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Biomedical subjects

E Greco

Publications and source records attributed to E Greco.

At least 19 recordsLinked to original sources
PubMed2006

Relationship between chronic tadalafil administration and improvement of endothelial function in men with erectile dysfunction: a pilot study.

Men with erectile dysfunction (ED) frequently have a disproportionate burden of comorbid vascular disorders including atherosclerotic disease. We investigated whether scheduled tadalafil is better than on-demand (OD) in improving endothelium-dependent vasodilatation of cavernous arteries in men with ED and whether this effect is also exerted on markers of endothelial function. We did an open-label, randomized, crossover study including 20 male outclinic patients aged 18 years or older (mean age 54 years) who had at least a 3-month history of ED of any severity or etiology. Tadalafil (20 mg) on alternate days (ADs) or OD was administered for 4 weeks. Primary end points were variations of basal inflow (peak systolic velocity (PSV)) and flow-mediated dilatation (FMD) of cavernous arteries compared with baseline at penile Duplex ultrasound. Secondary end points were variations of Q13-SIEDY scores regarding morning erections and of markers of endothelial function, that is, vascular cell adhesion molecule (VCAM), intercellular cell adhesion molecule, endothelin-1 (ET-1), insulin and C-reactive protein (CRP). PSVs and FMD were higher after AD treatment when compared with OD and baseline, respectively (P=0.0001), and improvements were maintained from 2 weeks after discontinuation (P<0.005). Patients receiving tadalafil AD experienced a significant improvement of morning erections as compared to AD treatment (P<0.0001); ET1, VCAM and CRP showed a robust decrease after chronic vs OD regimes (P<0.05), with concomitant increase in insulin levels (P<0.05), without any variation in blood pressure and other laboratory parameters. Chronic but not OD tadalafil improves endothelial function with sustained effects from its discontinuation. Chronic treatment also produces a dramatic increase in morning erections, which determines better oxygenation to the penis, thus providing a rationale for vascular rehabilitation.

Biomarkers↗
PubMed2006

Lysophosphatidic acid enhances antimycobacterial activity both in vitro and ex vivo.

Lysophosphatidic acid (LPA) is a polar lipid metabolite which is involved in a wide range of biological processes, including cell proliferation and migration, wound healing, and increase of endothelial permeability. The present study reports evidences showing that LPA is able to enhance the antimicrobial activity of human macrophages and of bronchoalveolar lavage cells from tuberculosis patients leading to intracellular growth control of Mycobacterium tuberculosis. Such antimicrobial activity is mediated by the activation of phospholipase D which in turn induces acidification of M. tuberculosis containing phagosomes and is associated with the enhanced expression of Cathepsin D. These results suggest the possible protective role of this lysophospholipid in the activation of innate antimycobacterial response.

Adjuvants, Immunologic↗
PubMed2006

Limiting the number of injected oocytes to three impairs ICSI outcomes in patients with nonobstructive azoospermia.

BACKGROUND: Since March 2004, only a maximum of three oocytes were allowed to be subjected to ICSI at one time in Italy. A previous study failed to show an impact of this restriction on fresh embryo transfer outcomes. The objective of this study was to compare ICSI outcomes before and after this restriction in patients with nonobstructive azoospermia. METHODS: Patients underwent testicular sperm extraction followed by ICSI. Biological (fertilization rate and the percentage of good-morphology zygotes and embryos) and clinical (clinical pregnancy and implantation rates) outcomes of the last 100 ICSI attempts before the restriction and outcomes of the first 100 ICSI attempts after the restriction were compared. RESULTS: Despite comparable fertilization rates (58.8% versus 59.2%; P > 0.05), there was a significant decrease in the percentage of good-morphology zygotes (41.1% versus 88.4%; P < 0.05) and embryos (36.7% versus 74.0%; P < 0.05) in the cohort of embryos transferred, clinical pregnancy rate (22.7% versus 42.4%; P < 0.05) and cumulative pregnancy rate from fresh and frozen embryo transfers (22.7% versus 53.5%; P < 0.05) after the restriction. CONCLUSION: The oocyte number restriction reduces dramatically the chance of achieving a clinical pregnancy in cases of nonobstructive azoospermia.

Adult↗
PubMed2006

Qualitative assessment of patient experiences related to extended pelvic resection for rectal cancer.

