Citations

Abstract BRCA1 and BRCA2 are the most important breast and ovarian cancer susceptibility genes. Biallelic mutations in BRCA2 can lead to Fanconi anemia and predisposition to cancers, whereas biallelic BRCA1 mutations have not been confirmed, presumably because one wild-type BRCA1 allele is required during embryogenesis. This study describes an individual who was diagnosed with ovarian carcinoma at age 28 and found to have one allele with a deleterious mutation in BRCA1, c.2457delC (p.Asp821Ilefs*25), and a second allele with a variant of unknown significance in BRCA1, c.5207T>C (p.Val1736Ala). Medical records revealed short stature, microcephaly, developmental delay, and significant toxicity from chemotherapy. BRCA1 p.Val1736Ala cosegregated with cancer in multiple families, associated tumors showed loss of wild-type BRCA1, and BRCA1 p.Val1736Ala showed reduced DNA damage localization. These findings represent the first validated example of biallelic deleterious human BRCA1 mutations and have implications for the interpretation of genetic test results. Significance: Accurate assessment of genetic testing data for BRCA1 mutations is essential for clinical monitoring and treatment strategies. Here, we report the first validated example of an individual with biallelic BRCA1 mutations, early-onset ovarian cancer, and clinically significant hypersensitivity to chemotherapy. Cancer Discov; 3(4); 399–405. ©2012 AACR. See related commentary by D'Andrea, p. 376 This article is highlighted in the In This Issue feature, p. 363

Over the last two decades there has been considerable deliberation, experience, and research in the arena of Health Information Technology (HIT), Electronic Medical Records (EMR), Electronic Health Records (EHR), and more recently, Electronic Personal Health Records (PHR). Despite the challenges involved in adopting these systems and technologies, there is consensus that they bring significant value to the delivery of trusted and affordable healthcare. The investment involved and the impact on customers, clinical and non-clinical staff, and processes are significant and far reaching. This chapter attempts to synthesize the vast amount of information, experience, and implementation perspectives related to Electronic Health Records with the intent of assisting healthcare institutions and key stakeholders make informed choices as they embark on designing, developing, and implementing an EHR. EHR considerations, challenges, opportunities, and future directions are also addressed. The chapter highlights the power of management engineering to facilitate planning, implementation, and sustainability of the EHR, a critical asset for a healthcare organization and the overall healthcare industry.

AbstractBackgroundTo investigate anatomical configuration of ciliary body and iris using ultrasound biomicroscopy as a predictor of malignant glaucoma development.DesignRetrospective study in a tertiary care hospital.ParticipantsCohort of 31 consecutive patients diagnosed with post‐surgical malignant glaucoma.MethodsAnterior chamber angle, iris and ciliary body configuration of involved eyes that had ultrasound biomicroscopy evaluation prior to the malignant glaucoma onset were evaluated. In cases with no presurgical ultrasound biomicroscopy exam of the involved eye, images from the fellow eye (imaged within 6 months) were analysed.Main Outcome MeasuresQualitative parameters.ResultsThirty‐one eyes (31 patients) had confirmed malignant glaucoma between 1996 and 2008. Most patients were women (65%) and had an anatomical narrow angle or angle‐closure glaucoma (77%). Mean intraocular pressure at diagnosis was 30.4 ± 13.5 mmHg. The most common operation was trabeculectomy with mitomycin C (55%, 17/31 eyes), combined (3/17) or not (14/17) with cataract extraction and intraocular lens implantation. Among these 31 cases, we were able to evaluate the ultrasound biomicroscopy images of 13 patients (13 eyes) including involved eyes imaged prior to the malignant glaucoma onset or eligible fellow eyes. A narrow angle with or without iridotrabecular contact was found in all eyes. A large and/or anteriorly positioned ciliary body associated with an iris root angulating forward and centrally, revealing a plateau iris configuration, was noticed in 85% (11/13) of these eyes.ConclusionIdentification of plateau iris configuration by ultrasound biomicroscopy should be considered as a possible predictor of post‐operative malignant glaucoma development.

To determine the range of neurodevelopmental diagnoses associated with intermediate (45-54 repeats) and premutation (55-200 repeats) range cytosine-guanine-guanine fragile X expansions, the medical records of children with intermediate or premutation range expansions were retrospectively reviewed, and all neurodevelopmental diagnoses were abstracted. Twenty-nine children (9 female, 20 male; age, 13 months to 17 years) with intermediate (n = 25) or premutation (n = 4) range expansions were identified with neurodevelopmental diagnoses, including global developmental delay/intellectual disability (n = 15), language and learning disorders (n = 9), attention-deficit hyperactivity disorder (n = 5), epilepsy (n = 5), and motor disorders (n = 12), including 2 boys younger than 4 years of age with tremor and ataxia. Thus, children with intermediate or premutation range fragile X cytosine-guanine-guanine expansions may be more susceptible than children without such expansions to other processes, both genetic and environmental, that contribute to neurodevelopmental disability.