bluuebunny/crossref_metadata_2025 huggingface dataset:
Ramipril Inhibits in vitro Human Mesangial Cell Proliferation and Platelet-Derived Growth Factor Expression
Authors: Grandaliano Giuseppe , Ranieri Elena , Monno Raffaella , Gesualdo Loreto , Schena Francesco P.
Published: April 2003

Angiotensin-converting enzyme (ACE) inhibitors are antihypertensive drugs that have been shown to reduce proteinuria and to slow down the progression of renal function deterioration in different models of chronic glomerular disease. Major pathogenetic features of progressive glomerular injury leading to glomerulosclerosis are mesangial cell proliferation and platelet-derived growth factor (PDGF) expression. The aim of the present study was to evaluate the effect of ramipril, an ACE inhibitor, on these two potential therapeutic targets. Thus, the effect of ramipril on DNA synthesis, cell proliferation and PDGF A and B chain gene expression in fetal calf serum (FCS)-activated cultured human glomerular mesangial cells was investigated. DNA synthesis was evaluated by tritiated thymidine incorporation, cell proliferation by direct cell counting and cell viability by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). PDGF A and B chain gene expressions were studied by Northern blot and RT-PCR, respectively. In a dose-dependent manner ramipril inhibited the FCS-induced DNA synthesis and cell proliferation. This effect was not dependent upon a toxic effect as demonstrated by MTT. The antiproliferative effect of ramipril was most likely independent of its ability to inhibit ACE present in the FCS and/or expressed by the cells, since a synthetic peptide that specifically inhibits ACE, at the same molar concentrations, did not inhibit FCS-stimulated DNA synthesis. Moreover, ramipril significantly reduced FCS-induced PDGF A and B chain gene expression. Finally, ramipril completely abolished the PDGF A and B chain gene expression induced by phorbol 12-myristate 13-acetate, a specific protein kinase C activator, suggesting a site of action downstream of this enzyme in the mitogenic signal transduction pathway. Our study would suggest that the modulatory action of ramipril on activated mesangial cell proliferation and PDGF expression is independent of its ability to inhibit ACE and could represent an additional mechanism in the renal protective effects of this drug.
Cystic Fibrosis Transmembrane Conductance Regulator in the Kidney: Clues to Its Role?
Authors: Wilson Patricia D.
Published: April 2003

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic adenosine monophosphate dependent, low-conductance chloride channel found on the apical plasma membrane of secretory epithelia. Surprisingly, since cystic fibrosis patients have no kidney phenotype, CFTR is highly expressed in the kidney, present from 12 weeks of gestation in the human metanephric kidney. As well as the mature, full-length, 165-kD wild-type protein (WT-CFTR) associated with renal tubule plasma membranes, intracellular, partially glycosylated forms are also seen in normal kidneys. In addition, a kidney-specific splice variant of CFTR translates a cytoplasmic truncated protein (TNR-CFTR), apparently associated with a specific small endosomal population, and is predominantly expressed in the renal medulla. WT-CFTR and TNR-CFTR show different patterns of developmental regulation, WT-CFTR being the major form expressed early in metanephric development when it is localized at the apical plasma membrane of developing collecting tubules. By contrast, TNR-CFTR expression increases with gestational age, reaching adult levels at 23 weeks. Evidence suggests that WT-CFTR plays a role in chloride secretion into the apical lumen of normal distal tubules. In autosomal dominant polycystic kidney disease, normally targeted CFTR at the apical plasma membrane in association with mislocalized Na-K-ATPase may result in abnormal fluid secretion into cysts. Similar colocalization of WT-CFTR and Na-K-ATPase at the apical plasma membranes is found in collecting tubules during development when it is speculated to play a role in the initiation of opening of the tubule lumen.
Transdifferentiation of Distal but Not Proximal Tubular Epithelial Cells from Human Kidney in Culture
Authors: Baer Patrick C. , Tunn Ulf W. , Nunez German , Scherberich Jürgen E. , Geiger Helmut
Published: April 2003

Human renal proximal and distal (thick ascending limb and early distal convoluted tubule) epithelial cells have been isolated according to their specific antigen expression. The cells were well characterized by flow cytometry, enzyme cytochemistry and electron microscopy and cultured for up to 3 months. Cultured tubular cells coexpressed cytokeratin and vimentin as intermediate filament proteins. While primary isolated cells, proximal as well as distal, revealed the phenotypic characteristics of their nephron origin, cultured distal cells showed the tendency to dedifferentiate/transdifferentiate. Distal cells lost their characteristic expression of Tamm-Horsfall glycoprotein and started de novo expression of the proximal marker proteins aminopeptidase M, γ-glutamyl transferase and dipeptidyl peptidase IV. The expression of these antigens by distal cells could be shown by flow-cytometric analysis and fluorescence microscopy. Enzyme activity assays revealed the activity of aminopeptidase M, γ-glutamyl transferase and dipeptidyl peptidase IV, but not of the proximal marker enzyme alkaline phosphatase. This antigenic shift could not be prevented in different culture media, and the original phenotype could not be restored. Cultured cells displayed characteristic hormonal stimulation patterns indicative of their proximal and distal origins, as shown by activation of adenylate cyclase by different peptide hormones. These results indicate that distal tubular cells possibly transdifferentiate to a more proximal phenotype in view of loss of the distal marker enzyme Tamm-Horsfall protein and de novo expression of proximal marker enzymes like dipeptidyl peptidase IV and aminopeptidase M.
Fibrogenic Effects of Cyclosporin A on the Tubulointerstitium: Role of Cytokines and Growth Factors
Authors: Johnson David W. , Saunders Heather J. , Johnson Fiona J. , Huq Syed O. , Field Michael J. , Pollock Carol A.
Published: April 2003

