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Biomedical subjects

Richard A Friedman

Publications and source records attributed to Richard A Friedman.

At least 19 recordsLinked to original sources
PubMed2006

Atrial flutter in infants.

OBJECTIVES: We sought to characterize the clinical nature of atrial flutter (AFL) in a large cohort of infants. BACKGROUND: There are no large studies describing the natural history of AFL in infants. Previous studies vary in the therapy used and expected prognosis. METHODS: We reviewed the records of all children younger than 1 year of age who were diagnosed with AFL at our hospital during the past 25 years, excluding those with previous cardiac surgery. RESULTS: We identified 50 infants with AFL. Most, 36 (72%), presented within the first 48 h of life. Congestive heart failure was evident in 10 infants, with 6 presenting at 1 day of age, and 4 presenting beyond 1 month of age. The remainder were asymptomatic. A large atrial septal defect was the only structural heart disease. Spontaneous conversion to sinus rhythm occurred in 13 (26%) infants. Sinus rhythm was restored in 20 of 23 (87%) attempts at direct current cardioversion and 7 of 22 (32%) attempts at transesophegeal pacing; 7 required antiarrhythmic therapy. An additional arrhythmia, all supraventricular, appeared in 11 (22%) infants. The recurrence of AFL developed in 6 infants; 5 of 6 of these incidents occurred within 24 h of the first episode. All patients with recurrence had an additional arrhythmia. CONCLUSIONS: Infants with AFL usually present within the first 2 days of life. No association was found with structural heart disease. Direct current cardioversion appears to be most effective at establishing sinus rhythm. Chronic AFL has the potential to cause cardiovascular compromise. Atrial flutter in the absence of other arrhythmias has a low risk of recurrence. Once in sinus rhythm, infants with AFL have an excellent prognosis and may not require chronic antiarrhythmic therapy.

Anti-Arrhythmia Agents↗
PubMed2006

Bridging the gap between biological and clinical informatics in a graduate training program.

Several training programs in biomedical informatics in the United States are attempting to integrate biological and clinical informatics. However, significant differences in the cultures underlying these two disciplines pose barriers to a uniform educational solution. This paper recounts the experience at Columbia University in adapting a graduate program with an initial focus on clinical informatics to train bioinformaticians. The analysis begins by considering the development of the medical and biological informatics cultures over a 17-year period. Then we review how two separate curricula evolved to serve the needs of each group. Interviews with bioinformatics students and faculty indicated some dissatisfaction with the curriculum that developed within clinical informatics. Their comments are considered in the light of an analysis of the relationship between the application domains of biomedical informatics as a discipline. In response, a new curriculum was developed in which bioinformatics and clinical informatics are regarded as subdivisions of the same subject. A key feature of this curriculum is a new course, Theory and Methods in Biomedical Informatics, which presents informatics principles in their general form, and illustrates their application with examples drawn from across the biomedical spectrum. The paper concludes with suggestions for integrating informatics training programs at other institutions.

Computational Biology↗
PubMed2006

Innovative techniques for placement of implantable cardioverter-defibrillator leads in patients with limited venous access to the heart.

BACKGROUND: Because of venous occlusion, intracardiac shunting, previous surgery, or small size placement of implantable cardioverter-defibrillator (ICD) leads may not be possible using traditional methods. The purpose of this study was to evaluate and describe innovative methods of placing ICD leads. METHODS: The records of all patients undergoing ICD implantation at our institution were reviewed to identify patients with nontraditional lead placement. Indications for ICD, method of lead and coil placement, defibrillation thresholds, complications, and follow-up results were reviewed retrospectively. RESULTS: Eight patients (aged 11 months to 29 years) were identified. Six patients with limited venous access to the heart (four extracardiac Fontan, one bidirectional Glenn, one 8 kg 11-month-old) underwent surgical placement of an ICD coil directly into the pericardial sac. A second bipolar lead was placed on the ventricle for sensing and pacing. Two patients with difficult venous access had a standard transvenous ICD lead inserted directly into the right atrium (transatrial approach) and then positioned into the ventricle. All patients had a defibrillation threshold of <20 J, although one patient required placement of a second coil due to an elevated threshold. There have been no complications and two successful appropriate ICD discharges at follow-up (median 22 months, range 5-42 months). CONCLUSIONS: Many factors may prohibit transvenous ICD lead placement. Nontraditional surgical placement of subcutaneous ICD leads on the pericardium or the use of a transatrial approach can be effective techniques in these patients. These procedures can be performed at low risk to the patient with excellent defibrillation thresholds.

