Childhood infections and common carotid intima media thickness in adolescence.

Atherosclerotic changes can be measured as changes in common carotid intima media thickness (CIMT). It is hypothesised that repeated infection-associated inflammatory responses in childhood contribute to the atherosclerotic process. We set out to determine whether the frequency of infectious diseases in childhood is associated with CIMT in adolescence. The study is part of the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) population-based birth cohort. At age 16 years, common CIMT was measured. We collected general practitioner (GP) diagnosed infections and prescribed antibiotics. Parent-reported infections were retrieved from annual questionnaires. Linear regression analysis assessed the association between number of infections during the first 4 years of life and common CIMT. Common CIMT measurement, GP and questionnaire data were available for 221 participants. No association was observed between the infection measures and CIMT. In a subgroup analysis, significant positive associations with CIMT were observed in participants with low parental education for 2-3 or ⩾7 GP diagnosed infections (+26.4 µm, 95% CI 0.4-52.4 and +26.8 µm, 95% CI 3.6-49.9, respectively) and ⩾3 antibiotic prescriptions (+35.5 µm, 95%CI 15.8-55.3). Overall, early childhood infections were not associated with common CIMT in adolescence. However, a higher number of childhood infections might contribute to the inflammatory process of atherosclerosis in subgroups with low education, this needs to be confirmed in future studies.

Exceptionally low rotavirus incidence in the Netherlands in 2013/14 in the absence of rotavirus vaccination.

An unexpected drop in rotavirus (RV) detections was observed in the Netherlands in 2014, without RV vaccination. The estimated decrease in RV detections and gastroenteritis consultations in under five year-olds, in January-April 2014, compared to the same months in previous years, was 72% and 36%, respectively. The low birth rate, mild winter, high RV incidence in the previous year and the introduction of RV vaccination in neighbouring countries may have contributed to this decrease.

Effect of 17-alpha hydroxyprogesterone caproate on cervical length in twin pregnancies.

OBJECTIVES: Previous studies on singleton pregnancies have indicated that progestogens may reduce the rate of cervical shortening during pregnancy. The aim of this study was to investigate whether treatment with 17-alpha hydroxyprogesterone caproate (17-OHPC) has an effect on cervical shortening in twin pregnancies. METHODS: This was a secondary analysis of patients who had participated in a multicenter randomized clinical trial on the effectiveness of 17-OHPC in preventing preterm birth in multiple pregnancies (the AMPHIA-trial). We included all trial participants with a twin gestation who had undergone repeat cervical length measurements during pregnancy. We performed a separate analysis of women with repeat measurements in centers where this was standard protocol for multiple pregnancies. The rate of cervical shortening for both the 17-OHPC group and the placebo group was analyzed using a linear mixed model. RESULTS: Of the 671 patients who participated in the trial, 282 (42%) had a twin pregnancy and underwent two or more cervical length measurements. Of these women, 140 were monitored in centers where repeat measurements were standard protocol. We observed an overall reduction of cervical length from 44.3 mm at 14-18 weeks to 30.0 mm at 30-34 weeks' gestation. In the 17-OHPC group, cervical length decreased by 1.04 mm each gestational week, while this was 1.11 mm per week for the placebo group (P = 0.6). For the overall group, each 10% decrease in cervical length led to an increase in the risk of preterm birth (hazard ratio, 1.14; 95% CI, 1.08-1.21). CONCLUSION: In women with a twin pregnancy, there is progressive shortening of the cervix during pregnancy, regardless of 17-OHPC use.

Limitations of ST analysis in clinical practice: three cases of intrapartum metabolic acidosis.

OBJECTIVE: To examine detailed intrapartum events in cases of neonatal metabolic acidosis despite monitoring using STAN (cardiotocography [CTG] plus ST waveform analysis of fetal electrocardiogram [ECG]). DESIGN: Retrospective case review. SETTING: High-risk pregnancies monitored by STAN. METHODS: Case note review was performed in newborns with metabolic acidosis where no significant ST changes in the fetal ECG occurred prior to birth. MAIN OUTCOME MEASURES: Metabolic acidosis. RESULTS: Detailed review of three cases identified poor signal quality, difficulties in CTG interpretation, failure to comply with STAN clinical guidelines and deterioration of the CTG without ECG alert as the leading causes of these adverse outcomes. CONCLUSIONS: The cases illustrate some of the pitfalls associated with the clinical application of the STAN technology which prevent severe metabolic acidosis being eradicated completely. It may be useful to expand the STAN guidelines protocol towards the identification of exceptional clinical situations, such as in our cases, and towards appropriate additional interventions, as this may lead to a further reduction in adverse neonatal outcomes.

Intramolecular photochemical dioxenone-alkene [2 + 2] cycloadditions as an approach to the bicyclo[2.1.1]hexane moiety of solanoeclepin A.

