Chlamydia, physical characteristics and diagnostic aspects

The investigations described in this thesis had several alms. As discussed in the diagnostics section, the detection of antibodies directed against C. trachomatis using the MIF is not only laborious, but the interpretation of the results is also subjective. The main objection against using an ELISA or an IPA in which serovar LGV2 is used as the sole antigen is that antibodies directed against other serovars are either not detected at all or detected unsatisfactorily (34). In the literature too, there is no general consensus on the sensitivity and the specificity of serology as compared with that of the tissue culture for detecting acute C. trachomatis infections. In order to overcome these objections, we developed a sensitive enzyme linked immunofluorescent assay (ELFA). Antibodies directed against 6 different antigens of C. trachoma/is can be detected using the ELFA. The antigens are chosen in such a way that antibodies against all C. trachomatis serovars can be detected. The contribution made by serology in the diagnostics of acute Chlamydia infection was investigated in two groups of patients. Initially, a group of men and women with uncomplicated infections who visited the outpatient department of the clinic for sexually transmitted diseases in Rotterdam was investigated in order to determine whether there was any correlation between the results of serology and those of the tissue culture. Later, a group of patients with complicated infections was also investigated. This group consisted of patients suffering from pelvic inflammatory disease who had been admitted to the department of Gynecology of the Dijkzigt Hospital in Rotterdam. It was also determined whether there was any correlation between the results of serology and those of the tissue culture and the polymerase chain reaction (PCRI. Little is known on the manner in which C. pneumoniae is transmitted from one host to another. A possible clue for transmission occurring via aerosols was reported by Hyman et al (42). He deduced this from the C. pneumoniae infections acquired by the laboratory personnel after an accident involving a centrifuge. Undoubtedly, an aqueous intermediate also influences the survival of C. pneumoniae during transmission. The spread of the organism must occur very efficiently as illustrated by the fact that about 50% of the population in the industrialized world has already acquired C.pneumoniae infection between the age of 5 and 15 years (39). Therefore, the aim of the subsequent studies was to investigate the influence of pH, ion concentrations and temperature on the survival of C. pneumoniae. The survival of C. pneumoniae in aerosols under various conditions was also investigated using a 114.5 L stainless steel aerosol chamber in which both the relative humidity and the temperature could be carefully controlled. The survival of other microorganisms including C. trachoma tis in aerosols was also investigated in order to determine whether there was any correlation with the survival of C. pneumoniae under the same conditions. C. trachomatis can be stored best for prolonged periods in SPG medium at a minimum temperature of -70°C 143). Optimum survival of C. pneumoniae can be achieved by cooling it at 4°C for 4 h prior to freezing 144). However, this method is cumbersome and expensive for transport and culture collections. A large number of pathogenic bacteria can be stored for a long time with a negligible loss in viability by lyophilization in a suitable medium (45,46). Consequently, investigations into the optimum media for lyophilization and different methods of freezing that may be suitable for the transport and storage of Chlamydia (chapter 61 were also pursued

Preconception maternal gastric bypass surgery and the impact on fetal growth parameters

Background: Bariatric surgery is increasingly performed in women of reproductive age. As bariatric surgery will result in postoperative rapid catabolic weight loss which potentially leads to fetal malnutrition and directly related impaired intra-uterine growth, it is advised to postpone pregnancy for at least 12–18 months after surgery. Objectives: To investigate the consequences of preconception gastric bypass surgery (pGB) on fetal growth parameters and maternal pregnancy outcome. Setting: Maasstad Hospital, The Netherlands, general hospital and Erasmus Medical Center, The Netherlands, university hospital. Methods: We included 97 pGB pregnancies (Maasstad hospital) and 440 non-bariatric pregnancies (Rotterdam Periconception cohort, Erasmus Medical Center). Longitudinal second and third trimester fetal growth parameters (head circumference, biparietal diameter, femur length, abdominal circumference, estimated fetal weight) were analyzed using linear mixed models, adjusting for covariates and possible confounders. Fetal growth and birthweight in pGB pregnancies were compared to non-bariatric pregnancies and Dutch reference curves. Maternal pregnancy outcome in the pGB group was compared to non-bariatric pregnancies. Results: All fetal growth parameters of pGB pregnancies were significantly decreased at 20 weeks’ gestation (P &lt; .001) and throughout the remaining part of pregnancy (P &lt; .05) compared with non-bariatric pregnancies (crude and adjusted models). In our cohort, gestational weight gain was not significantly associated with birthweight corrected for gestational age. Birthweight was significantly lower in pGB pregnancies (estimate –241 grams [95% CI, –342.7 to –140.0]) with a 2-fold increased risk of small-for-gestational-age (SGA) (adjusted odds ratio 2.053 [95% CI, 1.058 to 3.872]). Compared to the non-bariatric pregnancies, we found no significant differences in maternal pregnancy outcome. Conclusions: PGB is associated with overall reduced fetal growth trajectories and a 2-fold increased risk of SGA, without significant adverse consequences for maternal pregnancy outcome. We recommend close monitoring of fetal growth after pGB.</p

