Biomedical subjects

David Zurakowski

Publications and source records attributed to David Zurakowski.

At least 145 records · Page 8Linked to original sources

PubMed2003

Reliability of three classification systems measuring active motion in brachial plexus birth palsy.

BACKGROUND: Several classification systems for the categorization of function in patients with brachial plexus birth palsy have been proposed. The purpose of this investigation was to determine the intraobserver and interobserver reliability of the modified Mallet Classification, Toronto Test Score, and Hospital for Sick Children Active Movement Scale in the evaluation of these patients. METHODS: Eighty children with brachial plexus birth palsy were evaluated by two trained examiners on two different occasions. Intraobserver and interobserver reliability was determined with use of the kappa statistic. RESULTS: On the basis of the kappa statistic, intraobserver reliability was good to excellent for individual elements of the modified Mallet Classification, Toronto Test Score, and Active Movement Scale in all age-groups. Interobserver reliability for individual elements of these three systems ranged from fair to excellent. When aggregate Toronto Test and modified Mallet scores were assessed, positive intraobserver and interobserver correlations were noted (Pearson r = 0.70 to 0.98, p < 0.001). Internal consistency (test-retest reliability) as determined by the Cronbach alpha for the aggregate Toronto Test and modified Mallet scores was excellent for each age-group (alpha > 0.90, p < 0.001). CONCLUSIONS: The modified Mallet Classification, Toronto Test Score, and Active Movement Scale are reliable instruments for assessing upper-extremity function in patients with brachial plexus birth palsy. The natural history and surgical outcomes of these patients can now be conducted with use of these reliable outcomes instruments.

Adolescent↗

PubMed2003

Pullout strength of suture anchors used in rotator cuff repair.

BACKGROUND: Surgical treatment of rotator cuff tears may be complicated by osteoporosis of the proximal part of the humerus. The purpose of this study was to determine whether pullout strength of suture anchors is affected by the location of the anchor placement and by bone mineral density. We hypothesized that higher bone mineral density is associated with higher pullout strength of suture anchors. METHODS: Peripheral quantitative computed tomography was used to measure total, trabecular, and cortical bone mineral density in different regions of the lesser and greater tuberosities in seventeen cadaveric humeri. Suture anchors were inserted into individual regions and subjected to cyclic loading. Repeated-measures analysis of variance was used to assess differences in bone mineral density and load to failure between regions of interest. Pearson correlation was used to determine the association between bone mineral density and pullout strength of suture anchors. RESULTS: Total, trabecular, and cortical bone mineral densities were an average of 50%, 50%, and 10% higher, respectively, in the proximal part of the tuberosities compared with the distal part (p < 0.01). Within the proximal part of the greater tuberosity, trabecular bone mineral density of the posterior region and cortical bone mineral density of the middle region were, on the average, 25% and 16% higher, respectively, than the densities in the other regions (p < 0.01). Load to failure in the proximal part of the tuberosities was an average of 53% higher than that in the distal part (p < 0.01). The lesser tuberosity showed, on the average, a 32% higher load to failure than did the greater tuberosity (p < 0.01). Within the proximal part of the greater tuberosity, loads to failure in the anterior and middle regions were, on the average, 62% higher than the load to failure in the posterior region (p < 0.01). Overall positive correlations were found between bone mineral density and load to failure (0.65 </= r </= 0.74, p < 0.01). CONCLUSIONS: We found that pullout strength of suture anchors correlates well with bone mineral density of the tuberosities. Higher loads to failure were found in regions in the proximal part of the tuberosities. Placement of anchors in these regions may prevent anchor loosening, formation of a tendon-bone gap, and failure of the rotator cuff repair.

Aged↗

PubMed2003

Ganz reinforcement ring for reconstruction of acetabular defects in revision total hip arthroplasty.

