Biomedical subjects

Franco Zacchello

Publications and source records attributed to Franco Zacchello.

At least 19 recordsLinked to original sources

PubMed2006

Method for the quantification of underivatized amino acids on dry blood spots from newborn screening by HPLC-ESI-MS/MS.

In our study we have developed an HPLC-ESI-MS/MS method for qualitative and quantitative analysis of underivatized amino acids on dry blood spots. The sensitive and specific instrumental performances permitted the chromatographic separation of 40 amino acids and their isomers within 10 min. The method has been set up for cases of suspected metabolic diseases revealed by newborn screening. What is new is that it is applied on the same blood spots used for newborn screening, instead of plasma, in order to avoid involvement of doctors, increased anxiety for parents, stress for patients for plasma collection, long time of waiting and further costs for analysis.

Amino Acids↗

PubMed2005

Gender-sensitive association of CFTR gene mutations and 5T allele emerging from a large survey on infertility.

Human infertility in relation to mutations affecting the cystic fibrosis transmembrane regulator (CFTR) gene has been investigated by different authors. The role of additional variants, such as the possible forms of the thymidine allele (5T, 7T and 9T) of the acceptor splice site of intron 8, has in some instances been considered. However, a large-scale analysis of the CFTR gene and number of thymidine residues, alone and in combination, in the two sexes had not yet been addressed. This was the aim of this study. Two groups were compared, a control group of 20,532 subjects being screened for perspective reproduction, and the patient group represented by 1854 idiopathically infertile cases. Analyses involved PCR-based CFTR mutations assessment, reverse dot-blot IVS8-T polymorphism analyses, denaturing gradient gel electrophoresis (DGGE) and DNA sequencing. The expected 5T increase in infertile men was predominantly owing to the 5/9 genotypic class. The intrinsic rate of 5T fluctuated only slightly among groups, but some gender-related differences arose when comparing their association. Infertile men showed a significantly enriched 5T + CFTR mutation co-presence, distributed in the 5/9 and 5/7 classes. In contrast, females, from both the control and the infertile groups, showed a trend towards a pronounced reduction of such association. The statistical significance of the difference between expected and observed double occurrence of 5T + CFTR traits in women suggests, in line with other reports in the literature, a possible survival-hampering effect. Moreover, regardless of the 5T status, CFTR mutations appear not to be involved in female infertility. These results underline the importance of (i) assessing large sample populations and (ii) considering separately the two genders, whose genotypically opposite correlations with these phenomena may otherwise tend to mask each other.

Alleles↗

PubMed2005

Cystic fibrosis carriers have higher neonatal immunoreactive trypsinogen values than non-carriers.

Following cystic fibrosis (CF) neonatal screening implementation, a high frequency of heterozygotes has been reported among neonates with elevated immunoreactive trypsinogen (IRT) and normal sweat chloride levels. We studied the relationship between normal IRT values and CF heterozygosity: 10,000 neonates were screened for CF by IRT measurement and tested for 40 CF mutations; the 294 carriers detected were coupled with newborns negative to the same genetic testing, and the two groups' IRT levels compared. Heterozygotes had higher IRT levels than their controls (mean 35.32 vs. 27.58 microg/L, P<0.001). Even within normal trypsinogen range, the probability of being a CF carrier increases with neonatal IRT concentration.

Cystic Fibrosis↗

PubMed2005

CXCR3/CXCL10 expression in the synovium of children with juvenile idiopathic arthritis.

