Changes in circulating immunosuppressive cytokine levels of cancer patients after high intensity focused ultrasound treatment

Immunosuppression in a patient with malignant tumor is a major obstacle in cancer treatment. In this study, we investigated changes in the circulating level of all measured immunosuppressive cytokines in patients with malignancy before and after high intensity focused ultrasound (HIFU) treatment. Fifteen patients with solid malignancy were enrolled in this study and an enzyme-linked immunoabsorbent assay (ELISA) method was used to measure serum level of vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), transforming growth factor-beta2 (TGF-beta2), interleukin 6 (IL-6) and interleukin 10 (IL-10), respectively before and 1 wk after HIFU treatment. Among them, seven patients had distant metastasis and the remaining eight had no metastasis. All patients received one-session HIFU treatment for primary cancer, including complete ablation in eight patients without metastasis, and partial ablation in seven patients with metastases. The results showed that serum immunosuppressive cytokine levels decreased after HIFU treatment, and there were significant decreases of VEGF, TGF-beta1, and TGF-beta2 before and after HIFU treatment. Compared with the values in the metastatic patients, serum levels of immunosuppressive cytokines were significantly lower in the nonmetastatic patients after HIFU treatment. It is concluded that HIFU can decrease tumor-secreted immunosuppressive cytokine production in addition to its direct tumor destruction. This change may lessen tumor-induced immunosuppression and renew antitumor immunity after HIFU in cancer patients.     

The changes in leg blood flow during and after mild or severe acute hypoxaemia in healthy humans

The present study examines the leg blood flow changes in resting healthy humans during and after a 10‐min period of mild (PaO₂=5·60 kPa) or severe hypoxaemia (PaO₂=4·53 kPa) induced by breathing hypoxic gas mixtures. A Colour Duplex Scan system allowed to measure the cross‐sectional area (CSA) and mean blood flow (Qdot;) in a femoral artery (FA) and a femoral vein (FV) and also in an artery supplying leg muscles (medial gastrocnemius artery, MGA). During the mild as well as the severe hypoxaemia and their recovery periods, no significant variations of Qdot; and CSA occurred in FA and FV. During the mild hypoxaemia and the first 10 min of the recovery period, Qdot; and CSA of MGA increased (maximal changes: +84 and +20%, respectively). By contrast, a marked Qdot; decrease and a reduced CSA were measured in MGA during the severe hypoxaemia (?67 and ?60%, respectively). This reduced muscle blood flow was followed by a vasodilatation (CSA increase = +30%), which began 10 min after the hypoxaemia ended and persisted for a further 10‐min period. This study shows that the time course of muscle blood flow changes in response to acute hypoxaemia depends on the PaO₂ level. Reverse effects were measured during the mild or the severe hypoxaemia, whereas a post‐hypoxaemic vasodilatation occurred in all circumstances.     

Relation between changes in serum hypoxanthine levels by exercise and daily physical activity in the elderly.

Effect of exercise at mild intensity on the serum levels of hypoxanthine was studied in eleven healthy elderly subjects. They were divided into the active and sedentary groups according to their daily physical activity. They performed exercise testing to walk for 5 minutes keeping heart rate at approximately 70% of the maximum heart rate. Mean intensity of exercise estimated according to Karvonen's formula in the active or sedentary group was 41.8 +/- 9.6% or 34.1 +/- 6.1%, respectively. In the sedentary group, the serum hypoxanthine levels at 10 minutes after completion of walk load was significantly higher than that before exercise. Changes in the serum hypoxanthine levels in the active and sedentary groups were -0.97 +/- 1.36 and 0.80 +/- 0.57 micromol/liter, respectively (p < 0.05). This result suggests that mild intensity exercise increases the serum hypoxanthine concentration in the elderly leading inactive daily life, and physical activity suppresses an increase in the serum hypoxanthine levels by mild exercise.     