BACKGROUND: In revision total hip arthroplasty, bone loss due to loosening and migration of the acetabular component makes fixation of a new implant difficult. The purpose of this study was to evaluate the clinical and radiographic outcomes of the use of the Ganz reinforcement ring with nonstructural allograft in the reconstruction of acetabular defects. METHODS: Sixty-one acetabular revisions performed with use of the Ganz reinforcement ring and nonstructural allograft, between 1989 and 1992, in fifty-seven patients with aseptic loosening met our selection criteria. Eleven hips in eleven patients were lost to follow-up, leaving fifty hips available for evaluation five years or more following surgery. According to the American Academy of Orthopaedic Surgeons classification, twenty-four acetabular defects were Type II, twenty-four were Type III, and two were Type IV. Clinical and radiographic evaluations were carried out at a mean of six and nine years after surgery. Twelve more patients were lost to follow-up before the most recent evaluation. RESULTS: The mean Merle d'Aubigné composite score increased significantly compared with the preoperative score (p < 0.001). There were seven failures: six cases of aseptic loosening and one case of septic arthritis. Graft incorporation and bone remodeling occurred in all hips but three in which the ring fixation had been inadequate at the time of surgery. The Kaplan-Meier survivorship rate, with use of revision or loosening of the component as the criterion of failure, was 81% at ten years. Inadequate fixation of the implant at the time of surgery was the only multivariate predictor of failure (p = 0.003). CONCLUSIONS: Patients treated with acetabular revision with a Ganz reinforcement ring had reconstitution of periacetabular bone stock as well as good clinical and radiographic results, provided that the ring had been fixed adequately at the time of surgery. This procedure may not be the preferred approach for reconstructing segmental defects of the medial wall or pelvic discontinuity.

Acetabulum↗

PubMed2003

Comparison of oral pentobarbital sodium (nembutal) and oral chloral hydrate for sedation of infants during radiologic imaging: preliminary results.

OBJECTIVE: The purpose of this study was to compare the safety and efficacy of oral cherry-flavored pentobarbital sodium (Nembutal) and oral chloral hydrate to sedate infants undergoing radiologic imaging. SUBJECTS AND METHODS: We prospectively recorded data for all infants sedated with oral cherry-flavored pentobarbital sodium and oral chloral hydrate for imaging examinations between January 1997 and August 1999. The parameters recorded were each patient's age, weight, and American Society of Anesthesiologists classification; the time required to sedate; the total length of sedation time; the time required to discharge from the recovery room; and adverse events. The two-sample Student's t test and Fisher's exact test were used for statistical analysis. RESULTS: Oral pentobarbital sodium was administered to 317 infants. These infants had a mean age +/- SD of 6.9 +/- 3.1 months and a mean weight of 7.8 +/- 4.8 kg; they received a median dose of 4 mg/kg of body weight. Oral chloral hydrate was administered to 358 infants. These infants had a mean age of 5.9 +/- 3.3 months and a mean weight of 7.3 +/- 4.9 kg; they received a median dose of 50 mg/kg of body weight. The mean time required to sedate was 19 +/- 14 min for infants receiving oral pentobarbital sodium and 16 +/- 11 min for infants receiving oral chloral hydrate (p = 0.02); the mean time required to discharge was 100 +/- 35 min for infants in the oral pentobarbital sodium group and 103 +/- 36 min for infants in the oral chloral hydrate group (p = 0.31); the mean length of sedation was 81 +/- 34 min for the oral pentobarbital sodium group and 86 +/- 36 min for the oral chloral hydrate group (p = 0.07); and median American Society of Anesthesiologists classification for both groups was P1. Oral pentobarbital sodium was inadequate for sedation in one patient (0.3%) and chloral hydrate was inadequate for sedation in another (0.3%) (p = 1.00). Adverse events were recorded for five patients (1.6%) in the oral pentobarbital sodium group and for six patients (1.7%) in the chloral hydrate group (p = 0.99). CONCLUSION: Oral pentobarbital sodium is as safe and efficacious as oral chloral hydrate for sedating infants.

Administration, Oral↗

PubMed2003

Effects of IV pentobarbital with and without fentanyl on end-tidal carbon dioxide levels during deep sedation of pediatric patients undergoing MRI.

