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A Locatelli

Publications and source records attributed to A Locatelli.

At least 55 records · Page 3Linked to original sources
PubMed1999

Brain damage and hypoxia in an ovine fetal chronic cocaine model.

OBJECTIVE: To assess the development of brain damage in an ovine fetal chronic cocaine model. To evaluate the effect of isolated hypoxic tests on this model and to correlate hemodynamic findings (brain-sparing effect) following fetal hypoxia and the occurrence of brain damage. STUDY DESIGN: Fifteen ewes were divided into a control group (n=7) and a cocaine treated group (n=8). From day 65 to day 134 the cocaine treated animals received a daily (5 days per week) intramuscular injection (2 mg/kg cocaine) and the control animals a placebo injection (2 ml of isotonic solution). Both groups underwent hypoxic tests (cord compression (3 min) and aortic compression (1 min)) at 90 and 134 days. In addition, anesthesia for magnetic resonance imaging (MRI) examination was carried out at 125 days. Fetal blood samples were collected during both series of hypoxic tests and the cerebral and umbilical flows were monitored by Doppler. Samples from 25 brains (control n = 10; cocaine n= 15) were processed for light and electron microscopic examination. Quantification of brain damage was done on semithin sections from six areas of cortex and germinal matrix on each fetus. RESULTS: Similar forms of brain damage (selective neuronal loss limited to the parasaggital cortex, striatum, hippocampus and Purkinje cells) was present in both groups but lesions were more frequent in the cocaine treated group as shown by quantitative analysis for the proportion of abnormal capillaries (65% vs. 35%), capillary edema (61% vs. 34%) and abnormal neurons showing delayed neuronal degeneration (DND) (66% vs. 36%) in the cocaine and control group respectively. There was no significant difference in immunoreactivity for glial fibrillary acidic protein (GFAP) but it was more marked in the cerebellum of cocaine treated animals. Fetal blood samples showed a moderate sustained hypoxia and Doppler findings demonstrated the presence of a brain sparing effect associated with increased uterine and umbilical vascular resistance in the cocaine treated group. Nevertheless, the amplitude of the heart rate increase and cerebral dilatation was significantly lower in the cocaine treated animals. CONCLUSION: This ovine fetal chronic cocaine model showed the presence of brain damage. Cocaine treatment seems to potentiate the effect of the hypoxic tests. Independent of the cause, the brain damage developed in the presence of brain sparing effect, strongly suggesting that this phenomenon is a sign of a pathological fetal condition and no guarantee that it will prevent tissue damage.

Animals↗
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

What sounds reach fetuses: biological and nonbiological modeling of the transmission of pure tones.

In utero transmission of external and maternal sounds has been studied in pregnant women and in an animal model of human species, the sheep. These works, especially the most recent ones, suggest that local and environmental factors interfere in such a way that signals are attenuated in a complex manner as frequency increases. The present work investigated whether a plain rubber sphere which was filled with water could be considered as a reliable nonbiological model in a study describing the characteristics of sound transmission. A sweeping pure tone, presented externally, was measured inside the rubber sphere using a high signal-to-noise ratio experimental hydrophone. A paradigmatic three components curve was observed between 100 and 20,000 Hz. In the first component of the curve (low to midfrequencies between 100 and 1,000 Hz), the intensity of the inside signal remained stable. The second component of the curve was composed of higher frequencies with the inside pressure falling gradually, demonstrating attenuation of the external signal. The third component of the curve appeared above a critical frequency, the value of which depended on several model and environment parameters. In this component, a series of rapid peaks and drops of the inside high frequency pressure was observed, indicating the presence of resonance systems. Analyses were carried out on the effects of several acoustical parameters, including: the size of the sphere, the location of the hydrophone in the sphere, the distance between the signal source and the hydrophone, the location of the external reference microphone, and the acoustical structure of the environment. These parameters allowed for the definition of their respective roles in the in-utero transmission of external sounds. These data were then compared with measurements performed within a biological model--ewes--under close acoustical settings. The comparisons confirmed the validity of the measurements, suggesting that the model may be useful in studies of sound transmission in utero.

Acoustic Stimulation↗
PubMed1998

Successful treatment with ampicillin and fluoroquinolones of human endocarditis due to high-level gentamicin-resistant enterococci.

