Application of tandem mass spectrometry for the analysis of long-chain carboxylic acids

The application of MS-MS for the analysis of long-chain carboxylic acids and their esters has proved enormously successful but expensive. It is discussed mainly on basis of results obtained with different instruments with lesser attention to principles of the method, which have been adequately reviewed elsewhere. The use of electrospray ionization (ESI) has greatly increased the sensitivity of the method and has permitted assay of total lipid extracts. The combination of HPLC with electrospray and single quadrupole mass spectrometry, LC-ESI-CID-MS, rivals the triple quadrupole MS-MS application in many instances at considerably lower cost. However, LC-ESI-MS-MS remains the most desirable system at the present time for lipid ester analyses.     

A comparison of the shake test, optical density, L/S ratio (planimetric and stechiometric) and PG for the assessment of fetal lung maturity

Our aim was to determine the diagnostic accuracy and reliability of four tests for the assessment of fetal lung maturity (FLM): shake test, optical density at 650 nm (OD650), lecithin to sphingomyelin ratio (L/S) by planimetry and stechiometry, and presence of phosphatydylglycerol. Amniotic fluid was obtained from 74 patients at various gestational ages. The shake test and the OD650 were performed according to published methods L/S was determined by TLC (thin-layer chromatography) and the ratio assessed by planimetry and stechiometrically by measurement of organic phosphorus from the chromatographic spots. PG was assessed similarly by TLC. When correlated with gestational age at amniocentesis, all tests correlated positively: shake test (r = 0.46, p < 0.005); OD650 (r = 0.31, p < 0.005); planimetric L/S (r = 0.77, p < 0.005); stechiometric L/S (r = 0.52, p < 0.005) and PG (r = 0.54, p < 0.005). The diagnostic accuracy of each test was as follows: the shake test and the OD650 had a sensitivity of 50%, while the steciometric L/S had a sensitivity of 75%, the planimetric L/S and the presence of PG were 100%. All four tests demonstrated a specificity greater than 64%, the highest for the PG presence being (83%) and the shake test (86%). Predictive negative values for lung maturity were > 93% for all tests, with the highest for the planimetric L/S and presence of PG being (100%). The study confirms that the determination of L/S ratio is still superior to other tests in terms of overall diagnostic accuracy. In addition, it was found that presence of PG was highly associated with the absence of respiratory complications in the newborn.     

A high proportion of novel mutations in BRCA1 with strong founder effects among Dutch and Belgian hereditary breast and ovarian cancer families

We have identified 79 mutations in BRCA1 in a set of 643 Dutch and 23 Belgian hereditary breast and ovarian cancer families collected either for research or for clinical diagnostic purposes. Twenty-eight distinct mutations have been observed, 18 of them not previously reported and 12 of them occurring more than once. Most conspicuously, a 2804delAA mutation has been found 19 times and has never been reported outside the Netherlands. A common haplotype spanning > or = 375 kb could be identified for each of the nine examined recurrent mutations, indicating the presence of multiple BRCA1 founder mutations in the Dutch population. The 2804delAA mutation has been estimated to have originated approximately 32 generations ago. No specific breast or ovarian cancer phenotype could be assigned to any of the common mutations, and the ovarian cancer incidence among 18 families with the 2804delAA mutation was heterogeneous.     

Cisapride reduces neonatal postoperative ileus: randomised placebo controlled trial

AIM: To assess the efficacy of cisapride in reducing ileus persisting to the tenth postoperative day after neonatal abdominal surgery. METHODS: A prospective, randomised, double blind trial comparing rectal cisapride (1.4-2.3 mg/kg/day) with placebo over seven days was undertaken in 33 neonates. RESULTS: Seven of 12 (58%) patients receiving placebo and eight of 11 (73%) receiving cisapride achieved a first sustained feed during treatment. Of those receiving cisapride, the first sustained feed occurred at 2.3 days (SEM 0.6) compared with 4.7 days (SEM 0.8) with placebo. By the seventh day the mean daily net enteral balance was 69 (SEM 18) ml/kg in the cisapride subgroup and 17 (SEM 8) ml/kg for those receiving placebo. Stool was passed on 6.3 (SEM 0.4) treatment days in the cisapride subgroup compared with 4.1 (SEM 1.0) treatment days in the placebo subgroup. CONCLUSION: Cisapride is effective in neonates with a prolonged ileus after abdominal surgery.     

