Increased severity over generations of Charcot-Marie-Tooth disease type 1A

BACKGROUND: Charcot-Marie-Tooth type 1A (CMT1A) is an autosomal dominant polyneuropathy due to a 1.5 Mb tandem duplication in chromosome 17p11.2, containing the PMP22 gene. This mutation is not modified during inheritance. OBJECTIVES: We set forth to test the hypothesis that in a subgroup of CMT1A patients there is clinical anticipation, namely an increase in disease severity over generations. METHODS: Thirty-nine CMT1A mutation-positive patients in 16 families and 23 parent-offspring pairs were evaluated. This included 14 families with 2 generations and 2 families with 3 generations. Age of presentation was assessed by interviewing the patients and clinical severity was measured using the CMT neuropathy score (CMTNS). RESULTS: In 21/23 parent-child pairs and 14/16 families, there was an earlier age of presentation in children of genetically affected parents. The mean age of onset in the progeny was 12.61 years compared to 41.22 years in the parent generation, (p < 0.001).Mean severity in the younger generation was slightly higher than that of the parent generation. When corrected for the age difference, the trend for a worse phenotype in the younger generation became statistically significant (p < 0.02,Wilcoxon signed rank test). CONCLUSIONS: Our findings suggest that in a subgroup of CMT1A patients there is an increase in clinical severity over generations. The mechanism responsible for this observation remains unknown. Our findings should be validated on a larger cohort of CMT1A families.     

A review of the use of beeswax in skincare

Background

Beeswax is a naturally occurring product secreted from worker bees that has varied uses in modern day. In skincare, its function ranges from its role as an occlusive, helping to create a semi-occlusive skin barrier that minimizes transepidermal water loss; as a humectant, locking in hydration; and an emollient to soften and soothe the skin. As a natural substance, its use has been shown to help alleviate symptoms associated with common cutaneous conditions like dermatitis, psoriasis, and overgrowth of normal skin flora.

Aims

In this narrative review, we aim to describe current uses of beeswax in skincare that has been published in the literature.

Materials and methods

A review of beeswax related publications was performed by searching the PubMed database studies.

Results

A total of five clinical studies were included with three studies on animals and two studies in humans.

Discussion

Several studies show the benefits of topical beeswax in supporting the skin barrier.

Conclusion

Beeswax can be a low-cost, natural ingredient for use in products. Further studies with topical beeswax are warranted.     

Severe microcephaly with normal intellectual development: the Nijmegen breakage syndrome

A brother and sister are described with severe microcephaly of prenatal onset, normal intellectual and motor development, chromosomal breakage and cellular immunodeficiency, which is characteristic of the autosomal recessive condition, Nijmegen breakage syndrome. The proband was a girl who presented at 15 months, with normal developmental milestones and an extremely small head circumference of 36 cm. Twenty per cent of her lymphocytes showed spontaneous translocations involving chromosome 7p13, 7q35, 14q11, and 14q32. The lymphocytes also showed excessive x ray induced chromosome damage. She had T cell lymphopenia, but normal immunoglobulins, and a normal alpha fetoprotein. A brother was born shortly after her diagnosis was made. He also had extreme microcephaly of 28 cm, with similar spontaneous and x ray induced chromosomal breakage, and T cell lymphopenia. Neither child has clinical evidence of immunodeficiency. To test the hypothesis that Nijmegen breakage syndrome and ataxia telangiectasia are allelic disorders, haplotype analysis was carried out in the family using DNA markers spanning the AT locus on chromosome 11q22. The affected boy had a different haplotype from his affected sister. Thus in this family, the Nijmegen breakage syndrome is not allelic to the ataxia telangiectasia locus on chromosome 11q, and the two conditions are genetically distinct. The normal intellect in these children raises questions about normal brain development in the presence of severe microcephaly.     

Chemopreventive effects of 2-(allylthio)pyrazine on hepatic lesion, mutagenesis and tumorigenesis induced by vinyl carbamate or vinyl carbamate epoxide

2-(Allylthio)pyrazine (2-AP), synthesized for its possible use as a hepatoprotective agent, has been found to selectively inhibit rat hepatic cytochrome P450 2E1 (Kim et al., Biochem. Pharmacol., 53, 261- 269, 1997), while it enhances the activities of phase II detoxification enzymes such as glutathione S-transferase and epoxide hydrolase. As part of a program in evaluating the chemopreventive potential of 2-AP, we have determined its effects on hepatotoxicity, mutagenicity and tumorigenicity of vinyl carbamate (VC), a prototypic hepatocarcinogen preferentially activated by P450 2E1 to the ultimate carcinogenic metabolite vinyl carbamate epoxide (VCO), which undergoes detoxification by glutathione conjugation and oxirane hydrolysis. Administration of 2-AP (100 mg/kg body wt) to male Sprague-Dawley rats by gavage, 2 days, 1 day and 4 h prior to VC or VCO, markedly ameliorated the hepatotoxicity of these compounds as determined by decreased serum aspartate aminotransferase and alanine aminotransferase activities. Furthermore, 2-AP pre-treatment significantly suppressed the VC-induced hepatocarcinogenesis in infant male B6C3F1 mice. In a separate experiment, the multiplicities of skin tumors formed in female ICR mice treated with 5.8 micromol of VC or VCO were inhibited 58 and 70%, respectively, by pre-treatment with 2-AP by oral administration. The mutational spectrum of ras-oncogene in papillomas was not altered by 2-AP pre-treatment. 2-AP also inhibited the mutagenicity of VC in the Salmonella-microsome assay. Taken together, these findings suggest that 2-AP is a potential chemopreventive agent.      

Development and validation of a new instrument for testing functional health literacy in Japanese adults

This study aimed to develop a reliable and valid measure of functional health literacy in a Japanese clinical setting. Test development consisted of three phases: generation of an item pool, consultation with experts to assess content validity, and comparison with external criteria (the Japanese Health Knowledge Test) to assess criterion validity. A trial version of the test was administered to 535 Japanese outpatients. Internal consistency reliability, calculated by Cronbach's alpha, was 0.81, and concurrent validity was moderate. Receiver Operating Characteristics and Item Response Theory were used to classify patients as having adequate, marginal, or inadequate functional health literacy. Both inadequate and marginal functional health literacy were associated with older age, lower income, lower educational attainment, and poor health knowledge. The time required to complete the test was 10–15 min. This test should enable health workers to better identify patients with inadequate health literacy.