Distinguishing bipolar from unipolar depression: the importance of clinical symptoms and illness features.

BACKGROUND: Distinguishing bipolar disorder (BP) from major depressive disorder (MDD) has important relevance for prognosis and treatment. Prior studies have identified clinical features that differ between these two diseases but have been limited by heterogeneity and lack of replication. We sought to identify depression-related features that distinguish BP from MDD in large samples with replication. METHOD: Using a large, opportunistically ascertained collection of subjects with BP and MDD we selected 34 depression-related clinical features to test across the diagnostic categories in an initial discovery dataset consisting of 1228 subjects (386 BPI, 158 BPII and 684 MDD). Features significantly associated with BP were tested in an independent sample of 1000 BPI cases and 1000 MDD cases for classifying ability in receiver operating characteristic (ROC) analysis. RESULTS: Seven clinical features showed significant association with BPI compared with MDD: delusions, psychomotor retardation, incapacitation, greater number of mixed symptoms, greater number of episodes, shorter episode length, and a history of experiencing a high after depression treatment. ROC analyses of a model including these seven factors showed significant evidence for discrimination between BPI and MDD in an independent dataset (area under the curve = 0.83). Only two features (number of mixed symptoms, and feeling high after an antidepressant) showed an association with BPII versus MDD. CONCLUSIONS: Our study suggests that clinical features distinguishing depression in BPI versus MDD have important classification potential for clinical practice, and should also be incorporated as 'baseline' features in the evaluation of novel diagnostic biomarkers.

Genetic differentiation and phylogeography of gulls in the Larus cachinnans-fuscus group (Aves: Charadriiformes).

We studied mitochondrial genetic differentiation among nine taxa of large gulls of the Larus cachinnans-fuscus group, which form part of the circumpolar Herring Gull complex. Our primary interest was to see if there were unrecognized gene flow barriers, to what extent mitochondrial genetic population structure conformed to current taxonomic boundaries, and what it might reveal about possible differences in population history. Sequences (430 nucleotides) of the hypervariable control region I (HVR-I) were obtained from 580 individuals and proved highly informative within this recently diverged group of birds. Contrary to current classification, a basal split was revealed between an Atlantic-Mediterranean clade (atlantis, michahellis, armenicus) and a NW Palearctic-Central Asian clade (cachinnans, barabensis, mongolicus, fuscus-group). There was almost no mitochondrial gene flow between these two groups, although they are in geographical contact in two areas (eastern North Atlantic, Black Sea). Within each of the two major groups, there was strong phylogeographic structure with gene flow barriers between some neighbouring taxa (e.g. cachinanns vs. barabensis), but also a case of poor genetic differentiation between phenotypically distinct forms (barabensis vs. heuglini). At the subspecies level, current taxonomy corresponded well to molecular genetic structure: over 80% of the molecular genetic variance was partitioned among six (groups of) taxa. This is in sharp contrast to previous studies using allozymes and amplified fragment length polymorphism (AFLP) markers, which seemed to indicate extensive nuclear gene flow. Within-taxon haplotype phylogenies and mismatch distributions revealed contrasting demographic histories: cachinnans (Ponto-Caspian region) and atlantis (NE Atlantic) represent ancient lineages with large long-term population sizes, inland forms stem from very recent colonization events (barabensis, mongolicus) or passed through a population bottleneck (armenicus).

Susceptibility of Legionella pneumophila to eight antimicrobial agents including four macrolides under different assay conditions.

A comparison of agar dilution and microdilution susceptibility testing for eight antimicrobial agents, including roxithromycin, was performed against 48 isolates of Legionella pneumophila. For agar dilution tests, charcoal free agar (BSYE) and charcoal supplemented agar (BCYE) were used. In general, BSYE agar produced lower MICs than BCYE agar, except for imipenem. Microdilution testing data fell between the data obtained for the two agar media. The MBCs were two to sixteen fold higher than the MICs. Prolongation of the incubation time from 48 h to 72 h or growth in 5% CO2 did not influence the results. As tested by the microdilution method, an increase in the inoculum from 10(5) to 10(7) was associated with a two-fold increase in the MIC. Roxithromycin and two other investigational macrolides (A-56268 and rosaramicin) demonstrated better in-vitro activity than erythromycin.

Comparative in-vitro activities of A-56268 (TE-031) and erythromycin against 306 clinical isolates.

The inhibitory (MIC) and bactericidal (MBC) activities of a new macrolide A-56268 (TE-031) against 306 clinical aerobic bacterial isolates was compared with that of erythromycin. The MIC90/MBC90 ratios for A-56268 were: Campylobacter jejuni 4/16, Haemophilus influenzae 8/8-16, H. parainfluenzae 8/8-16, Legionella pneumophila 0.06/0.5, methicillin-sensitive isolates of Staphylococcus aureus 0.5/1, and coagulase negative staphylococci 1/8, methicillin resistant isolates of Staph. aureus and coagulase negative staphylococci greater than 16/ greater than 16, Streptococcus pneumoniae 0.06/0.125, streptococcus Group A 0.06/2-4, streptococcus Group B 0.06/8- greater than 16, streptococcus Groups C and G 0.125/8 and Str. faecalis 4/64. Compared with erythromycin, A-56268 had greater inhibitory and bactericidal activity against isolates of L. pneumophila, with an MIC90 16-fold less and an MBC90 eight-fold less than that of erythromycin. Except for enterococci, A-56268 showed inhibitory activity equal to or greater than that of penicillin G against isolates of streptococci and an MIC two-fold less than that of erythromycin. For other strains tested, the inhibitory and bactericidal activities of A-56268 and erythromycin were similar. The clinical importance of the differences between these two macrolides will depend on the pharmacokinetic and tissue penetration properties of the new compound.