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Biomedical subjects

V Romano

Publications and source records attributed to V Romano.

At least 37 records · Page 2Linked to original sources
PubMed1997

Two novel PAH gene mutations detected in Italian phenylketonuric patients.

We report the identification by denaturing gradient gel electrophoresis and sequence analysis of two new phenylalanine hydroxylase (PAH) gene mutations (IVS4nt-2 and N207S) in single chromosomes of two unrelated Italian phenylketonuric (PKU) patients. Interestingly, mutation Y204C, found on the second mutant allele of family F1, has been previously detected in Chinese patients. Haplotype analysis showed that the latter mutation is linked to the same haplotype (H4) in both Chinese and Italian patients, suggesting a common origin. In vivo assessment of mutation severity indicates that N207S is associated with classic PKU. The identification of these two new mutations further extends the remarkable heterogeneity of the PAH locus in the Italian population.

Child↗
PubMed1997

The STR252-IVS10nt546-VNTR7 phenylalanine hydroxylase minihaplotype in five Mediterranean samples.

IVS10nt546 (IVS10nt-11g-->a) is the most common molecular defect of the phenylalanine hydroxylase gene causing phenylketonuria in Mediterranean populations. Previous studies have proposed various and alternative hypotheses concerning the geographical origin and pattern of diffusion of this mutation in this area. In this study, this issue was re-examined on a large sample (149) of "Mediterranean" IVS10nt546 mutant alleles analysed with multiallelic intragenic polymorphisms. The analysis of intragenic microsatellite (STR) and minisatellite (VNTR) polymorphisms shows allelic heterogeneity of the IVS10nt546 mutation. Eight STR and three VNTR alleles were found in association with the splicing defect. Of the ten detected STR-VNTR combinations ("minihaplotypes"), we identified a predominant allelic association (VNTR7-STR252) embedded in a RFLP-haplotype 6 background, which seems to correspond to the ancestral gene originating in the Turkey-Israel area. Analysis of both absolute and relative gene frequencies of the STR252-IVS10nt546-VNTR7 minihaplotypes, shows statistically significant (P < 0.02) variations and may suggest gene flow from Turkey and/or Israel to Italy and Spain. The associated migratory events need not be unique in time (and people) but seem to suggest they may be traced back to the expansion of the Neolithic culture and people, thus allowing dating of the origin of this mutation to at least 5000-10000 years ago. Alternative hypotheses are discussed to explain, in light of the available historical and pre-historical evidence, the pattern of diffusion of the IVS10nt546 mutation in the Mediterranean basin.

Gene Frequency↗
PubMed1997

Human type I cytokeratin genes are a compact cluster.

A YAC clone (211F11) containing approximately 0.5 Mb of human DNA was isolated from a human genomic library by PCR-based screening with cytokeratin (KRT) 13-specific primers. The YAC clone was mapped by FISH to the long arm of chromosome 17 (17q12-->q21), a region to which several other type I KRT genes had been mapped previously. We now show by Southern blot hybridization and PFGE analyses that KRT13, 14, 15, and 16 are all contained within YAC clone 211F11. Long-range restriction mapping analysis of clone 211F11 and of two smaller YAC clones that were also isolated with KRT13-specific primers, suggests that KRT13, 14, 15, 16 and their linked type I genes KRT17 and 19, are contained in less than 150 kb of genomic DNA. According to our reconstruction it then appears that at least six type I KRT genes are arranged in a highly compact cluster. The three YACs reported in this study represent a new tool to dissect the molecular structure of the locus of the human type I KRT genes.

Base Sequence↗
PubMed1996

Micromegakaryocytes in a patient with partial deletion of the long arm of chromosome 11 [del(11)(q24.2qter)] and chronic thrombocytopenic purpura.

Thrombocytopenia or pancytopenia is frequently reported in patients with partial 11q deletion but there are no reports on bone marrow morphology of these patients. We report on a patient with partial deletion of the long arm of chromosome 11 [del(11)(q24.2qter)] and its classical clinical manifestations including chronic thrombocytopenic purpura in whom micromegakaryocytes were found in the bone marrow aspirate. This is the first report of the presence of micromegakaryocytes in the bone marrow of a patient with 11q deletion. Accurate examination of the bone marrow of other patients with the 11q deletion may clarify whether the observation of micromegakaryocytes is common in these patients. Micromegakaryocytes may indicate a defect of development. Two genes for two DNA binding proteins that are likely to be involved in hematopoiesis map in the 11q region: Ets-1, that maps to 11q24, close to D11S912, and the nuclear-factor-related-kB gene that maps to 11q24-q25. It is possible that these genes, when present in only one copy, result in thrombocytopenia or pancytopenia as observed in this patient.

