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L Cobellis

Publications and source records attributed to L Cobellis.

At least 19 recordsLinked to original sources

Modulation of apelin and APJ receptor in normal and preeclampsia-complicated placentas.

Apelin is an endogenous ligand of the human orphan receptor APJ. This peptide is produced through processing from the C-terminal portion in the pre-pro-protein consisting of 77 amino acid residues and exists in multiple molecular forms. Although the main physiological functions of apelin have not yet been clarified, it is known that apelin is involved in the regulation of blood pressure, blood flow and central control of body fluid homeostasis in different organs. Since human placenta is a tissue where vasculogenesis, blood pressure and flow are dramatically important to allow a normal embryonic and fetal growth and development, the aim of the present study was to investigate the immunohistochemical distribution of apelin and APJ in normal placentas throughout pregnancy and in preeclampsia-complicated placentas. Specifically, we observed that in normal placentas the expression levels of apelin decreased from the first to the third trimester of gestation in both cytotrophoblast and syncytiotrophoblast cells and in the stroma of placental villi, in contrast with increased expression levels of APJ in the cytoplasm of cytotrophoblast cells and in the cytoplasm of endothelial cells of normal placenta samples. In contrast, in preeclampsia-complicated pregnancies, we observed a very strong increase of expression levels of both apelin and APJ receptor in all the placental compartments, cytotrophoblast, syncytiotrophoblast and stroma with a particular increase in endothelial cells inside preeclamptic placental villi. Our data seem to indicate an important role of apelin and APJ in the regulation of fetal development through a correct regulation of human placenta formation during pregnancy. Moreover, the strong expression levels of apelin and APJ in preeclamptic placentas, suggest their possible involvement in the onset of this pathology.

Adult↗

The rectal pocket syndrome after stapled mucosectomy.

OBJECTIVE: Stapled rectal mucosectomy (SM) is less painful than manual haemorrhoidectomy but may be followed by unusual complications which may require reinterventions. The aim of the present study was to report on a particular postoperative complication, the rectal pocket syndrome (RPS). METHODS: Six patients, four females and two males, five with severe proctalgia and signs of intermittent sepsis and one with faecal soiling following SM, underwent clinical examination, proctoscopy (n = 5) anal manometry and ultrasound (n = 4) revealing a painful rectal intramucosal pocket with an endoluminal orifice at the level of the suture line. Four of them underwent a reintervention. RESULTS: At surgery, a faecolyth was found to be entrapped in the rectal pocket with an underlying chronic abscess in four patients. The cavity was laid open and curetted in all cases. One of the females needed a fistulotomy of a low intersphincteric track after one year. In none of the others did endorectal pocketing and abscess or prostatitis recur after a mean follow up of 25 months (range 2-60 months). The male patient still had moderate postevacuation pain and prostatitis possibly via a bacterial translocation after two months. Overall, the incidence of the post mucosectomy RPS at our Units was 2.5%. CONCLUSIONS: The RPS can occur after SM, is likely to be due to a failure of either the purse-string or of the staples causing a suture defect leading to an intramural sinus, and may be successfully treated by a transanal lay-open in most cases.

Abscess↗

[A fetal soft marker in obstetric ultrasonography: single umbilical artery].

The recent advancement in the field of ultrasonography allows for the prenatal precocious diagnosis of an ever increasing number of congenital defects found in various areas of the foetal body. These phenotype variants (markers) and/or morphological anomalies reveal in the majority of cases of a foetus with chromosome defects. They represent ''alarm bells'' that intrigue us to uncover any average case with more tests. It is for this that many more efforts are made to identify echographical markers which allow us to select among the pregnant women those that are not at risk and to advise those that may be of the existence of a specific cytogenetic test. One of these markers is actually represented by the single umbilical artery. This anomaly is made up of the presence of only two vessels (an artery and a vein) at the level of the umbilical cord, and its lack of an artery. The clinical meaning of this pathology is not yet completely known today. Often, in fact, when isolated, it is not associated with a chromosome defect and to other foetal pathologies. When, however, it is presented as associated to other soft markers or other structural anomalies, the risk of a chromosome defect is notably higher.

Abnormalities, Multiple↗

Third stage ovarian carcinoma--case report: the necessity of a multidisciplinary approach to treatment.

