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Biomedical subjects

D Zurakowski

Publications and source records attributed to D Zurakowski.

At least 37 records · Page 2Linked to original sources

Evidence that spinal segmental nitric oxide mediates tachyphylaxis to peripheral local anesthetic nerve block.

BACKGROUND: Tachyphylaxis to sciatic nerve blockade in rats correlates with hyperalgesia. Spinal inhibition of nitric oxide synthase with N(G)nitro-L-arginine methyl ester (L-NAME) has been shown to prevent hyperalgesia. Given systemically, L-NAME also prevents tachyphylaxis. The action of L-NAME in preventing tachyphylaxis therefore may be mediated at spinal sites. We compared systemic versus intrathecal potency of L-NAME in modulating tachyphylaxis to sciatic nerve block. METHODS: Rats were prepared with intrathecal catheters. Three sequential sciatic nerve blocks were placed. Duration of block of thermal nocifensive, proprioceptive and motor responses was recorded. We compared spinal versus systemic dose-response to L-NAME, and examined effects of intrathecal arginine on tachyphylaxis. An additional group of rats underwent testing after T10 spinal cord transection. In these rats duration of sciatic nerve block was assessed by determining the heat-induced flexion withdrawal reflex. RESULTS: L-NAME was 25-fold more potent in preventing tachyphylaxis given intrathecally than intraperitoneally. Intrathecal arginine augmented tachyphylaxis. Spinalized rats exhibited tachyphylaxis to sciatic block. CONCLUSION: The increased potency of intrathecal versus systemic L-NAME suggests a spinal site of action in inhibiting tachyphylaxis. Descending pathways are not necessary for the development of tachyphylaxis since it occurs even after T10 spinal cord transection. Thus tachyphylaxis, like hyperalgesia, is mediated at least in part by a spinal site of action.

Anesthetics, Local↗

Overexpression of human insulin-like growth factor-I promotes new tissue formation in an ex vivo model of articular chondrocyte transplantation.

Articular cartilage, the tissue that forms the gliding surface of joints, has a poor regenerative capacity. Insulin-like growth factor-I (IGF-I) is a polypeptide that is anabolic and mitogenic for cartilage. Transfection of articular chondrocytes with an expression plasmid vector containing the cDNA for human IGF-I under the control of the cytomegalovirus promoter/enhancer led to expression of the transgene and synthesis of biologically relevant amounts of IGF-I protein. Transplantation of transfected articular chondrocytes on to the surface of articular cartilage explants led to the formation of a new tissue layer on the cartilage explant surface. The new tissue was characterized by the presence of type II collagen and proteoglycan and by the absence of type I collagen, consistent with hyaline-like cartilage. The tissue formed by the chondrocytes expressing IGF-I was thicker and contained more cells than controls transfected with an expression plasmid vector containing the Escherichia coli (E. coli) beta-galactosidase (lacZ) gene. Transplantation of articular chondrocytes that overexpress human IGF-I also increased DNA synthesis and the synthesis of glycosaminoglycans by the underlying explant cartilage chondrocytes. These results identify a mechanism by which IGF-I may simultaneously promote chondrogenesis and shift cartilage homeostasis in an anabolic direction. The data further suggest that therapeutic growth factor gene transfer may be applicable to articular cartilage.

Analysis of Variance↗

Bispectral index monitoring in children undergoing mild hypothermic cardiopulmonary bypass.

BACKGROUND: In this prospective, cohort study of 15 children (median age 7.7 years, range 4.9-16.5 years) undergoing atrial septal defect repair, we evaluated changes in the Bispectral index (BIS) as a potential monitor of level of consciousness during cardiac anaesthesia. METHODS: Identical cardiac surgery, cardiopulmonary bypass (CPB) and anaesthetic techniques were used, including mild hypothermia and an early extubation protocol. BIS, mean arterial pressure, heart rate and tympanic temperature were recorded at baseline postinduction (Tbaseline), skin incision (Tincis), sternotomy (Tsternot), aortic cannulation (Tcann), nadir temperature (Tnadir), rewarmed (Trewarmed), immediate post-CPB (TpostCPB), chest drain insertion (Tdrains), sternal wires (Twire), skin closure (Tclosed) and spontaneous movement (Tmove). As a measure of stress response, serum lactate, glucose, norepinephrine and epinephrine levels were measured at Tbaseline, Tsternot, Tcann, Tnadir, Trewarmed and Tdrains. Explicit memory testing was undertaken prior to hospital discharge. RESULTS: BIS increased significantly during the rewarming phase (Trewarmed versus Tbaseline and Tnadir, P<0.001). Lactate, epinephrine and glucose levels were also significantly elevated at Trewarmed. There were no correlations between BIS and the increase in epinephrine, lactate and glucose during rewarming, nor with changes in heart rate or mean arterial pressure during surgery. All patients had an uneventful recovery without evidence for explicit recall. CONCLUSIONS: The increase in BIS during the rewarming phase could reflect an increase in conscious level, and is consistent with the reported risk for awareness during this phase of cardiac surgery.

