Survey of the effectiveness of masking noises during dental treatment--a pilot study.

OBJECTIVE: The aim of this study was to test the effectiveness of a newly developed system, using masking noises with specific frequencies and amplitudes, adjusted to typical noises experienced during dental treatment such as the high-speed hand-held drill. METHOD AND MATERIALS: In accordance with an analysis of typical noises experienced during dental treatment, masking noises with specific frequencies (frequency range 0.02 to 20 kHz) and amplitudes were created, with the aim of reducing the patients' awareness of typical treatment noises by overlaying frequencies. Two hundred fifty-four outpatients (113 males, 141 females) with a mean age of 32 years (+/- 10.5 years) were enrolled in this study. Patients were treated 15 minutes with and 15 minutes without the masking noise. Patients and practitioners filled out questionnaires aimed to evaluate the effectiveness of the system, sensitivity to noise (scale 0 to 10; 0 = effective, 10 = noneffective), psychologic aspects, and statements of fear. RESULTS: There was a significant reduction in patients' awareness of noise using this system during dental treatment. Most of the patients regarded the masking noise as a pleasureable supplementation to common treatment and would select this manner of dental treatment employing the device again (81.5%); 48.2% said they were more relaxed. The system does not, in principle, interfere with dental treatment, and in most instances, the device does not impede the communication between practitioners and patients. CONCLUSION: The present study demonstrates that using masking noises during dental treatment reduces the sensitivity to drill noise, reduces fear and stress, and may be useful in dental practice as an adjunct to common dental treatment.     

Standardisation of 31phosphorus-nuclear magnetic resonance spectroscopy determinations of high energy phosphates in humans

A procedure is described for standardising the determination of adenosine 5-triphosphate and phosphocreatine concentration ([ATP] and [PC], respectively, in absolute arbitrary units) in human muscle by nuclear magnetic resonance (NMR) spectroscopy. The individual ³¹phosphorus (²¹P)-NMR spectra obtained on equal hemispherical tissue volumes (muscle plus skin and fat) were corrected for the thickness of the skin and of the subcutaneous fat. The volumes investigated were standardised using an external reference. The procedure described made possible the comparison of high energy phosphate concentrations among different subjects. It was applied to the assessment of [ATP] and [PC] in four groups of sedentary subjects (children, and adults aged 20–35, 35–50 and over 50 years), and in a group of athletes (volleyball players). The [ATP] and [PC] were not statistically different in the groups investigated.     

Localizing a putative mutation as the major contributor to the development of sporadic Hirschsprung disease to the RET genomic sequence between the promoter region and exon 2

Hirschsprung disease (HSCR), a congenital disorder characterized by intestinal obstruction due to absence of enteric ganglia along variable lengths of the intestinal tract, occurs both in familial and sporadic cases. RET mutations have been found in approximately 50% of the families, but explains only a minority of sporadic cases. This study aims at investigating a possible role of RET in sporadic HSCR patients. Haplotypes of 13 DNA markers, within and flanking RET, have been determined for 117 sporadic HSCR patients and their parents. Strong association was observed for six markers in the 5' region of RET. The largest distortions in allele transmission were found at the same markers. One single haplotype composed of these six markers was present in 55.6% of patients versus 16.2% of controls. Odds ratios (ORs) revealed a highly increased risk of homozygotes for this haplotype to develop HSCR (OR>20). These results allowed us to conclude that RET plays a crucial role in HSCR even when no RET mutations are found. An unknown functional disease variant(s) with a dosage-dependent effect in HSCR is likely located between the promoter region and exon 2 of RET.     

What evidence is there for the existence of individual genes with antagonistic pleiotropic effects?

Classical evolutionary theory predicts the existence of genes with antagonistic effects on longevity and various components of early-life fitness. Quantitative genetic studies have provided convincing evidence that such genes exist. However, antagonistic pleiotropic effects have rarely been attributed to individual loci. We examine several classes of longevity-assurance genes: those involved in regulation of the gonad; the insulin-like growth factor pathway; free-radical scavenging; heat shock proteins and apoptosis. We find initial evidence that antagonistic pleiotropic effects are pervasive in each of these classes of genes and in various model systems--although most studies lack explicit studies of fitness components. This is particularly true of human studies. Very little is known about the early-life fitness effects of longevity loci. Given the possible medical importance of such effects we urge their future study.     

