Genetic stability of sexing strains based on the locus sw of Ceratitis capitata.

This report deals with the process of improving the stability of medfly, Ceratitis capitata, genetic sexing strains (GSS) based on the sw mutation on chromosome 2. This gene affects the rate of development as well as the eye colour and iridescence. The improved sexing strains were produced by mapping sw with deletions and then inducing and screening for new translocations with breakpoints close to the marker. The stability was assessed in large populations over many generations. Twenty-two new Y-2 translocations were identified and polytene chromosome analysis was performed to locate breakpoints. The translocation strains were ranked according to the distance of their breakpoints from sw. The map position of sw is region 20D on 2R. As data on the stability of the 22 strains accumulated, Cast 191 was shown to be the most promising as no recombination between sw and the male sex was found. After rearing the strain for 22 generations under semi-mass rearing conditions, with a population size of 15,000 adults and scoring 1000 flies per generation, only one such event was detected (estimated frequency = 3.1 x 10(-6)). Further tests are being carried out with this strain to assess its suitability as a genetic sexing strain for medfly Sterile insect technique (SIT).

Novel use of an established agent: Topotecan is anti-angiogenic in experimental Wilms tumor.

BACKGROUND/PURPOSE: Antiangiogenic agents offer a new approach to the treatment of aggressive neoplasms, yet very few agents are available for current use. The authors have shown previously the efficacy of antiangiogenic therapy in experimental Wilms tumor, using an investigative antibody. They hypothesized that topotecan, administered in a regimen targeting endothelial cells, would suppress tumor growth and angiogenesis in experimental Wilms tumor. METHODS: Experimental tumors were induced in the left kidneys of athymic mice by injection of cultured Wilms tumor cells. Topotecan (0.36, 0.6, 1.0, 2.0, and 3.0 mg/kg) or vehicle was injected intraperitoneally in 2 cycles over a 6-week period. Fluorescein angiograms and platelet endothelial cell adhesion molecule-1 staining of primary tumors were performed to ascertain vascular architecture. Endothelial apoptosis was assessed by TdT-mediated dUTP nick end labeling assay. RESULTS: Tumor weights were reduced significantly in treated versus control animals, even in the lowest-dose group. Endothelial cell staining and angiography results showed relatively sparse vascularity in treated xenografts. Endothelial apoptosis was observed in treated but not control tumors. CONCLUSIONS: Topotecan, delivered in an "antiangiogenic" regimen, even at very low doses, significantly inhibited growth of experimental Wilms tumors. No adverse effects were noted at low doses. Thus, the established chemotherapy agent topotecan may be useful in a novel role: as antiangiogenic therapy. J Pediatr Surg 36:1781-1784.

Congenital abdominal aortic aneurysm causing renovascular hypertension, cardiomyopathy, and death in a 19-day-old neonate.

A full-term baby girl who was sent home day of life 2 was admitted to the hospital on day of life 7 for respiratory distress and poor feeding. The child was found to be hypertensive and in heart failure. Further workup led to the diagnosis of a suprarenal abdominal aortic aneurysm, but the infant had deteriorated clinically with heart failure, modest renal failure, renovascular hypertension, and no operative cure. The child died on day of life 20. Early diagnosis and prompt surgical resection are essential to managing this rare and lethal condition.

Combination antiangiogenic therapy: increased efficacy in a murine model of Wilms tumor.

BACKGROUND/PURPOSE: Antibody to vascular endothelial growth factor (anti-VEGF) suppresses tumor growth and metastasis in experimental Wilms tumor. However, tumor growth accelerates if antibody is withdrawn. As recently shown, low-dose, frequently administered topotecan, a topoisomerase-1 inhibitor, has anti-angiogenic activity. The authors hypothesized that combined topotecan/anti-VEGF therapy would suppress tumor growth and metastasis more durably than either agent alone. METHODS: Xenografts were induced by intrarenal injection of human Wilms tumor cells in athymic mice (n = 59). Mice were divided into control (n = 10), anti-VEGF (n = 16), topotecan (n = 17), and topotecan plus anti-VEGF (n = 16) groups. All control and half the treated mice were killed at week 6. Remaining ("rebound") mice were maintained without treatment until week 8. Tumor vasculature was mapped by fluorescein angiography/PECAM immunostaining. Endothelial apoptosis was assessed by TUNEL assay. RESULTS: 6 weeks: Tumor weights were reduced significantly in treated mice (P <.003 v control). Seven of ten control and 1 of 25 treated mice displayed lung metastases (P <.003). Rebound tumors were largest in topotecan-only, intermediate in antibody-treated, and smallest in combination-treated mice. Immunostaining and angiography results showed sparse vascularity in treated xenografts. Endothelial apoptosis was observed only in treated tumors. CONCLUSION: Combination low-dose topotecan and anti-VEGF antibody therapy is antiangiogenic and suppresses tumor growth and metastasis in experimental Wilms tumor more durably than either agent alone.