BACKGROUND: Patients with locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) represent a complex management challenge. While there is potential for cure in a subset of patients, the cost in terms of morbidity can be high. Few descriptions of the physical, psychological, social, and emotional experiences of these patients exist. METHODS: Face-to-face interviews were completed with ten LARC and LRRC patients treated with multimodal therapy that included surgery. Patient opinions and experiences were explored in depth until information redundancy and common themes were delineated using qualitative research methods. Clinical information was obtained from the database. RESULTS: Nine of the ten patients were male, seven had LARC, and the median age was 71. Six themes were identified from the patient interviews. Themes reflected patients' highly focused desire to seek wellness and cure, but also revealed misunderstanding of their disease biology, probability of cure, therapeutic options, and treatment morbidity. CONCLUSIONS: Patient experiences confirm that this is challenging treatment to complete, and that patient understanding of pre-operative information is incomplete. Our findings underscore the need for a multidisciplinary approach when managing this patient population, with emphasis on both supportive care needs and the technically skilled delivery of surgery, chemotherapy, and radiotherapy.

Adult↗
PubMed2005

Killer genes in pancreatic cancer therapy.

This review describes: 1. The main genetic alterations found in pancreatic cancer (EGF-R overexpression, SST-2 somatostatin receptor loss of expression, k-ras, p53 mutations and DPC4 mutations) and the effect of their replacements by gene therapy on tumor growth; 2. The use of suicide genes (HSV-TK and CD) for pancreatic cancer gene therapy in vitro and in vivo; 3. The implications for pancreatic cancer treatment when using cytotoxic bacterial toxins; 4. Viral and non-viral delivery systems for the transfer of therapeutical genes into pancreatic cancer cells. Overall both the correction of pancreatic cancer cells main genetic alterations and the use of suicide genes allow only partial tumor regression in vitro and in vivo. The lack of a 100% effect for any studied strategy considered alone, indicates the need for combined therapies to achieve a satisfactory treatment of this tumor.

Animals↗
PubMed2005

The 2004 Italian legislation regulating assisted reproduction technology: a multicentre survey on the results of IVF cycles.

BACKGROUND: The new Italian law, passed in 2004, regulating assisted reproduction technology imposes that no more than three oocytes can be fertilized at one time and that all embryos obtained must be transferred simultaneously. Oocyte cryopreservation is allowed while embryo cryostorage is banned. The aim of this study was to evaluate the clinical impact of these limitations. METHODS: Seven Italian infertility centres were invited to collect data on IVF cycles performed over the first 4 months of application of the new legislation. As a control, all centres provided data on cycles performed in the same solar period, 1 year before. RESULTS: Data from 1861 cycles were obtained, 961 in the pre-law period and 900 in the post-law period. Pregnancy rate per oocyte retrieval and rate of multiple pregnancies in the pre- and post-law periods were 27.0 and 24.2% (P=0.18) and 25.8 and 20.9% (P=0.11) respectively. However, the prohibition to freeze embryos does appear to have markedly reduced the cumulative rate of success. CONCLUSIONS: The rate of success of IVF-ICSI cycles using fresh embryos is not significantly influenced by the new legislation while the prohibition to freeze embryos seems to result in a more relevant impact.

Adult↗
PubMed2005

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↗
PubMed2005

Use of a fully automated injector for self-administration of follitropin alpha in an IVF/ICSI programme.

Recombinant FSH (r-FSH) used for ovarian stimulation can currently be self-administered either by a conventional syringe or by a pen device. This randomized controlled trial compares the efficacy and convenience of a new, more sophisticated and fully automated injection device (Softinject(trade mark)) with the conventional syringe for r-FSH self-administration. A total of 300 women needing ovarian stimulation for IVF/intracytoplasmic sperm injection were randomized to the automated injector or the conventional syringe group. Patients of both groups had ovarian stimulation with follitropin alpha after pituitary desensitization with a gonadotrophin-releasing hormone agonist. State anxiety score, overall pain score and pregnancy rate were chosen as the main outcome measures. Patients in the automated injector group showed lower state anxiety (P < 0.01) and overall pain (P < 0.01) scores and a comparable pregnancy rate per started cycle as compared with the conventional syringe group. They needed lower doses of r-FSH (P < 0.05) and their stimulation was shorter (P < 0.05). It is concluded that the use of a fully automated injector for r-FSH self-administration reduces pain and stress as compared with the conventional syringe. This device can be used for any subcutaneously administered drug employed in ovarian stimulation.

Adult↗
PubMed2004

Clinical application of laser-assisted ICSI: a pilot study.