OBJECTIVE: IV pentobarbital is used in radiology departments for sedating pediatric patients undergoing diagnostic imaging. To our knowledge, no published studies have documented end-tidal carbon dioxide levels during sedation with IV pentobarbital. The purpose of this prospective study was to determine the effects of different doses of IV pentobarbital with or without fentanyl on end-tidal carbon dioxide levels during deep sedation of pediatric patients undergoing MRI. SUBJECTS AND METHODS: One hundred sixty-five patients (70 girls, 95 boys) having a mean age of 3.4 years received IV pentobarbital sedation with or without fentanyl for undergoing MRI from January through March 2002. Each child was sedated with 2-6 mg/kg of body weight of IV pentobarbital and an additional 1-3 micro g/kg of fentanyl if needed. After the administration of sedation, a 28-ft (8.5 m) nasal cannula with capnography capability was applied to each patient, and capnogram tracings and values were recorded every 5 min. RESULTS: Mean values of end-tidal carbon dioxide were between 37 and 42 mm Hg during 60 min of sedation for both groups. When IV pentobarbital was used alone, no significant difference was seen between patients who received 3-5 mg of pentobarbital and those who received more than 5 mg (p = 0.97, F test). CONCLUSION: End-tidal carbon dioxide levels remain within normal clinical range during sedation with IV pentobarbital with or without fentanyl. Our sedation protocol produced no significant deviations from normal respiratory parameters.

Adjuvants, Anesthesia↗

PubMed2003

Effect of functional bracing on subsequent knee injury in ACL-deficient professional skiers.

The effect of functional bracing on subsequent knee injury in anterior cruciate ligament (ACL) deficient professional skiers was evaluated. A cohort of 180 ACL-deficient skiers was identified from a knee screening of 9410 professional skiers from 1991-1997. An ACL-deficient knee was defined by an abnormal examination (Lachman or pivot-shift) and a > or = 5-mm KT-1000 manual maximum difference. The dependent variable was subsequent knee injury, which occurred in 12 knees. A significantly higher proportion of injuries occurred in nonbraced skiers compared with braced skiers (P = .005). The risk ratio for subsequent knee injury comparing nonbraced with braced skiers was 6.4 (13% and 2%, respectively). Univariate analysis revealed no significant effects of the other covariates. Logistic regression identified bracing status (P < .01; odds ratio = 8) and KT-1000 manual maximum difference (P = .02; odds ratio = 1.3) as significant multivariate risk factors for subsequent knee injury, controlling for covariates.

Adult↗

PubMed2002

Effects of pH management during deep hypothermic bypass on cerebral microcirculation: alpha-stat versus pH-stat.

OBJECTIVE: There is controversy regarding the optimal pH strategy during deep hypothermic bypass in children. We directly visualized the effects of the pH-stat and alpha-stat strategy on cerebral microcirculation (including leukocyte/endothelial cell interactions) in a piglet model using intravital fluorescence microscopy. METHODS: Two groups of 5 piglets (mean weight 9.6+/-1.3 kg) with a cranial window over parietal cerebral cortex underwent 10-minute normothermic bypass, 40-minute cooling on cardiopulmonary bypass ([CPB] Hct 30%, 100 mL/kg/min), 60-minute circulatory arrest at 15 degrees C, and 40-minute rewarming with alpha-stat (group alpha) or pH-stat (group pH). Plasma was labeled with fluorescein-ITC-dextran for assessment of microvascular diameter. Circulating leukocytes were labeled and observed in postcapillary venules for adhesion before and up to 120 minutes after CPB. Cerebral tissue oxygenation was evaluated by quantification of NADH autofluorescence, which increases during ischemia. RESULTS: At the end of normothermic bypass diameter of cerebrocortical microvessels increased to 116+/-9% (alpha) versus 119+/-10% (pH) of pre-CPB baseline values. During cooling microvascular diameter decreased in group alpha and significantly increased in group pH (89+/-11% (alpha) versus 132+/-13% (pH) at the end of cooling; P<0.001). During the first 10 minutes of rewarming, the cerebral microvascular diameter was significantly larger when the pH stat strategy was used. Tissue oxygenation at the end of cooling was significantly greater in the pH-stat group (P=0.008). On reperfusion, the pH-stat strategy resulted in significantly more rapid return of tissue oxygenation toward baseline although at the end of rewarming the metabolic recovery was complete in both groups. The whole body lactate during early rewarming was significantly less with the pH stat strategy. There was no significant difference between the groups regarding the number of adherent leukocytes throughout the time course of the experiment. CONCLUSIONS: pH-stat management increases tissue oxygenation during deep hypothermic bypass and after circulatory arrest. Leukocyte/endothelial cell interactions during hypothermic bypass are mild with both alpha-stat and pH-stat.

Animals↗

PubMed2002

Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells.

