Analysis of phenotypic features and FGFR2 mutations in Apert syndrome

A phenotypic and genotypic survey was conducted on 36 Apert syndrome patients. In all but one patient, an FGFR2 mutation, either S252W or P253R, was found in exon IIIa (exon U or 7). The frequency was 71% and 26%, for the mutations S252W and P253R, respectively. These mutations occur in the linker region between immunoglobulin-like domains II and III, which are involved in activation of the receptor by ligand binding and dimerization. The fact that one patient did not have a mutation in the same exon suggests further genetic heterogeneity in Apert syndrome. The frequencies of occurrence or means for measurements of 29 different clinical features (including severity of craniofacial features, syndactyly of the hands and feet, and multisystem involvement) were determined for all patients and for the two subgroups defined by their mutations. Comparison between the subgroups for the different clinical features was performed and suggested no statistically significant differences. These results are not unexpected, because the two common mutations for Apert syndrome alter FGFR2 at adjacent amino acids that are likely to have similar biological, and therefore phenotypic, consequences.     

Volume control: a reliable option in the management of ''refractory'' congestive heart failure

Light microscopic and ultrastructural features of a well-differentiated malignant cylindroma are described. The tumor was locally invasive but it neither recurred nor metastasized during the 3 years after surgery. This fact, together with the similar biologic behavior of two previously described, well-differentiated malignant cylindromas, suggests that these tumors possess either low or no metastatic potential.     

Estrogen and progesterone receptor status as prognostic indicators in patients with optimally cytoreduced stage IIIc serous cystadenocarcinoma of the ovary

BACKGROUND: Steroid receptor status as a prognostic indicator in gynecologic malignancies has been a focus of study for almost 20 years. Although shown to be of importance in assessing prognosis in some patients with endometrial cancer, their importance in assessing prognosis in patients with serous cystadenocarcinoma of the ovary is not established. METHODS: All cases of stage IIIc serous cystadenocarcinoma of the ovary operated on by the gynecologic oncology service from January 1, 1981, through December 31, 1989, were evaluated for their estrogen and progesterone receptor status, time to recurrence, length of survival, and level of primary cytoreduction as well as FIGO stage, grade, and histology, Fresh tissue was obtained and frozen at the time of surgery for the steroid assays. RESULTS: Ninety-six patients who had optimal primary cytoreductive surgery for their stage IIIc serous cystadenocarcinomas of the ovary and had their estrogen and progesterone receptor status established were found. Patients with an estrogen receptor level of less than or equal to 10 fmol/mg cytosol protein were shown to have a better mean survival (41 months) than patients with estrogen receptor levels greater than 10 fmol/mg cytosol protein (34 months) (P = 0.015). Five-year survival in the former group (38 patients) was 39.5% while 5-year survival in the latter group (58 patients) was 10.3% (P = 0.001). The was no correlation between progesterone status and survival (P > 0.05) in that same cohort of patients. CONCLUSIONS: In patients with optimally cytoreduced stage IIIc serous cystadenocarcinoma of the ovary, an estrogen receptor level of less than or equal to 10 fmol/mg cytosol protein may be indicative of a better prognosis. Progesterone receptor status does not appear to affect survival.     

Femoral and lateral femoral cutaneous nerve block for muscle biopsies in children

OBJECTIVE: Unintentional injuries are the number one cause of death for infants. Many of these injuries could be prevented if parents took additional safety precautions. In this study physicians' and parents' perspectives regarding the part that physicians play in educating first time parents about child safety issues were compared. METHODS: All pediatricians and family physicians in London, Ontario were surveyed by mail (68% return rate) regarding their practices, attitudes, and beliefs related to parent education about child safety issues. A sample of 114 first time mothers, including 38 each with 6, 12, and 18 month old infants, completed a telephone interview. All parents had physicians who had returned questionnaires. RESULTS: There was good correspondence between parents' and physicians' judgments about the safety issues most often covered, and what role physicians should adopt regarding parent education about child safety issues. In addition, they both agreed that parents seldom seek out safety information by asking questions. Relative to parent reports, however, physicians significantly overestimated the time they spent on safety issues and the degree of their direct involvement in communicating this information. The best predictor of time spent by physicians on safety issues was their rating of the importance of assuming the role of parent educator. The best predictor of parents asking questions about child safety was their rating of the adequacy of physicians' responses to previously asked questions. CONCLUSIONS: The results suggest that both physicians and parents contribute to undermine communication about child safety during well-baby visits.     

