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Abstract Background POLG1 mutations have been associated with MELAS-like phenotypes. However given several clinical differences it is unknown whether POLG1 mutations are possible causes of MELAS or give raise to a distinct clinical and genetic entity, named POLG1-associated encephalopathy. Case presentation We describe a 74 years old man carrying POLG1 mutations presenting with strokes, myopathy and ragged red fibers with some atypical aspects for MELAS such as late onset, lack of cerebral calcification and presence of frontal and occipital MRI lesions better consistent with the POLG associated-encephalopathy spectrum. Conclusion The lack of available data hampers a definite diagnosis in our patient as well as makes it difficult to compare MELAS, which is a clearly defined clinical syndrome, with POLG1-associated encephalopathy, which is so far a purely molecularly defined syndrome with a quite heterogeneous clinical picture. However, the present report contributes to expand the phenotypic spectrum of POLG1 mutations underlining the importance of searching POLG1 mutations in patients with mitochondrial signs and MELAS like phenotypes but negative for common mtDNA mutations.

Abstract Background Birth defects are a leading cause of neonatal and infant mortality in Italy, however little is known of the etiology of most defects. Improvements in diagnosis have revealed increasing numbers of clinically insignificant defects, while improvements in treatment have increased the survival of those with more serious and complex defects. For etiological studies, prevention, and management, it is important to have population-based monitoring which provides reliable data on the prevalence at birth of such defects. Methods We recently initiated population-based birth defect monitoring in the Provinces of Mantova, Sondrio and Varese of the Region of Lombardy, northern Italy, and report data for the first year of operation (1999). The registry uses all-electronic source files (hospital discharge files, death certificates, regional health files, and pathology reports) and a proven case-generation methodology, which is described. The data were checked manually by consulting clinical records in hospitals. Completeness was checked against birth certificates by capture-recapture. Data on cases were coded according to the four-digit malformation codes of the International Classification of Diseases, Ninth Revision (ICD-9). We present data only on selected defects. Results We found 246 selected birth defects in 12,008 live births in 1999, 148 among boys and 98 among girls. Congenital heart defects (particularly septal defects) were the most common (90.8/10,000), followed by defects of the genitourinary tract (34.1/10, 000) (particularly hypospadias in boys), digestive system (23.3/10,000) and central nervous system (14.9/10,000), orofacial clefts (10.8/10,000) and Down syndrome (8.3/10,000). Completeness was satisfactory: analysis of birth certificates resulted in the addition of two birth defect cases to the registry. Conclusion This is the first population-based analysis on selected major birth defects in the Region. The high birth prevalences for septal heart defect and hypospadias are probably due to the inclusion of minor defects and lack of coding standardization; the latter problem also seems important for other defects. However the data produced are useful for estimating the demands made on the health system by babies with birth defects.

Background: Prenatal ultrasound (US) detection of heterotaxy syndrome can be challenging, especially in identifying cardiovascular and associated anomalies. We present a new case of heterotaxy syndrome with anomalous systemic venous return (ASVR) fully displayed at autopsy. Case report: Left heterotaxy syndrome was diagnosed in a 19 weeks' of gestation fetus with right-sided stomach. The heart showed both ventricles with left morphology, a large ventricular septal defect, persistent left superior vena cava draining into the coronary sinus, ASVR with interrupted inferior vena cava (IVC) and azygous continuation. Autopsy dissection further identified the azygous draining into the left lower pulmonary vein (LLPV). Prenatal a-CGH on villous sampling showed 22q13.1 microduplication inherited from the father, not contributory to the phenotype. Conclusion/discussion: Heterotaxy syndrome requires US accuracy for anomaly identification, as they allow legal termination of pregnancy. Our case is unusual as IVC drained into the azygous vein and then into the LLPV. [ABSTRACT FROM AUTHOR]

