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Costantino Di Carlo

Publications and source records attributed to Costantino Di Carlo.

At least 19 recordsLinked to original sources
PubMed2026

Genomic Sequencing in Neonatal Encephalopathy and Suspected Hypoxic-Ischaemic Encephalopathy: A Systematic Review.

BACKGROUND: Neonatal encephalopathy (NE) is a major cause of neonatal mortality and long-term neurological disability. Although hypoxic-ischaemic encephalopathy (HIE) is the most common cause, several genetic disorders may mimic or coexist with hypoxic-ischaemic injury. Next-generation sequencing has emerged as a promising diagnostic tool in this setting. This systematic review evaluated the current evidence on genomic sequencing in NE. MATERIAL AND METHODS: A systematic review was conducted according to PRISMA 2020 guidelines and prospectively registered in PROSPERO. PubMed/MEDLINE, Embase, and Scopus were searched from inception to June 2026. Eligible studies included neonates (≤28 days) with NE, suspected or confirmed HIE, HIE mimics, or unexplained NE who underwent genomic sequencing. Whole-exome sequencing (WES), whole-genome sequencing (WGS), clinical exome sequencing (CES), rapid genomic sequencing, and targeted next-generation sequencing panels were considered. Study quality was assessed using the Newcastle-Ottawa Scale. RESULTS: Seven studies met the inclusion criteria. Considerable heterogeneity was observed regarding patient selection, sequencing strategies, and reported outcomes. Among diagnostic sequencing studies, diagnostic yield ranged from 23.5% to 53.1%. Pathogenic and likely pathogenic variants were identified in genes associated with developmental and epileptic encephalopathies, metabolic disorders, mitochondrial diseases, and neurodevelopmental syndromes, including SCN2A, KCNQ2, CACNA1A, STXBP1, PTPN11, BCOR, MMUT, COQ2, and GBE1. Genomic sequencing frequently refined or changed the initial diagnosis, improved prognostic assessment and genetic counselling, and, in selected cases, guided disease-specific treatment. One study investigated genetic susceptibility to hypoxic-ischaemic injury rather than diagnostic sequencing. CONCLUSIONS: Genomic sequencing provides clinically meaningful diagnoses in a substantial proportion of neonates with unexplained NE or atypical HIE presentations. Current evidence supports integrating genomic sequencing into the diagnostic evaluation of selected infants, although larger prospective studies are needed to define its optimal timing, clinical utility, and cost-effectiveness.

Humans↗
PubMed2006

Use of office hysteroscopy to empty a very large hematometra in a young virgin patient with mosaic Turner's syndrome.

OBJECTIVE: To describe the successful management of a hematometra using a 5-mm continuous flow operative office hysteroscope. DESIGN: Case report. SETTING: University of Naples "Federico II." PATIENT(S): A 13-year-old virgin patient affected by mosaic Turner's syndrome (45 X; 46 XX) was referred to the emergency room of the Department of Obstetrics and Gynecology after an episode of severe pelvic pain with metrorrhagia. A large hematometra was detected by transabdominal ultrasound scanning. INTERVENTION(S): Vaginoscopic hysteroscopy performed in outpatient setting. MAIN OUTCOME MEASURE(S): Complete resolution of the hematometra and related clinical symptoms. RESULT(S): Vaginoscopic approach avoided general anesthesia and preserved the integrity of her hymen. A chocolate-like fluid started to spill out from the uterine cavity as soon as the tip of hysteroscope passed through the internal uterine ostium. A transabdominal ultrasound performed 2 days later showed resolution of the hematometra. Success of the procedure was confirmed by the resolution of all clinical symptoms. CONCLUSION(S): In selected cases, with intact outflow tract, outpatient vaginoscopic hysteroscopy might represent the therapeutic technique of choice in case of hematometra, even in the case of virgin patients.

Adolescent↗
PubMed2006

Do serum leptin levels have a role in the prediction of pregnancy outcome in case of threatened miscarriage?

