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Biomedical subjects

Alexander Kadner

Publications and source records attributed to Alexander Kadner.

At least 19 recordsLinked to original sources

Distinct roles for glycine and GABA in shaping the response properties of neurons in the superior paraolivary nucleus of the rat.

The superior paraolivary nucleus (SPON) is a prominent periolivary cell group of the superior olivary complex. SPON neurons use gamma-aminobutyric acid (GABA) as their neurotransmitter and are contacted by large numbers of glycinergic and GABAergic punctate profiles, representing a dense inhibitory innervation from the medial nucleus of the trapezoid body (MNTB) and from collaterals of SPON axons, respectively. SPON neurons have low rates of spontaneous activity, respond preferentially to the offset of pure tones, and phase-lock to amplitude-modulated tones. To determine the roles of glycine and GABA in shaping SPON responses, we recorded from single units in the SPON of anesthetized rats before, during, and after application of the glycine receptor antagonist strychnine, the GABA(A) receptor antagonist bicuculline, or both drugs applied simultaneously. Strychnine caused a major increase in spike counts during the stimulus presentation, followed by the disappearance of offset spikes. In half of the recorded units, bicuculline caused moderately increased firing during the stimulus. However, in 86% of units bicuculline also caused a large increase in the magnitude of the offset response. Application of the drug cocktail caused increased spontaneous activity, dramatically increased spike counts during the stimulus presentation, and eliminated the offset response in most units. We conclude that glycinergic inhibition from the MNTB suppresses SPON spiking during sound stimulation and is essential in generating offset responses. GABAergic inhibition, presumably from intrinsic SPON collaterals, plays a subtler role, contributing in some cells to suppression of firing during the stimulus and in most cells to restrict firing after stimulus offset.

Acoustic Stimulation↗

Tricuspidisation of the aortic valve with creation of a crown-like annulus is able to restore a normal valve function in bicuspid aortic valves.

OBJECTIVE: To evaluate the early results of a new method to repair malfunctioning bicuspid aortic valves by creating a tricuspid valve with a crown-like (i.e. anatomic) annulus. MATERIAL AND METHODS: Twelve patients (ages from 10 to 27 years) with chronic regurgitation (and flow-dependent stenosis) of a bicuspid aortic valve underwent repair with the principle of creating a tricuspid valve and a crown-like annulus. The fused leaflets were trimmed and reinserted underneath the existing aortic annulus to create one new native cusp. The third leaflet was fashioned out of a xenopericard patch and was inserted underneath the existing annulus as well to restore the crown-like anatomy of a normal aortic annulus. A tricuspid aortic valve with a morphologically normal annulus was thus created, which resulted in improved coaptation of the leaflets. The repair was immediately assessed by transesophageal echocardiography (TEE) with the heart loaded at 50%. In two patients, a second run helped fine-tune the repair. Median cross-clamping time was 82 min. Follow-up ranged from 3 to 46 months (median 13 months). RESULTS: No significant complication occurred. The function of the aortic valve was excellent with trivial or mild regurgitation in 11 patients and moderate regurgitation in 1 patient. There was no stenosis across the valve. The repair remained stable over time. Remodelling of the left ventricle occurred as expected. CONCLUSIONS: Aortic valve repair is feasible in some dysfunctioning bicuspid aortic valves. Tricuspidisation of the valve can result in excellent systolic and diastolic functions. The creation of a crown-like annulus results in improved coaptation of the cusps and could lead to more reliable outcome. Although long-term results are needed, this anatomic correction seems to be a good alternative to valvular replacement in certain sub-groups of patients.

Adolescent↗

Low-frequency hearing loss in prenatally stressed rats.