To better direct repair following spinal cord injury (SCI), we designed an implant modeled after the intact spinal cord consisting of a multicomponent polymer scaffold seeded with neural stem cells. Implantation of the scaffold-neural stem cells unit into an adult rat hemisection model of SCI promoted long-term improvement in function (persistent for 1 year in some animals) relative to a lesion-control group. At 70 days postinjury, animals implanted with scaffold-plus-cells exhibited coordinated, weight-bearing hindlimb stepping. Histology and immunocytochemical analysis suggested that this recovery might be attributable partly to a reduction in tissue loss from secondary injury processes as well as in diminished glial scarring. Tract tracing demonstrated corticospinal tract fibers passing through the injury epicenter to the caudal cord, a phenomenon not present in untreated groups. Together with evidence of enhanced local GAP-43 expression not seen in controls, these findings suggest a possible regeneration component. These results may suggest a new approach to SCI and, more broadly, may serve as a prototype for multidisciplinary strategies against complex neurological problems.

Animals↗

PubMed2002

The development of a pediatric radiology sedation program.

BACKGROUND: An increase in the number of patients undergoing sedation for imaging procedures has led to many changes in practice over the past 10 years. OBJECTIVE: The purpose of this study was to compare and evaluate sedation practice changes in a pediatric radiology department during the last 5 years. MATERIALS AND METHODS: The radiology computer database and corresponding minutes of the Radiology Sedation Committee were reviewed to identify changes in sedation policy. Data from three blocks of time were analyzed to determine time to sedation, time to discharge, drug frequency, rates of adverse events, sedation failure, and paradoxical reaction. RESULTS: Specific practice changes undertaken over the 5-year period include: (1) increased speed of administration of IV pentobarbital, (2) alternating pentobarbital and fentanyl, (3) presedation with midazolam, and (4) administering oral pentobarbital to children under and (5) over 12 months of age. Based on data analysis, changes 1 and 4 were incorporated into the sedation policy, while changes 2, 3, and 5 were abandoned. Comparison of data from the three time segments revealed improvement in the time to sedation, sedation failure, adverse event, and paradoxical reaction rates. CONCLUSION: There is improvement in all aspects of patient outcomes with sedation, as a result of several changes in sedation practice.

Procedural Sedation↗

PubMed2002

Clinical outcome in chordoma: utility of flow cytometry in DNA determination.

STUDY DESIGN: A retrospective review of 100 patients with chordoma of the lumbar spine and sacrum. Twenty-three patients had flow cytometry data available and a minimum follow-up period of 5 years. OBJECTIVES: To determine whether DNA content and cell cycle analysis were associated with patient outcome. SUMMARY OF BACKGROUND DATA: DNA flow cytometry has been shown to be predictive for biologic behavior of various tumors. Chordoma has been evaluated in very small numbers of patients using DNA flow cytometric analysis, and the utility of DNA patterns in predicting outcome has not been clearly demonstrated. METHODS: Between January 1979 and December 1995, 100 patients underwent surgical resection for chordoma, and 23 had a minimum follow-up period of 5 years with flow cytometry data. DNA content and cell cycle analysis were determined by enzymatically staining cells with propidium iodide dye and passing them through a flow cytometer. DNA histograms were generated. Survivorship and freedom from local recurrence curves were constructed by the Kaplan-Meier method and compared by the log-rank test. RESULTS: The mean follow-up period was 7.3 years. For this group of 23 patients, mortality was 61% (14 patients) and local recurrence was 78% (18 patients). Eleven patients had tumors with diploid DNA content, and 12 patients had tumors with aneuploid DNA content. Metastases occurred in 4 of the 11 patients with a diploid pattern and 6 of the 12 with an aneuploid pattern. Six of the 11 patients with the diploid pattern died, in comparison with 8 of 12 patients with the aneuploid pattern. The Kaplan-Meier estimated survivorship (95% confidence interval) was 78% (66-90%) at a follow-up period of 5 years and 36% at a follow-up period of 10 years (22-50%), and no significant differences were found between patients with diploid and aneuploid patterns. CONCLUSIONS: Patients in whom metastases did not develop had a more favorable clinical outcome. DNA pattern was not associated with local recurrence or survival.

Adult↗

PubMed2002

Phenytoin blocks retinal ganglion cell death after partial optic nerve crush.

