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1.
Hum Reprod ; 28(10): 2838-47, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23756703

RESUMEN

STUDY QUESTION: Do patients with polycystic ovary syndrome (PCOS) have macroscopic and/or microscopic placental alterations? SUMMARY ANSWER: The placental structure in patients with PCOS, even in those with uncomplicated pregnancy, is altered. WHAT IS KNOWN ALREADY: The spectrum of pregnancy complications seems to have a common denominator: a defective trophoblast invasion and placentation. In women with PCOS, alterations in endovascular trophoblast invasion related to insulin resistance and hyperandrogenism have been observed. STUDY DESIGN, SIZE, DURATION: For this prospective case-control study, 30 pregnant patients with PCOS (cases) and 60 healthy pregnant women without PCOS features (controls) were enrolled and studied until delivery. Clinical, biochemical, ultrasonographic and obstetric data were recorded. The baseline clinical and biochemical data for screening for PCOS and for inclusion/exclusion were obtained before the seventh week of gestation. At delivery, placentas were collected and detailed macroscopic and microscopic analyses were performed. PARTICIPANTS, SETTING, METHODS: Cases and controls were matched for age and BMI (all <30 kg/m(2)). The matching procedure was one-to-two. Only subjects with spontaneous conception and uncomplicated pregnancies were included in the final analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Placental weight (P = 0.04), thickness (P = 0.02), density (P = 0.02) and volume (P = 0.01) were significantly inferior in women with, compared with those without PCOS. The placentas from patients with PCOS more frequently had an irregular shape (P = 0.03) and a higher cord coiling index (P = 0.02). Differences between cases and controls also concerned the extent of villous (P = 0.04) and intervillous (P = 0.01) spaces, the extent of fibrosis (P = 0.03), endovascular trophoblast (depth, extension and morphometry) (P < 0.05) and mitotic activity (P = 0.01). The percentage of patients with lesions [22/30 (73.3%) versus 25/60 (41.7%), respectively; P = 0.01] and the mean number of placental lesions (3.5 ± 2.1 versus 1.4 ± 1.1, respectively; P = 0.02) were higher in the PCOS than the control group. The odds ratio for placental alterations, adjusted for weight gain, was 2.8 (95% confidence interval 1.3-9.9). LIMITATIONS, REASONS FOR CAUTION: The main limitation of the study was the selection of a specific PCOS sample, which is probably not representative of the PCOS phenotype as a whole. In fact, we excluded patients with PCOS who were obese and who achieved a pregnancy following the use of ovulation inductors or assisted reproduction techniques. WIDER IMPLICATIONS OF THE FINDINGS: The present study is the first to demonstrate that the morphology and microscopic structure of placenta in patients with PCOS with an uncomplicated pregnancy are altered. Further studies are needed to assess a correlation of these changes with the increased risk of obstetric complications observed in some pregnancies of women with PCOS. STUDY FUNDING/COMPETING INTEREST(S): The authors declare no conflict of interest and no financial support for the research. TRIAL REGISTRATION NUMBER: N/A.


Asunto(s)
Placenta/patología , Síndrome del Ovario Poliquístico/patología , Estudios de Casos y Controles , Femenino , Humanos , Placentación , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/diagnóstico por imagen , Embarazo , Complicaciones del Embarazo/diagnóstico por imagen , Complicaciones del Embarazo/patología , Resultado del Embarazo , Ultrasonografía , Arteria Uterina/diagnóstico por imagen
2.
Hum Reprod ; 25(11): 2783-91, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20858697

RESUMEN

BACKGROUND: Clomiphene citrate (CC) is the first-line therapy for the induction of ovulation in infertile women with polycystic ovary syndrome (PCOS), but ∼20% of patients are unresponsive. The aim of the current study was to test the hypothesis that a 6-week intervention that consisted of structured exercise training (SET) and hypocaloric diet increases the probability of ovulation after CC in overweight and obese CC-resistant PCOS patients. METHODS: A cohort of 96 overweight and obese CC-resistant PCOS patients was enrolled consecutively in a three-arm randomized, parallel, controlled, assessor-blinded clinical trial. The three interventions were: SET plus hypocaloric diet for 6 weeks (Group A); 2 weeks of observation followed by one cycle of CC therapy (Group B); and SET plus hypocaloric diet for 6 weeks, with one cycle of CC after the first 2 weeks (Group C). The primary end-point was the ovulation rate. Other reproductive data, as well as anthropometric, hormonal and metabolic data, were also collected and considered as secondary end points. RESULTS: After 6 weeks of SET plus hypocaloric diet, the ovulation rate was significantly (P =0.008) higher in Group C [12/32 (37.5%)] than in Groups A [4/32 (12.5%)] and B [3/32 (9.4%)] with relative risks of 3.9 [95% confidence interval (CI) 1.1-8.3; P = 0.035] and 4.0 (95% CI 1.2-12.8; P = 0.020) compared with Groups A and B, respectively. Compared with baseline, in Groups A and C, a significant improvement in clinical and biochemical androgen and insulin sensitivity indexes was observed. In the same two groups, the insulin sensitivity index was significantly (P < 0.05) better than that in Group B. CONCLUSIONS: In overweight and obese CC-resistant PCOS patients, a 6-week intervention of SET and a hypocaloric diet was effective in increasing the probability of ovulation under CC treatment. The study was registered at Clinicaltrials.gov:NCT0100468.


