bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of carbon monoxide air pollution in pregnancy on neonatal nucleated red blood cells
Authors: Ziaei Saeideh , Nouri Kobra , Kazemnejad Anoshirvan
Published: January 2005

In an analytical cross‐sectional study, the effects of carbon monoxide air pollution on carboxyhaemoglobin (COHb) and absolute nucleated red blood cells (nRBC) of the cord venous blood, were evaluated in 41 newborns delivered by caesarean section at term to mothers who had lived in an air‐polluted area in the centre of Tehran during their pregnancies (study group). The parameters used were compared with 32 cord venous bloods of term caesarean‐delivered newborns of mothers living in a healthy air area outside the city during their pregnancies.

A significant difference was observed between the two groups in the cord COHb levels (mean ± SD 10.51 ± 4.79 vs. 1.58 ± 0.96, P < 0.001), cord nRBC (723.87 ± 275.23 × 106/L vs. 248.44 ± 160.79 × 106/L, P < 0.001). A significant correlation was found between ambient carbon monoxide and cord COHb in the study and control groups, respectively (r = 0.863, P = 0.0001; r = 0.691, P = 0.0001), and also cord COHb and cord nRBC in the study group (r = 0.360, P = 0.01).

Neonates born to mothers exposed to carbon monoxide air pollution had increased circulating absolute nRBC counts compared with those of the control group. We speculate that air pollution exposure in pregnancy should be avoided, because it may have negative effects on fetal oxygenation.
Influence of prenatal diagnosis and pregnancy termination of fetuses with birth defects on the perinatal mortality rate in Victoria, Australia
Authors: Davidson Natasha , Halliday Jane , Riley Merilyn , King James
Published: January 2005

Historical data show that in Victoria birth defects have accounted for approximately 25% of all perinatal deaths. Terminations of pregnancies (TOPs) for birth defects occurring at ≥20 weeks gestation are included in the population‐based perinatal data collection. These are classified as stillbirths or neonatal deaths. Some would have survived the perinatal period if no termination had taken place, and as a result they have the effect of increasing the perinatal mortality rate (PMR). Conversely, TOPs <20 weeks gestation, of fetuses with lethal birth defects that would have resulted in a perinatal death, are not included in the statistics and therefore reduce the PMR.

The aim of this study was to examine the effect on the PMR of TOPs following the prenatal detection of birth defects, taking into account the severity or ‘lethality’ of the birth defects. Data on live births, stillbirths, neonatal deaths and TOPs carried out because of a birth defect were collected from the Victorian Birth Defects Register (BDR) for 1989–2000. Birth defects were categorised into three groups, according to the estimated likelihood of a baby with that condition dying in the perinatal period: a ‘lethal’ birth defect was one where there was >50% likelihood of death, ‘possibly lethal’ 15–50% and ‘non‐lethal’ less than 15%. Based on these ‘lethality’ groups and associated assumptions about average survival rates beyond the neonatal period, the PMR was recalculated. TOPs for ‘non‐lethal’ birth defects at ≥20 weeks gestation increased the PMR by 3.8%. TOPs for ‘lethal’ birth defects <20 weeks decreased the PMR by 14.4%. The net effect on the overall PMR from TOPs for birth defects was a 10.6% decrease.
Neonatal serum p,p’‐DDE concentrations in Germany: chronological changes during the past 20 years and proposed tolerance level
Authors: Lackmann Gerd M.
Published: January 2005

p,p’‐DDE, the main metabolite of the insecticide DDT, is prenatally transmitted from mother to fetus. Many potential effects of low‐level exposure have been reported, including preterm delivery, growth retardation and neurological impairment, although scientific evidence is still lacking. We present p,p’‐DDE concentrations in full‐term human neonates over a time period of 20 years in Germany. Peripheral venous blood samples were taken from neonates born in 1984–85 (n = 80) and 1994–95 (n = 80), as well as cord blood samples from neonates born in 1998 (n = 199), and peripheral venous blood samples from neonates born in 2002 (n = 20). Blood specimens were immediately centrifuged, and serum was stored at −20°C until analysis. Serum p,p’‐DDE concentrations were determined with capillary gas chromatography followed by electron capture detection. Differences between study groups were tested for mean differences with the Kruskal‐Wallis test.

There were no differences between the study groups with regard to sex distribution, birthweight, gestational age, age of the mother, and smoking behaviour of the parents. We found a significant (P < 0.0001) chronological decline of neonatal serum p,p’‐DDE concentrations, with the highest values in 1984–85 (mean = 1.49 µg/L; range: 0.30–5.58) and the lowest in 2002 [mean = 0.18 µg/L; range: 0.07–0.54; tolerance level (95th percentile by rank) = 0.30 µg/L]. Neonatal p,p’‐DDE concentrations today are significantly lower than in the mid‐1990s, when many studies of adverse side effects of p,p’‐DDE were performed. The present results suggest that the neonatal burden of p,p’‐DDE now is so low that there may be no attendant health risks for newborns and children, however, further studies are warranted to elucidate possible long‐term health effects even of low‐level organochlorine pollution.
A dose‐response relationship between maternal smoking during late pregnancy and adult intelligence in male offspring
Authors: Mortensen Erik Lykke , Michaelsen Kim Fleischer , Sanders Stephanie A. , Reinisch June Machover
Published: January 2005

An association between maternal smoking during pregnancy and cognitive and behavioural development has been observed in several studies, but potential effects of maternal smoking on offspring adult intelligence have not been investigated. The objective of the present study was to investigate a potential association between maternal smoking during pregnancy and offspring intelligence in young adulthood. Adult intelligence was assessed at the mean age of 18.7 years by a military draft board intelligence test (Børge Priens Prøve) for 3044 singleton males from the Copenhagen Perinatal Cohort with information regarding maternal smoking during the third trimester coded into five categories (about 50% of the mothers were smokers). The following potential confounders were included as covariates in multivariable analyses: parental social status and education, single mother status, mother's height and age, number of pregnancies, and gestational age. In separate analyses, birthweight and length were also included as covariates.

