Biomedical subjects

P Vergani

Publications and source records attributed to P Vergani.

At least 19 recordsLinked to original sources

PubMed2006

Low incidence of hypertensive disorders of pregnancy in women treated with spiramycin for toxoplasma infection.

AIMS: Toxoplasma infection in pregnancy is usually treated with long-term administration of the macrolide spiramycin to prevent fetal malformations. We had empirically observed that treated patients seldom developed pregnancy-induced hypertension (PIH), a common and severe disorder of pregnancy whose aetiology and pathogenesis are still debated. Some clinical and experimental data suggest that infection could play a role in its development. METHODS: To test this hypothesis, we studied a cohort of 417 pregnant women treated with spiramycin because of seroconversion for Toxoplasma gondii and 353 low-risk women who did not take any antibiotic during pregnancy. PIH was defined as blood pressure>140/90 mmHg on two or more occasions, occurring after 20 weeks of gestational age. RESULTS: Seventeen (5.2%) women in the control group developed PIH compared with two (0.5%) in the case group. The odds of developing the disease were significantly lower in the treated subjects (odds ratio=0.092, 95% confidence interval 0.021, 0.399; P<0.001). CONCLUSIONS: Our results suggest that antibiotic treatment during pregnancy can reduce the incidence of PIH, thus opening new perspectives in its prevention and therapy.

Adult↗

PubMed2005

Control of the CFTR channel's gates.

Unique among ABC (ATP-binding cassette) protein family members, CFTR (cystic fibrosis transmembrane conductance regulator), also termed ABCC7, encoded by the gene mutated in cystic fibrosis patients, functions as an ion channel. Opening and closing of its anion-selective pore are linked to ATP binding and hydrolysis at CFTR's two NBDs (nucleotide-binding domains), NBD1 and NBD2. Isolated NBDs of prokaryotic ABC proteins form homodimers upon binding ATP, but separate after hydrolysis of the ATP. By combining mutagenesis with single-channel recording and nucleotide photolabelling on intact CFTR molecules, we relate opening and closing of the channel gates to ATP-mediated events in the NBDs. In particular, we demonstrate that two CFTR residues, predicted to lie on opposite sides of its anticipated NBD1-NBD2 heterodimer interface, are energetically coupled when the channels open but are independent of each other in closed channels. This directly links ATP-driven tight dimerization of CFTR's cytoplasmic NBDs to opening of the ion channel in the transmembrane domains. Evolutionary conservation of the energetically coupled residues in a manner that preserves their ability to form a hydrogen bond argues that this molecular mechanism, involving dynamic restructuring of the NBD dimer interface, is shared by all members of the ABC protein superfamily.

ATP-Binding Cassette Transporters↗

PubMed2001

Can a cyclo-oxygenase type-2 selective tocolytic agent avoid the fetal side effects of indomethacin?

We evaluated the efficacy and safety of nimesulide (100 mg orally twice daily for > 48 hours) in a pilot series of five women (two with twin pregnancies) at 24(+6) weeks (range 21(+3) - 27(+2)) in preterm labour which was unresponsive to intravenous ritodrine. Nimesulide therapy was continued for eight days (5-16) and was associated with a prolongation of pregnancy of 27 days (6-69). Oligohydramnios occurred in all seven fetuses after three to nine days of therapy, and in the five pregnancies that continued after discontinuation of nimesulide, it resolved within four days (2-7). None of the babies manifested permanent renal damage.

Administration, Oral↗

PubMed2000

Isolated fetal choroid plexus cysts: role of ultrasonography in establishment of the risk of trisomy 18.

