for the calculation of renal clearance, including filtration and secretory clearance. In addition, data on the localization, expression, substrates, and inhibitors of renal drug transporters are tabulated. The recent US Food and Drug Administration drug-drug interaction draft guidance as it pertains to the study of renal drug transporters is presented. Renal drug elimination in special populations and transporter splicing variants are also described.
Kuopio Atherosclerosis Prevention Study (KAPS)
Authors: Riitta Salonen, Kristiina Nyyssönen, Elina Porkkala, Juha Rummukainen, Rene Belder, Jong-Soon Park, Jukka T. Salonen
Journal: Circulation (1995)

Background The atherosclerotic progression–reducing effect of LDL cholesterol (LDL-C) lowering has been established in subjects with severe atherosclerotic disease but not in persons with elevated LDL cholesterols without severe atherosclerosis. KAPS (Kuopio Atherosclerosis Prevention Study) is the first population-based trial in the primary prevention of carotid and femoral atherosclerosis. Methods and Results The eligibility requirements were serum LDL-C ≥4.0 mmol/L and total cholesterol &lt;7.5 mmol/L. Out of a geographically defined population, 447 men aged 44 to 65 years (mean, 57) were randomized to pravastatin (40 mg/d) or placebo for 3 years. Less than 10% of the subjects had prior myocardial infarction. Thirty-nine men discontinued study medication; however, efficacy data were available for 424 men. The primary outcome was the rate of carotid atherosclerotic progression, measured as the linear slope over annual ultrasound examinations in the average of the maximum carotid intima-media thickness (IMT) of the far wall of up to four arterial segments (the right and left distal common carotid artery and the right and left carotid bulb). For the carotid arteries, at the overall mean baseline IMT of 1.66 mm, the rate of progression of carotid atherosclerosis was 45% (95% CI, 16 to 69%) less in the pravastatin (0.017 mm/y) than the placebo (0.031 mm/y) group ( P =.005). In the common carotid artery there was a treatment effect of 66% (95% CI, 30 to 95%; pravastatin 0.010 mm/y; placebo 0.029 mm/y; P &lt;.002) at the overall mean baseline IMT of 1.35 mm. A treatment effect of 30% (95% CI, −1% to 54%) was found for the carotid bulb (pravastatin, 0.028; placebo, 0.040; P =.056) at the overall mean baseline IMT of 2.0 mm. The treatment effect was larger in subjects with higher baseline IMT values, in smokers and in those with low plasma vitamin E levels. There was no significant treatment effect on atherosclerotic progression in the femoral arteries. Conclusions These data establish the antiatherogenic effect of LDL-C lowering by pravastatin in hypercholesterolemic men in a primary prevention setting and suggest a greater effect in smokers than in nonsmokers.
Beyond Histology: Translating Tumor Genotypes into Clinically Effective Targeted Therapies
Authors: Catherine B. Meador, Christine M. Micheel, Mia A. Levy, Christine M. Lovly, Leora Horn, Jeremy L. Warner, Douglas B. Johnson, Zhongming Zhao, Ingrid A. Anderson, Jeffrey A. Sosman, Cindy L. Vnencak-Jones, Kimberly B. Dahlman, William Pao
Journal: Clinical Cancer Research (2014)

Increased understanding of intertumoral heterogeneity at the genomic level has led to significant advancements in the treatment of solid tumors. Functional genomic alterations conferring sensitivity to targeted therapies can take many forms, and appropriate methods and tools are needed to detect these alterations. This review provides an update on genetic variability among solid tumors of similar histologic classification, using non-small cell lung cancer and melanoma as examples. We also discuss relevant technological platforms for discovery and diagnosis of clinically actionable variants and highlight the implications of specific genomic alterations for response to targeted therapy.
Low and High Magnesium Concentrations at Various Calcium Levels
Authors: BORYS SURAWICZ, EUGENE LEPESCHKIN, HERMAN C. HERRLICH
Journal: Circulation Research (1961)

