Cardiac performance and quality of life in patients who have undergone the Fontan procedure with and without prior superior cavopulmonary connection.

BACKGROUND: A superior cavopulmonary connection is commonly performed before the Fontan procedure in patients with a functionally univentricular heart. Data are limited regarding associations between a prior superior cavopulmonary connection and functional and ventricular performance late after the Fontan procedure. METHODS: We compared characteristics of those with and without prior superior cavopulmonary connection among 546 subjects enrolled in the Pediatric Heart Network Fontan Cross-Sectional Study. We further compared different superior cavopulmonary connection techniques: bidirectional cavopulmonary anastomosis (n equals 229), bilateral bidirectional cavopulmonary anastomosis (n equals 39), and hemi-Fontan (n equals 114). RESULTS: A prior superior cavopulmonary connection was performed in 408 subjects (75%); the proportion differed by year of Fontan surgery and centre (p-value less than 0.0001 for each). The average age at Fontan was similar, 3.5 years in those with superior cavopulmonary connection versus 3.2 years in those without (p-value equals 0.4). The type of superior cavopulmonary connection varied by site (p-value less than 0.001) and was related to the type of Fontan procedure. Exercise performance, echocardiographic variables, and predominant rhythm did not differ by superior cavopulmonary connection status or among superior cavopulmonary connection types. Using a test of interaction, findings did not vary according to an underlying diagnosis of hypoplastic left heart syndrome. CONCLUSIONS: After controlling for subject and era factors, most long-term outcomes in subjects with a prior superior cavopulmonary connection did not differ substantially from those without this procedure. The type of superior cavopulmonary connection varied significantly by centre, but late outcomes were similar.

Assessment of COVID-19 outbreaks in long-term care facilities.

BACKGROUND: The B.1.167.2 (Delta) variant quickly became the predominant circulating SARS-CoV-2 strain in the USA during summer 2021. Missouri identified a high number of outbreaks in long-term care facilities (LTCFs) across the state with low vaccination rates among LTCF staff members and poor adherence to mitigation measures within local communities. AIM: To describe COVID-19 outbreaks that occurred in Missouri LTCFs impacting staff and residents during the surge of the Delta variant. METHODS: Outbreaks of COVID-19 in 178 LTCFs were identified by the Missouri Department of Health and Senior Services. Case data from LTCFs with the highest burden of disease were analysed to assess disease transmission, vaccination status, and outcomes among residents and staff. Additional investigational measures included onsite visits to facilities with recent COVID-19 outbreaks in communities with substantial transmission to assess mitigation measures. FINDINGS: During April 22nd to July 29th, 2021, 159 COVID-19 cases among 72 staff members and 87 residents were identified in 10 LTCFs. More than 74.7% of resident cases were vaccinated compared to 23.6% of staff cases. Vaccinated residents had a lower proportion of hospitalizations and deaths reported compared to unvaccinated residents. Data analysis and contact-tracing efforts from a sample of the facilities suggest that staff members were likely a major factor in introducing SARS-CoV-2 virus into the facilities. Adherence to COVID-19 mitigation measures varied at the visited facilities. CONCLUSION: Data showed that vaccination rates varied between staff cases and resident cases in facilities with high-burden outbreaks. Differences were identified in mitigation practices in at least two facilities.

Laboratory measures of exercise capacity and ventricular characteristics and function are weakly associated with functional health status after Fontan procedure.

