Extraction of Buried P Waves from Printed Electrocardiograms

Background: Morphologic identification of ectopic P‐waves from surface ECGs can be challenging, particularly when the P‐wave is buried in the QRST wave complex. Because ECGs are often available on paper and not digitally, we developed a method of subtracting the T‐wave from the buried P‐wave complex on paper ECGs. Methods: To validate our system, an atrial extrastimulus was introduced during and following the T‐wave. The ECGs were scanned and then transformed from an image format to a digital format. A computer algorithm digitally subtracted a QRST with no buried P‐wave from one with a buried P‐wave, thus resulting in an extracted P‐wave. The extracted P‐waves were compared to the nonburied P‐wave by determining correlation coefficients and by visual grading by two independent reviewers. Results: Visual grading comparing the buried P‐wave with the exposed paced P‐wave was 94%. The median correlation coefficient was 85%. Conclusions: An ectopic atrial P‐wave obscured by a coincident QRST wave complex can be accurately derived from printed ECG using this PC‐based system. Addition of this technique to the existing methods may aid in the localization and ablation of ectopic atrial foci.     

Allogeneic bone marrow transplantation in a patieni with Shwachman-Diamond syndrome

Shwachman-Diamond syndrome (SDS) is a rare inherited disorder involving concomitant neutropenia and exocrine pancreatic insufficiency. About 25% of patients develop hematopoiesic malignancies. We describe a 24-year-old male patient with SDS who underwent allogeneic bone marrow transplantation (BMT) because of progression into acute myeloid leukemia (AML) following myelodysplastic syndrome (MDS). The BMT preparative regimen consisted of busulfan (16 mg/kg body wt.), followed by cyclophosphamide (120 mg/kg). Cyclosporin A and short methotrexate were used for graft-versus-host disease (GvHD) prophylaxis. The post-transplant period was complicated by staphylococcal septicemia, CMV infection, renal insufficiency, and acute GvHD grade III. Hematological recovery was delayed (post-transplant day +55). The patient was discharged at day +68 in complete remission without any evidence of MDS. RFLP fingerprint analysis showed complete engraftment of the donor's hematopoiesis. The patient's leukemia relapsed 9 months post-transplant, and death followed due to CMV infection and multiorgan failure. Despite the fatal course in this patient, allogeneic BMT could be an option for curative treatment of the hematopoietic failure in SDS. The interaction of BMT with pancreatic insufficiency still has to be ascertained.     

Corticobasal and ataxia syndromes widen the spectrum of C9ORF72 hexanucleotide expansion disease

Recently, a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 was reported as the cause of chromosome 9p21‐linked frontotemporal dementia‐amyotrophic lateral sclerosis (FTD‐ALS). We here report the prevalence of the expansion in a hospital‐based cohort and associated clinical features indicating a wider clinical spectrum of C9ORF72 disease than previously described. We studied 280 patients previously screened for mutations in genes involved in early onset autosomal dominant inherited dementia disorders. A repeat‐primed polymerase chain reaction amplification assay was used to identify pathogenic GGGGCC expansions. As a potential modifier, confirmed cases were further investigated for abnormal CAG expansions in ATXN2. A pathogenic GGGGCC expansion was identified in a total of 14 probands. Three of these presented with atypical clinical features and were previously diagnosed with clinical olivopontocerebellar degeneration (OPCD), atypical Parkinsonian syndrome (APS) and a corticobasal syndrome (CBS). Further, the pathogenic expansion was identified in six FTD patients, four patients with FTD‐ALS and one ALS patient. All confirmed cases had normal ATXN2 repeat sizes. Our study widens the clinical spectrum of C9ORF72related disease and confirms the hexanucleotide expansion as a prevalent cause of FTD‐ALS disorders. There was no indication of a modifying effect of the ATXN2 gene.     

Anatomic correlates of reduced hip extension during walking in individuals with mild‐moderate radiographic hip osteoarthritis

To identify radiographic and MR features of hip osteoarthritis (OA) related to reduced hip extension during walking. Sixty six subjects, were stratified into those with (n = 36, KL = 2, 3) and without (n = 30, KL = 0, 1) radiographic hip OA. Cartilage and labrum lesions were graded semi‐quantitatively on hip MRI. Alpha angle and lateral center edge (LCE) angle were measured. Sagittal kinematics and kinetics were calculated during walking at speed of 1.35 m/s using 3‐D motion capture. All subjects completed Hip disability and Osteoarthritis Outcome Score (HOOS), timed up and go, and 6 min walk tests. Variables were compared between the two groups using one‐way ANOVA (adjusting for age). Correlations of radiographic and MR parameters with peak hip extension were calculated. The OA group was older, had greater pain, and limitation of function. They also had lower peak hip extension and higher peak hip flexion; and worse acetabular and femoral cartilage lesions. Peak hip extension and flexion correlated with KL grade, cartilage lesions in the inferior and posterior femur. Reduced hip extension and greater hip flexion during walking are present in high functioning (HOOS > 85%) individuals with mild‐moderate hip OA, and are associated with cartilage lesions. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:527–534, 2015.     

Clinical features and outcome of T-cell acute lymphoblastic leukemia in childhood with respect to alterations at the TAL1 locus: a Pediatric Oncology Group study

Alteration of the TAL1 locus is the most common nonrandom genetic defect in childhood T-cell acute lymphoblastic leukemia (T-ALL). To determine if rearrangements of the TAL1 proto-oncogene confer a distinct leukemic phenotype, we studied leukemic peripheral blood or bone marrow samples from 182 children with newly diagnosed T-ALL enrolled on Pediatric Oncology Group treatment protocols. Forty-eight (26%) of the samples had a local rearrangement of the TAL1 locus. Demographic and clinical features were compared for patient subgroups with and without TAL1 rearrangements. The only clinical correlates that were significantly associated with TAL1 gene rearrangements were higher white blood cell count (P = .017) and higher hemoglobin (P = .007) at diagnosis. Immunophenotypically, samples with altered TAL1 were more likely to be CD2+ (P = .001) and lack CD10 (cALLa) expression (P = .007) than those without the rearrangement. There was a trend toward improved event-free survival (EFS) in patients with TAL1 rearrangements (4-year EFS was 44% +/- 7% for patients without the rearrangements v 59% +/- 11% for those with rearrangements), but the difference was not significant (P = .34). The role of TAL1 in leukemogenesis has yet to be clearly defined, and the prognostic significance of TAL1 gene rearrangements in T-ALL deserves further study.