All angiogenesis is not the same: Distinct patterns of response to antiangiogenic therapy in experimental neuroblastoma and Wilms tumor.

BACKGROUND/PURPOSE: Neuroblastoma and Wilms tumor exhibit different patterns of metastasis, invasion, and therapeutic response. Vascular endothelial growth factor (VEGF) is an angiogenic factor expressed in both tumors. The authors hypothesized that because the clinical behavior of these tumors differs, the response to anti-VEGF therapy would be distinct, and tumor vascular architectures would reflect this distinction. METHODS: Xenografts were induced by intrarenal injection of cultured cells in athymic mice. After 1 week, anti-VEGF antibody or vehicle were administered for 5 weeks before sacrifice. Additional animals were maintained for 3 weeks after termination of antibody injections to assess rebound growth of tumors. Fluorescein angiography was performed in selected animals. RESULTS: Neuroblastoma control and treated tumor weights were not significantly different (1.48 g v 0.77 g, P =.34). By comparison, as previously reported, antibody-treated Wilms tumors were growth inhibited. Angiograms of treated (but not control) neuroblastomas displayed novel rounded structures at vessel branches, which the authors term terminal vascular bodies (TVBs). Wilms tumor vessels displayed no such alteration. CONCLUSIONS: Neuroblastoma xenografts are less effectively suppressed by anti-VEGF antibody than Wilms tumors. Neuroblastoma vascular architecture displays a novel alteration during antibody administration, which attenuates when antibody is withdrawn. These studies suggest that angiogenesis is differently regulated in experimental neuroblastoma and Wilms tumor.

Highly specific antiangiogenic therapy is effective in suppressing growth of experimental Wilms tumors.

BACKGROUND/PURPOSE: Pathologic angiogenesis in tumors is a potential target for novel therapies. Vascular endothelial growth factor (VEGF) is an angiogenic promoter present in a wide variety of human tumors. VEGF is expressed as 4 isoforms; one of these, VEGF165, predominates in human tumors. The authors hypothesized that antagonism of VEGF165 by a specific aptamer would block tumor growth in an experimental model of Wilms tumor. METHODS: VEGF isoform expression in clinical (n = 2) and experimental tumors were evaluated by reverse transcription polymerase chain reaction (RT-PCR). Tumors were induced in NCR nude mice (n = 32) by intrarenal injection of 10(6) cultured Wilms tumor cells. At 1 week, aptamer (n = 16) or vehicle (n = 16) treatment was started and continued daily for 5 weeks. RESULTS: At 6 weeks tumors weighed 84% less in treated versus control animals (0.69 v 4.41 g; P <.028), without observed adverse effects and similar to suppression previously reported using nonisoform-specific anti-VEGF antibody (94% to 96%). CONCLUSIONS: Anti-VEGF165 aptamer effectively suppressed primary tumor growth in experimental animals with no observed adverse effects. Development of highly specific antiangiogenic therapies may be of particular benefit to pediatric patients.

The effect of cisplatin dose and surgical resection in children with malignant germ cell tumors at the sacrococcygeal region: a pediatric intergroup trial (POG 9049/CCG 8882).

