Intracellular events in anti-IgE nonreleasing human basophils.

Histamine release (HR) after activation of human basophils with anti-IgE demonstrates a great variability among different donors. To elucidate the biochemical basis of this phenomenon, we studied the activation of purified basophils from donors that barely demonstrated HR (less than 7%) after stimulation by anti-IgE, although IgE was present on these cells and formyl-methionyl-leucyl-phenylalanine (fMLP)-induced HR was normal. Basophils from anti-IgE "nonreleasers" demonstrated, in contrast to cells from "releasers," hardly any changes in cytosolic-free Ca++ concentration after addition of anti-IgE. However, anti-IgE treatment of basophils from these anti-IgE nonreleasers resulted in at least two intracellular changes. First, a profound inhibition (54.2% +/- 4.2%) of a subsequent fMLP-induced HR was observed. This inhibition caused by anti-IgE was also observed in basophils from anti-IgE releasers treated with wortmannin, an inhibitor of the anti-IgE-induced HR. The time course of the inhibition induced by wortmannin plus anti-IgE on the fMLP-induced HR (half-life maximum, 4 minutes; time of maximum concentration, 10 minutes) was comparable to the time course of the anti-IgE-induced HR. Second, anti-IgE did induce homotypic aggregation in these anti-IgE-nonreleasing basophils, like in anti-IgE-releasing basophils. These studies indicate that basophils not responding to anti-IgE with HR or cytosolic-free Ca++ concentration changes do generate intracellular signals that inhibit the subsequent response to a heterologous stimulus and induce homotypic aggregation.     

Relationship between blood pressure level, renal histopathological lesions and plasma renin activity in fawn-hooded rats

The fawn-hooded rat (FH rat) develops hypertension accompanied with focal and segmental glomerulosclerosis and proteinuria, resulting in premature death. In a first experiment the relationship between renal lesions and blood pressure at various ages was investigated. In a second experiment blood pressure was measured weekly from 10 to 38 weeks of age in a number of male FH rats, followed by examination of renal tissues at 40 weeks of age. Plasma renin activity (PRA) had also been determined in individual FH rats. FH rats aged 4.5 weeks had no renal morphological abnormalities. The severity of the glomerulosclerosis increased with age and showed a positive relationship with blood pressure. The scores of the proteinaceous tubular casts also increased with age and they, too, showed a positive correlation with blood pressure. The severity of glomerulosclerosis and proteinaceous casts at 40 weeks of age was related positively to the course of blood pressure throughout life. The final blood pressure level showed a positive correlation with final PRA values. Only FH rats with malignant nephrosclerosis had high PRA values. The renal glomerular and vascular lesions in the FH rat, most likely caused by the hypertension, progressively deteriorate to malignant nephrosclerosis. At that stage PRA values are increased and may be contributing to the development of renal vascular lesions and acceleration of the hypertension.     

Secondary traumatic stress and secondary posttraumatic growth in a sample of Dutch police family liaison officers

This study investigated secondary traumatic stress (STS) and secondary posttraumatic growth (SPG) in a sample of Dutch police family liaison officers (N = 224). Our study had two aims: (a) to identify potential risk and protective factors for STS and (b) to investigate the association between STS and SPG. None of the risk (caseload and a personal trauma history) and protective factors (age, work experience, and support by supervisors and coworkers) identified in previous research correlated with STS. However, a small positive association was found between STS and SPG. In the discussion section we warn against the use of interventions that aim to prevent STS until more is known about risk and protective factors for STS and provide directions for future research.     

Effectiveness of a Cognitive Behavioral Therapy-Based Indicated Prevention Program for Children with Elevated Anxiety Levels: a Randomized Controlled Trial

Childhood anxiety is a problem not only because of its negative consequences on the well-being of children but also because of its adverse effects on society and its role in mental disorders later in life. Adequate prevention might be the key in tackling this problem. The effectiveness of Coping Cat, as an indicated CBT-based prevention program in Dutch primary school children, was assessed by means of a randomized controlled trial. In total, 141 children aged 7–13 with elevated levels of anxiety and their mothers were included and randomly assigned to an intervention group and a waiting list control group. After screening, all participants completed baseline, post-intervention, and 3-month follow-up assessments. The results showed that Coping Cat, as an indicated prevention program, reduces children’s self-reported anxiety symptoms, with Cohen’s effect size d of 0.66 at the 3-month follow-up. A moderating effect was found for baseline anxiety level; specifically, children with high levels of baseline anxiety who received the Coping Cat program had lower anxiety levels at follow-up compared to children with high levels of anxiety in the control condition. No moderating effects of gender or age were found. An unexpected decline in anxiety levels from screening to pre-assessment was found in both groups, and this decline was stronger in the experimental group. These promising results warrant the implementation of Coping Cat as an indicated prevention program.     