OBJECTIVE: The significance of isolated choroid plexus cysts found by ultrasonographic scan during the second trimester as a marker for trisomy 18 is still debated. We analyzed our data and reviewed the series published in the English-language literature to calculate the likelihood ratio of trisomy 18 in the presence of isolated choroid plexus cysts; that is, the factor by which the individual risk of trisomy 18 is increased in the presence of isolated choroid plexus cysts. STUDY DESIGN: Likelihood ratios were calculated as ratio of the sensitivity to the false-positive rate. Sensitivity was defined as the rate of isolated choroid plexus cysts detected at midgestation among fetuses with trisomy 18. False-positive rate was defined as the rate of choroid plexus cysts detected at midgestation in the population without trisomy 18. The sensitivities of all published series reporting rates of choroid plexus cysts at the time of the first ultrasonographic examination between 14 and 24 weeks' gestation in populations with trisomy 18 and in low-risk populations were included in the analysis. To these we added all cases of trisomy 18 diagnosed at our institution during the period January 1, 1988, through June 30, 1998, in which prenatal ultrasonographic examination was performed between 14 and 24 weeks' gestation. RESULTS: The prevalence of second-trimester ultrasonographic detection of isolated choroid plexus cysts among fetuses with trisomy 18 was 6.7% (13/194), whereas that in the population without trisomy 18 was 0.9% (752/79,583). The likelihood ratio associated with isolated choroid plexus cysts was therefore 7.09 (95% confidence interval, 3.97-12.18). CONCLUSION: The presence of isolated second-trimester choroid plexus cysts increases the base risk of trisomy 18 by a factor of 7.09. This likelihood ratio can be multiplied by the risk calculated according to maternal age to obtain the individual risk of trisomy 18 and thus permit more accurate counseling of the patient.

Adult↗

PubMed2000

Critical appraisal of the use of nuchal fold thickness measurements for the prediction of Down syndrome.

OBJECTIVE: Nuchal fold thickness is the best ultrasonographic predictor of fetal trisomy 21. However, the risk assigned on the basis of the commonly used threshold of nuchal fold thickness >/=6 mm does not take into consideration the significant associations between nuchal fold thickness and gestational age and between maternal age and Down syndrome. We propose a new method of calculating Down syndrome probability that takes into account both gestational age at examination and previously assessed probability of Down syndrome. STUDY DESIGN: Nuchal fold thickness was measured at ultrasonographic examination at 14 to 22 weeks' gestation without previous knowledge of the fetal karyotype. Nuchal cystic hygromas were excluded from analysis. Statistical analyses included correlation, logistic regression to control for other ultrasonographic predictors of trisomy 21 and for maternal age, receiver operating characteristic curve, and likelihood ratios (defined as the ratio of the sensitivity to the false-positive rate). P <.05 was considered significant. RESULTS: Mean gestational age at ultrasonography was 16.9 weeks' gestation (range, 14-22 weeks' gestation). Mean (+/-SD) nuchal fold thickness in fetuses with trisomy 21 (4.7 +/- 1.6 mm; n = 29) was greater than in euploid fetuses (3.2 +/- 0.9; n = 780; P <.001). Logistic regression analysis established that nuchal fold thickness was a significant predictor of trisomy 21 independent both of the other ultrasonographic markers and of maternal age (P <.001). Regression analysis showed that nuchal fold thickness was significantly correlated with gestational age among both fetuses with trisomy 21 and euploid fetuses and that the regression line of fetuses with trisomy 21 had a slope similar to that of euploid fetuses. The difference between observed and expected nuchal fold thicknesses on the basis of the biparietal diameter (as a function of gestational age) was used to obviate the confounding effect of gestational age. Differences between observed and expected nuchal fold thicknesses were then used to calculate likelihood ratios. These likelihood ratios could then be multiplied by the individual prior probability to obtain a patient-specific Down syndrome probability. CONCLUSION: Nuchal fold thickness is correlated with gestational age in both euploid fetuses and fetuses with Down syndrome. Use of the difference between observed and expected nuchal fold thicknesses to determine likelihood ratios allows the calculation of individual posterior probabilities of Down syndrome that take into consideration both gestational age and maternal age.

Adult↗

PubMed2000

Risk factors for neonatal intraventricular haemorrhage in spontaneous prematurity at 32 weeks gestation or less.