Asunto(s)
Clomifeno/uso terapéutico , Dieta Reductora , Ejercicio Físico , Infertilidad Femenina/terapia , Estilo de Vida , Inducción de la Ovulación/métodos , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Adulto , Resistencia a Medicamentos , Ingestión de Energía , Femenino , Humanos , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Sobrepeso , Ovulación/efectos de los fármacos , Síndrome del Ovario Poliquístico/complicaciones , Embarazo
3.
BJOG ; 117(6): 711-21, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20236107

RESUMEN

OBJECTIVE: To study the impedance to blood flow through the uterine artery in pregnant women with polycystic ovary syndrome (PCOS), and to evaluate its predictive value for adverse pregnancy and perinatal outcomes in this population. DESIGN: Prospective case-control study. SETTING: Academic Departments of Obstetrics and Gynaecology in Italy. POPULATION: Seventy-three pregnant women with ovulatory PCOS (PCOS group) and 73 age- and body mass index-matched healthy pregnant controls (control group). METHODS: Serial Doppler velocimetry measurements of the uterine artery. MAIN OUTCOME MEASURES: Blood flow impedance indices and pregnancy/perinatal outcomes. RESULTS: A significantly (P < 0.05) higher rate of subjects with abnormal velocimetry findings was observed in the PCOS group than in the control group. In the PCOS group, the pulsatility index (PI) at first (P = 0.042) and mid-second (P = 0.039) trimesters of pregnancy, and bilateral notch at first (P = 0.025) and mid-second (P = 0.007) trimesters of pregnancy, were the strongest independent predictors of adverse outcomes. Conversely, in the control group, PI at the first trimester of pregnancy was a predictor of adverse outcomes only when combined with bilateral notch (P = 0.042), whereas at mid-second trimester of pregnancy PI (P = 0.033) and bilateral notch (P = 0.048) were independent predictors of adverse outcomes. CONCLUSIONS: Uterine artery Doppler indices are more commonly altered in pregnant patients with PCOS than in controls, showing a high predictive value for abnormal pregnancy/perinatal outcomes.


Asunto(s)
Síndrome del Ovario Poliquístico/fisiopatología , Complicaciones del Embarazo/fisiopatología , Arteria Uterina/fisiopatología , Útero/irrigación sanguínea , Adulto , Velocidad del Flujo Sanguíneo/fisiología , Estudios de Casos y Controles , Femenino , Humanos , Embarazo , Resultado del Embarazo , Primer Trimestre del Embarazo , Segundo Trimestre del Embarazo , Estudios Prospectivos , Ultrasonografía Doppler Dúplex/métodos , Ultrasonografía Prenatal/métodos , Arteria Uterina/diagnóstico por imagen , Resistencia Vascular/fisiología , Adulto Joven
4.
Eur J Gynaecol Oncol ; 29(1): 101-4, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18386478

RESUMEN

BACKGROUND: Neuroendocrine tumours are a heterogeneous group of separate clinico-pathological entities which have a common characteristic, i.e., expression of potential endocrine differentiation. In the ovary, the term "neuroendocrine" relates mainly to widely known carcinoids, but it may also be applied to rare neuroendocrine carcinomas as non-small cell type and small cell carcinomas of pulmonary type. In the literature only 11 cases of primary ovarian non-small cell neurendocrine carcinomas have been described and ten of these were associated with a surface epithelial ovarian tumour. Small cell neuroendocrine carcinoma of the ovary is a rare malignant tumour of the ovary. Advanced small cell carcinoma of the ovary is a very aggressive tumour with an overall poor prognosis and unfavourable outcome. CASE REPORT: The case reported is unique in the literature because the authors describe a rare case of endometrial metastasis of a primary ovarian non-small cell neurendocrine carcinoma without any surface epithelial ovarian tumour association. The tumour invaded up to less than half of the myometrium. The first symptoms were related to endometrial metastasis as metrorrhagia and pelvic pain while the asymptomatic presence of primary ovarian carcinoma was not acknowledged with physical examination, routine biochemistry, tumour markers, blood count and traditional transvaginal greyscale ultrasound. CONCLUSION: Magnetic resonance and three-dimensional (3D) ultrasonography with power Doppler are a great help in the diagnosis of ovarian localisation but only immunohistochemistry on histological material can provide a correct diagnosis. Immunohistochemistry expression of Ki67 is a useful marker of malignancy. Due to the rarity of this neoplasm, a general consensus for optimal treatment has yet to emerge. The reported biological aggressiveness of these tumours prompts combined treatment with radical surgery and adjuvant polychemotherapy.


