Hepatic artery thrombosis after adult living donor liver transplantation: the effect of center volume

BACKGROUND: To investigate whether center volume impacts the rate hepatic artery thrombosis (HAT) and patient survival after adult living donor liver transplantation (ALDLT). METHODS: Patients with HAT who were listed as Status 1 in the Organ Procurement Transplant Network database were included in the study. Recipients of ALDLT were compared to those who received a deceased donor liver transplant (DDLT). RESULTS: Recipients of ALDLT had a higher rate of HAT than recipients of DDLT. Centers that performed less than four adult ALDLT had a higher rate of HAT than other higher volume centers. "Novice" centers had a worse graft and patient survival than those with more experience in ALDLT. Recipients who had HAT experienced a worse patient survival than those who did not. CONCLUSIONS: Centers with higher volume have a lower rate of HAT and a better patient and graft survival in ALDLT. Clearer regulations and focus on overcoming the learning curve might be needed to increase the utilization of ALDLT.     

Mean airway pressure--significance during mechanical ventilation in neonates

Variations in PEEP with concomitant changes of DPP while MAP, PIP, flow, FIO2, and ventilator rate remained constant were investigated in nine neonates with RDS during the first and second days of life. After stabilization on baseline ventilator settings, PEEP was increased by 3 cm of H2O and DPP decreased in order to maintain balance MAP. Following a return to baseline settings, the PEEP was decreased by 3 cm of H2O and DPP increased sufficiently to maintain constant MAP. Arterial PaO2, PaCO2, pH, blood pressure, heart rate and a/APO2 ratios were measured before, during, between, and after the experimental conditions. Analysis revealed no significant changes in PaO2, a/APO2, blood pressure, or heart rate during baseline or experimental conditions. PaCO2 decreased significantly when PEEP was decreased and DPP increased, both on day 1 (37.2 +/- 2.4 vs 41.4 +/- 2.3 torr; P less than 0.025) and day 2 (42.1 +/- 2.6 vs 46.8 +/- 2.0 torr; P less than 0.05). Changes in pH were inversely related to PaCO2 changes. This study confirms the importance of MAP in determining oxygenation in newborn infants with RDS. However, ventilation was significantly affected by variation in PEEP and DPP despite a constant MAP.     

Ontogeny of VEGF, IGF-I, and GH in neonatal rat serum, vitreous fluid, and retina from birth to weaning

PURPOSE: Vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF)-I, and growth hormone (GH) are major regulators of physical growth, as well as normal and pathologic retinal development. Ocular tissues are protected by the blood-ocular barrier. This study was conducted to test the hypothesis that the ontogenic profiles of VEGF, IGF-I, and GH in the rat serum, vitreous fluid, and retina are compartment specific, and that the vitreous is a reservoir for retinal growth factors. METHODS: Sprague-Dawley rat pups were killed at birth (postnatal day [P]0) and at P7, P14, and P21. At death, serum, vitreous fluid, and retinal homogenates were analyzed for ontogeny of VEGF, IGF-I, and GH. RESULTS: VEGF levels were 10 times higher in the vitreous than in serum at all stages of development. Vitreous and serum VEGF levels progressively declined, with lowest concentrations at P21. Retinal VEGF levels increased with the highest concentration at P21. IGF-I levels in the vitreous decreased from P7 through P21. IGF-I levels in serum and retinal homogenates increased with advancing postnatal age. Although IGF-I levels were four times higher in the vitreous than in the retina at P0, equilibration was achieved at P21. GH levels in the vitreous were 10 times lower than serum levels, were decreased at P14 and P21, and remained unchanged from P0 through P21 in the retina. CONCLUSIONS: VEGF and IGF-I act in concert to promote retinal development with the vitreous fluid as a reservoir. The ontogenic profiles of VEGF, IGF-I and GH in the serum and ocular compartments are specific. These differences should be considered when therapies for ROP are proposed.     

Candidate DNA replication initiation regions at human trinucleotide repeat disease loci

The positions of DNA replication initiation regions (IRs) at three human trinucleotide repeat (TNR) disease loci were examined in order to characterize the role played by IRs in explaining the known locus-specific variation in TNR instability levels. Using three different normal cell lines, candidate IRs were identified at the HD, SCA-7 and SBMA loci. At each locus the IR is less than 3.6 kb from the CAG/CTG repeat tract. Preliminary studies with a cell line homozygous for an HD disease mutation indicated no change in the position of the candidate IR in spite of the mutation. Comparison with experimental results from model systems suggests that a complex relationship may exist between instability and the proximity and/or orientation of the repeats with respect to an IR.     