BACKGROUND: Patients after the Fontan procedure are at risk for suboptimal functional health status, and associations with laboratory measures are important for planning interventions and outcome measures for clinical trials. METHODS AND RESULTS: Parents completed the generic Child Health Questionnaire for 511 Fontan Cross-Sectional Study patients 6 to 18 years of age (61% male). Associations of Child Health Questionnaire Physical and Psychosocial Functioning Summary Scores (FSS) with standardized measurements from prospective exercise testing, echocardiography, magnetic resonance imaging, and measurement of brain natriuretic peptide were determined by regression analyses. For exercise variables for maximal effort patients only, the final model showed that higher Physical FSS was associated only with higher maximum work rate, accounting for 9% of variation in Physical FSS. For echocardiography, lower Tei index (particularly for patients with extracardiac lateral tunnel connections), lower indexed end-systolic volume, and the absence of atrioventricular valve regurgitation for patients having Fontan procedure at age <2 years were associated with higher Physical FSS, accounting for 14% of variation in Physical FSS. For magnetic resonance imaging, ratio of lower mass to end-diastolic volume and midquartiles of indexed end-systolic volume (nonlinear) were associated with higher Physical FSS, accounting for 11% of variation. Lower brain natriuretic peptide was significantly but weakly associated with higher Physical FSS (1% of variation). Significant associations for Psychosocial FSS with laboratory measures were fewer and weaker than for Physical FSS. CONCLUSIONS: In relatively healthy Fontan patients, laboratory measures account for a small proportion of the variation in functional health status and therefore may not be optimal surrogate end points for trials of therapeutic interventions.

Pathological response after chemoradiation for T3 rectal cancer.

OBJECTIVE: The aim of this study was to investigate the effect of preoperative chemoradiotherapy (CRT) on nodal disease in locally advanced rectal adenocarcinoma. METHOD: Thirty-two patients staged uT3N0 and 27 patients staged uT3N1 rectal adenocarcinoma who underwent pre-CRT staging using endoscopic ultrasound or rectal protocol CT were included. The median radiation dose was 50.4 Gy (range: 45-50.4 Gy) at 1.8 Gy per fraction and all patients received concurrent 5-FU or capecitabine-based chemotherapy. Low anterior resection or abdomino-perineal resection occurred at a median of 46 days (range: 27-112 days) after CRT. RESULTS: Eleven of 32 uT3N0 patients (34.4%) and 13 of 26 uT3N1 patients (50.0%) had ypN+ (P = 0.29). For patients with uT3N0, 10 of 20 (50.0%) with ypT2-3 and 1 of 12 (8.3%) with ypT0-1 were ypN+ (P = 0.02). For patients with uT3N1, 12 of 20 (60.0%) with ypT2-3 and 1 of 6 (16.7%) with ypT0-1 were ypN+ (P = 0.16). Overall, the ypN+ rate was 11.1% in the ypT0-yT1 group compared with 55.0% in the ypT2-yT3 group (P = 003). Among patients with uT3N0 disease, the ypN+ rate in patients who had surgery > 46 days vs 46 days vs 46 days vs

The impact of prenatal diagnosis of complex congenital heart disease on neonatal outcomes.

Prenatal diagnosis of congenital heart disease (CHD) is increasingly common. However, the current impact of prenatal diagnosis on neonatal outcomes is unclear. Between January 2004 and January 2008, a retrospective chart review of infants who underwent surgical repair of CHD before discharge at our institution was conducted. Obstetric and perioperative variables were recorded. Of 439 neonates, 294 (67%) were diagnosed prenatally (PREdx). Infants with PREdx had a lower mean birth weight (3.0 +/- 0.6 vs. 3.1 +/- 0.6 kg, p = 0.002) and gestational age (37.9 +/- 2.1 vs. 38.6 +/- 2.4 wk, p < 0.001) than those with postnatal diagnosis (POSTdx). Severe lesions were more likely to be PREdx: Neonates with single-ventricle (SV) physiology (n = 130 patients [31.2%]) had increased odds of PREdx (n = 113/130, odds ratio [OR] 4.7; 95% confidence interval [CI] 2.7-8.2, p < 0.001). PREdx was associated with decreased preoperative intubation (OR 0.62; 95% CI 0.42-0.95, p = 0.033), administration of antibiotics (OR 0.23; 95% CI 0.15-0.36, p < 0.001), cardiac catheterization (OR 0.54; 95% CI 0.34-0.85, p = 0.01), and emergency surgery (OR 0.18; 95% CI 0.06-0.5, p < 0.001) compared with POSTdx infants. There was no difference in APGAR scores, preoperative pH, day of life of surgery, operative complications, hospital length of stay, or overall mortality in the PREdx versus POSTdx groups, even when controlling for lesion severity. PREdx was not independently associated with neonatal mortality, despite having included more severe cardiac lesions. PREdx was significantly associated with decreased neonatal morbidity in terms of decreased use of preoperative ventilator, administration of antibiotics, cardiac catheterization, and emergency surgery.

