Need for less tight glucose control in early pregnancy after embryogenesis due to high risk of maternal hypoglycaemia in women with pre-existing diabetes can be compensated by good control in late pregnancy.

AIM: Poor glucose control is associated with adverse outcomes in pregnancies with pre-existing diabetes. However, strict glucose control increases the risk of severe hypoglycaemia, particularly in the first trimester. Therefore, we aimed to investigate whether less tight glucose control in the first trimester determines adverse outcomes or can be compensated for by good control in late pregnancy. METHODS: Retrospective data were collected from 517 singleton pregnancies complicated by pre-existing diabetes delivering between 2010 and 2017. Three hundred and thirty-six pregnancies fulfilled the inclusion criteria of having available HbA1c values either pre-conception or in the first trimester (65% type 1 diabetes, 35% type 2 diabetes). RESULTS: Higher HbA1c values in the first trimester were associated with increasing rates of large for gestational age (LGA) neonates, preterm delivery or neonatal intensive care unit admissions. Multiple regression analysis demonstrated third trimester HbA1c , type 1 diabetes, multiparity and excess weight gain, but not first trimester HbA1c , to be independently predictive for LGA. Pre-eclampsia and third trimester HbA1c increased the risk for preterm delivery. If HbA1c was ≤ 42 mmol/mol (6.0%) in the third trimester, rates of adverse outcomes were not significantly higher even if HbA1c targets of ≤ 48 mmol/mol (6.5%) had not been met in the first trimester. Good first trimester glucose control did not modify the rates of adverse outcomes if HbA1c was > 42 mmol/mol (6.0%) in the third trimester. CONCLUSIONS: Less tight glycaemic control, for example due to high frequency of severe hypoglycaemia in the first trimester, does not lead to increased adverse neonatal events if followed by tight control in the third trimester. Besides glycaemic control, excess weight gain is a modifiable predictor of adverse outcome.

Higher rates of large-for-gestational-age newborns mediated by excess maternal weight gain in pregnancies with Type 1 diabetes and use of continuous subcutaneous insulin infusion vs multiple dose insulin injection.

AIMS: To compare glycaemic control, maternal and neonatal outcomes in pregnancies with Type 1 diabetes, managed either by continuous subcutaneous insulin infusion, multiple daily insulin injection or switch from multiple daily insulin injection (MDI) to continuous subcutaneous insulin infusion (CSII) in early pregnancy. RESEARCH DESIGN AND METHODS: Data from 339 singleton pregnancies were retrospectively reviewed. HbA1c values were measured preconception and in each trimester. In a secondary analysis, use of CSII pre-pregnancy was compared with initiation of CSII during pregnancy. RESULTS: MDI was used in 140 pregnancies (41.3%) and CSII was used in 199 (58.7%), including 34 pregnancies (10.0%) during which the women switched to CSII. In pregnancies during which CSII was used duration of diabetes [median (interquartile range) 16.0 (8.0-23.0) years vs 11.0 (5.5-17.5) years; P<0.001] was longer, and the Institute of Medicine recommendations for appropriate weight gain were exceeded more often (64.8% vs. 50.8%; P=0.01). CSII use and pre-pregnancy BMI were independent predictors of excess weight gain. There was no difference in glucose control, but CSII was associated with higher birth weight [median (interquartile range) 3720 (3365-4100) g vs 3360 (3365-4100) g; P<0.001] and higher large-for-gestational-age (LGA) rate (44.7% vs. 33.6%; P=0.04) than MDI. HbA1c concentration in the third trimester and excess weight gain were predictive of LGA infants [odds ratio 2.33 (95% CI 1.54-3.51); P<0.001 and 1.89 (95% CI 1.02-3.51); P=0.04]. In pregnancies where CSII therapy was initiated in the first trimester and in those with pre-pregnancy use, similar glucose control and outcome was achieved. CONCLUSIONS: There was no advantage of CSII with respect to glycaemic control and neonatal outcomes. The rate of LGA neonates was higher in the CSII group, possibly mediated by excess maternal weight gain, which was more frequent than in women treated with MDI.

Distribution of indications and procedures within the framework of centers participating in the WAA apheresis registry.

The WAA apheresis registry was established in 2003 and an increasing number of centers have since then included their experience and data of their procedures. The registry now contains data of more than 74,000 apheresis procedures in more than 10,000 patients. This report shows that the indications for apheresis procedures are changing towards more oncological diagnoses and stem cell collections from patients and donors and less therapeutic apheresis procedures. In centers that continue to register, the total extent of apheresis procedures and patients treated have expanded during the latest years.

