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Biomedical subjects

M Bozzo

Publications and source records attributed to M Bozzo.

At least 19 recordsLinked to original sources

The evaluation of maternal parameters at diagnosis may predict HELLP syndrome severity.

OBJECTIVE: Hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, a severe manifestation of pre-eclampsia and/or intrauterine growth restriction (IUGR) of the fetoplacental unit, is classified into three classes, according to the lowest platelet count observed during the course of the disease. The aim of our work was to analyze the levels of lactate dehydrogenase (LDH), aspartate transferase (AST), alanine transferase (ALT) and platelets at the time of HELLP syndrome diagnosis, to find possible cut-off values that could predict the severity of the syndrome from its early onset. METHODS: A retrospective analysis of the clinical records of 26 patients consecutively diagnosed with classes 1 and 2 HELLP syndrome was performed. Platelet count (x 1000/ml), LDH (IU/l), AST (IU/l), ALT (IU/l), hemoglobin (g/dl), hematocrit (%) and D-dimer (log of titer) were determined at admission and compared with the most severe peak values. Receiver operating characteristic (ROC) curves were used to calculate the best cut-off value at admission which correlated with the development of class 1 HELLP syndrome (the most severe condition). The post-test probability of developing class 1 severity was calculated. RESULTS: Mean gestational age at diagnosis was 33.4 weeks (range 23-40 weeks). Peak values of LDH, AST and ALT were significantly higher in class 1 HELLP syndrome patients. The platelet count at admission was not informative in differentiating patients who would later develop class 1 or class 2 HELLP syndrome. According to the best cut-off values at admission for LDH, AST and ALT, the post-test probability to predict patients with class 1 HELLP syndrome was 74%, 71% and 78%, respectively. If all the three parameters were above the cut-off value, the probability increased to 90%. CONCLUSIONS: The LDH, AST and ALT values at admission blood test, and to a greater extent the combination of all three abnormal tests, could predict the severity of HELLP syndrome.

Adult↗

Temporal sequence of abnormal Doppler changes in the peripheral and central circulatory systems of the severely growth-restricted fetus.

OBJECTIVE: To identify the temporal sequence of abnormal Doppler changes in the fetal circulation in a subset of early and severely growth-restricted fetuses. METHODS: This was a prospective observational study in a tertiary care/teaching hospital. Twenty-six women who were diagnosed with growth-restricted fetuses by local standards before 32 weeks' gestation and who had abnormal uterine and umbilical artery Doppler velocimetry were enrolled onto the study. To compare Doppler changes as a function of time, pulsed-wave Doppler ultrasound was performed on five vessels in the fetal peripheral and central circulations. Doppler examinations were performed twice-weekly and on the day of delivery if the fetal heart rate tracing became abnormal. Doppler indices were scored as abnormal when their values were outside the local reference limits on two or more consecutive measurements. Biometry for assessment of fetal growth was performed every 2 weeks. Computerized fetal heart rates were obtained daily. Delivery was based on a non-reactive fetal heart rate tracing and not on Doppler information. Patients with a severely growth-restricted fetus who were delivered for maternal indications such as pre-eclampsia were excluded. Perinatal outcome endpoints included: intrauterine death, gestational age at delivery, newborn weight, central nervous system damage of grade 2 or greater, intraventricular hemorrhage and neonatal mortality. RESULTS: Mean gestational age and newborn weight at delivery were 29 (standard deviation (SD), 2) weeks and 818 (SD, 150) g, respectively. The sequence of Doppler velocimetric changes was described by onset time cumulative curves that showed two time-related events. First, for each vessel there was a progressive increase in the percent of fetuses developing a Doppler abnormality. Second, severely growth-restricted fetuses followed a progressive sequence of acquiring Doppler abnormalities which were categorized into 'early' and 'late' Doppler changes. Early changes occurred in peripheral vessels (umbilical and middle cerebral arteries; 50% of patients affected 15-16 days prior to delivery). Late changes included umbilical artery reverse flow, and abnormal changes in the ductus venosus, aortic and pulmonary outflow tracts (50% of patients affected 4-5 days prior to delivery). The time interval between the occurrence of early and late changes was significantly different (P < 0.0001) and late changes were significantly associated with perinatal death (P < 0.01). CONCLUSIONS: Doppler velocimetry abnormalities develop in different vessels of the severely growth-restricted fetus in a sequential fashion. Late changes in vascular adaptation by the severely growth-restricted fetus are the best predictor of perinatal death.

