Comparing induction of labour with oral misoprostol or Foley catheter at term: cost-effectiveness analysis of a randomised controlled multi-centre non-inferiority trial.

OBJECTIVE: To assess the costs of labour induction with oral misoprostol versus Foley catheter. DESIGN: Economic evaluation alongside a randomised controlled trial. SETTING: Obstetric departments of six tertiary and 23 secondary care hospitals in the Netherlands. POPULATION: Women with a viable term singleton pregnancy in cephalic presentation, intact membranes, an unfavourable cervix (Bishop score <6) without a previous caesarean section, were randomised for labour induction with oral misoprostol (n = 924) or Foley catheter (n = 921). METHODS: We performed economic analysis from a hospital perspective. We estimated direct medical costs associated with healthcare utilisation from randomisation until discharge. The robustness of our findings was evaluated in sensitivity analyses. MAIN OUTCOME MEASURES: Mean costs and differences were calculated per women induced with oral misoprostol or Foley catheter. RESULTS: Mean costs per woman in the oral misoprostol group and Foley catheter group were €4470 versus €4158, respectively [mean difference €312, 95% confidence interval (CI) -€508 to €1063]. Multiple sensitivity analyses did not change these conclusions. However, if cervical ripening for low-risk pregnancies in the Foley catheter group was carried out in an outpatient setting, with admittance to labour ward only at start of active labour, the difference would be €4470 versus €3489, respectively (mean difference €981, 95% CI €225-1817). CONCLUSIONS: Oral misoprostol and Foley catheter generate comparable costs. Cervical ripening outside labour ward with a Foley catheter could potentially save almost €1000 per woman. TWEETABLE ABSTRACT: Oral misoprostol or Foley catheter for induction of labour generates comparable costs.

High-power multi-megahertz source of waveform-stabilized few-cycle light.

Waveform-stabilized laser pulses have revolutionized the exploration of the electronic structure and dynamics of matter by serving as the technological basis for frequency-comb and attosecond spectroscopy. Their primary sources, mode-locked titanium-doped sapphire lasers and erbium/ytterbium-doped fibre lasers, deliver pulses with several nanojoules energy, which is insufficient for many important applications. Here we present the waveform-stabilized light source that is scalable to microjoule energy levels at the full (megahertz) repetition rate of the laser oscillator. A diode-pumped Kerr-lens-mode-locked Yb:YAG thin-disk laser combined with extracavity pulse compression yields waveform-stabilized few-cycle pulses (7.7 fs, 2.2 cycles) with a pulse energy of 0.15 µJ and an average power of 6 W. The demonstrated concept is scalable to pulse energies of several microjoules and near-gigawatt peak powers. The generation of attosecond pulses at the full repetition rate of the oscillator comes into reach. The presented system could serve as a primary source for frequency combs in the mid infrared and vacuum UV with unprecedented high power levels.

High-power Kerr-lens mode-locked Yb:YAG thin-disk oscillator in the positive dispersion regime.

We demonstrate a self-starting Kerr-lens mode-locked (KLM) Yb:YAG thin-disk oscillator operating in the regime of positive intracavity group-delay dispersion (GDD). It delivers 1.7 ps pulses at an average power of 17 W and a repetition rate of 40 MHz. Dispersive mirrors compress the pulses to a duration of 190 fs (assuming sech2 shape; Fourier limit: 150 fs) at an average power level of 11 W. To our knowledge, this is the first KLM thin-disk oscillator with positive GDD. Output powers of up to 30 W were achieved with an increased output coupler transmission and intracavity GDD. We demonstrate increase of the pulse energy with increasing positive intracavity GDD, limited by difficulties in initiating mode-locking.

High-dispersive mirrors for high power applications.

We report on the development and manufacturing of two different types of high-dispersive mirrors (HDM). One of them provides a record value for the group delay dispersion (GDD) of -4000 fs2 and covers the wavelength range of 1027-1033 nm, whereas the other one provides -3000 fs2 over the wavelength range of 1020-1040 nm. Both of the fabricated mirrors exhibit a reflectance of >99.9% and are well suited for intracavity applications. Mirrors of the second type have been successfully employed in a Kerr-lens mode-locked Yb:YAG thin-disk oscillator for the generation of 200-fs pulses with multi-10-W average power.

