CBRN considerations in a major incident

Chemical, biological, radiological and nuclear (CBRN) hazards may be encountered during any major incident. General considerations include modifications to triage, managing contaminated or contagious casualties, and the identification and appropriate management of intoxicated/infected/irradiated/injured casualties. In dealing with chemical incidents, characteristics such as toxicity, latency and persistency need to be understood in order to manage casualties appropriately in terms of triage category, life-saving interventions and assessment of contamination risk to responders. Biological agents can be differentiated into live agents (bacteria, viruses and fungi) and toxins. Live agent characteristics and management depend on pathogenicity, virulence, lethality, infectivity and transmissibility, whereas toxins are treated similarly to chemical agents. Radiological and nuclear hazards are managed similarly and may cause irradiation, contamination (external and internal) or a combination with or without trauma. A generic and structured approach is advised to deal with all major incidents including those with a suspected of confirmed CBRN hazard. All healthcare professionals that may be involved in the response to such an incident need to be familiar with the principles of CBRN incident management and of CBRN casualty management as described in this article.     

Chronic lung injury in preterm lambs. Disordered respiratory tract development

The cause of chronic lung disease of early infancy, often called bronchopulmonary dysplasia (BPD), remains unclear, partly because large-animal models that reliably reproduce BPD have not been available. We developed a model of BPD in lambs that are delivered prematurely and ventilated for 3 to 4 wk after birth to determine whether the histopathology of chronic lung injury in premature lambs mimics that which occurs in preterm infants who die with BPD, and to compare two ventilation strategies to test the hypothesis that differences in tidal volume (VT) influence histopathologic outcome. The two ventilation strategies were slow, deep ventilation (20 breaths/min, 15 +/- 2 ml/kg body weight VT; n = 5) or rapid, shallow ventilation (60 breaths/min, 6 +/- 1 ml/kg body weight VT; n = 5). Lambs were delivered at 125 +/- 4 d gestation (term = 147 d), treated with surfactant, and mechanically ventilated with sufficient supplemental oxygen to maintain normal arterial oxygenation (60 to 90 mm Hg). Quantitative histologic analysis revealed lung structural abnormalities for both groups of experimental lambs compared with lungs of control term lambs that were < 1 d old (matched for developmental age; n = 5) or 3 to 4 wk old (matched for postnatal age; n = 5). Compared with control lambs, chronically ventilated preterm lambs had pulmonary histopathology characterized by nonuniform inflation patterns, impaired alveolar formation, abnormal abundance of elastin, increased muscularization of terminal bronchioles, and inflammation and edema. Slow, deep ventilation was associated with less atelectasis, less alveolar formation, and more elastin when compared with rapid, shallow ventilation. We conclude that prolonged mechanical ventilation of preterm lambs disrupts lung development and produces pulmonary histopathologic changes that are very similar to those that are seen in the lungs of preterm infants who die with BPD. This chronic lung disease is not prevented by surfactant replacement at birth, does not appear to require arterial hyperoxia, and is influenced by VT.     

Clinical variability of Fanconi anemia (type C) results from expression of an amino terminal truncated Fanconi anemia complementation group C polypeptide with partial activity

Fanconi anemia (FA) is an autosomal recessive disease characterized by congenital anomalies, aplastic anemia, and cancer susceptibility. Mutations within the FA complementation group C (FAC) gene account for approximately 14% of diagnosed FA cases. Two mutations, one in exon 1 (delG322) and one in exon 4 (IVS4 + 4 A to T), account for 90% of known FAC mutations. The delG322 mutation results in a mild FA phenotype, while the IVS4 + 4 A to T mutation results in severe FA phenotype. To determine the molecular basis for this clinical variability, we analyzed patient-derived cell lines for the expression of characteristic mutant FAC polypeptides. All cell lines with the delG322 mutation expressed a 50-kD FAC polypeptides, FRP-50 (FAC-related protein), shown to be an amino terminal truncated isoform of FAC reinitiated at methionine 55. All cell lines with the IVS4 + 4 A to T mutation lacked FRP-50. Overexpression of a cDNA encoding FRP-50 in an FA(C) cell line resulted in partial correction of mitomycin C sensitivity. In conclusion, expression of an amino terminal truncated FAC protein accounts, at least in part, for the clinical heterogeneity among FA(C) patients.     

