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To assess the predictors of late rectal toxicity in a prospectively investigated group of patients treated at 70-80 Gy for prostate cancer (1.8-2 Gy fractions) with three-dimensional conformal radiotherapy.A total of 1,132 patients were entered into the study between 2002 and 2004. Three types of rectal toxicity, evaluated by a self-administered questionnaire, mainly based on the subjective objective management, analytic late effects of normal tissue system, were considered: stool frequency/tenesmus/pain, fecal incontinence, and bleeding. The data from 506 patients with a follow-up of 24 months were analyzed. The correlation between a number of clinical and dosimetric parameters and Grade 2 or greater toxicity was investigated by univariate and multivariate (MVA) logistic analyses.Of the 1,132 patients, 21, 15, and 30 developed stool frequency/tenesmus/pain, fecal incontinence, and bleeding, respectively. Stool frequency/tenesmus/pain correlated with previous abdominal/pelvic surgery (MVA, p=0.05, odds ratio [OR], 3.3). With regard to incontinence, MVA showed the volume receivingor=40 Gy (V40) (p=0.035, OR, 1.037) and surgery (p=0.02, OR, 4.4) to be the strongest predictors. V40 to V70 were highly predictive of bleeding; V70 showed the strongest impact on MVA (p=0.03), together with surgery (p=0.06, OR, 2.5), which was also the main predictor of Grade 3 bleeding (p=0.02, OR, 4.2).The predictive value of the dose-volume histogram was confirmed for bleeding, consistent with previously suggested constraints (V5055%, V6040%, V7025%, and V755%). A dose-volume histogram constraint for incontinence can be suggested (V4065-70%). Previous abdominal/pelvic surgery correlated with all toxicity types; thus, a modified constraint for bleeding (V7015%) can be suggested for patients with a history of abdominal/pelvis surgery, although further validation on a larger population with longer follow-up is needed.

Objectives of the study: to analyse the features and outcomes of different types of atrioventricular septal defects, detected during fetal life, as compared to postnatal data. Material and methods: We analysed retrospectively the data concerning 82 fetuses with atrioventricular septal defect, diagnosed from 19 through 37 weeks gestation with a median of 26 weeks. In 46 cases (56.1%), the diagnosis has been made before the age of 24 weeks. Results: Characteristics of the series – in 44 fetuses the atrioventricular septal defect was not associated with other cardiac anomalies, while 38 fetuses had a more complex form. Chromosomal anomalies were present in 33 of the fetuses (40.2%), more frequently in cases without associated intracardiac defects (56.8%). Trisomy 21 occurred in just over one quarter the series, and in 43.2% of cases without associated defects. In addition, 11% of fetuses had trisomy 18, and one had trisomy 13. Extracardiac anomalies were present in 12 of the fetuses (14.6%), more frequently in cases without associated abnormalities. Of fetuses with more complex defects, 46.4% had hypoplasia of the left ventricle and aorta. Complete atrioventricular block was present in 10 of the fetuses (12.2%), mainly in fetuses with other malformations, and particularly with left isomerism. Recurrence of congenital heart disease was observed in 5 of the fetuses (6.1%). Outcome: In 25 instances (30.5%) the parents opted for termination of pregnancy. Of 57 cases that continued through pregnancy, 9 fetuses died prior to term (15.8%), 32 died postnatally (56.13%) and only 16 fetuses (28.1%) survived. Overall, the mortality was higher in cases with associated malformations, in those with heart failure or those with atrioventricular block. Cardiac surgery was performed in 19 infants, with 5 dying postoperatively, and one late. Conclusions: Our data show a high prevalence of atrioventricular septal defect associated with other malformations when diagnosed during fetal life. This combination is less frequently associated with chromosomal and extracardiac anomalies, but more often with obstructive lesions of the left heart and with atrioventricular block. The association results in a less favourable outcome.

