Plasma oxalate concentration and oxalate distribution volume in patients with normal and decreased renal function

In twenty-one patients (sixteen male, five female) with various kidney diseases including primary hyperoxaluria type I (four patients), the plasma oxalate level was calculated from the isotopically determined oxalate clearance and the chemically determined urinary oxalate excretion. The apparent oxalate distribution volume was assessed as well. In patients with impaired kidney function (n = 12), the oxalate clearance was lower and the biological half-life and plasma concentration were higher than in patients with normal kidney function (n = 10). No differences were found in the oxalate-to-creatinine clearance ratio (mean value 1.93), urinary oxalate excretion and apparent oxalate distribution volume. A linear relation was found between the oxalate and creatinine clearance, while the clearance ratio was independent of the degree of renal failure. The apparent oxalate distribution volume was 1.45 times the estimated extracellular fluid volume. Because the isotopically determined plasma oxalate levels are lower than chemically measured ones, a quick and better estimation of plasma oxalate can be made from the urinary oxalate excretion and the creatinine clearance.     

Metabolic clearance rate of immunoreactive vasopressin in man

Abstract. Metabolic clearance of synthetic arginine vasopressin (AVP) has been measured in sixteen healthy subjects and ten uraemic patients on maintenance haemodialysis. Plasma AVP was measured using a specific radioimmunoassay at different intervals after a single injection of 2 μg AVP. The theoretical curve which fitted best with the disappearance curve was the sum of two exponentials in twenty-two subjects and of three exponentials in the other four. Metabolic clearance rate and the volume of fast initial distribution were 287·1 ml min^-1 (m²)^-1 and 219·3 ml/kg b.w., respectively, in normal subjects. Metabolic clearance rate was considerably lower in the uraemic group. This emphasizes the role of kidneys in the degradation of AVP and may account, at least in part, for the higher basal plasma value of this hormone observed in uraemic patients.     

Transthoracic electrical impedance as an index of extracellular fluid volume in man

Findings in 76 subjects without cardiac failure were analyzed to detect relationships between observed changes in transthoracic electrical impedance (TEI) and total body extracellular fluid volume (ECFV) during various manoeuvres and between absolute TEI and ECFV values. TEI was normalized to electrode distance (Z₀/gDel) and ECFV to lean body mass (ECFV/LBM). A distircet relation was found between percent changes of TEI and ECFV (r=-0.76, p<0.0001) and between absolute Z₀/el and ECFV/LBM values (r=-0.66, p<0.0001 for men; r=-0.61, p<0.0001 for women). It is concluded that in the same subject a change in TEI is possibly a sensitive index for a change in ECFV and that a single measurement of TEI, normalized to electrode distance, gives information about the state of hydration (ECFV) of patients without cardiac failure.     

Different plasma levels of nitric oxide in arterial and venous blood

Experimental investigations suggest that a basal release of nitric oxide (NO) occurs in arterial but not in venous endothelium. We therefore decided to compare plasma levels of NO in the arterial and venous circulation. Parallel blood samples were drawn from the radial artery and brachial vein in 15 healthy drug-free women. Nitric oxide levels were assessed by measuring plasma levels of nitrite and nitrate, the two stable oxidation products of NO metabolism. Plasma levels of NO metabolites in arterial blood were significantly higher than in the paired venous blood samples (45·1 ± 17·7 versus 22·5 ± 8·5 μmol l^?1, respectively, mean ± SD). The results of this preliminary study strongly suggest that the endothelial release of NO is probably different in arteries and veins in vivo; this is also consistent with previous literature indicating that basal release of NO occurs mainly from the endothelium of arteries but not from that of veins.     

