Prevention of neonatal macrosomia in gestational diabetes by the use of intensive dietary therapy and home glucose monitoring

This study was undertaken to determine if intensive dietary therapy, home blood glucose monitoring, and the selective use of insulin can be effective in preventing fetal macrosomia. All patients were screened at 24 to 28 weeks' gestation using a modification of O'Sullivan's criteria. The 153 patients diagnosed as gestational diabetics by the study protocol were placed on a 1800 to 2000 Kcal American Diabetes Association diet and taught home glucose monitoring. Insulin therapy was initiated only if blood glucose control was inadequate. There were no significant differences (p greater than 0.05) between the study and reference populations in regard to mean birthweight or the incidence of macrosomia. Since our study criteria for diagnosing gestational diabetes were slightly different from those of the National Diabetes Data Group (NDDG), data from 99 patients meeting the NDDG criteria were analyzed in a similar manner. No significant differences were found between this subgroup and the reference population. Since only 7.2% of our study patients required insulin, we conclude that the incidence of fetal macrosomia in gestational diabetes can be kept equal to that of the general population by a program of intensive dietary therapy and home glucose monitoring, with insulin being used only therapeutically, not prophylactically.     

Laryngeal and tracheal complications of prolonged intubation]

Based on a retrospective study of 595 patients having undergone prolonged intubation, the authors present the main complications encountered and, in particular, the mucous ulceration which appears to be systematic and is itself at the origin of secondary stenosizing or granulomatous sequelae. Research is still needed concerning the follow-up of the intubated patients in order to limit the pressures exerted between the cordal mucosa or the tracheal mucosa in contact with the endotracheal tube. A systematic check upon removal of the tube decreases the secondary sequelae by starting adapted antacid, anti-inflammatory and antibiotic treatments, as well as certain acts of laryngeal microsurgery and, in some cases, laryngeal rehabilitation for both the voice and deglutition.     

Siblings of childhood cancer survivors: How does this “forgotten” group of children adjust after cessation of successful cancer treatment?

Siblings of childhood cancer patients are labelled the “forgotten children” because they experience significant psychosocial distress and are isolated from support systems inside and outside the family. This study investigates the late consequences of the cancer experience for siblings. 60 siblings of cancer survivors were compared with control subjects on measures of psychosocial adjustment. No differences were found between siblings of cancer survivors and controls on emotional and behavioural problems and competence, suggesting that siblings adjust well to the period after cessation of treatment. The effect of demographic, family and disease-related characteristics on the siblings' psychosocial adjustment was limited. Whereas during treatment many psychosocial problems for siblings have been reported, this does not result in a heightened risk of psychological disturbance for siblings as a late effect. The implications for patient care are discussed.     

Depsides as non-redox inhibitors of leukotriene B(4) biosynthesis and HaCaT cell growth, 2. Novel analogues of obtusatic acid

Aseries of obtusatic acid analogues has been synthesized and evaluated as inhibitors of leukotriene B(4) (LTB(4)) biosynthesis and as antiproliferative agents. The 4-O-benzylated and the 4-O-demethylated congeners were the most potent inhibitors of LTB(4) production of the depside class of compounds, with IC(50) values in the submicromolar range. Furthermore, these compounds do not function as redox-based inhibitors because they were not reactive against a stable free radical, 2,2-diphenyl-1-picrylhydrazyl, and did not produce appreciable amounts of deoxyribose degradation as a measure of their potency to generate hydroxyl radicals. Some obtusatic acid congeners were also potent inhibitors of keratinocyte growth. Growth inhibition was not mediated by damage to the cell membrane, as the activity of lactate dehydrogenase released from the cytoplasm was in the control range.     

Coexpression of GSK-3beta corrects phenotypic aberrations of dorsal root ganglion cells, cultured from adult transgenic mice overexpressing human protein tau

Coexpression of constitutively active GSK-3beta[S9A] rescued the axonal pathology induced by overexpression of human tau in transgenic mice (Spittaels et al., (2000) J. Biol. Chem. 275, 41340-41349). We isolated dorsal root ganglion (DRG) neuronal cultures from adult tau4R- and tau4R x GSK-3beta-transgenic mice to define the mechanisms at the cellular and subcellular level. DRG from tau4R-transgenics showed a reduced sprouting capacity while density and stability of microtubules in the axonal processes were significantly increased. Video-enhanced contrast microscopy demonstrated a dramatic inhibition of fast axonal transport. Coexpression of GSK-3beta increased tau phosphorylation and reversed the effects on microtubule stability and saltatory motion. In DRG from GSK-3beta single transgenics, increased tau phosphorylation was evident without any major effects on microtubule stability or axonal transport. These observations support the hypothesis that excess tau competed with motor-proteins for binding to microtubules and/or that a rigid microtubular system inhibits axonal transport.     

