Clinical and imaging correlations of Treacher Collins syndrome: report of two cases.

Mandibulofacial dysostosis (Treacher Collins Syndrome) is an autosomal dominant genetic disorder that probably derives from inhibition of the facial structures from the first and second branchial arches. The facial pattern of the syndrome is a convex facial profile with a prominent nose above a retruded chin. The eyes are deformed by antimongoloid slant of the palpebral fissures and facial bones are hypoplastic. The alterations are caused by mutation in gene 5q32-33.1, which encodes the nucleolar phosphoprotein treacle. Computed tomography images are able to demonstrate craniofacial bones, allowing the morphological analysis of these bones in individuals with complex deformities. The purpose of this paper is to present the results of a clinical and computed tomography investigation of two patients with Treacher Collins syndrome.     

Relaxin down-regulates renal fibroblast function and promotes matrix remodelling in vitro.

BACKGROUND: Renal fibroblasts are important effector cells in tubulointerstitial fibrosis, with experimental antifibrotic strategies focusing on the functional down-regulation of these cells. Several experimental models of fibrosis have provided evidence for the effectiveness of the polypeptide hormone relaxin as a potential antifibrotic agent. This study was conducted to further elucidate the antifibrotic mechanisms of relaxin on renal fibroblasts in vitro. METHODS: Rat cortical fibroblasts were obtained from outgrowth culture of renal tissue isolated from kidneys 3 days post-unilateral ureteric obstruction and constituted 100% of cells studied. A relaxin radio-receptor assay was used to establish binding of relaxin to renal fibroblasts in vitro. Functional studies then examined the effects of H2 relaxin (0, 1, 10 and 100 ng/ml) on fibroblast kinetics, expression of alpha-smooth muscle actin (alpha-SMA), total collagen synthesis, collagenase production and collagen-I lattice contraction. CTGF mRNA expression was also measured by northern analysis. RESULTS: H2 relaxin bound with high affinity to rat renal fibroblasts, but receptor numbers were low. Consistent with its previously reported bimodal effect, transforming growth factor (TGF-beta 1) reduced fibroblast proliferation, an effect abrogated by H2 relaxin. Fibroblasts exposed to H2 relaxin (100 ng/ml) for 24 h demonstrated decreased immunostaining for alpha-SMA and reduced alpha-SMA protein expression compared with controls. There was a trend for a relaxin-mediated reduction in total collagen synthesis and alpha 1(I) mRNA expression with large dose-related increases in collagenase protein expression being observed. TGF-beta 1-stimulated collagen-I lattice contraction was significantly inhibited following co-incubation with 100 ng/ml relaxin. Incremental doses of H2 relaxin had no significant effect on CTGF mRNA expression. CONCLUSIONS: The findings of this study suggest that the antifibrotic effects of relaxin involve down-regulation of fibroblast activity, increase in collagenase synthesis and restructuring of collagen-I lattices, which are consistent with its known physiological role of matrix remodelling. Although there appears to be an interaction between TGF-beta 1 and H2 relaxin, this does not appear to involve a reduction in CTGF mRNA expression.     

Contemporary Models of Youth Development and Problem Prevention: Toward an Integration of Terms,Concepts, and Models

Over the past several years, increased interest in preventing youth problems and promoting healthy youth development has led youth and family practitioners, policy makers, and researchers to develop a wide range of approaches based on various theoretical frameworks. Although the growth in guiding frameworks has led to more complex models and a greater diversity in the options available to scholars and practitioners, the lack of an integrative conceptual scheme and consistent terminology has led to some confusion in the field. Here, we provide an overview of three approaches to youth development and problem prevention, critically examine their strengths and weaknesses, and offer some elaborations to help clarify, extend, and integrate the models. We conclude by discussing some general implications for researchers, practitioners, and policy makers.     

Estado actual del valor pronóstico de los marcadores moleculares en pacientes con cáncer colorrectal y la predicción de respuesta al tratamiento adyuvante

Colorectal cancer is one of the best studied of all malignant diseases interms of genetics and/or molecular prognostic factors. These factors, and relationships with prognosis, may have important implications especially in the design of surgical and adjuvant chemo-radiotherapy options. However, the true prognostic significance of all known factors has yet to be realised. We have reviewed the literature with specific focus on the role of molecular markers involved in prognosis and the prediction of response to adjuvant treatment.     

Neuronal development of the chick cerebral cortex. A Golgi study

The neuronal morphological development of the avian telencephalic cortex (DMC) is studied in Golgi-stained brain sections. The neuronal types at embryonic days 10, 13, 16, as well as of newborn chick are identified. The immature neurons are characterized by the presence of hair-like processes, growth cones and dendritic varicosities. These characteristics are absent in neuronal types of newborn chick. There are five patterns of differentiation, which produce six neuronal types in the newborn chick: horizontal neurons, pyramidal neurons, bipyramidal neurons, short axon multipolar neurons, long axon multipolar neurons and periventricular neurons. The morphological features of migrating embryonic cells are described. The dendritic spines appear in 16-day embryos in the majority of neuronal types.     