The accumulation of T cells in the synovial membrane is the crucial step in the pathophysiology of the inflammatory processes characterizing juvenile idiopathic arthritis (JIA). In this study, we evaluated the expression and the pathogenetic role in oligoarticular JIA of a CXC chemokine involved in the directional migration of activated T cells, i.e. IFNgamma-inducible protein 10 (CXCL10) and its receptor, CXCR3. Immunochemistry with an antihuman CXCL10 showed that synovial macrophages, epithelial cells, and endothelial cells bear the chemokine. By flow cytometry and immunochemistry, it has been shown that CXCR3 is expressed at high density by virtually all T lymphocytes isolated from synovial fluid (SF) and infiltrating the synovial membrane. Particularly strongly stained CXCR3+ T cells can be observed close to the luminal space and in the perivascular area. Furthermore, densitometric analysis has revealed that the mRNA levels for CXCR3 are significantly higher in JIA patients than in controls. T cells purified from SF exhibit a definite migratory capability in response to CXCL10. Furthermore, SF exerts significant chemotactic activity on the CXCR3+ T-cell line, and this activity is inhibited by the addition of an anti-CXCL10 neutralizing antibody. Taken together, these data suggest that CXCR3/CXCL10 interactions are involved in the pathophysiology of JIA-associated inflammatory processes, regulating both the activation of T cells and their recruitment into the inflamed synovium.

Adolescent↗

PubMed2005

Reduction of GAG storage in MPS II mouse model following implantation of encapsulated recombinant myoblasts.

BACKGROUND: Hunter syndrome, mucopolysaccharidosis type II (MPS II), is a X-linked inherited disorder caused by the deficiency of the enzyme iduronate-2-sulfatase (IDS), involved in the lysosomal catabolism of the glycosaminoglycans (GAG) dermatan and heparan sulfate. Such a deficiency leads to the intracellular accumulation of undegraded GAG and eventually to a progressive severe clinical pattern. Many attempts have been made in the last two to three decades to identify possible therapeutic strategies for the disorder, including gene therapy and somatic cell therapy. METHODS: In this study we evaluated the intraperitoneal implantation of allogeneic myoblasts over-expressing IDS, enclosed in alginate microcapsules, in the MPS II mouse model. Animals were monitored for 8 weeks post-implantation, during which plasma and tissue IDS levels, as well as tissue and urinary GAG contents, were measured. RESULTS AND CONCLUSIONS: Induced enzyme activity occurred both in the plasma and in the different tissues analyzed. A significant decrease in urinary undegraded GAG between the fourth and the sixth week of treatment was observed. Moreover, a biochemical reduction of GAG deposits was measured 8 weeks after treatment in the liver and kidney, on average 30 and 38%, respectively, while in the spleen GAG levels were almost normalized. Finally, the therapeutic effect was confirmed by histolochemical examination of the same tissues. Such effects were obtained following implantation of about 1.5 x 10(6) recombinant cells/animal. Taken together, these results represent a clear evidence of the therapeutic efficacy of this strategy in the MPS II mouse model, and encourage further evaluation of this approach for potential treatment of human beings.

Animals↗

PubMed2005

Exhaled breath condensate cysteinyl leukotrienes are increased in children with exercise-induced bronchoconstriction.

BACKGROUND: It is recognized that airway inflammation has a central role in the pathogenesis of asthma, but how it relates to exercise-induced bronchoconstriction (EIB) is not completely understood. OBJECTIVE: The aim of our study was to investigate the relationship between EIB and baseline concentrations of cysteinyl leukotrienes (Cys-LTs) and other inflammatory markers in exhaled breath condensate (EBC). METHODS: EBC was collected, and the fraction of exhaled nitric oxide (FE NO ) was measured in a group of 19 asthmatic children, after which they performed a treadmill exercise test. Fourteen healthy children were enrolled as control subjects. RESULTS: The asthmatic children were divided into the EIB group (decrease in FEV 1 , > or =12%) and the non-EIB group. The EBC was analyzed for the presence of Cys-LTs, leukotriene B 4 , and ammonia. Asthmatic patients with EIB (mean FEV 1 decrease, 23% +/- 3%) had higher Cys-LT concentrations than either asthmatic patients without EIB or control subjects (42.2 pg/mL [median] vs 11.7 pg/mL and 5.8 pg/mL; P < .05 and P < .001, respectively). Ammonia concentrations were lower in both the EIB and non-EIB groups than in control subjects (253.2 microM and 334.6 microM vs 798.4 microM; P < .01 and P < .05, respectively). No difference in EBC leukotriene B 4 levels was found among the 3 groups. Both asthmatic groups had higher FE NO levels than control subjects ( P < .001). EBC Cys-LT ( P < .01; r = 0.7) and FE NO ( P < .05; r = 0.5) values both correlated significantly with the postexercise FEV 1 decrease. CONCLUSION: this study shows that EBC Cys-LT values are higher in asthmatic children with EIB and correlate with the decrease in FEV 1 after exercise. These findings suggest that the pathways of both Cys-LT and nitric oxide are involved in the pathogenesis of EIB.

