Localized intraocular posttransplant lymphoproliferative disorder after pediatric liver transplantation.
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Antibodies, Viral↗
Biomedical subjects
Max R Langham
Publications and source records attributed to Max R Langham.
Hepatobiliary disorders.
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Biliary Tract Diseases↗
Expanded efficacy and indication of extracorporeal membrane oxygenation for preoperative pulmonary bleeding on pediatric cadaveric orthotopic liver transplantation.
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Cadaver↗
Expression of VEGF receptors in cocultured neuroblastoma cells.
BACKGROUND: VEGF is best known for its angiogenic properties. We have found that VEGF expression is increased in neuroblastoma cells cocultured with hepatocytes. In addition, we have previously shown that neuroblastoma cells cultured with exogenous VEGF have an increase in the expression of VEGF receptors. Therefore, we hypothesized that the expression of VEGF receptors would be up-regulated in neuroblastoma cells grown in the coculture environment. MATERIALS AND METHODS: Two neuroblastoma cell lines (IMR-32 or SK-N-DZ) are used. These cells are cultured alone and in a coculture system with hepatocytes. Message for VEGF and the VEGF receptors KDR, flt-1, flt-4, neuropilin 1 (NRP-1), and neuropilin 2 (NRP-2) are measured with RT-PCR. Flt-4, NRP-1, and NRP-2 protein expression is measured with Western blot. RESULTS: The receptors KDR and flt-1 are not detected in either cell line in either control or coculture conditions. Message for VEGF and flt-4 is significantly increased in the cocultured IMR-32 cells, while that for NRP-1 and NRP-2 is unchanged in these cells. VEGF and its receptors are unchanged in cocultured SK-N-DZ cells. CONCLUSIONS: Neuroblastoma cells express specific VEGF receptors that are differentially regulated in the different cell lines. These findings suggest that the heterogeneity of neuroblastomas may limit the utility of targeting VEGF and its receptors as sole treatments for the tumor, and that successful therapies will be dependent upon the specific biology of the tumor.
Blotting, Western↗
Surfactant does not improve survival rate in preterm infants with congenital diaphragmatic hernia.
BACKGROUND: Use of exogenous surfactant in congenital diaphragmatic hernia (CDH) patients is routine in many centers. The authors sought to determine the impact of surfactant use in the premature infant with CDH. METHODS: Data on liveborn infants with CDH from participating institutions were collected prospectively. Surfactant use and timing and outcome data were analyzed retrospectively. The authors evaluated the prenatal diagnosis patients as well. The outcome variable was survival to discharge. Odds ratios with confidence intervals were calculated. RESULTS: Five hundred ten infants less than 37 weeks' gestation were entered in the CDH registry. Infants with severe anomalies (n = 80) were excluded. Information on surfactant use was available for 424 patients. Infants receiving surfactant (n = 209) had a greater odds of death than infants not receiving surfactant (n = 215, odds ratio, 2.17, 95% CI: 1.5 to 3.2; P <.01). In prenatally diagnosed infants with immediate distress, there was a trend toward worse survival rates among those receiving surfactant at 1 hour (52 patients) versus those that did not (93 patients; odds ratio, 1.93, 95% CI: 0.96 to 3.9; P <.07). CONCLUSIONS: Surfactant, as currently used, is associated with a lower survival rate in preterm infants with CDH. The use of surfactant replacement in premature infants with CDH can be recommended only within the context of a randomized clinical trial.
Bias↗
Administration of prenatal betamethasone suppresses the adrenal-hypophyseal axis in newborns with congenital diaphragmatic hernia.
BACKGROUND: Congenital diaphragmatic hernia (CDH) is a condition that is characterized by pulmonary hypoplasia and pulmonary hypertension. Prenatal betamethasone often is administered to fetuses with CDH to improve pulmonary function. In this study, the authors investigate the possible role of the adrenal-hypophyseal axis in CDH in an animal model and subsequently in human infants with CDH. METHODS: Twin fetal sheep underwent creation of DH or a sham thoracotomy, and levels of plasma and lung ACTH and plasma cortisol were compared. For the human studies, plasma levels of ACTH, cortisol, and DHEA were measured in cord blood samples collected from 9 CDH (5 that received prenatal betamethasone) and compared with those of 14 normal newborns. In both studies, ACTH and cortisol levels were determined by radioimmunoassay (RIA). Human (DHEA) levels were determined by ELISA. RESULTS: Plasma ACTH and cortisol levels were elevated in fetal DH sheep compared with sham-operated controls; however, levels of ACTH in lung tissues were not different. Human newborns with CDH who have been exposed to prenatal steroids have significantly lower plasma ACTH, cortisol, and DHEA levels than normal newborns and CDH newborns not exposed to prenatal betamethasone. CONCLUSIONS: In an ovine model of CDH, the adrenal-hypophyseal axis appears up-regulated in DH fetuses compared with sham-operated animals. Conversely, the adrenal-hypophyseal axis in human CDH newborns appears normal but is suppressed by the administration of prenatal betamethasone.
