Microvascular reactivity and endothelial glycocalyx degradation when administering hydroxyethyl starch or crystalloid during off-pump coronary artery bypass graft surgery: a randomised trial.

The infusion of fluids to patients may affect tissue microcirculation and the endothelial glycocalyx. However, the effects of hydroxyethyl starch and crystalloid on endothelial glycocalyx degradation and microvascular reactivity have not been evaluated in detail. We hypothesised that hydroxyethyl starch may cause less endothelial glycocalyx degradation and better microvascular reactivity than that caused by crystalloid. We randomly allocated 120 patients undergoing off-pump coronary artery bypass graft surgery to receive up to 20 ml.kg-1 of either hydroxyethyl starch 670/0.75 or crystalloid for intra-operative fluid resuscitation. Crystalloid was then infused to meet ongoing fluid requirements. During the peri-operative period, vascular occlusion tests were performed to assess microvascular reactivity, and serum syndecan-1 was measured as an index of endothelial glycocalyx degradation. The median (IQR [range]) fluid infused during surgery was significantly less in the hydroxyethyl starch group than the crystalloid group; 2800 (2150-3550 [1400-7300]) vs. 3925 (3100-4725 [1900-6700]) ml, respectively, p < 0.001. Vascular occlusion test parameters, including tissue oxygen saturation, occlusion and recovery slope did not differ significantly between the groups. Peri-operative changes in syndecan-1 were not significantly different between the groups. We conclude that, in patients undergoing off-pump coronary artery bypass graft surgery, compared with crystalloid, the use of hydroxyethyl starch 670/0.75 did not result in significant differences in microvascular reactivity or endothelial glycocalyx degradation.

A Comparison of the Effects of Sevoflurane and Desflurane on Corrected QT Interval Prolongation in Patients Undergoing Living Donor Liver Transplantation: A Prospective Observational Study.

BACKGROUND: QT interval prolongation has frequently been observed in patients with advanced liver disease. We investigated the influence of inhalation anesthetics on the corrected QT (QTc) interval prolongation during surgery in patients undergoing living-donor liver transplantation. METHODS: Our study included 43 patients who were assigned to 2 groups: sevoflurane (n = 22) or desflurane anesthesia (n = 21). QTc intervals were measured at perioperative determined time points and calculated using Fridericia's formula. RESULTS: Intraoperative QTc intervals increased during the peri-intubation period versus baseline (P = .003) and were prolonged during the peri-reperfusion period (P < .001). However, there was no significant difference in intraoperative QTc interval changes between patients given sevoflurane or desflurane (P = .59). CONCLUSIONS: In this prospective observational study, there was no significant difference in QTc intervals between sevoflurane and desflurane. QTc intervals increased during intubation and reperfusion relative to preoperative values in patients given either sevoflurane or desflurane.

Effects of Palonosetron on Perioperative Cardiovascular Complications in Patients Undergoing Noncardiac Surgery With General Anesthesia: A Retrospective Cohort Study.

We retrospectively investigated whether palonosetron administered during the induction of general anesthesia is associated with an increased risk of perioperative cardiovascular complications in a single tertiary center cohort consisting of 4,517 palonosetron-exposed patients and 4,517 propensity score-matched patients without palonosetron exposure. The primary endpoint was a composite of perioperative cardiovascular complications, including intraoperative cardiac arrhythmia, intraoperative cardiac death, and myocardial injury within the first postoperative week, and there was no significant difference between the groups (odds ratio [OR] = 1.04; 95% confidence interval [CI] = 0.92-1.19). As secondary endpoints, intraoperative cardioversion, cardiac compression, use of cardiovascular drugs, postoperative hospital stay, and in-hospital mortality showed no differences between the groups. However, the palonosetron group showed decreased intraoperative hypotension (OR = 0.88; 95% CI = 0.79-0.97) and length of postoperative intensive care unit (ICU) stay (4.26 ± 9.86 vs. 6.14 ± 16.75; P = 0.026). Palonosetron did not increase the rate of perioperative cardiovascular complications, and can therefore be used safely during anesthetic induction.

Relationship between early postoperative C-reactive protein elevation and long-term postoperative major adverse cardiovascular and cerebral events in patients undergoing off-pump coronary artery bypass graft surgery: a retrospective study.

