Uterine leiomyoma cytogenetics. III. Interphase cytogenetic analysis of karyotypically normal uterine leiomyoma excludes possibility of undetected trisomy 12.

Uterine leiomyoma, a benign tumor that histopathologically is rather homogeneous, was recently characterized cytogenetically. About 40% of the investigated tumors are associated with clonal chromosome abnormalities and five different subgroups have been identified, characterized by trisomy 12, t(12;14)(q14-15;q23-24), del(7q), t(1;2)(p36;p24), and 6p rearrangements. In our survey of 76 cases, trisomy 12 was observed in 10% of the abnormal cases. To exclude a possible underscoring of this abnormality, we reexamined 15 of the cases with normal karyotype by interphase cytogenetics using a chromosome 12 alphoid DNA probe.

Uterine leiomyoma cytogenetics. II. Report of forty cases.

Chromosome analysis of 40 cultured uterine leiomyomas revealed the presence of clonal changes in 32.5% of them, confirming the cytogenetic heterogeneity within this type of tumor, mostly referable to a few cytogenetic subgroups. Preferential involvement of 12q14-15 and 14q23-24 bands in reciprocal and complex translocations was most commonly observed. Deletions of chromosome 7 and changes of chromosomes 1, 2, and to a lesser extent, chromosomes 19 and 22 were also found. Constitutional karyotype of patients bearing tumors with karyotypic abnormalities was examined. In one patient, two cells were found with t(12;14)(q14-15;q23-24) translocation and two with del(14)(q13q23-24). The latter rearrangement was also present as a clonal change in the tumor.

[Preoperative levels of CA 125 and risk factors in adenocarcinoma of the endometrium]. / Livelli preoperatori del CA 125 e fattori di rischio nell'adenocarcinoma dell'endometrio.

Preoperative serum CA 125 levels were measured in 61 patients with various FIGO stage endometrial adenocarcinoma and they were compared with stage of disease, grading and pelvic lymph nodes involvement. Serum CA 125 levels in excess of 35 U/ml were detected in 19 patients (31.1%): circulating levels exceeding 65 U/ml were also found in 15 patients (24.5). Rising concentrations were associated with increasing stages. Grading and lymph nodes involvement were correlated with the presence of elevated serum levels (more than 65% for grade two or three and more than 80% in patients with positive lymph nodes). Preoperative high concentrations of CA 125 suggest the presence and the probability of advanced endometrial cancer. The cases with elevated CA 125 serum levels seems to be a higher risk for extrauterine tumor progression and lymphatic space invasion: the preoperative presence of the antigen imposes an accurate intraoperative surgical staging and a careful follow-up for preventing recurrence or metastases.

5-(2-bromoethyl)-2'-deoxyuridine: a selective inhibitor of herpes simplex viruses in vitro.

A new pyrimidine analog, 5-(2-bromoethyl)-2'-deoxyuridine (BEUdR), was tested in vitro for antiviral activity on Herpes simplex virus types 1 and 2. As reference compounds, ACG, BVUdR and PAA were used. Compared to ACG and BVUdR, BEUdR resulted less potent on both HSV-1 and HSV-2. However, a 50% inhibition of the multiplication of uninfected cells could be obtained only at very high BEUdR concentration (ID50 = 8500 microM). This makes BEUdR the least toxic analog known and gives it a selective index comparable to, if not better, than of ACG and BVUdR.

Uterine leiomyoma cytogenetics. I. Rearrangements of chromosome 12.

Cytogenetic investigation on 19 benign tumors of uterine smooth muscle was carried out after short-term cultures. Clonal chromosome abnormalities were present in four cases; 15 had normal karyotypes. All four cases with abnormal karyotype showed changes of chromosome 12. In three cases, chromosome 12 was involved in structural rearrangements with chromosome X, 1, and 4, respectively. Breakpoints on this chromosome occurred in different regions. The fourth case had trisomy 12 and an extra deleted chromosome 2, del(2)(p22). These findings confirm the involvement of chromosome 12 in uterine leiomyoma.

A specific translocation, t(12;14)(q14-15;q23-24), characterizes a subgroup of uterine leiomyomas.

We have cytogenetically investigated short-term cultures initiated from 34 uterine leiomyomas, all of which were histologically completely benign. Clonal chromosome abnormalities were detected in five cases, a normal female complement in 22, whereas, in the remaining seven tumors no karyotype could be established. Apparently identical reciprocal translocations, t(12;14)(q14-15;q23-24), were found as the sole abnormality in four tumors. The fifth abnormal case contained a t(2;14)(p11;p11). We conclude that chromosome aberrations may be found in myomas of the uterus, and that t(12;14)(q14-15;q23-24) characterizes a subset of these tumors.

