Effects and safety of delayed versus early umbilical cord clamping in newborns of HIV-infected mothers.

OBJECTIVE: To investigate the effect of a 2 minutes-delayed cord clamp (DCC) versus early cord clamp (ECC) on neonate haemoglobin concentration 24 hours and 1 month after birth, and assess the safety of DCC concerning the risk of HIV infection. DESIGN: Sixty-four mother-infant peers were enrolled. All mothers were on stable ARV therapy. Viral load, CD4+ count and blood haemoglobin (Hb) concentrations 24 hours before delivery were collected from all mothers and their infants. METHODS: All patients were enrolled at the Department of Paediatrics, AO FBF Sacco Hospital in Milan, and were followed until 18 months after birth. Women with haematological diseases and obstetrical complications were excluded. All of 64 mother and infants couples (32 ECC group and 32 DCC group) completed the study. ECC and DCC are defined as application of umbilical clamp within 30 seconds and 120 seconds after birth, respectively. RESULTS: Mean birth weight was significantly higher in the DCC compared with ECC group. Mean Hb levels at birth were significantly higher in DCC than in ECC group (p = .05): this difference persisted at 1 month of life. All newborns showed negative viral load. CONCLUSIONS: DCC 2 minutes after birth is proven to be a safe procedure, particularly beneficial in newborns from HIV mothers. The risk of anemia is significantly decreased at 24 hours after birth and persists at age of 1 month without any increased risk of neonatal jaundice or polycitemia.

Phenotypic heterogeneity and mutational spectrum in a cohort of 45 Italian males subjects with X-linked ectodermal dysplasia.

Ectodermal dysplasias (EDs) are a group of genetic disorders characterized by the abnormal development of the ectodermal-derived structures. X-linked hypohidrotic ectodermal dysplasia, resulting from mutations in ED1 gene, is the most common form. The main purpose of this study was to characterize the phenotype spectrum in 45 males harboring ED1 mutations. The study showed that in addition to the involvement of the major ectodermal tissues, the majority of patients also have alterations of several minor ectodermal-derived structures. Characterizing the clinical spectrum resulting from ED1 gene mutations improves diagnosis and can direct clinical care.

Ectodermal dysplasias: the p63 tail.

Various combinations of limb anomalies, ectodermal dysplasias and orofacial clefts characterize heterozygous mutations in the transcription factor gene p63. The causative gene is crucial during embryonic ontogenesis, mostly in the development of limbs and other ectodermal derived tissues. The pattern of mutations in six different p63-related syndromes (EEC syndrome, AEC syndrome, ADULT syndrome, LMS syndrome, RHS syndrome, SHFM syndrome) shows genotype-phenotype correlations. The most frequent p63 mutation syndrome is the EEC syndrome, characterized by ectrodactyly, ectodermal dysplasia and cleft lip/palate. Ectodermal dysplasia is characterized by ectrodactyly often associated with syndactyly, sparse hair, dry skin, hypo-anodontia, dysplastic nails and alterations in sebaceous glands, mammary glands and nipples. The third hallmark of the EEC syndrome is orofacial clefting, in particular lip and palate. p63 mutations also cause the other five inherited syndromes: symptoms are overlapping, but each of these diseases has its own characteristic phenotypic features: for instance AEC syndrome (ankyloblepharon-ectodermal defects-cleft lip/palate) has as distinctive feature ankyloblepharon, while mammary glands and nipples hypoplasia are frequent findings in LMS syndrome and in ADULT syndrome (acro-dermato-ungual-lacrimal-tooth syndrome). The latter can be distinguished from other p63 syndromes by the absence of orofacial clefting and by prominent ectodermal signs. The narrowest genotype-phenotype correlation is in the EEC and AEC syndromes. All EEC missense mutations are clustered in the DNA binding domain and do not bind to DNA; in contrast, all missens mutations reported in AEC syndrome are localized in the α-motif domain, and it has been demonstrated that they disrupt interaction with other proteins. LMS and ADULT syndrome have their own unique mutated amino-acid residues. Only two amino-acid residues are known to be mutated amongst ADULT syndrome: asparagines 6 and arginine 298. Although R298 is in the DNA binding domain, it is functionally different from the EEC mutations, because its substitution by glutamine does not lead to a loss of DNA binding, but to a gain of transactivation activity of the ∆Np63γ isoform. In this paper we discuss the consistent phenotypic features associated with these gain of function mutations.

Detection of bacteria in red blood cell concentrates by the Scansystem method.

Bacterial contamination remains one of the major risks associated with blood product transfusion. The kinetics of bacterial growth in red blood cell concentrates (RBCC) is different than otherwise due to storage at 4 degrees C, conditions in which most bacteria do not survive. Psychrophilic bacteria such as Yersinia enterocolitica, however, can proliferate from a very low level of contamination to clinically significant levels at 4 degrees C and are known to cause severe transfusion-related infections. A screening method allowing the early detection of very low levels of bacteria in RBCC would improve transfusion safety. The Scansystem method has been previously described for detection of bacteria in platelet concentrates. We present here a modification of the system for detection of low levels of bacteria in RBCC. The Scansystem RBC kit protocol requires three steps, i.e., the agglutination and selective removal of RBCs, a labeling stage during which bacteria are labeled with a DNA-specific fluorophore, and finally recovery of bacteria on the surface of a black membrane for analysis using the Scansystem. The entire procedure from sampling to result can be completed in 90 min. Both gram-negative and gram-positive bacteria in RBCC are detected with a higher sensitivity than with currently available culture-based methods. The Scansystem RBC kit is shown to be sensitive enough to identify low-level bacterial contamination in a single unit tested in a pool of up to 20 RBCC samples (detection limit of between 1 and 10 CFU/ml depending on the bacterial strain). The method therefore lends itself to incorporation into high-sample-throughput screening programs.

Rapid screening method for detection of bacteria in platelet concentrates.

Public awareness has long focused on the risks of the transmission of viral agents through blood product transfusion. This risk, however, pales in comparison to the less publicized danger associated with the transfusion of blood products contaminated with bacteria, in particular, platelet concentrates. Up to 1,000 cases of clinical sepsis after the transfusion of platelet concentrates are reported annually in the United States. The condition is characterized by acute reaction symptoms and the rapid onset of septicemia and carries a 20 to 40% mortality rate. The urgent need for a method for the routine screening of platelet concentrates to improve patient safety has long been recognized. We describe the development of a rapid and highly sensitive method for screening for bacteria in platelet concentrates for transfusion. No culture period is required; and the entire procedure, from the time of sampling to the time that the final result is obtained, takes less than 90 min. The method involves three basic stages: the selective removal of platelets by filtration following activation with a monoclonal antibody, DNA-specific fluorescent labeling of bacteria, and concentration of the bacteria on a membrane surface for enumeration by solid-phase cytometry. The method offers a universal means of detection of live, nondividing, or dead gram-negative and gram-positive bacteria in complex cellular blood products. The sensitivity is higher than those of the culture-based methods available at present, with a detection limit of 10 to 10(2) CFU/ml, depending upon the bacterial strain.