Citations

ABSTRACT The results for a real-time PCR assay, using the LightCycler Strep B analyte-specific reagents (Roche Diagnostics Corporation, Indianapolis, Ind.), were compared to a direct plate method combined with a broth enrichment culture method for detection of group B streptococcus colonization in pregnant women. Two separate evaluations were conducted using two different automated nucleic extraction instruments, the MagNA Pure LC instrument (Roche Diagnostics Corporation) and the lower-capacity MagNA Pure Compact instrument (Roche Diagnostics Corporation). The sensitivities, specificities, and positive and negative predictive values for the different evaluation methods were as follow: for the LightCycler Strep B assay with MagNA Pure LC, 100, 97, 90, and 100%, respectively; for the LightCycler Strep B assay with MagNA Pure Compact, 92.5, 99, 97, and 97.5%, respectively. The LightCycler Strep B assay combined with either MagNA Pure LC or MagNA Pure Compact extraction is a suitable method for detecting group B streptococcus colonization in pregnant women. An advantage of the LightCycler assay over culture is the considerably reduced turnaround time for results.

PD (Parkinson's disease) is an aetiologically heterogeneous disorder characterized by a clinical phenotype consisting of resting tremor, rigidity and bradykinesia. Motor symptoms are associated with a progressive loss of dopaminergic neurons, with Lewy body inclusions within surviving neurons. Although heritability studies have shown evidence of familial aggregation, twin studies have provided limited support for a genetic aetiology. Nevertheless, classical linkage methods have nominated 11 regions of the genome and pathogenic mutations have been identified in several genes, including α-synuclein, parkin, ubiquitin C-ter-minal hydrolase L1, oncogene DJ-1, PTEN-induced protein kinase 1 and microtubule-associated protein tau. Most recently, heterozygous mutations in LRRK2 (leucine-rich repeat kinase 2) were found to cause late-onset, autosomal-dominant PD. Despite their consistent clinical phenotype, family members with LRRK2 mutations can have variable α-synuclein and tau pathologies. Lrrk2 is a member of the Roc (Ras of complex proteins) family, with Ras GTPase and MAPKKK (mitogen-activated protein kinase kinase kinase) catalytic domains. Thus its discovery highlights vesicle dynamics and secondary-messenger signalling in disease pathophysiology. To diagnose a disease accurately and effectively treat it, requires an understanding of its molecular pathogenesis. Herein, we provide an overview of the genetics of PD, how these discoveries are revolutionizing long-held beliefs and more importantly how this knowledge may be translated into patient therapy.

The tau (MAPT) locus exists as two distinct clades, H1 and H2. The H1 clade has a normal linkage disequilibrium structure and is the only haplotype found in all populations except those derived from Caucasians. The H2 haplotype is the minor haplotype in Caucasian populations and is not found in other populations. It shows no recombination over a region of 2 Mb with the more common H1 haplotype. The distribution of the haplotype and analysis of the slippage of dinucleotide repeat markers within the haplotype suggest that it entered Homo sapiens populations between approx. 10000 and 30000 years ago. However, sequence comparison of the H2 haplotype with the H1 haplotype and with the chimp sequence suggests that the common founder of the H1 and H2 haplotypes was far earlier than this. We suggest that the H2 haplotype is derived from Homo neanderthalensis and entered H. sapiens populations during the co-existence of these species in Europe from approx. 45000 to 18000 years ago and that the H2 haplotype has been under selection pressure since that time, possibly because of the role of this H1 haplotype in neurodegenerative disease.

How many people do you know who have physical problems they attribute to computer use? (I wear wrist braces at night myself, so that my mild carpal-tunnel syndrome doesn't bother me much during the day.) Many of us seem to have the impression that such problems arise mainly from poor hardware design... or perhaps from an overindulgence in gaming, with its incessant, repetitive arm/wrist/hand/finger movements. But is it that simple? In this Whiteboard column, Doug Anderson points out how interaction design and usability efforts can overlook such problems, and urges us to pay more attention to them. I would add one more suggestion to his list of ideas: Even when longitudinal usability testing is not feasible, we can monitor our applications and systems in long-term use and note any physical problems that tend to appear among our users. ---Elizabeth Buie

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, safety, dosage, and administration of alvimopan, a peripherally acting μ-opioid receptor antagonist, in the management of postoperative ileus (POI). DATA SOURCES: A literature search (1980–October 2004%) applying the terms alvimopan, ADL 8–2698, and LY246736 was conducted using MEDLINE. Information was also obtained from scientific congress abstracts and data on file with the manufacturer. STUDY SELECTION AND DATA EXTRACTION: Studies and abstracts investigating alvimopan and POI were considered for inclusion; however, they were restricted to English-language articles. DATA SYNTHESIS: Alvimopan is a novel, peripherally acting μ-opioid receptor antagonist that is currently under evaluation for the management of POI. POI presents significant clinical challenges that can delay patient recovery and contribute to increased morbidity and prolonged hospitalization after surgery. Clinical trials have demonstrated that alvimopan, at oral doses of 6 and 12 mg, can accelerate time to recovery of gastrointestinal (GI) function and time to hospital discharge following abdominal surgery. The incidence of adverse events with alvimopan therapy was shown to be similar to that of placebo. CONCLUSIONS: Alvimopan is well tolerated and effective at accelerating GI recovery and time to discharge in patients who have undergone bowel resection or hysterectomy when administered prior to surgery and twice daily thereafter until discharge or for up to 7 days. Alvimopan potentially offers significant benefits for patients with POI over currently available treatments.

Dendritic cells (DCs) are classified in two states: immature DCs (iDCs), which perform sentinel functions, sampling for antigen and danger signals, and mature DCs (mDCs), which exhibit enhanced antigen-presenting functions but are no longer capable of acquiring antigen. We now describe DCs with a different activation phenotype: cells having the strong antigen-presenting functions of mDCs and the antigen-acquiring functions of iDCs. We have described an antibody that binds the costimulatory molecule B7-DC and activates DCs. The resulting phenotype is distinct from iDCs or mDCs matured by using Toll-like receptor (TLR) agonists. Ability to take up antigen increases, while expression of B71/2 costimulatory and MHC molecules remains unchanged. DCs matured with TLR agonists and then superactivated through B7-DC exhibit a previously unrecognized phenotype. These DCs recover the ability to take up antigen, which is normally lost after treatment with TLR-3 and TLR-9 agonists, yet retain the high expression of costimulatory and MHC molecules and strong antigen-presenting functions of mDCs. Immunization using TLR agonists and B7-DC XAb (cross-linking antibody) together as adjuvant resulted in substantially increased cytolytic T cell responses, particularly when minimal peptide antigens were used. By stimulating DCs with two distinct activation signals, a previously unrecognized phenotype exhibiting augmented antigen-presenting functions was obtained.