Impetigo herpetiformis occurring during N-butyl-scopolammonium bromide therapy in pregnancy: case report.

Impetigo herpetiformis (IH) is a rare dermatosis arising during the third trimester of pregnancy which is generally considered as a form of pustular psoriasis of unknown aetiology. Clinically it is characterized by erythematous plaques surrounded by sterile pustules associated with fever, diarrhea, sweating and increasing risk of stillbirth for placental insufficiency. We describe a case of developed erythematous plaques surrounded by pustules localised initially to the trunk of a 35-year-old woman at the 34th week of gestation after 5 days of treatment with N-Butyl-Scopolammonium, and which later involved the upper and lower limbs. Skin histology confirmed the diagnosis of generalised pregnancy pustular psoriasis (impetigo herpetiformis). IH is reported to be associated with hypocalcemia, hypoparathyroidism, use of oral contraceptives and bacterial infections. This is the first report suggesting the potential role of drugs other than oral contraceptives in the pathogenetic mechanism of this disease. In this case an adverse cutaneous reaction to BB could be the cause of the development of Koebner isomorphism.

Fetal surgery for spina bifida aperta: to be or not to be?

Fetal SBA (spina bifida aperta) has been operated upon in more than 213 cases in the USA in the last 8 years. Indications and results still remain controversial. Our group reproduced successfully Meuli's model in sheep and reviewed the literature on SBA and the Internet updated sites on the theme. Then we reviewed the follow-up of all cases operated upon postnatally in 20 years at a Neurosurgery Department in Rome. We published all the data regarding the three above-mentioned steps. This paper contains reflections on the three, and our opinion on the correct approach to prenatally diagnosed SBA, as far as fetal surgery is concerned.

There is poor agreement between manual auscultatory and automated oscillometric methods for the measurement of blood pressure in normotensive pregnant women.

OBJECTIVE: To assess the agreement between manual auscultatory arterial blood pressure values and the values obtained by an automated oscillometric device in normotensive pregnant patients. METHODS: Arterial blood pressure was determined concomitantly by a Dinamap 1846 sx/p device and by one observer (I, IV, V Korotkoff sounds) blinded to the Dinamap values. Agreement between methods was tested and graded according to the protocol of the British Hypertension Society. RESULTS: A total of 490 observations were performed. Differences were observed between the manual auscultatory method and the Dinamap method. In monitoring normotensive pregnant patients with a Dinamap device, an error was made of about 10 mmHg in 22% of the observations for systolic arterial blood pressure (BP); in 11% for diastolic arterial BP (IV sound); and in 15% for diastolic arterial BP (V sound). According to the British Hypertension Society protocol, the overall grade reached was 'C'. CONCLUSIONS: Although an underestimation of only 10 mmHg was shown, this can be of great importance in delaying a correct diagnosis of pre-eclampsia. The assessment of agreement of the Dinamap 1846 sx/p device in hypertensive pregnant patients should also be determined. A prospective study could be useful to determine the effectiveness of an automated device in detecting hypertensive disease in pregnancy.

Activity and expression of 15-hydroxyprostaglandin dehydrogenase in cultured chorionic trophoblast and villous trophoblast cells and in chorionic explants at term with and without spontaneous labor.

OBJECTIVE: The aim of this study was to investigate whether any changes occurred at term before and with labor in the 15-hydroxyprostaglandin dehydrogenase messenger ribonucleic acid level and in the 15-hydroxyprostaglandin dehydrogenase activity in cultured chorionic and villous trophoblast cells and in chorionic explants. STUDY DESIGN: Twelve placentas (labor group [vaginal delivery], n = 6; nonlabor group [elective cesarean delivery], n = 6) were collected. Chorionic trophoblast and villous trophoblast cells and chorionic disks were obtained, cultured, and incubated with 282-nmol/L prostaglandin F(2)(alpha). Medium was collected to measure the 13,14-dihydro-15-keto metabolite of prostaglandin F(2)(alpha), and the cells and disks were snap-frozen to quantify 15-hydroxyprostaglandin dehydrogenase messenger ribonucleic acid expression by Northern blot analysis. RESULTS: The formation of the 13,14-dihydro-15-keto metabolite of prostaglandin F(2)(alpha) was significantly lower in the labor group than in the nonlabor group for both sets of cultured cells and for chorionic explants. 15-Hydroxyprostaglandin dehydrogenase messenger ribonucleic acid expression was lower in the chorionic trophoblast cells and chorionic disks of the labor group than those of the nonlabor group. However, the 15-hydroxyprostaglandin dehydrogenase messenger ribonucleic acid level in the villous trophoblast cells did not differ between the labor and nonlabor groups. CONCLUSION: Prostaglandin metabolic activity in the chorion is reduced significantly at the time of labor.

