Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 13 de 13
Filter
1.
Brain Inj ; 35(8): 886-892, 2021 07 03.
Article in English | MEDLINE | ID: mdl-34133258

ABSTRACT

Background: The Brain Injury Guidelines (BIG) provide a validated framework for categorizing patients with small intracranial haemorrhages (ICH) who could be managed by acute care surgery without neurosurgical consultation or repeat head computed tomography in the absence of neurological deterioration. This replication study retrospectively applied BIG criteria to ICH subjects and only included BIG1 and BIG2 subjects.Methods: The trauma registry was queried from 2014 to 2019 for subjects with a traumatic ICH <1 cm, Glasgow Coma Scale score of 14/15 and not on anticoagulation therapy. Patients were then categorized under BIG 1 or BIG2 and outcomes were evaluated.Results: Two hundred fourteen subjects were reviewed (88 BIG1 and 126 BIG2). Twenty-three subjects had worse repeat imaging, but only one had worsening exam that resolved spontaneously. None required neurosurgical intervention. One died of non-neurological causes.Conclusions: Retrospective analysis supported our hypothesis that patients categorized as BIG1 or BIG2 could have been safely managed by acute care surgeons without neurosurgical consultation or repeat head imaging. A review of minor worsening on repeat imaging without changes in neurological exams and no need for neurosurgical interventions supports this evidence-based approach to the management of small intracranial haemorrhages.


Subject(s)
Intracranial Hemorrhage, Traumatic , Critical Care , Glasgow Coma Scale , Humans , Intracranial Hemorrhages/diagnostic imaging , Intracranial Hemorrhages/etiology , Retrospective Studies
2.
Radiology ; 290(3): 783-792, 2019 03.
Article in English | MEDLINE | ID: mdl-30561278

ABSTRACT

Purpose To evaluate ability of radiomic (computer-extracted imaging) features to distinguish non-small cell lung cancer adenocarcinomas from granulomas at noncontrast CT. Materials and Methods For this retrospective study, screening or standard diagnostic noncontrast CT images were collected for 290 patients (mean age, 68 years; range, 18-92 years; 125 men [mean age, 67 years; range, 18-90 years] and 165 women [mean age, 68 years; range, 33-92 years]) from two institutions between 2007 and 2013. Histopathologic analysis was available for one nodule per patient. Corresponding nodule of interest was identified on axial CT images by a radiologist with manual annotation. Nodule shape, wavelet (Gabor), and texture-based (Haralick and Laws energy) features were extracted from intra- and perinodular regions. Features were pruned to train machine learning classifiers with 145 patients. In a test set of 145 patients, classifier results were compared against a convolutional neural network (CNN) and diagnostic readings of two radiologists. Results Support vector machine classifier with intranodular radiomic features achieved an area under the receiver operating characteristic curve (AUC) of 0.75 on the test set. Combining radiomics of intranodular with perinodular regions improved the AUC to 0.80. On the same test set, CNN resulted in an AUC of 0.76. Radiologist readers achieved AUCs of 0.61 and 0.60, respectively. Conclusion Radiomic features from intranodular and perinodular regions of nodules can distinguish non-small cell lung cancer adenocarcinomas from benign granulomas at noncontrast CT. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Nishino in this issue.


Subject(s)
Adenocarcinoma/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Granuloma/diagnostic imaging , Lung Diseases/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Radiographic Image Interpretation, Computer-Assisted/methods , Solitary Pulmonary Nodule/diagnostic imaging , Tomography, X-Ray Computed/methods , Adolescent , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Support Vector Machine
3.
J Med Imaging (Bellingham) ; 5(2): 024501, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29721515

ABSTRACT

Differentiation between benign and malignant nodules is a problem encountered by radiologists when visualizing computed tomography (CT) scans. Adenocarcinomas and granulomas have a characteristic spiculated appearance and may be fluorodeoxyglucose avid, making them difficult to distinguish for human readers. In this retrospective study, we aimed to evaluate whether a combination of radiomic texture and shape features from noncontrast CT scans can enable discrimination between granulomas and adenocarcinomas. Our study is composed of CT scans of 195 patients from two institutions, one cohort for training ([Formula: see text]) and the other ([Formula: see text]) for independent validation. A set of 645 three-dimensional texture and 24 shape features were extracted from CT scans in the training cohort. Feature selection was employed to identify the most informative features using this set. The top ranked features were also assessed in terms of their stability and reproducibility across the training and testing cohorts and between scans of different slice thickness. Three different classifiers were constructed using the top ranked features identified from the training set. These classifiers were then validated on the test set and the best classifier (support vector machine) yielded an area under the receiver operating characteristic curve of 77.8%.