Adolescent↗
PubMed2006

Therapeutic levels of intravenous procainamide in neonates: a retrospective assessment.

STUDY OBJECTIVES: To evaluate dosing and pharmacokinetic parameters of intravenous continuous-infusion procainamide in neonates, and to identify dosage regimens and factors leading to therapeutic procainamide levels and minimal adverse events. DESIGN: Retrospective, observational study. SETTING: Pediatric hospital. PATIENTS: . Twenty-one patients (seven preterm, 14 full term) younger than 30 days who received continuous-infusion procainamide therapy for more than 15 hours or had two consecutive therapeutic procainamide levels obtained while receiving therapy between June 1, 2002, and December 31, 2005. MEASUREMENTS AND MAIN RESULTS: Data on demographics, dosing, drug levels, and adverse effects were collected. Doses that achieved therapeutic levels were documented, and procainamide clearance was calculated and evaluated with regard to renal function and gestational age in patients who were at steady state. Mean clearance and mean N-acetylprocainamide (NAPA):procainamide ratios were compared between preterm and term neonates. No patients experienced hemodynamic instability or other adverse effects due to procainamide. Procainamide was given as a mean +/- SD 9.6 +/- 1.5-mg/kg bolus in 20 of 21 patients before continuous infusion. The mean +/- SD dose at which two therapeutic levels were achieved was 37.56 +/- 13.52 microg/kg/minute. Procainamide clearance was 6.36 +/- 8.85 ml/kg/minute and correlated with creatinine clearance (r=0.78, p<0.00001) and age at day of sampling (r=0.49, p<0.00001). The NAPA:procainamide ratio at steady state was 0.84 +/- 0.53; two patients were determined to be fast acetylators (ratio > 1). Preterm infants had lower mean clearance rates (p<0.001) but higher NAPA:procainamide ratios (p<0.01) than those of term infants. Five patients experienced seven supratherapeutic levels while receiving therapy; four of these patients were preterm, and all had creatinine clearances less than 30 ml/minute/1.73 m(2). Three patients had four pairs of levels obtained after discontinuation of procainamide, and elimination rate constant and half-life were calculated. CONCLUSION: Procainamide can be safely used in neonates, with no short-term adverse effects. The dosage regimen for intravenous procainamide required to achieve therapeutic levels in neonates is similar to that of older infants and children. Doses may need to be reduced in premature infants and in those with renal dysfunction.

Acecainide↗
PubMed2005

Lung adenocarcinoma global profiling identifies type II transforming growth factor-beta receptor as a repressor of invasiveness.

RATIONALE: Lung adenocarcinoma histology and clinical outcome are heterogeneous and associated with tumor invasiveness. OBJECTIVES: We hypothesized that invasiveness is associated with a distinct molecular signature and that genes differentially expressed in tumor or adjacent stroma will identify cell surface signal transduction and matrix remodeling pathways associated with the acquisition of invasiveness in lung adenocarcinoma. MAIN RESULTS: Microarray analysis of microdissected noninvasive bronchioloalveolar carcinoma (BAC) and invasive adenocarcinoma and adenocarcinoma-mixed type with BAC features identified transcriptional profiles of lung adenocarcinoma invasiveness. Among the signature set that was lower in adenocarcinoma-mixed compared with BAC was the type II transforming growth factor beta (TGF-beta) receptor, suggesting downregulation of TGFbetaRII is an early event in lung adenocarcinoma metastasis. Immunostaining in independently acquired specimens demonstrated a correlation between TbetaRII expression and length of tumor invasion. Repression of TGFbetaRII in lung cancer cells increased tumor cell invasiveness and activated p38 mitogen-activated protein kinases. Microarray analysis of invasive cells identified potential downstream mediators of TGFbetaRII with differential expression in lung adenocarcinomas. CONCLUSIONS: The repression of type II TGF-beta receptor may act as a significant determinant of lung adenocarcinoma invasiveness, an early step in tumor progression toward metastasis.

Adenocarcinoma↗
PubMed2005

Atrioventricular junction ablation and pacemaker therapy in patients with drug-resistant atrial tachyarrhythmias after the Fontan operation.

