Alteration in plasma levels of nonprotein sulfhydryl compounds and S-nitrosothiols in chronic renal failure patients

BACKGROUND: Uremia is accompanied by the elevated nitric oxide (NO) synthesis, and it has not yet been established how this influences the levels of nonprotein sulfhydryl compounds (NPSH) and formation of S-nitrosothiols (SNT). METHODS: Our study was designed to determine plasma levels of SNT and NPSH in chronic renal failure (CRF) patients, who were hemodialysed (HD) or were not on hemodialysis treatment (ND), and in the control group. RESULTS: In ND patients, the plasma levels of SNT were significantly increased (11.25+/-2.08 nmol/ml, p<0.01), while NPSH levels were simultaneously decreased (66.67+/-15.0 nmol/ml, p<0.05) in comparison with the control subjects (SNT: 8.75+/-2.08 nmol/ml, NPSH: 86.66 nmol/ml). In HD patients, plasma concentration of SNT before hemodialysis was significantly lower than in the control group (0.150+/-0.042 nmol/mg protein vs. control: 0.175+/-0.075 nmol/mg protein), and no significant change was observed after dialysis (0.142+/-0.058 nmol/mg protein, p<0.05). The level of NPSH in HD patients before dialysis was significantly decreased in comparison with the control subjects, both, when the results were calculated per 1 ml of plasma (45.96+/-17.87 nmol/ml) and per 1 mg of protein (0.70+/-0.25 nmol/mg protein). In the postdialysis samples, NPSH rose (79.15+/-22.9 nmol/ml, p<0.001 which corresponds to 1.30+/-0.55 nmol/mg protein, p<0.001) as compared to the level before dialysis. CONCLUSIONS: Firstly, plasma SNT level was found to be increased in CRF patients who were not treated with hemodialysis, while in HD patients, it dropped below the control values. It indicates that hemodialysis disturbs an equilibrium of reactions involved in S-nitrosothiols formation most probably by removing low molecular weight S-nitrosylating compounds. Secondly, the increased level of NPSH after each hemodialysis session indicates reestablished antioxidant capacity of plasma and suggests the existence of dialysable compounds, which via unknown mechanism become responsible for the decreased level of thiols.     

Serum soluble interleukin 6 (IL-6) receptor and IL-6/soluble IL-6 receptor complex in systemic juvenile rheumatoid arthritis.

By using a sandwich ELISA, soluble human IL-6 receptor (sIL-6 R) levels were measured in the sera of 20 healthy children and of 25 patients with systemic juvenile rheumatoid arthritis (JRA). In patients with systemic JRA, serum sIL-6 R levels (114.6 +/- 37.7 ng/ml) were significantly lower (P < 0.01) than those of healthy children (161.2 +/- 45.5 ng/ml). Serum sIL-6 R levels were negatively correlated (r = -0.610, P < 0.001) with serum IL-6 levels measured with the B9 cells. The serum IL-6/sIL-6 R complex was detected using an ELISA based on a monoclonal antibody to IL-6 for capture and on a monoclonal antibody to human sIL-6 R for detection. Healthy controls had little, if any, detectable serum IL-6/sIL-6 R complex (OD 0.024 +/- 0.027), while the majority of patients with systemic JRA presented measurable serum IL-6/sIL-6 R complex (OD 0.492 +/- 0.546). IL-6 levels estimated in the circulating IL-6/sIL-6 R complexes were in the range of nanograms per milliliter and approximately 20-fold higher than those measured by the B9 cells. Since serum C-reactive protein concentrations were much more correlated with serum levels of IL-6/sIL-6 R complexes (r = 0.713, r2 = 0.51, P < 0.0001) than with the serum IL-6 levels measured with the B9 cells (r = 0.435, r2 = 0.19, P = 0.05), the large quantities of serum IL-6 present in IL-6/sIL-6 R complexes appear to be biologically relevant in vivo, at least as far as the induction by IL-6 of acute phase protein production.     

