Bye-bye urinary gonadotrophins? Recombinant FSH: a real progress in ovulation induction and IVF?

Whether recombinant gonadotrophin products do, indeed, represent progress for routine ovulation induction and IVF cycles, in comparison with urinary products, has remained controversial. Here we review published data with regard to respective risks, outcomes and cost for both medication options. Safety considerations favour recombinant products, while overall outcome and cost considerations favour urinary gonadotrophins. Outcome, however, appears to differ, based on age and ovarian function, with younger patients benefiting from the FSH/LH combination offered by urinary products, while older women and young women with ovarian resistance, apparently benefiting from pure FSH stimulation. Young women with poor ovarian reserve may be best stimulated with a pure FSH/antagonist protocol. We conclude that under current pricing structures in the United States, recombinant gonadotrophins do not represent a major progress for the treatments of ovulation induction and IVF. They, however, allow for an improved selectivity of stimulation protocols. The creation of recombinant FSH/LH products and cost adjustments for recombinant products, may affect these conclusions in favour of recombinant products.     

Proteomics of exhaled breath condensate: a realistic approach in children with asthma?

Cite this as: E. Dompeling and Q. Jöbsis, Clinical & Experimental Allergy, 2011 (41) 299–301.     

Novel in silico technology in combination with microarrays: a state-of-the-art technology for allergy diagnosis and management?

‘Allergen microarrays, in poly-sensitized allergic patients, represent a real value added in the accurate IgE profiling and in the identification of allergen(s) to administer for an effective allergen immunotherapy.’ Allergen microarrays (AMA) were developed in the early 2000s to improve the diagnostic pathway of patients with allergic reactions. Nowadays, AMA are constituted by more than 100 different components (either purified or recombinant), representing genuine and cross-reacting molecules from plants and animals. The cost of the procedure had suggested its use as third-level diagnostics (following in vivo– and in vitro–specific IgE tests) in poly-sensitized patients. The complexity of the interpretation had inspired the development of in silico technologies to help clinicians in their work. Both machine learning techniques and expert systems are now available. In particular, an expert system that has been recently developed not only identifies positive and negative components but also lists dangerous components and classifies patients based on their potential responsiveness to allergen immunotherapy, on the basis of published algorithms. For these characteristics, AMA represents the state-of-the-art technology for allergy diagnosis in poly-sensitized patients.     

Cetirizine-induced downregulation of airway fibroblast proliferation and function: a rationale for a different approach to allergy treatment?

Recently, airway fibroblasts captured the attention of both allergists and basic scientists since they are no longer considered as mere bystanders, as far as allergic airway diseases are concerned. The aim of the present study was to assess the effects of different Cetirizine (Cet) concentrations (0.01, 0.05, 0.1 mg/ml) on human airway fibroblast proliferation and on CD54 expression. By means of flow cytometry analysis, we evaluated CD54 expression by airway fibroblasts in basal conditions or after gammaIFN stimulation in the presence of Cetirizine; we also evaluated the effect of the drug on cell proliferation by a [3H]thymidine incorporation assay. All of the tested doses of Cetirizine were able to significantly reduce CD54 upregulation induced by gammaIFN; concerning the fibroblast proliferation, we observed a dose-dependent inhibition of [3H]thymidine incorporation. These results show that Cetirizine exerts a biologic effect directly on human airway fibroblasts, suggesting a new rationale in the use of this compound.     

Scared to lose control? General and health locus of control in females with a phobia of vomiting

The term emetophobia (i.e., a fear of vomiting) exists as rather an elusive predicament, often eluding conventional treatment. The present study involved 149 participants, consisting of 51 emetophobics, 48 phobic controls (i.e. those who suffered from a different phobia), and 50 nonphobic controls. Participants were administered the Rotter (1966) Locus of Control Scale and the Health Locus of Control Scale by B.S. Wallston, Wallston, Kaplan, and Maides (1976). Significant differences were found among the three groups; specifically, that emetophobics had a significantly higher internal Locus of Control Scale score with regard to both general and health-related issues than did the two control groups. It is suggested that vomiting phobics may have a fear of losing control, and that their vomiting phobia is reflective of this alternative, underlying problem. More research is required to explore the association between emetophobia and issues surrounding control; however, the current study suggests that it may be helpful for therapists to consider this aspect when treating a patient with vomiting phobia.     

Gas plasma treatment: a new approach to surgery?

In this survey we analyse the status quo of gas plasma applications in medical sciences. Plasma is a partly ionized gas, which contains free charge carriers (electrons and ions), active radicals, and excited molecules. So-called nonthermal plasmas are particularly interesting, because they operate at relatively low temperatures and do not inflict thermal damage to nearby objects. In the past two decades nonthermal plasmas have made a revolutionary appearance in solid state processing technology. The recent trends focus on using plasmas in health care, for "processing" of medical equipment and even living tissues. The major goal of tissue treatment with plasmas is nondestructive surgery: controlled, high-precision removal of diseased sections with minimum damage to the organism. Furthermore, plasmas allow fast and efficient bacterial inactivation, which makes them suitable for sterilization of surgical tools and local disinfection of tissues. Much research effort must be undertaken before these techniques will become common in medicine, but it is expected that a novel approach to surgery will emerge from plasma science.     