Ovarian carcinoma, part of a heterogeneous group of tumours, is the main cause of death by gynaecological neoplasms. The diagnosis, in general, is delayed. Multiorgan diffusion, the necessity of a surgical operation and strong chemotherapy, and the eventual pathology due to patient age are all factors that require a multidisciplinary approach. In fact the case, here reported, refers to a patient who came under our observation for a bilateral ovarian mass discovered casually during an abdominal ultrasound exam carried out for renal colic. Excellent cytoreduction with peritoneal cytology, total abdominal hysterectomy, bilateral salpingo-oophorectomy (Figure 2), bilateral pelvic lymphadenectomy, total omentectomy, removal of nodules from the mesentery, the colon and three nodules in the abdominal wall thickness was executed. The histological report was G3, angioinvasive bilateral ovarian endometrioid adenocarcinoma. Metastasis was found only in one left obturator lymph node out of 17 lymph nodes removed. All of the removed abdominal, mesenteric and intestinal nodules were neoplastic. It is concluded that the complexity of similar cases always requires a multidisciplinary approach as in our case, involving an oncologist, hematologist, surgeon, gynaecologist, radiologist, anaesthesiologist, and nursing staff in the management of third stage ovarian cancer patients to obtain the best treatment thus guaranteeing a higher survival rate and better quality of life.

Aged↗

[Fetal and maternal amniocentesis complications].

AIM: The aim of this study was to estimate the incidence of complications due to the prenatal invasive diagnosis performed by amniocentesis at the Department of Prenatal Diagnosis of the Second University of Naples. METHODS: A total of 1.580 patients who underwent amniocentesis from January 2001 to December 2003, were submitted to a telephone interview concerning the complications that occurred after the invasive diagnosis. RESULTS: Only 1.416 patients out of the total patients interviewed answered correctly to the questionnaire. The complications that occurred in the first 24 h from amniocentesis (early complications) included light contractions and lipothymia respectively in 8.3% and 6.7% of cases; losses of amniotic fluid took place in 1.06% while bleedings were observed in 0.85% of cases. The incidence of abortions occurred in the week following amniocentesis was 0.78%. Preterm labor occurred in only 6% of the patients submitted to amniocentesis, spontaneous labor at term in 43% and cesarean section in 51%. The Apgar index at birth was normal in 95.7% of cases. In the remaining 4.3% pathologies like hypoglycemia or respiratory distress, which promptly regressed, were observed. Early complications and the incidence of abortions were significantly and independently associated with the double needle puncture but not with maternal age or the placenta specimen obtained during amniocentesis. CONCLUSIONS: A careful observation of the technique and the protocol, as well as a careful selection of patients are necessary presuppositions in order to further decrease the occurrence of complications due to amniocentesis.

Adult↗

A therapeutic algorithm for early-stage endometrial cancer: indications, patient selection, and feasibility.

Endometrial cancer is the most widely spread gynaecologic neoplasm in industrial countries. Mode of spread includes direct extension, lymphatic and haematic diffusion. Lymphatic involvement, particularly, is a topic of wide debate due to the strong therapeutic implications associated with it. In this regard, anatomic-surgical staging is better in that it corresponds to real conditions whereas clinical-instrumental staging is still today incomplete.

Algorithms↗

Management of poor responders in IVF.

Correct controlled ovarian stimulation is of paramount importance in assisted reproductive technologies. Therefore, analysis of the ovarian reserve of the patient is mandatory to tailor the best ovarian stimulation regimen. When the ovarian reserve is reduced, the induction of a multifollicular growth remains a challenge. Several factors could be associated with reduced ovarian response. However, reduced ovarian reserve either in older patients or in young patients represents the most frequent aetiological factor. Whatever is the aetiology, one of the main problems is how to predict a reduced ovarian response, and although several tests have been suggested, no very accurate predictive test is available. A variety of different stimulation protocols have been suggested but the lack of any large-scale, prospective, randomized, controlled trials of the different management strategies and the lack of a uniform definition of the population may result in comparisons of heterogeneous groups of patients, making it difficult to draw any definitive conclusions. Natural cycle IVF may represent an easy and cheap approach in the management of this group of patients. Although no controlled large prospective randomized studies are available to compare the natural IVF procedure with ovarian stimulation IVF in poor responder patients, the efficacy of natural cycle IVF is hampered by high cancellation rates mainly due to untimely LH surge. The use of gonadotrophin-releasing hormone antagonists in the late follicular phase, which reduces the premature LH rise rate, and the improvements in laboratory conditions and fertilization techniques, increase the embryo transfer rates, making this procedure more cost-effective.