Levels of anti-inflammatory cytokines interleukin-2, interleukin-8, and soluble interleukin-2 receptor in blood of patients with various forms of ischemic heart disease

AIM: To quantify interleukin-8 (IL-8), interleukin-2 (IL-2) and soluble receptor of IL-2 (sIL-2r) in blood serum of patients with various forms of ischemic heart disease (IHD). MATERIAL AND METHODS: Levels of IL-8, IL-2 and sIL-2r were measured with enzyme immunoassay (EIA) in the serum of 75 patients with IHD: angina of effort (group 1), progressive angina (group 2) and acute myocardial infarction (group 3). The EIAs were performed at admission and 2 weeks later. RESULTS: Baseline levels of IL-2 in group 1 and 2 patients were close (9.1 +/- 1.6 and 10.1 +/- 3.8 pg/ml) being significantly lower in group 3 (0.81 +/- 0.57 pg/ml, p < 0.01). 14 days of therapy did not change the values noticeably. IL-8 level was the highest in group 1 (94.2 +/- 27.6, 20.03 +/- 7.4, 22.47 +/- 4.8 pg/ml, respectively). sIL-2r in the three groups did not vary greatly (73.95 +/- 12.23, 89.46 +/- 18.17, 89.2 +/- 14.17 pg/ml, respectively). SIL-2r levels rose in 2 weeks in group 3 (to 147.67 +/- 18.17 pg/ml). CONCLUSION: It is confirmed that IL-2, IL-8 and sIL-2r take part in pathogenesis of IHD. IL-2 and IL-8 levels are persistently high in anginal patients while in patients with acute myocardial infarction they are low. Low concentrations of IL-2 in the latter may be attributed to high levels of its soluble receptor.     

Increased circulating concentrations of interleukin 2 receptor during rejection episodes in heart- or kidney-transplant recipients

Concentrations of interleukin 2 receptor (sIL-2R) have been suggested as a marker of rejection episodes after organ transplantation. To evaluate the analytical performance of a "sandwich-type" enzyme immunoassay method for sIL-2R and to verify whether increased concentrations of sIL-2R might be a useful marker of allograft rejection, we quantified sIL-2R in serum samples from heart- or kidney-transplant patients. The mean (+/- SD) pre-transplant value of sIL-2R (592 +/- 209 kilo-units/L) in heart-transplant patients was significantly higher (P less than 0.01) than that observed in controls (350 +/- 101 kilo-units/L). After heart transplantation, the concentrations of sIL-2R slowly decreased to baseline in successfully treated patients but increased significantly (1129 +/- 215 kilo-units/L; P less than 0.01) during acute rejection crisis. However, severe infections were also associated with a significant increase of sIL-2R, so the sIL-2R test is not specific for allograft rejection. The mean pre-transplant concentration of sIL-2R was also increased (1943 +/- 878 kilo-units/L) in 26 renal-transplant patients; after transplantation, this value returned to normal, as did that for creatinine, but persisted steadily high in five patients who experienced acute tubular necrosis. In this group of patients, the sIL-2R concentration increased by 1.5- to fourfold, both during acute rejection episodes and in clinically evident infection; thus measurement of creatinine and sIL-2R concentrations can help to distinguish between rejection, infection, and cyclosporine toxicity. In two episodes of mild cyclosporine-induced nephrotoxicity, we observed slight increases in serum creatinine (which returned to baseline when the cyclosporine dose was decreased) not associated with an increase in sIL-2R. We conclude that systematic monitoring of sIL-2R together with other biochemical and clinical markers may be useful in the management of kidney-transplant patients.     

Plasma beta-thromboglobulin and platelet factor 4 in patients with chronic renal failure and effect of hemodialysis