Maternal cigarette smoking during the third trimester, adjusted for the seven covariates, showed a negative association with offspring adult intelligence (P = 0.0001). The mean difference between the no‐smoking and the heaviest smoking category amounted to 0.41 standard deviation, corresponding to an IQ difference of 6.2 points [95% confidence interval 0.14, 0.68]. The association remained significant when further adjusted for birthweight and length (P = 0.007). Both unadjusted and adjusted means suggested a dose‐response relationship between maternal smoking during pregnancy and offspring adult intelligence. When subjects with missing data were excluded, essentially the same results were obtained in the reduced sample (n = 1829). These results suggest that smoking during pregnancy may have long‐term negative consequences on offspring adult intelligence.
Risk factors for pre‐eclampsia in nulliparous and parous women: the Jerusalem Perinatal Study
Authors: Funai E. F. , Paltiel O. B. , Malaspina D. , Friedlander Y. , Deutsch L. , Harlap S.
Published: January 2005

Pre‐eclampsia has been described as a ‘disease of first pregnancies’ and many believe that its occurrence in a later pregnancy signals a fundamentally different entity. We sought to compare risk factors in first and subsequent pregnancies. We studied 1319 cases of pre‐eclampsia recorded in a historical cohort of 82 436 deliveries in Jerusalem in 1964–76. Logistic regression was used to control for covariates. The adjusted odds ratio (OR) for pre‐eclampsia in first births was 2.58 (95% confidence interval[CI] 2.23, 2.97), compared with all later birth order groups, between which there were no detectable differences in risk. Other risk factors included increasing maternal age, diabetes (OR 5.64, 95% CI 4.33, 7.35), multiple gestations (OR 3.38, 95% CI 2.54, 4.49), fetal haemolytic disease (OR 2.24, 95% CI 1.43, 3.50) and lower maternal education. The risk of pre‐eclampsia was not associated with the mother's employment outside the home and did not differ between immigrants vs. Israeli‐born mothers or between groups of women whose fathers had been born in Western Asia, North Africa or Europe. Effects of each risk factor were similar within first and subsequent births. These results lend no support to the hypothesis that there is a fundamental difference between pre‐eclampsia in a first pregnancy compared with that occurring in a later pregnancy; conclusions may be moderated, however, by the knowledge that the incidence of pre‐eclampsia was low in this historical cohort.
Perinatal mortality rates: adjusting for risk factor profile is essential
Authors: Rankin Judith , Pearce Mark S. , Bell Ruth , Glinianaia Svetlana V. , Parker Louise
Published: January 2005

Perinatal mortality has long been used as a comparative measure of health and health care across regions, countries and over time. Recently, the validity of the measure has been questioned. Using data from a population‐based survey of late fetal losses, stillbirths and infant deaths, the Northern Perinatal Mortality Survey, we demonstrate the potential for inaccuracy of crude measures of perinatal mortality. Such measures are generally not adjusted for characteristics of the population (e.g. birthweight, maternal age, plurality, gender) which are known to affect risk of adverse pregnancy outcome when comparing temporal or geographical trends. We also show the effect of standardising for these factors on the most frequent causes of perinatal death. We recommend the construction of a ‘standard birth population’ for calculating standardised perinatal mortality rates that would improve direct comparisons between populations.
The twin placenta: framework for gross analysis in fetal origins of adult disease initiatives
Authors: Salafia Carolyn M. , Maas Elizabeth
Published: January 2005

Current data strongly support that a wide variety of adult health risks are influenced by intrauterine life events. Twins may have the same (identical, monozygous) or different (fraternal, dizygous) genes, but their relationship to their outside world, via their placentas, is rarely equal. Monochorionic twins and dichorionic twins both resemble and differ from singletons. In the balance between the similarities and the differences, we may find the answer to the interpretation of twin studies, and appropriately apply them to the ‘fetal origins’ hypothesis.
Can we generalise from findings in twins?
Authors: Morley Ruth
Published: January 2005

A number of recent studies have used data from twins to shed light on the causal pathways underlying the observed association between birthweight and cardiovascular risk factors or coronary heart disease. The issue of whether findings from twin studies are generally informative, or whether factors associated with twinning preclude generalisation, is considered here. It is concluded that the association between birthweight and later health may differ quantitatively between twins and singletons, but evidence regarding blood pressure suggests it may not differ qualitatively. However, more information is needed on a number of gestational and maternal factors, and on measures of health other than blood pressure. Placentation and issues relating to infertility and its treatment need to be recorded and, together with gestation length, may need to be taken into account in analyses.
Determinants of birthweight and intrauterine growth in liveborn twins
Authors: Loos Ruth J. F. , Derom Catherine , Derom Robert , Vlietinck Robert
Published: January 2005

