The success of sorafenib in prolonging survival of patients with hepatocellular carcinoma (HCC) makes therapeutic inhibition of angiogenesis a component of treatment for HCC. To enhance therapeutic efficacy, overcome drug resistance and reduce toxicity, combination of antiangiogenic agents with chemotherapy, radiotherapy or other targeted agents were evaluated. Nevertheless, the use of antiangiogenic therapy remains suboptimal regarding dosage, schedule and duration of therapy. The issue is further complicated by combination antiangiogenesis to other cytotoxic or biologic agents. There is no way to determine which patients are most likely respond to a given form of antiangiogenic therapy. Activation of alternative pathways associated with disease progression in patients undergoing antiangiogenic therapy has also been recognized. There is increasing importance in identifying, validating and standardizing potential response biomarkers for antiangiogenesis therapy for HCC patients. In this review, biomarkers for antiangiogenesis therapy including systemic, circulating, tissue and imaging ones are summarized. The strength and deficit of circulating and imaging biomarkers were further demonstrated by a series of studies in HCC patients receiving radiotherapy with or without thalidomide. 相似文献
Background: Few studies have examined the use of ultrasound for sciatic nerve localization. The authors evaluated the usefulness of low-frequency ultrasound in identifying the sciatic nerve at three locations in the lower extremity and in guiding needle advancement to target before nerve stimulation.
Methods: In this prospective observational study, 15 volunteers underwent sciatic nerve examination using a curved ultrasound probe in the range of 2-5 MHz and a Philips-ATL 5000 unit (ATL Ultrasound, Bothell, WA) in the gluteal, infragluteal, and proximal thigh regions. Thereafter, an insulated block needle was advanced inline with the ultrasound beam to reach the nerve target, which was further confirmed by electrical stimulation. The quality of sciatic nerve images, ease of needle to nerve contact, threshold stimulating current, and resultant motor response were recorded.
Results: The sciatic nerve was successfully identified in the transverse view as a solitary predominantly hyperechoic structure on ultrasound in all of the three regions examined. The target nerve was visualized easily in 87% and localized within two needle attempts in all patients. Nerve stimulation was successful in 100% after two attempts with a threshold current of 0.42 +/- 0.12 (mean +/- SD) eliciting foot plantarflexion or dorsiflexion. 相似文献
The aim of this study was to examine the predictors of long-term survival (>24 months) in patients with gall bladder cancer.
A retrospective review of 117 cases of gall bladder cancer resected between 1989 and 2000. The resections included 80 simple
cholecystectomies and 37 extended procedures. Patients with survival >24 months (n=44) were compared with those having survival
<24 months (n=73) for 17 prognostic factors. Overall median survival was 16 months with a 5-year survival of 27%. T status
(P=.000) and adjuvant chemoradiotherapy (P=.001) were independent predictors of long-term survival. Survival advantage was
seen in T3N+ve disease (P=.007) with extended procedures. Complete (R0) resection was attained in 30 patients with a 5-year
survival advantage of 30% as compared with incomplete (R1) resection (P=.0002). Adjuvant chemoradiotherapy improved survival
in simple cholecystectomy group (P=.0008) but no advantage was seen after extended procedures. Stage III (P=.001) and node-positive
disease (P=.0005) had significant benefit with adjuvant therapy. Poor differentiation and vascular invasion were associated
with poor long-term survival. R0 resection was associated with prolonged survival. Extended procedures improved survival in
patients with T3N+ve disease. Addition of chemoradiotherapy made significant improvement in long-term survival in stage III
and node-positive lesions and in patients undergoing simple cholecystectomy. R0 resection predicted long-term survival in
gall bladder cancer. T3 N+ve disease had better survival after extended procedures. Adjuvant chemoradiotherapy improved survival
in stage III and node-positive disease. Poor differentiation and vascular invasion were adverse predictors of survival. 相似文献
Background Despite improving surgical techniques, treatment of heart valve disease in children remains controversial. Somatic growth
and adequate anticoagulation are of concern when children undergo valve replacement. We conducted this study to evaluate the
performance of valves in this age group.
Methods 42 children under the age of 13 years who underwent valve replacement were included in this study. Totally, 50 valves were
implanted in 42 patients: 48 were mechanical prostheses, two were bioprosthetic both in pulmonary position. 37 (74%) valves
were implanted in mitral position, 10 (20%) in aortic position, 1 (2%) in tricuspid position and 2 (4%) in pulmonary position.
Preoperatively, 14 (33,3%) patients were in New York Heart Association (NYHA) class IV, while 27 (64.2%) were in NYHA class
III.
Results There were 2 (4.7%) hospital deaths and 2 (4.7%) late deaths while 2 (4.7%) patients were lost to follow up. The mean follow
up period was 9.4 yrs. 35 (83.3%) patients are in NYHA Class I and free of all medications except warfarin. 3 (7.1%) patients
have undergone 5 successful pregnancies. The median INR was 2.23. Major thrombo-embolic episode occurred in 1 (2.3%) patient.
Conclusions In view of the problems of sizing, anticoagulation and need for re-operation at an early age, there is a reluctance to replace
valves in children. This study shows that despite these problems, valve replacement can be undertaken safely and successfully
in children, when repair has failed or not technically feasible. 相似文献
Background Beating heart surgery has now become the commonest technique of doing Coronary Artery Bypass Graft Surgery (CABG) in our country.
It is being used even in such high risk situations like diffuse coronary disease and Critical Left Main stem Stenosis (LMCS)
with good results. The aim of this study is to retrospectively review our results in Off-Pump Coronary Artery Bypass Surgery
(OPCAB) in patients with critical left main stem stenosis.
