Cross-reactivity between nickel and palladium demonstrated by systemic administration of nickel

Concomitant patch test reactions to nickel and palladium have frequently been reported in patients undergoing investigation because of suspected allergic contact dermatitis. Theoretically, these reactions can be explained by multiple, concomitant, simultaneous sensitization as well as cross-sensitization. We studied whether concomitant reactions to nickel and palladium could represent cross-sensitization in females hypersensitive to combinations of nickel, palladium and cobalt. Females were patch tested with serial dilutions of nickel sulfate, cobalt chloride and palladium chloride on the upper back. 1 month later, when the patch test reactions were gone, the patients were randomized into 2 groups that were challenged orally with either nickel or placebo. 1 day later, the areas of previous positive patch test reactions were read in a blind way looking for flare-up reactions. Nickel provocation but not placebo yielded flare-up reactions on sites previously tested with nickel (P = 0.012) and palladium (P = 0.006), but were also observed on sites previously tested with cobalt, even though this was not statistically significant. Flare-up reactions of previous patch test reactions to nickel and palladium after oral challenge with nickel speak in favour of a cross-reactivity mechanism.     

Nickel-elicited systemic contact dermatitis from a peripheral intravenous catheter

Nickel-elicited systemic contact dermatitis is a well-known entity, although it is far less common than allergic contact dermatitis. In most of the cases, the main way of nickel administration is oral. Clinical manifestations are miscellaneous including pompholyx, diffuse exanthema, flexural dermatitis or baboon syndrome. Systemic nickel dermatitis induced by venous catheters is very uncommon, but it is probably underdiagnosed. We report here 2 patients with diffuse recurrent maculopapular rash corresponding to nickel-elicited systemic contact dermatitis. They were both perfused during the last episode with the assistance of a peripheral polyurethane venous catheter during or just before the cutaneous eruption. At the base of the catheter, there was a small metallic eyelet on which dimethylglyoxime test was positive, indicating a release of nickel. Then, we measured nickel release in normal use conditions and found high nickel levels, although the manufacturer denied that nickel could be released. This diagnosis is important to know because such exanthema often occurred during postoperative or postpartum period. Its frequency is probably underestimated because it is often considered as a cutaneous drug reaction. To our knowledge, only 2 cases have been reported in the literature.     

Neurotoxicity of carbonyl sulfide in F344 rats following inhalation exposure for up to 12 weeks

Carbonyl sulfide (COS), a high-priority Clean Air Act chemical, was evaluated for neurotoxicity in short-term studies. F344 rats were exposed to 75-600 ppm COS 6 h per day, 5 days per week for up to 12 weeks. In rats exposed to 500 or 600 ppm for up to 4 days, malacia and microgliosis were detected in numerous neuroanatomical regions of the brain by conventional optical microscopy and magnetic resonance microscopy (MRM). After a 2-week exposure to 400 ppm, rats were evaluated using a functional observational battery. Slight gait abnormality was detected in 50% of the rats and hypotonia was present in all rats exposed to COS. Decreases in motor activity, and forelimb and hindlimb grip strength were also detected. In rats exposed to 400 ppm for 12 weeks, predominant lesions were in the parietal cortex area 1 (necrosis) and posterior colliculus (neuronal loss, microgliosis, hemorrhage), and occasional necrosis was present in the putamen, thalamus, and anterior olivary nucleus. Carbonyl sulfide specifically targeted the auditory system including the olivary nucleus, nucleus of the lateral lemniscus, and posterior colliculus. Consistent with these findings were alterations in the amplitude of the brainstem auditory evoked responses (BAER) for peaks N3, P4, N4, and N5 that represented changes in auditory transmission between the anterior olivary nucleus to the medial geniculate nucleus in animals after exposure for 2 weeks to 400 ppm COS. A concentration-related decrease in cytochrome oxidase activity was detected in the posterior colliculus and parietal cortex of exposed rats as early as 3 weeks. Cytochrome oxidase activity was significantly decreased at COS concentrations that did not cause detectable lesions, suggesting that disruption of the mitochondrial respiratory chain may precede these brain lesions. Our studies demonstrate that this environmental air contaminant has the potential to cause a wide spectrum of brain lesions that are dependent on the degree and duration of exposure.     