Interleukin-10 modifies the effects of interleukin-1beta and tumor necrosis factor-alpha on the activity and expression of prostaglandin H synthase-2 and the NAD+-dependent 15-hydroxyprostaglandin dehydrogenase in cultured term human villous trophoblast and chorion trophoblast cells.

The concentrations of tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta), two inflammatory cytokines in amniotic fluid, have been shown to rise during chorioamnionitis. This is probably related to activation of the immune system in order to intensify the inflammatory process and to protect the maternal and fetal organism from infectious agents. These cytokines activate the PG biosynthetic pathway in several tissues, but few studies have examined effects on PG-metabolizing enzymes. When PGs are produced by increased synthesis and/or decreased metabolism at the chorio-decidual interface, labor can be induced. Interleukin-10 (IL-10) is known to act as an antiinflammatory cytokine. The goals of this study were to evaluate the interaction of IL-10 with IL-1beta and TNFalpha on PG synthesis and to determine the effects of IL-10, IL-1beta, and TNFalpha on PG metabolism using purified cultures of villous trophoblast and chorion trophoblast cells prepared from placentas of patients at term. Cells were treated with IL-1beta and TNFalpha with or without IL-10 for various times up to 24 h. Levels of messenger ribonucleic acid (mRNA) encoding PGH synthase-2 (PGHS-2) and NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (PGDH) were quantified by Northern blotting, and PGE2 and 13,14-dihydro-15-keto-PGF2alpha (PGFM) output in the medium was measured by RIA. IL-1beta increased PGHS-2 mRNA and PGE2 output from villous and chorion trophoblasts and decreased PGDH mRNA in villous trophoblasts (all P < 0.05). These effects were reversed by IL-10. We found no change in PGHS-2 mRNA or PGE2 output in either trophoblast type treated with TNFalpha, but TNFalpha reduced PGDH mRNA in villous trophoblast, and this effect was reversed by IL-10 (both P < 0.05). We conclude that proinflammatory cytokines can influence PG output through effects on PG synthesis and metabolism and that these effects may be opposed by an antiinflammatory cytokine. These interactions may be important in the progression of preterm labor with underlying infection and in term labor in regions of the uterus where cytokine production is increased.

Prostaglandin dehydrogenase and the initiation of labor.

In summary, these studies have suggested that prostaglandin dehydrogenase may have a central role to play in the mechanisms which determine biologically active prostaglandin concentrations within human fetal membranes and placenta at the time of labor, at term or preterm. Moreover, our studies indicate that the regulation of PGDH may by multifactorial (figure 3). In certain regions of the membranes, we suggest that PGDH expression may be influenced by levels of anti-inflammatory and pro-inflammatory cytokines. In other regions of the membranes, we suggest that PGDH may be regulated at a transcriptional level by competing activities of progesterone and cortisol. The action of progesterone could be effected through systemically-derived steroid, or by locally synthesized steroid, acting in a paracrine and/or autocrine fashion. The effects of cortisol in placenta must be due to glucocorticoid derived from the maternal or fetal compartment, since the placenta lacks the hydroxylases required for endogenous cortisol production. However, metabolism of cortisol by 11 beta-HSD-2 reduces the potency of this glucocorticoid in placental tissue. In chorion however, cortisol may be formed locally, from cortisone, in addition to its being derived from the maternal circulation and/or from the amniotic fluid. Our current studies do not allow us to delineate whether the effects of progesterone and cortisol on PGDH are exerted through the glucocorticoid receptor (GR) or progesterone receptor (PR) or both. It is possible that through pregnancy, PGDH activity is maintained by progesterone acting either through low levels of PR in membranes, or, more likely, acting through GR. At term, elevated levels of cortisol compete with and displace progesterone from GR, resulting in inhibition of PGDH transcription and activity. In this way, local withdrawal of progesterone action would be effected within human intrauterine tissues, without requiring changes in systemic, circulating progesterone concentrations. Since glucocorticoids appear also to increase expression of prostaglandin synthesizing enzymes within the amnion and chorion, directly by upregulating PGHS-2, or indirectly through the intermediary action of a paracrine effector such as CRH, their role in coordinating processes of parturition remains central. Further understanding of the regulation of PGDH may be of therapeutic importance. For example, it is possible that PGDH activity in lower segment chorion may be reduced in those patients with premature cervical softening, or may be particularly high in those patients with an unfavorable cervix, presenting with a low Bishop score and poor progression at the time of labor. If the enzyme in this region crucially determines the passage and availability of biologically active prostaglandins from amnion and chorion to underlying cervix, then pharmacologic manipulation of PGDH activity may effectively regulate PG transfer in these clinical conditions. Glucocorticoids appear to have a central role in promoting production of agents that are uterotonic to myometrial activity. It is likely that these activities explain the transient increments in uterine contractility reported in patients receiving prenatal corticosteroids to promote fetal pulmonary maturity [11]. Recognition of this physiology suggests that careful monitoring of these patients is advised, and would argue further against repeated, indiscriminate, use of glucocorticoids in patients with an inappropriate diagnosis of threatened preterm labor.