Criminal victimisation in people with severe mental illness: A multi-site prevalence and incidence survey in the netherlands

Background: Although crime victimisation is as prevalent in psychiatric patients as crime perpetration (and possibly more so), few European figures for it are available. We therefore assessed its one-year prevalence and incident rates in Dutch severely mentally ill outpatients, and compared the results with victimisation rates in the general population. Method: This multisite epidemiological survey included a random sample of 956 adult severe

Validation of the surgical fear questionnaire in adult patients waiting for elective surgery

Objectives: Because existing instruments for assessing surgical fear seem either too general or too limited, the Surgical Fear Questionnaire (SFQ) was developed. The aim of this study is to assess the validity and reliability of the SFQ. Methods: Based on existing literature and expert consultation the ten-item SFQ was composed. Data on the SFQ were obtained from 5 prospective studies (N = 3233) in inpatient or day surgery patients. These data were used for exploratory factor analysis (EFA), confirmatory factor analysis (CFA), reliability analysis and validity analysis. Results: EFA in Study 1 and 2 revealed a two-factor structure with one factor associated with fear of the short-term consequences of surgery (SFQ-s, item 1-4) and the other factor with fear of the long-term consequences of surgery (SFQ-l, item 5-10). However, in both studies two items of the SFQ-l had low factor loadings. Therefore in Study 3 and 4 the 2-factor structure was tested and confirmed by CFA in an eight-item version of the SFQ. Across all studies significant correlations of the SFQ with pain catastrophizing, state anxiety, and preoperative pain intensity indicated good convergent validity. Internal consistency (Cronbach's alpha) was between 0.765-0.920 (SFQ-total), 0.766-0.877 (SFQ-s), and 0.628-0.899 (SFQ-l). The SFQ proved to be sensitive to detect differences based on age, sex, education level, employment status and preoperative pain intensity. Discussion: The SFQ is a valid and reliable eight-item index of surgical fear consisting of two subscales: fear of the short-term consequences of surgery and fear of the long-term consequences.This study was conducted with departmental funding and supported by a grant from The Netherlands Organisation for Scientific Research (Zon-MW, http://www.zonmw.nl/en/), grant no. 110000007. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Quantification of Calcyclin and Heat Shock Protein 90 in Sera from Women with and without Preeclampsia by Mass Spectrometry

Purpose: The objective of present study is to determine serum levels and placental distribution of two interacting proteins calcyclin and heat shock protein 90 in preeclampsia. Experimental design: Maternal serum levels of calcyclin and heat shock protein 90 are compared throughout pregnancy from the first trimester till term among women with preeclampsia (n = 43) and age-matched normotensive pregnant controls (n = 46). A serum-based 2D LC-MS assay using Parallel Reaction Monitoring is applied to quantify both calcyclin and heat shock protein 90. Results: Serum levels of calcyclin are significantly lower in patients with preeclampsia in the second trimester of pregnancy as compared to controls (p < 0.05). Serum levels of heat shock protein 90 are significantly higher in patients with preeclampsia in the third trimester as compared to controls (p < 0.001). Conclusion and clinical relevance: Both interacting proteins calcyclin and heat shock protein 90 are notably changed in preeclamptic patients compared to controls. Calcyclin is already decreased before the onset of preeclampsia in the second trimester and HSP90 is strongly increased in the third trimester. This suggests that these proteins may play a role in the pathogenesis of preeclampsia and ought to be investigated in large cohort studies as molecular biomarkers

Multicenter Comparison of Molecular Tumor Boards in The Netherlands:Definition, Composition, Methods, and Targeted Therapy Recommendations