We investigated the possibility that hearing thresholds are altered in prenatally stressed rats raised in a normal auditory environment. Pregnant dams were assigned randomly to prenatally stressed and control groups. Half of the dams were subjected to the mild stressors of handling, exposure to a novel cage and saline injection at random times during lights-on daily. The hearing thresholds of young adult male offspring were assessed by recording auditory-evoked brainstem responses to 0.5, 1, 2, 4, 8, 16, 32 and 64 kHz pure tones. The resultant audiograms showed that prenatally stressed offspring had significantly higher hearing thresholds than control animals at 1, 2 and 4 kHz (t-tests, P<0.05). The threshold shifts caused by prenatal stress averaged 7.7 dB across frequencies. We conclude that prenatal stress causes low-frequency hearing loss, possibly due to increased vulnerability to noise-induced hearing loss, accelerated cochlear degeneration and/or disrupted cochlear development.

Acoustic Stimulation↗

Application and adjustment of artificial chordae to the mitral valve using an approach through the aortic valve.

Insertion of artificial chordae or shortening of native ones on the mitral valve with precise determination of their length can be done through the aortic annulus. This route was used to correct a prolapse of the anterior leaflet in 7 patients and resulted in stable repair with no residual insufficiency (4 patients) or trivial residual insufficiency (3 patients).

Aortic Valve↗

Brain natriuretic peptide and magnetic resonance imaging in tetralogy with right ventricular dilatation.

BACKGROUND: Cardiac volumetry by magnetic resonance imaging can guide the timing for reoperation in minimally symptomatic or asymptomatic patients with pulmonary insufficiency after corrected tetralogy of Fallot. Pro-brain natriuretic peptide (BNP) is a marker of ventricular dysfunction and wall stress, and levels may complement magnetic resonance imaging in cardiac assessment before and after pulmonary valve replacement. METHODS: Between May 2004 and October 2005, 23 consecutive patients with corrected tetralogy, severe pulmonary insufficiency, and right ventricular end-diastolic volume index greater than 150 mL/m2 underwent elective pulmonary valve replacement. Plasma proBNP levels and magnetic resonance imaging were obtained before and 6 months after pulmonary valve replacement. RESULTS: There was no surgical mortality or morbidity. Preoperative right ventricular end-diastolic volume index correlated with pulmonary insufficiency, and inversely so with left ventricular ejection fraction, reflecting interventricular interaction. Preoperatively (r = -0.47) and 6 months postoperatively (r = -0.54), log BNP was inversely correlated with right ventricular ejection fraction. Mean preoperative proBNP levels, right ventricular end-diastolic volume index, and pulmonary insufficiency significantly (p < 0.0001) diminished 6 months after pulmonary valve replacement (231 versus 114 ng/L, 184 versus 109 mL/m2, and 44% versus 2%, respectively). CONCLUSIONS: Plasma proBNP is elevated in patients with corrected tetralogy, severe pulmonary insufficiency, and right ventricular dilatation, and it significantly diminishes 6 months after pulmonary valve replacement, mirroring magnetic resonance imaging-documented better right ventricular ejection fraction and smaller right ventricular end-diastolic volume index. Pro-brain natriuretic peptide complements magnetic resonance imaging for cardiac assessment in patients requiring pulmonary valve insertion. Future validation of cutoff levels are required to establish proBNP as a useful diagnostic and follow-up tool in patients with chronic pulmonary insufficiency and failing right ventricles.

Biomarkers↗

Closure of restrictive ventricular septal defects through a right axillary thoracotomy.

