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Biomedical subjects

Hanns Helmer

Publications and source records attributed to Hanns Helmer.

8 recordsLinked to original sources

Amnionitis with Ureaplasma urealyticum or other microbes leads to increased morbidity and prolonged hospitalization in very low birth weight infants.

OBJECTIVE: To investigate the influence of culture proven intrauterine infection on preterm morbidity and to test the effect of antimicrobial treatment. METHODS: Retrospective cohort study conducted between October 1997 and February 2001 in patients with preterm premature rupture of membranes or preterm labor. Vaginal swabs were sampled and amniocentesis for microbiologic culture of the amniotic fluid was performed. Patients with Ureaplasma urealyticum in the amniotic fluid were treated with josamycin. Infants were followed post partum according to birth weight, gestational age, APGAR score and infant morbidity. RESULTS: In 49 eligible patients, 40% of cultures were positive, 22% for Ureaplasma urealyticum, 12% for other bacteria and 6% for candida. Children of mothers with positive amniotic fluid cultures had significantly lower gestational ages (26+4 weeks for Ureaplasma urealyticum [p=0.04] and 25+5 weeks for other microorganisms [p=0.0017] versus 28+6 weeks for mothers with negative amniotic fluid cultures) and lower birth weights (975 g [n.s.] and 828 g [p=0.0072] versus 1,041 g) but were appropriate for their gestational ages. 33.3% and 66.7% versus 24% of the children were mechanically ventilated [n.s.], duration of mechanical ventilation was 5.3 [p=0.02] and 10.1 days [p=0.04] versus 1.4 days, and prevalence of chronic lung disease was 38% and 33% versus 11% [n.s.]. Prevalence of severe intraventricular hemorrhage (12.5% [n.s.] and 33% [p=0.04] versus 3.4%) and nosocomial infections (50% for both groups of positive cultures versus 10.3% for negative cultures, p=0.02 and 0.03, respectively) was higher and median length of stay was significantly longer (121 [p=0.02] and 107 days [p=0.03] versus 60 days) in these patients. Maternal positive vaginal swab cultures were not associated with any of the above-mentioned factors. In none of the patients treated with macrolids for proven Ureaplasma urealyticum amnionitis could the microbes be eradicated. CONCLUSION: Maternal positive amniotic fluid cultures have been associated with lower gestational age and lower birth weight. Rate of infant morbidity was higher and length of stay was significantly longer in this group. Positive vaginal swabs were not predictive for infant morbidity. Treatment of mothers showing positive amniotic fluid cultures with macrolids was not effective.

Chorioamnionitis↗

Induction of labor at term using isosorbide mononitrate simultaneously with dinoprostone compared to dinoprostone treatment alone: a randomized, controlled trial.

OBJECTIVE: We aimed to determine whether isosorbide mononitrate (IMN) given simultaneously with dinoprostone in term pregnancies is superior to dinoprostone alone to promote delivery. STUDY DESIGN: One hundred and twenty nulliparous women at term were randomly assigned to receive per vaginam IMN 40 mg or placebo in addition to 3 mg dinoprostone 2 times daily for up to 2 days. Analysis was by intention to treat. RESULTS: Baseline characteristics of both groups were comparable. The induction to delivery intervals did not differ between the IMN and the placebo group (26.4 +/- 14.4 vs 23.4 +/- 14.8 hours, P = .408). IMN resulted in more headache compared to placebo (32/55 [58.2%] vs 2/55 [3.6%], P < .001). CONCLUSION: Vaginally administered IMN does not play a role in promoting delivery in term pregnancy if given at the same time as dinoprostone. This might reflect its relaxant effect on the uterine fundus, which may overcome its cervical softening effect.

Administration, Intravaginal↗

MRI of fetal acquired brain lesions.

