Roles of poly(ADP-ribosyl)ation and PARP in apoptosis, DNA repair, genomic stability and functions of p53 and E2F-1.
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Biomedical subjects
Publications and source records attributed to B Haddad.
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Fistula in ano has been reported as a rare complication of midline episiotomy. We report here 3 cases of fistula in ano complicating mediolateral episiotomy. One was suprasphincteric and 2 were transsphincteric. All patients had perineal pain and chronic suppuration. Before referral, 2 patients underwent incision and drainage alone. As a definitive procedure fistulotomy was performed, and long-term functional results have been satisfactory.
OBJECTIVE: Our purpose was to determine whether second-trimester maternal serum beta(2)-microglobulin levels could be used to predict subsequent development of preeclampsia. STUDY DESIGN: We first did a cross-sectional study to compare serum concentrations of beta(2)-microglobulin between women with preeclampsia and normotensive women. Serum beta(2)-microglobulin concentrations of 11 consecutive patients hospitalized for preeclampsia were compared with those of 11 normotensive women hospitalized for threatened premature labor. The second part of the study consisted of a nested case-control study in which each woman in whom preeclampsia ultimately developed was matched with 2 women who remained normotensive throughout gestation. For that purpose a total of 450 consecutive healthy nulliparous women were studied prospectively. Blood samples were collected between 20 and 24.9 weeks' gestation and frozen at -20 degrees C until assay after groups had been selected. RESULTS: In the cross-sectional study serum beta(2)-microglobulin levels were significantly higher in women with preeclampsia than in control women (1.87 +/- 0.36 mg/L vs 1.01 +/- 0. 12 mg/L; t = 7.61; P <.0001). Among the 450 women who were followed up prospectively, preeclampsia developed in 7 (1.5 %). Fourteen of the women who remained normotensive were matched with the 7 women in whom preeclampsia ultimately developed. No difference was found in early serum beta(2)-microglobulin concentrations between women in whom preeclampsia subsequently developed and those who remained normotensive throughout gestation (1.02 +/- 0.12 vs 0.95 +/- 0.12 mg/L). CONCLUSIONS: Serum beta(2)-microglobulin levels do not predict subsequent preeclampsia.
OBJECTIVE: Our purpose was to evaluate the outcome of infants who underwent successful resuscitation after initial Apgar scores of 0 at both 1 and 5 minutes. STUDY DESIGN: Eligible infants were identified through the perinatal database at the University of Tennessee, Memphis. Hospital records and long-term outcomes, where available, of babies who met the above criteria occurring between January 1986 and February 1999 were reviewed. RESULTS: Thirty-three of 81,603 infants (0.4/1000 births) met our study criteria. Twenty-two (67%) babies died during hospitalization. Mortality decreased significantly from 100% for babies with a birth weight of <750 g to 38% for those weighing > or =2500 g at birth (P =.03). All 6 babies delivered before 26 weeks' gestation died. The incidence of 10-minute Apgar scores >0 was significantly higher among survivors than among those who subsequently died (82% vs 33%, P <.05). Nine survivors had hypoxic-ischemic encephalopathy diagnosed before discharge. Of the 7 infants with available follow-up, 4 had significant persisting morbidity. Two infants had normal neurologic examinations at follow-up. CONCLUSION: Survival in babies born with 1- and 5-minute Apgar scores of 0 is predicted by birth weight, gestational age, and 10-minute Apgar score. Long-term sequelae are common but not ensured.
OBJECTIVE: This study was undertake to determine risk factors for adverse maternal outcomes among women with HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. STUDY DESIGN: Maternal medical records of pregnancies complicated by HELLP syndrome managed between July 1, 1992, and April 30, 1999, were reviewed. Risk factors evaluated included maternal age, parity, race, previous preeclampsia, chronic hypertension, gestational age at diagnosis, mean arterial blood pressure, nadir blood platelet count (<50,000 cells/microL vs > or =50,000 cells/microL), and peak serum levels of aspartate aminotransferase and lactate dehydrogenase. Maternal outcome variables analyzed included eclampsia, abruptio placentae, disseminated intravascular coagulopathy, pulmonary edema, pleural effusion, ascites, acute renal failure, liver hematoma, need for transfusion of blood products, cesarean delivery, and death. Statistical analysis was performed with the Student t test, the chi(2) test, and logistic regression analysis. RESULTS: A total of 183 women with HELLP syndrome were studied. Eclampsia was present in 6%, abruptio placentae was present in 10%, and disseminated intravascular coagulopathy was present in 8%. Forty-one women (22%) required transfusion of blood products. Incidence of eclampsia significantly decreased with increasing gestational age, from 16% at < or =28 weeks' gestation to 3% at >32 weeks' gestation (P <.05) and was higher among African American patients than among white patients (12% vs 3%; P <.05). Logistic regression analysis showed an independent relationship between eclampsia and race (P <.05). Incidence of abruptio placentae was higher among women with previous preeclampsia than among women without this clinical history (26% vs 5%; P <.05). Disseminated intravascular coagulopathy was significantly associated with abruptio placentae (P <.0001) and acute renal failure (P <.0001). A nadir platelet count of <50, 000/microL, a peak serum aspartate aminotransferase level of >150 U/L, and a peak serum lactate dehydrogenase level of >1400 U/L were not independent risk factors for adverse outcome. CONCLUSIONS: Among women with HELLP syndrome, African American race is a risk factor for eclampsia. Both acute renal failure and abruptio placentae are associated with disseminated intravascular coagulopathy. Laboratory parameters of HELLP syndrome are not independent risk factors for adverse maternal outcome.