Total anorectal reconstruction with a double dynamic graciloplasty after abdominoperineal reconstruction for low rectal cancer

PURPOSE: Total anorectal reconstruction with a double dynamic graciloplasty was performed after abdominoperineal reconstruction (APR) for low rectal cancer. In four patients an additional pouch was constructed to improve neorectal motility and capacity. The aim of this study was to evaluate the results in the first 20 patients and to report on the preliminary results of patients with an additional pouch. METHODS: Twenty patients with a mean age of 52 (range, 25–71) years and a rectal tumor at a mean of 3 (range, 0–5) cm from the anal verge were treated. In 14 patients the Miles resection, colon pull-through, and construction of a neosphincter were performed in one session. Six patients had the double graciloplasty at an average of 4.1 (range, 1.1–8.8) years after APR. In four patients a pouch was constructed with an isolated segment of distal ileum. RESULTS: After a mean follow-up of 24 (range, 1–60) months after APR, none of the patients developed local recurrence, whereas four patients developed distant metastasis. Fifteen of 20 patients were available for evaluation, and 5 patients were still in training. Of these 15 patients, 8 patients were continent (53 percent), 2 patients were incontinent, and in 5 patients the perineal stoma was converted to an abdominal stoma. Failures were attributable to necrosis of the colon stump (n=2) and incontinence (n=3). At 26 weeks mean resting pressure was 44 (standard deviation (SD), 28) mmHg, and mean pressure during stimulation was 90 (SD, 46) mmHg at a mean of 35 (SD, 1.2) volts at 52 weeks. Mean defecation frequency was three times per day (range, 1–5). Of the eight patients who were continent, six used daily enemas. Mean time to postpone defecation was 11 (range, 0–30) minutes. CONCLUSION: In experienced hands, the double dynamic graciloplasty is an oncologically safe procedure that can have an acceptable functional outcome in a well-selected group of patients. However, to improve the outcome, further modifications will be necessary. So far, the addition of a pouch has not resulted in improved outcome. Supported by the Profileringsfonds of the Maastricht University Hospital, The Netherlands, and by the Stichting Fondsenwervingsactie Volksgezondheid, Amsterdam, The Netherlands. Read in part at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1995.     

Implications of postvaccination hepatitis B surface antigenemia in the management of exposures to body fluids.

A neonate vaccinated against HBV was the source of an occupational exposure to blood. She was tested for hepatitis B surface antigen and found to be positive, leading to unnecessary treatment, retesting, and concern. Evaluation of the infectious status of HBV should rely on other means if vaccination has recently occurred.     

Molecular biology in prostate cancer

Summary Genes involved in cancer generation are usually tumor suppressors and oncogenes. Progressive genetic alterations in these genes are involved in the mechanisms of tumorigenesis. In prostate cancer, additionally several chromosomal loci that should harbor mutated genes have been proposed. Some genes have been found altered in prostate cancer, such as PTEN, TP53, AR, RNASEL (HPC1), ELAC2 (HPC2), CDKN2A and MSR1 and those can be natural targets for new strategies of treatment. Besides, gene therapy has been suggested to be suitable for prostate cancer treatment. This approach includesex vivo corrective therapy, suicide, and antisense therapy.     

The complex enterprise of modelling prenatal exposure to cigarettes: what is ‘enough’?

While there is a burgeoning body of research linking smoking during pregnancy to problem behaviour in offspring, a major criticism of this work has been the crude measurement of exposure in these studies (e.g. retrospective, self-reported only) that could lead to biased estimates. To address this issue, we used a pregnancy cohort with repeated prospective measures of exposure as well as biological assays to generate estimates of exposure patterns using a range of modelling techniques. In this paper we report on the analytical approaches we have developed, including patterns of exposure over time and best-estimate approaches that combine self-report and cotinine measures, and compare their predictive value in relation to different dimensions of fetal growth as a first step towards examining the utility of greater precision of exposure measurement.
Surprisingly, in this sample the more complex assessments of exposure, including biological measures, generally did not perform better than simple indicators of exposure based on repeated self-report measures, with one exception: a combined self-report cotinine 'best estimate' of third trimester exposure was uniquely associated with lower brain : body ratio. Further study is needed using more sophisticated cotinine assays and testing prediction of a range of outcomes to ascertain whether these findings represent true differences or are specific to the sample, methods and outcomes used. Such research will inform the development of guidelines for adequate exposure characterisation in developmental studies.