Atherosclerosis in survivors of Kawasaki disease.

OBJECTIVES: To test the hypothesis that long-term survivors of low-risk Kawasaki disease (KD) have ongoing vascular inflammation and dysfunction and a higher risk of accelerated atherosclerosis than healthy control subjects. STUDY DESIGN: Twenty-eight patients with KD (7-20 years after acute illness) and 27 age-matched healthy control subjects were examined for medical and dietary history, serum markers of atherosclerotic risk and inflammation, carotid intimal-medial thickness (CIMT) with vascular ultrasound scanning and arterial stiffness with applanation tonometry. RESULTS: Patients and control subjects were similar in age, sex, body mass index, waist-to-hip ratio, blood pressure, cigarette smoking, family history, diet, high-density lipoprotein cholesterol level, lipoprotein (a) level, homocysteine level, glucose level, insulin level, CIMT, arterial stiffness, C-reactive protein level, and inflammatory cytokine level. Levels of total cholesterol and apolipoprotein B were significantly higher in patients with KD than in control subjects. CONCLUSIONS: There was no evidence of increased atherosclerosis. Small but significant differences in cholesterol and apolipoprotein B levels could suggest increased future risk for atherosclerosis and warrant further study.

Functional state following the Fontan procedure.

BACKGROUND: Despite improvements in outcomes after completion of the Fontan circulation, long-term functional state varies. We sought to identify pre- and postoperative characteristics associated with overall function. METHODS AND RESULTS: We analyzed data from 476 survivors with the Fontan circulation enrolled in the Pediatric Heart Network Fontan Cross-sectional Study. Mean age at creation of the Fontan circulation was 3.4 plus or minus 2.1 years, with a range from 0.7 to 17.5 years, and time since completion was 8.7 plus or minus 3.4 years, the range being from 1.1 to 17.3 years. We calculated a functional score for the survivors by averaging the percentile ranks of ventricular ejection fraction, maximal consumption of oxygen, the physical summary score for the Child Health Questionnaire, and a function of brain natriuretic peptide. The mean calculated score was 49.5 plus or minus 17.3, with a range from 3 to 87. After adjustment for time since completion of the circulation, we found that a lower score, and hence worse functional state, was associated with: right ventricular morphology (p less than 0.001), higher ventricular end-diastolic pressure (p equals 0.003) and lower saturations of oxygen (p equals 0.047) prior to completion of the Fontan circulation, lower income for the caregiver (p equals 0.003), and, in subjects without a prior superior cavopulmonary anastomosis, arrhythmias after completion of the circulation (p equals 0.003). The model explained almost one-fifth (18%) of the variation in the calculated scores. The score was not associated with surgical centre, sex, age, weight, fenestration, or the period of stay in hospital after completion of the Fontan circuit. A validation model, using 71 subjects randomly excluded from initial analysis, weakly correlated (R equals 0.17, p equals 0.16) with the score calculated from the dataset. CONCLUSIONS: Right ventricular morphology, higher ventricular end-diastolic pressure and lower saturations of oxygen prior to completion of the Fontan circuit, lower income for the provider of care, and arrhythmias after creation of the circuit, are all associated with a worse functional state. Unmeasured factors also influence outcomes.

Coronary artery involvement in children with Kawasaki disease: risk factors from analysis of serial normalized measurements.

