An epidemic of occupational contact dermatitis from an immersion oil for microscopy in laboratory personnel

Since November 1997, 14 successive cases of occupational contact dermatitis were observed in 13 laboratory technicians and 1 physician, working in a genetics laboratory in Leuven (Belgium) in 3 laboratories of bacteriology in Strasbourg, Montbeliard and Angers, and in the laboratory of hematology in Bordeaux (France). The dermatitis, located on the hands, forearms and face, relapsed after each exposure to an immersion oil for microscopy. Patch tests performed in 10 patients were positive to epoxy resin (ER) in the European standard series (10/10 patients) and to newly formulated Leica immersion oil (7/7), 1 patient testing negatively with the former oil. A breakdown performed in 2 patients with the oil's ingredients confirmed sensitization to liquid modified ER components, contained at >80% concentration in the oil. The presence of DGEBA was demonstrated by HPLC analysis at a +/-30% rate. Although the safety data sheet indicated a revision of the formula, nobody was alerted to the risk of sensitization and the need for skin protection. ERs, as a source of occupational allergy, can provoke epidemics of contact dermatitis in industry. This report of epidemic contact dermatitis from ERs, used for their optical properties in an immersion oil for microscopy, emphasizes the need for perpetual vigilance in occupational medicine and the usefulness of multicentre contacts in dermato-allergology.     

Selective activation of the fatty acid synthesis pathway in human prostate cancer

A substantial subset of breast, colorectal, ovarian, endometrial and prostatic cancers displays markedly elevated expression of immunohistochemically detectable fatty acid synthase, a feature that has been associated with poor prognosis and that may be exploited in anti-neoplastic therapy. Here, using an RNA array hybridisation technique complemented by in situ hybridisation, we report that in prostate cancer fatty acid synthase expression is up-regulated at the mRNA level together with other enzymes of the same metabolic pathway. Contrary to the observations that in many cell systems (including androgen-stimulated LNCaP prostate cancer cells) fatty acid and cholesterol metabolism are co-ordinately regulated so as to supply balanced amounts of lipids for membrane biosynthesis, storage or secretion, no changes in the expression of genes involved in cholesterol synthesis were found. These findings point to selective activation of the fatty acid synthesis pathway and suggest a shift in the balance of lipogenic gene expression in a subgroup of prostate cancers.     

Deodorants: an experimental provocation study with isoeugenol

Axillary dermatitis is common and overrepresented in people with contact allergy to fragrances. Many people suspect their deodorants to be the incriminating products. In order to investigate the significance of isoeugenol in deodorants for the development of axillary dermatitis when used by people with and without contact allergy to isoeugenol, patch tests with deodorants and ethanol solutions with isoeugenol, as well as repeated open application tests (ROAT) with roll-on deodorants with and without isoeugenol at various concentrations, were performed in 35 dermatitis patients, 10 without and 25 with contact allergy to isoeugenol. A positive ROAT was observed only in patients hypersensitive to isoeugenol (P<0.001) and only in the axilla to which the deodorants containing isoeugenol had been applied (P<0.001). Deodorants containing isoeugenol in the concentration range of 0.0063-0.2% used 2 times daily on healthy skin can thus elicit axillary dermatitis within a few weeks in people with contact allergy to isoeugenol.     

The influence of synovial fluid on adenovirus‐mediated gene transfer to the synovial tissue

Objective

To determine the effect of synovial fluid (SF) from rheumatoid arthritis (RA) patients on adenovirus type 5 (Ad5)–mediated gene transfer to synoviocytes, and to explore new strategies for vector development based on the neutralization data obtained.

Methods

SF was derived from 63 randomly selected RA patients. Ten samples were used to study the effect of SF on Ad5‐mediated gene transfer in synoviocytes. IgG and <100‐kd fractions were purified from these 10 SF, and their effect on gene transfer was determined. Neutralizing activity against wild‐type Ad5 (wt‐Ad5), wt‐Ad26, wt‐Ad34, wt‐Ad35, and wt‐Ad48 was tested in the SF from the remaining 53 patients.

