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.     

Peripheral noxious stimulation induces CREM expression in dorsal horn: involvement of glutamate

Thermal washout curves have been proposed as noninvasive tools for analysing lower airway dimensions and pulmonary blood flow, but how upper airway heat transfer affects these washout curves is unclear. The present study was designed to compare extrathoracic and tracheobronchial contributions to thermal washout curves. Respiratory frequency, air ambient temperature, and body core temperature (tc) were varied in six male subjects before and after immersion in cold (1.1 degrees C) water for up to 2 h under three conditions: 1) control: ambient temperature (tamb) = 25 degrees C, rectal temperature change (delta tre) = 0 degrees C; 2) pre-immersion: tamb = 4 degrees C, delta tre = 0 degrees C; and 3) post-immersion: tamb = 25 degrees C, delta tre = -0.7 degrees C. Both peak expiratory nasal (tpn) and oral (tpo) airstream temperatures were measured. Each subject was tested twice. Expiratory tpo was generally higher than tpn in all conditions. Increasing breathing rates lowered tpn and tpo in the control and cold air environments. Orifice temperatures, which are presumed to reflect upper airway blood temperatures, correlated with both tpn and tpo. Lowering tc had no effect on washout curves during quiet breathing and affected only tpn during rapid breathing. The results suggest that while tracheobronchial conditions may contribute to thermal washout curves, extrathoracic conditions predominate. Strong correlations between orifice temperatures, peak expiratory nasal temperatures and peak expiratory oral temperature demonstrate the dominant role of upper airway heat exchange in determining thermal washout curves.