An experimental animal model of intestinal obstruction to simulate in utero therapy for jejunoileal atresia.

OBJECTIVE: To obtain 'intestinal atresia-like' conditions in the fetal lamb model to subsequently allow in utero surgical repair. METHODS: Six time-dated pregnant sheep underwent general anesthesia at 75 days of gestation (term 145 +/- 5 days). After maternal laparotomy and hysterotomy, the fetal abdomen was opened. Once the jejunoileal intestinal loop was identified, the mesenteric vessels were isolated, ligated, and sectioned in 2 fetuses, and in the remaining 5 fetuses the bowel loop was ligated. Two further fetuses were used as controls and underwent sole laparotomy. Of the group of 7 fetuses 2 were reoperated at 100-105 days of gestational age and underwent intestinal recanalization. Eight fetuses were delivered at term by cesarean section and the remaining 1 by spontaneous delivery. One newborn underwent neonatal entero-enteric anastomosis. RESULTS: 4 out of 6 fetuses survived, in utero intestinal or vascular ligation having provoked an 'intestinal atresia-like' picture. The animal operated at birth died. The 2 control fetuses and the 2 fetuses with in utero intestinal recanalization survived until term. CONCLUSION: The present study shows that in utero treatment of intestinal obstruction is possible in an experimental model.

Fetal infection from rubeovirus or cytomegalovirus: correlation among maternal serological profiles, invasive diagnostic procedures, and long-term follow-up.

Different variables influence the possibility that maternal viral infection may be transmitted to the fetus, although not all fetal infections result in fetal "illness" with consequent fetopathy. As concerns the fetus, prenatal diagnosis includes invasive techniques necessary for fetal tissue sampling. These techniques carry some risks. The fetal infectious risk, as determined by maternal clinico-serological profile and according to sonographic investigation, always should be weighed against the risks and benefits of invasive diagnostic procedures. The present study re-elaborates the criteria necessary for defining fetal risk as related to the maternal serological profile. In the 26 mothers with rubeola infection, the incidence of fetal mortality was 7.7%. Fetal prognosis worsens with the precocity of eruption. In these cases the esantema is the most reliable prognostic element as an indication to perform the invasive procedure. In the 15 patients with cytomegalovirus infection, no fetal or postnatal losses occurred. Morbidity occurred in 13.3% of cases, and the two ill fetuses were classified in the same risk group. In this group of patients, the maternal serological profile is a significant predictor of fetal morbidity.

Conventional ultrasonography and color Doppler velocimetry of uterine leiomyomas.

The role of uterine leiomyomas as causative factor of sterility is controversial. Submucosal myomas, in particular, can interfere with fertility and be associated to obstetric complications as abruption of placenta, post-partum metrorrhagia and puerperal sepsis. With ultrasonography, immediate and long-term information can be drawn on changes in the features of myomas. However, to-date, there are no reliable noninvasive exams to assess the nature and growth pattern of myomas. With Doppler velocimetry in ovarian malignancies a vascularization significantly different from that observed in benign tumors, is detected. It has been hypothesized that within benign tumors, as myomatous masses, tissues with different cell proliferation rates could be characterized by different vascular patterns. In a group of myomas shown to have central arterial vessels at Doppler examination, significant correlations were assessed between resistance indices of analyzed vessels and percentage of cell in the proliferative phase evaluated with cytofluorimetry. The myomatous tissue with high cell proliferation rate seems to have higher vascular resistances.

Cardiopulmonary bypass in pregnancy.

The cardiopathic patient can sustain acute heart failure during pregnancy. In such cases, if open heart operation is necessary to save the patient's life, the fetus could be seriously compromised after exposure to cardiopulmonary bypass. From 1958 to 1992, 69 reports of cardiac operations during pregnancy with the aid of cardiopulmonary bypass have been published. Maternal mortality was 2.9%. Embryofetal mortality was 20.2%. Examining only the last 40 patients, maternal and embryofetal mortality were 0.0% and 12.5%, respectively. Embryofetal mortality was 24.0% when hypothermia was used, compared with 0.0% while operating in normothermia. Maternal mortality did not change. The use of hypothermia during cardiopulmonary bypass provoked uterine contractions in several patients. Hypothermia decreases O2 exchange through the placenta. Pump flow and mean arterial pressure during cardiopulmonary bypass seem to be the most important parameters that influence fetal oxygenation. We speculate that cardiac operation is not a contraindication to pregnancy prolongation.

Cocaine during pregnancy: a critical review of the literature.