Asunto(s)
Carcinoma Neuroendocrino/secundario , Neoplasias Endometriales/secundario , Neoplasias Ováricas/patología , Carcinoma Neuroendocrino/complicaciones , Carcinoma Neuroendocrino/diagnóstico por imagen , Neoplasias Endometriales/complicaciones , Neoplasias Endometriales/diagnóstico por imagen , Femenino , Humanos , Metrorragia/etiología , Persona de Mediana Edad , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/diagnóstico por imagen , Dolor Pélvico/etiología , Ultrasonografía
5.
Hum Reprod ; 23(3): 642-50, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18158291

RESUMEN

BACKGROUND: Lifestyle modifications are successfully employed to treat obese and overweight women with polycystic ovary syndrome (PCOS). The aims of the current pilot study were (i) to compare the efficacy on reproductive functions of a structured exercise training (SET) programme with a diet programme in obese PCOS patients and (ii) to study their clinical, hormonal and metabolic effects to elucidate potentially different mechanisms of action. METHODS: Forty obese PCOS patients with anovulatory infertility underwent a SET programme (SET group, n = 20) and a hypocaloric hyperproteic diet (diet group, n = 20). Clinical, hormonal and metabolic data were assessed at baseline, and at 12- and 24-week follow-ups. Primary endpoint was cumulative pregnancy rate. RESULTS: The two groups had similar demographic, anthropometric and biochemical parameters. After intervention, a significant improvement in menstrual cycles and fertility was noted in both groups, with no differences between groups. The frequency of menses and the ovulation rate were significantly (P < 0.05) higher in the SET group than in diet group but the increased cumulative pregnancy rate was not significant. Body weight, body mass index, waist circumference, insulin resistance indexes and serum levels of sex hormone-binding globulin, androstenedione and dehydroepiandrosterone sulphate changed significantly (P < 0.05) from baseline and were significantly different (P < 0.05) between the two groups. CONCLUSIONS: Both SET and diet interventions improve fertility in obese PCOS patients with anovulatory infertility. We hypothesize that in both interventions an improvement in insulin sensitivity is the pivotal factor involved in the restoration of ovarian function but potentially acting through different mechanisms.


Asunto(s)
Anovulación/terapia , Ejercicio Físico , Síndrome del Ovario Poliquístico/dietoterapia , Síndrome del Ovario Poliquístico/terapia , Reproducción , Adulto , Estudios de Cohortes , Femenino , Humanos , Insulina/fisiología , Estilo de Vida , Proyectos Piloto , Síndrome del Ovario Poliquístico/fisiopatología , Embarazo , Índice de Embarazo
6.
Hum Reprod ; 22(2): 578-85, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17050549

RESUMEN

BACKGROUND: During the childbearing years, the standard fertility-sparing treatment for bilateral borderline ovarian tumours (BOTs) is the unilateral oophorectomy plus controlateral cystectomy. The aim of the present study was to compare the effects of two laparoscopic fertility-sparing surgical procedures for the treatment of bilateral BOTs on recurrence and fertility in young women who desire to conceive as soon as possible. METHODS: Thirty-two women affected by bilateral early-stage BOTs who desired to conceive were randomized to receive bilateral cystectomy (experimental group, n=15) or oophorectomy plus controlateral cystectomy (control group, n=17). At the first recurrence after childbearing completion, each patient was treated with non-conservative standard treatment. Recurrences and reproductive events were recorded. RESULTS: After a follow-up period of 81 months (19 inter-quartile; 60-96 range), the cumulative pregnancy rate (CPR) (14/15 versus 9/17; P=0.003) and the cumulative probability of first pregnancy (P= 0.011) were significantly higher in the experimental than in control group. No significant (P=0.358) difference between groups was detected in cumulative probability of first recurrence. CONCLUSIONS: The laparoscopic bilateral cystectomy followed by non-conservative treatment performed at the first recurrence after the childbearing completion is an effective surgical strategy for patients with bilateral early-stage BOTs who desire to conceive as soon as possible.