Significantly increased levels of plasma beta-thromboglobulin (beta-TG) (76.8 +/- 25.5 ng/ml, p less than 0.01) were observed in 24 patients with chronic renal failure (blood urea nitrogen (BUN) greater than 20 mg/100 ml), as compared with normal subjects (13.2 +/- 5.6 ng/ml). The increase in beta-TG was highly correlated with BUN (r = 0.651, p less than 0.01), creatinine (r = 0.778, p less than 0.01) and creatinine clearance ( t = -0.723, p less than 0.01). Plasma platelet factor 4 (PF4) and normal 5.0 +/- 2.0 ng/ml) also increased significantly to 8.5 +/- 3.4 ng/ml (p less than 0.01). However, statistical correlation between beta-TG and PF4 was not found in these patients. The reason is thought to be due to differences in molecular weight (PF4 8,000 MW; beta-TG 36,000 MW) and half-life time (PF4 30 min; beta-TG 100 min), and due to the difficulty in calculating statistically the correlation because of the narrow distribution of PF4 levels. The high levels of beta-TG (89.4 +/- 3.4 ng/ml) showed a further increase (109.4 +/- 5.8 ng/100 ml, p less than 0.01) after dialysis. This is thought to be due to hemoconcentration, because other blood factors such as RBC, WBC, platelets, fibrinogen, etc were elevated by about 20% during hemodialysis and because no adhesion of platelets to the cellulose membrane did occur. The increase in PF4 levels at 15 min (55.2 +/- 19.6 ng/ml, p less than 0.01) and 1 hr (23.7 +/- 8.4 ng/ml, p less than 0.01) of hemodialysis from the level before it (7.7 +/- 1.3 ng/ml) is thought to be caused the effect of heparin infusion. The change in PF4 was not accompanied by the change in beta-TG. During hemodialysis the decrease of other platelet functions such as adhesiveness, aggregation induced by ADP, collagen and PF3 remained unchanged.     

急性白血病患者血清sIL-2R,MCP-1及IFN-γ联合检测的临床意义

目的 探讨急性白血病患者血清可溶性白细胞介素-2受体(soluble interleukin-2 receptors,sIL-2R),单核细胞趋化蛋白-1(monocyte chemotactic protein-1,MCP-1)及γ-干扰素(interferon-γ,IFN-γ)联合检测的临床意义。方法 选取2015年6月～2018年7月收治的急性白血病患者86例为观察组,另选同期接受体检的健康者86例为对照组,对两组血清sIL-2R,MCP-1及 IFN-γ水平予以检测,并观察三种指标联合检测与单独检测的诊断准确度、特异度、灵敏度。结果 观察组血清sIL-2R,MCP-1和IFN-γ分别为492.57±35.28 U/ml,18.25±2.71 μg/L和16.32±3.02 pg/ml,与对照组156.31±18.45 U/ml,4.91±0.93 μg/L和33.46±5.28 pg/ml对比,差异均有统计学意义(t=78.325,43.178,26.132,均P<0.01); 急性淋巴细胞白血病患者血清sIL-2R,MCP-1和IFN-γ分别为563.18±39.54 U/ml,22.53±2.85 μg/L和10.26±2.14 pg/ml,与急性髓细胞白血病患者(431.27±33.17 U/ml,14.74±2.69 μg/L和18.63±2.51 pg/ml)对比,差异均有统计学意义(t=23.702,18.434,23.532,均P<0.01); sIL-2R,MCP-1和IFN-γ联合检测准确度、特异度和灵敏度分别为86.05%,87.04%和84.38%,与单项检测对比,均明显升高,差异有统计学意义(P<0.05)。结论 急性白血病患者血清sIL-2R,MCP-1及 IFN-γ水平存在明显异常,且不同类型急性白血病患者上述指标有较大差异,三者联合检测在急性白血病诊断中具有较高价值。     

胃癌患者血清和组织中sIL-2R水平的临床观察及其意义

目的　研究胃癌患者血清及组织中可溶性白细胞介素 2受体 (sIL 2R)变化的临床意义。方法　采用双抗体夹心ELISA法 ,对 5 8例胃癌患者手术前后、32例胃良性疾病患者 (慢性浅表性胃窦炎患者 2 6例 ,功能性消化不良 6例 )及 36例健康体检者血清sIL 2R水平进行检测 ;同时检测了胃癌及胃良性疾病者活检组织中sIL 2R的浓度。结果　胃癌患者血清sIL 2R(U /L)为 911± 179,明显高于胃良性疾病者 (30 3± 2 0 )和健康体检者 (30 1± 15 ) ,P <0 .0 0 1。胃癌组织中sIL 2R为 934± 197明显高于胃良性疾病胃粘膜组织 (311± 2 0 ) ,P <0 .0 0 1。胃癌按Ⅰ～Ⅳ级分期的不同 ,sIL 2R在血清和组织中逐渐增高 ,且各期之间进行比较均P <0 .0 0 1;其中Ⅰ期 (11例 )、Ⅱ期 (10例 )、Ⅲ期 (2 2例 )术后血清sIL 2R明显下降 (各自P <0 .0 0 1) ;而Ⅳ期患者 (15例 )手术前后无明显变化且有所增高 ;手术切除组 (46例 ,根治或姑息手术 )术后sIL 2R明显降低 (P <0 .0 0 1) ,而探查者或胃空肠吻合术者 (12例 ) ,术后血清sIL 2R反而增高。结论　动态观察血清及组织sIL 2R的变化可作为胃癌的诊断、手术方法的选择、疗效评价及预后监测有意义的参考指标。     

