[Oral misoprostol against vaginal dinoprostone for labor induction at term: a randomized comparison]. / Prospektiv randomisierte Studie zum Vergleich von Misoprostol oral mit Dinoproston vaginal bei der Geburtseinleitung am Termin.

BACKGROUND: It was the objective of this study to compare the efficacy and safety of oral misoprostol with those of vaginal dinoprostone for the induction of labour at term. PATIENTS AND METHODS: Between 2003 and 2006 224 pregnant women were included in our prospective randomised clinical trial. All of them were admitted for induction of labor at term. Half of the patients received oral misoprostol, initially at a test dose of 25 microg, followed by 50 microg and 100 microg every 4 hours. The control group received 3 mg vaginal dinoprostone every 6 hours. Primary endpoints were time interval until delivery and mode of delivery as well as maternal and neonatal outcome, secondary endpoints were side effects and costs. RESULTS: In the dinoprostone group, the median time interval until delivery was 17.6 hours compared to 24.1 hours in the misoprostol group. Without the test dose, the difference was no longer significant. After dinoprostone induction, more patients had a vaginal delivery within 24 hours (n=60, 53.6%, vs. n=46, 41.1%). The frequencies of spontaneous deliveries and emergency Caesarean sections did not differ between the groups. The rate of vacuum extractions was higher in the misoprostol group (23 vs. 11, i. e. 20.5 vs. 9.8%, p<0.05). With regard to side effects there was no significant difference. No case of hyperstimulation was documented. CONCLUSION: Oral misoprostol is effective and safe for induction of labour at term. In addition, it is much cheaper and independent of storage conditions. At the doses and with the administration intervals used in this study, dinoprostone was slightly more effective than misoprostol.

X chromosomal and autosomal loss of heterozygosity and microsatellite instability in human cervical carcinoma.

The study analyzes tumor material and normal tissue from 27 patients with pure squamous cell carcinoma of the uterine cervix for loss of heterozygosity (LOH) and microsatellite instability (MSI) on 14 autosomal and 11 X chromosomal loci. Overall, 4-40% of the informative cases showed LOH at autosomal regions with the highest frequency at 3p (21-40%) and a marked frequency at 2q35-q37.1 (12.5%) and 17p13.3 (10%), representing regions with putative tumor suppressor gene (TSG) function. The frequency of X chromosomal LOH ranged from 4% to 20%, with a maximum at Xq28 (20%) and Xq11.2-q12 (17%), again indicating alterations in TSG. A 12% LOH was seen at Xq21.33-q22.3, a region encoding a protein with a regulatory function in the cell cycle via cyclin-dependent kinases. MSI was detected in autosomal regions in up to 7% in regions linked to the X chromosome in up to 11%, probably indicating alterations of mismatch repair mechanisms. Our results and those obtained from the literature suggest that autosomal LOH and MSI in carcinomas of the cervix uteri are predominantly found at regions with putative TSG function. Beside TSG alterations, X chromosomal LOH is probably more strongly connected to disturbances in cell cycle regulation.

Comparison of reflectometric interference spectroscopy with other instruments for label-free optical detection.

On the basis of kinetic measurements of biomolecular interactions, a reflectometric interference spectroscopy (RIfS) setup is compared with two commercial instruments. These instruments are based on evanescent wave techniques, surface plasmon resonance (SPR) (represented by BIAcore 2000) and resonant mirror (RM) technique (using IAsys plus). All methods allow a label-free and time-resolved optical detection of biomolecular interaction. These methods are mainly used in biomolecular interaction analysis (BIA). They provide practical techniques for quantifying equilibrium constants and rate constants over several orders of magnitude. The general parameters of the three detectors, namely baseline noise and drift as well as overall sensitivity and limits of detection were compared. The fluid handling and the related implications on the measurements have also been considered. The interaction between thrombine and thrombine inhibitor (TI) was investigated as a test system with the three different methods and the kinetic rate constants were determined and compared. For this TI was immobilized on the surface and binding of thrombine was monitored time-resolved. Determination of the kinetic rate constants could prove that the RIfS set-up is comparable with SPR using BIAcore 2000 and RM technique represented by IAsys plus.

p53 in surgically treated and pathologically staged cervical cancer: correlation with local tumor progression, but not with lymphatic spread.