We explored the relationship of umbilical cord insertion and fusion of placentas with birthweight in monozygotic monochorionic (MZ MC), monozygotic dichorionic (MZ DC), and dizygotic (DZ) twins. In addition, we evaluated some of the possible factors responsible for the restricted intrauterine growth of twins compared with singletons. The birthweight of 4529 liveborn twin pairs of the East Flanders Prospective Twin Survey was prospectively recorded, placentas were examined, and site of umbilical cord insertion was determined after delivery. Birthweight of 76 490 liveborn singletons was obtained from the Study Centre for Perinatal Epidemiology (SPE). Infants with a peripheral cord insertion weighed 150 g less (P < 0.001) than infants with a central cord insertion. DZ infants had a significantly (P < 0.001) higher incidence of central cord insertion than MZ DC and MZ MC infants. MZ DC infants with fused placentas and a peripheral cord insertion weighed on average 300 g less (P < 0.01) than infants with separate placentas and a central cord insertion. In DZ infants, fusion of the placentas did not affect birthweight. Twins gain less weight per week of gestation than singletons from 32 weeks onwards (twins: 128 g, 156 g, 75 g and singletons: 118 g, 251 g, 149 g, weeks 27–31,32–36, 37–42 respectively). From week 32 onwards, parity, birth rank, cord insertion and number of placentas also influenced birthweight of twins. We conclude that the difference between the birthweights of DZ, MZ DC, and MZ MC infants may originate from the least favourable antenatal situation, namely fused placentas with a peripheral cord insertion, which occurs most frequently in MZ twins. Gestation is the main determinant of birthweight. Other placental and maternal factors have a modest but significant influence on prenatal growth.
Twin‐to‐twin transfusion syndrome: a model for the fetal origins of adult health
Authors: Chescheir Nancy C.
Published: January 2005

Twin‐to‐twin transfusion syndrome (TTTS) is a complication of monochorionic, diamniotic twins that results from unbalanced blood flow from one to the other in utero. The increased rate of functional heart disease among the recipient twins in these pregnancies is a model for the theory of fetal origins of adult health. Potential mechanisms for heart disease include alterations in the hormonal environment within the fetal bodies, blood pressure‐driven alterations in blood flow and blood vessel distensibility, abnormal differentiation of fetal myocardial cells and changes in coronary artery growth. Although there are no large studies showing adult consequences of this fetal physiological disturbance, paediatric problems certainly exist and predict an increased risk of adult disease.
Gender mix: does it modify birthweight – outcome association?
Authors: Derom Robert , Derom Catherine , Loos Ruth J. F. , Thiery Evert , Vlietinck Robert , Fryns Jean‐Pierre
Published: January 2005

Gender mix, especially the supposed hormone transfer in utero of the male fetus to his female co‐twin, is a highly debated controversial subject. It occurs in animals (free‐martin syndrome in the cow) but its existence in man has not been convincingly demonstrated. Two aspects of gender mix effects in man, birthweight and cognitive development, were studied in the Belgian East Flanders Prospective Twin Survey, a large population‐based registry of multiple maternities, characterised by accurate data on pregnancy, placental structure and zygosity. The birthweight of the female member of the pair is not influenced by the male co‐twin but, unexpectedly, the female twin enhances to a slight degree the birthweight of her male co‐twin by prolonging the gestation for a few days. Also unexpectedly, in an opposite direction, the cognitive development, as measured by the IQ (WISC‐R) of the female twin rises as compared with controls if her birthweight exceeds that of her male co‐twin.
Intrauterine environmental and genetic influences on the association between birthweight and cardiovascular risk factors: studies in twins as a means of testing the fetal origins hypothesis
Authors: IJzerman Richard G. , Boomsma Dorret I. , Stehouwer Coen D. A.
Published: January 2005

Evidence has accumulated that low birthweight is associated with several risk factors for cardiovascular disease. However, it is not known whether or not these associations are due to a programmed response to intrauterine malnutrition or genetic factors influencing both birthweight and cardiovascular risk factors. Twin studies offer a unique opportunity to distinguish between intrauterine and genetic origins of the association between birthweight and cardiovascular risk. In our twin cohort, low birthweight was associated with insulin resistance, lower HDL and shorter height within both dizygotic and monozygotic twin pairs, suggesting that these associations are, at least in part, independent of genetic factors. In contrast, low birthweight was associated with blood pressure, total and LDL cholesterol, fibrinogen and sympathetic activation within dizygotic twin pairs, but not within monozygotic twin pairs. These differences between dizygotic and monozygotic twins suggest that these associations are, at least in part, due to genetic factors. Therefore, both intrauterine environmental and genetic factors appear to play a role in the association between birthweight and cardiovascular risk factors. In the future, strategies may be developed targeted at improving or preventing impaired intrauterine growth. However, the effects of interventions that comprise changes in environment within the normal range may be limited due to the possible important role of genetic factors.
Gender mix in twins and fetal growth, length of gestation and adult cancer risk
Authors: Luke Barbara , Hediger Mary , Min Sung‐Joon , Brown Morton B. , Misiunas Ruta B. , Gonzalez‐Quintero Victor Hugo , Nugent Clark , Witter Frank R. , Newman Roger B. , Hankins Gary D. V. , Grainger David A. , Macones George A.
Published: January 2005

This study evaluated the effect of gender mix (the gender combinations of twin pairs) on fetal growth and length of gestation, and reviewed the literature on the long‐term effects of this altered fetal milieu on cancer risk. In singletons, it is well established that females weigh less than males at all gestations, averaging 125–135 g less at full term. This gender difference is generally believed to be the result of the effect of androgens on fetal growth. The gender difference in fetal growth is greater before the third trimester and less towards term, with males growing not only more, but also earlier than females. Plurality is a known risk factor for reduced fetal growth and birthweight. Compared with singletons, the mean birthweight percentiles of twins fall substantially (by 10% or more) below the singleton 10th percentile by 28 weeks, below the singleton 50th percentile by 30 weeks, and below the singleton 90th percentile by 34 weeks. In unlike‐gender twin pairs, it has been reported that the female prolongs gestation for her brother, resulting in a higher birthweight for the male twin than that of like‐gender male twins. Other researchers have demonstrated that females in unlike‐gender pairs had higher birthweights than females in like‐gender pairs.