OBJECTIVE: Our purpose was to determine whether the onset of the HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome in women at < or =28.0 weeks' gestation is associated with an increased risk of adverse maternal and perinatal outcomes in comparison with the risk for women with severe preeclampsia but without the HELLP syndrome at a similar gestational age. STUDY DESIGN: Sixty-four patients with either the HELLP syndrome (n = 32) or severe preeclampsia but absent HELLP syndrome laboratory test results (n = 32), admitted at < or =28.0 weeks' gestation between July 1, 1992, and April 30, 1999, were studied. Maternal and perinatal outcomes were compared between the 2 groups. Statistical analysis was performed by the Student t test and the Fisher exact test. RESULTS: There were no significant differences between the 2 groups regarding African-American race (59% vs 75%), nulliparity (50% vs 56%), or the use of corticosteroids (59% vs 78%). There were no maternal deaths. One woman with the HELLP syndrome had a liver hematoma. The rate at which transfusion of blood products was required was significantly greater in women with the HELLP syndrome than in those with severe preeclampsia only (25% vs 3%; P <.05). There were no significant differences between the 2 groups with respect to eclampsia (16% vs 13%), abruptio placentae (6% vs 9%), disseminated intravascular coagulopathy (13% vs 0%), pulmonary edema (13% vs 6%), acute renal failure (3% vs 0%), pleural effusion (3% vs 3%), or ascites (6% vs 16%). No significant differences were found between the 2 groups with respect to neonatal death (11% vs 17%), respiratory distress syndrome (78% vs 86%), or composite neonatal morbidity. CONCLUSIONS: Except for the need for transfusion of blood products in women with the HELLP syndrome, onset at < or =28.0 weeks' gestation is not associated with an increased risk of adverse maternal or neonatal outcomes in comparison with the risk for women with severe preeclampsia but without the HELLP syndrome at a similar gestational age.
OBJECTIVE: The aim of this study was to determine whether plasma concentrations of vascular endothelial growth factor and placental growth factor are altered in women with severe preeclampsia. STUDY DESIGN: We performed a case-control study to compare plasma concentrations of vascular endothelial growth factor and placental growth factor between women with severe preeclampsia and normotensive women admitted for delivery. Twenty-one women with severe preeclampsia were matched for gestational age and ethnicity with 21 normotensive women. Vascular endothelial growth factor and placental growth factor concentrations were measured with a specific antigen-capture enzyme-linked immunosorbent assay. RESULTS: Women with severe preeclampsia demonstrated significantly lower plasma concentrations of both vascular endothelial growth factor (6.36 +/- 3.96 pg/mL vs 18.65 +/- 5.98 pg/mL; P <.0001) and placental growth factor (138 +/- 119 pg/mL vs 531 +/- 340 pg/mL; P <.0001) than did women with normotensive pregnancy. Logistic regression analysis showed an independent association between plasma vascular endothelial growth factor concentration and plasma placental growth factor concentration and preeclampsia. CONCLUSION: Patients with severe preeclampsia had decreased maternal serum concentrations of both vascular endothelial growth factor and placental growth factor.
Prostaglandins are known to induce cervical ripening and this effect may be mediated by an increase in glycosaminoglycan (GAG) concentration. The aim of this study was to assess the effects of progesterone on prostaglandin E(2) (PGE(2))-induced changes in GAG synthesis by human cervical cells in culture. Human cervical fibroblasts were obtained by cervical biopsies in hormonally active women and cultured. Cells were submitted to an incubation with progesterone or control medium. A second incubation was then performed with increasing concentrations of PGE(2). GAG synthesis by the cervical cells was assayed after extraction, by incorporation of [(3)H]-glucosamine and [(35)S]-sulphate into GAGs. It was found that progesterone alone induced a dose-dependent increase in GAG synthesis. After pre-incubation with progesterone, PGE(2) further increased [(3)H]-glucosamine and [(35)S]-sulphate uptake. However, when expressed as percentage of stimulation, the stimulatory effect of PGE(2) on GAG synthesis was inhibited at high progesterone concentrations. Therefore we concluded that, although high concentrations of progesterone increase the overall synthesis of GAG, they may also play a preventative role against PGE(2)-induced changes in GAG production during pregnancy.