Acetates↗

PubMed2005

Neurologic outcome in children after extracorporeal membrane oxygenation: prognostic value of diagnostic tests.

This report presents the long-term (36 months) neurologic outcome in 12 neonates and 9 children who survived after extracorporeal membrane oxygenation and attempts to identify its prognostic indicators through a prospective study in the pediatric intensive care unit of a university hospital. Outcome assessment, neurodevelopmental tests, electroencephalogram, auditory evoked potentials, visual evoked potentials, and somatosensory evoked potentials, cerebral sonography, or cerebral tomography were evaluated at the end of bypass and at 6, 12, 24, and 36 months after extracorporeal membrane oxygenation. "Before extracorporeal membrane oxygenation" variables (oxygenation index, pH, oxygen arterial partial pressure) and "during extracorporeal membrane oxygenation" variables (pH, oxygen arterial partial pressure, duration of bypass, clotting activated time, electroencephalogram) were also analyzed. A negative neurologic outcome (Glasgow Outcome Score different from "good recovery" or neurodevelopmental score less than 70) 12 months after extracorporeal membrane oxygenation was documented in 8.3% of neonates and in 30% of children who survived. There was no further change in subsequent evaluations (24 and 36 months follow-up). The most abnormal electroencephalogram during extracorporeal membrane oxygenation, the first electroencephalogram, neuroimaging score, and somatosensory evoked potentials after extracorporeal membrane oxygenation treatment were associated with negative neurologic outcome. The study documented that neonates and children treated with extracorporeal membrane oxygenation require long-term follow-up; electroencephalogram, neuroimaging score, and somatosensory evoked potentials have prognostic value for abnormal neurologic outcome.

Adolescent↗

PubMed2005

Knowledge gained by pediatric residents after neonatal resuscitation program courses.

BACKGROUND: The efficacy of the Neonatal Resuscitation Program (NRP) courses was previously evaluated, demonstrating good retention of knowledge in the participants. However, there is a lack of information regarding the participants' performance in relation to the different steps of neonatal resuscitation. We aimed to assess the knowledge gained and retained by pediatric residents who participated in a NRP course in relation to the different steps. METHODS: An 80-item questionnaire derived from the standard test contained in the American Heart Association and American Academy of Pediatrics Neonatal Resuscitation Manual was given to 25 pediatric residents before, immediately after and 6 months after the course. RESULTS: The percentages of correct answers significantly improved from before (37.6 +/- 3.1%) to immediately after the course (94.1 +/- 0.9%) (P < 0.001). The percentages at the 6 months follow-up test (62.7 +/- 2.2%) significantly decreased from posttest (P < 0.001), but remained significantly higher with respect to pretest performance (P < 0.001). The percentages of correct answers were different among the four neonatal resuscitation steps during the entire study (pretest, posttest and follow-up test). CONCLUSIONS: The knowledge gained by pediatric residents participating in the NRP course was very high, but was only partially retained over time. In particular, it was different among the four steps of neonatal resuscitation suggesting further studies on teaching resuscitation.

Child↗

PubMed2005

Office spirometry in primary care pediatrics: a pilot study.