There is only limited information about the prognostic value of p53 immunostaining in cervical cancer. The purpose of this study was to assess the clinical significance of p53 and prognosis in operatively treated cervical carcinoma. A hundred and fourteen primary surgically treated cervical carcinomas (CX) were obtained from the so called Wertheim Archive in the Department of Obstetrics and Gynecology at the University of Leipzig. These included 105 squamous cell cancer (SCC) and nine adenocarcinomas (AC). No cases received neoadjuvant therapy. For immunohistochemical analysis, the cases were tested with the monoclonal antibody DO-7 (DAKO Diagnostics, Denmark). Two hundred tumor cell nuclei were counted for positive nuclear immunostaining, regardless of staining intensity. Cases were stated as positive when a minimum of 10% nuclei showed positive staining. Fresh frozen tissue was available from 21 CX for p53-mutation analysis (exons 4-9) using PCR-based amplification and SSCP-analysis. Of the squamous cell cancers (SCC), 63.8% showed positive nuclear p53-immunostaining; adenocarcinomas (AC) were completely negative (P = 0.0000, Chi2-test). Stage-by-stage analysis revealed no differences in p53-expression. However, combining pT1b- and pT2-cases, the difference in positive immunostaining reached statistical significance (44.4% vs. 71.7%; P = 0.007). There were no differences in p53-reactivity regarding the presence of pelvic lymph node metastases, tumor grading, relapse-free survival and tumor recurrence. In addition, only 5% of CX with positive p53-immunostaining showed genomic alterations in mutational analysis. p53-immunoreactivity showed significant correlation with local tumor progression but not with lymphatic spread, lacking any prognostic impact in surgically treated cervical cancer. There is no correlation of p53-immunostaining with the occurrence of p53-gene mutations in cervical cancer.

Unusual T-cell receptor-delta gene rearrangement patterns revealed by screening of a large series of childhood acute lymphoblastic leukaemia by multiplex polymerase chain reaction.

Rearrangements of the T-cell receptor (TCR) and immunoglobulin genes are considered as useful clonal markers in lymphoproliferative disorders of B- and T-cell lineage, and are frequently used for the detection of minimal residual disease (MRD). In this paper, we report on the unexpected results of an extensive analysis of TCR-delta chain gene rearrangement frequencies and patterns in leukaemic bone marrow DNA samples collected from 438 children with initial (n = 112) or relapsed (n = 326) acute lymphoblastic leukaemia (ALL). By applying a previously described multiplex polymerase chain reaction, the overall incidence of non-deleted TCR-delta gene rearrangements in ALL was 47% (206/438), 52% in initial ALL (58/112) and 45% in relapsed ALL (148/326). As expected, the majority of B-cell precursor (BCP) ALL had incomplete Vdelta2-Ddelta3 or Ddelta2-Ddelta3 TCR-delta gene rearrangements, whereas most T-ALL showed complete rearrangements of the TCR-delta gene locus (Vdelta1-Jdelta1, Vdelta2-Jdelta1, Vdelta3-Jdelta1). However, unexpectedly, 5/206 rearranged TCR-delta alleles in BCP-ALL showed a complete Vdelta-(Ddelta)-Jdelta gene rearrangement pattern, and 3/31 T-ALL had an incomplete recombination. Theoretically, complete TCR-delta gene rearrangements should not occur in cells other than T-lymphocytes and have only been reported once previously in BCP-ALL. The data contribute to the discussion about the reliable screening for clonal markers in ALL.

Identity testing in cervical carcinoma in case of suspected mix-up.

The histopathologic diagnosis is the cornerstone of modern oncology. But mix-ups of specimens can occur at any stage. The resection of a 1.2 cm polypoid cervical mass in a 25-year-old woman showed a poorly differentiated adenocarcinoma prospectively staged as T1b1 (International Federation of Gynecology and Obstetrics IB1). Even after complete embedding and serial sectioning of the whole cervix of the hysterectomy specimen after radical hysterectomy, only adenocarcinoma in situ, but no invasive tumor, was seen. To exclude a mix-up of the specimens, identity testing of the paraffin-embedded material was performed by microsatellite analysis. For both materials, we established identical results after testing the microsatellite loci HumTH01, HumVWA, HumFGA, HumACTBP2, HumF13B, and HumD8S1132. The resulting probability of identity came to 99.9999%, excluding a mix-up of the specimens. Archival paraffin-embedded specimens can be used to establish identity and can prevent the wrong patient from having major surgery.

Multiplex PCR for simultaneous detection of the most frequent T cell receptor-delta gene rearrangements in childhood ALL.

A rapid and simple multiplex polymerase chain reaction (PCR) is described that is capable of identifying the six most frequent rearrangements of the T cell receptor (TCR)-delta gene segments in childhood acute lymphoblastic leukemia (ALL). The PCR products amplified in a single reaction are of different size for each TCR-delta gene rearrangement. Therefore, they are readily and unambiguously distinguished after agarose gel electrophoresis and assigned to a specific V-D-J gene rearrangement. There is no need for labor-intensive and time-consuming Southern blot hybridization or nested PCR. To evaluate the multiplex assay we chose 45 DNA samples of childhood ALL analyzed beforehand for TCR-delta gene rearrangements by Southern blot and single PCR of which 30 showed TCR-delta gene rearrangements. The multiplex PCR results corresponded to the Southern blot and single PCR analyses. The described multiplex PCR enables the detection of clonal markers in about 50% of patients in order to monitor minimal residual disease (MRD) in prospective studies with a high turnover of samples.