QMS in the third stability zone with a transverse magnetic field applied.

We report here a study using a quadrupole mass spectrometer (QMS) in which a static magnetic field is applied transversely to the body of the mass filter operating in stability zone 3. Significant improvement in QMS performance was obtained under certain magnetic field conditions, and these have been explained in terms of our theoretical model. The theoretical approach assumed in the model is that the QMS contains hyperbolic rods as electrodes and that the magnetic field acts over the full length of the mass filter assembly. Our latest analysis also predicts for what values of operating parameters an enhancement of the quadrupole resolution is achieved when a transverse magnetic field is applied. The model predicts instrument resolution R > 5000 for Ar with a 100 mm long mass filter and R > 3500 for a HT and D(2) mixture with a 200 mm long mass filter via application of a transverse magnetic field.

Tazarotene cream for the treatment of facial photodamage: a multicenter, investigator-masked, randomized, vehicle-controlled, parallel comparison of 0.01%, 0.025%, 0.05%, and 0.1% tazarotene creams with 0.05% tretinoin emollient cream applied once daily for 24 weeks.

OBJECTIVE: To assess the safety and efficacy of 4 concentrations of tazarotene cream in the treatment of facial photodamage. DESIGN: Prospective weekly multicenter, investigator-masked, randomized, parallel-group study. SETTING: University hospitals and clinical research centers. PATIENTS: Three hundred forty-nine subjects with facial photodamage. INTERVENTION: Daily topical application of tazarotene cream (0.01%, 0.025%, 0.05%, and 0.1%) compared with its vehicle and with 0.05% tretinoin emollient cream. RESULTS: Tazarotene cream and tretinoin cream significantly improved mottled hyperpigmentation and fine wrinkles. At week 24, treatment success rates based on global responses were 67% (39 of 58 subjects) with 0.1% tazarotene, 52% (30 of 58 subjects) with 0.05% tazarotene, 36% (21 of 58 subjects) with 0.025% tazarotene, 41% (24 of 59 subjects) with 0.01% tazarotene, 55% (32 of 58 subjects) with 0.05% tretinoin, and 22% (13 of 58 subjects) with vehicle. Local adverse events, although more frequent with tazarotene at higher concentrations, were generally mild to moderate. CONCLUSIONS: Tazarotene in a cream formulation is safe and is associated with positive changes in the treatment of photodamaged facial skin.

A pilot study to determine the effect of tazarotene gel 0.1% on steroid-induced epidermal atrophy.

BACKGROUND: Repeated applications of a corticosteroid can induce epidermal atrophy. This study was performed to investigate whether the adjunctive use of tazarotene gel 0.1% might help to minimize the development of steroid-induced epidermal atrophy. METHODS: Each of 24 healthy volunteers received the following six treatments (applied 6 days per week for 4 weeks), which were randomized to each of six sites on their forearms: no treatment, tazarotene vehicle, tazarotene vehicle + tazarotene gel 0.1%, diflorasone diacetate 0.05% ointment, diflorasone diacetate 0.05% ointment + tazarotene vehicle, or diflorasone diacetate 0.05% ointment + tazarotene gel 0.1%. RESULTS: The mean epidermal thickness was increased by 20% (NS) and 62% (P < or = 0.0005) after applications of tazarotene vehicle and tazarotene gel 0.1%, respectively. Application of diflorasone diacetate reduced the mean epidermal thickness by 43% (P < or = 0.0005). Concomitant application of tazarotene gel 0.1% with diflorasone diacetate did not entirely prevent atrophy, but was shown to ameliorate 37% of the epidermal atrophy induced by diflorasone diacetate alone (P < or = 0.003 compared with steroid monotherapy). CONCLUSIONS: Tazarotene gel 0.1% significantly reduces epidermal atrophy induced by diflorasone diacetate 0.05% ointment.

Synchronous activity of inhibitory networks in neocortex requires electrical synapses containing connexin36.

