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Biomedical subjects

W Rath

Publications and source records attributed to W Rath.

At least 217 records · Page 12Linked to original sources

[The influencing of rat-tail tumors with and without irradiation].

In a collective of 200 Wistar rats, the influence of anticoagulants upon the rat tail tumor (Walker 256 carcinosarcoma) was checked with and without irradiation. After implantation of the tumor and development of a certain definite tumor volume, the animals were divided into four different groups of 50 rats each. The first one was the control group without any manipulation, the second received an one-stage X-irradiation with 2500 R SD directed to the tail tumor, the third was treated with an oral dose of Phenprocoumon which was added to the daily drinking quantity (0.1 mg/kg body weight), and the fourth group was given an one-stage X-irradiation together with the oral Phenprocoumon treatment. The influence of these different treatments on the growth of the primary tumor, on the incidence of metastases and on the death rate was checked up. The best therapeutical effect was observed with combined radiation and Phenprocoumon treatment. The therapy resulted in an almost complete growth rate depression of the primary tumor, in an early tendency of remission of the primary tumor, a 42 per cent decrease of the incidence of metastases to the lung, and a 42 per cent increase of the survival rate. With regard to the frequency of metastases and to the survival rate, treatment with Phenprocoumon alone showed significantly better results as sole radiation treatment.

Animals↗

The importance of early laboratory screening methods for maternal and fetal outcome in cases of HELLP syndrome.

Over a period of 5 years and 3 months 50 patients with HELLP syndrome were treated at our hospitals. All of these patients fulfilled the criteria of this syndrome described by Weinstein. Pre-eclampsia with HELLP syndrome was either diagnosed correctly by the referring doctor or on admission by the obstetrician on the basis of the laboratory findings. The median time interval between admission and delivery was 3 hours (range: 0.5-40 hours). In 49 patients, Caesarean section was performed, one patient developed a HELLP syndrome 18 hours after vaginal delivery. The median gestational age at delivery was 35 weeks (range: 26-40). Only three of 51 infants died before delivery, and there was one neonatal death, resulting in a perinatal mortality of 7.8%. Apgar scores below 7 occurred in 15 of the newborns after 1 min and in only 2 after 5 min. In 47 cases, Caesarean section and hospital course were free of complications; in three patients postoperative hemorrhages required relaparotomy, in two of these patients puerperal hysterectomy had to be performed. In our experience, the relevant laboratory parameters should be determined in any pregnant women with right upper quadrant pain independent of the severity of pre-eclampsia in order to diagnose HELLP syndrome as soon as possible. Both early control and follow-up of the laboratory parameters and immediate delivery--by Caesarean section, if necessary--may lead to a reduction of maternal mortality and morbidity and to an improvement of perinatal results.

Adult↗

Progestins, progesterone receptor modulators, and progesterone antagonists change VEGF release of endometrial cells in culture.

The influences of the synthetic progestin, medroxyprogesterone acetate (MPA), the progesterone receptor modulator J867, and the antagonist ZK137316 were studied in vitro on isolated endometrial epithelial cells, as well as endometrial fibroblasts. We evaluated the expression of estrogen receptor alpha (ER) and the progesterone receptor (PR) by RT-PCR. ER and PR were strongly expressed in the fibroblasts and epithelial cells under treatment with 10(-8) M 17beta-estradiol (E(2)). Treatment with 10(-6) M J867 or ZK137316 upregulated the PR expression as did E(2), in contrast to treatment with 10(-6) M MPA, which caused a downregulation of PR in epithelial cells, but not in fibroblasts. In addition, the vascular endothelial growth factor (VEGF) release into the cell culture medium was analyzed by a VEGF-ELISA. VEGF which plays an important role in angiogenesis, is regulated by steroid hormones as well as hypoxia. E(2) stimulates VEGF release into the medium in both cell types. MPA reduces VEGF release significantly in the fibroblast cell culture, but increases it in the epithelial cell culture. ZK137316, in the presence or absence of E(2), reduces VEGF release in fibroblast cell culture. J867 increases the VEGF production in fibroblasts only in the presence of E(2). Both compounds show no significant effects, compared to E(2), in epithelial cell culture. The different results for the epithelial cells and fibroblasts indicate that the pharmacological effects of PR modulators (PRMs) and progesterone antagonists (PAs) may be cell specific and depend on the presence or absence of partial progestagenic agonistic activities. This observation opens up new perspectives for various clinical applications.