Early postnatal dexamethasone influences matrix metalloproteinase-2 and -9, and their tissue inhibitors in the developing rat lung

In order to test the hypothesis that early postnatal exposure to dexamethasone (Dex) influences matrix metalloproteinases (MMP)-2 and -9, as well as their tissue inhibitors (TIMP-1 and -2) in the developing rat lung, newborn rats (3 litters/group) were treated with low Dex (0.1 mg/kg/day, IM), high Dex (0.5 mg/kg/day), or equivalent volumes of saline at 5 days postnatal age (P5), P6, and P7. Lung weight and lung MMP and TIMP levels were determined at sacrifice (7 days postinjection, P14; at weaning, P21; and at adolescence, P45, n = 10/group and time). Dex did not adversely affect lung weight or lung MMP-2 levels, which peaked in all groups at P21 and then fell by P45. In contrast, Dex decreased TIMP-2 at all time intervals, but achieved statistical significance only at P45. An imbalance in MMP-2/TIMP-2 ratio was noted at P21, with elevations occurring in the low and high Dex-treated groups. Lung MMP-9 levels remained comparable with controls during low Dex treatment. However, high Dex exposure resulted in elevated lung MMP-9 levels at P21 and P45. Lung TIMP-1 levels increased only with high Dex exposure at P14 and P21, whereas the lung MMP-9/TIMP-1 ratio was elevated at P21 in the high Dex group, and at P45 in both Dex-treated groups. These data provide evidence that early postnatal dexamethasone results in an imbalance between gelatinase-A and -B, and their tissue inhibitors in the developing rat lung. These changes may be responsible, in part, for some of the known maturational effects of steroids on lung structure in the newborn.     

Regulation of retinal vascular endothelial growth factor and receptors in rabbits exposed to hyperoxia

PURPOSE: To evaluate the molecular responses of vascular endothelial growth factor (VEGF) and its receptors to dexamethasone (Dex) and celecoxib (Cel) during hyperoxia and during hyperoxia followed by recovery in room air, in newborn rabbit retinas. METHODS: Newborn rabbits at 3 days postnatal age (n = 96) received room air or oxygen (80%-100%) for 4 days, during which they were administered saline (Sal), Dex, vehicle (Veh), or Cel (n = 12/treatment group). Six animals from each group were killed immediately after hyperoxia (or room air) and the remainder exposed to room air for 5 days. Retinal mRNA expression of VEGF(121), VEGF(165), VEGF receptor-1 (VEGFR-1, or Flt-1), and VEGFR-2 (or KDR/Flk-1) was determined. RESULTS: Hyperoxia resulted in increased retinal expression of mRNA of the VEGF splice variants in the groups treated with Sal, Dex, and Veh, whereas a decrease in VEGF(121) was noted in the Cel-treated group. In contrast, retinal Flt-1 receptor mRNA was markedly increased in the Cel-treated group only, whereas retinal VEGFR-2 (KDR/Flk-1) receptor mRNA was suppressed in all the treatment groups. Hyperoxia followed by recovery in room air resulted in a minimal decrease in expression of retinal Flt-1 mRNA in the Sal and Dex groups. Cel treatment abolished its expression. CONCLUSIONS: The findings of increased retinal expression of VEGF mRNA in the newborn rabbit in response to hyperoxia are most likely due to species differences. Selective targeting of VEGF(121) and Flt-1 mRNA by Cel may represent one regulatory pathway for their anti-inflammatory effects. Further studies are needed to evaluate the therapeutic benefits of cyclooxygenase (COX)-2 inhibitors for the treatment and/or prevention of diseases associated with neovascularization.     

Renal calcification incidence in very low birth weight infants

Serial ultrasound examinations were performed on 31 neonates with birth weights of less than 1,500 g for the detection of renal calcifications. Renal calcifications occurred in 20 (64%) of the infants at a mean age of 39.3 +/- 26.7 days of life. Infants with renal calcifications had shorter gestations (28.2 +/- 1.8 v 31 +/- 1.4 weeks, P less than .004) and lighter birth weights (924 +/- 195 v 1,338 +/- 100 g, P less than .004) than those infants without renal calcifications (n = 11). Furosemide administration was more common in the infants with renal calcifications (65% v 9.1%, P less than .001). The mean total dose of furosemide administered before renal calcifications were noted was 9.59 +/- 7.25 mg/kg. The 20 neonates with renal calcifications had a mean urine calcium level of 12.0 +/- 6.8 mg/kg/24 hours, mean urine calcium to creatinine ratio of 1.32 +/- 1.03 (range 0.3 to 4.45), and a mean alkaline phosphatase concentration of 961 +/- 327 IU. Initial parathyroid hormone levels were not different between the two groups, and subsequent determinations in infants with renal calcifications did not differ significantly from initial values. Renal calcifications are fairly common among very low birth weight infants, particularly in those receiving supplemental calcium and furosemide therapy. Although long-term implications of such findings are not known, close monitoring of renal function by serial determinations of urine calcium and urine calcium to creatinine ratios may identify those infants at risk for renal calcifications.