HNF1A gene mutations and premature ovarian failure (POF): evidence from a clinical paradigm combining MODY 3 and POF.

Premature ovarian failure (POF) defines the occurrence of ovarian failure prior to the age of 40. It occurs in one out of 100 women but is very rare before age 20 (1:10,000). Maturity-onset diabetes of the young (MODY), caused by mutations in the HNF1A gene, is also a rare disorder; all types of MODY account for 1-2% of adult diabetic cases. These two rare nosologic entities coexisted in an adolescent girl evaluated for delayed puberty. Although this combination could represent a chance association, an interrelation might exist. We examined HNF1A expression in human fetal and adult ovaries by immunohistochemistry using a polyclonal HNF1A antibody. HNF1A protein was expressed in both the fetal and adult human ovaries. Based on these findings, we hypothesize that HNF1A participates in ovarian organogenesis and/or function and that mutations in the HNF1A gene might represent another molecular defect causing POF, possibly in combination with other genetic factors. The study underlines the importance of rare clinical paradigms in leading the way to elucidation of the pathogenetic mechanisms of rare diseases.

Effects of Glucocorticoids on Bone: What we can Learn from Pediatric Endogenous Cushing's Syndrome.

Chronic exposure to supraphysiologic levels of glucocorticoids (GCs) is associated with impaired bone mineral density, an increase in fracture rates, and, in growing children, compromised linear growth. GCs inhibit bone formation in part by decreasing the number of osteoblasts and by increasing bone resorption by stimulating osteoclasts. While GCs are used to treat many chronic diseases, it is difficult to isolate the effects of the steroids on the bone from the effects of the underlying disease itself. Investigation into the effects of GC exposure on the bone in endogenous Cushing syndrome have contributed to our understanding of bone microarchitecture, growth, healing, and regeneration. We now know that GCs negatively impact bone marrow derived-mesenchymal stromal cells. In children with Cushing syndrome, the potential reversibility of deleterious effects of chronic GC exposure on bone provides insight into the pathophysiology behind pure GC excess.

Sucrose and dental caries: a review of the evidence.

The aim of this study was to conduct a review of the literature to assess the relationship between quantity and pattern of sucrose use and dental caries. Using hand and electronic methods (MEDLINE, EMBASE) the literature was searched for epidemiological papers concerning any relationship of sugars and dental caries published since 1856. Superficial hand searching was carried out between 1856 and 1940, detailed hand searching 1940-1966 and electronic 1966-2007. Selection criteria were set based on, but not confined to, Cochran style standards. Investigations were categorized as A, fulfilling all criteria; B1, relevant fulfilling 19 of 23 criteria; B2, relevant but fulfilling only between 12 and 18 of the selection criteria; and C, all other papers. There were 95 papers meeting most (more than 12) or all of the selected criteria. Only 1 paper was graded A; 31 as B1. There were in addition some 65 as B2 and all the rest as C, which were discarded. There were a wide variety of study designs and those graded A or B1 comprised 23 ecological cross-sectional, 7 cohort and 2 case control studies. Summary results showed that 6 papers found a positive, significant relationship of sugar quantity to dental caries, 19 of 31 studies reported a significant relationship of sugar frequency of use to dental caries. The balance of studies does not demonstrate a relationship between sugar quantity, but a moderately significant relationship of sugar frequency to dental caries.