The tolerance of ambiguity in late cochlear-implanted pre-lingually deaf juveniles

OBJECTIVES: To examine the ambiguity tolerance, i.e. the ability to perceive new, contradictory and complex situations as positive challenges, of pre-lingually deafened adolescents who received a cochlear implant after their eighth birthday and to identify those dimensions of ambiguity tolerance which correlate significantly with specific variables of their oral communication. DESIGN AND SETTING: Clinical survey at an academic tertiary referral center. Participants and main outcome measures: A questionnaire concerning communication and subjectively perceived changes compared to the pre-cochlear implant situation was completed by 13 pre-lingually deafened patients aged between 13 and 23 years, who received their cochlear implants between the ages of 8 and 17 years. The results were correlated with the 'Inventory for Measuring Ambiguity Tolerance'. RESULTS: The patients showed a lower ambiguity tolerance with a total score of 134.5 than the normative group with a score of 143.1. There was a positive correlation between the total score for ambiguity tolerance and the frequency of 'use of oral speech', as well as between the subscale 'ambiguity tolerance towards apparently insoluble problems' and all five areas of oral communication that were investigated. Comparison of two variables of oral communication, which shows a significant difference pre- and postoperatively, yields a positive correlation with the subscale 'ambiguity tolerance towards the parental image'. CONCLUSIONS: Pre-lingually deafened juveniles with cochlear implant who increasingly use oral communication seem to regard the limits of a cochlear implant as an interesting challenge rather than an insoluble problem.

Alternative splicing of pre-mRNA in cancer: focus on G protein-coupled peptide hormone receptors

Through alternative splicing, multiple different transcripts can be generated from a single gene. Alternative splicing represents an important molecular mechanism of gene regulation in physiological processes such as developmental programming as well as in disease. In cancer, splicing is significantly altered. Tumors express a different collection of alternative spliceoforms than normal tissues. Many tumor-associated splice variants arise from genes with an established role in carcinogenesis or tumor progression, and their functions can be oncogenic. This raises the possibility that products of alternative splicing play a pathogenic role in cancer. Moreover, cancer-associated spliceoforms represent potential diagnostic biomarkers and therapeutic targets. G protein-coupled peptide hormone receptors provide a good illustration of alternative splicing in cancer. The wild-type forms of these receptors have long been known to be expressed in cancer and to modulate tumor cell functions. They are also recognized as attractive clinical targets. Recently, splice variants of these receptors have been increasingly identified in various types of cancer. In particular, alternative cholecystokinin type 2, secretin, and growth hormone-releasing hormone receptor spliceoforms are expressed in tumors. Peptide hormone receptor splice variants can fundamentally differ from their wild-type receptor counterparts in pharmacological and functional characteristics, in their distribution in normal and malignant tissues, and in their potential use for clinical applications.

Rapid diagnostic tests for the home-based management of malaria, in a high-transmission area

Rapid diagnostic tests (RDT) are sometimes recommended to improve the home-based management of malaria. The accuracy of an RDT for the detection of clinical malaria and the presence of malarial parasites has recently been evaluated in a high-transmission area of southern Mali. During the same study, the cost-effectiveness of a 'test-and-treat' strategy for the home-based management of malaria (based on an artemisinin-combination therapy) was compared with that of a 'treat-all' strategy. Overall, 301 patients, of all ages, each of whom had been considered a presumptive case of uncomplicated malaria by a village healthworker, were checked with a commercial RDT (Paracheck-Pf). The sensitivity, specificity, and positive and negative predictive values of this test, compared with the results of microscopy and two different definitions of clinical malaria, were then determined. The RDT was found to be 82.9% sensitive (with a 95% confidence interval of 78.0%-87.1%) and 78.9% (63.9%-89.7%) specific compared with the detection of parasites by microscopy. In the detection of clinical malaria, it was 95.2% (91.3%-97.6%) sensitive and 57.4% (48.2%-66.2%) specific compared with a general practitioner's diagnosis of the disease, and 100.0% (94.5%-100.0%) sensitive but only 30.2% (24.8%-36.2%) specific when compared against the fulfillment of the World Health Organization's (2003) research criteria for uncomplicated malaria. Among children aged 0-5 years, the cost of the 'test-and-treat' strategy, per episode, was about twice that of the 'treat-all' (U.S.$1.0. v. U.S.$0.5). In older subjects, however, the two strategies were equally costly (approximately U.S.$2/episode). In conclusion, for children aged 0-5 years in a high-transmission area of sub-Saharan Africa, use of the RDT was not cost-effective compared with the presumptive treatment of malaria with an ACT. In older patients, use of the RDT did not reduce costs. The question remains whether either of the strategies investigated can be made affordable for the affected population.

Delayed gadolinium-enhanced magnetic resonance imaging (dGEMRIC) of hip joint cartilage in femoroacetabular impingement (FAI): Are pre- and postcontrast imaging both necessary?

