Frontiers of rapid itch relief: a review of methylprednisolone aceponate.

In a paediatric population, the successful management of childhood atopic dermatitis (AD) should include the careful evaluation and selection of available therapies, based not only on demonstrated safety and tolerability in small children and infants, but also on their evidence-based, anti-pruritic benefits. Moreover, the speed of anti-pruritic effect should be considered a significant parameter in treatment selection. The fourth-generation topical corticosteroid (TC) methylprednisolone aceponate (MPA) is a potent anti-inflammatory agent with a demonstrated fast and effective itch relief profile in children and infants (as young as 2 months) with AD. Compared with traditional TCs, MPA has a significantly improved therapeutic index; that is, increased potency without a proportionate increase in side effects. In addition to its established efficacy, the once-daily application and broad range of available formulations make MPA an optimal choice for acute and maintenance therapy in paediatric patients with AD-related pruritus.

Multiple surface antigen mutations in five blood donors with occult hepatitis B virus infection.

Occult hepatitis B virus (HBV) infection is characterized by the presence of HBV DNA while the HBV surface antigen (HBsAg) remains undetectable. The HBV genomes in five asymptomatic blood donors with occult HBV infection and low viremia (<10 to 1,000 HBV DNA copies/mL, genotype D) were studied. An unusually large number of amino acid mutations was present in the immunodominant a-determinant of HBsAg (respectively 3, 6, 7, 10, and 10 mutations). Comparison of the HBV genomes in two donors to a consensus HBV genotype D sequence showed a most prominent hotspot of genetic variation in HBV nucleotides 480-570, encoding the HBsAg a-determinant. The phylogenetic comparison of separate donor HBV genes to the HBV genes of 11 reference strains (genotypes A-H) showed the donor HBV surface genes to form an outgroup, while the HBV polymerase, core and X genes closely cluster with the HBV genotype D reference strain. Maybe the HBV strains in this study represent a natural end-stage of seemingly cleared HBV infection, in which HBV maintains a low level of possibly non-infectious replication, after sacrificing its immunologically offending surface antigen, thus avoiding final clearance by the immune system.

Curative isosorbide-5-mononitrate treatment, in opposition to the beneficial preventive one, aggravates the prothrombotic and proconstrictor state in cyclosporine-induced hypertensive rats.

1. The aim of the present study was to evaluate the effect of preventive and curative isosorbide-5-mononitrate (Is-5-Mn) treatment on the development of hypertension, cGMP content, thromboxane (TX) A(2)/prostaglandin (PG) I2 balance, the peripheral serotonergic system, platelet activation, lipid peroxidation and plasma lipids in cyclosporine A (CsA)-induced hypertensive rats. 2. Control, CsA (5 mg/kg per day) and Is-5-Mn (150 mg/kg per day, b.i.d.) rat groups were treated orally over a period of 7 weeks. The preventive Is-5-Mn group (Is-5-Mn + CsA) was first treated for 2 weeks with Is-5-Mn, followed by 7 weeks with both drugs; the curative Is-5-Mn group (CsA + Is-5-Mn) was treated for a period of 7 weeks with CsA and with both drugs for an additional 5 weeks. The control group received oral vehicle. 3. Whereas in the group undergoing preventive treatment the CsA-induced increase in blood pressure (BP), compared with the control group, was avoided, in the group undergoing curative treatment, the increase in BP was even higher. The decreased arterial cGMP content in the CsA group was prevented and reverted when Is-Mn was administered either preventatively or curatively with CsA. Platelet TXA2 production, although unaffected in the Is-5-Mn + CsA group, was significantly higher in the CsA + Is-5-Mn group compared with the group receiving CsA alone. Furthermore, plasma TXA2 was reduced following preventive Is-5-Mn treatment, but was worsened in the group undergoing curative therapy. Aortic PGI2 synthesis was identical in all groups. Consequently, the TXA2/PGI2 ratio was only altered in the CsA + Is-5-Mn group, demonstrating a markedly higher value. In both groups treated simultaneously with CsA and Is-5-Mn, a higher platelet 5-hydroxytryptamine (5-HT) content was obtained compared with CsA treatment alone, but only preventive treatment with Is-5-Mn resulted in a significant reduction in plasma 5-HT. Changes in ADP and collagen-induced platelet aggregation paralleled those of plasma 5-HT and TXA2: the hyperaggregation profile of the CsA group, although partially prevented, was not reverted by simultaneous treatment with Is-5-Mn and CsA. Lipid peroxidation and lipid profile values also worsened in the CsA + Is-5-Mn group compared with the group administered CsA alone. 4. In conclusion, the beneficial effects of concomitant Is-5-Mn and CsA treatment were demonstrated when Is-5-Mn was administered preventatively because not only was arterial hypertension prevented, but platelet aggregation and plasma TXA2 and 5-HT levels were also reduced. In contrast, following curative treatment, the BP, platelet/vascular vasoconstrictor balance, lipid peroxidation and plasma lipids were aggravated, recommending a judicious evaluation of the impact of nitrate therapy throughout the period of its administration.