Objective To assess fetal and maternal outcomes in women with systemic sclerosis (SSc). Methods Prospectively collected data on 99 women with SSc from 25 Italian centers were analyzed retrospectively. Women with SSc were observed during 109 pregnancies (from 2000 to 2011), and outcomes were compared to those in the general obstetric population (total of 3,939 deliveries). The maternal age at conception was a mean ± SD 31.8 ± 5.3 years, and the median disease duration at conception was 60 months (range 2–193 months). Results SSc patients, compared to the general obstetric population, had a significantly increased frequency of preterm deliveries (25% versus 12%) and severe preterm deliveries (

Ganciclovir was administered 'in utero' for 12 days in a 29-week-old fetus with ascertained congenital human cytomegalovirus (HCMV) infection, thrombocytopenia and elevated gamma-glutamyl transferase (gammaGT) value. Efficacy of therapy was shown by reduction in virus titer of amniotic fluid and fetal urine, disappearance of viral DNA in fetal blood, and normalization of platelet count and gammaGT value. However, stillbirth occurred at 32 weeks of gestation and HCMV inclusion bodies were detected in kidneys, lungs, heart and pancreas at autopsy. During therapy, side-effects,possibly related to ganciclovir administration, were observed.

We performed a scanning electron microscopic study of fimbrial biopsies from two patients with Rokitansky's syndrome and from three fertile patients in the same period of the menstrual cycle as controls. In the patient samples we observed irregular running and frequent conglutination of the mucosal folds. Ciliated cells appeared reduced in number compared with controls, and cilia were often agglutinated. Some areas contained nonciliated cells, dome-shaped or giant as observed in the menopause, with rare microvilli, suggesting disturbances of cellular growth and trophism of the tubes in patients with Rokitanskys syndrome.

The endometrium of an infertile patient with Kartagener's syndrome showed initial secretory phase characteristics at SEM, whereas TEM analysis demonstrated several alterations in the central and peripheral microtubular distribution in 87% of the cilia examined. Such aspects seemed appropriate for a normal implantation, but the ciliary immotility or dyskinesia could cause an altered flow of the endometrial secretions and compromise the upstream movement of the spermatozoa.

Objective: To assess hematologic and biochemical blood variables in growth-restricted fetuses and relate them to biophysical measurements. Methods: Blood was sampled from 22 growth-restricted fetuses. All had normal karyotypes and no congenital infections. Venous pH, partial pressure of oxygen, hematocrit, glucose, uric acid, urea, creatinine, total protein, total and direct bilirubin, aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, alkaline phosphatase, lactic dehydrogenase, amylase, pseudocholinesterase, creatinine kinase, triglycerides, and cholesterol were measured and compared with our reference range. Results: Ultrasound measurements of abdominal circumference correlated with fetal pH (r = 0.64), partial pressure of oxygen (r = 0.52), glucose (r = 0.67), total bilirubin (r = −0.54), lactic dehydrogenase (r = −0.48), and triglyceride levels (r = −0.65). Compared with fetuses with present end-diastolic velocities in the umbilical artery, the eight with absent end-diastolic velocities had lower pH (median z score −4.31), partial pressure of oxygen (median z score = −2.39), glucose (median z score = −2.01), and cholesterol (median z score = −2.34), and higher γ-glutamyltransferase (median z score = 2.43), lactic dehydrogenase (median z score = 3.75), urea (median z score = 1.33), creatinine (median z score = 1.23), and triglyceride levels (median z score = 1.71). Only triglycerides correlated with abdominal circumference, independent of Doppler results. Conclusion: Growth-restricted fetuses with absent end-diastolic velocities in the umbilical artery had more marked acidemia, hypoxemia, hypoglycemia, and abnormal liver function than those with end-diastolic velocities. Triglyceride levels were inversely related to fetal size independent of Doppler results. High triglyceride levels might reset fetal homeostatic mechanisms, leading to disturbances of lipid metabolism in later life.

