Myopia is a common, complex trait with considerable economic and social impact and, in highly affected individuals, ocular morbidity. We performed a classic twin study of 506 unselected twin pairs and inferred the heritability of refractive error to be 0.89 (95% confidence interval 0.86-0.91). A genomewide scan of 221 dizygotic twin pairs, analyzed by use of optimal Haseman-Elston regression methods implemented by use of generalized linear modeling, showed significant linkage (LOD >3.2) to refractive error at four loci, with a maximum LOD score of 6.1 at 40 cM on chromome 11p13. Evidence of linkage at this locus, as well as at the other linkage peaks at chromosomes 3q26 (LOD 3.7), 8p23 (LOD 4.1), and 4q12 (LOD 3.3), remained the same or became stronger after model fit was checked and outliers were downweighted. Examination of potential candidate genes showed the PAX6 gene directly below the highest peak at the 11p13 locus. PAX6 is fundamental to identity and growth of the eye, but reported mutations usually result in catastrophic congenital phenotypes such as aniridia. Haplotype tagging of 17 single-nucleotide polymorphisms (SNPs), which covered the PAX6 gene and had common minor allele frequencies, identified 5 SNPs that explained 0.999 of the haplotype diversity. Linkage and association analysis of the tagging SNPs showed strong evidence of linkage for all markers with a minimum chi 21 of 7.5 (P=.006) but no association. This suggests that PAX6 may play a role in myopia development, possibly because of genetic variation in an upstream promoter or regulator, although no definite association between PAX6 common variants and myopia was demonstrated in this study.

The CYP 17 and CYP 19 genes encode 17alpha-hydroxylase/17,20-lyase and aromatase, respectively, both involved in sex hormone synthesis. We investigated the association between 2 common polymorphisms in 1) the promoter region (T-->C substitution) of CYP 17, and 2) exon 3 (G-->A) of CYP 19, bone mineral density (BMD) and serum androgen/estradiol, in a case-control study of 252 postmenopausal women aged 64.5 +/- 9.2 yr (mean +/- SD). There was no significant difference in serum estradiol concentrations between cases (n = 136) and controls (n = 116). The CYP 19 genotype was significantly associated with serum estradiol (P = 0.002). Women with the AA genotype had higher serum estradiol concentrations compared with those with the GG genotype (P = 0.03). In older women, those with the CYP 19 GA and GG genotypes had an increased prevalence of osteoporosis (P = 0.04) and fractures (P = 0.003). We found no significant association between CYP 17 genotype and serum androgens and estradiol concentrations. However, a significant association was seen between BMD values at the femoral neck with CYP 17 genotype in cases (P = 0.04) and in the whole study population (P = 0.012). Subjects with the CC genotype had significantly lower BMD (mean +/- SD: TT, 0.7 +/- 0.16; CC, 0.6 +/- 0.08 g/cm(2); P = 0.006). In conclusion, both CYP 17 and CYP 19 are candidate genes for osteoporosis in postmenopausal women.

Oestrogen inhibits bone resorption, at least in part, by regulating the production of several cytokines, including interleukin-6 (IL-6), IL-1, receptor activator of nuclear factor B ligand (RANKL) and osteoprotegerin (OPG) by cells of the osteoblastic lineage. The selective oestrogen receptor modulator raloxifene (RAL) acts on bone in a similar manner to oestrogen, although the mechanisms of action of RAL on osteoblasts still remain unclear. We investigated and compared the effects of 17-oestradiol (E 2 ) and RAL on the regulation of IL-6, IL-1, RANKL and OPG in vitro in primary human osteoblastic (HOB) cells and in an immortalised clonal human bone marrow stromal cell line (HCC1) with osteoblastic characteristics. We tested E 2 and RAL at concentrations ranging from 10 -12 to 10 -6 M. IL-6, IL-1 and IL-1 , OPG and RANKL were measured by ELISA. RANKL and OPG mRNA steady state level was assessed by quantitative PCR analysis. Both E 2 and RAL led to a significant reduction in IL-6 production in the HOB cells, although the effect was more marked with E 2 (P<0·05). IL-1 and IL-1 also decreased significantly following treatment with E 2 and RAL in the HCC1 cells (E 2 (10 -8

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We examined changes in the nutritional status of elderly patients with chest infection for a period of 3 months after discharge from hospital, including the effects of nutritional supplementation on well-being and functional status as well as on nutritional indices. Eighty-one subjects admitted to an acute medical ward aged 65 years and over with chest infection were recruited consecutively, and randomized to receive supplement (500 ml of Ensure liquid daily) for 1 month, or no supplement, on discharge. Assessment at baseline, 1, 2 and 3 months included a questionnaire to determine health, mental and functional status, and anthropometric measurements. Biochemical nutritional status was assessed at baseline, 1 and 3 months, and dietary intake (24 h recall method) at 1 and 3 months. During recovery, both supplement and non-supplement groups showed improvement in various measures of well-being and biochemical status. In addition, the former group showed improvement in more anthropometric measurements, in thiamine and pyridoxine status, while the non-supplement group showed a lower level of functional ability after 3 months. Various measures of well-being and biochemical status of the water-soluble vitamins were better in the supplement groups. We conclude that nutritional supplementation may have a role in helping elderly patients to recover from chest infections.

Plasma total T4 (TT4), T3 (TT3), free T4 (FT4), free T3 (FT3), thyroxine binding globulin, hCG, and erythrocyte zinc content were measured in 43 women with uncomplicated pregnancy and in 71 patients admitted with hyperemesis gravidarum. Plasma concentration of thyroid hormones in hyperemesis subjects showed wide variability and 32% of subjects had high TT4 (higher than mean +2 sd of normal pregnant subjects), 33% had high FT4, 20% had high TT3, and 20% had high FT3. Red cell zinc content, a tissue marker of thyroid status, in the hyperthyroxinemic subjects was not different from that of normothyroxinemic hyperemesis subjects or of subjects with uncomplicated pregnancy. The elevated TT4 concentration decreased spontaneously in all but two of the hyperemesis subjects to normal pregnant levels. The plasma FT4 concentration at presentation correlated with plasma hCG in hyperemesis gravidarum (partial correlation coefficient r = 0.411, P< 0.01), but not in normal pregnancy (partial correlation coefficient r = 0.043) after allowing for the effect of gestational age. We conclude that approximately one third of hyperemesis subjects show transient hyperthyroxinemia and suggest that hCG or a molecular variant of hCG may stimulate the thyroid gland. Nausea and vomiting are common symptoms in pregnancy and occur in over 50% of pregnant women (Evans et al. 1986). Hyperemesis gravidarum, however, is relatively rare and occurs in about 0.2% of all pregnancies in Hong Kong (Chin et al.