Inhibitory interneurons often generate synchronous activity as an emergent property of their interconnections. To determine the role of electrical synapses in such activity, we constructed mice expressing histochemical reporters in place of the gap junction protein Cx36. Localization of the reporter with somatostatin and parvalbumin suggested that Cx36 was expressed largely by interneurons. Electrical synapses were common among cortical interneurons in controls but were nearly absent in knockouts. A metabotropic glutamate receptor agonist excited LTS interneurons, generating rhythmic inhibitory potentials in surrounding neurons of both wild-type and knockout animals. However, the synchrony of these rhythms was weaker and more spatially restricted in the knockout. We conclude that electrical synapses containing Cx36 are critical for the generation of widespread, synchronous inhibitory activity.

Analysis of host responses of guinea pigs during Helicobacter pylori infection.

Host responses of guinea pigs infected with Helicobacter pylori were investigated. Passaged H. pylori colonised the stomach for up to 13 weeks after infection, but after 1 month the number of bacteria fell sharply. Specific antibodies, predominantly of the IgG2 subtype, were present from week 3 onwards. Antibodies to urease A and flagella were abundant. Severe inflammation of the gastric mucosa and damage to the stomach epithelium was seen. Infiltrates of mononuclear cells and eosinophils were found near the parietal glands. As infection progressed, inflammation and tissue damage became more localised and more variable between individual animals. These parameters can be used as markers for colonisation of the stomach by H. pylori.

Negative genetic correlation for adult fitness between sexes reveals ontogenetic conflict in Drosophila.

Because of their distinctive roles in reproduction, females and males are selected toward different optimal phenotypes. Ontogenetic conflict between the sexes arises when homologous traits are selected in different directions. The evolution of sexual dimorphism by sex-limited gene expression alleviates this problem. However, because the majority of genes are not sex-limited, the potential for substantial conflict may remain. Here we assess the degree of ontogenetic conflict in the fruit-fly, Drosophila melanogaster, by cloning 40 haploid genomes and measuring their Darwinian fitness in both sexes. The intersexual genetic correlations for juvenile viability, adult reproductive success, and total fitness were used to gauge potential conflict during development. First, as juveniles, where the fitness objectives of the two sexes appear to be similar, survival was strongly positively correlated across sexes. Second, after adult maturation, where gender roles diverge, a significant negative correlation for reproductive success was found. Finally, because of counterbalancing correlations in the juvenile and adult components, no intersexual correlation for total fitness was found. Highly significant genotype-by-gender interaction variance was measured for both adult and total fitness. These results demonstrate strong intersexual discord during development because of the expression of sexually antagonistic variation.

Tazarotene plus UVB phototherapy in the treatment of psoriasis.

BACKGROUND: The addition of oral retinoids to phototherapy may accelerate and enhance antipsoriatic efficacy, but can result in systemic adverse events and additional laboratory monitoring costs. OBJECTIVE: Our purpose was to determine whether the topical addition of tazarotene to UVB phototherapy improves efficacy without problems related to photosensitivity. METHODS: Bilateral target plaques were randomized to receive two of the following, one on each plaque once daily for 14 days: tazarotene 0.1% gel, vehicle gel, or no treatment. Thereafter, the same treatments were continued 3 times per week, plus UVB phototherapy 3 times per week, for an additional 67 days. RESULTS: Tazarotene plus UVB phototherapy achieved faster and significantly greater reductions in plaque elevation and scaling throughout treatment and achieved at least 50% improvement from the pretreatment baseline with a significantly lower median cumulative UVB exposure than vehicle gel plus UVB light or UVB phototherapy alone. No case of unusual photosensitivity was noted in the tazarotene plus UVB treatment group. CONCLUSION: The addition of tazarotene to UVB phototherapy improves and accelerates efficacy and maintains acceptable safety and tolerability.

