First trimester supratentorial and infratentorial abnormalities in fetuses with open spina bifida.

OBJECTIVES: To examine whether supratentorial, infratentorial, and calvarial manifestations of open spina bifida (OSB) occur in the first-trimester. METHODS: Supratentorial (midbrain curvature, thalamic height), infratentorial (fourth ventricle diameter, brain-stem diameter [BSD], ratio of BSD to BSD-occipital bone diameter [BSOB]), and calvarial (frontomaxillary facial [FMF] angle) parameters were measured in stored midsagittal facial images at 110-136 weeks of 500 normal and 10 open spina-bifida fetuses by 3 blinded examiners. RESULTS: OSB fetuses displayed a larger midbrain curvature (93.26 ± 6.97 versus 97.79 ± 10.04, p < .05), decreased FMF angle (84.10 ± 5.44 versus 78.46 ± 5.82, p < .001), smaller fourth ventricle diameter (0.25 ± 0.04 mm versus 0.18 ± 0.05 mm, p < .001), smaller BSD (0.29 ± 0.04 mm versus 0.23 ± 0.04 mm; p < .001), and increased BSD to BSOB ratio (0.64 ± 0.71 versus 0.73 ± 0.93, p < .03) than normal controls, respectively. Thalamic height was not significantly altered. Detection rates of OSB were highest for fourth ventricle diameter and FMF angle (60% and 40%, respectively, at 95% specificity). BSD, BSD to BSOB ratio, midbrain curvature yielded sensitivities of 30% with 95% specificity. Two-dimensional discrimination for pairs of measures combining fourth ventricle diameter with FMF angle increased sensitivity to 90% with specificity of 90.7%. CONCLUSIONS: Our findings suggest that supratentorial, infratentorial, and calvarial changes consistent with the Chiari-II malformation are already established in first-trimester fetuses with OSB.

Reporte de un caso de glomerulonefritis rápidamente progresiva por anticuerpos antimembrana basal glomerular / Case report of rapidly progressive glomerulonephritis due to anti-glomerular basement membrane antibodies

RESUMEN Una vez más en medicina interna no podemos, aún, prescindir de los métodos invasivos para alcanzar un diagnóstico. Los avances diarios en el hallazgo de nuevas herramientas paraclínicas no permiten reemplazar aquellos métodos de certeza como la anatomía patológica. El caso presentado es una muestra de ello. Se trata de una mujer de 27 años de edad, con antecedente de tiroiditis de Hashimoto que consulta por presentar severo deterioro de la función renal asociado a oligoanuria. Realizamos una revisión del tratamiento de las glomerulonefritis rápidamente progresivas por anticuerpos antimembrana basal glomerular, serológicamente negativas.

ABSTRACT Once again in internal medicine we cannot do a diagnosis without invasive methods. Daily advances in the finding of new paraclinical tools do not allow the replacement of certain methods such as pathological anatomy. The case presented is a sample of this. This is a 27-year-old woman with a history of Hashimoto's thyroiditis who consults for presenting severe impairment of kidney function associated with oligoanuria. We performed a review of the treatment of the rapidly progressive glomerulonephritis for serologically negative anti-GBM antibodies.

Ab-initio molecular dynamics and hybrid explicit-implicit solvation model for aqueous and nonaqueous solvents: GFP chromophore in water and methanol solution as case study.

Solute-solvent interactions are proxies for understanding how the electronic density of a chromophore interacts with the environment in a more exhaustive way. The subtle balance between polarization, electrostatic, and non-bonded interactions need to be accurately described to obtain good agreement between simulations and experiments. First principles approaches providing accurate configurational sampling through molecular dynamics may be a suitable choice to describe solvent effects on solute chemical-physical properties and spectroscopic features, such as optical absorption of dyes. In this context, accurate energy potentials, obtained by hybrid implicit/explicit solvation methods along with employing nonperiodic boundary conditions, are required to represent bulk solvent around a large solute-solvent cluster. In this work, a novel strategy to simulate methanol solutions is proposed combining ab initio molecular dynamics, a hybrid implicit/explicit flexible solvent model, nonperiodic boundary conditions, and time dependent density functional theory. As case study, the robustness of the proposed protocol has been gauged by investigating the microsolvation and electronic absorption of the anionic green fluorescent protein chromophore in methanol and aqueous solution. Satisfactory results are obtained, reproducing the microsolvation layout of the chromophore and, as a consequence, the experimental trends shown by the optical absorption in different solvents.