Cutaneous field stimulation of sensory nerve fibers reduces itch without affecting contact dermatitis

BACKGROUND: A new technique, cutaneous field stimulation (CFS), which activates electrically unmyelinated C-fibers, is used to treat localized itch. Its action is similar to that of capsaicin, the pungent agent in hot peppers, which enhances delayed allergic reactions. The aim of the study was to investigate how experimental contact dermatitis responds to CFS. METHODS: Twelve patients with contact dermatitis in response to nickel were treated by CFS for 1 h each for four consecutive days. A flexible plate containing electrodes was applied to a test area on the upper arm and was stimulated by a constant current (0.8 mA). On the fifth day, patients were provoked by epicutaneous application of nickel sulfate (allergic contact dermatitis) and benzalkonium chloride (irritant contact dermatitis), and by intradermal tuberculin (delayed immunologic reaction). Twelve other patients with IgE-mediated allergy were treated by CFS on the lower arm for 1 h and were then pricked with histamine and allergen extracts (wheal volume was measured) and were tested using benzoic acid (nonimmunologic contact urticaria; closed test). Ten of these patients were also treated by CFS for four days, and experiments were performed on the fifth day. RESULTS: Test reactions to nickel, benzalkonium, and tuberculin were found to be unaffected by CFS treatment. Although allergic prick test reactions were enhanced (by 28%) after a single CFS treatment, the associated itch was significantly reduced both after single and repeated CFS treatments (by 65% and 38%, respectively). CONCLUSIONS: Repeated use of CFS to reduce itch has no adverse effects on contact dermatitis.     

结晶型NiS诱发恶性转化细胞中的p16基因和FHIT基因的变化

目的 检测结晶型NiS诱发永生化人支气管上皮细胞系(16HBE)恶性转化过程中脆性组氨酸三联体基因(FHIT)和p16基因的变化,探讨镍化合物致癌的分子机制。方法 采用RT-PCR、DNA序列分析、银染PCR—SSCP方法检测恶性转化细胞、成瘤细胞中FHIT基因和p16基因的变化。结果 与对照组16HBE相比,转化细胞、成瘤细胞p16基因第2外显子、第2-3外显子末见突变,mRNA表达末见异常;FHIT基因第5,6,7,8外显子及第1-4外显子、第5-9外显子末见突变,但发现转化细胞、成瘤细胞FHIT基因的mRNA失表达或出现异常转录本;对其中FHIT基因第5-9外显子的一异常转录本测序分析显示,FHIT第6,7,8外显子缺失,第5,9外显子异常拼接,且中间插入一个36bp的小片段。结论 在结晶型NiS诱发16HBE恶性转化过程中,p16基因在DNA和mRNA水平末见异常改变,提示p16基因在镍致癌过程中可能不发挥作用;FHIT基因在mRNA水平出现缺失或异常转录本,表明FHIT基因在镍致癌过程中可能发挥一定作用;镍诱导的FHIT基因异常,可能是将外源致癌物、染色体脆性部位不稳定性和细胞恶变相联系起来的一个分子事件,FHIT基因可能是镍等外源致癌物作用的主要靶基因之一。     

Mortality experience among employees at a hydrometallurgical nickel refinery and fertiliser complex in Fort Saskatchewan, Alberta (1954-95)

OBJECTIVE—To study the mortality experience of workers at a hydrometallurgical nickel refinery and fertiliser complex in Fort Saskatchewan, Alberta, Canada.
METHODS—A total of 1649 male employees of Sherritt International who worked for at least 12 continuous months during the years 1954 to 1978 at the Fort Saskatchewan, Alberta hydrometallurgical nickel refinery and fertiliser complex were followed up for an additional 17 years. Mortality was ascertained from the Canadian mortality data base maintained by Statistics Canada and covered the years 1954-95. Statistics were analysed with Monson's computer program.
RESULTS—Total mortality, when compared with the Canadian population, was significantly below expectation. Fewer deaths were found for circulatory disease, ischaemic heart disease, respiratory disease, neoplasms, digestive cancer, and accidents, poisonings, and violence. Among the 718 men in the group exposed to nickel, there were no deaths due to nasal cavity or paranasal sinus cancer. Fewer deaths were found for all causes, circulatory disease, ischaemic heart disease, neoplasms and digestive cancer. Lower death rates were observed than expected for respiratory malignancies and cancer of the bronchus and lung.
CONCLUSION—No association was found in this study between exposure to nickel concentrate or metallic nickel in the hydrometallurgical refining process and the subsequent development of respiratory cancer.


Keywords: epidemiology; nickel workers; mortality