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Biomedical subjects

A Locatelli

Publications and source records attributed to A Locatelli.

At least 37 records · Page 2Linked to original sources

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↗

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↗

4-Aminopyridine derivatives with antiamnesic activity.

Acetylcholine (Ach) enhancement, useful in the treatment of Alzheimer's disease (AD), may be obtained by means of ion channel modulators such as 4-aminopyridine (4-AP). 4-AP is also the central ring of tacrine, the first drug approved for the treatment of AD. The synthesis and pharmacological activity of three 4-AP derivatives, prepared with the aim of improving their antiamnesic activity, is here described. In two of these compounds 4-AP is connected to 4-aminobutyric acid (GABA), whereas in the third it is connected to 2-indolinone, i.e., the skeleton of linopirdine, another Ach enhancing agent. The new compounds showed potent antiamnesic activity in comparison with piracetam.

4-Aminopyridine↗

Potential antitumor agents. Part 29(1): synthesis and potential coanthracyclinic activity of imidazo[2,1-b]thiazole guanylhydrazones.

This paper reports the synthesis of new imidazo[2,1-b]thiazole guanylhydrazones which were tested as potential antitumor agents. Three of these derivatives (those bearing a 3- or 4-nitrophenyl group) were the most potent and one of these showed a mild effect as CDK1 inhibitor. These same three derivatives were also tested as positive inotropic agents and two of them were more potent than amrinone at 10(-5) M. These two guanylhydrazones could be useful coanthracyclinic agents.

Animals↗

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↗

Evidence that luteinizing hormone-releasing hormone statin from ovine rete testis fluid is immunologically related to alphaC inhibin.

LHRH Statin is a putative gonadal protein that increases the interval between two consecutive LHRH pulses. The present work was aimed at analyzing the immunological homology between LHRH Statin and the N-terminal region of the alphaC subunit of inhibin. Thus, rete testis fluid (RTF) proteins were purified by immunoaffinity chromatography using antibodies against residues 1-7 plus 7-30 (experiment 1, A-fractions) and 14-28 of the alphaC inhibin subunit (experiment 2, B-fractions), and the LHRH Statin activity of the fractions was examined by intracerebroventricular administration in castrated rams followed by RIA of plasma LH levels in 15-min blood samples. Fractions that bound to the immunoaffinity column with low affinity were eluted with 0.5 M NaCl, pH 7.4 (-F2); then highly bound fractions were eluted sequentially in acidic (pH 2.5, -F3) followed by basic conditions (pH 11.5, -F4). In experiment 1, RTF (40 microg, n = 4) and highly bound fractions (A-F3, 30 ng, n = 8, 150 ng, n = 3; A-F4, 120 ng, n = 5) decreased LH mean plasma levels between 4 and 6 h after injection by 39%, 29%, 43%, and 37%, respectively (P<0.001 to 0.01), while the weakly bound fractions (A-F2, 180 ng, n = 4) and albumin control (40 microg, n = 4) had no activity. In experiment 2, RTF (100 microg, n = 4) and B-F3 (100 ng, n = 3) decreased plasma LH levels by 48% and 38%, respectively (P<0.001 to 0.05), whereas B-F4 (100 ng, n = 4) and albumin control (100 microg, n = 4) had no effect. A fraction obtained from B-F3 by gel filtration had significant LHRH Statin activity (63%, n = 6, P<0.001). PAGE with colloidal gold staining revealed 3 high molecular weight bands and 5 low molecular weight bands in B-F3. The 3 high molecular weight bands were shown to belong to the clusterin family and did not appear to have LHRH Statin activity. The 5 low molecular weight bands were all labeled by anti-alphaC inhibin antibodies. Collectively, these results strongly suggest that LHRH Statin has some homology with the 14-28 alphaC inhibin sequence.

Animals↗

Stallion epididymal fluid proteome: qualitative and quantitative characterization; secretion and dynamic changes of major proteins.

Proteins present in and secreted into the lumen of various regions of the stallion epididymis were characterized qualitatively and quantitatively by two-dimensional electrophoresis. Using this proteomic approach, 201 proteins were found in the lumen and 117 were found that were secreted by the epithelium in various parts of the organ. Eighteen proteins made up 92.6% of the total epididymal secretory activity, lactoferrin (41.2%) and clusterin (24.8%) being the most abundant. Procathepsin D, HE1/CTP (cholesterol transfer protein), GPX (glutathione peroxidase), beta-N-acetyl-hexosaminidase, and PGDS (prostaglandin D2 synthase) were the other major compounds secreted. The most abundant proteins found in the luminal fluid were albumin and the secreted proteins: lactoferrin, PGDS, GPX, HE1/CTP, and hexosaminidase. Three main secretory epididymal regions were identified from the protein pattern, i.e., regions E0-E2, E3-E5, and E6-E9. Region E0-E2 was characterized by the secretion of clusterin (53%), PGDS (44%), and GPX (6%). Region E3-E5 had the highest number of secreted proteins, the highest protein concentrations (60-80 mg/ml), and the highest spermatocrit value (85%). Lactoferrin (60% in E4), clusterin (29% in E3), hexosaminidase (10% in E3), and procathepsin D (6.9% in E4) were the most abundant proteins in this region. Region E6-E9, in which few region-specific secreted compounds were found, was characterized by a high quantity of lactoferrin in the luminal fluid (2-14 mg/ml). Comparison between the secretion of the major proteins and their concentrations in the lumen throughout the organ showed that the behavior of each protein is specific, in particular for the three isoforms of clusterin.

