Impaired gonadal function in a woman with multiple symmetric lipomatosis.

Multiple symmetric lipomatosis (MSL, OMIM 151800), is a rare disease characterised by the growth of uncapsulated masses of abnormal adipose tissue around the neck, shoulders or other parts of the trunk and typically associated with high ethanol intake. We describe the case of a 33 year-old woman with MSL and secondary amenorrhea. Despite the presence of an ovarian failure confirmed by undetectable serum levels of inhibin B and anti-Müllerian hormone, the patient had normal serum levels of estrone and gonadotropins coexisting with a biological adrenal hyperandrogenism. We suggest that the adrenal hyperandrogenism observed in our patient could be attributed to an impairment of the cytochrome p450 function, inducing a relative 21-hydroxylase deficiency/insufficiency, related to alcohol abuse and that the increased peripheral aromatization of androgens in estrogens lead to normal circulating levels of estrone. The result is the absence of gonadotropin elevation despite primary ovarian failure. The peculiar functional pattern of brown adipocytes in patients with MSL may contribute to this biological phenomenon with an additive effect related to alcohol consumption. Altogether, these data could help to better define the peculiar pituitary-gonadal profile observed in this rare syndrome and in some cases of women with heavy alcohol consumption.

WNT4 deficiency--a clinical phenotype distinct from the classic Mayer-Rokitansky-Kuster-Hauser syndrome: a case report.

The pathways leading to female sexual determination in mammals are incompletely defined. Loss-of-function mutations in the WNT4 gene appear to cause developmental abnormalities of sexual differentiation in women and mice. We recruited six patients with different degrees of Müllerian abnormalities, with or without renal aberrations and a normal female 46,XX karyotype. A clear androgen excess was found only in one patient. This 19-year-old woman was affected by primary amenorrhoea, absence of Müllerian ducts derivatives, clinical (acne and hirsutism) and biochemical (repeatedly high levels of testosterone) signs of androgen excess. Direct sequencing of her WNT4 gene followed by functional studies in human ovarian cells (OVCAR3) was performed. This patient carried the novel R83C loss-of-function dominant negative mutation in her WNT4, confirming the role of WNT4 in the development and maintenance of the female phenotype in women. Our study can also help refine the phenotype of WNT4 deficiency in humans. In fact, it appears that at least in this limited casuistic small group of patients, the absence of a uterus (and not other Müllerian abnormalities) and the androgen excess are the pathognomonic signs of WNT4 defects, suggesting that this might be a clinical entity distinct from the classic Mayer-Rokitansky-Kuster-Hauser syndrome.

[Laparoscopic appendectomy as first choice intervention in the treatment of inflammatory diseases of the appendix. Analysis of 397 laparoscopic interventions]. / L'appendicectomia laparoscopica come intervento di scelta nel trattamento delle malattie infiammatorie dell'appendice. Analisi di 397 interventi laparoscopici.

Despite the increasingly widespread use of laparoscopy, especially for gallbladder diseases, laparoscopic appendectomy has not yet met with universal acceptance. The aim of the present retrospective study was to illustrate the technical aspects and the results of 397 laparoscopic appendectomies carried out at the Surgical Department of the San Giovanni Battista Hospital in Zagarolo, Rome, from January 1993 to December 2000. The patients included 260 females with a mean age of 35.5 years and 137 males with a mean age of 38.5 years. All the appendectomies were carried out laparoscopically, with a conversion index of 0%, by two surgeons, utilising only three trocars and the Veress needle technique. Mean operating time was 22.5 min (range: 15-30 min). The mean postoperative hospital stay was 1.5 days. Morbidity was 1.76% (7 cases) and mortality nil. The authors emphasise the numerous advantages of laparoscopic techniques in their experience, including the excellent cosmetic results, reduced postoperative pain, rapid functional recovery, and lower incidences of adhesions, wound infections and laparocele, and believe that laparoscopic appendectomy is a reliable operation for treating all inflammatory diseases of the appendix.

[Videolaparoscopic treatment of varicocele: retrospective study of 165 cases]. / Trattamento videolaparoscopico del varicocele: studio retrospettivo su 165 casi.

