Girirajan S.,Howard Hughes Medical Institute |
Rosenfeld J.A.,Perkin Elmer Corporation |
Coe B.P.,Howard Hughes Medical Institute |
Parikh S.,Cleveland Clinic |
And 37 more authors.
New England Journal of Medicine | Year: 2012
BACKGROUND: Some copy-number variants are associated with genomic disorders with extreme phenotypic heterogeneity. The cause of this variation is unknown, which presents challenges in genetic diagnosis, counseling, and management. METHODS: We analyzed the genomes of 2312 children known to carry a copy-number variant associated with intellectual disability and congenital abnormalities, using array comparative genomic hybridization. RESULTS: Among the affected children, 10.1% carried a second large copy-number variant in addition to the primary genetic lesion. We identified seven genomic disorders, each defined by a specific copy-number variant, in which the affected children were more likely to carry multiple copy-number variants than were controls. We found that syndromic disorders could be distinguished from those with extreme phenotypic heterogeneity on the basis of the total number of copy-number variants and whether the variants are inherited or de novo. Children who carried two large copy-number variants of unknown clinical significance were eight times as likely to have developmental delay as were controls (odds ratio, 8.16; 95% confidence interval, 5.33 to 13.07; P = 2.11×10 -38). Among affected children, inherited copy-number variants tended to co-occur with a second-site large copy-number variant (Spearman correlation coefficient, 0.66; P<0.001). Boys were more likely than girls to have disorders of phenotypic heterogeneity (P<0.001), and mothers were more likely than fathers to transmit second-site copy-number variants to their offspring (P = 0.02). CONCLUSIONS: Multiple, large copy-number variants, including those of unknown pathogenic significance, compound to result in a severe clinical presentation, and secondary copy-number variants are preferentially transmitted from maternal carriers. (Funded by the Simons Foundation Autism Research Initiative and the National Institutes of Health.) Copyright © 2012 Massachusetts Medical Society. All rights reserved.
Gortmaker S.L.,Harvard University |
Polacsek M.,University of New England at Biddeford |
Letourneau L.,Maine Quality Counts |
Rogers V.W.,Kids CO OP |
And 5 more authors.
Childhood Obesity | Year: 2015
Background: We evaluated the impact of a brief primary-care-based intervention, The Maine Youth Overweight Collaborative (MYOC), on BMI (kg/m2) z-score change among participants with obesity (BMI ≥95th percentile for age and sex), overweight (BMI ≥85th and <95th percentile), and healthy weight (≥50th and <85th percentile). Methods: A quasi-experimental field trial with nine intervention and nine control sites in urban and rural areas of Maine, MYOC focused on improvements in clinical decision support, charting BMI percentile, identifying patients with obesity, appropriate lab tests, and counseling families/patients. Retrospective longitudinal record reviews assessed BMI z-scores preintervention (from 1999 through October 2004) and one postintervention time point (between December 2006 and March 2008). Participants were youth ages 5-18 having two visits before the intervention with weight percentile greater than or equal to 95% (N=265). Secondary analyses focused on youths who are overweight (N=215) and healthy weight youth (N=506). Results: Although the MYOC intervention demonstrated significant provider and office system improvements, we found no significant changes in BMI z-scores in intervention versus control youth pre- to postintervention and significant flattening of upward trends among both intervention and control sites (p<0.001). Conclusions: This brief office-based intervention was associated with no significant improvement in BMI z-scores, compared to control sites. An important avenue for obesity prevention and treatment as part of a multisector approach in communities, this type of primary care intervention alone may be unlikely to impact BMI improvement given the limited dosage - an estimated 4-6 minutes for one patient contact. © Copyright 2015, Mary Ann Liebert, Inc. 2015.
Hay C.M.,Maine Medical Center |
Lachance J.A.,Maine Medical Partners |
Lucas F.L.,Center for Outcomes Research and Evaluation |
Smith K.A.,Center for Outcomes Research and Evaluation |
Jones M.A.,Maine Medical Center
Journal of Lower Genital Tract Disease | Year: 2016
Objective Vulvar squamous cell carcinoma (VSCC) develops through 2 distinct molecular pathways, one involving high-risk human papillomavirus (HPV) infection and the other through early p53 suppressor gene mutation. We sought to evaluate the influence of p53 mutation, HPV status, and p16 expression on local recurrence and disease-specific mortality in early stage VSCC. Materials and Methods We performed a retrospective chart review of all patients with stage I VSCC at the Maine Medical Center from 1998 to 2007 (n = 92). Tumor size, depth of invasion, lymphatic/vascular space invasion, and growth pattern were recorded. Paraffin-embedded tissue blocks were stained by immunohistochemistry for p16 and p53; high-risk HPV was detected by polymerase chain reaction assay. Margin distance was determined by a gynecologic pathologist. Survival analyses were conducted to examine predictors of VSCC recurrence and disease-specific mortality. Results Age, depth of invasion, lymphatic/vascular space invasion, growth pattern, and margin status were not significant predictors of recurrence or disease-specific mortality. Tumor size of greater than 4.0 cm indicated a 4-fold increase in disease-specific mortality but did not significantly increase recurrence. p16-Positive patients were less likely to recur and had no VSCC-related deaths. Human papillomavirus-positive patients were less likely to recur and had no VSCC-related deaths. p53-positive patients were 3 times more likely to recur and nearly 7 times more likely to die from vulvar cancer. Conclusions Our findings suggest that HPV and the surrogate biomarker p16 indicate a less aggressive type of vulvar cancer. p53 positivity was associated with poor prognosis and significantly increased both recurrence and disease-specific mortality. © 2016, American Society for Colposcopy and Cervical Pathology.