尿毒症患者血清瘦素水平的临床研究

目的研究慢性肾功能不全患者血液透析前、后的血清瘦素水平与健康人群血清瘦素的关系,并初步探讨血清瘦素水平与营养不良的关系.方法选择尿毒症患者(血液透析前、连续血液透析三次后)及正常对照组各30例,于空腹取血,应用放射免疫分析法测定血清中瘦素水平,同时检测肾功能、血浆白蛋白水平等.结果正常人的血清瘦素水平与尿毒症患者血液透析前的血清瘦素水平无显著性差异(P>0.05),两组血清瘦素水平与体重指数(BMI)呈明显正相关(P<0.05),且女性血清瘦素水平均分别高于男性(P<0.05);尿毒症患者血液透析后的血清瘦素水平与正常对照组差异有显著性(P<0.05),血液透析组的血清瘦素水平与血尿素氮、肌酐、白蛋白等无相关性,血液透析组的肌酐、尿素氮高于对照组(P<0.01);血液透析前与血液透析后的血清瘦素水平无显著性差异(P>0.05).结论尿毒症患者血液透析前的血清瘦素水平与对照组差异无显著性,而血液透析后的血清瘦素与对照组差异有显著性;尿毒症患者和正常对照组女性血清瘦素水平均明显高于男性;尿毒症患者血液透析后血清瘦素水平与患者营养不良无明显相关关系;血液透析无法对瘦素起到清除作用.     

Pregnancy decreases immunoreactive parathyroid hormone level in rats with chronic renal failure

Normal pregnancy is associated with an increase in serum parathyroid hormone and 1,25-dihydroxyvitamin D3 (calcitriol). The effect of pregnancy on these hormones in chronic renal failure (CRF) is unknown. The present work was undertaken to study the changes of serum immunoreactive parathyroid hormone (iPTH) and calcitriol in pregnant rats with CRF. The following experimental groups were studied: CRF1 (5/6 nephrectomized virgin female rats), CRF2 (5/6 nephrectomized pregnant rats at day 20-21 of pregnancy), CRF3 (5/6 nephrectomized rats 2 weeks after delivery) and their respective sham-operated control groups: N1, N2 and N3. The 5/6 nephrectomy (CRF1) resulted in renal failure with very high serum iPTH (100+/-18 pg/ml) and low calcitriol levels (10.6+/-4.3 pg/ml) compared with normal rats [N1: 14+/-2.5 pg/ml (P<0.001) and 18.2+/-4.2 pg/ml (P<0.01) respectively]. The pregnancy in CRF rats (CRF2) resulted in normalization of serum iPTH levels (18.2+/-5.41 pg/ml), which was associated with a parallel increase in serum calcitriol (29.4+/-8.0 pg/ml) similar to that in pregnancy of normal rats (N2). Two weeks after delivery the CRF rats (CRF3) once again had high serum iPTH (87+/-17 pg/ml) and low calcitriol levels (9.3+/-1.2 pg/ml), similar to those observed in non-pregnant uraemic rats (CRF1). It is concluded that pregnancy decreases serum iPTH in 5/6 nephrectomized CRF rats most probably by the increased level of calcitriol synthesized by the feto-placental unit.     

Differential effect of chronic renal failure on the pharmacokinetics of lidocaine in patients receiving and not receiving hemodialysis

