Nesiritide in infants and children with congestive heart failure.

OBJECTIVES: Nesiritide (synthetic B-type natriuretic peptide) has been shown to be effective in the management of acute decompensated heart failure in adults. The role of nesiritide in pediatric heart failure has not been examined. In the present study, we reviewed our initial experience with nesiritide in children with primary heart failure or low cardiac output after heart surgery. METHODS: Nesiritide was administered in an open-label fashion to patients with heart failure who were already receiving inotropic and diuretic therapy. Between July 2003 and August 2004, 30 patients aged 5 days to 16.7 yrs (median age, 4.6 months) received nesiritide therapy. Diagnoses included single-ventricle congenital defect (n = 5), two-ventricle congenital defect (n = 13), heart transplant (n = 5), and dilated cardiomyopathy (n = 7). Sixteen patients were started on nesiritide within 2 wks of corrective or palliative heart surgery. The majority of subjects (n = 24) received an initial bolus dose. Continuous infusion dosage ranged between 0.005 and 0.02 microg.kg.min. Nesiritide was discontinued for possible side effects in two patients (arrhythmia and hypotension). Duration of therapy ranged from 1 to 24 days (median, 4 days). RESULTS: Administration of nesiritide was associated with improvement in fluid balance from positive 0.8 +/- 1.9 mL.kg.hr at baseline to negative 0.3 +/- 1.8 mL.kg.hr after 24 hrs of therapy (p = .02). There was a nonsignificant trend toward a reduction in right atrial pressure (9.2 +/- 3.9 vs. 11.2 +/- 4.1, p = .08). CONCLUSIONS: Nesiritide is well tolerated in children with heart failure and is associated with improved diuresis. Further prospective studies will be needed to compare nesiritide with other vasoactive agents and examine the cost-efficacy of this therapy.     

Initial experience in 115 patients with the retrievable Cook Celect vena cava filter

The aim of this study was to evaluate our experience with the retrievable Cook Celect inferior vena cava (IVC) filter (William Cook, Europe) with regard to insertion, efficiency, ease of retrieval, and any associated complications. A retrospective review was performed of 115 patients (41 female, 74 male, mean age 47.97 years) who underwent Cook Celect IVC filter insertion between December 2005 and October 2007. Filter insertion was successful in all patients. Of the 115 filters inserted, 57 have been successfully retrieved (49.6%) to date. The successful retrieval rate from attempted retrieval was 93.4%. The mean dwell time of successfully retrieved filters was 114.9 days (range 14–267 days). Failed retrievals were due to a thrombosed vena cava (n = 1) and endothelialisation of the filter (n = 3). In the failed retrieval group the mean implantation time was 142 days (range 78–211 days). While this is the first retrospective clinical study on the Cook Celect filter, results to date are promising. We demonstrated an efficacious filter with a high successful retrieval rate of 93.4% and a low complication rate. The filter was assessed with extended dwell times (range 14–267 days). Failed retrieval secondary to hook endothelialisation continues to be an issue with this filter. We recognize that a limitation of our study was the lack of systematic follow‐up for clinically silent complications. Further studies to evaluate longer term outcomes and effectiveness of this filter are warranted.     

Prevalence of periodontal pathogens in subgingival lesions, atherosclerotic plaques and healthy blood vessels: a preliminary study

Background and Objective:  Previous studies have reported different periodontal bacteria in atherosclerotic lesions, but their involvement in plaque formation remains unclear. The aim of the present study was to investigate the presence of 20 periodontal bacteria in atherosclerotic samples and healthy blood vessels (used as controls) and to clarify their relationship in regard to clinical and bacteriological periodontal status.
Material and Methods:  The day before vascular surgery the patients had a thorough periodontal examination and bacteriological samples were taken from periodontally diseased sites. Atheromatous plaques, internal mammary arteries and saphenous veins were harvested during surgery. A DNA–DNA hybridization procedure was used to screen periodontal and vascular samples for the 20 selected bacterial species.
Results:  Periodontal samples from the severe periodontitis group were found to have a higher prevalence and biomass of bacterial species than the moderate periodontitis group. In vessel samples, the prevalence of the same 20 bacterial species analyzed together was similar in the two groups, except for saphenous veins.
Conclusion:  The presence of periodontal pathogens in atherosclerotic plaques and in apparently healthy vessels appeared to reflect a higher level of bacteremia rather than infection of endothelial cells.     

Radioresistant cervical cancer shows upregulation of the NHEJ proteins DNA-PKcs, Ku70 and Ku86

Background:

Radiotherapy is central in the treatment of cervical cancer. The formation of DNA double-strand breaks is considered to be critical for the radiotherapeutic effect. The non-homologous end joining (NHEJ) proteins DNA–PKcs, Ku70 and Ku86 have a major role in repairing DNA lesions. The objective of this study was to analyse if the expression of DNA–PKcs, Ku70 and Ku86 and their downstream signalling molecules p53, p21 and Mdm-2 are altered in residual cervical tumours after radiotherapy.

Methods:

Retrospective analysis of 127 patients with cervical cancer stage IB-IIA treated with preoperative radiotherapy and radical surgery, revealed residual tumour in the cervical specimen in 30 patients. In 22 cases tumour material from residual and corresponding primary tumour were retrieved and the expression of DNA–PKcs, Ku86, Ku70, p53, p21 and Mdm-2 were assessed by immunohistochemistry.