Idiopathic varicocele is a common condition that is present in approximately 15% of the general male population. The mechanism by which varicocele exerts a deleterious effect on testicular function and semen quality remains unknown. Nevertheless, it is generally regarded as a significant factor in male infertility. Varicocelectomy is accomplished with a variety of approaches: the inguinal and high retroperitoneal procedures are still commonly accepted methods, but laparoscopic varicocelectomy is currently proving an increasingly popular procedure. The authors report the results of a retrospective study of 165 laparoscopic varicocelectomies performed from 1993 to 2000 and conclude that this approach is simple, safe and effective and should be recommended as the treatment of choice.

Correlation of Doppler and placental immunohistochemical features in normal and intrauterine growth-retarded fetuses.

The aim of this study was to correlate and compare Doppler and anatomical placental findings obtained from 48 normal and 35 intrauterine growth-retarded (IUGR) fetuses. The IUGR group consisted of 19 fetuses from pregnancies complicated by pre-eclampsia and 16 from healthy mothers. Color Doppler evaluation of umbilical, spiral and uterine arteries was performed. Placental specimens from both normal and growth-retarded fetuses were obtained at the time of delivery. Placental specimens were evaluated using histochemical and immunohistochemical techniques. A progressive decrease in the pulsatility index was observed in umbilical, spiral and uterine arteries throughout pregnancy in the normal-growth fetuses. High umbilical artery pulsatility index values were obtained in 29 out of the 35 growth-retarded fetuses, six of them showing absent or reversed end-diastolic umbilical artery flow pattern. A total of 13 IUGR fetuses showed high resistance uterine artery flow velocity waveforms. Increased pulsatility index values were obtained from the spiral arteries of 16 growth-retarded fetuses. Abnormal histological and histochemical placental patterns were observed in all the growth-retarded fetuses with umbilical artery Doppler abnormalities. The presence of a peculiar dendritic cell subpopulation, strongly resembling the Langerhans cells, expressing the HLA-DR+/CD1+ phenotype, was detected in all growth-retarded fetuses, whether there was maternal pathology or not. Our data show uterine and spiral artery data as being ineffective in the monitoring of IUGR fetuses. The placental extracellular matrix seems to play an important role in the regulation of the umbilical circulation. The presence of CD1+ cells as a sign of a possible immunological mechanism in the pathogenesis of the intrauterine growth retardation is discussed.

Angiogenesis: a new diagnostic aspect of obstetric and gynecologic echography.

An ultrasounds triplex system (pulsed Doppler, Color mode, B mode) has been employed to study ovarian and uterine circulatory changes in fertile, infertile and postmenopausal patients. PI and mean percentage variation of PI mean values have been used. No difference has been detected in uterine haemodynamics between fertile women and those infertile patients getting pregnant by IVF-ET procedure. Patients who did not obtain the pregnancy showed different uterine and endometrial Color Doppler patterns. Furthermore, a typical endometrial blood flow has been detected both in fertile patients and infertile patients who get pregnant. Color Doppler seems to be an useful tool in the monitoring of fibroids blood supply and the uterine blood supply, especially for the clinical monitoring of GnRH analogues therapies. The technique has been also employed for the study of ectopic pregnancy. The evaluation of both uterine and throphoblast haemodynamics has resulted in a good indicator of the pregnancy progression. Concerning the ovarian pathology the color Doppler evaluation has been useful to differentiate ovarian malignant cysts from inflammatory or disfunctional masses. Nevertheless, the most interesting results have been obtained from the study of endometrial and ovarian tumors. Indeed, in the most cases, a mass supply blood flow has been detected, although in some cases no angiogenetic color flow has been found. No difference has been found in uterine artery velocimetry between malign or benign pathologies. Furthermore, histological data supporting our findings are presented.

[Effects of danazol on the endometrium during peri-menopausal meno-metrorrhagia]. / Effetti del danazolo sull'endometrio nella menometrorragia perimenopausale.

Perimenopausal abnormal bleeding is one of the most common gynecological problems. We have assessed the effectiveness of danazol 200 mg daily for 3 months in 42 patients with perimenopausal abnormal bleeding without any previous treatment and in 23 patients previously treated with norethisterone or medroxyprogesterone acetate but with a recurrence of bleeding 2 months after the end of the treatment. In the overall population treated by danazol at the end of treatment we had: bleeding normalized in 88.2% and hysteroscopic patterns, showing regression of hyperplasia in 95% of cases. The endometrial effects were maintained 2 months after the end of treatment with an increase of the hyperplastic pictures at 4 (26%) and up to 12 months (60%). We had amenorrhea in 10% of patients at the end of treatment and in 2 cases only treatment was discontinued for severe side effects. The comparison of these better results with those obtained by progesterone agents and with those of a preliminary experience with GnRH agonists had led us to consider the importance of an additional endometrial effects exerted by danazol. Particularly the immunosuppressive properties of this drug, as we have shown in "in vitro" conditions, can determine a decreased secretion of growth factors by local immune cells which in turn can further explain the endometrial antiproliferative action of this drug.