Two cases of endocarditis, one caused by high-level gentamicin-resistant Enterococcus durans and the other by high-level gentamicin- and glycopeptide-resistant Enterococcus faecalis. successfully treated with a combination of ampicillin and a fluoroquinolone are reported. Both strains were susceptible to ampicillin. Enterococcus faecalis was susceptible to ciprofloxacin and to ofloxacin, but Enterococcus durans was moderately resistant to these agents. Microbiological and clinical cure was obtained with a 6-week course of ampicillin plus ciprofloxacin in one case and with ofloxacin in the second case due to intolerance to ciprofloxacin. The efficacy of the treatment was predicted in vitro by time-kill studies and by adequate serum bactericidal titres.

Aged↗
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

Chronology of events accompanying follicular atresia in hypophysectomized ewes. Changes in levels of steroidogenic enzymes, connexin 43, insulin-like growth factor II/mannose 6 phosphate receptor, extracellular matrix components, and matrix metalloproteinases.

The chronology of changes in levels of some proteins known to be altered during atresia of ovarian follicles was studied in ewes hypophysectomized at the end of the follicular phase of the estrous cycle. This study was performed by quantitative immunohistochemistry and zymography on large antral follicles (diameter > 3.5 mm) normally destined to ovulate, recovered 24, 36, or 72 h after pituitary ablation. The process of atresia was followed by comparing healthy follicles from intact ewes, with early atretic follicles recovered 24 h after hypophysectomy, clearly atretic follicles recovered 36 h after hypophysectomy, and late atretic follicles recovered 72 h after hypophysectomy. The earliest events of atresia induced by hypophysectomy were detected in theca and consisted of a strong decrease in levels of fibronectin (p < 0.001) and insulin-like growth factor II/mannose 6 phosphate (IGF-II/M6P) receptors (p < 0.05), occurring within the first 24 h following pituitary ablation. In intact animals, similar changes were observed in theca of early atretic follicles, suggesting that these changes may be important events involved in the onset of follicular atresia. In parallel, intrafollicular levels of matrix metalloproteinase-2 and -9 were shown to increase as early as 24 h after hypophysectomy, and a further increase was observed until 72 h after hypophysectomy. These early events were followed by the disappearance of P450 aromatase in granulosa cells 36 h after hypophysectomy (p < 0.05), and a progressive decrease in levels of P450 17alpha-hydroxylase in the theca interna and of gap junction protein connexin-43 in granulosa cells; these markers were still detectable in late atretic follicles 72 h after hypophysectomy. The increase in levels of fibronectin, type IV collagen, laminin, and IGF-II/M6P receptors within granulosa cell layers (p < 0.05) was significant only in late atretic stages, suggesting that these changes may be consequences rather than causes of atresia.

Animals↗
PubMed1998

Intrauterine infusion of high doses of pig trophoblast interferons has no antiluteolytic effect in cyclic gilts.

In the pig species, the preimplanting trophoblast is known to synthesize and secrete high amounts of interferon during early development. Previous experiments in cyclic gilts using total conceptus secretory proteins suggested that porcine trophoblastic interferons, unlike those of ruminants, exert no effect on the luteal cycle. In the present experiment, cyclic Meishan gilts were divided into two groups, cannulated on both uterine horns, and given daily injections of either a placebo or increasing doses of a mixture of recombinant interferon-gamma and interferon-delta, on Days 11-14 of the estrous cycle. In treated gilts, the injected doses were much higher than those previously found in uterine perfusates from pregnant gilts. However, no significant differences could be found between the control (n = 4) and the treated (n = 5) group concerning the days of the estrous cycle for mid-decrease of progesterone (control: Day 14.5+/-0.57 [mean+/-SD]; treated: Day 15+/-1.25), the day of estrus (control: Day 19+/-0.96; treated: Day 19.6+/-0.55), and the subsequent ovulation rate (control: 14+/-2.2 corpora lutea; treated: 13.1+/-1.1 corpora lutea). These data confirm that pig trophoblastic interferons, unlike those of ruminants, do not themselves exert an antiluteolytic effect. A possible synergistic effect of embryonic estrogens on the luteal functions of nonpregnant sows remains to be determined.