In this study we aimed to establish which clinical and histopathological factors are associated with early-onset neonatal intraventricular haemorrhage (IVH) in non-iatrogenic preterm delivery before 32 weeks of gestation. We retrospectively reviewed all singleton pregnancies delivered before 32 weeks of gestation after spontaneous onset of preterm labour or preterm membrane rupture during the period January 1993 to June 1997. Clinical and histopathological data in cases with IVH diagnosed at neonatal cranial ultrasound within 72 h of birth (n = 17) were compared with those of neonates not experiencing this complication (non-IVH) (n = 54). Histological lesions analysed were those of acute inflammation and those on a uteroplacental vascular basis. Statistical methods included the Wilcoxon rank sum test, Fisher's exact test, and logistic regression analysis. A P<0.05 was considered significant.IVH and non-IVH groups were not significantly different in birthweight, gestational age at delivery, cord pH at birth, rates of 5-min Apgar score below 7, caesarean delivery, diagnosis of clinical chorioamnionitis or antenatal administration of steroids. Respiratory distress syndrome was more frequently diagnosed in the IVH than non-IVH group (64 per cent versus 33 per cent, P=0.02). Placental acute inflammatory or uteroplacental vascular lesions were present in 100 per cent of IVH neonates versus 22 per cent of non-IVH cases (P<0.001). Logistic regression analysis demonstrated that only respiratory distress syndrome (P = 0.04) and histological evidence of acute placental inflammation (P = 0.02) were significantly and independently associated with IVH. Histopathological evidence of acute inflammatory placental lesions is the best predictor of occurrence of neonatal IVH.

Adult↗

PubMed2000

Role of amnioinfusion in the management of premature rupture of the membranes at <26 weeks' gestation.

OBJECTIVE: We sought to evaluate whether serial amnioinfusions for persistent oligohydramnios can affect the perinatal and long-term outcomes in extreme cases of preterm premature rupture of membranes. STUDY DESIGN: All singleton pregnancies with preterm premature rupture of membranes at <26 weeks' gestation and lasting >4 days between January 1991 and June 1998 were included. Amniotic fluid volume was assessed as the maximum cord-free pocket with serial ultrasonographic examinations. Consenting women with persistent (>4 days) oligohydramnios (amniotic fluid </=2 cm) received serial transabdominal amnioinfusions to maintain an amniotic fluid pocket >2 cm. The pregnancy, neonatal, and long-term neurologic outcomes of the cases that spontaneously maintained a median amniotic fluid pocket >2 cm (amnioinfusion-not-necessary group) were compared with those of women with oligohydramnios who underwent amnioinfusion but continued to have a median amniotic fluid pocket after preterm premature rupture of membranes </=2 cm (persistent oligohydramnios group) and with those of women in whom oligohydramnios was alleviated by the procedure for at least 48 hours (successful amnioinfusion group). Statistical analysis included the Wilcoxon rank-sum test and the Fisher exact test, with a 2-tailed P <.05 considered significant. RESULTS: Among the 49 women included in the study, 13 (26.5%) did not have oligohydramnios, the neonatal survival rate was 92%, and normal fetal lung development and neurologic outcome were achieved in all survivors. The remaining 36 women had oligohydramnios, and all underwent serial amnioinfusions, which successfully restored a median amniotic fluid pocket >2 cm for >/=48 hours in 11 (30%) patients. This successful amnioinfusion group was comparable with the persistent oligohydramnios group (n = 25) in gestational age at first amnioinfusion (median, 20.2 weeks; range, 16-25.6 weeks; vs median, 20.3 weeks; range, 16.5-24.2 weeks; P =.4), number of amnioinfusions (median, 3; range, 1-9; vs median, 3; range, 1-5; P =.4), and interval between amnioinfusions (median, 6 days; range, 4-14 days; vs median, 8 days; range, 6-43 days; P =. 1). However, patients in the persistent oligohydramnios group had a significantly shorter interval to delivery, lower neonatal survival (20%), and higher rates of pulmonary hypoplasia (62%) and abnormal neurologic outcomes (60%) than the patients in the groups in which amnioinfusion was not necessary or was successful (all P </=.01). CONCLUSION: Pregnancies with preterm premature rupture of membranes-related oligohydramnios at <26 weeks' gestation in which serial amnioinfusions successfully alleviate oligohydramnios have a perinatal outcome that is significantly better than the outcome in those with persistent oligohydramnios and is comparable with gestations with preterm premature rupture of membranes in which oligohydramnios never develops.

Adult↗

PubMed2000

Critical reappraisal of the utility of sonographic fetal femur length in the prediction of trisomy 21.

