Mid- and long-term outcome of extremely low birth weight (ELBW) infants: an analysis of prognostic factors.

OBJECTIVE: To evaluate morbidity and long-term neurological outcome in a group of extremely low birth weight infants (ELBW; <1000 g) and to correlate the neurological outcome in a small group of intrauterine growth retarded (IUGR) infants with Doppler indices in the umbilical artery. METHODS: One hundred and eighty-three live births with birth weight <1000 g and gestational age < or=34 weeks were included in the study. Neonatal mortality and morbidity were evaluated. At 24 months of corrected age an evaluation of the neurological development of the children was made by pediatric neuropsychiatrists. The children were classified as: normal, with minor neurological sequelae, and with major neurological sequelae. The evaluation of umbilical artery velocimetry was applied to 84 fetuses presenting with IUGR and the velocimetric patterns were correlated with neurological outcome. RESULTS: In the 183 infants discharged from the Department of Neonatology, respiratory distress syndrome (RDS) was the most frequent pathology (76.6%); less frequent were bronchopulmonary dysplasia (BPD; 19.5%), patent ductus arteriosus (PDA; 29.7%) and necrotizing enterocolitis (NEC; 5.5%). Retinopathy of prematurity (ROP) affected 34 children (26.6%), and 14.8% of the children developed intraventricular hemorrhage (IVH) and 14.1% periventricular leukomalacia (PVL). Out of the 183 infants included in the study, 107 had a neurological assessment at two years: 22 (20.6%) suffered from severe neurological sequelae, 20 (18.7%) from minor neurological sequelae, and 65 (60.7%) had a normal neurological development. In 84 IUGR fetuses a Doppler evaluation of the umbilical artery was performed: the incidence of neurologically normal children was 67% in the group with normal umbilical velocimetry, 93% in the group with increased umbilical resistances, and 59% in those with absent or reversed end-diastolic velocity (ARED). CONCLUSIONS: This study, confirms that an extremely low birth weight implies a high risk of perinatal mortality and neonatal morbidity, but that the most significant variable that can be correlated to the long-term neurological outcome is the gestational age.

Carboplatin and piroxicam therapy in 31 dogs with transitional cell carcinoma of the urinary bladder.

Invasive transitional cell carcinoma (TCC) of the urinary bladder responds poorly to medical therapy. Combining platinum chemotherapy with a cyclooxygenase (cox) inhibitor has shown promise against canine TCC, where the disease closely mimics the human condition. A phase II clinical trial of carboplatin combined with the cox inhibitor, piroxicam, was performed in 31 dogs with naturally occurring, histopathologically confirmed, measurable TCC. Complete tumour staging was performed before and at 6-week intervals during therapy. Tumour responses in 29 dogs included 11 partial remissions, 13 stable disease and five progressive disease. Two of the 31 dogs were withdrawn prior to the re-staging of the tumour. Gastrointestinal toxicity was observed in 23 dogs. Hematologic toxicity was noted in 11 dogs. The median survival was 161 days from first carboplatin treatment to death. In conclusion, carboplatin/piroxicam induced remission in 40% of dogs providing evidence that a cox inhibitor enhances the antitumour activity of carboplatin. The frequent toxicity and limited survival, however, do not support the use of this specific protocol against TCC.

Improved ion chromatography-integrated pulsed amperometric detection method for the evaluation of biogenic amines in food of vegetable or animal origin and in fermented foods.

An improved method for the simultaneous determination of underivatized biogenic amines, cadaverine, putrescine, spermidine, histamine, tyramine and some amino acids precursors, histidine and tyrosine, in food products, based on ion-exchange chromatography (IC) with integrated pulsed amperometric detection (IPAD) has been developed. The method was successfully used for the analysis of biogenic amines and amino acids in food both of vegetable (kiwi, Actinidia chinensis) and animal origin, (fish, pilchard), as well as in fermented foods, such as cheese (Emmenthal) and dry sausages (salami). The method was also successfully used to study the changes in biogenic amines during the ripening of dry fermented sausages (salami). The analytes were extracted from foods with perchloric acid and the extracts were purified by liquid-liquid partition using n-hexane. Determination of biogenic amines was performed through cation-exchange chromatography with isocratic elution and IPAD. The detection limits for the analytes under investigation were found to range from 1.25 to 2.50 ng, at a signal-to-noise ratio of 3:1. Average recoveries ranged from 85.5 to 97.4% and R.S.D. values ranged from 3.4 to 8.8. The proposed method offers a number of advantages over our previous IPAD method, such as the application to a larger number of analytes and matrices, a simpler extraction procedure and clean-up, isocratic elution using low acid and base concentrations, an improved chromatographic separation and a lower detection limit.

Determination of diarrheic shellfish toxins in mussels by microliquid chromatography-tandem mass spectrometry.