Female↗

Apoptosis and human placenta: expression of proteins belonging to different apoptotic pathways during pregnancy.

Apoptosis occurs during normal development and it is important for the right balance between the loss of old, non-functional cells and the formation of new cells in different organs and tissues. Apoptosis is triggered by different cell-type-specific signals which involve several pathways, such as mitochondrial and receptor-mediated pathways, resulting in caspase cascade activation. Several studies have suggested that apoptosis plays an important role in the normal development, remodelling and aging of the placenta. Moreover, it has been demonstrated that apoptosis increases as pregnancy progresses suggesting that it is a normal physiological phenomenon throughout gestation. In the last years, it has been hypothesized that the process known as syncytial fusion is directly or indirectly related to apoptotic events. In particular, it has been suggested that cytotrophoblast cells early express most important apoptotic proteins that translocate in the syncytiotrophoblast with the fusion. This suggests that apoptosis has a central role in the villous trophoblast turnover. Recently, another important involvement of apoptotic processes in human placenta has been demonstrated. In particular, the apoptosis, mainly through Fas-FasL or TRAIL-R-TRAIL signalling, may be a defence mechanism against rejection of the fetal allograft by maternal immune system. The whole data suggest that regulation of apoptotic events is important to allow a correct development, differentiation and function of the placenta throughout pregnancy and that an unbalance of this process leads to severe pathologies such as pre-eclampsia and intrauterine growth retardation. Therefore, due to its extensive proliferation and invasive properties, the placenta mimics a malignant tumor and represents an interesting model to evaluate those processes leading to carcinogenesis.

Animals↗

Activin, inhibin and the human breast.

Activins and inhibins are growth factors involved in cell differentiation and proliferation. Human breast tissues such as normal mammary tissue, fibroadenoma, and breast cancer express inhibin and activin mRNA and proteins. Activin A and its binding protein, follistatin, are also present in human milk during the first week of lactation. Using immunohistochemistry, we have observed that the inhibin/activin alpha, betaA, and betaB subunits are present in normal breast tissue regardless of menstrual cycle phase or menopause, as well as in fibrocystic disease, and breast tumors. The mRNAs encoding all three activin/inhibin subunits are expressed in breast carcinoma, fibroadenoma, and normal mammary tissue. The betaA subunit gene expression is higher in either local or metastatic breast carcinoma than in normal tissue. In addition, dimeric activin A is detectable in homogenates of breast cancer tissue at concentrations twice as high as in non-neoplastic adjoining tissue. Recent evidence suggests that some of the activin A produced by breast carcinoma is released into systemic circulation. In women with breast cancer, serum activin A levels are often elevated, and a significant decrease is observed in the first and second days following tumor excision. The role of activin and inhibin as endocrine and/or paracrine factors in the breast is still uncertain. Activin has complex effects on cell growth during branching morphogenesis, but it is generally considered as an inhibitor of cell proliferation as in vitro studies have shown that activin A treatment of breast cancer cells arrests cell growth. Inhibin is generally considered as a tumor suppressor, but its possible role in the breast is less understood.

Activins↗

Immunohistochemical distribution of proteins belonging to the receptor-mediated and the mitochondrial apoptotic pathways in human placenta during gestation.