OBJECTIVE: The aim of this study was to investigate the validity of office spirometry in primary care pediatric practices. METHODS: Ten primary care pediatricians undertook a spirometry training program that was led by 2 pediatric pulmonologists from the Pediatric Department of the University of Padova. After the pediatricians' training, children with asthma or persistent cough underwent a spirometric test in the pediatrician's office and at a pulmonary function (PF) laboratory, in the same day in random order. Both spirometric tests were performed with a portable turbine flow sensor spirometer. We assessed the quality of the spirometric tests and compared a range of PF parameters obtained in the pediatricians' offices and in the PF laboratory according to the Bland and Altman method. RESULTS: A total of 109 children (mean age: 10.4 years; range: 6-15) were included in the study. Eighty-five (78%) of the spirometric tests that were performed in the pediatricians' offices met all of the acceptability and reproducibility criteria. The 24 unacceptable test results were attributable largely to a slow start and failure to satisfy end-of-test criteria. Only the 85 acceptable spirometric tests were considered for analysis. The agreement between the spirometric tests that were performed in the pediatrician's office and in the PF laboratory was good for the key parameters (forced vital capacity, forced expiratory volume in 1 second, and forced expiratory flow between 25% and 75%). The repeatability coefficient was 0.26 L for forced expiratory volume in 1 second (83 of 85 values fall within this range), 0.30 L for forced vital capacity (81 values fall within this range), and 0.58 L/s for forced expiratory flow between 25% and 75% (82 values fall within this range). In 79% of cases, the primary care pediatricians interpreted the spirometric tests correctly. CONCLUSIONS: It seems justifiable to perform spirometry in pediatric primary care, but an integrated approach involving both the primary care pediatrician and certified pediatric respiratory medicine centers is recommended because effective training and quality assurance are vital prerequisites for successful spirometry.

Adolescent↗

PubMed2004

Low exhaled nitric oxide in school-age children with bronchopulmonary dysplasia and airflow limitation.

Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, may be associated with long-term airflow limitation. Survivors of BPD may develop asthma-like symptoms in childhood, with a variable response to beta(2)-agonists. However, the pathologic pathways underlying these respiratory manifestations are still unknown. The aim of this study was to measure exhaled nitric oxide (FE(NO)) and lung function in a group of 31 school-age survivors of BPD. They showed variable degrees of airflow obstruction (mean FEV(1) 77.8 +/- 2.3% predicted) unresponsive to beta(2)-agonists in 72% of the subjects. Their FE(NO) values (geometric mean [95% confidence interval]: 7.7 [+/- 1.1] ppb) were significantly lower than in a group of healthy matched control subjects born at term (10.7 [+/- 1.1] ppb, p < 0.05) and a group of preterm children without BPD (9.9 [+/- 1.1] ppb, p < 0.05). The children with BPD were also compared with a group of 31 patients with asthma with a comparable airflow limitation (FEV(1) 80.2 +/- 2.1% predicted) and showed FE(NO) values four times lower than in those with asthma (24.9 [+/- 1.2] ppb, p < 0.001). In conclusion, unlike children with asthma, school-age survivors of BPD have airflow limitation associated with low FE(NO) values and lack of reversibility to beta(2)-agonists, probably as a result of mechanisms related to early life structural changes in the airways.

Adrenergic beta-Agonists↗

PubMed2004

Leukotrienes and 8-isoprostane in exhaled breath condensate of children with stable and unstable asthma.

BACKGROUND: Cysteinyl-leukotrienes (cys-LTs) and 8-isoprostane are biomarkers of airway inflammation and oxidative stress. OBJECTIVE: The aim of this study was to evaluate cys-LT and 8-isoprostane levels in exhaled breath condensate (EBC) of children with different degrees of asthma severity. METHODS: EBC was collected from 14 steroid-naive children with mild persistent asthma, 13 children with stable mild- to-moderate persistent asthma treated with inhaled corticosteroids (ICS), 9 ICS-treated children with unstable asthma, and 19 healthy children. RESULTS: In the three groups of asthmatic children, EBC concentrations of cys-LTs and 8-isoprostane were significantly higher than in control children (steroid-naive asthmatic children: cys-LTs median, 10.8 pg/mL, P <.001, 8-isoprostane, 16.2 pg/mL, P <.001; ICS-treated stable asthmatic children: cys-LTs, 12.7 pg/mL, P <.001, 8-isoprostane, 18.1 pg/mL, P <.001; children with unstable asthma: cys-LTs, 106.0 pg/mL, P <.01, 8-isoprostane, 29.7 pg/mL, P <.01; control children: cys-LTs, 4.3 pg/mL, 8-isoprostane, 3.5 pg/mL). Cys-LT levels were higher in children with unstable asthma than in the other two asthmatic groups (P <.05). FE(NO) levels were significantly higher in steroid-naive and in children with unstable asthma compared with ICS-treated children with stable asthma (P <.01). CONCLUSIONS: Our study shows that EBC cys-LTs and 8-isoprostane concentrations are higher in asthmatic children than in healthy control children, with scattered values in patients with unstable asthma. These findings suggest that EBC eicosanoid measurement may have useful clinical implications for investigating phenotype differences among asthmatic patients.