Recovery from withdrawal of inhaled nitric oxide and kinetics of nitric oxide-induced inhibition of nitric oxide synthase activity in vitro

Objective: To examine the kinetics of successful nitric oxide (NO) withdrawal in vivo and in vitro.¶Design and setting: Prospective study in a university pediatric intensive care ward and research laboratory.¶Patients and materials: Nineteen patients with acute respiratory distress syndrome (ARDS) or persistent pulmonary hypertension of the newborn (PPHN). Primary porcine pulmonary artery cells in vitro.¶Interventions: NO inhalation and withdrawal in patients; exposure to NO donor sodium nitroprusside (SNP) and gaseous NO in vitro.¶Measurements and results: In patients: a slight, but significant, increase of oxygenation index (OI) from 4.57 ± 0.24 cmH₂O/torr (mean ± SEM) to 4.90 ± 0.26 cmH₂O/torr after withdrawal of NO (p < 0.001). Recovery of OI (4.43 ± 0.23 cmH₂O/torr) 30 min after weaning, a significant drop after 4 h (3.72 ± 0.17 cmH₂O/torr; p < 0.001), values restored after 12 h.¶In vitro: NO synthase (NOS) activity was significantly lower in SNP-incubated cells (20.0 ± 4.0 μm/min) than in control cells (37.6 ± 7.0 μm/min; p < 0.05). Thirty minutes after SNP withdrawal there was NOS activity of 35.8 ± 10.0 μm/min with a significant increase by 4 h (p < 0.05). No alteration of endothelial NOS (ENOS) mRNA expression by NO (Northern Blot).¶Conclusion: In patients there is a slight, but significant, reversible increase of OI after successful weaning from NO. In vitro, NO leads to a reversible decrease of ENOS activity on a post mRNA level, resembling clinical observations.     

Relationship between physical factors and tibial motion in healthy subjects: 2D and 3D analyses

This study was undertaken to determine the relationship between physical factors and vertical axial rotation through the tibial shaft caused by passive knee and subtalar joint rotation in healthy subjects. The data collected were analyzed in detail to determine the relationship between various physical parameters, such as age, body mass, height, and sex, and tibial rotation. A total of 484 healthy subjects were examined with the measuring the vertical axial rotation through tibial shaft (MVARTS) system. Evaluators passively measured internal and external tibial rotation. The effects of any 2 simultaneous variables and outcomes with a single variable were analyzed; the results were documented graphically. Data were also examined through multiple regression analysis (stepwise regression). Agreement between right and left internal tibial rotations was observed to be strong, as was agreement between right and left external rotations. Female patients exhibited a greater amount of internal/external rotation than did male patients. Differences between female and male patients were noted to be significant. A highly significant and inverse relationship between physical parameters and tibial rotations was noted. Findings suggest that as age, body mass, and height increase, tibial motion is reduced.     

Carboxyhemoglobin formation as an unexpected side effect of inhaled nitric oxide therapy in severe acute respiratory distress syndrome

OBJECTIVE: To report an unexpected cause of carboxyhemoglobinemia associated with inhaled nitric oxide therapy in severe acute respiratory distress syndrome. DESIGN: Case report. SETTING: Medical critical care unit at Lausanne University Hospital. PATIENT: One female patient with acute respiratory distress syndrome treated with inhaled nitric oxide, who developed a simultaneous increase in blood methemoglobin and carboxyhemoglobin. CONCLUSIONS: Potential pathophysiologic mechanisms linking acute respiratory distress syndrome, inhaled nitric oxide, methemoglobin, and carboxyhemoglobin are discussed. Since carboxyhemoglobin has a negative influence on oxygen-carrying capacity, this effect may potentially offset the beneficial influence (if any) of inhaled nitric oxide on arterial PO2. This observation does not support the use of inhaled nitric oxide in the treatment of acute respiratory distress syndrome.     

Effect of a nitric oxide donor (glyceryl trinitrate) on nociceptive thresholds in man

Several animal studies suggest that nitric oxide (NO) plays a role in central and peripheral modulation of nociception. Glyceryl trinitrate GTN) exerts its physiological actions via donation of NO. The purpose of the present study was to examine the effect of this NO donor on nociceptive thresholds in man. On two different study days separated by at least , week 12 healthy subjects received a staircase infusion of GTN (0.015, 0.25. 1.0 ,2.0 mg/kg/min. 20 min each dose) or placebo in a randomized double-blind crossover design. Before the infusion and after 15 min of infusion on each dose, pressure pain detection and tolerance thresholds were determined by pressure a gometry (Somomedic AB, Sweden) in three different anatomic regions (finger, a temporal region with interposed myofascial tissue and a temporal region without interposed myofascial tissue. Relative to placebo, the three higher GTN doses induced a decrease in both detection and tolerance thresholds in the temporal region with interposed myofascial tissue ( p =0.003 detection and p =0.002 tolerance threshold: Friedman). No such changes were observed in the other two stimulated regions. These results could reflect central facilitation of nociception by NO. However, we regard convergence, of nociceptive input from pericranial myofascial tissue and from cephalic blood vessels dilated by NO as a more likely, explanation of our findings.     