Asunto(s)
Infertilidad Femenina/prevención & control , Neoplasias Ováricas/cirugía , Índice de Embarazo , Adulto , Cistectomía , Femenino , Humanos , Laparoscopía , Recurrencia Local de Neoplasia/cirugía , Neoplasias Ováricas/patología , Ovariectomía , Embarazo
7.
Eur J Obstet Gynecol Reprod Biol ; 119(1): 87-93, 2005 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-15734091

RESUMEN

In women with polycystic ovary syndrome (PCOS) weight loss is associated with an improvement in insulin sensitivity and a reduction of the insulin concentration in the plasma. It is clear, then, that the first therapeutic approach that can be considered in obese PCOS patients for restoration of the menstrual cycle should be a diet. The aim of our study was to examine the effect of long-term caloric restriction on the clinical and biochemical abnormalities in obese PCOS women. The results obtained make it clear that caloric restriction for 4 weeks causes an increase in SHBG and decreases of free testosterone and insulin, with consequent improvement of the clinical picture.


Asunto(s)
Obesidad/dietoterapia , Obesidad/fisiopatología , Síndrome del Ovario Poliquístico/fisiopatología , Restricción Calórica , Femenino , Humanos , Insulina/sangre , Resistencia a la Insulina/fisiología , Obesidad/complicaciones , Ovario/fisiopatología , Síndrome del Ovario Poliquístico/complicaciones , Globulina de Unión a Hormona Sexual/análisis , Testosterona/sangre
9.
Clin Exp Obstet Gynecol ; 30(1): 67-9, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-12731750

RESUMEN

A case of cervical pregnancy after curettage for presumptive intrauterine blighted ovum is presented. The woman was successfully treated by vacuum evacuation and curettage. A 29-year-old woman, gravida 2, nulliparous, was admitted to our department at ten weeks and two days of gestation after a diagnosis of cervical pregnancy. She had been treated by curettage five days before for an initial diagnosis of intrauterine blighted ovum. Ultrasound scan examination revealed a gestational sac without foetus in the cervix four days after the first curettage. Vacuum evacuation and curettage of the cervical canal were performed and a Foley catheter was also inserted and left in place for three days. The patient was discharged in good condition on the fourth postoperative day.


Asunto(s)
Dilatación y Legrado Uterino , Óvulo/patología , Embarazo Ectópico/diagnóstico por imagen , Adulto , Errores Diagnósticos , Femenino , Humanos , Embarazo , Ultrasonografía , Hemorragia Uterina
10.
Minerva Ginecol ; 55(1): 63-7, 2003 Feb.
Artículo en Italiano | MEDLINE | ID: mdl-12598845

RESUMEN

BACKGROUND: The Dandy-Walker Syndrome (DWS) is a congenital malformation of the structures of the posterior cranial fossa with failure of the Luschka and Magendie foramina, which connect the ventricular system to the subarachnoid space, to open. In this syndrome, the cerebellar vermis may be absent or hypoplastic, the hemispheres small, the encephalic trunk and cervical spinal bone marrow flattened, complete or partial absence of cerebellar vermis, cystic dilatation of IV ventricle and frequently hydrocephalus. METHODS: We evaluated 56 cases of fetal malformations of the central nervous system from January 1998 to May 2001. Of these 56, 11 regarded the Dandy-Walker Syndrome. Ultrasound examinations were carried out at the 9(th) and 10(th) weeks, at the 21(st)-23(rd) weeks and at the 31(st) to 34(th) weeks of gestation so as to assess foetal anatomy and morphology. RESULTS: The results of the 11 pregnancies with Dandy-Walker Syndrome were as follows: 3 spontaneous miscarriages (at the 15(th), 18(th) and 20(th) weeks of gestation), 5 therapeutic abortions, 3 term pregnancies. Of the 3 newborns we were only able to follow the clinical course of two of them; both newborns underwent an intervention for ventriculo-peritoneal fluid derivation. At the moment both babies, aged respectively 30 and 25 months, are in good physical, intellectual and behavioural condition. CONCLUSIONS: Bearing in mind the notable clinical and socioeconomic importance of this malformation, we consider foetal morphological ultrasound to be a valid instrument for the correct management of pregnancy. Identification of lesions makes use of the comparison of ultrasound data with the results of histopathological examinations.


