Controversies in the Management of Functional Constipation in Children.

PURPOSE OF REVIEW: Functional constipation (FC) in children is a common health problem with reported worldwide prevalence rates up to 32.2%. The majority of children with constipation respond to oral laxative treatment. After 5 years of intensive treatment, however, approximately 50% of children remain symptomatic. To discuss the evidence for new treatments in these children, including pre- and probiotics, pelvic physiotherapy, prucalopride, sacral nerve stimulation, and surgery, and to highlight the controversies surrounding them. RECENT FINDINGS: Pre- and probiotics and prucalopride are not effective in the treatment of childhood constipation. Pelvic physiotherapy and sacral nerve stimulation are promising treatment options but larger trials are needed. Surgery for pediatric constipation is the treatment of last resort. Large, well-designed placebo-controlled trials with proper outcome measures, as suggested by the Rome foundation pediatric subcommittee on clinical trials, are necessary to provide more insight regarding the efficacy of new treatments in childhood constipation.

Energetics and hemodynamic changes of normal and various right heart bypass (Fontan) circulations in lambs under varying respiration parameters.

The Fontan circulation or one of its many modifications is a common surgical procedure implemented in children with congenital heart defects to improve pulmonary circulation. Two modifications are the atriopulmonary connection (AP) and the modified total cavopulmonary connection (TCPC). Successful AP and TCPC operations performed in lambs show respiration has a major influence on systemic and pulmonary hemodynamics. Instantaneous pressure and flow waveforms are obtained before and after the procedure and energies are calculated. Hemodynamic changes in relevant vessels are also acquired. Time delays due to respiration will be calculated and transfer functions computed. The purpose of this study is to examine these waveforms and energy gains/losses under varying respiration parameters in order to aid in determining an optimal surgical protocol as well as assist in the development an accurate computer simulation model.

The effect of incorporating vessel compliance in a computational model of blood flow in a total cavopulmonary connection (TCPC) with caval centerline offset.

BACKGROUND: The total cavopulmonary connection (TCPC), a palliative correction for congenital defects of the right heart, is based on the corrective technique developed by Fontan and Baudet. Research into the TCPC has primarily focused on reducing power loss through the connection as a means to improve patient longevity and quality of life. The goal of our study is to investigate the efficacy of including a caval offset on the hemodynamics and, ultimately, power loss of a connection. As well, we will quantify the effect of vessel wall compliance on these factors and, in addition, the distribution of hepatic blood to the lungs. METHODS: We employed a computational fluid dynamic model of blood flow in the TCPC that includes both the non-Newtonian shear thinning characteristics of blood and the nonlinear compliance of vessel tissue. RESULTS: Power loss in the rigid-walled simulations decayed exponentially as caval offset increased. The compliant-walled results, however, showed that after an initial substantial decrease in power loss for offsets up to half the caval diameter, power loss increased slightly again. We also found only minimal mixing in both simulations of all offset models. CONCLUSIONS: The increase in power loss beyond an offset of half the caval diameter was due to an increase in the kinetic contribution. Reduced caval flow mixing, on the other hand, was due to the formation of a pressure head in the offset region which acts as a barrier to flow.

Long term results of lung transplantation for cystic fibrosis.