The balance between cell death and cell proliferation and its regulation are essential features of many physiological processes and are particularly important in fetal morphogenesis and adult tissue homeostasis. Apoptosis is a type of cell suicide that is activated in two main ways: through a receptor-mediated pathway or through a mitochondrial pathway. We have investigated the immunohistochemical distribution of proteins belonging to these two pathways in human placenta during gestation by comparing their expression levels between the first and third trimester of gestation. In the first trimester, the receptor-mediated pathway prevails over the mitochondrial pathway with a moderate/intense expression of its three components, viz., Fas ligand (FasL), Fas, and caspase-8, and weak positivity of anti-apoptotic FLIP, these proteins being mainly localized in the cytotrophoblast compartment. In the third trimester of gestation, there is an increased expression of mitochondrial pathway proteins, viz., Apaf-1 and caspase-9. We have also investigated the expression level of caspase-3, the primary effector caspase of both pathways, and have observed that it is moderately expressed during gestation, being mainly localized in the cytotrophoblast during the first trimester and in both placental compartments during the third trimester of gestation. Thus, both pathways actively function in human placenta to execute cell death. By means of immunoelectron microscopy, we have further shown that, in human placenta, the two proteins of the mitochondrial pathway together with caspase-3 are localized both in the cytoplasm and in the nucleus. In particular, Apaf-1 and caspase-9 are distributed near to the nuclear envelope suggesting an important role for these two proteins in disrupting the nuclear-cytoplasmic barrier.

Adult↗

Cumulative pregnancy rates after transfer of fresh and thawed embryos.

Frozen-thawed embryo transfer is an effective procedure that allows further possibilities of pregnancy in addition to those obtained after the fresh in vitro fertilization (IVF). In our follow-up study we analysed all fresh embryo transfer procedures and every frozen-thawed embryo transfer performed from January 2000 to December 2001 evaluating the cumulative pregnancy rates. The study population was divided into two groups according to the female age: <38 years (group I) and >38 years (group II). All the best embryos were chosen for transfer and all the supernumerary good quality embryos were cryopreserved on the day of transfer. The embryos were then thawed and manipulated using a new technique. In group I, 527 patients (619 cycles) underwent fresh embryo transfer and in 232 of them (238 cycles) the embryos were frozen (44% per patients and 38.4% per cycle). In group II, 156 patients (193 cycles) underwent fresh embryo transfer and in 14 of them (15 cycles) the embryos were frozen (9% per patient and 7.8% per cycle). The pregnancy rate of group I patients that had their supernumerary embryos frozen (232 patients and 238 cycles) was 47.4% per cycle and 48.7% per patient whereas in the same population of group II patients (14 patients and 15 cycles) the clinical pregnancy rate was 35.7% per cycle and 38.5% per patients. The cumulative clinical pregnancy rate after transfer of fresh and thawed embryos was: group I, 74% per cycle and 76% per patients; group II, 42.8% per cycle and 46.1% per patient. Frozen-thawed embryo transfer is a cost-effective practice.

Adult↗

Pattern of expression of cyclin D1/CDK4 complex in human placenta during gestation.

Progression through the cell cycle in eukaryotic cells is controlled by a family of protein kinases, termed cyclin-dependent kinases (CDKs), and their specific partners, the cyclins. In particular, the control of mammalian cell proliferation occurs largely during the G1 phase of the cell cycle. Five mammalian G1 cyclins have been enumerated to date: cyclins D1, D2, and D3 (D-type cyclins), and cyclins E and E2. By the use of immunohistochemistry and immunoelectron microscopy, we observed that in the first trimester of gestation of human placenta, cyclin D1 was distributed in the nuclei of the cytotrophoblast compartment together with a weak positivity of endothelial cells surrounding blood vessels. The endothelial positivity of cyclin D1 strongly increased in the third trimester of gestation. Moreover, we observed the subcellular localization of cyclin D1 that was present both in the stroma of placental villi and in the nuclei of syncytiotrophoblast cells. Therefore, we observed that CDK4 was localized in the nuclei of the cytotrophoblast compartment during the first and third trimesters and it also had a nuclear positivity in the endothelial cells of blood vessels at the end of the third trimester of gestation. In conclusion we may hypothesize that cyclin D1/CDK4 complex functions to regulate the cell cycle progression in the proliferative compartment of human placenta, the cytotrophoblast, during the first trimester through interaction with p107 and p130. Therefore, cyclin D1 and CDK4 seem to be involved in the control of placental angiogenesis during the third trimester of gestation.

Cell Cycle↗

Umbilical endometriosis in pregnancy: a case report.