Adolescent↗

Bispectral index monitoring during infant cardiac surgery: relationship of BIS to the stress response and plasma fentanyl levels.

BACKGROUND: We evaluated the relationship of the bispectral index (BIS) to commonly used indices of depth of anaesthesia in 19 infants enrolled in a prospective study of the stress response to hypothermic cardiopulmonary bypass. METHODS: Group 1 (n=8) received high-dose fentanyl by bolus technique; group 2 (n=6) received high-dose fentanyl by continuous infusion; and group 3 (n=5) received a fentanyl-midazolam infusion. Blood pressure (BP), heart rate (HR) and plasma epinephrine, norepinephrine, cortisol, ACTH, glucose, lactate and fentanyl were analysed 15 min postinduction, 15 min poststernotomy, 15 min on CPB during cooling and during skin closure. RESULTS: Mean BIS (SD) values for all 19 patients were 45.3 (12.3), 40.4 (14.5), 24.4 (12.4) and 47.9 (13.9), at the successive time points. No significant differences were observed in changes in BIS over time between the groups. A significant correlation was found 15 min postinduction between BIS and BP (systolic r=0.51, mean r=0.56) in all groups, but not between BIS and HR. BIS did not correlate with BP or HR at any other time point. There was no significant correlation between BIS and hormonal, biochemical or plasma fentanyl levels for any group at any time point. CONCLUSIONS: We were unable to demonstrate a relationship between the BIS and haemodynamic, metabolic or hormonal indices of anaesthetic depth. Further evaluation of the BIS algorithm is required in neonates and infants.

Anesthetics, Intravenous↗

Excitotoxicity can be mediated through an interaction within the optic nerve; activation of cell body NMDA receptors is not required.

Axonal trauma leads to a series of pathologic events that can culminate in neuronal death. Although the precise mechanisms of retinal ganglion cell death after optic nerve crush in the rat model have not been elucidated, glutamate antagonists can protect retinal ganglion cells after optic nerve axotomy. We therefore explored whether a glutamate congener was toxic if applied directly within the optic nerve, or if toxicity depended upon an interaction at the cell body level. NMDA reduced retinal ganglion cell survival when applied directly into the rat optic nerve. Glutamate can be toxic if administered within the optic nerve; a direct effect at the cell body is not necessary. Future work will help to additionally unravel the steps by which axotomy induces excitotoxic damage to ganglion cells, and perhaps indicate protective interventions.

Animals↗

Long-term results of the lateral tunnel Fontan operation.

OBJECTIVES: Completion of a total cavopulmonary anastomosis with an intra-atrial lateral tunnel is known to yield good early and midterm results. In this study, we sought to determine the long-term outcome (10 years) after a lateral tunnel Fontan procedure. METHODS: Between October 1987 and December 1991, 220 patients (aged 11 months to 32 years) with a wide range of underlying diagnoses underwent a fenestrated or nonfenestrated lateral tunnel Fontan procedure at our institution. Current follow-up information was available for 196 patients (94%, mean follow-up = 10.2 +/- 0.6 years). Risk factor analysis included patient-related and procedure-related variables, with death, failure, and bradyarrhythmia or tachyarrhythmia as outcome parameters. RESULTS: There were 12 early deaths (<30 days or hospital death), 7 late deaths, 4 successful takedown operations, and 4 heart transplantations. Kaplan-Meier estimated survival was 93% at 5 years and 91% at 10 years, and freedom from failure was 90% at 5 years and 87% at 10 years. Freedom from new supraventricular tachyarrhythmia was 96% at 5 years and 91% at 10 years; freedom from new bradyarrhythmia was 88% at 5 years and 79% at 10 years. Three patients had evidence of protein-losing enteropathy. Multivariable risk factors for development of supraventricular tachyarrhythmia included heterotaxy syndrome, atrioventricular valve abnormalities, and preoperative bradyarrhythmia. Risk factors for bradyarrhythmia included systemic venous anomalies. The sole risk factor for late failure was a previous coarctation repair. CONCLUSION: The lateral tunnel Fontan procedure results in excellent long-term outcome even when used in patients with diverse anatomic diagnoses. The incidence of atrial tachyarrhythmia is low and mainly depends on the underlying cardiac morphology and preoperative arrhythmia. The good long-term outcome after an intracardiac lateral tunnel Fontan procedure should serve as a basis for comparison with other surgical alternatives.