Trasplante renal en la enfermedad de Fabry: una historia de idas y vueltas / Kidney transplant in Fabry disease: a round-trip story

La enfermedad de Fabry es una patología por depósito lisosomal causada por mutaciones en el gen GLA que resulta en la deficiencia de alfa galactosidasa A. Dentro de las complicaciones tardías más comunes se encuentra la insuficiencia renal terminal. Por medio de una revisión bibliográfica en la base PUBMed se busca evidenciar si el trasplante renal representa una opción terapéutica indiscutible para el tratamiento de la nefropatía de Fabry. Hallazgos demuestran la posibilidad de la terapia de reemplazo enzimático que permite proteger al sistema cardiovascular y nervioso del daño progresivo por acumulo lisosomal.

Fabry disease is a lysosomal storage disorder caused by mutations in the GLA gene that results in alpha galactosidase A deficiency. One of the most common late complications is end stage renal disease. Through a bibliographic review in the PUBMed database, we seek to demonstrate whether kidney transplantation represents an indisputable therapeutic option for the treatment of Fabry nephropathy. Findings demonstratethepossibility of enzymereplacementtherapythatprotects the cardiovascular and nervoussystemfromprogressivedamagebylysosomalaccumulation.

Brain stem/brain stem occipital bone ratio and the four-line view in nuchal translucency images of fetuses with open spina bifida.

Objective: Brain stem depth/brain stem occipital bone distance (BS/BSOB ratio) and the four-line view, in images obtained for nuchal translucency (NT) screening in fetuses with open spina bifida (OSB).Methods: Single center, retrospective study based on the assessment of NT screening images of fetuses with OSB. A ratio between the BS depth and the BSOB distance was calculated (BS/BSOB ratio) and the four-line view observed, and the sensitivity for a BS/BSOB ratio superior/equal to 1, and for the lack of detection of the four-line view were calculated.Results: There were 17 cases of prenatal diagnosis OSB. In six cases, the suspicion on OSB was raised during NT screening, in six cases, the diagnosis was made before 20 weeks and in five cases during anomaly scan. The BS/BSOB ratio was superior/equal to 1 in all 17 cases, and three lines, were visualized in 15/17 images of the OSB cases, being the sensitivity 100% (95% CI, 81 to 100%) and 88% (95% CI, 65 to 96%).Conclusion: Assessment of BS/BSOB ratio and four-line view in NT images is feasible detecting affected by OSB with high sensitivity. The presence of associated anomalies or of an enlarged NT enhances the early detection.

Color Doppler score: a new approach for monitoring a large placental chorioangioma.

We employed color Doppler score as an innovative approach for the prenatal diagnosis and monitoring of a large placental chorioangioma case diagnosed at 26 weeks and the subjective semiquantitative assessment of the vascularization. The blood flow was assessed by a color Doppler score based on the intensity of the color signal with the following value ranges: (1) no flow, (2) minimal flow, (3) moderate flow, and (4) high vascular flow. Weekly examinations were programmed. Initially, a color Doppler score 3 was assigned, remaining unchanged at the following two exams and decreasing to Score 2 in the following 2 exams and to Score 1 thereafter. The ultrasonographic scan showed an increase of the mass size at the second and third exams and was followed by an arrest of the growth persisting for the rest of the pregnancy. Some hyperechogenic spots inside the mass appeared at the end. Expectant management was opted for, and the delivery was at 39, 2 weeks and maternal and fetal outcomes were favourable. The color Doppler score employed for assessment of vascularization in successive examinations proved to be an important tool for the prediction of the chorioangioma involution, and this new approach of monitoring allowed effective surveillance and successful tailored management.

A Case of Enlarged Intracranial Translucency in a Fetus with Blake's Pouch Cyst.

The intracranial translucency (IT) is a recently introduced marker of open spina bifida (OSB). In this study, we describe a case of a fetus affected by Blake's pouch cyst which showed alterations of BS/BSOB ratio at the first trimester screening.

Umbilical vein volume flow in monochorionic twin pairs at 11-14 weeks.