Phenytoin is a well-characterized sodium channel blocker in widespread use as an anticonvulsant. In 1972, Becker and co-workers reported that phenytoin could reverse visual field loss from glaucoma. The authors therefore explored whether phenytoin could protect retinal ganglion cells from optic nerve crush. The optic nerve of Long-Evans rats was partially crushed; animals were given a single dose of either intraperitoneal phenytoin or vehicle. A third group underwent sham optic nerve crush. In a second set of experiments, the effect of phenytoin was compared to the N -methyl- D -receptor antagonist, memantine. Retinal ganglion survival was evaluated 1 week later. In addition, the effect of memantine and phenytoin on glutamate-induced intracellular calcium fluxes was evaluated.Phenytoin and memantine significantly reduced ganglion cell loss after optic nerve crush, and blunted the rise in intracellular calcium seen after administration of glutamate. Co-administration of the two agents, however, did not increase ganglion cell survival, and had no effect on ganglion cell calcium fluxes. Phenytoin can preserve retinal ganglion cells after partial optic nerve crush. This effect was not additive with a glutamate antagonist, suggesting that both agents alone are equally protective at saving the same population of ganglion cells at risk. In fact, the neuroprotective effect of the combined administration of phenytoin and memantine was significantly less than either of the two drugs alone. Phenytoin is known to decrease neuronal firing and neurotransmitter release; this may underlie its ability to serve as a neuro-protectant in this experimental paradigm.

Analysis of Variance↗

PubMed2002

Combination of alpha-stat strategy and hemodilution exacerbates neurologic injury in a survival piglet model with deep hypothermic circulatory arrest.

BACKGROUND: The optimal pH strategy and hematocrit during cardiopulmonary bypass with deep hypothermic circulatory arrest (DHCA) remain controversial. We studied the interaction of pH strategy and hematocrit and their combined impact on cerebral oxygenation and neurological outcome in a survival piglet model including monitoring by near-infrared spectroscopy (NIRS). METHODS: Thirty-six piglets (9.2+/-1.1 kg) underwent DHCA under varying conditions with continuous monitoring by NIRS (pH-stat or alpha-stat strategy, hematocrit 20% or 30%, DHCA time 60, 80, or 100 minutes). Neurological recovery was evaluated daily. The brain was fixed in situ on postoperative day 4 and a histological score (HS) for neurological injury was assessed. RESULTS: Oxygenated hemoglobin (HbO2) and total hemoglobin signals detected by NIRS were significantly lower with alpha-stat strategy during cooling (p < 0.001), suggesting insufficient cerebral blood supply and oxygenation. HbO2 declined to a plateau (nadir) during DHCA. Time to nadir was significantly shorter in lower hematocrit groups (p < 0.01). Significantly delayed neurologic recovery was seen with alpha-stat strategy compared with pH-stat (p < 0.05). The alpha-stat group had a worse histological score compared with those assigned to pH-stat (p < 0.001). Neurologic impairment was estimated to be over 10 times more likely for animals randomized to alpha-stat compared with pH-stat strategy (odds ratio = 10.7, 95% confidence interval = 3.8 to 25.2). CONCLUSIONS: Combination of alpha-stat strategy and lower hematocrit exacerbates neurological injury after DHCA. The mechanism of injury is inadequate cerebral oxygenation during cooling and a longer plateau period of minimal O2 extraction during DHCA.

Animals↗

PubMed2002

Protective effects of protein kinase C during myocardial ischemia require activation of phosphatidyl-inositol specific phospholipase C.

BACKGROUND: Protein kinase C (PKC) activation during myocardial ischemia is thought to be cardioprotective. However, the mechanism of ischemia-induced PKC activation remains unclear. We hypothesized that ischemic PKC activation occurs through activation of phosphatidyl-inositol specific phospholipase C (PI-PLC) and protects the heart from ischemic injury. METHODS: Isolated rabbit hearts were subjected to 20 minutes of normothermic ischemia and reperfusion. The PI-PLC inhibitor U73122 (0.5 micromol/L), its inactive analogue U73343 (0.5 micromol/L), or the PKC inhibitor chelerythrine (2 micromol/L) were given just before ischemia. Another group received U73122 plus the direct PKC activator phorbol 12-myristate-13-acetate (PMA, 10 pmol/L). Measurements included contractile function, intracellular calcium, PI-PLC activity, and translocation of PKC isoforms. RESULTS: PI-PLC activity increased during myocardial ischemia and was inhibited by U73122. PI-PLC inhibition prevented the ischemic translocation of PKC-alpha, PKC-epsilon, and PKC-eta, and impaired cardiac recovery and cytosolic calcium regulation without significant changes in energy metabolism. PMA restored both contractile function and PKC translocation pattern in U73122-treated hearts. Direct PKC inhibition with chelerythrine mimicked the effects of U73122. CONCLUSIONS: PI-PLC mediates PKC translocation during myocardial ischemia. Inhibition of PI-PLC or PKC activation, or both, during ischemia significantly impairs postischemic myocardial recovery.