Differences in the Frequency of Use of Epidural Analgesia between Immigrant Women of Turkish Origin and Non-Immigrant Women in Germany - Explanatory Approaches and Conclusions of a Qualitative Study.

Introduction: The starting point of this study was the considerably lower rate of epidural analgesia use among women of Turkish origin in Germany compared to non-immigrant women in the German Research Foundation (DFG)-funded study entitled "Perinatal Health and Migration Berlin". The study aimed to identify possible differences in the women's attitudes towards epidural analgesia. Methods: Exploratory study with semi-structured interviews, interviews lasting 17 minutes on average were conducted with 19 women of Turkish origin and 11 non-immigrant women at a Berlin hospital. The interviews were subjected to a qualitative content analysis. Results: Immigrant women of Turkish origin in Germany more frequently ascribe meaning to the pain associated with vaginal delivery. They more frequently categorically reject the use of epidural analgesia, 1) for fear of long-term complications such as paralysis and back pain and 2) based on the view that vaginal delivery with epidural analgesia is not natural. Information on epidural analgesia is frequently obtained from a variety of sources from their social setting, in particular, by word of mouth. The women in both groups stated that they would take the decision to use epidural analgesia independent of their partner's opinion. Discussion: The differences in epidural analgesia use rates observed correspond to the women's attitudes. For the immigrant women of Turkish origin in Germany, the attitude towards using epidural analgesia is based in part on misinformation. In order to enable the women to make an informed decision, epidural analgesia could receive a stronger focus during childbirth courses.

Adverse events in apheresis: An update of the WAA registry data.

Apheresis with different procedures and devices are used for a variety of indications that may have different adverse events (AEs). The aim of this study was to clarify the extent and possible reasons of various side effects based on data from a multinational registry. The WAA-apheresis registry data focus on adverse events in a total of 50846 procedures in 7142 patients (42% women). AEs were graded as mild, moderate (need for medication), severe (interruption due to the AE) or death (due to AE). More AEs occurred during the first procedures versus subsequent (8.4 and 5.5%, respectively). AEs were mild in 2.4% (due to access 54%, device 7%, hypotension 15%, tingling 8%), moderate in 3% (tingling 58%, urticaria 15%, hypotension 10%, nausea 3%), and severe in 0.4% of procedures (syncope/hypotension 32%, urticaria 17%, chills/fever 8%, arrhythmia/asystole 4.5%, nausea/vomiting 4%). Hypotension was most common if albumin was used as the replacement fluid, and urticaria when plasma was used. Arrhythmia occurred to similar extents when using plasma or albumin as replacement. In 64% of procedures with bronchospasm, plasma was part of the replacement fluid used. Severe AEs are rare. Although most reactions are mild and moderate, several side effects may be critical for the patient. We present side effects in relation to the procedures and suggest that safety is increased by regular vital sign measurements, cardiac monitoring and by having emergency equipment nearby.

"Pregnant and Operating": Evaluation of a Germany-wide Survey Among Female Gynaecologists and Surgeons.

The current law on the protection of expectant and nursing mothers largely rules out surgical activities during pregnancy for female doctors who perform surgical roles in hospitals. The proportion of female junior staff in gynaecology amounts to 80 %, and, for many of these women, surgical further training is not possible following official notification of an existing pregnancy. In a Germany-wide survey of female gynaecologists and surgeons using a questionnaire, it was determined to what extent female doctors worked in surgery during pregnancy, whether it led to complications in the pregnancy, when the employer was notified about the pregnancy, and what desire for change there is with regard to the law on the protection of expectant and nursing mothers. The data from 164 female doctors, of which 136 are gynaecologists and 28 surgeons, was evaluated. On average, the pregnancy was announced during the 14th week of pregnancy (WOP), and the doctor was not allowed to perform surgical activities in the 21st WOP. Female doctors in higher professional roles tended to announce the pregnancy later and ended their surgical activities later. There was no link between the time of ceasing surgical activities and an increased occurrence of complaints or complications during the pregnancy. In total, only 53 % of respondents had an appraisal during pregnancy and 75 % wanted a change in the law on the protection of expectant and nursing mothers.

Comparison of Perinatal Data of Immigrant Women of Turkish Origin and German Women - Results of a Prospective Study in Berlin.

