Christina Giannakopoulou

Urine Interleukin-8 as a Marker of Vesicoureteral Reflux in Infants

OBJECTIVE. Vesicoureteral reflux (VUR) is a common finding in children presenting with urinary tract infection (UTI) and prenatally diagnosed urinary tract dilatation and in relatives of index patients. Children with VUR are at risk for ongoing renal damage with subsequent infections. Detecting VUR and renal scarring currently depends on imaging modalities with associated problems of radiation, invasiveness, and expense. Noninvasive methods would greatly facilitate diagnosis and would also help in identifying relatives of index cases who should be screened. Interleukin-8 (IL-8) is produced by epithelial cells of the renal tract in response to inflammatory stimuli and has been shown to increase during acute UTI. The objective of this study was to assess the urine levels of IL-8 as a noninvasive marker of VUR in infants in the absence of a recent UTI episode. METHODS. We evaluated urine concentrations of IL-8 in 59 infants aged 1 month to 2 years. All infants were free of UTI for a minimum of 3 weeks before IL-8 evaluation. Infants were divided into 3 groups: group A, subjects with proven VUR (24 infants aged 0.15–1.95 years, median 0.43); group B, subjects with a history of UTI but negative investigation for VUR (14 infants aged 0.32–1.95 years, median 0.57); and group C, subjects without any history of acute or chronic condition that might impair renal function (21 infants aged 0.08–1.92 years, median 0.33). IL-8 concentrations were determined by a commercially available quantitative enzyme-linked immunosorbent assay. To avoid dilution effects, urinary levels of IL-8 were expressed as the ratio of cytokine-to-urinary creatinine. RESULTS. Results were presented as medians and ranges. The Kruskal-Wallis test, the Mann-Whitney rank sum U test, and the Spearman rank order correlation test were performed for the univariate analysis. Two-tailed P values were calculated and the conventional level of significance P < .05 was applied in all cases. Infants in groups A and B had been free of UTI for a period of 3 to 52 weeks (median, 5.0 weeks) and 3 to 78 weeks (median, 4.5 weeks), respectively, before IL-8 determination. No significant difference was noted in the length of the UTI-free period between groups A and B (P = .469). Urine creatinine concentrations did not differ among groups A, B, and C (medians 1.15, 2.25, and 1.15 μmol/mL, respectively; P = .080). The median urine IL-8/creatinine concentrations (pg/μmol) were 40.5 (range, 2.04–3874) in group A, 1.91 (range, 0.001–386) in group B, and 2.47 (range, 0.002–55.6) in group C. Urine IL-8/creatinine concentrations were significantly higher in group A than both in group B (P = .0003) and in group C (P < .0001). No significant difference was observed between groups B and C (P = .749). In group A, no significant correlation was shown between IL-8/creatinine concentrations and the presence of renal parenchymal damage (P = .506), reflux grade (P = .770), or time from UTI (P = .155). A receiver-operator characteristic curve was constructed by plotting the sensitivity versus the specificity for different cutoff concentrations of IL-8/creatinine. With a cutoff concentration of urinary IL-8/creatinine at 5 pg/μmol, the sensitivity of this marker in diagnosing VUR was 88%, the specificity 69%, the positive prognostic value 66%, and the negative prognostic value 89%. In higher cutoff concentrations, specificity of the marker increased but sensitivity rapidly decreased. CONCLUSIONS. We present evidence that urine IL-8 concentrations remain elevated in infants with VUR even in the absence of UTI and that a cutoff of 5 pg/μmol IL-8/creatinine is of high sensitivity and adequate specificity for diagnosing VUR. Elevated urine IL-8 levels in VUR and renal scarring have already been reported; however, the present study is, to our knowledge, the first to confirm significant differences between infants with VUR and infants with a history of UTI alone and healthy controls, and to suggest a reliable cutoff concentration for diagnosing VUR. Our findings additionally suggest that inflammatory process in VUR is ongoing even after UTI has resolved, pointing against the currently held belief that sterile reflux cannot harm kidneys. The chronic inflammatory cell infiltrate associated with reflux nephropathy rather than VUR itself might offer an explanation for the secretion of IL-8, which may well be independent of reflux grade. Using urine IL-8 for diagnosing VUR is not free of limitations, because IL-8 may be elevated as a result of urinary tract manipulation or undetected UTI. In addition, this study focused on infants and not in older children with longstanding VUR. Increased urine IL-8 concentrations after UTI has resolved is a promising noninvasive marker for an initial screening for VUR in infancy with high sensitivity and adequate specificity.