Activity of interferon beta in condylomata with dysplastic lesion of the uterine cervix.

The effectiveness of interferon beta in the treatment of condylomata of the cervico-vaginal tract associated with CINs was evaluated in 25 patients. Human fibroblastic interferon (IFN beta) was administered by intra and perilesional infiltration at a dosage of 3 x 10(6) IU/day for 5 consecutive days the first week and every other day the second. The treatment showed: complete regression in 61.76% of CIN I and 58.69% of CIN II; partial regression in 26.47% of CIN I and 21.73% of CIN II. The picture remained unvaried in 11.76% of CIN I and 19.56% of CIN II.

HSV2 and cervical intraepithelial neoplasia: cytological, histological and serological features.

An epidemiological investigation on the incidence of HSV2 infection in 1216 women with acute or recurrent vulvovaginitis was performed. HSV2 research was carried out by means of clinical, cytological, colposcopic, histologic examinations and vaginal pad cultures and antibody titration. Of the patients examined, 12.6% presented signs of genital herpes; among the diagnostic techniques used, the most reliable proved to be the serological method. Incidence of HSV2 was higher among women in the under privileged social classes, those who had sexual relations with different partners and those who were multiparous. A higher percentage of dysplastic and/or neoplastic lesions of the uterine cervix among HSV2 positive (P less than 0.025) with respect to controls was also found. A higher incidence of neoplastic pathologies among women who are positive for HSV2 was therefore confirmed.

Hormonal profile and androgen status during the menstrual cycle in women with acne.

The androgen excess in women with acne can play an important role in gynecological endocrinology. LH, FSH, PRL, Testosterone (T), Androstenedione (A), Deydroepiandrosterone sulphate (DHEA-S) and Progesterone (P) were investigated in 21 women with uncomplicated idiopathic acne during the menstrual cycle. LF/FSH ratio greater than 3 was found in 7 cases (36.8%). Total T values were high in 90.4% of the whole group of women with acne (mean +/- SD 618.6 +/- 253.6, normal range 92-352 pg/ml). An ovulatory pattern of P was found in 66.65% of women with acne. Hyperprolactinemia was found in 23.6% of cases. The common denominator for ovulatory dysfunction in these women seems to be elevated LH levels, rather than elevated T levels.

Embryonal carcinoma in two cases of androgen insensitivity syndrome: clinical, endocrinological and pathological features.

Embryonal carcinoma in two cases of complete androgen insensitivity syndrome (CAIS) is reported. In both cases gonadectomy carried out for prophylactic purposes led to the discovery of a localized embryonal carcinoma with areas of anaplastic seminoma in one case. In non-neoplastic tissue, gonad morphology in both cases was typical of AIS. Prevalently hypotrophic aspects, especially in the interstitial gland, were found in case 2. This may explain the different endocrine profile in the two cases before gonadectomy. Our study, aside from series of psycho-sexual problems, shows, according to all Authors, that the most serious complication is the high risk of malignancy after puberty in patients with AIS.

Antigenic and cytochemical characterization of cells adhering to intrauterine contraceptive devices.

Eighteen copper intrauterine devices (IUDs), removed after 25 months of use, were examined to evaluate cells adhering to them (IAC). By means of monoclonal antibodies, the antigenic phenotype of IAC was studied, along with some IAC cytochemical properties. Sixty percent of IAC were identified as granulocytes based on morphological, cytochemical, and antigenic characteristics. A small proportion of IAC were shaped like large foreign-body macrophages, with multiple picnotic nuclei, and diffused alpha naphthyl acetate esterase (ANAE) activity. Some IAC identified as macrophages from a morphological view point also showed dipeptidyl-diaminopeptidase IV (DAPIV) reactivity, previously described only in T-helper lymphocytes. Most IAC identified as macrophages reacted with the monoclonal antibodies OKM1 and HLA-DR, and showed ANAE activity in the form of small multiple granules. The hypothesis that IUD-adhering macrophages with an ANAE+, DAPIV+, OKM1+, and HLA-DR+ phenotype could play a role in the inactivation of spermatozoa can be proposed.

Carcinoma IB of the endometrium: spread and prognostic factors.