Prevalencia de portadores faríngeos de 'Streptococcus pyogenes' en escolares de la Comunidad Valenciana / Prevalence of pharyngeal carriage os "Streptococcus pyogenes" among elementary school children in the Community of Valencia, Spain

Objetivo: Determinar la prevalencia de portadores de estreptococo betahemolítico del grupo A (EBHGA) en niños escolares de la Comunidad Valenciana al comienzo del in-vierno.Material y métodos: Estudio transversal. Se aleatorizaron 36 aulas escolares (clusters), de 1.° a 6.° de EGB de 50 colegios de las provincias de Valencia y Castellón, y se obtuvo un exudado faríngeo en al menos 7 niños sanos de cada aula que no habían recibido antibioticoterapia en los 10 días previos. Las torundas se sembraron en agar sangre y las colonias betahemolíticas crecidas fueron identificadas como EBHGA mediante las pruebas de sensibilidad a bacitracina y aglutinación con un antisuero específico adsorbido a partículas de látex. Resultados: Se obtuvieron 252 muestras de exudado faríngeo, de las que se aisló EBHGA en 4 casos (1,6 por ciento; IC 95 por ciento: 0,60-3,85 por ciento). No se produjo más de un caso en una misma aula. Conclusiones: La prevalencia de portadores de EBHGA en escolares, en una muestra representativa de la Comunidad Valenciana, es menor de la descrita en otros estudios (AU)

[Sensitivity of group A beta-hemolytic Streptococcus isolated from pediatric pharyngotonsillitis to erythromycin and clarithromycin: a primary care multicenter study]. / Sensibilidad a eritromicina y claritromicina de aislados de Streptococcus betahemolítico del grupo A productores de faringoamigdalitis en la edad pediátrica: estudio multicéntrico en atención primaria. Grupo Español para el Estudio de la Sensibilidad a Macrólidos en Atención Primaria.

BACKGROUND: The recent increase in the prevalence of macrolide-resistant group A beta-haemolytic Streptococcus (BHSGA) strains reported in some areas in Spain and several neighboring countries underscores the need to perform a periodic surveillance, with the adequate methodology, of the level of its susceptibility to these antimicrobials which are frequently used in our country for the treatment of acute streptococcal pharingotonsillitis and respiratory tract infections. PATIENTS AND METHODS: The susceptibility of 293 isolates of BHSGA to the macrolides erythromycin and clarithromycin was evaluated by the broth microdilution procedure recommended by the NCCLS (1997). The isolates were prospectively obtained from children with acute pharyngotonsillitis (n = 757) who were seen at primary care centers in ten Spanish cities. RESULTS: An overall prevalence of 8.9 and 7.8% erythromycin- and clarithromycin-resistant BHSGA isolates was respectively found. The percentage of resistant isolates varied considerably among the different cities subjected to study (0-33%). Overall, the intrinsic activity of clarithromycin (MIC50 and MIC90 of 0.007 and 0.25 mg/ml, respectively) was slightly higher than that of erythromycin (MIC50 and MIC90 of 0.015 and 0.5 mg/ml, respectively). All strains studied were uniformly susceptible to penicillin. CONCLUSIONS: Macrolide antibiotics, erythromycin and clarithromycin, continue to be highly active against BHSGA. The mean level of resistant strains found in Spain from community acquired infections and recovered prospectively is comparable to that of our neighboring countries.

