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1.
Katie Mycock Lin Zhan Gavin Taylor-Stokes Gary Milligan Debanjali Mitra 《Current oncology (Toronto, Ont.)》2021,28(1):678
Background: Palbociclib is a selective cyclin-dependent kinase (CDK) 4/6 inhibitor used in combination with aromatase inhibitors or fulvestrant for patients with hormone receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer (ABC/MBC). Palbociclib was the first CDK 4/6 inhibitor approved for HR+/HER2− ABC/MBC treatment in Canada in combination with letrozole (P+L) as an initial endocrine-based therapy (approved March 2016), or with fulvestrant (P+F) following disease progression after prior endocrine therapy (approved May 2017). The Ibrance Real World Insights (IRIS) study () collected real-world outcomes data for palbociclib-treated patients in several countries, including Canada. Methods: This retrospective chart review included women with HR+/HER2− ABC/MBC receiving P+L or P+F in Canada. Physicians reviewed medical records for up to 14 patients, abstracting demographic and clinical characteristics, treatment patterns, and clinical outcomes. Progression-free rates (PFRs) and survival rates (SRs) at 6, 12, 18, and 24 months were estimated via Kaplan–Meier analysis. Results: Thirty-three physicians examined medical records for 247 patients (P+L, n = 214; P+F, n = 33). Median follow-up was 8.8 months for P+L and 7.0 months for P+F. Most patients were initiated on palbociclib 125 mg/d (P+L, 90.2%; P+F, 84.8%). Doses were reduced in 16.6% of P+L and 14.3% of P+F patients initiating palbociclib at 125 mg/d. The PFR for P+L was 90.3% at 12 months and 78.2% at 18 months; corresponding SRs were 95.6% and 93.0%. For P+F, 6-month PFR was 91.0%; 12-month SR was 100.0%. Conclusions: Dose reduction rates were low and PFR and SR were high in this Canadian real-world assessment of P+L and P+F treatments, suggesting that palbociclib combinations are well tolerated and effective. NCT03159195相似文献
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Bhabatosh Biswas Dipayan Ghosh Rupak Bhattacharjee Ashis Patra Subir Basuthakur Rajarshi Basu 《Indian Journal of Thoracic and Cardiovascular Surgery》2004,20(2):88-90
Introduction Hydatid cysts of the lung are quite frequent in our country. Some patients have additional cysts in the liver. Though most
of the liver cysts remain asymptomatic for long time, but may be symptomatic with increasing size. Surgical removal is the
treatment of choice for both lung & liver cysts. Aim of the study was to establish suitability of one stage surgery for pulmonary
& hepatic hydatid cysts.
Methods From 1996 through 2003 we operated on 216 pulmonary hydatid cysts, out of which 42 patients had hydatid cysts in the right
lung as well as in the right lobe of liver. Right thoracotomy was done to remove the lung hydatids followed by phrenotomy
to remove the liver cysts.
Results Right thoracotomy was done in 42 patients having hydatid cysts of lung & liver. In 36 patients, cysts were removed, bronchial
leaks were sutured & residual cavities were obliterated. Out of rest 6 patients, having dense adhesions or destruction of
pulmonary parenchyma, 4 had segmentectomy & 2 had lobectomy. Right phrenotomy was then done with radial incision above the
palpated liver cysts. Hydatid cyst was removed from liver. Cavity and remaining pericystic liver tissue was inverted with
sutures. Water seal chest drain & subdiaphragmatic drain were placed. Post operative albendazole was continued for 3 months
in the dose of 10–20 mg/kg with a gap of 2 weeks after each month. Post operative recovery was uneventful in most of the cases.
However, air leak continued for almost 3 weeks in 4 patients & 3 months in one patient. There was no death.
Conclusion Surgical management of pulmonary and hepatic hydatids with one stage right thoracotomy & phrenotomy is a suitable option.