Aims: The aim of the study was to compare obstetrical process indicators and outcomes for German women with women of Turkish origin residing in Germany. Do women of Turkish origin attend antenatal examinations as frequently as non-immigrant women? Are high-risk pregnancies and anemia more common among immigrant women? Are the rates for epidural analgesia (PDA) and combined spinal-epidural analgesia (CSE) during delivery the same for immigrant women compared to German women? Are there identifiable differences in the mode of delivery and in perinatal outcomes? Patient Population/Methods: Data were obtained from 3 maternity clinics in Berlin for the period 2011 to 2012. The questionnaires covered socio-demographic factors and information on prenatal care as well as immigration/acculturation. The data obtained from these questionnaires was supplemented by information obtained from the official maternal record of prenatal and natal care (Mutterpass) and perinatal data recorded by the clinic. Results: The response rate was 89.6 %; the data of 1277 women of Turkish origin who had immigrated to Germany or whose family had immigrated and of 2991 non-immigrant women in Germany were included in the study. Regression analysis showed no statistically significant difference in the number of antenatal examinations between immigrant and non-immigrant women. Women of Turkish origin born in Germany had a significantly higher risk of postpartum anemia. PDA/CSE rate, arterial umbilical cord pH and 5-minute Apgar scores did not differ. The incidence of cesarean sections (elective and secondary) was significantly lower in the population of immigrant women of Turkish origin. Conclusion: Outcomes for most perinatal parameters were comparable for immigrant and non-immigrant women. These results indicate that the achieved standards of antenatal care and medical care during pregnancy are similar for Turkish immigrant women compared to non-immigrant women in maternity clinics in Berlin. The higher rates of anemia among immigrant women should be targeted by preventive measures.

Career and Family - Are They Compatible?: Results of a Survey of Male and Female Gynaecologists in Germany.

Purpose: Nowadays, most gynaecologists are female and the compatibility of job-related career and family life is an upcoming issue. The working group "Gender and Career" of the German Society for Gynaecology and Obstetrics (DGGG) designed a survey to reflect the present situation with a focus on the compatibility of career and family. Material and Methods: A web-based 74-item survey was filled out by members of the DGGG. In total, there were 1037 replies, 75 % female (n = 775) and 25 % male (n = 261) gynaecologists. Results: 62 % of the female and 80 % of the male respondents had already finished their doctoral theses and 2 % female and 13 % male had finished their PhD. Mean number of children was 1.06 (SD 1.08) in female and 1.68 (SD 1.34) in male gynaecologists. The majority of females desired day care for their children, but only 5 to 13 % of employers offer any day care. 88 % of the female and 72 % of the male physicians think that job-related career and family are not compatible. Conclusion: The majority of female gynaecologists wished to have professional child care, but most employers or other institutions do not offer this. This might be one of the reasons why career and family appear incompatible.

[Risk management in hospitals: standard operating procedures in aviation as a model for structuring medical communication]. / Risikomanagement zur Fehlervermeidung im Krankenhaus: Standard Operating Procedures aus der Luftfahrt als Vorbild für eine strukturierte Kommunikation im Klinikalltag.

AIM: The working conditions for medical staff in German hospitals with emergency units are characterised by stress peaks. In such moments mistakes are more likely to be made. Communication problems and misunderstandings caused by these settings are the most frequent causes for blunders, errors and mistakes. The aim is to show an easy way to reduce the incidence of these problems. METHOD: Within this prospectively randomised trial we compare the ability of 50 physicians to remember standardised information on patient's data passed on to them in a briefing. Half of the subjects used the so called 5-finger method as an easy means of memorising standardised information. The other 25 physicians memorised the patient's data in the usual way. In order to assess the information recalled by the subjects, all of them were asked to answer 15 questions on the data they had been given an hour earlier. RESULTS: The subjects who used the 5-finger method were able to give on average 9.88 (of 15) correct answers and thus remembered significantly (p = 0.031) more information than the members of the control group. CONCLUSION: Communication errors caused by homophony, ambiguity, anticipation and mental models are can be avoided in well-structured communication situations. The rules for such a type of communication can easily be learned and applied. Standardised communication has already proved to reduce the error rates in aviation. We conclude that it can be helpful to introduce standardised communication rules such as the 5-finger method in medical communication.

[Endoscopic appendectomy in gynecology]. / Die endoskopische Appendektomie in der Gynäkologie.

From 1987 to 1997 we treated 406 patients with appendicitis. 392 patients were treated by endoscopic appendectomy, 14 patients underwent laparotomy for appendectomy. Among these 406 patients we found 4 patients with primary pelvic inflammatory disease, 18 patients with endometriosis, 15 pregnant patients and 13 patients older than 60 year's. The difficulties during the laparoscopic operation were unimportant and we could keep them under control by laparoscopic. 13 patients developed severe complications during the postoperative period. For this reason we do not perform a prophylactic appendectomy during gynaecological laparoscopies. We present in this paper our results and indications for the endoscopic appendectomy.