The clinical utility of cyclosporin A (CyA) as an immunosuppressive agent has been significantly limited by the frequent occurrence of chronic nephrotoxicity, characterised by tubular atrophy, interstitial fibrosis and progressive renal impairment. The pathogenesis of this condition remains poorly understood, but has been postulated to be due to either direct cytotoxicity or indirect injury secondary to chronic renal vasoconstriction. Using primary cultures of human proximal tubule cells (PTCs) and renal cortical fibroblasts (CFs) as an in vitro model of the tubulointerstitium, we have been able to demonstrate that clinically relevant concentrations of CyA are directly toxic to these cells and promote fibrogenesis by a combination of suppressed matrix metalloproteinase activity and augmented fibroblast collagen synthesis. The latter effect occurs secondary to the ability of CyA to stimulate autocrine secretion of insulin-like growth factor-I by CFs and paracrine secretion of transforming growth factor-β1 by PTCs. Many of these pro-fibrotic mechanisms are completely reversed by concurrent administration of the angiotensin-converting enzyme inhibitor, enalaprilat, which has proven efficacy in preventing chronic CyA nephropathy in vivo. These studies highlight the unique potential that human renal cell cultures offer for studying the role of local cytokine networks in tubulointerstitial disease and for developing more effective treatment strategies which specifically target fibrogenic growth factor activity following nephrotoxic injuries.
Tissue Culture of Human Renal Epithelial Cells Using a Defined Serum-Free Growth Formulation
Authors: Sens Donald A. , Detrisac Carol J. , Sens Mary Ann , Rossi Mike R. , Wenger Sharon L. , Todd John H.
Published: April 2003

Background: Development of the culture of renal epithelial cells in a serum-free growth medium was driven by the need to examine the effects of hormones and other effector molecules on differentiated cell function without interference from the complex mixture of substances in serum. The present report details this laboratory’s cumulative experience in the use of a defined growth medium for the propagation of epithelial cells from adult, fetal, and malignant human renal tissue. Methods: Routine cell culture technology was used to determine the capability of a defined growth medium to support the growth of renal epithelial cells isolated by collagenase dissociation of tissue from adult and fetal kidneys, renal cell carcinoma, and Wilms’ tumors. Results: The defined growth medium formulation consistently allows the isolation and growth of transporting renal epithelial cells from both normal adult and fetal kidneys. This growth medium only rarely supports the growth of epithelial cells from renal cell carcinomas and Wilms’ tumors. Conclusions: The method developed for the culture of human proximal tubule cells requires minimal cell culture expertise and equipment, and results in the repeatable isolation of transporting epithelial cell cultures that retain features of differentiated proximal tubule cells.
Caldesmon Isoform Associated with Phenotypic Modulation of Mesangial Cells
Authors: Okamoto Kazunori , Kashihara Naoki , Yamasaki Yasushi , Kanao Koichiro , Maeshima Yohei , Sekikawa Takashi , Sugiyama Hitoshi , Murakami Takuro , Makino Hirofumi
Published: April 2003

Caldesmon (CaD) is a major calmodulin- and actin-binding protein distributed in smooth muscle cells (SMC) and nonmuscle cells. There are at least two high-molecular-weight CaD (h-CaD) isoforms and four low-molecular-weight CaD (l-CaD) isoforms produced by alternative splicing. Isoformal interconversion is associated with phenotypic modulations of vascular SMC. We investigated the CaD isoform in human and rat glomerular mesangial cells (MC) to characterize the phenotypic changes of MC involved in glomerular diseases. A Western blot analysis and reverse-transcription analysis using exon-specific primers revealed that one l-CaD isoform lacking exons 1, 3b and 4 was predominantly expressed in human cultured MC. The expression of this isoform was markedly enhanced in anti-Thy1.1 nephritis rats and streptozotocin-induced diabetic rats, while little expression was observed in the normal glomerulus. Isoformal interconversion did not occur during the phenotypic changes of MC. These data suggested that the activated MC resembled dedifferentiated SMC in terms of the CaD expression pattern, and that CaD is a useful marker of the phenotypic modulations of MC.
Phenotypic Plasticity and Terminal Differentiation of the Intercalated Cell: The Hensin Pathway
Authors: Al-Awqati Qais , Vijayakumar S. , Takito J. , Hikita C. , Yan L. , Wiederholt Tonio
Published: April 2003

The intercalated cell of the collecting tubule exists in a spectrum of types. The alpha form secretes acid by an apical H+ ATPase and a basolateral Cl:HCO3 exchanger which is an alternatively spliced form of the red cell band 3 (kAE1), while the beta form secretes HCO3 by having these transporters on the reverse membranes. In a clonal cell line of the beta form we found that seeding density causes this conversion. A new protein, termed hensin, was deposited in the extracellular matrix of high-density cells which on purification reversed the polarity of the transporters. Hensin also induced the expression of the microvillar protein, villin, and caused the appearance of the apical terminal web proteins, cytokeratin 19 and actin, all of which led to the development of an exuberant microvillar structure. In addition, hensin caused the beta cells to assume a columnar shape. All of these studies demonstrate that the conversion of polarity in the intercalated cell, at least in vitro, represents terminal differentiation and that hensin is the first protein in a new pathway that mediates this process. Hensin, DMBT1, CRP-ductin, and ebnerin are alternately spliced products from a single gene located on human chromosome 10q25–26, a region often deleted in several cancers, especially malignant gliomas. Hensin is expressed in many epithelial cell types, and it is possible that it plays a similarly important role in the differentiation of these epithelia as well.
Arginase in Glomerulonephritis
Authors: Waddington Simon N. , Cattell Victoria
Published: April 2003