Renal handling of urate in healthy man in hyperuricaemia and renal insufficiency: circadian fluctuation, effect of water diuresis and of uricosuric agents

Abstract. To differentiate between extrarenal and renal causes of hyperuricaemia and gout, clearances of urate and creatinine were monitored for 31/2 days in fifty-two individuals (seven with a history of gout) with no gross impairment of renal function (creatinine clearance 52–137 ml/min). Dietary purine intake was kept constant. Monophasic circadian fluctuations of fractional urate excretion (= urate clearance over creatinine clearance) were observed with peak values in the afternoon, about 50% higher than during the night. Circadian fluctuations of urinary flow rate were almost identical. However, enhancement of urinary flow rate due to water diuresis had no effect on urate clearance. Despite wide variation of plasma urate concentrations among different individuals (±30% SD), daily urate excretion varied little (± 4% SD) and did not correlate with plasma urate ( r = 0–03). Thus extrarenal factors appear not to account for the occurrence of hyperuricaemia in these patients. In contrast, a clearcut negative correlation was apparent between plasma urate concentration and fractional urate clearance ( r = -0 72), which could fully account for the variations of plasma urate concentration. To elucidate further the mechanism responsible for antiuricosuria in hyperuricaemic patients, the effects of the uricosuric agents benzbromarone and probenecid were tested. A clearcut correlation was apparent between control fractional urate excretion and uricosuric effect of both benzbromarone and probenecid ( r = 0–83 and 0–88, respectively), suggesting that anti-uricosuria was due to defective secretion. In an additional series, the uricosuric effect of probenecid was tested in ten patients with renal insufficiency. In these patients the uricosuric effect was clearly blunted, indicating that urate reab-sorption is reduced in renal insufficiency.     

Arterio-venous concentration difference of [51Cr]EDTA after a single injection in man. Significance of renal function and local blood flow

Summary. The present investigation was undertaken in order to study (1) the difference in arterial (C_a) and venous (C_v) concentration of [⁵¹Cr]EDTA (ethylenediaminetetra-acetate) after a single intravenous injection, (2) the impact of different physiological variables on this difference, and (3) the error introduced in the measurement of renal plasma clearance and total plasma clearance by using venous blood samples instead of arterial. In 13 patients with GFR ranging from 29 to 150 ml min^-1, C_a was higher than C_v immediately after the injection. After mean 38 min (range 12–82 min) the two curves crossed, and 180–300 min post-injection (p.i.) C_v was 5·9% higher than C_a (range 0·5–13·9%, P<0·001). The more reduced renal function, the smaller was the concentration difference. The areas under the arterial and the venous plasma concentration curves did not differ significantly at either 0–∞ or 0–300 min p.i., whereas the venous area 0–100 min p.i. underestimated the arterial area in the same period by 4·1% (P<0·05). In a computer simulation model, variation in the forearm capillary permeability–surface area product did not have any significant influence on the C_v–C_a difference, whereas the difference was very sensitive to even small changes in forearm blood flow within the physiological range. For measurement of renal plasma clearance it is recommended to use one long period: from the time of injection until 300 min p.i. or longer. If the clearance period is too short, the use of venous samples will overestimate the true renal clearance. Plasma clearance determined by venous and arterial blood samples does not differ significantly as long as the concentration is followed from the time of injection and a long period is applied. When simplified plasma clearance techniques are used, different results may be obtained from venous and arterial samples. The simplified techniques using venous blood samples—which usually include some empirical corrections—should be sufficiently reliable in daily clinical practice provided the forearm blood flow is reasonably high, e.g. exposure to cold should be avoided.     