Measurement of femur length (FL) has been advocated as part of a genetic sonogram for the prediction of Down syndrome (DS). However its predictive ability has been inconsistent. We have studied the diagnostic value of this sonographic parameter in a prospective cohort of women with singleton gestations undergoing genetic sonogram between 14 and 22 weeks because of advanced maternal age or family history of aneuploidies. Genetic sonograms were performed at a mean gestational age of 17.0 weeks (range 14-22). DS was diagnosed in 30 fetuses, while 888 were euploid. Mean+/-SD observed/expected (O/E) values of FL (1.00+/-0.10 versus 0.97+/-0.01, p=0.07) were not significantly different between euploid and DS fetuses. Comparison of the regression equations of FL versus biparietal diameter revealed that while the intercepts were not significantly different between euploid and DS fetuses, the difference in slopes reached significance (p=0.04) suggesting that the predictive ability of FL may increase with advancing gestational age. In addition, a MEDLINE search (National Library of Medicine) was conducted for articles published between 1985 and 1998 on fetal femur length in the prediction of trisomy 21. Review of the published literature on the subject suggests that FL is not a consistent or reliable sonographic predictor of DS. Published thresholds of FL should not be used outside of the Institution from which they originated, and each Institution should establish whether this parameter has predictive ability in its own population.

Adult↗

PubMed1999

Mutations in the yeast two pore K+ channel YKC1 identify functional differences between the pore domains.

The K+ channel of Saccharomyces cerevisiae encoded by the YKC1 gene includes two pore-loop sequences that are thought to form the hydrophilic lining of the pore. Gating of the channel is promoted by membrane depolarisation and is regulated by the extracellular K+ concentration ([K+]o) both in the yeast and when expressed in Xenopus oocytes. Our previous work showed that substitutions of equivalent residues L293 and A428 within the pore-loops had qualitatively similar effects on both the [K+]o-sensitivity of channel gating and its voltage-dependence. Here, we report that mutations of equivalent residues N275 and N410, N-terminal from the K+ channel signature sequences of the two pores, have very different actions on channel gating and, in this case, are without effect on its voltage-sensitivity. The mutation N410D slowed current activation in a [K+]o-dependent manner and it accelerated deactivation, but without significant effect on the apparent affinity for K+. The N275D mutant, by contrast, had little effect on the [K+]o-sensitivity for activation and it greatly altered the. [K+]o-dependence of current deactivation. Neither mutant affected the voltage-dependence of the steady-state current nor the ability for other alkali cations to substitute for K+ in regulating gating. The double mutant N410D-N275D showed characteristics of N410D in the [K+]o-sensitivity of current activation and of N275D in the [K+]o-sensitivity of deactivation, suggesting that little interaction occurs between pore domains with mutations at these sites. The results indicate that the two pore domains are not functionally equivalent and they suggest that the regulation of gating by external K+ is mediated by K+ binding at two physically distinct sites with different actions.

Animals↗

PubMed1999

Ultrasonographic differential diagnosis of fetal intracranial interhemispheric cysts.