Adolescent↗

Valve-sparing operation for balloon-induced aortic regurgitation in congenital aortic stenosis.

OBJECTIVE: Aortic regurgitation after balloon dilation of congenital aortic stenosis may be treated with valve repair as an alternative to replacement. METHODS: Charts and echocardiograms of all patients undergoing aortic valve operations after balloon dilation of congenital aortic stenosis at our institution between January 1988 and December 1999 were reviewed. RESULTS: Twenty-one patients underwent valvuloplasty for predominant aortic regurgitation 9 months to 15 years (mean, 6.1 years) after balloon dilation. The mean +/- SD age at the time of the operation was 11 +/- 7 years. Aortic regurgitation was caused by a combination of commissural avulsion (10), cusp dehiscence with retraction (9), cusp tear (5), central incompetence (2), perforated cusp (1), or cusp adhesion to the aortic wall (1). Repair techniques included commissural reconstruction with a pericardial patch (8), pericardial patch cusp augmentation (6), primary suture repair (6), raphae release and debridement (4), commissurotomy (4), commissural resuspension with sutures (3), and cusp release (1). There were no deaths. At a mean follow-up of 30.1 months (range, 9 months-8 years), all patients were asymptomatic, and the grade of aortic regurgitation had been significantly reduced (P <.001). Left ventricular end-diastolic dimension z scores and proximal regurgitant jet/aortic anulus diameter ratios were significantly reduced (P <.001) and remained so over time. Freedom from reoperation for late failure was 100%, and overall freedom from reintervention was 80% at 3 years. CONCLUSION: Aortic valve repair for balloon-induced aortic regurgitation is reproducible and durable at medium-term follow-up.

Adolescent↗

Long-term results after early primary repair of tetralogy of Fallot.

OBJECTIVE: Early primary repair of tetralogy of Fallot has been routinely performed at Children's Hospital, Boston, since 1972. We evaluated the long-term outcome of this treatment strategy including the influence of a transannular patch. METHODS: Fifty-seven patients less than 24 months of age (median 8 months) underwent primary repair of tetralogy of Fallot between January 1972 and December 1977. Thirty-one patients had a transannular patch. Survival and freedom from reintervention were determined by the Kaplan-Meier method with 95% confidence intervals. RESULTS: There were 8 early deaths, and 1 patient died 24 years after initial repair. Recent follow-up was obtained for 45 of the 49 long-term survivors (92%). Median follow-up was 23.5 years. Ten patients underwent reintervention, 8 of whom underwent relief of right ventricular outflow tract obstruction. Right ventricular outflow tract obstruction occurred in 6 patients without a transannular patch and 2 with a transannular patch (33% vs 6%, P =.04). One pulmonary valve replacement was performed at another institution 20 years after the repair. Forty-one long-term survivors were in New York Heart Association class I and 4 were in class II. Actuarial survival was 86% at 20 years (95% confidence intervals = 80%-92%). Freedom from reintervention was 93% at 5 years (95% confidence intervals = 87%-99%) and 79% at 20 years (95% confidence intervals = 70%-86%). No significant differences were found between patients with and without a transannular patch (survival, P =.34; freedom from reintervention, P =.09, log-rank tests). CONCLUSIONS: Long-term survival is excellent and the freedom from reintervention is satisfactory after early primary repair of tetralogy of Fallot in the 1970s. Use of a transannular patch does not reduce late survival and is associated with a lower incidence of right ventricular outflow tract obstruction.

Exercise Tolerance↗

Stress response in infants undergoing cardiac surgery: a randomized study of fentanyl bolus, fentanyl infusion, and fentanyl-midazolam infusion.

