Bronchopulmonary dysplasia and very low birthweight: Lung function at 11 years of age

Objective : To determine the relationship between lung function at 11 years of age and bronchopulmonary dysplasia (BPD) in very low birthweight (VLBW) children.
Methodology : This study comprised 154 consecutive surviving VLBW children, divided into three groups with respect to their neonatal respiratory morbidity: group I developed BPD; group II required assisted ventilation but did not develop BPD; and group III required no assisted ventilation. Lung function tests were measured on 120/154 (77.9%) children at 11 years of age. The relationship between various lung function variables and neonatal lung disease was analysed by multiple linear regression.
Results : Several lung function variables reflecting airflow were significantly diminished in the BPD group ( n = 15), and residual volume was significantly higher. Despite poorer lung function overall, few children in the BPD group had lung function abnormalities in the clinically significant range ( n = 2 [13.3%] with a forced expired volume in 1 s <75% predicted; n = 2 [13.3%] with a forced vital capacity <75% predicted; n = 1 [6.7%] with a residual volume/total lung capacity >35%). There were no significant differences in lung function variables between group II ( n = 41) and group III ( n = 64). Changes in lung function tests between 8 and 11 years did not vary significantly between the three groups.
Conclusions : VLBW children with BPD in the newborn period have poorer lung function at 11 years of age than other surviving VLBW children without BPD, although few have lung function abnormalities in the clinically significant range.     

A Ruptured Pancreaticoduodenal Artery Aneurysm Repaired by Combined Endovascular and Open Techniques

Aneurysms of the pancreaticoduodenal arteries (PDA) are rare, accounting for <2% of all visceral aneurysms. An association with celiac artery stenosis has been reported. Many present with rupture, and a high mortality can be expected. Treatment is therefore challenging. Arterial ligation, anuerysmectomy, or bypass has been the mainstay of treatment. We recently treated a patient (who had no celiac axis) with a ruptured PDA aneurysm with combined open and endovascular techniques. A 46-year-old man was transferred to our hospital with a 1-day history of abdominal pain and syncope. On admission, an abdominal and pelvis computerized tomographic (CT) scan identified a large mesenteric hematoma, a 1.9 cm PDA aneurysm, and an occluded celiac axis. Mesenteric angiography revealed no active aneurysm leak and a stenotic superior mesenteric artery (SMA) origin. All hepatic blood flow originated from the stenotic SMA via markedly enlarged PDA collaterals. The patient was brought to the operating room, where absence of the celiac axis was confirmed. An aorto-to-proper hepatic and SMA bypass was performed using a bifurcated polyester graft. The next day, the patient was brought to the angiography suite, where the PDA aneurysm was coiled. Postprocedure CT scans confirmed thrombosis of the aneurysm. Ruptured mesenteric artery aneurysms are a challenging problem for the vascular surgeon. PDA aneurysms are rare and often occur in an unfavorable location. There appears to be an association with anatomic anomalies of the mesenteric circulation. Prompt invasive and noninvasive diagnostic studies aid in the definitive management of this often fatal problem. Combined endovascular and open techniques can be used for successful treatment.     

Genotypes of glutathione transferase M1 and P1 and their significance for lung DNA adduct levels and cancer risk

The A-G polymorphism at codon 104 in the glutathione S-transferase P1 (GSTP1) gene was examined in 138 male lung cancer patients and 297 healthy controls. The patients had significantly higher frequency of the GG genotype (15.9%) and a lower frequency of AA (38.4%) than the controls (9.1% and 51.5%, respectively). The level of hydrophobic DNA- adducts were determined in lung tissue from 70 current smokers. Patients with the GG genotype had a significantly higher adduct level than patients with AA (15.5 +/- 10.2 vs 7.9 +/- 5.1 per 10(8) nucleotides, P = 0.006). We also analyzed the deletion polymorphism in the GSTM1 gene in 135 male patients and 342 controls. The patients were stratified according to histology, smoking dose, age, adduct level and mutational types found in the tumors (Ki-ras and p53 genes). The results consistently indicated that the GSTM1 null genotype was associated with a slightly increased lung cancer risk. When the combined GST M1 and P1 genotypes were examined, patients with the combination null and AG or GG had significantly higher adduct levels than all other genotype combinations (P = 0.011). The distribution of combined genotypes was also significantly different in cases and controls, mainly due to increased frequency of the combination GSTM1 null and GSTP1 AG or GG among patients.      

Is a NAD pyrophosphatase activity necessary for Haemophilus influenzae type b multiplication in the blood stream?

Haemophilus influenzae has an absolute requirement for factor V because it lacks all the biosynthetic enzymes necessary for the de novo synthesis of NAD. Factor V can be provided as either nicotinamide adenosine dinucleotide (NAD), nicotinamide mono-nucleotide (NMN) or nicotinamide riboside (NR) in vitro, but little is known about the source or the mechanism of uptake for factor V in vivo. Recently, a hypothetical open reading frame (ORF), termed nadN, was identified to encode a gene product essential for H. influenzae growth on NAD. Here, we report its role in the virulent H. influenzae serotype b strain Eagan. Our results indicate that NadN of type b Eagan strains is involved in NAD uptake and in processing NAD to NR, which appears to be the substrate for an as yet unidentified cytoplasmic membrane NR transport system. Furthermore, we present data showing that H. influenzae type b nadN mutants are able to survive as well as Eagan, in vivo in the five-day-old infant rat model of human invasive disease. NAD pyrophosphatase and NMN 5'-nucleotidase activities were present in rat and human serum, implying that under infection conditions H. influenzae may obtain NR directly from its host.     

