Elastolytic activity of alveolar macrophages in chronic bronchitis: comparison of current and former smokers

We have compared the macrophage elastolytic activity of a group of current and former smokers with irreversible airflow obstruction. Elastolytic activity was determined in an initial bronchoalveolar lavage cell population and in alveolar macrophages cultured for three days, to investigate whether enhanced macrophage elastolytic activity alone is a determining factor in the susceptibility of some smokers to obstructive lung disease. Twenty current smokers and 12 former smokers who had abstained from smoking for at least three years were studied. All patients had spirometric evidence of irreversible air flow obstruction. Current smokers had a cell yield (mean +/- SD) of 138.7 +/- 36.4 X 10(6) cells (alveolar macrophages 94.2% +/- 2.1%) compared with 31.4 +/- 14.1 X 10(6) cells (macrophages 86.5% +/- 4.7%) in former smokers. Elastolytic activity in the initial lavage cell population from current and former smokers, measured with the synthetic elastase substrate succinyl-L-alanyl-L alanyl-L-alanine-p-nitroanilide, and expressed as the equivalent of 1 microgram of porcine pancreatic elastase, was respectively 0.113 +/- 0.003 and 0.096 +/- 0.004 microgram pancreatic elastase/mg cell protein. After three days in culture macrophage elastolytic activity in the current and former smokers' cells was respectively 0.107 +/- 0.006 and 0.011 +/- 0.001 microgram pancreatic elastase/mg cell protein (p less than 0.05). The elastase activity of the cultured alveolar macrophages from five current smokers had the inhibitor profile of a metalloproteinase. Our results indicate that enhanced macrophage elastolytic activity alone is not a determining factor in the susceptibility of some smokers to develop obstructive lung disease.     

Morbid obesity treated by gastroplasty: radionuclide gastric emptying studies

Mechanisms by which gastroplasty for morbid obesity causes weight loss are poorly understood. We studied the role of altered gastric emptying in 50 patients before surgery, 1-4 weeks after surgery, and 2-24 months after surgery using technetium-99m pentetate in water for liquid meals and a Tc-99m styrene divinylbenzene copolymer resin in oatmeal for semisolid meals. We determined the emptying half-times of the stomach before and after surgery in the proximal and distal compartments. The proximal compartment emptied promptly in the early and late postoperative periods. The distal compartment emptied liquids at rates similar to those before surgery, while the late postoperative emptying of semisolids was significantly faster. The stoma connecting the two compartments thus permits rapid transit of liquids and semisolids without delay of distal compartment emptying. No correlation was seen between the emptying half-times or changes thereof and eventual weight loss. Delayed gastric emptying is therefore not the mechanism for satiety and weight loss after gastroplasty has been performed.     

Pax3 mRNA is decreased in the hearts of rats with experimental diaphragmatic hernia

Rats with nitrofen-induced congenital diaphragmatic hernia (CDH) have heart hypoplasia and cardiovascular malformations. The mechanism of action of nitrofen involves changes in neural crest signaling. Pax3 function is required for cardiac neural crest cells to complete their migration to the developing heart. The aim of this study was to examine whether Pax3 expression is changed at two gestational endpoints in rat embryos or fetuses exposed to nitrofen. On day E9.5 of gestation, pregnant rats received either 100 mg of nitrofen (n=10) or vehicle alone (control, n=10). The fetuses were recovered on E15 or E21. Their hearts were dissected out and weighed. Pax3 mRNA expression was determined by real-time polymerase chain reaction. We used two-tailed Students t-tests to compare groups, with a threshold of significance of p<0.05. Compared with controls, nitrofen-exposed fetuses had heart hypoplasia in terms of heart/body weight ratio (0.62±0.10% vs. 0.77±0.17%, p<0.05). Pax3 mRNA expression in the heart was significantly decreased on E15 in nitrofen-treated embryos (32.94±17.11 U vs. 55.09±11.56 U, p<0.05), and it was still decreased, although not significantly, in the hearts of nitrofen-exposed fetuses recovered on E21 (15.67±5.56 U vs. 20.51±5.92 U, not significant). In conclusion, Pax3 is underexpressed in the hearts of nitrofen-exposed embryonal rats before the end of gestation. The mechanism of action of Pax3 should be further investigated because it could be one of the targets for future prenatal transplacental intervention.Paper presented at the XVIIth International Symposium of Pediatric Surgical Research, Liverpool, United Kingdom, 1–2 October, 2004.     

D2 lymphadenectomy in the management of gastric cancer

Background Gastric carcinoma is a significant cause of death in Ireland. Surgery offers the best option of cure, but the five-year survival following resection remains dismal at 10–15%. Experience from Japan and from some Western units suggest that an extended (D2) lymphadenectomy in association with gastrectomy increases the prospect of cure, but concern about the morbidity and mortality of this operation and lack of evidence from randomised studies has limited its acceptance. Aims This study reports the experience of a specialist upper gastrointestinal unit with D2 gastrectomy in a four-year audit. Methods Sixty-two resections were performed for gastric cancer. Results Nineteen patients were deemed unsuitable for the D2 procedure and underwent a more limited lymphadenectomy (DO or D1). Forty-three patients underwent D2 resection, 12 with an oesophagogastrectomy, 22 with total gastrectomy and nine with a sub-total distal resection. Eight patients undergoing D2 resection had extended resections, five with splenectomy and three with a distal pancreatectomy. Post-operative complications occurred in 31% of patients. Thirty-day and 90-day mortality were zero. Median survival was 822 days in the D2 group (range 120–1,320). Conclusions These results show that a D2 gastrectomy can be performed with a low morbidity and mortality and a median survival of greater than two years.