INTRODUCTION: Drug-resistant intraatrial reentrant tachycardia (IART) occurs frequently after the Fontan operation and is a major cause of morbidity and rarely mortality. We describe our experience with AV junction ablation after pacemaker implantation in postoperative Fontan patients with drug-resistant IART. METHODS AND RESULTS: We performed retrospective analysis of Fontan patients with IART and attempted radiofrequency ablation (RFA) of the AV junction. Seven patients (6 male) were identified, with a mean age at Fontan of 9.3 years (range 5.8-13.3) and a median age at RFA of 18 years (range 14.5-23.3). Mean follow-up prior to RFA was 764 +/- 235 days and after RFA 1,541 +/- 1,235 days. IART was refractory to antiarrhythmic drugs in all patients, and all had undergone pacemaker placement. Mean onset of IART was 44.1 months (range 0-142) after Fontan. Mean duration of atrial arrhythmia prior to RFA was 72 +/- 48 m (range 16-148). Ablation of the AV junction was successful or partially successful in all patients. Complete AV block occurred in 6 patients. Normal AV conduction was not seen during a mean follow-up of 1,541 days. The mean number of antiarrhythmic medications decreased from 2.8 +/- 1.5 to 0.7 +/- 0.8 (P <0.05). CONCLUSION: In Fontan patients with drug-resistant IART, RFA of the AV junction with prior pacemaker implant is an effective therapeutic option. Despite the introduction of pacemaker dependence, this option should be considered in patients who did not respond to RFA of IART or who are at high operative risk for Fontan conversion.

Adolescent↗
PubMed2004

Molecular signatures in biopsy specimens of lung cancer.

Gene expression profiles of resected tumors may predict treatment response and outcome. We hypothesized that profiles derived from lung tumor biopsies would discriminate tumor-specific gene signatures and provide predictive information about outcome. Lung carcinoma specimens were obtained from 23 patients undergoing computed tomography-guided transthoracic biopsy or endobronchial brushing for undiagnosed nodules. Excess tissue was processed for gene profiling. We built class prediction models for lung cancer histology and for cancer outcome. The histology model used an F test to identify 99 genes that were differentially expressed among lung cancer subtypes. The histology validation set class prediction accuracy rate was 86%. The outcome model used the maximum difference subset algorithm to identify 42 genes associated with high risk for cancer death. The outcome training set class prediction accuracy rate was 87%. In conclusion, gene expression profiles of biopsy specimens of lung cancers identify unique tumoral signatures that provide information about tissue morphology and prognosis. The use of specimens acquired from lung biopsy procedures to identify biomarkers of clinical outcome may have application in the management of patients with lung cancer. The procedures are safe and feasible; the efficacy and utility of this strategy will ultimately be determined by prospective clinical trials.

Adult↗
PubMed2004

Clinical course of atrial ectopic tachycardia is age-dependent: results and treatment in children < 3 or > or =3 years of age.

OBJECTIVES: We assessed the clinical presentation, natural history, and treatment response of atrial ectopic tachycardia (AET) in children <3 years of age (group 1) compared with those > or =3 years of age (group 2). BACKGROUND: Atrial ectopic tachycardia is a common cause of chronic supraventricular tachycardia in children and can be resistant to pharmacologic therapy. Radiofrequency ablation (RFA) can eliminate AET arising from a single focus. METHODS: A retrospective review identified all children at Texas Children's Hospital diagnosed with AET from March 1991 to November 2000. Data obtained included clinical presentation, echocardiographic evaluation, response to antiarrhythmic therapy, spontaneous resolution, and outcomes of radiofrequency and surgical ablation. RESULTS: Sixty-eight children were identified (22 children <3 years and 46 children > or =3 years of age). Control of AET with antiarrhythmic therapy was achieved in 91% of the younger children but only 37% of the older children (p < 0.001). There was a higher rate of spontaneous resolution in the younger group (78%) compared with the older group (16%) (p < 0.001). Radiofrequency ablation was performed in 35 of the older children, with ultimate success in 74%. Surgical intervention was required for six children. CONCLUSIONS: Younger children respond to antiarrhythmic therapy and have a high incidence of AET resolution, thus warranting a trial of antiarrhythmic therapy. In children > or =3 years, AET is unlikely to resolve spontaneously, and antiarrhythmic medications are frequently ineffective. Thus, RFA should be considered early in the course of treatment for these children; however, surgical intervention may be necessary.

Adolescent↗
PubMed2004

Late pacemaker requirement after pediatric orthotopic heart transplantation may predict the presence of transplant coronary artery disease.