4.
Ann Thorac Surg ; 104(1): 290-295, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28410635

ABSTRACT

BACKGROUND: Electromagnetic navigational bronchoscopy (ENB) is a commonly used technique to obtain biopsies of peripheral pulmonary lesions. Little is known about risk factors for complications with this procedure. The aim of this study was to assess the complication rate associated with ENB and the relationship of complications to patient- and procedure-related factors. METHODS: Consecutive ENB procedures at an academic medical center between May 11, 2011, and September 11, 2015, were reviewed retrospectively. Preoperative characteristics, including pulmonary function, procedure characteristics, and the occurrence of complications, were recorded. RESULTS: In all, 361 procedures were performed on 341 patients. Complications occurred in 30 of 361 (8.3%), the most common of which was pneumothorax (27, 7.5%). Complications were not related to age, sex, American Society of Anesthesiologists grade, or pulmonary function test result. Patients with complications had longer procedure times (50 versus 73 minutes, p = 0.03), and had more interventional modalities used (2.4 versus 3.2, p = 0.001). Multiple logistic regression demonstrated that bronchoalveolar lavage was significantly associated with complications (odds ratio 6.40; 95% confidence interval: 1.68 to 24.3, p = 0.006). CONCLUSIONS: Electromagnetic navigational bronchoscopy is safe, and the rate of complications is not elevated among patients with poor lung function. Bronchoalveolar lavage performed during ENB was associated with elevated risk of complications and should be studied further.


Subject(s)
Bronchoscopy/methods , Electromagnetic Phenomena , Lung Diseases/diagnosis , Pulmonary Disease, Chronic Obstructive/etiology , Aged , Biopsy/methods , Female , Humans , Imaging, Three-Dimensional , Incidence , Male , Ohio/epidemiology , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Retrospective Studies , Severity of Illness Index , Tomography, X-Ray Computed , Video Recording
5.
Minim Invasive Surg ; 2016: 7690632, 2016.
Article in English | MEDLINE | ID: mdl-28053785

ABSTRACT

Background. Minimally invasive esophagectomy (MIE) techniques offer similar oncological and surgical outcomes to open methods. The effects of MIE on hospital costs are not well documented. Methods. We reviewed the electronic records of patients who underwent esophagectomy at a single academic institution between January 2012 and December 2014. Esophagectomy techniques were grouped into open, hybrid, MIE, and transhiatal (THE) esophagectomy. Univariate and multivariate analyses were performed to assess the impact of surgery on total hospital cost after esophagectomy. Results. 80 patients were identified: 11 THE, 11 open, 41 hybrid, and 17 MIE. Median total cost of the hospitalization was $31,375 and was similar between surgical technique groups. MIE was associated with higher intraoperative costs, but not total hospital cost. Multivariable analysis revealed that the presence of a complication, increased age, American Society of Anesthesiologists class IV (ASA4), and preoperative coronary artery disease (CAD) were associated with significantly increased cost. Conclusions. Despite the association of MIE with higher operation costs, the total hospital cost was not different between surgical technique groups. Postoperative complications and severe preoperative comorbidities are significant drivers of hospital cost associated with esophagectomy. Surgeons should choose technique based on clinical factors, rather than cost implications.