UNLABELLED: There have been significant changes in the management of neonates and infants undergoing cardiac surgery in the past decade. We have evaluated in this prospective, randomized, double-blinded study the effect of large-dose fentanyl anesthesia, with or without midazolam, on stress responses and outcome. Forty-five patients < 6 mo of age received bolus fentanyl (Group 1), fentanyl by continuous infusion (Group 2), or fentanyl-midazolam infusion (Group 3). Epinephrine, norepinephrine, cortisol, adrenocortical hormone, glucose, and lactate were measured after the induction (T1), after sternotomy (T2), 15 min after initiating cardiopulmonary bypass (T3), at the end of surgery (T4), and after 24 h in the intensive care unit (T5). Plasma fentanyl concentrations were obtained at all time points except at T5. Within each group epinephrine, norepinephrine, cortisol, glucose and lactate levels were significantly larger at T4 (P values < 0.01), but there were no differences among groups. Within groups, fentanyl levels were significantly larger in Groups 2 and 3 (P < 0.001) at T4, and among groups, the fentanyl level was larger only at T2 in Group 1 compared with Groups 2 and 3 (P < 0.006). There were no deaths or postoperative complications, and no significant differences in duration of mechanical ventilation or intensive care unit or hospital stay. Fentanyl dosing strategies, with or without midazolam, do not prevent a hormonal or metabolic stress response in infants undergoing cardiac surgery. IMPLICATIONS: We demonstrated a significant endocrine stress response in infants with well compensated congenital cardiac disease undergoing cardiac surgery, but without adverse postoperative outcome. The use of large-dose fentanyl, with or without midazolam, with the intention of providing "stress free" anesthesia, does not appear to be an important determinant of early postoperative outcome.

Anesthetics, Intravenous↗

The effects of thoracic epidural analgesia with bupivacaine 0.25% on ventilatory mechanics in patients with severe chronic obstructive pulmonary disease.

UNLABELLED: Optimal analgesia is important after thoracotomy in pulmonary-limited patients to avoid pain-related pulmonary complications. Thoracic epidural anesthesia (TEA) can provide excellent pain relief. However, potential paralysis of respiratory muscles and changes in bronchial tone might be unfavorable in patients with end-stage chronic obstructive pulmonary disease (COPD). Therefore, we evaluated the effect of TEA on maximal inspiratory pressure, pattern of breathing, ventilatory mechanics, and gas exchange in 12 end-stage COPD patients. Pulmonary resistance, work of breathing, dynamic intrinsic positive end-expiratory pressure, and peak inspiratory and expiratory flow rates were evaluated by assessing esophageal pressure and airflow. An increase in minute ventilation (7.50 +/- 2.60 vs 8.70 +/- 2.10 L/min; P = 0.04) by means of increased tidal volume (0.46 +/- 0.16 vs 0.53 +/- 0.14 L/breath; P = 0.003) was detected after TEA. These changes were accompanied by an increase in peak inspiratory flow rate (0.48 +/- 0.17 vs 0.55 +/- 0.14 L/s; P = 0.02) and a decrease in pulmonary resistance (20.7 +/- 9.9 vs 16.6 +/- 8.1 cm H(2)O. L(-1). s(-1); P = 0.02). Peak expiratory flow rate, dynamic intrinsic positive end-expiratory pressure, work of breathing, PaO(2), and maximal inspiratory pressure were unchanged (all P > 0.50). We conclude that TEA with bupivacaine 0.25% can be used safely in end-stage COPD patients. IMPLICATIONS: Thoracic epidural anesthesia with bupivacaine 0.25% does not impair ventilatory mechanics and inspiratory respiratory muscle strength in severely limited chronic obstructive pulmonary disease patients. Thus, thoracic epidural anesthesia can be used safely in patients with end-stage chronic obstructive pulmonary disease.

Adult↗

Hemostatic changes in pediatric neurosurgical patients as evaluated by thrombelastograph.

