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91.
Incidence of BK with Tacrolimus Versus Cyclosporine and Impact of Preemptive Immunosuppression Reduction 总被引:8,自引:0,他引:8
Daniel C. Brennan Irfan Agha Daniel L. Bohl Mark A. Schnitzler Karen L. Hardinger Mark Lockwood Stephanie Torrence Rebecca Schuessler Tiffany Roby Monique Gaudreault-Keener Gregory A. Storch 《American journal of transplantation》2005,5(3):582-594
Our purposes were to determine the incidence of BK viruria, viremia or nephropathy with tacrolimus (FK506) versus cyclosporine (CyA) and whether intensive monitoring and discontinuation of mycophenolate (MMF) or azathioprine (AZA), upon detection of BK viremia, could prevent BK nephropathy. We randomized 200 adult renal transplant recipients to FK506 (n = 134) or CyA (n = 66). Urine and blood were collected weekly for 16 weeks and at months 5, 6, 9 and 12 and analyzed for BK by polymerase chain reaction (PCR). By 1 year, 70 patients (35%) developed viruria and 23 (11.5%) viremia; neither were affected independently by FK506, CyA, MMF or AZA. Viruria was highest with FK506-MMF (46%) and lowest with CyA-MMF (13%), p = 0.005. Viruria >/= 9.5 log(10) copies/mL was associated with a 3-fold increased risk of viremia and a 13-fold increased risk of sustained viremia. After reduction of immunosuppression, viremia resolved in 95%, without increased acute rejection, allograft dysfunction or graft loss. No BK nephropathy was observed. Choice of calcineurin inhibitor or adjuvant immunosuppression, independently, did not affect BK viruria or viremia. Viruria was highest with FK506-MMF and lowest with CyA-MMF. Monitoring and preemptive withdrawal of immunosuppression were associated with resolution of viremia and absence of BK nephropathy without acute rejection or graft loss. 相似文献
92.
Najat C Daw Wayne L Furman Clinton F Stewart Lisa C Iacono Mark Krailo Mark L Bernstein Janet E Dancey Rose Anne Speights Susan M Blaney James M Croop Gregory H Reaman Peter C Adamson 《Journal of clinical oncology》2005,23(25):6172-6180
PURPOSE: Epidermal growth factor receptor is expressed in pediatric malignant solid tumors. We conducted a phase I trial of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in children with refractory solid tumors. PATIENTS AND METHODS: Gefitinib (150, 300, 400, or 500 mg/m2) was administered orally to cohorts of three to six patients once daily continuously until disease progression or significant toxicity. Pharmacokinetic studies were performed during course one (day 1 through 28). RESULTS: Of the 25 enrolled patients, 19 (median age, 15 years) were fully evaluable for toxicity and received 54 courses. Dose-limiting toxicity was rash in two patients treated with 500 mg/m2 and elevated ALT and AST in one patient treated with 400 mg/m2. The maximum-tolerated dose was 400 mg/m2/d. The most frequent non-dose-limiting toxicities were grade 1 or 2 dry skin, anemia, diarrhea, nausea, and vomiting. One patient with Ewing's sarcoma had a partial response. Disease stabilized for 8 to > or = 60 weeks in two patients with Wilms' tumor and two with brainstem glioma (one exophytic). At 400 mg/m2, the median peak gefitinib plasma concentration was 2.2 microg/mL (range, 1.2 to 3.6 microg/mL) and occurred at a median of 2.3 hours (range, 2.0 to 8.3 hours) after drug administration. The median apparent clearance and median half-life were 14.8 L/h/m2 (range, 3.8 to 24.8 L/h/m2) and 11.7 hours (range, 5.6 to 22.8 hours), respectively. Gefitinib systemic exposures were comparable with those associated with antitumor activity in adults. CONCLUSION: Oral gefitinib is well tolerated in children. Development of the drug in combination with cytotoxic chemotherapy will be pursued. 相似文献
93.
Practical management of patients with non-small-cell lung cancer treated with gefitinib. 总被引:7,自引:0,他引:7
Neelam T Shah Mark G Kris William Pao Leslie B Tyson Barbara M Pizzo Murk-Hein Heinemann Leah Ben-Porat Dana L Sachs Robert T Heelan Vincent A Miller 《Journal of clinical oncology》2005,23(1):165-174
PURPOSE: The use of gefitinib, the first drug approved to inhibit the epidermal growth factor receptor tyrosine kinase, is indicated in patients with non-small-cell lung cancer with tumors progressive after chemotherapy. The unique mechanism of action of this agent leads to distinctive patterns of response and toxicity in persons with lung cancer. Many of the principles of management relevant to gefitinib are distinct from those with conventional cytotoxic drugs. To meet this need, we present practical guidelines on the use of gefitinib in patients with non-small-cell lung cancer. METHODS: This article reviews gefitinib's indications, dosing, response phenomena, and patterns of relapse in individuals with radiographic response. RESULTS: We present our recommendations for the management of rash and diarrhea caused by this agent. CONCLUSION: This information can guide practitioners and help them inform their patients about what to expect when they receive gefitinib. 相似文献
94.