PURPOSE: This study was designed to evaluate (1) the efficacy of standard or high-dose cisplatin with etoposide and bleomycin and (2) the role of surgical resection in infants and children with malignant germ cell tumors of the sacrococcygeal region (SCT). METHODS: Seventy-four of 317 children presenting to Pediatric Oncology Group (POG)/Children's Cancer Group (CCG) institutions from 1990 through 1996 with malignant germ cell tumors had malignant SCT. There were 62 girls and 12 boys with a median age of 21 months (range, 3 days to 37 months) and median serum alpha-fetoprotein of 35,500 ng/mL. Twelve had undergone resection of a benign SCT as a newborn. Forty-four (59%) had evidence of metastatic disease at time of diagnosis. Presentation by type (Altman classification) was I, 0; II, 2; III, 30; and IV, 42. The initial procedure was biopsy in 45 and resection in 29. Patients were assigned randomly to receive 4 cycles of chemotherapy with etoposide (E) and bleomycin (B) and either high-dose cisplatin (200 mg/m(2) per cycle; HDP) or standard dose cisplatin (100 mg/m(2) per cycle; P). After completion of chemotherapy, 42 of 45 initially treated with biopsy underwent resection. RESULTS: Overall 4-year survival rate is 90% (SE = 4%) and 4-year event-free survival (EFS) is 84% (SE = 6%). Event-free survival data for subgroups of interest are as follows: 4-yr EFS% (SE) P Values Mets (44) 88 (6).48 No Mets (30) 80 (8) HDP EB (37) 89 (6).21 P EB (37) 78 (7) Initial Resection (29) 90 (7).50 Delayed Resection (42) 83 (7) Complete Resection (49) 90 (5).19 CR/PR Partial Resection (22) 77 (10) Biopsy Only (3) 33 (27).005 (3 way) CONCLUSIONS: (1) The current survival rate of malignant sacrococcygeal tumors is excellent even with metastases. (2) Delayed surgical resection is not associated with an adverse outcome. (3) In this subset the treatment comparison was inconclusive however, followed the trend in the overall study of more than 300 children in which the high-dose cisplatin group had superior EFS (P<.05).

Suppression of primary tumor growth in a mouse model of human neuroblastoma.

BACKGROUND/PURPOSE: Neuroblastoma is the most common tumor of the abdomen in children. Consistently effective treatments are lacking for aggressive disease. The authors previously reported that therapy with anti-vascular endothelial growth factor (VEGF) antibodies suppresses both growth and metastasis in an experimental model of Wilms' tumor. The authors hypothesized that, in a parallel model of neuroblastoma, anti-VEGF treatment would inhibit (1) growth and (2) metastasis. METHODS: Primary tumors were established in the kidneys of nude mice. In cohort 1 (n = 42), mice were killed at 3 time-points, and tissues were evaluated histologically. Tumors were assayed for VEGF. In cohort 2 (n = 28), anti-VEGF antibody or vehicle was administered. Tumor weights and the incidence of metastases in the 2 groups were compared. VEGF deposition was evaluated by immunohistochemistry. RESULTS: Mice displayed large tumors with liver and lung metastases. VEGF levels in tumors increased over time. Antibody-treated animals displayed significantly smaller tumors, but incidence and size of metastases were unaffected. VEGF was localized to tumor stroma immunohistochemically, with no difference in pattern observed in control and antibody-treated tumors. CONCLUSIONS: Anti-VEGF antibodies inhibit primary tumor growth in experimental neuroblastoma, but not metastasis. This may contrast with the effect of the same antibody in a parallel model of Wilms' tumor.

Anti-VEGF antibody suppresses primary tumor growth and metastasis in an experimental model of Wilms' tumor.

BACKGROUND/PURPOSE: Vascular endothelial growth factor (VEGF) has been shown previously to correlate with tumor growth and metastasis in an experimental model of anaplastic Wilms' tumor. The authors hypothesized that treatment with anti-VEGF antibodies would suppress both primary tumor growth and metastasis in this model. METHODS: Tumors were induced in the right kidneys of nude mice by the injection of cultured Wilms' tumor cells. After 1 week, anti-VEGF treatment was begun with injection of either vehicle or an anti-VEGF antibody intraperitoneally. Mice were killed after 4.5 weeks of treatment and tumor weights and the incidence of metastases evaluated. RESULTS: Anti-VEGF treatment resulted in a greater than 95% reduction in tumor weight (P < .0001). Anti-VEGF treatment also abolished the establishment of lung metastases (40% in control animals, P < .003). Cessation of treatment resulted in rebound tumor growth. CONCLUSION: Anti-VEGF therapy can suppress both primary tumor growth and the establishment of metastases in experimental anaplastic Wilms' tumor.

ECMO in the newborn.

