Plasma and urinary soluble adhesion molecule expression is increased during first documented acute pyelonephritis.

BACKGROUND: The degree of inflammatory reaction and leucocyte trafficking during acute pyelonephritis has been related to the risk of developing renal parenchymal scarring. Adhesion molecules play a central role in leucocyte recruitment during inflammation. AIMS: (1) To determine whether circulating and urinary concentrations of E-selectin and intercellular adhesion molecule 1 (ICAM-1) were abnormal during first documented acute pyelonephritis; (2) to investigate whether circulating or urinary concentrations were predictive for the development of abnormalities on DMSA imaging. METHODS: Plasma and urine samples were collected from 40 children with a first episode of acute pyelonephritis within one week of infection (acute sample) and at six weeks (late sample). Control samples were collected from 21 healthy age matched controls and 18 age matched controls with febrile illness not secondary to urinary tract infection. RESULTS: Plasma and urinary sE-selectin were higher in acute samples (median 176.3 ng/ml and 0.12 ng/mmol respectively) compared with late (97.8 ng/ml and 0.029 ng/mmol) and both control (65.6 ng/ml and 0 ng/mmol) and febrile control (urine 0 ng/mmol) samples. Plasma sICAM-1 was higher in acute samples (428 ng/ml) than controls (365.2 ng/ml), and acute sICAM-1 urine concentrations were higher than febrile control concentrations (3.2 v 0.7 ng/mmol). No correlations were detected between sE-selectin or sICAM-1 and acute or late DMSA scan changes. CONCLUSION: Plasma and urinary sE-selectin and sICAM-1 are significantly increased during acute pyelonephritis, though no correlation exists between the presence of high plasma or urine concentrations and DMSA scan changes, both during acute infection and six weeks post-infection.     

Circulating soluble adhesion molecule levels in children with acute lymphoblastic leukaemia

The aim of this study was to evaluate levels of serum soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin) as parameters of disease activity and to monitor the response to treatment in children with acute lymphoblastic leukaemia (ALL). The above soluble adhesion molecules were determined in the serum of 35 children with ALL and 30 healthy children (control group) of the same age range. The samples were obtained before treatment, 6 months after the beginning of the treatment (remission of the disease), 6 months after the end of the treatment and during relapse of the disease. The mean levels of sICAM-1, sVCAM-1 and sE-selectin at the onset of the disease were 646.6 ± 80.9 ng/ml, 1786 ± 151.8 ng/ml and 140.5 ± 17.3 ng/ml, respectively. These values were significantly higher (P < 0.001) than those of the control group, which were, 245.8 ± 25.7 ng/ml, 798.6 ± 78.9 ng/ml and 44.7 ± 18.2 ng/ml respectively. During remission, the mean levels did not differ significantly from those of the control group. After the end of the treatment the mean levels again did not show any significant differences compared to the control group. During relapse the soluble adhesion molecule mean levels (923.9 ± 110.1 ng/ml, 2945.7 ± 349.9 ng/ml and 258.2 ± 5.1 ng/ml) were significantly higher (P < 0.001) than those of the control group and also than those obtained during remission and after the end of the treatment (P < 0.001). Pearson's correlation coefficient r was computed in order to detect possible linear correlations between: (1) sICAM-1 and sVCAM-1 (r = 0.632); (2) sICAM-1 and sE-selectin (r = 0.788) and (3) sVCAM-1 and sE-selectin (r = 0.752). All three cases correspond to P < 0.001, thus indicating strong linear correlations. Conclusion The levels of soluble circulating adhesion molecule levels can be utilized for monitoring disease activity of ALL and its response to treatment, as well as for early detection of relapse. Strong linear correlations between the three soluble adhesion molecules tested suggest that each of them may be sufficient as an indicator. Received: 5 August 1996 / Accepted: 13 February 1997     

Cell adhesion molecule expression in coronary artery aneurysms in acute Kawasaki disease

