Contribution of CD4+ and CD8+ T lymphocyte subsets to the cytokine secretion patterns induced in mice during sensitization to contact and respiratory chemical allergens.

Chemical allergens of different types, those that cause in humans allergic contact dermatitis or occupational asthma induce in mice divergent immune responses characteristic, respectively, of T-helper 1 (Th1)- and Th2-type cell activation. Such responses are associated with the development of different cytokine secretion patterns by draining lymph node cells (LNC), such that contact allergens stimulate vigorous interferon-gamma (IFN-gamma) production, but little secretion of the Th2 cytokines interleukin-4 and interleukin-10 (IL-4 and IL-10), whereas the converse pattern is provoked by respiratory allergens. Using selective depletion with antibody and complement we have here examined the relative contribution of CD4+ and CD8+ T lymphocytes to the cytokine secretion patterns of draining LNC isolated from mice sensitized to chemical allergens. Mice received repeated topical applications of respiratory allergens, trimellitic anhydride (TMA) or diphenylmethane diisocyanate (MDI), or of contact allergens 2,4-dinitrochlorobenzene (DNCB) or formaldehyde. Thirteen days following the initiation of exposure the production by draining LNC of IL-10, IFN-gamma and mitogen (concanavalin A)-inducible IL-4 was measured by enzyme-linked immunosorbent assay (ELISA) after various periods of culture. It was found that the high levels of IL-4 and IL-10 secretion stimulated by TMA or MDI, and the lower levels of these cytokines induced by DNCB or formaldehyde, were in all cases dependent upon the presence of CD4- cells. In contrast, the comparatively high concentrations of IFN-gamma observed following exposure to contact allergens were found to be derived from CD4+ cells, and in the case of DNCB from CD8+ cells also. The low levels of IFN-gamma induced by treatment with TMA or MDI were associated largely or wholly with CD8+ cells. These data indicate that the type 2 cytokine responses induced to different extents by both contact and respiratory chemical allergens are almost exclusively a function of CD4+ cells, but that IFN-gamma is produced by either CD4+ cells in the case of contact allergens or largely by CD8+ cells in the case of chemical respiratory allergens.     

Assessment of immunotoxicity in female Fischer 344/N and Sprague Dawley rats and female B6C3F1 mice exposed to hexavalent chromium via the drinking water

Sodium dichromate dihydrate (SDD), an inorganic compound containing hexavalent chromium (Cr(VI)), is a common environmental contaminant of groundwater sources due to widespread industrial use. There are indications in the literature that Cr(VI) may induce immunotoxic effects following dermal exposure, including acting as both an irritant and a sensitizer; however, the potential immunomodulatory effects of Cr(VI) following oral exposure are relatively unknown. Following the detection of Cr(VI) in drinking water sources, the National Toxicology Program (NTP) conducted extensive evaluations of the toxicity and carcinogenicity of SDD following drinking water exposure, including studies to assess the potential for Cr(VI) to modulate immune function. For the immunotoxicity assessments, female Fischer 344/N (F344/N) and Sprague Dawley (SD) rats and female B₆C₃F₁ mice were exposed to SDD in drinking water for 28 consecutive days and evaluated for alterations in cellular and humoral immune function as well as innate immunity. Rats were exposed to concentrations of 0, 14.3, 57.3, 172, or 516?ppm SDD while mice were exposed to concentrations of 0, 15.6, 31.3, 62.5, 125, or 250?ppm SDD. Final mean body weight and body weight gain were decreased relative to controls in 250?ppm B₆C₃F₁ mice and 516?ppm SD rats. Water consumption was significantly decreased in F344/N and SD rats exposed to 172 and 516?ppm SDD; this was attributed to poor palatability of the SDD drinking water solutions. Several red blood cell-specific parameters were significantly (5–7%) decreased in 250?ppm mice; however, these parameters were unaffected in rats. Sporadic increases in the spleen IgM antibody response to sheep red blood cells (SRBC) were observed, however, these increases were not dose-dependent and were not reproducible. No significant effects were observed in the other immunological parameters evaluated. Overall, exposure to Cr(VI) in drinking water had limited effects on the immune system in both rats and mice.     