Arginase metabolizes L-arginine to L-ornithine and urea. Two arginase isoforms, AI (liver arginase) and AII (ubiquitously expressed, functions unknown), have been identified. It is clear that arginases potentially have important roles in addition to urea generation for high concentrations are present at inflammatory sites. Regulation occurs through cytokines, substrate competition and products of nitric oxide (NO) metabolism. The functions of arginases at inflammatory sites are unknown, but may include regulation of apoptosis and NO production and generation of structural and cellular protein precursors. In glomerulonephritis there is increased arginase activity in nephritic glomeruli following a pattern similar to that in wound healing. The level can be further increased by NO inhibition suggesting substrate competition. The potential sources in the inflamed glomerulus include infiltrating leucocytes and mesangial cells, and the predominant isoform expressed is AI (AII predominates under physiological conditions). The recent identification of different isoforms of arginase has been an important step towards understanding the significance of arginase activity in glomerulonephritis.
Cloning of Rabbit Cct6 and the Distribution of the Cct Complex in Mammalian Tissues
Authors: Schwartz George J. , Kittelberger Ann M. , Segel George B.
Published: April 2003

Cct6 protein is one of the subunits of the Cct complex involved in ATP-dependent folding of cellular proteins. We used the cDNA of the human CCT6 subunit to obtain a full-length cDNA from a rabbit kidney cortex library. Two transcripts of 2 and 2.5 kb were detected in rabbit kidney and liver by Northern analysis. The rabbit CCT6 was 93% identical to the human gene; the deduced amino acid sequence was 97% identical. A phylogenetic analysis of Cct6 proteins from mouse, rabbit, human, and yeast showed greater similarities of Cct6 protein among the species than among other Cct subunits. The ATP-binding sites were perfectly conserved among mammals and yeast, supporting the role of Cct complex in ATP-dependent protein folding. Using a polyclonal antibody to human Cct6 protein and Western analysis, we found expression of this subunit in a variety of rabbit organs and tissues, as well as in bovine testes, human lymphocytes, human and rabbit reticulocytes, and in two cultured kidney cell lines. We also found Cct1 protein by Western analysis in several rabbit organs as well as in bovine testes. These data characterize the rabbit Cct6 subunit and compare it to its homologues. The Western analyses support the concept that Cct complex is widely distributed among tissues and highly conserved among eukaryotes.
Murine Models of Renal Disease: Possibilities and Problems in Studies Using Mutant Mice
Authors: Anders Hans-Joachim , Schlöndorff Detlef
Published: April 2003

The elucidation of the pathogenesis of human renal disease at the molecular level has been facilitated by the growing field of gene targeting and the development of mouse strains with single-gene deletions – the ‘knock-out’ mice. Experimental nephrology, therefore, requires well-characterized and reliable models of human renal disease that can be induced reproducibly in mice. Today surgical procedures for the induction of renal ischemia, chronic renal failure, and ureter obstruction are feasible in mice. Models of mesangioproliferative or crescentic glomerulonephritis, glomerulosclerosis, and tubulointerstitial disease are readily available; however, these depend heavily on the mouse genetic background. Attention to the genetic background and appropriate backcrossing are, therefore, of great importance in the design and interpretation of experimental studies, especially in transgenic mice. Simple murine models displaying the clinical features of other human renal diseases such as IgA nephropathy, membranous glomerulonephritis, and renal vasculitis are still lacking. Mouse strains that spontaneously develop distinct renal pathologies similar to lupus nephritis and focal-segmental glomerulosclerosis can be intercrossed with transgenic mice to study the impact of single-gene deletions on the renal phenotype. The present review provides a survey about currently available spontaneous and inducible murine models of renal disease with special attention to problems and future perspectives for their use in transgenic animals.
Immunological Function of Tubular Epithelial Cells: The Functional Implications of CD40 Expression
Authors: van Kooten Cees , Woltman Andrea M. , Daha Mohamed R.
Published: April 2003

Tubulo-interstitial inflammation in the kidney is characterized by the presence of activated T cells. Both by the local production of cytokines, as well as by direct cell-cell interactions, these activated T cells might affect the immune and inflammatory response. Recently it has been demonstrated that these kidney-infiltrating T cells express CD40 ligand and that tubular epithelial cells (TECs) express CD40. In the present review we will discuss the potential implications of CD40-CD40L interactions for the activation of TECs and its immunological function.
Immune Recognition of Glomerular Antigens
Authors: Phelps R.G.
Published: April 2003

Autoimmunity is thought to cause most varieties of glomerulonephritis including membranous nephropathy, minimal-change nephropathy, Goodpasture’s disease and possibly IgA nephropathy. Much effort has been and is directed at understanding the mechanisms of immune system driven inflammation and of the consequent renal injury and repair or scarring. The purpose of this article is to focus attention on the way the immune system recognizes kidney autoantigens, a process that must be a pivotal in the initiation of autoimmune kidney disease.
Reciprocal Regulation of LTA4 Hydrolase Expression in Human Monocytes by γ-Interferon and Interleukins 4 and 13: Potential Relevance to Leukotriene Regulation in Glomerular Disease
Authors: Montero Angel , Nassar George M. , Uda Susumu , Munger Karen A. , Badr Kamal F.
Published: April 2003