短期高原旅行中健康成人心肺功能的变化

目的:跟踪监测心肺功能多项指标,评估健康成人短期高海拔休息与运动状态下的心肺功能及随时间和海拔高度变化特点。方法:以2003-09/10深圳至西藏穿越雅鲁藏布江大峡谷20名雅江行队员为观察对象,男14人,女6人,高原旅行1个月,海拔高度从500～5400m。监测观察对象的血压(平均动脉压)、呼吸、心率、脉搏血氧饱和度以及呼吸心率乘积和收缩压心率乘积,分别于休息时、运动时记录各项指标,分析比较不同海拔高度、不同入高原时间(出发前,入高原第1,2,3,4周)心肺功能指标的变化。结果:按意向处理分析,进入结果分析对象20人:①性别差异情况:血压、呼吸、脉搏血氧饱和度等测试指标男女性别上无明显差别(P>0.05)。②不同海拔高度对健康成人静息和运动状态下心肺功能的影响:平均动脉压、心率、呼吸、收缩压心率乘积、呼吸心率乘积随海拔升高而呈上升趋势(P<0.05),血氧饱和度随海拔升高而呈下降趋势(P<0.01)。③进入高原不同时间段健康成人的心肺功能变化:入高原后第1周平均动脉压、呼吸频率、心率、收缩压呼吸乘积、心率呼吸乘积明显高于其他时间段(P<0.05～0.01),血氧饱和度入高原后明显低于其他时间段(P<0.05～0.01)。进入高原第4周时的平均动脉压、呼吸频率、心率和血氧饱和度的值与出发前无差别(P>0.05)。结论:①在平原和短期进入高原状态对健康成人心肺功能变化无性别差异。②高原缺氧对健康成人短期高原旅行的影响较明显,尤其在进入高原第1周内。急性高原疾病亦发生在进入高原的第1周内,随着高原居住时间的增加,机体逐渐适应高原缺氧。③机体对高原缺氧的反应与在高原停留的时间长短和适应程度有关。     

Changes in serum carbohydrate-deficient transferrin and gammaglutamyl transferase after moderate wine consumption in healthy males

Serum carbohydrate-deficient transferrin (CDT) concentrations and gamma-glutamyl transferase (GGT) activities were measured in the fasting serum of healthy male subjects before and after 4 weeks consumption each day of 375 ml wine or 500 ml grape juice. After wine consumption, serum CDT concentrations rose in 38 of 48 individual test procedures, and the mean ± SEM increased from 17.8 ± 0.86 u/l to 20.9 ± 1.14 u/l (t_o = 4.66; P <0.001). Serum GGT activity rose in 35 of these test procedures, and the mean ± SEM increased from 19.6 ± 1.40 u/l to 22.3 ± 1.79 u/l (t_o = 3.58; P <0.001). When wine consumption was followed by 2 weeks of abstinence from alcohol, significant reductions in both CDT and GGT were noted, virtually reaching baseline levels. No significant change in either index occurred after 4 weeks of consuming grape juice. The correlation between CDT and GGT was rather low, suggesting that their responses to alcohol occur by different mechanisms. The results indicate that the response of CDT to alcohol dose is continuous, and that even moderate consumption can cause significant elevations in a healthy population. J. Clin. Lab. Anal. 12:92–97, 1998. © 1998 Wiley-Liss, Inc.     

Changes in serum erythropoietin levels during chemotherapy for lung cancer.

Serial serum erythropoietin (EPO) levels were measured in 12 adult lung cancer patients during cancer chemotherapy. In major cases, EPO levels increased significantly after chemotherapy while the hemoglobin (Hb) remained at initial levels. EPO fell gradually or rapidly to initial levels after a peak, although the patients were anemic. The increase of EPO levels was linearly related to the decrease in Hb (y = 17.48x + 1.003). The mechanism of the rapid increase of EPO is not simply explained by anemia, but might be related to new synthesis, corresponding to depressed bone marrow.     

Changes in femur stress after hip resurfacing arthroplasty: response to physiological loads

BACKGROUND: Hip resurfacing arthroplasty is being increasingly considered as an alternative to total hip arthroplasty in young, active patients. Hip resurfacing arthroplasty is reported to preserve the normal joint mechanics. However, there is concern, in the short term, due to frequent occurrence of femoral neck fractures. METHODS: We evaluated changes in femoral mechanics after hip resurfacing arthroplasty. We used an experimentally validated, distributed material finite element model of a cadaveric femur before and after hip resurfacing arthroplasty. Bone stiffness and strength values representing normal, elderly and osteoporotic bone were used. For a physiological load case, bone strains were compared with literature values for total hip arthroplasty and a risk of fracture scalar calculated. FINDINGS: The changes in peak stresses after hip resurfacing arthroplasty were low in relation to the failure strength of bone and the fracture risk was low. The intact and implanted finite element models showed bone strains after hip resurfacing arthroplasty were closer to the intact condition than after total hip arthroplasty. INTERPRETATION: The bone stresses predicted after resurfacing in both the normal and aged femoral neck were not sufficient to be a potential cause of fracture.     

