Renal excretion of endothelin in children

Endothelin (ET) is a peptide with profound vasoconstrictive potential. First isolated from porcine endothelial cell supernatant, it is produced also by smooth muscle, epithelial and circulating cells. Besides vasoconstriction, a wide spectrum of biological activities of ET (via activation of membrane receptors) has been described. These include regulation of other hormones and neurotransmitters, cellular growth and proliferation, bronchoconstriction, and, in the kidney, natriuresis and water diuresis. ET exerts its effects mainly in an autocrine and paracrine fashion. A high concentration of ET is found in urine, compared with plasma originating mainly from the kidney itself. In this review we focus on the role of urinary excretion of ET in children. ET excretion was determined under different physiological and pathological conditions. In premature infants and newborns, the daily excretion of ET (corrected for body surface) was higher than in older children; it was constant, and comparable to the values in healthy adults after the age of 2 years. Renal ET excretion correlated positively with urine flow in both healthy and sick children. Conditions with tubular and/or collecting duct cell damage, such as severe hypoxia, hemolytic-uremic syndrome, renal transplantation, diabetes mellitus, chronic renal failure, and contrast media cytotoxicity were characterized by elevated urinary excretion of ET. In conclusion, the renal excretion of ET is influenced by several factors, probably reflecting the intrarenal ET production. ET has a low specificity with regard to renal injury. Received May 7, 1996; received in revised form January 14, 1997; accepted January 17, 1997     

Temporomandibular joint: morphology and signal intensity characteristics of the disk at MR imaging

Magnetic resonance (MR) imaging has been used in the temporomandibular joint (TMJ) primarily to define the disk position. This report examines altered morphology and signal intensity characteristics of the TMJ disk as they relate to the severity of internal derangement. Two hundred sixteen joints in 133 patients with a history of such derangement. were imaged with MR. Disk position, signal intensity, morphology, and the presence of osteoarthritis were determined for each joint. The normal disk was not anteriorly displaced and had a normal "bow-tie" shape. A grade 1 disk was anteriorly displaced and had a normal shape; a grade 2 disk was anteriorly displaced and had an abnormal shape. Forty (19%) joints were considered normal; none of these exhibited osteoarthritis. One hundred thirty-nine (64%) joints were grade 1; osteoarthritis was found in 17%. Thirty-seven (17%) were grade 2; osteoarthritis was found in 95%. All forty normal joints had high or intermediate signal intensity in the disk. Osteoarthritic joints had a higher percentage of disks with diminished intensity (P less than .0001). Severe or untreated osteoarthritis is known to be a complication of TMJ internal derangements; hence this grading system seems to correlate with the severity of internal derangement.     

Irreversible shock of rats after acute renal vein thrombosis

Summary After occlusion of the renal veins rats die quickly in progressive shock (within 4.5 h), but after ligating the renal hilum of both Kidneys they survive 27 h. To learn why renal vein occlusion is so rapidly lethal, and what substances are given off and by what method from the hemorrhagically infarcted kidneys, we studied eight groups of rats, each containing at least seven animals. The groups differed in the combination of hilar structures (renal veins, ureters, lymphatics) ligated. We compared: survival times, changes in blood pressure, blood volume, levels of plasma kinins, adenosine, and lactate, changes of blood pH, responses to Indomethacin, Trasylol^®, and plasma expanders, tubular and capillary flow rates, histopathological changes in organs and cerebral blood flow and changes in the blood coagulation system. Our results suggest that the venous stasis, anoxia, and hemorrhagic necrosis caused by bilateral venous occlusion release into renal lymphatics toxic substances which reach the systemic circulation and induce irreversible shock. We have excluded prostaglandins and adenosine as the toxic substances inducing shock but could not rule out an action of the kallikrein-kinin-system. We postulate that the striking degenerative changes occurring in the arterioles of the brain after bilateral venous occlusion may mean these vessels are especially susceptible to high levels of lactic acid and that this may explain why these animals die so quickly. Our conclusions should help not only in understanding why high levels of lactate in shock portend a poor prognosis but also help in formulating appropriate therapy for circulatory failure of renal origin and for protracted hypotension after extensive tissue injury.The studies were supported by the German Research Foundation within the SFB 90 Cardiovasculäres SystemPresented in part: Jäckh and Steinhausen, 1976; Dallenbach et al., 1978; Zimmerhackl et al., 1979We dedicate this paper to Wilhelm Doerr, Dr. med., Professor of Pathology, University of Heidelberg on the occasion of his 65th birthday (August 25th, 1979)     

Behandlung des hyperammonämischen Komas bei Neugeborenen und Säuglingen durch Hämodialyse oder Hämofiltration

