Can exposure limitations for well‐known contact allergens be simplified? An analysis of dose–response patch test data

Background. Allergic contact dermatitis is triggered by chemicals in the environment. Primary prevention is aimed at minimizing the risk of induction, whereas secondary and tertiary prevention are aimed at reducing elicitation. Objectives. To identify the elicitation doses that will elicit an allergic reaction in 10% of allergic individuals under patch test conditions (ED₁₀ patch test) for different allergens, and to compare the results with those for different allergens and with animal data indicating sensitizing potency from the literature. Materials and methods. The literature was searched for patch test elicitation studies that fulfilled six selected criteria. The elicitation doses were calculated, and fitted dose–response curves were drawn. Results. Sixteen studies with eight different allergens–methylchloroisothiazolinone/ methylisothiazolinone, formaldehyde, nickel, cobalt, chromium, isoeugenol, hydroxyiso hexyl 3‐cyclohexene carboxaldehyde, and methyldibromo glutaronitrile–were selected. The median ED₁₀ value was 0.835 µg/cm². The ED₁₀ patch test values were all within a factor of 7 from the lowest to the highest value, leaving out three outliers. No obvious patterns between the sensitization and elicitation doses for the allergens were found. Conclusions. We found a rather small variation in the ED₁₀ patch test between the allergens, and no clear relationship between induction potency and elicitation threshold of a range of allergens. This knowledge may stimulate thoughts on introducing a generic approach for limitations in exposure to well‐known allergens.     

Analysis of polymorphisms in the circadian-related genes and breast cancer risk in Norwegian nurses working night shifts

Introduction

Some studies have suggested that night work may be associated with an increased risk of breast cancer in nurses. We aimed to explore the role of circadian gene polymorphisms in the susceptibility to night work-related breast cancer risk.

Methods

We conducted a nested case-control study of Norwegian nurses comprising 563 breast cancer cases and 619 controls within a cohort of 49,402 Norwegian nurses ages 35 to 74 years. We studied 60 single-nucleotide polymorphisms (SNPs) in 17 genes involved in the regulation of the circadian rhythm in cases and controls. The data were analyzed in relation to the two exposure variables "maximum number of consecutive night shifts ever worked" and "maximum number of consecutive night shifts worked for at least 5 years." The odds of breast cancer associated with each SNP was calculated in the main effects analysis and in relation to night shift work. The statistically significant odds ratios were tested for noteworthiness using two Bayesian tests: false positive report probability (FPRP) and Bayesian false discovery probability (BFDP).

Results

In the main effects analysis, CC carriers of rs4238989 and GG carriers of rs3760138 in the AANAT gene had increased risk of breast cancer, whereas TT carriers of BMAL1 rs2278749 and TT carriers of CLOCK rs3749474 had reduced risk. The associations were found to be noteworthy using both the FPRP and BFDP tests. With regard to the effect of polymorphisms and night work, several significant associations were observed. After applying FPRP and BFDP in women with at least four night shifts, an increased risk of breast cancer was associated with variant alleles of SNPs in the genes AANAT (rs3760138, rs4238989), BMAL1 (rs2290035, rs2278749, rs969485) and ROR-b (rs3750420). In women with three consecutive night shifts, a reduced risk of breast cancer was associated with carriage of variant alleles of SNPs in CLOCK (rs3749474), BMAL1 (rs2278749), BMAL2 (rs2306074), CSNK1E (rs5757037), NPAS2 (rs17024926), ROR-b (rs3903529, rs3750420), MTNR1A (rs131113549) and PER3 (rs1012477).

Conclusions

Significant and noteworthy associations between several polymorphisms in circadian genes, night work and breast cancer risk were found among nurses who had worked at least three consecutive night shifts.     

Serum IgE Antibodies to the Scabies Mite

ABSTRACT: Porcine scabies, mites, Sarcoptes scabiei var. suis are more readily available in sufficient quantities than are human scabies mites. Circulating IgE antibodies specific to porcine scabies mites were found in 6 (30%) of 20 scabies patients with an RAST score of at least 2. Seven patients had elevated serum total IgE levels. Correlation between the RAST values, the duration of pruritus, and the IgE levels was not found. The results do not prove the existence of antibodies specific to porcine scabies mites but strongly support this assumption.     