It avoids additional laparotomy and thereby additional cost & hospital stay. Results are quite satisfactory. 相似文献
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Rupak Mukherjee Preecha Laohakunakorn M. Charles Welzig Kathryn S. Cowart J. Philip Saul 《Journal of interventional cardiac electrophysiology》2003,9(3):309-315
Background: Radiofrequency (RF) lesion size in vitro is positively correlated with applied power and catheter tip temperature. However, the relation between RF lesion size, power, and tip temperature in vivo remains unclear. We hypothesized that due to flow, anatomy and tip contact effects in vivo, increased tip temperature would be inversely related to applied power and RF lesion size.
Methods: RF lesions were created on the endocardium of 16 pigs using 5, 6, and 7 Fr catheters. The ablation generator was set to achieve a temperature of 70°C. RF lesions were created in different regions of the heart so as to encompass a wide range of blood flow and catheter movement conditions. RF lesions were measured acutely (DIMEN, mm) and correlated with average power applied (POWER, W), and average tip temperature (TEMP, °C). The POWER and TEMP relation was also examined.
Results: For TEMPs below 55°C, the power output from the generator was typically maximized at 50 W. At TEMPs above 55°C, POWER decreased exponentially with increasing TEMP {POWER = 50 – exp(-((41-TEMP)/7)), r = 0.98, p < 0.05}. Further, DIMEN tended to be inversely related to TEMP (Slope: –0.07 ± 0.04, r = –0.15, p = 0.07); but, was positively related to POWER (Slope: 0.04 ± 0.02, r = 0.23, p < 0.05). These relations varied by tip size and estimated local blood flow characteristics.
Conclusion: In vivo, variable tissue contact and flow yield DIMEN-POWER-TEMP relations opposite to those found in vitro. These counterintuitive results suggest that maximum in vivo RF lesion size is achieved when power is maximized at tip temperatures between 50 and 60°C. 相似文献
6.
Protection Against Chemically-Induced Oxidative Gastrointestinal Tissue Injury in Rats by Bismuth Salts 总被引:1,自引:0,他引:1
Debasis Bagchi Owen R. Carryl Minh X. Tran Manashi Bagchi Phillip J. Vuchetich Roger L. Krohn Siddhartha D. Ray Sekhar Mitra Sidney J. Stohs 《Digestive diseases and sciences》1997,42(9):1890-1900
Oxygen free radicals (OFR) are implicated in thepathogenesis of stress, chemically induced gastriclesions, and gastrointestinal injury. Theconcentration-dependent scavenging abilities of bismuthsubsalicylate (SBS), colloidal bismuth subcitrate (CBS), andselected OFR scavengers, including superoxide dismutase(SOD), catalase, mannitol, and allopurinol were examinedagainst biochemically or chemically generated superoxide anion, hydroxyl radical, andhypochlorite radical plus hypochlorous acid based on achemiluminescence assay. Furthermore, both gastric (GM)and intestinal mucosa (IM) were individually exposed in vitro to these free radical generatingsystems, and the concentration-dependent protectiveabilities of SBS and CBS against lipid peroxidation (LP)were compared with selected OFR scavengers. In addition, 24-hr fasted rats were orally treated with thenecrotizing agents 0.6 M HCl, 0.2 M NaOH, 80% ethanol,and aspirin (200 mg/kg). The extent of tissue injury inthe GM and IM was determined by assessing LP, DNA fragmentation, and membrane microviscosity.Dose- and time-dependent in vivo protective abilities ofCBS (100 mg/kg) and SBS (15 mg/kg) were also assessed.Following incubations with superoxide anion and hydroxyl radical generating systems in thepresence of 125 mg SBS/liter, approximately 47% and 61%inhibitions were observed in the chemiluminescenceresponse, respectively, while 48% and 46% inhibitions were observed with 125 mg CBS/liter. SBS andCBS exerted similar abilities towards hypochloriteradical plus hypochlorous acid. Approx. 3.1- and3.7-fold increases in LP were observed in the GM and IMof rats following oral administration of 0.6 MHCl. Pretreatment of the rats with SBS and CBS decreased0.6 M HCl-induced LP in the GM by approx. 39% and 27%,respectively, with similar decreases in LP in the IM. SBS exhibited better protectiveabilities towards 0.6 M HCl and 0.2 m NaOH-induced GMand IM injury as compared to CBS. SBS and CBS providedsimilar protection towards 80% ethanol-induced gastric injury, while CBS exerted a superior protectiveability towards aspirin-induced gastric injury. Theresults demonstrate that both SBS and CBS can scavengereactive oxygen species and prevent tissue damage produced by OFR. 相似文献
7.