6.
Clin J Am Soc Nephrol ; 10(8): 1364-70, 2015 Aug 07.
Article in English | MEDLINE | ID: mdl-26220816

ABSTRACT

BACKGROUND AND OBJECTIVES: Inappropriate medication use is common in the care of patients with CKD. The feasibility of a simple mobile health tool designed to advise patients on safe medication usage in CKD was examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Participants with predialysis CKD (defined as eGFR<60 ml/min per 1.73 m(2)) in the Safe Kidney Care Cohort Study were recruited for home usability testing of a novel medication inquiry system between January and September of 2013. Testing was through two mobile platforms: (1) short messaging service text or (2) personal digital assistant (e.g., iPod Touch). Twenty participants (one half assigned to one device and one half assigned to the other device) were enrolled and received an in-center tutorial on device usage before the end of the study visit. Participants were subsequently mailed three sample pill bottles with the name of randomly selected medications and asked to input these medications into the medication inquiry system. The medication inquiry system response options were as follows: (1) safe in CKD, (2) not safe in CKD, (3) use with caution/speak with your health care provider, or (4) error message (for an incorrectly inputted medication). Participants were asked to record the response issued by the medication inquiry system for each medication sent for usability testing. A user satisfaction survey was administered after completion of the protocol. RESULTS: All participants owned a mobile telephone, but few owned a smartphone. Of 60 total medication queries, there were only three recorded errors, two of which occurred in the short messaging service texting group. Overall satisfaction with the application was high, with slightly higher satisfaction noted in the personal digital assistant group compared with the short messaging service group. CONCLUSIONS: The mobile health medication inquiry system application had general ease of use and high acceptance across two platforms among individuals representative of the CKD population. Tailored mobile health technology may improve medication safety in CKD.


Subject(s)
Health Knowledge, Attitudes, Practice , Home Care Services , Medication Errors/prevention & control , Patient Satisfaction , Renal Insufficiency, Chronic/therapy , Telemedicine/methods , Aged , Attitude to Computers , Cell Phone , Computers, Handheld , Feasibility Studies , Female , Health Literacy , Humans , Male , Middle Aged , Renal Insufficiency, Chronic/diagnosis , Risk Factors , Surveys and Questionnaires , Telemedicine/instrumentation , Text Messaging
7.
Am J Kidney Dis ; 66(4): 621-9, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25979348

ABSTRACT

BACKGROUND: Promoting medication adherence is a recognized challenge for prescribers. In this study, we examine whether lower medication adherence is associated with adverse safety events in individuals with decreased estimated glomerular filtration rates (eGFRs). STUDY DESIGN: Cross-sectional baseline analysis of prospective cohort. SETTING & PARTICIPANTS: Baseline analysis of the Safe Kidney Care (SKC) Cohort Study, a prospective study of individuals with eGFRs<60 mL/min/1.73 m(2) intended to assess the incidence of disease-specific safety events. Kidney transplant recipients were excluded. PREDICTOR: Self-reported medication adherence based on responses to 3 questions ascertaining degree of medication regimen adherence. OUTCOMES: Adverse safety events were self-reported at baseline (class I events), such as hypoglycemia or fall thought to be related to a medication, or detected incidentally during the baseline visit (class II events), for example, hypotension or hyperkalemia. Potential drug-related problems (DRPs) were determined by analyzing participants' medications with respect to dosing guidelines based on their screening eGFRs at the time of medication reporting. MEASUREMENTS: Relationship between medication adherence and disease-specific patient safety events. RESULTS: Of 293 SKC participants, 154 (53%) were classified as having lower medication adherence. After multivariable adjustment, lower medication adherence was significantly associated with a class I or II safety event (prevalence ratio [PR], 1.21; 95% CI, 1.04-1.41) and potential DRPs (PR, 1.29; 95% CI, 1.02-1.63). Lower medication adherence was also significantly associated with multiple (≥2) class I events (PR, 1.71; 95% CI, 1.18-2.49), multiple class I or II events (PR, 1.35; 95% CI, 1.04-1.76), and multiple potential DRPs (PR, 2.11; 95% CI, 1.08-2.69) compared with those with higher medication adherence. LIMITATIONS: Use of self-reported medication adherence rather than pharmacy records. Clinical relevance of detected safety events is unclear. CONCLUSIONS: Lower medication adherence is associated with adverse safety events in individuals with eGFRs<60 mL/min/1.73 m(2).


Subject(s)
Medication Adherence/statistics & numerical data , Patient Safety/statistics & numerical data , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/drug therapy , Self Report , Aged , Cohort Studies , Cross-Sectional Studies , Drug Therapy, Combination , Drug-Related Side Effects and Adverse Reactions , Female , Glomerular Filtration Rate/physiology , Humans , Kidney Function Tests , Male , Middle Aged , Poisson Distribution , Prospective Studies , Severity of Illness Index
8.
Clin J Am Soc Nephrol ; 10(3): 435-42, 2015 Mar 06.
Article in English | MEDLINE | ID: mdl-25710806