Analyses from our consortium on 2491 twin pregnancies with known chorionicity showed longer gestations and faster rates of fetal growth in both males and females in unlike‐gender pairs compared with like‐gender male or female pairs, although these differences were not statistically significant. The post‐natal effects for females growing in an androgenic‐anabolic environment include increased sensation‐seeking behaviour and aggression, lowered visual acuity, more masculine attitudes and masculinising effects of the auditory system and craniofacial growth. In contrast, there is no evidence to suggest that there might be a similar feminising effect on males from unlike‐gender pairs. This hormonal exposure in utero may influence adult body size and susceptability to breast cancer.
Transplantation tolerance in pediatric recipients: Lessons and challenges
Authors: Tinckam Kathryn J. , Sayegh Mohamed H.
Published: January 2005

Abstract:  Clinical transplantation tolerance has remained an elusive goal in the 50 yr since it was first described in experimental animals. Greater understanding of the molecular mechanisms responsible for allorecognition have allowed for the development of promising immunosuppressive strategies that may bring us closer to reproducible induction of tolerance; consideration of past successes and failures from both clinical and basic science is required to define future challenges facing this field. This article reviews mechanisms of self and transplantation tolerance, translation of basic science research to clinical protocols in animals and human beings, the changing role of immunosuppression, complications following tolerance induction and controversies surrounding the choice of patients for tolerance trials with a focus on issues relevant to pediatric patients. The role of the Immune Tolerance Network is discussed along with realistic goals for tolerance induction in human beings over the next decade.
Development of hepatopulmonary syndrome and portopulmonary hypertension in a paediatric liver transplant patient
Authors: Shah Tahir , Isaac John , Adams David , Kelly Deirdre ,   the Liver Units
Published: January 2005

Abstract:  Background:  Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPH) are pulmonary vascular disorders which occur in patients with severe liver disease and/or portal hypertension. Although these syndromes are frequently diagnosed in patients undergoing assessment for liver transplantation, they seldom occur in the same patient.

Method:  This report describes a female paediatric patient, born with extra‐hepatic biliary atresia, who required liver transplantation, at the age of 15, for secondary biliary cirrhosis. She had severe HPS prior to her first liver transplant, which resolved rapidly following surgery, as well as indirect evidence for PPH. She required a second liver transplant 1 yr later for chronic rejection. Whilst evaluating the patient for a third liver transplant, 4 yr later, severe PPH was discovered. The patient died 3 months later from right heart failure.

Conclusion:  HPS and PPH may coexist however they may show differing responses to liver transplantation with progression of PPH despite the resolution of HPS.
Extended family studies for the identification of allogeneic stem cell transplant donors in Jewish and Arabic patients in Israel
Authors: Klein T. , Yaniv I. , Stein J. , Narinsky R. , Finkelstein Y. , Garty B. Z.
Published: January 2005

Abstract:  HLA‐identified donors are the best source of allogeneic hematopoietic stem cell transplants, and are available in approximately 40% of cases. If no HLA‐identical core family member is found, an extended family search may be performed. The aim of the study was to summarize the 10‐year (1990–1999) experience of our tertiary care center with extended family donor search. During this period, 356 patients and 2659 of their family members were tissue‐typed; 239 patients were Jewish (67%) and 117 were Arabic (33%). An HLA‐identical core‐family donor was identified for 168 patients (47%): 95 Jewish (40%) and 73 Arabic (62%) (p < 0.0001); 49 patients (14%) had more than one potential donor. An extended family search (grandmother/grandfather, aunts, uncles, etc.) was performed in 38 of the remaining families, which were found to be consanguineous: five Jewish and 33 Arabic. One HLA match was found in the Jewish families (20%) and 21 in the Arabic families (64%). The odds ratio for an Arabic patient to find a donor in the extended family search was 8.75, as opposed to a Jewish patient. Overall, HLA‐matched donors were found by core and extended family search for 53% of the patients. The rate for Arabic patients was 80% and for Jewish patients, 40% (p < 0.001). This difference may be explained by the greater number of siblings and higher rate of consanguinity in the Arabic population. In conclusion, an extended family search for potential HLA‐matched donors is worthwhile, especially in distinct ethnic populations with high consanguinity, such as Israeli Arabs.
Severe neutropenia and thrombocytopenia following cardiac transplantation in a child
Authors: Chitlur Meera , Abella Esteban , Singh Tajinder P. , Savaşan Süreyya
Published: January 2005