BACKGROUND AND OBJECTIVES: The effect of chronic renal failure (CRF) on the pharmacokinetics of lidocaine, a drug cleared almost exclusively by hepatic metabolism, has thus far only been evaluated in patients undergoing regular hemodialysis. This study had 2 objectives: (1) to investigate the effect of CRF on the pharmacokinetics of lidocaine in both patients undergoing hemodialysis and patients not undergoing hemodialysis and (2) to test the effects of plasma from the patients examined and of lidocaine metabolites possibly accumulated in vivo on lidocaine biotransformation in vitro. METHODS: In a clinical investigation we studied the kinetics of lidocaine and its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), after intravenous injection of 1 mg/kg lidocaine in 15 healthy volunteers (creatinine clearance [CL(cr)] >80 mL/min x 1.73 m(-2)), 10 subjects with moderate renal insufficiency (CL(cr) between 30 and 60 mL/min x 1.73 m(-2)), 10 subjects with severe renal insufficiency (CL(cr) <30 mL/min x 1.73 m(-2)), and 10 functionally anephric patients undergoing long-term hemodialysis. In experiments in vitro we determined the effects of plasma and GX on the formation rate of the primary lidocaine metabolite, MEGX, by use of human liver microsomes. RESULTS: In patients not undergoing hemodialysis, lidocaine kinetic parameters were altered in proportion to the degree of renal function impairment, but only in patients with severe renal insufficiency were differences statistically significant: clearance was about half that of control subjects (mean +/- SD, 6.01 +/- 2.54 mL/min x kg versus 11.87 +/- 2.97 mL/min x kg; P < .001), and half-life was approximately doubled (4.55 +/- 1.71 hours versus 2.24 +/- 0.55 hours, P < .001). No such alterations were observed in patients undergoing regular hemodialysis, whose values were similar to those of the control group. The steady-state volume of distribution and MEGX levels were independent of renal function, whereas GX levels were more than double those of control subjects (P < .05) in all CRF groups. No inhibitory effect of plasma was observed, for any of the subjects examined, on lidocaine biotransformation in vitro. GX was found to be a competitive inhibitor, but its apparent inhibition constant value (52 +/- 6 micromol/L) was 2 orders of magnitude higher than its concentrations in vivo. CONCLUSIONS: Our in vivo findings have both clinical and methodologic implications: (1) Lidocaine dose adjustment may be required in patients with severe renal insufficiency who are not receiving hemodialysis. (2) Results of studies evaluating the effect of CRF on metabolic drug disposition are not of general validity, unless both patients undergoing hemodialysis and patients not undergoing hemodialysis have been examined. Our in vitro observations exclude that impairment of lidocaine disposition is the result of direct inhibition of metabolizing enzymes by accumulated metabolites or uremic toxins. Alternative mechanisms, suggested by the results of recent in vitro studies, are discussed.     

sIL-2R在恶性淋巴细胞增殖性疾病中的改变

目的：探讨可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）在恶性淋巴细胞增殖性疾病中的改变及其临床意义。方法：用酶联免疫吸附法测定６０例恶性淋巴细胞增殖性疾病患者血清ｓＩＬ－２Ｒ水平，用流式细胞仪（ＦＣＭ）检测其中４３例患者外周血单个核细胞中ＣＤ４＋、ＣＤ８＋细胞数。将患者以不同病期，是否伴有感染等情况分组进行比较，并对３例非霍奇金淋巴瘤（ＮＨＬ）患者进行治疗前后的ｓＩＬ－２Ｒ随访。结果：多发性骨髓瘤、ＮＨＬ及急性淋巴细胞白血病患者血清ｓＩＬ－２Ｒ含量高于正常人，其水平与疾病的临床分期、病程密切相关。上述患者外周血单个核细胞中ＣＤ４＋细胞数与ＣＤ８＋细胞数的比值明显低于正常人。血清ｓＩＬ－２Ｒ水平在此类疾病中与感染无关。结论：在恶性淋巴细胞增殖性疾病中，ｓＩＬ－２Ｒ水平随着疾病的进展及机体免疫功能的下降而明显升高，可作为一个有效的临床监测指标。     

Soluble interleukin-2 receptors increase during the active periods in cluster headache