BACKGROUND: Few data are available regarding pacemaker implantation after pediatric orthotopic heart transplantation. The purpose of this study was to assess the incidence, indications and associations with regard to pacemaker placement in children who have undergone orthotopic heart transplantation. METHODS: We performed a retrospective study of all patients undergoing orthotopic heart transplantation at our institution from October 1984 to March 2001. Data obtained included demographics, indications for pacemaker, presence of transplant coronary artery disease and long-term follow-up. Patients were divided into: Group 1, patients requiring a pacemaker within 3 months of transplantation; and Group 2, patients requiring a pacemaker beyond 3 months. RESULTS: Pacemakers were required in 7 of 106 (6.6%) transplant recipients. Pacing indications for patients in Group 1 (n = 2) were persistent bradycardia with pause-related ventricular arrhythmia and atrial flutter with resultant sinus pauses of up to 4 seconds. In Group 2 patients (n = 5), indications for pacing were high-grade atrioventricular (AV) block in 1 patient and episodic sinus pauses up to 3.3 seconds associated with syncope/dizziness in the remaining 4 patients. All patients in Group 2 had transplant coronary disease diagnosed within 1 year of pacemaker implantation. All had resolution of symptoms and no complications after implantation. CONCLUSIONS: Pacemakers are infrequently required after cardiac transplantation in children. Despite not meeting classic symptomatic sinus bradycardia criteria, pacemaker placement should be considered post-transplantation in patients with episodic sinus pauses and dizziness or syncope. Patients who present with the aforementioned symptoms or high-grade AV block should be evaluated closely for the presence or development of transplant coronary artery disease, as it may be their first symptom.

Bradycardia↗
PubMed2003

Frequency of recurrence among infants with supraventricular tachycardia and comparison of recurrence rates among those with and without preexcitation and among those with and without response to digoxin and/or propranolol therapy.

Approximately 60% of children with supraventricular tachycardia (SVT) develop their initial episode by 1 year of age. Despite resolution in most of these patients by 1 year, approximately 30% of the SVT will recur. We performed a retrospective review of all patients <1 year of age with SVT between January 1984 and December 2000. Recurrence was defined as documented SVT at >1 year of age. Patients were divided into: (1) a first line (FL) group (controlled with digoxin and/or propranolol) and (2) a second line (SL) group (requiring additional antiarrhythmics). The groups were divided based on the presence of preexcitation. The FL group included 116 patients, 20 of whom (17%) had Wolff-Parkinson-White (WPW) syndrome. The SL group included 34 patients, 21 of whom (62%) had WPW (p <0.001). Recurrence of SVT occurred in 32 patients (28%) in the FL group and in 23 patients (68%) in the SL group (p <0.001). SVT recurred in 36 of 41 patients (88%) with WPW compared with 19 of 109 patients (17%) without WPW syndrome (p <0.001). Logistic regression analysis demonstrated that the presence of WPW syndrome was associated with a 29-fold higher odds of SVT recurrence (p <0.001), and that patients with WPW syndrome were more likely to require additional antiarrhythmic therapy (p <0.001). Thus, patients with WPW syndrome who had SVT at <1 year of age have 29-fold higher odds of recurrence at >1 year of age versus those patients with preexcitation. These patients are also more likely to require additional antiarrhythmic therapy to control SVT. Furthermore, children with WPW syndrome who are refractory to treatment with digoxin and/or propranolol are at increased risk of SVT recurrence.

Age of Onset↗
PubMed2003

The use of implantable cardioverter-defibrillators in pediatric patients awaiting heart transplantation.