Adult↗
PubMed1996

Liver involvement in white patients with sickle-cell disease.

BACKGROUND: Liver involvement and cholelithiasis are common complications of sickle-cell disease. The incidence of clinically evident hepatic damage reported in the literature for black people varies from 15% to 30%, while no data are reported for white people. OBJECTIVE: To evaluate the liver involvement in 40 patients with homozygous sickle cell anemia (the beta 5 beta 5 form of sickle-cell disease) and 102 patients with double-heterozygous hemoglobin S and beta-thalassemia (65 with the beta 5 beta 0th and 37 with the beta 5 beta +th form of sickle-cell disease). SETTING: The Department of Pediatric Hematology and Oncology, University of Catania, Catania, Italy. PATIENTS: Outpatients with sickle-cell disease. RESULTS: We found that, in our patients, liver disease seems to be clinically irrelevant: only 2 of the 142 patients examined had notable alterations in hepatic function. Cholelithiasis was found in 42.1% of the subjects with the beta 5 beta 5 form of sickle-cell disease and in 26.8% of the subjects with the beta 5 beta th form. Age-related analysis revealed a greater incidence of cholelithiasis during the first years of life in the patients with the beta 5 beta 5 form of the disease than in patients with the beta 5 beta th form. CONCLUSION: Our data showed that liver involvement in sickle-cell disease is clinically irrelevant, reflecting the fact that the clinical expression of sickle-cell disease in Sicilian patients is moderate.

Adolescent↗
PubMed1996

Temperature and pressure effects during erbium laser stapedotomy.

BACKGROUND AND OBJECTIVES: Laser-assisted stapedotomy has become a well-established alternative to the mechanical drilling method. The goal of this study is to quantify the mechanical and thermal tissue effects and to determine optimum erbium laser parameters for safe clinical treatment. STUDY DESIGN/MATERIALS AND METHODS: On an inner ear model, time-resolved pressure measurements and Schlieren optical flash photography were performed during the perforation of the stapes foot plate using an erbium laser at 2.79 microns. The laser radiation was transmitted via an optical zirconium fluoride fiber. The laser-treated foot plates were investigated by light microscopy and scanning electron microscopy to visualise the laser-induced tissue effects. RESULTS: Perforation of the stapes foot plate can be performed with a few erbium laser pulses with high precision and a thermal damage zone of < 10 microns. Strong pressure transients were found to be generated by the bone ablation process and the collapse of a vapor channel created in the perilymph after fenestration. CONCLUSION: From the comparison of the laser-induced pressure with the limit graph to avoid hearing defects published by Pfander, an unobjectionable use of the erbium laser is deduced for fluences < 10 J/cm2. The erbium laser seems to represent an ideal instrument for middle ear surgery with all the advantages (precision, fiber optic transportable, high ablation efficiency, safety) desired for clinical application.

Erbium↗
PubMed1996

Experimental and clinical results of fiberoptic argon laser stapedotomy.

Since 1992 a small air-cooled opthalmological argon laser (Argus system, 3 W max.) equipped with a fiberoptic microhandpiece has been used for stapedotomy at the Inselspital, Berne. The microhandpiece has been developed especially for otological purposes in our electronic laboratory. In order to measure the effect of argon laser pulses applied through the handpiece to the ear, we performed temperature measurements in a saline-filled inner ear model by using ultrathin (2 microns thick), ultrafast (4 ns) thermosensitive rhodamine-coated polyurethane films. Multiple laser pulses of 1-2.5 W and 0.1 s duration - as used in clinical applications - produced a temperature elevation of about 1 degree C in the liquid of the inner ear model. The local laser effect was then examined histologically on the isolated stapes. The thermal damage zone around the stapedotomy perforation was limited to about 100 microns. In a clinical study we compared the results of argon laser stapedotomy (n = 54) with those of a skeeter microdrill stapedotomy (n = 29). Substantial hearing gains were found in all cases in both groups. In the laser stapedotomy group the mean residual air-bone gap (0.5-2 kHz) was 10 dB or less in all cases but one. Inner ear function remained unchanged except for a 40-dB loss at 4000 Hz in one case. Transient vertigo with nystagmus occurred in one case. Facial nerve dysfunction did not occur in any patient. The most important advantage of the laser found was the absence of mechanical trauma to the stapes. Stapes luxation and a floating footplate were avoided. In contrast, thick footplates were more easily perforated with the skeeter. Use of an argon laser equipped with a fiberoptic microhandpiece and a skeeter microdrill as needed seems particularly advantageous for stapedotomy.

