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Biomedical subjects

Eduard Gratacós

Publications and source records attributed to Eduard Gratacós.

9 recordsLinked to original sources

Placental angiogenic growth factors and uterine artery Doppler findings for characterization of different subsets in preeclampsia and in isolated intrauterine growth restriction.

OBJECTIVE: The purpose of this study was to evaluate possible relationships between placental markers and endothelial dysfunction in preeclampsia and intrauterine growth restriction. STUDY DESIGN: A prospective study was conducted in 76 patients with preeclampsia and 37 patients with intrauterine growth restriction that were classified as early onset (<34 weeks of gestational age) or late onset, and 40 control subjects. Plasma levels of placental growth factor, soluble fms-like tyrosine kinase-1, vascular cell adhesion molecule-1, and uterine artery Doppler indices were measured. RESULTS: In early-onset preeclampsia and intrauterine growth restriction, placental growth factor was lower and soluble fms-like tyrosine kinase-1 and vascular cell adhesion molecule-1 higher than in control subjects, although all changes were more pronounced in preeclampsia. In late-onset preeclampsia, those patients with abnormal uterine artery Doppler indices had higher soluble fms-like tyrosine kinase-1 and vascular cell adhesion molecule-1 levels. CONCLUSION: Biochemical changes in early-onset preeclampsia and intrauterine growth restriction point to a common placental disorder and a state of endothelial dysfunction, which may require interaction with other factors to explain the maternal disease in preeclampsia. Data in late-onset preeclampsia suggest that a proportion of them may occur with minimal placental involvement.

Adult↗

Atherogenic lipoprotein subfraction profile in preeclamptic women with and without high triglycerides: different pathophysiologic subsets in preeclampsia.

Abnormal lipid metabolism has been proposed as a pathogenic factor of preeclampsia, although whether it is a constant feature in all preeclamptic patients is unclear. We assessed whether plasma triglyceride (TG) levels can distinguish a subgroup of preeclamptic women with alterations in lipoprotein profile from those with normal lipid metabolism and can be used to identify 2 distinct pathogenic groups in preeclampsia. This prospective study included 34 women with preeclampsia and 23 healthy pregnant women. Preeclamptic women were further subclassified into normal-TG (<250 mg/dL) and high-TG (>or=250 mg/dL) groups on the basis of the 90th percentile in our population. Low-density lipoproteins (LDLs) were ultracentrifuged and were separated into 4 subfractions, and lipid distribution in the subfractions was analyzed in all study groups. Vascular cell adhesion molecule-1 was also measured as a marker of endothelial dysfunction. Sixteen women with preeclampsia had high TGs (47% vs 13% in control subjects, P<.001). This subgroup showed a significant shift in lipid distribution, mainly, TGs, toward the small, dense LDL subfractions. However, preeclamptic patients in the normal-TG subgroup showed LDL subfraction lipid distribution similar to that of healthy pregnancies. Vascular cell adhesion molecule-1 levels were significantly elevated in preeclamptic patients in comparison with those in control subjects regardless of TG levels. The presence of a proatherogenic lipoprotein profile, previously described in preeclampsia, is characterized by increased small dense LDL and is exclusive to a subset of preeclamptic patients with high TG levels. These findings support the concept of heterogeneous pathogenic lines in preeclampsia and the use of subclassifications in pathophysiologic research on this condition.

Adult↗

Conservative versus surgical treatment for complex neonatal ovarian cysts: outcomes study.

OBJECTIVE: Prenatally diagnosed complex ovarian cysts are most often managed surgically in an attempt to save the ovary. Nevertheless, published surgical results disclose that most patients undergo oophorectomy or salpingo-oophorectomy. We assessed whether a surgical or conservative approach was more appropriate by comparing the long-term outcome of infants treated by both methods. A hypothesis for the cause of complex cysts is presented. CONCLUSION: Clinical evidence questions the use of surgery for asymptomatic complex ovarian cysts. Histologic analysis suggests gonad maldevelopment as the origin of complex neonatal ovarian cysts.

Female↗

A comprehensive study of oxidative stress and antioxidant status in preeclampsia and normal pregnancy.

Oxidative stress has been increasingly postulated as a major contributor to endothelial dysfunction in preeclampsia (PE), although evidence supporting this hypothesis remains inconsistent. This study aimed to analyze in depth the potential role of oxidative stress as a mechanism underlying endothelial damage in PE and the pregnant woman's susceptibility to the disease. To this end, indicative markers of lipoperoxidation and protein oxidation and changes in antioxidant defense systems were measured in blood samples from 53 women with PE and 30 healthy pregnant controls. Results, analyzed in relation to disease severity, showed PE women, compared with women with normal pregnancy, to have: (1) significantly enhanced antioxidant enzyme SOD and GPx activities in erythrocytes; (2) similar plasma alpha-tocopherol levels and significantly increased alpha-tocopherol/lipids in both mild and severe PE; (3) significantly decreased plasma vitamin C and protein thiol levels; (4) similar erythrocyte glutathione content, total plasma antioxidant capacity, and whole plasma oxidizability values; (5) significantly elevated plasma total lipid hydroperoxides, the major initial reaction products of lipid peroxidation, in severe PE; (6) no intracellular or extracellular increases in any of the secondary end-products of lipid peroxidation, malondialdehyde or lipoperoxides; (7) similar oxidative damage to proteins quantified by plasma carbonyl levels, immunoblot analysis, and advanced oxidation protein products assessment; and (8) significantly elevated and severity-related soluble vascular cell adhesion molecule-1 serum levels reflecting endothelial dysfunction. No correlations were found among plasma levels of circulating adhesion molecules with regard to lipid and protein oxidation markers. Globally, these data reflect mild oxidative stress in blood of preeclamptic women, as oxidative processes seem to be counteracted by the physiologic activation of antioxidant enzymes and by the high plasma vitamin E levels that would prevent further oxidative damage. These results do not permit us to conclude that oxidative stress might be a pathogenetically relevant process causally contributing to the disease.

