Gwenn E. McLaughlin

Intestinal transplantation in children: A summary of clinical outcomes and prognostic factors in 108 patients from a single center

We performed 124 intestinal transplants on 108 children (median age, 1.5 years) since 1994. Initial graft types included isolated intestine (I) (n = 26), liver and intestine (LI) (n = 26), multivisceral (MV) (n = 50), and multivisceral without liver (MMV) (n = 6). Four groups were defined by type of induction therapy: none, OKT3, or cyclophosphamide (August 1994-December 1997, n = 25), early experience with daclizumab (January 1998-December 2000, n = 26), recent experience with daclizumab (January 2001–April 2004, n = 40), and Campath-1H (January 2001-April 2004, n = 17). Actuarial patient survival at 1 year for groups 1–4 was 44% ± 10%, 54% ± 10%, 83% ± 6%, and 41% ± 12%, respectively, with group 3 having the most favorable survival (P = 0.0004). Using Cox stepwise regression, the hazard rate of developing severe rejection was significantly higher in patients with transplant type I or LI (P = 0.0002), with no difference between these groups (P = 0.24) but a significantly higher rate for LI versus MV (P = 0.005). Three factors associated with improved patient survival were recipient of MV or MMV (P = 0.008), age at transplantation greater than 1 year (P = 0.01), and use of daclizumab (P = 0.0006). Cause-specific hazard analysis revealed a decreased rate of rejection-related mortality for recipients of MV or MMV (P = 0.0007), whereas age greater than 1 year indicated a lower rate of infection-related mortality (P = 0.0009). Pediatric intestinal transplantation provides an increasingly realistic chance of survival, particularly with the more recent use of daclizumab and multivisceral transplantation. A protective effect of multivisceral transplantation appears to exist with respect to the development of severe rejection.

Subcellular distribution of CFTR in rat intestine supports a physiologic role for CFTR regulation by vesicle traffic.

Abstract. The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated chloride channel critical to intestinal anion secretion. In addition to phosphorylation, vesicle traffic regulates CFTR in some epithelial cells. Studies of cultured intestinal cells are conflicting regarding the role of cAMP-dependent vesicle traffic in regulating chloride transport. Whether CFTR is present in vesicular compartments within chloride secretory cells in the intestine is unknown and the role of cAMP-dependent vesicle insertion in regulating CFTR and intestinal fluid secretion remains unclear. The purpose of this study was to: (1) examine and quantify the subcellular distribution for CFTR in rat intestine, (2) further define the ultrastructure of the previously identified CFTR High Expresser (CHE) cell, and (3) examine the cellular distribution of CFTR following cAMP stimulation in vivo. Using the sensitive techniques of cryoimmunogold electron microscopy we identified CFTR in subapical vesicles and on the apical plasma membrane in crypt, Brunner glands, and CHE cells. cAMP stimulation in rat proximal small intestine produced a fluid secretory response and was associated with an apical redistribution of CFTR, supporting a physiologic role for cAMP-dependent CFTR vesicle insertion in regulating CFTR in the intestine.

Adenovirus infection in pediatric liver and intestinal transplant recipients: Utility of DNA detection by PCR

To evaluate the incidence of adenovirus (AdV) infection in pediatric liver and intestinal transplant recipients, the records of patients with possible AdV infection were reviewed for demographic data, symptomatology, methods of diagnosis, treatment and outcome. To evaluate the impact of polymerase chain reaction (PCR) amplification and identification of AdV DNA as a diagnostic test, the incidence and outcome of AdV before and after the introduction of PCR were compared. Adenovirus infection was identified in 4.1% of liver recipients and 20.8% of intestinal transplant recipients. The overall incidence of AdV did not increase over time, even following the introduction of PCR for virus detection. The higher incidence of AdV in the pediatric intestinal transplant recipients may be attributed to the frequent application of PCR methodology to intestinal biopsy material. Detection of AdV by PCR was associated with reduced mortality compared with detection by culture, either because of earlier detection of invasive disease or because PCR detects the presence of latent as well as active AdV.

Effect of corticosteroids on survival of children with acquired immunodeficiency syndrome and Pneumocystis carinii -related respiratory failure

The medical records of patients with acquired immunodeficiency syndrome were reviewed to evaluate the effect of our adoption to the pediatric population of the National Institutes of Health recommendation for adjunctive corticosteroid therapy in adults with Pneumocystis carinii pneumonia. In 21 episodes of P. carinii-related respiratory failure, only adjunctive corticosteroids were associated with a significant improvement in survival to successful removal of the tracheal tube, from a historical rate of 11% to 91%.

Lower respiratory tract viral infections in pediatric abdominal organ transplant recipients: A single hospital inpatient cohort study

Respiratory viral infections are a major cause of morbidity and mortality in solid organ transplant recipients. Early detection of a viral etiology of a LRTI in a febrile transplant recipient can theoretically reduce the use of antibiotics, trigger modification of immunosuppression and prompt appropriate isolation procedures to reduce nosocomial infections. We retrospectively evaluated pediatric abdominal organ transplant recipients hospitalized with respiratory illnesses to determine the viral pathogens identified by various methods including multiplex RT‐PCR performed on nasopharyngeal or endotracheal aspirates. Among 30 symptomatic subjects (median age, 2.5 yr) evaluated using this methodology, 25 (83%) were positive for at least one virus. Rhinovirus was the most frequently identified virus (14 subjects). RSV was identified in five subjects with associated mortality of 40%. Parainfluenza, influenza, metapneumovirus, and adenovirus were also identified. This study indicates that rhinovirus is a significant cause of morbidity in this single center cohort of pediatric abdominal organ transplant recipients.

