Risk of recurrence of birth defects in Washington State

A population-based study was conducted using maternally-linked birth certificate records from Washington State for 1980–93 to evaluate the risk of birth defect occurrence among infants with pre-viously affected siblings, relative to infants whose siblings did not have birth defects. The risks of recurrence of similar and dissimilar defects were estimated, and the effects of change in paternity and/or city of residence were evaluated as proxies of genetic and environmental effects. At the first birth on record, 3322 women were identified in the linked certificates as giving birth to a child with a birth defect; 6620 women whose first birth did not result in an infant with a defect were randomly selected for comparison. Women with a malformed infant had an in-creased risk of having a malformed infant at the subsequent birth (Relative Risk = 1.9, [95% Confidence Interval (CI) = 1.5–2.4]), which did not vary by intervening changes in partner or residence. The risk of recurrence of the same general type of defect [RR = 11.7, 95% CI = 9.7–19.50] was much greater than that of occurrence of a dissimilar defect [RR = 1.5, 95% CI = 1.1–1.9]. This was consistent for all defect categories, and did not vary markedly by changes in partner or residence.     

The effect of aquatic therapy on functional mobility of infants and toddlers in early intervention.

PURPOSE: The purpose of this study was to determine the effect of aquatic therapy (AT) as an adjunct to home-based early intervention (EI) on differences in children's functional mobility. METHODS: Thirty-seven children of ages six to 30 months (x = 24.2; SD = 8.5) with delayed functional mobility participated in this study. The AT group (n = 15) received weekly AT in a community pool in addition to home-based EI with a physical therapist (PT) or occupational therapist (OT). A randomly selected comparison group (n = 22) received home-based EI with a PT or OT. Baseline and postintervention scores on the Gross Motor Subsection of the Mullen Scales of Early Learning were compared between the AT and comparison group. RESULTS: The AT group demonstrated significantly greater (p < 0.05) gains in functional mobility than the comparison group. CONCLUSION: AT is a useful adjunct to EI to improve children's functional mobility.     

The Significance of Histology and Morphometry in Predicting Lymph Node Metastases in Patients with Squamous Cell Carcinoma of the Vulva

The material consists of a series of 73 patients with squamous cell carcinoma of the vulva. The site and the size of the primary tumor and the histological status of the lymph nodes of the groin were known. Two pathologists evaluated nuclear hyperchromatism, nuclear polymorphism, histological differentiation, number of mitoses, inflammatory response, and vascular invasion and graded these parameters from one to three. The reliability of the histopathological grades evaluated by the κ coefficient showed considerable interobserver variation. Despite this a model which included the subjective parameter nuclear hyperchromatism could predict patients without lymph node metastases. The model consisted of patients with tumors which were not situated on the clitoris, were less than 40 mm in diameter, and exhibited only slight hyperchromatism. The model fitted 19 (26%) and 14 (19%) of the patients with two different pathologists evaluating the nuclear hyperchromatism and none of these patients had lymph node metastases. The quantitative parameter—mean nuclear volume—determined by morphometry was of no diagnostic value for the prediction of patients without groin node metastases at the time of operation.     

Hyper-recombination and mutator effects of the mms9-1, mms13-1, and mms21-1 mutations in Saccharomyces cerevisiae

Summary Spontaneous mitotic intragenic and intergenic recombination at various sites is enhanced 10 to 100 fold in the methyl methanesulfonate (MMS)-sensitive mutants mms9-1, mms13-1, and mms21-1 of Saccharomyces cerevisiae. All three mutants show elevated rates of spontaneous mutation. Sporulation is reduced in diploids homozygous for any of the three mutations, and a deficiency in meiotic recombination and meiotic chromosome segregation is observed. Pleiotropic effects on cell viability, growth rate, and radiation sensitivity, in combination with the alterations in recombination and mutagenesis displayed by mutant strains, suggest that the MMS9, MMS13, and MMS21 genes play important roles in DNA replication and/or genetic recombination.     

Quantitation of Ergosterol Content: Novel Method for Determination of Fluconazole Susceptibility of Candida albicans

MIC end points for the most commonly prescribed azole antifungal drug, fluconazole, can be difficult to determine because its fungistatic nature can lead to excessive "trailing" of growth during susceptibility testing by National Committee for Clinical Laboratory Standards broth macrodilution and microdilution methods. To overcome this ambiguity, and because fluconazole acts by inhibiting ergosterol biosynthesis, we developed a novel method to differentiate fluconazole-susceptible from fluconazole-resistant isolates by quantitating ergosterol production in cells grown in 0, 1, 4, 16, or 64 microg of fluconazole per ml. Ergosterol was isolated from whole yeast cells by saponification, followed by extraction of nonsaponifiable lipids with heptane. Ergosterol was identified by its unique spectrophotometric absorbance profile between 240 and 300 nm. We used this sterol quantitation method (SQM) to test 38 isolates with broth microdilution end points of /=64 microg/ml (resistant) and 10 isolates with trailing end points by the broth microdilution method. No significant differences in mean ergosterol content were observed between any of the isolates grown in the absence of fluconazole. However, 18 susceptible isolates showed a mean reduction in ergosterol content of 72% after exposure to 1 microg of fluconazole/ml, an 84% reduction after exposure to 4 microg/ml, and 95 and 100% reductions after exposure to 16 and 64 microg of fluconazole/ml, respectively. Ten SDD isolates showed mean ergosterol reductions of 38, 57, 73, and 99% after exposure to 1, 4, 16, and 64 microg of fluconazole/ml, respectively. In contrast, 10 resistant isolates showed mean reductions in ergosterol content of only 25, 38, 53, and 84% after exposure to the same concentrations of fluconazole. The MIC of fluconazole, by using the SQM, was defined as the lowest concentration of the drug which resulted in 80% or greater inhibition of overall mean ergosterol biosynthesis compared to that in the drug-free control. Of 38 isolates which gave clear end points by the broth microdilution method, the SQM MIC was within 2 dilutions of the broth microdilution MIC for 33 (87%). The SQM also discriminated between resistant and highly resistant isolates and was particularly useful for discerning the fluconazole susceptibilities of 10 additional isolates which gave equivocal end points by the broth microdilution method due to trailing growth. In contrast to the broth microdilution method, the SQM determined trailing isolates to be susceptible rather than resistant, indicating that the SQM may predict clinical outcome more accurately. The SQM may provide a means to enhance current methods of fluconazole susceptibility testing and may provide a better correlation of in vitro with in vivo results, particularly for isolates with trailing end points.     

Parent-child factors and their effect on communicating BRCA1/2 test results to children

The purpose of the present study was to evaluate the likelihood and the effect of parent-child factors on communicating about maternal genetic test results for breast/ovarian cancer risk. Subjects were 42 mothers enrolled in a hereditary breast cancer research program who reported on their interactions with 68 target children. Predictor variables (demographic, clinical, and psychological) were assessed at baseline after mothers participated in a comprehensive genetic counseling/education session and provided a blood sample for BRCA1/2 mutation analysis. Maternal communication of test results to children was assessed 1 month after mothers learned their mutation status. The rate of disclosure to pediatric-age children was 53%. Older children were more likely to be informed of their mothers' test results than were younger children. Maternal disclosure of genetic test results to children was also more likely to occur in the presence of more open parent-child communication styles, though the act of disclosing did not appear to impact communication style. These findings suggest that in addition to developmental phase, family behavioral interactions and communication styles are strongly predictive of whether or not mothers choose to share cancer genetic risk information with their children.