OBJECTIVE: To determine whether maternal serum leptin levels can predict pregnancy outcome in cases of threatened miscarriage. DESIGN: Observational study. PATIENTS: Fifty-seven women with normal pregnancy (group A), 19 women with threatened miscarriage who delivered at term (group B), 22 women with threatened miscarriage with subsequent miscarriage (group C) and 27 women with delayed miscarriage (group D). MEASUREMENTS: Maternal serum leptin was determined using a commercial radioimmunoassay (RIA) kit. RESULTS: Serum leptin levels were not significantly different among groups A, B and C [median (range) 17.6 (10.1-26.5), 18.2 (12.5-25.6) and 17.3 (11.2-27.6) microg/l, respectively]. Women in group D showed significantly lower serum leptin levels in comparison with other groups [14 (6.7-21.3) microg/l; P < 0.05]. CONCLUSIONS: Serum leptin levels in the first trimester of pregnancy may not be the primary indicator of miscarriage in cases of threatened abortion.

Abortion, Spontaneous↗
PubMed2005

Bleeding patterns during continuous estradiol with different sequential progestogens therapy.

OBJECTIVE: : To evaluate the effects on monthly bleeding of four different progestogens administered in association with transdermal estradiol in a continuous sequential estrogen-progestin therapy (CS-EPT). DESIGN: : This prospective, open, randomized, clinical trial included 100 healthy postmenopausal women. Patients were randomized into four treatment groups, each consisting of 25 women. Treatment consisted of 50 mug/day transdermal 17beta-estradiol for all women combined to receive four different progestogens (group A: medroxyprogesterone acetate, 10 mg/day; group B: nomegestrol acetate, 5 mg/day; group C: dydrogesterone, 10 mg/day; group D: micronized progesterone, 200 mg/day) per os from the 14th to 25th day of each 28-day cycle. The duration of treatment was 12 cycles. Patients were asked to record in a daily diary the occurrence of any vaginal bleeding, the days of application of each patch, the days of assumption of the different progestogens, and the exact moment of bleeding onset. RESULTS: : A total of 937 cycles could be evaluated. In 690 cycles (73.6%), regular progestogen-related bleeding was reported. Among the other cycles, we observed 73 episodes of amenorrhea (7.8%, each one lasting one cycle), 78 episodes of irregular bleeding (8.3%), and 96 episodes of spotting (10.2%). Patients receiving nomegestrol acetate had a significantly higher incidence of regular progestogen-associated bleeding in comparison with those receiving medroxyprogesterone acetate or natural progesterone, and patients receiving dydrogesterone had a significantly higher incidence of regular progestogen-associated bleeding in comparison with those receiving natural progesterone. CONCLUSION: : Our data suggest that CS-EPT generally leads to regular withdrawal bleeding in women without uterine pathology. Micronized progesterone seems to induce more irregular bleeding episodes.

Administration, Cutaneous↗
PubMed2005

Evaluation of skeletal status by quantitative ultrasonometry in postmenopausal women without known risk factors for osteoporosis.

The objective of our study was to evaluate bone density in Italian postmenopausal women without clinical risk factors for osteoporosis resident in the Naples area using quantitative ultrasonometry of bone (QUS). Subjects were 1149 Italian postmenopausal women (age: 54.9 +/- 5.0 years (mean +/- standard deviation); range: 45-74 years) resident in the Naples area. Clinical risk factors for osteoporosis resulting in exclusion from the study were family history of osteoporosis, dietary, smoking and alcohol habits, personal history of fractures and/or metabolic diseases. The following QUS parameters were calculated: amplitude-dependent speed of sound (AD-SoS), T-score and Z-score. We found significant inverse correlations between AD-SoS and age (r = - 0.23), time since menopause (r = - 0.25) and body mass index (BMI) (r = - 0.16). The same was observed for T-score. In contrast, Z-score showed a significant positive correlation with age and time since menopause, and a negative correlation with BMI. A T-score suggestive of high risk for osteoporosis (less than -3.2) was found in 1.6% of subjects, while a T-score suggestive of moderate risk for osteoporosis (between -3.2 and -2) was found in 19.3% of patients. In this group of women without clinical risk factors for osteoporosis we found a very low prevalence of QUS results suggesting a high risk for osteoporosis. However, a condition of 'moderate' risk for osteoporosis was present in a remarkable percentage of these women.

Absorptiometry, Photon↗
PubMed2004

Effects of two types of hormonal contraception--oral versus intravaginal--on the sexual life of women and their partners.