A number of epidemiological indices suggest that the use of cocaine in Italy is increasing, thus explaining the importance of scientific interest in this field. There is considerable disparity between the scientific papers published in the literature concerning the damaging effects on fetus and mother linked to the use of cocaine during pregnancy. The main problem consists of the method used to identify those patients using cocaine. These methods are burdened by a high level of false negatives: subjects who often use a variety of active pharmacological substances are identified and the methods are not always suitable for classifying subjects according to useful clinical parameters. This is reflected in the poor quality of data concerning the epidemiology and clinical aspects of cocaine abuse during pregnancy. A careful selection of the best scientific papers published in the literature shows that the effects on the maternal organism are slight, whereas those on the fetus are more severe. Compared to controls, the use of cocaine is associated with a high percentage of cardiac malformations, preterm delivery, low birth weight and minor anomalies of the nervous system. Results relating to sudden neonatal death are discordant. This paper shows that the use of cocaine is often underestimated both in epidemiological terms and from the fetal point of view. This behaviour is linked to the belief that the effects of cocaine are benign.

The duration of hypertension in the puerperium of preeclamptic women: relationship with renal impairment and week of delivery.

OBJECTIVE: The purpose of the study was to determine whether the duration of hypertension in the puerperium of preeclamptic women was related to certain clinical features of disease severity. STUDY DESIGN: We studied 269 singleton pregnancies divided into two groups: 159 with gestational hypertension and 110 with preeclampsia. The normalization time of blood pressure in puerperium was estimated as the interval between the delivery day and the first day when each of two to four self-measurements per day of diastolic blood pressure was observed to be < or = 80 mm Hg for at least 3 consecutive days. RESULTS: Normalization time was shorter in gestational hypertension than in preeclampsia (6 +/- 5.5 [means +/- SD] vs 16 +/- 9.5, respectively, p < 0.0001). Normalization time of gestational hypertension showed a significant correlation with uric acid (r = 0.20, p < 0.025); normalization time of preeclampsia displayed significant correlations with the week of delivery (r = -0.34, p < 0.005), uric acid (r = 0.34, p < 0.025), and urea nitrogen (r = 0.29, p < 0.025), respectively. After stratification by parity, in both groups the correlations of normalization time with renal data were observed only among multiparous women, whereas in preeclampsia the link of normalization time with the week of delivery remained highly significant in both subgroups. CONCLUSIONS: The differences observed between gestational hypertension and preeclampsia suggest that distinct mechanisms or a different maternal answer to the same mechanism(s), in maintaining high blood pressure in puerperium, are present in the two groups. Normalization time might reflect the recovery time of the endothelial damage in preeclampsia.

Pregnancy outcome in women with cardiac valve prosthesis.

Twenty-one pregnancies in 16 women who conceived after cardiac valve replacement were reviewed. Oral anticoagulants were discontinued before conception or as soon as possible for subcutaneous heparin treatment (8000-14,000 IU every 8-12 h) and resumed in the second trimester until the last period of pregnancy when oral anticoagulants were replaced again by heparin. No therapeutic abortion was performed. The spontaneous abortion rate was found to be 14.3% (3/21). Preterm delivery (< or = 37 weeks) and low birth weight babies (< 2500 g) were 29.4% (5/17) and 35.3% (6/17), respectively, significantly more frequent than those of the control group (P < 0.02 and P < 0.0005). No significant statistical difference was found when the rate of spontaneous abortion [14.3% (3/21)] and the rate of fetal growth retardation [11.8% (2/17)] were compared with the control group. The majority of thromboembolic events (6/7) occurred during heparin regimen in three mothers; one of them subsequently died. No coumarin embryopathy was observed and the physical and mental development in the 16 surviving children was good. This study confirms: (1) the increased rate of preterm delivery and infants weighing < 2500 g; (2) the increased risk of maternal thrombosis related to heparin use; and (3) the good follow-up in the surviving children.

[Continuous subcutaneous administration of terbutaline in the therapy of threatening premature labour]. / Uso della somministrazione continua sottocutanea di terbutalina nella terapia della minaccia di parto pretermine.

The purpose of this study was to evaluate the tocolytic efficacy of terbutaline, administered subcutaneously in a low-dose continuous infusion, and intermittent high-dose boluses. The population study consisted of 13 women admitted with the diagnosis of Threatened Preterm Labour. Before starting chronic infusion by terbutaline, patients received 48 hour of therapy with intravenous MgSO4 for acute tocolysis. Therapy with microinfusor was continued until the 37th week of gestation or until labor. The mean gestational age at the beginning of therapy was 25.6 +/- 3.5 and pregnancies were prolonged an average of 65.5 +/- 29 days. In any case uterine activity was diminished by terbutaline therapy in all patients. Patient tolerance was excellent and there were no significant complications due to the therapy.