OBJECTIVES: We reviewed our experience with lung transplant for cystic fibrosis (CF) over a 10-year period to identify factors influencing long-term survival. METHODS: One hundred and twenty-three patients with CF have undergone 131 lung transplant procedures at our institution; 114 have had bilateral sequential lung transplants (DLTX) and nine have had bilateral lower lobe transplants from living donors. Three patients had retransplant for acute graft failure, and five had late retransplant for bronchiolitis obliterans syndrome (BOS). Kaplan-Meier survival was calculated for the entire cohort and for subsets at higher risk of death to determine factors predicting a better outcome. RESULTS: Actuarial survival for the entire group of DLTX CF patients was 81% at 1 year, 59% at 5 years, and 38% at 10 years. Lobar transplant was associated with a poorer survival (37.5% at 1 and 5 years). Among DLTX patients, colonization with Burkholderia cepacia was present in 22 patients and was associated with poorer outcome (1- and 5-year survival 60 and 36% in B. cepacia patients vs. 86 and 64% in non-cepacia patients). DLTX patients younger than age 20 (n=22) had a similar survival to patients age 20 or older (n=90). Being on a ventilator at the time of transplant was not associated with poorer survival (n=8). BOS affects increasing numbers of survivors with time. Five CF patients have been retransplanted due to BOS with one operative death and 1-year survival of 60%. CONCLUSIONS: DLTX has acceptable long term survival in CF adults and children with end stage disease. CF patients colonized with B. cepacia have a worse outcome but transplantation is still warranted.

Lung transplantation for cystic fibrosis: effective and durable therapy in a high-risk group.

BACKGROUND: The purpose of this study was to review our experience with lung transplantation in patients with end-stage cystic fibrosis. METHODS: Eight-two patients with cystic fibrosis have undergone bilateral lung transplantation (n=76) or bilateral lower lobe transplantation (n=6) since October 1990. RESULTS: Actuarial survival for the entire cohort is 79% at 1 year and 57% at 5 years. The development of bronchiolitis obliterans syndrome is the leading cause of death after the first year. Freedom from bronchiolitis obliterans syndrome is 84% at 1 year and 51% at 3 years. Pulmonary function tests improve dramatically in recipients. There was no association between death within 1 year and recipient age, weight, graft ischemic time, cytomegalovirus seronegativity, or the presence of pan-resistant organisms. Similarly, there was no association between the development of bronchiolitis obliterans syndrome within 2 years and ischemic time, number of rejection episodes, cytomegalovirus seronegativity, or the presence of panresistant organisms. CONCLUSIONS: Despite their poor nutritional status and the presence of multiply resistant organisms, patients with cystic fibrosis can undergo bilateral lung transplantation with acceptable morbidity and mortality.

Anatomically sound, simplified approach to repair of "complete" atrioventricular septal defect.

BACKGROUND: There are few congenital anomalies of the heart that have benefited more from thorough anatomic analysis than the complex anomaly known as atrioventricular septal defect in the setting of common atrioventricular junction. Recent advances in understanding the anatomy of this lesion have led to alternative methods of repairing these defects. METHODS: The medical records of 21 consecutive patients undergoing repair of complete atrioventricular septal defect have been reviewed. Nine of these patients had a standard one- or two-patch repair, and 12 had direct closure of the ventricular element of the defect. RESULTS: Direct closure resulted in significantly shorter pump and cross-clamp times. Follow-up for an average of 34 months suggests that when direct closure can be performed, the results are comparable with those of the more standard technique. CONCLUSIONS: Our initial success with this approach is encouraging; however, longer follow-up is required to establish whether it will be broadly applicable.

One hundred consecutive thymectomies for myasthenia gravis.

BACKGROUND: Between June 1997 and November 1993, 100 consecutive thymectomies for myasthenia gravis were performed at University of North Carolina Hospitals in Chapel Hill. METHODS: A consistent, planned protocol involving preoperative, intraoperative, and postoperative care was followed. All thymectomies were performed through a median sternotomy with removal of all visible thymus and perithymic fat in the anterior mediastinum. RESULTS: There was no perioperative mortality or longterm morbidity. Mean postoperative hospital stay was 6.3 days (range, 3 to 18 days). Ninety-six percent of the patients were extubated the day of the operation, and all patients were extubated within 24 hours. Mean postoperative intensive care unit stay was 1.2 days (range, 1 to 4 days). After a mean follow-up of 65 months (range, 1 to 199 months), 78% of all patients are improved by at least one modified Osserman classification when their current status is compared with their worst preoperative disease severity. In fact, 69% of patients with mild disease preoperatively (class I, II, or III maximal severity) are in pharmacologic remission (asymptomatic without regular medication), whereas 29% of patients with severe disease (class IV or V) are in remission (p = 0.0001). CONCLUSIONS: Our programmatic approach to thymectomy through a sternotomy has shown minimal morbidity and mortality. It is beneficial to myasthenics at both ends of the age and severity spectrum.