The prognostic factors and their intercorrelation in 47 patients with IB endometrial cancer are presented. The data reveal the particular behaviour of the lymphatic involvement: five patients (10.6%) showed metastases to pelvic lymph nodes and six patients (12.8%) had paraaortic node metastases; altogether two women (4.2%) had histological evidence of involvement of pelvic and paraaortic nodes. Both histological grade and depth of myometrial invasion showed a characteristic relationship with the lymphatic spread: the percentage of lymph node metastases seems to bear relation to progression of myometrial penetration (M2-M3) and to histological differentiation (G2-G3).

Immunoperoxidase localization of HSV2 antigens in cervical dysplasia and carcinoma.

The AA. have evaluated by means of the immunohistochemical technique the incidence of herpetic phlogosis in 76 women with neoplastic pathologies of the uterine cervix. The patients were submitted to cytologic, colposcopic and histologic examination for CIN. The HSV2 positivity by immunohistochemical method was demonstrated in 53 (35.3%) cases of CIN and invasive carcinoma. The results confirm the frequent association between HSV2 and cervical carcinoma and they support a specific therapeutic approach to be made in the prevention and clinical management of the carcinoma.

Short term treatment with ketoconazole: effects on gonadal and adrenal steroidogenesis in women.

Ketoconazole, an imidazole derivative, is a large spectrum antifungal agent. The drug is known to cause a decrease in plasma androgens and adrenal steroids in normal men; it is also an active drug in the treatment of malignant tumors of the prostate. To examine the antiandrogenic action of this drug in women, we measured several gonadal and adrenal steroids in 21 normally menstruating women before and after receiving oral ketoconazole (200 mg twice daily) for 5 days. Plasma testosterone (T) decreased from a basal level of 0.35 to 0.25 ng/ml (+/- SEM) (P less than 0.001); dihydrotestosterone (DHT) from a basal level of 190.62 +/- 23.2 to 159.75 +/- 19.43 pg/ml (P less than 0.02); dehydroepiandrosterone sulphate (DHEA-S) from 1.42 +/- 0.44 to 1.15 +/- 0.19 micron/ml (P less than 0.02). Plasma 17 beta-estradiol (E2) decreased from a basal level of 97.42 +/- 29.37 to 54.32 +/- 9.9 pg/ml (P less than 0.05). In contrast, plasma 17-OH-progesterone (17-OHP) levels increased from a basal level of 44.81 +/- 8.21 to 71.81 +/- 15.81 ng/100 ml (P less than 0.05). These results confirm that the ketoconazole blocks the conversion of progestins into androgens. The decrease in the plasma concentration of E2 suggest a direct effect of the ketoconazole on the ovary. It is likely that the effect of the drug, both at the level of the ovaries and of the adrenal gland, is dose-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Management, therapy and outcome of treatment in women with pelvic endometriosis.

Sixty-four cases of endometriosis treated between 1980 and 1985 were reclassified according to the R-A.F.S. Twenty-eight of the patients (43.7%) were followed for 24-39 months: in this group we evaluated the efficiency of medical treatment (Danazol), combined medical and conservative surgical or definitive surgical treatment on the basis of the persistence, complete or partial regression of the symptoms. In this group of patients the symptoms regressed completely in 39.28% of the cases; in 28.57% there was a partial regression and persistence or recurrence of the symptoms were reported in 32.14%. These results suggest that the classification system is a key to interpreting treatment.

Control of homozygous beta-thalassemia by carrier screening and antenatal diagnosis in Sardinians.

This paper reports the present results of an ongoing program aimed at preventing homozygous beta-thalassemia by means of heterozygote screening and antenatal diagnosis in the Sardinian population. Screening based on the knowledge of carrier frequency and types of thalassemia prevalent in this population was designed to discover all heterozygotes except the few silent beta-thalassemia carriers. Most of the couples at risk were informed and accepted testing. Information was conveyed by mass media, midwives and marriage registry offices. Antenatal diagnosis was accepted by the majority of the couples counselled. The results of antenatal testing were very accurate. There was only one misdiagnosis out of 949 pregnancies tested. This risk of fetal loss was 7.5%. The program was highly effective, as shown by the decline of the incidence of the homozygous state from 1:205 live births in 1976 to 1:557 in 1981.

Effect of thyrotropin-releasing hormone in pituitary-thyroid system function infertile women after surgical castration.

The Authors evaluate the effect of surgical castration on thyroid function of fertile women, and the response of TSH to TRH before and 30 days after castration.