Photodamage pilot study: a double-blind, vehicle-controlled study to assess the efficacy and safety of tazarotene 0.1% gel.

BACKGROUND: Tazarotene, a potent acetylenic retinoid for topical use, might be expected to benefit photodamaged skin, including improving the classical signs of fine wrinkles, mottled hyperpigmentation, and roughness. OBJECTIVE: Our purpose was to determine the efficacy and safety of tazarotene 0.1% gel in the treatment of photodamaged dorsal forearm skin. METHODS: Ten healthy female volunteers, aged 45 to 65 years, with moderately photodamaged forearm skin applied tazarotene 0.1% gel to one arm and vehicle gel to the other once daily for 12 weeks. The study was a double-blind, randomized, paired-comparison evaluation conducted at a single site. RESULTS: Tazarotene showed beneficial effects for several efficacy variables. It was more efficacious than vehicle in reducing skin roughness and fine wrinkling based on objective measurements. Tazarotene also corrected epidermal atrophy and atypia and improved skin hydration properties. CONCLUSION: In this 12-week pilot study tazarotene redressed abnormalities associated with photo-damaged skin.

A network of electrically coupled interneurons drives synchronized inhibition in neocortex.

The neocortex has at least two different networks of electrically coupled inhibitory interneurons: fast-spiking (FS) and low-threshold-spiking (LTS) cells. Agonists of metabotropic glutamate or acetylcholine receptors induced synchronized spiking and membrane fluctuations, with irregular or rhythmic patterns, in networks of LTS cells. LTS activity was closely correlated with inhibitory postsynaptic potentials in neighboring FS interneurons and excitatory neurons. Synchronized LTS activity required electrical synapses, but not fast chemical synapses. Tetanic stimulation of local circuitry induced effects similar to those of metabotropic agonists. We conclude that an electrically coupled network of LTS interneurons can mediate synchronized inhibition when activated by modulatory neurotransmitters.

Genetic diversity in Helicobacter pullorum from human and poultry sources identified by an amplified fragment length polymorphism technique and pulsed-field gel electrophoresis.

Helicobacter pullorum was first isolated from the faeces and carcasses of poultry and has been associated with human gastroenteritis. The aim of this study was to examine interstrain genetic diversity within H. pullorum. Two fingerprinting techniques were used: amplified fragment length polymorphism (AFLP) and pulsed field gel electrophoretic (PFGE) analysis. The 20 strains examined were from four countries and comprised 13 human isolates and seven poultry isolates. Their identity was confirmed by a species-specific PCR assay. The human and poultry isolates had distinct genotypes and most strains showed a high degree of genetic diversity. Genotyping also indicated a clonal origin for two strains from the same poultry flock, and established a close relatedness between three chicken carcass isolates from a processing plant. It is concluded that these two genotyping techniques will provide a useful basis for future epidemiological investigations of H. pullorum in poultry, and may provide a link with its possible causal role in human gastrointestinal infections.

Two networks of electrically coupled inhibitory neurons in neocortex.

Inhibitory interneurons are critical to sensory transformations, plasticity and synchronous activity in the neocortex. There are many types of inhibitory neurons, but their synaptic organization is poorly understood. Here we describe two functionally distinct inhibitory networks comprising either fast-spiking (FS) or low-threshold spiking (LTS) neurons. Paired-cell recordings showed that inhibitory neurons of the same type were strongly interconnected by electrical synapses, but electrical synapses between different inhibitory cell types were rare. The electrical synapses were strong enough to synchronize spikes in coupled interneurons. Inhibitory chemical synapses were also common between FS cells, and between FS and LTS cells, but LTS cells rarely inhibited one another. Thalamocortical synapses, which convey sensory information to the cortex, specifically and strongly excited only the FS cell network. The electrical and chemical synaptic connections of different types of inhibitory neurons are specific, and may allow each inhibitory network to function independently.