Animals↗
PubMed1998

Evidence that the mediobasal hypothalamus is the primary site of action of estradiol in inducing the preovulatory gonadotropin releasing hormone surge in the ewe.

Although a neural site of action for estradiol in inducing a LH surge via a surge of GnRH is now well established in sheep, the precise target(s) for estrogen within the brain is unknown. To address this issue, two experiments were conducted during the breeding season using an artificial model of the follicular phase. In the first experiment, bilateral 17beta-estradiol microimplants were positioned in either the medial preoptic area (MPOA) or the mediobasal hypothalamus (MBH), and LH secretion was monitored. An initial negative feedback inhibition of LH secretion was observed in ewes that had estradiol microimplants located in the MPOA (6 of 6 ewes) or caudal MBH in the vicinity of the arcuate nucleus (4 of 4). In contrast, a normal LH surge was only found in animals bearing estradiol microimplants in the MBH (5 of 10). Detailed analysis of estradiol microimplant location with respect to the estrogen receptor-alpha-immunoreactive cells of the hypothalamus revealed that 4 of the 5 ewes exhibiting a LH surge had microimplants located bilaterally within or adjacent to the area of estrogen receptor-expressing cells of the ventromedial nucleus. Two of these ewes exhibited a LH surge without showing any form of estrogen negative feedback. In the second experiment, we used the technique of hypophyseal portal blood collection to monitor GnRH secretion directly at the time of the LH surge induced by estradiol delivered either centrally or peripherally. Central estradiol implants induced the GnRH surge. The duration and mean plasma concentration of GnRH during the surge were not different between animals given peripheral or central MBH estradiol implants. Cholesterol-filled MBH microimplants did not evoke a GnRH surge. We conclude that the ventromedial nucleus is the primary site of action for estradiol in stimulating the preovulatory GnRH surge of the ewe, whereas the MPOA and possibly the caudal MBH are sites at which estrogen can act to inhibit LH secretion. These data provide evidence for the sites within the ovine hypothalamus responsible for mediating the bimodal influence of estradiol on GnRH secretion and suggest that different, and possibly independent, neuronal cell populations are responsible for the negative and positive feedback actions of estradiol.

Animals↗
PubMed1998

Aortic arch surgery: retrospective analysis of outcome and neuroprotective strategies.

BACKGROUND OBJECTIVE: To review intra- and postoperative data regarding surgical reconstruction of the aortic arch performed at our cardiosurgical centre during the past four years, and thus to deepen understanding of neurologic morbidity and of what constitutes the most effective neuroprotection. EXPERIMENTAL DESIGN: Retrospective study. SETTING: Regional University Hospital. PATIENTS: 29 patients who underwent reconstruction of aneurysm or dissection of the aortic arch. Intervention. Surgical replacement of the diseased aorta during deep hypothermia, alone or with selective cerebral perfusion (antegrade or retrograde). MEASURES: Overall mortality rate, neurologic morbidity rate, duration of extracorporeal circulation, of hypothermic circulatory arrest or of selective cerebral perfusion. Evaluation of the importance to neurological outcome of age, modality of operation (emergency or routine), biochemical parameters (glycemia, hematocrit) and perfusion technique. Recording of postoperative time of arousal, and possible correlation with length of selective cerebral perfusion. RESULTS: We observed a mortality rate of 39% (11 deaths) and a neurologic morbidity rate of 34%. Hypothermic circulatory arrest alone did not assure valid neuroprotection (5 cases, all with severe neurologic impairment), while better results were obtained with selective cerebral perfusion, especially antegrade (14 cases, with only 7% of neurologic morbidity rate). Hyperglycemia (>250 mg%) proved to be significantly associated (p=0.002) with increased incidence of adverse neurologic outcome, and the same association was observed between emergency status and adverse neurologic outcome (p=0.002). Moreover, we found an unexpected linear correlation between time of selective cerebral perfusion and postoperative time of arousal (r=0.728, p=0.000). CONCLUSIONS: Deep hypothermic circulatory arrest with selective cerebral perfusion currently represent a valid therapeutic option for brain preservation during reconstruction of the aortic arch in adults. It is mandatory to carry out a tight control of perfusion parameters (flow, pressures and temperature gradients) and biochemical variables (avoidance of hyperglycemia and modified ultrafiltration for fluid balance).