Family factors and life events as risk factors for behavioural and emotional problems in children

The aim of this study was to identify groups of children at increased risk of behavioural or emotional problems on the basis of socio-demographic characteristics, family characteristics, and recent life events with a focus on unemployment and divorce or separation. We obtained data on the Child Behavior Checklist (CBCL) from a community-based national sample of 4480 parents of school-aged children and interviewed them about their demographic and family characteristics and about the child's recent life events. Results showed that family characteristics and recent life events were more strongly associated with children's risks of behavioural and emotional problems as measured by the CBCL than other demographic characteristics. Risks were somewhat higher for children who had experienced parental unemployment and divorce or separation recently, as compared to those who had experienced these events in the more distant past. We conclude that children with recent experience of parental unemployment or parental divorce or separation are at a relatively high risk of behavioural and emotional problems as reported by parents. Although relatively high, the risks that were found do not justify restriction of screening for behavioural and emotional problems to these children.     

Differential expression of stress proteins in human adult astrocytes in response to cytokines

Various lines of evidence suggest a close relationship between heat shock proteins (hsp) and several autoimmune diseases such as arthritis, diabetes and multiple sclerosis. While enhanced expression of hsp in autoimmune diseases is often regarded as a non-specific bystander effect of the inflammatory process, surprisingly little is known on hsp regulation by inflammatory mediators such as cytokines. In this study cytokine-induced expression of hsp60, hsp27 and alphaB-crystallin was studied in cultures of primary human adult astrocytes at the mRNA as well as at the protein level. We show differential hsp expression patterns in response to pro-inflammatory and immunoregulatory cytokines. Hsp60 expression was found to be enhanced in response to cytokines as diverse as IL-1beta, TNF-alpha, IL-4, IL-6 and IL-10. Upregulation of hsp27, however, was primarily induced by immunoregulatory cytokines like IL-4, IL-6 and TGF-beta whereas alphaB-crystallin expression was found to be enhanced by the pro-inflammatory cytokine TNF-alpha only. None of the cytokines studied was able to enhance expression of all three hsp simultaneously. These results show that in human astrocytes induced expression of hsp27 and alphaB-crystallin is dependent on the presence of a defined set of stimuli, while induced expression of hsp60 is a much less selective event. This highly differential pattern of hsp expression in response to inflammatory mediators known to play an important role in the pathogenesis of autoimmune diseases indicates that hsp responses are specific rather than non-specific bystander responses.     

Six years of comprehensive, clinical, performance-based assessment using standardized patients at the Southern Illinois University School of Medicine.

By the end of 1990-91, the Southern Illinois University School of Medicine had had six years of experience with comprehensive, performance-based examinations of senior medical students' levels of clinical competence; this report assesses the psychometric aspects of the six examinations given during that period. The examinations were aimed at determining the students' readiness for postgraduate training. Compared with other clinical performance-based assessments that use standardized patients (SPs), these examinations had two important and unique features: (1) the examinations assessed a comprehensive range of clinical skills and reasoning; and (2) they approximated the challenges of real clinical practice wherein a practitioner's skills need to be orchestrated and prioritized in order to meet the challenges of the case encountered. Each year, the performance-based assessment given was an intensive clinical examination requiring each student to work up 13 to 18 SP problems over a three-day period. To administer an examination to an entire class of students took three weeks. Because all students after the first year of administration (1986) were required to pass these examinations, the fairness of test design and scoring and the setting of performance standards for the examinations became important issues for the faculty. The results, accumulated over six years and based on a total of 6,804 student-patient encounters involving 405 students, indicate that this kind of clinical performance-based examination can discriminate a wide range of students' clinical performances. The results provide evidence for the examinations' test security, content validity, construct validity, and reliability.     

Cannabis--psychosis pathway independent of other types of psychopathology

AIMS: To investigate if associations between cannabis use and psychotic symptoms occur independently, or occur as a consequence of previous-other types of-psychopathology. METHODS: A 14-year follow-up study of 1580 initially 4- to 16-year-olds who were drawn randomly from the Dutch general population was conducted. At initial assessment, psychopathology was assessed with the Child Behavior Checklist. Across the 14-year follow-up period, cannabis use and psychotic symptoms were assessed with the Composite International Diagnostic Interview (CIDI). Because cannabis use is generally condoned in The Netherlands, false-negative reports of cannabis use may occur less frequently than in countries with stricter drug policies, which supports the value of the present study. RESULTS: Survival analyses indicated that the association between cannabis use and psychotic symptoms occurred independently of initial CBCL scores. CONCLUSIONS: The link between cannabis use and psychotic symptoms is specific, and does not depend on the earlier presence of other types of psychopathology. This indicates that research aimed at unraveling mechanisms that are responsible for this specific association is useful. Further, given the fact that cannabis use seemed to be a specific risk factor for future psychotic symptoms, prevention aimed against cannabis use may prohibit the onset of psychotic symptoms in vulnerable individuals.