Oral findings in Carpenter syndrome.

Acrocephalopolysyndactyly Type II (Carpenter Syndrome) is determined by autosomal recessive inheritance. Only some 40 cases have been described. Variable clinical signs have been described including prolonged retention of primary teeth and hypodontia. This paper describes the oral and dental findings in a family containing two affected brothers. The family pedigree is informative, as the mother has had children by three partners. The two affected individuals are full brothers. The first affected brother has delayed dental development, severe hypodontia and small tooth crown size. Mesio-distal and bucco-lingual dimensions were measured on the study models and compared with population data. The younger brother also has delayed dental development but only mild hypodontia. Their half sister has severe hypodontia but no signs of Carpenter Syndrome. This family study demonstrates two affected individuals with typical clinical features and a pedigree compatible with autosomal recessive inheritance. Small tooth crown size has been shown by standardized measurement and evidence advanced that hypodontia is not part of the syndrome but a coincidental finding which segregates independently. We have also shown that the marked delay in emergence of teeth is associated more with problems of tooth eruption, possibly related to the bony abnormalities, than to a generalized delay in dental development.

Inhibition of breast cancer tissue aromatase activity and estrogen concentrations by the third-generation aromatase inhibitor vorozole.

In about one-third of advanced breast cancers, estrogen deprivation causes tumor regression. Estrogen concentrations in tumor tissue seem to depend largely on local production. The aromatase enzyme complex is thought to be the key enzyme in this respect. In the present study, the effect of the new third-generation nonsteroidal aromatase inhibitor vorozole (Rivizor) on tumor tissue aromatase activity and estrogen concentrations was evaluated. During 7 days preceding mastectomy, 11 postmenopausal breast cancer patients were treated with 2.5 mg of vorozole once daily. Eight patients could be evaluated. Intratumoral aromatase activity and estrone and estradiol levels were measured and compared to the values of nine untreated postmenopausal breast cancer patients. In treated patients, median tissue aromatase activity was 89% lower than that in controls (P < 0.001). Similarly, median tissue estrone and estradiol concentrations were 64 and 80% lower, respectively, in treated patients (P = 0.001 and P < 0.05, respectively). These results support the hypothesis that depleting the tumor of estrogens, thus impairing estrogenic stimulation, is an important mechanism in the antitumor activity of aromatase inhibitors.

High-affinity growth hormone binding protein, insulin-like growth factor I and insulin-like growth factor binding protein 3 in adults with growth hormone deficiency.

The high-affinity growth hormone binding protein (GHBP) circulates in human blood and represents the extracellular domain of the growth hormone (GH) receptor. The effects of GH deficiency on GHBP in adults are not clear. The aim of this study was to evaluate serum GHBP levels in adults with GH deficiency and to assess whether GHBP measurement may contribute to the diagnosis of adult GH deficiency, based on a two-step model. We measured insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP-3) and GHBP levels in serum samples of 36 patients with adult-onset GH deficiency. The GHBP levels were measured by FPLC size-exclusion chromatography; IGF-I and IGFBP-3 levels were measured by RIA. Serum GHBP levels were elevated above the upper limit of the 95% confidence interval in 26 patients, whereas IGF-I and IGFBP-3 levels were low in 10 patients and in 16 patients, respectively. The combination of low serum IGF-I and low IGFBP-3 levels was found in 10 patients. In nine patients, serum IGF-I levels were low, with elevated GHBP levels. Low serum IGF-I, low IGFBP-3 and elevated GHBP levels were found in five patients. Only four out of 36 patients had serum IGF-I, IGFBP-3 and GHBP levels that were within the 95% confidence interval of the control values. We conclude that adults with acquired GH deficiency have elevated GHBP levels in comparison to healthy subjects. We suggest that measurement of GHBP levels might contribute to the diagnosis of adult GH deficiency, though further research is required to study the additional value of GHBP measurements.

Iron-deficiency anaemia in young children requiring dental extractions under general anaesthesia.

The aim of the study was to determine the prevalence of iron-deficiency anaemia in children less than 6 years of age who attended for outpatient general anaesthesia for dental extractions. Pre- or peri-operative capillary blood samples were taken from 109 children (70 white Caucasian and 39 ethnic-minority children). The haemoglobin concentration (Hb), mean cell volume (MCV) and red cell porphyrin (RCP) value were determined for each subject. 19% of the children were found to be anaemic (Hb < 11 g/dl) and there was no statistically significant difference for mean Hb or prevalence of anaemia between white Caucasian and ethnic-minority children. A significantly greater proportion of the ethnic-minority children were iron deficient, as indicated by low MCV and high RCP. There were no statistically significant differences between anaemic and non-anaemic subjects with regard to sex or social class, but a significantly greater mean number of extractions were performed in the anaemic children.

The onset of eruption of permanent teeth amongst South African Indian children.

A total of 1036 Indian children were examined to determine the mean ages of eruption for the first permanent molars, and the permanent central and lateral incisors. The youngest observed age for the eruption of any permanent tooth was 5.00 years for girls and 4.94 for boys. Mandibular teeth erupted earlier than maxillary teeth and teeth in females erupted between 1 and 6 months earlier than in males. Comparison of the results of the present study to one in South African black children showed that Indian children's teeth erupt some 3.5-7 months later than those of black children, a difference that was statistically significant.

The onset of eruption of the permanent dentition amongst South African black children.

One thousand and twenty-four children with a mean age of 6.41 yr were examined to determine the mean ages of eruption for the first permanent molars and the permanent central and lateral incisors. The youngest observed age for the eruption of any permanent tooth amongst girls was 4.50 yr and amongst boys, 4.31 yr. The eruption ages were on the whole later than those reported in most African studies, but were very similar to those found for Kenyan African and American blacks.