Blood Circulation↗

HELLP syndrome and factor V Leiden.

The association of thrombophilia and obstetrical complications is documented and well consistent with the hypothesis of an insufficient placental perfusion due to fibrin deposition as a major underlying pathophysiological mechanism. Factor V Leiden is one of the most frequent thrombophilic mutations. A high prevalence of this mutation has recently been reported in a group of 21 German women with haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. In this respect, we studied the prevalence of factor V Leiden in 18 women who were consecutively diagnosed at our Department of Obstetrics and Gynaecology as having HELLP syndrome, between 1995 and 1999. Women were tested either at the time of diagnosis or months or years after delivery for coagulation parameters, protein C (PC), protein S (PS), antithrombin III, lupus-like anticoagulant, anticardiolipin antibodies (ACA), activated protein C (APC) resistance and detection of the G1691A mutation (factor V Leiden). In all women, the parameters studied were normal and in none of the investigated cases was the G1691A mutation found. HELLP being a severe form of preeclampsia, we think that the reported association between factor V Leiden and HELLP may reflect the well-known association with preeclampsia.

Adult↗

Mutations in the thrombomodulin and endothelial protein C receptor genes in women with late fetal loss.

Late fetal loss can be associated with placental insufficiency and coagulation defects. Thrombomodulin (TM) and the endothelial protein C receptor (EPCR) are glycoprotein receptors expressed mainly on the endothelial surface of blood vessels and also in the placenta; they both play a key physiological role in the protein C anticoagulant pathway. Defects in these proteins might play an important role in the pathogenesis of late fetal loss. We performed a case-control study in 95 women with unexplained late fetal loss (> 20 weeks), to elucidate whether TM or EPCR gene mutations were associated with an increased risk for this complication of pregnancy. The control group comprised 236 women who gave birth to at least one healthy baby and had no history of late fetal death or obstetrical complications. The entire TM and EPCR genes, including the promoter region, were screened. In total, five mutations were identified in the TM gene in 95 patients and three in 236 control subjects, and two mutations were identified in the EPCR gene in 95 patients and one in 236 control subjects. The relative risk for late fetal loss when having a mutation in the TM or EPCR gene was estimated by an odds ratio of 4.0 (95% CI 1.1-14.9). In conclusion, identified mutations in the TM and EPCR genes of women with unexplained fetal loss are more prevalent compared with women with no obstetrical complications.

Abortion, Habitual↗

Reduction of subcutaneous mass, but not lean mass, in normal fetuses in Denver, Colorado.

OBJECTIVE: To test the hypothesis that reduced birth weight in normal fetuses born at moderately high altitude (Denver), compared with the birth weight in normal fetuses born at sea level (Milan), is caused by a reduction in both lean mass and subcutaneous fat mass. STUDY DESIGN: Ninety-four normal singleton pregnancies (46 in Denver, 48 in Milan) had serial ultrasonographic axial images obtained to assess subcutaneous tissues of fetuses as a measure of body fat. The abdominal wall thickness and mid upper arm and mid thigh were examined. The equation was: Subcutaneous tissue equals total cross-sectional area minus bone and muscle area. Lean mass included the area of muscle and bone, head circumference, and femur length. RESULTS: Gestational age at delivery was similar between groups. Birth weight was less at Denver's altitude (2991 +/- 79 g versus 3247 +/- 96 g; P =.04). Abdominal wall thickness, mid upper arm, and mid thigh subcutaneous tissues measurements were significantly reduced at Denver's altitude and increased further in significance with advancing gestational age. Lean mass measurements were similar between groups. CONCLUSIONS: The reduced birth weight of the newborns in Denver was the result of a reduction in fetal subcutaneous fat tissue and not lean mass. Ultrasonography can be used to follow subcutaneous measurements longitudinally and to detect differences, and potentially disease processes, in study populations.

Adipose Tissue↗

Early and persistent reduction in umbilical vein blood flow in the growth-restricted fetus: a longitudinal study.