Intrarenal arteriosclerosis and impairment of kidney function in NIDDM subjects.

It is currently under debate whether the pathogenesis of end-stage renal failure in non-insulin-dependent diabetes mellitus (NIDDM) is a consequence of microangiopathy alone. The aim of this study was to investigate intrarenal arteriosclerosis and its correlation with kidney function in NIDDM. In 36 diabetic subjects, and in 10 age- and sex-matched healthy control subjects we measured kidney volume and resistive index of the interlobar arteries by duplex Doppler ultrasonography. Clinical and metabolic parameters, renal function and vascular sequelae of the disease were also evaluated. In diabetic subjects resistive index (median 0.72, range 0.54-0.79) was higher than in control subjects (median 0.62, range 0.57-0.66) (2p < 0.002). Kidney volume and resistive index correlated with age (p < 0.004), body mass index (p < 0.001), mean blood pressure (p < 0.001), total and LDL cholesterol (p < 0.01) and creatinine clearance (p < 0.001 and < 0.01, respectively). Kidney volume also correlated with HbA1 (p < 0.01) and resistive index with uric acid (p < 0.01). Lower body macroangiopathy was associated with increased resistive index and reduced kidney volume (2p < 0.05), while upper body macroangiopathy and microangiopathy were not. Our data suggest that macroangiopathy rather than microangiopathy is mainly responsible for impairment of kidney function in NIDDM. The resistive index of interlobar arteries seems to be a reliable marker of intrarenal arteriosclerosis and can be used as a non-invasive, easily available parameter of its evolution.

Genetic interactions between HOP1, RED1 and MEK1 suggest that MEK1 regulates assembly of axial element components during meiosis in the yeast Saccharomyces cerevisiae.

During meiosis, axial elements are generated by the condensation of sister chromatids along a protein core as precursors to the formation of the synaptonemal complex (SC). Functional axial elements are essential for wild-type levels of recombination and proper reductional segregation at meiosis I. Genetic and cytological data suggest that three meiosis-specific genes, HOP1, RED1 and MEK1, are involved in axial element formation in the yeast Saccharomyces cerevisiae. HOP1 and RED1 encode structural components of axial elements while MEK1 encodes a putative protein kinase. Using a partially functional allele of MEK1, new genetic interactions have been found between HOP1, RED1 and MEK1. Overexpression of HOP1 partially suppresses the spore inviability and recombination defects of mek1-974; in contrast, overexpression of RED1 exacerbates the mek1-974 spore inviability. Co-overexpression of HOP1 and RED1 in mek1-974 diploids alleviates the negative effect of overexpressing RED1 alone. Red1p/Red1p as well as Hop1p/Red1p interactions have been reconstituted in two hybrid experiments. Our results suggest a model whereby Mek1 kinase activity controls axial element assembly by regulating the affinity with which Hop1p and Red1p interact with each other.

Cost-effectiveness analysis of different strategies for treating duodenal ulcer. Helicobacter pylori eradication versus antisecretory treatment.

