Osteogenesis imperfecta and other skeletal dysplasias presenting with increased nuchal translucency in the first trimester.

We present two case reports of osteogenesis imperfecta associated with increased nuchal translucency in the first trimester. We also review the literature of first trimester diagnosis of skeletal dysplasias and their association with increased nuchal translucency.

Thermal tissue damage following laser and large loop conization of the cervix.

OBJECTIVE: To compare thermal injury zones produced with laser and diathermy loop conization. METHODS: Excisional cervical specimens (cones and cervices) were obtained from 40 consecutive women who underwent abdominal hysterectomy. The subjects were assigned to have either laser or diathermy loop conization (20 in each group). The duration of each procedure was recorded. Histopathologic measurements of thermal injury zones were performed in all specimens. RESULTS: The techniques produced cone specimens of similar depth. The mean depth of thermal injury produced with laser conization in cone specimens (mean +/- standard deviation 0.49 +/- 0.16 mm) and cervical craters (0.58 +/- 0.24 mm) was significantly greater (P < .001) than the corresponding depth in cone specimens (0.22 +/- 0.09 mm) and cervical craters (0.27 +/- 0.11 mm) obtained by diathermy loop excision. The mean time of the two procedures was also significantly different (P < .001); laser conization 11 +/- 4.5 minutes and loop conization 2 +/- 1.2 minutes. CONCLUSION: For routine conization, loop diathermy causes less thermal damage to the specimen and is a faster procedure than laser.

Effects of ball cauterization following loop excision and follow-up colposcopy.

OBJECTIVE: To investigate whether central diathermy ball cauterization after loop excision affects satisfactory colposcopy at follow-up. METHODS: One hundred one consecutive women with the squamocolumnar junction visible at the ectocervix scheduled for loop excision were assigned alternately into two groups. In group A, diathermy ball cauterization was applied to the entire crater following excision. In group B, cauterization was avoided in a 2-3-mm zone around the new os. The women were re-examined 4 months postoperatively by colposcopy and microcolpohysteroscopy with specific intention to identify the location of the squamocolumnar junction. The examiners performing colposcopy and microcolpohysteroscopy were not aware of each other's interpretation, or of the method of cauterization used. RESULTS: Follow-up colposcopy was satisfactory in 12 women in group A (24%) and 47 women in group B (92.2%) (P <.001). Forty-three women (86%) in group A and ten in group B (19.6%) had the squamocolumnar junction partly or fully located within the cervical canal (P <.001). Microcolpohysteroscopy located the squamocolumnar junction at a mean depth of 4.5 +/- 2.4 mm (+/- standard deviation [SD]) in the women in group A and 1 +/- 0.9 mm in group B (P <.001). Microcolpohysteroscopy could not be performed in 13 women in group A (26%) and one woman in group B (2%) (P <.001). CONCLUSION: Diathermy ball cauterization at the new cervical os after loop excision results in a shift of the squamocolumnar junction toward the endocervical canal, and predisposes to cervical stenosis, thereby decreasing satisfactory colposcopy rates.

Effect of metoclopramide on maternal and fetal prolactin secretion during labor.

The effect of acute and chronic maternal administration of metoclopramide on prolactin levels in serum of umbilical vein and artery was investigated in 30 women with normal term pregnancy during labor. Serum maternal prolactin increased significantly when 20 mg metoclopramide was given intravenously 30 to 45 minutes before vaginal delivery. Prolactin values in serum of umbilical vessels did not change as compared with control values when metoclopramide was given to the mother either as a 20-mg intravenous bolus injection or per os for the last 4 days of pregnancy until delivery. Oral administration of metoclopramide in late pregnancy evoked a significant increase in maternal serum prolactin levels. It is suggested that, in humans, therapeutic doses of metoclopramide administered to the mother in late pregnancy stimulate maternal, but not fetal, prolactin secretion.

Double-blind evaluation of miconazole tampons, compared with clotrimazole vaginal tablets, in vaginal candidiasis.

Fifty-one patients with vaginal candidiasis and positive cultures in Nickerson medium were treated either with two miconazole tampons daily for five days (26 patients, median age 28 years) or with one clotrimazole vaginal tablet daily for six days (25 patients, median age 36 years) in a randomized double-blind trial. Seven days after the end of the treatment, 24 (92%) patients in the miconazole group and 19 (76%) in the clotrimazole group had negative cultures. One month after the end of the treatment, the relapse rate was significantly (P less than 0.05) higher in the clotrimazole group. Symptoms subsided rapidly in both groups. No unwanted effects were reported.

