TRIPTOSINE, AN L-5-HYDROXYTRYPTOPHAN DERIVATIVE, REDUCES ALCOHOL CONSUMPTION IN ALCOHOL-PREFERRING RATS

Triptosine is a new L-5-hydroxytryptophan derivative whose effecthas been studied in the Long-Evans alcohol-preferring rat. Atan oral dose of 100 mg/kg once daily, triptosine reduced alcoholconsumption by 42% in the second week of treatment and increasedthat of water by 80%. The results suggest that this precursorof serotonin might play an important role in diminishing preferencefor alcohol and reaccustoming the animal to water, without exertingan anorexic effect.     

In vivo treatment with recombinant IL-12 protects C57BL/6J mice against secondary alveolar echinococcosis

Using an experimental model of hepatic Echinococcus multilocularis infection in C57BL/6J mice, intraperitoneal administration of 0.8 μg of recombinant IL-12 to mice with an established infection was shown to reduce the parasite burden as soon as two weeks after the end of treatment. At that time, in vitro Echinococcus multilocularis -induced spleen T cell proliferative responses as well as IFN-γ and IL-5 production were higher in IL-12 treated mice than in untreated mice. Administration of 0.8 μg of IL-12 at the time of infection was shown to be without effect on the parasite establishment. However, this treatment greatly inhibited the subsequent metacestode development. Indeed, ten weeks after infection, it induced a complete healing in 37.5% of mice. At that time, the development of metastases was inhibited in 68.75% of IL-12-treated mice. This reduction of parasite burden was mainly associated with a strong proliferation of spleen cells to E. multilocularis antigen and with a high IFN-γ production. Altogether, our results show that IL-12 is of crucial importance in inhibiting the larval growth after the metacestode establishment in the liver and suggest that this cytokine could be of potential value in the treatment of human alveolar echinococcosis .     

Molecular detection of t(8;21)/AML1-ETO in AML M1/M2: correlation with cytogenetics,morphology and immunophenotype

The t(8;21) identifies a subgroup of acute myeloid leukaemia (AML) with a relatively good prognosis which may merit different treatment. It is associated predominantly, but not exclusively, with AML M2, and corresponds to rearrangements involving the AML1 and ETO genes. AML1-ETO positive, t(8;21) negative cases are well recognized but their incidence is unknown. In order to determine optimal prospective AML1-ETO RT-PCR screening strategies, we analysed 64 unselected AML M1 and M2 cases and correlated the results with other biological parameters. Molecular screening increased the overall detection rate from 8% to 14%. AML1-ETO was found in 3% (1/32) of AML M1 and 25% (8/32) of M2, including three patients without a classic t(8;21) but with chromosome 8 abnormalities. It was more common in younger patients. Correlation with morphology enabled development of a scoring system which detected all nine AML1-ETO-positive cases with a false positive rate of 7% (4/55). Although certain AML1-ETO-positive cases demonstrated characteristic immunological features (CD19 and CD34 expression, CD33 negativity), each of these markers was insufficiently specific to permit prediction in an individual case. We conclude that initial routine prospective molecular screening for AML1-ETO in all AMLs, combined with standardized morphological and immunological analysis, is desirable in order to produce improved prognostic stratification and to determine whether screening can ultimately be restricted to appropriate subgroups.     

VJ REARRANGEMENTS OF THE TCRγ LOCUS IN PERIPHERAL T-CELL LYMPHOMAS: ANALYSIS BY POLYMERASE CHAIN REACTION AND DENATURING GRADIENT GEL ELECTROPHORESIS

Using Southern blotting for the diagnosis of clonality in peripheral T-cell lymphomas (PTCLs), analysis of the T-cell receptor (TCR) γ gene rearrangement was shown to be more informative than that of the TCR β gene rearrangement. In order to amplify every VJγ rearrangement, a polymerase chain reaction (PCR) procedure using newly designed GC-clamp primers has been developed. All primers can be mixed in a single multiplex PCR. PCR products are analysed by denaturing gradient gel electrophoresis (DGGE), providing tumour-specific imprints inasmuch as the procedure characterizes N sequence polymorphism at the VJ junctions. In a series of 30 PTCL cases, the PCR procedure demonstrated 27 cases to be clonally rearranged and failed in three cases. PCR was more accurate than Southern blotting, showing 47 rearranged γ alleles, four of which were undetectable on the Southern blot. When lymphomas were studied at different sites and at relapse, the DGGE pattern remained unchanged. In PTCL, the proposed PCR is helpful for the diagnosis and staging of the disease and should improve the follow-up monitoring. The undetectability of clonal rearrangements in a few cases is discussed in the light of concepts of lymphomagenesis and T-cell differentiation.     