Lung transplantation after previous thoracic surgical procedures.

BACKGROUND: This study examined results of lung transplantation after previous thoracic surgical procedures. METHODS: Twenty percent of the 69 isolated lung transplantations performed at the University of North Carolina between January 1990 and June 1993 were in patients who had undergone a previous thoracic surgical procedure, and an additional 10% had undergone a previous chest tube placement. RESULTS: No statistically significant increase in morbidity or mortality was observed between those having undergone a previous procedure or chest tube placement and all other patients. Specifically, the length of intubation, length of hospital stay, hospital mortality, or the number of patients who experienced major early complications was not significantly different between these groups. A statistically significant increase in the number of blood products used was observed in the patients with previous thoracic surgical procedures but not with patient having had previous chest tube placements. However, when the data were reanalyzed with respect to the use of cardiopulmonary bypass, those patients requiring bypass had a markedly poorer outcome that reached statistical significance in all of the parameters studied: hospital death, incidence of major complications, length of intubation, hospital stay, incidence of bleeding, and number of blood products used. CONCLUSIONS: We conclude that although increased bleeding may be encountered, lung transplantation can be performed successfully in patients who have had previous thoracic surgical procedures without increased major morbidity or mortality; however, the use of cardiopulmonary bypass has been associated with significantly increased morbidity and mortality in our patient population.

Effect of size (mis)matching in clinical double-lung transplantation.

Current United Network for Organ Sharing policy requires listing lung transplant recipients with an acceptable donor weight range, but lung size is a function of height, age, sex, and race. Frequently, lung transplant recipients are underweight, which results in a large discrepancy between donor and recipient weights. We reviewed our experience with size discrepancy between donors (D) and recipients (R) of 49 double-lung transplant (DLTX) procedures since July 1990. Pneumoreduction procedures were performed in 11 recipients of lungs judged to be too large at the time of DLTX (right middle lobectomy, 2; lingulectomy, 2; both, 6; right middle lobectomy and bilateral apical resections, 1). Predicted forced vital capacity (FVC) and total lung capacity (TLC) of donors and recipients were calculated. Donors were larger than recipients in general (D:R height = 1.02; D:R weight = 1.46), and, as a result, recipient-predicted lung volumes were smaller than donor-predicted lung volumes (D:R FVC = 1.1; D:R TLC = 1.1). Recipients undergoing pneumoreduction procedures had a significantly greater size discrepancy between donors and recipients; thus, both the ratio of D:R and the difference between D and R predicted FVC and TLC were significantly greater among recipients who underwent pneumoreduction, compared with nonreduced recipients. For recipients in the pneumoreduction group, predicted FVC and TLC were recalculated, with a proportionate amount subtracted based on the number of pulmonary segments removed. When the "corrected" FVC and TLC of the donors were compared with recipient-predicted FVC and TLC, there was no longer any significant difference between reduced and non-reduced groups, which implies that visual estimate of size mismatch at surgery is an accurate measure of size discrepancy. Post-DLTX spirometry showed identical improvement in FVC in patients who had pneumoreduction and those who did not, and survival at 6 months was identical in both groups. We conclude that pneumoreduction had no adverse effect on survival or post-DLTX spirometry, allowing safe use of larger donors in small recipients. Also, because lung size is more a function of height than weight, this study challenges the United Network for Organ Sharing practice of listing recipients with an acceptable donor weight range.

Improved results of lung transplantation for patients with cystic fibrosis.