BACKGROUND: The pathogenesis of coronary artery aneurysm (CAA) formation in acute Kawasaki disease (KD) remains unclear. Cell adhesion molecules mediate cell-cell and cell-matrix interactions and regulate leukocyte migration, angiogenesis and tissue remodeling. We hypothesized that cell adhesion molecules are expressed in acute KD CAA. METHODS:: P-selectin, E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and integrin beta1 were immunolocalized in coronary arteries from 6 acute KD patients and 7 controls. RESULTS: In endothelial cells of adventitial neovasculature in KD CAA, P-selectin and integrin beta1 were expressed in all of 6 patients, and E-selectin and/or VCAM-1 were expressed in 4 of 6. Endothelial cells in controls and in nonaneurysmal KD coronary arteries expressed P-selectin and integrin beta1, but not E-selectin or VCAM-1. Integrin beta1 was expressed on infiltrating leukocytes in 5 of 6 KD CAA and on fibroblasts in 6 of 6; these findings were absent in controls and in nonaneurysmal KD coronary arteries. CONCLUSIONS: The lack of widespread expression of E-selectin or VCAM-1 on endothelial cells of acute KD coronary arteries was surprising and suggests that inflammatory cell infiltration into KD coronaries is not simply the result of widespread up-regulation of cell adhesion molecules on endothelial cells by circulating cytokines. Rather, inflammatory cells may be directed to specific areas of the coronary arteries targeted by a pathogen causing KD. Our results suggest that E-selectin and VCAM-1 expression on neovasculature may contribute to neoangiogenesis and prolonged CAA inflammation and that integrin beta1 might be involved in fibroblastic remodeling of acute KD CAA.     

Hyponatraemia and hyperkalaemia in acute pyelonephritis without urinary tract anomalies

Abstract Three children with severe hyponatraemia and hyperkalaemia associated with acute pyelonephritis are reported. All were very young male infants in a poor general condition and seriously dehydrated. Diagnostic procedures did not detect obstructive uropathy or vesico-ureteric reflux.Conclusion Hyponatraemia and hyperkalaemia occurs in young infants with severe acute pyelonephritis in the absence of obstructive uropathy or vesico-ureteric reflux. The severe inflammation of the kidney itself may explain the electrolyte disturbance by a transient resistance of the distal tubule to aldosterone.     

Renal parenchymal volume during and after acute pyelonephritis measured by ultrasonography.

A total of 47 children with acute pyelonephritis were investigated using water delay ultrasonographic equipment (Octoson) for determination of renal parenchymal volume by the stepped section technique. Thirty two patients were repeatedly investigated every to every other week up to seven weeks. Median renal parenchymal volume during acute pyelonephritis of the right kidney was 2.70 cm3/kg body weight and of the left kidney 3.10 cm3/kg; this was significantly larger than the volume of control kidneys, which was 1.82 and 2.07 cm3/kg, respectively. The most enlarged kidneys were found among the youngest children. A significant successive decrease in renal size was found during the first four to five weeks after the acute pyelonephritis. Because of enlargement of the kidneys during acute pyelonephritis we suggest that the first renal size determination to be used for following renal growth should be performed after at least four to six weeks.     

神经细胞粘附分子及OCT-4蛋白在隐睾中的病理表达及意义

目的 探讨神经细胞粘附分子(NCAM)及转录因子OCT-4在人隐睾中的病理表达及意义.方法 48例隐睾患儿,年龄6个月～13.1岁,平均3岁,单侧43例,双侧5例,共50个隐睾组织活检样本.免疫组化法检测生精小管和间质内NCAM、OCT-4的表达情况.结果 50个样本中,NCAM生精小管内阴性、睾丸间质细胞(Lc)阳性、OCT-4阴性的牛理规律表达率为38%(19/50).NCAM牛精小管、Lc中病理表达率为58%(29/50).NCAM生精小管内阳性病理表达率为30%(15/50),与年龄、睾丸位置无相关性(P>0.05).NCAM于Lc内阴性病理表达率为32%(16/50),与睾丸位置无相关性(P>0.05),但随年龄增加,阳性表达率增加(P<0.05).OCT-4阳性病理表达率为12%(6/50),与睾丸位置无相关性(P>0.05).结论 NCAM和OCT-4在隐睾中的病理性表达反映了生殖母细胞的迁移分化障碍或延迟,可以被作为预测隐睾生殖潜能和癌变趋势的可靠分子标志物.     