Background Molecular tumor boards (MTBs) provide rational, genomics-driven, patient-tailored treatment recommendations. Worldwide, MTBs differ in terms of scope, composition, methods, and recommendations. This study aimed to assess differences in methods and agreement in treatment recommendations among MTBs from tertiary cancer referral centers in The Netherlands. Materials and Methods MTBs from all tertiary cancer referral centers in The Netherlands were invited to participate. A survey assessing scope, value, logistics, composition, decision-making method, reporting, and registration of the MTBs was completed through on-site interviews with members from each MTB. Targeted therapy recommendations were compared using 10 anonymized cases. Participating MTBs were asked to provide a treatment recommendation in accordance with their own methods. Agreement was based on which molecular alteration(s) was considered actionable with the next line of targeted therapy. Results Interviews with 24 members of eight MTBs revealed that all participating MTBs focused on rare or complex mutational cancer profiles, operated independently of cancer type-specific multidisciplinary teams, and consisted of at least (thoracic and/or medical) oncologists, pathologists, and clinical scientists in molecular pathology. Differences were the types of cancer discussed and the methods used to achieve a recommendation. Nevertheless, agreement among MTB recommendations, based on identified actionable molecular alteration(s), was high for the 10 evaluated cases (86%). Conclusion MTBs associated with tertiary cancer referral centers in The Netherlands are similar in setup and reach a high agreement in recommendations for rare or complex mutational cancer profiles. We propose a "Dutch MTB model" for an optimal, collaborative, and nationally aligned MTB workflow. Implications for Practice Interpretation of genomic analyses for optimal choice of target therapy for patients with cancer is becoming increasingly complex. A molecular tumor board (MTB) supports oncologists in rationalizing therapy options. However, there is no consensus on the most optimal setup for an MTB, which can affect the quality of recommendations. This study reveals that the eight MTBs associated with tertiary cancer referral centers in The Netherlands are similar in setup and reach a high agreement in recommendations for rare or complex mutational profiles. The Dutch MTB model is based on a collaborative and nationally aligned workflow with interinstitutional collaboration and data sharing

Study protocol for a prospective cohort study to investigate Hemodynamic Adaptation to Pregnancy and Placenta-related Outcome: the HAPPO study

INTRODUCTION: The importance of cardiovascular health in relation to pregnancy outcome is increasingly acknowledged. Women who develop certain pregnancy complications, in particular preeclampsia, are at higher risk for future cardiovascular disease. Independent of its outcome, pregnancy requires a substantial adaptive response of the maternal cardiovascular system. In the Hemodynamic Adaptation to Pregnancy and Placenta-related Outcome (HAPPO) study, we aim to examine longitudinal maternal haemodynamic adaptation to pregnancy from the preconception period onwards. We hypothesise that women who will develop adverse pregnancy outcomes have impaired cardiovascular health before conception, leading to haemodynamic maladaptation to pregnancy and diminished uteroplacental vascular development. METHODS AND ANALYSIS: In this prospective cohort study embedded in the Rotterdam periconception cohort, 200 women with a history of placenta-related pregnancy complications (high-risk group) and 100 women with an uncomplicated obstetric history (low-risk group) will be included. At five moments (preconception, first, second and third trimester and postdelivery), women will undergo an extensive examination of the macrocirculatory and microcirculatory system and uteroplacental vascular development. The main outcome measures are differences in maternal haemodynamic adaptation to pregnancy between women with and without placenta-related pregnancy complications. In a multivariate linear mixed model, the relationship between maternal haemodynamic adaptive parameters, (utero)placental vascularisation indices and clinical outcomes (occurrence of pregnancy complications, embryonic and fetal growth trajectories, miscarriage rate, gestational age at delivery, birth weight) will be studied. Subgroup analysis will be performed to study baseline and trajectory differences between high-risk and low-risk women, independent of subsequent pregnancy outcome. ETHICS AND DISSEMINATION: This study protocol was approved by the Medical Ethics Committee of the Erasmus MC, Rotterdam, the Netherlands (MEC 2018-150). Results will be disseminated to the medical community by publications in peer-reviewed journals and presentations at scientific congresses. Also, patient associations will be informed and the public will be informed by dissemination through (social) media. TRIAL REGISTRATION NUMBER: NL7394 (www.trialregister.nl)