[Water Birth: experience at a university clinic and a district hospital in Austria]. / Gebären im Wasser. Erfahrungen einer Universitätsklinik und eines Bezirkskrankenhauses in Osterreich.

PURPOSE AND METHODS: In a retrospective case-control study, 265 water deliveries (with cephalic presentation) carried out at an Austrian university clinic and a district hospital were compared with a group of spontaneous births (without any surgical intervention) matched for age, gestational age and parity regarding the most important fetal and maternal obstetric parameters. RESULTS: 4.3% of all births at the university clinic and 13% of those at the district hospital took place in the water. Austrian women and women with a higher educational level were more numerous in this group. The duration of the different stages of birth was not essentially changed by the delivery in water. The cord blood pH of the water babies (median 7.29 and 7.35, respectively) was better than that of the control group (median 7.26), which may however be due to a positive selection of the women giving birth in the water. The number of episiotomies was markedly lower for water births (14 and 4%) than for land births (48%). In contrast, water births showed distinctly more first- and second-degree perineal tears (36 and 41%) and labial tears (23 and 21%) than the control group (perineal 23%; labial 7%). Women assigned to water birth needed fewer analgesics (8 and 9%) than the controls (64%). In puerperium, the haemoglobin values after water birth and after land birth did not differ. The infectious morbidity of the mother and child was not higher after water birth. CONCLUSIONS: Water birth is to be considered a safe method for a healthy mother and a healthy, full-term fetus with cephalic presentation (if the appropriate criteria are used at hospital wards with a specific infrastructure).

Neopterin is an independent prognostic variable in females with breast cancer.

BACKGROUND: Neopterin, produced by human monocytes/macrophages upon stimulation by interferon-gamma, is a sensitive marker for monitoring Th1-cell immune response in humans. In malignant diseases, the frequency of increases in neopterin in the serum and urine of patients depends on tumor stage and type. METHODS: In a retrospective study comprising 129 females with breast cancer, urinary neopterin/creatinine ratios were measured at the time of diagnosis. Tumor characteristics were determined concomitantly. RESULTS: Urinary neopterin was increased in 18% of the patients. It did not correlate with tumor size or lymph node status, but it was influenced by the presence of distant metastases (P <0.05) and by tumor differentiation (P = 0.01). When product-limit estimates were calculated after follow-up for up to 13 years (median follow-up, 56 months), the presence of distant metastases (P <0.001), neopterin (P <0.001), tumor size (P = 0.001), and lymph node status (P <0.01) were significant predictors of survival. By multivariate analysis, a combination of the variables presence of distant metastases (P <0. 001), neopterin (P <0.01), and lymph node status (P <0.05) was found to jointly predict survival. In lymph node-negative patients without distant metastases, the relative risk of death associated with increased neopterin concentrations was 2.5 compared with patients with neopterin concentrations within the reference interval. CONCLUSION: Urinary neopterin provides additional prognostic information in patients with breast cancer.

Pre-eclampsia: a disorder of placental mitochondria?

Pre-eclampsia is a common, pregnancy-induced, multisystem disease leading to severe complications in the mother and foetus. The aetiology of pre-eclampsia remains a mystery, but a growing body of evidence suggests that a mitochondrial defect might cause the impairement of differentiation and invasion of the trophoblast that leads to this disorder. This hypothesis is the topic of ongoing studies that, if confirmed, would be highly relevant to preventative strategies for this disease.

Childbirth as a biological model for stress? Associations with endocrine and obstetric factors.