Methods This study is a retrospective analysis of the data of patients who underwent primary coronary artery bypass surgery. During
the period from April 2003 to September 2005 a total of 64 patients underwent OPCAB procedure for critical LMCS. During the
same period 10 patients underwent CABG on Cardio Pulmonary Bypass (CPB). The age range was 36–77yrs. The sex distribution
was M: F 53∶10. Ten patients were done as emergency. 2 of them were on Intra Aortic Balloon Pump (IABP) support preoperatively.
10 patients were high risk with a Euro score of ≥5.
Results Left Internal Mammary Artery (LIMA) was used in 78% of cases. Average grafts per patient was 2.96. The median ventilation
time was 5.91 hrs. New IABP insertion in postoperative period was required in 1 patient. One patient was reexplored for bleeding.
There was one perioperative myocardial infarction. 57% of patients did not need any blood transfusion. There was no conversion
to CPB. There was no operative mortality. Inotropes were used in ten cases.
Conclusions OPCAB is a safe method of revascularization in patients with critical LMCS. Preoperative IABP is useful in patients with cardiogenic
shock. However, there is a place for CPB in patients needing additional procedures like Mitral Valve repair (MV repair) or
Dor's procedure or when the vessels are very diffusely diseased. Those patients who are unstable despite IABP support may
be managed by Beating heart On Pump (BHOP) technique. 相似文献
The effects of daily oral administration of a high dose of 10 mg norethisterone acetate (NET-Ac.)/kg/day over 14 weeks on serum lipid and lipoprotein parameters as well as on blood coagulation were investigated in female monkeys (M. fascicularis). Measurements of lipids and lipoprotein cholesterol were performed in weeks —5 and — 1 before treatment and in weeks 4, 8 and 12 after treatment. In addition, various blood coagulation and fibrinolytic parameters were determined in weeks 11–14 after treatment with NET-Ac. Furthermore, the serum levels of norethisterone (NET) were determined in order to monitor the real systemic compound exposure and revealed that Cmax and AUC (0–3 h) values reached for norethisterone in this experiment in monkeys were about 25 times higher than those obtained after an oral contraceptive dose of NET-Ac. in women.
The results of lipid and lipoprotein cholesterol determinations showed decreases in serum total lipids, phospholipids, triglycerides and total cholesterol associated with similar decreases in HDL-, LDL- and VLDL-cholesterol fractions after NET-Ac.-treatment in monkeys. These effects were observed from week 4 onwards and maintained their magnitude up to week 12 after treatment. Since both HDL- and LDL-cholesterol fractions decreased, the HDL/LDL-ratio remained almost unchanged. Thus, the results obtained in this study after high-dose treatment with NET-Ac. in monkeys did not indicate any changes of lipid and lipoprotein parameters which in humans are supposed to be associated with an increased risk of cardiovascular lesions, namely a decrease in HDL- and increase in LDL-cholesterol fractions.
The results of blood coagulation and fibrinolytic parameters showed increased antithrombin-III and plasminogen levels besides minor changes in other parameters, thus indicating that NET-Ac. -treatment does not contribute to an increased risk of cardiovascular thrombotic events in the cynomolgus monkey. 相似文献
Summary We have investigated whether the pharmacokinetics and pharmacodynamics of the ACE inhibitor benazepril hydrochloride are altered with proteinuria by studying 8 patients with major proteinuria of different causes who were given a single dose of 10 mg p.o.The maximum plasma concentration of benazepril was found between 0.5 and 2 h after dosing (median 1 h). Its elimination was almost complete within 6 h. Peak plasma levels of benazeprilat, the active metabolite of benazepril, were observed between 1 and 6 h (median 2.5 h). The elimination of benazeprilat from plasma was biphasic, with mean initial and terminal half-lives of 3.0 and 17.3 h, respectively. On average, the pharmacokinetic parameters of benazepril and benazeprilat in the patients did not differ from those in a historical control group of healthy volunteers, but intersubject variability in the AUC and half-lives of benazeprilat was greater in the patients.Plasma ACE was completely inhibited from 1.5 to 6 h after dosing, and at 48 h the mean inhibition was still 42 %. Plasma renin showed substantial intersubject variation. Mean supine blood pressure (systolic/diastolic) was reduced from baseline by a maximum of 18/13 mm Hg at 6 h. Proteinuria was diminished after benazepril in 7 patients.In conclusion, the results of this study suggest that proteinuria in the nephrotic range does not require a change in benazepril dosage. 相似文献
Dantrolene seems to be the causal therapy in malignant hyperthermia (MH) crisis but the complex mechanisms of MH and dantrolene therapy are still not fully understood. The influence of dantrolene on ryanodine-induced contractures has been reported in animal studies only. In the present study 20 patients from] 7 families were tested for MH using the protocol of the European Malignant Hyperthermia Group. In addition ryanodine-induced contractures were evaluated following bolus application of 10.0 μmol · 1-1 ryanodine. After pretreatment with 1 μimol · 1-1 dantrolene ryanodine-provoked contractures developed significantly later in MHS (15.8±1.8 min) and MHN (46.0±4.2 min) muscle specimens than after ryanodine alone (MHS 4.8±0.7 min), (MHN 13.7±0.9 min). They were no longer observed in either group after pretreatment with 5 μimol · 1-1 dantrolene. We conclude that dantrolene is able to attenuate ryanodine-induced contractures dose-dependendy, and therefore it is speculated that dantrolene could specifically act at the ryanodine receptor binding site. 相似文献