Enhanced renal production of cyclic GMP and reduced free water clearance during sodium nitroprusside infusion in healthy man

Abstract. A 90–min intravenous infusion of the direct vasodilator sodium nitroprusside (SNP) was compared with a placebo infusion in 32 healthy control subjects in order to study the acute effects of SNP on renal haemodynamics, tubular function evaluated by the lithium clearance technique, the plasma levels of atrial natriuretic peptide (ANP), angiotensin II (Ang II), aldosterone (Aldo) and arginine vasopressin (AVP) and the tubular transport of cGMP (T_cGMP). SNP infusion induced a significant reduction in mean arterial blood pressure (from 89.5 to 81.5 mmHg), urinary output (from 7.7 to 4.5 ml min^-1), free water clearance (from 4.0 to 1.3 ml min-^I) and ANP (from 3.3 to 2.5 pmoll-¹) and a significant increase in heart rate (from 57 to 64 beats min^-l), Ang II (from 11 to 18 pmoll^-1), Aldo (from 189 to 308 pmol L^-1) and in the tubular secretion of cGMP (T_cgmP from 28.8 to 214.4 pmol min^-1), (all values are medians and changes from baseline to 90 min after infusion start). Glomerular filtration rate, renal plasma flow, urinary sodium excretion, lithium clearance and plasma level of AVP were not significantly changed. It is concluded that SNP infusion in healthy subjects decreases urinary output and free water clearance without any change in sodium excretion, indicating a dissociation between the salt and water retaining effects of SNP in the early phase of treatment, probably due to an enhanced distal tubular water reabsorption of water. It is suggested that this increase in reabsorption of water in the distal parts of the nephron during SNP infusion may be mediated by an increase of cGMP production in the kidney, as indicated by the increase in T_cGMP during the SNP infusion.     

Routine Determination of GFR in Renal Transplant Recipients by HPLC Quantification of Plasma Iohexol Concentrations and Comparison With Estimated GFR

Estimated glomerular filtration rate (eGFR) methods are not sufficiently reliable in renal transplant recipients (RTR) and should be replaced by iohexol plasma clearance measurement. However, this method has poor availability in health centers. The aim of our study was to develop a high‐performance liquid chromatography (HPLC) method for plasma iohexol measurement in routine practice and to evaluate its plasma clearance as a reference of GFR. We developed an HPLC method using UV detection. We evaluated sample storage conditions to provide recommendations for routine practice. Then, we compared GFRbased on plasma iohexol clearance (GFR‐iohexol) to eGFR using modification of diet in renal disease, Cockcroft and Gault, and CDK‐EPIequations in 40 RTR. The method was validated over a concentration range of 15–300 μg/l. Excellent linearity (r > 0.998), inter‐ and intraday precision (CV < 3.3%), and accuracy (>96.8%) were complied with ICH guidelines. We also demonstrated excellent samples stability (9 days). Although eGFR methods are not references in RTR, we found a correct concordance between eGFR and GFR‐iohexol in our population. To conclude, our method is simple, rapid, accurate, and reliable for routine clinical and research use especially in RTR. J. Clin. Lab. Anal. 26:376‐383, 2012. © 2012 Wiley Periodicals, Inc.     

Determination of cytosolic citrulline and nitrate as indicators of nitric oxide in bladder cancer: possible association with basic fibroblast growth factor

Background: Nitric Oxide (NO) and nitrosamines have been implicated in bladder carcinogenesis. Apart from its implication in carcinogenesis, NO contributes to the regulation of tumor angiogenesis via angiogenic peptides exemplified by basic fibroblast growth factor (bFGF).

Objectives and methods: In order to examine NO pattern in normal, schistosomal, and malignant bladder cytosols, we have used a combined approach by measuring nitrate and the amino acid citrulline. The results were correlated to bFGF, which were measured in bladder cytosols by an EIA method.

Results: Comparison between normal, schistosomal, and malignant bladder groups showed that patients with schistosomiasis and bladder cancer had significantly higher cytosolic nitrate, citrulline, and bFGF levels. There were no apparent correlations between these investigated parameters and tumor histologic features. The level of citrulline was strongly correlated to nitrate level and both were correlated to bFGF level in bladder cancer and schistosomiasis groups.

Conclusions: Our findings indicate that NO and bFGF were significantly elevated in schistosomiasis and bladder cancer compared to normal bladders. Moreover, the consistent association of NO with bFGF found in the present work, support the hypothesis that the angiogenic peptide bFGF may be modulated by NO and suggest a useful target in antiangiogenic therapy in bladder cancer.     