OBJECTIVE: To report the midterm results of an alternative minimally invasive approach for closure of ventricular septal defects (VSD) through a muscle-sparing minithoracotomy at the right midaxillary line. MATERIAL AND METHODS: From September 2003 to December 2005, 22 patients (median age, 5 years; range, 1.5-12 years) underwent a right lateral axillary thoracotomy for closure of a perimembranous VSD. Special features of the approach included an incision between the anterior and posterior axillary fold, a muscle-sparing preparation over the fourth intercostal space, and the establishment of cardiopulmonary bypass with inguinal and superior vena cava cannulation. The ascending aorta was cross clamped and cardioplegic arrest was instituted. The VSDs were all approached through a right atriotomy and closed directly (17 patients) or with a patch (5 patients). Three patients underwent concomitant aortic valve repair. RESULTS: There was no mortality or significant surgical morbidity. Median cross-clamp and cardiopulmonary bypass times were 46 and 104 min, respectively. Follow-up was complete and ranged from 2 to 22 months (median, 20 months). All patients were in sinus rhythm. Echocardiography revealed no residual defects with competent aortic and tricuspid valves. The length of the incision ranged from 4 to 6 cm, was away from the mammary gland, and remained entirely covered by the adducted arm. All children recovered right shoulder function within days, and cosmetic results were very satisfying. One patient developed iliac artery stenosis following inguinal artery cannulation. CONCLUSION: Closure of perimembranous VSDs in older children can be safely performed through a right axillary thoracotomy without compromising the accuracy of the repair. The cosmetic results are excellent.

Cardiopulmonary Bypass↗

Neurons in the medial nucleus of the trapezoid body and superior paraolivary nucleus of the rat may play a role in sound duration coding.

We describe neurons in two nuclei of the superior olivary complex that display differential sensitivities to sound duration. Single units in the medial nucleus of the trapezoid body (MNTB) and superior paraolivary nucleus (SPON) of anesthetized rats were studied. MNTB neurons produced primary-like responses to pure tones and displayed a period of suppressed spontaneous activity after stimulus offset. In contrast, neurons of the SPON, which receive a strong glycinergic input from MNTB, showed very little or no spontaneous activity and responded with short bursts of action potentials after the stimulus offset. Because SPON spikes were restricted to the same time window during which suppressed spontaneous activity occurs in the MNTB, we presume that SPON offset activity represents a form of postinhibitory rebound. Using characteristic frequency tones of 2- to 1,000-ms duration presented 20 dB above threshold, we show that the profundity and duration of the suppression of spontaneous activity in MNTB as well as the magnitude and first spike latency of the SPON offset response depend on stimulus duration as well as on stimulus intensity, showing a tradeoff between intensity and duration. Pairwise comparisons of the responses to stimuli of various durations revealed that the duration sensitivity in both nuclei is sharpest for stimuli <50 ms.

Acoustic Stimulation↗

Aortic sinus-left atrial fistula after interventional closure of atrial septal defect.

A 3-year-old boy underwent interventional closure of an atrial septal defect using an Amplatzer septal occluder. After 4 weeks, an aortic sinus-to-left atrial fistula was detected by echocardiography in an asymptomatic child. The device was surgically explanted with fistula and atrial septal defect closure. Follow-up was uneventful.

Aortic Diseases↗

In the footsteps of senning: lessons learned from atrial repair of transposition of the great arteries.

The Senning operation has evolved from being the initial surgical correction that allowed survival in complete transposition of the great arteries to an integral part of the anatomic repair of congenitally corrected transposition. In patients with complete transposition, the Senning operation has given satisfactory initial and long-term surgical results, but the potential for right ventricular failure and atrial arrhythmias have drastically reduced its indications in the current era. The long-term follow-up and pertinent postoperative issues of the Senning operation will be reviewed, along with its newfound role in the anatomic repair of congenitally corrected transposition.

Arrhythmias, Cardiac↗

Early results of the bovine jugular vein graft used for reconstruction of the right ventricular outflow tract.