Adenosine Triphosphate↗

PubMed2002

Valved homograft replacement of aneurysmal pulmonary arteries for severely symptomatic absent pulmonary valve syndrome.

BACKGROUND: Patients with absent pulmonary valve syndrome (APVS) with respiratory distress (RD) have previously had a high mortality. In 1990 we adopted a strategy of primary repair including total replacement of the aneurysmal central pulmonary arteries (PAs) for patients with RD. METHODS: Retrospective review was made of 54 consecutive patients with APVS between 1960 and 1998. Median age and weight were 4 months and 4.8 kg. RD was present in 23 patients (10 neonates, 16 required ventilation). Fifteen patients had repair with homograft replacement of the PAs and VSD closure (group 1). Twenty-seven patients had transannular patch with VSD closure with PA-plasty (group 2, n = 21) or without PA plasty (group 3, n = 6). Twelve had miscellaneous procedures (group 4); in 6 the VSD was left open. RESULTS: Operative, 1-, 5-, and 10-year survivals were 83%, 80%, 78%, and 78%, respectively. Risk factors for operative mortality in multivariate analysis were RD (p = 0.04), neonates (p = 0.02), weight less than 3 kg (p = 0.02), open VSD (p = 0.02) and surgery before 1990 (p = 0.04). Since 1990 operative mortality has decreased to 11% (p = 0.04). RD was the only time-related predictor of survival in multivariate analysis (p = 0.004). In patients with RD, survival with homograft was 73% versus 41% with other techniques (p = 0.2). Mean follow-up was 72 +/- 50 months. There were no significant differences in freedom from reintervention rates among the surgical groups (p = 0.08). CONCLUSIONS: Aggressive homograft replacement of the central pulmonary arteries has been associated with improved survival in patients with APVS especially in neonates with severe RD.

Abnormalities, Multiple↗

PubMed2002

Coagulation factor abnormalities in patients with single-ventricle physiology immediately prior to the Fontan procedure.

BACKGROUND: Coagulation abnormalities have been reported following the Fontan operation and have been attributed to various aspects of Fontan-associated physiology. Using age-matched controls, this study evaluated coagulation abnormalities in children who had undergone a bidirectional Glenn procedure to test the hypothesis that coagulation abnormalities are present before the Fontan operation. METHODS: Coagulation factors were assayed in 38 children (mean age 34.4 +/- 15 months) immediately before the Fontan operation; 37 healthy children (mean age 33 +/- 17 months) were assayed as controls. Concentration of factors II, V, VII, VIII, IX, and X and of antithrombin III, plasminogen, proteins C and S, fibrinogen, serum albumin, and liver enzymes were measured. Normal reference intervals based on the control patients were determined using 95% confidence limits. Patient demographic data, hemodynamic variables, and elapsed time after the Glenn procedure were evaluated as possible predictors of coagulation abnormalities. RESULTS: Concentrations of protein C; factors II, V, VII, and X; plasminogen; and antithrombin III were significantly lower before the Fontan operation compared with age-matched controls (p < 0.01); no specific hemodynamic variables were predictive of a pro- or anticoagulant deficiency. There were significant positive correlations between patients who had abnormally low factor VII, protein S, and protein C levels and a longer interval between the bidirectional Glenn procedure and the Fontan operation (p < 0.001). CONCLUSIONS: Coagulation abnormalities that could predispose patients to increased risk for clotting or bleeding are evident early in the course of staged single-ventricle repair.

Blood Coagulation Factors↗

PubMed2002

Improving results of the modified Fontan operation in patients with heterotaxy syndrome.