Diagnostic value of anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies for inflammatory bowel disease: high prevalence in patients with celiac disease

Both celiac disease and inflammatory bowel disease (IBD) are characterized by chronic diarrhea and the presence of distinct (auto)antibodies. In the present study we wanted to determine the prevalence of serological markers for inflammatory bowel disease, i.e., perinuclear antineutrophil cytoplasmic antibodies (pANCA) and/or anti-Saccharomyces cerevisiae antibodies (ASCA), in 37 patients with biopsy-confirmed celiac disease (Marsh IIIb/c). The majority of the patients was positive for IgA (auto)antibodies typically associated with celiac disease, i.e., antiendomysium antibodies (EMA) (86.5%), antigliadin antibodies (AGA) (73%), and antirecombinant human tissue transglutaminase antibodies (rh-tTGA) (86.5%). Four patients with selective IgA deficiency could be identified by analyzing EMA, AGA, and rh-tTGA for the IgG isotype. The prevalence of pANCA and ASCA, markers that are used for IBD, was unexpectedly high in our cohort of patients with celiac disease: 8 patients were positive for pANCA (IgG) and 16 patients were positive for ASCA (IgG and/or IgA). These results indicate that the presence of pANCA or ASCA in the serum of patients with chronic diarrhea does not exclude celiac disease. A prospective study is required to determine whether pANCA and/or ASCA identify patients at risk for developing secondary autoimmune disease.     

Physics-Driven CFD Modeling of Complex Anatomical Cardiovascular Flows—A TCPC Case Study

Recent developments in medical image acquisition combined with the latest advancements in numerical methods for solving the Navier-Stokes equations have created unprecedented opportunities for developing simple and reliable computational fluid dynamics (CFD) tools for meeting patient-specific surgical planning objectives. However, for CFD to reach its full potential and gain the trust and confidence of medical practitioners, physics-driven numerical modeling is required. This study reports on the experience gained from an ongoing integrated CFD modeling effort aimed at developing an advanced numerical simulation tool capable of accurately predicting flow characteristics in an anatomically correct total cavopulmonary connection (TCPC). An anatomical intra-atrial TCPC model is reconstructed from a stack of magnetic resonance (MR) images acquired in vivo. An exact replica of the computational geometry was built using transparent rapid prototyping. Following the same approach as in earlier studies on idealized models, flow structures, pressure drops, and energy losses were assessed both numerically and experimentally, then compared. Numerical studies were performed with both a first-order accurate commercial software and a recently developed, second-order accurate, in-house flow solver. The commercial CFD model could, with reasonable accuracy, capture global flow quantities of interest such as control volume power losses and pressure drops and time-averaged flow patterns. However, for steady inflow conditions, both flow visualization experiments and particle image velocimetry (PIV) measurements revealed unsteady, complex, and highly 3D flow structures, which could not be captured by this numerical model with the available computational resources and additional modeling efforts that are described. Preliminary time-accurate computations with the in-house flow solver were shown to capture for the first time these complex flow features and yielded solutions in good agreement with the experimental observations. Flow fields obtained were similar for the studied total cardiac output range (1–3 l/min); however hydrodynamic power loss increased dramatically with increasing cardiac output, suggesting significant energy demand at exercise conditions. The simulation of cardiovascular flows poses a formidable challenge to even the most advanced CFD tools currently available. A successful prediction requires a two-pronged, physics-based approach, which integrates high-resolution CFD tools and high-resolution laboratory measurements.     

Age, gender and litter-related variation in T-lymphocyte cytokine production in young pigs

The capacity of farm animals to produce cytokines could be an important determinant of robustness and health. From research in rodents and humans it appears that the production and the balance of T helper 1 (Th1) and T helper 2 (Th2)-type cytokines influences susceptibility to autoimmune and infectious diseases. It is known that pigs show a large variation in many immune response parameters. So far the extent of individual variation in the production of Th1- and Th2-type cytokines in commercial outbred pigs has not been reported. In the current experiment we determined mRNA expression, as well as protein production of cytokines in 32 pigs from eight litters. From each litter two male and two female pigs were tested at 2, 5 and 8 weeks of age. Two Th1-type cytokines, interleukin (IL)-2 and interferon (IFN)-gamma, and two Th2-type cytokines, IL-4 and IL-10, were measured after phytohaemagglutinin (PHA)-stimulation of blood mononuclear cells. Cytokine production and the Th1/Th2-ratio were highly variable. The variation in cytokine protein production was moderately consistent across ages, i.e. pigs that produced high levels of cytokine at 2 weeks of age tended to do so as well at 5 and 8 weeks of age. Cytokine production tended to increase with age, and gilts and boars differed in their IL-2/IL-4 ratio. Unexpectedly, age, gender and litter effects often differed for mRNA and protein production data. We hypothesize that cytokine production is a consistent trait in pigs, especially at the protein production level. Future investigations in more animals and across a wider age range are necessary.     