OBJECTIVE: The aims of this investigation were to measure corticotropin-releasing hormone (CRH), corticotropin (ACTH) and cortisol before, during and after delivery searching for an endocrine intercorrelation of the hypothalamic-pituitary-adrenal (HPA) axis and to correlate these findings with obstetrical variables. METHODS: Blood was sampled from 50 women with singleton pregnancies at term without uterine contractions, during delivery (after full cervical dilatation) and on the 4th postnatal day. Hormones were measured by radioimmunoassay (RIA). The correlation between obstetric variables, sociodemographic and endocrine data were evaluated using the Spearman rank coefficient. Group comparisons for continuous variables were calculated using the Mann-Whitney U test and Kruskal-Wallis test. RESULTS: Maternal plasma ACTH and cortisol increased significantly during labor, declining toward the 4th postnatal day (p < 0.001) and showing a significant intercorrelation (p < 0.01). Compared to women without uterine contractions CRH rose during labor (p < 0.05) and decreased rapidly to the 4th postnatal day (p < 0.001). No correlations between CRH and ACTH or cortisol were observed. None of the obstetrical variables (parity, newborn's weight, duration of delivery) revealed any significant correlation with ACTH. Analgetic medication (pethidine hydrochloride) was not able to influence the endocrine response to labor stress. CONCLUSIONS: Stressful experience during childbirth has an impact on endocrine response. However, this is not fully evident along the HPA axis in a simple biological model with monocausal dependencies. This 'biological stress model' is not sensitive enough to detect different childbirth conditions and the hormones in the maternal compartment have partially fetal (placental) origin.

[Prediction of preeclampsia:new hypotheses, new approaches]. / [Prädiktion der Präeklampsie: neue Hypothesen, neue Ansätze]

Preeclampsia is a multisystem disorder affecting 5.8% of primigravidas. It is a progressive disease with a very variable mode of presentation and rate of progression. Of all the features of the syndrome, hypertension and pregnancy-induced proteinuria are the classic clinical manifestations. This disease causes severe complications of the mother and the fetus. Neither are factors available for prediction, nor are there strategies for prevention and therapy of this disease. The accumulated evidence strongly suggests that failure or incomplete trophoblastic invasion (end of first, beginning of second trimester) of the spiral arteries, resulting in narrowed spiral arteries and subsequent endothelial damage, is responsible for the occurrence of this disease (third trimester). The reason for trophoblastic failure is not known. After clinical symptoms have occurred, only symptomatic therapeutic options are available. In this paper, we discuss potential ways to find specific and sensitive predictive parameters according to the current knowledge of the pathophysiology of this pregnancy-induced severe disorder.

Respiratory defect as an early event in preservation-reoxygenation injury of endothelial cells.

Characterization of preservation injury in endothelial cells has been primarily accomplished by measurement of cell viability. To analyze early events and cellular mechanisms of preservation-reoxygenation injury, we developed high-resolution respirometry for the study of mitochondrial function in endothelial cells, to provide a quantitative marker for sublethal stress. Cultured human umbilical vein endothelial cells were stored for 4 and 8 hr at 4 degrees C under an atmosphere of 95% N2 and 5% CO2 in University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions. Respiration of suspended cells, measured after reoxygenation in growth medium at 37 degrees C, was significantly reduced in all treatments in comparison to controls not subjected to cold preservation. In contrast, trypan blue staining was unchanged after 4 hr of preservation and was significant only after 8 hr. After 8 hr of cold storage in UW and HTK solutions, respiration was 64+/-5% and 49+/-6%, respectively, of controls (46.5+/-3.3 pmol O2 x s(-1 x 10(-6) cells), indicating significantly better protection by UW solution than HTK solution. A titration regimen with substrate (succinate), uncoupler (carbonyl cyanide p-trifluoromethoxyphenylhydrazone), and inhibitors of complexes I and III (rotenone and antimycin A) resulted in identical respiratory response patterns in all treatments. The plasma membrane remained impermeable to succinate. Inner mitochondrial membrane function was preserved as indicated by a constant relative increase of respiration after uncoupling. These results demonstrate that loss of catalytic capacity for respiration constitutes an early event in preservation-reoxygenation injury, whereas membrane damage is not a primary defect. Respirometric evaluation of sublethal cell injury and localization of cell damage may provide selective guidelines for further optimization of strategies in organ preservation.

Assessment of endothelial preservation in human cell cultures.