Since the first use in neonates in 1974, extracorporeal membrane oxygenation (ECMO) has been a life-saving technology for newborns with respiratory and cardiac failure. ECMO has been used to treat a variety of cardio-respiratory problems, including meconium aspiration syndrome (MAS), persistent pulmonary hypertension of the neonate (PPHN), congenital diaphragmatic hernia (CDH), sepsis, and cardiac anomalies. For this group of high-mortality neonates, ECMO has produced a survival of 76% in all newborns treated. This review article will examine the current selection criteria for ECMO, the clinical management of neonates on ECMO and discuss the long-term outcome of neonates treated with ECMO.

Complete surgical excision is effective treatment for children with immature teratomas with or without malignant elements: A Pediatric Oncology Group/Children's Cancer Group Intergroup Study.

PURPOSE: To determine whether the 3-year event-free survival (EFS) of children with completely resected immature teratomas is greater than 85%. PATIENTS AND METHODS: Patients with immature teratomas treated at Pediatric Oncology Group or Children's Cancer Group institutions were eligible. Pathology was centrally reviewed to confirm diagnosis and tumor grading. Follow-up included physical examination, measurement of tumor markers (alpha fetoprotein and human chorionic gonadotropin), and imaging. All patients were monitored for events, defined as tumor recurrence, second malignancy, or death. RESULTS: Seventy-three children (median age, 7.8 years) with extracranial immature teratomas were enrolled on study. Primary tumor sites included ovarian (n = 44), testicular (n = 7), and extragonadal (n = 22). However, on review, 23 patients had foci of yolk sac tumor (n = 21) or primitive neuroectodermal tumor (n = 2), whereas 50 had pure immature teratomas. Twenty-five patients had increased alpha fetoprotein (n = 18), human chorionic gonadotropin (n = 5), or both (n = 2); nine had foci of yolk sac tumor on review. Pathology review identified 23 patients with grade 1, 29 with grade 2, and 21 with grade 3 immature teratomas. With a median follow-up of 35 months, the overall 3-year EFS was 93% (95% confidence interval, 86% to 98%), with 3-year EFS of 97.8%, 100%, and 80% for patients with ovarian, testicular, and extragonadal tumors, respectively. Only four of 23 patients with immature teratoma and malignant foci developed recurrence, suggesting that surgical resection followed by close observation are effective treatment. Overall, five patients had disease recurrence 4 to 7 months from diagnosis, and four (80%) are disease free after platinum-based therapy. The fifth patient has residual tumor after cisplatin, etoposide, and bleomycin treatment requiring further therapy. CONCLUSION: Surgical excision is safe and effective treatment for 80% to 100% of children with immature teratoma.

Pathological angiogenesis in a murine model of human Wilms' tumor.

BACKGROUND/PURPOSE: Pathological vascular architecture is a feature of neoangiogenic processes such as diseases of the retina and tumor growth. The authors hypothesized that experimental human Wilms' tumors would display a vascular architecture similar to retinal diseases that are driven by vascular endothelial growth factor (VEGF). METHODS: Human Wilms' tumors were established in the right kidneys of nude mice. After 4.5 weeks of tumor growth, fluorescein angiograms were performed before death. Representative sections of tumors and contralateral, control kidneys were evaluated by fluorescent microscopy. RESULTS: Fluorescein angiograms demonstrated a characteristic pathological architecture. Vascular tortuosity, capillary tufting, and hemorrhage were noted. These features were not present in normal kidneys. CONCLUSIONS: Vascular architecture of Wilms' tumor displays the specific features previously described in diseases of the retina, which have been shown to be driven by VEGF, suggesting that neoangiogenesis in this model is also VEGF driven.

Metastasis correlates with production of vascular endothelial growth factor in a murine model of human Wilms' tumor.

BACKGROUND/PURPOSE: The growth and spread of solid tumors are critically dependent on the induction of angiogenesis. We hypothesized that vascular endothelial growth factor (VEGF) would be detected in Wilms' tumors, and that both growth and metastasis would parallel VEGF levels in a murine model. METHODS: Primary tumors were established in the right kidneys of nude mice (n = 21). Mice were killed at 3, 4.5, or 6 weeks. Tumor-bearing and control kidneys were subjected to enzyme-linked immunosorbent assay (ELISA) for VEGF. Representative sections were assessed by histology and immunohistochemistry. Lungs were examined for metastases. Clinical specimens of Wilms' tumor (n = 12) also were assayed for VEGF. RESULTS: The authors detected VEGF by ELISA with increasing frequency, and in increasing quantity, as experimental Wilms' tumors were grown over time. Immunohistochemistry demonstrated accumulation of VEGF in areas of viable tumor. Lung metastases occurred in 8 of 10 animals with VEGF-positive tumors, but in only 3 of 11 animals with VEGF-negative tumors, an association that was statistically significant. VEGF was found in 10 of 12 clinical Wilms' tumor specimens tested. CONCLUSIONS: VEGF is present in both clinical and experimental Wilms' tumors. In a murine model, absolute VEGF levels increase as primary tumors grow, and VEGF production is significantly associated with tumor metastasis.