Asunto(s)
Síndrome de Dandy-Walker/diagnóstico por imagen , Enfermedades Fetales/diagnóstico por imagen , Ultrasonografía Prenatal , Aborto Espontáneo/etiología , Aborto Terapéutico , Adulto , Autopsia , Síndrome de Dandy-Walker/embriología , Síndrome de Dandy-Walker/patología , Síndrome de Dandy-Walker/cirugía , Femenino , Enfermedades Fetales/embriología , Enfermedades Fetales/patología , Feto/patología , Humanos , Recién Nacido , Masculino , Embarazo , Resultado del Tratamiento , Derivación Ventriculoperitoneal
11.
Minerva Ginecol ; 54(2): 185-7, 2002 Apr.
Artículo en Italiano | MEDLINE | ID: mdl-12032457

RESUMEN

Purpose of this paper is to evaluate the risk of ateletasis in patients that underwent surgery of the abdomen (cesarean section), since the reflex of cough in these patients is notably altered for the limitation of the diaphragmatic excursions, due to analgesic contracture. The inhibition of cough's reflex causes retention of secretions with consequent bronchial obstruction and atelectasis. Personal experience in 6 cases of atelectasis following cesarean section is reported.


Asunto(s)
Cesárea/efectos adversos , Complicaciones Posoperatorias , Atelectasia Pulmonar/etiología , Adulto , Ambroxol/uso terapéutico , Expectorantes/uso terapéutico , Femenino , Humanos , Embarazo , Atelectasia Pulmonar/diagnóstico , Atelectasia Pulmonar/diagnóstico por imagen , Atelectasia Pulmonar/terapia , Radiografía Torácica , Factores de Tiempo
12.
J Assist Reprod Genet ; 19(1): 14-8, 2002 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11893010

RESUMEN

PURPOSE: To test the effects of type of embryo transfer catheter, transfer difficulty, and observations after the transfer procedure on pregnancy and implantation rates in an IVF programme. METHODS: Patients were prepared for IVF using standard protocols. Embryo transfer was performed using either Edwards-Wallace or TDT catheter. The difficulty of transfer was graded by a clinician and biologist. Blood observed inside the catheter after the transfer procedure was scored as endometrial damage. Pregnancy and implantation rates were scored. RESULTS: Type of embryo transfer catheter and the observation of blood did not significantly affect pregnancy and implantation rates when transfer was performed by a single operator. CONCLUSIONS: In the hands of experienced, skilled operators, neither choice of transfer catheter and difficulty of transfer nor observations of blood on the transfer catheter caused any significant reduction in outcome to the patient.


Asunto(s)
Cateterismo/instrumentación , Transferencia de Embrión/instrumentación , Fertilización In Vitro/métodos , Adulto , Cateterismo/métodos , Implantación del Embrión , Endometrio/cirugía , Femenino , Humanos , Embarazo , Resultado del Embarazo
13.
Hum Reprod ; 16(9): 1875-9, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11527891

RESUMEN

BACKGROUND: The aim of this study was to investigate the effects of adding human menopausal gonadotrophin (HMG) during controlled ovarian stimulation in normoovulatory normogonadotrophic patients showing an initial suboptimal response to a standardized long protocol therapy with recombinant FSH (rFSH) (300 IU/day). METHODS: A total of 43 such patients were randomized in two groups. In Group A, 150 IU rFSH was substituted by 150 IU HMG after day 8 of stimulation. The stimulation protocol of Group B involved a simple increase of the daily rFSH dose to 375 IU after day 8. A total of 40 BMI and age matched patients with an optimal ovarian response formed the control group (Group C). RESULTS: The mean Group A serum concentration of oestradiol on the day of HCG administration and average number of oocytes retrieved were significantly higher than Group B (P < 0.001) and equivalent to Group C. A total of 10 pregnancies (50%) in Group A, 8 (34.8%) in Group B and 19 (47.5%) in the control group were achieved. CONCLUSIONS: The data suggest that LH supplementation improves the ovarian outcome in patients characterized by an inadequate initial response to rFSH therapy in a long protocol.


Asunto(s)
Fármacos para la Fertilidad Femenina/uso terapéutico , Fertilización In Vitro , Hormona Folículo Estimulante/uso terapéutico , Gonadotropinas/sangre , Menotropinas/uso terapéutico , Hipófisis/metabolismo , Terapia Recuperativa , Adulto , Gonadotropina Coriónica/uso terapéutico , Regulación hacia Abajo , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Hormona Luteinizante/sangre , Oocitos , Embarazo , Índice de Embarazo , Proteínas Recombinantes/uso terapéutico , Manejo de Especímenes
14.
J Chromatogr B Biomed Sci Appl ; 753(2): 427-31, 2001 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-11334360