Cell Culture Techniques↗

A large keratan sulfate proteoglycan present in human cervical mucous appears to be involved in the reorganization of the cervical extracellular matrix at term.

OBJECTIVE: To elucidate the function of keratan sulfate proteoglycan (KS-PG) in the human uterine cervix, we analyzed its distribution with respect to physiologic conditions. METHODS: Immunohistochemistry was used to localize KS bearing proteoglycans (mAb 5D4) and decorin (mAb 6B6) in the lower uterine segment. Proteins present in cervical mucous were labeled with biotin, glycosaminoglycan chains were digested enzymatically, and the samples were analyzed by Western blot. RESULTS: Decorin was detected throughout the extracellular matrix, in tissues from menstruating nonpregnant women, in early pregnancy, from women who had cesarean at term, at postpartum hysterectomy, and from postmenopausal women. In menstruating nonpregnant women, in early pregnancy (first trimester), and in postmenopausal women, KS-PG was detectable only in epithelial, mucous-producing cells. Interestingly, in samples obtained either at the time of cesarean at term (lower uterine segment) or after postpartal hysterectomy, KS-PG was detectable throughout the extracellular matrix, indicating that the expression of KS-PG is associated with reorganization of the tissue. Biochemical analysis of the KS present in mucous revealed a core protein in the range of 220 kDa, suggesting an identity with the large KS-PG described previously. CONCLUSION: At parturition, a large KS-PG, which is virtually exclusively present in the cervical mucous of either early or nonpregnant women, was detected in the extracellular matrix. This finding indicates that cervical ripening is accompanied not only by quantitative but also by qualitative changes in the composition of the extracellular matrix.

Adult↗

The distribution of macrophages in spiral arteries of the placental bed in pre-eclampsia differs from that in healthy patients.

Placental bed biopsies taken during caesarean section from 10 patients with pre-eclampsia and six healthy pregnancies were studied. We applied antibodies against cytokeratin and different macrophage markers to analyse the distribution of invasive extravillous trophoblast cells as compared to that of macrophages in myometrial segments of uteroplacental arteries. The data were evaluated quantitatively. We found a clear inverse relationship between local infiltration with macrophages and trophoblast invasion. In pre-eclampsia, vessel cross-sections prevailed which were characterized by large numbers of macrophages but a low degree of trophoblast invasion. In contrast, in normal third trimester pregnancies the respective arterial segments had a high degree of trophoblast invasion but were largely void of macrophages. These data suggest causal links between macrophages and inhibition of intra-arterial trophoblast invasion in pre-eclampsia.

Adult↗

[Concentration of estrogen and progesterone receptors in the lower uterine segment at term labor].

BACKGROUND: To determine cytosol estrogen and progesterone receptor concentrations in the human lower uterine segment in different stages of cervical dilatation during parturition at term. PATIENTS AND METHODS: Biopsy specimens of the lower uterine segment were obtained from 51 women undergoing non-elective cesarean section at term. The stage of cervical dilatation at the time of cesarean section was < 2 cm (N = 14), 2 to < 4 cm (N = 13), 4 to 6 cm (N = 11) or > 6 cm (N = 13). The cytosolic estrogen and progesterone receptor concentrations were determined by enzyme immunoassays. RESULTS: Median estrogen receptor concentrations at < 2 cm and at 2-< 4 cm cervical dilatation were 2.12 fmol/mg protein and 2.03 fmol/mg protein, respectively. After a significant drop at 4-6 cm cervical dilatation (median: 1.08 fmol/mg protein), estrogen receptor concentrations raised again at > 6 cm cervical dilatation (median: 2.00 fmol/mg protein). Median progesterone receptor concentration was 84.7 fmol/mg protein at < 2 cm cervical dilatation, diminished significantly at 2-< 4 cm cervical dilatation (36.6 fmol/mg protein) and increased at further cervical dilatation (4-6 cm: 75.7 fmol/mg protein; > 6 cm: 83.7 fmol/mg protein). CONCLUSIONS: These data suggest that predominantly a decrease in cytosolic concentration of the progesterone receptor at the beginning of the active phase of first stage labor may play a crucial role in the hormonal control of cervical dilatation during parturition at term.

Adult↗

[Nausea and vomiting in early pregnancy/hyperemesis gravidarum. Current status of psychosomatic factors].