BACKGROUND: Data relating to the influence of hormonal contraception on sexual life are conflicting and mostly they refer to oral contraceptives. In this randomized, controlled, prospective study we compared the effect of an intravaginal hormonal contraceptive with the effect of a combined oral contraceptive on sexual function. METHODS: Fifty-one healthy women with a permanent partner and an active sexual life were randomly divided in two groups according to a computer-generated randomization list: 26 women (group A) used an intravaginal contraceptive releasing 120 microg/day of etonogestrel and 15 microg/day of ethinylestradiol (EE) and 25 women (group B) used an oral contraceptive containing 20 microg di EE and 150 microg of desogestrel. Twenty-five women participated in the study as control group (group C). A specific questionnaire was completed by the patients and their partners at the start of the study and after cycles 3 and 6 of contraceptive use. RESULTS: Within 3 months of contraceptive use, women from both groups A and B reported a global improvement in sexual function. A statistically significant increase in sexual fantasy was reported only by patients of group A. Whereas partners of the women in both groups A and B reported an improvement in sexual function after 3 months of contraceptive intake, only patients' partners of group A reported a significant increase in sexual interest, complicity and sexual fantasy. CONCLUSIONS: Both hormonal contraceptives tested were seen to have a positive effect on some aspects of sexual function. The intravaginal contraceptive ring seems to exert a further positive effect on the psychological aspect of both women and their partners, which is evident from an improved complicity and sexual satisfaction.

Administration, Intravaginal↗
PubMed2004

Estrogen and raloxifene modulate leptin and its receptor in hypothalamus and adipose tissue from ovariectomized rats.

Obesity, from declining estrogen levels after menopause, increases the risk of heart disease, diabetes, and hypertension. Ovariectomy (OVX) in rats is a good model of estrogen insufficiency. The ensuing mild obesity is useful to study how hypoestrogenism alters adiposity. This study examines the hypothesis that in ovariectomized (OVX) rats modification of estrogen levels or treatment with a selective estrogen receptor modulator, raloxifene (RAL), alters leptinemia and modulates leptin receptor (Ob-R) abundance in hypothalamus and white adipose tissue, similar to the modification of adipose status induced by hypoestrogenism. Mid- and long-term studies (7 and 22 wk) were conducted to monitor the change in leptinemia in rats after estrogen loss by OVX and after estrogen replacement by 17beta-estradiol (OVX+E(2)) or RAL treatment (OVX+RAL). Leptin was significantly higher in OVX rats vs. controls, in a time-dependent manner. This effect was reversed by both E(2) and RAL treatment at 7 wk (P < 0.05) and 22 wk (P < 0.001). Moreover, E(2) or RAL treatment reversed the OVX-induced increases in food intake, body weight, and fat mass content; the modifications of serum parameters were examined to evaluate the different lipid profiles. We also evaluated Ob-R expression in hypothalamus and adipose tissue by Western blot analysis. The expression of the long functional isoform (Ob-Rb) increased at 7 wk only in adipose tissue and decreased at 22 wk in OVX rats in both tissues; these effects were reversed by E(2) or RAL treatment. We provide evidence that central and peripheral Ob-Rb expression is related to modification of estrogen levels.

Adaptation, Physiological↗
PubMed2004

Estrogen-progestogen induced hematocolpometra following allogeneic stem cell transplant.

OBJECTIVES: Gynecological manifestation of chronic graft-versus-host disease (cGVHD) has been invariably described in association with its extensive form. We have also observed it in a patient with the limited cGVHD form. DESIGN: We here describe our experience of gynecological complications in a population of 30 women who were followed up in a single center 12-120 months after allogeneic stem cell transplant (allo-SCT) due to hematological malignancies. All of them manifested premature ovarian failure because of the received treatments. RESULTS: Three out of 14 women who were affected by cGVHD developed hematocolpometra after estrogen + progestogen therapy (EPT) introduction, due to uterine and vaginal dystrophy and synecchiae. Extensive cGVHD, including dermal and mucosal localization, was present in two women while the third had only liver involvement. None of our patients had received radiation therapy or had a posttransplant history of infection. Local application of estrogens consistently improved the gynecological complication. However, vaginal synecchiae tended to relapse when local treatment was interrupted, despite no other apparent evidence of active cGVHD. CONCLUSIONS: All women with cGVHD should undergo gynecological examination before introducing EPT, to avoid unpleasant complication as hematocolpometra. Vaginal and cervical synecchiae should be treated with prolonged local treatments, and temporary use of continuous EPT regimens may be preferable in these women. Moreover, close monitoring by pelvic exam and ultrasonography is advisable during the initial cycles to detect any complication caused by possible intrauterine adhesions undetected during the previous gynecological examination.