OBJECTIVE: We have previously shown, in a cross-sectional study, that the reduction in umbilical vein blood flow in intrauterine growth-restricted fetuses is due to reduced umbilical vein velocity. The purpose of this longitudinal study in intrauterine growth-restricted fetuses was to determine whether the umbilical vein velocity reduction, which, in turn, reduces blood flow, persists throughout gestation or represents a late event that precedes indicated delivery. STUDY DESIGN: Twenty-one intrauterine growth-restricted fetuses with an abnormal umbilical artery velocimetry underwent serial sonographic and Doppler examinations from 23 to 36 weeks of gestation. Umbilical vein diameter and velocity were measured, and umbilical vein absolute (milliliters per minute) and weight-specific blood flow (milliliters per minute per kilogram) were calculated. Umbilical vein diameter, velocity, and blood flow were expressed per abdominal circumference. Intrauterine growth-restricted findings were compared to local reference data. RESULTS: Intrauterine growth-restricted fetuses showed persistent reductions in umbilical vein blood flow per abdominal circumference and weight-specific blood flow (milliliters per minute per kilogram) from the time of diagnosis of intrauterine growth-restriction. Umbilical vein velocity was reduced in the intrauterine growth-restricted fetuses, although umbilical vein diameter did not change. CONCLUSION: Reduction of umbilical vein blood flow is an early finding in intrauterine growth-restricted fetuses, and it can persist for several weeks until delivery. This reduction in blood flow is due to reduced umbilical vein velocity.

Adult↗

Doppler investigation in intrauterine growth restriction--from qualitative indices to flow measurements: a review of the experience of a collaborative group.

In 1997 we started a collaboration among three groups, combining our experience with Doppler examination of the human fetus, blood flow studies on fetal lamb, and mathematical modeling of human circulation. In preliminary investigations on fetal lambs, the same Doppler method designed for the human fetus was used to measure venous blood flow in the umbilical veins of seven fetal lambs. Doppler measurements and diffusion technique groups for umbilical venous flow were 210.8+/-18.8 and 205.7+/-38.5 ml/min/kg, respectively (p = 0.881). In human pregnancy the interobserver variabilities for the vein diameter, mean velocity, and absolute umbilical venous blood were 2.9%, 7.9%, and 12.7%, respectively. A cross-sectional study allowed us to establish normal reference values. Venous blood flow/kg of estimated fetal weight showed a nonsignificant linear reduction with gestational age, from 128.7 ml/min/kg at 20 weeks to 104.2 ml/min/kg at 38 weeks. In a series of 37 growth-restricted fetuses, the UV flow per kilogram was significantly lower in the more severe growth-restricted fetuses (abdominal circumference below the second percentile and abnormal umbilical arterial p.i.) than in normal comparable fetuses (p < 0.001). In a series of 140 normal fetuses, we calculated that the absolute blood flow rate in the ductus venosus (DV) increases significantly with advancing gestational age from 20 to 38 weeks of gestation (from 23.2+/-9.6 ml/min to 43.5+/-21.5 ml/min). This means that the percentage of umbilical blood flow shunted through the DV decreases significantly during gestation (from 50% at midgestation to 20% at 38 weeks). In a series of 45 growthrestricted fetuses, delivered because of nonreactive fetal heart rate (group 2) and for other reasons but still with a normal heart rate pattern (group 1), we measured the ductal inlet diameter. In these fetuses, the diameters at the ductal isthmus, normalized for the dimension of the abdominal circumference (inlet diameter/abdominal circumference), were significantly larger (group 1 = 6.8+/-2.3; group 29.4+/-2.8 ) than in the control group (6.1+/-0.3). This means that in this subset of fetuses the amount of blood shunted can be increased as a compensatory mechanism.

Female↗

Mutations in coagulation factors in women with unexplained late fetal loss.

BACKGROUND: Factor V and prothrombin-gene mutations are independent risk factors for venous thrombosis; it is debated whether a mutation in the gene encoding methylenetetrahydrofolate reductase, an enzyme involved in homocysteine metabolism, also increases the risk of venous thrombosis. Whether any of these mutations is associated with an increased risk of late fetal death is not known. METHODS: We studied 67 women with a first episode of unexplained late fetal loss (fetal death after 20 weeks or more of gestation) and 232 women who had had one or more normal pregnancies and no late fetal losses. All the women were tested for the presence of three gene mutations. Women with other thrombophilic conditions were excluded from the study. RESULTS: Eleven of the 67 women with late fetal loss (16 percent) and 13 of the 232 control women (6 percent) had either the factor V or the prothrombin mutation. The relative risks of late fetal loss in carriers of the factor V and prothrombin mutations were 3.2 (95 percent confidence interval, 1.0 to 10.9) and 3.3 (95 percent confidence interval, 1.1 to 10.3), respectively. Thirteen percent of the women whose fetuses died and 20 percent of the control women were homozygous for the mutation in the methylenetetrahydrofolate reductase gene (relative risk, 0.8; 95 percent confidence interval, 0.5 to 1.2). CONCLUSIONS: Both the factor V and the prothrombin mutations are associated with an approximate tripling of the risk of late fetal loss.