Adolescent↗

PubMed2003

Flow limitation in infants with bronchopulmonary dysplasia and respiratory function at school age.

Bronchopulmonary dysplasia is associated with abnormalities in lung function during infancy, yet many infants recover with no respiratory problems in the long term. We therefore did a longitudinal study of pulmonary function in 18 children with moderate to severe bronchopulmonary dysplasia. Forced expiratory volume in 1 s (FEV1) and forced mid-expiratory flow (FEF25-75) at school age were lower than normal in 15 of 18 children, and both showed a significant positive correlation with the maximal flow at functional residual capacity (Vmax(FRC)) at 24 months of age (r=0.68 and 0.85, respectively). Our results suggest that assessment of respiratory function during infancy can help to identify children with bronchopulmonary dysplasia at risk of incomplete recovery of respiratory function during childhood.

Bronchopulmonary Dysplasia↗

PubMed2003

Acute surgical abdomen as presenting manifestation of Kawasaki disease.

Ten children (4.6%) among a cohort of 219 with Kawasaki disease (KD) had their onset with severe abdominal complaints. Incomplete KD presentation at the time of acute abdomen was present in nine of 10 patients. Acute abdominal pain and distension, vomiting, hepatomegaly, and jaundice were the most common symptoms at onset. Hematemesis was present in one; toxic shock syndrome requiring care in the intensive care unit occurred in four. Five patients had laparotomy, three had percutaneous transhepatic biliary drainage, and one had a gastrointestinal endoscopy. Postoperative diagnosis was gallbladder hydrops with cholestasis in five, paralytic ileus in three, appendicular vasculitis in one, and hemorrhagic duodenitis in one. All patients completely recovered, but 50% developed coronary aneurysms despite early intravenous gammaglobulin treatment. Acute surgical abdomen can be the presenting manifestation of KD. In older children with fever, rash, and acute abdominal pain or hematemesis, KD should be considered in the differential diagnosis.

Abdomen, Acute↗

PubMed2002

Systolic and diastolic performance late after the Fontan procedure for a single ventricle and comparison of those undergoing operation at <12 months of age and at >12 months of age.

To evaluate whether surgical history can influence systolic and diastolic properties of a functional single left ventricle after Fontan operation, we echocardiographically investigated 31 patients (mean age 93.7 months; range 21 to 276); 21 patients were >12 months of age (group A) and 10 were <12 months of age (group B) at the time of the Fontan and/or cavopulmonary procedure. In group A we found persistent abnormalities of left ventricular mass index (95.9 vs 64.1 g/m(2), p <0.05) at long-term follow-up, whereas group B had normal left ventricular mass (61.9 vs 64.1 g/m2, p = NS). In contrast, a diastolic pattern characterized by augmented late diastolic filling was present in both patient groups regardless of age at operation and length of follow-up (E/A in group A 1.3 +/- 0.4, E/A in group B 1.6 +/- 1.5, E/A in controls 1.7 +/- 0.6; A vs B, p = NS; A vs controls, p <0.05). We concluded that patients with a single left ventricle who undergo an unloading procedure performed within the first year of life have complete normalization of left ventricular mass, although a diastolic filling pattern suggestive of augmented compliance persists, regardless of the age at operation.