BACKGROUND: Most studies of coronary artery involvement and associated risk factors in Kawasaki disease have used the Japanese Ministry of Health dichotomous criteria. Analysis of serial normalized artery measurements may reveal a broader continuous spectrum of involvement and different risk factors. METHODS AND RESULTS: Clinical, laboratory, and echocardiographic measurements obtained at baseline and 1 week and 5 weeks after presentation were examined in 190 Kawasaki disease patients as part of a clinical trial of primary therapy with pulse steroids in addition to standard intravenous immunoglobulin. Maximum coronary artery z score normalized to body surface area was significantly greater than normal at all time points, decreasing significantly over time from baseline. A maximal z score > or = 2.5 at any time was noted in 26% of patients. Japanese Ministry of Health dimensional criteria were met by 23% of patients. Significant independent factors associated with greater z score at any time included younger patient age, longer interval from disease onset to treatment with intravenous immunoglobulin, lower serum IgM level at baseline, and lower minimum serum albumin level. z scores of the proximal right coronary artery were higher than those in the left anterior descending branch. CONCLUSIONS: Analyses of serial normalized coronary artery measurements in optimally treated Kawasaki disease patients demonstrated that for most patients, measurements are greatest at baseline and subsequently diminish; baseline measurements appear to be good predictors of involvement during early follow-up. When a more precise assessment is used, risk factors for coronary artery involvement are similar to those defined with arbitrary dichotomous criteria.

Controversies in the management of anal high-grade squamous intraepithelial lesions.

Anal squamous dysplasia is recognized as a spectrum of disease that ranges from low-grade intraepithelial lesions (LSIL) to high-grade squamous intraepithelial lesions (HSIL) to invasive anal squamous cell carcinoma (SCC). Recent reports have shown a significant increase in both the incidence and prevalence of both HSIL and anal SCC, particularly in immunocompromised patients and in men who have sex with men. These lesions are associated with chronic infection with the human papillomavirus. The natural history is unknown, yet reports of untreated patients have shown progression rates of up to 50% in high risk patients. There are controversies as to the optimal management of patients with HSIL. However, there is evidence that screening of high-risk patients with anal cytology is useful in identifying those that require further evaluation. Examination of the anorectal region is enhanced with the use of high resolution anoscopy. Treatment modalities vary in terms of morbidity and success rates. Wide local excision is associated with significant morbidity. Newer therapies such as topical immunomodulation, photodynamic therapy and therapeutic vaccines have been proposed, but long-term follow-up is unavailable. High resolution anoscopy can be used in the office or in the operating room to direct therapy. Using a comprehensive approach of cytology and office-based and/or operating room procedures directed with high resolution anoscopy results in clearance of HSIL in up to 80% of patients, malignant progression in 1%, and less morbidity than wide local excision.

Frequency of development of aortic cuspal prolapse and aortic regurgitation in patients with subaortic ventricular septal defect diagnosed at <1 year of age.

The natural history of aortic cuspal prolapse and aortic regurgitation (AR), studied most commonly in subpulmonic ventricular septal defect (VSD), has not been well defined in isolated, unrepaired VSD diagnosed during infancy. This study aimed to define the incidence and progression of aortic cuspal prolapse and AR in patients with subaortic VSDs diagnosed at <1 year of age who had no aortic cuspal prolapse or AR at presentation and did not require surgery within the first year of life. Patients had yearly follow-up, and data regarding clinical course, physical examination, and echocardiography were obtained. Comparisons were made between patients who developed aortic cuspal prolapse and AR and those who did not. One hundred patients, with a mean age at VSD diagnosis of 0.1 +/- 0.5 years, followed for a mean of 7.1 +/- 10.1 years, were studied. Aortic cuspal prolapse developed in 14 patients (14%) at a mean age of 7.1 +/- 6 years (range 0.4 to 18.4). AR murmurs were heard in 6 patients (6%) at a mean age of 5.1 +/- 3.1 years, all of whom had aortic cuspal prolapse and underwent VSD closure and aortic valvuloplasty. In conclusion, aortic cuspal prolapse and clinical AR are not uncommon in patients with subaortic VSDs. Long-term follow-up of patients with subaortic VSDs should include the serial evaluation of aortic valve anatomy and function.

Spontaneous regression of left ventricular dilation in children with restrictive ventricular septal defects.