Greaney M.L.,Harvard University |
Lees F.D.,University of Rhode Island |
Lynch B.,Maine Medical Partners |
Sebelia L.,University of Rhode Island |
Greene G.W.,University of Rhode Island
Journal of Nutrition Education and Behavior | Year: 2012
Objective: To explore (1) how migration influenced physical activity and dietary behaviors among Latino immigrants and (2) participants' perception of concepts related to a Health at Every Size (HAES) approach to weight maintenance (mindful eating, taking care of oneself). Methods: Four focus groups (n = 35), homogenous by sex, were conducted in Spanish. Results: Male and female participants spoke of being less physically active and eating less healthful diets since immigrating. Noted barriers to being physically active and eating a healthful diet included time and financial constraints. Participants were interested in the HAES concepts but thought these ideas conflicted with their cultural upbringing. For women, putting family first was identified as a barrier to taking care of oneself. Conclusions and Implications: An HAES approach may be a useful in promoting weight maintenance in this population, as participants were interested in key concepts, but it would be important that HAES interventions incorporate cultural traditions. © 2012 Society for Nutrition Education and Behavior.
PubMed | Holland Orthopaedic & Arthritic Center and Maine Medical Partners
Type: Journal Article | Journal: The Journal of bone and joint surgery. American volume | Year: 2016
Porous tantalum has been used effectively in hip, knee, and reverse shoulder arthroplasty implants. However, a first-generation porous tantalum glenoid component for use in anatomic shoulder arthroplasty previously demonstrated failure, with failure usually preceded by the appearance of intra-articular metallic debris. After redesign, the component was reintroduced in 2009. The purpose of the current study was to evaluate the radiographic and clinical outcomes of the redesigned glenoid component.Sixty-eight patients undergoing total shoulder arthroplasty received a Trabecular Metal porous tantalum glenoid component (73 components; 5 patients underwent staged bilateral procedures). No polymethylmethacrylate cement was used (off-label usage in the U.S.). A grading system to assess metallic debris formation was developed using radiographs of the previous generation of porous tantalum glenoid components that failed. Radiographs from the current series were independently reviewed by 2 shoulder arthroplasty specialists, and their results were compared. Glenoid components were evaluated for signs of bone ingrowth and metallic debris formation.Sixty-six (90%) of the 73 components were evaluated at a minimum of 2 years of follow-up (mean radiographic follow-up of 50.8 months; range, 24 to 68 months). Of these, 92.4% demonstrated minimal or no glenoid radiolucency. Overall, the prevalence of metallic tantalum debris formation was 44% (29 of 66). Sequential radiograph review demonstrated that the incidence of metallic debris formation increased for each year of follow-up, with radiographs from 2, 3, 4, and 5 years of follow-up demonstrating a metallic debris incidence of 23%, 36%, 49%, and 52%, respectively. Additionally, the severity of metallic debris formation increased with follow-up duration. There was no component dissociation or revision due to implant breakage in this series.The porous tantalum glenoid component studied had excellent short-term component fixation. However, the development of metallic debris, increasing in both overall incidence and degree of severity over time, raises concern for potential failure of this glenoid component. Longer follow-up is required.Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Steinberg P.L.,Maine Medical Partners |
Munver R.,Hackensack Medical Center |
Ghavamian R.,Montefiore Medical Center
Journal of Endourology | Year: 2011
Background and Purpose: Conventional wisdom and small animal studies suggest repeated hilar clamping during partial nephrectomy is deleterious to renal function. We describe the impact of repeated renal hilar clamping during laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RPN) on the overall function of the operated kidney. Patients and Methods: A retrospective analysis of all patients undergoing RPN or LPN with repeated hilar clamping was performed. Patient and tumor characteristics were recorded. All patients had preoperative and postoperative mercaptoacetyltriglycine (MAG)3 renal scans, and the change in function was calculated. Change in glomerular filtration rate (GFR) was calculated with the modified Modification of Diet in Renal Disease equation as well. Results: Seven patients were studied with an average age of 60 and a body mass index of 32. Tumors averaged 3.6 cm, and there were four and three right- and left-sided tumors, respectively. The reasons for repeated clamping were bleeding in three patients and either gross or microscopic positive margins in four patients, all of whom had repeated resection. The average initial clamp time was 20 minutes, and the average reclamp time was 12 minutes. The average operative time was 185 minutes. and average blood loss was 171 mL. All renal units were functioning postoperatively. The average change in absolute renal function on the operated kidney was -4.9%, and the relative loss of function was -10%, both measured on MAG3 scan. The average GFR before surgery was 61.4 (mL/min/1.73m 2); after surgery, the average GFR was 57.1 (mL/min/1.73m 2), for an average loss of -7%. The range of change in GFR was from 0% to -23%. Conclusions: Although not optimal, repeated clamping of the renal hilum during partial nephrectomy to control bleeding or to obtain a clear surgical margin is associated with minimal loss of renal function. © Copyright 2011, Mary Ann Liebert, Inc.
