Mast cells and exosomes in hyperoxia-induced neonatal lung disease.

Chronic lung disease of prematurity (CLD) is a frequent sequela of premature birth and oxygen toxicity is a major associated risk factor. Impaired alveolarization, scarring, and inflammation are hallmarks of CLD. Mast cell hyperplasia is a feature of CLD but the role of mast cells in its pathogenesis is unknown. We hypothesized that mast cell hyperplasia is a consequence of neonatal hyperoxia and contributes to CLD. Additionally, mast cell products may have diagnostic and prognostic value in preterm infants predisposed to CLD. To model CLD, neonatal wild-type and mast cell-deficient mice were placed in an O2 chamber delivering hyperoxic gas mixture [inspired O2 fraction (FiO2 ) of 0.8] (HO) for 2 wk and then returned to room air (RA) for an additional 3 wk. Age-matched controls were kept in RA (FiO2 of 0.21). Lungs from HO mice had increased numbers of mast cells, alveolar simplification and enlargement, and increased lung compliance. Mast cell deficiency proved protective by preserving air space integrity and lung compliance. The mast cell mediators ß-hexosaminidase (ß-hex), histamine, and elastase increased in the bronchoalveolar lavage fluid of HO wild-type mice. Tracheal aspirate fluids (TAs) from oxygenated and mechanically ventilated preterm infants were analyzed for mast cell products. In TAs from infants with confirmed cases of CLD, ß-hex was elevated over time and correlated with FiO2 Mast cell exosomes were also present in the TAs. Collectively, these data show that mast cells play a significant role in hyperoxia-induced lung injury and their products could serve as potential biomarkers in evolving CLD.

Acute and subacute toxicity studies of Aegle marmelos Corr., an Indian medicinal plant.

This study was designed to elucidate the toxicity of the widely used plant Aegle marmelos in rats. We have taken total alcoholic, total aqueous, whole aqueous and methanolic extracts isolated from the leaves of A. marmelos and studied their toxic effects. Acute, subacute and LD(50) values were determined in experimental rats. The dead animals were obtained from primary screening studies, LD(50) value determination experiments and acute studies subjected to postmortem studies. The external appearance of the dead animals, the appearance of the viscera, heart, lungs, stomach, intestine, liver, kidney, spleen and brain were carefully noted and any apparent and significant features or differences from the norm were recorded. Following the chronic administration of A. marmelos for 14 days, the vital organs such as heart, liver, kidney, testis, spleen and brain were carefully evaluated by histopathological studies and any apparent and significant changes or differences from the norm were studied. From the acute administration of A. marmelos, the LD(50) values were determined using graphical method. The hearts stopped in systolic stand-still in the acute experiments. There were no remarkable changes noticed in the histopathological studies after 50 mg/kg body wt of the extracts of A. marmelos when administered intraperitoneally for 14 days successively. Pathologically, neither gross abnormalities nor histopathological changes were observed. After calculation of LD(50) values using graphical methods, we found a broad therapeutic window and a high therapeutic index value for A. marmelos extracts. Intraperitoneal administration of the extracts of the leaves of A. marmelos at doses of 50, 70, 90 and 100 mg/kg body wt for 14 consecutive days to male and female Wistar rats did not induce any short-term toxicity. Collectively, these data demonstrate that the extracts of the leaves of A. marmelos have a high margin of drug safety.

Role of steroids in croup and beta agonists in bronchiolitis.

The administration of corticosteroids by various routes in the treatment of croup remains controversial as studies with varying designs and outcome measures have reported conflicting results. However, meta-analysis supports the use of steroids in croup. A dose equivalent to or greater than 100 mg/kg body weight of hydrocortisone, administered orally or parenterally appears to be effective. Nebulized budesonide in a dose of 1,000 micrograms, when dosages are given 30 minutes apart is also effective. The L-epinephrine is as effective as racemic epinephrine and should be used to relieve symptoms with or without steroids. Summarizing the value of beta agonists, for treatment of bronchiolitis is rather challenging. Beta agonists offer significant relief to only a subgroup of infants, with bronchiolitis, albeit, it remains a challenge to identify these infants prospectively. Availability of RSV immune globulin for prevention of RSV disease in high-risk infants and better defining the role of ribavirin for selected patients may offer additional avenues to the treating physician.

Bipolar versus monopolar sphincterotomy: a prospective trial.