RESUMEN

The objective of this study was to determine the concentration of free L-amino acids and in particular of L-arginine in the plasma of pregnant women affected by preeclampsia compared to healthy pregnant women in order to know if an alteration in the concentrations of these amino acids occurs in preeclamspia. Twelve pregnant women affected by preeclampsia and twelve pregnant control women, ages 28-35 years old and at the 35-36 weeks of pregnancy were studied. The blood analysis of free amino acids was carried out by using a high performance liquid chromatographic (HPLC) fluorometric method and OPA-NAC as derivatizing agent for the amino acid determination. In the blood of women affected by preeclampsia L-arginine is markedly reduced compared to controls (about five-fold lower, P<0.01). The other amino acids also are significantly reduced, but to lesser extents (about 1.5 times lower, P<0.05). Thus, the determination of L-arginine in the blood of pregnant women could potentially constitute an additional marker for the early diagnosis of preeclampsia.


Asunto(s)
Arginina/sangre , Preeclampsia/sangre , Adulto , Aminoácidos/sangre , Aminoácidos/aislamiento & purificación , Arginina/aislamiento & purificación , Estudios de Casos y Controles , Femenino , Humanos , Embarazo , Reproducibilidad de los Resultados , Espectrometría de Fluorescencia
15.
Endocrinology ; 141(10): 3862-70, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11014243

RESUMEN

In this study, using an enzymatic HPLC method in combination with D-aspartate oxidase, we show that N-methyl-D-aspartate (NMDA) is present at nanomolar levels in rat nervous system and endocrine glands as a natural compound, and it is biosynthesized in vivo and in vitro. D-aspartate (D-Asp) is its natural precursor and also occurs as an endogenous compound. Among the endocrine glands, the highest quantities of D-Asp (78 +/- 12 nmol/g) and NMDA (8.4 +/- 1.2 nmol/g) occur in the adenohypophysis, whereas the hypothalamus represents the area of the nervous system where these amino acids are most abundant (55 +/- 9 and 5.6 +/- 1.1 nmol/g for D-Asp and NMDA, respectively). When D-Asp is administered to rats by ip injection, there is a significant uptake of D-Asp into the adenohypophysis and a significant increase in the concentration of NMDA in the adenohypophysis, hypothalamus and hippocampus, suggesting that D-Asp is an endogenous precursor for NMDA biosynthesis. Experiments conducted on tissue homogenates confirm that D-Asp is the precursor of the NMDA and that the enzyme catalyzing this reaction is a methyltransferase. S-adenosyl-L-methionine (SAM) is the methyl group donor. In vivo experiments consisting of ip injections of sodium D-aspartate show that this amino acid induced a significant serum PRL elevation and this effect is dose and time dependent. In vitro experiments conducted on isolated adenohypophysis or adenohypophysis coincubated with the hypothalamus, showed that the release of PRL is caused by a direct action of D-Asp on the pituitary gland and also mediated by the indirect action of NMDA on the hypothalamus. Then, the latter induces the release of a putative factor that in turn stimulates the adenohypophysis reinforcing the PRL release. In conclusion, our data suggest that D-Asp and NMDA are present endogenously in the rat and are involved in the modulation of PRL release.


Asunto(s)
Ácido Aspártico/fisiología , Agonistas de Aminoácidos Excitadores/metabolismo , N-Metilaspartato/fisiología , Prolactina/metabolismo , Animales , Ácido Aspártico/metabolismo , Ácido Aspártico/farmacología , Agonistas de Aminoácidos Excitadores/farmacología , Hipocampo/metabolismo , Hipotálamo/metabolismo , Masculino , N-Metilaspartato/biosíntesis , N-Metilaspartato/metabolismo , N-Metilaspartato/farmacología , Hipófisis/metabolismo , Adenohipófisis/metabolismo , Ratas , Ratas Wistar
16.
Clin Exp Obstet Gynecol ; 26(3-4): 213-6, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10668160

RESUMEN

OBJECTIVE: Hirsutism is considered as a skin disease due to increased 5 alpha-reductase activity in the pilosebaceous unit and finasteride is a drug that inhibits this enzymatic activity. This study showed the effectiveness of a chronic treatment with a selective 5 alpha-reductase inhibitor, finasteride, in idiopathic and PCOS-associated hirsutism. METHODS: Finasteride was administered orally at a daily dose of 5 mg for a period of 12 months to 20 women with IH and 20 women with PCOS. MAIN OUTCOME MEASURES: Each group was submitted to clinical (with Ferriman-Gallwey method) and serum hormonal (FSH, LH, 17 beta-estradiol, total and free T, delta 4-androstenedione, DHEAS; dihydrotestosterone, 3 alpha-androstanediol glucuronide) studies at baseline and after 3, 6 and 12 months of treatment. RESULTS: After 3 months of finasteride treatment, a significant decrease in the average hirsutism scores was recorded both in IH (p < 0.0001) and PCOS patients (p < 0.0001). A progressive significant decrease of hirsutism score was observed in IH patients after 6 and 12 months (p < 0.002) and in PCOS patients after 6 but not 12 months. In fact, the maximal therapeutic effect on the hirsutism was obtained after 12 months in the IH and 6 months in PCOS group.