Adrenocortical tumors (ACT) in children under 15 years of age exhibit some clinical and biological features distinct from ACT in adults. Cell proliferation, hypertrophy and cell death in adrenal cortex during the last months of gestation and the immediate postnatal period seem to be critical for the origin of ACT in children. Studies with large numbers of patients with childhood ACT have indicated a median age at diagnosis of about 4 years. In our institution, the median age was 3 years and 5 months, while the median age for first signs and symptoms was 2 years and 5 months (N = 72). Using the comparative genomic hybridization technique, we have reported a high frequency of 9q34 amplification in adenomas and carcinomas. This finding has been confirmed more recently by investigators in England. The lower socioeconomic status, the distinctive ethnic groups and all the regional differences in Southern Brazil in relation to patients in England indicate that these differences are not important to determine 9q34 amplification. Candidate amplified genes mapped to this locus are currently being investigated and Southern blot results obtained so far have discarded amplification of the abl oncogene. Amplification of 9q34 has not been found to be related to tumor size, staging, or malignant histopathological features, nor does it seem to be responsible for the higher incidence of ACT observed in Southern Brazil, but could be related to an ACT from embryonic origin.
OBJECTIVE: To investigate the usefulness of grade II uterine diastolic notch to predict maternal or perinatal outcome during conservative management of preeclampsia. STUDY DESIGN: We reviewed medical charts of 35 pregnant women admitted for hypertension and > or =1+ urine dipstick protein determination and who had a uterine Doppler examination at admission. Grade I notch was defined as a 'nadir' in early diastole higher than half of peak diastolic notch velocity. Grade II diastolic notch was defined as a 'nadir' in early diastole lower than half of peak diastolic notch velocity. RESULTS: Thirty-one preeclamptic women were admitted at 30.1+/-3 weeks. Of them, 23 had a grade I notch (group I) and eight a grade II notch (group II). Rates of abruptio placenta, eclampsia, thrombocytopenia, stillbirth, birth weight < or = 3rd centile, fetal distress before delivery and neonatal death were similar in the two groups. Rates of delivery before 32 weeks and newborn spending more than 48 h in neonatal intensive care unit were significantly higher in group II. Admission-to-delivery interval was significantly lower in group II (2.6+/-1.5 vs. 9.4+/-8.7 days, P<0.05). CONCLUSION: Grade II notch seems to identify in preeclamptic women those with a higher risk of early pregnancy termination.
The possibility of using first trimester maternal serum human chorionic gonadotrophin (HCG) profiles to predict fetal growth retardation (FGR) was tested in 236 women with singleton pregnancies obtained after in-vitro fertilization (IVF). Pregnancies were monitored by serial analysis (two or more) of serum HCG at at least 48 h intervals. Serum was obtained between the 13th and the 35th day after conception (i.e. on the day of IVF). Early miscarriage occurred in 23.7% and FGR in 10.9% of pregnancies. Serum HCG profiles were higher than the 90th and lower than the 10th percentile in 12.3% and 19.5% of the cases respectively. FGR was significantly more frequent in women with serum HCG profiles lower than the 10th percentile than in women with normal profiles (45.5% versus 7.2%; P < 0.001), with a relative risk of 6.5 (95% confidence interval 2.7-15.6). FGR rates were similar in women with normal and high profiles of serum HCG. Pre-eclampsia and premature delivery rates were similar in women with normal and abnormal profiles of serum HCG. First trimester serum HCG should be further investigated as a potential marker of FGR.
Our purpose was to analyse the reproductive performance of women with obstructed hemivagina after surgical treatment. After laparoscopic exploration of 42 cases (mean age: 18 years), didelphic and complete septate uterus were found in 78 and 22% of cases respectively. Resection of vaginal septum and hemihysterectomy with ipsilateral hemicolpectomy were performed in 88% and 12% of the cases, respectively, between 1970 and 1997. Long-term results were assessed by a questionnaire and obtained for 38 patients (mean years after treatment and range: 6.5; 1-23). Dysmenorrhoea and abdominal pain were resolved in 87% and 100% of the cases, respectively. Nine patients experienced 20 pregnancies (13 living children, four early spontaneous abortions, two early terminations and one ectopic pregnancy). Nine offspring (69% of live births) were delivered after 37 weeks. Four patients had four pregnancies ipsilateral to blind hemivagina after vaginal septum resection (two living children, one early spontaneous abortion and one ectopic pregnancy). These results suggest that laparoscopic exploration and resection of vaginal septum are the appropriate treatments for obstructed hemivagina. Subsequent reproductive performance was comparable to that reported following treatment of the associated uterine malformation.