Amino Acid Sequence↗

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↗

[Risk factors and neonatal outcomes in shoulder dystocia].

BACKGROUND: Shoulder dystocia (SD) is a rare obstetrical complication but linked with a high perinatal morbidity and mortality rate. SD has been associated to a series of maternal and fetal risk factors due to a multifactorial etiology. This study analyzes the incidence of SD, its morbidity and associated risk factors. METHODS: Cases of SD occurred at the St. Gerardo Hospital (Monza) between January 1992 trough December 1997 have been retrospectively reviewed. Obstetrical and feto-neonatal data regarding cases of SD were compared to data regarding all the cephalic vaginal deliveries occurred in the same period in our Center. RESULTS: A total of 14,157 cephalic vaginal deliveries were included in this study, of these 21 infants (0.15%) had SD. A significantly higher incidence of SD cases was found in fetal macrosomia, maternal diabetes, induction of labor by PGE2, use of obstetrical vacuum, length of first stage of labor > 4 hours in multiparas and > 8 hours in nulliparas, and length of second stage > 60 minutes, regardless of parity. A closed association was also observed between SD and birth trauma as brachial plexus injury and humerus fracture. CONCLUSION: The incidence of SD in our population (0.15%) is below the average reported in the literature (0.37-1.1%). The well-known risk factors, whose low positive predictive value can nevertheless modify obstetrical management, are confirmed.

Algorithms↗

Monitoring aspects during port-access cardiac surgery.

OBJECTIVE: To report the experience gained at our Cardiosurgical Centre with the recently introduced port-access technique. METHODS EXPERIMENTAL DESIGN: Prospective collection of data from the month of October 1997. SETTING: Regional University HospitaL Patients: Adult patients undergoing coronary bypass graft or mitral valve surgery. INTERVENTIONS: Port-access technique makes it possible to carry out open-heart procedures through a minithoracotomy and extrathoracic cardiopulmonary bypass with a set of properly designed catheters (Heartport EndoCPB system) for cardioplegia delivery and heart venting. MEASURES: Transesophageal echography and pressure traces are the main monitoring tools used for the correct placement of these catheters and for the clinical management of the patient. RESULTS: Sixty-two cases have been performed so far. A complete description of the procedure, with monitoring aspects and problems encountered is thoroughly presented. CONCLUSIONS: The major differences with traditional cardiac surgery are that interruption of myocardial perfusion is not achieved through a transversal clamp but through an endovascular occlusive balloon and that thoracic access is by minithoracotomy. Unlike traditional open surgery, the surgeon has no direct vision of the position of the clamp and the anesthesiologist can not visually inspect the contractile state of the heart. The operative team has to cope with a multifaceted system of monitored variables that must be continuously integrated and interpreted. Tight cooperation and continuous communication between anaesthesiologist, surgeons and perfusionist appear to be more important than in any other cardiac operation.

Adult↗

Imidazo[2,1 -b]thiazolylmethylene- and indolylmethylene-2-indolinones: a new class of cyclin-dependent kinase inhibitors. Design, synthesis, and CDK1/cyclin B inhibition.

Compounds containing a 2-indolinone moiety linked to imidazothiazole and indole fragments were studied as cyclin-dependent kinase inhibitors. The activity of all the new derivatives was tested in vitro against CDK1/cyclinB and the selectivity towards two other kinases was determined for the most promising compounds. The binding mode of one representative compound was investigated by means of a three-dimensional model of the inhibitor-CDK1 complex. The work allowed us to identify (2-chloroindolyl)methylene-2-indolinone as a new lead of a class of CDK1/cyclinB inhibitors, whose potency can be improved by the introduction of suitable variations on the basic molecular skeleton.

Binding Sites↗

Intracerebroventricular administration of copper-zinc superoxide dismutase inhibits pulsatile luteinizing hormone secretion in ovariectomized ewes.