OBJECTIVE: To investigate whether cytokines are altered during the active period of cluster headache. BACKGROUND: Patients with cluster headache show activation of the hypothalamus in PET studies and via endocrinologic parameters. Data also suggest an inflammatory process occurs in cluster headache. A connection between the presumed inflammatory cause, an immunological activation, and the hypothalamus could be generated by certain cytokines. DESIGN AND METHODS: ELISA was used to determine the serum levels of soluble interleukin-2 receptors, interleukin-1, interleukin-6, and 2 soluble interleukin-6 receptors (sIL-6R and soluble gp130) in 18 patients with cluster headache (6 women and 12 men) during the cluster period and in 17 healthy controls who were headache-free (3 women and 14 men). RESULTS: Patients with cluster headache had significantly increased soluble interleukin-2 receptors (413.6+/-223 U/mL vs. 290.0+/-112 U/mL; P <.05) compared with controls. Serum levels of interleukin-1 (0.29+/-0.30 pg/mL vs. 0.13+/-0.13 pg/mL, n.s.), interleukin-6 (0.87+/-0.6 pg/mL vs. 0.91+/-0.7 pg/ml; n.s.), soluble interleukin-6 receptors (33,131+/-8,349 pg/mL vs. 35,063+/-7,606 pg/mL; n.s.), or soluble gp130 (289+/-59 pg/mL vs. 283+/-20 pg/mL; n.s.) did not differ between the 2 groups, although patients with cluster tended to have higher interleukin-1 values. CONCLUSIONS: Because elevated soluble interleukin-2 receptors indicate T cell activation, our findings suggest immune activation during cluster headache. Because interleukin-2 can activate the hypothalamus and stimulate the release of Corticotropin-releasing Factor (CRF), interleukin-2 could link a putative immunological cause of cluster headache with the observed hypothalamic activation. Systemic changes of interleukin-1 or the interleukin-6 system do not seem to play a role in cluster headache, as no alterations of serum levels were observed. Even so, unchanged serum levels do not exclude limited local production.     

Low doses of recombinant erythropoietin in the treatment of renal anemia in patients on chronic hemodialysis and ambulatory peritoneal dialysis]

AIM: A comparative study of efficiency and safety of low-dose erythropoietin (EP) in two groups of patients with chronic renal failure (CRF): patients on chronic hemodialysis (CHD) and patients on continuous ambulatory hemodialysis (CAHD). MATERIALS AND METHODS: 51 CRF adult patients with renal anemia on hemodialysis entered the trial: 34 CHD and 17 CAHD patients. EP compounds were injected s.c. in a dose 1000-2000 U 2-3 times a week. RESULTS: EP treatment provided a rapid correction of renal anemia in the majority of patients. After 3-month EP therapy a mean increment of Hct (Hct delta) was much greater (p < 0.05) in CAHD than CHD patients (12.2 +/- 6.0 and 9.0 +/- 5.1%, respectively), though EP dose were the same in both the groups. CONCLUSION: Low doses of recombinant human EP injected subcutaneously were effective and safe for correction of anemia in both CHD and CAHD. In CAHD patients EP effectiveness was much higher than in CHD patients.     

Elevated serum levels of soluble interleukin-2 receptors in small cell lung carcinoma

The presence of the soluble form of the interleukin-2 receptors (sIL-2R) was evaluated in the serum of 21 patients with small cell lung carcinoma (SCLC) and 37 patients with non-small cell lung carcinoma (non-SCLC) by means of an enzyme-linked immunosorbent assay. The sIL-2R level was measured serially in patients with SCLC both during and after therapy. The mean serum level of sIL-2R in patients with SCLC was 3.8 times higher than that of 47 healthy controls and was 1.9 times higher than in 37 patients with non-SCLC. Six patients with SCLC had very high levels of sIL-2R, ranging from five to 52 times the mean level observed in normal controls. Tumor cells in the pleural fluid of the patient with highest levels were positive with monoclonal antibodies to IL-2R (CD25), NKH-1, OKDR, and OKT9. A longitudinal study in this patient showed a good correlation between tumor activity and sIL-2R levels. Also, the sIL-2R levels decreased in patients responding to therapy. These results suggest that some SCLCs secrete sIL-2R and that the serial measurements of the serum sIL-2R levels can be used as a noninvasive tumor marker in this disease.     