Regulation of growth and epidermal growth factor receptor levels of LNCaP prostate tumor cells by different steroids.

The growth of LNCaP cells, derived from a lymph-node carcinoma of the human prostate, was stimulated by different hormones. Optimal growth (3- to 4-fold increase in DNA content per culture versus controls) was observed at 0.1 nM R1881 (a synthetic androgen), 1 nM progesterone or 10 nM estradiol. Triamcinolone acetonide had no effect. Dihydrotestosterone maximally stimulated cell growth at 10 nM. When the culture medium was changed 4 times in 6 days instead of twice, optimal growth was observed at 1 nM dihydrotestosterone. This indicates that a rapid metabolism of dihydrotestosterone influenced growth response. LNCaP cells contained considerable amounts of androgen receptors (920 fmol/mg cytosol protein) while progestagen, estrogen and glucocorticoid receptors were absent. The affinity of steroids for the androgen receptor decreased in the order of: R1881 (relative binding affinity: 100.0) greater than dihydrotestosterone (67.7) greater than progesterone (29.4) greater than testosterone (23.8) greater than estradiol (4.3) greater than triamcinolone acetonide (less than 0.1). Effects on cell growth of these steroids paralleled their affinity for the androgen receptor. The number of EGF receptors per cell increased in a dose-dependent manner upon treatment with various hormones. Again the amount of steroid needed for maximal effects reflected the affinity of the steroid for the androgen receptor. An approximately 2-fold increase in EGF receptor number was observed within 24 hr and before an increase in growth could be detected. Actinomycin-D and cycloheximide inhibited the hormonally induced increase in EGF receptor numbers.

Fluorescent ligands, used in histocytochemistry, do not discriminate between estrogen receptor-positive and receptor-negative human tumor cell lines.

A cell line containing estrogen receptors (MCF-7) and a cell line lacking estrogen receptors (PC-93) were used for a comparison of biochemical and histochemical procedures to detect estrogen receptors. We evaluated three different fluorescent estrogen derivatives: 17 beta-estradiol-6-carboxymethyloxime-bovine serum albumin-fluorescein isothiocyanate, 17 beta-estradiol-17-hemisuccinate-fluoresceinamine, and coumestrol. The main results were: The relative binding affinities of these ligands for the estrogen receptor were between 0.1 and 2% of the affinity of estradiol. Fluorescent staining of the cells showed no relation to the presence of estrogen receptors. Staining was not suppressed with excess estradiol-17 beta, which is known to prevent binding of low affinity ligands to estrogen receptors. Cells with intact membranes were not stained after treatment with the albumin-linked estrogen derivative; only cells with damaged cell membranes were stained. Treatment of cells with 17 beta-estradiol-17-hemisuccinate-fluoresceinamine resulted in a fluorescent labeling of the cytoplasm in intact and artificially damaged cells. Coumestrol caused only fluorescence of the cytoplasm in intact cells. It is concluded that estrogen receptors cannot be detected with these low affinity ligands. Fluorescence of these cells is probably due to binding of the ligands to low affinity binding sites. The presence of these low affinity binding sites appears not to be related to the presence or absence of estrogen receptors and can therefore not be used to discriminate between estrogen receptor-positive and receptor-negative tumor cells.

Fluorescent androgen derivatives do not discriminate between androgen receptor-positive and -negative human tumor cell lines.

For the evaluation of histochemical procedures for detection of androgen receptors, three human tumor cell lines have been used: PC-93 and NHIK-3025, both biochemically characterized as androgen receptor-positive, and EB-33, biochemically characterized as androgen receptor-negative. The binding of three fluorescent ligands, testosterone-17 beta-hemisuccinate-bovine serum albumin-fluorescein isothiocyanate, testosterone-17 beta-hemisuccinate-fluoresceinamine, and 5 alpha-dihydrotestosterone-17 beta-hemisuccinate-fluoresceinamine, to the cells was evaluated. The relative binding affinities of the ligands for the androgen receptors were low (less than 5% when compared to methyltrienolone). Treatment of the cells with the androgen-fluoresceinamine derivatives resulted in a fluorescent labeling of the cytoplasm in both intact and "freeze-damaged" cells of the three cell lines. This staining was independent of the presence of receptors. Nuclei were not stained. Incubation of intact cels with the protein-linked conjugate did not result in significant cellular fluorescence. Only cells with damaged membranes showed a positive histochemical reaction, both in nucleus and cytoplasm, irrespective of the receptor content of the cells. The fluorescence intensity was not suppressed with excess 5 alpha-dihydrotestosterone or methyltrienolone, which are known to prevent binding of low affinity ligands to androgen receptors. From these results it is concluded that androgen receptors cannot be detected by these fluorescent ligands with low affinity for the receptor. The observed fluorescence of the cells is therefore due to binding of the ligands to other binding sites. The visualization/histochemical demonstration of these binding sites does not appear to be related to the presence of androgen receptors.

Prevalence of chronic periodontitis in 13-15-year-old children. A radiographic study.

The bitewing radiographs of 1,731 English and Danish schoolchildren aged 13--15 years were examined to assess the prevalence of chronic periodontitis. Only one child (0.06%) was found to be affected in comparison with the high prevalence of 51.5% reported by Hull et al. (1975). Minute qualitative changes in the radiographic appearance of the alveolar crest, or changes in the visual representation of the width of the periodontal ligament space are not reliable or valid criteria for assessing chronic periodontitis. Horizontal bone loss observed on radiographs, which can be accurately measured using the cemento-enamel junction as a reference point, is a useful diagnostic criterion for the measurement of chronic periodontitis.