Role of ductus venosus in distribution of umbilical blood flow in human fetuses during second half of pregnancy. Am J Physiol Heart Circ Physiol 279: H1256-H1263, 2000.--Color Doppler sonography was used to study umbilical and ductus venosus (DV) flow in 137 normal fetuses between 20 and 38 wk of gestation. Hepatic flows were also evaluated. In all parts of the venous circulation examined, blood flow increased significantly with advancing gestational age. The weight-specific amniotic umbilical flow did not change significantly during gestation (120 [+ or -] 44 ml [multiplied by] [min.sup.-1] [multiplied by] [kg.sup.-1]), whereas DV flow decreased significantly (from 60 to 17 ml [multiplied by] [min.sup.-1] [multiplied by] [kg.sup.-1]). The percentage of umbilical blood flow shunted through the DV decreased significantly (from 40% to 15%); consequently, the percentage of flow to the liver increased. The right lobe flow changed from 20 to 45%, whereas the left lobe flow was approximately constant (40%). These changes are related to different patterns of growth of the umbilical veins and DV diameters. The present data support the hypothesis that the DV plays a less important role in shunting well-oxygenated blood to the brain and myocardium in late normal pregnancy than in early gestation, which leads to increased fetal liver perfusion. fetal hemodynamics; ultrasonography; umbilical flow repartition; hepatic flow; vessel growth

This report describes an indirect identification method for Cryptococcus neoformans serotypes developed using combined restriction enzyme pattern analysis of two PCR-amplified portions of the capsule-associated genes CAP10 and CAP59. The method relies on the recognition of the sequence conformation of nine serotype-related polymorphic sites by the analysis of four restriction profiles. A 610 nucleotides long trait of the CAP10 gene was digested with the enzymes Sty I or Sal I and a 597 nucleotides long trait of the CAP59 gene was digested with the enzymes Sal I or EcoRV+PstI. The resulting profiles, reported as a string of four numbers, defined for each strain an intrinsically coherent allelic profile closely correlated to the serotype. We analyzed by this method 172 C. neoformans strains obtained from different sources. All the serotype A strains examined and all the strains of the B-C serotypes group were recognized by specific allelic profiles, but serotypes B and C could not be distinguished from each other. Of the serotype D strains, 84% were characterized by a unique allelic pattern, while the remaining 16% were genotypically indistinguishable from the AD serotype organisms among which differences in the ploidy number and evidence of recombination could be recognized. [ABSTRACT FROM AUTHOR]

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Several in vitro studies with a new medical device (Myfungar) containing 0.5% of piroctone olamine (CAS 68890-66-4, octopirox) in a hydroxypropyl chitosan hydroalcoholic solution were performed. The chemical name of the active ingredient is 1-hydroxy-4-methyl-6 (2,4,4-trimethylpentyl)-2(1H)-pyridone; combination with 2-amino-ethanol (1:1). The antimycotic activity was determined in the most common fungi responsible of nail infections such as Candida parapsilosis, Scopulariopsis brevicaulis or Trichophyton rubrum. The minimum inhibitory concentration (MIC), found by means of the broth dilution susceptibility method, ranged between 0.0003% and 0.006% for all pathogens considered. The in vitro permeation study was performed by using bovine hoof membranes inserted in a modified Gummer vertical permeation cell. The experiment showed, at 30 h, a retention of the product in the nail membranes by 11.1% of the applied dose. No piroctone permeation through bovine hoof membranes could be detected by HPLC due to the limit of quantitation of this method. On the other hand, permeation of nail membranes has been demonstrated by a biological assay: the study of in vitro permeation through bovine hoof membranes, performed by biological assay, showed dose-dependent inhibition rings of T. rubrum growth by the tested device, placed either on disks for antibiogram or on nail fragments. The placebo did not show any inhibition. In vitro experimental infection by T. rubrum showed a preventive activity of the tested device on fungal growth as well as a curative activity, as the pathogen was eradicated by the tested solution in previously infected nails.