Cardiac troponins and left ventricular hypertrophy in hemodialysis patients

BACKGROUND: Cardiovascular diseases are the leading cause of death in hemodialysis patients. Left ventricular (LV) hypertrophy is an important predictor of cardiovascular morbidity and mortality in these patients. Cardiac troponins (cTnT and cTnI) are indicators of myocardial cell damage. AIM: The aim of this study was to determine prevalence of LV hypertrophy, prevalence of elevated serum cTnT and cTnI in hemodialysis patients, and identify the correlation between cardiac troponins and LV hypertrophy. METHODS: The study included 115 hemodialysis patients (71 men and 44 women), mean age 53.30 +/- 12.17 years, mean time on dialysis 4.51 +/- 4.01 years and average Kt/Vsp 1.17 +/- 0.23. Mean serum cTnT was 0.14 +/- 0.23 ng/ml, mean serum troponin I 0.20 +/- 0.48 ng/ml. Mean LV posterior wall thickness in diastole (LVPWd) was 11.44 +/- 2.09 mm, mean LV interventricular septal wall thickness in diastole (IVSd) 11.21 +/- 2.12 mm, mean LV end diastolic volume index (iLVEDV) 100.80 +/- 34.62 mL/m2 and mean LV mass index (LVMi) 143.85 +/- 41.21 g/m2. RESULTS: We found statistically significant positive correlations (p <0.05) between serum troponin T concentration, IVSd, LVPWd and iLVEDV. A highly significant positive correlation (p < 0.01) was found between serum troponin T and LVMi. One-year follow-up showed that patients with cardiac troponin T > 0.10 ng/ml and cardiac troponin I > 0.15 ng/ml had significantly lower (p < 0.01) survival rate than patients with troponin T < or = 0.10 ng/ml and troponin I < or = 0.15 ng/ml. CONCLUSION: A significant positive correlation exists between serum troponin T concentration and echocardiographic indicators of LV hypertrophy in hemodialysis patients. Patients with higher serum levels of cardiac troponins have lower survival rates during one year follow up.     

Pharmacokinetics of ofloxacin in severe chronic renal failure

The pharmacokinetics of ofloxacin were studied in patients with severe renal impairment. In five healthy subjects and nine patients with chronic renal failure (CRF) (creatinine clearance [CCR] less than 20 ml/min) receiving 100 mg of ofloxacin orally in the fasted state, the serum concentration was measured over the subsequent 48 hours. Intracorporeal dynamics were examined, employing a one-compartment open model. Ofloxacin levels were measured using the paper disk method. The half-life of ofloxacin was markedly prolonged, to 23.1 +/- 7.0 hr in the CRF group versus 2.9 +/- 0.5 hr for healthy subjects. In the CRF group, the maximum concentration and area under the curve were greater than in healthy subjects. There were no significant differences in volume of distribution between the two groups. The renal clearance of ofloxacin decreased from 261.0 +/- 46.6 ml/min in healthy subjects to 8.0 +/- 4.7 ml/min in the CRF group and correlated significantly with CCR in the CRF group (r = .88, P less than 0.01). There were no significant differences in nonrenal clearance between the two groups. The 24-hour renal excretion of ofloxacin averaged 91.9 +/- 5.4% and 14.1 +/- 5.5% of the dose in the healthy and CRF groups, respectively. In three hemodialysis patients on the regular hollow-fiber dialyser, the dialysance of ofloxacin was about 50% that of creatinine. Based on these findings, a reduction in the dose of ofloxacin is necessary in patients with CRF. In the hemodialyzed patients, its high dialyzability should be considered when deciding dose regimens.     

Measurement of urinary annexin V by ELISA and its significance as a new urinary-marker of kidney disease

To confirm the significance of excretion of annexin V into the urine and the change of urinary annexin V concentration in kidney disease, a sandwich enzyme-linked immunosorbent assay (ELISA) was developed using two monoclonal antibodies. Urinary annexin V concentration was measured in healthy individuals and patients with kidney and other diseases. Urinary annexin V did not change over a range of pH between 5.0 and 8.0, and was stable during the course of the study for 24 h at room temperature and for 8 days at 4 degrees C. The mean urinary annexin V concentration in 105 normal healthy individuals was 1.5+/-1.5 ng/ml, while that in patients with nephrotic syndrome and systemic lupus erythematosis (SLE) nephritis was 9.3+/-9.1 and 6.6+/-6.7 ng/ml, respectively, and that in IgA nephropathy and chronic renal failure was 2.6+/-2.1 and 1.3+/-0.7 ng/ml, respectively. Annexin level correlated with urinary protein concentration (r=0. 717), but not the serum creatinine concentration, blood urea nitrogen (BUN) and 24-h creatinine clearance. Mean urinary annexin V concentration in patients with ischemic heart disease, hypertension, and diabetes mellitus was 1.4+/-1.0, 1.4+/-1.1, and 1.7+/-1.3 ng/ml, respectively. In one case of relapsing nephrotic syndrome, the urinary annexin V concentration was markedly increased in the early phase after admission and then decreased. This patient later required hemodialysis. These results suggest that a high urinary annexin V concentration may be an indicator of acute renal injury related to the urinary protein level.     