Zusammenfassung Das hyperammon?mische Koma ist eine akut lebensbedrohliche Stoffwechselentgleisung. Die h?ufigsten kongenitalen Ursachen sind Enzymdefekte im Harnstoffzyklus und im Abbau von organischen S?uren. Die Frühdiagnose und eine sofortige aggressive Therapie sind die entscheidenden Voraussetzungen zur Vermeidung irreversibler Hirnsch?den und letaler Verl?ufe. Das Therapieziel ist eine rasche Senkung des Ammoniaks und anderer neurotoxischer Metaboliten. Die therapeutischen Grundprinzipien beinhalten 1. eine restriktive Proteinzufuhr unter dem Erhalt essentieller Aminos?uren, 2. die Unterbrechung des Proteinkatabolismus mittels hochkalorischer Ern?hrung, 3. eine medikament?se Aktivierung alternativer Wege der Stickstoffausscheidung sowie 4. apparative Blutreinigungsverfahren. Das optimale Dialyseverfahren ist umstritten. Wir haben 4 Neugeborene und S?uglinge in einem hyperammon?mischen Koma im Rahmen von Stoffwechselerkrankungen mittels H?modialyse oder H?mofiltration behandelt. Die Kasuistiken best?tigen die Effektivit?t und Komplikationsarmut beider Verfahren. Diskussion: In der Behandlung von lebensbedrohlichen Hyperammon?mien bei Neugeborenen und S?uglingen sind H?modialysen und H?mofiltrationen die Behandlungsmethoden der Wahl. Die invasive Blutreinigung ist mit einer konsequenten di?tetischen und medikament?sen Therapie zu optimieren. Der prognostische Nutzen einer effizienten Blutreinigung bei ausgepr?gter Hyperammon?mie rechtfertigt einen unverzüglichen Transport in das n?chstgelegene p?diatrische Dialysezentrum.      

Kryptorchismusdiagnostik mittels MRT

Zusammenfassung Ziel: Untersucht wurde die Treffsicherheit der MRT bei der Lokalisationsdiagnostik nichtpalpabler Hoden. Material und Methode: 17 Jungen im Alter von 11 Monaten bis 9 Jahren wurden zur Lokalisationsdiagnostik eines oder beider nichtpalpabler Hoden (insgesamt 20 Hoden) mittels MRT (1T-Ger?t, Magnetom Expert, Siemens) im Zeitraum von 1992–1995 untersucht. Die Lokalisationen wurden in: Bauchhoden und hohe und tief gelegene Leistenhoden eingeteilt. Die Patienten wurden anschlie?end laparoskopisch oder offen operiert und der evtl. vorhandene hochstehende Hoden im Skrotum fixiert. Ergebnisse: 16 Hoden (80%) wurden durch die MRT-Diagnostik pr?operativ richtig lokalisiert bzw. eine Anorchie richtig diagnostiziert. Zwei Hoden (10%) wurden falsch lokalisiert, 2 Hoden (10%) wurden in der MRT beschrieben, obwohl eine Anorchie vorlag. Von unseren 5 Anorchief?llen konnten mittels MRT nur 3 diagnostiziert werden. Schlu?folgerung: Die MRT erreicht eine gute Trefferquote (80% positive Vorhersagewahrscheinlichkeit) in der pr?operativen Lokalisationsdiagnostik des nichtpalpablen Hodens. Da die MRT eine Anorchie nicht mit ausreichender Sicherheit von einem Kryptorchismus differenzieren kann, kann ein fehlender Hodennachweis in der MRT die endoskopische Diagnostik nicht substituieren. Bei geplanter endoskopischer Diagnostik kann im Regelfall auf die pr?operative MRT-Diagnostik verzichtet werden.      

Mobilization of early hematopoietic progenitor cells with BB-10010: a genetically engineered variant of human macrophage inflammatory protein- 1 alpha

BB-10010 is a genetically engineered variant of human macrophage inflammatory protein-1 alpha with improved solution properties. We show here that it mobilizes stem cells into the peripheral blood. We investigated the mobilizing effects of BB-10010 on the numbers of circulating 8-day spleen colony-forming units (CFU-S8), CFU-S12, and progenitors with marrow repopulating ability (MRA). A single subcutaneous dose of BB-10010 caused a twofold increase in circulating numbers of CFU-S8, CFU-S12, and MRA 30 minutes after dosing. We also investigated the effects of granulocyte colony-stimulating factor (G- CSF) and the combination of G-CSF with BB-10010 on progenitor mobilization. Two days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA progenitors by 25.7-, 19.8-, and 27.7-fold. A single administration of BB-10010 after 2 days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA even further to 38-, 33-, and 100- fold. Splenectomy resulted in increased circulating progenitor numbers but did not change the pattern of mobilization. Two days of treatment with G-CSF then increased circulating CFU-S8, CFU-S12, and MRA by 64-, 69-, and 32-fold. A single BB-10010 administration after G-CSF treatment further increased them to 85-, 117-, and 140-fold, respectively, compared with control. We conclude that BB-10010 causes a rapid increase in the number of circulating hematopoietic progenitors and further enhances the numbers induced by pretreatment with G-CSF. BB- 10010 preferentially mobilized the more primitive progenitors with marrow repopulating activity, releasing four times the number achieved with G-CSF alone. Translated into a clinical setting, this improvement in progenitor cell mobilization may enhance the efficiency of harvest and the quality of grafts for peripheral blood stem cell transplantation.