Abstract:  Hematological complications have been occasionally described after cardiac transplantation. We are reporting a 5‐yr‐old child who developed sequential severe neutropenia and thrombocytopenia following cardiac transplantation while on tacrolimus‐based immune suppression therapy. There was no improvement in blood counts following a change in immune suppression to cyclosporine A. The neutropenia was associated with a maturation arrest in the bone marrow. The occurrence of thrombocytopenia coincided with rising anti‐herpes virus 6 IgG titers suggesting a possible contributory role. Neutropenia resolved following treatment with rituximab, and the thrombocytopenia responded to Dapsone therapy eventually. This case points out the potential multifactorial pathogenesis of cytopenias following cardiac transplantation with differing response to various immune suppressive therapies.
Immune mechanisms in the pathogenesis of bronchiolitis obliterans syndrome after lung transplantation
Authors: Jaramillo Andrés , Fernández Félix G. , Kuo Elbert Y. , Trulock Elbert P. , Patterson G. A. , Mohanakumar T.
Published: January 2005

Abstract:  Lung transplantation is recognized as the only viable treatment option in a variety of end‐stage pulmonary diseases. However, the long‐term survival after lung transplantation is limited by the development of obliterative bronchiolitis, and its clinical correlate bronchiolitis obliterans syndrome (BOS), which is considered to represent chronic lung allograft rejection. Histopathologically, BOS is an inflammatory process that leads to fibrous scarring of the terminal and respiratory bronchioles and subsequent total occlusion of the airways. The specific etiology and pathogenesis of BOS are not well understood. The current premise is that BOS represents a common lesion in which different inflammatory insults such as ischemia‐reperfusion, rejection, and infection can lead to a similar histological and clinical outcome. However, the low incidence of BOS in non‐transplanted individuals and the observation that early development of BOS is predicted by the frequency and severity of acute rejection episodes indicate that alloimmune‐dependent mechanisms play a crucial role in the pathogenesis of BOS. The evidence presented in this review indicates that BOS is the result of humoral and cellular immune responses developed against major histocompatibility complex molecules expressed by airway epithelial cells of the lung allograft. This process is aggravated by alloimmune‐independent mechanisms such as ischemia‐reperfusion and infection. Currently, treatment of BOS is frequently unsuccessful. Therefore, a better understanding of the immunopathogenesis of BOS is of paramount importance toward improving long‐term patient and graft survival after lung transplantation.
Acute neurological complications after hematopoietic stem cell transplantation in children
Authors: Rubin Johanna , Wide Katarina , Remberger Mats , Gustafsson Britt
Published: January 2005

Abstract:  Children undergoing hematopoietic stem cell transplantation (HSCT) may develop toxicity‐related neurological complications (NC). Known risk factors include total body irradiation (TBI) and the use of busulfan or cyclosporine A, but other risk factors might also be of importance. The medical records of 144 children (0–18 yr) who underwent their first HSCT at Karolinska University Hospital (Huddinge) between 1995 and 2002 were reviewed retrospectively concerning pretransplantation parameters and clinical course during the first 3 months after HSCT. Sibling donors were used in 49 transplantations, unrelated donors in 88 and haploidentical donors in seven cases. Nineteen patients (13%) developed NC within the first 3 months after HSCT. A significant association was seen between pretransplant viral status, defined as a higher number of positive herpes group viral serologies in the recipient before transplantation, and NC (p = 0.04). A significant association was also seen for CMV‐positive recipients and NC (p = 0.01) as well as for disturbances in serum levels of sodium, potassium and calcium and NC. No association was found between sex, age at HSCT, underlying disease, previous neurological symptoms, the conditioning regimen, GVHD, donor type and NC. Number of positive herpes group viral serologies in the recipient before transplantation and certain electrolyte disturbances may contribute to neurological complications after HSCT.
Intra‐individual variation of cystatin C and creatinine in pediatric solid organ transplant recipients
Authors: Podracka Ludmila , Feber Janusz , Lepage Nathalie , Filler Guido
Published: January 2005

Abstract:  There is controversy about the feasibility of cystatin C (CysC) as a marker of glomerular filtration rate (GFR) post‐transplant (Tx). We studied intra‐patient variability of CysC in comparison with serum creatinine (SCr) in 20 children (11 males, mean age 11.5 ± 6.4 yr) with solid organ transplants (14 kidney, four liver, and two combined liver + kidney transplants). The mean age at Tx was 7.0 ± 5.6 yr. A total of 178 simultaneous SCr and CysC measurements (median 8 per patient) were analyzed. In addition, GFR was calculated using the Schwartz and a novel CysC‐based formula. Intra‐individual coefficient of variations (CV) was calculated as ratio of standard deviation over mean. The mean CV was significantly lower for SCr (7.71 ± 4.16%) when compared with CysC (10.27 ± 4.87, p = 0.04), but was no longer significantly different when excluding patients with a bladder augment. The CV of the GFR estimated by Schwartz formula (7.44 ± 3.77) was significantly lower than GFR calculated from CysC (12.52 ± 7.37), p = 0.001. The mean ratio between the Schwartz GFR and the GFR calculated from CysC was 102.6 ± 12.8%, not significantly different from 100% (p = 0.3796). The only potential confounding factors to explain increased CV after Tx were gender and bladder augmentation, whereas calcineurin inhibitors or steroids did not influence CV. With the limitation of a small number of subjects, our data suggest that the CysC and the CysC‐calculated GFR is equivalent but not better than SCr and Schwartz formula. We therefore conclude that measurement of CysC can be used for longitudinal intra‐individual follow‐up of renal function post‐Tx.
Surgical complications in live‐donor pediatric and adolescent renal transplantation: Study of risk factors
Authors: Shokeir Ahmed A. , Osman Yasser , Ali‐El‐Dein Bedeir , El‐Husseini Amr , El‐Mekresh Mohsen , Shehab‐El‐Din Ahmed B.
Published: January 2005

