Biomedical subjects

David S Feldman

Publications and source records attributed to David S Feldman.

At least 19 recordsLinked to original sources

PubMed2006

Calculation of rotational deformity in pediatric supracondylar humerus fractures.

OBJECTIVE: Supracondylar humerus fractures (SCHF) are common in the pediatric population. Cubitus varus deformity (CVD) is the most common long-term complication of SCHFs and may lead to elbow instability and deficits in throwing or extension. Distal fragment malrotation in the axial plane disposes to fragment tilt and CVD; however, no simple method of assessing fracture malrotation exists. This study tested a mathematical method of measuring axial plane malrotation in SCHFs based on plain radiographs. DESIGN: A pediatric SCHF model was made, and x-rays were taken at known intervals of rotation. Five independent, blinded observers measured these films. Calculated rotation for each data set was compared to the known rotation. The identical protocol was performed for an aluminum phantom. RESULTS: The reliability and agreement of the rotation values were good for both models. CONCLUSIONS: This method is a reliable, accurate, and cost-effective means of calculating SCHF distal fragment malrotation and warrants clinical application.

Child↗

PubMed2006

Detection of coronary artery disease in orthotopic heart transplant recipients with 64-detector row computed tomography angiography.

Cardiac transplant recipients develop coronary artery disease in the form of cardiac allograft vasculopathy (CAV), and still undergo annual left heart catheterizations for detection at most centers. We prospectively enrolled 20 cardiac transplant recipients scheduled for annual left heart catheterization with X-ray coronary angiography (XRA) to also undergo electrocardiographically gated coronary computed tomography angiography (CTA), which was performed on a 64-detector computed tomography scanner. CTA detected more CAV vs XRA in 4 patients and less CAV in 0 patient, resulting in good overall agreement between the two modalities (kappa = 0.69). CTA may be superior to conventional catheter-based angiography to identify non-obstructive vessel wall disease that may go unrecognized with catheter-based angiography alone.

Adult↗

PubMed2006

Interobserver and intraobserver reliability of radiographic evidence of bone healing at osteotomy sites.

Plain radiographs are commonly used to evaluate the degree of bone healing after an osteotomy and the application of an external fixator. The purpose of the study was to assess intraobserver and interobserver reliability in determining bone healing, defined as bridging callus across three of four cortices, of osteotomy sites on radiographs. Substantial intraobserver reliability and a high intraobserver percentage agreement were found. Interobserver reliability was moderate and interobserver percentage agreement was less than half for agreement between all involved orthopaedic surgeons. The lower reliability across surgeons suggests that the determination of the extent of the bone healing is subjective.

Bone and Bones↗

PubMed2005

Abnormal intrastore calcium signaling in chronic heart failure.

Diminished Ca release from the sarcoplasmic reticulum (SR) is an important contributor to the impaired contractility of the failing heart. Despite extensive effort, the underlying causes of abnormal SR Ca release in heart failure (HF) remain unknown. We used a combination of simultaneous imaging of cytosolic and SR intraluminal [Ca] in isolated cardiomyocytes and recordings from single-ryanodine receptor (RyR) channels reconstituted into lipid bilayers to investigate alterations in intracellular Ca handling in an experimental model of chronic HF. We found that diastolic free [Ca] inside the SR was dramatically reduced because of a Ca leak across the SR membrane, mediated by spontaneous local release events (Ca sparks), in HF myocytes. Additionally, the magnitudes of intrastore Ca depletion signals during global and focal Ca release events were blunted, and [Ca]SR recovery was slowed after global but not focal Ca release in HF myocytes. At the single-RyR level, the sensitivity of RyRs to activation by luminal Ca was greatly enhanced, providing a molecular mechanism for the maintained potentiation of Ca sparks (and increased Ca leak) at reduced intra-SR [Ca] in HF. This work shows that the diminished SR Ca release characteristic of failing myocardium could be explained by increased sensitivity of RyRs to luminal Ca, leading to enhanced spark-mediated SR Ca leak and reduced intra-SR [Ca].

Animals↗

PubMed2005

Silent strokes in patients with heart failure.