Patients with cystic fibrosis pose particular challenges for lung transplant surgeons. Earlier reports from North American centers suggested that patients with cystic fibrosis were at greater risk for heart-lung or isolated lung transplantation than other patients with end-stage pulmonary disease. During a 3 1/2 year period, 44 patients with end-stage lung disease resulting from cystic fibrosis underwent double lung transplantation at this institution. During the same interval, 18 patients with cystic fibrosis died while waiting for lung transplantation. The ages of the recipients ranged from 8 to 45 years, and mean forced expiratory volume in 1 second was 21% predicted. Seven patients had Pseudomonas cepacia bacteria before transplantation. Bilateral sequential implantation with omentopexy was used in all patients. There were no operative deaths, although two patients required urgent retransplantation because of graft failure. Cardiopulmonary bypass was necessary in six procedures in five patients and was associated with an increased blood transfusion requirement, longer postoperative ventilation, and longer hospital stay. Actuarial survival was 85% at 1 year and 67% at 2 years. Infection was the most common cause of death within 6 months of transplantation (Pseudomonas cepacia pneumonia was the cause of death in two patients), and bronchiolitis obliterans was the most common cause of death after 6 months. Actuarial freedom from development of clinically significant bronchiolitis obliterans was 59% at 2 years. Results of pulmonary function tests improved substantially in survivors, with forced expiratory volume in 1 second averaging 78% predicted 2 years after transplantation. Double lung transplantation can be accomplished with acceptable morbidity and mortality in patients with cystic fibrosis.

Lung transplantation for mechanically ventilated patients.

As lung transplantation has become more successful, the selection criteria have broadened; however, some relative contraindications to lung transplantation are controversial. Some programs consider mechanical ventilation to be a major contraindication to lung transplantation because airway colonization with bacteria may lead to nosocomial infection and respiratory muscle deconditioning may necessitate prolonged postoperative ventilatory support. We report our experience of seven double lung transplant procedures on six patients requiring mechanical ventilation. Five patients with cystic fibrosis required preoperative mechanical ventilation for 7 to 19 days (mean, 10.7 days). One patient with acute lung injury required 115 days of preoperative mechanical ventilatory support. Only the latter patient required prolonged (27 days) postoperative mechanical ventilation because of respiratory muscle weakness; the others were extubated in 1 to 19 days (mean, 7.8 days). No early complications related to bacterial infection were seen. Two patients required temporary hemodialysis for transient kidney failure. Three patients had postoperative neurologic residua; one patient had a transient hemiparesis, and seizures developed in two patients. One patient died 3 months after transplantation from severe central nervous system complications with no evidence of pulmonary problems; and two patients died 17 months after transplantation, one of them receiving a second double lung transplant for obliterative bronchiolitis. Except for the patient who required prolonged preoperative ventilatory support, mechanical ventilation did not appear to play a role in the outcome of these patients. The posttransplantation hospital stay and hospital charges for patients requiring pretransplantation ventilatory support were not significantly different from those for other lung transplant recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Anomalous course of the left brachiocephalic vein.

An anomalous course of the left brachiocephalic vein beneath the aortic arch was identified in 7 patients undergoing surgical repair of congenital cardiac malformations. Six of these patients had the morphologic features of tetralogy of Fallot including severe obstruction to the right ventricular outflow tract and a right aortic arch. A review of the literature reveals this to be an uncommon anomaly. When it is present, however, it is frequently associated with a ventricular septal defect, obstruction of the right ventricular outflow, and aortic arch anomalies. This anomaly can be documented by echocardiography, at cardiac catheterization, or intraoperatively. The presence of a subaortic left brachiocephalic vein may have implications for the conduct of surgical procedures, especially in the setting of tetralogy of Fallot.

Blastomycosis in transplant recipients: report of a case and review.

Fungi cause serious, often fatal infections in immunocompromised hosts. Recipients of solid organ and bone marrow transplants are predisposed to invasive fungal infections with Candida species, Aspergillus species, and Cryptococcus neoformans. In contrast, infections with Blastomyces dermatitidis have rarely been diagnosed in transplant recipients. We describe a patient who received an orthotopic heart transplant and developed recurrent disseminated blastomycosis. Other reported cases of blastomycosis in transplant recipients are summarized. Clinical presentation, treatment options, and morbidity associated with infections with B. dermatitidis in transplant patients are reviewed.