The follicle-stimulating hormone threshold level for follicle maturation in superovulated cycles.

OBJECTIVE: To compare the FSH threshold level for follicle growth up to the preovulatory stage between superovulated and natural cycles. DESIGN: Normally cycling women were investigated during an untreated spontaneous cycle (control) and three cycles treated with FSH. SETTING: Infertility clinic in a university hospital. PATIENTS: Thirteen normally ovulating women with unexplained infertility. INTERVENTIONS: Follicle-stimulating hormone was injected at the single dose of six ampules on cycle day 2 without extra FSH (FSH + 0 cycle) or with extra FSH from cycle day 4 onward at the daily dose of either one ampule (FSH + 1 cycle) or two ampules (FSH + 2 cycle). MAIN OUTCOME MEASURES: Serum FSH and E2 during the follicular phase. Number of follicles and growth rate by ultrasound. RESULTS: Multiple follicular development occurred in all FSH treated cycles. In these cycles the growth rate of the first (dominant) follicle was similar to that in the control cycles. In the presence of physiological concentrations of FSH (control and FSH + 0 cycles), only one follicle was > 15 mm at midcycle. When serum FSH values increased (FSH + 1 and FSH + 2 cycles), the growth rate of the second and third in order follicles and subsequently the number of the preovulatory follicles (> 15 mm) increased in proportion to the FSH increment. CONCLUSIONS: Follicles recruited by exogenous FSH in the early follicular phase of the cycle require supraphysiological concentrations of FSH throughout the follicular phase to become preovulatory. The extra FSH acts through an increase in the growth rate of these follicles.

Association of estrogen receptor gene polymorphisms with endometriosis.

OBJECTIVE: To explore the association of the estrogen receptor two-allele (point) polymorphism and multiallele (microsatellite) polymorphism with endometriosis. DESIGN: Case-control study. SETTING: Genetics and Endoscopy Unit, Department of Obstetrics and Gynecology, Ioannina University HOSPITAL, Ioannina, Greece. PATIENT(S): Fifty-seven women with surgically and histologically diagnosed endometriosis of stages I-IV. INTERVENTION(S): Diagnostic laparoscopy. MAIN OUTCOME MEASURE(S): Frequency and distribution of the estrogen receptor gene polymorphisms. RESULT(S): There was a statistically significant difference between the patients and the controls in the frequency of the two-allele Pvu II polymorphism (0.72 vs. 0.49) and in the median repeats of the (TA)n multiallele polymorphism (15 vs. 20 repeats). In both groups, linkage was found between the fewer (TA)n repeats (range, 12-19) and the positive Pvu II polymorphism. CONCLUSION(S): The variability of the estrogen receptor gene likely contributes to the pathogenesis of endometriosis.

A study of the kinetics of cephapirin and cephalexin in pregnancy.

The kinetics of cephapirin and cephalexin were studied in 60 pregnant women after the administration of single 1 g doses of the antibiotics given by the intramuscular and oral route, respectively. Maternal serum, amniotic fluid and cord serum concentrations were measured at intervals after the dose by the agar diffusion method. The results showed that the mean peak concentration of cephalexin in maternal serum, after 1 hour, was significantly greater than that of cephapirin. Both antibiotics crossed the placenta barrier and reached levels in the amniotic fluid and cord serum adequate for the in vitro inhibition of pathogens involved in materno-foetal infections.

Immunohistochemical localization of metallothionein in human breast cancer in comparison with cathepsin D, stromelysin-1, CD44, extracellular matrix components, P53, Rb, C-erbB-2, EGFR, steroid receptor content and proliferation.