Trend of severe abdominal injuries from bicycle accidents in children: a preventable condition

Aim: Bicycle riding is a common recreational and sport activity enjoyed by many children. Bicycle accidents are a common cause of abdominal injuries. We aim to establish the trend and the associated risk factor(s) of bicycle‐related abdominal injuries. Methods: A retrospective review of all children admitted following bicycle accidents to a single tertiary referral centre was carried out over an approximately 5‐year period. The data were tabulated and regression analyses were carried out. Results: Over the study period, 196 children were admitted into the Emergency Department. Abdominal injuries (16%) were the third largest group after orthopaedic and head injuries. There were 19 major visceral injuries, seven of whom underwent major surgeries. Forty‐two percent (8/19) of these major injuries were related to stunts. Over the same period, no child with head injury required any surgical intervention. In addition, there was a definite trend that abdominal injuries were accounting for greater percentage of bicycle‐related injuries in children. Conclusions: Severe intra‐abdominal trauma following bicycle injuries appears to be seen more often in adolescent males, especially when related to BMX stunts. These injuries have surpassed head injuries as the prime cause of morbidity from bicycle accidents. These injuries are largely preventable.     

Pheochromocytoma and paraganglioma: comparison of MR imaging with CT and I-131 MIBG scintigraphy

To ascertain the magnetic resonance (MR) imaging characteristics of pheochromocytomas and paragangliomas and to compare MR with computed tomography (CT) and iodine-131 metaiodobenzylguanidine (I-131 MIBG), 19 patients (18 with pheochromocytomas, one with a paraganglioma) were studied. The 18 patients with pheochromocytomas had had positive findings with I-131 MIBG scintigraphy. Abdominal pheochromocytomas were generally hypointense compared with normal liver on T1-weighted MR images and extremely hyperintense on T2-weighted MR images. MR imaging was preferable to CT in the evaluation of primary pheochromocytomas due to superior tissue characterization, particularly in the patient with hypertension and borderline catecholamine levels. For patients with recurrent or metastatic disease, the data suggest that I-131 MIBG scintigraphy is the examination of choice.     

Pathophysiology of respiratory disease and its significance to anaesthesia

Significant changes occur in the respiratory physiology of healthy patients during anaesthesia. In patients with underlying respiratory pathology, these changes in respiratory physiology may lead to clinical problems during the conduct of anaesthesia and the perioperative period. An understanding of the disease processes that can affect the lungs and pleura allows the anaesthetist to account for the potential complications of these conditions and manage the anaesthetic accordingly.     

The efficacy of removable devices to offload and heal neuropathic plantar forefoot ulcers in people with diabetes: a single‐blinded multicentre randomised controlled trial

Non‐removable offloading is the ‘gold standard’ treatment for neuropathic diabetic plantar forefoot ulcers. However, removable offloading is the common ‘standard of care’. We compared three removable offloading devices for ulcer healing efficacy. In this multicentre, randomised controlled trial, 60 persons with neuropathic diabetic plantar forefoot ulcers were randomly assigned to wear a custom‐made knee‐high cast [BTCC (bivalved TCC)], custom‐made ankle‐high cast shoe or a prefabricated ankle‐high forefoot‐offloading shoe (FOS). Primary outcome was healing at 12 weeks. Dynamic plantar pressures, daily stride count and treatment adherence were assessed on a randomly selected subset (n = 35). According to intention‐to‐treat analysis, 58% of patients healed with BTCC [OR 0·77 (95% CI 0·41–1·45) versus FOS], 60% with cast shoe [OR 0·81 (95% CI 0·44–1·49) versus FOS] and 70% with FOS (P = 0·70). Mean ± SD peak pressure in kPa at the ulcer site was 81 ± 55 for BTCC, 176 ± 80 for cast shoe and 107 ± 52 for FOS (P = 0·005); stride count was 4150 ± 1626, 3514 ± 1380 and 4447 ± 3190, respectively (P = 0·71); percentage of 2‐week intervals that patients wore the device <50% of time was 17·3%, 5·2% and 4·9%, respectively. Non‐significant differences in healing efficacy between the three devices suggest that, when non‐removable offloading is contraindicated or not available, each can be used for plantar forefoot ulcer offloading. Efficacy is lower than previously found for non‐removable offloading maybe because suboptimal adherence and high stride count expose the patient to high repetitive stresses. These factors should be carefully considered in decision making regarding ulcer treatment.