Delivery of antiplaque agents from dentifrices, gels, and mouthwashes.

Antiplaque agents delivered from toothpastes, gels, or mouthrinses can augment mechanical oral hygiene procedures to control the formation of supragingival plaque and the development of early periodontal disease. Clinically effective antiplaque agents are characterized by a combination of intrinsic antibacterial activity and good oral retention properties. The overall oral retention of an antiplaque agent is determined by the strength and rate of association of the agent with its receptor sites and the accessibility of these sites. The substantivity of an antiplaque agent and its clearance from the oral cavity are determined by the rate of dissociation of the agent from the receptor sites and the salivary composition and flow rate. Positively charged and non-charged organic molecules, metal ions, enzymes, and surface-active agents have all been considered as antiplaque agents. To exert clinical antiplaque activity, an antimicrobial agent must be formulated in a chemically compatible delivery vehicle to give optimal release and uptake to the sites of action in a biologically active form during its time of application. In principle, antiplaque activity may be enhanced by combining antimicrobial agents with broadly similar, but complementary, modes of action. Alternatively, the activity of a single agent may be increased by use of a retention aid to enhance oral substantivity. Substantial evidence exists to demonstrate the validity of the first approach. However, there are few data, as yet, to support the effectiveness of the second. The oral mucosa is the bulk retention site for all clinically proven antiplaque agents. Plaque, the pellicle-coated tooth surface, and saliva are probably all sites of biological action. A detailed understanding of the interactions between agents and the various receptor sites, and of the importance of these receptor sites to biological activity, is generally lacking.     

Errare humanum est ... but it is also human to prevent errors

Identification errors remain the most serious and the most common type of error in blood transfusion practice. Adverse events may occur when a patient has similar or identical identifiers to another patient (a ‘doppelgänger’), is doubly registered (a ‘duplicate registration’), or when registration details are derived from two or more separate sources (a ‘hybrid registration’). Such categorization provides a valuable conceptual framework for the development of appropriate risk management strategies. Distinguishing doppelgängers from duplicate registrations is not always easy. A search of the Harefield Hospital Patient Administration System (PAS) database revealed 39 registrations that shared a forename, surname and date of birth with at least one other registration. Thirty‐seven of these cases involved a duplicate registration, one involved a hybrid registration, and one involved a doppelgänger. A national strategic tracing service is available in the UK to help resolve difficult cases. Little attention has been directed at the extent to which risk reduction strategies in this area are in conflict with political and regulatory agendas. Most notable are initiatives that aim to preserve patient confidentiality. The less that is known about an individual, the greater is the risk he will be mistaken for someone who possesses similar identifiers to himself. An important, but largely unexplored, contributor to patient identification errors is innate cognitive bias. The fundamental concept underlying all blood transfusion – unique patient identity – is inherently ambiguous and vulnerable to a range of misperceptions, particularly with regard to the twin themes of coincidence and uniqueness. A major challenge will be to develop approaches in practice and education that are suitably informed by insights gleaned from cognitive and evolutionary psychology.     

Prevention of Postinfectious Asthma in Children by Reducing Self-Inoculatory Behavior

Recent studies have shown that the spread of infectious nasalsecretions from hand-to-hand or hand-to-object, followed byself-inoculation is an efficient means of viral transmission.The present study was designed to investigate whether self-inoculationbehavior in asthmatic children could be reduced and, if so,whether this reduction would reduce the frequency of infectionand asthma. Sixteen subjects aged 4 to 8, all diagnosed withpostinfectious asthma, were assigned to a treatment (differentialreinforcement of other behavior and contingent education) orplacebo control condition. Results indicate that self-inoculatorybehavior, infection, and asthma were signjficantly reduced.These findings may indicate an important role for behavioralmedicine inpostinfectious asthma.     

Competitive control of the self-renewing T cell repertoire

We develop a mathematical model for the self-renewing part of the T cell repertoire. Assuming that self-renewing T cells have to be stimulated by immunogenic MHC-peptide complexes presented on the surfaces of antigen-presenting cells, we derive a model of T cell growth in which competition for MHC-peptide complexes limits T cell clone sizes and regulates the total number of self-renewing T cells in the animal. We show that for a sufficient diversity and/or degree of cross-reactivity, the total T cell number hardly depends upon the diversity of the T cell repertoire or the diversity of the set of presented peptides. Conversely, for repertoires of lower diversity and/or cross-reactivity, steady-state total T cell numbers may be limited by the diversity of the T cells. This provides a possible explanation for the limited repertoire expansion in some, but not all, mouse T cell re-constitution experiments. We suggest that the competitive interactions described by our model underlie the normal T cells numbers observed in transgenic mice, germ-free mice and various knockout mice.      

Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi- generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease- causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.      

IMPT1, an imprinted gene similar to polyspecific transporter and multi- drug resistance genes

Human chromosome 11p15.5 and distal mouse chromosome 7 include a megabase-scale chromosomal domain with multiple genes subject to parental imprinting. Here we describe mouse and human versions of a novel imprinted gene, IMPT1 , which lies between IPL and p57 KIP2 and which encodes a predicted multi-membrane-spanning protein similar to bacterial and eukaryotic polyspecific metabolite transporter and multi- drug resistance pumps. Mouse Impt1 and human IMPT1 mRNAs are highly expressed in tissues with metabolite transport functions, including liver, kidney, intestine, extra-embryonic membranes and placenta, and there is strongly preferential expression of the maternal allele in various mouse tissues at fetal stages. In post-natal tissues there is persistent expression, but the allelic bias attenuates. An allelic expression bias is also observed in human fetal and post-natal tissues, but there is significant interindividual variation and rare somatic allele switching. The fact that Impt1 is relatively repressed on the paternal allele, together with data from other imprinted genes, allows a statistical conclusion that the primary effect of human chromosome 11p15.5/mouse distal chromosome 7 imprinting is domain-wide relative repression of genes on the paternal homolog. Dosage regulation of the metabolite transporter gene(s) by imprinting might regulate placental and fetal growth.      

In vivo NGF deprivation reduces SNS expression and TTX-R sodium currents in IB4-negative DRG neurons

Recent evidence suggests that changes in sodium channel expression and localization may be involved in some pathological pain syndromes. SNS, a tetrodotoxin-resistant (TTX-R) sodium channel, is preferentially expressed in small dorsal root ganglion (DRG) neurons, many of which are nociceptive. TTX-R sodium currents and SNS mRNA expression have been shown to be modulated by nerve growth factor (NGF) in vitro and in vivo. To determine whether SNS expression and TTX-R currents in DRG neurons are affected by reduced levels of systemic NGF, we immunized adult rats with NGF, which causes thermal hypoalgesia in rats with high antibody titers to NGF. DRG neurons cultured from rats with high antibody titers to NGF, which do not bind the isolectin IB4 (IB4(-)) but do express TrkA, were studied with whole cell patch-clamp and in situ hybridization. Mean TTX-R sodium current density was decreased from 504 +/- 77 pA/pF to 307 +/- 61 pA/pF in control versus NGF-deprived neurons, respectively. In comparison, the mean TTX-sensitive sodium current density was not significantly different between control and NGF-deprived neurons. Quantification of SNS mRNA hybridization signal showed a significant decrease in the signal in NGF-deprived neurons compared with the control neurons. The data suggest that NGF has a major role in the maintenance of steady-state levels of TTX-R sodium currents and SNS mRNA in IB4(-) DRG neurons in adult rats in vivo.