Equipment Design↗
PubMed1996

PAH deficiency in Italy: correlation of genotype with phenotype in the Sicilian population.

The results of the neonatal screening for phenylalanine hydroxylase (PAH) deficiency in Sicily show that its incidence is higher than previously reported for mainland Italians and that non-PKU HPA is in excess of classical and mild PKU. The latter finding suggests that a high number of non-PKU HPA mutations would occur in the Sicilian population compared to populations with an inverted PKU/non-PKU HPA ratio. Previous studies have identified 40 mutations accounting for the majority (98%) of mutant alleles underlying PAH deficiency in Sicily. In order to study the molecular basis of the distribution of PAH deficiency phenotypes in the Sicilian population, we have correlated 31 of those mutations with clinical and metabolic phenotypes in 12 mentally retarded patients, 14 treated patients with classic or mild PKU, and 13 subjects presenting the non-PKU HPA phenotype. The present study proposes a tentative classification for a large number (26) of PAH gene mutations which may represent an additional tool for establishing a differential diagnosis for PAH deficiency in the Sicilian population.

Amino Acid Metabolism, Inborn Errors↗
PubMed1996

Preliminary studies on the molecular basis of hyperphenylalaninemia in Egypt.

Mutation analysis at the phenylalanine hydroxylase (PAH) locus was undertaken in 56 Egyptian hyperphenylalaninemic patients. Selected screening for 11 known mutations and denaturing Gradient gel electrophoresis (DGGE) analysis of the entire coding sequence and exon/intron boundaries led to the identification of a new mutation (I224T), four previously described mutations, and several polymorphisms. Overall, 18 mutant alleles could thus be characterized. In contrast to the high mutation detection rate typical of the DGGE-based scanning approach, only 6 of 16 mutant alleles tested were identified. Since BH4 deficiency could not be excluded in any of these patients, the latter results may be explained by the occurrence of mutations affecting the genes controlling the synthesis and recycling of tetrahydrobiopterin: the cofactor of PAH. An alternative hypothesis is also discussed.

Alleles↗
PubMed1996

Lead in human blood from children living in Campania, Italy.

Blood lead (PbB) levels were determined in children living in Campania (in Naples and in a rural zone in the district of Caserta). Atmospheric lead (PbA) concentration in these considered areas was monitored for 1 yr (1993-1994). The children tested were questioned about common sources of lead, other than atmospheric, relating to their living and dietary habits. The PbB levels in children living in Naples were, at the 50th percentile, 13.8 micrograms/dl in males and 13.7 micrograms/dl in females; in children living in the rural area the median PbB levels were 8.9 micrograms/dl in males and and 8.8 micrograms/dl in females. The annual mean values of atmospheric lead were 1.15 +/- 0.24 micrograms/m3 in Naples and 0.23 +/- 0.07 micrograms/m3 in the rural area. Significant and congruent mean differences between urban and rural sites were found in children's blood and concurrent air lead. Considering the PbB level of 10 micrograms/dl as the maximum level that is not associated any known adverse effect in children, the Neapolitan group can be considered at risk of chronic intoxication by lead.

Adolescent↗
PubMed1995

Plastic hollow waveguides: properties and possibilities as a flexible radiation delivery system for CO2-laser radiation.

BACKGROUND AND OBJECTIVES: One significant inconvenience of the CO2 laser is the lack of flexible fibers essential for endoscopic applications. The goal of this study is to test the feasibility of hollow waveguides in view of a practical use in medicine. STUDY DESIGN/MATERIALS AND METHODS: Various types of plastic hollow waveguides for flexible delivery of CO2 laser radiation were examined. The transmission losses, divergence angle, damage threshold, and input and output beam profiles were determined. The interaction process between radiation transmitted through these guides with soft as well as hard tissues was studied. RESULTS: Plastic hollow waveguides can transmit high power (up to 50 W) with low losses (straight guide 1 dB/m) even through bendings. The divergence angle is < 13 degrees. Cutting quality and extent of thermal damage are comparable to incisions performed with a free laser beam. CONCLUSION: The results of this study show good cutting quality and durability of these flexible plastic hollow waveguides, which render possible to deliver CO2 radiation in the power range needed for most surgical applications with affordable transmission losses. Plastic hollow waveguides are, therefore, a real alternative to replace the mirror arms.