Transmission ionization chambers for measurements of air collision kerma integrated over beam area. Factors limiting the accuracy of calibration

Kerma-area product meters (KAP meters) are frequently used in diagnostic radiology to measure the integral of air-collision kerma over an area A (integral of A Kc,air dA) perpendicular to the x-ray beam. In this work, a precise method for calibrating a KAP meter to measure integral of A Kc,air dA is described and calibration factors determined for a broad range of tube potentials (40-200 kV). The integral is determined using a large number of TL dosimeters spread over and outside the nominal field area defined as the area within 50% of maximum Kc,air. The method is compared to a simplified calibration method which approximates the integral by multiplying the kerma in the centre of the field by the nominal field area Anom. While the calibration factor using the precise method is independent of field area and distance from the source, that using the simplified method depends on both. This can be accounted for by field inhomogeneities caused by the heel effect, extrafocal radiation and scattered radiation from the KAP meter. The deviations between the calibration factors were as large as +/- 15% for collimator apertures of 5-100 cm2 and distances from the source of 50-160 cm. The uncertainty in the calibration factor using the precise method was carefully evaluated and the expanded relative uncertainty estimated to be +/- 3% with a confidence level of 95%.     

Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening

V79 (Chinese hamster lung fibroblast) cell lines expressing a functional recombinant phenobarbital-inducible rat liver UDP-glucuronosyltransferase (UGT), i.e., UGT2B1, were established. Western blot analysis of positive colonies, using anti-rat liver UGT antibodies, revealed the presence of an immunoreactive polypeptide of the expected molecular mass of 52 kDa. The substrate specificity of the recombinant enzyme toward > 100 compounds was determined. Phenolic and alcoholic substrates included 4-methylumbelliferone, 4-hydroxybiphenyl, chloramphenicol, and testosterone, but a range of carboxylic acids of both endogenous (medium-chain saturated fatty acids, long-chain polyunsaturated fatty acids, and bile acids) and exogenous (profen nonsteroidal anti-inflammatory drugs, fibrate hypolipidemic agents, and sodium valproate) origin were also accepted, indicating that the enzyme was capable of forming both ether- and ester-type glucuronides from various structurally unrelated compounds. Determination of apparent kinetic constants for the glucuronidation by UGT2B1 of selected aglycones revealed a high maximal velocity toward the 3-position of morphine (49.3 +/- 2.2 nmol/min/mg of protein), compared with other known substrates such as 4-methylumbelliferone (2.67 +/- 0.11 nmol/min/mg of protein) or clofibric acid (0.06 +/- 0.02 nmol/min/mg of protein). To gain a better insight into the mechanisms underlying the apparently wide substrate specificity of UGT2B1, series of structurally related compounds were tested as potential substrates. The rate of glucuronidation of unbranched saturated fatty acids and omega,omega,omega-triphenylalkanoic acids increased progressively with increasing alkyl chain length and then declined, with the best substrates in these two homologous series being decanoic acid and 4,4,4-triphenylbutanoic acid, respectively. Glucuronidation of para-substituted phenols always proceeded at a higher rate than that of the corresponding para-substituted benzoic acids. This could mean that the aglycon hydroxyl group was better positioned in the enzyme active site in the case of phenols. Alternatively, if the initial interaction with the enzyme required the aglycon to be in the protonated uncharged form, then the observation could be explained by the difference in ionization between phenols and benzoic acids at the incubation pH used. The introduction of a bulky alkyl group into the para-position led to increases of up to 300-fold in the rate of glucuronidation, probably as a result of the increased aglycon lipophilicity. Finally, the enzyme showed a degree of stereo- and regiospecificity, preferring (S)-ibuprofen to the R-enantiomer (Vmax/Km, 3.06 and 1.10 microliters/min/mg of protein, respectively) and glucuronidating lithocholic acid but not hyodeoxycholic acid, which differs by only a single hydroxyl group.(ABSTRACT TRUNCATED AT 400 WORDS)