BRL 17421, a novel beta-lactam antibiotic, highly resistant to beta-lactamases, giving high and prolonged serum levels in humans

BRL 17421 is a new semisynthetic beta-lactam antibiotic with an unusual spectrum of antibacterial activity. The compound exhibits exceptional stability to a wide range of bacterial beta-lactamases and is active against the majority of Enterobacteriaceae, including strains highly resistant to many of the penicillins and cephalosporins currently available. Among the clinical isolates of Enterobacteriaceae tested, the frequency of strains resistant to BRL 17421 was found to be low, and there was a slow rate of emergence of resistance during in vitro studies. BRL 17421 was highly active against Haemophilus influenzae and Neisseria gonorrhoeae, including beta-lactamase-producing strains. The compound was markedly less active against Pseudomonas aeruginosa and Bacteroides fragilis than against the Enterobacteriaceae. Against the gram-positive bacteria, BRL 17421 showed a very low level of activity. BRL 17421 was found to be 85% bound to human serum, and the antibacterial activity was diminished two- to fourfold in the presence of human serum. Against experimental infections in mice, the activity of BRL 17421 reflected the properties observed in vitro. Studies in human volunteers showed unusually high and prolonged serum concentrations of the compound after parenteral dosage, with a serum half-life of about 5 h, and approximately 85% of the dose was recovered unchanged in the urine. BRL 17421 was poorly absorbed after oral administration. The compound was well tolerated after intramuscular and intravenous administration in volunteers, with no adverse side effects.     

Soluble serum Klotho levels in healthy subjects. Comparison of two different immunoassays

Objective

Soluble serum Klotho is a new biomarker linked to chronic kidney disease, cardiovascular disease and diabetes. This study describes the evaluation and comparison of two different immunoassays and establishment of assay specific reference intervals in adults.

Design and methods

Serum Klotho concentrations were determined in 120 healthy adults aged 19–66 years. Blood samples were collected, and stored sera were assayed for Klotho according to age and gender. In addition several other clinical and laboratory characteristics were determined in the cohort and compared to the levels of serum Klotho.

Results

Serum Klotho levels were significantly higher in time-resolved fluorescence immunoassay (TRF) compared to an ELISA (IBL) and no correlation was found between the assays. No signal was obtained in either assay when the standard curve was switched between the two different immunoassays. The median serum Klotho concentration using TRF was 61 ng/mL (2.5–97.5% reference limits; 11–181 ng/mL) for males and 99 ng/mL (2.5–97.5% reference limits; 19–316 ng/mL) for females while the ELISA gave a mean value of 472 pg/mL (2.5–97.5% reference limits; 204–741 pg/mL) with no difference between genders. Concentrations of serum Klotho were independently associated with estimated glomerular filtration rate (eGFR) and body weight using TRF whereas serum Klotho concentrations were associated with age using the ELISA.

Conclusion

Comparison of two different immunoassays for serum Klotho indicate, that the protein exists in human beings in different forms which may function as independent factors and whose role and potential value as biomarkers needs to be evaluated separately. Reference intervals specific for the different forms recognized by the different assays were calculated in this study.     

急性脑卒中后并发血管性认知障碍患者的血清半胱氨酸蛋白酶抑制剂C水平变化

目的 探讨急性脑卒中后并发血管性认知障碍(VCI)患者的血清半胱氨酸蛋白酶抑制剂(Cys)C水平的变化及其临床意义,为VCI患者的早期诊断及治疗提供依据.方法 选择2012年12月至2013年12月东营市人民医院神经内科和神经外科收治的120例急性脑卒中患者为研究对象,纳入研究组,按脑卒中后是否并发VCI将其分为VCI亚组(n=60)和非VCI亚组(n=60);并选择同期于本院门诊体检的年龄≥50岁、无认知功能减退主诉的60例受试者纳入对照组.采用《简易精神状态评价量表》(MMSE)系统评价VCI亚组患者认知功能,并根据MMSE评分结果评价其VCI严重程度.采用全自动生化分析仪免疫比浊法检测研究组与对照组血清Cys C水平,并进行比较,同时对VCI亚组患者血清Cys C水平与VCI严重程度之间的关系进行统计学分析.本研究遵循的程序符合东营市人民医院人体试验委员会所制定的伦理学标准,得到该伦理会批准,分组征得受试对象本人的知情同意,并与之签订临床研究知情同意书.结果 VCI亚组、非VCI亚组及对照组3组受试者性别构成、年龄、受教育年限、原发性高血压、糖尿病等社会人口学资料比较,差异均无统计学意义(P＞0.05).VCI亚组患者血清Cys C水平为(1.68±0.46) mg/L,高于非VCI亚组[(0.88±0.42) mg/L]和对照组[(0.83±0.32) mg/L],且3者比较,差异有统计学意义(F=12.99,P＜0.05).VCI亚组患者中,VCI不同严重程度患者血清Cys C水平比较,差异有统计学意义(F=7.98,P＜0.05).其中,MMSE评分≤13分的重度VCI患者为19例,其血清Cys C水平最高,为(1.92±0.36) mg/L;MMSE评分为≥14～20分的中度VCI患者为23例,其血清Cys C水平为(1.33±0.41) mg/L;MMSE评分为≥21～24分的轻度VCI患者为18例,其血清Cys C水平最低,为(1.09±0.28) mg/L.3者比较,差异有统计意义(F=7.98,P＜0.05).VCI亚组患者血清Cys C水平越高,其VCI程度越严重.VCI亚组患者Cys C水平与MMSE评分的Spearmen相关系数的双变量相关分析结果示,MMSE评分与VCI患者血清CysC水平呈负相关关系(r=-0.421,P=0.039).结论 急性脑卒中患者血清Cys C水平与其VCI的发生、发展有关.血清Cys C水平可作为急性脑卒中患者VCI早期诊断的外周血生物学标志物之一,为VCI的早期诊断与治疗提供生物学依据.     