ABSTRACT

BACKGROUND AND OBJECTIVES: Chronic pain in predialysis CKD is not fully understood. This study examined chronic pain in CKD and its relationship with analgesic usage. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data include baseline visits from 308 patients with CKD enrolled between 2011 and 2013 in the Safe Kidney Care cohort study in Baltimore, Maryland. The Wong-Baker FACES Pain Rating Scale measured chronic pain severity. Analgesic prescriptions and over-the-counter purchases were recorded up to 30 days before visits, and were classified as a drug-related problem (DRP) based on an analgesic's nephrotoxicity and dose appropriateness at participants' eGFR. Participants were sorted by pain frequency and severity and categorized into ordinal groups. Analgesic use and the rate of analgesics with a DRP were reported across pain groups. Multivariate regression determined the factors associated with chronic pain and assessed the relationship between chronic pain and analgesic usage. RESULTS: There were 187 (60.7%) participants who reported chronic pain. Factors associated with pain severity included arthritis, taking ≥12 medications, and lower physical function. Use of nonsteroidal anti-inflammatory drugs was reported by seven participants (5.8%) with no chronic pain. Mild and severe chronic pain were associated with analgesics with a DRP, with odds ratios of 3.04 (95% confidence interval [95% CI], 1.12 to 8.29) and 5.46 (95% CI, 1.85 to 16.10), respectively. The adjusted rate of analgesics with a DRP per participant increased from the group with none to severe chronic pain, with rates of 0.07 (95% CI, 0.04 to 0.13), 0.12 (95% CI, 0.07 to 0.20) and 0.16 (95% CI, 0.09 to 0.27), respectively. CONCLUSIONS: Chronic pain is common in CKD with a significant relationship between the severity of pain and both proper and improper analgesic usage. Screening for chronic pain may help in understanding the role of DRPs in the delivery of safe CKD care.


Subject(s)
Analgesics, Non-Narcotic/administration & dosage , Analgesics, Opioid/administration & dosage , Chronic Pain/drug therapy , Glomerular Filtration Rate , Renal Insufficiency, Chronic/physiopathology , Aged , Analgesics, Non-Narcotic/adverse effects , Analgesics, Opioid/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Arthritis/complications , Arthritis/drug therapy , Chronic Pain/complications , Female , Humans , Inappropriate Prescribing , Longitudinal Studies , Male , Middle Aged , Pain Measurement , Patient Safety , Renal Insufficiency, Chronic/complications , Self Medication
9.
J Am Soc Nephrol ; 25(7): 1564-73, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24556352

ABSTRACT

Patients with CKD are at high risk for adverse safety events because of the complexity of their care and impaired renal function. Using data from our observational study of predialysis patients with CKD enrolled in the Safe Kidney Care study, we estimated the baseline frequency of adverse safety events and determined to what extent these events co-occur. We examined patient-reported adverse safety incidents (class I) and actionable safety findings (class II), conditioned on participant use of drugs that might cause such an event, and we used association analysis as a data-mining technique to identify co-occurrences of these events. Of 267 participants, 185 (69.3%) had at least one class I or II event, 102 (38.2%) had more than one event, and 48 (18.0%) had at least one event from both classes. The adjusted conditional rates of class I and class II events ranged from 2.9 to 57.6 per 100 patients and from 2.2 to 8.3 per 100 patients, respectively. The most common conditional class I and II events were patient-reported hypoglycemia and hyperkalemia (serum potassium>5.5 mEq/L), respectively. Reporting of hypoglycemia (in patients with diabetes) and falling or severe dizziness (in patients without diabetes) were most frequently paired with other adverse safety events. We conclude that adverse safety events are common and varied in CKD, with frequent association between disparate events. Further work is needed to define the CKD "safety phenotype" and identify patients at highest risk for adverse safety events.