BACKGROUND: This study is an assessment of early results of bovine jugular vein grafts (BJV) used to reconstruct the right ventricular outflow tract. METHODS: Ninety-three consecutive BJV implantations performed between May 2001 and August 2003 were included in this study. The median age was 7.2 years. Indications included various forms of tetralogy of Fallot and pulmonary atresia (56 patients), aortic valve disease requiring a Ross procedure (21 patients), truncus arteriosus (8 patients), d-transposition of the great arteries with ventricular septal defect and pulmonary stenosis (5 patients) and miscellaneous (3 patients). Additional plasty of the intrapericardial pulmonary arteries was performed in 41 patients. Follow-up was complete with a mean duration of 20.3 +/- 5.8 months. RESULTS: There were 3 patients (3.2%) with early deaths and 2(2.2%) with late deaths, but none were related to the bovine jugular vein grafts. Twelve bovine jugular vein grafts needed reintervention; 11 were due to development of a stenotic membrane at the anastomosis site and one was due to somatic outgrowth of the child (10 conduit replacements and two balloon dilatations). Overall freedom from reintervention was 91.6% and 83.5% at 12 and 24 months, respectively. Small size (< or = 14 mm) conduits show respective rates of 80.7% and 63.6%, whereas larger sizes were 98% and 96%, free from reintervention at 12 and 24 months. CONCLUSIONS: Bovine jugular vein grafts, when used for reconstruction of the right ventricular outflow tract, showed good early-term results. Attrition of small size bovine jugular vein grafts, due to development of a stenotic process at the anastomotic site needs to be closely observed. Longer follow-up is needed to allow a more definitive comparison with other established options.

Adolescent↗

Early insertion of a pulmonary valve for chronic regurgitation helps restoration of ventricular dimensions.

BACKGROUND: This study assesses the results of early insertion of a pulmonary valve for chronic pulmonary regurgitation based on right ventricular volume measurements. METHODS: Valved conduits were prospectively inserted in 39 patients (aged 14 to 39 years) when the right ventricular (RV) end-diastolic volume index on magnetic resonance imaging (MRI) exceeded 150 mL/m2. Changes in morphology and function of the RV were prospectively analyzed by an MRI at 6 months postoperatively (available in 21 patients). RESULTS: There were no early or late deaths. All conduits showed good function at a median 15 month follow-up. Postoperative RV end-systolic and end-diastolic volumes showed a significant positive correlation (p = 0.005 and p < 0.0001), while postoperative left ventricular (LV) ejection fraction showed a significant negative correlation (p = 0.03) with preoperative RV end-diastolic volume index. Seven patients who achieved normal RV end-diastolic volume index (< or = 100 mL/m2) (group 1) when compared with 14 remaining patients (group 2) showed that they differed significantly with respect to their preoperative RV end-diastolic volume index (170.3 +/- 21.1 vs 203.6 +/- 35.6; p = 0.02) and postoperative LV ejection fraction (59.9 +/- 4.2 vs 54 +/- 7%, p = 0.03). CONCLUSIONS: Our results show that the improvement in ventricular dimensions and functions directly correlates with the timing of pulmonary valve insertion. Early insertion leads to normalization and late insertion leads only to improvement. These observations, along with a low morbidity for these reoperations, justify earlier reintervention in cases of chronic pulmonary regurgitation. A RV end-diastolic volume index of 150 mL/m2 seems to be a practical cutoff value to prescribe pulmonary valve insertion.

Adolescent↗

Left heart atrial and ventricular epicardial pacing through a left lateral thoracotomy in children: a safe approach with excellent functional and cosmetic results.

OBJECTIVE: Left heart atrial and ventricular epicardial pacing through a left lateral thoracotomy is an alternative approach for lead insertion in children, avoiding venous access complications and right ventricular stimulation, without compromising sporting or musical activities. We analyzed the survival and performance of left atrial and left ventricular epicardial pacing leads, and present mid-term follow-up data. METHODS: Seventy-five bipolar steroid eluting pacing leads (Medtronic CapSure Epi 4968) were implanted in 41 children, aged 8.6+5.1 years. Pacing systems included 34 DDDR and 7 VVIR. Pacing leads were inserted through a muscle-sparing left lateral thoracotomy, and sutured to the left atrial appendage or atrium, and to the left ventricle. The generators were buried behind the abdominal muscles or between the thoracic muscle layers. Congenital heart disease with previous cardiac surgery was present in 25 children. Indications for pacing were post-operative heart block (n=14), sinus node disease (n=13), congenital heart block (n=9), and various (n=5). Threshold values and measured data were obtained at 6-month intervals. The mean follow-up was 3.8+2.9 years. RESULTS: There was no mortality or major morbidity, with excellent functional and cosmetic results. Lead survival was 94 and 86% for atrial leads, and 97 and 86% for ventricular leads, at 1 and 5 years, respectively. There were five reoperations for lead fracture (n=2), insulation break (n=1), oversensing (n=1), and infection (n=1). Device reprogramming was required in three instances. In the absence of acute lead failure, mid-term follow-up shows very satisfactory and stable lead performance. CONCLUSIONS: Left heart atrial and ventricular epicardial pacing leads inserted through a left lateral thoracotomy demonstrate a high probability of survival, with favorable pacing characteristics, and optimal sensing thresholds at mid-term follow-up. Epicardial left heart pacing is reliable, and easy access can be achieved through a cosmetic and functional muscle-sparing left lateral thoracotomy.