We investigated the umbilical vein volume flow (UVVF) at 11-14 weeks in monochorionic-diamniotic (MCDA) twins, focusing on the occurrence of complications. We considered 87 MCDA pregnancies. We used "E-flow" to detect the umbilical vein and measured the mean velocities and diameters of veins, also calculating the UVVF. Pregnancies were divided into four groups: a (twin-to-twin transfusion, TTTS); b (selective intrauterine growth restriction, sIUGR); c (discordance of fluid, DF); and d (with "normal" outcome). The main outcome of the study was the assessment of the difference of UVVF between twin 1 and twin 2 (larger and smaller twin). In eight of eight pairs of group a and seven of seven pairs of group b, the UVVF of fetuses 1 were significantly different than fetuses 2 (P<0.05). The UVVFs of fetuses 2 of group a were significantly lower in respect to the UVVFs of fetuses 2 of group d (P<0.05). We provide evidence of an important difference in UVVF in pairs that successively developed TTTS or sIUGR. The smaller fetuses of group a (TTTS) showed a lower venous return than fetuses 2 of group d (normal). First-trimester UVVF is lower in fetuses with a smaller crown-rump length in twin pairs at risk of TTTS or IUGR.

Screening and Invasive Testing in Twins.

Prenatal screening and testing for trisomy 21 in twin pregnancies poses a number of challenges: the exact estimate of the a priori risk of trisomy 21, the choice of prenatal screening test and/or invasive techniques to employ for the diagnosis and the impact of the result on the options of treatment in case of discordant results within a twin pair or among multiples. These different aspects are discussed below while recognizing that many issues remain unresolved.

First trimester diagnosis of sirenomelia by 2D and 3D ultrasound.

A case of sirenomelia in a 27-year-old woman detected at 11 weeks 5 days of gestation is presented. It was suspected by two-dimensional sonography and color Doppler imaging. Three-dimensional ultrasound confirmed the final diagnosis. With detailed evaluation of the acquired volumes, valuable information was obtained about the anatomical as well as pathological features of the fetus.

Conjoined twins in a trichorionic quadruplet pregnancy after intracytoplasmic sperm injection and quarter laser-assisted zona thinning.

OBJECTIVE: To describe the occurrence and management of conjoined twins (CTs) in a trichorionic quadruplet pregnancy after the transfer of three embryos obtained by intracytoplasmic sperm injection (ICSI) that had undergone assisted zona hatching (AZH) using a noncontact laser. DESIGN: Case report. SETTING: Private and public IVF centers. PATIENT(S): A 38-year-old nulliparous woman. INTERVENTION(S): IVF, diagnosis by two-dimensional, three-dimensional, and four-dimensional ultrasound, selective termination at 12 weeks gestation. MAIN OUTCOME MEASURE(S): Clinical follow-up and delivery. RESULT(S): After diagnosis, counselling, and selective termination, the subsequent prenatal course was uneventful, and two healthy boys were delivered by elective cesarean section at 38 weeks gestation. CONCLUSION(S): Monozygotic twinning (MZT) and CTs could complicate multifetal pregnancies obtained by assisted reproduction techniques. The relationship between CTs, IVF, and AZH should be better studied to fully understand the mechanisms that lead to MZT (with the possible role of AZH) and CTs in MZT, in particular. Three-dimensional and four-dimensional ultrasound improve prenatal assessment of the condition. Selective embryo reduction is a safe procedure for the management of these pregnancies.

Changes in the approach for invasive prenatal diagnosis in 35,127 cases at a single center from 1977 to 2004.

OBJECTIVES: To evaluate the changes in the approaches used for invasive prenatal diagnosis for beta-thalassemia and karyotyping at a single center from 1977 to 2004. METHODS: For beta-thalassemia, in 1977 placentacentesis, in 1982 amniocentesis, in 1983 fetoscopy and cordocentesis, in 1983 trancervical chorionic villi sampling (TC-CVS), in 1984 cardiocentesis, in 1986 transabdominal CVS, and in 2002 preimplantation genetic diagnosis (PGD) were introduced. For karyotyping, in 1977 amniocentesis, in 1983 cordocentesis and cardiocentesis and TC-CVS, in 1986 TA-CVS and in 1991 hepatic vein sampling were introduced. Rates of approaches used were retrospectively considered, for 5 different groups (1977-1981; 1982-1985; 1986-1993; 1994-1999; 2000-2004). RESULTS: 35,127 invasive prenatal diagnoses were considered, and 42 PGD included. For beta-thalassemia 6,547 diagnoses were performed and 42 PGD. Since 1986-1993, TA-CVS was the only approach used except for 42 PGD in the 2000-2004 group. For karyotyping 28,538 diagnoses were performed. Amniocentesis and TA-CVS have been the most frequently used in the last years, while cordocentesis and hepatic vein sampling have shown a decline after their introduction. CONCLUSION: TA-CVS is now the only technique used for beta-thalassemia. For karyotype, amniocentesis and TA-CVS are the most frequently used procedures. Obstetrical and laboratory experience, the availability of screening, and other individual factors, have influenced the choice, towards an earlier approach in pregnancy.