Immunology and fertilization.

The whole fertilization process can be affected by the presence of iso or auto-antibodies or even Fab fragments against specific antigens involved in fertilization like FA1 sperm surface antigen and ZP1, ZP2 and ZP3 oocyte surface antigens. These knowledges can be used to develop a natural vaccine (FA1 seems to be able to inhibit fertilization). The involvement of HLA in the fertilization process is still disputed but it is surely involved. Clinical and experimental aspects are surveyed.

Immunohistochemical detection of terminal complement complex and S protein in normal and pre-eclamptic placentae.

Terminal complement complex and S protein were searched for in term placentae obtained from 13 women with normal pregnancy and 15 patients with moderate or severe form of pre-eclampsia. Terminal complement complex was found to localize in the fibrinoid material of the decidua of the basal plate, in the stroma of the chorionic villi and in the vessel walls, as subendothelial deposits. S protein had a quite different distribution, being detected in the syncytiotrophoblast located both in the chorionic villi and in the decidua of the basal plate (DBP) and also on the endothelial cells of fetal stem vessels. Mild deposits of C3 were found in the decidua of the basal plate and also in the stroma and on the basal membranes of the villi. Reactivity for C9 neoantigen was also observed in the cytoplasm of some cells, which were recognized to be macrophages by the presence in their cytoplasm of acid phosphatase and by their reaction with a monoclonal antibody specific for macrophages. Differences in complement deposition in normal and pre-eclamptic placentae were essentially quantitative. Possible mechanisms of complement activation are discussed.

[Subpopulations of immunocompetent cells in the placenta in normal pregnancy and in EPH gestosis]. / Subpopulacija imunokompetentnih stanica u placenti u fizioloskim trudnocama i kod EPH gestoza.

An effort of cellular element investigations in placentas of 8 physiological pregnancies and 7 EPH gestoses is performed with the aid of specific monoclonal antibodies by the indirect immunohistochemical method. The average mean of parturient ages (primiparae and pluriparae) was 24 years in EPH gestoses. By the aid of monoclonal antibodies OKT4, OKT8, OKT11, OKT6 and OKDR, Dako-macrophage, 2H4 (Coulter) murine type, immunocompetent cells were identified in the decidua, in the stroma of chorionic villi, in the intervillous space, and in the fibrinoid masses. The semiquantitative indirect method of the immunohistochemical cellular investigation was performed by the aid of optic microscopy in 20 fields per every cutting (section) of the placental tissue. The immunocompetent active cell distribution did not reveal any special difference in the frequency of placental tissues of physiogical pregnancies and EPH gestoses, but OKT11+ cells were present in the major number in gestoses (in decidua). OKT8+ and OKDR+ cells were found in a similar number in both populations, while OKT6+ were not found at all in any investigated tissue.

Glycosaminoglycans in human breast cancer: morphological and biochemical study.

The authors evaluate the distribution and the content of glycosaminoglycans (GAG) in neoplastic tissue from mastectomy specimens of 15 patients treated for an infiltrating ductal carcinoma NOS, in comparison to normal tissue of the opposite quadrant. Neoplastic tissues contain a marked amount (5 mg/g dry defatted tissue) of GAG, in comparison to normal ones (2.2 mg/g dry defatted weight). In stellate carcinomas GAG are localized near the interface with the host tissue and are constituted mainly of chondroitin sulfates and hyaluronate. These data are confirmed by electrophoretic analysis.

Lithium treatment of hypothermia caused by electric shock.

Prostaglandins have hyperthermic as well as hypothermic effects, and lithium, which inhibits the conversion of dihomogammalinolenic acid to PGE1, can produce hyperthermia. Electroconvulsive shock raises prostaglandin F in rat cerebral cortex and in the case presented here lithium normalized temperature in a patient who became hypothermic after she accidentally received an electric shock.