Is serum Cystatin-C a suitable marker of renal function in children?

Cystatin C (Cys-C) is a low-molecular weight (13 kDa) protein that is a member of the cysteine protease family and is produced by all nucleated cells. In normal conditions, serum Cys-C is almost completely filtered by the renal glomerulus and largely catabolized by proximal tubular cells. Since serum Cys-C levels are closely correlated with the glomerular filtration rate (GFR), serum Cys-C assay has been introduced as a marker of renal function in patients with kidney diseases. In this review, we focus on studies reported during the past decade in which serum Cys-C levels have been compared to serum creatinine levels as a marker of GFR in pediatric populations. All but one of these studies showed diagnostic superiority or equivalence of serum Cys-C levels vs serum creatinine levels in children. The recent evidence from clinical trials generally supports the use of serum Cys-C assays as a renal function test in pediatric patients. However, clinicians should be cognizant of extrarenal conditions and pharmacological factors that can influence the results of serum Cys-C assays.     

Recognition of pathogenically relevant house dust mite hypersensitivity in adults with atopic dermatitis: a new approach?

BACKGROUND: The pathogenic importance of the ubiquitous house dust mite, Dermatophagoides pteronyssinus (Dp), in atopic dermatitis is unclear. OBJECTIVE: We aimed to explore the relevance of Dp hypersensitivity in adult patients with atopic dermatitis by using an in vivo topical challenge method and in vitro assays for T-cell reactivity. METHODS: Dp and control skin prick test solutions were applied to the cubital fossae of 20 patients twice daily for 4 days; the severity of dermatitis and pruritus in the challenge sites were determined before and after testing. The same solutions were used in PBMC proliferation assays that included 10% fresh, autologous serum, the latter aimed at maximizing IgE facilitated allergen presentation. RESULTS: Although most patients had markedly elevated Dp-specific serum IgE levels, only 6 of 20 patients developed increases in cubital fossa dermatitis severity and pruritus scores that were greater at sites of application of Dp solution than at control sites. In addition, PBMC proliferation in response to Dp solution in the presence of autologous serum was significantly greater in the in vivo challenge-positive patients than in those who did not respond to challenge. A subgroup of patients (7/20) also developed transient but pronounced contact urticaria at sites of Dp application. CONCLUSION: These findings suggest that hypersensitivity to Dp might be clinically relevant in approximately one third of the adult atopic dermatitis population studied. They also point to methods of identifying patients who might respond to house dust avoidance measures.     

Is anxiety a suitable measure of decision aid effectiveness: a systematic review?

Several trials have employed anxiety measures to assess decision aid effectiveness. This study employed a systematic review method to integrate their findings. The affective impact of decision aids and the appropriateness of anxiety as a measure of decision aid effectiveness are explored. From 11,361 citations generated from searching electronic databases and journals, 26 randomised controlled trials evaluated patient decision aids; 10 included anxiety measures (HADS; STAI). The data were too heterogeneous to integrate statistically. No studies showed an increase in anxiety from exposure to decision aids versus usual care. Some patterns emerged between level of anxiety and characteristics of the decision. As raised levels of anxiety are associated with both more effective decision strategies and stressful health interventions, anxiety is an inappropriate measure to employ when evaluating decision aids. Future research needs to investigate the relationship between affect, cognition and decision aids in order to facilitate effective patient decision making.     

Detection of an Archaic Clone of Staphylococcus aureus with Low-Level Resistance to Methicillin in a Pediatric Hospital in Portugal and in International Samples: Relics of a Formerly Widely Disseminated Strain?

Close to half of the 878 methicillin-resistant Staphylococcus aureus (MRSA) strains recovered between 1992 and 1997 from the pediatric hospital in Lisbon were bacteria in which antibiotic resistance was limited to beta-lactam antibiotics. The other half were multidrug resistant. The coexistence of MRSA with such unequal antibiotic resistance profiles prompted us to use molecular typing techniques for the characterization of the MRSA strains. Fifty-three strains chosen randomly were typed by a combination of genotypic methods. Over 90% of the MRSA strains belonged to two clones: the most frequent one, designated the "pediatric clone," was reminiscent of historically "early" MRSA: most isolates of this clone were only resistant to beta-lactam antimicrobials and remained susceptible to macrolides, quinolones, clindamycin, spectinomycin, and tetracycline. They showed heterogeneous and low-level resistance to methicillin (MIC, 1.5 to 6 microg/ml), carried the ClaI-mecA polymorph II, were free of the transposon Tn554, and showed macrorestriction pattern D (clonal type II::NH::D). The second major clone was the internationally spread and multiresistant "Iberian" MRSA with homogeneous and high-level resistance to methicillin (MIC, >200 microg/ml) and clonal type I::E::A. Surprisingly, the multidrug-resistant and highly epidemic Iberian MRSA did not replace the much less resistant pediatric clone during the 6 years of surveillance. The pediatric clone was also identified among contemporary MRSA isolates from Poland, Argentina, The United States, and Colombia, and the overwhelming majority of these were also associated with pediatric settings. We propose that the pediatric MRSA strain represents a formerly widely spread archaic clone which survived in some epidemiological settings with relatively limited antimicrobial pressure.     