Immature teratomas in children: pathologic considerations: a report from the combined Pediatric Oncology Group/Children's Cancer Group.

Pediatric germ cell tumors (n = 135) with a major component of immature teratoma (IT) registered on Pediatric Oncology Group/Children's Cancer Group treatment protocols from 1990 to 1995 were reviewed. Sixty cases were pure IT with no malignant component and 75 were mixed tumors with a major component of IT. Foci of yolk sac tumor (YST) were present in all 75 mixed tumors; additional malignant components were present in 15. The IT component was as follows: 47% grade 3, 29% grade 2, 24% grade 1. There were no significant correlations between tumor grade and patient age by specific subsets or overall (all p > 0.10). Significant correlations were detected between stage and the presence of foci of YST (p = 0.0145) and grade and the presence of foci of YST (p < 0.001). Serum alpha-fetoprotein concentrations were elevated at diagnosis in 96% of ovarian tumors with foci of YST and were mildly elevated (< 60 ng/dL) in only 16% of tumors without YST. Overall 2- to 6-year survival rate was 96% and was related to the presence of YST. Central pathologic review revealed aspects of morphologic diagnosis that were most frequently misinterpreted by contributing pathologists. These included the classification of differentiating tissues as immature and the failure to recognize two well-differentiated patterns of YST (the hepatoid pattern resembling fetal liver and the well-differentiated glandular pattern resembling fetal lung or intestine). Such foci were often overlooked. The authors conclude that the presence of microscopic foci of YST, rather than the grade of IT, per se, is the only valid predictor of recurrence in pediatric IT at any site.

Pressure- versus volume-cycled ventilation in liquid-ventilated neonatal piglet lungs.

BACKGROUND/PURPOSE: If the goal of partial liquid ventilation (PLV) with perfluorocarbons in the management of respiratory failure is to improve dynamic lung compliance (Cdyn) and pulmonary vascular resistance (PVR) while sustaining O2 delivery, the optimal ventilatory management is unclear. The authors asked if volume-cycled or pressure-limited ventilation had different effects on PVR, cardiac index (CI), and Cdyn in uninjured and injured neonatal piglet lungs. METHODS: Anesthetized piglets (6 to 8 kg) were ventilated after tracheostomy. Cdyn was measured by in-line Fleisch pneumotach/PC data acquisition terminal. Thermodilution instrumentation allowed determination of both CI and PVR. Volume-control or pressure-limited ventilation was established in uninjured or injured (surfactant deficiency induced by saline lavage at 18 mL/kg) animals. After a stable 30-minute baseline, animals were assigned randomly to one of four groups: group I (n = 9), uninjured animals plus volume-cycled ventilation (intermittent mandatory ventilation [IMV], 10 bpm; tidal volume [TV], 15 mL/kg, positive end-expiratory pressure [PEEP], 5 cm H2O; FIO2, 1.0; and PLV for 150 minutes); group II (n = 9), uninjured animals plus pressure-limited ventilation (IMV, 10 bpm; peak inspiratory pressure (PIP), 25 cm H2O, PEEP, 5 cm H2O, FIO2, 1.0; and PLV for 150 minutes); group III (n = 7), injured animals plus volume-cycled ventilation (IMV, 10 bpm; TV, 15 mL/kg; PEEP, 5 cm H2O; FIO2, 1.0 for 30 minutes, followed by saline injury for group IV (n = 7), injured animals plus pressure-limited ventilation (IMV, 10 bpm; PIP, 25 cm H2O; PEEP, 5 cm H2O; FIO2, 1.0 for 30 minutes, followed by saline injury, and PLV rescue). Comparison within and between groups was accomplished by repeated measures analysis of variance (ANOVA) with Tukey correction. RESULTS: There was no significant difference between volume-cycled or pressure-limited ventilation in healthy lungs; however, in the setting of lung injury, dynamic compliance was 1.44 +/- 0.15 after 180 minutes in the volume-cycled group and 0.91 +/- 0.10 in the pressure-limited group after the same interval (mL/cm H2O x kg +/- SEM). Similarly, PVR was 100 +/- 6 in the volume-cycled group and 145 +/- 12 in the pressure-limited group after 180 minutes of lung injury (mm Hg/L/kg x min +/- SEM). Cardiac index declined significantly in all groups independent of ventilatory mode. CONCLUSIONS: These results suggest that in the setting of lung injury, Cdyn and PVR improved significantly when volume-cycled, compared with pressure-limited ventilation was used. Although no difference existed between ventilatory modes in healthy lungs, pressure-limited ventilation, when combined with PLV in injured lungs, had adverse effects on lung compliance and pulmonary vascular resistance. Volume-cycled ventilation may optimize the ability of perfluorocarbon to recruit collapsed or atelectatic lung regions.