OBJECTIVE: Ultrasonographic differentiation between intracranial supratentorial interhemispheric pathologic cystlike lesions and those related to physiologic median structures is essential because the latter have no clinical relevance, whereas the former may carry a poor prognosis. We reviewed our experience with 19 consecutive cases of interhemispheric hypoechoic lesions without parenchymal involvement diagnosed between January 1990 and June 1997 to establish their clinical significance and provide prenatal ultrasonographic criteria to distinguish between pathologic cystlike lesions and those related to physiologic midline structures. STUDY DESIGN: All patients underwent targeted prenatal scans of intracranial anatomy to establish the relationship between the fluid collections and the surrounding parenchymal and ventricular structures. In addition, a detailed anatomic survey was performed to rule out associated malformations. Follow-up, including neurologic examination, imaging, autopsy evaluation, or a combination was performed in all cases. Statistical analysis used the Wilcoxon rank sum test, the Fisher exact test, and the chi2 test for trend. P <.05 was considered significant. RESULTS: Cystlike lesions related to physiologic median structures (n = 12) included enlargement of the cavum septi pellucidi (n = 3), enlargement of the cavum vergae (n = 2), and cysts of the velum interpositum (n = 7). These lesions were unilocular and had a median size of 10 mm (range 10-30 mm); they resolved in 5 cases and remained stable in the remainder. They were not associated with overt abnormalities, other than borderline ventriculomegaly in 2 cases. Pediatric follow-up (median 26 months, range 3-84 months) showed normal neurodevelopment in all cases. Pathologic cystlike lesions (n = 7) were significantly larger (median 40 mm, range 10-80 mm, P =.004) and had a significantly worsening trend, growing more at serial prenatal ultrasonographic examinations (P =.039) than fluid collections related to physiologic median structures. Moreover, prenatal ultrasonographic evidence of associated intracranial abnormalities, in the form of partial or total agenesis of the corpus callosum and overt hydrocephalus, was present in 5 of 7 cases of pathologic cystlike lesions and in none of the 12 related to physiologic structures (P =.002). Median gestational age at diagnosis was not different between those with cystlike lesions related to physiologic median structures and those with pathologic lesions (30 and 31 weeks, respectively). Among the latter group, 1 pregnancy was voluntarily terminated, 1 infant died at 4 months of age, 2 infants had neurodevelopmental delay, and 3 infants were neurologically healthy at a mean follow-up of 43 months. Cyst shunting was necessary in 5 of 6 cases. CONCLUSIONS: Interhemispheric cystlike lesions related to physiologic structures can be prenatally distinguished from pathologic fluid collections on the basis of location, cyst size, change in size with time, and absence of associated anomalies.

Brain Diseases↗

PubMed1999

Amnioreduction in emergency cerclage with prolapsed membranes: comparison of two methods for reducing the membranes.

To evaluate the effectiveness of amnioreduction in pregnancies requiring emergency cerclage placement, we performed a retrospective case-control study of all consecutive pregnant women with cervical dilation and effacement with prolapse of the fetal membranes in vagina between 16 and 26 weeks' gestation, who required placement of a McDonald emergency cerclage during the period January 1991-December 1997. Duration of pregnancy prolongation, rate of delivery before 32 weeks, and duration of neonatal hospital stay were compared between women in whom amniochorionic membranes were reduced at the time of cerclage placement using only intracervical Foley balloon catheter (controls; n = 7) and those who in addition underwent amnioreduction to facilitate cerclage placement (n = 9). Statistical analysis utilized Fisher's exact test and Wilcoxon rank sum test. A p value <0.05 was considered significant. There were no procedure-related ruptures of membranes. Gestational age at cerclage and rate of positive cervico-vaginal cultures were not different between the two groups. Gestation was prolonged for a median of 100 days (range 4 to 144 days) in the amnioreduction group and 10 days (2 to 133) among controls (p = 0.3). The rate of delivery before 32 weeks was significantly lower (1/7 vs. 6/8, p = 0.03) and the duration of neonatal hospital admission significantly shorter (median 3 vs. 37 days, p = 0.001) in the amnioreduction group than among controls. The amount of amniotic fluid withdrawn ranged from 220 to 340 mL. These findings suggest that amnioreduction at the time of emergency cerclage placement is associated with a lower rate of extreme prematurity and related neonatal morbidity.

Adult↗

PubMed1999

Hepatitis C virus infection is associated with a higher incidence of cholestasis of pregnancy.

To investigate a possible relationship between hepatitis C virus infection and cholestasis of pregnancy, we identified all cases of cholestasis of pregnancy (145/16,271) and hepatitis C virus infection (63/16,271) between January 1992 and December 1997. Serologic screening was performed universally. The rate of cholestasis of pregnancy was greater in women whose hepatitis C virus antibodies were positive rather than negative [15.9% (10/63) vs 0.8% (135/16,208), P < 0.001]. Among women with cholestasis of pregnancy, mean (standard deviation) gestational age at onset of symptoms and at delivery was significantly lower among women whose hepatitis C virus antibodies were positive compared with negative women: 28.9 (3.2) vs 34.3 (3.5) weeks, P < 0.001 and 36.3 (0.9) vs 37.0 (1.6) weeks, P = 0.03, respectively. These findings suggest that early occurrence of cholestasis of pregnancy may be an indication for serologic testing for hepatitis C virus.