OBJECTIVES: To determine the frequency of complications, specifically pancreatitis, associated with endoscopic sphincterotomy, comparing the standard, monopolar electrocautery current to the bipolar system. METHODS: One-hundred consecutive patients requiring ERCP and sphincterotomy, 50 patients in each group, were randomized to receive a sphincterotomy using either the bipolar system (Bitome) or the standard monopolar system. Cannulation with the selected sphincterotome was successful in 92 patients, but crossover to the other system was necessary in eight patients, five bipolar and three monopolar. The performance of sphincterotomy was conducted similarly and by the same investigator. Excessive manipulation of the papilla during difficult cannulation was avoided, and no pre-cut, needle knife, or wire-guided assisted cannulation techniques were used in either group. RESULTS: Complications were assessed during follow-up review of charts and telephone interviews. Pancreatitis did not occur in the bipolar group; however, six patients in the monopolar group developed clinical and biochemical evidence of pancreatitis (p < 0.047). CONCLUSIONS: Sphincterotomy using bipolar technology appears to reduce the frequency of pancreatitis when compared to monopolar technology in a prospective, randomized fashion. Because bipolar electrocautery current is localized to the accessory tip, radiofrequency does not encounter impedance through the patient's body mass, and tissue injury is reduced. This fact may account for the decreased incidence of pancreatitis in the bipolar group. Larger studies are called for to support this conclusion.

Stent-guided sphincterotomy.

Performing sphincterotomy when either Billroth II gastrectomy or complicated periampullary diverticula are present may increase the risk of complications. In addition a sphincterotomy on the main pancreatic sphincter or the papilla of Santorini presents complicated problems. Stent-guided sphincterotomy has been utilized in 229 patients presenting to our institution from 1983 through 1992. They were performed in 67 patients who had undergone Billroth II gastrectomy, 23 with periampullary diverticula, 57 with pancreas divisum, and 82 with a history of recurrent pancreatitis. To prevent ductal injury or perforation, a stent is first inserted into the biliary or pancreatic duct to guide the sphincterotomy incision. The sphincterotomy is performed using electrocautery current delivered through a "needle knife" sphincterotome. Pancreatitis occurred in 19 patients (8.3%). It was mild in 17 and moderate in two patients. One patient experienced severe hemorrhage requiring surgery. No mortality or perforations occurred. The stent-guided needle knife sphincterotomy approach is an effective technique. It has a low complication rate even in these difficult anatomic conditions. It assures that the incision precisely follows the duct when performing pancreatic sphincterotomy.

Endoscopic sphincterotomy for biliary pancreatitis: an alternative to cholecystectomy in high-risk patients.

Recurrent biliary pancreatitis frequently is associated with an intact gallbladder containing stones. This condition has been effectively treated by removing the gallbladder, but there is evidence that endoscopic sphincterotomy might obviate the need for cholecystectomy in some patients. We performed prophylactic sphincterotomy in 49 patients who presented with biliary pancreatitis more than once and who were considered at risk for surgery. The majority (39 patients) were treated electively after resolution of pancreatitis, while the remainder (10 patients) were treated urgently during their index admission because of continuing symptoms. No patient experienced recurrent pancreatitis over a mean follow-up period of 48 months. No mortality occurred in this endoscopic series, and no significant morbidity was experienced. Based on our results, we advocate performing sphincterotomy in the aged patient or younger patients considered at high risk for surgery who present with a history of recurrent pancreatitis and cholelithiasis.

Stent Scraping for Histology: An Alternative Method for Obtaining Tissue to Rule out Neoplasia.

Despite improvement in diagnostic modalities, confirmation of a histologic diagnosis of cancer of the biliary tree and pancreas remains elusive. Attempts to collect positive cytology specimens from vigorous brushings or washings obtained at endoscopy or percutaneously are often unsuccessful. In our unit, we have increased the yield by obtaining tissue scraped from prostheses that have been previously placed in either the bile duct or the pancreatic duct. The stents are first flushed with saline to collect cytology specimens, after which, they are bisected and scraped, and these contents are prepared in a manner similar to that used to prepare biopsy samples. Twelve of 16 scraped samples, 9 bile duct and 3 pancreas, were positive for adenocarcinoma. The cytology specimens were positive in only 4 of the 12. We recommend this method of sampling from material contained within prostheses as an adjunct when previous brushings, washings, or biopsies are negative.