Animals↗
PubMed1995

Phenylketonuria mutations and their relation to RFLP haplotypes at the PAH locus in Czech PKU families.

A detailed study of the mutant phenylalanine hydroxylase (PAH) gene from the eastern part of the Czech Republic (Moravia) is reported. A total of 190 mutant alleles from 95 phenylketonuria (PKU) families were analyzed for 21 prevalent Caucasian mutations and restriction fragment length polymorphism/variable number of tandem repeats (RFLP/VNTR) haplotypes. Eighty per cent of all mutant alleles were found to carry 11 mutations. The most common molecular defect was the mutation R408W (55.3%), with a very high degree of homozygosity (34.6%). Each of four other mutations (R158Q, R243X, G272X, IVS12nt1) accounted for more than 3% of PKU alleles. Rarely present were mutations IVS10nt546 (2.6%), R252W (2.6%), L48S (2.1%), R261Q (1.6%), Y414C (1.0%) and 165T (0.5%). Mutations that have been predominantly described in southern Europe (IVS7nt1, A259V, Y277D, R241H, T278N) were not detected. A total of 14 different mutant haplotypes were observed. Three unusual genotype-haplotype associations were identified (R158Q on haplotypes 2.3 and 7.8 and R252W on haplotype 69.3). There was a strong association between the mutation R408W and haplotype 2.3 (54.7%). Heterogeneity was found at mutations R408W (haplotypes 2.3 and 5.9), R158Q (haplotypes 4.3, 2.3 and 7.8) and IVS10nt546 (haplotypes 6.7 and 34.7). The molecular basis of PKU in the Moravian area appears to be relatively homogeneous in comparison with other southern and western European populations, thus providing a good starting point for prenatal diagnosis and early clinical classification.

Base Sequence↗
PubMed1995

Low serum levels of interleukin-6 in children with post-infective acute thrombocytopenic purpura.

Interleukin-6 plays an important role in host defense mechanisms and it appears to be a major mediator of the acute-phase response. IL-6 is also an important thrombocytopoietic factor. High serum levels of IL-6 are present in reactive thrombocytosis. The number and function of circulating platelets are the major factors that affect megakaryocytopoiesis by thrombopoietin. High levels of thrombopoietin have been observed in patients with thrombocytopenic purpura. To evaluate a possible thrombopoietin-like function of IL-6, we measured IL-6 levels in the serum of patients affected by post-infective acute thrombocytopenic purpura using a sensitive ELISSA assay. As controls, we studied normal subjects and patients with reactive thrombocytosis. No significant difference was observed between thrombocytopenic patients and normal controls. High IL-6 levels were present in patients with reactive thrombocytosis. In conclusion, we had not observed high levels of IL-6 in acute thrombocytopenic purpura and, very probably, IL-6 is not involved in the regulation of platelet mass for the hemostatic function. The thrombocytopoietic activity of IL-6 is another acute-phase response and it is consistent with the other functions of this cytokine. This suggests an active participation of platelets in host defense mechanisms.

Adolescent↗
PubMed1995

Congenital dyserythropoietic anemia type II associated with G6PD Seattle in a Sicilian child.

A 2-year-old Sicilian boy was investigated because of chronic nonspherocytic hemolytic anemia (CNSHA) associated with hepatosplenomegaly. Appropriate studies revealed deficiency of glucose-6-phosphate dehydrogenase type Seattle (G6PD Seattle). In addition, bone marrow morphology, serological studies and analysis of red cell membrane proteins revealed congenital dyserythropoietic anemia (CDA) type II (or HEMPAS). Because G6PD Seattle on its own does not cause CNSHA, we believe that the clinical manifestations in this patient are essentially due to the CDA type II abnormality. However, the coexistence of these two different red cell abnormalities may affect the clinical picture specifically by making CDA type II more hemolytic than it would have been otherwise.

Anemia, Dyserythropoietic, Congenital↗