OBJECTIVES: To test the hypothesis that left ventricular (LV) dilation associated with pressure-restrictive ventricular septal defect (VSD) often remains stable or regresses spontaneously, calling into question the role of interventional management for such defects. STUDY DESIGN: We analyzed 96 serial echocardiograms from 33 unoperated patients with a moderate-to-large VSD with LV dilation (LV end-diastolic dimension [LVED] z score >2.0) at enrollment who were followed for more than 2 years. Records of 125 surgical patients also were reviewed. Patients were evaluated for evidence of persistent or progressive LV dilation; signs or symptoms of congestive heart failure (CHF), failure to thrive (FTT), or pulmonary hypertension (PAH); as well as acquired ventricular outflow obstruction or aortic regurgitation. LVED z scores at enrollment versus latest follow-up were compared using paired t tests. A random-effects model with random intercept and slope was fitted to account for repeated observations for each patient. RESULTS: Mean age at enrollment was 4.6 +/- 3.2 years, and mean follow-up was 7.8 +/- 4 years (range, 2.8 to 22 years), during which mean LVED z score decreased from 3.0 +/- 0.6 to 1.2 +/- 1.3 (P < .01). LVED z score decreased in 29 of the 33 patients, and decreased to <2 in 26 of these 29 (79%). CONCLUSIONS: Most patients with pressure-restrictive VSD with moderate-to-severe LV dilation without CHF, FTT, or PAH will experience spontaneous resolution of LV dilation and can avoid cardiac surgery or catheter-based intervention.

Beta-blocker therapy does not alter the rate of aortic root dilation in pediatric patients with Marfan syndrome.

OBJECTIVE: To test the hypothesis that chronic beta-blocker therapy in pediatric patients with Marfan syndrome alters the rate of aortic root dilation. Beta-blockade has been advocated as preventive therapy for Marfan syndrome based on reports indicating a decreased rate of aortic root dilation in treated patients. STUDY DESIGN: Patients with Marfan syndrome (n = 63) followed at Children's Hospital of Pittsburgh or Children's Hospital of New York-Presbyterian who had > or =18 months of echocardiographic follow-up were studied. All clinical data and 213 serial echocardiograms were reviewed, and aortic root dimensions were measured. Patients were divided into 2 groups for comparison: untreated (n = 34) and treated (n = 29). RESULTS: At study entry, the 2 study groups were comparable in terms of age, sex, body surface area (BSA), aortic root measurements, heart rate, and corresponding z scores. Follow-up duration in each group was similar. At last follow-up, heart rates and heart rate z scores were lower in the treated group. Rates of change of aortic root measurements (P = .52) and the corresponding z scores were not statistically different between the 2 group at the study's end. CONCLUSIONS: This study suggests that that beta-blocker therapy does not significantly alter the rate of aortic root dilation in children with Marfan syndrome. Based on these data, the recommendation of lifetime beta-blocker therapy instituted during childhood should be reassessed.

Ross procedure in infants and toddlers followed into childhood.

BACKGROUND: The Ross procedure is commonly used to treat aortic valve disease in pediatric and adult patients. For infants, data are limited regarding survival, reintervention, autograft growth, and function. METHODS AND RESULTS: The Ross procedure was performed in 27 infants <18 months of age (median age 5.7 months). All patients had congenital aortic stenosis (AS); associated lesions included subAS (n=9), supravalvular AS (n=2), coarctation (n=5), and interrupted aortic arch (n=2). Median follow-up was 6.1 years (range 0.2 to 12.9). There were 3 early deaths and no late deaths. Freedom from reintervention for homograft dysfunction was 87% at 8 years; freedom from autograft reintervention was 100%. Follow-up echocardiograms were available in 17 patients. Estimated peak autograft gradient was 55 mm Hg in one patient and <10 mm Hg in 16. Mild autograft insufficiency was seen in 4 patients; 13 had none. Autograft diameter was measured early postoperatively and at latest follow-up. The mean z score increased from 0.63 to 3.2 (P<0.01) at the annulus and from 0.26 to 2.2 (P<0.01) at the sinus. In a subgroup, the mean autograft z score increased significantly from the postoperative period to 1 year for both the annulus (0.72 to 3.2, P<0.01) and the sinus (0.26 to 2.2, P<0.01), but remained unchanged thereafter. CONCLUSIONS: The Ross procedure effectively relieves AS in infants. Homograft reintervention occurred in 13% within 8 years. No patient developed significant autograft insufficiency or required autograft reintervention during the follow-up period. Dilatation of the autograft occurred during the first year after surgery and stabilized thereafter.