Cholestasis↗

PubMed1999

Accuracy of prenatal ultrasonographic diagnosis of duplex renal system.

Duplex renal system is a rare congenital anomaly of the urinary tract that can be diagnosed in utero. The purpose of this study was to establish the optimal diagnostic criteria for fetal renal duplication in a population undergoing prenatal sonographic screening. Between January 1989 and June 1997 we found 11 cases of duplex renal system, 10 of which were correctly identified in utero at a median gestational age of 28 weeks (range, 20 to 38 weeks), and one of which was a false-negative diagnosis. Prenatal diagnosis of duplex renal system can be made in utero during the second half of pregnancy in the presence of two or more of the following signs: hydronephrosis limited to one pole in a kidney with two separate, noncommunicating renal pelves; ipsilateral megaureter; and ureterocele.

Female↗

PubMed1999

Best second trimester sonographic markers for the detection of trisomy 21.

We analyzed all genetic sonograms obtained during a 6 year period to establish the independent ability of the following sonographic markers of aneuploidy in the diagnosis of trisomy 21: structural anomalies, cardiac abnormalities, nuchal fold thickness of 6 mm or greater, bowel echogenicity, choroid plexus cysts, and renal pyelectasis. With the exception of bowel echogenicity and choroid plexus cysts, the sonographic markers were more common in trisomy 21 than euploid fetuses (all P < 0.001). Logistic regression analysis demonstrated that cardiac anomalies (odds ratio = 255; 95% confidence interval, 25, 2592), other structural anomalies (odds ratio = 25; 95% confidence interval, 6, 97), and nuchal fold thickness of 6 mm or greater (odds ratio = 13; 95% confidence interval, 3, 50) were the only independent predictors of trisomy 21. The false-positive rate and sensitivity were 5.3% (48 of 898) and 59.2% (13 of 22), respectively, when any of the sonographic markers significant at univariate analysis was considered, and 3.1% (28 of 898) and 54.5% (12 of 22), respectively, when any of the predictors at multivariate analysis was present. Because a considerable overlap of sonographic markers exists among trisomy 21 fetuses, use of those that are not independent predictors leads to an increase in false-positive rate without a gain in sensitivity.

Adult↗

PubMed1998

Mutations in the pore regions of the yeast K+ channel YKC1 affect gating by extracellular K+.

The product of the Saccharomyces cerevisiae K+-channel gene YKC1 includes two pore-loop sequences that are thought to form the hydrophilic lining of the pore. Gating of the channel is promoted by membrane depolarization and is regulated by extracellular K+ concentration ([K+]o) both in the yeast and when expressed in Xenopus oocytes. Analysis of the wild-type current now shows that: (i) [K+]o suppresses a very slowly relaxing component, accelerating activation; (ii) [K+]o slows deactivation in a dose-dependent fashion; and (iii) Rb+, Cs+ and, to a lesser extent, Na+ substitute for K+ in its action on gating. We have identified single residues, L293 and A428, at equivalent positions within the two pore loops that affect the [K+]o sensitivity. Substitution of these residues gave channels with reduced sensitivity to [K+]o in macroscopic current kinetics and voltage dependence, but had only minor effects on selectivity among alkali cations in gating and on single-channel conductance. In some mutants, activation was slowed sufficiently to confer a sigmoidicity to current rise at low [K+]o. The results indicate that these residues are involved in [K+]o sensing. Their situation close to the permeation pathway points to an interaction between gating and permeation.

Cations, Monovalent↗

PubMed1998

Clinical outcome of mild fetal ventriculomegaly.