Human oocyte survival after intracytoplasmic sperm injection (ICSI) can be compromised by abnormal oolemma breakage patterns during the penetration of the microinjection needle. We previously reported a case of repeated ICSI failures associated with abnormal oolemma breakage in which a substantial improvement and successful pregnancy were achieved by performing ICSI through a laser-drilled hole in the zona pellucida (laser-assisted ICSI). This study was undertaken to compare the efficacy of laser-assisted ICSI with that of conventional ICSI in patients whose oocytes present this particular feature. Oocytes treated by laser-assisted ICSI (n=140) survived better (97.9% versus 85.7%; P<0.05) and tended to form more two-pronucleated zygotes (78.6% versus 69.2%; P=0.07) and less zygotes with three or more pronuclei (2.8% versus 7.8%; P=0.06) as compared with sibling oocytes treated by conventional ICSI (n=140). These data show that laser-assisted ICSI is suitable for oocytes with propensity for sudden oolemma breakage during conventional ICSI. The reduction of oocyte damage with laser-assisted ICSI as compared to conventional ICSI may be useful in other clinical indications where only few oocytes are available or when the oocyte survival after ICSI can be supposed to be compromised.

Female↗
PubMed2004

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↗
PubMed2004

Polscope analysis of meiotic spindle changes in living metaphase II human oocytes during the freezing and thawing procedures.

BACKGROUND: The clinical efficacy of the current methods used for cryopreservation of metaphase II human oocytes is low. Meiotic spindle disorders are thought to be largely responsible for this situation. METHODS: Supernumerary fresh metaphase II human oocytes were cryopreserved in 1,2-propanediol with 0.1 M sucrose using a slow freezing/rapid thawing programme. Meiotic spindles were analysed in these living metaphase II oocytes at sequential steps of the freezing and thawing procedures with the use of a computer-assisted polarization microscopy system (Polscope). RESULTS: The meiotic spindle was detected in all 56 oocytes (from 16 patients) before freezing and remained visible in all these oocytes throughout the preparation for freezing up to the time that they were loaded into cryopreservation straws. Immediately after thawing, the spindle was visible in 35.7% of oocytes, but it disappeared in all of the thawed oocytes during the subsequent washing steps. However, the spindle reappeared in all surviving thawed oocytes after washing (57.4%), by 3 h of incubation at 37 degrees C in culture medium. CONCLUSIONS: The current techniques of oocyte freezing and thawing inevitably cause meiotic spindle destruction. All spindles observed in thawed oocytes result from post-thaw reconstruction.

Cell Survival↗
PubMed2004

Altered glucose metabolism and proteolysis in pancreatic cancer cell conditioned myoblasts: searching for a gene expression pattern with a microarray analysis of 5000 skeletal muscle genes.

BACKGROUND AND AIMS: We verified whether conditioned media (CM) from pancreatic cancer cell lines (MIAPaCa2, CAPAN-1, PANC-1, BxPC3) alter glucose metabolism and gene expression profiles (microarray experiment with a platform of 5000 skeletal muscle cDNA) in mice myoblasts. METHODS: Myoblasts were incubated with control or pancreatic cancer CM for 24 and 48 hours. RESULTS: Lactate significantly increased in CM compared with non-conditioned myoblasts. No variations in expression levels of the main genes involved in glycolysis were found in CM myoblasts. Propionyl coenzyme A carboxylase and isocitrate dehydrogenase 3 beta genes, which encode enzymes of the tricarboxylic acid cycle, were overexpressed, while IGFIIR and VAMP5 genes were underexpressed in CM myoblasts. PAFAH1B1 and BCL-2 genes (intracellular signal transduction) and the serine protease cathepsin G (proteolysis), were overexpressed in CM myoblasts. Tyrosine accumulation in CM myoblasts suggested that proteolysis overcomes protein synthesis. Sorcin, actin alpha, troponin T1, and filamin A were underexpressed in CM myoblasts. CONCLUSIONS: Our findings demonstrate that pancreatic cancer cell conditioned media enhanced lactate production and induced proteolysis, possibly by altering expression levels of a large number of genes, not only those involved in protein biosynthesis and degradation or glucose metabolism, but also those involved in the tricarboxylic acid cycle and in vesicle traffic.

Aged↗
PubMed2004

[Etiopathogenesis of endometriosis related infertility].