Abortion, Spontaneous↗

Umbilical vein blood flow in growth-restricted fetuses.

OBJECTIVE: To determine whether umbilical blood flow is reduced in a subset of growth-restricted (IUGR) fetuses when expressed as flow per kilogram or flow per unit of specific sonographic fetal measurements. DESIGN: Prospective. SUBJECTS: Thirty-seven IUGR fetuses were examined by Doppler ultrasound within 4 h of the last non-stress test prior to delivery. This population was divided into three groups of varying clinical severity according to the characteristics of umbilical arterial pulsatility index (PI) and heart rate. METHODS: Absolute and weight-specific umbilical vein (UV) flow were calculated from measurements of UV diameter and UV mean velocity. Umbilical vein diameter, velocity and UV flow were calculated also per unit head (HC) or abdominal circumference (AC) and correlated with gestational age. RESULTS: Umbilical vein flow (UVf) per kilogram fetal weight was significantly lower in the more severe IUGR fetuses (abnormal umbilical arterial PI) than in normally grown comparable fetuses (P < 0.001). Umbilical vein flow per unit HC was significantly lower in the three groups (P < 0.001) than in the control population. The UV diameter/HC ratio was normal whereas UV velocity/HC ratio was significantly lower in IUGR fetuses than in comparable controls. CONCLUSIONS: The present study clearly establishes that umbilical venous blood flow is reduced in IUGR fetuses on a weight-specific basis. The sonographic growth parameter which best distinguishes umbilical flow differences of IUGR fetuses from normal fetuses is the head circumference.

Adult↗

Comparison of low- and high-altitude Doppler velocimetry in the peripheral and central circulations of normal fetuses.

OBJECTIVE: Our aim was to test the hypothesis that Doppler velocimetry of the peripheral and central circulations in normal fetuses is not affected by moderately high altitude (Denver, Colo-1609 m) compared with sea level (Milan, Italy-40 m). STUDY DESIGN: One hundred nineteen patients with singleton pregnancies underwent Doppler waveform analysis of the following: umbilical artery, uterine artery, middle cerebral artery, ductus venosus, and the tricuspid and mitral valves. RESULTS: Birth weights were reduced at Denver's altitude (P<.001). The early/late diastolic inflow ratios of the atrioventricular valves increased with gestational age (P<.01), whereas systolic/diastolic ratios of the uterine and umbilical arteries decreased with gestational age (P<.01). There were no Doppler velocimetry differences in any vessel between Denver's and Milan's altitudes. CONCLUSIONS: Gestational age has the same effect on Doppler index at both high and low altitudes. Moderately high altitude does not affect uteroplacental or fetal vascular Doppler index and may reflect normal acclimatization in the smaller Denver fetuses.

Adult↗

Blood flow through the ductus venosus in human fetus: calculation using Doppler velocimetry and computational findings.

The present study was performed to assess a new method to calculate the blood flow rate through the ductus venosus (DV) in normal human fetuses using available echo-Doppler data. Color Doppler sonographic unit was used to study DV flow in 26 normal fetuses between 20 and 36 wk of gestation. Maximal velocity flow tracings and vessel diameters were obtained at the isthmic and the outlet portion of the DV. Time-averaged velocities in the DV were measured from the recorded tracings. The velocity distribution in the two investigated cross-sectional areas of the DV was evaluated by means of computational model simulations and the velocity shape coefficients h(in) and h(out), (i.e., the ratios between the maximal and mean spatial velocities) were calculated as a function of vessel geometry. These values allowed us to convert maximal Doppler velocities into mean spatial velocities for each fetus. Blood flow rate was evaluated both at the isthmus and at the outlet of the vessel by means of two formulae based on the ultrasonographic measures and the results of the computational model. The value of the DV blood flow rate was calculated as the average between the results provided by the two formulae. The velocity distributions both at the isthmus (h(in) = 0.677 +/- 0.040) and the outlet (h(out) = 0.374 +/- 0.072) of the ductus are skewed toward the inner wall. Ductus geometry, i.e., the isthmic/outlet diameter ratio, affects the shape of the velocity profiles in the vessel, particularly that at the outlet. The coefficients of variation for repeated measurements of the ductal diameters were 9.5 +/- 7.7% and 6.7 +/- 4.9% at the isthmus and the outlet, respectively. The two formulae gave values statistically identical for the time-average blood flow rate (36.3 +/- 22.1 vs. 39.4 +/- 24.0 mL/min; R = 0.946, p = NS). The mean percent difference between the results of the two formulae was 7.1%. Thus, in human fetuses, the use of the two formulae based on both Doppler data and computational model simulations makes it possible to calculate the ductal flow rate. When the difference between the calculations of the two formulae exceeds the 30% of their average value, it is convenient to adopt the flow rate value calculated at the isthmus instead of the average of the two measures. The measurements at the outlet of the ductus were more difficult to obtain, and the spatial velocity profile at the outlet depends more on the DV anatomy.