High-power 200 fs Kerr-lens mode-locked Yb:YAG thin-disk oscillator.

We demonstrate a power-scalable Kerr-lens mode-locked Yb:YAG thin-disk oscillator. It delivers 200 fs pulses at an average power of 17 W and a repetition rate of 40 MHz. At an increased (180 W) pump power level, the laser produces 270 fs 1.1 µJ pulses at an average power of 45 W (optical-to-optical efficiency of 25%). Semiconductor-saturable-absorber-mirror-assisted Kerr-lens mode locking (KLM) and pure KLM with a hard aperture show similar performance. To our knowledge, these are the shortest pulses achieved from a mode-locked Yb:YAG disk oscillator and this is the first demonstration of a Kerr-lens mode-locked thin-disk laser.

A prospective study on parental coping 4 months after termination of pregnancy for fetal anomalies.

OBJECTIVE: To identify short-term factors influencing psychological outcome of termination of pregnancy for fetal anomaly, in order to define those patients most vulnerable to psychopathology. STUDY DESIGN: A prospective cohort of 217 women and 169 men completed standardized questionnaires 4 months after termination. Psychological adjustment was measured by the Inventory of Complicated Grief (ICG), the Impact of Event Scale (IES), the Edinburgh Postnatal Depression Scale (EPDS), and the Symptom Checklist-90 (SCL-90). RESULTS: Women and men showed high levels of posttraumatic stress (PTS) symptoms (44 and 22%, respectively) and symptoms of depression (28 and 16%, respectively). Determinants of adverse psychological outcome were the following: high level of doubt in the decision period, inadequate partner support, low self-efficacy, lower parental age, being religious, and advanced gestational age. Whether the condition was Down syndrome or another disability was irrelevant to the outcome. Termination did not have an important effect on future reproductive intentions. Only 2% of women and less than 1% of men regretted the decision to terminate. CONCLUSION: Termination of pregnancy (TOP) for fetal anomaly affects parents deeply. Four months after termination a considerable part still suffers from posttraumatic stress symptoms and depressive feelings. Patients who are at high risk could benefit from intensified support.

[Pregnancy and chemotherapy; an apparent contradiction]. / Zwangerschap en chemotherapie; een schijnbare tegenstelling.

Two women aged 34 and 32, were diagnosed with cancer during pregnancy. The 34-year-old woman with breast cancer diagnosed during the first trimester of pregnancy, had just undergone breast-conserving surgery. She chose to have an abortion before adjuvant chemotherapy was started. A year after chemotherapy ended she became pregnant again and gave birth to a healthy child. After 3 years there were no signs of metastases. In the 32-year-old woman with a malignant lymphoma diagnosed during the third trimester of pregnancy, chemotherapy had to be started because she developed V. cava superior syndrome. The dyspnoea disappeared and a week after the first treatment she gave birth to a healthy child. A year after completion of treatment she was in complete remission and her child was developing well. Pregnancy is not always a contraindication for starting chemotherapy. However, in order to reduce the risk to mother and child as much as possible, the duration of the pregnancy as well as different groups of cytostatic drugs have to be taken into consideration. A multidisciplinary approach to mother and child is essential.

Carbon source-dependent transcriptional regulation of the QCR8 gene in Kluyveromyces lactis. Identification fo cis-acting regions and trans-acting factors in the KlQCR8 upstream region.

The QCR8 gene of the yeast K1uyveromyces lactis is transcriptionally regulated by the carbon source in the growth medium. Deletion analysis of the KlQCR8 promoter shows that an element located between -144 bp and -113 bp specifically controls induction of QCR8 gene expression on non-fermentable carbon sources. Specific and differential protein-binding to the activating sequence was observed with extracts from glucose- and ethanol/glycerol-grown cells. Induction of the reporter gene and protein-binding was dependent on the presence of a functional KlCAT8 gene, suggesting that, in K. lactis, K1Cat8p acts in the transcriptional regulation of respiratory function. The activating element contains no other known regulatory sites but two elements required for RNA holoenzyme functioning, raising the intriguing possibility of carbon source-dependent regulation by a subunit of the RNA polymerase holoenzyme in K. lactis.