BACKGROUND: Inflammation plays a key role in the pathogenesis of vascular occlusive diseases, such as myocardial infarction and stroke. Additionally, these conditions are predicted by C-reactive protein (CRP), a general inflammation marker. We hypothesized that the inflammation induced by surgery itself augments vascular occlusive disease. We retrospectively evaluated the relationship between postoperative CRP elevation and postoperative major adverse cardiovascular and cerebral events (MACCE) in patients undergoing off-pump coronary artery bypass surgery (OPCAB). METHODS: The electronic medical records of 1046 patients who underwent OPCAB were reviewed retrospectively. The relationship between postoperative serum CRP and long-term postoperative MACCE (median follow-up 28 months) was investigated. RESULTS: Patients were divided into quartiles according to maximum postoperative CRP levels (<18, 18-22, 22-27, ≥27 mg dl(-1)). The adjusted hazard ratios (HRs) were 2.15, 2.45, and 2.81, respectively (P=0.004), compared with the lowest quartile (<18 mg dl(-1)). In the multivariate analysis, the postoperative CRP quartile (HR 2.81; P=0.004), postoperative non-use of statins (HR 1.86; P=0.003), and postoperative maximum troponin I (HR 1.02; P<0.001) independently predicted postoperative MACCE, while preoperative CRP did not (P=0.203). Several parameters were correlated with postoperative maximum CRP level: body temperature (P=0.001) and heart rate (P<0.001) at the end of surgery; intraoperative last lactate (P<0.001) and base excess (P<0.001); and red blood cell transfusion (P=0.019). CONCLUSIONS: Postoperative CRP elevation was associated with long-term postoperative MACCE in OPCAB patients. This was mitigated by postoperative statin medication. Furthermore, postoperative CRP elevation was associated with intraoperative parameters reflecting hypoperfusion and inflammation.

Congenital lymphangiomatosis and an enteric duplication cyst in a young dog.

A two-year-old female poodle with abdominal distention was diagnosed with concurrent enteric duplication cyst and lymphangiomatosis. Both lesions were shown as cystic structures, but some characteristic features of enteric duplication cyst were identified including a thick cyst wall and shared blood supply with the duodenum. Although it was challenging to discriminate between the types of cyst based on diagnostic imaging, this report describes the characteristics of each type of lesion using several different imaging modalities.

Effect of palonosetron on the QTc interval in patients undergoing sevoflurane anaesthesia.

BACKGROUND: Palonosetron is a recently introduced 5-HT3 receptor antagonist for postoperative nausea and vomiting. Detailed standardized evaluation of corrected QT (QTc) interval change by palonosetron under sevoflurane anaesthesia is lacking. We evaluated QTc intervals in patients who are undergoing surgery with sevoflurane anaesthesia and receive palonosetron. METHODS: Our study included 100 patients who were undergoing elective surgery under sevoflurane anaesthesia. The patients were randomly assigned to two groups: those who received an i.v. injection of palonosetron 0.075 mg immediately before induction of anaesthesia (pre-surgery group, n=50) and those who received it after surgery in the recovery room (post-surgery group, n=50). QTc intervals were measured before operation, intraoperatively (baseline, immediately after tracheal intubation, and at 2, 10, 15, 30, 60, and 90 min after administration of palonosetron or placebo), and after operation (before and at 3, and 10 min after administration of palonosetron or placebo). QTc intervals were calculated using Fridericia's, Bazett's, or Hodges formulas. RESULTS: The perioperative QTc intervals were significantly increased from the baseline values, but were not affected by the pre- or post-surgical timing of palonosetron administration. CONCLUSIONS: There was no significant difference in the QTc intervals during the perioperative period, whether 0.075 mg of palonosetron is administered before or after sevoflurane anaesthesia. Palonosetron may be safe in terms of QTc intervals during sevoflurane anaesthesia. Clinical trial registration ClinicalTrials.gov: NCT01650961.

Natural killer T cells are dispensable in the development of allergen-induced airway hyperresponsiveness, inflammation and remodelling in a mouse model of chronic asthma.

Natural killer T (NK T) cells have been shown to play an essential role in the development of allergen-induced airway hyperresponsiveness (AHR) and/or airway inflammation in mouse models of acute asthma. Recently, NK T cells have been reported to be required for the development of AHR in a virus induced chronic asthma model. We investigated whether NK T cells were required for the development of allergen-induced AHR, airway inflammation and airway remodelling in a mouse model of chronic asthma. CD1d-/- mice that lack NK T cells were used for the experiments. In the chronic model, AHR, eosinophilic inflammation, remodelling characteristics including mucus metaplasia, subepithelial fibrosis and increased mass of the airway smooth muscle, T helper type 2 (Th2) immune response and immunoglobulin (Ig)E production were equally increased in both CD1d-/- mice and wild-type mice. However, in the acute model, AHR, eosinophilic inflammation, Th2 immune response and IgE production were significantly decreased in the CD1d-/- mice compared to wild-type. CD1d-dependent NK T cells may not be required for the development of allergen-induced AHR, eosinophilic airway inflammation and airway remodelling in chronic asthma model, although they play a role in the development of AHR and eosinophilic inflammation in acute asthma model.