Adolescent↗

Right axillary incision: a cosmetically superior approach to repair a wide range of congenital cardiac defects.

OBJECTIVES: We sought to evaluate the safety of a right axillary incision, a cosmetically superior approach than anterolateral thoracotomy, to repair various congenital heart defects. METHODS: All the patients who were approached with this incision between March 2001 and October 2004 were included in the study. There were 80 patients (median age, 4 years) with atrial septal defect closure (38 patients), repair of partial abnormal pulmonary venous return (14 patients), partial atrioventricular canal (16 patients), and perimembranous ventricular septal defect (12 patients). The surgical technique involved peripheral and central cannulation for institution of cardiopulmonary bypass. Electrically induced ventricular fibrillation was used for defects located in front of the atrioventricular valves, and cardioplegic arrest was used for those located at the level or behind these valves. RESULTS: The repair was possible without need for conversion to another approach. One patient sustained a transient neurologic deficit. The patients were all in excellent condition after a mean follow-up of 14 months. The cardiac defect was repaired with no residual defect in 75 patients and with trivial residual defect in 5 patients (3 with mitral valve regurgitation, 1 with atrial septal defect, and 1 with ventricular septal defect). The incision healed properly in all, and the thorax showed no deformity. CONCLUSION: The right axillary incision provides a quality of repair for various congenital defects similar to that obtained by using standard surgical approaches. Because it lies more laterally and is hidden by the resting arm, it provides superior cosmetic results compared with conventional incisions, including the anterolateral thoracotomy. Finally, the incision is unlikely to interfere with subsequent development of the breast.

Adolescent↗

Human umbilical cord cells for cardiovascular tissue engineering: a comparative study.

OBJECTIVE: Tissue engineering of viable, autologous cardiovascular replacements with the potential to grow, repair and remodel represents an attractive approach to overcome the shortcomings of available replacements for the repair of congenital cardiac defects. Currently, vascular myofibroblast cells represent an established cell source for cardiovascular tissue engineering. Cell isolation requires the invasive harvesting of venous or arterial vessel segments prior to scaffold seeding, a technique which may not be preferable, especially in pediatric patients. This study evaluates cells isolated from human umbilical cord artery, umbilical cord vein and whole cord as alternative autologous cell sources for cardiovascular tissue engineering. METHODS: Cells were isolated from human umbilical cord artery (UCA), umbilical cord vein (UCV), whole umbilical cord (UCC) and saphenous vein segments (VC), and were expanded in culture. All three expanded cell groups were seeded on bioabsorbable copolymer strips and grown in vitro for 28 days. Isolated cells were characterized by flow cytometry, histology, immunohistochemistry, proliferation assays and compared to VC. Morphological analysis of the seeded polymer strips included histology, immunohistochemistry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and uniaxial stress testing. RESULTS: UCA, UCV and UCC demonstrated excellent cell growth properties comparable to VC. Following isolation, all three cell groups showed myofibroblast-like morphology and characteristics by staining positive for alpha-smooth muscle actin (ASMA) and vimentin. Histology and immunohistochemistry of seeded polymers showed good tissue and extracellular matrix formation containing collagen I, III and elastin. TEM showed viable myofibroblasts and the deposition of collagen fibrils and progressive growing tissue formation, with a confluent surface, was observed in SEM. No difference was found among the mechanical properties of UCA, UCV, UCC and VC tissue engineered constructs. CONCLUSIONS: Tissue engineering of cardiovascular constructs by using UCA, UCV and UCC is feasible in an in vitro environment. Cell growth, morphology, characteristics and tissue formation were comparable between UCA, UCV, UCC and VC. UCC represent an attractive, readily available autologous cell source for cardiovascular tissue engineering offering the additional benefits of utilizing juvenile cells and avoiding the invasive harvesting of intact vascular structures.