Abstract:  To report the surgical complications among our pediatric and adolescent renal transplants and to analyze the different factors that may influence the occurrence of such complications. Methods: A total of 250 pediatric and adolescent renal transplants were included in this study. Of these patients, there were 154 boys and 96 girls with a mean age of 15.4±3.7 yr (range 5–20 yr). All patients received their kidneys from living donors. Four patients underwent renal retransplantation. Surgical complications were reported and their incidence was correlated with several pretransplant, technical and post‐transplant risk factors by both univariate and multivariate analyses. The impact of surgical complications on graft and patient survival was computed using the Kaplan–Meier technique. Results: Among the 250 patients, 35 surgical complications were encountered in 33 patients. These complications included urinary leakage in 10 patients, ureteric stricture in 11 patients, complicated lymphocele in eight patients, hematoma necessitating surgical exploration in two patients, wound dehiscence in one patient, stone of the graft ureter in one patient and renal artery stenosis in two patients. The incidence of urological complications (ureteral stenosis, urinary leakage and stone disease) was 8.8% and vascular complications 0.8%. Small ureteric leakage (four patients) was treated by endourologic techniques, whereas leaks associated with ureteral necrosis required open revision. Endourologic treatment was attempted in early and mild cases of ureteric obstruction. In late and severe cases, surgery was performed. On univariate analysis, the factors that significantly affected the incidence of surgical complications were recipient's age, lower urinary tract abnormalities, the type of primary urinary recontinuity, the time to diuresis, and height and weight of the patients. On multivariate analysis, the type of primary urinary continuity was the only factor that sustained statistical significance. Neither patient nor graft survival was affected by the occurrence of surgical complications. Conclusion: Primary urinary continuity is the only risk factor that affects the incidence of surgical complications among pediatric and adolescent live donor renal transplants, with the extravesical technique of Lich‐Gregoir providing the best results. Surgical complications in pediatric and adolescent renal transplantation can be minimized if basic principles of careful transplant techniques are used. Prompt identification and treatment of any complication is paramount to graft and patient survival.
Gastrointestinal leukocytoclastic vasculitis: An adverse effect of sirolimus
Authors: Nagarajan Suja , Friedrich Tara , Garcia Manuel , Kambham Neeraja , Sarwal Minnie M.
Published: January 2005

Abstract:  An 18‐yr‐old Hispanic female with end‐stage renal disease secondary to chronic glomerulonephritis of unknown etiology underwent cadaveric renal transplantation. She was placed on a steroid‐free protocol with tacrolimus and mycophenolate mofetil (MMF) for maintenance immunosuppression. Approximately 8 months post‐transplantation, MMF was replaced by sirolimus (SRL) because of persistent leukopenia. Four months after the initiation of SRL, the patient began to experience chronic, constant periumbilical abdominal pain in the absence of vomiting, diarrhea or melena. Esophagogastroduodenoscopy and CT scans revealed significant diffuse mucosal thickening of the antrum, duodenum, and jejunum; leukocytoclastic vasculitis was identified on antral biopsy. A repeat biopsy after reduction of sirolimus dose by 50% over 6 months showed mild chronic inflammation of stomach and duodenum with some improvement in abdominal pain. Discontinuation of SRL and replacement with low dose MMF resulted in complete resolution of pain and normalization of gastrointestinal anatomy by imaging studies within 2 months. In light of this report, drug‐induced leukocytoclastic vasculitis caused by SRL should be considered in the differential diagnosis of chronic abdominal pain in a patient with organ transplantation.
Liver transplantation utilizing pediatric cadaver donor livers
Authors: Tanaka Hideaki , Verran Deborah , Shun Albert , Dorney Stuart , Stormon Michael , Fisher Jodi , McCaughan Geoff
Published: January 2005

Abstract: This is a review of a unit's experience with the use of pediatric (up to 15 yr of age), cadaver donor livers for orthotopic liver transplantation (OLTx). The records of 86 patients who underwent 90 OLTx with pediatric donor allografts from January 1986 to September 2002 were reviewed. A total of 69 of 90 (77%) allografts from pediatric donors were used for pediatric (P) recipients, and 21 of 90 (23%) for adult (A) recipients. Donor demographics were: mean donor age 8.5 (0–15) yr; donor sex 53 males/37 females; cause of death head injury 55/90 (61%), cerebral ischaemia 14 of 90 (15%), cerebrovascular 13 of 90 (15%), other eight of 90 (9%). Whole OLTx were performed in 44 of 69 (64%) P group and 20 of 21 (95%) A group. Reduced‐size OLTx (13 left lateral lobe, 10 left lobe, one right lobe, one split left lateral lobe) were performed in 25 of 69 (36%) P group vs. in one of 21 (5%) A group, (right lobe split) (p < 0.005). The median follow up was 8.8 yr. The graft loss in the P recipients was 19 of 69 (27.5%) vs. eight of 21 (38.1%) in A recipients. Graft loss for reduced size P OLTx was nine of 25 (36%) vs. 10/44 (22.7%) for whole allograft P OLTx (p = NS). Underlying cause of P graft loss were: chronic rejection six (32%); patient mortality six (32%); vascular four (21%); other three (15%). Underlying cause of A graft loss were: patient mortality four (50%), acute rejection two (25%) and vascular two (25%). OLTx‐utilizing pediatric cadaver donor allografts provides acceptable outcomes, including use of reduced‐size grafts in pediatric recipients. Vascular complications and chronic rejection tend to be more common in pediatric recipients, whilst patient mortality and graft loss from acute rejection are more common in adult recipients.
Successful bone marrow transplantation in a patient with c‐mpl‐mutated congenital amegakaryocytic thrombocytopenia from a carrier donor
Authors: Muraoka Kenji , Ishii Eiichi , Ihara Kenji , Imayoshi Miyoko , Miyazaki Sumio , Hara Toshiro , Hamasaki Yuhei
Published: January 2005