Adolescent↗
PubMed2004

A mutation in the follicle-stimulating hormone receptor as a cause of familial spontaneous ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) occurs mainly after excessive stimulation of the ovaries by exogenous gonadotropins administrated in the context of in vitro fertilization procedures (iatrogenic OHSS). Recently, spontaneous and recurrent occurrence of the disease (spontaneous OHSS) was shown in two families to be caused by mutations affecting the follitropin receptor (FSHr). The two mutant FSHr (T449I, D567N) harbor aminoacid substitutions in the serpentine portion of the receptor and display abnormally high sensitivity to the pregnancy hormone hCG, thus providing a satisfactory explanation to the phenotype. In addition, mutant D567N showed also increased sensitivity to thyrotopin (TSH) and displayed increase in basal (ligand-independent) activity. In this report, we describe a new familial case of recurrent OHSS. The affected women were heterozygous for a different mutation involving codon 449, where an alanine was substituted for threonine. Similar to D567N, the T449A FSHr mutant shows an increase of its sensitivity to both hCG and TSH, together with an increase in basal activity. Together with the two previous studies, this report shows that inappropriate stimulation of the FSHr by hCG is a cause of spontaneous OHSS.

Adult↗
PubMed2004

A mutation in the follicle-stimulating hormone receptor as a cause of familial spontaneous ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) occurs mainly after excessive stimulation of the ovaries by exogenous gonadotropins administrated in the context of in vitro fertilization procedures (iatrogenic OHSS). Recently, spontaneous and recurrent occurrence of the disease (spontaneous OHSS) was shown in two families to be caused by mutations affecting the follitropin receptor (FSHr). The two mutant FSHr (T449I, D567N) harbor aminoacid substitutions in the serpentine portion of the receptor and display abnormally high sensitivity to the pregnancy hormone hCG, thus providing a satisfactory explanation to the phenotype. In addition, mutant D567N showed also increased sensitivity to thyrotopin (TSH) and displayed increase in basal (ligand-independent) activity. In this report, we describe a new familial case of recurrent OHSS. The affected women were heterozygous for a different mutation involving codon 449, where an alanine was substituted for threonine. Similar to D567N, the T449A FSHr mutant shows an increase of its sensitivity to both hCG and TSH, together with an increase in basal activity. Together with the two previous studies, this report shows that inappropriate stimulation of the FSHr by hCG is a cause of spontaneous OHSS.

Adult↗
PubMed2003

Effect of tibolone on breast symptoms resulting from postmenopausal hormone replacement therapy.

OBJECTIVE: To evaluate the incidence of breast symptoms in a population treated with various hormone replacement therapy (HRT) regimens and to detect the variations in breast symptomatology after HRT changing to tibolone administration. METHODS: This prospective placebo-controlled clinical trial was conducted on healthy women on HRT reporting breast symptoms. A questionnaire was given to each woman to detect breast symptomatology. Breast tenderness and mastalgia were evaluated using a visual analogue scale (VAS). According to the choice of the each woman with breast symptoms, the HRT was changed to tibolone (2.5 mg/day per os) or to calcium carbonate (1 tab/day, placebo group). The duration of treatment was of 12 months. After 6 and 12 months breast symptomatology was re-evaluated. RESULTS: Among the 600 screened women, 64 (10.7%) were suffering from breast symptomatology. After 6 and 12 months of treatment with tibolone or placebo, mean VAS score for breast tenderness and for mastalgia resulted significantly (P<0.05) decreased, without differences between groups, in comparison with basal value. Only one woman had no improvement from the breast symptoms with tibolone administration. CONCLUSIONS: Shifting from classical HRT to tibolone is followed by a significant reduction of breast symptomatology in postmenopausal women with breast complaints similar to that obtained with treatment withdrawal.