9-Benzyladenines: potent and selective cAMP phosphodiesterase inhibitors

A 6-year-old Quarter Horse gelding with acute onset of a grade-4/5 lameness of the left forelimb 21 days after an encounter with a porcupine was examined. Quills had been removed by the referring veterinarian, and the horse had been treated with antibiotics and hydrotherapy for 14 days. The horse was pyretic and had effusion in the digital synovial sheath. Signs of pain were elicited on palpation of the area. A tentative diagnosis of septic tenosynovitis caused by a porcupine quill was made. Exploratory tenoscopy revealed large amounts of fibrin in the sheath and a 1.2-cm quill. Bacteriologic culture of synovial fluid yielded a pure growth of Staphylococcus aureus. The horse improved dramatically after tenoscopic removal of the quill, debridement of fibrin, and lavage to dilute inflammatory mediators and bacteria, debridement of fibrin, discovery and removal of a quill, and complete evaluation of the sheath for prognostic purposes. Tenoscopy can provide a means for direct observation and enhance the ability of clinicians to debride a septic synovial sheath in a minimally invasive manner.     

Preparation of SiB4±x and SiB6 plates by chemical vapour deposition of SiCl4 + B2H6 system

SiB_4±x and SiB₆ plates were prepared by chemical vapour deposition (CVD) using SiCl₄, B₂H₆ and H₂ gases under the conditions of deposition temperatures (T _dep) from 1323–1773 K, total gas pressures (P _tot) from 4–40 kPa and B/Si source gas ratio (m _B/Si=2B₂H₆/SiCl₄) from 0.2–2.8. The effects of CVD conditions on the morphology, structure and composition of the deposits were examined. High-purity and high-density SiB_4±x and SiB₆ plates about 1 mm thick were obtained at the deposition rates of 71 and 47 nm s⁻¹, respectively. The lattice parameter, composition and density of CVD SiB_4±x plates were dependent on their non-stoichiometry. The lattice parameter,a, was 0.6325 nm, butc ranged from 1.262–1.271 nm.The B/Si atomic ratio ranged from 3.1–5.0, and the density ranged from 2.39–2.45×10³ kg m⁻³. The CVD SiB₆ plates showed constant values of lattice parameters (a=1.444 nm,b=1.828 nm,c=0.9915 nm), composition (B/Si=6.0) and density (2.42×10³ kg m⁻³), independent of CVD conditions.     

High performance liquid chromatographic separation of stereoisomeric bile acids as their UV-sensitive esters

High performance liquid chromatographic separation of a series of mono-, di- and trihydroxylated 5β-cholanic acids which differ only in position and configuration of hydroxyl groups at positions C-3, C-7 and/or C-12, is reported. The C-24 free acids were derivatized to four different classes of UV-sensitive esters, i.e.,p-bromophenacyl (BP),m-methoxyphenacyl (MP), 4-nitrophthalimidemethyl (NPM) and 9-anthrylmethyl (AM) esters, and chromatographed on two, variants of C₁₈ reversed-phase columns (Nova-Pak C₁₈ and Zorbax ODS) with methanol-water systems as mobile phase. Separation efficiency and elution order of some isomeric pairs were influenced by both the structure of the C-24 ester groups and the nature of the columns used. Excellent chromatographic properties were found for those derivatives, particularly for the NPM esters.     

Relationship between local immune response to Helicobacter pylori and the diversity of disease: investigation of H. pylori-specific IgA in gastric juice

In order to evaluate the relationship between local immune response to Helicobacter pylori and the diversity of disease, 77 asymptomatic subjects who underwent a health examination were studied. Helicobacter pylori-specific IgG in serum and H. pylori-specific IgA in gastric juice were measured by ELISA, and the measured IgA titre was classified into two grades, low or high. Histological classification of gastritis was performed according to the Sydney system. Cytokines in gastric juice were also measured, and the cytotoxin-associated gene A (cagA) status of H. pylori was tested by PCR. Of the 65 subjects who were positive for H. pylori-specific IgG in serum, 38 (58.5%) were classified as H. pylori-specific IgA low titre in gastric juice and 27 (41.5%) had high titres. In the IgG-positive, IgA-low group, the rate of peptic ulcers (especially duodenal ulcers) in endoscopic findings was higher (P < 0.05); the score of activity and the density of H. pylori were higher (P < 0.001 and P < 0.05, respectively); the score of metaplasia was lower (P < 0.05); and the level of interleukin-1 beta was lower (P < 0.05) than in the IgG-positive, IgA-high group. The positive rate of the cagA gene was 84.4% and there was no significant difference between the two groups. There were differences in endoscopic and histological findings between the IgG-positive, IgA-low and the IgG-positive, IgA-high groups. It is suggested that persons infected with H. pylori can be divided into two different states of disease according to local immune response.