Changes in symptoms and pain intensity of cancer patients after enrollment in palliative care at home

This study describes the activities and interventions carried out by an at-home palliative care team treating cancer patients who died within two years of being enrolled in a palliative care program. It analyzes which changes in symptoms and pain occurred and which sociodemographic and medical characteristics were related to these changes. The analysis is based on 102 cancer patients. Data were collected through systematic registration during the palliative care process. At enrollment, patients were interviewed by the coordinating general practitioner concerning their sociodemographic background, medical history, psychological status, and symptoms. During the palliative care process, symptoms and functioning of the patients were recorded by the physician and nurses. The results show that cancer patients enrolled in palliative care at home have many symptoms, often associated with metastatic disease and comorbidities. The palliative care teams delivered frequent and various interventions. The number of symptoms decreased considerably, as did pain intensity and the intensity of other symptoms. Patients living in urban areas and with low income particularly benefited from a reduction in the number of symptoms they displayed. Cancer patients who needed palliative care benefited significantly from this at-home palliative care service.     

Effect of apolipoprotein E polymorphism on serum uric acid levels in healthy subjects.

BACKGROUND: We have previously shown that apolipoprotein E (apo E-) polymorphism may affect serum creatinine concentration and predicted glomerular filtration rate in healthy individuals. On the other hand, there are limited data regarding the possible influence of apo E- polymorphism on serum uric acid (SUA) levels. METHODS: Two hundred ninety (148 male, 142 female) apparently healthy white individuals were studied. apo E- genotypes, serum lipid parameters including apolipoproteins, insulin resistance using the homeostasis model assessment (HOMA) as a marker, serum and urine creatinine levels, and serum and urine uric acid concentration were determined in all participants. RESULTS: The apo E-2 allele was associated with lower serum levels of total cholesterol, higher levels of triglycerides and apo E-, and increased serum creatinine concentration compared with the apo E-3 and apo E-4 alleles in our population. Furthermore, the apo E-2 allele was associated with higher SUA levels (321.3+/-101.1 micrmol/L [5.4+/-1.7 mg/dL]) compared with the apo E-3 allele (261.8+/-89.2 micromol/L [4.4+/-1.5 mg/dL]; p= .012) and the apo E-4 allele (243.9+/-65.4 micromol/L [4.1+/-1.1 mg/dL]; p= .010), whereas the apo E-2 allele was associated with a nonsignificantdecrease in the fractional renal excretion of uric acid (FEUA) compared with the apo E-3 and apo E-4 alleles (7.9+/-2.2% vs 8.7+/-4.2% vs 8.9+/-5.1%, respectively; p = .53). These observations remained statistically significant when the effect of apo E- polymorphism on SUA levels was adjusted for gender, age, systolic and diastolic blood pressure, body mass index, serum creatinine, and triglyceride and apo E- levels, as well as for HOMA index and FEUA. CONCLUSIONS: Our data provide evidence, for the first time, that the apo E-2 allele is independently associated with increased SUA levels in healthy individuals.     