The use of non-prescribed medication in the first 3 months of life in rural South Africa

OBJECTIVE: This paper describes the use of non-prescribed medications given to a cohort of infants in the first 3 months of life in a rural South African district, and discusses some of the implications for primary health care. METHODS: As part of an ongoing study on breastfeeding, a cohort of 110 infants were visited at home at 6 and 12 weeks of age. Any medications given to the infant since the last visit, the reasons for their administration, and any visits made to traditional healers were recorded via a semi-structured questionnaire. Determinants of administration of non-prescribed medication were analysed, including maternal age, education, infant gender and socio-economic factors. RESULTS: A total of 107 (97%) infants received non-prescribed medications in the first 3 months of life: 98 (89%) rectally and 64 (58%) orally. The most common enema contained traditional Zulu medicine made from herbs, given more than once weekly, usually for perceived constipation; the most common oral medication was gripe water, given once daily, mainly for 'colic' or 'wind'. Twenty-nine (26%) mothers had consulted a traditional healer, most commonly because of concerns about a capillary naevus, thought to cause pain. Mothers with a 'clean' water supply were more likely to give non-prescribed oral medications than those without (OR=2.7 and P=0.0223), whilst those who had no education were less likely to administer them than those who had completed school (OR=0.19 and P=0.0326). CONCLUSIONS: Non-prescribed medications are given almost universally to young infants in our area, irrespective of socio-economic class. Health professionals need to be aware of the extent of, and reasons for, administration of non-prescribed medications to young infants, so that effective health messages can be targeted at mothers and caregivers.     

Bilateral occurrence of pheochromocytoma in patients with the multiple endocrine neoplasia syndrome type 2A (Sipple's syndrome)

Two kindreds with the multiple endocrine neoplasia type 2A syndrome were studied. Of one of these we examined 150 members, 20 of whom were treated with thyroidectomy for medullary carcinoma and nine with bilateral adrenalectomy for pheochromocytoma. Of the second kindred 59 members were examined, seven of whom were thyroidectomized and seven treated with bilateral adrenalectomy. Pheochromocytomas were invariably found on both sides, even in four cases in which the adrenals on one side appeared to be completely normal, not only at preoperative roentgenologic examination but also on inspection during the operation. The microscopic finding of micronodules and a cluster of abnormal medullary cells identical with those found in pheochromocytomas in one of the apparently normal adrenals represents a first stage in the development of diffuse medullary hyperplasia as well as nodular hyperplasia. This is in accordance with the fact that in the MEN type 2A syndrome pheochromocytomas are always multicentric and multiple in origin. On the basis of these findings we conclude that all patients with the MEN 2A syndrome who show symptoms and signs of active pheochromocytoma should be subjected to bilateral adrenalectomy, even when one or both of the adrenals appear to be normal at roentgenologic investigation.     

Anal intraepithelial neoplasia and squamous cell carcinoma in HIV‐infected adults

Anal cancer is one of the most common non‐AIDS‐defining malignancies in the era of combination antiretroviral therapy. Its precursor lesion, anal intraepithelial neoplasia (AIN), is highly prevalent in HIV‐infected populations. More than 90% of anal squamous cell cancers are attributable to human papillomavirus (HPV). While the biology of HPV‐related intraepithelial neoplasia is consistent across lower anogenital sites, the natural history of AIN is not well established and cannot be assumed to be identical to that of cervical intraepithelial neoplasia. Screening strategies to prevent anal cancer should be developed based on robust natural history data in HIV‐infected and uninfected populations. Likewise, treatments need to be tested in randomized clinical trials, and reserved for those at significant risk of progression to cancer. This review covers the epidemiology, pathogenesis and immunology of HPV infection, AIN and anal cancer, and summarizes the current diagnosis, screening and treatment strategies in HIV‐infected adults.     

Lack of microbiota reduces innate responses and enhances adaptive immunity against Listeria monocytogenes infection

The intestinal microbiota influences not only metabolic processes, but also the mucosal and systemic immune systems. Here, we compare innate and adaptive immune responses against the intracellular pathogen Listeria monocytogenes in germfree (GF) and conventional mice. We show that animals without endogenous microbiota are highly susceptible to primary infection with impaired activation and accumulation of phagocytes to the site of infection. Unexpectedly, secondary infection with otherwise lethal dose resulted in survival of all GF animals which cleared bacteria more rapidly and developed a stronger antilisterial CD8⁺ memory T‐cell response compared to conventional mice. In summary, lack of the intestinal microbiota impairs early innate immunity, but enhances activation and expansion of memory T cells.