Reversal of acute tacrolimus-induced renal vasoconstriction by theophylline in rats.

Objective To determine whether theophylline, a nonselective adenosine receptor antagonist and phosphodiesterase inhibitor, reverses the acute declines in renal blood flow and glomerular filtration rate induced by high-dose tacrolimus in rats. Design Prospective, randomized, placebo-controlled experimental study. Setting University-based basic science research laboratory. Subjects Adult male Sprague-Dawley rats. Interventions After mechanical ventilation and instrumentation under isoflurane and nitrous oxide anesthesia, animals received either tacrolimus 0.5 mg/kg intravenously or vehicle and 1 hr later either theophylline 4 mg/kg intravenously or vehicle. Measurements and Main Results By using radiolabeled microspheres, renal blood flow was measured in three groups: control (n = 5), tacrolimus plus vehicle (n = 6), and tacrolimus plus theophylline (n = 6) at four time points—baseline and 60, 75, and 90 mins after tacrolimus or vehicle (the latter two time points being 15 and 30 mins after theophylline or vehicle, respectively). Whole blood tacrolimus and serum theophylline concentrations were measured. In a separate group of animals, by using 51Cr-EDTA, glomerular filtration rate was measured in two groups: tacrolimus plus vehicle (n = 5) and tacrolimus plus theophylline (n = 5) at baseline and over two consecutive 20-min time periods beginning 61 mins posttacrolimus. Urine flow rate also was measured. Following tacrolimus, both renal blood flow and glomerular filtration rate declined in parallel by approximately 33% and 50% from baseline after 75 and 90 mins, respectively (p < .05 by two-way repeated-measures analysis of variance). Theophylline completely reversed these tacrolimus-induced decreases in renal blood flow and glomerular filtration rate. Urine flow rate also increased in response to theophylline. Conclusions Low-dose theophylline reverses tacrolimus-induced declines in renal blood flow and glomerular filtration rate observed in an acute model of tacrolimus toxicity. Theophylline’s effect in chronic toxicity remains to be determined.

Management of a traumatic pulmonary pseudocyst using high-frequency oscillatory ventilation

High-frequency ventilation is indicated when acute hypoxemic respiratory failure is associated with an ongoing air leak. This report describes the successful use of high-frequency oscillatory ventilation in a child with pulmonary contusions and traumatic pulmonary pseudocysts who experienced severe air leak syndrome on conventional mechanical ventilation.

Cerebral blood flow during partial liquid ventilation in surfactant-deficient lungs under varying ventilation strategies.

Objective To test the hypothesis that cerebral and other regional organ blood flow would be maintained during partial liquid ventilation (PLV) in an animal model of acute lung injury during different ventilation strategies. Design A prospective, randomized study. Setting Animal research facility. Subjects Sixteen piglets, 2 to 4 wks of age. Interventions Severe lung injury was induced in infant piglets by repeated saline lavage and high tidal volume ventilation. Animals were then randomized to either conventional volume controlled ventilation or PLV. Measurements and Main Results Organ blood flow was determined in both groups using radiolabeled microspheres under four conditions: high mean airway pressure, P―aw; high Paco2, high P―aw; normal Paco2; low P―aw, high Paco2; low P―aw, normal Paco2. There were no differences in cerebral blood flow during conventional ventilation and PLV, regardless of ventilation strategy. Conclusions These results suggest in an acute lung injury model, PLV does not affect cerebral blood flow or other regional organ blood flow over a range of airway pressures.

Nonsurgical Care of Intestinal and Multivisceral Transplant Recipients: A Review for the Intensivist

Intestinal and multivisceral transplantation has evolved from an experimental procedure to the treatment of choice for patients with irreversible intestinal failure and serious complications related to long-term parenteral nutrition. Increased numbers of transplant recipients and improved survival rates have led to an increased prevalence of this patient population in intensive care units. Management of intestinal and multivisceral transplant recipients is uniquely challenging because of complications arising from the high incidence of transplant rejection and its treatment. Long-term comorbidities, such as diabetes, hypertension, chronic kidney failure, and neurological sequelae, also develop in this patient population as survival improves. This article is intended for intensivists who provide care to critically ill recipients of intestinal and multivisceral transplants. As perioperative care of intestinal/multivisceral transplant recipients has been described elsewhere, this review focuses on common nonsurgical complications with which one should be familiar in order to provide optimal care. The article is both a review of the current literature on multivisceral and isolated intestinal transplantation as well as a reflection of our own experience at the University of Miami.

Open lung biopsy in pediatric patients with respiratory failure after abdominal transplantation.

Abstract:  To understand the utility of open lung biopsy (OLB) in the evaluation of respiratory failure in pediatric abdominal organ transplant we reviewed the records of nine children in this patient population who underwent an OLB. Eight of nine patients had undergone a previous non‐diagnostic bronchoalveolar lavage. Biopsies were performed at the bedside in the pediatric intensive care unit and tissue was processed by the Department of Pathology with special stains for infectious agents. There were no significant complications of OLB. A specific treatable etiology was identified in four patients (respiratory syncytial virus, adenovirus, graft‐vs.‐host disease and post‐transplant lymphoproliferative disease), leading to a change in therapy and survival in two. Overall survival was 44%. Given the low morbidity, OLB as performed in this study appears appropriate in this patient population.