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Biomedical subjects

P Heyl

Publications and source records attributed to P Heyl.

4 recordsLinked to original sources

Attempted vaginal birth after cesarean section: a multicenter comparison of outpatient prostaglandin E(2) gel with expectant management.

Objective: To compare the clinical effectiveness and safety of outpatient administration of an intracervical prostaglandin (PG) E(2) gel with expectant management for women with an unfavorable cervix who wish to attempt a vaginal birth after cesarean section.Study Design: This outpatient study was a randomized, multicenter investigation involving pregnant women at term with one previous low transverse cesarean section. Each had an unfavorable cervix (Bishop score </=4) and was a candidate for vaginal delivery. Those randomly assigned to receive the gel, rather than expectant management, were given a 0.5 mg dose of PGE(2) (Prepidil) intracervically at 39 weeks gestation. This cervical ripening treatment was repeated at weekly office visits for up to 3 doses.Results: Of the 294 cases, 143 received the gel while 151 underwent expectant management. No differences between the two groups were found for maternal demographics, race, parity, or predose Bishop score. The rates of repeat cesarean section did not differ (P =.68) with use of the gel (61, 42%) or with expectant therapy (48, 45%). The onset of active labor, the duration of labor among those delivering vaginally, and the 1-minute and 5-minute Apgar scores were not different between the two groups. No uterine rupture was apparent, and adverse effects during labor were as likely to occur in the two groups.Conclusions: Although its safety was confirmed for outpatient use and for persons with a prior cesarean delivery, intracervical prostaglandin E(2) gel did not improve the chance of a vaginal birth after a cesarean delivery.

Journal Article↗

Hexadecylphosphocholine differs from conventional cytostatic agents.

Alkylphosphocholines, and especially their main representative hexadecylphosphocholine (HPC), show high anticancer activity in methylnitrosourea (MNU)-induced autochthonous rat mammary carcinoma. The regression of MNU-induced rat mammary carcinoma during HPC treatment can be evaluated by computed tomography and sonography. This allows a noninvasive monitoring of therapy in vivo (tumor size, morphology, and blood supply). Both diagnostic modalities can show a rapid concentric decrease in tumor volume as well as the appearance of cystic, scarry, and necrotic areas in the tumor tissue as a result of HPC treatment. In addition, prior to, during and after therapy tumor perfusion can be assessed by color Doppler sonography in vivo. A more than 4-fold difference in HPC efficacy was observed when the colony growth of explanted MNU-induced mammary carcinoma cells was measured in the methylcellulose colony assay (IC50 = 180 mumol HPC/l) and the Hamburger Salmon colony assay (IC50 = 740 mumol HPC/l). In the latter assay, growth of concomitantly seeded untransformed cells, especially of fibroblasts, is much lower than in the methyl-cellulose colony assay. We therefore assume that the antitumor efficacy of HPC against MNU-induced mammary carcinoma is enhanced by neighboring cells such as fibroblasts. Cell culture experiments with the three MNU-induced rat mammary carcinoma cell clones 1-C-2, 1-C-30, and 1-C-32 revealed IC50 values in the range of 50-70 mumol HPC/l. The volume of 1-C-2 cells increased up to 4-fold after 72 h of permanent exposure to 100 mumol HPC/l, a concentration that completely inhibited proliferation of tumor cell numbers without being cytotoxic. Nucleotide triphosphate levels dropped significantly after 24 h and were slowly restored in spite of continued exposure. After 72 h, they nearly reached those levels observed in plateau-phase cells. This suggests that HPC-induced growth inhibition has similarities with physiologically occurring growth arrest. Finally, replication of RNA viruses and DNA viruses was suppressed 30-fold and 7-fold, respectively, at low concentrations of HPC (12 mumol/l), which caused no or negligible growth inhibition in the virus-harboring cells, thus demonstrating specific antiviral activity of HPC. From these observations we conclude that HPC differs in many important aspects from conventional cytostatic agents and is certainly worth following-up in further investigations.

Animals↗

Effect of miltefosine on transplanted methylnitrosourea-induced mammary carcinoma growing in Fischer 344 rats.

Miltefosine (hexadecylphosphocholine, HPC, CAS 58066-85-6) was investigated in transplanted primary methylnitrosourea-induced PYH mammary carcinoma of F344 rats. The therapy was performed in the 5th and 10th passage. At first HPC (113 mg/kg body weight) significantly reduced the median tumor volume, but a loss of activity was observed in the 10th passage. To explain the loss of sensitivity and to obtain information on the mechanism of action histology, cytoskeleton and hormone receptor content were investigated. The most important change was observed in the histopathology of the tumor. The initial tubular papillary adenocarcinoma was transformed into a malignant adenoacanthoma with epithelial structure. Vimentin as an endothelial marker of the cytoskeleton was equally expressed in all passages. Cytokeratin was weakly expressed in the earlier passages and intensively present in the late passages. The histopathological change from tubular adenocarcinoma to malignant adenoacanthoma might be caused by an overgrowth of the primary epithelial tumor cells or by a real transformation in the morphological characteristics of the tumor, which may occur during repeated transplantation.

Adenocarcinoma↗

3H-dopamine clearance from the intravascular compartment of the maternal and fetal rhesus monkey.

The clearance of epinephrine and norepinephrine from the intravascular compartment has previously been demonstrated in both pregnant and nonpregnant models. With the use of the pregnant rhesus monkey, this study describes the clearance of dopamine from the fetal and maternal intravascular compartments. In both, the dopamine clearance was biphasic with an initial half-life of 1.5 minutes in fetal blood and 1.0 minute in maternal blood. These studies also confirmed that dopamine does not significantly cross the placenta in an intact form. These observations are consistent with those made for the other two major catecholamines.

Animals↗