Follistatin and activin A in extra-embryonic coelomic and amniotic fluids and maternal serum in early pregnancy

Follistatin is a specific binding protein which controls bioavailability of activins and inhibins which have an important role in fetal development. In the first trimester of pregnancy bioactive dimeric inhibins are found at high concentrations in the extra- embryonic coelomic fluid, but the distribution of follistatin and activins is not known. We have used recently developed immunoassays for follistatin, activin A and activin AB to determine their presence in the intrauterine compartments during early pregnancy. Follistatin was present in highest concentrations in the extra-embryonic coelomic fluid (11.72 +/- 1.70 ng/ml; median +/- SEM), with less in maternal serum (6.35 +/- 4.58) and lowest amounts in amniotic fluid (0.97 +/- 0.52). Follistatin concentrations in extra-embryonic coelomic fluid were highly correlated with both dimeric inhibin isoforms. Activin A was present in only barely detectable amounts in some samples of extra- embryonic coelomic fluid (41% of samples) and maternal serum (26%) and was undetectable in all amniotic fluid samples. Activin AB was undetectable in all compartments. The presence of follistatin in the amniotic and extra-embryonic coelomic fluids may regulate the availability of bioactive activins and inhibins which are released into the intrauterine compartments during the development of the fetus and placenta in early pregnancy.      

Effect of hypertransfusion on bone marrow regeneration in sublethally irradiated mice. I. enhanced granulopoietic recovery

Hypertransfusion can enhance recovery from neutropenia in certain clinical and experimental situations. We have studied the pattern of myeloid recovery in mice hypertransfused after receiving 350 rads whole body irradiation. Both hypertransfused and control groups showed the degenerative phase, abortive rise, and regenerative phase that has been described following sublethal irradiation. The blood granulocyte counts in the hypertransfused group returned to normal more rapidly and were maintained at a significantly higher level during the regenerative phase. This difference is not the result of a shift in granulocytes from the marrow granulocyte reserve or marginal granulocyte pool to the circulating pool, but is associated with significantly enhanced bone marrow granulopoiesis. While the total bone marrow cellularity of the hypertransfused mice is less than that of the control mice, the hypertransfused group contains more CFU-GM and myeloid cells during the regenerative phase. The enhanced granulopoiesis is not due to increased colony-stimulating activity (CSA) levels in the hypertransfused mice, as the CSA levels were significantly lower in this group compared to the controls prior to and during the initial phase of granulopoietic recovery. This study suggests that hypertransfusion increases the rate of recovery of myelopoiesis by increasing the number of precursors available for myeloid differentiation from an earlier stem cell compartment.     

Pediatric liver transplantation. Part II. Diagnostic imaging in postoperative management

The postoperative diagnostic imaging examinations of 44 children who underwent 59 orthotopic liver transplantations were reviewed. The imaging modalities used for the evaluation of suspected complications include plain roentgenography, ultrasonography (US), computed tomography (CT), nuclear scintigraphy, arteriography, percutaneous and operative cholangiography, and endoscopic retrograde cholangiopancreatography. The main postoperative complications included ischemia, thrombosis (hepatic artery and portal vein), infarction, obstruction or leakage of the biliary anastomosis, hepatic and perihepatic infection, and allograft rejection. US, the most frequently used abdominal imaging modality, was best suited for detection of biliary duct dilatation, fluid collections in or around the transplanted liver, and hepatic arterial, inferior vena caval, and portal vein thrombosis. CT was especially helpful in corroborating findings of infection and in locating abscesses. Technetium 99m sulfur colloid (early- and late-phase imaging) provided a sensitive, although nonspecific, means of assessing allograft vascularization and morphology. Angiography showed vascularity most clearly, and cholangiography was the most useful in the assessment of bile duct patency. A diagnostic imaging algorithm is proposed for evaluation of suspected complications.     

Aerobic growth deficient Haemophilus influenzae mutants are non-virulent: implications on metabolism

We investigated aerobic metabolism in Haemophilus influenzae to better understand its essential physiological growth pathways. We describe the isolation and characterization of transposon insertions leading to knockout mutations in lpdA, encoding dihydrolipoamide dehydrogenase. H. influenzae Rd lpdA::Tn10d-cat mutants were unable to grow aerobically and an H. influenzae type b lpdA::Tn10d-cat mutant was significantly attenuated in an infant rat infection model. Since LpdA is a functional subunit of both pyruvate dehydrogenase (aceEF) and alpha-ketoglutarate dehydrogenase (sucAB) the phenotype of the lpdA mutant was further explored by creating separate knockout mutants in the sucAB and aceEF loci. DeltaaceEF and deltasucAB mutants were both significantly attenuated in virulence in the infant rat, but only the sucAB mutant was able to grow aerobically. We therefore conclude that the ability for aerobic growth is critical for invasive disease, and furthermore that a TCA cycle enzyme, alpha-ketoglutarate dehydrogenase, appears to contribute a key metabolic function in vivo, but is not required for growth under laboratory conditions.