Anomalous right coronary artery arising from the pulmonary artery: a report of 7 cases and a review of the literature.

OBJECTIVE: To determine the experience with anomalous right coronary artery arising from the pulmonary artery (ARCAPA) at our institution. BACKGROUND: Anomalous right coronary artery from the pulmonary artery is a rare congenital defect affecting 0.002% of the population. Unlike anomalous left coronary artery from the pulmonary artery (ALCAPA), ARCAPA generally has not been considered to be a lethal defect in infancy or childhood, although case reports of sudden death exist. The natural history of ARCAPA is difficult to describe because of the relatively small number of cases reported. Medical knowledge of this defect has been collected from case reports alone. No pediatric series of ARCAPA has been published. METHODS: Hospital databases were retrospectively searched for cases of ARCAPA diagnosed at the New York Presbyterian Hospital over the past 25 years. A comprehensive literature search for case reports of ARCAPA was performed. RESULTS: Seven pediatric cases are described. The cases range in clinical presentation from a young infant with tetralogy of Fallot to an adolescent with chest pain on exertion. Only 1 patient came to medical attention because of chest pain; 6 patients were asymptomatic. In these 6, ARCAPA was diagnosed upon evaluation of either a murmur (3) or associated congenital heart disease (3). All 7 patients have undergone repair. One patient died after repair of complex tetralogy of Fallot/pulmonary atresia. One patient developed a thrombus in the dilated right coronary artery years after repair. The thrombus resolved with anticoagulation. CONCLUSIONS: Anomalous right coronary artery from the pulmonary artery is an uncommon coronary anomaly that, unlike ALCAPA, rarely leads to sudden death. Surgical correction is low risk and should be considered for all patients.

Pulmonary position cryopreserved homografts: durability in pediatric Ross and non-Ross patients.

OBJECTIVE: The purpose of this study was to evaluate the outcome and risk factors for implant failure in pediatric patients who underwent pulmonary position homograft placement for right ventricular outflow tract obstruction compared with conduit placement as a component of the Ross operation. Actuarial 5-year survivals for cryopreserved right ventricle-to-pulmonary artery homografts range from 55% to 94% at all ages. It is not known whether there is a difference in homograft durability when utilized for right ventricular outflow tract obstruction or as part of the Ross operation. METHODS: The records of all pediatric patients receiving a right ventricle-to-pulmonary artery homograft from July 1989 through October 2003 were reviewed. Ninety-eight consecutive patients were studied (26 Ross, 72 non-Ross). In addition to Ross versus non-Ross comparisons, other potential risk factors for homograft failure analyzed included age at operation, follow-up time, type of surgery, and homograft type and size. RESULTS: Ross and non-Ross patients were comparable in age at the time of the operation and follow-up time. Homograft failure rates were 12% and 51% for Ross and non-Ross patients, respectively. Freedom from reintervention was 93% in the Ross and 66% in the non-Ross group at 5 years (P = .019). On multivariate analysis, non-Ross operation and age less than 2 years were significant predictors of homograft failure. CONCLUSIONS: 1. Pediatric patients undergoing the Ross operation have longer homograft survival than pediatric patients treated for right ventricular outflow tract obstruction, independent of age. 2. Homografts placed in patients less than 2 years of age have shorter homograft survival.

The significance of pretreatment CD4 count on the outcome and treatment tolerance of HIV-positive patients with anal cancer.