Ultrasonographic and radiologic visualization of the developing embryonic skeleton.

We investigated the development of the skeleton in the embryonic and early fetal period both with ultrasonography and radiology. Eight normal embryos/fetuses were studied weekly with real-time transvaginal sonography between 8 and 16 weeks of gestation to establish the ultrasonographic characteristics of normal ossification. Additionally, ossification was studied in radiographs obtained from five embryos/fetuses between 9 and 14 weeks of gestation. Ossification centers, visualized as increased echogenicity of the bone, were recognized with ultrasonography from 9 weeks onwards. The appearance of primary ossification centers as observed by transvaginal ultrasonography was at the same gestational age or at most 1 week later than when obtained with radiography or whole-specimen staining techniques. Transvaginal ultrasonography enables early visualization of ossification centers in the embryo and fetus. Detailed knowledge of the development of ossification of the skeleton may contribute to early prenatal diagnosis of skeletal dysplasias.

The amdA regulatory gene of Aspergillus nidulans: characterization of gain-of-function mutations and identification of binding sites for the gene product.

Genetic evidence suggests that the amdA gene of Aspergillus nidulans encodes a protein which controls the expression of the amdS and aciA structural genes. The amd166 and amd1666 mutations in the 5' regulatory region of amdS lead to higher levels of amdA-dependent amdS expression. We show here that the putative DNA binding domain of amdA is capable of binding specific regions of the amdS and aciA promoters in vitro and this region includes sequences duplicated and triplicated in the amd166 and amd1666 mutations, respectively. Footprinting analysis has shown that AmdA binds to two sites in this region represented by the sequences 5'-GCGGGG-3' and 5'-GAGGGG-3'. A number of gain-of-function mutations in amdA were localized to a region rich in acidic and hydrophobic amino acid residues and shown to be involved in transcriptional activation by studies of fusions with the GAL4 DNA binding domain in Saccharomyces cerevisiae. Therefore, both an increased probability of AmdA binding to the amdS promoter and an increased activation potential of AmdA can result in higher levels of expression.

Cloning and characterization of the NADPH cytochrome P450 oxidoreductase gene from the filamentous fungus Aspergillus niger.

In this paper, we describe the cloning and molecular characterization of the Aspergillus niger cytochrome P450 reductase (CPR) gene, cprA. Attempts to clone the cprA gene by heterologous hybridization techniques were unsuccessful. Using the polymerase chain reaction (PCR) with degenerate primers based on conserved regions found in cpr genes from other organisms, we were able to isolate a fragment that contained part of the gene. With the aid of this fragment, a genomic fragment containing the entire coding region and 5' and 3' untranslated ends of the cprA gene was isolated and sequenced. The cprA gene was introduced in multiple copies in A. niger strain N402 using the amdS transformation system. One of the resulting transformants, AB2-2, showed a 14-fold increase in CPR activity, indicating that the cloned cprA gene is functional. We analyzed the induction of cprA gene expression by several generally used cytochrome P450 inducers but did not find any induction of cprA gene expression. However, A. niger cprA gene expression could be induced by benzoic acid, which is the substrate of the highly inducible A. niger cytochrome P450 gene, bphA (cyp53). On the basis of a comparison of the deduced protein sequence of the A. niger cprA gene with CPR proteins isolated from other organisms, the structure-function relationship of some conserved regions is discussed.

Emergency cerclage: a review.

The treatment of patients with cervical incompetence presenting with advanced cervical changes in the second trimester remains a challenge to every obstetrician. Cerclage operation may be the only hope for prolonging gestation until fetal viability is reached. A retrospective study on so-called emergency cervical cerclage in 20 patients with supposed cervical incompetence in the late second trimester is presented, together with a review of comparable studies published between 1980 and 1992. It is concluded that emergency cerclage can be of benefit, and that the pregnancy is saved in the majority of cases, although the incidence of complications, often due to infection, is high. Many patients require prolonged hospitalization or bed rest and few pregnancies reach full term. There is a particularly high rate of infectious complications and attention must be focused on preventing chorioamnionitis to improve the outcome of the procedure in the future.