Background/Aims: Leukotriene A4 (LTA4) hydrolase catalyzes the final step in the synthesis of leukotriene B4 (LTB4). TH-1- and TH-2-derived cytokines may regulate LTB4 synthesis by monocytes through their actions on the expression of LTA4 hydrolase. Methods: Freshly isolated monocytes were incubated with pro- and anti-inflammatory cytokines for 36 h. mRNA expression was determined by Northern blot, protein expression was determined by Western blot and LTB4 synthesis was determined by ELISA. Results: Interferon-γ (a TH-2-derived cytokine) increased significantly LTA4 hydrolase mRNA expression, whereas interleukin (IL)-4 and IL-13 (both TH-2-derived cytokines) decreased LTA4 hydrolase mRNA expression in these cells. The same effects were seen on the expression of immunoreactive LTA4 hydrolase after incubating the monocytes with either TH-1- or TH-2-derived cytokines. The monocyte-derived cytokine IL-1β did not show any significant effect on LTA4 hydrolase mRNA expression. When LTB4 release was measured, both IL-1β and interferon-γ significantly increased LTB4 production by monocytes, while TH-2 cytokines (IL-4 and IL-13) decreased it. Conclusion: The opposing effects of TH-1- and TH-2-derived cytokines on the expression of LTA4 hydrolase mRNA may regulate LTB4 synthesis by monocytes during inflammation.
Reduction in Mean Glomerular Pore Size Coincides with the Development of Large Shunt Pores in Patients with Diabetic Nephropathy
Authors: Oberbauer Rainer , Nenov Vesselin , Weidekamm Claudia , Haas Martin , Szekeres Thomas , Mayer Gert
Published: April 2003

The glomerular size selectivity was determined by neutral dextran clearance sieving technique and plasma cystatin C levels in two groups of patients with long-standing type I diabetes mellitus and different stages of albuminuria but normal glomerular filtration rate and in a group of healthy controls. The sieving characteristics of the glomerular filter were determined using a mathematical model of log normal pore size distribution. Patients with albuminuria above 200 μg/min exhibited a significant increase of cystatin c plasma concentrations and a significant reduction in mean glomerular filtration slit size. Only these patients exhibited large, unrestrictive pores in the glomerular filter (shunt). The plasma cystatin c levels correlated significantly with 26-angstrom neutral dextran plasma levels in microalbuminuric patients and in patients with albuminuria above 200 μg/ min. We conclude that a reduction in average pore size of the glomerular filter does not occur earlier than the development of large shunt pores. The renal clearance of cystatin c in patients with proteinuric diabetic nephropathy but a normal glomerular filtration rate is reduced due to its molecular size.
Postnatal Follow-Up of Hydronephrosis Detected by Prenatal Ultrasound: The Natural History
Authors: Kitagawa H. , Pringle K.C. , Stone P. , Flower J. , Murakami N. , Robinson R.
Published: April 2003

Babies with hydronephrosis detected antenatally who were born at or referred to our hospital from 1990 to 1995 were followed up with ultrasound (U/S), micturating cystourethrogram (MCU) or nuclear medicine studies after birth. One hundred and three patients were diagnosed antenatally at 17–42 weeks gestation. Twelve cases were excluded from the analysis of the results because of incomplete data. Fifty-one (56%) patients had hydronephrosis without organic obstruction, and 80% of these became normal in 3 years. Fifteen patients (17%) had a normal scan 4 days after birth. This suggests the possibility of antenatal spontaneous regression. Seven (8%) had a ureterocele and 4 (5%) had pelviureteric junction (PUJ) obstruction. Four (5%) had vesicoureteric reflux, and 4 (5%) had primary megaureter. Two (2%) had posterior urethral valves (PUV), 3 (3%) had refluxing primary megaureter, and 1 (1%) had urethral atresia. Fifteen patients (17%) underwent surgical intervention. Six had a nephrectomy, 1 a vesicostomy, 3 an Anderson-Hynes pyeloplasty, 3 had the ureterocele unroofed, 1 had a ureteric reimplant, and 1 ablation of valves. In 42 infants with 60 abnormal kidneys, the renal anteroposterior diameter of the pelvis was measured. Retrospectively, 48 kidneys diagnosed as having hydronephrosis, antenatally had a renal pelvis diameter ≥4 mm before 33 weeks gestation or ≥7 mm after 33 weeks gestation. One patient with PUJ obstruction lost kidney function, but there is no good marker to detect these patients. Early unroofing of ureteroceles may rescue kidney function. Our follow-up protocol for antenatal hydronephrosis is U/S at 4 days, 1 month and 1 year of age. An MCU is not required unless the ureter is seen on antenatal U/S. If dilatation persists past 1 month, a radionucleotide (MAG3) scan and repeat U/S are performed at 3 months. The methods for assessing obstruction and the indications for surgical intervention in these patients require reexamination.
Maternal Weight Differences Do Not Explain Ethnic Differences in Biochemical Screening
Authors: Bryant-Greenwood Peter K. , O’Brien Joseph E. , Huang Xiaohua , Yaron Yuval , Ayoub Mazin , Johnson Mark P. , Evans Mark I.
Published: April 2003