BACKGROUND: The prevalence of asymptomatic strokes detected by brain imaging in a large cohort of patients with congestive heart failure (CHF) and reduced ejection fraction (EF) is unknown. METHODS AND RESULTS: The present study was conducted to assess the prevalence of cerebrovascular accidents (CVA) diagnosed by routine brain imaging in neurologically asymptomatic patients with CHF who were being evaluated for heart transplantation. A comprehensive review of clinical data in a consecutive case series of 168 adult patients being evaluated was conducted. Patients at a high risk of having cerebral infarction (ie, history of transient ischemic attack or stroke, paroxysmal or chronic atrial fibrillation, intracardiac thrombi, and prosthetic valves) were excluded. Brain imaging was performed as part of a routine pre-heart transplant evaluation protocol. The prevalence of silent ischemic strokes was 34%. Multiple logistic regression analysis revealed a 2.3 (95% CI 1.05-5.03) times increased risk of silent strokes if a patient was African American. Traditional risk factors such as age, gender, hypertension, and diabetes mellitus were not predictive of CVA in this population. CONCLUSION: Patients with CHF and a left ventricular EF less than 20% being evaluated for heart transplantation have a high prevalence of ischemic CVA. The role of anticoagulation in this high-risk group of patients should be further explored.

Adolescent↗

PubMed2005

Canine nonischemic left ventricular dysfunction: a model of chronic human cardiomyopathy.

BACKGROUND: The mechanisms of cardiac remodeling during chronic heart failure remain poorly defined. We sought to advance a chronic canine model of nonischemic cardiomyopathy. METHODS AND RESULTS: Male dogs (n = 6) received decremental right ventricular apical tachypacing (12 months) to achieve and maintain stable left ventricular (LV) dysfunction. After 10 months of tachypacing, 120 beats/min was sufficient to maintain stable LV dysfunction. Electrocardiography, echocardiography, and tissue Doppler imaging were done to evaluate electrophysiology, LV dimensions and function, and dyssynchrony during normal sinus rhythm. The 6-minute walk test was used to evaluate functional capacity. We observed increases in both QRS duration (P < .0001) and QRS amplitude (P < .0001). LV fractional shortening was reduced from a baseline of 38.0 +/- 1.4% to 11.2 +/- 1.4% (P < .0001). LV end-diastolic dimension increased from 3.8 +/- 0.1 cm at baseline to 5.3 +/- 0.3 cm (P < .0001); LV end-systolic dimension increased from 2.3 +/- 0.1 cm to 4.7 +/- 0.2 cm (P < .0001). LV mass increased from 85.9 +/- 3.5 g at baseline to 179 +/- 13.7 g (P < .0001). There was evidence of LV dyssynchrony (P < .04) during both normal sinus rhythm and right ventricular tachypacing, compared with control dogs. The distance a dog walked in 6 minutes was significantly less at 12 months compared with normal controls (540 +/- 32 m versus 277 +/- 64 m, P < .008). CONCLUSION: This nonischemic model of canine cardiomyopathy reproduces many aspects of chronic human heart failure including reduced fractional shortening, dilated ventricular dimensions, increased LV mass, decreased functional capacity, and dyssynchrony.

Animals↗

PubMed2005

Effects of conversion from cyclosporine to tacrolimus on left ventricular structure in cardiac allograft recipients.

Twelve heart transplant recipients selected for conversion from cyclosporine to tacrolimus because of adverse effects of cyclosporine therapy underwent echocardiography at baseline and 6 months after conversion. Left ventricular mass decreased by 24% and left ventricular geometry returned toward normal at 6 months after conversion, without significant changes in blood pressure.

Cyclosporine↗

PubMed2005

Mechanisms of disease: beta-adrenergic receptors--alterations in signal transduction and pharmacogenomics in heart failure.