Chronic congestive heart failure. Description and survival of 190 consecutive patients with a diagnosis of chronic congestive heart failure based on clinical signs and symptoms.

The prognosis, and clinical findings related to prognosis, were examined in a consecutive series of 190 patients under 76 years of age (mean 64 years) with congestive heart failure (CHF). The aetiology of CHF was ischaemic heart disease in 66%, hypertension in 11% and cardiomyopathy in 23%. The 2-year mortality was 32%. Median left ventricular ejection fraction (LVEF) was 0.30, range 0.06 to 0.74. Eight per cent were in New York Heart Association (NYHA) class I, 46% in II, 44% in III and 2% in IV. Multivariate analysis, excluding exercise test variables, revealed seven variables with independent, significant prognostic information, (hazard ratios for death in brackets): ln (natural logarithm) (LVEF) (3.19), NYHA class III+IV (2.72), plasma urea > 7.6 mmol.l-1 (2.22), serum creatinine > 121 mumol.l-1 (2.05), serum sodium < or = 137 mmol.l-1 (2.03), pulmonary congestion on X-ray (1.86), and age > 65 years (1.86). Multivariate analysis, including exercise testing, showed the following variables to contain independent, significant prognostic information: increase in heart rate during maximal exercise < or = 35 min-1 (3.5), ln (LVEF) (3.7), serum creatinine > 121 mumol.l-1 (2.9), maximal exercise time < or = 4 min (2.3), serum sodium < or = 137 mmol.l-1 (2.5), ischaemic heart disease (2.0) and plasma urea > 7.6 mmol.l-1 (1.9). In conclusion, patients with CHF have a high risk of death despite intensive medical treatment. LVEF is a strong predictor of mortality. Both NYHA class and exercise variables have strong independent prognostic information as regards mortality in combination with LVEF, but are mutually exclusive.

Neurobehavioral effects of long-term exposure to xylene and mixed organic solvents in shipyard spray painters.

A cross-sectional study was performed in shipyard painters exposed to organic solvents and age-matched referents. The work duties of the painters mainly involved spray painting with solvent-based paints containing > 50% xylene. Testing methods consisted of a symptoms questionnaire, measurement of peripheral sensory and motor nerve parameters and computerized performance tests. Results indicate that complaints regarding mood changes, equilibrium and fatigue were more severe in painters than in referents, but were not related to the estimated life-time exposure index. Decreased nerve function was observed in the lower extremities and to some extent in the upper extremities. The refractory period appeared to be a sensitive parameter in motor nerves. Most neurophysiological parameters investigated were significantly related to the exposure index. Behavioral testing revealed impairment of simple visuo-motor performance and complex perceptual coding. A relationship between effects on perceptual coding and the exposure index was also demonstrated.

[Ultrasonically guided drainage of pleural empyema]. / Ultralydvejledt draenage af pleuraempyem.

Sufficient drainage of the infected pleural space may be difficult without other image guidance than simple frontal and lateral chest radiograms. When the suspected empyema is difficult to locate we recommend insertion of a 10F pigtail catheter guided by ultrasound. This is illustrated by two patient histories. The method is safe, with the advantage of a precise localisation of the drainage catheter in relation to the empyema, the lung and the diaphragm.

Some variants of lethal neonatal short-limbed platyspondylic dysplasia: a radiological ultrasonographic, neuropathological and histopathological study of 22 cases.

Data on twenty-two infants with lethal neonatal short-limbed platyspondylic dysplasia are reported. Thanatophoric dysplasia (TD) is the most frequent diagnosis in this group. TD combined with a cloverleaf skull (CS), has been variably classified. TD type 1 with curved femora is rarely combined with CS; TD type 2 with straight femora is almost always associated with CS. Other varieties of TD, known as 'Torrance', 'San Diego' or 'Luton' types, are separate entities. Apart from the differences in radiography and osteochondrohistology, the temporal-lobe abnormalities seen in TD were absent in one of the cases of the 'Torrance' variety. There were also differences in the composition of the cartilage glycosaminoglycans between this case and TD. Nearly all of the cases of these different types mentioned in the literature, including those of this study group, have been sporadic and may result from new dominant mutations. Documentation and classification by full (postmortem) radiography and osteochondrohistology is essential for two reasons. It will be the foundation for the clinical geneticist to inform the parents about the risk of recurrence. It will also be the basis for a biochemical or molecular-biological classification in the near future.