Intracerebroventricular (i.c.v.) injection of an inhibitor of nitric oxide synthase (NOS) abolishes pulsatile luteinizing hormone (LH) secretion. It has been demonstrated that structural and functional analogs of copper-zinc superoxide dismutase (Cu,Zn-SOD) inhibit neuronal NOS. The present study examined the ability of Cu,Zn-SOD to affect pulsatile LH release in the ewe. Bovine Cu,Zn-SOD was administrated into the third cerebral ventricle of unanesthetized, freely moving, ovariectomized (OVX) ewes. Jugular blood samples were taken every 15 min for 5 h before and 8 h after i.c.v. injections. In a pilot trial using three OVX ewes, i.c.v. injection of Cu,Zn-SOD at a dose of 0.5, 1.0 or 2.0 microg in 100 microl saline decreased plasma LH levels and abolished LH pulses, without affecting FSH secretion. In the main experiment, i.c.v. injection of 100 microl saline had no effect on mean LH levels and LH pulse frequency, whereas i.c.v. injection of Cu,Zn-SOD at a dose of 1 microg/100 microl saline significantly (P < 0.01) decreased mean LH levels and LH pulse frequency. In conclusion, this study provides the first evidence for the role of Cn,Zn-SOD in the control of LH secretion at the level of the brain in female mammals.

Animals↗

The xenotransplantation of goat and human hematopoietic cells to sheep fetuses.

Hematopoietic xenografts were carried out in three experiments using goat fetal liver (44-48 days, experiments I and II) or purified human CD 34+ cells (experiment III) as the donor cells. Recipients were sheep fetuses at 41-47 days of gestation. Goat fetal liver cells were either injected without any pretreatment or stimulated by preincubation in a culturing in goat phytohemagglutinin-stimulated lymphocyte supernatant. Human CD 34+ myeloid progenitor cells were purified from bone marrow by minimacs immunomagnetic purification and cultured in medium supplemented with stem cell factor, IL3, and IL6. Goat-sheep chimerism was assessed by flow cytometry analysis (FCA) of peripheral blood and bone marrow cells using a mouse anti-goat CD 45 monoclonal antibody and by karyotype analysis of peripheral blood from goat/sheep chimeras. Human cell engraftment was assessed by polymerase chain reaction amplification of the human DAX1 gene in blood and bone marrow DNA from sheep which had received human cells. In the three experiments, a mean of 76% (26 of 34) of injected fetuses were born alive without any clinical evidence of graft-versus-host disease. Three lambs were found to be goat/sheep chimeric after flow cytometry analysis (peripheral blood and bone marrow) and karyotype (peripheral blood) analysis. Both tissues continued to express goat cells at 6 or 12 months (last assessment) depending on the experiment. No human chimerism was detected using polymerase chain reaction amplification in peripheral blood and bone marrow of any of the six sheep grafted with human cells. These data and those also obtained on other species (human, pig/sheep) show that it is possible to carry out hematopoietic xenografts using the sheep fetus as recipient provided both donor and recipient fetal cells are processed during the period of tolerance to foreign antigens.

Aging↗

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↗

Cerebral MRI on fetuses submitted to repeated cocaine administration during the gestation: an ovine model.

The aim of this study was to determine the role of Magnetic Resonance Imaging (MRI) in investigating fetal cerebral lesions induced by long term exposure to cocaine during sheep pregnancy. Cerebral Magnetic Resonance Imaging was performed on two groups of fetuses at 125 days of gestation (normal gestation: 145 days). The control group consisted of eight fetuses of four pregnant ewes. The study group consisted of eight fetuses of four pregnant ewes receiving daily 140 mg/kg injection of cocaine from day 60 until delivery. The following MR sequences were applied: T1-weighted FLASH, and T2-weighted Fast-Spin-Echo. Cerebral images were evaluated semi quantitatively using the following criteria: Heterogenicity, contrast between grey and white matter, contours irregularity, hyposignal, lateral ventricle sizes. The brightness distribution and homogenicity of the images were analysed by means of edge pair distributions using a new computerized method originally designed for ultrasound images analysis developed by Ultrasight inc (USA). (1) Flash T1: Heterogenic areas and irregular contours were more frequent in cocaine exposed fetuses. The contrast between grey and white matter was more important in the cocaine group. Hyposignal was found only in the cocaine group. Enlarged lateral ventricle occurred more frequently in the cocaine group. (2) Spin echo T2: The contrast between grey and white matter was higher and the contours of the brain more irregular in the cocaine group. Heterogenicity and hyposignal were also more frequent in this group but the difference with the control group was not significant. The computerized analysis of the contrast density on the cerebral images showed that 88% of the areas exceeding the reference level concerned the cocaine group, while only 14% of the areas exceeding the reference level concerned the control group. Long term exposure to cocaine induces cerebral tissue modifications, in favor of an advanced maturation and the development of hypoxic lesions. The histology of the brains confirmed in the cocaine group, the existence of hypoxic lesions with gliosis, perivascular edema and hemorrhages, and neuronal death.

Animals↗