Antipyrine clearance and metabolite formation: the influence of liver volume and smoking

The influence of liver volume and cigarette smoking on antipyrine clearance and metabolite formation was studied in seventeen volunteers (eight smokers, nine non-smokers). Inter-test coefficient of variation of liver volume (as determined by ultrasound) was 6.3%. The mean antipyrine clearance was 49.3 +/- 18.3 ml min-1 and when normalized for liver volume 36.1 +/- 10.1 ml min-1 l-1. The antipyrine clearance per unit volume of liver was significantly higher in smokers (43.0 +/- 10.5 ml min-1 l-1), than in non-smokers (30.0 +/- 4.6 ml min-1 l-1) (P less than 0.01). No significant difference was found between the two groups as to the excreted amounts of 4-hydroxyantipyrine (OHA), norantipyrine (NORA), and 3-hydroxymethylantipyrine (HMA). Normalized for liver volume the mean clearances for production (Clm) of these metabolites were significantly higher in the group of smokers than in the group of non-smokers. The greatest change was observed for OHA formation. However, analysis of variance showed that the differences in the percentages of change of the mean Clm of these metabolites in the two groups are not significant.     

尿电导率的影响因素及其作为肾脏功能评估指标的分析探讨

目的 探讨尿电导率变化的影响因素,并分析其作为肾脏功能评估指标的临床价值.方法 使用全自动尿中有形成分分析仪UF-1000i（简称UF-1000i）检测3000名患者的尿电导率数值,并对结果进行分组分析.结果 健康新生儿与健康老年人尿电导率比健康成人对照组低,但差异无统计学意义;孕晚期妇女尿电导率与健康女性对照组相比,明显降低,差异具有统计学意义.肾病综合征组、肾小球肾炎组尿电导率较健康对照组明显降低,差异具有统计学意义.结论 年龄对尿电导率具有一定影响;尿电导率对于了解妊娠期妇女妊娠发展过程中肾脏浓缩稀释功能的变化具有一定的临床价值;在具有肾脏疾病的患者中,尿电导率可以作为肾脏功能损伤进展严重程度和肾脏浓缩稀释功能好坏的重要参考指标.     

胸腔内血容量指数在感染性休克患者液体管理中的应用

目的 探讨胸腔内血容量指数(ITBVI)在感染性休克患者液体管理中的应用价值.方法 采用前瞻性临床观察研究方法,将入住重症监护病房(ICU)的33例感染性休克患者分为两组.ITBVI组17例患者接受脉搏指示连续心排血量(PiCCO)监测,以ITBVI作为液体管理的指导指标;对照组16例患者以中心静脉压(CVP)作为液体管理的指导指标.对比两组患者治疗1 d和3 d时的急性生理学与慢性健康状况评分系统I(APACHE I)评分、感染相关器官功能衰竭评分系统(SOFA)评分、血管活性药物评分,以及补液72 h内两组患者的液体管理数据.结果 ①ITBVI组3 d时APACHE I、SOFA和血管活性药物评分(分)均较1 d时显著下降[21.3±6.2比25.4±7.2,6.1±3.4比9.0±3.5,5.0(0,8.0)比20.0(8.0,35.0),均P＜0.01];而对照组则均无显著变化.②虽然ITBVI组48～72 h液体出量(ml)大于对照组(2 421±868比1 721±934,P=0.039),但ITBVI组与对照组0～72 h的液体出入量和平衡量(ml)比较差异均无统计学意义(入量:9 918±137比10 529±1 331,出量:6 035±1 739比5 827±2 897,平衡量:3 882±1 889比4 703±2 813,均P＞0.05).③在快速补液试验中,ITBVI组与对照组患者除0～6 h胶体液入量[ml:250(125,500)比250(69,250)]差异无统计学意义(P＞0.05)外,其余时段液体入量(ml)ITBVI组均比对照组高[0～6 h晶体液:250(150,250)比125(105,125),6～72 h晶体液:125(125,250)比100(56,125),0～72 h晶体液:250(125,250)比125(75,125),6～72 h胶体液:125(106,250)比75(50,125),0～72 h胶体液:200(125,250)比100(50,125),均P＜0.01].结论 与以CVP指导相比,用ITBVI指导感染性休克患者的液体管理显示,3 d时患者病情较1 d改善,这种改善可能得益于对血容量状态的准确判断和适当的快速补液速度.     