Metallothionein (MT) is a low molecular weight, cysteine-rich, zinc-binding protein that may have a function in cellular repair processes, growth and differentiation. Using a monoclonal antibody (E9) to metallothionein, we investigated the immunohistochemical expression of MT in routinely fixed and paraffin-embedded tissue from 98 cases of female breast carcinomas. The MT expression was studied in comparison with the expression of the basement membrane (BM) antigens (type IV collagen, laminin), fibronectin, cathepsin D, adhesion molecule CD44, p53 protein, the pRb, c-erbB-2 oncoprotein, EGFR, stromelysin-1, proliferation indices (Ki-67, PCNA), steroid receptor content as well as with other conventional clinicopathological parameters of breast cancer. Strong MT expression was observed in the majority of tumour cells in 18.4% of tumours, focal MT positivity in 13.3% and almost complete lack of MT expression in 68.4% of cases (mean value 33.36 +/- 26.36). The MT expression in carcinoma cells was strongly associated with the DCIS component of the tumour (p < 0.0001). High values of MT were correlated with low steroid receptor status (p = 0.08 for ER receptor and p = 0.019 for PgR receptor content). MT positive cases were correlated with stromelysin-1 expression (p = 0.059) and cathepsin D (p = 0.058). These findings suggest that MT expression is characteristic of the early phase of breast carcinogenesis, possibly regulated by hormones, and could be a new potential prognostic marker in breast cancer.

Spontaneous evolution of human papillomavirus infection in the uterine cervix.

BACKGROUND: Little is known about the natural history and the malignant potential of low-grade cervical intraepithelial neoplasia associated with human papillomavirus (HPV) infection. Cervical cancer remains the second most frequent cause of death in women across the world. Epidemiologic and molecular studies have shown that human papillomavirus (HPV) is associated with cervical carcinogenesis. In this prospective study we examined the behavior of low-grade cervical intraepithelial lesions associated with HPV infection over a 6-year period. MATERIAL AND METHODS: During 1992, women with Papanicolaou smears reporting koilocytotic atypia (HPV effect) with or without grade 1 cervical intraepithelial neoplasia (HPV +/- CINI, low grade squamous intraepithelial lesions, LgSIL), along with colposcopic impression of LgSIL were included to the study. Between 1992 and 1998 all women underwent repeat Papanicolaou smears, colposcopic evaluation and HPV DNA testing every six months. HPV typing of cervical scrapes was done by PCR. RESULTS: A total of 330 women completed at least 6 years of follow up. Among women with high-risk HPV types (16/18), the presence of dysplasia (grade 1 cervical intraepithelial neoplasia) was significantly correlated with the progression of the lesion; 29% of cases with HPV + CINI (15 out of 75) progressed to more severe lesions versus only 9% of cases with HPV infection (18 out of 225), P < 0.001, chi-square test. The incidence of histologically confirmed progressive lesions was significantly greater in women with mild dysplasia (18 out of 75, 24%) compared to women without dysplasia (13 out of 255, 5%), P < 0.001, chi-square test. CONCLUSIONS: In our study HPV typing was not predictive of the evolution of low-grade intraepithelial lesions associated with HPV infection. Standard cytologic screening and colposcopy are the most effective means of monitoring low-grade lesions.

Bacteriological cultures of removed intrauterine devices and pelvic inflammatory disease.

Intrauterine devices (IUDs) are highly effective, long-term methods of contraception. Although evidence of a direct association between IUD use and pelvic inflammatory disease (PID) is scarce, concerns about PID related to IUDs use has limited their use throughout the world. We designed this study to examine the effect of IUDs on PID. For the study, we recruited 200 participants from among women who requested an IUD as a means of contraception. The IUDs were removed 36 months later or in case of PID. No PID cases were recorded during the follow-up period. Prior to IUD insertion, 121 women (60.5%) had symptoms and/or signs of lower genital tract infection, whereas during the follow-up period 179 women (89.5%) had symptoms and/or signs of lower genital tract infection. The Papanicolaou smears were negative for Actinomyces throughout the study period. Also, cultures for sexualy transmitted disease microorganisms were negative throughout the study period. Following IUD removal, 189 IUD cultures (94.5%) were positive. The bacterial flora of the removed IUDs consisted of common aerobic and anaerobic microorganisms that do not account for PID. The most common microorganisms identified were Staphylococcus coagulase negative, Eschericia coli, and Enterococcus faecalis. IUDs are a very effective and safe method of contraception if potential recipients are selected carefully. Culture of the removed IUDs and therapeutic management of women with positive cultures are not recommended when women are asymptomatic for PID.

High HbF in pregnancy is associated with the Xmn I polymorphism at the -158bp of the G gamma-globin gene.