Gene therapy progress and prospects: noninvasive imaging of gene therapy in living subjects.

Recent progress in the development of noninvasive imaging technologies should allow molecular imaging to play a major role in the field of gene therapy. These tools have recently been validated in gene therapy models for continuous quantitative monitoring of the location(s), magnitude, and time variation of gene delivery and/or expression. This article reviews the use of radionuclide, magnetic resonance, and optical imaging technologies, as they have been used in imaging gene delivery and gene expression for gene therapy applications. The studies published to date lend support that noninvasive imaging tools will help to accelerate preclinical model validation, as well as allow for clinical monitoring of human gene therapy.

Determination of the prognostic value of [(18)F]fluorodeoxyglucose uptake by using positron emission tomography in patients with non-small cell lung cancer.

The aim of this study was to determine whether quantitative information obtained from [(18)F]fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) has a prognostic significance for patients with non-small cell lung cancer (NSCLC). We investigated (18)F-FDG PET imaging of 73 patients with NSCLC. The maximum standardized uptake value (SUV(max)) was significantly different between the histopathological types of tumour (squamous cell carcinoma (n=37, 12.4+/-5.1), adenocarcinoma (n=30, 8.2+/-5.8), bronchioloalveolar carcinoma (n=4, 2.6+/-1.7), <0.01). In the univariate analysis of all patients, staging (P=0.0001), tumour cell type (P=0.013), and a SUV(max) greater than 7 (P=0.0011) was correlated with survival. However, a multivariate analysis identified staging and SUV(max) greater than 7 were affected survival adversely. The mortality rate of patients with group I disease (stage I to stage IIIA) was 5.8 times lower than that of patients with group II disease (stage IIIB to stage IV). Patients with a high SUV(max) (> or =7) had a 6.3 times higher mortality than those with a low SUV(max)(<7). By multivariate analysis of patients with squamous cell carcinoma, only grouping affected survival (P=0.008, relative risk=4.3). In the case of adenocarcinoma, the SUV(max) (>10) correlated exclusively with poorer survival (P=0.031, relative risk=11.152). (18)F-FDG uptake correlated with survival in NSCLC. Especially in adenocarcinomas, the SUV(max) was complementary to other known prognostic factors.

Focal pulmonary uptake during Tc-99m myocardial perfusion SPECT imaging.

PURPOSE: To evaluate the incidence and origin of abnormal focal pulmonary uptake during myocardial perfusion SPECT imaging (MSPECT). METHODS: For evaluation of chest pain, 790 men and 581 women (mean age, 56 +/- 13 years) underwent MSPECT. All of them received adenosine for pharmacologic stress and Tc-99m tetrofosmin (TF, n = 817) or Tc-99m sestamibi (MIBI, n = 554) for myocardial perfusion imaging. RESULTS: Review of chest radiography with or without computed tomography revealed 111 (8.1%) focal pulmonary diseases. Among them, 38 (34.2%) showed focal pulmonary uptake (TF, 22; MIBI, 16); 27 (30.7%) of 88 showed previous pulmonary tuberculosis; 2 of 10 (20%) benign pulmonary nodules; 4 of 5 (80%) metastatic lung cancers; 2 of 4 (50%) primary lung cancers; and 3 of 4 (75%) pneumonias. No difference in uptake was noted for the two imaging agents. Intensity of uptake did not vary with origin of the uptake. Focal abnormal pulmonary uptake was found in 2.8% of patients undergoing MSPECT and in 34.2% of patients in whom radiological examinations showed regional pulmonary disease. In patients with abnormal pulmonary uptake on MSPECT, 16% had a malignant lesion, whereas 75% of patients with a pulmonary nodule shown on radiography and focal pulmonary uptake on MSPECT had a malignant lesion. CONCLUSIONS: Although the incidence of abnormal pulmonary uptake during MSPECT was very low, the incidence of malignant lesions in the patients with nodular pulmonary uptake was relatively high.