Beta-adrenergic signaling is an important regulator of myocardial function. During the progression of heart failure (HF), a reproducible series of biochemical events occurs that affects beta-adrenergic receptor (beta-AR) signaling and cardiac function. Furthermore, there are pathophysiologic alterations in the expression and regulation of proteins that are regulated by beta-ARs during HF. Analyses of these complex signaling pathways have led to a better understanding of HF mechanisms and the use of beta-adrenergic antagonists, which have notably altered HF-related morbidity and mortality. Despite therapeutic advances that have affected beta-AR signaling, HF remains a leading cause of hospitalization and a principal cause of death in industrialized nations. In this review, we summarize current insights into beta-adrenergic signal-transduction pathways, the best-described beta-AR polymorphisms, and therapies that target the beta-AR pathway in HF.

Adrenergic beta-Antagonists↗

PubMed2004

Practical application of human B-type natriuretic peptide as a therapeutic intervention in the perioperative setting.

The use of human B-type natriuretic peptide (BNP, nesiritide) as a therapeutic intervention is now well established for patients with acute decompensated heart failure. Nesiritide mimics the actions of endogenous BNP by binding to and stimulating receptors in the heart, kidney, and vasculature. Postsurgical patients are typically managed with various combinations of vasodilators, diuretics, and inotropes. Many of these therapeutic interventions lack significant proof of efficacy and are potentially deleterious to these patients, despite the acute hemodynamic improvement that results from their use. Use of nesiritide may supplant some of these therapies as an equally efficacious and possibly safer alternative in patients with decompensated heart failure. Nesiritide is a unique, balanced vasodilator that markedly decreases the signs and symptoms of heart failure in perioperative patients, and also may decrease the need for inotropic agents. This review summarizes nesiritide's mechanism of action and addresses special concerns and practical considerations for cardiothoracic surgeons and anesthesiologists. Overall, nesiritide appears to be an effective and safe therapeutic option in perioperative patients with decompensated heart failure.

Acute Disease↗

PubMed2004

Human B-natriuretic peptide improves hemodynamics and renal function in heart transplant patients immediately after surgery.

BACKGROUND: B-natriuretic peptide (BNP) is effective in the treatment of decompensated heart failure, but has not specifically been evaluated in the immediate postoperative cardiac transplant population. OBJECTIVE: To determine if BNP can favorably alter hemodynamics in the perioperative setting after heart transplantation. METHODS AND RESULTS: We administered (human)BNP ((h)BNP, Nesiritide) to 10 consecutive patients with preexisting renal insufficiency and elevated filling pressures. All patients had failed to respond to inotropes and escalating doses of diuretics. BNP was started 48 hours after transplantation, and continued for 48 to 72 hours. Intravascular hemodynamics were measured. With (h)BNP therapy, the pulmonary capillary wedge pressure, central venous pressure, and mean pulmonary artery pressure were all attenuated, whereas the cardiac output was significantly increased. The mean urine output increased significantly in the first 24 hours of therapy with no increase in diuretics. Implementation of BNP therapy allowed for a reduction of patients' inotropes and diuretics, while decreasing serum BNP levels. CONCLUSION: An improvement in cardiac hemodynamics and renal function was observed with administration of (h)BNP in these postsurgical patients with elevated filling pressures and acute on chronic renal insufficiency. This study demonstrates that posttransplant patients retain the capacity to respond to exogenous BNP immediately after surgery.

Acute Kidney Injury↗

PubMed2004

Surgical technique for an 'almost' percutaneous triple pelvic osteotomy for femoral head coverage in children 6-14 years of age.

A relatively simple triple pelvic osteotomy using two cosmetically small skin incisions can provide excellent coverage of the femoral head. An adductor approach and a bikini approach are used to do the osteotomy. The 'almost' percutaneous pelvic osteotomy successfully increases femoral head coverage in a concentric hip joint. The VCA angle of Lequesne and the center-edge angle of Wiberg both show significant improvement in the coverage of the femoral head. Three-dimensional computed tomography scanograms may provide a more graphic representation before and after surgery. Preoperatively, this is especially useful in evaluating posterior acetabular coverage of the femoral head. The almost percutaneous pelvic osteotomy is another possible triple pelvic osteotomy for procedures for hip dysplasia. It has a relatively low learning curve in comparison with other triple pelvic osteotomies for hip dysplasia in children aged 6-14 years. With careful patient selection, femoral head coverage can be improved with small incisions that are cosmetically acceptable.