Asunto(s)
Inhibidores Enzimáticos/administración & dosificación , Finasterida/administración & dosificación , Hirsutismo/tratamiento farmacológico , Adolescente , Adulto , Inhibidores Enzimáticos/uso terapéutico , Femenino , Finasterida/uso terapéutico , Hirsutismo/etiología , Humanos , Síndrome del Ovario Poliquístico/complicaciones , Resultado del Tratamiento
17.
J Endocrinol Invest ; 20(9): 513-8, 1997 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9413804

RESUMEN

GABAergic drugs affect PRL secretion in both rat and man. Sodium valproate (SV) inhibits GABA transaminase so increasing the endogenous GABAergic tone. The aim of this study was to evaluate the effects of SV at low and high doses on PRL release in healthy subjects and hyperprolactinemic patients. Fifteen patients with prolactinomas, 8 patients with non-tumoral hyperprolactinemia and 10 healthy subjects were studied: in non consecutive days, all subjects received placebo and SV at the dose of 400 and 800 mg po. Serum PRL levels were assessed 30, 15 and 5 min before and every 30 min for 4 hours after administration. SV at the dose of 400 mg induced a significant decrease of serum PRL in healthy subjects (p < 0.05), whereas no effect was noted in both tumoral and non-tumoral hyperprolactinemia. The administration of 800 mg SV induced a significant decrease of PRL levels in healthy subjects and in patients with non-tumoral hyperprolactinemia (p < 0.05). Conversely, in prolactinomas a paradoxical increase of serum PRL concentration (p < 0.05) was observed 120 min after the administration of the drug. These data confirm the inhibitory activity of SV on PRL release in healthy subjects, and suggest the existence of a partial resistance to GABA in non-tumoral hyperprolactinemia. In prolactinomas, the paradoxical PRL increase after high dose of SV suggests the existence of a complete pituitary resistance to GABA. This finding might be explained by the appearance of the stimulatory effect of GABA at hypothalamic level that could have been unmasked by the lack of pituitary GABA effects on adenomatous lactotrophs.


Asunto(s)
GABAérgicos/administración & dosificación , Hiperprolactinemia/fisiopatología , Neoplasias Hipofisarias/metabolismo , Prolactina/metabolismo , Prolactinoma/metabolismo , Ácido Valproico/administración & dosificación , Adolescente , Adulto , Femenino , GABAérgicos/farmacología , Humanos , Cinética , Persona de Mediana Edad , Prolactina/sangre , Ácido Valproico/farmacología , Ácido gamma-Aminobutírico/farmacología
18.
Panminerva Med ; 39(3): 174-7, 1997 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9360417

RESUMEN

OBJECTIVE: To ascertain whether the prognostic value of desmoplastic reaction and lymphocytic infiltration are a good prognostic index to estimate survival in breast cancer patients. METHODS: From 1987 to 1994, the authors have evaluated the prognostic value of desmoplastic reaction and lymphocytic infiltration related to rode state in 34 patients with breast cancer. For statistical analysis and comparison of means the "t"-test was used. The significance level was 0.01. RESULTS: The group of patients with abundant desmoplastic reaction shows an overall survival rate lower than the group with poor desmoplastic reaction (p < 0.01) and the survival of the group with abundant desmoplastic reaction was related to lymphnodal status. CONCLUSIONS: Many prognostic factors have been shown during these years, some connected to patient, some connected to neoplasm and others connected to the treatment. Recently many other prognostic factors have been recognized, among which the possible prognostic role of desmoplasia has been carefully valued. Certainly, today the prognostic value of desmoplastic reaction and lymphocytic infiltration cannot take the place of usual prognostic factors in the evaluation of breast cancer patient yet the desmoplastic reaction is a good prognostic index to estimate the survival in these patients.