BACKGROUND: Impairment of microcirculation due to endothelial cell damage must be considered a limiting factor in organ preservation. The present study aims at a quantitative assessment of preservation-induced injury in cultured human endothelial cells. METHODS: Monolayer cultures of human umbilical vein endothelial cells were exposed to cold (40 degrees C) hypoxic storage in University of Wisconsin solution, histidine-tryptophane-ketoglutarate solution, Euro-Collins solution, and saline solution. Cellular integrity was evaluated by viable cell count, ultrastructural analysis, and prostacyclin release after 24, 48, and 72 hours of storage and subsequent 6 hours of reincubation in culture medium at 37 degrees C. Expression of intercellular adhesion molecule-1 was investigated after 6, 12, and 24 hours of cold preservation and after 6 hours of rewarming. RESULTS: Cellular viability was best maintained with University of Wisconsin and histidine-tryptophane-ketoglutarate solutions with no significant reduction of cell count up to 72 hours; Euro-Collins solution and saline solution caused a significant decline in cell numbers after 24 hours (p < 0.05). Morphology was best preserved by University of Wisconsin solution. Prostacyclin values were elevated after 24 hours in Euro-Collins solution and saline solution, after 48 hours in histidine-tryptophane-ketoglutarate, Euro-Collins, and saline solutions, and after 72 hours in Euro-Collins solution (p < 0.05, compared with University of Wisconsin solution). ICAM expression was weak after cold storage (24 hours) in University of Wisconsin solution, moderate after incubation in histidine-tryptophane-ketoglutarate and Euro-Collins solutions and intensive after storage in saline solution. In contrast, rewarming caused intensive expression of intercellular adhesion molecule-1 in all experimental groups as compared with controls, which showed baseline expression at any time. CONCLUSIONS: From our results we conclude that in this model cellular integrity is best protected by University of Wisconsin solution, increased prostacyclin release is consistent with morphologic alterations and intercellular adhesion molecule-1 expression is clearly up-regulated in endothelial cells under reperfusion conditions after cold hypoxic storage.

Decreased plasma tryptophan in pregnancy.

OBJECTIVE: To examine levels of serum tryptophan and its degradation product kynurenine in uncomplicated pregnancy, according to the week of pregnancy and the concentrations of neopterin. METHODS: Plasma was analyzed from 45 healthy pregnant women (15 in each trimester), 15 healthy puerperas, and 20 nonpregnant controls. Tryptophan and kynurenine were measured by reverse-phase, high-performance liquid chromatography, and neopterin by radioimmunoassay. RESULTS: In healthy pregnant women, tryptophan values decreased (median first trimester: 72 mumol/L; second trimester: 51 mumol/L; third trimester: 46 mumol/L; P < .001) in a manner correlated with the duration of pregnancy (Spearman rank correlation coefficient ra = -0.771, P < .001) and normalized in the puerperium (median 60 mumol/L). No change in kynurenine, a tryptophan degradation product, was observed, but the ratio of kynurenine to tryptophan increased during pregnancy and correlated positively with gestational age (ra = 0.714, P < .001). In addition, an inverse correlation existed between neopterin and tryptophan concentrations (ra = -0.566, P < .001), as well as a positive one between neopterin and the kynurenine to tryptophan ratio (ra = 0.660, P < .001). CONCLUSION: Tryptophan levels decrease during normal pregnancy and the decrease may be related to immune activation phenomena.

Activated cellular immunity and decreased serum tryptophan in healthy pregnancy.

We analyzed plasma samples from 45 randomly selected healthy pregnant women and from 20 healthy nonpregnant female controls of corresponding age. Tryptophan and kynurenine concentrations were measured by reverse-phase high performance liquid chromatography. The kynurenine per tryptophan ratio was calculated to allow a more accurate estimate of tryptophan degradation. In addition, neopterin was measured by radioimmunoassay. There were significantly lower tryptophan concentrations in pregnant women compared to nonpregnant controls. Kynurenine per tryptophan ratios were increased in pregnant women in the 3rd trimester. Significant correlations existed between neopterin increase and tryptophan decrease as well as kynurenine increase and tryptophan decrease. Also significant correlations between week of pregnancy and lower tryptophan and higher kynurenine per tryptophan ratio were found (p < 0.01). From our data, cellular immune activation is likely to be the cause of enhanced tryptophan degradation during pregnancy.

Tissue polypeptide antigen during parturition and puerperium.