Adolescent↗

PubMed2002

Exhaled carbon monoxide levels after a course of oral prednisone in children with asthma exacerbation.

BACKGROUND: Fractional exhaled nitric oxide (FE(NO)) and exhaled carbon monoxide (ECO) have been proposed as markers of airway inflammation and oxidative stress. OBJECTIVE: The aim of this study was to assess the effect of oral prednisone treatment on FE(NO) and ECO levels in a group of 30 asthmatic children with asthma exacerbation. METHODS: Thirty asthmatic children with asthma exacerbation were treated with oral prednisone for 5 days (1 mg/kg/day). Before and after prednisone therapy, ECO was measured by means of a chemical analyzer and FE(NO) was measured by means of a chemiluminescence analyzer. ECO and FE(NO) were also measured in a group of healthy nonatopic children. RESULTS: Before therapy, both ECO values and FE(NO) values were higher in asthmatic children (ECO, 3.2 +/- 0.2 ppm; FE(NO) online, 74.9 +/- 6.2 ppb; FE(NO) offline, 20.2 +/- 1.4 ppb) than in healthy controls (ECO, 2.0 +/- 0.2 ppm [P <.01]; FE(NO) online, 10.1 +/- 0.8 [P <.0001]; FE(NO) offline, 5.9 +/- 0.4 ppb [P <.0001]). An overlap in ECO values was found between healthy controls and asthmatic children. After prednisone therapy, there was a significant reduction in FE(NO) values (FE(NO) online, 40.6 +/- 4.6 ppb [P <.0001]; FE(NO) offline, 11.1 +/- 0.8 ppb [P < 0.0001]) and a slight but nonsignificant decrease in ECO values (2.7 +/- 0.2 ppm [P = not significant]) in the asthmatic group. No significant correlation between ECO values and FE(NO) values was found in either the asthmatic children or the controls. CONCLUSIONS: After a course of prednisone therapy, in children with asthma exacerbation there is a significant decrease in FE(NO) but no significant change in ECO levels. This possibly suggests that ECO is less sensitive than FE(NO) to inhibition by corticosteroids.

Administration, Oral↗

PubMed2002

Protein turnover, lipolysis, and endogenous hormonal secretion in critically ill children.

OBJECTIVES: The catabolic state is a major contributor to morbidity and mortality of critical illness and may be related to endocrine changes. We studied whether protein and lipid turnover correlate with insulin and growth and thyroid hormone plasma levels in critically ill infants. DESIGN: Prospective clinical study. SETTING: Pediatric intensive care unit. PATIENTS: Twelve critically ill children and ten age-matched controls. MEASUREMENTS: We measured lipolysis and protein turnover by infusing albumin-bound uniformly 13C palmitic acid and 2H3-leucine for 3 hrs and 2H5-glycerol for 5 hrs to critically ill infants. Simultaneously, we measured serum growth hormones, insulin, C-peptide, thyroid-stimulating hormone, T4, T3, albumin, retinol binding protein (RBP), and prealbumin. Hormone and serum protein levels were also measured in six children when recovered from critical illness. Ten healthy age-matched children served as controls for hormone serum levels comparison. RESULTS: Palmitic acid and glycerol turnover were 5.6 +/- 2.2 micromol/kg/min and 12.2 +/- 7.3 micromol/kg/min, respectively, whereas alpha-ketoisocaproic turnover was 4.9 +/- 2.8 micromol/kg/min. Alpha-ketoisocaproic turnover positively correlated (R = 0.7, p = .03) with duration of pediatric intensive care unit admission and with prealbumin and RBP serum levels (R = 0.9, p = .001). Insulin-like growth factor binding protein (IGFBP)-2 was significantly higher and IGFBP-3 was significantly lower in critically ill children (p = .03 and p = .04 vs. recovery phase, respectively). No other hormonal differences were found. Serum albumin was significantly lower in sick children. We found a significant correlation between prealbumin and RBP and IGFBP-3 (R = 0.6, p = 0.03 and R = 0.6, p = .04, respectively). Alpha-ketoisocaproic turnover positively correlated with IGFBP-1 (R = 0.79, p = .01) and did not correlate with insulin-like growth factor I (R = -0.5, p = .15 [not significant]) No other correlations were found. Lipid turnover measurements did not correlate with any endogenous hormone levels or with duration of critical illness. CONCLUSION: Protein turnover but not lipolysis correlated with a persisting critically ill condition, serum prealbumin, RBP, and plasma IGFBP-1.