Results

Seven of 10 SF samples inhibited Ad5‐mediated gene transfer. Purified antibodies exhibited inhibition patterns similar to those seen with unfractionated SF. In 5 of 10 SF samples, low molecular weight fractions inhibited gene transfer at low dilutions. Neutralization of wt‐Ad35 by SF from RA patients was less frequent than neutralization of other wt‐Ad tested (4% versus 42–72%; n = 53).

Conclusion

SF from 70% of the RA patients contained neutralizing antibodies that hamper Ad5‐mediated gene transfer to synoviocytes. The activity of neutralizing antibodies may be circumvented in the majority of RA patients when vectors based on an Ad35 backbone are used.

     

Factors influencing the reinforcing value of fruit and unhealthy snacks

Objective

The present study investigated the reinforcing value of healthy and unhealthy snack food in adolescents (n = 108, aged 14–16 years). Moderation by access to different foods, sex and the personality trait reward sensitivity is tested.

Methods

In a computerized Food Reinforcement Task, adolescents could earn portions of a healthy and an unhealthy snack following an identical progressive reinforcement schedule for both food types. Reinforcing value of food was indexed by the number of button presses for each food type. Participants were allocated randomly to two-order condition: fruit–snack versus snack–fruit. Reward sensitivity was assessed with the Dutch age-downward version of Carver and White’s BIS/BAS scale.

Results

Results showed that the reinforcing value of an unhealthy snack is higher than that of fruit, with participants making more button presses for unhealthy snacks, M = 1280.40, SD = 1203.53, than for fruit, M = 488.04, SD = 401.45, F(1,48) = 25.37, p < 0.001. This effect is stronger in boys (β = ?1367.67) than in girls (β = ?548.61). The effect is only present in the snack–fruit condition, not in the fruit–snack condition, indicating that access to food moderates the effect of food type. There is no evidence for moderation by reward sensitivity.

Conclusions

Results point to the importance of simultaneously increasing barriers to obtain unhealthy food and promoting access to healthy food in order to facilitate healthy food choices.

     

Severe resistance to insulin and insulin-like growth factor-I in cells from a patient with leprechaunism as a result of two mutations in the tyrosine kinase domain of the insulin receptor

We studied the biological properties of insulin receptors (IRs) and insulin-like growth factor-I (IGF-I) receptors in cultured fibroblasts from a patient with leprechaunism (leprechaun Par-1). Patient cells displayed normal insulin binding capacity and affinity. Basal in vivo auto phosphorylation and in vitro exogenous kinase activity of patient IRs were elevated twofold to threefold compared with control receptors, and insulin had no further effect on these processes. Moreover, patient IRs were unable to promote the stimulation of metabolic and mitogenic pathways. IR substrate-1 (IRS-1) and mitogen-activated protein (MAP) kinase tyrosine phosphorylation and glycogen and DNA synthesis were not increased in the basal state in patient fibroblasts and were also insensitive to the stimulatory effect of insulin. As for IGF-I, although binding and receptor kinase activity were normal, the ability to stimulate glycogen and DNA synthesis was altered in patient cells. Two mutant alleles of the IR gene were detected by denaturing gradient gel electrophoresis (DGGE) and direct sequencing. The maternal allele contained a point mutation in exon 18 encoding the tryptophan-for-arginine substitution at position 1092, and the paternal allele had a point mutation in exon 20 substituting lysine for glutamic acid at codon 1179. Thereby, leprechaun Par-1 was a compound heterozygote for two missense mutations located in the IR β-subunit. The present investigation provides the first evidence that leprechaunism can be causally related to structural alterations in the tyrosine kinase domain of the IR. These alterations result in severe impairment of insulin and IGF-I action.     

