Epidemiology of paediatric trauma admissions at Queen Elizabeth Central Hospital,Blantyre

We conducted an audit of paediatric trauma admissions to QECH, Blantyre, in September 2003. There were 107 trauma cases representing 8.8% of all paediatric admissions and mean age was 6 years. The commonest cause of trauma was falls (42.9%) followed by burns (31.8%) and road traffic accidents (14.9%). Of the road traffic accidents, only one case was a passenger, the rest were pedestrians hit by moving vehicles. Fracture of limbs was the commonest injury sustained (44.9%) and burns the second commonest injury (31.8%). Most (52.6%) children were brought into hospital within 24 hours of injury while 26.3% came in between 24 hours and 48 hours and 21.1% after 48 hours or more. Death occurred in 7.5% of cases. The mean number of days in hospital was 8.9 days.     

Increased Fecal Levels of Chromogranin A, Chromogranin B, and Secretoneurin in Collagenous Colitis

Interactions between the enteric nervous system and the immune system are suggested to play an important role in the pathophysiology of inflammatory bowel disease (IBD). This study aims to determine if chromogranin A (CgA), chromogranin B (CgB), and secretoneurin (SN) are detectable in feces (F) from patients with collagenous colitis (CC) and to compare the levels found in patients with ulcerative colitis (UC) and Crohn’s disease (CD) before and during treatment. Patients with CC (n = 12) were studied before and after 3, 7, 28, and 56 days of treatment. Patients with IBD (UC, n = 21; CD, n = 11) were studied before and after 28 and 56 days of treatment. Clinical data were recorded, and fecal samples were collected at each occasion. F-CgA, F-CgB, and F-SN were measured by RIA. Eleven patients with CC, 21 with UC, and 10 with CD achieved remission. On inclusion, CC patients had higher levels of F-CgA, F-CgB, and F-SN than patients with IBD and controls. Patients with IBD expressed markedly lower levels of F-SN than controls. During treatment, F-SN in CC patients decreased to control levels but remained low in IBD patients. No change was found in F-CgA or F-CgB in any of the groups. In conclusion, CgA, CgB, and SN are detectable in feces, and CC patients express higher values than patients with IBD and controls. During treatment, F-SN decreased to control levels in CC. These findings suggest that the enteric nervous system is clearly involved in the pathophysiology of CC.     

The C5a receptor antagonist PMX205 ameliorates experimentally induced colitis associated with increased IL-4 and IL-10

Background and Purpose

Anti-complement therapies have not been advanced for treating the inflammatory bowel diseases (IBDs) despite a growing body of evidence that blocking C5a protects against induced colitis in rodents. The purpose of this study was to further build on this evidence by examining the efficacy, mechanism and specificity of a potent, non-competitive and orally active C5a receptor (CD88) antagonist, PMX205, in the dextran sulphate sodium (DSS) model of murine innate colitis.

Experimental Approach

Mice with DSS added to their drinking water were orally administered 100 or 200 μg day⁻¹ PMX205 in prophylactic and therapeutic regimens. Clinical illness, colon histology and local generation of inflammatory mediators were measured to evaluate the impact of PMX205 on disease.

Key Results

PMX205 significantly prevented DSS-induced colon inflammation in both regimens, associated with lower pro-inflammatory cytokine production and nitrotyrosine staining in colon sections. Additionally, the levels of anti-inflammatory cytokines IL-4 and IL-10 were increased. PMX205 had no significant effect on C5a levels. The beneficial effect of PMX205 was seen in two strains of mice of differing sensitivities to DSS inflammation, but was inactive in mice lacking CD88.

Conclusions and Implications

Pharmacological inhibition of C5a activity by PMX205 is efficacious in preventing DSS-induced colitis, providing further evidence that targeting CD88 in IBD patients could be a valuable therapeutic option.     