Pregnancies in women with chronic hypertension are at increased risk of superimposed pre-eclampsia, abruptio placentae, fetal growth retardation and prematurity. The frequencies of these complications are increased in those women who have high-risk chronic hypertension, ie severe hypertension or pre-existing cardiovascular or renal diseases, as well as in those with target organ damage. Such women should receive antihypertensive therapy and close management to improve maternal and fetal outcome. In women with low-risk chronic hypertension, antihypertensive treatments do not improve pregnancy outcome. Prophylactic low-dose acetylsalicylic acid treatment does not reduce the frequency of superimposed pre-eclampsia nor does it improve perinatal outcome in these pregnancies.
OBJECTIVE: To determine the incidence, features, and surgical treatment of vulvovaginal lesions in toxic epidermal necrolysis. METHODS: Acute genital lesions were studied retrospectively in 40 women hospitalized for toxic epidermal necrolysis in a dermatologic intensive care unit. A questionnaire was sent to evaluate sequelae and their effects on sexual activity. Examination and surgical treatment were proposed to patients with symptomatic sequelae. RESULTS: Twenty-eight of the 40 patients reported genital lesions during the acute phase of toxic epidermal necrolysis. No specific treatment was carried out during the acute period. Sequelae were observed in five cases, of which three involved the lower genital tract and two the vulva exclusively. The two patients with exclusive vulval involvement did not attempt any sexual activity. The other three patients with both vulval and vaginal lesions were unable to have normal sexual intercourse. Two of the three patients were treated surgically. One patient succeeded in having intercourse, but surgery failed to relieve dyspareunia. CONCLUSION: Genital involvement is frequent during toxic epidermal necrolysis but rarely leads to symptomatic sequelae. Surgery for synechiae is sometimes necessary to recover sexual activity because the vulvovaginal canal is stenotic. Because of the partial effect on pain relief after surgery, a preventive approach should be tried.
This article reports our clinical experience since 1994 with rigid-motion tracking of bone fragments during craniofacial surgical procedures, using a virtual reality approach. Three noncollinear infrared diodes are fixed to the skull base. A pointer is used to register anatomic features on the patient to those on the computerized tomography-based model of the patient within a computer work station. Three diodes are then attached to each fragment just before the osteotomy is completed. Rigid motions of the fragment are thus tracked and reported to the surgeon by using virtual reality techniques. Errors in fragment positioning are reported both graphically and numerically with respect to a precomputed optimum fragment position. This guidance system allows multisegment midface osteotomies to be performed more precisely. The main problems encountered so far have been devascularization-infection and difficulties in maintaining correct position during application of rigid fixation. Devascularization-infection problems have been addressed by minimizing surgical exposure of the bone. Soft-fixation plates and temporary Kirschner wire fixation have helped with intermediate positioning, but an intraoperative mechanical positioning device would be useful in the future.
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The histological picture of severe stage dysplasia or undifferentiated vulvar intraepithelial neoplasia III is similar in three clinical entities, which should be distinguished because they differ with regard to clinical characteristics, development, prognosis and treatment. They are: 1. Bowen's disease in the menopausal female, which is a precancerous state that in 10 to 30% of cases develops to invasive epidermal cancer. Surgical excision is required. 2. Bowen's papulosis in the young female, known only since the last 2 decades, is the most frequent. It is clinically highly polymorphic. Since it can regress spontaneously and short- and mid-term malignant transformation is rare, conservative treatment should be given. 3. Extensive, patchy Bowen's papulosis in the young female is associated with intraepithelial cervical neoplasia in 85% of cases and with immune deficiency in 30% of cases. Fortunately, it is rare because its risk of malignant transformation is high. Its treatment has not been fully defined but should be as conservative as possible. This clinical distinction is not accepted in the English literature but to us seems of major importance given the need to apply appropriate treatment in each case.
OBJECTIVE: To assess issues and management of longitudinal vaginal septum. STUDY DESIGN: The charts of 202 patients referred for a longitudinal vaginal septum over a 24 year period were reviewed. RESULTS: The most common septa were complete and high partial. Associated uterine malformations were frequent (87.8% of the cases), especially in complete or partial high septum (99.4%). The septum was asymptomatic in 56.4% of the cases. Obstetrical concerns are mainly related to a uterine malformation, but a thick septum may be responsible for dystocia. CONCLUSION: Less than half of the vaginal septa are symptomatic enough to require surgical treatment. However, for obstetrical issues management should include a thorough evaluation of uterine anatomy and preventive section of the septum even when asymptomatic.