Relationship between expression of the sodium/iodide symporter and 131I uptake in recurrent lesions of differentiated thyroid carcinoma.

The sodium/iodide symporter (NIS) is known to be responsible for the active accumulation of iodide within the thyroid gland. We evaluated the relationship between the expression of NIS in primary or lymph node lesions and iodine-131 uptake in recurrent lesions of differentiated thyroid cancer. In 67 patients with differentiated thyroid cancer (5 follicular and 62 papillary carcinomas), the expression of NIS was analysed by immunohistochemical staining using polyclonal antibodies against human NIS. We used paraffin block tissues of primary tumours or metastatic lesions, and also assessed 131I uptake in recurrent lesions of thyroid cancer on post-operative 131I whole-body scan. Immunohistochemical staining was positive in 22 patients (32.8%), including 2 of 5 follicular and 20 of 62 papillary carcinomas. Recurrence was confirmed in 40 patients pathologically or clinically by serum thyroglobulin, 131I scan, fluorine-18 fluorodeoxyglucose positron emission tomography and/or computed tomography. Among these 40 patients, 28 showed positive uptake on 131I scan. Fourteen tumour specimens out of 28 (50%) were positive by NIS immunohistochemical staining. The remaining 12 patients with recurrent cancer showed negative 131I scans, and all specimens were negative by NIS immunohistochemical staining. Thus, NIS immunohistochemical staining predicted 131I uptake in recurrent cancer with a 100% positive predictive value and a 46.2% negative predictive value. There was no difference in the positivity of NIS according to the site of recurrence on 131I scan. Outcome of 131I therapy could be assessed in 22 of the 28 patients who showed 131I uptake in recurrent lesions. Patients with positive NIS immunostaining responded to 131I therapy better than did patients with negative immunostaining (P<0.05). In conclusion, NIS immunohistochemical staining showed a high positive predictive value in predicting iodine uptake. Positive immunohistochemical staining of human NIS in primary or lymph node lesions may predict 131I accumulation and effectiveness of 131I therapy in recurrent lesions.

Relationship between expression of the sodium/iodide symporter and (131)I uptake in recurrent lesions of differentiated thyroid carcinoma.

The sodium/iodide symporter (NIS) is known to be responsible for the active accumulation of iodide within the thyroid gland. We evaluated the relationship between the expression of NIS in primary or lymph node lesions and iodine-131 uptake in recurrent lesions of differentiated thyroid cancer. In 67 patients with differentiated thyroid cancer (5 follicular and 62 papillary carcinomas), the expression of NIS was analysed by immunohistochemical staining using polyclonal antibodies against human NIS. We used paraffin block tissues of primary tumours or metastatic lesions, and also assessed (131)I uptake in recurrent lesions of thyroid cancer on postoperative (131)I whole-body scan. Immunohistochemical staining was positive in 22 patients (32.8%), including 2 of 5 follicular and 20 of 62 papillary carcinomas. Recurrence was confirmed in 40 patients pathologically or clinically by serum thyroglobulin, (131)I scan, fluorine-18 fluorodeoxyglucose positron emission tomography and/or computed tomography. Among these 40 patients, 28 showed positive uptake on (131)I scan. Fourteen tumour specimens out of 28 (50%) were positive by NIS immunohistochemical staining. The remaining 12 patients with recurrent cancer showed negative (131)I scans, and all specimens were negative by NIS immunohistochemical staining. Thus, NIS immunohistochemical staining predicted (131)I uptake in recurrent cancer with a 100% positive predictive value and a 46.2% negative predictive value. There was no difference in the positivity of NIS according to the site of recurrence on (131)I scan. Outcome of (131)I therapy could be assessed in 22 of the 28 patients who showed (131)I uptake in recurrent lesions. Patients with positive NIS immunostaining responded to (131)I therapy better than did patients with negative immunostaining (P<0.05). In conclusion, NIS immunohistochemical staining showed a high positive predictive value in predicting iodine uptake. Positive immunohistochemical staining of human NIS in primary or lymph node lesions may predict (131)I accumulation and effectiveness of (131)I therapy in recurrent lesions.

Dipyridamole modulated Tc-99m sestamibi lung SPECT in small cell lung cancer.