Adult↗

Increased polymorphonuclear infiltration and iatrogenic amniotic band after closure of fetoscopic access sites with a bioactive membrane in the rabbit at midgestation.

OBJECTIVE: This study was undertaken to evaluate the efficacy and safety of closing the fetoscopy access site in a midgestational rabbit model by using a commercially available bioactive membrane. STUDY DESIGN: Fetoscopy was performed in a total of 100 gestational sacs in 20 does at midgestation (23 days, term = 31 days). In 50 cases (group 1), the fetoscopic access port was closed with a 5-mm patch of biocompatible matrix derived from porcine small intestine containing growth factors (transforming growth factor-beta and fibroblast growth factor-beta). Fifty sacs served as positive controls (group 2) and 55 unoperated fetuses were used as negative controls (group 3). At 30 days of gestation, a second-look laparotomy was performed. Outcome parameters were fetal weight, fetal lung weight, fetal lung-to-body weight ratio, and microscopy of the plugging site. RESULTS: Membrane integrity after fetoscopy was restored in 28 of the 40 (70%) of cases in group 1 versus 13 of the 32 (41%) in group 2 (P =.012). Birth weights were comparable (group 1: 30.65 +/- 5.68 g; group 2: 29.70 +/- 5.05 g; group 3: 29.52 +/- 6.25 g; NS), but fetal lung weight (group 1: 0.964 +/- 0.20 g; group 2: 0.798 +/- 0.17 g; P <.01) and fetal lung-to-body weight ratio (group 1: 0.032 +/- 0.0067; group 2: 0.027 +/- 0.0082; P <.05) were significantly higher in the study group. In group 1, cellular proliferation was significantly increased. Polymorphonuclear infiltration was observed in 19 of the 40 (48%) cases in group 1 versus 5 of the 32 (16%) cases in group 2 (P <.05). In one treated sac, a fibrous band joining the two fetal legs without constriction was present. CONCLUSION: The use of a bioactive membrane improved fetal membrane repair rates and decreased incidence of pulmonary hypoplasia in the rabbit but increased polymorphonuclear infiltration. In one amniotic sac, a situation comparable to amniotic band syndrome was documented.

Amniotic Band Syndrome↗

Monochorionic diamniotic twins: complications and management options.

PURPOSE OF REVIEW: Monochorionic compared with dichorionic twins have disproportionately high fetal loss rates, perinatal mortality and morbidity. This is because of the unpredictable vascular anastomoses and the often asymmetrical distribution of the single placenta between both twins. RECENT FINDINGS: The pathophysiology of twin-to-twin transfusion syndrome is usually explained on an angioarchitectural basis, although certain hemodynamic and hormonal factors also may be involved. The results of the large randomized trials on amnioreduction, fetoscopic laser coagulation and septostomy are still awaited. An update is given on hardware and instruments required for fetoscopic laser. Subsequently, the problem of the monochorionic twin set with severe early discordant growth is addressed. Several etiological mechanisms have been proposed, but little is known of its natural history. Also, umbilical artery Doppler waveforms may not have the same predictive value as in singletons. Prophylactic laser coagulation of the vascular anastomoses to protect against the adverse effects of single intrauterine demise, has so far not been shown to confer any benefit in outcome. Finally, pathophysiology and management of discordant structural and chromosomal anomalies in monochorionic twins are discussed. Laser and monopolar coagulation, which can be introduced through a needle, may be used for selective feticide in early pregnancy or low hemodynamic conditions. Bipolar coagulation seems more effective at later gestational ages and normal hemodynamic conditions. SUMMARY: Our insight into the complications associated with monochorionic twins has increased in recent years. It is hoped that this will lead to better surveillance and ultimately an improved outcome for these high-risk pregnancies.

Amnion↗

Increased susceptibility to low density lipoprotein oxidation in women with a history of pre-eclampsia.