UNLABELLED: Thromboembolic events are a known complication in neurosurgical patients. There is evidence to suggest that a hypercoagulable state may develop perioperatively. Thrombelastograph (TEG) coagulation analysis is a reliable method of evaluating hypercoagulability. We evaluated coagulation by using TEG data in pediatric neurosurgical patients undergoing craniotomy to determine whether a hypercoagulable state develops intraoperatively or postoperatively. Thirty children undergoing craniotomy for removal of a tumor or seizure focus were studied. Blood was analyzed with TEG) data by using native and celite techniques, at three time points for each patient: preoperatively after induction of anesthesia; intraoperatively during closure of the dura; and on the first postoperative day. Compared with preoperative indices, closing and postoperative celite TEG values were indicative of hypercoagulability with shortened coagulation time values (P < 0.001), prolonged alpha angle divergence values (P < 0.001), and above-normal TEG coagulation indices (P < or = 0.002). Reaction time values were shortened, and maximal amplitude of clot strength values were prolonged but did not reach statistical significance. Hypercoagulation develops early after resection of brain tissue in pediatric neurosurgical patients as assessed by using TEG data. Further studies are needed to determine the clinical significance of this hypercoagulable state. IMPLICATIONS: Hypercoagulability in postoperative neurosurgical patients has been demonstrated in the adult population, but few studies have dealt with the pediatric population. We found that children undergoing craniotomy for focal resection, lobectomy, and hemispherectomy are hypercoagulable as detected by thrombelastograph coagulation analysis. Further studies are needed to determine whether this is clinically significant.

Adolescent↗

Optimizing intrapulmonary perfluorocarbon distribution: fluoroscopic comparison of mode of ventilation and body position.

OBJECTIVE: Partial liquid ventilation with the perfluorochemical, perflubron, has been shown to improve lung mechanics and enhance gas exchange in the treatment of severe acute lung injury. However, the most effective strategy to provide optimal intrapulmonary distribution of perflubron has not been fully accessed. The objective of this study was to examine the effect of body position (supine vs. rotational) and mode of ventilation (conventional mechanical ventilation [CMV] vs. high-frequency oscillatory ventilation [HFOV]) on perflubron distribution and oxygenation improvement. DESIGN: Prospective, randomized, animal trial. SETTING: Research laboratory at a university medical center. SUBJECTS: Twenty healthy piglets (4.5-6.6 kg). INTERVENTIONS: Subjects underwent repetitive saline lavage to achieve a uniform degree of lung injury and then were randomized to either CMV or were converted to HFOV. Within each ventilator group, animals were randomized to supine positioning (S) or rotational positioning with alternation between supine and prone position (R) during incremental dosing of three 5-mL/kg doses of perflubron. MEASUREMENTS AND MAIN RESULTS: Arterial blood gas tensions, hemodynamic variables, and the oxygenation index were recorded after each dose of 5 mL/kg. Lateral cinefluoroscopic images after each dose were digitized for computer analysis of density. A density index was calculated for a 2-cm2 window in three dorsal and three ventral lung regions. Uniformity of distribution was calculated by comparing the mean density among the six regions. Oxygenation improvements were compared between groups. There were no significant differences in hemodynamic variables or gas exchange after lung injury in the four groups. Rotational positioning produced significantly more uniform perflubron distribution during both CMV and HFOV. This effect was independent of the mode of ventilation. The mean ventral density index was affected by rotating position and HFOV mode of ventilation after 10 mL/kg of perflubron, and rotating position was affected only after 15 mL/kg of perflubron. There was a significant reduction in the oxygenation index from baseline to end lavage in both CMV groups, as well as all of the animals that were rotated. CONCLUSION: Perflubron is more uniformly dispersed when dosed in a rotational fashion with alternation between supine and prone position during incremental dosing. This effect is independent of mode of ventilation. There was no relationship between oxygenation improvements and nondependent perflubron distribution. CMV and rotating dosing both led to a significant decrease in the oxygenation index after a 15 mL/kg dose of perflubron. This information has important impact on the future development of dosing strategies and clinical trial design.

Animals↗

Cysteine metabolism and whole blood glutathione synthesis in septic pediatric patients.