Nuchal translucency and nasal bone for trisomy 21 screening: single center experience.

AIM: To evaluate the feasibility and diagnostic accuracy of fetal nuchal translucency and nasal bone assessment at 11-14 weeks for screening of trisomy 21 at a single center. METHODS: Nuchal translucency measurement and nasal bone evaluation in relation to the fetal karyotype for singleton fetuses were retrospectively assessed at the Ospedale Microcitemico, Cagliari, Italy, in a three-year period (2001-2004). Nuchal translucency was considered enlarged if greater than or equal to the 95th centile for crown-rump length (CRL) of the reference ranges, and nasal bone was described as present or absent during the evaluation of the fetal facial profile. Sensitivity and specificity for trisomy 21 were assessed for nuchal translucency and absent nasal bone. RESULTS: Among 32,000 cases recorded in the database including fetuses from 11 to 14 weeks, 16,654 fetuses were included in the study with both nuchal translucency measurement and nasal bone evaluation. Median maternal age was 32 years (range, 14-49). In 854 fetuses (5.1%), nuchal translucency was greater than the 95th centile, and 744 (87.1%) of them had a normal karyotype. Among 141 (0.8%) diagnosed cases of chromosomopathies, there were 96 cases of trisomy 21. Nuchal translucency was enlarged in 110 chromosomopathies and in 72 trisomies 21. Sensitivity was 75.0% (95% confidence interval [CI], 65.5-82.6), and specificity 95.5% (95% CI, 95.2-95.8). In fetuses with enlarged nuchal translucency and normal karyotype, there were 30 structural defects (4%), and among these, 15 heart defects (2%). Measurement of nuchal translucency was possible in all cases where it was attempted. In 13 cases (0.1%), it was not possible to determine the visibility of the nasal bone. In 16,486 cases, the nasal bone was defined as visible and in 155 cases (0.9%) the nasal bone was described as absent. The nasal bone was absent in 56 trisomies 21 and in 23 other chromosomopathies, as well as in 76 normal karyotype fetuses. The sensitivity was 58.3% (95% CI, 48.3-67.7) and specificity 99.5% (95% CI, 99.4-99.6). The sensitivity of enlarged nuchal translucency and nasal bone was 80.2% (95% CI, 71.1-86.9). CONCLUSIONS: Enlarged nuchal translucency and absent nasal bone are useful markers of trisomy 21 in the first trimester ultrasound screening, increasing the sensitivity of detection of affected fetuses.

Nuchal translucency measurement at different crown-rump lengths along the 10- to 14-week period for Down syndrome screening.

OBJECTIVES: To evaluate the screening accuracy for Down syndrome of nuchal translucency (NT) measurement at different crown-rump length (CRL) subgroups along the 10- to 14-week period. METHODS: NT was classified 'enlarged' if greater than or equal to 1.5 and 2.0 multiples of the regressed median. Accuracies for Down syndrome (formula=[(TP + TN)/(TP + TN + FP + FN)]x100, where TP: true positive, TN: true negative, FP: false positive, FN: false negative) were evaluated in four classes of CRL: 38-44 mm, 45-54 mm, 55-70 mm, and 71-84 mm, and compared. RESULTS: Of 20 743 fetuses, 20 611 were with no chromosomal abnormalities and 132 were with Down syndrome. Down syndrome fetuses with enlarged NT were 99 (greater than or equal to 1.5 MoM) and 86 (greater than or equal to 2.0 MoM). Sensitivity decreased with gestation, while specificity increased, resulting in increasing likelihood ratios with gestation for each of the CRL groups (8.1, 14.1, 16.3, 17.1 with the use of the 1.5 MoM cut-off, and 13.2, 27.1, 50.1, 84.1 for the 2.0 MoM cut-off). The accuracy increased with gestation (89%, 95%, 95%, 96% with the use of the 1.5 MoM cut-off, and 94%, 97%, 98%, 99% for the 2.0 MoM cut-off, for each of the CRL groups), differences being statistically significant between periods in half of the comparisons. CONCLUSIONS: Although sensitivity of NT assessment for Down syndrome screening decreased as gestation advanced from the 10th to the 14th week, accuracy showed a remarkable increase. These changes should be taken into account in defining and improving the Down syndrome screening policies.