BACKGROUND: Although Hyperemesis gravidarum (HG) is still a disease of unknown aetiology psychosocial aspects are involved in the genesis of this disease. MATERIALS AND METHODS: Based on experiences in our department and on actual literature psychosocial aspects and therapeutic approaches of HG are presented. RESULTS: Predisposing factors of HG are stress, inadequate information about pregnancy or delivery and problems in the marital relationship. Feelings of ambivalence towards pregnancy, a distorted perception of reality, the unconscious refusing of a wanted child and the worry about a relation between nutrition of the foetus and the HG have influence on the development of the HG. The role of the social context, especially the mother, of expectations towards vomiting and of secondary gain in the genesis and the evaluation of HG is explained. Therapeutical approaches beside the known somatic therapies are acupuncture, the electric stimulation of the N. vestibularis and different methods of psychotherapy, which can include the partner or other persons from the social context. In some cases an intensified therapy under in-patient conditions can improve therapeutic results. DISCUSSION: Psychosocial factors are involved not only in the genesis of HG, but also in the duration and intensity of symptoms as well as in the resistance especially, towards isolated somatic therapeutical approaches. CONCLUSIONS: When psychosocial factors are taken into account in the search for a cause and the treatment of HG results of treatment are more successful and persist over a longer time.

Female↗

[Lung maturation therapy with glucocorticoids in threatened premature labor. Considerations of risk-benefit in evidence-based medicine].

Prematurity is a major cause of perinatal morbidity and mortality. Antenatal administration of glucocorticoids improves the neonatal outcome of preterm born infants. 1994 the NIH published recommendations for the use of glucocorticoids for women at risk of preterm delivery. A recent evaluation by the Cochrane Collaboration in 1999 showed that antenatal administration of glucocorticoids significantly reduced the rate of RDS and IVH in the gestational age between 24 and 34 weeks. Consequences of repeated courses of antenatal glucocorticoids are not sufficiently studied. The effectivity and safety regarding birth weights, infectious diseases, and the best timing remains unknown. Administration of glucocorticoids lowers fetal activity and heart rate variability. Effects on fetal growth, maternal and fetal immunosystem, and the development of atopic diseases are controversely discussed. Thus preterm labour not leading to a cervical ripening is not necessarily a reason for antenatal glucocorticoids. Antenatal glucocorticoids with PROM do not lower the rate of RDS but of IVH. No prospective randomized trial evaluated the effectivity of antenatal glucocorticoids in diabetes mellitus and IUGR. In preeclampsia beta-methason could improve the rate of RDS and the neonatal outcome. Still our knowledge of antenatal glucocorticoid administration is not sufficient. But despite possible (longtime-) risks for mother and child the administration of glucocorticoids according to the guidelines of the NIH is a major part in the treatment of prematurity and improves the outcome of premature infants. The indication for multiple courses of glucocorticoids should be considered carefully.

Evidence-Based Medicine↗

[Effect of thrombophilic factors on thromboembolism and other pregnancy complications].

Pulmonary embolism and/or deep vein thrombosis are a major cause of maternal mortality. In a number of adverse pregnancy outcome including preeclampsia, recurrent spontaneous abortion, restricted fetal growth and fetal death a role for thrombophilia (acquired and hereditable) has been postulated. Monitoring of acquired factors such as antiphospholipid-antibodies and hereditable factors (factor V Leiden, prothrombin mutation) may help predict the occurrence of pregnancy complications. Low molecular weight heparins (LMWH), since their introduction well established during pregnancy, and the rate of adverse fetal outcomes are related to co-morbidity maternal conditions rather than to the treatment itself. The use of LMWH is recommended for all moderate risk and high-risk pregnant patients.

Blood Coagulation Factors↗

[Dopplersonography of the ductus venosus: assessment, evaluation and actual clinical importance].

The ductus venosus (DV) connects the intra-abdominal umbilical vein with the infundibulum of the IVC and develops during pregnancy to a trumpet-shaped structure with a narrow isthmus that accelerates the blood jet crossing the IVC directly to the left atrium via the foramen ovale avoiding mixing with deoxygenated blood from the right chamber. In animal studies, blood flow and doppler sonographically analyzed blood flow velocity waveforms mainly is controlled by heart rate and central venous pressure. The velocity waveform of the DV contains two peak components: the first indicates systolic velocity of the ventricle, the second peak diastolic velocity. A nadir is seen during atrial contraction. In animal studies, DV blood velocity in hypoxemia is influenced by central venous pressure and heart rate. The determination of the DV/UV ratio reflects the redistribution of blood flow, increases in hypoxemia and is therefore more reliable than blood velocity measurement for the detection and evaluation of fetal distress. In cases with severely growth-restricted fetuses, recipient twin in TTTS (twin-to-twin transfusion syndrome), tachyarrhythmia-induced cardiomyopathia and congenital heart disease, the measurement and interpretation of DV Doppler waveform pulsatility seems to be a useful tool that provides important information on the fetal condition and outcome. In cases of zero or reverse flow during atrial contraction in most cases the delivery of the fetus is indicated. An improvement of morbidity and mortality using Doppler sonography of the DV has not yet been proven. In cases of fetuses with or without chromosomal aberrations with major defects of the heart it can be used in addition to the standard screening methods of the first trimester of pregnancy for detection of heart failure.