Asunto(s)
Neoplasias de la Mama/patología , Linfocitos Infiltrantes de Tumor/patología , Adulto , Anciano , Neoplasias de la Mama/diagnóstico , Femenino , Humanos , Persona de Mediana Edad , Pronóstico
19.
Gynecol Endocrinol ; 10(4): 257-64, 1996 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-8908526

RESUMEN

During the years 1991-1994, 97 anovulatory infertile women with polycystic ovarian syndrome (PCOS) were treated with laparoscopic electrocautery of the ovarian surface after they had failed to ovulate under ovarian stimulation. To assess the endocrinological and clinical outcome and in an attempt to determine the mechanism of action, the serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), androstenedione, testosterone and dehydroepiandrosterone sulfate (DHEAS) were determined before and after laparoscopic ovarian cautery. Fifty regularly cycling women undergoing laparoscopy for investigation of infertility or tubal ligation served as controls. In patients with PCOS but not in controls, the reduction of androgen levels and normalization of cycle length were highly significant. In contrast, LH and FSH levels rose during the first 2 days after the operation. These results resemble those reported after ovarian wedge resection. Ovulation was obtained in 90% (81 of 90) and pregnancy in 81.1% (73 of 90) of the patients; that increased to 84.4%, including the non-responders (nine patients) treated with clomiphene citrate (CC), after electrocautery. The response to ovarian electrocautery was influenced by body weight, with an ovulation rate of 95-96% in the slim and moderately obese women, decreasing to 81-82% in the really obese ones. When ovulation was established, the pregnancy rate was independent of body weight. However, a striking relationship was detected between smoking habits and pregnancy rate subsequent to ovarian electrocautery, ranging from 24% in smokers to 92% in non-smoking couples. In 30 second-look operations, de novo adhesions were found in 23.3% of the patients (7 of 30). Therefore, ovarian electrocautery is an effective procedure to improve the intraovarian mechanism of selecting a dominant follicle for patients with PCOS in whom initial medical management fails, and it appears to be one of the possible treatments for this disease. A possible postoperative complication may be adhesion formation that seem to be lower than after ovarian wedge resection.


Asunto(s)
Androstenoles/sangre , Electrocoagulación/métodos , Infertilidad Femenina/cirugía , Laparoscopía , Ovario/cirugía , Síndrome del Ovario Poliquístico/cirugía , Adulto , Androstenodiona/sangre , Androstenodiona/metabolismo , Androstenoles/metabolismo , Peso Corporal , Estudios de Cohortes , Deshidroepiandrosterona/sangre , Deshidroepiandrosterona/metabolismo , Electrocoagulación/efectos adversos , Femenino , Hormona Folículo Estimulante/sangre , Hormona Folículo Estimulante/metabolismo , Humanos , Hormona Luteinizante/sangre , Hormona Luteinizante/metabolismo , Concentración Osmolar , Ovulación/fisiología , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/fisiopatología , Complicaciones Posoperatorias , Embarazo , Índice de Embarazo , Estudios Prospectivos , Reoperación , Testosterona/sangre , Testosterona/metabolismo , Factores de Tiempo , Adherencias Tisulares/etiología , Resultado del Tratamiento
20.
Fertil Steril ; 66(1): 61-5, 1996 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8752612

RESUMEN

OBJECTIVE: To determine of the clinical and hormonal effects of finasteride (Proscar; Merck, Sharp, and Dohme, Rahway, NJ) in the treatment of idiopathic hirsutism and hirsutism in patients with polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: Istitute of Obstetrics and Gynecology, University of Naples "Federico II." PATIENTS: Ten women affected by idiopathic hirsutism and 15 women with PCOS. INTERVENTIONS: Finasteride was administered orally at a daily dose of 5 mg for a period of 6 months. MAIN OUTCOME MEASURES: Rating of hirsutism with the Ferriman-Gallwey method; serum androgen assays. RESULTS: Finasteride produced a reduction in the average hirsutism scores ( > 50% in all patients), whereas no change was observed in serum T, androstenedione, and DHEAS levels. A significant reduction was measured in serum dihydrotestosterone and 3 alpha, 17 beta-androstenediol glucuronide levels. CONCLUSIONS: This study demonstrates that symptomatic hirsutism has to be considered as a skin disease associated with the increased activity of the 5 alpha-reductase. It also indicates that the selective 5 alpha-reductase inhibitor, finasteride, is very effective and well tolerated in the treatment of both idiopathic hirsutism and of hirsutism in patients with PCOS.


Asunto(s)
Inhibidores Enzimáticos/uso terapéutico , Finasterida/uso terapéutico , Hirsutismo/tratamiento farmacológico , Adulto , Andrógenos/sangre , Femenino , Hirsutismo/sangre , Hirsutismo/etiología , Humanos , Síndrome del Ovario Poliquístico/complicaciones , Resultado del Tratamiento
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