Increased plasma and ventricular fluid interleukin-6 levels in patients with head injury

The cytokine interleukin-6 (IL-6) plays a major role in initiating the acute phase response, especially in the production of acute phase reactants such as C-reactive protein. The objectives of this study were to determine whether plasma or ventricular fluid IL-6 levels were elevated at time of admission after head injury and whether plasma IL-6 levels related temporally to clinical improvement of levels of acute phase reactants. Thirty patients with Glasgow Coma Scale (GCS) scores of 3 through 10 were observed for 15 days after head injury. Peak elevation of plasma IL-6 occurred on admission (85 +/- 12 U/ml; normal level is less than 2 U/ml) and then decreased during the hospital course to a level of 29 +/- 4 U/ml on day 15. Plasma IL-6 levels decreased significantly faster in patients with admission peak 24-hour GCS scores of 8 through 10 compared with patients with GCS score less than 8 (p less than 0.01). Patients had markedly elevated and variable ventricular fluid IL-6 levels on admission (mean 3880 +/- 2022 U/ml; normal, less than 2 U/ml). A temporal relationship was found between plasma IL-6 levels and multiple acute phase reactants thought to be mediated by IL-6. We conclude that plasma and ventricular fluid levels of IL-6 are elevated after head injury and that plasma IL-6 level is temporally related to acute phase reactants and clinical improvement. We suggest that IL-6 may play an etiologic role in many of the metabolic or nutritional sequelae of head injury.     

Soluble interleukin-2 receptor: elevated levels in serum and synovial fluid of patients with rheumatoid arthritis

Soluble interleukin-2 receptor (sIL-2R) levels were quantitated in the serum and synovial fluid (SF) of patients with rheumatoid arthritis (RA) and degenerative joint disease (DJD). A sandwich immunoassay, employing two monoclonal antibodies against distinct epitopes on the IL-2R, was utilized for measurement. We found a striking elevation of sIL-2R in RA SF as compared with DJD SF (RA, 1319 +/- 135; DJD, 416 +/- 59; p less than 0.001). RA serum sIL-2R levels were also significantly elevated over DJD levels. There was no interaction between rheumatoid factor (RF) and sIL-2R. RA patients with elevated sIL-2R levels had significantly longer disease duration, higher c-reactive protein (CRP) levels in serum and SF, and higher RF levels in serum and SF. The groups were similar in regard to other laboratory variables. The presence of elevated levels of sIL-2R in RA serum and SF confirms the presence of a heightened immune reactivity and in vivo activation of lymphocytes in RA.     

Serum Erythropoietin levels and inhibitors of erythropoiesis in patients with chronic renal failure

The role of various factors in erythropoiesis was studied in 13 predialysis patients and 41 hemodialysis patients. Serum erythropoietin (ESF) was measured by the fetal mouse liver cell bioassay in vitro. The effect of uremic sera on heme synthesis and erythroid progenitor cell (CFU-E) formation was examined using normal human bone marrow cultures. Serum ESF levels in both predialysis (99.9 +/- 45.0 mU/ml) and dialysis (141.2 +/- 109.7 mU/ml) patients were significantly higher than those in normal controls (42.0 +/- 25.8 mU/ml), although the titers were not sufficiently increased to correct the anemia. Serum ESF concentrations did not correlate with hemoglobin level or inhibition of both heme synthesis and CFU-E formation. Bone marrow CFU-Es in uremic patients were normal in the number, the responsiveness to ESF and the percentage in S-phase. Significant decrease in heme synthesis was observed in dialysis patients. The degree of inhibition of CFU-E formation showed a relationship to hemoglobin levels in uremic patients. By the CFU-E formation assay, the difference in inhibitory effects of the sera obtained from dialysis patients immediately before and after a hemodialysis was significant only under a low ESF concentration (0.125 U/ml) but not under a high concentration (1.0 U/ml). In conclusion, inhibition of heme synthesis and CFU-E formation, in addition to inadequate ESF production, plays an important role in renal anemia.