Congenital diaphragmatic hernia survival and use of extracorporeal life support at selected level III nurseries with multimodality support.

BACKGROUND: Congenital diaphragmatic hernia (CDH) has been cited to have a mortality rate of 50%. There have been multiple studies at individual institutions demonstrating potential benefits from various strategies including extracorporeal life support (ECLS), delayed repair, and lower levels of ventilator support. There has been no multicenter survey of institutions offering these modalities to describe the current use of ECLS and survival of these infants. In addition, the relationship between the number of patients with CDH managed at an individual institution and outcome has not been evaluated. METHODS: We queried 16 level III neonatal intensive care centers on the use of ECLS and survival of infants with CDH who were treated during 2 consecutive years (1993 to 1995). Data are presented as mean +/- SEM, median, and range. RESULTS: Data were collected on 411 patients. Of these, 71% +/- 8% were outborn and 8% +/- 3% were considered nonviable. Overall survival of CDH infants was 69% +/- 4% (range, 39% to 95%). The survival rate of infants on ECLS was 55% +/- 4%, whereas survival of infants not requiring ECLS was significantly increased at 81% +/- 5% (p = 0.005). The mean rate of ECLS use was 46% +/- 2%. There was no correlation between the number of cases per year at an individual institution and overall survival, ECLS survival, or ECLS use (r = 0.341, 0.305, and 0.287, respectively). There was also no correlation between case volume at an individual institution and ECLS survival (r = 0.271). CONCLUSIONS: The current survival rate and rate of ECLS use in infants with CDH at level III neonatal intensive care units in the United States are 69% +/- 4% and 46% +/- 2%, respectively. There is no correlation between the yearly individual center experience with managing CDH and rate of ECLS use or outcome.

Evaluation and management of pediatric solid ovarian tumors.

Solid ovarian tumors are uncommon in the pediatric population, but when they occur, they are a major source of anxiety for the patient and her family. The pediatric surgeon will be relied on to diagnose these tumors because they usually present as abdominal pain with a mass. The diagnostic evaluation consists of a carefully obtained history and physical examination, ultrasound examination, serum assay for tumor markers, and further radiographic evaluation as indicated. Two thirds of malignant tumors in children are germ cell tumors, and most of these are dysgerminomas or endodermal sinus tumors. A multimodal, team-oriented approach to therapy is crucial. Reproductive organ-sparing surgery with salpingo-oophorectomy, ascites sampling, nodule biopsy, omentectomy, and contralateral ovarian biopsy as indicated, may be curative for stage I tumors; more advanced or highly aggressive tumors should be treated with cytoreduction surgery and will require platinum-based chemotherapy. Postinduction surgery is indicated for progressive or recurrent disease. One third of tumors are physiologically active stromal tumors that often become apparent because of hormonal effects. Epithelial tumors, common in the adult, are uncommon in children and are of mild to moderate malignant potential. Other miscellaneous tumors and benign lesions are less common.

Changes in pulmonary vascular resistance in response to partial liquid ventilation.

