Serum levels of soluble E-selectin are associated with the clinical course of metastatic disease in patients with liver metastases from breast cancer

Increasing evidence indicates that the expression of the endothelial adhesion molecule E-selectin is associated with progression and metastasis of breast cancer. Patients with liver metastases also show increased serum levels of the soluble form of E-selectin. It was our aim to compare serum levels of soluble E-selectin (sES) in such patients with the biology of the primary tumor and the course of the metastatic disease under therapy. We examined 69 patients with liver metastases from breast cancer who were selected to receive systemic tumor therapy because of progressive disease (n = 44) or newly detected liver metastases (n = 25). Serum concentrations of sES were measured before each therapy cycle using a specific ELISA. Serum concentrations of sES before the start of therapy were compared to clinical parameters and histopathological findings referring to the primary tumor. Secondly, serum levels of sES were compared to serum concentrations of the corresponding tumor markers. We observed a possible trend for certain unfavorable prognostic parameters (e.g., young women, low-graded tumors, human epidermal growth factor receptor 2 overexpression) to be related to higher serum levels of sES. Serum levels of sES were correlated with tumor marker levels in a logarithmical relation (r = 0.44, P < 0.0005). In some cases it could be demonstrated that serum levels of sES changed similarly to the course of tumor marker levels. We conclude that serum levels of sES are associated with the clinical course of liver metastases from breast cancer. Further investigations are needed to clarify if serum levels of sES may serve as tumor marker in certain clinical situations. E-selectin should be evaluated as a possible target for antimetastatic therapy studies.     

Outcome after elective labor induction in nulliparous women: a matched cohort study

OBJECTIVE: To determine whether elective induction of labor in nulliparous women is associated with changes in fetomaternal outcome when compared with labor of spontaneous onset.Study Design: All 80 labor wards in Flanders (Northern Belgium) comprised a matched cohort study. From 1996 through 1997, 7683 women with elective induced labor and 7683 women with spontaneous labor were selected according to the following criteria: nulliparity, singleton pregnancy, cephalic presentation, gestational age at the time of delivery of 266 to 287 days, and birth weight between 3000 and 4000 g. Each woman with induced labor and the corresponding woman with spontaneous labor came from the same labor ward, and they had babies of the same sex. Both groups were compared with respect to the incidence of cesarean delivery or instrument delivery and the incidence of transfer to the neonatal ward. RESULTS: Cesarean delivery (9.9% vs 6.5%), instrumental delivery (31.6% vs 29.1%), epidural analgesia (80% vs 58%), and transfer of the baby to the neonatal ward (10.7% vs 9.4%) were significantly more common (P <.01) when labor was induced electively. The difference in cesarean delivery was due to significantly more first-stage dystocia in the induced group. The difference in neonatal admission could be attributed to a higher admission rate for maternal convenience when the women had a cesarean delivery. CONCLUSION: When compared with labor of spontaneous onset, elective labor induction in nulliparous women is associated with significantly more operative deliveries. Nulliparous women should be informed about this before they submit to elective induction.     

Comparison of the in-vitro activity of amodiaquine and its main metabolite, monodesethyl-amodiaquine, in Plasmodium falciparum

After its rehabilitation for therapeutic use in uncomplicated falciparum malaria, there is renewed interest in amodiaquine. After oral administration, the drug undergoes rapid metabolism to monodesethyl-amodiaquine, and in patients with normal hepatic function the parent drug usually becomes undetectable within a few hours. The main antimalarial activity is therefore mainly due to the metabolite. In a comparative study in northwestern Thailand, 21 fresh isolates of Plasmodium falciparum were tested, in parallel, for their in-vitro sensitivity to both compounds, using the WHO micro-test Mark II, measuring the inhibition of schizont maturation. The geometric mean cut-off concentrations of schizont maturation were 1826 nM (related to blood) for amodiaquine, and 1654 nM for monodesethyl-amodiaquine. The log-probit regressions for both compounds showed good fits to the data points. The EC50 values were 331 nM and 291 nM, and the EC90 values 1337 nM and 993 nM for amodiaquine and monodesethyl-amodiaquine, respectively. Differences between regression slopes and effective concentrations were well below statistical significance. Both compounds showed highly significant activity correlation. These findings suggest that the sensitivity of Plasmodium falciparum to amodiaquine closely reflects its sensitivity to monodesethyl-amodiaquine.     

Quantification of blood flow in brain tumors: comparison of arterial spin labeling and dynamic susceptibility-weighted contrast-enhanced MR imaging

PURPOSE: To implement an arterial spin labeling technique that is feasible in routine examinations and to test the method and compare it with dynamic susceptibility-weighted contrast material-enhanced magnetic resonance (MR) imaging for evaluation of tumor blood flow (TBF) in patients with brain tumors. MATERIALS AND METHODS: Thirty-six patients with histologically proven brain tumors were examined at 1.5 T. A second version of quantitative imaging of perfusion by using a single subtraction with addition of thin-section periodic saturation after inversion and a time delay (Q2TIPS) technique of pulsed arterial spin labeling in the multisection mode was implemented. After arterial spin labeling, a combined T2- and T2*-weighted first-pass bolus perfusion study (gadopentetate dimeglumine, 0.2 mmol/kg) was performed by using a double-echo echo-planar imaging sequence. In regions of interest, maps of absolute and relative cerebral blood flow were computed and analyzed with arterial spin labeling and dynamic susceptibility-weighted contrast-enhanced MR imaging, respectively. RESULTS: Both techniques yielded the highest perfusion values in imaging of glioblastomas and the lowest values in imaging of two low-grade gliomas that both showed strong gadopentetate dimeglumine enhancement. There was a close linear correlation between dynamic susceptibility-weighted contrast-enhanced MR imaging and arterial spin labeling in the tumor region of interest (linear regression coefficient, R = 0.83; P <.005). Blood flow is underestimated with arterial spin labeling at low flow rates. High- and low-grade gliomas can be distinguished at the same level of significance with both methods. Absolute TBF is less important for tumor grading than is the ratio of TBF to age-dependent mean brain perfusion. CONCLUSION: Arterial spin labeling is a suitable method for assessment of microvascular perfusion and allows distinction between high- and low-grade gliomas.     