OBJECTIVE: Our purpose was to evaluate the outcome of fetuses with mild cerebral ventriculomegaly. STUDY DESIGN: We prospectively collected all cases of mild cerebral ventriculomegaly (transverse diameter of the atrium of the cerebral lateral ventricles between 10 and 15 mm) diagnosed antenatally between January 1990 and December 1996. Associated ultrasonographic abnormalities including markers of aneuploidy, presence of chromosomal anomalies, structural malformations detected at birth, and neurologic outcome were recorded. Outcome information was available on all cases. In addition, published series of cases of fetal mild cerebral ventriculomegaly were reviewed to identify prognostic indicators. RESULTS: Eighty-two cases fulfilled the inclusion criteria: 48 were isolated and 34 were associated with other ultrasonographic markers or anomalies. Among the 45 surviving euploid isolated cases, neurologic follow-up was normal at a mean age of 28 months (range 3 to 72 months). Male fetuses and those with a transverse atrial size <12 mm had a good prognosis. Ventricular atria > or =12 mm were more often associated with other anomalies (56% vs 6%) and, when isolated, with abnormal postnatal neurodevelopment (23% vs 3%). Aneuploidy was present in two cases of isolated mild cerebral ventriculomegaly, both of which were associated with advanced maternal age, and in seven cases associated with other anomalies. CONCLUSIONS: Mild cerebral ventriculomegaly should prompt targeted ultrasonographic examination, inclusive of markers of aneuploidies, visualization of the corpus callosum, and echocardiogram as well as serologic evaluation for congenital infections. In isolated mild cerebral ventriculomegaly genetic counseling should take into account clinical, laboratory, and ultrasonographic findings. A review of the published series suggests that cognitive or motor delay is predominantly mild and that it occurs in about 9% of cases of isolated mild cerebral ventriculomegaly.

Adult↗

PubMed1998

Congenital toxoplasmosis: efficacy of maternal treatment with spiramycin alone.

PROBLEM: The evidence supporting an additional benefit of a combined regimen of pyrimethamine-sulfonamides compared with spiramycin alone in the secondary prevention of congenital toxoplasmosis was critically evaluated. METHOD OF STUDY: We reviewed the series of cases published in the English literature on antiparasitic treatment of acute toxoplasmosis infection in pregnancy, using spiramycin until fetal infection is documented, then using cycles of spiramycin alternated with combined pyrimethamine-sulfonamide therapy. We then compared the occurrence of overt disease among infected offspring (both severe, represented by ophthalmologic or cerebral abnormalities, and mild occurrences, represented by asymptomatic intracranial calcifications and retinal scars without visual impairment) between the published case series and our consecutive series of cases treated during a 10-year period (January 1986-December 1995) with spiramycin alone. RESULTS: The prevalence of fetal infection in our series was 7.8% (12/154), similar to that reported after alternated regimens (7.0%). The rate of overt disease among infected fetuses is not different after treatment with alternated regimens than after continuous antibiotic spiramycin therapy [23% (19/82) vs. 10% (1/10); relative risk, 2.3; 95% confidence interval, 0.4, 47.0]. The pharmacokinetics of the drugs used may account for this finding. CONCLUSION: The treatment of acute toxoplasmosis in pregnancy with an alternated antibiotic regimen of pyrimethamine-sulfonamide is not more efficacious at preventing overt neonatal disease than treatment with continuous spiramycin alone.

Anti-Infective Agents↗

PubMed1997

Extracellular K+ and Ba2+ mediate voltage-dependent inactivation of the outward-rectifying K+ channel encoded by the yeast gene TOK1.

Gating of the yeast K+ channel encoded by the Saccharomyces cerevisiae gene TOK1, unlike other outward-rectifying K+ channels that have been cloned, is promoted by membrane voltage (inside positive-going) and repressed by extracellular K+. When expressed in Xenopus laevis oocytes, the TOK1p current rectified strongly outward, its activation shifting in parallel with the K+ equilibrium potential when the external K+ concentration ([K+]o) was increased above 3 mM. Analysis of the TOK1p current indicated that two kinetic components contributed to the conductance and the voltage sensitivity of the conductance. By contrast, the [K+]o sensitivity of the current was accommodated entirely within the slow-relaxing component; it was diminished near 1 mM [K+]o, and at submillimolar concentrations the voltage dependence of the TOK1p conductance was insensitive to [K+]o. External Rb+, the K+ channel blockers Cs+ and Ba2+--but not Na+, Ca2+ or Mg2+--substituted for K+ in control of TOK1p activation, indicating a specificity in cation interaction with the TOK1p gate. These and additional results indicate that external K+ acts as a ligand to inactivate the TOK1p channel, and they implicate a gating process mediated by a single cation binding site within the membrane electric field, but distinct from the permeation pathway.

Animals↗