Acetabulum↗

PubMed2004

Nesiritide for the treatment of congestive heart failure.

Nesiritide (Natrecor) is a recombinant form of the human B-type natriuretic peptide (BNP) that has been shown, through several studies, to have beneficial natriuretic, diuretic and vasodilatory effects in the treatment of congestive heart failure (CHF). Nesiritide mimics the actions of endogenous BNP by binding to and stimulating receptors in the heart, kidney and vasculature. Nesiritide functions as both a potent venous and arterial vasodilator and has been shown to improve cardiac haemodynamics more rapidly and to a greater extent than intravenous nitroglycerin, as well as having fewer side effects. When compared in an open-label trial, nesiritide has also been shown to be less proarrhythmic than dobutamine. The major adverse effect of nesiritide, as with other vasodilators, is symptomatic hypotension, which occurred infrequently in clinical trials. Overall, nesiritide represents an effective and safe therapeutic option for the treatment of decompensated CHF.

Diuretics↗

PubMed2003

Correction of tibial malunion and nonunion with six-axis analysis deformity correction using the Taylor Spatial Frame.

OBJECTIVE: To determine the effectiveness of six-axis analysis deformity correction using the Taylor Spatial Frame for the treatment of posttraumatic tibial malunions and nonunions. DESIGN: Retrospectively reviewed, consecutive series. Mean duration of follow-up was 3.2 years (range 2-4.2 years). SETTING: Tertiary referral center for deformity correction. PATIENTS/PARTICIPANTS: Eighteen patients were included in the study (11 malunions and 7 nonunions). All deformities were posttraumatic in nature. The mean number of operations before the application of the spatial frame was 2.6 (range 1-6 operations). All patients completed the study. INTERVENTION: Six-axis analysis deformity correction using the Taylor Spatial Frame (Smith & Nephew, Memphis, TN) was used for correction of posttraumatic tibial malunion or nonunion. Nine patients had bone grafting at the time of frame application. One patient with a tibial plafond fracture simultaneously had deformity correction and an ankle fusion for a mobile atrophic nonunion. Two patients had infected tibial nonunions that were treated with multiple débridements, antibiotic beads, and bone grafting at the time of spatial frame application. A rotational gastrocnemius flap was used to cover a proximal third tibial defect in one patient. The average length of time the spatial frame was worn, time to healing, was 18.5 weeks (range 12-32 weeks). MAIN OUTCOME MEASUREMENTS: Assessment of deformity correction in six axes, knee and ankle range of motion, incidence of infection, and return to preinjury activities. RESULTS: Of the 18 patients treated with the Taylor Spatial Frame, with adjunctive bone graft as necessary, 17 achieved union and significant correction of their deformities in six axes (ie, coronal angulation and translation, sagittal angulation and translation, rotation, and shortening). Fifteen patients returned to their preinjury activities at last follow-up. CONCLUSION: Six-axis analysis deformity correction using the Taylor Spatial Frame is an effective technique to treat posttraumatic malunions and nonunions of the tibia, with several advantages over previously used devices.

Adolescent↗

PubMed2003

A method for the early evaluation of the Ponseti (Iowa) technique for the treatment of idiopathic clubfoot.

The Ponseti casting technique is reported to have a high success rate in the treatment of idiopathic clubfoot. Non-operative treatment of clubfoot provides a lower complication rate, less pain, and higher function as the patient ages than operative treatment. To demonstrate serial post-treatment change in clubfeet over time, three clubfoot rating systems were utilized in the current study. Patients compliant with the Ponseti technique and treated before the age of 7 months, had a 92% success rate at an early follow-up after casting was completed. It is not the purpose of this article to analyze the long-term clubfoot treatment result but to establish tools which can be used to judge initial success with the Ponseti technique. Complications are few and minor, limited to equipment used and cast technique.

Casts, Surgical↗

PubMed2002

Selective inhibition of heterotrimeric Gs signaling. Targeting the receptor-G protein interface using a peptide minigene encoding the Galpha(s) carboxyl terminus.