Blood Flow Velocity↗

[Prevention of pre-eclampsia by low-dose acetylsalicylic acid--a critical appraisal].

Pre-eclampsia has been shown to be associated with platelet activation and excessive release of vasoconstricting thromboxane preceding the onset of the disease. Low-dose acetylsalicylic acid (ASA) substantially inhibits thromboxane formation and may thus prevent pre-eclampsia from developing. In agreement with this hypothesis early randomised trials reported on promising reductions in pre-eclampsia risk and possible fetal growth retardation. Subsequent multicentre trials during the nineties failed to confirm a large benefit, which may in part be explained by late initiation of treatment, low dosages, low patient compliance and wide inclusion of women with concomitant disorders such as chronic hypertension, diabetes mellitus and kidney disease. A recent systematic review of all randomised trials showed an acceptable safety profile and a significant but only moderate reduction in the risk of pre-eclampsia regardless of gestation at trial entry or dose of ASA. There is now growing evidence that the earlier ASA treatment is started, the greater the reduction in the risk of pre-eclampsia is. Moreover, ASA has much stronger effects at higher (80 - 150 mg/day) than at lower doses in the protection against pre-eclampsia and the prevention of severe fetal growth retardation. No clinically important effects, however, have been found in patients with chronic hypertension, kidney disease or diabetes mellitus. In contrast, low dose ASA (100 mg/day) might benefit women with unfavourable obstetric history, in particular those with severe fetal growth retardation or pre-eclampsia with onset at < 32 weeks. The crucial time for starting treatment may be before 16 weeks and daily ingestion before bedtime appears useful. To start low-dose ASA at 20 - 24 weeks gestation seems only justified in women with abnormal uterine Doppler flow.

Aspirin↗

[Prenatal diagnosis of hepatic hemangioendothelioma and peripartual management].

Infantile hepatic hemangioendothelioma is a benign hepatic tumor that can be associated with life-threatening perinatal complications. A 38-year-old gravida 3 para 2 was referred to our hospital with preterm labor at 33.6 gestational weeks. Fetal abdominal circumference was estimated sonographically above the 97 th percentile. Because of pathologic CTG, the fetus was delivered by caesarean section (APGAR-scores 0/0/7, pH: 7.15). After cardiopulmonary reanimation and intensive care of the fetus, the prenatally suspected hemangioma of the liver was confirmed by computer tomography. The day after, liver segments V, VI, and VII were resected because of lung compression. During the operation, reanimation was necessary two more times. Two days later, ductus arteriosus Botalli was occluded. After stabilization, the neonate was treated with prednisone because of tumor residues. If a large hyperechogenic mass in the fetal liver is seen prenatally, diagnosis of fetal hemangioma should be considered. In order to prevent serious cardiovascular complications, continual clinical surveillance is indicated.

Adult↗

Differential diagnosis, prognostic factors, and clinical treatment of proliferative Brenner tumor of the ovary.

Brenner tumors are rare ovarian tumors displaying benign, borderline or proliferative, and malignant variants. The case of a 63-year-old woman with a proliferative Brenner tumor is presented and the histomorphological differential diagnosis of this tumor entity is compared to that of its benign and malignant counterparts. Light microscopy, immunohistochemistry, and electron microscopy were performed to allow discrimination from the other subtypes. Despite a considerable overlap of pathological features the differential diagnosis of proliferative Brenner tumor could be established. Electron microscopy allowed assessment of characteristic infoldings of the nuclear membrane that proved to be a valuable ultrastructural criterion. Considering that the vast majority of Brenner tumors are benign, precise identification of the small proportion of malignant tumors allows the extent of surgical therapy to be adapted.

Biomarkers, Tumor↗