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Rajesh Venkataraman Karthik R. Vaidyanathan Madhu N. Sankar Kotturathu M. Cherian 《Journal of cardiac surgery》2009,24(4):443-445
Abstract Dissection of the pulmonary autograft is an extremely rare complication requiring emergent treatment as there is a chance of rupture and proximal aortic involvement. The autograft dissection can involve the aortic annulus, causing separation of leaflets from the annulus in addition to causing annular dilatation, thereby precluding resuspension of leaflets. The usual treatment in such cases is to perform the Bentall procedure, which involves placing a valved conduit (usually mechanical valve) and thereby necessitating anticoagulation. This report describes a case of successful valve-sparing aortic root replacement following the Ross procedure with dissection of autograft. 相似文献
3.
J Smith S Karthik J P A Lodge J A C Thorpe 《European journal of cardio-thoracic surgery》2004,26(3):652-654
A 63-year-old man presented with a 2 month history of intermittent right subcostal and shoulder tip pain. Preoperative imaging confirmed a locally advanced right lower lobe lung tumour involving the diaphragm and liver. Bronchoscopic biopsy confirmed squamous cell carcinoma and mediastinoscopy was negative. The patient underwent a right bilobectomy with resection of the right hemi-diaphragm and a right hemi-hepatectomy. His postoperative recovery was satisfactory and he remains well 18 months after the surgery. We believe that in selected cases, patients with locally advanced lung tumours invading the liver may have a survival advantage following resection. 相似文献
4.
Venkatakrishnan A Stecenko AA King G Blackwell TR Brigham KL Christman JW Blackwell TS 《American journal of respiratory cell and molecular biology》2000,23(3):396-403
In cystic fibrosis (CF), inflammatory mediator production by airway epithelial cells is a critical determinant of chronic airway inflammation. To determine whether altered signal transduction through the nuclear factor (NF)-kappaB pathway occurs in CF epithelial cells and results in excessive generation of inflammatory cytokines, we evaluated tumor necrosis factor (TNF)-alpha-induced production of the NF-kappaB-dependent cytokine interleukin (IL)-8 and activation of NF-kappaB in three different human bronchial epithelial cell lines: (1) BEAS cells that express wild-type CF transmembrane conductance regulator (CFTR), (2) IB3 cells with mutant CFTR, and (3) C38 cells, which are "corrected" IB3 cells complemented with wild-type CFTR. Treatment of cells with TNF-alpha (30 ng/ml) resulted in markedly elevated NF-kappaB activation and production of IL-8 by IB3 cells compared with BEAS and C38 cells. Despite the differences in NF- kappaB activation, no differences in basal levels of IkappaB-alpha or TNF-alpha- induced IkappaB-alpha processing and degradation were detected among the cell lines. In contrast, the basal level of IkappaB-beta was increased in the IB3 cells. Treatment with TNF-alpha resulted in increased formation of hypophosphorylated IkappaB-beta and increased nuclear localization of IkappaB-beta in IB3 cells compared with the other cell types. These findings provide additional evidence of a dysregulated inflammatory response in CF. 相似文献
5.
M. Karthik Selvaraj Tapan Kumar Das Nikhil Joseph Martin M. Shyam Sundar David V. Rajan 《Indian Journal of Orthopaedics》2021,55(3):723
IntroductionLatarjet procedure is commonly performed for recurrent anterior shoulder instability with glenoid side bone loss. Classic Latarjet procedure can be performed using specially designed drill guides, jigs, or by freehand technique. Here we have described a technical note on classic Latarjet procedure performed with freehand technique utilizing simple rulers and caliper. The functional and radiological outcomes of our patients have also been analysed.Material and Methods149 open classic Latarjet procedures were performed using our technique between March 2015 and July 2018. The mean age of the patients was 32.95 years (Range 22–59 years). The functional outcome of the patients was measured using Western Ontario Shoulder Instability (WOSI) and Oxford Shoulder Instability Score (OSIS) at 2 years of follow-up. Screw and graft positioning were studied in 24 consecutive patients with a postoperative computed tomography (CT) scan.ResultsThere was no incidence of recurrent subluxation or dislocation post-surgery. Mean OSIS score increased from 15.63 ± 3.20 preoperatively to 42.44 ± 3.88 postoperatively (p value < 0.05). WOSI score decreased significantly from 62.54% ± 8.24 to 10.26 ± 6.33 postoperatively at 2-year follow-up (p value < 0.05). Postoperative CT scan also showed satisfactory screw placement in all patients.ConclusionOpen Latarjet procedure performed using freehand technique provides good functional and radiological outcomes in patients with recurrent anterior shoulder instability with glenoid side bone loss.Supplementary InformationThe online version contains supplementary material available at 10.1007/s43465-021-00385-7. 相似文献