Trisomy 3 in low-grade B-cell lymphomas of mucosa-associated lymphoid tissue

Characteristic chromosomal aberrations have been associated with subtypes of non-Hodgkin's lymphoma with distinct clinicopathologic features. Low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) form such a group and might be expected to be characterized by a specific cytogenetic abnormality. Metaphase analyses of MALT lymphoma are rare due to problems with fresh tissue collection and poor in vitro proliferation. However, the small number of published series suggests that chromosome trisomies, particularly trisomy 3, might be characteristic of these tumors. The application of interphase cytogenetic techniques to routinely processed material allows the examination of a large series of archival cases and is particularly useful for the demonstration of chromosome trisomies. We have used this technique to analyze 70 cases of low-grade MALT lymphoma from various sites and found trisomy 3 in 60%. This finding compares with 16% in low- grade nodal B-cell lymphoma and 27% in primary splenic lymphoma of marginal zone type (splenic lymphoma with villous lymphocytes). These results provide further evidence that low-grade MALT lymphomas from all sites form a single pathologic entity distinct from nodal B-cell lymphomas. Although MALT lymphoma and primary splenic lymphoma may arise from marginal zone B cells, they are genetically distinct.     

Movements and home range of a common species of tree–shrew,Tupaia glis,surrounding houses of otoacariasis cases in Kuantan,Pahang, Malaysia

ObjectiveTo document movement patterns, home range, nesting behaviour and social organization of 5 individuals (3 males and 2 females) of a common species of tree-shrew, Tupaia glis (T. glis) surrounding houses of otoacariasis cases.MethodsEach shrew was fitted with a transmitter chip radio-collar which operates between the frequencies of 154.13 MHz to 154.21 MHz. Each transmitter was then tracked with a Portable Telemetry Receiver (Sirtrack, New Zealand) fitted with a 3-element Yagi antenna. Collared shrews were located using standard methods of ground-based triangulation. Each location was taken from at least 2 directional fixes and a minimum of 3 compass bearings. Fixes were taken hourly for each collared individual from the time of emergence from nest (beginning of activity) till time of entry into the nest (end of activity) every day for 5 to 7 continuous days. Three series of radio telemetry observations were carried out. The bearings, time and positions of an observer were recorded and later plotted on a graph paper in order to derive coordinates of the collared animal. [These coordinates then analyzed using Ecological Software Solutions (Biotas Version 1.03)].ResultsNests were found in a jack fruit tree, long bushes, and 2 houses. Daily telemetry detections demonstrated 2 individuals of different sex having nests (or a nest) in the same house. All shrews emerged from and returned to their nests between 0601 to 0659 hours and 1901 to 1959 hours, respectively. Both the time of exit from and entry into nest were the same between sexes (P>0.05). Their average total active period was 4.90 to 7.00 hours with a total daily travel distant of 270 m to 382 m. A male and a female shrew can move as far as 3 285 m and 4 591 m, respectively. Active movements of T. glis were during daytime. They regularly entered some houses in the area during day and night except for one individual which visited during daytime only. The sizes of home range and core area for the shrews were 2.00–3.40 ha and 0.05–0.42 ha, respectively. Generally, the mean home range size of females was 20.8% larger than that of males. Females covered a 15.4% slightly higher daily movement range compared to males.ConclusionsThis is the first radio telemetry study in Malaysia to monitor movements and home range of shrews carrying ticks on their body. It demonstrates that shrews are potential carriers of ticks from wild into the houses and their compounds based on their total active periods spent moving around from fruit orchards, secondary forest, plantations and other vegetations to trees in compound of 4 to 7 houses and vice versa. There are also evidences showing shrews have close contact with humans.     