To our knowledge, this is the first case reported in the literature of umbilical endometriosis in a pregnant woman. We report a case of umbilical endometriosis in a pregnant woman at 16 weeks of gestation. The patient revealed a reddish-brown polypoid nodule within the umbilical depression, with the typical history of monthly bleeding from the umbilicus. A nodule biopsy, testing of serum levels of CA-125 and a transabdominal ultrasound examination were performed. The diagnosis of endometriosis was confirmed by pathological examination. Serum levels of CA-125 were slightly increased and the pelvic ultrasound examination did not identify ovarian cysts of a possible endometriotic nature. The patient was also examined at 24 weeks' gestation, after delivery and in the late postpartum period. No therapy was given and the lesion resolved spontaneously 2 months after the biopsy was taken.

Adult↗

Implantation in patients over 40 and raising FSH levels--a review.

There is an evident decline of female fertility with age. This decline is mainly due to increased risk of pregnancy termination either after conception or after embryo implantation. Very likely the major cause of this embryo and pregnancy loss is chromosomal aneuploidies caused mostly by increasing rates of 'poor quality' oocytes. This phenomenon can be explained either by an age dependent accumulation of damage and/or by the hypothesis that the defective oocytes are there in the ovaries from the fetal life. 'Good quality' oocytes are ovulated first, leaving 'poor quality' oocytes to be ovulated later in life. Besides the quality of the oocytes which is mainly responsible of the embryo quality (we have not to forget a paternal effect) the process of implantation is dependent upon two variables: the probability of a viable embryo and that of a receptive uterine environment. From the oocyte donation model it seems that the endometrium also plays a minor role in human reproductive ageing as it does in some laboratory animals. However, besides some macroscopic possible causes which may play a role in the reduction of the age-related endometrial receptivity, there are so many endometrial factors possibly related to its receptivity which need to be further studied especially in older women.

Adult↗

High plasma concentrations of di-(2-ethylhexyl)-phthalate in women with endometriosis.

BACKGROUND: Emerging evidence suggests a potential role for ubiquitous environmental contaminants in the physiopathology of endometriosis. Di-(2-ethylhexyl)-phthalate (DEHP), the most commonly used plasticizer in flexible polyvinylchloride (PVC) formulations, is a widespread environmental contaminant with potentially adverse effects on fertility in animal models. In the present study, we tested the hypothesis that DEHP and/or and its main metabolite, mono-ethylhexyl phthalate (MEHP), play a role in the pathogenesis of endometriosis. METHODS: Specimens of blood and peritoneal fluid were collected in a group of women with endometriosis (n = 55), and in age-matched control women (n = 24). Concentrations of DEHP and MEHP were measured in plasma and peritoneal fluid by using high performance liquid chromatography (HPLC). Differences between groups were tested using the Fisher's exact test, Wilcoxon-test, and Kruskal-Wallis analysis of variance. RESULTS: Endometriotic women showed significantly higher plasma DEHP concentrations than controls (median 0.57 micro g/ml, interquartile range: 0.06-1.23; values range: 0-3.24 versus median 0.18 micro g/ml, interquartile range: 0-0.44; values range: 0-1.03; P = 0.0047) and 92.6% of them had detectable DEHP and /or MEHP in the peritoneal fluid. No significant differences in either the DEHP/MEHP plasma concentrations (P >/= 0.31) or DEHP/MEHP peritoneal fluid concentrations (P >/= 0.66) were observed in the endometriotic patients as a function of the disease stage at the time of diagnosis. CONCLUSIONS: The present findings showed for the first time an association between DEHP plasma concentrations and endometriosis, suggesting a possible role for phthalate esters in the pathogenesis.

Adult↗

Ovarian hyperstimulation syndrome: distinction between local and systemic disease.

The ovarian hyperstimulation syndrome (OHSS) is an iatrogenic, unpredictable and potentially life-threatening complication in patients submitted to pharmacological ovarian stimulation. Information on risk factors, etiopathogenetic mechanisms, prevention strategies and therapeutic management is continuously updated. The present study retrospectively analyzed 123 women affected by different grades of OHSS as a result of pharmacological ovulation induction. Hospital admission was suggested in 14 patients with severe OHSS, whereas patients with moderate or mild OHSS were followed in the out-patient section of our department. The results confirmed the efficacy of the therapeutic scheme adopted. The syndrome is localized to the ovaries at the time that the condition is triggered; when organs different from the ovaries become involved, OHSS assumes systemic aspects. The different clinical signs are the basis of a proposal of a local and systemic classification.

Adult↗