In previous work, we and others have shown that serum levels of α-fetoprotein, human chorionic gonadotropin, and estriol vary among the four commonly defined racial/ethnic groups seen in the United States: white, African-American, Asian, and Hispanic. We have suggested that better sensitivity and specificity could improve screening sensitivity and specificity. However, it has been argued that systematic weight differences among the groups could explain the variation. We evaluated the results from 208,257 patients having screening and found systematic weight differences. However, these differences were not as large as the racial/ethnic differences, showing that weight does not fully explain the discrepancy, and, therefore, four separate data bases give more accurate results.
Therapeutic Amnioinfusions and Fetal Fibronectin Pattern in a Case with Preterm Ruptured Membranes That Resealed
Authors: De Carolis Sara , Carducci Brigida , De Santis Lidia , Ferrazzani Sergio , Noia Giuseppe , Merola Annamaria , Caruso Alessandro
Published: April 2003

Objective: Determination of fetal fibronectin (fFN) levels in a patient at risk of preterm delivery and having premature rupture of the membranes. Patient and Methods: The present case report concerns a pregnant woman with premature rupture of the membranes at 16 weeks of gestation who was submitted to repeated therapeutic transabdominal amnioinfusions and had a spontaneous resolution of the rupture at 32 weeks of gestation. Results: A good pregnancy outcome was observed. High cervicovaginal fFN levels were observed during the period of membrane rupture with following drop of fFN levels during this period and spontaneous reseal of the membranes. Conclusions: Active expectant management, using repeated amnioinfusions, probably played a useful role in the therapeutic success of this pregnancy. Further, fFN was a reliable marker of the rupture of membranes. The possible role of fFN in the clinical management of high-risk pregnancies is confirmed.
Prenatal Diagnosis of Cloacal Dysgenesis Sequence: Differential Diagnosis from Other Forms of Fetal Obstructive Uropathy
Authors: Qureshi Faisal , Jacques Suzanne M. , Yaron Yuval , Kramer Ralph L. , Evans Mark I. , Johnson Mark P.
Published: April 2003

Cloacal dysgenesis sequence (CDS) is a rare cause of fetal obstructive uropathy (FOU). The prenatal differentiation of CDS from other FOU is important because CDS is not amenable to in utero surgical intervention in the form of vesicoamniotic shunts. We evaluated the prenatal characteristics of 8 fetuses with CDS, including a pair of monozygotic twins concordant for CDS, in order to identify features that would enable differentiation from other forms of FOU. Pathologic examination in each of the 8 fetuses confirmed characteristic features of absent anal, genital, and urinary orifices associated with a smooth perineum and abnormal phallic development. Associated abnormalities included dysplastic kidneys in 6, hydroureters in 5, intraluminal colonic calcifications in 2, and hypoplastic lungs in 5. Five of these fetuses initially presented as posterior urethral valve syndrome. Six fetuses had megacystis, and 4 underwent vesicocenteses to evaluate urinary electrolytes, all of which were in the ‘poor-risk’ category. Six fetuses were male and 2 female, contradicting earlier claims that CDS occurs only in females. Evaluation of candidates for in utero surgical intervention should include fetal karyotype, and CDS should be suspected in cases of FOU in whom the karyotype reveals a male fetus and sonographic evaluation demonstrates colonic calcifications or abnormal phallic development. Diagnostic microendoscopy may be of benefit in such cases.
Fatal Sepsis due to Escherichia coli after Second-TrimesterAmniocentesis
Authors: Ayadi Seamy , Carbillon Lionel , Varlet Catherine , Uzan Michelle , Pourriat Jean-Louis
Published: April 2003

The case of a pregnant woman (16th week) needing an amniocentesis is reported. She rapidly developed a septic shock. Despite vaginal delivery, curettage and antibiotherapy, the patient deteriorated with the onset of an acute respiratory distress syndrome and a typical disseminated intravascular coagulation. Bacteriological data showed positive blood cultures to Escherichis coli. Amniotic liquid was positive to the same E. coli. Cultures obtained from instruments, disinfectant solutions and gel used during the procedure were negative. On the contrary, amniotic and fetal cultures were positive to E. coli and Clostridium perfringens. She died 2 days later.The incidence of septic shock following amniocentesis is very low but we report the first case of fatal sepsis and multiorgan failure, due to E. coli and C. perfringens. The mechanisms of infection are discussed: contamination from the instruments, systemic dissemination of bacteria coming from an asymptomatic intra-amniotic infection, and inoculation of the placenta with a needle passing through the bowel.
Very Prolonged Membrane Rupture and Delayed Delivery of the Second Twin
Authors: Bakos Oddvar , Cederholm Maria , Kieler Helle
Published: April 2003

Objectives: To present the complications of twin pregnancies with delayed delivery of the second twin, 32 days after expulsion of the first twin. Case: A 29-year-old woman with a twin pregnancy at gestational age 13 weeks and 5 days presenting with a rupture of the membranes of the first twin. At 21 completed weeks the umbilical cord prolapsed and at 23 weeks the first twin was stillborn with the placenta in the uterus. After maternal septicemia the second twin was delivered by cesarian section, at 28 complete weeks, liveborn. The mother and child were discharged from hospital 10 weeks later, corresponding to 38 completed weeks of pregnancy. Conclusions: A very early premature rupture of membrane (PROM) occurs more often in twin pregnancies. The delivery of one twin most often results in expulsion of the second twin. With PROM there is a great risk of chorioamnionitis, as in our case, which resulted in an acute cesarean section. In this case, conservative management achieved a viable fetus in spite of very early and serious complications.
Twin-to-Twin Transfusion Syndrome: Polyhydramnios-Associated Changes in Maternal Plasma Volume and Maternal Plasma Aldosterone Concentrations
Authors: van Peborgh P. , Morineau G. , Bussières L. , Escourrou P. , Ville Y.
Published: April 2003