C-Peptide↗

PubMed2002

Connexin 26 preverbal hearing impairment: mutation prevalence and heterozygosity in a selected population.

The objective of this investigation was to determine the prevalence of Cx26 mutations in familial and sporadic cases of non-syndromic preverbal hearing impairment (HI). Molecular analysis of the Connexin 26 (Cx26/GJB2) gene was performed in 271 non-consanguineous individuals from the north of Italy, enrolled in the study because of the presence of non-syndromic preverbal sensorineural HI. One hundred and forty-six subjects (group 1) were referred from different ENT, paediatric and clinical genetic services, while 125 individuals (group 2) underwent Cx26 analysis based on precise anamnestic and clinical criteria for non-syndromic HI and low risk of acquired deficit. All of the cases were also classified as familial or sporadic due to the presence or absence of other documented childhood HI in the family. Of the total 271 individuals, 36.9% were positive for Cx26 mutations: 37 belonged to group 1 and 63 to group 2, which delineates a statistically significant difference between the two groups. The difference is mainly attributable to sporadically occurring cases. No significant differences between group 1 and group 2 were found regarding the prevalence of the common 35delG variant and the number of unidentified putative Cx26 alleles, although these latter were shown to be higher in sporadically occurring cases of the unselected group 1. The difference observed in Cx26 prevalence can be explained by the clinical selection of group 2, which ensures minimum risk of including cases of acquired HI. In particular, in cases of sporadically occurring HI, the use of a defined protocol increases the chances of a positive molecular result, improving genetic counselling and the possibility of establishing better genotype-phenotype correlation. Our data raise questions about the possible interpretation of Cx26 heterozygosity in a selected population of hearing-impaired individuals.

Adolescent↗

PubMed2000

Thrombotic microangiopathy associated with parvovirus B 19 infection after renal transplantation.

Human parvovirus B19 is considered an etiologic agent of aplastic anemia in immunosuppressed patients. Microscopic vasculitis, with or without renal involvement, has recently been attributed to this viral infection in immunocompetent patients. This study describes four cases of thrombotic renal graft microangiopathy presumably secondary to B19 infection. Twelve to 50 days after transplantation, four patients presented a renal graft dysfunction with creatinine rising to 360 to 1088 micromol/L and requiring hemodialysis in three cases. Renal involvement appeared after a systemic illness characterized by fever, fatigue and arthralgia, aplastic anemia (hemoglobin ranged from 5.3 to 7.8 g/dl), and thrombocytopenia. A thrombotic microangiopathy was observed in the renal biopsies, and the parvovirus B19 genome was isolated by PCR from the specimens. All four patients also became IgM-positive for parvovirus. Three of the four renal biopsies taken at the time of transplantation (T0) from the same patients were found positive for the B19 genome. Graft function recovered, with resolution of the aplastic anemia, within 22 to 110 d. Twenty biopsies performed as routine controls or for suspected acute rejection and nine T0 biopsies of patients with no signs of B19 infection were used. The B19 genome was found in two of 20 posttransplant biopsies and in one of nine T0 biopsies. The temporal association between aplastic anemia and the onset of thrombotic graft microangiopathy, isolation of the viral genome in renal specimens, seroconversion, and endothelial tropism of the virus suggests that B19 could be the etiologic agent of thrombotic microangiopathy in these cases. The development of the disease after infection could depend on other detrimental cofactors, which make the patient more susceptible to microthrombi formation in the renal microvasculature. The renal graft could represent the route of B19 transmission.

Adolescent↗