Helicobacter pylori has recently been recognised as a causative agent for duodenal ulcer, and the efficacy of various combinations of antibacterials and antisecretory agents in eradicating this pathogen has been assessed. The objective of this study was to determine the efficiency of 2 treatment strategies for patients with H. pylori-positive duodenal ulcer. Cost effectiveness was analysed for antisecretory therapy (omeprazole 20 mg/day for 4 weeks), and eradication therapy (triple therapy: omeprazole 40 mg/day plus clarithromycin 1 g/day plus amoxicillin 2 g/day for 1 week). In a Markov model, a hypothetical cohort of 5000 patients was followed for 10 years through 6 disease states. Cyclic eradication therapy (i.e. in the first duodenal ulcer episode and in relapses) was the most cost effective [21 Spanish pesetas (Pta) per day free of symptoms (DFS); Pta128 = $US1 (October 1995)] of the eradication options evaluated [antisecretory in the first episode, then eradication for relapses (Pta22.3/DFS), and eradication therapy first, then antisecretory therapy (Pta27.3/DFS)]. Antisecretory therapy alone was less cost-effective (Pta39/DFS) than each of the 3 eradication options. Eradication treatment in the first episode of duodenal ulcer and relapses has savings in direct costs per patient of up to 56% compared with antisecretory therapy alone. Sensitivity analyses showed the model to be very robust. It is, therefore, advisable to treat initial episodes of H. pylori-positive duodenal ulcer and relapses with triple therapy. The improved cost-effectiveness ratio was largely explained by the long term reduction in relapses obtained with the eradication strategies.

Antimicrobial susceptibility of Streptococcus pneumoniae isolated from pediatric carriers in Spain.

The in vitro activity of several beta-lactam agents, macrolides, and cotrimoxazole was investigated against 53 Streptococcus pneumoniae isolates recovered from healthy children. The rates of resistance to penicillin or amoxicillin, cefaclor, and cefuroxime were 30%, 51%, and 37%, respectively. No cefotaxime-resistant isolates were found. Rates of resistance to erythromycin, clarithromycin, and cotrimoxazole were 22.6%, 13.2%, and 83%, respectively. Pneumococci with divergent antimicrobial susceptibility profiles (susceptible or moderately resistant vs. resistant isolates) coexisted in 32% samples, with divergencies more often involving beta-lactam agents and/or macrolides. In five of these samples, isolates belonged to different serotypes.

MSH5, a novel MutS homolog, facilitates meiotic reciprocal recombination between homologs in Saccharomyces cerevisiae but not mismatch repair.

Using a screen designed to identify yeast mutants specifically defective in recombination between homologous chromosomes during meiosis, we have obtained new alleles of the meiosis-specific genes, HOP1, RED1, and MEK1. In addition, the screen identified a novel gene designated MSH5 (MutS Homolog 5). Although Msh5p exhibits strong homology to the MutS family of proteins, it is not involved in DNA mismatch repair. Diploids lacking the MSH5 gene display decreased levels of spore viability, increased levels of meiosis I chromosome nondisjuction, and decreased levels of reciprocal exchange between, but not within, homologs. Gene conversion is not reduced. Msh5 mutants are phenotypically similar to mutants in the meiosis-specific gene MSH4 (Ross-Macdonald and Roeder 1994). Double mutant analysis using msh4 msh5 diploids demonstrates that the two genes are in the same epistasis group and therefore are likely to function in a similar process--namely, the facilitation of interhomolog crossovers during meiosis.

A comparison of laparoscopic and open hernia repair as a day surgical procedure.

To evaluate the merits of laparoscopic inguinal hernia repair (LHR) compared to conventional open hernia repair (OHR) a randomized study has been conducted. All patients were day surgical cases, of which 44 were randomized to a standardized OHR under local anesthetic (LA) and 42 to an LHR under general anesthesia (GA). Fifteen LHR patients had bilateral repairs. Operative time for OHR was 30.5 min, for unilateral LHR 35 min, and for bilateral LHR 60 min. OHR patients were discharged after a median of 134.5 min, which was significantly shorter than LHR patients, whose median discharge was 225 min (P < 0.01). Pain scores, activity levels, analgesia requirements, and time taken to return to work were not significantly different following surgery in either group (P < 0.05). There have been two recurrent hernias and one small bowel obstruction in the LHR group. We conclude that both repairs can be successfully performed as day surgical procedures. The added cost of LHR at this stage does not warrant its widespread use in unilateral hernia repairs. Which procedure is adopted should be individualized; however, patients with bilateral hernias on presentation can be successfully managed as day cases, obviating the need for hospitalization or two operations.