Adrenocorticotropic Hormone↗
Combined resection of the liver and inferior vena cava for hepatic malignancy.
OBJECTIVE: The objective of this paper is to review the results of combined resection of the liver and inferior vena cava for hepatic malignancy. The morbidity and mortality along with preliminary survival data are assessed in order to determine the utility of this aggressive approach to otherwise unresectable tumors. SUMMARY BACKGROUND DATA: Involvement of the inferior vena cava has traditionally been considered a contraindication to resection for advanced tumors of the liver because the surgical risks are high and the long-term prognosis is poor. Progress in liver surgery allows resection in some cases. METHODS: Twenty-two patients undergoing hepatic resection from 1997 to 2003, that also required resection and reconstruction of the inferior vena cava (IVC), were reviewed. The median age was 49 years (range 2 to 68 years). Resections were carried out for: hepatocellular carcinoma (n = 6), colorectal metastases (n = 6), cholangiocarcinoma (n = 5), gastrointestinal stromal tumor (n = 2), hepatoblastoma (n = 2), and squamous cell carcinoma in 1 patient. Liver resections performed included 13 right trisegmentectomies, 6 right lobectomies extended to include the caudate lobe, and 3 left trisegmentectomies. Complex ex vivo procedures were performed in 2 cases using venovenous bypass while the other 20 cases were performed using varying degrees of vascular isolation. In situ cold perfusion of the liver was used in 1 case. The IVC was reconstructed with ringed Gore-Tex tube graft (n = 14), primarily (n = 6), or with Gore-Tex patches (n = 2). RESULTS: There were 2 perioperative deaths (9%). One cirrhotic patient died of liver failure 3 weeks post operatively and 1 patient with cholangiocarcinoma died of pulmonary hemorrhage secondary to a cavitating pulmonary infection after aspiration pneumonia 6 weeks after resection. Six patients had evidence of postoperative liver failure that resolved with supportive management and 2 patients required temporary dialysis. All vascular reconstructions were patent at last follow-up. With median follow-up of 26 months, 5 patients have died of recurrent malignancy at 44, 40, 32, 26, and 24 months, while an additional patient is alive with disease at 31 months. Actuarial 1-, 3-, and 5-year survivals were 85%, 60%, and 33%, respectively. CONCLUSIONS: IVC involvement by hepatic malignancy does not necessarily preclude resection. Liver resection with reconstruction of the inferior vena cava can be performed in selected cases. The increased risk associated with the procedure appears to be balanced by the possible benefits, particularly when the lack of alternative curative approaches is considered.
Adolescent↗
Differential expression of Bcl-2 and Bax may enhance neuroblastoma survival.
BACKGROUND/PURPOSE: Aggressive tumors may alter their expression of Bcl-2 proteins to decrease apoptosis and increase survival. The authors reported previously that neuroblastoma cells have diminished apoptosis when placed in coculture with hepatocytes to stimulate a metastatic environment. It was hypothesized that the expression of proapoptotic (Bax) and prosurvival (Bcl-2 and Mcl-1) proteins would be altered in neuroblastoma cells grown in a cell culture model of metastatic neuroblastoma. METHODS: Human neuroblastoma cells (IMR-32) were grown alone or in coculture with human hepatocytes for 2, 3, or 4 days. Bcl-2, Mcl-1, and Bax mRNA were measured with reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Bcl-2, an antiapoptotic protein, was significantly increased in cocultured neuroblastoma cells by day 4. Bax, a proapoptotic protein, was significantly diminished by day 3. No significant change in Mcl-1 occurred in this study. CONCLUSIONS: When neuroblastoma cells placed in coculture, the prosurvival protein, Bcl-2, is upregulated whereas the proapoptotic protein, Bax, is downregulated. The combination of these changes can maximally enhance the survival rate of neuroblastoma cells in coculture. The propensity for neuroblastoma to either metastasize or regress may be associated with its ability to differentially regulate the expression of different members of the Bcl-2 protein family.
Apoptosis↗
VEGF receptors are differentially expressed by neuroblastoma cells in culture.