Plasma noradrenaline in cirrhosis: a study of kinetics and temporal relationship to ascites formation

The kinetics of plasma noradrenaline (NA) were studied in 14 patients with cirrhosis and ascites and 13 normal subjects. [3H]noradrenaline ([3H] NA) was infused intravenously to steady state and the spillover of NA into plasma and its clearance from plasma calculated. The increase in plasma NA in the cirrhotic patients was due to an increase in NA spillover (14.5 vs 3.9 nmol min-1m-2; P less than 0.001). NA plasma clearance was also increased in the cirrhotic patients (3.5 vs 2.11 min-1m-2; P less than 0.01). Plasma NA and dihydroxyphenylglycol (DHPG), a metabolite of NA of which a portion is formed after re-uptake of NA into sympathetic nerve endings, were then measured in 23 patients with cirrhosis and ascites, 17 patients with cirrhosis who had never had ascites, and 34 normal subjects. Both plasma NA and DHPG were significantly increased in the patients with ascites (NA 4.7, DHPG 14.7 nmol l-1 and in the patients with cirrhosis but no ascites (NA 3.8, DHPG 12.0 nmol l-1) compared with normal subjects (NA 1.9, DHPG 8.8 nmol 1-1). Therefore, the increase in plasma NA in cirrhosis is due to increased activity of the sympathetic nervous system rather than interference with the metabolism of NA or impaired neuronal uptake of NA. This increase appears to precede the development of ascites.     

Biotransformation of orally administered ursodeoxycholic acid in man as observed in gallbladder bile, serum and urine

Abstract. The aim of this study was to evaluate the biotransformation of orally administered ursodeoxycholic acid in man. The distribution of ursodeoxycholic acid and its metabolites in gallbladder bile, in serum and in urine with emphasis on separation of their unconjugated, amidated and sulfated species in particular, was investigated. Seven gallstone patients were given 750 mg of ursodeoxycholic acid daily for 2–3 weeks. Six gallstone patients who did not receive ursodeoxycholic acid served as controls. Ursodeoxycholic acid became the major bile acid in gallbladder bile contributing 43% to total bile acids. 2% of biliary ursodeoxycholic acids were in the unconjugated form, 87% in the amidated form and 11% in the sulfated form. Iso-ursodeoxycholic acid was found in bile in small amounts and was present only as the sulfated species and not as the amidated one. Other metabolites of ursodeoxycholic acid tentatively identified in bile were 1β, 12β, 6α- and 21,22-hydroxylated derivatives of ursodeoxycholic acid. Lithocholic acid in bile tended to increase under ursodeoxycholic acid treatment and was positively correlated to ursodeoxycholic acid. The concentration of cholic acid in bile decreased significantly whereas the levels of deoxycholic acid and chenodeoxycholic acid did not change. Total bile acid concentration in serum and excretion of bile acids in urine increased from 5.4 ± 1.1 to 18.4 ± 9.5 μmol l^-1 (mean ± SD, P < 0.005) and from 5.6 ± 1.3 to 13.1 ± 7.9 μmol g^-1creatinine (mean ± SD, P < 0.05) after ursodeoxycholic acid ingestion mainly due to spillover and excretion of ursodeoxycholic acid. Ursodeoxycholic acid became the major bile acid in serum and urine contributing 46% and 50% to total bile acids. 14% ursodeoxycholic acid in serum were in the unconjugated form, 42% in the amidated form and 45% in the sulfated form; the percentages in urine were 11%, 23% and 66%. Iso-ursodeoxycholic acid was higher in serum and urine than in bile and contributed 16% and 8% to total bile acids. Iso-ursodeoxycholic acid was present in serum and urine only as the unconjugated and sulfated species. Other iso-bile acids and 3β-hydroxy-5-cholenoic acid were found in bile only in traces, but contributed 8% to total bile acids in serum and 10% in urine. In serum and urine the sulfated form of lithocholic acid prevailed and was significantly enhanced after ursodeoxycholic acid ingestion. Further metabolites of ursodeoxycholic acid in urine were tentatively identified to be hydroxylated at postitions 1β, 5α, 6α and 22 and contributed about 10–15% of urinary UDCA.