In the last years the entire scientific community has devoted remarkable resources to the understanding of endometriosis. In spite of this, endometriosis remains one of the most complex gynecological diseases, in nearly all of its physiopathological aspects and implications. In particular, the association between endometriosis and infertility has proven to be complex and it has been widely discussed. It is generally accepted that moderate/severe endometriosis related sterility is due to mechanical factors, namely to the distortion/subversion of the regular pelvic anatomy. On the contrary, the factors behind infertility/subfertility related to minimal/mild endometriosis are less clear. None of the hypothesized mechanisms exhaustively explained the infertility related to endometriosis, while it is possible that such disease is caused by multiple factors altogether. The aim of this thorough review of the international literature is to analyze the main etiological factors (i.e. alterations in oocyte maturation and/or growth, defects of fertilization, impairments of implantation or aberrant immunological mechanisms) that are potentially involved, as well as the role that each of the above mentioned factors has in determining the endometriosis related infertility/subinfertility.

Adult↗
PubMed2003

Suicide gene therapy with HSV-TK in pancreatic cancer has no effect in vivo in a mouse model.

AIM: To study in vivo whether pancreatic cancer tumour growth and metastasis can be modified by a gene construct with HSV-TK suicide gene and IL2 co-expression. METHODS: Seventy-eight female SCID mice were i.p. inoculated with retrovirally transduced or control MIA PaCa 2, CAPAN-1 and PANC-1 cell lines. The animals were then randomly selected for saline or ganciclovir (GCV) treatment from the second week, for a total of two weeks. RESULTS: Most inoculated mice developed tumour nodules and spleen metastases. The liver was colonized by control CAPAN-1 and MIA PaCa 2, but not by PANC-1. Tumours in transduced MIA PaCa 2 cell injected mice were smaller, and in transduced CAPAN-1 injected mice larger, than in control-inoculated mice. There were increased pancreatic and decreased spleen metastases from transduced CAPAN-1, and diminished liver involvement from transduced MIA PaCa 2. No differences were found between mice inoculated with transduced and control PANC-1 cell lines. GCV treatment had no effect on tumour's size or metastases. CONCLUSIONS: The HSV-TK suicide gene does not confer GCV sensitivity to pancreatic cancer in this in vivo model. Different pancreatic cancer cell lines cause different growth and metastasis patterns after inoculation in SCID mice, possibly because of variations in their inherent characteristics. The different effects of our vector on cell growth and metastasis may be attributable to the effects of the immunostimulatory cytokine IL2.

Animals↗
PubMed2003

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↗
PubMed2003

Birth of a healthy female after preimplantation genetic diagnosis for Charcot-Marie-Tooth type X.

The X-linked dominant form of Charcot-Marie-Tooth syndrome (CMTX) is a clinically and genetically heterogeneous hereditary disorder of the peripheral nerves caused by mutations in the GJB1 gene that encodes a gap junction protein named connexin 32 (Cx32). Clinically, CMTX is characterized by peripheral motor and sensory deficit with muscle atrophy. A couple with a previous history of pregnancy termination after being diagnosed positive for CMTX by chorionic villus sampling, was referred for preimplantation genetic diagnosis (PGD). The female partner carried the causative H94Q, characterized by a C-->G substitution in codon 94 of exon 2 of the GJB1 gene. Embryos obtained after intracytoplasmic sperm injection (ICSI) were evaluated for the presence of the mother's mutation using polymerase chain reaction (PCR), followed by mutation analysis performed using the minisequencing method. Amelogenin sequences on the X and Y chromosomes were also co-amplified to provide a correlation between embryo gender and mutation presence. A single PGD cycle was performed, involving nine fertilized oocytes, five of which developed into good quality embryos useful for biopsy. Two unaffected embryos were transferred, resulting in a singleton pregnancy followed by the birth of a healthy female.

Adult↗
PubMed2003

Genetic control of serum IgE levels: a study of low molecular weight protein tyrosine phosphatase.

Protein tyrosine phosphatases (PTPases) have recently been recognized as important modulators of various signal transduction pathways in immune cells. Genetic polymorphisms have been described in genes codifying for members of this family of enzymes, and the genetics of PTPases is predicted to play an important role in the etiology of immune diseases and of their clinical variability. The low molecular weight protein tyrosine phosphatase (ACP1 or LMPTP) is one of the few PTPases with a known genetic polymorphism, and has been proposed to be associated with atopic dermatitis in a small sample from an Italian population. In this paper we describe the association of the ACP1 polymorphism with total IgE levels in two independent samples from English and Italian populations. In both the samples the mean value of serum IgE is lower among subjects carrying the BC genotype than in other ACP1 genotypes. The BC genotype is associated with the highest total ACP1 enzymatic activity. Our data suggest that one or both of the ACP1 isoforms exert an inhibitory role on some signal transduction pathway relevant for IgE hyperproduction.

DNA Primers↗