Determination of salivary digoxin with a dry strip immunometric assay.

Analysis of salivary digoxin using a rapid dry chemistry, enzyme-labeled immunometric assay (ELIA) was compared with fluorescence polarization immunoassay (FPIA). Saliva and serum samples were obtained from 40 hospitalized patients who were taking digoxin chronically and from 8 patients just prior to treatment with digoxin. Unstimulated saliva samples were collected from 20 patients; however, saliva volumes from 10 pediatric patients were inadequate to permit analysis by FPIA, and 1 other had unmeasurable concentrations by both methods. Stimulated saliva was collected by having patients chew a small piece of Parafilm for 1-2 min. Salivary digoxin was analyzed using the same procedure recommended for serum digoxin by each manufacturer. There were no significant differences found between ELIA and FPIA determinations of unstimulated or stimulated salivary digoxin, serum digoxin, or saliva/serum concentration ratios. The saliva/serum ratio of the unstimulated group was approximately twice that of the stimulated group (p less than 0.01) by both methods, suggesting that salivary digoxin concentration decreases with increased saliva production rate. Excellent correlations were found between ELIA and FPIA salivary digoxin concentrations and between stimulated saliva and serum concentrations by both assays. Weaker correlations were observed between unstimulated saliva and serum concentrations. There was no evidence of assay interference with either method in eight nondigitalized patients, each taking an average of 6.5 medications. The ELIA appears to provide equivalent results compared with the FPIA for the determination of salivary digoxin concentration. Further investigations are needed before salivary digoxin concentration monitoring can be recommended as an acceptable alternative to serum monitoring.

Single lung transplantation for eosinophilic granulomatosis.

A 26-year-old woman with end-stage lung disease due to eosinophilic granulomatosis had single right lung transplantation with an excellent function result that persists beyond 9 months of follow-up. Single lung transplantation offers excellent palliation to selected patients with end-stage lung disease.

Isolated lung transplantation for end-stage lung disease: a viable therapy.

Since January 1990, we have performed 29 isolated lung transplantations in 28 patients with end-stage lung disease (12 single, 16 bilateral). Recipient diagnoses were: cystic fibrosis (11), chronic obstructive pulmonary disease (6), pulmonary fibrosis (6), eosinophilic granulomatosis (1), postinfectious lung disease (1), adult respiratory distress syndrome (1), and primary pulmonary hypertension (2). There have been four deaths, two in patients with pulmonary fibrosis and two in patients with primary pulmonary hypertension. Four patients have undergone transplantation while on ventilatory support for respiratory failure (2 with cystic fibrosis, 1 having redo lung transplantation with cystic fibrosis, and 1 with adult respiratory distress syndrome); all of these have survived. Six patients required cardiopulmonary bypass, which was associated with increased transfusion requirement. All patients 2 months after discharge have returned to an active life-style, except for 2 patients who currently await retransplantation. Preoperative pulmonary rehabilitation has resulted in significant improvement in exercise performance in all patients. Immunosuppression consists of cyclosporine, azathioprine, and antilymphoblast globulin (University of Minnesota), withholding systemic steroids in the early postoperative period. We have employed bronchial omentopexy in all but four transplants; there has been one partial bronchial dehiscence, two instances of bronchomalacia requiring internal stenting, and one airway stenosis. Cytomegalovirus disease has been seen frequently (15 cases), but has responded well to treatment with ganciclovir. Other complication shave included one drug-related prolonged postoperative ventilation, thrombosis of a left lung after bilateral lung transplantation requiring retransplantation, five episodes of unilateral phrenic nerve palsy after bilateral lung transplantation (4 resolved), and the requirement of massive transfusion (greater than 10 units) in 5 patients.(ABSTRACT TRUNCATED AT 250 WORDS)