Cardioselectivity of alpha-tocopherol analogues, with free radical scavenger activity, in the rat.

MDL74270 (6-acetyloxy-3,4-dihydro-N,N,N,2,5,7, 8-heptamethyl-2H-1-benzopyran-2-ethanaminium, 4-methylbenzenesulfonate) is a quaternary amine analogue of alpha-tocopherol with free radical scavenger properties. Rats were injected iv with [14C]MDL74270 (0.91 mg/kg), and whole blood and heart tissue were sampled. Five min after drug, the heart tissue/blood ratio (T/B) of radioactivity was 3.5, whereas at 1 hr it was 20.1 and remained at this value up to at least 6 hr. After iv administration the t 1/2 of radioactivity in blood was 6.3 hr, but po blood levels could not be quantified. The 0- to 96-hr urinary elimination of radioactivity was 39.9 +/- 5.7% of the dose after iv and only 1.2 +/- 0.4% after po administration, conversely, 44.7 +/- 5.2% was excreted in feces after iv and 79.1 +/- 17.4% after po administration. These results confirmed poor oral absorption of the compound. Tissue distribution of [14C]MDL74270 was compared with that of its tertiary amine analogue [14C]MDL74366 in rat heart, skeletal muscle, brain, and whole blood, after iv administration (1 mg/kg). The heart T/B was above 20, 1-6 hr after [14C]MDL74270, whereas it was less than 2 after [14C]MDL74366. Over the 1- to 6-hr time interval, skeletal muscle T/B varied from 1.8 to 5 compared with 1.5 to 0.6 for [14C] MDL74366. Brain T/B was higher after the tertiary amine compound. Results showed marked cardioselectivity of radioactivity after [14C] MDL74270. Differential centrifugation of heart homogenates showed that radioactivity was equally distributed between the major subcellular fractions studied.(ABSTRACT TRUNCATED AT 250 WORDS)     

Laparoscopic-assisted percutaneous endoscopic gastrostomy in children and adolescents.

OBJECTIVE: Pediatric gastric access for long-term enteral feeding may be performed via a laparotomy, laparoscopy, or a percutaneous approach. In children and adolescents, laparoscopic-assisted gastrostomy may be difficult due to a thick abdominal wall. Therefore, if the abdominal wall is estimated to be >2 cm on physical examination, or in children in whom a percutaneous endoscopic gastrostomy was unsuccessfully attempted by a gastroenterologist, we routinely perform a laparoscopic-assisted percutaneous endoscopic gastrostomy. METHODS: From January 1998 through February 2003, we retrospectively reviewed 15 cases of a laparoscopic-assisted percutaneous endoscopic gastrostomy. Instruments used to perform this technique are a percutaneous endoscopic gastrostomy kit, an Olympus flexible endoscope, and one 5-mm STEP port placed through an infraumbilical incision for a 5-mm, 30-degree scope. RESULTS: Age range was 2 years to 20 years (mean, 10). Operative time ranged from 20 minutes to 45 minutes. When a concurrent laparoscopic Nissen fundoplication was performed (n = 6), the percutaneous endoscopic gastrostomy was placed after completion of the Nissen fundoplication. No intraoperative complications occurred, and all tubes were successfully placed. Feeds were instituted the following day and advanced to goal. To date, no postoperative complications have occurred, and revision has not been necessary. CONCLUSIONS: Laparoscopic-assisted percutaneous endoscopic gastrostomy in children and adolescents is safe and effective. Utilizing laparoscopy permits evaluation of the peritoneum and lysis of adhesions, if necessary. Moreover, laparoscopy provides excellent exposure for accurate placement of the PEG, while avoiding injury to other organs.     

A prospective study of tobacco use and multiple myeloma: evidence against an association

The relationship between the use of cigarettes and other tobacco products and the risk of multiple myeloma was examined in a cohort of nearly 250,000 American veterans followed prospectively for 26 years. Compared with men who had never used tobacco, the risk of death from myeloma was not increased among current (relative risk [RR]=0.9, 95 percent confidence interval [CI]=0.8–1.2) or former (RR=1.0, CI=0.8–1.3) cigarette smokers, nor among users of chewing tobacco or snuff (RR=1.0, CI=0.4–2.3). Risk was only slightly and nonsignificantly increased among pipe or cigar smokers (RR=1.2, CI=0.9–1.5). There was no indication of increasing risk with amount of tobacco used or earlier age at first use. With over 90 percent power to detect a 30 percent increased risk of this tumor occuring among current cigarette smokers, this study provides the strongest evidence to date against an association of cigarette smoking with multiple myeloma.Epidemiology and Biometry Program, Division of Cancer Etiology, National Cancer Institute. Westat, Inc. Rockville, MD. National Cancer Institute, 6130 Executive Blvd, Room 418, Rockville, MD 20892, USA.     

Association of high levels of serum antibody to staphylococcal toxic shock antigen with nasal carriage of toxic shock antigen-producing strains of Staphylococcus aureus

Forty-four asymptomatic male subjects were examined for their nasal carriage of strains of Staphylococcus aureus capable of producing staphylococcal toxic shock antigen (TSA), an exotoxin implicated in the pathogenesis of toxic shock syndrome. In addition, the levels of antibody to TSA in sera from these subjects were determined by an enzyme-linked immunosorbent assay. S. aureus was isolated from the anterior nares of 23 subjects. Of those 23 isolates of S. aureus, 9 were found to produce TSA. All individuals carrying strains of S. aureus capable of producing TSA had high to moderate levels of antibody to TSA. In contrast, those individuals carrying strains not producing TSA had levels of antibody to TSA ranging from high to nondetectable. A second examination of nasal samples from 42 of these subjects revealed that 86% of those carrying S. aureus initially still carried S. aureus after a period of 3 months; all subjects found to carry TSA-producing strains initially and that were examined a second time yielded TSA-producing strains once again.     

Previously unrecognized congenital progeroid disorder

We report on a 5-year-old girl with a progeroid disorder and compare her to a previously reported woman now in her forties, whom she resembles to a striking degree. Common manifestations include pre- and post-natal growth retardation, markedly diminished subcutaneous fat, wrinkled skin, abnormally scant hair growth, hypoplastic distal phalanges with hypoplastic nails, umbilical hernia, large open anterior fontanelle, and normal cognitive and motor development. Both patients have had a prematurely aged appearance since birth. These 2 patients appear so different from previously reported patients with progeroid disorders that they may represent a separate entity.