Soluble receptors to tumour necrosis factor and interleukin-6 in urine during acute pyelonephritis

We compared the urinary concentrations of soluble TNF-I (sTNF-RI), TNF-II receptors, and soluble IL-6 receptor (sIL-6R) standardized to urinary creatinine concentrations, in children with acute pyelonephritis, in children with non-renal fever and in healthy controls. These levels were related to the acute inflammatory response in the kidneys and later renal scarring, as determined by acute and 1-y follow-up with ^99mTC-dimercaptosuccinic acid scintigraphy (DMSA). The concentrations of the soluble receptors were measured using enzyme immunoassay (EIA). The urinary levels of sTNF-RI were significantly higher in children with acute pyelonephritis (median 1320 pg/mmol) than in children with non-renal fever, children 6 weeks after acute pyelonephritis and healthy controls (873, 251 and 477 pg/μmol, respectively). Median sTNF-RII urine levels were also higher in acute pyelonephritis (4123 p/μmol) than in the three control groups (2000, 964 and 1850 pg/μmol, respectively). In contrast, the highest urinary sIL-6R concentrations were found in healthy children (median 420 pg/μmol). compared to those with acute pyelonephritis (235 pg/μmol), children with non-renal fever and children 6 weeks after pyelonephritis (137 and 50 pg/μmol, respectively). No significant difference was found in any of the urinary soluble receptor levels in children with or without DMSA uptake defects at the acute or the 1-y follow-up scintigraphy. In conclusion, although the urinary soluble TNF receptor levels were higher during acute pyelonephritis, this observation was not useful for deciding which children needed follow-up after acute pyelonephritis.     

Alterations of urinary carbon dioxide tension, electrolyte handling and low molecular weight protein excretion in acute pyelonephritis

Renal tubular function tests were performed in 45 children suffering from upper and lower urinary tract infections. Determinations were made of the urinary carbon dioxide tension in maximally alkaline urine as an index of distal tubular H+-ion secretion, of urinary protein excretion, and of urinary sodium and phosphate handling. Urinary PCO2 was low (2.7 +/- 13.9 mmHg) in acute pyelonephritis compared to values in healthy children (52 +/- 32 mmHg) or those with cystitis (48 +/- 34 mmHg). At the onset of pyelonephritis an elevated fractional excretion of sodium (1.38 +/- 0.38 vs. 0.50 +/- 0.20%) and decreased phosphate reabsorption (69.2 +/- 7.1 vs. 90.4 +/- 4.9%) were also observed. Significantly elevated urinary low molecular weight protein excretion was also found in pyelonephritis. These data indicate the existence of proximal and distal tubular dysfunction at the onset of acute bacterial pyelonephritis.     

Relationship among vesicoureteral reflux, P-fimbriated Escherichia coli, and acute pyelonephritis in children with febrile urinary tract infection.