HbF was measured in the peripheral blood of 354 women during the first trimester of pregnancy. In those (n = 6) with HbF > 3% and in 30 randomly selected pregnant women with normal HbF values, analysis of the G gamma content and the Xmn I polymorphism was performed. The frequency of the Xmn I polymorphism was significantly higher (P < 0.001) in the group with high HbF (0.67) compared to the control group (0.10). The G gamma chain content evaluation revealed a newborn ratio in all 6 high HbF subjects. Six months after delivery, HbF was measured in all women with high HbF during pregnancy, revealing normal values. These results suggest that the presence of the Xmn I polymorphism is a strong inducer for the elevation of HbF during pregnancy.

Incomplete excision of CIN in conization: further excision or conservative management?

The aim of this study was to investigate the experience of the further management in 112 cases with histological diagnosis of incomplete excision of CIN in cone biopsy. Two groups of women were studied. The women in the first group (n = 78) had a second excision while the women in the second group (n = 34) underwent conservative management with cytology and colposcopy. The histologic, cytologic and colposcopic findings in the women of both groups were compared. From the first group 38% had a second cone, 62% an hysterectomy; in 5 cases the second cone was followed by hysterectomy and the histology was negative in 75% and 65%, respectively. No indication of residual disease was found within 2-10 years of follow-up in any of the women in the second group. According to our study and being aware of the natural history of CIN, we can conclude that the decision for further excision should not be based exclusively on the histology report of involved margins, but should only be taken after careful cytological and colposcopic selection of the cases.

A combined approach for the early detection of ovarian cancer in asymptomatic women.

The purpose of this study was to investigate the effectiveness of the combined procedure including pelvic examination and serum CA-125 determination, as a screening method for the early detection of ovarian cancer. In 2000 women over 45 years old, without any evidence of adnexal disease, pelvic examination and serum CA-125 determination were performed. When either the findings of the pelvic examination were ambiguous or positive, or the serum CA-125 level was > 35 U/ml, further investigation including ultrasonography and laparoscopy or laparotomy was done. Among 174 women with clinical findings of adnexal disease there were 15 (8.62%) who had serum CA-125 > 35 U/ml. Among 18 women with elevated serum CA-125 (> 35 U/ml) there were 15 women (83.33%) who had clinical findings of adnexal disease. In 15 women further investigation was suggestive of adnexal disease and surgical exploration revealed three cases of malignancy. One case of serious ovarian cystadenocarcinoma stage Ia, one case of borderline ovarian tumour and one case of metastatic carcinoma from the right kidney. The other 12 women had benign adnexal masses or pelvic endometriosis. In our study this combined approach had sensitivity 100%, specificity 99.70% and P.P.V. 22%. According to these data, the procedure could be a potential component of a strategy aimed to the early detection of ovarian cancer, regardless of the financial cost.

Carcinoembryonic antigen (CEA) in normal and pre-eclamptic pregnancies (values in maternal blood, amniotic fluid and umbilical cord blood).

Values of carcinoembryonic antigen (CEA) were measured by radioimmunoassay in 100 pregnant women divided into 4 groups. In group 1 (49 normal pregnancies) and 2 (17 pre-eclamptic pregnancies), the estimation of CEA was done in maternal vein blood, umbilical cord blood and in amniotic fluid. In group 3 (20 normal pregnancies) CEA was measured separately in blood of the two umbilical vessels as well as in maternal vein blood. In group 4 (14 pregnancies with small-for-date infants) CEA was estimated in umbilical cord blood. The values in amniotic fluid of normal and pre-eclamptic pregnancies were more than 20 times higher than in the other two compartments. A significant correlation was found between the amniotic fluid and umbilical cord blood values (r = 0.500; P < 0.05), as well as between the values in umbilical artery and vein (r = 0.792; P < 0.001). Thus, it is thought that CEA is transferred from the amniotic cavity to the umbilical cord while a part of CEA perhaps is produced by the placenta. Umbilical cord blood values of small-for-date fetuses do not differ significantly from the normal. On the contrary, significantly lower values were obtained in umbilical cord blood and in amniotic fluid of pre-eclamptic women as compared to the normal, but this finding is not useful clinically because of the large standard deviation.

The role of deoxyribonuclease I in amniotic fluid during pregnancy and labour.