Objective: Our aim was to evaluate the consequences of polyhydramnios on maternal plasma volume and maternal serum aldosterone and atrial natriuretic peptide (ANP) concentrations in monochorionic twin pregnancies complicated by twin-to-twin transfusion syndrome (TTTS). Methods: The maternal plasma volume, ionograms as well as plasma ANP and aldosterone concentrations were compared in normal monochorionic diamniotic twin pregnancies and in TTTS. Results: The maternal plasma volume was normal in TTTS despite severe polyhydramnios. The plasma aldosterone concentration was higher in pregnancies complicated by TTTS. Conclusion: The high plasma aldosterone concentration is likely to maintain normal plasma volume despite progressive extravascular volume enhancement. This suggests that TTTS is present early in pregnancy as a chronic phenomenon starting before its clinical expression and may trigger compensatory maternal hyperaldosteronism.
Debate about Ultrasound Screening Policies
Authors: Antsaklis Aris J.
Published: April 2003

Routine ultrasound examination is defined as a screening procedure performed on the total obstetric population usually at 18–20 weeks of gestation as opposed to the selective use of ultrasound that might provide more information for a problem that is suspected on clinical grounds. Standard ultrasound examination includes a comprehensive examination of fetal anatomy as part of routine ultrasound. It is important for the clinician to realise that the comprehensive examination of fetal anatomy is an essential, not optional, part of the routine examination. Screening may lead to unnecessary anxiety if there is a false-positive result, or to a false sense of security if there is a false-negative result. The routine offering of obstetric ultrasound screening is the central issue in the general question of whether every woman should receive an obstetric ultrasound examination. The majority of countries have adopted the following diagnostic strategy. All pregnancies must be ultrasonographically tested in accordance with the protocols commonly recommended. The ultrasonography done at 18–20 weeks, which is known to be fundamental for diagnosing prenatal malformations, must always be performed at level II. High-risk pregnancies of malformations are to be selected in the first level of screening and referred to level II for further study. There is extensive literature neither supporting an improvement in perinatal morbidity or mortality nor an overall reduction in unnecessary intervention with routine ultrasound. The role of routine ultrasonography and its validity as a screening test for fetal malformation in a low-risk population is still the object of debate.
Persisting Spongy Myocardium
Authors: Winer N. , Lefèvre M. , Nomballais M.F. , David A. , Rival J.M. , Gournay V. , Debillon T. , Rozé J.C. , Boog G.
Published: April 2003

Persisting spongy myocardium (also known as noncompaction of the ventricular myocardium) is a rare and special form of cardiomyopathy. The few cases reported in the literature were detected postnatally and involved a high rate of cardiovascular complications. This anomaly of endomyocardial morphogenesis, which occurs during the embryonic phase at the stage of cardiac partitioning, is characterised by an excessive number of prominent trabeculae and by intertrabecular recesses within the myocardial wall. Antenatal detection is difficult in the absence of an associated malformation, which is the general situation. We report a case of antenatal cardiomyopathy which led to therapeutic abortion. The diagnosis of persisting spongy myocardium was made during fetopathologic examination.
First-Trimester Multifetal Pregnancy Reduction: Evaluation of Technical Aspects and Risks from 2,756 Cases in the Literature
Authors: Dechaud Hervé , Picot Marie Christine , Hedon Bernard , Boulot Pierre
Published: April 2003

Objective: To evaluate the technical aspects, efficacy and safety of first-trimester multifetal pregnancy reduction in the management of multifetal pregnancies, an analysis of the international literature on first-trimester multifetal pregnancy reduction was made. Materials: Thirty-three studies were selected from an international review of the literature. Total fetal loss rate, risk of fetal loss after the procedure with the different techniques and gestational age at delivery were the main parameters studied. The Kruskal-Wallis test and Mann-Whitney test were used for statistical analysis. Results: 2,756 multifetal pregnancy reductions were performed (2,145 transabdominal, 363 transcervical, and 248 transvaginal procedures). Total fetal loss rates were different: 16.7% for the transabdominal, 24.8% for the transcervical and 10.9% for the transvaginal procedure (p = 0.03). The risk of fetal loss was 12% for the transabdominal, 20% for the transcervical, and 10% for the transvaginal approach at less 24 weeks of gestation (p = 0.04). There was no difference for the gestational age at the time of the procedure, the initial and final number of embryos, and the gestational age at delivery. Conclusion: Because the transvaginal approach seems to be the safer procedure, surgeons may opt for it. The transcervical approach has a high fetal loss rate and should be excluded.
Early Transvaginal Measurement of Transcerebellar Diameter in Down Syndrome
Authors: Guariglia Lorenzo , Rosati Paolo
Published: April 2003

Objective: To evaluate the screening utility of early transvaginal measurement of the transverse cerebellar diameter for identification of Down syndrome fetuses. Method: Measurements of the transverse cerebellar diameter were obtained by transvaginal sonography between 11 and 16 weeks of gestation in 544 fetuses with a normal karyotype and in 37 Down syndrome fetuses. Results: The transverse cerebellar diameter was found to show a fairly constant increment of values throughout the period evaluated with a linear relationship to the gestational age. The measurements obtained in Down syndrome fetuses are within the normal range for gestational age. Conclusion: The transverse cerebellar diameter cannot be considered a useful tool in the detection of Down syndrome in early pregnancy.
An Experimental Animal Model of Intestinal Obstruction to Simulate in utero Therapy for Jejunoileal Atresia
Authors: Patricolo Mario , Noia Giuseppe , Rossi Lorenzo , Zangari Andrea , Pomini Francesco , Catesini Carlo , Filippetti Renzo , Galli Tommaso , Iacobelli Barbara Daniela , Capuano L.G. , Romano Domenico , Mancuso Salvatore , Rivosecchi Massimo
Published: April 2003