Factors affecting dental fear in French children aged 5–12 years

International Journal of Paediatric Dentistry 2010; 20: 366–373 Background. While dental anxiety is often correlated with prior negative dental experience, prevention of dental anxiety should in theory include early exposure to the dental setting. Objective. We set out to evaluate factors affecting dental fear in French children. Methods. Dental fear was evaluated using a visual analogue scale (DF‐VAS) in a group of 1303 French children (681 boys and 622 girls) aged 5–11 years (mean: 8.12 years, SD: 1.42 years). Indicators of caries and oral hygiene were evaluated on dental examination. Indicators of well‐being related to oral health, dental experience, and oral health education were collected via a structured interview. Results. Dental fear was scored low in 75.7% (DF‐VAS 0–3), moderate in 16.7% (DF‐VAS 4–6), and high in 7.6% (DF‐VAS 7–10). DF‐VAS decreased statistically with experience of a prior dental visit. Children who had at least one decayed tooth presented a higher level of dental fear than those with no decay, while children with fillings were significantly less anxious than those without previous dental care. Conclusions. This study shows that for children aged 5–12 years, prior experience of the dental setting can act as a positive component of dental fear.     

The Future of Atrial Fibrillation Therapy

Today management of atrial fibrillation (AF) centers on restoration and maintenance of normal sinus rhythm or control of the ventricular rate response to AF. Current guidelines state that rhythm and rate control strategies should be considered therapeutically equivalent, but recognize that no "one size fits all," an approach consistent with growing recognition of the heterogeneity of AF. As data from the Sotalol Amiodarone Atrial Fibrillation Efficacy Trial clearly demonstrate, conventional antiarrhythmics have a role in highly symptomatic AF accompanied by decreased quality of life. However, for many AF patients such drugs lack efficacy, have potentially serious side effects, and are poorly tolerated. In parallel with the development of more effective and safer antiarrhythmics, nontraditional approaches to prevention and treatment of AF are being explored. Treatments not considered "antiarrhythmic" that may prevent or forestall AF include aggressive antihypertensive therapy with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and some, but not all, beta-blockers and calcium channel antagonists, especially when used as adjunctive therapy. Other approaches include statins, steroids, and fish oil to reduce atrial fibrosis and inflammation, and pacemakers to prevent bradycardia-mediated AF and as a pacing preventive strategy in selected patients. Ablative techniques with potential to cure AF are gaining popularity, but are not yet simple, straightforward, and risk-free procedures. In the future, treatment of AF will progress beyond today's focus on AF as a purely electrocardiographic disease toward a patient and context-specific management strategy involving multiple treatment modalities.     

Whole blood levels of δ-aminolaevulinic acid dehydratase in patients with psoriasis and mycosis fungoides on topical therapy and on photochemotherapy

δ-Aminolaevulinic acid dehydratase levels in whole blood were found to be raised in sixteen patients with severe psoriasis receiving photochemotherapy, normal in thirty psoriatic patients on topical therapy only and significantly reduced in twelve patients with mycosis fungoides receiving photochemotherapy. In another six mycosis fungoides patients on topical therapy only, the reduction did not reach statistical significance.     

Do Permanent Pacemakers Need an Insulative Coating? Results of a Prospective Randomized Double-Blind Study

During conventional manufacturing of implanted pulse generators (IPGs), an insulative coating is often applied to prevent local muscle stimulation and myopotential sensing in unipolar pacing. This can limit the orientation of the IPG into its pocket, be a potential source of muscle stimulation via coating scratches, and result in an increase in IPG production costs. We hypothesized that advances in the design and construction of current IPCs and leads obviates the need for an insulative coating of the IPG. Using a double-blind prospective randomized design, 39 patients were implanted with either coated or uncoated otherwise identical IPGs (19 dual, 20 single chamber). All testing was done in unipolar and bipolar mode in both channels. A strength-duration curve for muscle stimulation was constructed for all patients with muscle stimulation. Myopotential sensing was established during isometric exercise. At 6-month follow-up when tested in unipolar mode, 3 of 15 (20%) patients with coated IPCs and 3 of 20 (15%) with uncoated IPCs had muscle stimulation at 5.0 V/ 1.5 ms or lower (P = NS). No patients in either population had muscle stimulation at their normally programmed output. Myopotential sensing occurred in all patients in unipolar mode at a mean of 2.29 ± 1.3 mV and 2.73 ± 1.14 mV for coated versus uncoated, respectively (P = NS). The statistical power of these negative observations was 80%. An insulative coating for pacemakers does not appear to alter sensing performance or cause a significant difference in the occurrence or characteristics of muscle stimulation.