Significance of hypocarbia in the development of periventricular leukomalacia in preterm infants

Abstract Background : Despite rapid advances in the management of preterm infants, periventricular leukomalacia (PVL) remains a considerable problem in neonatal intensive care. The aim of this study was to determine whether hypocarbia is associated with the development of PVL in mechanically ventilated, preterm infants and to emphasize the importance of avoiding this disturbance.

Risk factors for periventricular leukomalacia

Objective. To identify risk factors implicated in the development of periventricular leukomalacia (PVL) and to evaluate the possible association between PVL with neonatal morbidity. Design. Retrospective case control study. Setting. Medical records of neonates admitted to a University Hospital between January 2000 and December 2005. Population. Sixty‐nine neonates with PVL born at gestational ages from 24 to 34 weeks. Forty‐three of these had a cystic form of PVL (cPVL), whereas 26 had transient periventricular echodensities (PVE). Methods. Each case was matched for gestational age and year of birth with one control. The maternal and neonatal medical records were searched. All data was compared between cases with PVL and controls, as well as between cases with cPVL and those with PVE. Stepwise logistic regression analysis was conducted to identify the independent predictors of PVL. Results. Neonates with PVL suffered more frequently from intraventricular hemorrhage (IVH), respiratory distress syndrome type I (RDS I), seizures, sepsis, required more days of both mechanical ventilation and oxygen administration, while the duration of their hospitalization was longer compared to controls. Also, they were born more frequently to mothers who suffered from preterm premature rupture of membranes (PPROM) and clinical chorioamnionitis. We found that male gender, PPROM, preeclampsia, hypocarbia and IVH were independently associated with PVL. Conclusions. This study revealed that preterm neonates born to mothers with PPROM or preeclampsia, as well as neonates who presented with hypocarbia or suffered from IVH, appeared to be at high risk for the development of PVL.

Interleukin-6 in preterm premature rupture of membranes as an indicator of neonatal outcome

Background.  The aim of this study was to investigate whether the levels of interleukin‐6 (IL‐6) can be used as markers of adverse outcome in preterm neonates born after preterm premature rupture of membranes (PPROM).

Infantile myofibromatosis with visceral involvement and complete spontaneous regression.

Infantile myofibromatosis is an unusual mesenchymal disorder characterized by the proliferation of tumors in the skin, muscle, bone, and viscera. Two types can be distinguished; the solitary type, defined by the presence of one nodule in the skin, muscle, bone or subcutaneous tissue; and the multicentric type which can be divided into two sub‐types. In the first sub‐type the lesions are multicentric but without visceral involvement, while in the second, visceral involvement is present. The prognosis of the disease depends on whether visceral involvement is present. Solitary and multicentric nodules without visceral involvement usually have excellent prognosis with spontaneous regression of lesions within 1 to 2 years of diagnosis. On the other hand, visceral lesions are associated with a significant morbidity and mortality, resulting from vital organ obstruction, failure to thrive, or infection. Death in these cases often occurs at birth, or soon after, and is usually due to cardio‐pulmonary or gastrointestinal complications. The case being reported here, is that of a female newborn who had multiple skin, subcutaneous tissue, skeletal muscle, bone, and lung lesions immediately after bith. At the age of three years, the child is in good health, her psychomotor development is in accordance with her age group, and the lesions have completely regressed. This is a case of the multicentic type of infantile myofibromatosis with visceral involvement, where all lesions have spontaneously regressed. This is a rarity since the prognosis in the majority of such cases is poor.

Multimodal cancer chemotherapy during the first and second trimester of pregnancy: a case report.

This paper reports treatment with combined chemotherapy during pregnancy. A 39-year-old woman with breast cancer was given adjuvant chemotherapy including cyclophosphamide, methotrexate and 6-fluorouracil from the 6th to the 24th week of gestation. The possibility of teratogenic effects on the fetus was explained to the patient however she refused to terminate the pregnancy. A 30-week male infant with only a minor malformation was delivered. The authors reviewed the literature regarding chemotherapeutic agents given during the first trimester of pregnancy. Most cytotoxic drugs have teratogenic effects on experimental animal subjects. However, actual data on human fetuses are sparse because of the variety of therapeutic regimens and the rarity of administering chemotherapy during pregnancy. The long-term effects of exposure to cytotoxic drugs in utero, needs further research.