Ninety-four children with febrile urinary tract infection were studied prospectively to determine the relationship between vesicoureteral reflux, P-fimbriated Escherichia coli, and acute pyelonephritis, and to evaluate the diagnostic reliability of commonly used clinical and laboratory observations. By using renal scan with dimercaptosuccinic acid labeled with technetium 99m as the standard of reference, we documented acute pyelonephritis in 62 (66%) of 94 patients. Vesicoureteral reflux was demonstrated in 29 (31%) of the total group and in only 23 (37%) of 62 patients with pyelonephritis. Of the 70 E. coli urinary isolates, 48 (69%) were P-fimbriated, including 30 (64%) of 47 isolates from patients with pyelonephritis and 18 (78%) of 23 isolates from patients with normal renal scans. The prevalence of P-fimbriated E. coli in patients with pyelonephritis and vesicoureteral reflux was 46%, compared with 71% in those with pyelonephritis who had no concurrent vesicoureteral reflux (p = 0.222). Multiple clinical and laboratory variables commonly used in the diagnosis of acute pyelonephritis did not adequately predict the presence or absence of parenchymal involvement. These data show the following: (1) Acute pyelonephritis in the absence of demonstrable vesicoureteral reflux is common. (2) Febrile urinary tract infections in children are commonly associated with P-fimbriated E. coli, both in the presence and absence of vesicoureteral reflux. (3) The presence of P fimbriae alone does not fully explain the pathophysiology of renal parenchymal invasion by bacteria in the absence of vesicoureteral reflux. (4) The diagnosis of acute pyelonephritis in children with febrile urinary tract infections on the basis of clinical and laboratory observations is unreliable.     

惊厥后脑内神经细胞黏附分子的表达及川芎嗪干预作用

目的 研究幼年大鼠反复惊厥后大脑皮质神经细胞黏附分子（NCAM）早晚期表达的变化及川芎嗪的干预影响，探讨NCAM在幼年期惊厥性脑损伤发病机制中的作用及对川芎嗪脑损伤的可能保护机制。方法 96只20日龄健康SD大鼠随机分为3组：正常对照组、惊厥组及川芎嗪干预组，通过三氟乙醚反复吸入制作幼年大鼠惊厥动物模型。用免疫组化（SP）法以及逆转录聚合酶链反应（RT-PCR）方法检测各组动物反复惊厥结束后第1天、第7天大脑皮质组织中NCAM的表达。结果 （1）反复惊厥结束后第1天惊厥组大脑皮质组织NCAM表达下降，与对照组比较差异有显著性（P〈0．05）。在反复惊厥后第7天惊厥组大脑皮质组织中NCAM表达较第1天增高（P〈0．05），但与对照组比较差异无显著性。（2）川芎嗪干预组在反复惊厥后第1天、第7天大脑皮质NCAM表达均较惊厥组显著增高（P〈0．05），且大脑皮质NCAM的表达在反复惊厥后第7天明显高于反复惊厥后第1天。结论 （1）反复惊厥后幼年大鼠NCAM表达由早期暂时降低，后逐渐增高，在晚期接近正常，提示NCAM参与了幼年期惊厥性脑损伤修复。（2）川芎嗪干预组在反复惊厥后早晚期均能上调NCAM的表达，提示川芎嗪对幼年期惊厥性脑损伤的保护机制可能与促进大脑皮质NCAM的表达增高有关。     

Plasma digoxin concentrations and urinary excretion during a 'simpler' regimen of infant digitalization.

We have measured the plasma concentrations in sick neonates and infants being administered digoxin by a safer regimen. In the presence of normal renal function the plasma concentrations appear to be satisfactory.     

Plasma somatostatin and cholecystokinin levels in sick preterm infants during their first six weeks of life

Abstract The present study reports the levels of plasma somatostatin and cholecystokinin in 19 preterm infants with asphyxia [ n =10, GA (median; range) 26; 23–30 weeks] and respiratory distress syndrome ( n = 14, GA 27; 23–29 weeks) compared with preterm infants without any of these conditions (reference group, n = 59, GA 33; 25–36 weeks). In the reference group 37 infants received phototherapy and their peptide levels were compared with those not receiving phototherapy ( n = 22). Plasma somatostatin and cholecystokinin were analysed by specific radioimmunoassays on day 1, day 3–4 and at 6 weeks of life. Plasma somatostatin levels, but not cholecystokinin levels, of reference infants were inversely related to gestational age on day 1 and day 3–4. Asphyxiated infants and infants with respiratory distress syndrome had significantly higher somatostatin levels than reference infants on day 1 and day 3–4. These differences disappeared when the levels were adjusted for gestational age. Plasma cholecystokinin levels were not influenced by respiratory distress syndrome and asphyxia. Phototherapy did not affect plasma somatostatin and cholecystokinin levels.