Climbing fiber representation of the renal afferent nerve in the vermal cortex of the cat cerebellum.

In order to understand how the cerebellum may participate in various autonomic functions, it is necessary to first determine the occurrence and distribution of the various visceral inputs in the cerebellar cortex and their relation to other cerebellar afferents. This study examines the organization of climbing fiber responses (complex spikes) of Purkinje cells elicited by electrical stimulation of the renal afferent nerve and their relationship to climbing fiber responses representing the body surface. Visceral and somatic afferent responses were mapped in the lateral vermal cortex of lobules V to VII in chloralose-anesthetized cats. Extracellular single-unit recordings were made from 628 Purkinje cells, of which 14% had climbing fiber responses induced by renal afferent nerve stimulation. Except for one Purkinje cell, the renal climbing fiber input converged with somatic induced climbing fiber input. Tactile stimulation also elicited 54% of cells, which were unresponsive to the renal afferent nerve stimulation. The occurrence and distribution of the climbing fiber responses elicited by renal afferent nerve stimulation varied between lobules V, VI, and VII for the proportion of responsive units, the onset latencies, and topological organization. More renal responsive units were encountered in lobules V (18%) and VII (17%) than in lobule VI (6%), the average latency of renal climbing fiber responses was significantly longer in lobule VII than in lobules V and VI, and the latencies were also different among various parasagittal planes in lobules V and VII. The proportional representation of various body areas for cells with renal and somatic convergent input was different than for cells with only somatic representation. Proportionally, the forelimb had the greatest representation in lobule V, split receptive fields were frequently represented in lobule VI, and the face was well represented in lobule VII. The results of this study, in conjunction with studies showing climbing fiber representation of the vagal and splanchnic nerves, further substantiate role of the cerebellum in autonomic functions.

[Endoscopic percutaneous transhepatic cholelithotripsy in the treatment of complicated stones in the deep biliary tracts]. / Endoskopisk perkutan transhepatisk kolelitotripsi til behandling af vanskelige sten i de dybe galdeveje.

The results of endoscopic percutaneous transhepatic cholelithotripsy in seven patients with stones in the deep biliary passages which could not be treated by endoscopic papillotomy (EST) or extracorporeal shock wave lithotripsy (ESWL) are presented. A new dilator technique combined with mechanical or laser-lithotripsy was employed. All of the patients were relieved of the stones after uncomplicated course. It is concluded that endoscopic percutaneous cholelithotripsy which can be carried out under local anaesthesia, should be offered to patients with stones in the deep biliary passages which are not accessible to conventional treatment with EST or ESWL.

Vagal and somatic representation by the climbing fiber system in lobule V of the cat cerebellum.

The organization of the climbing fiber representation of the vagal afferents and the body surface in the vermal and intermediate zones of lobule V was examined in cats anesthetized with alpha-chloralose. Extracellular single-unit recordings were made from 428 Purkinje cells. Electrical stimulation of the vagus nerve elicited climbing fiber responses in 40% of the cells, most of which had convergent somatic input. Activation of A delta vagal afferent fibers accounted for 65% of the responses, whereas the A beta fibers involved 27% and the C fibers included 8% of the responses. The responses driven by vagal nerve stimulation were encountered throughout the lobule, although a significantly increased representation of the vagus was identified for 3 longitudinal 0.5 mm wide sectors (two in the vermis and one in the intermediate region). In the vermis, the fine-grain organization consisted of a mixture of representations of the various parts of the body surface with and without convergent vagal input, although there was little convergence in the medial vermis where many of the responses were elicited by only vagal nerve stimulation. In the intermediate cortex, most of the vagal climbing fiber representation was convergent with forelimb input. These results suggest that vagal input into the cerebellum could have important modulatory effects on the cerebellar somatosensory input.