Response to cytarabine ocfosfate (YNK01) in a patient with chronic lymphocytic leukemia refractory to treatment with chlorambucil/prednisone, fludarabine, and prednimustine/mitoxantrone.

Cytarabine ocfosfate (YNK01) is a novel orally applicable prodrug of cytosine arabinoside. Recent pharmacokinetic studies have revealed a prolonged release of the cytotoxic agent cytosine arabinoside (araC) from hepatocytes into the systemic circulation, resulting in a half-life of approximately 24 h for araC. The specific pharmacokinetic characteristics of cytarabine ocfosfate lead to a prolonged exposure of leukemic cells to this antineoplasstic agent during the 14-day cycle. the oral applicability during outpatient treatment and the sustained antineoplastic activity of araC against slowly proliferating leukemic B-cells suggest that cytarabine ocfosfate might be a useful drug in the treatment of chronic lymphocytic leukemia. Four years after diagnosis of B-CLL, a 50-year-old patient was started on cytarabine ocfosfate. Sequentially, the patient's disease had proved refractory to treatment with chlorambucil/prednisone (31 months), fludarabine (5 months), and prednimustine/mitoxantrone (3 months). These established regimens were discontinued because of increasing lymphocytosis, significant thrombocytopenia, and progressive B-symptoms. Following three cycles of cytarabine ocfosfate B-symptoms resolved, lymphadenopathy disappeared, and thrombocytopenia was significantly reduced. The patient has been free of these symptoms on a dosage of 1500 mg cytarabine ocfosfate/day (cycle of 14 days with intervals of 14-21 days) for 24 months and remains in an ongoing partial remission.

[Effect of surgical laparoscopy on prognosis of early and limited ovarian malignancies]. / Der Einfluss der operativen Laparoskopie auf die Prognose früher und begrenzter Ovarialmalignome.

9375 laparoscopies were performed at our clinic between 1987 and 1993. In this patient group the incidence of early or localised stages of ovarial malignomas FIGO I and II is 0.9 per cent. 81 laparoscopies were performed on patients suffering from localised stages of ovarial malignomas. 32% (n = 26) of these laparoscopised patients suffering from ovarial malignomas were subjected to extended diagnostic-surgical laparoscopy. These 26 localised stages of ovarial malignomas on which tumour-aggressive laparoscopy had been performed, were followed up and the relevant literature studied and processed. In 23 of the patients thus subjected to tumour-aggressive laparoscopic surgery we did not observe any deterioration of the prognosis during the treatment period (1-8 years). Problematic postoperative courses were seen in 3 patients; the reasons for this are discussed in the present paper. Measures resulting in opening of the tumours during diagnostic-surgical laparoscopy are neither accidental nor unforeseen incidents, but are rather part of an overall surgical strategy. If safety techniques are adopted-as described in this paper-diagnostic-surgical laparoscopy can be performed even during localised stages of ovarial malignomas without any presently recognisable adverse effect on patient prognosis.

Detection and determination of the major metabolites of [3H]cytosine arabinoside by high-performance liquid chromatography.

An ion-pair high-performance liquid chromatographic assay involving solid-phase scintillation detection was established for the rapid identification and determination of all major metabolites of tritium-labelled cytosine arabinoside (Ara-C) in an in vitro system. In a single run of 50 min, Ara-C, Ara-CMP, Ara-CDP-choline, Ara-CDP, Ara-U, Ara-UMP, Ara-CTP, Ara-UDP and Ara-UTP can be measured. The method is fast, sensitive, with limits of detection ranging from 40 to 200 pg (absolute), and highly reproducible.

Pharmacokinetics of Ara-CMP-Stearate (YNK01): phase I study of the oral Ara-C derivative.