Absorbable Implants↗

Emergency stent-graft placement for hemorrhage control in acute thoracic aortic rupture.

OBJECTIVE: To report mid-term results of stent-graft (SG) implantation in acute thoracic aortic rupture as alternative to conventional open surgery with its associated high morbidity and mortality rates. METHODS: Out of a series of 69 patients undergoing thoracic aortic SG implantation since 1998, 24 (mean age 57+/-19 years, range 20-85-years-old) patients were treated on an emergency basis for hemorrhage control. The indication for SG placement was acute traumatic aortic rupture in 15 patients, type B dissection with contained rupture in 3 patients, penetrating aortic ulcer with periaortic hematoma in 3 patients, and thoracic aortic aneurysm rupture in 3 patients. Preoperative assessment was done by computed tomography (CT) scanning and echography. Patients were treated in the angiography suite by implantation of Excluder (n = 18) Talent (n = 4) Corvita (n = 1) and Vanguard (n = 1) self-expanding grafts. Local anesthesia was the most frequently used anaesthesiologic technique. RESULTS: Technical success rate of SG deployment was 100%. The early postoperative mortality was 12.5% (3 of 24). One patient suffered temporary paraplegia (4%). There was no intervention-related mortality during the mean follow-up of 34.1 months. Two secondary endoleaks were successfully treated with additional SG placement at 2 and 12 months postoperative, respectively. CONCLUSIONS: Emergency SG repair to control hemorrhage in patients with an acute thoracic aortic rupture is a less-invasive attractive and rational treatment option, especially if associated lesions or co-morbidity may interfere with the surgical outcome. Long-term follow-up results will be helpful to clarify procedure durability bounded by material failure and postoperative aneurysm or aortic wall remodelling.

Acute Disease↗

Anatomic reconstruction of recurrent aortic arch obstruction in children.

OBJECTIVE: Anatomical reconstruction of the aortic arch following aortic arch surgery is challenging. The placement of an extra-anatomical aortic bypass has been proposed for these difficult cases. This approach is not ideal in children due to possible long-term complications. This study presents the results of our policy to reconstruct the aortic arch in recurrent obstruction in children, which are not amenable to balloon dilatation. METHODS: Seven children with a median age of 8 years (range 1 month-15 years) were operated for aortic arch obstruction following correction of an aortic coarctation. Six children presented another intra-cardial lesion (2 subaortic membranes; 2 VSDs, 1 ostium stenosis of the left main coronary artery, and 1 mitral valve insufficiency). The surgical approach involved a sternotomy, cardiopulmonary support using two arterial inflow cannulas (one above and one below the aortic arch), and moderate hypothermia. Enlargement of the aortic arch was performed by a sliding plasty in four patients and by a patch plasty in three patients. Associated cardiac defects were corrected as well. RESULTS: It was technically possible to perform the planned operation in all patients. All patients survived and none presented significant postoperative complications. There were no residual gradients in six patients and a gradient of 10 mmHg in one patient postoperatively. One patient showed transient recurrent nerve palsy which recovered within 6 weeks. Follow-up echocardiographic and MRI studies revealed a normal appearing aortic arch with laminar flow. CONCLUSIONS: Although more demanding, an anatomical reconstruction of the aortic arch can be performed in infants and children with recurrent obstruction of the aortic arch with excellent initial results. This approach may prove superior to an extra-anatomic bypass in the long-term.

Adolescent↗