White R.R.,Maine Medical Partners
Techniques in Orthopaedics | Year: 2013
Fixation of periprosthetic femur fractures around total hip implants without cerclage cables or strut grafts. Periprosthetic fractures around total hip stems are challenging fractures because it is difficult to gain proximal fixation in the area of the femoral stem. The bone is often osteoporotic and locking fixation is preferred over conventional fixation. Most locking plates do not have the ability to angle the screws around the stem and still lock into the plate. Surgeons have resorted to the use of cerclage cables to fix the plate to the bone and allograft cortical struts to improve the strength of the fixation construct. With the advent of polyaxial locking screws and a plate that is wider at the proximal end of the plate, it is now possible to gain bicortical locking fixation around most total hip stems. This eliminates the need for both cables and strut grafts. This paper describes the implants and techniques to accomplish this fixation and stabilize these complex fractures in a more biologically friendly manner. © 2013 by Lippincott Williams & Wilkins.
White R.R.,Maine Medical Partners
Techniques in Orthopaedics | Year: 2013
Periprosthetic tibia fractures are unusual and very little is written about them and their treatment. For fractures adjacent to the tibial component revision, arthroplasty is an option. Reduction and fixation can be difficult because of the small proximal segment and the presence of an implant stem. However, with newer locking plates, internal fixation of these fractures can be accomplished. For fractures of the shaft, conventional techniques of ORIF should be considered and can be effective. This paper shows an example of each of these fractures. © 2013 by Lippincott Williams & Wilkins.
Mcmillan H.J.,Harvard University |
Santagata S.,Harvard University |
Shapiro F.,Harvard University |
Batish S.D.,Athena Diagnostics |
And 3 more authors.
Neuromuscular Disorders | Year: 2010
We report two new MPZ mutations causing congenital hypomyelinating neuropathies; c.368_382delGCACGTTCACTTGTG (in-frame deletion of five amino acids) and c.392A > G, Asn131Ser. Each child had clinical and electrodiagnostic features consistent with an inherited neuropathy, confirmed by sural nerve biopsy. The cases illustrate the clinically heterogeneity that exists even within early-onset forms of this disease. They also lend additional support to the emerging clinical and laboratory evidence that impaired intracellular protein trafficking may represent the cause of some congenital hypomyelinating neuropathies. © 2010 Elsevier B.V.
PubMed | Maine Medical Partners
Type: Journal Article | Journal: Journal of endourology | Year: 2011
Conventional wisdom and small animal studies suggest repeated hilar clamping during partial nephrectomy is deleterious to renal function. We describe the impact of repeated renal hilar clamping during laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RPN) on the overall function of the operated kidney.A retrospective analysis of all patients undergoing RPN or LPN with repeated hilar clamping was performed. Patient and tumor characteristics were recorded. All patients had preoperative and postoperative mercaptoacetyltriglycine (MAG)3 renal scans, and the change in function was calculated. Change in glomerular filtration rate (GFR) was calculated with the modified Modification of Diet in Renal Disease equation as well.Seven patients were studied with an average age of 60 and a body mass index of 32. Tumors averaged 3.6 cm, and there were four and three right- and left-sided tumors, respectively. The reasons for repeated clamping were bleeding in three patients and either gross or microscopic positive margins in four patients, all of whom had repeated resection. The average initial clamp time was 20 minutes, and the average reclamp time was 12 minutes. The average operative time was 185 minutes. and average blood loss was 171 mL. All renal units were functioning postoperatively. The average change in absolute renal function on the operated kidney was -4.9%, and the relative loss of function was -10%, both measured on MAG3 scan. The average GFR before surgery was 61.4 (mL/min/1.73m(2)); after surgery, the average GFR was 57.1 (mL/min/1.73m(2)), for an average loss of -7%. The range of change in GFR was from 0% to -23%.Although not optimal, repeated clamping of the renal hilum during partial nephrectomy to control bleeding or to obtain a clear surgical margin is associated with minimal loss of renal function.