The blockade of heptahelical receptor coupling to heterotrimeric G proteins by the expression of peptides derived from G protein Galpha subunits represents a novel means of simultaneously inhibiting signals arising from multiple receptors that share a common G protein pool. Here we examined the mechanism of action and functional consequences of expression of an 83-amino acid polypeptide derived from the carboxyl terminus of Galpha(s) (GsCT). In membranes prepared from GsCT-expressing cells, the peptide blocked high affinity agonist binding to beta(2) adrenergic receptors (AR) and inhibited beta(2)AR-induced [35S]GTPgammaS loading of Galpha(s). GsCT expression inhibited beta(2)AR- and dopamine D(1A) receptor-mediated cAMP production, without affecting the cellular response to cholera toxin or forskolin, indicating that the peptide inhibited receptor-G(s) coupling without impairing G protein or adenylyl cyclase function. [35S]GTPgammaS loading of Galpha(q/11) by alpha(1B)ARs and Galpha(i) by alpha(2A)ARs and G(q/11)- or G(i)-mediated phosphatidylinositol hydrolysis was unaffected, indicating that the inhibitory effects of GsCT were selective for G(s). We next employed the GsCT construct to examine the complex role of G(s) in regulation of the ERK mitogen-activated protein kinase cascade, where activation of the cAMP-dependent protein kinase (PKA) pathway reportedly produces both stimulatory and inhibitory effects on heptahelical receptor-mediated ERK activation. For the beta(2)AR in HEK-293 cells, where PKA activity is required for ERK activation, expression of GsCT caused a net inhibition of ERK activation. In contrast, alpha(2A)AR-mediated ERK activation in COS-7 cells was enhanced by GsCT expression, consistent with the relief of a downstream inhibitory effect of PKA. ERK activation by the G(q/11)-coupled alpha(1B)AR was unaffected by GsCT. These findings suggest that peptide G protein inhibitors can provide insights into the complex interplay between G protein pools in cellular regulation.

Animals↗

PubMed2002

Percutaneous fixation in clubfoot surgery: a radiographic and gait study.

Twenty patients with Type II clubfeet were evaluated an average of 3.1 years after complete surgical soft tissue release. A pinned group had fixation of the talonavicular and calcaneocuboid joints and a non-pinned group had no fixation. The control group consisted of 10 children without foot ailments. Radiographic measurements of talocalcaneal and talus-first metatarsal angles and frequencies of dorsal and medial navicular subluxation were not different for the two treatment groups. Foot progression angle was not significantly different for the two treatment groups, but was significantly different between all clubfoot patients (3.6 degrees of in-toeing) and the control group (5.0 degrees of out-toeing). Tourniquet time was significantly greater for the pinned than for the non-pinned group, but the duration of surgery was similar. Similar radiographic and gait measurement findings suggest that clubfoot surgery with and without percutaneous fixation have comparable outcomes.

Case-Control Studies↗

PubMedDate not supplied

Natural course of large spontaneous pneumothorax.

A large pneumothorax was detected on chest x-ray film in a 41-year-old woman. She declined recommendations for evacuation of the air trapped in her right chest. The condition spontaneously resolved during 3 months after being detected.

Adult↗

PubMedDate not supplied

Predicting the need for tenotomy in the Ponseti method for correction of clubfeet.

The purpose of this study was to determine how to predict the need for tenotomy at the initiation of the Ponseti treatment. Fifty clubfeet (35 patients) were prospectively rated according to Pirani and Dimeglio scoring systems. Tenotomies were performed in 36 of 50 feet (72%). Those that underwent tenotomy required significantly more casts (P = 0.005). Of 27 feet with initial Pirani scores > or = 5.0, 85.2% required a tenotomy and 14.8% did not; 94.7% of the Dimeglio Grade IV feet required tenotomies. Following removal of the last cast, there was no significant difference between those that did and did not have a tenotomy. Children with clubfeet who have an initial score of > or = 5.0 by the Pirani system or are rated as Grade IV feet by the Dimeglio system are very likely to need a tenotomy. At the end of casting, feet were equally well corrected whether or not they needed a tenotomy.

Achilles Tendon↗