Ara-CMP-Stearate (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate, YNK 01, Fosteabine) is the orally applicable prodrug of cytosine-arabinoside (Ara-C). During a phase I study in patients with advanced low-grade non-Hodgkin lymphomas or acute myeloid leukemia, the pharmacokinetic parameters of Ara-CMP-Stearate (kindly provided by ASTA Medica, Frankfurt, Germany) were determined by HPLC analysis. Seventy-two hours after a first starting dose which served for the determination of baseline pharmacokinetic parameters, Ara-CMP-Stearate was administered over 14 days by daily oral application. Ara-CMP-Stearate was started at a dose of 100 mg/day and was escalated in subsequent patients to 200 mg/day and 300 mg/day. Plasma and urine concentrations of Ara-CMP-Stearate, Ara-C and Ara-U were measured during the initial treatment phase and within 72 h after the end of the 14-day treatment cycle. So far six patients have been treated with 100 mg/day, three with 200 mg/day and another six with 300 mg/day. One patient was treated consecutively with 100 mg, 300 mg and 600 mg. Fitting the results of the plasma concentration measurements of Ara-CMP-Stearate to a one-compartment model, the following pharmacokinetic parameters were obtained (average and variation coefficient VC). Ara-CMP-Stearate dose-independent parameters: lag time = 1.04 h (0.57); tmax = 5.72 h (0.30); t1/2 = 9.4 h (0.36). Dose-dependent parameters: at 100 mg: AUC = 1099 ng/h/ml (0.31); concentration(max) = 53.8 ng/ml (0.28); at 200 mg: AUC = 2753 ng/h/ml (0.32); concentration(max) = 154.8 ng/ml (0.46); at 300 mg: AUC = 2940 ng/h/ml (0.66); concentration(max) = 160.0 ng/ml (0.59). The long lag time and late tmax can be explained by resorption in the distal part of the small intestine. No Ara-CMP-Stearate was detected in urine samples (limit of detection = 500 pg/ml). Pharmacokinetic parameters of Ara-C following Ara-CMP-Stearate application showed the following characteristics: t1/2 = 24.3 h (0.39); AUC (100 mg) = 262 ng/h/ml (0.93); AUC (200 mg) = 502 ng/h/ml (0.87); AUC (300 mg) = 898 ng/h/ml (1.07). Since Ara-CMP-Stearate causes intravascular hemolysis after intravenous administration, it was not possible to determine its bioavailability by comparing the AUC after oral and i.v. application. Instead, the renal elimination of Ara-U, as the main metabolite of Ara-C was measured during the first 72-h period and after the last application.(ABSTRACT TRUNCATED AT 400 WORDS)

Highly sensitive high-performance liquid chromatographic assay for 1-beta-D-arabinofuranosylcytosine-5'-stearyl phosphate (cytarabine-ocfosfate).

An ion-pair HPLC method for the determination of 1-beta-D-arabinofuranosylcytosine-5'-stearyl phosphate (cytarabine-ocfosfate I) was developed, using a phenyl-bonded column under reversed-phase conditions with a mobile phase of acetonitrile-buffered water (pH 6.8) (50:50) for isocratic elution. A reproducible sample clean-up was achieved by solid-phase extraction. In order to reach the low limit of detection of 2 ng/ml, an enrichment switching system was used. The present validation leads to a limit of quantification of 5 ng/ml with a coefficient of variation (C.V.) of 10%. The total time of measurement was shortened by a back-flush procedure to restore the conditions after each run. UV detection at 275 nm was applied. The recoveries for plasma samples ranged from 56.4 to 64.1%, regardless of drug concentrations. The intra-assay C.V. was about 4% (40 measurements at four different concentrations). The inter-assay recovery (ten measurements over ten days) at a plasma concentration of 50 ng/ml was 57% with a C.V. of 8.25%. Based on this HPLC method, the pharmacokinetics of I were measured during a clinical phase I/II study.

Patterns of structural deterioration due to ischemia in Purkinje fibres and different layers of the working myocardium.

Cellular and mitochondrial swelling are regarded as typical intra-ischemic alterations ("IIA"), contraction band lesions (CBL), in contrast, as products of post-ischemic reperfusion. The occurrence of both types of structural deterioration was investigated in Purkinje fibres and subendocardial and intramural working myocardium: initially after St. Thomas- or HTK cardioplegia, then during ensuing global ischemia up to the "practical limit of resuscitability", and following post-ischemic reperfusion. Generally, Purkinje fibres are not better preserved than neighbouring working myocardium. Comparing St. Thomas- and HTK cardioplegia, considerable quantitative, but not qualitative differences in the reaction patterns of different cell types or layers arise. Immediately after cardioplegia, CBL are completely lacking in both cell types. During ischemia, CBL occur occasionally in Purkinje fibres and seldom in subendocardial working myocardium, "IIA" predominate. During post-ischemic reperfusion "IIA" tend to reverse in all layers, whereas CBL are found to remain in the subendocardial cell types. In intramural layers, CBL occur only during reperfusion. Thus, we deduce that cardioplegia only modulates the severity of "IIA" and the frequency of CBL, but cannot abolish the particular sensitivity of subendocardial Purkinje fibres to global ischemia. Prerequisites for the development of irreversible CBL are on the one hand ischemic metabolic alterations and corresponding energy deficits, and, on the other hand, a supply of oxygen. The oxygen may be inadequately supplied via diffusion during ischemia or may be subsequently provided by reperfusion.