OBJECTIVE: To investigate whole body in vivo cysteine kinetics and its relationship to whole blood glutathione (GSH) synthesis rates in septic, critically ill pediatric patients and controls. DESIGN: Prospective cohort study. SETTING: Multidisciplinary intensive care unit and pediatric inpatient units at a children's hospital. PATIENTS: Ten septic pediatric patients and ten controls (children admitted to the hospital for elective surgery). INTERVENTIONS: Septic patients (age, 31 months to 17 yrs) and controls (age, 24 months to 21 yrs) received a 6-hr primed, constant, intravenous tracer infusion of l-[1-13C]cysteine. Blood samples were obtained to determine isotopic enrichment of plasma cysteine and whole blood [1-13C]cysteinyl-glutathione by gas-chromatography mass spectrometric techniques. The plasma flux and oxidation rate of cysteine and the fractional and absolute synthesis rates of GSH were determined. Septic patients received variable protein and energy intake, as per routine clinical management, and controls were studied in the early postabsorptive state. MEASUREMENTS AND MAIN RESULTS: Plasma cysteine fluxes were increased in the septic patients when compared with the controls (68.2 +/- 17.5 [sd] vs. 48.7 +/- 8.8 micromol x kg(-1) x hr(-1); p <.01), and the fraction of plasma cysteine flux associated with oxidative disposal was similar among the groups. The absolute rates of GSH synthesis in whole blood were decreased (p <.01) in the septic patients (368 +/- 156 vs. 909 +/- 272 micromol x L(-1) x day(-1)). The concentration of whole blood GSH also was decreased in the septic group (665.4 +/- 194 vs. 1059 +/- 334 microM; p <.01) CONCLUSIONS: Whole blood glutathione synthesis rates are decreased, by about 60%, in critically ill septic children receiving limited nutritional support. Plasma cysteine fluxes and concentration of cysteine were increased in the septic patients, suggesting a hypermetabolic state with increased protein breakdown. The mechanisms whereby GSH synthesis rates are decreased in these patients are probably multifactorial, presumably involving an inflammatory response in the presence of limited nutritional support. The role of nutritional modulation and the use of cysteine prodrugs in maintaining GSH concentration and synthesis remain to be established.

Adolescent↗

Elevated serum hepatocyte growth factor in children and young adults with inflammatory bowel disease.

BACKGROUND: Elevated serum levels of several potent angiogenesis factors, including vascular endothelial growth factor and basic fibroblast growth factor have been described in children with active inflammatory bowel disease. Angiogenesis-promoting cytokines may promote inflammation by increasing vascular permeability but also mediate tissue repair by activating fibroblasts. Hepatocyte growth factor (HGF) is another angiogenesis-promoting cytokine that is increased in colon cancer tissues. We therefore evaluated serum HGF levels in individuals with Crohn disease and ulcerative colitis. METHODS: Serum samples were obtained from 60 patients with Crohn disease, 31 with ulcerative colitis, and 38 controls with functional abdominal pain and other gastrointestinal illnesses. Disease activity for Crohn disease patients was determined using the pediatric Crohn disease activity index, and for ulcerative colitis patients using the Kozarek score. The HGF levels were measured by enzyme-linked immunosorbent assay. RESULTS: Serum HGF levels were significantly ( P < 0.001) higher for Crohn disease patients (1439 +/- 84 pg/mL) and ulcerative colitis patients (1384 +/- 107 pg/mL) than for control patients (807 +/- 50 pg/mL). Serum HGF levels also rose with increasing disease activity in individuals with both Crohn disease and ulcerative colitis. CONCLUSION: Serum HGF is elevated in children and young adults who have Crohn disease or ulcerative colitis. Levels of serum HGF correlate directly with disease activity. The raised serum HGF suggests that HGF may mediate angiogenesis and vascular permeability in the mucosa of children with inflammatory bowel disease. Alternatively, the raised serum HGF may be an epiphenomenon of inflammation.

Adolescent↗

Autologous chondrocyte implantation of the knee: multicenter experience and minimum 3-year follow-up.

OBJECTIVE: To determine clinical outcome and graft survivorship in patients undergoing autologous chondrocyte implantation (ACI) for the repair of chondral defects of the knee. DESIGN: Prospective cohort study. SETTING: 19 centers in the United States. PATIENTS: 50 patients (37 males, 13 females). Mean age was 36 years (range: 19-53). Defects were grade III or IV with a mean size of 4.2 cm 2. All patients had a minimum of 36 months postoperative follow-up. MAIN OUTCOME MEASUREMENTS: Clinician and patient evaluation based on the modified Cincinnati Knee Rating System. Graft failure was defined as replacement or removal of the graft due to mechanical symptoms or pain. RESULTS: Clinician and patient evaluation indicated median improvements of 4 and 5 points, respectively, at 36 months following ACI (p < 0.001). Previous treatment with marrow stimulation techniques and size of defect did not impact the results with ACI. The most common adverse events reported were adhesions and arthrofibrosis and hypertrophic changes. Three patients had graft failure and required reimplantation or treatment with alternative cartilage repair techniques. Kaplan-Meier estimated freedom from graft failure was 94% at 36 months postoperatively (95% CI = 88-100%). CONCLUSIONS: These results of this study indicate excellent graft survivorship using ACI as well as substantial improvement in functional outcome.