Adult↗
PubMed1998

In vivo cardiotonic activity of pyridylmethylene-2-indolinones.

The synthesis of 5-chloro-3-pyridylmethylene-2-indolinone is reported. This compound was subjected to an in vivo cardiotonic assay with 10 analogs whose synthesis and in vitro cardiotonic activity were previously reported. All the compounds tested (except the 5-hydroxyindole derivative) showed significant positive inotropic activity. The 3-pyridyl derivative without substituents at the indole system was the most active of the whole series.

Animals↗
PubMed1998

Disposition of Cremophor EL in humans limits the potential for modulation of the multidrug resistance phenotype in vivo.

The purpose of the present study was to characterize the distribution and elimination kinetics of the paclitaxel vehicle Cremophor EL (CrEL), a polyoxyethylated castor oil that can modulate P-glycoprotein-mediated multidrug resistance in vitro. The pharmacokinetics of CrEL were studied using noncompartmental models in 23 patients with histological proof of malignant solid tumors, receiving paclitaxel as a 3-h i.v. infusion at dose levels ranging from 100-225 mg/m2 (corresponding to CrEL doses of 8.33-18.8 ml/m2). Serial plasma samples were obtained before and up to 72 h after drug administration, and were analyzed for the presence of CrEL by a novel colorimetric dye-binding microassay. The area under the plasma concentration versus time curves and the peak plasma levels of CrEL increased from 253+/-36.8 (mean+/-SD) to 680+/- 180 microl.h/ml, and from 3.40+/-0.10 to 6.58+/-0.52 microl/ml, respectively, consistent with linear pharmacokinetics. Disappearance of CrEL from the central plasma compartment was characterized by a terminal elimination half-life of 84.1+/-20.4 h, resulting in extended persistence of substantial levels even at 1 week after paclitaxel treatment. The observed volume of distribution was extremely low and averaged 3.70+/-0.49 liters/m2, implying that the tumor delivery of CrEL is insignificant. Our results indicate that CrEL is a relatively slow clearance compound and that its distribution is limited to the central plasma compartment. Hence, CrEL is not likely to play a role in reversing P-glycoprotein-mediated multidrug resistance to paclitaxel in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

[Minimally invasive surgery with the Port-Access method. Preliminary experience].

METHODS: Data from the initial experience of 40 patients operated on with the Port-Access technique are reported. Indication to surgery was mitral disease in 24 patients and coronary stenosis in 16 patients. Mean age was 52 years (range 32-75). Operations performed were: 8 mitral valvuloplasties, 16 valve replacements, 9 single CABG (associated with an MVR in one case), 1 double CABG, 6 triple CABG and one quadruple CABG. Coronary endarterectomy was performed in 5 patients and left atrial isolation was associated with MV surgery in 5 cases. RESULTS: There were no operative deaths and every patient was discharged after a mean postoperative stay of 5.5 days (range 3-30). Postoperative course was complicated in 7 patients: surgical revision was necessary in 4 patients due to bleeding (through the mini-thoracotomy incision in 3 cases), 1 pacemaker was implanted for A-V block, one retained pulmonary catheter was removed through the mini-thoracotomy without the aid of cardiopulmonary bypass and in one case, there was an emergency conversion to median sternotomy due to a ventricular fibrillation unresponsive to usual resuscitative maneuvers a few hours after surgery. Some of these complications can be ascribed to the learning phase of this new technique and should disappear as experience is increased. CONCLUSIONS: Port-Access surgery is a new minimally invasive technique that utilizes a cardiopulmonary bypass with femoral access and a specialized catheter system that provides endoaortic clamping, pulmonary artery venting and myocardial preservation with infusion of cardioplegic solution in the aortic bulb or in the coronary sinus. Major contraindications to this technique are iliac-femoral disease or severe dilatation of ascending aorta. The aim of the Port-Access technique is to combine the aesthetic and functional advantages of the minimally invasive surgery with the wide range of surgical options that cardiopulmonary bypass can afford (to operate on atrioventricular valves and perform all the CABG that the patient need), without the limitations characteristic of the classic minimally invasive direct coronary artery bypass (MIDCAB) technique.

Adult↗