Abstract:  Congenital amegakaryocytic thrombocytopenia (CAMT) is characterized by severe thrombocytopenia and the absence of megakaryocytes in bone marrow. Furthermore, mutation of the c‐mpl gene has been identified as a cause of this disorder. The only curative treatment is allogeneic stem cell transplantation (SCT). The current report describes a patient exhibiting c‐mpl mutation in both alleles who underwent transplantation of allogeneic bone marrow donated by her brother, a c‐mpl mutated carrier, employing a fludarabine‐based conditioning regimen. Engraftment and reconstitution of hematopoietic cells was rapid and without complications. These findings suggest that the carrier donor displaying the c‐mpl mutation can serve as a donor source for SCT.
Low toxicity and efficacy of 153samarium‐EDTMP and melphalan as a conditioning regimen for secondary acute myelogenous leukemia
Authors: Rodriguez Vilmarie , Erlandson Linda , Arndt Carola A. S. , Wiseman Gregory A. , Anderson Peter M.
Published: January 2005

Abstract:  We report the case of a 15‐yr‐old girl who developed secondary acute myelogenous leukemia (AML) 4 yr after completion of therapy for metastatic Ewing sarcoma (primary right acetabulum with metastatic disease to the lungs). Peripheral blood stem cells were collected after the second cycle of chemotherapy with the plan for future consolidation with high‐dose chemotherapy and autologous stem cell rescue; however, because of the patient's excellent response to chemotherapy and surgery, therapy was completed without the need for high‐dose chemotherapy. No human leukocyte antigen (HLA)‐matched related donor was available for a bone marrow transplant. Because of previous lung radiation, high‐dose samarium [30 mCi/kg of samarium‐153 ethylenediaminetetramethylenephosphonate (153Sm‐EDTMP) day −14] and melphalan (140 mg/m2 day −2) were chosen as the conditioning regimen to avoid potential lung complications. The patient received an infusion of 6.1 × 108/kg mononuclear autologous cells on day 0. She achieved engraftment on day +23. Three years after transplantation, she continues to have complete remission. Samarium and melphalan constitute a well‐tolerated regimen with potential antileukemic activity.
Pediatric renal transplantation: Single center experience
Authors: Mir Sevgi , Erdoğan Hakan , Serdaroğlu Erkin , Kabasakal Caner , Hoşcoşkun Cüneyt
Published: January 2005

Abstract:  Although renal transplantation (RTx) is actually the first choice of treatment for children with end‐stage renal disease, the number of transplanted children remains low in comparison with adults. The experience of the individual pediatric transplant center is very important in the outcome of pediatric transplant recipients. In this study, our pediatric renal transplantation experience is presented. We retrospectively analyzed the results of 72 pediatric renal transplants performed at Ege University Pediatric Nephrology Transplantation Center between June 1989 and May 2003. They were 40 girls, 32 boys and their mean RTx age was 13.27±3.73 yr (range 3–20 yr). Thirty‐eight (52.8%) of the transplanted kidneys came from a living related donor, and 34 (47.2%) from a cadaveric donor. Preemptive RTx was performed in one patient and a second RTx was performed in one patient after two‐period hemodialysis. Hypertension (31.9%), acute rejection (27.8%) and chronic rejection (13.9%) were the most common complications. Cytomegalovirus (CMV) infection occurred in 15 children (20.8%), none of whom died or lost their graft as a result of the infection. Pretransplant acquired hepatitis C virus (HCV) infection was detected in 12 patients (16.7%). Urinary tract infections (UTIs) were seen in 31 (43.1%) recipients. The 1, 5 and 10 yr graft survival rates were 91, 84 and 77%, respectively, and corresponding patient survival rates were 97, 84 and 77%, respectively by Kaplan–Meier method. The graft and overall survival was not correlated with sex, donor type, treatment modality, acute rejection episodes, hypertension, UTIs, CMV and HCV infection.
Fulminant hepatic failure: Wilson's disease or autoimmune hepatitis? Implications for transplantation
Authors: Santos R. G. , Alissa F. , Reyes J. , Teot L. , Ameen N.
Published: January 2005

Abstract:  Fulminant hepatic failure (FHF) accounts for 10–15% of pediatric liver transplants in the USA annually. Because the onset of FHF may be the first presentation of Wilson's disease (WD) and autoimmune hepatitis (AIH) in previously asymptomatic adolescents, determination of the etiology of FHF is critical as treatment and prognosis differ between these two entities. Patients with AIH may be salvaged by medical treatment. On the contrary, liver transplantation is currently the only life saving therapeutic option available for patients with WD who present with fulminant liver failure. To establish the diagnosis of WD and AIH in the setting of FHF remains challenging for diagnosticians and decisions regarding liver transplantation may be necessary before a diagnosis is firmly established. We report a previously asymptomatic patient who presented with FHF and clinical and laboratory features suggestive of both WD and AIH and who underwent successful therapeutic liver transplantation before the diagnosis of WD could be confirmed.
Extrahepatic bile duct atresia and viral involvement
Authors: Fjær Rannveig Bremer , Bruu Anne‐Lise , Nordbø Svein Arne
Published: January 2005