Blood Flow Velocity↗

Prospective study of a PACS: information flow and clinical action in a medical intensive care unit.

PURPOSE: To prospectively compare efficiency and outcome of a standard film-only system with those of a digital picture archiving and communication system (PACS). MATERIALS AND METHODS: The film-only system, which used either analog film or computed radiography (CR) hard copy, was compared with a PACS, which used CR images displayed on a multiviewer in the radiology department and a workstation in the medical intensive care unit. A random sample of nonroutine, bedside chest radiographs was studied. RESULTS: Within 20 minutes of completion of radiography, 246 of 328 (75%) of the images were available at the workstations; it took 1.8 hours for 238 of 317 (75%) of the images to be displayed on the multiviewer. When the workstation was used, the staff did not access the image information earlier, but clinical actions were initiated more promptly in response to imaging findings. Consultation with radiologists decreased from 507 of 561 (90%) images with hard copies to 70 of 249 (28%) with the workstation. CONCLUSION: Use of a PACS improves the delivery of chest images, facilitates the initiation of clinical actions, and decreases input by radiologists.

Computer Systems↗

Color-Doppler velocimetry of uterine arteries in pregnant and nonpregnant patients during multiovulation induction for IVF.

OBJECTIVES: To evaluate uterine artery resistance during multiovulation induction in relation to the implantation rate in patients attending in vitro fertilization (IVF) cycles. PATIENTS: Multiovulation induction for IVF was monitored by daily determination of the pulsatility index (PI) of the uterine arteries, obtained by a transvaginal probe (6.5 MHz) implemented with color-flow imaging. Doppler data were obtained from 5 days before hCG administration to the day of follicular aspiration. One IVF cycle was monitored in 70 patients. In 17 patients, 41 IVF cycles were monitored until a successful attempt occurred. RESULTS: In the 70 patients studied during one IVF attempt, the PI of the uterine arteries significantly varied (P < 0.001) in the different phases of the cycle. In the 24 patients who conceived, a significantly lower PI (P < 0.03) was found throughout the cycle. This result was mainly due to a highly significant difference of PI values observed the day after hCG administration (P < 0.005). In the 17 patients who conceived after 1 to 4 negative in vitro fertilizations, no significant difference in PI was observed in the uterine artery resistance in cycles in which implantation was or was not successful. CONCLUSIONS: Uterine artery resistance varies significantly during phases of the induction therapy. Uterine artery resistance is lower throughout the course of multiovulation induction in patients with higher pregnancy rates. The PI on the day after hCG administration was the best index of pregnancy rate. Low uterine artery resistance was present even in negative attempts in patients who eventually achieved a successful implantation. PI values < or = 3 can be considered a favorable prognostic factor for future IVF cycles.

Adult↗

Insemination of HIV-negative women with processed semen of HIV-positive partners.

Many HIV-discordant couples want to have children so much that they are willing to abandon condom-protected sexual intercourse irrespective of the risks. Previous testing in our laboratory showed that gradient centrifugation followed by a swim-up procedure effectively removed HIV-1-infected cells from the semen of HIV-seropositive men. 85 HIV-discordant couples were screened for fertility; 29 women were found suitable for a timed insemination course with the processed semen of their HIV-seropositive partner. None of the inseminated women seroconverted, and 17 pregnancies were achieved in 15 women. All 10 babies born to these mothers remain HIV seronegative. The findings may help in the counselling of such couples and also give them hope of having healthy babies.

Centrifugation, Density Gradient↗