BACKGROUND/PURPOSE: Vascular endothelial growth factor (VEGF) is best known for its angiogenic properties, but its mitogenic capacity may be more important for tumorigenesis. The ability of VEGF to induce specific biologic activities may be dependent on the amount and type of VEGF receptors present. The authors hypothesize that neuroblastoma cells express specific VEGF receptors and that their expression may be altered when the cells are exposed to differing cytokines and culture environments. METHODS: Four groups of human neuroblastoma cells (IMR-32) are studied. (1) Control cells: cultured in standard media. (2) VEGF cells: VEGF added to the media. (3) Tumor necrosis factor alpha (TNF-alpha) cells: TNF-alpha added to the media. (4) Serum starved cells: cultured in serum-depleted media. Reverse transcriptase polymerase chain reaction (RT-PCR) is utilized to measure the VEGF receptors flt-1, KDR/flk-1, flt-4, neuropilin 1 (NRP-1), and neuropilin 2 (NRP-2). RESULTS: Flt-1 and KDR are not detected in any groups. Flt-4, NRP-1, and NRP-2 are present in the IMR-32 cells, and their expression is significantly increased by the administration of VEGF. Neuroblastoma cells cultured with TNF-alpha or in serum-depleted media have a significant decrease in the expression of these receptors. CONCLUSIONS: The authors show that neuroblastoma cells express specific VEGF receptors that may be altered by mitogenic or apoptotic stimuli. Specifically targeting VEGF and its receptors may be another therapeutic strategy for the treatment of neuroblastoma.
Culture Media, Serum-Free↗
CO2 splenoportography: preliminary results.
OBJECTIVE: Previously, splenoportography with 18-gauge needles provided excellent portal imaging. However, because of concern about bleeding, this technique was replaced with arterial portography and noninvasive techniques, which are not always accurate. We present a modification of splenoportography using CO2 and an ultrafine needle in eight patients whose previous imaging studies were inconclusive. CONCLUSION: CO2 splenoportography is safe and expedient and provides adequate visualization of the portal system for surgical planning in selected patients.
Adolescent↗
Neuroblastoma, apoptosis, and growth factors.
Neuroblastoma is the most common extracranial tumor of childhood. This tumor is associated with alterations in apoptosis and is affected by various growth factors and cytokines. In this short review we will discuss recent findings in our laboratory where we have been studying a cell culture model of neuroblastoma.
Apoptosis↗
Twenty years of progress in congenital diaphragmatic hernia at the University of Florida.
Over the past 20 years the clinical paradigms underlying the care of children with congenital diaphragmatic hernia (CDH) have undergone profound changes. The purpose of this work is to provide an historic review of research and clinical studies related to CDH at the University of Florida (UF) and Shands Children's Hospital during the chairmanship of Edward M. Copeland, III, M.D. and to present our current clinical results. During Dr Copeland's tenure survival for newborns symptomatic with CDH treated at UF/Shands Children's Hospital has improved from less than 20 per cent to 85 per cent. Clinical observations have suggested and research studies at UF using a fetal lamb model have confirmed that fetal distress can occur late in gestation, which may predispose infants with CDH to pulmonary hypertension. However, our patient experience has confirmed that the most significant cause of mortality in human infants is not pulmonary hypertension but iatrogenic injury to their hypoplastic lungs. Strict avoidance of barotrauma in these babies has been the most important clinical advance during these two decades. Significant clinical and research problems remain including defining optimal prenatal care, management of complications during the first few weeks of life, and development of strategies to accelerate lung growth. Dramatic improvements in survival have resulted in children who manifest a number of clinical problems that were not evident when most of these patients died early in infancy. Our experience at Shand's Children's Hospital/UF indicates that feeding problems, respiratory infections, and management of subtle or overt neurologic complications may become major issues for some of these survivors and their families.
Abnormalities, Multiple↗
Caspase 3 expression is altered in a coculture model of neuroblastoma.
BACKGROUND: Previously, we demonstrated that neuroblastoma cells cocultured with hepatocytes are protected from apoptosis, while apoptosis is upregulated in the hepatocytes. The mechanisms responsible for these findings are unknown. We hypothesize that caspase 3, a cysteine protease central to the apoptotic pathway, will be altered in this coculture model that simulates metastatic neuroblastoma. METHODS: Control human neuroblastoma cells and liver cells are plated in standard media. For the study group, a noncontact, coculture system is used. Hepatocytes are plated on cell culture inserts, placed above a growing layer of neuroblastoma cells, and incubated. Activated caspase 3 is measured after 1, 2, 3, or 4 days. RESULTS: Activated caspase 3 levels are significantly decreased in the cocultured neuroblastoma cells on days 2, 3, and 4. Conversely, cocultured hepatocytes have a significant increase in caspase 3 activation at all time periods, with the largest difference seen after 1 day in coculture. CONCLUSIONS: The capacity for neuroblastoma to differentially alter caspase 3 activation may provide a significant survival advantage for the neuroblastoma cells in metastatic environments. Understanding the mechanisms for this altered regulation may lead to improved and better targeted therapy for this malignancy.