Levels of bone collagen markers in preterm infants: relation to antenatal glucocorticoid treatment

Although the beneficial effects of antenatally administered glucocorticoids are well documented, data on the potential of adverse consequences are limited. The objective of this study was to determine the effects of antenatally administered glucocorticoids on biochemical markers of bone metabolism of 55 preterm infants with a gestational age of 24–34 weeks who were enrolled in the study. Neonates were divided into two groups according to antenatal exposure to corticosteroids. There were no significant differences between the groups in clinical characteristics and anthropometric variables. We studied blood levels of osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (PICP), and carboxy-terminal telopeptide of type I collagen (ICTP) at the time of delivery, on postnatal day 10, and at 2 and 4 months of life. Comparing the groups, we found statistically significant reduction in PICP levels at birth in corticosteroid-exposed neonates (P < 0.05). The levels of bone markers increased progressively on the first days of life. There were no significant differences between groups in bone markers at 10 days or at 2 and 4 months of life. We found no significant difference for bone markers between groups of infants exposed to single or repeated maternal corticosteroid treatments. In summary, antenatal glucocorticoid treatments are suggested to have a negative impact on fetal bone formation as reflected by low PICP levels at birth. However, this negative effect on bone markers seems to be a temporary effect that subsides on the first days of life and afterward.

Outcome of Toxoplasmosis Acquired during Pregnancy following Treatment in Both Pregnancy and Early Infancy

Objectives: Congenital toxoplasmosis is associated with clinical dilemmas as untreated infants may have a guarded prognosis and as treatment may induce severe side effects. The aim of this study was to investigate the outcome of infants born to mothers with toxoplasmosis acquired during pregnancy, following administration of appropriate regimens both during pregnancy and early infancy. Study Design: All 35 infants, born to mothers with toxoplasmosis acquired during pregnancy, and referred to the major Neonatal Department in Crete, Greece, during the 7-year period 1997–2003 were included. All neonates were evaluated soon after birth and on a regular follow-up. Results: Almost all mothers received spiramycin from diagnosis through labor and 2 received pyrimethamine and sulfadiazine. At birth, infants had IgG antibody titers ranging from 1/1,350 to 1/109,350. All infants initially received pyrimethamine, sulfadiazine and folinic acid but in only 4 cases treatment was continued beyond the second month of life. Transient neutropenia was commonly observed. A follow-up period of 1.2–8.2 years did not reveal any remarkable sequelae. Conclusions: Our findings suggest that effective treatment both during pregnancy and early infancy is safe and may contribute to a good outcome of infants born to mothers with toxoplasmosis acquired during pregnancy.

Intravenous immunoglobulin treatment in a girl with juvenile dermatomyositis

of muscles and skin. Various treatments have been used to date in children, including steroids, immunosuppressive drugs and, more recently, plasmapheresis and total body irradiation. However, all treatments have serious adverse effects.1,2 The use of intravenous immunoglobulin has been limited to refractory cases of juvenile dermatomyositis.1,3 We report the rapid improvement and long-lasting remission of a girl with dermatomyositis treated from the beginning with intravenous immunoglobulin alone and thus avoiding longterm steroid therapy and the use of immunosuppressive agents and their severe adverse effects.

Infantile myofibromatosis: a case study and review of literature.

Infantile myofibromatosis is an unusual condition generally presenting in the newborn period. The case being reported is that of a female newborn who had multiple lesions that involved skin, subcutaneous tissue, skeletal muscles, bone, and lungs. The disease was diagnosed because of the easily palpable skin tumors and subcutaneous nodules that were obvious immediately after birth. The diagnosis was established by histopathological examination of one nodule that showed a spindle‐celled mesenchymatogenic lesion demonstrating the morphological and immuno‐phenotype characteristics of myofibroblastic differentiation. The histologic picture, combined with the clinical manifestations and the imaging findings, are consistent with infantile myofibromatosis. The physical condition of the newborn was excellent and remains so six months later. The tumors of the skin and the subcutaneous nodules have gradually regressed without therapy. At the age of six months, four (4) nodules are palpable; the infant is under continuous observation.