Novel method for rapid determination of clarithromycin sensitivity in Helicobacter pylori.

A novel PCR-hybridization assay, performed in single closed capillaries, was developed to detect clarithromycin resistance-associated gene mutations in Helicobacter pylori. Mutations were detected by thermal analysis in 33 of 34 (97%) resistant isolates but not in 66 isolates determined to be sensitive by conventional antibiotic assays. The method was rapid and reproducible, and it reduced PCR product contamination risk.

Tazarotene gel is safe and effective in the treatment of acne vulgaris: a multicenter, double-blind, vehicle-controlled study.

Retinoids reverse the abnormal pattern of keratinization seen in acne vulgaris. Tazarotene is the first of a novel family of topical receptor-selective acetylenic retinoids. This study evaluates the safety and efficacy of topical tazarotene 0.1% and 0.05% gels, in comparison to vehicle gel, applied once daily for 12 weeks, in the treatment of mild-to-moderate facial acne vulgaris. A total of 446 patients with facial acne vulgaris were enrolled, and 375 patients, ranging in age from 14 to 44 years, were evaluable in this multicenter, double-blind, randomized study. In comparison to vehicle gel, treatment with tazarotene 0.1% gel resulted in significantly greater reductions in noninflammatory and total lesion counts at all follow-up visits, and inflammatory lesion counts at Week 12. Tazarotene 0.05% gel resulted in significantly greater reductions in noninflammatory and total lesion counts than vehicle gel at Weeks 8 and 12. At Week 12, treatment success rates were 68% and 51% for tazarotene 0.1% and 0.05%, respectively (40% for vehicle gel). Tazarotene gel was an effective, safe, and generally well-tolerated therapy for the treatment of acne vulgaris.

Tazarotene 0.1% gel plus corticosteroid cream in the treatment of plaque psoriasis.

BACKGROUND: Topical corticosteroids are often used in the treatment of psoriasis, but long-term use may be associated with serious adverse events such as tachyphylaxis or atrophy of the skin. Tazarotene, a new topical retinoid, has demonstrated significant clinical benefits but can cause mild to moderate local irritation. OBJECTIVE: We evaluate whether a combination treatment of topical tazarotene and a topical corticosteroid would increase efficacy while reducing the incidence of local adverse events associated with a topical retinoid. METHODS: Three hundred patients enrolled in an investigator-masked study were randomly assigned to 1 of 4 treatment groups: tazarotene 0.1% gel in combination with placebo cream, or with a low-, mid-, or high-potency corticosteroid cream, for 12 weeks of treatment and a posttreatment follow-up at week 16. RESULTS: Tazarotene 0.1% gel in combination with a mid- or high-potency corticosteroid, when compared with tazarotene plus placebo cream, achieved significantly greater reductions in scaling, erythema, and overall lesional severity, and a decreased incidence of adverse events. CONCLUSION: All tazarotene combinations (including tazarotene plus placebo) were highly effective in rapidly reducing the severity of psoriasis. Combining tazarotene with a topical corticosteroid increased efficacy while reducing the incidence of local adverse events.

Use of an amplified-fragment length polymorphism technique to fingerprint and differentiate isolates of Helicobacter pylori.

Amplified-fragment length polymorphism (AFLP) analysis is the name given to a genotypic technique in which adapter oligonucleotides are ligated to restriction enzyme fragments and then used as target sites for primers in a PCR amplification process. The amplified fragments are electrophoretically separated to give strain-specific band profiles. We have developed a single-enzyme approach that did not require costly equipment or reagents for the fingerprinting of strains of Helicobacter pylori. The method was assessed with 46 isolates of H. pylori from 28 patients, and the results were compared with those from other genotypic tests. The AFLP profiles derived from HindIII fragments differentiated strains of H. pylori from unrelated individuals and confirmed the common origin of strains in some family members. AFLP analysis was also applied to investigate persistent infection following antibiotic therapy. Overall, the modified technique was relatively rapid and technically simple yet gave reproducible and discriminatory results. AFLP analysis samples variation throughout the genome and is a valuable addition to the existing genotypic fingerprinting methods for H. pylori.

