BRCAPRO validation, sensitivity of genetic testing of BRCA1/BRCA2, and prevalence of other breast cancer susceptibility genes.

PURPOSE: To compare genetic test results for deleterious mutations of BRCA1 and BRCA2 with estimated probabilities of carrying such mutations; to assess sensitivity of genetic testing; and to assess the relevance of other susceptibility genes in familial breast and ovarian cancer. PATIENTS AND METHODS: Data analyzed were from six high-risk genetic counseling clinics and concern individuals from families for which at least one member was tested for mutations at BRCA1 and BRCA2. Predictions of genetic predisposition to breast and ovarian cancer for 301 individuals were made using BRCAPRO, a statistical model and software using Mendelian genetics and Bayesian updating. Model predictions were compared with the results of genetic testing. RESULTS: Among the test individuals, 126 were Ashkenazi Jewish, three were male subjects, 243 had breast cancer, 49 had ovarian cancer, 34 were unaffected, and 139 tested positive for BRCA1 mutations and 29 for BRCA2 mutations. BRCAPRO performed well: for the 150 probands with the smallest BRCAPRO carrier probabilities (average, 29.0%), the proportion testing positive was 32.7%; for the 151 probands with the largest carrier probabilities (average, 95.2%), 78.8% tested positive. Genetic testing sensitivity was estimated to be at least 85%, with false-negatives including mutations of susceptibility genes heretofore unknown. CONCLUSION: BRCAPRO is an accurate counseling tool for determining the probability of carrying mutations of BRCA1 and BRCA2. Genetic testing for BRCA1 and BRCA2 is highly sensitive, missing an estimated 15% of mutations. In the populations studied, breast cancer susceptibility genes other than BRCA1 and BRCA2 either do not exist, are rare, or are associated with low disease penetrance.     

Comparison of morbidities in very low birthweight and normal birthweight infants during the first year of life in a developing country

Objective : To compare the morbidities in the very low birthweight (VLBW; < 1500 g) and normal birthweight (NBW; ± 2500 g) Malaysian infants during the first year of life.
Methodology : Prospective observational cohort study of consecutive surviving VLBW infants and randomly sampled NBW infants born in the Kuala Lumpur Maternity Hospital between 1 December 1989 and 31 December 1992. Infants were followed up regularly during the first year of life, after correction for prematurity.
Results : Compared with NBW infants ( n = 106), VLBW infants ( n = 127) had significantly higher risk of failure to thrive (odds ratio [OR] = 8.0, 95% confidence intervals [Cl]: 1.1 to 354.3), wheezing (OR = 3.7, 95% Cl: 1.6 to 9.3), rehospitalization (OR = 2.3, 95% Cl: 1.1 to 5.0), cerebral palsy (OR = 8.6, 95% Cl: 2.0 to 77.6), neurosensory hearing loss (OR = 12.0, 95% Cl: 1.7 to 513.6) and visual loss (7.9 vs 0%, P = 0.002). The mean mental developmental index (MDI) and mean psychomotor developmental index (PDI) at 1 year of age were significantly lower among VLBW infants (MDI 99 [SD = 28], PDI89 [SD = 25]) than NBW infants (MDI 106 [SD = 18], PDI 101 [SD = 18]) (95% Cl for difference between means being MDI: -14.1 to -1.7; and PDI: -17.6 to -6.0). Logistic regression analysis showed that among VLBW infants: (i) male sex, Malay ethnicity and bronchopulmonary dysplasia were significant risk factors associated with wheezing; (ii) longer duration of oxygen therapy during the neonatal period, seizures after the post-neonatal period and wheezing were significant risk factors associated with rehospitalization; and (iii) longer duration of oxygen therapy during the neonatal period was a significant risk factor associated with adverse neurodevelopmental outcome during the first year of life.
Conclusions : Compared with NBW infants, VLBW Malaysian infants had significantly higher risks of physical and neurodevelopmental morbidities.     

Ectopic bone formation in children and adolescents with head injuries: its management

During an 11-year prospective study at Kennedy Memorial Hospital for Children (Brighton, MA), ectopic bone formation occurred in 22 of 145 children and adolescents admitted in coma following head injury. Subsequent deformities and limitation of motion were an impediment to rehabilitation in 15 of these patients, who recovered from the coma. Several bone excision procedures, either alone or in conjunction with other physical and/or pharmacological modes of treatment, were followed by recurrence of ectopic bone until salicylates were used. The latter eliminated or minimized recurrence of ectopic bone. The study suggests a useful role for salicylates not only in preventing recurrence, but also in minimizing the occurrence of ectopic bone formation in these patients.     

Pulse oximetry for monitoring during ward analgesia: Epidural morphine versus parenteral narcotics

A pulse oximeter was used to monitor oxygen saturation in 20 women following cesarean delivery. The patients were randomly assigned to one of two groups. Group A received conventional parenteral narcotics for relief of post-operative pain and group B received epidural morphine. All patients were monitored overnight, and data were stored continuously. There were no statistically significant differences in the low saturation values between the two groups. However, the group A desaturation episodes occurred an average of 2.7±1.9 hours after the parenteral narcotics were administered, and the group B desaturation episodes occurred an average of 13.7±5.9 hours after the epidural morphine was administered.     

小藤铃儿草的生物碱成分

自小藤铃儿草Dactylicapnos torulosa(Hook.f ct Thomas.)Hutchins中分得六个单体,通过UV,IR,MS,¹HNMR和¹³CNMR解析,鉴定了四个,其中一个为新化合物,命名为紫金龙碱(zijinlongine,Ⅰ),其他三个为已知化合物:氯化1-甲氧基小檗碱(1-methoxylberberium chloride,Ⅱ),氯化三乙基苯胺(triethylphcnylamium chloride,Ⅲ)和异紫堇定(isocorydine,Ⅳ)。Ⅱ和Ⅲ系首次从植物中得到。