Selective priming of peripheral blood eosinophils in patients with idiopathic hypereosinophilic syndrome

The idiopathic hypereosinophilic syndrome (HES) is characterised by blood eosinophilia associated with organ involvement. Elevated numbers of blood neutrophils have been observed during episodes of active HES. However, an increased responsiveness of eosinophils to chemotactic and chemokinetic stimuli may explain the selective eosinophil infiltration of the tissue. We have studied the migratory responses of blood eosinophils and neutrophils from 9 patients with HES and from 13 healthy control subjects. Chemokinetic and chemotactic responses to factors acting on both cell types were analysed by means of a modification of the Boyden chamber technique. We found increased migratory responses of the eosinophils, but not of the neutrophils, from the patients with HES. Increased blood neutrophil counts in three of the patients did not coincide with alterations of the neutrophil migratory responses. Our finding of increased migratory responses of eosinophils from patients with HES towards non-specific chemoattractants suggests selective priming of eosinophils in this disease. Interleukin (IL)-5 has previously been shown to prime eosinophils for migratory responses, and successful anti-IL-5 therapy of patients with HES indicates an important role for this cytokine in the development of hypereosinophilia.     

Albumin stimulation of eosinophil migration involves PI3-kinases and is associated with diminished eosinophil CD49d and CD49f expression

BACKGROUND: Albumin is known to induce chemokinesis and facilitate chemotaxis of human granulocytes in the Boyden chamber assay, but its mechanisms of action remain obscure. We have previously found that IL-2 inhibits albumin-stimulated eosinophil migration. The aim of this study was to identify the mechanisms behind the effects of albumin and IL-2 on the migration of human eosinophils. METHODS: Purified eosinophils were preincubated with inhibitors of signal transduction molecules before incubation with or without albumin and IL-2. The migration assay was performed in a 48-well microchemotaxis chamber. The effect of albumin and IL-2 on cell size and on the surface expression of adhesion molecules was studied with flow cytometry. RESULTS: Albumin-stimulated migration was inhibited by the PI3-kinase inhibitors wortmannin and LY-294002, but not by the PKC inhibitor RO-31-8220. IL-2 had no effect after preincubation with wortmannin or LY-294002. In contrast, the inhibitory effect of IL-2 remained after preincubation with RO-31-8220. Albumin increased the cell size as measured by forward scatter, and the expression of CD49d and CD49f decreased after incubation with albumin. IL-2 affected neither the expression of adhesion molecules nor the forward scatter. CONCLUSIONS: The stimulation of eosinophil migration by albumin is mediated by PI3-kinase, and the increase in cell size caused by albumin indicates activation of the cells. Decreased expression of CD49d and CD49f by albumin may diminish the adhesiveness of the cells, which in turn may facilitate migration. These are novel findings that indicate an active role for albumin in eosinophil migration.     

Characterization of ZK 245186, a novel,selective glucocorticoid receptor agonist for the topical treatment of inflammatory skin diseases

Background and purpose:

Glucocorticoids are highly effective in the therapy of inflammatory diseases. Their value, however, is limited by side effects. The discovery of the molecular mechanisms of the glucocorticoid receptor and the recognition that activation and repression of gene expression could be addressed separately opened the possibility of achieving improved safety profiles by the identification of ligands that predominantly induce repression. Here we report on ZK 245186, a novel, non-steroidal, low-molecular-weight, glucocorticoid receptor-selective agonist for the topical treatment of inflammatory dermatoses.

Experimental approach:

Pharmacological properties of ZK 245186 and reference compounds were studied in terms of their potential anti-inflammatory and side effects in functional bioassays in vitro and in rodent models in vivo.

Key results:

Anti-inflammatory activity of ZK 245186 was demonstrated in in vitro assays for inhibition of cytokine secretion and T cell proliferation. In vivo, using irritant contact dermatitis and T cell-mediated contact allergy models in mice and rats, ZK 245186 showed anti-inflammatory efficacy after topical application similar to the classical glucocorticoids, mometasone furoate and methylprednisolone aceponate. ZK 245186, however, exhibits a better safety profile with regard to growth inhibition and induction of skin atrophy after long-term topical application, thymocyte apoptosis, hyperglycaemia and hepatic tyrosine aminotransferase activity.

Conclusions and implications:

ZK 245186 is a potent anti-inflammatory compound with a lower potential for side effects, compared with classical glucocorticoids. It represents a promising drug candidate and is currently in clinical trials.This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009