PURPOSE: In this study, the authors wanted to determine whether dipyridamole-modulated MIBI (dipyridamole-MIBI) could enhance the prediction of the response to chemotherapy in patients with small cell lung cancer. METHODS: Twenty-seven patients with biopsy-proved small cell lung cancer (25 men, 2 women; mean age, 61 +/- 7 years) underwent dipyridamole-MIBI SPECT 3 to 7 days before starting chemotherapy (80 mg/m2 etoposide and 80 mg/m2 cisplatin every 3 or 4 weeks for at least two cycles). Tomographic images before and after dipyridamole (0.84 mg/kg) were acquired 1 hour after injection of 370 (10 mCi) and 1,110 (30 mCi) MBq MIBI, respectively. The response to chemotherapy was grouped as specified as complete response (CR), partial (PR), no change (NC), or progressive disease (PD), according to the change in tumor size on chest roentgenography and CT. Patients showing CR and PR were classified as responders, and those who showed NC and PD were considered nonresponders. RESULTS: Among the 27 patients, 22 were responders (3 CR, 19 PR) and 5 were nonresponders (3 NC, 2 PD). The tumor-to-normal lung ratio (T:NL) of responders was significantly higher than that of nonresponders. The diagnostic accuracy of the T:NL ratio to differentiate responders and nonresponders was 33.3%, with a cutoff value of 2.5, which was significantly improved to 77.8% when an increased T:NL ratio after dipyridamole was assigned to a nonresponder. Furthermore, all patients with CR showed diminished T:NL ratios after dipyridamole, and all patients with NR showed an increased T:NL ratio after dipyridamole. CONCLUSION: Dipyridamole-MIBI SPECT could enhance the prediction of response to chemotherapy in patients with small cell lung cancer.

Technetium-99m-MIBI uptake in small cell lung cancer.

UNLABELLED: Patients with small cell lung cancer (SCLC) often fail to respond to chemotherapy due to multidrug resistance (MDR). Technetium-99m-MIBI was reported to be a suitable transport substrate of P-glycoprotein, which is a cytoplasmic membrane protein encoded by the MDR gene. The purpose of this study was to evaluate whether or not the degree of MIBI uptake in SCLC or its retention on delayed imaging correlated with response to chemotherapy. METHODS: Twenty-five patients (19 men, 6 women; mean age 59 +/- 10 yr) with biopsy-proven SCLC had MIBI SPECT 3-7 days before starting chemotherapy. Imaging was acquired 1 and 4 hr after injection of 740 MBq MIBI using a single-head rotating gamma camera. Tumor-to-normal lung uptake ratio (T/NL) was measured. Percent retention (%R) was measured as: %R = 100 x (T/NL at 4 hr)/(T/NL at 1 hr). All patients received VAP chemotherapy (VP-16 100 mg/m2, adriamycin 40 mg/m2, cisplatin 25 mg/m2) every 4 wk for at least three times. Response to chemotherapy was grouped as complete remission, partial remission and no remission according to the change of tumor size on chest radiograph and CT images. Differences in T/NL and %R among the three groups were analyzed using ANOVA. RESULTS: T/NL of patients with complete remission (n = 7) and partial remission (n = 10) were significantly higher than that of no remission (n = 8) in 1 hr and 4 hr. T/NL at 1 hr in three groups were 2.75 +/- 0.78, 2.35 +/- 0.31 and 1.65 +/- 0.36, respectively. T/NL at 4 hr in three groups was 2.61 +/- 0.94, 2.48 +/- 0.50 and 1.66 +/- 0.42, respectively. However, %R was not different among three groups. Percent retention in three groups was 109.40 +/- 22.10, 96.71 +/- 14.25 and 103.59 +/- 28.43, respectively. CONCLUSION: SCLC with a higher MIBI uptake was more likely to respond to chemotherapy than that with a lower uptake. However, there was a considerable overlap of MIBI uptake among subjects. No significant correlation between the MIBI retention between 1 hr and 4 hr, and the response to chemotherapy was noted.

Characterization of a novel NTP-dependent 3' exoribonuclease from yeast mitochondria.

We have purified and characterized a novel exoribonuclease that was isolated from the mitochondria of Saccharomyces cerevisiae. The enzyme degraded RNA in a 3' to 5' direction and was dependent on nucleotide triphosphates for activity. All eight of the standard ribo- and deoxyribonucleotide triphosphates supported activity with an apparent Km ranging from 20 to 90 uM. The enzyme also exhibited an RNA-dependent ATPase activity. Evidence suggests that in vivo the enzyme may associate with mitochondrial factors which can alleviate the dependence on nucleotide triphosphates for enzymatic activity. A model is discussed for the role of the enzyme in regulating the turnover of mitochondrial RNAs.