Five aliphatic 5-esters of 5-iodo-2deoxyuridine (IDU) were synthesized via an acid chloride alcoholysis reaction. The solubility in pH 7.4 phosphate buffer, lipophilicity as determined by partition experiments in octanol/pH 7.4 buffer, and cytotoxicity of these potential prodrugs were evaluated. The esters showed a 43- to 250-fold increase in lipophilicity and a 1.6- to 14-fold decrease in aqueous solubility relative to IDU. At a concentration of 50 µM, all esters showed reduced cytotoxicity toward uninfected Vero cells relative to IDU. 相似文献
8.
Problems associated with the use of 5-iodo-2-deoxyundine (IDU) in the treatment of herpes simplex keratitis can be attributed largely to the polar nature of IDU resulting in its poor permeability across the lipoidal epithelial layer of the corneal membrane. Five aliphatic 5-esters of IDU were synthesized and evaluated as prodrugs for potential use in the treatment of deep ocular infections such as stromal keratitis, iritis, and even retinitis. A parabolic relationship between in vitro corneal membrane permeability and carbon chain length of prodrugs is evident. For a given prodrug, enzymatic hydrolysis proceeded most readily in iris–ciliary body, followed by cornea and aqueous humor. An increase in carbon chain length made the prodrugs more enzymatically labile but more resistant to chemical hydrolysis at pH 7.4 and 34°C. The 5-butyryl ester of IDU exhibited an approximately fourfold increase in aqueous humor IDU concentration relative to IDU at 25 min following instillation of 25-µl 5 mM solutions. 相似文献
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10.
Mahmoudi M Willgoss D Cuttle L Yang T Pat B Winterford C Endre Z Johnson DW Gobé GC 《The Journal of pathology》2003,200(3):396-405
Caveolae and their proteins, the caveolins, transport macromolecules; compartmentalize signalling molecules; and are involved in various repair processes. There is little information regarding their role in the pathogenesis of significant renal syndromes such as acute renal failure (ARF). In this study, an in vivo rat model of 30 min bilateral renal ischaemia followed by reperfusion times from 4 h to 1 week was used to map the temporal and spatial association between caveolin-1 and tubular epithelial damage (desquamation, apoptosis, necrosis). An in vitro model of ischaemic ARF was also studied, where cultured renal tubular epithelial cells or arterial endothelial cells were subjected to injury initiators modelled on ischaemia-reperfusion (hypoxia, serum deprivation, free radical damage or hypoxia-hyperoxia). Expression of caveolin proteins was investigated using immunohistochemistry, immunoelectron microscopy, and immunoblots of whole cell, membrane or cytosol protein extracts. In vivo, healthy kidney had abundant caveolin-1 in vascular endothelial cells and also some expression in membrane surfaces of distal tubular epithelium. In the kidneys of ARF animals, punctate cytoplasmic localization of caveolin-1 was identified, with high intensity expression in injured proximal tubules that were losing basement membrane adhesion or were apoptotic, 24 h to 4 days after ischaemia-reperfusion. Western immunoblots indicated a marked increase in caveolin-1 expression in the cortex where some proximal tubular injury was located. In vitro, the main treatment-induced change in both cell types was translocation of caveolin-1 from the original plasma membrane site into membrane-associated sites in the cytoplasm. Overall, expression levels did not alter for whole cell extracts and the protein remained membrane-bound, as indicated by cell fractionation analyses. Caveolin-1 was also found to localize intensely within apoptotic cells. The results are indicative of a role for caveolin-1 in ARF-induced renal injury. Whether it functions for cell repair or death remains to be elucidated. 相似文献