Muscle necrosis in the extremities: evaluation with Tc-99m pyrophosphate scanning--a retrospective review

A retrospective review was done of 34 extremities studied between 1981 and 1985 with technetium-99m pyrophosphate scanning; 22 were subsequently amputated. Results of detailed pathologic examination or immediate postoperative examination of the resected extremity were available in 16 cases. In these cases, scanning had allowed correct prediction of the level of amputation and of the specific areas of muscle infarction in 13 cases. In the one case in which amputation was performed for infection rather than muscle necrosis, the lack of necrosis was correctly predicted with the scan. The limited results of this study indicate that the Tc-99m pyrophosphate scan allows the location of necrotic muscle to be predicted accurately and may therefore be a useful adjunct in determining the best level for ultimate amputation. Special caution is required in those cases in which muscle necrosis is due to acute causes (e.g., traumatic thrombosis) rather than chronic vascular disease.     

Very low prevalence of germline MSH6 mutations in hereditary non-polyposis colorectal cancer suspected patients with colorectal cancer without microsatellite instability

Hereditary non-polyposis colorectal cancer (HNPCC) is caused by mutations in one of the mismatch repair genes MLH1, MSH2, MSH6, or PMS2 and results in high-level microsatellite instability (MSI-high) in tumours of HNPCC patients. The MSI test is considered reliable for indicating mutations in MLH1 and MSH2, but is questioned for MSH6. Germline mutation analysis was performed in 19 patients with an MSI-high tumour and absence of MSH2 and/or MSH6 protein as determined by immunohistochemistry (IHC), without an MLH1 or MSH2 mutation, and in 76 out of 295 patients suspected of HNPCC, with a non-MSI-high colorectal cancer (CRC). All 295 non-MSI-high CRCs were analysed for presence of MSH6 protein by IHC. In 10 patients with an MSI-high tumour without MSH2 and/or MSH6 expression, a pathogenic MSH6 mutation was detected, whereas no pathogenic MSH6 mutation was detected in 76 patients with a non-MSI-high CRC and normal MSH6 protein expression. In none of the 295 CRCs loss of MSH6 protein expression was detected. The prevalence of a germline MSH6 mutation is very low in HNPCC suspected patients with non-MSI-high CRC. Microsatellite instability analysis in CRCs is highly sensitive to select patients for MSH6 germline mutation analysis.     

The effects of antioxidant supplementation during Percoll preparation on human sperm DNA integrity

The integrity of sperm DNA is crucial for the maintenance of genetic health. A major source of damage is reactive oxygen species (ROS) generation; therefore, antioxidants may afford protection to sperm DNA. The objectives of the study were, first, to measure the effects of antioxidant supplementation in vitro on endogenous DNA damage in spermatozoa using the single cell gel electrophoresis (comet) assay and, second, to assess the effect of antioxidant supplementation given prior to X-ray irradiation on induced DNA damage. Spermatozoa from 150 patients were prepared by Percoll centrifugation in the presence of ascorbic acid (300, 600 microM), alpha tocopherol (30, 60 microM), urate (200, 400 microM), or acetyl cysteine (5, 10 microM). DNA damage was induced by 30 Gy X-irradiation. DNA strand breakage was measured using the comet assay. Sperm DNA was protected from DNA damage by ascorbic acid (600 microM), alpha tocopherol (30 and 60 microM) and urate (400 microM). These antioxidants provided protection from subsequent DNA damage by X-ray irradiation. In contrast, acetyl cysteine or ascorbate and alpha tocopherol together induced further DNA damage. Supplementation in vitro with the antioxidants ascorbate, urate and alpha tocopherol separately has beneficial effects for sperm DNA integrity.      

Successful biventricular cardiac resynchronization therapy in a failing Fontan patient: Implications of ventriculo‐ventricular interdependency in single ventricle physiology

We describe a Fontan patient with severe heart failure who was successfully treated with biventricular cardiac resynchronization therapy (CRT). Our case shows that strain imaging might play a crucial role in guiding placement of pacing leads and in characterizing the electromechanical substrate associated with a favorable CRT response. Furthermore, we demonstrate for the first time that ventriculo‐ventricular interdependency seems an important mechanical concept, which can be utilized to augment cardiac performance in failing Fontan patients with a functional hypoplastic ventricle.