Breastfeeding and tacrolimus: is it a reasonable approach?

Evaluation of: Bramham K, Chusney G, Lee J, Lightstone L, Nelson-Piercy C. Breastfeeding and tacrolimus: serial monitoring in breast-fed and bottle-fed infants. CJASN 8(4), 563–567 (2013).

Successful pregnancy after transplantation has become more common and more recipients are choosing to breastfeed their infants, despite the controversy surrounding the safety of breastfeeding while the mother is taking immunosuppressive medications, such as tacrolimus. Data collected to date by the National Transplantation Pregnancy Registry have not revealed specific problems related to breastfeeding; however, individual circumstances must be considered when counseling transplant recipients regarding breastfeeding. Bramham et al. reported on a series of transplant recipients who were maintained on tacrolimus during pregnancy and lactation and concluded that women should not be discouraged from breastfeeding while on tacrolimus. Recently, other authors have also supported the option of breastfeeding while recipients are maintained on tacrolimus. Herein, we review the Bramham article and discuss the key issues to be considered regarding the compatibility of breastfeeding and immunosuppression.     

Antagonism of α2A-adrenoceptor: a novel approach to inhibit inflammatory responses in sepsis

Sepsis is a systemic inflammatory response syndrome (SIRS) when an infection is the etiology of SIRS. Our previous studies have indicated that the release of the sympathetic neurotransmitter, norepinephrine (NE), from the gut is increased in sepsis, and that NE potentiates endotoxin-induced tumor necrosis factor (TNF)-α upregulation via the A subtype of α₂-adrenoceptors (i.e., α_2A-AR) expressed on the surface of Kupffer cells. A specific antagonist for α_2A-AR, 2-[(4,5-dihydro-1H-imidazol-2-yl) methyl]-2,3-dihydro-1-methyl-1H-isoindole maleate (BRL-44408 maleate), reduces TNF-α secretion in cultured Kupffer cells. We, therefore, hypothesize that administration of BRL-44408 maleate inhibits inflammatory responses and reduces organ injury in sepsis. To study this, sepsis was induced in male rats by cecal ligation and puncture (CLP). At 5 h after CLP, BRL-44408 maleate (0.3125, 0.625, 1.25, 2.5, or 5.0 mg/kg BW) or vehicle (1-ml normal saline) were administered intravenously over a period of 30 min. Blood and intestinal samples were collected at 20 h after CLP. Serum levels of TNF-α, interleukin (IL)-6, IL-10, keratinocyte-derived chemokine (KC), macrophage inflammatory protein-2 (MIP-2), liver enzymes (i.e., aspartate aminotransferase (AST) and alanine aminotransferase (ALT)), and lactate were measured. The intestinal levels of TNF-α, IL-6, and myeloperoxidase (MPO) activities were also analyzed. In additional groups of animals, the necrotic cecum was excised at 20 h post-CLP, and the 10-day survival was recorded. Our results showed that serum levels of proinflammatory cytokines (TNF-α and IL-6), anti-inflammatory cytokine (IL-10), chemokines (KC, MIP-2), liver enzymes (AST and ALT), lactate, and intestinal levels of TNF-α, IL-6, and MPO were significantly elevated at 20 h after CLP. Administration of BRL-44408 maleate significantly reduced serum levels of proinflammatory cytokines, chemokines, liver enzymes, and lactate, and dramatically decreased TNF-α, IL-6, and MPO levels in the gut. However, it has no statistical effects on the elevated serum levels of IL-10. Moreover, BRL-44408 maleate at the doses of 2.5 or 5.0 mg/kg BW significantly increased the survival rate after CLP and cecal excision. In conclusion, modulation of the sympathetic nervous system by blocking α_2A-AR appears to be a novel treatment for inflammatory conditions such as sepsis.     

Is there a risk of prion disease after the administration of urinary-derived gonadotrophins?

Concern has been raised recently about the possibility of prion proteins appearing in the urine of animals and, possibly, humans affected by prion disease [scrapie, bovine spongiform encephalopathy (BSE) and Creutzfeldt Jakob disease (CJD)]. A debate has started in which the suggestion has been made that the purification of human urine for the provision of gonadotrophins should be discontinued. The alternative would be to use recombinantly-derived gonadotrophin preparations. The recombinant products, however, rely upon bovine serum during the cell culture process and could potentially also be exposed to abnormal prion proteins. It is reassuring that the different types of gonadotrophin preparations that are currently available are produced with either urine or bovine serum that is sourced from countries that at the present time appear to be free of BSE and new variant CJD. We can therefore be reassured that the gonadotrophins that we use therapeutically appear to be equally safe.