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K Venkatakrishnan L L von Moltke D J Greenblatt 《Journal of clinical pharmacology》1999,39(6):567-577
The human cytochrome P450 (CYP) isoforms mediating nortriptyline 10-hydroxylation have been identified using kinetic studies on heterologously expressed human CYPs and chemical inhibition studies on human liver microsomes. Nortriptyline was metabolized to E-10-hydroxynortriptyline by human lymphoblast-expressed CYPs 2D6 (Km 2.1 microM) and 3A4 (Km 37.4 microM) with high and low affinity, respectively, whereas CYPs 1A2, 2A6, 2B6, 2C9, 2C19, and 2E1 had no detectable activity. Human liver microsomal nortriptyline E-10-hydroxylation displayed biphasic kinetics. The high-affinity component (Km 1.3 +/- 0.4 microM, n = 11 livers) was selectively inhibited by the CYP 2D6 inhibitor quinidine, whereas the CYP3A4 inhibitor ketoconazole selectively inhibited the low-affinity component (K(m) 24.4 +/- 7 microM, n = 11 livers). Inhibition by ketoconazole increased with increasing substrate concentration, whereas the reverse was true for quinidine. The Vmax of the low-affinity component in human liver microsomes was significantly correlated (r2 = 0.84) with the relative activity factor for CYP3A4, a measure of the amount of catalytically active enzyme. A simulation of the relative contribution of CYPs 2D6 and 3A4 to net nortriptyline hydroxylation rate suggested that the relative contribution of CYP3A4 is only 20% even at the higher end of the therapeutic range. Induction of CYP3A4 will increase its importance and increase the net metabolic rate, whereas inhibition of CYP3A4 will be of little importance due to its minimal relative contribution under uninduced conditions. The identification of CYP3A4 as a low-affinity nortriptyline E-10-hydroxylase explains the ability of poor metabolizers of debrisoquin to hydroxylate nortriptyline, as well as the increased in vivo clearance via this pathway caused by CYP3A4-inducing drugs such as pentobarbital, carbamazepine, and rifampin. 相似文献
8.
Preeti Kumari Omkara Swami Muddineti Sri Vishnu Kiran Rompicharla Pratyusha Ghanta Adithya Karthik B B N Balaram Ghosh 《Drug delivery》2017,24(1):209-223
Polymeric micelles have been widely explored preclinically as suitable delivery systems for poorly soluble chemotherapeutic drugs in cancer therapy. The present study reported the development of cholesterol (Ch)-conjugated poly(D,L-Lactide) (PLA)-based polymeric micelles (mPEG–PLA-Ch) for effective encapsulation and delivery of curcumin (CUR) at the tumor site. Cholesterol conjugation dramatically affected the particle size and improved drug loading (DL) and encapsulation efficiency (EE). mPEG–PLA-Ch-CUR showed bigger hydrodynamic diameter (104.6?±?2.1?nm, and 169.3?±?1.52?nm for mPEG–PLA and mPEG–PLA-Ch, respectively) due to increased size of the hydrophobic core. The newly developed polymer exhibited low critical micelles concentration (CMC) (25?μg/mL) which is close to lipid-based polymer, PEG-phosphatidyl ethanolamine (12.5?μg/mL) compared to mPEG–PLA (50?μg/mL). mPEG–PLA-Ch micelles exhibited relatively higher EE (93.74?±?1.6%) and DL (11.86?±?0.8%) compared to mPEG–PLA micelles (EE 91.89?±?1.2% and DL 11.06?±?0.8%). mPEG–PLA-Ch micelles were internalized by the cancer cells effectively and exhibited higher cytotoxicity compared to free CUR in both, murine melanoma (B16F10) and human breast cancer (MDA-MB-231) cells. mPEG–PLA-Ch exhibited satisfactory hemocompatibility indicating their potential for systemic application. Further, mPEG–PLA-Ch-CUR demonstrated higher rate of reduction of tumor volume in B16F10-xenografted tumor-bearing mice compared to free CUR. At the end of 22 days, the tumor reduced to 1.87-fold (627.72?±?0.9?mm3 versus 1174.68?±?1.64?mm3) compared to the treatment with free CUR. In conclusion, the experimental data in vitro and in vivo indicated that the newly developed CUR-mPEG–PLA-Ch micelles may have promising applications in solid tumors. 相似文献
9.