Systemic inflammatory mediators and cystic fibrosis genotype

Abstract. Morbidity and mortality in cystic fibrosis patients is mainly attributed to pulmonary infection and inflammation. Chemokines play a pivotal role in the inflammatory process. Although genotype-phenotype correlation in cystic fibrosis patients has been defined, a clear relationship between the defect in the cystic fibrosis transmembrane regulator (CFTR) gene and pulmonary inflammation has not been established. The aim of this study was to assess whether serum chemokines levels in cystic fibrosis patients correlate with genotype and pulmonary function tests, as well as with other clinical characteristics. Serum levels of interleukin-8, RANTES, and monocyte chemoattractant protein-1 were measured in 36 cystic fibrosis patients grouped according to their genotype. Group A included 25 patients who carried two mutations associated with a pathological sweat test and pancreatic insufficiency (F508, W1282X, G542X, N1303K, S549R). Group B included 11 compound heterozygote patients who carried one mutation known to cause mild disease with borderline or normal sweat test and pancreatic sufficiency (3849+10kb C to T, 5T). Associations between chemokine levels, genotype, pulmonary function, Pseudomonas aeruginosa colonization, age, sweat chloride level, and pancreatic and nutritional status were examined. Mean interleukin-8 and monocyte chemoattractant protein-1 levels were significantly higher in group A than group B (11.4±2.1 pg/ml vs. 5±0.9 pg/ml and 157±16 pg/ml vs. 88.8±16.4 pg/ml, respectively) (P<0.01). No difference in RANTES levels were found between groups. interleukin-8 levels were inversely related to forced expiratory volume in 1 s (r=-0.37, P<0.02), while there was no association between the latter and RANTES and monocyte chemoattractant protein-1 levels. The Pseudomonas colonization rate was higher among group A patients than group B (88% vs. 40%, P<0.01). No relationship was found between measured chemokines and age, sweat chloride levels, and pancreatic and nutritional status. Our study demonstrates an association between interleukin- 8, forced expiratory volume, and cystic fibrosis genotype. Hence, elevated interleukin-8 serum levels could serve as an indicator of an early inflammatory process and encourage the initiation of anti-inflammatory treatment.     

Distinct modulation by interferon-gamma (IFN-γ) of CD23 expression on B and T lymphocytes of atopic subjects

The low-affinity IgE receptor (FcεRII/CD23) plays a role in IgE production. Cytokines participating in IgE synthesis also modulate CD23 expression on lymphocytes, but whether this modulation is different in atopic subjects remains unclear. We studied CD23 expression on B and T lymphocytes in 10 asthmatic patients with Dermatophagoides pteronyssinus hypersensitivity and 10 healthy non-atopic subjects. Studies were performed by flow cytometry, in phytohaemagglutinin (PHA) or IL-4-stimulated mononuclear cell cultures, alone or in the presence of IFN-γ. Soluble CD23 (sCD23) released in the culture supernatants was measured by enzyme-linked immunoassay. Both PHA and IL-4 induced the expression of CD23 on lymphocytes of atopic and non-atopic subjects. Whereas PHA increased both the percentage and mean fluorescence intensity of CD23⁺ B and T cells, IL-4 alone did not increase the percentage of CD23⁺ T cells. The effects of IFN-γ were different in both groups, since it was able to reduce the percentage of PHA-stimulated CD23⁺ T cells only in non-atopic individuals. In non-atopic subjects more than atopic, levels of sCD23 were increased in the supernatants of PHA and IL-4 cultures. These results show that the modulation of CD23 expression is different on B and T cells, and that IFN-γ acts differently in atopic and non-atopic individuals.