OBJECTIVES: To evaluate the susceptibility to oxidation of low density lipoprotein (LDL) in women with a history of pre-eclampsia. DESIGN: A case-control study. SETTING: The departments of obstetrics and gynaecology at two university teaching hospitals. POPULATION: Women delivering one to three years before enrollment, 35 who were diagnosed with severe pre-eclampsia and 35 controls matched for age, body mass index (BMI), smoking and parity. METHODS: Plasma samples were analysed for total cholesterol, high density lipoprotein (HDL) cholesterol, LDL cholesterol, triglycerides and lipoprotein A. The in vitro susceptibility to oxidation of LDL was measured and expressed in minutes (lag time). Results are expressed as mean and standard deviation. MAIN OUTCOME MEASURES: Serum lipid profile and in vitro susceptibility to oxidation of LDL. RESULTS: Mean LDL cholesterol (116 [37] vs 98 [20] mg/dL, P < 0.05) and trygliceride (112 [56] vs 78 [38] mg/dL, P < 0.05) levels were significantly higher in the groups of women who had pre-eclampsia compared with controls. The rest of the measured lipid parameters were similar between the two study groups. The susceptibility to oxidation of LDL was also significantly higher in the pre-eclampsia group (lag time: 37.9 [8.4] vs 44.8 [9.1] minutes, P < 0.01). CONCLUSION: Women with a history of pre-eclampsia have significant differences in lipid parameters and an increased susceptibility to lipoprotein oxidation when compared with women who had a normal pregnancy one to three years after delivery.

Adult↗

Nitrous oxide amniodistention compared with fluid amniodistention reduces operation time while inducing no changes in fetal acid-base status in a sheep model for endoscopic fetal surgery.

OBJECTIVE: Our purpose was to evaluate in a sheep model for endoscopic fetal surgery the impact of nitrous oxide-gas amniodistention compared with fluid amniodistention on duration of surgery, hemorrhagic events, and fetomaternal acid-base status. STUDY DESIGN: Pregnant ewes (n = 16) at 92 to 104 days of gestation (term, 145 days) underwent amniodistention with Hartmann's solution (group I, n = 8) or nitrous oxide (group II, n = 8) at 38 degrees C. Endoscopic tracheal clipping according to a standardized surgical protocol was performed in all animals. The duration of fetoscopy (from insertion of first cannula until removal of last one), fetal surgery (fetal skin incision to skin closure), and number of bleeding episodes was recorded. Maternal and fetal blood gas values (pH, PO2, and PCO2) were measured at baseline and every 15 minutes during the experiment. Videotapes of the operations were assessed independently and scored by a visual analog scale in terms of smoothness of the operation and control of hemorrhagic events. RESULTS: Mean duration of fetoscopy (+/-SEM) (68 +/- 16 minutes vs 92 +/- 23 minutes) and fetal surgery (19 +/- 6 minutes vs 42 +/- 18 minutes) as well as number of bleeding episodes (1.9 +/- 0.8 minutes vs 5.8 +/- 2.1 minutes) was significantly reduced in animals operated with use of nitrous oxide amniodistention. In both groups, fetal and maternal blood gases remained unchanged during the entire experiment. Visual analog scale (VAS) scores were significantly higher for procedures conducted with use of gas distention. CONCLUSION: In a lamb model for fetal surgery, gas amniodistention with use of nitrous oxide results in a quicker operation procedure with less bleeding compared with fluid amniodistention, and without adverse side effects on fetomaternal acid-base status.

Acid-Base Equilibrium↗

Feasibility of retroviral vector-mediated in utero gene transfer to the fetal rabbit.

OBJECTIVES: Successful treatment or prevention of severe hereditary diseases could conceivably be achieved by genetic intervention early in development. Viral vector-mediated fetal gene transfer is proving a valuable tool to test the above concept in relevant animal models. Although the pregnant rabbit is a well-recognized model for fetal therapy, few preclinical assays have used it to validate fetal gene transfer approaches. In this preliminary study we assessed for the first time the feasibility of retroviral vector-mediated in utero gene transfer in the fetal rabbit. METHODS: Different amounts of the vesicular stomatitis virus G pseudotyped MFG(nls)LacZ retroviral vector, expressing a nuclear-localized beta-galactosidase reporter protein were injected intraperitoneally and -hepatically into 20- to 22-day-old fetuses. At 8-9 days post-treatment, the pups were sacrificed and the tissues harvested for analysis. Evidence of gene transfer was obtained by PCR amplification of proviral sequences within genomic DNA isolated from the treated samples. Transgenic beta-galactosidase expression was assessed by X-gal histochemical staining. RESULTS: By intraperitoneal injection 43% of the viable fetuses treated (3/7) showed evidence of successful LacZ gene transfer and low-level beta-galactosidase expression into liver and heart, whereas by intrahepatic injection roughly 38% (3/8) of the livers were positive for LacZ gene transfer and expression. The success rate for the viable fetuses rose to 67% positive livers (4/6) when a near double amount of recombinant virus was injected using a 10-fold concentrated virus stock. In terms of short-term safety, fetal and maternal survival rates approached 80% of treated fetuses, and 100% of treated does. CONCLUSIONS: The pregnant rabbit is a useful and reliable model allowing the design of further studies to optimize the conditions for effective, safer, and persistent retroviral vector-mediated fetal gene transfer.

Animals↗