Intra-strain variation in expression of lipopolysaccharide by Helicobacter pylori.

Intra-strain variation in the expression of lipopolysaccharide (LPS) by two clinical isolates of Helicobacter pylori was examined. Lipopolysaccharide was prepared from successive cultures of individual colonies from each strain, separated by SDS-PAGE, and detected by silver staining and by immunoblotting. The genetic 'relatedness' of the colonies was investigated using PCR-RFLP analysis of the urease and vacuolating cytotoxin genes. Although individual colonies of each of the two strains examined appeared to have the same genetic origins, variation in the expression of their long-chain LPS was observed. The same LPS profiles were maintained by individual colonies over four subcultures on solid media containing 10% (v/v) defibrinated horse blood.

Once-daily tazarotene gel versus twice-daily fluocinonide cream in the treatment of plaque psoriasis.

BACKGROUND: A new class of topical receptor-selective acetylenic retinoids, the first of which is tazarotene, has been developed. OBJECTIVE: Our purpose was to compare the safety, efficacy, and duration of therapeutic effect of 12 weeks of once-daily tazarotene 0.1% and 0.05% gel with that of twice-daily fluocinonide 0.05% cream in the treatment of patients with plaque psoriasis. METHODS: Three hundred forty-eight patients with plaque psoriasis were enrolled and 275 patients completed a multicenter, investigator-masked, randomized, parallel-group clinical trial. RESULTS: Both tazarotene gels were as effective as fluocinonide in reducing plaque elevation after 1 week of treatment, and tazarotene 0.1% gel was similar to fluocinonide in reducing scaling of trunk/limb lesions at all study weeks except week 4. Tazarotene 0. 1% gel was similar to fluocinonide in reducing scaling of knee/elbow lesions at weeks 8 and 12. Fluocinonide had a significantly greater effect on erythema than tazarotene at weeks 2 through 8. However, treatments were not significantly different at week 12, and tazarotene demonstrated significantly better maintenance of therapeutic effect after cessation of therapy. CONCLUSION: Tazarotene 0.1% and 0.05% gels were safe and effective in the treatment of mild-to-moderate plaque psoriasis.

Campylobacter infections : species identification and typing.

Campylobacters are the most frequently identified cause of acute bacterial diarrhea in humans in England and in many other developed countries. Although C jejuni and C coli are numerically the most important species in cases of campylobacter enteritis, there is a growing awareness that some of the other 13 species of Campylobactermay also be linked with human disease. However, precise identification of these organisms is rarely carried out in clincal laboratories, and the significance of most species or subtypes in causing human disease is unknown.

Detection and Typing of Helicobacter pylori.

Helicobacter pylori is a curved mlcroaerobic bacterium that was first lsolated from human antral gastric biopsy material in 1982 by Marshall and colleagues in Perth, Western Australia (1). Since then, enormous interest has developed in the micro-organism that now appears to be one of the most common human bacterial pathogens, estimated to be infecting at least one third of the world population (2). Although most Individuals appear to be asymptomatic H. pylon is implicated as a key risk factor in a number of gastrointestinal diseases, including duodenal and gastric ulceration and gas- tric cancer (3). Most clinical and basic research aspects have been exten- sively reviewed (4), but some key features of the general epidemlology of H pylon infections are as follows:

Azelaic acid 20% cream (AZELEX) and the medical management of acne vulgaris.

Azelaic acid 20% cream (AZELEX) is a novel anti-acne agent with antimicrobial activity and keratinization-normalizing properties. In acne it is broadly comparable in efficacy to 0.05% tretinoin, 5% benzoyl peroxide, and 2% erythromycin, but is less irritating than tretinoin and benzoyl peroxide.