Isaac Samuel M.D. Mark A. Yorek Ph.D. Asgar Zaheer Ph.D. Rory A. Fisher Ph.D. 《Journal of gastrointestinal surgery》2006,10(7):950-959
Using a unique surgical model (the donor rat model), we showed previously that duodenal replacement of bile-pancreatic juice,
obtained fresh from a donor rat, ameliorates ligation-induced acute pancreatitis. We hypothesize that bile-pancreatic juice
exclusion from gut exacerbates Akt/nuclear factor-kB (NF-kB) pathway activation and induces chemokine production in ligation-induced acute pancreatitis. We compared rats with bile-pancreatic
duct ligation to those with duodenal bile-pancreatic juice replacement fresh from a donor rat beginning immediately before
duct ligation. Sham control rats had ducts dissected but not ligated. Rats were killed 1 or 3 hours after operation (n=7/group).
Akt activation (immunoblotting, immune-complex kinase assay, and ELISA), inhibitory protein I-kB (I-kB) activation (immunoblotting), and production of chemokines MCP-1 and RANTES (ELISA) were measured in pancreatic homogenates.
NF-kB was quantitated in nuclear fractions using electrophoretic mobility shift assay. Duct ligation produced significant increases
in pancreatic Akt, IkB, and NF-kB activation and production of MCP-1 and RANTES. Activation of the Akt/NF-kB pathway and increased MCP-1 and RANTES production in response to duct ligation were significantly reduced by bile-pancreatic
juice replacement (ANOVA, P<0.05). Bile-pancreatic juice exclusion stimulates Akt/NF-kB pathway activation and increases chemokine production in ligation-induced acute pancreatitis.
Presented at the annual meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 16, 2005 (poster). 相似文献
95.
Kimberly A. Varker Edward W. Martin Dori Klemanski Bryan Palmer Manisha H. Shah Mark Bloomston 《Journal of gastrointestinal surgery》2007,11(12):1680-1685
Background
Transarterial chemoemobolization (TACE) is commonly used to treat metastatic carcinoid tumors; however, the management of
progressive disease is less clear. We sought to determine if patients with disease progression after TACE would benefit from
repeat TACE.
Methods
The records of 27 patients undergoing repeat TACE for radiologic or symptomatic progression after TACE for metastatic carcinoid
were reviewed and compared to 122 undergoing first TACE. Overall and progression-free survivals were estimated by the Kaplan–Meier
method.
Results
Mean disease-free interval after first TACE was 11.8 months. Radiologic response was observed in 61% compared to 82% after
first TACE (p = 0.058); hormone response in 64% compared to 80% (p = 0.159); and symptomatic response in 77% compared to 92% (p = 0.053). The complication rate after repeat TACE was lower than after first TACE (p = 0.03). Median overall survival was similar after repeat (28.1 months) and first TACE (33.3 months) (p = 0.53). Progression-free survival was shorter after repeat TACE but not significantly so. No factor examined could predict
survival after repeat TACE.
Conclusion
Repeat TACE for patients with hepatic carcinoid metastases failing first TACE or having evidence of disease progression is
safe and offers a viable treatment option.
Presented at the 48th Annual Meeting of The Society for Surgery of the Alimentary Tract, Washington, DC, May, 2007. 相似文献
96.
97.
98.
99.
Background
Chronic plantar heel pain (CPHP) is one of the most common musculoskeletal disorders of the foot, yet its aetiology is poorly understood. The purpose of this study was to examine the association between CPHP and a number of commonly hypothesised causative factors. 相似文献100.
Mark A. Trimble Salvador Borges-Neto Stuart Smallhelser Ji Chen Emily F. Honeycutt Linda K. Shaw Jaekyeong Heo Robert A. Pagnanelli E. Lindsey Tauxe Ernest V. Garcia Fabio Esteves Frank Seghatol-Eslami G. Neal Kay Ami E. Iskandrian 《Journal of nuclear cardiology》2007,14(3):298-307
Background Cardiac resynchronization therapy (CRT) is approved for the treatment of patients with advanced systolic heart failure and
evidence of dyssynchrony on electrocardiograms. However, a significant percentage of patients do not demonstrate improvement
with CRT. Echocardiographic techniques have been used for more accurate determination of dyssynchrony. Single photon emission
computed tomography (SPECT) myocardial perfusion imaging has not previously been used to evaluate cardiac dyssynchrony. The
objective of this study is to evaluate mechanical dyssynchrony as described by phase analysis of gated SPECT images in patients
with left ventricular dysfunction, conduction delays, and ventricular paced rhythms.
Methods and Results A novel count-based method is used to extract regional systolic wall thickening amplitude and phase from gated SPECT images.
Five indices describing the phase dispersion of the onset of mechanical contraction are determined: peak phase, phase SD,
bandwidth, skewness, and kurtosis. These indices were determined in consecutive patients with left ventricular dysfunction
(n=120), left bundle branch block (n=33), right bundle branch block (n=19), and ventricular paced rhythms (n=23) and were
compared with normal control subjects (n=157). Phase SD, bandwidth, skewness, and kurtosis were significantly different between
patients with left ventricular dysfunction, left bundle branch block, right bundle branch block, and ventricular paced rhythms
and normal control subjects (all P<.001) Peak phase was significantly different between patients with right ventricular paced rhythms and normal control subjects
(P=.001).
Conclusions A novel SPECT technique for describing left ventricular mechanical dyssyn-chrony has been developed and may prove useful in
the evaluation of patients for CRT.
This study was funded in part by a research grant from the Medtronic-Duke Strategic Alliance, of which Dr Borges-Neto is the
primary investigator. 相似文献