BACKGROUND: This multicenter study evaluated experience with implantable cardioverter defibrillators (ICD) as a bridge to orthotopic heart transplantation (OHT) in children. METHODS: The application of ICD therapy continues to expand in pediatric populations, due in part to improved technology and new indications, including the prevention of sudden death while awaiting OHT. METHODS: We performed a retrospective review of ICD databases at 9 pediatric transplant centers. RESULTS: Twenty-eight patients (16 males) underwent implantation or had a preexisting ICD while awaiting OHT between 1990 and 2002. The median age at implant was 14.3 years (11 months to 21 years) with a median weight of 49 kg (11.7-88 kg). Diagnoses included cardiomyopathy (n=22), and congenital heart disease (n=6). Indications for ICD implantation included ventricular tachycardia/fibrillation (n=23), syncope (n=5), aborted sudden death with no documentation of rhythm disturbance (n=5), ventricular ectopy (n=1), and poor function (n=5). Of the 28 ICDs, 23 were implanted by a transvenous approach and 5 by epicardial route. There were 55 defibrillator discharges in 17 patients, 47 (85%) of which (in 13 patients) were appropriate. The 8 inappropriate discharges (in 6 patients) were triggered by sinus tachycardia, inappropriate sensing, and atrial flutter. The mean time from implantation to first appropriate shock was 6.9 months (1 day to 2.6 years). Twenty-one patients underwent transplantation during the study period, whereas 2 died while awaiting a donor. Morbidity included a lead fracture, 3 episodes of electromechanical dissociation, and 1 episode of electrical storm. CONCLUSIONS: ICD implantation represents an effective bridge to transplantation in pediatric patients. The complication rate is low, with inappropriate device discharge due primarily to sinus tachycardia or atrial flutter. There is a high incidence of appropriate ICD therapy for malignant ventricular arrhythmias in this highly selected group of patients.

Adolescent↗
PubMed2002

The emergence of protocadherin-PC expression during the acquisition of apoptosis-resistance by prostate cancer cells.

In order to identify gene products associated with the development of acquired therapeutic resistance by prostate cancer cells, we created two novel apoptosis-resistant prostate cancer cell lines, LNCaP-TR (phorbol-ester [TPA]-Resistant) and LNCaP-SSR (Serum Starvation-Resistant) by repeated transient exposure of cultured human LNCaP cells to apoptotic stimuli followed by expansion of surviving cell populations. These cell lines were found to be cross-resistant to the alternative selective agent and also hormone-resistant when xenografted into castrated male immunodeficient mice. RNA from the LNCaP-TR line was comparatively screened using a subtractive hybridization-PCR procedure. This allowed us to identify a 249 bp cDNA fragment that hybridized to a 4.8 kb mRNA preferentially expressed by the apoptosis-resistant cells. Using RACE procedures, we cloned and sequenced the complete 4.8 kb cDNA. It is an unusual member of the protocadherin gene family containing two large overlapping open reading frames encoding homologous polypeptides, one having a signal sequence and the other lacking a signal sequence and we refer to it as protocadherin-PC. LNCaP cells directly transformed with protocadherin-PC cDNA were comparatively resistant to phorbol-ester induced apoptosis. Antibody recognition studies demonstrating the cytoplasmic nature of the protcadherin-PC translation product and its propensity to bind beta-catenin suggest that it might influence the apoptotic sensitivity of prostate cancer cells through a unique mechanism.

Adenocarcinoma↗
PubMed2002

Flecainide and sotalol: a new combination therapy for refractory supraventricular tachycardia in children <1 year of age.

OBJECTIVES: The goal of this study was to assess the efficacy and safety of the combination therapy of flecainide and sotalol for the treatment of refractory supraventricular tachycardia (SVT) in children <1 year of age. BACKGROUND: Supraventricular tachycardia in infants can be refractory to single-drug as well as standard combination medical therapy. Radiofrequency ablation (RFA) is the definitive treatment of refractory SVT; however, interventional therapy poses a high risk of morbidity and mortality in this age group. METHODS: A retrospective review was performed identifying infants who required flecainide and sotalol to control refractory SVT. Patient age, previous drug therapy, duration of treatment, flecainide levels and corrected QT intervals were recorded; 24 h Holter monitoring was utilized to gauge efficacy of treatment. Efficacy was defined as suppression of SVT to no more than rare nonsustained episodes or slowing of SVT to a clinically tolerable rate. RESULTS: Ten patients (median age: 29 days, range: 1 to 241 days) failed at least two antiarrhythmic agents including either flecainide or sotalol as single agents before initiating combination therapy. Efficacy was achieved in all patients. The failure rate for therapy was reduced from 100% to 0% (95% confidence interval: 0% to 26%). The median doses used were: flecainide 100 mg/m(2)/day (range: 40 to 150 mg/m(2)/day) and sotalol 175 mg/m(2)/day (range: 100 to 250 mg/m(2)/day). Median duration of therapy was 16 months (range: 5 to 35 months). No proarrhythmia occurred. CONCLUSIONS: The combination of flecainide and sotalol can safely and effectively control refractory SVT and may obviate the need for RFA in children <1 year.

Anti-Arrhythmia Agents↗