Acquired fetal brain damage is suspected in cases of destruction of previously normally formed tissue, the primary cause of which is hypoxia. Fetal brain damage may occur as a consequence of acute or chronic maternal diseases, with acute diseases causing impairment of oxygen delivery to the fetal brain, and chronic diseases interfering with normal, placental development. Infections, metabolic diseases, feto-fetal transfusion syndrome, toxic agents, mechanical traumatic events, iatrogenic accidents, and space-occupying lesions may also qualify as pathologic conditions that initiate intrauterine brain damage. MR manifestations of acute fetal brain injury (such as hemorrhage or acute ischemic lesions) can easily be recognized, as they are hardly different from postnatal lesions. The availability of diffusion-weighted sequences enhances the sensitivity in recognizing acute ischemic lesions. Recent hemorrhages are usually readily depicted on T2 (*) sequences, where they display hypointense signals. Chronic fetal brain injury may be characterized by nonspecific changes that must be attributable to the presence of an acquired cerebral pathology. The workup in suspected acquired fetal brain injury also includes the assessment of extra-CNS organs that may be affected by an underlying pathology. Finally, the placenta, as the organ that mediates oxygen delivery from the maternal circulation to the fetus, must be examined on MR images.

Brain Injuries↗

Frequently asked questions on tocolytics.

The majority of drugs that are used today for tocolysis have been developed for clinical conditions other than preterm labour. Obstetricians started to use these drugs as tocolytics because of their additional influence on uterine smooth muscle relaxation, accepting their cardiovascular (side) effects. Because the majority of these drugs are used off label, today's strict criteria to evaluate drugs for their predominant use in pregnancy have not been applied; therefore, we also lack sufficient peri- and neonatal follow up data for these drugs. This problem is compounded as our understanding of the regulation of myometrial smooth muscle contraction and relaxation is still incomplete.

Female↗

The quality of nifedipine studies used to assess tocolytic efficacy: a systematic review.

OBJECTIVE: To assess the quality of studies of nifedipine used to treat spontaneous preterm labor. DESIGN: A systematic review of study quality using a novel validity assessment tool, examining method-specific and topic-specific items in the domains of selection, performance and measurement biases. DATA SOURCES: Medline (1996-2003), EMBASE (1996-2003), BIOSIS (1993-2003), Current Contents (1995-2003), DERWENT DRUGFILE (1983-2003), Cochrane Database of Systematic Reviews. Bibliographies of existing meta-analyses and systematic reviews of nifedipine as a tocolytic. METHODS OF STUDY SELECTION: Forty-five studies evaluating the effectiveness of nifedipine were identified. DATA EXTRACTION: Each study was assessed for 40 method-specific and topic-specific items of quality in duplicate using piloted data extraction forms. Disagreements between assessors were settled by consensus/arbitration. DATA SYNTHESIS: Very few of the studies complied with adequacy criteria of quality for either method-specific or topic-specific items. There was no improvement in quality over time. The quality of method-specific items was significantly poorer when compared with topic-specific items of quality overall (P<0.0001) and in the domains of selection bias (P<0.0001) and performance bias (P<0.0001). CONCLUSION: Studies of the effectiveness of nifedipine as a tocolytic are of poorer quality with respect to method-specific items than topic-specific items. These deficiencies should be highlighted in meta-analyses or systematic reviews which measure efficacy and should influence the generation of guideline statements or recommendations for the use of nifedipine as a tocolytic. A large randomized trial fulfilling the quality items is necessary to assess the real efficacy of nifedipine in preterm labor.

Female↗

Transcriptional regulation of the human chorionic gonadotropin beta gene during villous trophoblast differentiation.

Expression of the trophoblast-specific subunit of human chorionic gonadotropin, CGbeta, is associated with fusion of cytotrophoblasts into a multinuclear syncytium. Here, we studied regulation of the CGbeta5 gene in trophoblasts undergoing in vitro syncytialization. Transfection of luciferase reporters harboring different lengths of the CGbeta5 upstream sequence revealed that the proximal promoter region (-345 to +114) is sufficient to govern differentiation-dependent induction. Mutational analyses suggested that two selective promoter factor (Sp) and three activating protein 2 (AP-2) recognition sequences are necessary for full activity of the promoter. During syncytialization these elements interacted with increasing amounts of the transcription factors Sp1, Sp3, and AP-2alpha in electrophoretic mobility shift assay, but only AP-2alpha binding rose upon elevation of cAMP levels with forskolin. Increasing expression of different isoforms of Sp1 and Sp3 could also be detected by Western blot analyses. Sp1/Sp3 localized to syncytial nuclei both in differentiated cultures and in term placental tissue, suggesting assembly of functional transcriptional complexes. Costaining of the transcription factors with E-cadherin on term placental sections revealed that 47 and 33% of cytotrophoblast nuclei were negative for Sp1 and Sp3, respectively. In contrast, immunohistochemistry of early tissue demonstrated expression of Sp1 in the majority of cyto- and syncytiotrophoblasts, whereas Sp3 was absent from the syncytium. Sp1 and Sp3 induced wild-type/mutant promoter constructs upon transfection in Sp-deficient SL-2 cells, indicating that the Sp elements function as activating sequences. The data suggest that increasing concentrations of Sp1, Sp3, and AP-2alpha enhance transcription of CGbeta in differentiating term trophoblasts, whereas a different combination of factors may control expression in early placentas.