Objective: To obtain ‘intestinal atresia-like’ conditions in the fetal lamb model to subsequently allow in utero surgical repair. Methods: Six time-dated pregnant sheep underwent general anesthesia at 75 days of gestation (term 145 ± 5 days). After maternal laparotomy and hysterotomy, the fetal abdomen was opened. Once the jejunoileal intestinal loop was identified, the mesenteric vessels were isolated, ligated, and sectioned in 2 fetuses, and in the remaining 5 fetuses the bowel loop was ligated. Two further fetuses were used as controls and underwent sole laparotomy. Of the group of 7 fetuses 2 were reoperated at 100–105 days of gestational age and underwent intestinal recanalization. Eight fetuses were delivered at term by cesarean section and the remaining 1 by spontaneous delivery. One newborn underwent neonatal entero-enteric anastomosis. Results: 4 out of 6 fetuses survived, in utero intestinal or vascular ligation having provoked an ‘intestinal atresia-like’ picture. The animal operated at birth died. The 2 control fetuses and the 2 fetuses with in utero intestinal recanalization survived until term. Conclusion: The present study shows that in utero treatment of intestinal obstruction is possible in an experimental model.
Prenatal Diagnosis and Fetopathological Findings in a Fetus with Ring Chromosome 18
Authors: Thies U. , Bartels I. , von Beust G. , Bink K. , Hansmann I. , Rehder H. , Suren A. , Zoll B.
Published: April 2003

We report on a fetus with ring chromosome 18 and monosomy 18 mosaicism [mos 45,XX,–18/46,XX,r(18)] detected in cultured amniotic fluid cells at 15 weeks’ gestation. Chromosome analysis of fetal blood, cultured chorionic villi and fetal fibroblasts confirmed the aberrant karyotype. The aberrant chromosome complement could not be detected in a short-term culture of chorionic villi (46,XX in 21 metaphases). These findings suggest that the aberrant karyotype was a postzygotic event. Fetal ultrasound was normal and the parents decided to terminate the pregnancy at 21 weeks’ gestation. Autopsy revealed multiple abnormalities including facial dysmorphy, partial agenesis of the corpus callosum and an interatrial septal defect.
Changes in Survival of Twins Delivered after Twin-Twin Transfusion Syndrome versus Preterm Singletons over the Calendar Years 1970–1994
Authors: Skupski Daniel W.
Published: April 2003

Objective: The use of serial amniotic fluid volume reduction for the treatment of twin-twin transfusion syndrome (TTTS) became available about 1986 and may account for a recent increase in survival of TTTS twins. To determine whether the increase in survival has been due to advances in neonatal care rather than the advent of amnioreduction, the current study evaluated whether increases in survival of preterm TTTS twins were greater than increases in survival of preterm singletons from studies before 1986 compared to studies after 1986. Methods: Medline literature search identified all reported cases of TTTS and all reports of severely preterm neonatal survival. Studies were divided into groups according to gestational age at birth (≤27 vs. >27 weeks) and midyear of each study (≤1986 vs. >1986). Comparison was performed of the increase in survival from pre-1986 studies to post-1986 studies between preterm singletons and TTTS twins. Results: When comparing studies from before 1986 to after 1986, there was no difference in the increase in survival between preterm (>27 weeks) TTTS twins (67–92%) and preterm (>27 weeks) singletons (79–91%) (p = NS). When comparing studies from before 1986 to after 1986, there was a greater increase in survival among severely preterm (≤27 weeks) TTTS twins (0–22%) than among severely preterm (≤27 weeks) singletons (47–57%) (p = 0.036). Conclusions: Because of the paucity of data on TTTS twins and the retrospective nature of this study, conclusions are limited. There appears to be some basis for the belief that amnioreduction improves survival in TTTS twins delivered at ≤27 weeks’ gestation. These results confirm the need for a randomized, controlled trial of expectant management versus amnioreduction for the treatment of TTTS.
Intrathoracic Alimentary Tract Duplication Cysts Treated in utero by Thoracoamniotic Shunting
Authors: MartínezFerro Marcelo , Milner Ross , Voto Liliana , Zapaterio Jorge , Cannizzaro Claudia , Rodríguez Susana , Bonifacino Graciela , Sanchez José María , Adzick N. Scott
Published: April 2003

Alimentary tract duplication cysts are rarely diagnosed in utero. We report two fetal patients that presented with intrathoracic alimentary tract duplication cysts, mediastinal shift and hydrops. In one fetus, the cyst continued into the fetal abdomen and pelvis through a left diaphragmatic hernia. Despite successful ultrasound-guided needle aspirations in both fetuses, there was rapid reaccumulation of the fluid and recurrence of the mediastinal shift, prompting the placement of a thoracoamniotic shunt. In one fetus, there was rapid resolution of the mediastinal shift with the disappearance of the hydrops within 2 weeks. The second fetus suffered an intrauterine demise 2 days after the shunt placement. Postnatal resection in the surviving infant revealed a large cyst consistent with an intrathoracic duplication of the stomach. The autopsy of the second fetus revealed an intrathoracic duplication cyst of the stomach and proximal small intestine.
Perinatal Findings in a Male Fetus with Congenital Megacystis and Anorectal Malformations
Authors: Chen Chih-Ping , Wang Wayseen , Lin Shuan-Pei , Sheu Jin-Cherng , Tsai Jeng-Daw
Published: April 2003