The purpose of this study was to assess if delayed gadolinium MRI of cartilage using postcontrast T(1) (T(1Gd)) is sufficient for evaluating cartilage damage in femoroacetabular impingement without using noncontrast values (T(10)). T(1Gd) and DeltaR(1) (1/T(1Gd) - 1/T(10)) that include noncontrast T(1) measurements were studied in two grades of osteoarthritis and in a control group of asymptomatic young-adult volunteers. Differences between T(1Gd) and DeltaR(1) values for femoroacetabular impingement patients and volunteers were compared. There was a very high correlation between T(1Gd) and DeltaR(1) in all study groups. In the study cohort with Tonnis grade 0, correlation (r) was -0.95 and -0.89 with Tonnis grade 1 and -0.88 in asymptomatic volunteers, being statistically significant (P < 0.001) for all groups. For both T(1Gd) and DeltaR(1), a statistically significant difference was noted between patients and control group. Significant difference was also noted for both T(1Gd) and DeltaR(1) between the patients with Tonnis grade 0 osteoarthritis and those with grade 1 changes. Our results prove a linear correlation between T(1Gd) and DeltaR(1), suggesting that T(1Gd) assessment is sufficient for the clinical utility of delayed gadolinium MRI of cartilage in this setting and additional time-consuming T(10) evaluation may not be needed.

Gingival recession following apical surgery in the esthetic zone: a clinical study with 70 cases

The present study evaluated gingival recession 1 year following apical surgery of 70 maxillary anterior teeth (central and lateral incisors, canines, and first premolars). A visual assessment of the mid-facial aspect of the gingival level and of papillary heights of treated teeth was carried out using photographs taken at pre-treatment and 1-year follow-up appointments. In addition, changes in the gingival margin (GM) and clinical attachment levels (CAL) were calculated with the use of clinical measurements, that is, pre-treatment and 1-year follow-up pocket probing depth and level of gingival margin. Changes in GM and CAL were then correlated with patient-, tooth-, and surgery-related parameters. The following parameters were found to significantly influence changes in GM and CAL over time: gingival biotype (P < 0.05), with thin biotype exhibiting more gingival recession than thick biotype; pre-treatment pocket probing depth (PPD) (P < 0.03), with cases of pre-treatment PPD < 2.5 mm demonstrating more attachment loss than cases of PPD > or = 2.5 mm; and type of incision (P < 0.01), with the submarginal incision showing considerably less gingival recession compared with the intrasulcular incision, papilla-base incision or papilla-saving incision. The visual assessment using pre-treatment and 1-year follow-up photographs did not demonstrate significant changes in gingival level or papillary height after apical surgery. In conclusion, gingival biotype, pre-treatment PPD, and type of incision may significantly influence changes in GM and CAL following apical surgery in maxillary anterior teeth.

Potential clinical utility of polymerase chain reaction in microbiological testing for sepsis

OBJECTIVES: To evaluate the potential improvement of antimicrobial treatment by utilizing a new multiplex polymerase chain reaction (PCR) assay that identifies sepsis-relevant microorganisms in blood. DESIGN: Prospective, observational international multicentered trial. SETTING: University hospitals in Germany (n = 2), Spain (n = 1), and the United States (n = 1), and one Italian tertiary general hospital. PATIENTS: 436 sepsis patients with 467 episodes of antimicrobial treatment. METHODS: Whole blood for PCR and blood culture (BC) analysis was sampled independently for each episode. The potential impact of reporting microorganisms by PCR on adequacy and timeliness of antimicrobial therapy was analyzed. The number of gainable days on early adequate antimicrobial treatment attributable to PCR findings was assessed. MEASUREMENTS AND MAIN RESULTS: Sepsis criteria, days on antimicrobial therapy, antimicrobial substances administered, and microorganisms identified by PCR and BC susceptibility tests. RESULTS: BC diagnosed 117 clinically relevant microorganisms; PCR identified 154. Ninety-nine episodes were BC positive (BC+); 131 episodes were PCR positive (PCR+). Overall, 127.8 days of clinically inadequate empirical antibiotic treatment in the 99 BC+ episodes were observed. Utilization of PCR-aided diagnostics calculates to a potential reduction of 106.5 clinically inadequate treatment days. The ratio of gainable early adequate treatment days to number of PCR tests done is 22.8 days/100 tests overall (confidence interval 15-31) and 36.4 days/100 tests in the intensive care and surgical ward populations (confidence interval 22-51). CONCLUSIONS: Rapid PCR identification of microorganisms may contribute to a reduction of early inadequate antibiotic treatment in sepsis.