Plasma nitrite concentration decreases after hyperoxia-induced oxidative stress in healthy humans

The aim of this study was to measure plasma nitrite, the biochemical marker of endothelial nitric oxide (^?NO) synthesis, before and after hyperoxia, in order to test the hypothesis that hyperoxia‐induced vasoconstriction is a consequence of reduced bioavailability of ^?NO caused by elevated oxidative stress. Ten healthy men breathed 100% normobaric O₂ for 30 min between 15th and 45th min of the 1‐h study protocol. Plasma nitrite and malondialdehyde (MDA), arterial stiffness (indicated by augmentation index, AIx) and arterial oxygen (P_tcO₂) pressure were measured at 1st, 15th, 45th and 60th minute of the study. Breathing of normobaric 100% oxygen during 30 min caused an increase in P_tcO₂ (from 75 ± 2 to 412 ± 25 mm Hg), AIx (from ?63 ± 4 to ?51 ± 3%) and MDA (from 152 ± 13 to 218 ± 15 nm ) values and a decrease in plasma nitrite (from 918 ± 58 to 773 ± 55 nm ). During the 15‐min recovery phase, plasma nitrite, AIx and MDA values remained altered. This study suggests that the underlying mechanism of hyperoxia‐induced vasoconstriction may involve reduced ^?NO bioavailability caused by elevated and sustained oxidative stress.     

Sputum levels of fluconazole in humans.

We measured fluconazole levels in sputum samples obtained from 11 bronchiectatic volunteers at 4 and 24 h after a single oral dose of 150 mg of fluconazole. Levels in sputum were similar to levels in plasma at both times.     

大鼠脑缺血再灌注后血清神经元特异性烯醇化酶变化及吲哚美辛的干预作用

目的:探讨大鼠脑缺血再灌注后血清神经元特异性烯醇化酶(neuro-specificenolase,NSE)水平和脑组织病理改变及吲哚美辛对脑缺血再灌注后的保护作用。方法:采用线栓法将SD大鼠制成大脑中动脉再灌注模型。第1部分将80只SD大鼠分成脑缺血2h再灌注后1,2,3,4,5d5个实验组。观测各组血清NSE,脑梗死灶体积及脑组织病理形态变化。第2部分探讨吲哚美辛对大鼠脑缺血再灌注后的保护作用,将30只SD大鼠分成对照组(脑缺血2h再灌注后3d),2个治疗组分别于再灌注前、后1h给药存活至再灌注后3d,观察组同前。结果:①脑缺血再灌注后脑梗死灶体积逐渐增大,第3天达高峰(P<0.05)。②血清NSE水平在脑缺血再灌注后逐渐升高,第3天达高峰(P<0.05),然后逐渐下降。③血清NSE水平与脑梗死灶体积呈正相关(r=0.92,P<0.001)。④病理检查可见神经组织缺血坏死改变于第3天最明显,并且在第3天时缺血脑组织中中性粒细胞浸润最明显。⑤两个治疗组脑梗死灶体积和血清NSE水平均明显小于对照组(P<0.001),脑组织病理形态改变轻微,中性粒细胞浸润不明显,再灌注前1h用药组效果更明显,但两个用药组之间无显著差异。结论:①血清NSE水平与脑梗死灶体积呈正相关,血清NSE可以作为脑缺血再灌注后神经元损害程度的标志物,还可以作为对脑缺血再灌注损伤保护作     

Serum levels of ischemia-modified albumin in healthy volunteers after exercise-induced calf-muscle ischemia.

BACKGROUND: Ischemia-modified albumin (IMA) is an emerging marker of ischemia. To investigate the applicability of IMA for the diagnosis of skeletal muscle ischemia, we examined IMA changes as measured by the albumin-cobalt binding test, in a group of healthy volunteers after standardized exercise-induced calf muscle ischemia. METHODS: A total of 12 healthy volunteers underwent standardized exercise on a plantar flexion pedal. Ischemic conditions were achieved by inflating a femoral blood pressure cuff at incremental pressures of 0, 60, 90, 120 and 150 mm Hg. Calf muscle ischemia was identified by synchronous 31P magnetic resonance spectroscopy, measuring intracellular concentrations of phosphocreatine (PCr) and inorganic phosphate (Pi). In addition, IMA, serum albumin, lactate, troponin T (TnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at baseline and at 5, 10, 30, 360 and 720 min after cuff release. RESULTS: Magnetic resonance spectroscopy showed calf muscle ischemia in all participants upon exercise and cuff inflation. Circulating IMA concentrations increased significantly after cuff release (p=0.03) and returned to baseline within 30 min. While we found a significant negative correlation with albumin, there was no association of IMA levels with lactate or intracellular levels of PCr or Pi in samples obtained at baseline and post-ischemia. TnT and NT-proBNP remained within the normal range throughout the observation period in all participants. CONCLUSIONS: IMA may represent a clinical marker for skeletal muscle ischemia, although its lack of specificity requires careful clinical interpretation of data. The short period of IMA elevation after ischemic exercise requires standardized conditions for use as a diagnostic tool and hints at IMA applicability as a marker of prolonged or chronic ischemia.