Changes in nuchal translucency thickness in normal and abnormal karyotype fetuses.

OBJECTIVE: To investigate the dynamic trend of the nuchal translucency thickness between fetuses with normal and abnormal karyotype. DESIGN: Prospective observational study. SETTING: Ospedale Microcitemico, Cagliari, Italy. POPULATION: A cohort of 305 first trimester fetuses. METHODS: Fetuses with a nuchal translucency greater than or equal to the 95th centile were invited for a second nuchal translucency measurement. The finding of an 'increased or unchanged' or 'diminished' thickness was compared in fetuses with normal and abnormal karyotype. MAIN OUTCOME MEASURES: Nuchal translucency and karyotype. Median maternal age was 35 years (min 17, max 44) and median crown-rump length at first visit was 50 mm (min 38, max 80). A second nuchal translucency measurement was carried out in 292 fetuses, resulting in increased or unchanged values in 95 cases and decreased nuchal translucency in 197 cases. Two hundred and twenty-six (77.4%) fetuses had normal karyotype and 66 (22.6%) had abnormal karyotype (44 trisomies 21, 10 trisomies 18, 5 trisomies 13, 4 cases of 45 X0, 1 case of 47,XXY, 1 case of 47,XXX and 1 translocation). In the 66 chromosomally abnormal fetuses, the second nuchal translucency measurement was enlarged or unchanged in 37 (56%), and diminished in 29 (44%), while in the 226 normal fetuses the second nuchal translucency measurement was enlarged or unchanged in 58 cases (25%) and diminished in 168 (75%) (relative risk 2.6, 95% confidence interval 1.7-4.0). CONCLUSION: In fetuses with abnormal karyotype, the second nuchal translucency measurement tends to be increased or unchanged, while in normal cases the size of nuchal translucency is generally reduced.

Absence of fetal nasal bone and aneuploidies at first-trimester nuchal translucency screening in unselected pregnancies.

OBJECTIVES: The absence of nasal bone (NB) has been noted in trisomy 21 fetuses at first-trimester ultrasound, in high-risk pregnancies. In this study, the nasal bone was evaluated in relation to fetal karyotype, in unselected pregnancies. METHODS: From September 2001 to September 2002, the fetal facial profile was examined at the 11 to 14 weeks' scan for screening by nuchal translucency (NT). Risks for trisomy 21 were calculated using the Fetal Medicine Foundation's software, and the presence or absence of NB was noted. Prenatal karyotype and pregnancy outcomes were recorded. RESULTS: NT screening was performed in 5532 fetuses from 5425 pregnancies (85 twins, 8 triplets, 2 quadruplets). The visualization of fetal profile was obtained in 5525 fetuses (99.8%), and in 5491 fetuses (99.4%) the NB was present and in 34 cases (0.6%) it was absent. Fetal karyotype and pregnancy outcome were available in 3503 pregnancies, and 40 chromosomal abnormalities were diagnosed (27 trisomies 21, 5 trisomies 18, 2 trisomies 13, 3 Turner syndromes, 1 partial trisomy 9 and 2 others). The NB was absent in 19 (70%) trisomies 21, 4 trisomies 18 (80%), 2 Turner syndromes (66%), in the partial trisomy 9, in 7 normal karyotype fetuses (0.2%), and in a case with spontaneous first-trimester abortion before prenatal diagnosis. A significant difference was found between NT thickness, expressed as a multiple of the median, in trisomy 21 fetuses with present and absent nasal bone. CONCLUSIONS: The absence of NB at 11 to 14 weeks is more frequent in fetuses with trisomy 21 and other aneuploidies than in normal karyotype fetuses.

Neural tube defects in the offspring of thalassemia carriers.

OBJECTIVES: The risk of neural tube defects (NTDs) is negatively correlated with maternal folate levels in early pregnancy. Thalassemia carriers often have reduced red cell folate contents. The aim of this study was to verify whether thalassemia carriers are at increased risk of having offspring with a NTD. METHODS: We retrospectively evaluated the prevalence of thalassemia carriers among 75 women who had prenatal diagnoses of NTDs made at our center. RESULTS: The prevalence of beta-thalassemia carriers among the affected pregnancies was significantly higher than in the general population (22.5 versus 14%, p < 0.05, chi(2) test). CONCLUSION: Although inconclusive, these data indicate that folate supplementation is mandatory among women with thalassemia who are planning a pregnancy.