This article reviews the metabolic pharmacokinetic drug-drug interactions with the systemic antifungal agents: the azoles ketoconazole, miconazole, itraconazole and fluconazole, the allylamine terbinafine and the sulfonamide sulfamethoxazole. The majority of these interactions are metabolic and are caused by inhibition of cytochrome P450 (CYP)-mediated hepatic and/or small intestinal metabolism of coadministered drugs. Human liver microsomal studies in vitro, clinical case reports and controlled pharmacokinetic interaction studies in patients or healthy volunteers are reviewed. A brief overview of the CYP system and the contrasting effects of the antifungal agents on the different human drug-metabolising CYP isoforms is followed by discussion of the role of P-glycoprotein in presystemic extraction and the modulation of its function by the antifungal agents. Methods used for in vitro drug interaction studies and in vitro-in vivo scaling are then discussed, with specific emphasis on the azole antifungals. Ketoconazole and itraconazole are potent inhibitors of the major drug-metabolising CYP isoform in humans, CYP3A4. Coadministration of these drugs with CYP3A substrates such as cyclosporin, tacrolimus, alprazolam, triazolam, midazolam, nifedipine, felodipine, simvastatin, lovastatin, vincristine, terfenadine or astemizole can result in clinically significant drug interactions, some of which can be life-threatening. The interactions of ketoconazole with cyclosporin and tacrolimus have been applied for therapeutic purposes to allow a lower dosage and cost of the immunosuppressant and a reduced risk of fungal infections. The potency of fluconazole as a CYP3A4 inhibitor is much lower. Thus, clinical interactions of CYP3A substrates with this azole derivative are of lesser magnitude, and are generally observed only with fluconazole dosages of > or =200 mg/day. Fluconazole, miconazole and sulfamethoxazole are potent inhibitors of CYP2C9. Coadministration of phenytoin, warfarin, sulfamethoxazole and losartan with fluconazole results in clinically significant drug interactions. Fluconazole is a potent inhibitor of CYP2C19 in vitro, although the clinical significance of this has not been investigated. No clinically significant drug interactions have been predicted or documented between the azoles and drugs that are primarily metabolised by CYP1A2, 2D6 or 2E1. Terbinafine is a potent inhibitor of CYP2D6 and may cause clinically significant interactions with coadministered substrates of this isoform, such as nortriptyline, desipramine, perphenazine, metoprolol, encainide and propafenone. On the basis of the existing in vitro and in vivo data, drug interactions of terbinafine with substrates of other CYP isoforms are unlikely. 相似文献
10.
Beatrice C. Go Cammille C. Go Kevin Chorath Alvaro Moreira Karthik Rajasekaran 《世界耳鼻咽喉头颈外科杂志(英文)》2022,8(2):107
ObjectiveManagement of postoperative pain after head and neck cancer surgery is a complex issue, requiring a careful balance of analgesic properties and side effects. The objective of this review is to discuss the efficacy and safety of multimodal analgesia (MMA) for these patients.MethodsPubmed, Cochrane, Embase, Scopus, and clinicaltrials.gov were systematically searched for all comparative studies of patients receiving MMA (nonsteroidal anti‐inflammatory drugs (NSAIDs), acetaminophen, anticonvulsants, local anesthetics, and corticosteroids) for head and neck cancer surgeries. The primary outcome was additional postoperative opioid usage, and secondary outcomes included subjective pain scores, complications, adverse effects, and 30‐day outcomes.ResultsA total of five studies representing 592 patients (MMA, n = 275; non‐MMA, n = 317) met inclusion criteria. The most commonly used agents were gabapentin, NSAIDs, and acetaminophen (n = 221), NSAIDs (n = 221), followed by corticosteroids (n = 35), dextromethorphan (n = 40), and local nerve block (n = 19). Four studies described a significant decrease in overall postoperative narcotic usage with two studies reporting a significant decrease in hospital time. Subjective pain scores widely varied with two studies reporting reduced pain at postoperative day 3. There were no differences in surgical outcomes, medical complications, adverse effects, or 30‐day mortality and readmission rates.ConclusionMMA is an increasingly popular strategy that may reduce dependence on opioids for the treatment of postoperative pain. A variety of regimens and protocols are available for providers to utilize in the appropriate head and neck cancer patient. 相似文献