The purpose of this study was to detect the presence, and determine the normal values and the significance of DNase I in the amniotic fluid and in human placentas. Fifty-one pregnant women at 16-22 weeks of gestation and 89 women in spontaneous labour at term were recruited to the study. DNase I activity was measured in amniotic fluid and cytoplasmic extracts from the fetal portion of placentas by using a spectrophotometric technique (DNA precipitation assay) and nucleic acid electrophoresis, following degradation of the DNA by the enzyme. DNase I activity was undetectable in the placental cytoplasmic extracts. In the second trimester of pregnancy DNase I activity was detectable in amniotic fluid (2.3+/-0.64x10(5) U/l). During labour DNase I activity was also detectable, but reduced levels were observed in the presence of clear amniotic fluid, compared to second trimester levels, (1.9+/-0.44x10(5) U/l, P<0.001), whereas higher levels were found in the presence of meconium-stained amniotic fluid compared to both second trimester and clear amniotic fluid at labour (11.4+/-4.1x10(5) U/l, P<0.001 and P<0.001, respectively). Three out of 17 fetuses with meconium-stained amniotic fluid (18%) developed perinatal infection. In conclusion, the detection of DNase I activity in the amniotic fluid of second and third trimester indicates a physiological role in human pregnancy. DNase I activity normally decreases at term, compared to second trimester levels, but increases significantly in the presence of meconium.

Recombinant human erythropoietin treatment of postpartum anemia. Preliminary results.

OBJECTIVES: The aim of this study was to investigate the efficacy of recombinant human erythropoietin (rHuEpo) in postpartum anemia. STUDY DESIGN: At the University Hospital of Ioannina, rHuEpo was administrated subcutaneously to twenty anemic women (hemoglobin [Hb]<10 g/dl), for 15 days following delivery; all were given iron and folic acid per os. Twenty other women (the control group) with postpartum anemia (Hb<10 g/dl), received only iron and folic acid. The Mann-Whitney U-test was used for the comparison of hematological indices between the two groups, on days 1, 3, 5, 10, 15 and 40 postdelivery. RESULTS: On day 3, reticulocyte counts were significantly higher in the women who received rHuEpo, as compared to the controls (P<0.05). The mean Hb value increased to >2 g/dl in the group undergoing rHuEpo therapy as compared to 0.7 g/dl in the control group on day 5 (P<0.05). Furthermore, two women in the control group required blood transfusions, while no transfusions were required by the rHuEpo group. CONCLUSIONS: rHuEpo administration is useful for a more rapid amelioration of hematological indices in women with postpartum anemia. Further, the dose given in this study was not associated with significant side-effects.

Pyometra.

Thirteen cases of pyometra without preoperative diagnosis in which vaginal or abdominal surgery was performed, are analysed in the present paper. The histologic examination revealed endocervicitis in all cases, while positive cultures for bacteria were found preoperatively in only eight of the above cases, thus, pyometra was considered to be a symptom of obstruction of the cervical canal.

Carcinoembryonic antigen in high risk pregnancies.

The significance of carcinoembryonic antigen (CEA) measurement was evaluated in 25 pregnant women with diabetes mellitus, 15 Rh negative sensitized and nine prolonged pregnancies. Another 114 women with normal pregnancy served as controls. Values in maternal and umbilical cord serum and in amniotic fluid did not change appreciably through 24-42 weeks' gestation. No significant difference in maternal serum, cord serum and amniotic fluid CEA values was found between diabetic, Rh negative sensitized and normal pregnancies at the corresponding weeks. Similar findings were obtained in prolonged pregnancies, except the values in amniotic fluid which were significantly higher than in normal pregnancies due to the presence of meconium. These results suggest that the measurement of CEA in high risk pregnancies is not useful in predicting fetal condition.

Toxoplasma antibodies and spontaneous abortion.

One hundred and fifty-two women with spontaneous abortion were investigated by hemagglutination (HA) and immunofluorescence antibody (IFA) tests for toxoplasmosis. In 48 cases, quantitive immunoglobulin (Ig) studies and mouse inoculation with gestational material were performed. Positive toxoplasma antibody titers were observed in 62 cases (40.8%) using HA and in 52 cases (38.2%) using IFA. This prevalence was significantly higher than that observed in 80 normal women who served as controls. Toxoplasma gondii was isolated in two cases. No correlation was found between antibody titers and IgG, IgM or IgA levels. We conclude that toxoplasmosis should be considered as the cause of abortion when a patient's antibody titer exceeds 1:256.