BACKGROUND/PURPOSE: Partial liquid ventilation (PLV) with perfluorocarbons decreases pulmonary vascular resistance (PVR) in injured piglet lungs without supplemental oxygen. These PVR changes may result either from direct mechanical effects or improved arterial oxygenation. In an uninjured hypoxic model of elevated PVR the authors asked the following questions: (1) Does prophylactic or therapeutic PLV ameliorate the PVR response to hypoxia? (2) Do prophylactic and therapeutic PLV have different PVR effects? (3) Does supplemental oxygen modify PVR response to PLV? METHODS: Piglet (3 to 4 kg) lungs were isolated in situ without ischemia, hypoxia, or reperfusion injury. Pulmonary artery (PA) and left atrial (LA) cannulae were attached to a blood-primed extracorporeal membrane oxygenation (ECMO) perfusion circuit with a flow (QPA) of 80 mL/kg/min. Pressure-limited, volume-cycled ventilation (PIP < 25 mm Hg, Tv = 15 mL/kg) was initiated. PLV with perfluorodecalin (15 mL/kg) was administered endotracheally. Continuously monitored blood gas parameters allowed airway and extracorporeal adjustment of FiO2 to produce a PO2 appropriate to the experimental phase. PVR was calculated as (PPA - PLA/QPA). After a stable 30-minute normoxic baseline, animals were assigned randomly to three groups. In group I, control (n = 7), PVR was measured for 150 minutes in hypoxic lungs (FiO2 = 0.07, PPAO2 = 40 mm Hg, SPAO2 = 70%). In group II, prophylactic (n = 8), PLV was administered, followed by 90 minutes of hypoxia, and 60 minutes of oxygen recovery (FiO2 = 0.21-0.30, PPAO2 > 100 mm Hg, SPAO2 = 100%). In group III, therapeutic (n = 8), after 30 hypoxic minutes, PLV was administered and maintained for 90 minutes, followed by a 60-minute oxygen recovery phase. Results were expressed as mean +/- SEM. Statistical analysis of groups was performed by repeated measures of analysis of variance (ANOVA) and Tukey correction. RESULTS: In group I normoxic gas-ventilated PVR was 174+/-12 mm Hg/L/kg/min. After 90 hypoxic minutes PVR was 318+/-37 (P < .01 vbaseline). In group II baseline PVR was 183+/-14. PVR after 30 normoxic minutes of PLV was 199+/-14 (P = ns v baseline). After 90 hypoxic minutes, PVR was 350+/-31 (P < .01 v baseline, and PLV alone) followed by a decrease to 192+/-19 after 60 minutes of oxygen recovery (P = ns v baseline or PLV alone). In group III baseline PVR was 160+/-17 and 325+/-29 after 30 hypoxic minutes. After 90 hypoxic minutes of PLV, PVR was 366+/-22 (P = ns v hypoxia control, P < .01 v normoxic baseline). PVR recovered to 189+/-19 after 60 minutes of oxygen recovery (P = ns v baseline). CONCLUSIONS: Prophylactic/therapeutic PLV had no effect on hypoxia-induced increases in PVR and did not differ from each other. Although PLV alone decreases PVR in the injured lung without supplemental oxygen, elevated PVR associated with hypoxia was ameliorated only by supplemental oxygen in the liquid ventilated lung.

Incidence and outcome of primary Epstein-Barr virus infection and lymphoproliferative disease in pediatric heart transplant recipients.

BACKGROUND: The objective of this study was to assess the relationship between Epstein-Barr virus (EBV) infection and posttransplantation lymphoproliferative disease (PTLD) in pediatric heart transplant recipients. EBV is implicated in the development of PTLD. However, the relationship between primary EBV infection and PTLD is not well understood. METHODS: Serial EBV titers were determined prospectively in 50 children before and after heart transplantation. Results were correlated with the development of PTLD. The clinical presentation, management, and outcome of PTLD were characterized. RESULTS: Before transplantation, EBV titers were positive in 19 and negative in 31 patients. After transplantation, all EBV-positive patients remained positive; 1 developed PTLD. Among EBV-negative patients, 12 of 31 remained negative; none developed PTLD. Nineteen patients demonstrated serologic evidence of primary EBV infection after heart transplantation; 12 developed PTLD. Mean follow-up after heart transplantation was 3.3 years (range 0.4 to 8.4 years). Mean time from heart transplantation to histologic confirmation of PTLD was 29 months (range 3 to 72 months). Survival with PTLD was 92%. CONCLUSIONS: Twelve of 13 pediatric heart transplant recipients who developed PTLD had evidence of primary EBV infection. Serial monitoring of EBV titers may lead to earlier identification and improved treatment of PTLD.