The tumour and cytoskeleton protein tissue polypeptide antigen (TPA) was determined in maternal serum taken during the second stage of labour and on the 4th postpartum day. Pregnant women at term (weeks 38-42) served as a control group. TPA levels of women during parturition (median 169 U/l) were higher than those of the control group (median 108.5 U/l) and those of women on the 4th postpartum day (median 66.5 U/l); p < 0.0001 in each case. The correlation between duration of labour and TPA concentration was positive and significant (rs = 0.3; p = 0.03). A significant negative correlation was found between placental weight and maternal serum TPA levels during parturition (rs = -0.3; p = 0.03). The decline of TPA after delivery indicated a serum half-life for TPA of less than 4 days.

[Kallikrein (urine) in pregnancy-induced hypertension]. / Kallikrein (Harn) bei schwangerschaftsinduzierten Hochdruckerkrankungen.

Total, active and inactive renal kallikrein were compared between 25 patients with hypertensive disorders of pregnancy and 25 healthy pregnant women of corresponding gestational age. Values of all three fractions were twice as high in healthy women than in hypertensive patients and differed with statistical significance. A longitudinal examination of renal kallikrein during pregnancy showed a physiological decrease of values from the 16th-20th week until term. Asymptomatic women, who developed hypertension later on, showed decreased renal kallikrein values.

IUD-associated pelvic actinomycosis: a report of five cases.

Five cases of intrauterine device (IUD)-associated tuboovarian actinomycosis are presented. The patients' ages ranged from 33 to 49 years and their IUD usage from 2 to 12 years. Clinical features of the cases included stenosis of the sigmoid colon in 4 cases, ureteric or bladder obstruction in two cases, and rectal fistula in a further instance. All patients were successfully treated postoperatively with penicillin or ampicillin. An initial diagnosis of ovarian carcinoma was considered in all cases. Although Actinomyces is difficult to differentiate histopathologically from microorganisms and other substances that cause the Splendore-Hoeppli phenomenon, morphological diagnosis permits a quicker and more practical approach than bacterial cultures in the establishment of postoperative antibiotic treatment. Intraoperative frozen-section diagnosis of an acute inflammatory process permits the surgeon to make an immediate decision in order to avoid extensive surgery when ovarian carcinoma is suspected.

[Activated macrophages in the pathologic mechanism of pregnancy-induced hypertension]. / Aktivierte Makrophagen im Pathomechanismus schwangerschafts-induzierter Hochdruckerkrankungen.

Patients with hypertensive disorders of pregnancy demonstrated higher neopterin/creatinine ratios (urine) and elevated plasma levels of interleukin-6, tumor necrosis factor alpha and neopterin. A participation of macrophages in the pathomechanism of preeclampsia can thus be assumed.

[Differential diagnostic and therapeutic considerations of nipple adenoma]. / Differentialdiagnostische und therapeutische Uberlegungen zum Mamillenadenom.

Adenoma of the nipple is a rare benign tumour of the nipple ducts. Clinically, it simulates the Paget's disease. Histologically, papillary adenocarcinoma and intraductal papillary carcinoma must be differentiated in order to avoid excessive or inadequate therapy. Two cases are discussed.

Tumor markers in hypertensive disorders of pregnancy.

Plasma levels of tumor markers (CEA, TPA, CA 15.3, CA 125, alpha-fetoprotein) for 50 patients with hypertensive disorders of pregnancy were compared with those of 50 healthy women with singleton pregnancies and 50 healthy non-pregnant controls. With the exception of CEA all tumor marker values were higher in pregnant women, these differences being statistically significant (all p < 0.0001). Alpha-fetoprotein was lower in hypertensive than in healthy pregnant women (p = 0.0004), whereas CEA, CA 15.3 and CA 125 showed no statistically significant differences. TPA values in patients with hypertensive disorders of pregnancy (median 190 U/l) were 2.7 times higher than those of healthy pregnant controls (median 70.5 U/l) with a statistically significant difference (p < 0.0001). The individual degrees of disease severity demonstrated increasing TPA medians (pregnancy-induced hypertension: 106.5 U/l; pre-eclampsia: 200 U/l; HELLP syndrome: 339 U/l). TPA levels correlated positively with clinical severity of disease and negatively with fetal (rs = -0.58; p < 0.0001) and placental weight (rs = 0.44; p = 0.01).