We report the perinatal findings in a male fetus with congenital megacystis and anorectal malformations. A 17-year-old primipara was referred to our department at 13 weeks of gestation for management of a 4.6 × 3.8 cm massive intra-abdominal fetal mass consistent with megacystis. The fetal thorax was severely compressed. We used a 22-gauge needle to perform intrauterine fetal vesicocentesis, removing 30 ml of fetal urine, decreasing the fetal bladder diameter/crown-rump length ratio from 65.7 to 17%. Cytogenetic analysis revealed a 46, XY karyotype. Intermittent bladder aspiration was performed weekly from 13 to 20 weeks of gestation and every 2–3 weeks from 21 to 35 weeks of gestation for the purpose of decompression. Mild dilation of both renal pelves was noted beginning at 20 weeks of gestation, however, neither progression of hydronephrosis nor development of oligohydramnios was noted. At 36 weeks of gestation, a live male neonate was delivered with a normal phallus, duodenal atresia, mild congenital heart defects, a distended bladder, bilateral hydronephrosis, megaureters, imperforate anus with rectovesical fistula, cryptorchidism and bilateral vesicoureteric reflux. The postnatal renal function was normal. He underwent serial operations including colostomy, anoplasty with repair of rectovesical fistula, duodeno-duodenostomy, bilateral re-implantation of ureters, orchiopexy and reduction cystoplasty. At 20 months of age, the child had normal renal function. The intravenous pyelogram showed normal functional kidneys, moderate megaureters and moderate megacystis. He underwent clean intermittent catheterization for residual urine. The recurrent urinary tract infections were under control.
Analysis of Umbilical Artery Flow Parameters during Fetal Variable Decelerations Using Computerized Doppler Waveforms
Authors: Tadmor O. , Bocker Y. , Rabinowitz R. , Aboulafia Y. , Yagel S. , Stark M. , Diamant Y.Z. , Nitzan M.
Published: April 2003

Umbilical artery velocity waves were obtained by Doppler ultrasonography before, during, and after 20 episodes of fetal heart rate (FHR) variable decelerations (VD) during the active stage of labor in 8 women. During 50% of the VD periods, the umbilical artery resistance flow parameters increased significantly (p < 0.01). The increase in resistance preceded the decrease in FHR in six episodes (30%) of VD (AR-VD group; arterial resistance VD) and did not precede the change in FHR in another ten episodes (50%) of VD (VR-VD group; venous resistance VD). In the AR-VD group the FHR accelerations occurred before the decelerations in only 1 case (17%), while in the VR-VD group FHR accelerations preceded the decelerations in 8 out of the 10 episodes (80%). Using these Doppler studies, it may be possible to differentiate between two groups of VD: AR-VD – which are caused by umbilical artery occlusion and thus preceded by a measurable increase in umbilical artery resistance – and VR-VD – which are not preceded by a measurable increase in umbilical artery resistance and may be caused by fetal hypoxia.
Assessment of Triplet Fetal Growth by Using Cross-Sectional Analysis of the Birth Weight
Authors: Vignal J. , Daures J.P. , Vergnes C. , Giacalone P.L. , Boulot P.
Published: April 2003

Objective: To model the growth of triplets. Method: Statistical analysis using data of a consecutive series of 76 triplet gestations (223 livebirths). Results: The best model to describe the growth was linear regression (r = 0.76; r2 = 0.577; p < 0.0001; y = –2,858.05 + 139.66x). 34.2% of the sets had an intratriplet discordance rate of at least 25%, and 11.8% of the triplets had a maximum discordance rate over 40%. Conclusions: (1) Triplet fetal growth is strongly related to the gestational age; (2) the growth of each triplet in a same set may considerably differ, and (3) the use of singleton curves for triplet growth assessment is inadequate.
Prenatal Diagnosis of Congenital Neuroblastoma
Authors: Heling Kai S. , Chaoui Rabih , Hartung John , Kirchmair Felicita , Bollmann Rainer
Published: April 2003

Objective: Advances in prenatal diagnostics during the last 10 years have enabled the examiner to detect even rare fetal disorders such as fetal tumours. Congenital neuroblastoma is the most frequent solid neoplasm in infancy, with a retroperitoneal cystic or solid mass being a sonographic sign of the conditions. Methods: We present 4 cases of neuroblastoma showing suspicious prenatal ultrasound findings. The investigation comprises detection during pregnancy, typical sonographic signs, as well as the postnatal outcome. In addition, a review of the literature is undertaken with a focus on prenatal sonographic signs of congenital neuroblastomas. Results: In all 4 cases, a cystic tumour was detected during the 3rd trimester of pregnancy by means of B-mode sonography. One boy died of disseminated metastases at the age of 26 months. The other 3 survived after surgery and have remained healthy. Conclusions: The detection of a cystic suprarenal mass is suspicious of a congenital neuroblastoma. The delivery should take place at a perinatal centre.
Evolution of Left Ventricular Diseasein the Fetus
Authors: Fesslová V. , Papa M. , De Caro E. , Marasini M.
Published: April 2003

A fetal case is described that showed a rapid progression from the features of initial left ventricular fibroelastosis at 20 weeks of gestation to a more marked dilation at 22 weeks and finally to a hypoplastic left ventricle with aortic stenosis at 24 weeks of gestation. This case confirms the evolutive character of left ventricular disease during fetal life.