Breast↗
PubMed2003

Maternal serum and umbilical cord blood leptin concentrations with fetal growth restriction.

OBJECTIVE: To ascertain whether fetal growth restriction is associated with alterations of leptin concentrations in umbilical cord blood and maternal serum. METHODS: Maternal serum and umbilical cord blood leptin concentrations were determined by immunoradiometric assay at term in 43 women with uncomplicated singleton pregnancies (group A) and in 27 women with singleton pregnancies complicated by fetal growth restriction (group B), all with normal pregravid body mass index (BMI). RESULTS: Maternal serum leptin concentrations were significantly higher in group B compared with group A (45.0 ng/mL [range 34.2-54.9] versus 29.0 ng/mL [range 24.7-33.3]; P<.01). Umbilical cord blood leptin levels were significantly lower in group B compared with group A (8.4 ng/mL [range 3.6-13.2] versus 13.1 ng/mL [9.7-16.5]; P<.01). Maternal serum leptin levels were not significantly correlated with maternal BMI or with neonatal birth weight in either group. Umbilical cord blood leptin concentrations were significantly correlated with neonatal birth weight in both groups. CONCLUSION: Growth restricted fetuses at term show umbilical cord blood leptin concentrations significantly lower than those in normal fetuses, suggesting that fetal adipose tissue is a major source of leptin. Maternal serum leptin concentrations are higher in the presence of a growth restricted fetus. This increase might be due to an intrinsic placental mechanism, by which small placentas produce more leptin as a compensatory mechanism, or to early hypoxia.

Adult↗
PubMed2003

Serum leptin levels in patients with premenstrual syndrome treated with GnRH analogues alone and in association with tibolone.

OBJECTIVE: Leptin seems to regulate reproductive function and it has been hypothesised that its secretion may be induced by oestrogens. Changes in its levels has been advocated as a determinant in the pathogenesis of premenstrual syndrome (PMS). We evaluated serum leptin levels in patients affected by PMS and in controls to establish: (i) if induced hypoestrogenism has an impact on leptin concentrations; (ii) if the administration of tibolone modifies the effects of hypoestrogenism on serum leptin levels; and (iii) if the improvement in PMS symptomatology can be correlated to changes in serum leptin levels. DESIGN: Prospective, randomized study. PATIENTS: Twenty-eight women affected by PMS and 20 unaffected controls. Affected patients were randomly assigned to two groups to receive leuprolide acetate (3.75 mg intramuscularly) plus tibolone (2.5 mg/day) (group A; n = 14) or plus placebo (group B; n = 14), at the onset of the vasomotor symptoms. MEASUREMENTS: Serum leptin, oestradiol and progesterone levels, PMS signs and symptoms evaluated during a 2 months' pretreament period and after 2 months of therapy. RESULTS: No differences in leptin levels among the three groups and within the same group at all time evaluated were observed. Oestradiol and progesterone concentrations were significantly lower in all groups during treatment in comparison with pretreatment values. Before therapy, leptin levels were positively correlated both with oestradiol and progesterone in the follicular and luteal phase in all groups. This correlation was lost after treatment. All PMS patients showed a significant improvement of the symptomatology. CONCLUSIONS: Hypoestrogenism induced by GnRH analogues (GnRHa) does not seem to influence leptin levels in normal women and those with PMS, and the addition of tibolone does not impact on these levels. Because PMS symptomatology did significantly improve during treatment with GnRHa alone, or in associtation with tibolone, it is unlikely that changes in leptin levels could have an important role in the pathophysiology of PMS.

Adult↗
PubMed2002

Glucose regulates insulin mitogenic effect by modulating SHP-2 activation and localization in JAr cells.