Abstract:  Several etiological factors have been suggested in the pathogenesis of extrahepatic biliary atresia (EHBA); congenital, metabolic, infectious, and multifactorial. Herein we present a study of 10 children with EHBA, the aim being to explore viral infection as a possible cause of their condition. During a period of 2 yr, all infants with EHBA were included in a study and examined on viral disease on admittance for Kasai operation. In eight of the 10 children and in one parental couple the laboratory results suggested recent or persistent viral infection. Four infections were caused by cytomegalovirus (CMV) and another five by Epstein–Barr virus (EBV). CMV‐DNA was detected in two liver biopsies, EBV‐DNA in one liver biopsy. In a control group of 10 patients matched by age and tested by PCR in serum and viral antibodies, no sign of viral infections were detected. CMV or EBV infection were present in an unexpectedly high proportion of infants with EHBA, justifying exhaustive examination on viral disease in these children.
Sodium ferric gluconate for post‐transplant anemia in pediatric and young adult renal transplant recipients
Authors: Gillespie Robert S. , Symons Jordan M.
Published: January 2005

Abstract:  Post‐transplant anemia is a widespread problem among pediatric renal transplant recipients. Many clinicians treat post‐transplant anemia in a manner similar to treatment of anemia in dialysis patients, including the use of intravenous iron, such as sodium ferric gluconate (SFG). Data on pediatric dosing of SFG are limited to rare small series containing few or no renal transplant recipients. We conducted a retrospective chart review of practice patterns at our institution to evaluate doses used, hemoglobin response and adverse events. We identified 15 renal transplant recipients who received SFG during the 28‐month study period. Data from 14 of these patients were available for analysis. Patients received between one and six doses of SFG to yield a total dose of 100–1000 mg or 2.7–23.7 mg/kg. The largest doses given during a single infusion ranged from 1.9 to 6.4 mg/kg. The mean hemoglobin level increased from 101 ± 16 to 114 ± 21 g/L (p = 0.0092) following SFG therapy. Adverse events were recorded for three patients. Treatment with SFG appears to yield some improvement in anemia in renal transplant recipients, but the paucity of published information on this topic highlights the need for stronger data, particularly with respect to pediatric patients.
Ascites after orthotopic liver transplantation in children
Authors: Herzog Denise , Martin Steven , Lallier Michel , Alvarez Fernando
Published: January 2005

Abstract:  Ascites is a poorly understood postoperative complication of orthotopic liver transplantation (OLT). It is associated with additional morbidity and can prolong hospitalization considerably. The incidence, the factors predictive of occurrence and the etiology of this complication are not known. The charts of 118 patients with 138 OLT were analyzed according to the following criteria: ascites lasting longer than the first 10 postoperative days, assessed by loss of ascitic fluid through drainage tubes, surgical wounds or paracentesis, with a peak volume of ≥10 mL/kg/day. Patients were divided into three groups: Group 1, no ascites; Group 2, ascites associated with postoperative complications, including chylus ascites; and Group 3, ascites not associated with postoperative complications. Postoperative ascites occurred in 43 of 138 OLT (31.2%). Patients with biliary atresia, preoperative portal hypertension, postoperative pleural effusion or at retransplantation had ascites significantly more often. In 32 of 138 (23.2%) OLT, ascites was associated with postoperative complications, including thrombosis, abdominal infections, intestinal perforation, biliary leak, pancreatitis, and chylus ascites. In 11 of 138 (7.9%) OLT, ascites was the only postoperative complication (group 3). Group three patients were significantly older, and had lower preoperative platelet counts and preoperative ascites more often than group 1 patients. The primary liver diseases were mainly cystic fibrosis of the pancreas, congenital hepatic fibrosis, and North American Indian childhood cirrhosis. The serum‐ascites albumin gradient suggested a hepatic origin of ascites. Postoperative ascites is associated with the duration and degree of preoperative portal hypertension. We speculate that the mechanism involved includes a disproportion between venous blood volume and liver uptake capacity of the donor organ.
Reversal of tacrolimus‐related hypertrophic obstructive cardiomyopathy 5 years after kidney transplant in a 6‐year‐old recipient
Authors: Jarzembowski Tomasz M. , John Eunice , Panaro Fabrizio , Manzelli Antonio , Cabrera Antonio , Greco Andreas , Varga Peter , Sankary Howard , Testa Giuliano , Benedetti Enrico
Published: January 2005

Abstract:  Hypertrophic obstructive cardiomyopathy (HOCM) is an unusual but serious side‐effect of tacrolimus (TAC) based immunosuppression primarily affecting pediatric patients after solid organ transplant. TAC‐induced HOCM has already been described in patients after liver, bowel and heart transplant shortly after the procedure. Herein, we present the first case report of TAC‐induced HOCM in a young renal transplant recipient 5 yr after renal transplant. The condition was diagnosed by ECHO and EKG and successfully treated by discontinuation of TAC followed by conversion to cyclosporine (CsA).