Results:

Residual tumours showed increased frequency of DNA–PKcs (P=0.037), Ku70 (P=0.018), Ku86 (P=0.008) positive cells. A correlation in DNA–PKcs expression between primary and residual tumours was found. The frequency of p21-positive cells was decreased (P=0.007) in residual tumours whereas no change in p53 or Mdm-2-positive cells were observed.

Conclusion:

Our results show that cervical carcinoma surviving radiotherapy have an increased DNA–PK expression. Studies on larger patient cohorts are needed to allow an interpretation that an upregulation of DNA–PK function may be part of a radioresistance mechanism within this tumour type.     

Hemodynamic and Electrocardiographic Effects of Early Pulmonary Valve Replacement in Pediatric Patients After Transannular Complete Repair of Tetralogy of Fallot

In adults, pulmonary value replacement (PVR) shows improvement in right ventricular (RV) volume and function and reduces QRS duration. In addition, RV volume correlates with QRS duration and QRS change. This has not been shown in pediatric patients. The purpose of this study was to evaluate serial magnetic resonance imaging (MRI) and electrocardiogram measurements before and after early PVR in a pediatric population with repaired Tetralogy of Fallot and whether QRS duration and QRS change correlated with RV volume. A retrospective review of MRIs and electrocardiograms was conducted on 10 patients. Median age at repair was 2.1 ± 0.7 years, and median age at PVR was 11.5 ± 2.0 years. There were significant decreases in RV end diastolic volume (EDV)/body surface area (BSA) (p < 0.0004), end systolic volume (ESV)/BSA (p = 0.02), RVEDV/left ventricular (LV) EDV (p < 0.001), RV ejection fraction (p < 0.04), RV stroke volume (SV)/BSA (p < 0.0002), and (RVSV - LVSV)/BSA (p = 0.0007). No significant change in QRS duration occurred (p = 0.08). QRS duration (pre-r = 0.44, p = 0.20; post-r = 0.34, p = 0.33) and QRS change (r = −0.08, p = 0.83) did not correlate with RVEDV. We propose early consideration of PVR in pediatric patients. PVR improves RV volumes and function and may provide beneficial electromechanical effects by slowing the progression of QRS duration.     

Closure of Symptomatic Ventricular Septal Defects: How Early Is Too Early?

With improvements in technology and surgical technique, pediatric cardiologists are challenging surgeons to close symptomatic ventricular septal defects (VSDs) in ever smaller patients. Although delaying surgery may facilitate operative repair, early intervention decreases the period of time these patients require therapy to prevent heart failure, maintains growth, and minimizes exposure to increased pulmonary pressures. To evaluate early intervention, we compare the outcomes of VSD closure in different-sized children. From December 2002 to July 2005, 225 patients underwent closure of a VSD. These patients were divided into four weight-based groups: <4 kg (group 1, n = 28), 4 to 6 kg (group 2, n = 93), 6 to 10 kg (group 3, n = 47), and >10 kg (group 4, n = 57). We reviewed operative and postoperative data, and comparisons were made between the groups. Median weights and ages at the time of surgery were 3.5 kg and 77 days (group 1), 4.9 kg and 128 days (group 2), 7.1 kg and 309 days (group 3), and 18.2 kg and 190 days (group 4). Operative data included cardiopulmonary bypass (CPB), aortic cross-clamp, and procedure times. CPB (p = 0.064), cross-clamp (p = 0.665), and procedure (p = 0.187) times were not significantly affected by decreasing weight. Postoperative continuous data included duration of ventilation and length of intensive care unit (ICU) and hospital stay. Ventilation (p = 0.667) and ICU (p = 0.976) times and length of hospital stay (p = 0.905) were also unaffected by decreasing weight. Postoperative catagoric data included complications and presence of a residual VSD. There was no significant difference in complications (p = 0.763) or residual VSD (p = 0.696) between groups. There was no mortality and no persistent heart block requiring placement of a permanent pacemaker. With improvements in technology and surgical technique, safe and effective VSD closure can be performed in increasingly smaller children. Earlier repair decreases the period of time these patients require aggressive medical therapy to prevent heart failure and maintain growth. It also decreases the period of time for which they are exposed to increased pulmonary pressures and are at risk for infectious respiratory complications. It does not appear to affect operative or postoperative outcomes.     

Pre-Hospital Discharge Car Safety Seat Testing in Infants Following Congenital Heart Surgery

The purpose of this study was to expand the American Academy of Pediatrics’ (AAP) car safety seat testing recommendation to include high-risk infants following cardiac surgery. Car safety seat testing (≤4 days prior to discharge) was retrospectively reviewed for 66 postoperative infants. Car safety seat testing was performed according to AAP guidelines. Failure of the test was defined as the occurrence of apnea, bradycardia, or oxygen desaturation. Average birth weight was 3.1 ± 0.5 kg. Two patients were born <37 weeks of gestation. Surgical procedures included modified Blalock–Taussig shunt (15), arterial switch operation (12), Norwood–Sano modification (11), coarctation repair (8), repair of tetralogy of Fallot (6), repair of truncus arteriosus (4), repair of total anomalous pulmonary venous return (3), pacemaker (2), repair of interrupted aortic arch and ventricular septal defect (VSD) (1), repair of coarctation/VSD (1), orthotopic heart transplant (1), repair of VSD (1), and patent ductus arteriosus ligation (1). Average age at discharge was 28 ± 21 days. Four patients (6%) failed car safety seat testing secondary to a decrease in oxygen saturation. One of four passed on retesting after parental education; three of 4 (75%) were discharged home in a supine car safety seat. There was no relationship between the type of surgery and car safety seat test failure. It may be beneficial to extend the AAP recommendations for car safety seat testing to include this high-risk patient population.