OBJECTIVE: Because individuals with Down syndrome appear to be protected from the development of atherosclerosis, we aimed to assess whether blood lipid and lipoprotein concentrations are different from controls in fetuses with trisomy 21. STUDY DESIGN: Eighteen fetuses with trisomy 21 and seven with trisomy 18 undergoing blood sampling at 18 to 36 weeks' gestation were matched by gestational age and size with an equal number of controls. Cholesterol and triglycerides were assayed in all fetuses and compared with the reference range constructed from 157 normal fetuses. High-density lipoproteins and apoproteins A and B were assayed in eight fetuses with trisomy 21, four with trisomy 18, and an equivalent number of controls. RESULTS: When compared with the reference range, fetuses with trisomy 21 had significantly increased cholesterol levels (median Z score 2.31, 95% confidence interval 1.57 to 3.08, p = 0.0001). Cholesterol and apoprotein A concentrations were also significantly higher than in fetuses with normal karyotypes matched by gestational age and size at sampling, whereas other lipids and lipoproteins were similar. There were no differences between fetuses with trisomy 18 and their matched controls. A value of fetal cholesterol ≥85 mg/dl had a sensitivity of 72% and specificity of 95% in detecting fetuses with trisomy 21. CONCLUSIONS: Fetuses with trisomy 21 have abnormalities of lipid metabolism that are specific and may be genetically determined. The finding of high cholesterol levels in fetuses undergoing blood sampling for indications other than karyotyping should prompt investigation of fetal chromosomes because of the increased risk of trisomy 21. The mechanism through which high levels of cholesterol during prenatal life are not leading to increased risk of atherosclerosis remains to be elucidated.(Am J Obstet Gynecol 1997;176:540-3

To construct reference ranges for fetal pH, oxygen pressure (PO2), and hematologic and biochemical blood constituents, which can be used to analyze changes with gestation and differences with maternal values, thus elucidating some aspects of fetal biology and the effects of the maternal and placental environments.We assayed venous pH, PO2, hematocrit, glucose, uric acid, urea, creatinine, total protein, total and direct bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, lactic dehydrogenase, amylase, pseudocholinesterase, creatine kinase, triglycerides, and cholesterol concentrations in 157 fetuses and 134 mothers who underwent fetal blood sampling from 18 to 37 weeks' gestation. None of the fetuses was infected or had chromosomal, hematologic, or hormonal abnormalities.All the variables analyzed were similar in fetuses sampled at the placental cord insertion (n = 125) or at the intrahepatic vein (n = 32). Maternal and fetal concentrations of glucose (r = 0.79, P.001), urea (r = 0.96, P.001), creatinine (r = 0.83, P.001), and uric acid (r = 0.94, P.001) correlated significantly, and their differences exhibited significant changes: the maternal-fetal differences of glucose and urea increased, whereas those of uric acid and creatinine decreased with advancing gestation. Fetal pH and PO2 decreased with gestational age, whereas hematocrit increased, similar to what has been described previously. All of the other variables, with the exception of amylase and cholesterol, changed significantly during the investigated period of pregnancy. Gestational age explained at least 40% of the variance in values of fetal total protein, pseudocholinesterase, alanine aminotransferase, creatine kinase, and triglycerides, but only 3-25% of the variation in the remainder. Most enzymes were higher in the fetus than in the maternal circulation, and all except alkaline phosphatase increased with gestational age. The maternal-fetal glucose difference correlated significantly with hematocrit, pH, and PO2, independent of gestational age and independent of each other.With the exception of aspartate aminotransferase, all of the analyzed fetal variables were different from the maternal values, and most changed with gestational age. The mechanisms leading to these fetal specificities remain mostly uncertain, but the provision of reference ranges for several blood constituents may be useful in the differential diagnosis of fetal disease.

We treated 36 women with laparoscopically proven endometriosis with danazol 600 mg/d (n = 17) or gestrinone 5.0 mg/wk (n = 19) for 6 months. Endometrial samples were obtained before and at 3 and 6 months of treatment and were studied by light, scanning, and transmission electron microscopy. At 3 months of treatment, the endometria of the danazol-treated patients were more atrophic than those of the women who received gestrinone. Some cell organelle involution was evident in patients of both treatment groups. After 6 months of treatment, marked endometrial atrophy was observed in all the patients, including those in whom spotting had occurred. The ultrastructural investigation demonstrated complete involution of the cytoplasmic organelles with cytoplasmic collapse in glandular cells of patients treated with danazol, whereas in the gestrinone group degeneration phenomena were observed in both nucleus and cytoplasm. Irregular secretory transformation was seen in the endometria of patients in both groups. Long-term treatment with danazol caused endometrial atrophy similar to that induced by gestrinone, but it appeared earlier; thus, the former drug seems preferable in short-term treatment.