Adult↗

Mannan-binding lectin enhances susceptibility to visceral leishmaniasis.

Levels of the serum opsonin mannan-binding lectin (MBL) were directly correlated with the probability of developing visceral leishmaniasis. Monocytes infected with MBL-opsonized Leishmania chagasi promastigotes secreted higher levels of tumor necrosis factor alpha and interleukin-6 than cells infected with nonopsonized parasites. Our findings indicate that MBL can modulate the clinical outcome of infection with L. chagasi and the function of infected macrophages.

Adolescent↗

Sedatives used in pediatric imaging: comparison of IV pentobarbital with IV pentobarbital with midazolam added.

OBJECTIVE: This study was designed to evaluate safety, efficacy, and success of adding IV midazolam to an established IV pentobarbital protocol for pediatric sedation for radiologic imaging. Outcomes included sedation and discharge times as well as adverse events SUBJECTS AND METHODS: This prospective study compared two different sedation protocols developed by the radiology sedation committee and approved by the hospital sedation committee at our institution. Patients in the pentobarbital group received IV pentobarbital alone, and patients in the pentobarbital--midazolam group received a combination of IV pentobarbital and midazolam. A total of 1070 infants and children were enrolled, and sedation data were entered into a computer database and reviewed at bimonthly radiology sedation committee meetings for safety, efficacy, efficiency, failed sedations, and adverse outcomes. RESULTS: Mean age distribution, sex, American Society of Anesthesiologists physical status classification, fasting status, weight, and types of examinations were similarly distributed between the two study groups. Analysis of variance indicated longer times were required to sedate and to discharge patients who had received pentobarbital--midazolam (p < 0.001 for both times), even after adjusting for differences in the patients' ages and weights. The pentobarbital--midazolam group required more time to be successfully sedated and more time to discharge from the recovery room. The rates of adverse events and failed sedations were similar for both groups. CONCLUSION: Midazolam does not have a beneficial effect on pentobarbital sedation and has no effect on the rate of adverse events. The prolonged time needed both to sedate and to discharge (timed from the initial dose of sedation) pediatric patients who have received midazolam should discourage physicians from combining it with pentobarbital for pediatric sedation.

Child, Preschool↗

Coagulation abnormalities in pediatric and adult patients after sclerotherapy or embolization of vascular anomalies.

OBJECTIVE: The purpose of our study was to examine the coagulation status in patients with vascular anomalies who had undergone sclerotherapy or embolization. SUBJECTS AND METHODS: Ours was a prospective pilot study of 29 patients who had undergone sclerotherapy or embolization of large vascular anomalies. Fibrinogen, platelet, and d-dimer levels and prothrombin time were obtained before, immediately after, and on the day after the procedure. RESULTS: Five patients with venous malformations had positive d-dimer levels before the procedure. A subgroup analysis revealed a relationship between the type of agent used and the change in coagulation status. Specifically, a positive relationship was found between the use of dehydrated alcohol or sodium tetradecyl sulfate and a disruption in coagulation profiles as evidenced by a decrease in platelets and fibrinogen, an increase in prothrombin time, and a conversion from negative to positive d-dimers. In contrast, sclerotherapy or embolization with cyanoacrylic, polyvinyl alcohol foam particles, or platinum microcoils was not associated with coagulation disturbances. CONCLUSION: The coagulation disturbances that occur in response to dehydrated alcohol or sodium tetradecyl sulfate sclerotherapy or embolization could compromise the patient's clotting ability. Patients who receive dehydrated alcohol or sodium tetradecyl sulfate during a preoperative sclerotherapy or embolization may experience coagulation disturbances that could increase the risk of bleeding, thrombosis, or hematoma. This patient population may benefit from the use of glue, foam, or coils as a substitute for dehydrated alcohol or sodium tetradecyl sulfate.

Adolescent↗