Responses of neurons in the inferior colliculus of the rat to AM and FM tones

The responses of units in the inferior colliculus of the urethane-anaesthetized rat were recorded extracellularly. They responded to sinusoidal AM and FM tones with a modulation of their spike discharge usually at the same, or occasionally at twice, the modulation rate of the stimulus. The modulation depth of the response initially increased with the modulation depth of the stimulus, hut usually saturated or decreased at higher stimulus depths. The units showed a bandpass tuning to stimulus modulation rate which was independent of modulation depth and, in all cases, the most effective modulation rate was below 120 Hz. The modulated response to temporally varying stimuli could not be predicted from the pure tone discharge patterns or, in some cases, the unit's mean firing rate to modulated tones; temporally varying stimuli gave temporally varying responses. When compared with the data available from units at other levels in the auditory system, the results indicate a trend in which units at successively higher levels in the pathway respond most effectively to progressively lower rates of modulation.     

Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study

Rationale, aims and objectives Many clinical guidelines for cardiovascular disease (CVD) prevention contain risk estimation charts/calculators. These have shown a tendency to overestimate risk, which indicates that there might be theoretical flaws in the algorithms. Total cholesterol is a frequently used variable in the risk estimates. Some studies indicate that the predictive properties of cholesterol might not be as straightforward as widely assumed. Our aim was to document the strength and validity of total cholesterol as a risk factor for mortality in a well‐defined, general Norwegian population without known CVD at baseline. Methods We assessed the association of total serum cholesterol with total mortality, as well as mortality from CVD and ischaemic heart disease (IHD), using Cox proportional hazard models. The study population comprises 52 087 Norwegians, aged 20–74, who participated in the Nord‐Trøndelag Health Study (HUNT 2, 1995–1997) and were followed‐up on cause‐specific mortality for 10 years (510 297 person‐years in total). Results Among women, cholesterol had an inverse association with all‐cause mortality [hazard ratio (HR): 0.94; 95% confidence interval (CI): 0.89–0.99 per 1.0 mmol L^?1 increase] as well as CVD mortality (HR: 0.97; 95% CI: 0.88–1.07). The association with IHD mortality (HR: 1.07; 95% CI: 0.92–1.24) was not linear but seemed to follow a ‘U‐shaped’ curve, with the highest mortality <5.0 and ≥7.0 mmol L^?1. Among men, the association of cholesterol with mortality from CVD (HR: 1.06; 95% CI: 0.98–1.15) and in total (HR: 0.98; 95% CI: 0.93–1.03) followed a ‘U‐shaped’ pattern. Conclusion Our study provides an updated epidemiological indication of possible errors in the CVD risk algorithms of many clinical guidelines. If our findings are generalizable, clinical and public health recommendations regarding the ‘dangers’ of cholesterol should be revised. This is especially true for women, for whom moderately elevated cholesterol (by current standards) may prove to be not only harmless but even beneficial.     

Book Review

Implantable Cardioverter-Defibrillators. A Comprehensive Textbook. N.A. Mark Estes III Antonis S. Manolis, Paul J. Wang. 929 pp. Marcel Dekker Co., New York, ISBN: 0-8247-9194-0. US $195.00     

Brown Bowel Syndrome

The brown bowel syndrome (BBS) is a rare disease characterized by malabsorption and accumulation of lipofuscin in the smooth muscle cells of the muscularis externa of the small intestine. Recently, we incidentally observed a case of BBS in a colon operated on because of a neoplasm. Our ultrastructural investigation, which demonstrated changes in the mitochondria, further supports the significance of mitochondrial damage in BBS.     

Observer variability in the assessment of type and dysplasia of colorectal adenomas,analyzed using kappa statistics

PURPOSE: The aim of this study was to establish the intraobserver and interobserver variability in the assessment of histologic type (tubular, villous, and tubulovillous) and grade of cytologic dysplasia (mild, moderate, and severe) in colorectal adenomas. METHODS: One hundred eighty-seven slides of adenomas were assessed twice by three experienced pathologists, with an interval of two months. Results were analyzed using kappa statistics. RESULTS: For agreement between first and second assessment (both type and grade of dysplasia), kappa values for the three specialists were 0.5345, 0.9022, and 0.4100, respectively. Agreement was better for type than for dysplasia. The strength of agreement was moderate for Observers A and C and almost perfect for Observer B. Agreement between all three observers was seen in 35.2 percent for both type and dysplasia in 61 percent for type and in 47.8 percent for dysplasia. The kappa values for Observer A vs. B and Observer C vs. B were 0.3480 and 0.3770, respectively (both type and dysplasia). Values for type were better than for dysplasia, but agreement was only fair to moderate. CONCLUSION: The interobserver agreement was moderate to almost perfect, but the intraobserver agreement was only fair to moderate. A simpler classification system or a centralization of assessments would probably increase kappa values.Supported by grants from the Danish Cancer Society, Danish Medical Research Council (Grant 12-6355), Thomas Bartholin's Fund, Gundelach Meller's Fund, and Emmy Lange, born Kramp's Fund.