Return of genetic results in the familial dilated cardiomyopathy research project.

The goal of the Familial Dilated Cardiomyopathy (FDC) Research Project, initiated in 1993, has been to identify and characterize FDC genetic cause. All participating individuals have been consented for the return of genetic results, an important but challenging undertaking. Since the inception of the Project we have enrolled 606 probands, and 269 of these had 1670 family members also enrolled. Each subject was evaluated for idiopathic dilated cardiomyopathy (IDC) and pedigrees were categorized as familial or sporadic. The coding regions of 14 genes were resequenced in 311 to 324 probands in five studies. Ninety-two probands were found to carry nonsynonymous rare variants absent in controls, and with Clinical Laboratory Improvement Amendment of 1988 (CLIA) compliant protocols, relevant genetic results were returned to these probands and their consented relatives by study genetic counselors and physicians in 353 letters. In 10 of the 51 families that received results >1 year ago, at least 23 individuals underwent CLIA confirmation testing for their family's rare variant. Return of genetic results has been successfully undertaken in the FDC Research Project. This report describes the methods utilized in the process of returning research results. We use this information as a springboard for providing guidance to other genetic research groups and proposing future directions in this arena.

Neonatal tuberculosis: neonatal intensive care unit considerations in the United States.

According to the World Health Organization, more than 2 billion people, equal to one third of the world's population, are infected with Mycobacterium tuberculosis (TB) bacilli, the microbes that cause TB. In addition, over the past decade, the incidence of postnatal TB in infants has shown an escalating trend in response to the global increase in TB. In providing the best possible care for infants in newborn nurseries and NICU, providers must recognize the trends of TB and multidrug resistant TB in infants globally and consider the possible effects on health care in the United States. The potential risk factors, clinical manifestations, diagnostic strategies, and management plans, specific to the care of infants in the neonatal intensive care unit, is vastly important in maintaining a high index of suspicion for neonatal TB.

Clinical and genetic issues in familial dilated cardiomyopathy.

Idiopathic dilated cardiomyopathy (IDC) is characterized by left ventricular dilatation and systolic dysfunction after known causes have been excluded. Idiopathic dilated cardiomyopathy occurring in families, or familial dilated cardiomyopathy (FDC), may occur in 20% to 50% of IDC cases. Sixteen genes have been shown to cause autosomal dominant FDC, but collectively may account for only a fraction of genetic causation; it is anticipated that additional genes causative of FDC will be discovered. Familial dilated cardiomyopathy demonstrates incomplete penetrance, variable expression, and significant locus and allelic heterogeneity, making clinical and genetic diagnosis complex. Echocardiographic and electrocardiographic screening of first-degree relatives of individuals with IDC and FDC is indicated, as detection and treatment are possible before the onset of advanced symptomatic disease. Genetic counseling for IDC and FDC is also indicated to assist with family evaluations for genetic disease and with the uncertainty and anxiety surrounding the significance of clinical and genetic evaluation. Genetic testing is not yet commonly available, but its emergence will provide new opportunities for presymptomatic diagnosis.

Clinical characteristics of 304 kindreds evaluated for familial dilated cardiomyopathy.

BACKGROUND: Familial dilated cardiomyopathy (FDC) is dilated cardiomyopathy of unknown cause occurring in 2 or more closely related family members. METHODS AND RESULTS: Members of 304 families suspected to have FDC were evaluated by family history (FH) and medical record review and were categorized as affected with idiopathic dilated cardiomyopathy (IDC), unaffected, unknown, or no data. Pedigrees were categorized with confirmed FDC, probable FDC, possible FDC or IDC based on strength of evidence. Of the 304 pedigrees, 125 were categorized as confirmed FDC, 48 were probable FDC, 72 were possible FDC, and 59 had sporadic, nonfamilial IDC. Numbers of living first- and second-degree family members, and median number of relatives available for FH was greatest with confirmed FDC, and diminished for probable and possible FDC, and IDC categories. LV dimensions increased and LV function worsened in index patients along the spectrum from confirmed FDC, probable FDC, possible FDC and IDC, and a greater proportion of IDC patients underwent heart transplant. However, the age of onset, duration of disease, the time to death or heart transplant, and most other findings were similar among the 4 categories. CONCLUSION: Clinical characteristics of IDC and FDC are similar, precluding an FDC diagnosis from clinical features only.

Single-agent gefitinib in patients with untreated advanced non-small-cell lung cancer and poor performance status: a Minnie Pearl Cancer Research Network Phase II Trial.

BACKGROUND: Patients with advanced non-small-cell lung cancer (NSCLC) and poor performance status (PS) are often excluded from trials. Gefitinib is a safe oral agent that may benefit these patients. PATIENTS AND METHODS: Seventy-two patients with poor PS and advanced NSCLC were enrolled onto this study of gefitinib 250 mg per day given orally until disease progression, with evaluation at 8 weeks. Eligible patients had no previous chemotherapy, an Eastern Cooperative Oncology Group PS of 2/3, and stage IIIB/IV NSCLC. Quality of life (QOL) and symptom response (SR) scores were calculated using the Functional Assessment of Cancer-Lung questionnaire. Patient characteristics included a median age of 75 years; PS of 2/3; and bronchoalveolar (n=3), adenocarcinoma (n=29), squamous cell (n=21), large-cell (n=11), and unspecified histology (n=6). Mean treatment duration was 4 months (range, 3 days to 18 months), and median duration of follow-up was 12 months. Grade 3/4 toxicities included rash and diarrhea. RESULTS: Among 70 patients assessed for response, there were 3 partial responses (4%), 32 patients with stable disease (46%), and 18 with progressive disease (26%). Median progression-free survival (PFS) and overall survival (OS) were 3.7 months and 6.3 months, respectively. Six-month and 1-year PFS and OS rates were 35% and 21% and 50% and 24%, respectively. Eighty-two percent and 48% of patients reported improvements or no change in QOL and SR, respectively. CONCLUSION: Gefitinib demonstrates modest efficacy and is well tolerated as initial therapy in advanced NSCLC for patients with poor PS.