Cumulative risk of developing polyps or malignancy at the ileal pouch-anal anastomosis in patients with familial adenomatous polyposis

Restorative proctocolectomy with an ileal pouch-anal anastomosis is performed in an increasing number of patients with familial adenomatous polyposis (FAP). Two techniques are currently used to construct an ileal pouch-anal anastomosis: (1) a double-stapled anastomosis between the pouch and the anal canal and (2) mucosectomy with a hand-sewn iteoanal anastomosis at the dentate line. Although this procedure is thought to abolish the risk of colorectal adenoma, an increasing number of case reports have been published concerning the development of adenoma at the anastomotic site. The purpose of this study was to evaluate the overall cumulative risk of developing adenomatous polyps after ileal pouch-anal anastomosis and to compare the cumulative risk after either anastomotic technique. A total of 126 consecutive FAP patients undergoing a restorative proctocolectomy were identified from polyposis registries in The Netherlands, Denmark, Italy, Germany, and New York. Life-table analysis was used to calculate the cumulative risk of developing polyps in 97 patients with at least 1 year of endoscopic follow-up (median 66 months, range 12 to 188 months). A double-stapled anastomosis was used in 35 patients, whereas in 62 patients a handsewn anastomosis with a mucosectomy was performed. In 13 patients polyps developed at the anastomotic site, four with severe and four with moderate dysplasia. None of the patients developed a carcinoma at the anastomotic site. The cumulative risk of developing a polyp at the anastomotic site was 8% (95% confidence interval 2% to 14%) at 3.5 years and 18% (95% confidence interval 8% to 28%) at 7 years, respectively. The risk of developing a polyp at the anastomotic site within 7 years was 31 % for patients with a double-stapled vs. 10% for patients with a hand-sewn anastomosis with mucosectomy (P = 0.03 [log-rank test]). Because FAP patients undergoing a restorative proctocolectomy with either a double-stapled or hand-sewn anastomosis have a substantial risk of developing adenomatous polyps at the anastomotic site, lifelong endoscopic surveillance is mandatory in both groups. Presented at the Thirty-Ninth Annual Meeting of The Society for Surgery of the Alimentary Tract, New Orleans, La., May 17–20, 1998.     

Phylogeny and taxonomy of the family Arthrodermataceae (dermatophytes) using sequence analysis of the ribosomal ITS region.

The internal transcribed spacer (ITS) region, covering the ITS1, ITS2 and 5.8S ribosomal DNA was used to evaluate phylogenetic relationships within the fungal family Arthrodermataceae. Sequences of variable length, ranging between 522 and 684 base pairs were aligned. An unrooted consensus tree based on parsimony analysis showed Trichophyton to be polyphyletic, and Microsporum to be paraphyletic. Non-monophyly of these two genera is in conflict with traditional classification. But this relation is not strongly supported by bootstrap analysis. Phylogenetic analysis showed that the two known members of the genus Epidermophyton grouped widely apart from each other. Within Trichophyton, our results suggest a separation of human pathogenic species and primarily geophilic species. Bootstrap support for these two groups is fairly high and both groups are recognized by current taxonomy. Three lineages were revealed within the T. mentagrophytes species complex. Microsporum canis, M. audouinii and M. equinum were found to be closely related. The topology of the tree was robust to various methods of analysis (parsimony and distance) and a different weighting scheme. Weighting of transversions over transitions did not improve the status of poorly supported branches of the tree.     

Mannose-binding lectin (MBL) as prognostic factor in paediatric oncology patients

Deficiency of mannose-binding lectin (MBL) has been suggested to influence duration of febrile neutropenia and prognosis in paediatric oncology patients. However, there is no consensus on the definition of MBL deficiency. In a cohort of children with cancer, we investigated (i) how to determine MBL deficiency and (ii) whether MBL is a prognostic factor for disease severity. In 222 paediatric oncology patients, 92 healthy children and 194 healthy adults, MBL plasma levels and MBL2 genotype (wild-type: A, variant: O) were determined. Event-free survival (EFS), overall survival (OS) and paediatric intensive care unit (PICU) admissions were recorded prospectively. In febrile neutropenic patients admitted to the PICU, disease severity was assessed by clinical, microbiological and laboratory parameters. An optimal cut-off value for MBL deficiency was determined to be < 0·20 μg/ml. Wild-type MBL2 genotype patients, including the XA/XA haplotype, had increased MBL levels compared to healthy individuals. MBL deficiency was associated with decreased EFS (P = 0·03), but not with need for PICU admission. A trend for a twice increased frequency of septic shock (80% versus 38%, P = 0·14), multiple organ failure (40% versus 17%, P = 0·27) and death (40% versus 21%, P = 0·27) was observed in the absence of microbiological findings. MBL deficiency was associated with decreased EFS and possibly with an increased severity of disease during PICU admission after febrile neutropenia in the absence of any association with microbiological findings. These findings suggest prognosis to be worse in MBL-deficient compared to MBL-sufficient paediatric oncology patients.