A synthesis of the bicyclo[2.1.1]hexane substructure of solanoeclepin A (1), the most active natural hatching agent of potato cyst nematodes, was approached via an intramolecular [2 + 2] photocycloaddition. Aldehyde 12 containing the dioxenone chromophore served as a useful starting material, allowing the synthesis of a variety of photocycloaddition substrates via Grignard addition or via a Nozaki-Hiyama-Kishi reaction. Photolysis of the unsubstituted alkene 14 led to the expected crossed cycloadduct bicyclo[2.1.1]hexane 15 according to the so-called rule of five. However, several functionalized alkenes 18, 20, and 31 exhibited a complete reversal of cycloaddition regioselectivity, providing straight cycloadducts bicyclo[2.2.0]hexanes 21-26 and 4, respectively. Their structures were proved by a combination of extensive NMR measurements, X-ray analyses, and subsequent retro-aldol reactions. The latter de Mayo process allowed the formation of spiro-[3.5]nonane 35 and spiro[3.4]octane 36 as well as the cyclobutanes 37 and 38. Finally, the cyclization of the more rigid lactone precursor 28 occurred in high yield in the desired fashion with complete regio- and stereoselectivity to give 3 containing the core bicyclo[2.1.1]hexane skeleton of the natural product.

Histopathology of retrieved allografts of the femoral head.

From November 1994 to March 1997, we harvested 137 grafts of the femoral head from 125 patients for donation during total hip arthroplasty according to the guidelines of the American Associations of Tissue Banks (AATB) and the European Association of Musculo-Skeletal transplantation (EAMST). In addition to the standards recommended by these authorities, we performed histopathological examination of a core biopsy of the retrieved bone allograft and of the synovium. Of the 137 allografts, 48 (35.0%) fulfilled all criteria and were free for donation; 31 (22.6%) were not regarded as suitable for transplantation because the serological retests at six months were not yet complete and 58 (42.3%) were discarded because of incomplete data. Of those discarded, five showed abnormal histopathological findings; three were highly suspicious of low-grade B-cell lymphoma, one of monoclonal plasmacytosis and the other of non-specific inflammation of bone marrow. However, according to the standards of the AATB or EAMST they all met the criteria and were eligible for transplantation. Our findings indicate that the incidence of abnormal histopathology in these retrieved allografts was 3.6%. Since it is essential to confirm the quality of donor bones in bone banking, we advise that histopathological screening of donor bone should be performed to exclude abnormal allografts.

Counting mitoses by image processing in Feulgen stained breast cancer sections: the influence of resolution.

Counting of mitotic cells has been shown to be of prognostic value in breast cancer in different retrospective studies. Up to now the number of mitoses is assessed mainly manually according to a standardized but strict protocol. Although such a manual procedure is reasonably reproducible, automatic counting of mitotic cells offers the potential for greater objectivity and reproducibility. This paper describes the influence of resolution on automatic recognition by image processing of mitotic cells in Feulgen stained breast cancer sections. Using the image recording, correction and segmentation procedure described in a previous study, five specimens were analyzed: one was used to serve as a training set and four were put aside for later use as independent test set. For each slide, objects from a pre-selected area were recorded at increasing resolution. For each object, contour features and optical density measurements were computed and stored in a data file for statistical analysis. The results showed that increased resolution using a 40x objective lowered the number of misclassified mitoses compared with a 20x objective (overall mean percentage of misclassified mitoses over training and all test specimens: 20x, 24.57; 40x, 7.96). The number of misclassifications of non-mitoses was almost stable per specimen but varied between specimens (19-42%) due to differences among tissues. Given the improvement in classifying mitoses and the possibility to evaluate interactively the measurement result, the described semi-automated mitoses pre-screener of histological sections may be suitable for further testing in a clinical setting.

Quantitative microscopical and confocal laser scanning microscopy for intermediate endpoint biomarkers in breast cancer: potential and reproducibility.

Diagnostic quantitative pathological (QP) determinations are increasingly used in our hospital. The number of requests for QP for reference materials is rising rapidly. This is understandable; quantitative assessments have a strong prognostic value and can be very reproducible, depending on the care taken with a number of factors including cell and tissue processing, application of the appropriate stains, and the measurement protocol used. As to the latter, systematic random sampling gives the best intra- and interobserver agreement (with correlation coefficients between observers for certain features > or = 0.94). Flow cytometric determinations are often regarded as more reproducible than interactive morphometry due to the high speed of the assessments, the large number of objects measured per specimen, and the lack of observer interaction. Indeed, flow cytometrically assessed DNA ploidy is very reproducible, even though the % S-phase fraction is much more variable. Unlike image cytometry (ICM), visual inspection of cells is not easily accomplished with flow cytometry (FCM). With ICM, the fully automated measurement of DNA in thousands of cells is possible in 3-5 minutes, with a very low coefficient of variation (< or = 2% for the diploid and tetraploid peak of liver cell nuclei). ICM also allows measurement of texture features. However, quantitative immunohisto/cytochemical determinations may not always be as reproducible as sometimes believed. Recently, we found large variations in the measurements, made by a commercially available image processing instrument, of the estrogen and progesterone receptors, Ki-67, cathepsin D, and neu protein overexpression in breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Cognitive processing and the development of concepts by deaf students.

An examination of experimental learning models revealed that they all refer to the critical component of processing. The authors define processing as an activity that is employed to encourage students to reflect, describe, analyze, and communicate in some way that which was recently experienced. The authors describe a cognitive processing hierarchy and show how it relates to the characteristics of hearing-impaired students. They also share techniques for designing and leading processing activities.