A fast, sensitive, and specific procedure for determining toxins that cause diarrheic shellfish poisoning (DSP) using microliquid chromatography coupled with tandem mass spectrometry (micro-LC-MS-MS) is reported. The lipophylic polyether acidic toxins okadaic acid (OA), its isomer dinophysistoxin-2 (DTX-2), the 35-methylokadaic acid dinophysistoxin-1 (DTX-1), and the novel toxin dinophysistoxin-1B (DTX-2B; recently isolated from Irish mussels) were extracted from shellfish tissues with acetone and chromatographed by isocratic elution at 10 microL/min with CH3 CN-H2O, 80 + 20 (v/v), containing 0.1% trifluoroacetic acid, through a C18 reversed-phase column (1.0 mm id). The chromatograph is coupled via an ion spray interface to an atmospheric pressure ionization source. Collision-induced-dissociation (CID) ion mass spectra of the protonated molecule, [M + H]+, at m/z 805 for OA, DTX-2, and DTX-2B and at m/z 819 for DTX-1, were obtained in MS-MS experiments to identify 2 diagnostic fragment ions for each analyte that could be used for selected-reaction-monitoring (SRM) micro-LC-MS-MS analysis. The CID spectrum of DTX-2B confirmed it to be a new OA isomer, like DTX-2. Standard curves obtained by SRM micro-LC-MS-MS were linear (r2 > or = 0.9992) over the range 0.05-1.00 micrograms/mL (i.e., 0.10-2.00 micrograms toxin/g hepatopancreas), and a detection limit of 15 pg/injection was obtained for each DSP toxin. Average recoveries ranged from 95 to 101%, and coefficients of variation ranged from 1.8 to 3.4%. This novel SRM micro-LC-MS-MS method was used to confirm acidic DSP toxins in Irish and Italian toxic mussels. It offers a high degree of specificity because analyte confirmation is based on retention time, molecular weight, structural information obtained from the presence of 2 diagnostic fragments for each analyte, and ion ratios. OA was found in both Irish (< or = 0.7 micrograms/g hepatopancreas) and Italian (< or = 1.5 micrograms/g hepatopancreas) mussels. DTX-1 was found only in Italian mussels (< or = 0.3 micrograms/g hepatopancreas). DTX-2 (< or = 6.1 micrograms/g hepatopancreas) and DTX-2B (< or = 0.08 micrograms/hepatopancreas) were unique to Irish shellfish.

First report of pectenotoxin-2 (PTX-2) in algae (Dinophysis fortii) related to seafood poisoning in Europe.

Pectenotoxin-2 (PTX-2), a polyether-lactone included in the neutral class of diarrhoetic shellfish poisoning (DSP) toxins, has been unambiguously detected in Dinophysis fortii collected in the northern Adriatic Sea (Emilia Romagna coasts). This is the first report of such a toxin in Europe. This lipid soluble toxin was identified both in crude methanolic phytoplankton extract and in the neutral fraction obtained by extract chromatography on a basic alumina column. The techniques used were reversed phase high-performance liquid chromatography followed either by UV diode-array detection (LC-UV-DAD) or by mass spectrometry (LC-MS) and tandem mass spectrometry (LC-MS-MS) using an atmospheric-pressure ionization source and an ionspray interface. Okadaic acid (OA) was also found in the D. fortii specimens and quantified as 15 pg/cell. Although quantitation of PTX-2 was not possible due to the lack of pure toxin, the high PTX-2:OA ratio suggested PTX-2 was significant in the D. fortii specimens. The presence of PTX-2 in a region with no previous report of DSP neutral toxic compounds may indicate a risk of human poisoning. Serious efforts should therefore be made to develop suitable routine methods capable of detecting the presence of PTXs in biological materials of marine origin, in order to assure the wholesomeness of seafood products.

Detection of diarrhoetic shellfish toxins in mussels from Italy by ionspray liquid chromatography-mass spectrometry.

Direct detection of okadaic acid (OA), dinophysistoxin-1 (DTX-1) and some of their related compounds in toxic mussels (Mytilus galloprovincialis) is reported using ionspray liquid chromatography-mass spectrometry (LC-ISP-MS). This was employed to analyse diarrhoetic shellfish poisoning (DSP) toxins in mussels collected from coastal areas of the northern and southern Adriatic Sea. DTX-1 was found in some samples from both the northern and southern Adriatic and this is the first report of the unambiguous identification of this toxin in Italian mussels. The low levels found indicate that this toxin did not play a significant role in toxicity in these samples. Okadaic acid was found in all the mussels examined, although its concentration was not always sufficient to account for DSP toxicity. Furthermore, two related compounds of OA were detected in all the samples and one related DTX-1 compound was observed in some samples from the northern Adriatic. All three compounds are still to be identified, but it is possible that these substances are involved in mussel DSP toxicity in the Adriatic Sea.