Caspase 3↗
Fryns syndrome in children with congenital diaphragmatic hernia.
PURPOSE: Fryns syndrome is characterized by multiple congenital anomalies including Congenital Diaphragmatic Hernia (CDH), and has a reported poor prognosis with a survival rate during the neonatal period of approximately 15%. This report details the management and outcome of patients with Fryns syndrome and CDH. METHODS: Records of all liveborn patients with CDH between 1995 and 2001 in 83 hospitals were entered into the CDH database. Those with Fryns syndrome were reviewed retrospectively. RESULTS: A total of 1,833 patients were entered in the database, 23 of these had Fryns (1.3%). All patients experienced early distress requiring intubation. Ten patients (43%) were found to have other major anomalies. Seven patients underwent surgical repair at an average age of 7.5 days (range, 6 hours to 14 days). Mortality rate was 83% compared with 33% of patients with unilateral CDH (P =.01). Ten patients died within the first 24 hours. The parents of 6 patients withdrew support. Of the 4 survivors, 3 have marked developmental delay, whereas the fourth has not yet undergone formal assessment. CONCLUSIONS: The prognosis of infants with Fryns syndrome and congenital diaphragmatic hernia remains grim. Early genetic counseling and recognition of lethal anomalies may assist in determining which patients may survive.
Abnormalities, Multiple↗
Hepatic vein reconstruction for resection of hepatic tumors.
SUMMARY BACKGROUND DATA: Involvement of the hepatic veins requiring reconstruction has traditionally been considered a contraindication to resection for advanced tumors of the liver because the surgical risks are high and the long-term prognosis poor. Recent advances in liver surgery gleaned from split and live donor liver transplantation that necessitate hepatic vein reconstruction can be applied to hepatic resection in some cases. METHODS: Sixteen patients who underwent hepatic resection requiring hepatic vein reconstruction from 1996-2001 were reviewed. The mean age was 43 years (range 2-61). Nine patients were resected for hepatocellular carcinoma (HCC), five patients for colorectal metastases, and one patient each for hepatoblastoma and cholangiocarcinoma. In six patients with HCC and cirrhosis, the right hepatic vein was reconstructed to provide venous outflow to liver segments not adequately drained by a remaining major hepatic vein. Four of these six patients required the use of Gore-Tex (W. L. Gore & Associates, Inc., Newark, DE) interposition grafts. In the 10 other cases the entire venous outflow from the remnant liver was reconstructed or reimplanted into the inferior vena cava primarily (n = 8) or using segments of the portal vein from the resected side of the liver as a graft (n = 2). Ex-vivo procedures with the use of veno-venous bypass were required in two cases and in-situ cold perfusion of the liver was used in one case. RESULTS: There were two perioperative deaths (12%). One patient died of liver failure 3 weeks after right trisegmentectomy with reconstruction of the left hepatic vein and one patient died at 3 months after resection due to sepsis from a segment of small bowel that perforated into a diaphragmatic hernia. Four patients had evidence of postoperative liver failure that resolved with supportive management and one patient required temporary dialysis. All vascular reconstructions were patent at last followup. With median followup of 23 months, 3 patients have died of recurrent malignancy at 14, 18 and 30 months, while an additional patient went on to die of progressive liver failure at 22 months. Actuarial 1 and 3 year survival was 88% and 50% respectively. CONCLUSION: Hepatic vein involvement by hepatic malignancy does not necessarily preclude resection. Liver resection with reconstruction of the hepatic veins can be performed in selected cases. The increased risk associated with the procedure appears to be balanced by the possible benefits, particularly when the lack of alternative curative approaches is considered.
Adolescent↗
Small watercraft injuries in children.
The speed and use of small watercraft have increased dramatically in recent years. We report our experience with pediatric trauma resulting from small watercraft accidents. We conducted a retrospective chart review including all children admitted with injuries sustained in small watercraft accidents. Sixteen children were included; nine were injured in jet ski accidents and seven in accidents involving other craft. Jet ski accidents tended to result in more serious injuries (closed-head injuries, hollow and solid viscus injuries, chest trauma, spinal injuries leading to paralysis, and death) than those sustained in accidents with small boats. Skin and soft-tissue injuries and long-bone fractures were the most frequent injuries following accidents with other small boats. Six of eight children (75%) injured on jet skis required operative interventions. Only three of seven (43%) children in other watercraft accidents required surgery (P < 0.05 jet ski vs other watercraft). When compared with children injured in accidents involving small boats those involved in jet ski accidents tended to have more serious injuries and require operative intervention more frequently. A high index of suspicion for serious injuries must be maintained when evaluating children with this mechanism of injury.
Accidents↗