BACKGROUND: Historically the Fontan operation in patients with single ventricle heterotaxy syndrome and atrial isomerism has been associated with high mortality. We studied whether recent modifications of the surgical technique have improved outcome. METHODS: A retrospective review of 135 patients with heterotaxy syndrome who underwent a Fontan operation between 1981 and 2000 was performed. RESULTS: There were 93 patients with right isomerism and 42 with left isomerism. Anomalies of venous return included 25 patients with extracardiac pulmonary venous connection (19%) and 37 patients with an interrupted inferior vena cava (27%). Thirty-six patients (27%) had at least moderate atrioventricular valve regurgitation. The type of Fontan procedure included 17 patients with an atriopulmonary Fontan connection, 67 with a lateral tunnel modification, 19 with an intraatrial tube graft, 25 with an extracardiac tubegraft, and 7 with an intra-extra atrial tube graft. A fenestration was placed in 93 patients (78%). Early mortality was 19% before 1991, 3% since 1991, and no patient has died early since 1993. Ten-year survivals were 70% for Fontan operations before 1990 and 93% for Fontan operations after 1990. Thirty-two patients (23%) had prolonged pleural effusions. Risk factors for death included anomalous pulmonary venous connection (p = 0.02) and higher preoperative pulmonary vascular resistance (p = 0.002). Sixty-two patients (47%) had some form of early postoperative arrhythmia. At 10 years, freedom from late bradyarrhythmia and late tachyarrhythmia were 78% and 70%, respectively. Preoperative arrhythmias, older age at operation, and anatomic features were each independent predictors of late arrhythmia. CONCLUSIONS: The Fontan operation can now be performed in patients with heterotaxy syndrome with excellent survival. However, morbidity in terms of postoperative arrhythmias and prolonged pleural effusions remains significant. Fontan staging, appropriate choice of Fontan modification, aggressive treatment of concomitant malformations, and use of a baffle fenestration contribute to improved outcome.

Abnormalities, Multiple↗

PubMed2002

Effects of anti-glaucoma medications on ganglion cell survival: the DBA/2J mouse model.

We studied whether several agents, approved or undergoing trials in human glaucoma, were effective in preventing ganglion cell loss in the DBA/2J mouse. Adult DBA/2J mice were treated with timolol, pilocarpine, brimonidine, dorzolamide, or NMDA-receptor antagonist memantine. Surviving retinal ganglion cells of treated and control mice were retrogradely labeled with fluorogold and counted after whole mount preparation. In treated mice, only memantine and timolol had significant effects on retinal ganglion cell survival (P<0.0001, analysis of variance). Brimonidine was lethal to these mice, and these retinae were not analyzed further. The DBA/2J mouse represents a promising candidate for further experimentation in ocular hypertension.

Aging↗

PubMed2002

Effectiveness of muscimol-containing microparticles against pilocarpine-induced focal seizures.

PURPOSE: To investigate the efficacy of in situ lipid-protein-sugar particles (LPSPs) in mitigating the epileptogenic and histologic effects of intrahippocampal pilocarpine in rats. METHODS: LPSPs with and without muscimol were produced by spray-drying, sized by Coulter counter, and muscimol content determined by high-pressure liquid chromatography (HLPC). Particles, free muscimol or saline, were injected into the hippocampi of Sprague-Dawley rats before 40 mM pilocarpine, and seizure activity was scored. The trajectories of behavioral scores between groups were compared with two-way repeated measures analysis of variance. Animals were killed after 2 weeks. Brain sections were stained (Timm and thionin) and scored. RESULTS: LPSPs were 4 to 5 microm in diameter, and contained 0 or 2% (wt/wt) muscimol. In vitro, muscimol was released over a 5-day period. Intrahippocampal injections of normal saline and blank LPSPs did not deter seizure activity from pilocarpine. The rise of the trajectory in behavior scores in animals given LPSPs containing 5 microg muscimol was significantly slower than in those receiving saline, blank particles, or 5 microg of unencapsulated muscimol. There was less apparent neuronal injury and CA3 and supragranular mossy fiber sprouting in hippocampi of animals receiving muscimol-containing particles than in animals that did not receive muscimol. Hippocampi of animals that received 5 microg of encapsulated muscimol showed less supragranular sprouting than did those receiving 5 microg of unencapsulated muscimol, but showed no difference in cell loss or CA3 sprouting. CONCLUSIONS: Focally delivered biodegradable microparticles loaded with muscimol are effective in reducing seizure activity from pilocarpine in animals and mitigate the histologic effects.

Animals↗