PURPOSE: To assess the outcome and tolerance of HIV-positive patients with anal cancer to standard therapy based on their pretreatment CD4 count. METHODS AND MATERIALS: Between 1991 and 1997, 17 HIV-positive patients with anal cancer and documented pretreatment CD4 counts were treated at the University of California, San Francisco or its affiliated hospitals with either concurrent chemotherapy and radiation or radiation alone. The outcome and complications of treatment were correlated with the patients' pretreatment CD4 count. RESULTS: Disease for all 9 patients with pretreatment CD4 counts > or = 200 was controlled with chemoradiation. Although four required a treatment break of 2 weeks because of toxicity, none required hospitalization. Of the 8 patients with pretreatment CD4 counts < 200, 4 experienced decreased counts, intractable diarrhea, or moist desquamation requiring hospitalization. Additionally, 4 of these 8 ultimately required a colostomy either for a therapy-related complication or for salvage. Nevertheless, 6/7 in this group who received concurrent chemotherapy and radiation had their disease controlled, whereas the patient treated with radiation alone failed and required a colostomy for salvage. CONCLUSION: Patients with CD4 > or = 200 had excellent disease control with acceptable morbidity. Patients with CD4 < 200 had markedly increased morbidity; however, disease was ultimately controlled in 7/8 patients.

Vasoactive intestinal polypeptide receptor binding sites in the human gastrointestinal tract: localization by autoradiography.

Vasoactive intestinal polypeptide (VIP) is a putative neurotransmitter in both the brain and peripheral tissues. To define possible target tissues of VIP we have used quantitative receptor autoradiography to localize and quantify the distribution of [125I]VIP receptor binding sites in histologically normal human surgical specimens. While the distribution of VIP binding sites was different for each gastrointestinal segment examined, specific vasoactive intestinal polypeptide binding sites were localized to the mucosa, the muscularis mucosa, the smooth muscle of submucosal arterioles, the circular and longitudinal smooth muscle of the muscularis externa, the myenteric plexus, and lymph nodules. In most segments, the mucosal layer expressed the highest concentration of VIP binding sites, with the duodenal and jejunal mucosa showing the highest density of receptors. These results identify putative VIP target tissues in the human gastrointestinal tract. In correlation with physiological data, VIP binding sites appear to be involved in the regulation of a variety of gastrointestinal functions including mucosal ion transport, gastric secretion, hemodynamic regulation, gastric and intestinal motility, neuronal excitability, and modulation of the immune system.

Outcome of idiopathic restrictive cardiomyopathy in children.

Eighteen children with idiopathic restrictive cardiomyopathy (IRC) were studied in an attempt to identify potential predictors of poor outcome. Four patients presented with low cardiac output (CO) syndrome. Fourteen remaining patients were minimally symptomatic at presentation but developed a low CO syndrome at a mean of 2.8 +/- 2.3 years after diagnosis. At the time of development of low CO in the 18 patients, mean left ventricular end-diastolic pressure was 27 mm Hg, right ventricular end-diastolic pressure was 18 mm Hg, cardiac index was 2.5 L/min/m(2), and pulmonary vascular resistance index (PVRI) was 8.8 U-m(2). Eleven of the 18 patients underwent cardiac transplantation. One died perioperatively from donor right-sided cardiac failure and 10 survived. Six were not transplanted and died, including 3 in whom transplantation was precluded secondary to extremely elevated PVRI. One patient is alive with right-sided cardiac failure. Ten of our 18 patients had pulmonary hypertension (PVRI >6 U-m(2)) at the time of referral for cardiac transplant and/or development of low CO syndrome. In comparison, children with dilated cardiomyopathy who were referred for heart transplant during the same time period had a PVRI that was significantly lower (5.2 U-m(2)). Elevated PVRI was associated with death (p <0.01) and 40% of our children with pulmonary hypertension were precluded from receiving an orthotopic heart transplant because their pulmonary hypertension was so severe. No risk factors for the development of pulmonary hypertension were identified; therefore, all children with IRC should undergo serial monitoring of their PVRI, and any increase should prompt a transplant evaluation.