The glucose effect on cell growth has been investigated in the JAr human choriocarcinoma cells. When JAr cells were cultured in the presence of 6 mm glucose (LG), proliferation and thymidine incorporation were induced by serum, epidermal growth factor, and insulin-like growth factor 1 but not by insulin. In contrast, at 25 mm glucose (HG), proliferation and thymidine incorporation were stimulated by insulin, serum, epidermal growth factor, and insulin-like growth factor 1 to a comparable extent, whereas basal levels were 25% lower than those in LG. HG culturing also enhanced insulin-stimulated insulin receptor and insulin receptor substrate 1 (IRS1) tyrosine phosphorylations while decreasing basal phosphorylations. These actions of glucose were accompanied by an increase in cellular tyrosine phosphatase activity. The activity of SHP-2 in HG-treated JAr cells was 400% of that measured in LG-treated cells. SHP-2 co-precipitation with IRS1 was also increased in HG-treated cells. SHP-2 was mainly cytosolic in LG-treated cells. However, HG culturing largely redistributed SHP-2 to the internal membrane compartment, where tyrosine-phosphorylated IRS1 predominantly localizes. Further exposure to insulin rescued SHP-2 cytosolic localization, thereby preventing its interaction with IRS1. Antisense inhibition of SHP-2 reverted the effect of HG on basal and insulin-stimulated insulin receptor and IRS1 phosphorylation as well as that on thymidine incorporation. Thus, in JAr cells, glucose modulates insulin mitogenic action by modulating SHP-2 activity and intracellular localization.

3T3 Cells↗
PubMed2002

Bone metabolism in postmenopausal women who were treated with a gonadotropin-releasing hormone agonist and tibolone.

OBJECTIVE: To study the bone metabolism in postmenopausal women who have been treated with gonadotropin-releasing hormone agonist (GnRH-a) and tibolone. DESIGN: Prospective, open, controlled clinical trial. SETTING: Department of Gynecology and Obstetrics, University of Catanzaro, Catanzaro, Italy. PATIENT(S): One hundred twenty perimenopausal women with symptomatic uterine leiomyomas (groups A and B), and 40 healthy control women who underwent a normal spontaneous menopause (group C). INTERVENTION(S): Treatment for 12 months with leuprolide acetate plus tibolone (group A) or hysterectomy with bilateral oophorectomy (group B). MAIN OUTCOME MEASURE(S): Lumbar spine bone mineral density (BMD) and bone turnover markers at entry into the study, after medical treatment (only group A), and 12 months after discontinuation medical treatment (group A) or after surgery (group B). The same parameters were noted in healthy women before and 12 months after menopause (retrospective control group, group C). RESULT(S): At the women's entry into the study, no significant difference in BMD and bone turnover markers was detected between groups A and B. In group A, no significant variation in BMD or bone turnover markers was observed 12 months after medical treatment in comparison with baseline. At 12 months after discontinuation of treatment (in women who had achieved menopause) and after surgery, we observed a statistically significant decrease in BMD and in bone turnover markers in both groups in comparison with baseline. At 12 months after they became menopausal, we also observed a statistically significant reduction in BMD and in bone turnover markers in control group C. At the same 12-month follow-up visit, a statistically significant difference in BMD and in bone turnover markers was detected when comparing groups A and B with group C. CONCLUSION(S): Women previously treated with GnRH-a and tibolone similar to women who are menopausal as a result of surgery, have higher bone loss after menopause.

Antineoplastic Agents, Hormonal↗
PubMed2002

Menstrual status and serum leptin levels in anorectic and in menstruating women with low body mass indexes.

OBJECTIVE: To evaluate serum leptin levels in anorectic women, menstruating women with low body mass indexes (BMI) and normally menstruating women with normal BMI. DESIGN: Prospective study. SETTING: University clinics. PATIENT(S): Fourteen amenorrheic patients with anorexia nervosa (group A), 11 menstruating women with a BMI <18 kg/m(2) (group B), and 20 normal controls. MAIN OUTCOME MEASURE(S): Determination of BMI, caloric intake, total fat mass, ovarian volume, and serum leptin, insulin-like growth factor I, FSH, LH, E(2), PRL, and TSH levels. INTERVENTION(S): None. RESULT(S): Mean BMI and fat mass were similar in groups A and B and significantly higher in controls. Mean caloric intake was significantly lower in group A than in group B and controls. Median serum leptin levels were significantly lower in group A than in group B and controls, and significantly lower in group B than in controls. Median serum insulin-like growth factor I levels were significantly lower in group A than in group B and controls. Binary segmentation analysis of groups A and B showed that LH was the most relevant variable in differentiating the two groups, followed by leptin. CONCLUSION(S): A threshold of leptin levels exist above which, even in the presence of low body mass indexes, the menstrual function is preserved.

Adult↗