Subject(s)
Drug-Related Side Effects and Adverse Reactions/complications , Drug-Related Side Effects and Adverse Reactions/epidemiology , Renal Insufficiency, Chronic/complications , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Self Report
10.
J Antimicrob Chemother ; 69(1): 228-33, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23887864

ABSTRACT

OBJECTIVES: Laboratory tests are usually requested for monitoring during outpatient parenteral antimicrobial therapy (OPAT), but these recommendations are not always followed. The purpose of this study was to determine whether rehospitalization during the OPAT course is associated with the availability of these test results to the treating physician. METHODS: Electronic health records (EHRs) from all patients in the Cleveland Clinic OPAT registry with start dates from 1 January to 28 February 2011 were reviewed in a retrospective cohort study. Comprehensive data on patient and OPAT characteristics were obtained for the first OPAT course per patient. Availability of laboratory test results was defined as documentation of results of at least one recommended test in the health system's EHR. Proportions of patients rehospitalized were compared for OPAT courses with test results available and non-available. Adjustments were made for patient age, hospital length of stay, anticipated OPAT duration, OPAT site and Charlson comorbidity index score. RESULTS: Four hundred patients received OPAT during the study period; 60% at home, 36% in skilled nursing facilities or long-term acute care facilities and 4% in other settings. Recommended monitoring laboratory test results were available to infectious disease physicians in 291 (73%) OPAT episodes. There were 82 patient readmissions (21%) while on OPAT. In a multivariable logistic regression model, non-availability of recommended test results was independently associated with readmissions while on OPAT (adjusted OR 2.53; 95% CI 1.36-4.73). CONCLUSIONS: Non-availability of recommended test results to treating physicians for patients on OPAT is associated with increased readmissions during OPAT.


Subject(s)
Ambulatory Care/methods , Anti-Bacterial Agents/administration & dosage , Bacterial Infections/drug therapy , Infusions, Parenteral , Patient Readmission/statistics & numerical data , Adult , Aged , Cohort Studies , Female , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Outpatients , Retrospective Studies , Treatment Outcome
11.
J Med Internet Res ; 15(11): e251, 2013 Nov 15.
Article in English | MEDLINE | ID: mdl-24240617

ABSTRACT

BACKGROUND: Health information technology has become common in the care of patients with chronic diseases; however, there are few such applications employed in kidney disease. OBJECTIVE: The aim of the study was to evaluate the use of a website providing disease-specific safety information by patients with predialysis chronic kidney disease. METHODS: As part of the Safe Kidney Care (SKC) study, an educational website was designed to provide information on safety concerns in chronic kidney disease. Phase I study participants were provided a medical alert accessory with a unique ID number, the Safe Kidney Care website, and an in-person tutorial on the use of the Internet and accessing the SKC website at baseline. Participants were asked to visit the website and enter their unique ID as frequently as they desired over the next 365 days or until their annual follow-up visit, whichever occurred first. Participants' visits and dwell times on specific safety modules were tracked using embedded webpage PHP scripts linked to a MySQL database, enabling the collection of website usage statistics. RESULTS: Of 108 Phase I participants, 28.7% (31/108) visited the website from 1-6 times during the observation period (median follow-up 365 days). Median access time was 7 minutes per visit (range <1-46) and 13 minutes per person (range <1-123). The three most frequently visited pages were "Renal function calculator", "Pills to avoid", and "Foods to avoid". High school education and frequent Internet use were significantly associated with website entry (P=.02 and P=.03, respectively). CONCLUSIONS: Preliminary results show general interest in a Web-based platform designed to improve patient safety in chronic kidney disease. TRIAL REGISTRATION: Clinicaltrials.gov NCT01407367; http://clinicaltrials.gov/show/NCT01407367 (Archived by WebCite at http://www.webcitation.org/6KvxFKA6M).


Subject(s)
Internet , Kidney Failure, Chronic/psychology , Patient Education as Topic/methods , Aged , Female , Humans , Male , Middle Aged , Prospective Studies
12.
Clin J Am Soc Nephrol ; 8(12): 2123-31, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24052221