Base Sequence↗

Exploring the role of Tractocile in everyday clinical practice.

The purpose of this retrospective study is to evaluate the effects of atosiban (Tractocile available in Austria since February 2000) for routine treatment of women with threatened preterm delivery. The advantage of this drug compared to other tocolytic agents is its specific action on reproductive tissues without the accompanying severe side effects. Women (n = 208) were retrospectively evaluated. Diagnoses at admission were preterm labour (n = 117), preterm rupture of membranes (n = 65), incompetent cervix (n = 19) and vaginal bleeding (n = 7). Gestational age was between weeks 21 and 33 of pregnancy. Preterm labour was defined as >/=4 uterine contractions/30 min and cervical length <30 mm examined by vaginal ultrasound and/or detection of vaginal fetal fibronectin. Tocolytic effectiveness was determined as the number of women having a diagnosis of preterm labour who were still pregnant after 48 hours and after 7 days. The influence on the frequency of contractions before and 3-12 hours after the start of treatment was assessed. Maternal side effects, perinatal and neonatal morbidity and transfers to the NICU were also evaluated. The proportion of women who remained undelivered was 78.7% after 48 hours, and 64.3% after 7 days. Atosiban decreased the frequency of contractions from 5.4/30 min before treatment to 1.6 contractions/30 min after the start of treatment. At the initial bolus application, 20.2% of women presented drug-related side effects, such as nausea, vertigo and flush over a short period of 1-2 minutes. During infusion, side effects possibly related to atosiban could be detected in 6% of women. Mean length of stay was 11.8 days in the NICU and 30.9 days in intermediate care. Twenty-three children developed intraventricular haemorrhage (I-IV). In conclusion, atosiban is an effective tocolytic drug in the treatment of preterm labour and preterm rupture of the membranes. It has significantly less side effects due to its lack of cardiovascular activity.

Drug Evaluation↗

Production of oxytocin receptor and cytokines in primary uterine smooth muscle cells cultivated under inflammatory conditions.

OBJECTIVE: We studied the production of the oxytocin receptor and interleukins in human uterine smooth muscle cells cultured in vitro in the presence of cytokines that were shown to be elevated in gestational diseases such as intrauterine infections and chorioamnionitis. METHODS: Human uterine smooth muscle cells were cultured in the absence or presence of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), or lipopolysaccharide (LPS). Additionally, cells were cultivated under hypoxic conditions (3.5% oxygen). After 6, 12, 24, and 48 hours of incubation, oxytocin receptor mRNA was measured from total RNA using quantitative, competitive reverse transcriptase-polymerase chain reaction. Secreted cytokines (IL-1beta, IL-6, or IL-8) were quantitated from supernatants after 6, 12, 24, and 48 hours of stimulation by commercially available enzyme-linked immunosorbent assay. RESULTS: In nonstimulated cultures basal secretion of IL-1beta, IL-6, and IL-8 was detectable. Supplementation of IL-1beta induced a statistically significant decrease in oxytocin receptor mRNA abundance, whereas IL-6, TNFalpha, LPS, or hypoxia did not significantly affect oxytocin receptor gene expression. The cytokines IL-1 and TNFalpha induced IL-6 and IL-8 release, whereas secretion of the two interleukins was not altered in the presence of LPS or hypoxia. Expression of IL-1beta was not significantly induced under inflammatory or hypoxic culture conditions. CONCLUSION: The constitutive and cytokine-inducible expression of interleukins from uterine smooth muscle cells suggests that the myometrium may contribute to the overall production of inflammatory mediators in the uterus that are thought to govern term- or infection-induced preterm labor. Down-regulation of the oxytocin receptor under IL-1beta in myometrial cells may indicate that initiation and maintenance of labor could be partially limited under severe inflammatory conditions such as chorioamnionitis.

Cells, Cultured↗