Electrocardiograms, ventricular monophasic action potentials registered with suction and intracellular microelectrodes, and pressure curves were recorded simultaneously in isolated rabbit hearts perfused with oxygenated Krebs-Henscleit solution containing varying calcium/magnesium ratios. The duration of the action potential and Q-T interval was not affected by low and high magnesium concentrations unless calcium was omitted or significantly reduced. When Mg was completely absent, solutions free of calcium or with one-sixteenth of the "normal" Ca concentration caused a progressive prolongation of the action potential and Q-T interval until they occupied the entire cardiac cycle. When Mg concentration was low (0.075 to 0.6 mM/L.), the prolongation occurred at a slower rate and was less pronounced. With higher Mg concentrations (1.2 to 19.2 mM/L.), the initial lengthening of the action potential and Q-T interval was followed by a gradual shortening. The higher the Mg concentration employed, the shorter was the period of the initial lengthening, and the more pronounced was the subsequent shortening. These observations can be best explained by assuming that calcium-like action of Mg on the plateau of the action potential becomes apparent only when Ca is absent or significantly decreased. The depression of contractility by calcium deficiency proceeded at the same rate at all studied Mg concentrations. The findings are discussed in relation to the electrocardiographic patterns encountered in clinical cal cium and magnesium deficiency.
Site and mechanism of action of trichlormethiazide in rabbit distal nephron segments perfused in vitro.
Authors: T Shimizu, K Yoshitomi, M Nakamura, M Imai
Journal: Journal of Clinical Investigation (1988)

To determine the exact site and mechanism of action of thiazide diuretics, effects of 10(-4) M trichlormethiazide (TCM) on NaCl transport were examined in the distal convoluted tubule (DCT), the connecting tubule (CNT) and the cortical collecting duct (CCD) of rabbit kidney by the in vitro microperfusion technique. TCM added to the lumen decreased lumen-to-bath 36Cl flux (JCl(LB)) only in the CNT without changing the transmural voltage (VT). In the DCT, 10(-4) M furosemide did not change JCl(LB) even if it was added to the lumen with 10(-4) M TCM, whereas 10(-5) M amiloride in the lumen decreased the lumen-to-bath 22Na flux (JNa(LB)) and VT. In the CNT, TCM added to the lumen did not affect the bath-to-lumen 36Cl flux. Addition of TCM to the bath slightly decreased JCl(LB). Luminal addition of 10(-4) M TCM also decreased JNa(LB). Amiloride at 10(-5) M in the lumen decreased both JNa(LB) and VT. Addition of TCM with 10(-5) M amiloride further decreased JNa(LB) without affecting VT, indicating that TCM affects the electroneutral Na+ transport, which is distinct from the amiloride-sensitive conductive Na+ pathway. When Na+ was removed from the lumen, JCl(LB) was markedly decreased, but addition of TCM did not cause further decrease in JCl(LB). Furosemide did not affect JCl(LB), but addition of both 10(-4) M TCM and furosemide decreased JCl(LB), indicating that Na+-K+-2Cl- cotransport is not involved in the action of TCM. Removal of HCO3- slightly decreased JCl(LB), and TCM caused further decrease in JCl(LB). Amiloride at 10(-3) M, a concentration supposed to inhibit the Na+/H+ antiport, slightly decreased JCl(LB), and addition of TCM caused a further marked decrease in JJl(LB). The similar results were also obtained when the combined effects of 10(-3) M 4,4'-diisothiocyano-stilben-2,2'-disulfonate(DIDS) and 10(-4) M TCM were examined. These findings suggest that the parallel antiport of Na+/H+ and Cl-/HCO3- is not involved in the action of TCM. By excluding other possible mechanisms involving neutral Na+-dependent Cl- transport, we conclude that TCM inhibits Na+-Cl- cotransport in the luminal membrane of the rabbit CNT.