ABSTRACT

BACKGROUND AND OBJECTIVES: The Agency for Healthcare and Research Quality patient safety indicators track adverse safety events in hospitalized patients but overlook safety incidents specific to CKD. This study considers candidate CKD-pertinent patient safety indicators and compares them with the Agency for Healthcare and Research Quality patient safety indicators. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using a national Veterans Health Administration database of hospitalized veterans from fiscal year 2005, 247,160 hospitalized veterans with prehospitalization measures of renal function were retrospectively examined for proposed CKD patient safety indicators versus Agency for Healthcare and Research Quality patient safety indicators using International Classification of Diseases, Ninth Revision diagnosis codes. Candidate CKD-pertinent patient safety indicators included in-hospital acute kidney failure; in-hospital congestive heart failure (and related diagnostic codes); electrolyte disturbances; and medication errors, poisoning, and intoxication. Patients with a prehospital estimated GFR<60 ml/min per 1.73 m(2) (CKD group) were compared with a non-CKD group. For CKD patient safety indicators, hospitalizations were excluded if the admitting condition was a potential cause of the secondary condition. Regression methods were used to present adjusted rates in study groups of interest. RESULTS: The CKD patient safety indicators were generally more common than the Agency for Healthcare and Research Quality patient safety indicators in all groups, tended to occur in different patients than those patients who experienced Agency for Healthcare and Research Quality patient safety indicators, and were more common in the CKD group than the non-CKD group, except for hypoglycemia, hypokalemia, and hyponatremia. The adjusted composite CKD patient safety indicators rate (per 1000 patient-hospitalizations) was 398.0 (95% confidence interval, 391.2 to 405.0) for patients in the CKD group and 250.0 (95% confidence interval, 247.4 to 252.7) for patients in the non-CKD group. The prevalence ratio of CKD patient safety indicators to Agency for Healthcare and Research Quality patient safety indicators was 23.4 (95% confidence interval, 21.9 to 25.0). CONCLUSION: The candidate CKD patient safety indicators that occur in hospitalized patients are distinct from the Agency for Healthcare and Research Quality patient safety indicators and tend to be more common in CKD than non-CKD patients. These measures have the potential to serve as sentinel tools for identifying patients with CKD who warrant examination for disease-pertinent safety events.


Subject(s)
Health Status Indicators , International Classification of Diseases , Medical Errors/classification , Patient Safety , Quality Indicators, Health Care , Renal Insufficiency, Chronic/classification , United States Agency for Healthcare Research and Quality , Acute Kidney Injury/classification , Acute Kidney Injury/etiology , Adult , Aged , Female , Glomerular Filtration Rate , Heart Failure/classification , Heart Failure/etiology , Hospitalization , Humans , International Classification of Diseases/standards , Kidney/physiopathology , Male , Medical Errors/prevention & control , Medication Errors/classification , Medication Errors/prevention & control , Middle Aged , Patient Safety/standards , Quality Indicators, Health Care/standards , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/physiopathology , Renal Insufficiency, Chronic/therapy , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , United States , United States Agency for Healthcare Research and Quality/standards , United States Department of Veterans Affairs , Veterans Health , Water-Electrolyte Imbalance/classification , Water-Electrolyte Imbalance/etiology
13.
J Pediatr ; 157(1): 62-8, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20304423

ABSTRACT

OBJECTIVE: To test the hypothesis that some functionally significant variants in the gene encoding member A3 of the ATP Binding Cassette family (ABCA3) are not detected using exon-based sequencing approaches. STUDY DESIGN: The first of 2 female siblings who died from neonatal respiratory failure was examined for mutations with sequence analysis of all ABCA3 exons and known regulatory elements within the 5' untranslated region. Lung tissue from both siblings was immunostained for ABCA3 and examined with electron microscopy. Segregation of ABCA3 alleles was determined with analysis of polymorphisms in the parents and all children. RESULTS: No mutations were identified with ABCA3 sequence analysis in the first affected infant. Affected siblings were concordant for their ABCA3 alleles, but discordant from those of their unaffected siblings. ABCA3 protein was not detectable with immunostaining in lung tissue samples from both affected infants. Electron microscopy demonstrated small, dense lamellar bodies, characteristically seen with ABCA3 mutations. CONCLUSIONS: The segregation of ABCA3 alleles, absence of ABCA3 immunostaining, lung pathology, and ultrastructural findings support genetic ABCA3 deficiency as the cause of lung disease in these 2 infants, despite the lack of an identified genetic variant.


Subject(s)
ATP-Binding Cassette Transporters/metabolism , Lung Diseases/genetics , Lung/metabolism , ATP-Binding Cassette Transporters/genetics , Autopsy , Child , Chromosome Segregation , Exons , Family , Fatal Outcome , Female , Genetic Predisposition to Disease , Genotype , Humans , Lung/ultrastructure , Lung Diseases/complications , Lung Diseases/metabolism , Lung Diseases/pathology , Male , Microscopy, Electron , Mutation , Pedigree , Polymorphism, Single Nucleotide , Respiratory Insufficiency/etiology , Siblings
SELECTION OF CITATIONS
SEARCH DETAIL
...