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A J McCabe

Publications and source records attributed to A J McCabe.

10 recordsLinked to original sources
PubMed2001

Upregulation of keratinocyte growth factor in the tracheal ligation lamb model of congenital diaphragmatic hernia.

PURPOSE: Congenital diaphragmatic hernia (CDH) carries a high mortality rate of 60% because of associated anomalies, pulmonary hypoplasia, pulmonary hypertension, and type II cell dysfunction. Prenatal tracheal ligation has been shown to improve lung growth in experimental models. This could be caused by a direct effect of increased endothoracic pressure in utero, secondary to the induction of specific growth factors, or both. Keratinocyte growth factor (KGF) is involved in normal lung organogenesis and is a potent mitogen of alveolar type II cells. The authors have therefore investigated the protein and mRNA levels of keratinocyte growth factor in the lung tissue of control, CDH, and CDH tracheal ligation lambs. METHODS: Eight lambs had left-sided diaphragmatic hernias surgically created at 80 days' gestation. Tracheal ligation was performed at 110 days in 4 lambs, and they were delivered by cesarean section at 140 to 145 days. Twin littermates served as controls. The lungs were dissected en bloc and snap frozen. KGF protein levels were determined by ELISA. Total RNA was isolated, and a RNase protection assay was performed using an ovine cDNA probe for KGF, and a human cDNA probe for GAPDH (house keeping control). Densitometric analysis was used to quantify the relative amounts of mRNA in each sample. RESULTS: There was a significant decrease in the KGF protein levels of the CDH samples (110 v 73.2 pg/mg protein, P =.02). This decrease was mirrored by a significant fall in the level of mRNA expression for KGF (0.694 v 0.235, P = .02). Tracheal ligation normalized the KGF protein levels (96.1 pg/mg protein). This elevation of KGF protein was accompanied by an upregulation of KGF gene expression to control levels (0.56). CONCLUSIONS: Tracheal ligation clearly is accompanied by an upregulation of keratinocyte growth factor protein and gene expression. It is not yet clear whether keratinocyte growth factor is solely responsible for the growth observed in these tracheal ligation preparations. Further growth factor blocking experiments are required.

Animals↗
PubMed2001

Myeloperoxidase activity as a lung injury marker in the lamb model of congenital diaphragmatic hernia.

PURPOSE: The antioxidant system is the primary intracellular defense system of the lung against oxygen toxicity (neutrophil sequestration). The CDH lamb model antioxidant system is deficient. It is hypothesized that pulmonary neutrophil sequestration may play a part in the acute lung injury of CDH patients. Myeloperoxidase (MPO) is a major constituent of neutrophil cytoplasmic granules and its activity therefore is a direct measure of neutrophil presence and an indirect indicator of lung injury. METHODS: Eight lambs had left-sided diaphragmatic hernias surgically created at 80 days' gestation and were delivered by cesarean section at 140 to 145 days. Eight littermate lambs served as controls. Lambs were either killed before ventilation or were ventilated conventionally for 4 hours with 100% O(2) and then killed. The lungs were dissected en bloc and snap frozen. The samples were homogenized, sonicated, freeze-thawed, and separated by density centrifugation. Supernatants were analyzed for myeloperoxidase (MPO) activity by spectrophotometry with o-dianisidine dihydrochloride and hydrogen peroxide at 460 nm. The MPO activity was normalized to the protein content of the supernatant and expressed as units of MPO activity per milligram of protein. RESULTS: There was significantly more MPO activity in the CDH-ventilated lungs than controls similarly ventilated (3,203 +/- 665 versus 1,220 +/- 194, P =.001). There was no difference in MPO activity between the CDH and control lungs (318 +/- 57 v 348 +/- 61; P =.5). There was no difference between right and left lungs in any group. CONCLUSION: Ventilation and hyperoxia leads to neutrophil accumulation in lung tissue, which is most pronounced in the CDH lung tissue. This is a further clue to the pathophysiology of iatrogenic lung injury in CDH. The myeloperoxidase assay may now be used to evaluate antenatal or postnatal antioxidant therapies for iatrogenic lung injury in CDH.

Animals↗
PubMed2000

The effect of low-dose fish oil supplementation on serum growth factors in healthy humans.

OBJECTIVE: To examine the effect of low-dose fish oil supplementation on specific growth factors, purported to play a central role in lesion formation, and also on the total growth factor activity of serum, as assessed by the induction of DNA synthesis in cultured human arterial smooth muscle cells. DESIGN: Randomized placebo-controlled double-blind intervention study. SETTING: Free-living population. SUBJECTS: Sixty-three healthy volunteers, 37 males and 26 females. INTERVENTIONS: Four treatment regimes with subjects receiving 0, 0.3,0.6 or 0.9 g/day of n-3 PUFA for an 8 week period. Blood samples were taken at baseline and following the 8 week intervention. All samples were analysed in batch following completion of the study. RESULTS: Consumption of fish oil had no effect on serum platelet-derived growth factor (PDGF), or transforming growth factor beta (TGFbeta) concentration. Furthermore, fish oil supplementation did not alter the total growth factor activity of serum. CONCLUSIONS: Results indicate that low-dose fish oil supplementation, equivalent to about two portions of fatty fish per week and providing less than 1 g n-3 PUFA/day, does not alter the levels of the major serum growth factors and does not modify total serum growth factor activity in healthy human volunteers. SPONSORSHIP: European Union shared cost project (FAIR-CT-95-0085).

Adult↗
PubMed2000

Bioavailability of n-3 polyunsaturated fatty acids (PUFA) in foods enriched with microencapsulated fish oil.

OBJECTIVE: Incorporation of fish oil into food products provides a means of increasing n-3 fatty acid intake, particularly in populations where fish consumption remains low. The aim of the present study was to evaluate the bioavailability of n-3 PUFA in microencapsulated fish-oil-enriched foods compared with an equal amount of n-3 PUFAs contained in fish oil capsules. METHODS: Twenty-five healthy female volunteers were randomly assigned to one of two groups for the 4-week intervention: one group received 0.9 g of n-3 PUFA/day as fish oil capsule (capsule group), while the second group (food group) received an equal amount of n-3 PUFA/day from enriched foods. Baseline and post-intervention samples were analysed for platelet fatty acid composition. RESULTS: There was no significant difference in the change in platelet arachidonic acid (AA), eicosapentaenoic acid (EPA), or docosahexaenoic acid (DHA) between the two groups following the intervention. CONCLUSIONS: The results indicate that n-3 PUFA from microencapsulated fish-oil-enriched foods are as bioavailable as n-3 PUFA in a capsule. Fortification of foods with microencapsulated fish oil, therefore, offers an effective way of increasing n-3 PUFA intakes and status in line with current dietary recommendations.

Adult↗
PubMed1999

Observation of splenic trauma: when is a little too much?

A 12-year-old boy was treated conservatively for a grade II splenic laceration. On discharge, he was instructed to avoid contact sports, running, and strenuous physical activity. Thirty-eight days later, after diving off the side of a swimming pool, he had abdominal pain, nausea, and diaphoresis. On admission, he was hemodynamically unstable. Results of a diagnostic lavage showed gross blood. At laparotomy, a fractured spleen was found, and splenectomy was performed. He recovered without complication. This case questions the activity restrictions placed on patients with conservatively managed splenic trauma. Avoidance of only contact sports and heavy exertion may be inadequate.

Child↗