Topographic mapping of retinal function with the SLO-mfERG under simultaneous control of fixation in Best's disease

PURPOSE: To introduce the scanning laser ophthalmoscope-evoked mfERG (SLO-mfERG) as a new method to measure focal retinal function. METHODS: Sixty-two healthy individuals and 12 patients with Best's disease were examined. mfERGs were recorded using a scanning laser ophthalmoscope as a stimulator and trigger device (He-Neon 632.8 nm) as well as a fundus-monitoring system (Infrared 730 nm). RESULTS: Amplitudes in the central concentric area were found to be significantly lower in patients with Best's disease than in healthy controls, while no significant differences were found for the more peripheral areas. CONCLUSION: SLO-mfERG is a reliable new technique for topographic mapping of retinal function under simultaneous control of fixation.     

Comparative study on the chronology of third molar mineralization in a Japanese and a German population

In Germany, a sharp increase in forensic age estimations of living persons has been observed in recent years. German law defines four legally relevant age limits: 14, 16, 18 and 21 years. In these age groups, radiographic assessment of the mineralization status of third molars is of particular importance. So far, the influence of ethnicity on the mineralization rate has been insufficiently analyzed. A total of 3031 orthopantomograms of 1597 Japanese and 1434 Germans aged between 12 and 26 years were examined. The mineralization status of third molars was evaluated on the basis of the classification proposed by Demirjian. For the individual mineralization stages, the study presents the mean values and standard deviations (SD) separately for both populations and sexes. The majority of probands from both the Japanese and the German population achieved the C stage and the late G and H stages of third molar development at similar ages. Significant differences between Japanese and Germans were observed, however, with regard to the D, E and F stages defined by Demirjian. Japanese men and women achieved the D, E and F stages approximately 2-3 years later than German men and women. In addition to forensic age determination in living persons, the presented reference data can also be used for age estimations of unidentified deceased persons and skeletons.     

Psychiatric symptomatology and prodromal Alzheimer's disease

The aim of this study was to determine the prevalence of psychiatric symptoms among nondemented individuals with memory changes and whether such symptoms predict progression of functional decline or diagnosis of Alzheimer disease (AD). A semi-structured interview was administered at baseline to controls (n = 32) and to nondemented subjects with memory changes (n = 112) and to each subject's collateral source. The interview assessed the impact of cognition on functional abilities in daily life and a variety of psychiatric symptoms, including symptoms of psychosis, depression, and personality change. Participants were followed annually for 3 years to determine who had progressive functional decline and who progressed to meet clinical criteria for AD. Those diagnosed with AD on follow-up had more symptoms of personality change, such as agitation and passivity, at baseline than those who did not progress to meet clinical criteria for AD. Mild depressive symptoms were also more common among individuals at baseline who subsequently 'converted' to AD. Symptoms of personality change were associated with a more rapid increase in functional difficulty over time, whereas depressive symptoms were not. Changes in personality are more common among subjects with memory changes who go on to develop AD. Particular types of personality change, such as agitation and passivity, are related to progression of functional difficulty over time. Depressive symptoms, although common in prodromal AD, are not associated with a more rapid functional decline.     

Childhood social and early developmental factors associated with mental health service use

Background: The aim of this study was to determine the influence of family and child variables on the pathway to mental health care in children. Methods: A blinded, matched case control study was conducted, involving a retrospective analysis of prospectively collected data from routine examinations at the Youth Health Care Division from the Municipal Health Centre Maastricht (YHCD), where all children in a geographically defined area from foetal life through to age 19 years are periodically screened. The sample included 400 children, 80 referred to the Community Mental Health Centre in Maastricht and 320 matched controls, aged 6–13 years. Results: The most potent risk factors associated with mental health service use were: being small at birth, having a younger mother at delivery, living in a one-parent family, having a divorced mother and/or unemployed father, observations of externalising behaviour and/or motor developmental problems, speech problems and experiencing several adverse family circumstances. The group of variables pertaining to the family (e. g. one-parent family, parental mental health problems, etc.) influenced mental health service independently of the group of variables pertaining to the child (e. g. birth length, speech problems, etc.) and vice versa. Several combinations of risk factors, under realistic prevalence estimates, had positive predictive values of up to 26 %. Conclusion: Pathways to child psychiatric care are heavily influenced by the child's family environment as well as by deviance in social, motor and speech development. Independence of child developmental effects suggests these are not merely on the causal pathway between adverse family environment and psychiatric service use outcome. Combinations of risk factors may be useful to develop a screening approach with the possibility of early prevention. Accepted: 5 September 2002 Correspondence to Prof. Jim van Os