In vitro tests in drug hypersensitivity diagnosis

The diagnosis of a drug hypersensitivity reaction (DHR) is a challenging task because multiple and complex mechanisms are involved. Better understanding of immunologic pathomechanisms in DHRs and rapid progress in cellular-based in-vitro tests can help to adjust the correct diagnostic strategy to individual patients with different clinical manifestations of drug allergy. Thus, drug hypersensitivity diagnosis needs to rely on a combination of medical history and different in vivo and in vitro tests. In this article, the authors discuss current in vitro techniques, most recent findings, and new promising tools in the diagnosis of T-cell-mediated drug hypersensitivity.

Radiological factors related to pre-operative hearing levels in patients with vestibular schwannomas

The pathogenetic mechanism of hearing loss in patients with vestibular schwannomas (VS) remains unclear. Our aim was to determine the radiological and clinical parameters that might be related to hearing. The radiological images and charts of 99 patients were reviewed. Image processing software was used to analyse the maximal tumor diameter in three planes; its volume; its extension cranially, caudally, anteriorly and posteriorly; the width and length of the intrameatal tumor portion, its shape and consistency; and the tumor-fundus distance. These parameters were correlated with the patient's pre-operative hearing range. The degree of hearing correlated significantly with the tumor size, volume and coronal diameter, the degree of intrameatal tumor growth, and the distance between the lateral tumor end and the fundus (p < 0.05). No correlation was found regarding tumor extension, shape and consistency, the presence of hydrocephalus, or the extent of erosion of the internal auditory canal. Loss of hearing in the VS appears to be multifactorial. Determining the radiological parameters related to the hearing level can help to clarify the pathophysiological mechanisms involved.

Prognostic clinical and radiological parameters for immediate facial nerve function following vestibular schwannoma surgery

OBJECTIVE: The paper aims to define the parameters available before surgery which could predict immediate facial nerve function after excision of a vestibular schwannoma (VS). METHODS: Ninety-nine patients with VS operated consecutively by a single surgeon using an identical surgical technique have been evaluated retrospectively. Data were collected regarding patients' sex, age at onset of symptoms and at surgery, initial symptoms, neurological status at presentation, early post-operative neurological status and complications. The main radiological parameters included in the study were tumour extension pattern, diameters, shape, and volume, as well as extent of bony changes of the internal auditory canal. RESULTS: As the tumour stage and volume increase, facial nerve function is worse after surgery (p < 0.001 and p < 0.05, respectively). Concomitantly, larger extra-meatal tumour diameters in three dimensions (sagittal, coronal and axial) led to worse function (p < 0.01). Anterior and/or caudal tumour extension (p = 0.001 and p = 0.004, respectively) had more significant correlation than posterior and/or cranial extension (p = 0.022 and p = 0.353, respectively). Polycyclic VS had the worst prognosis, followed by the tumours with oval shape. The extent of intra-meatal tumour growth does not correlate with immediate facial nerve outcome. The different angles, lengths and diameters of the internal auditory channel showed no significant correlation with facial nerve outcome. Patients with headache as an initial symptom and those with gait instability and/or pre-operative poor facial nerve function had significantly worse immediate facial nerve outcome. CONCLUSION: Our data suggests that the analysis of the radiological and neurological patient data prior to surgery could give reliable clues regarding the immediate post-operative facial nerve function.

Sleepiness and vigilance tests

Objective assessments of subjective complaints such as sleepiness, tiredness or fatigue using sleepiness and vigilance tests aim to identify its causes and to judge the fitness to drive or to work of the affected person. "Vigilance" comprises wakefulness, alertness and attention and is therefore not merely reciprocal to sleepiness. Since it is a complex phenomenon with several dimensions it is unlikely to be appropriately assessed by one single "vigilance test". One important dimension of vigilance discussed here is wakefulness with its counterpart of overt sleep and the whole spectrum of various levels in between. The transit zone between full wakefulness and overt sleep is mainly characterised by the subjective complaint of sleepiness, which cannot be measured directly. Only the consequences of reduced wakefulness such as a shortened sleep latency, slowed cognitive function and prolonged reaction time can be measured objectively. It is, therefore, more promising to combine a battery of subjective and objective tests to answer a specific question in order to achieve the most appropriate description for a given clinical or medicolegal situation. However even then we must keep in mind that many other important aspects of fitness to drive / fitness to work such as neurological, psychiatric and neuropsychological functions including risk taking behaviour are not covered by vigilance tests. A comprehensive, multidisciplinary approach is essential in such situations.

In vitro allergy tests compared to intradermal testing in horses with recurrent airway obstruction

Recurrent airway obstruction (RAO) is a common condition in stabled horses characterised by small airway inflammation, airway neutrophilia and obstruction following exposure of susceptible horses to mouldy hay and straw and is thus regarded as a hypersensitivity reaction to mould spores. However, the role of IgE-mediated reactions in RAO remains unclear. The aim of the study was to investigate with a serological IgE ELISA test (Allercept), an in vitro sulfidoleukotriene (sLT) release assay (CAST) and with intradermal testing (IDT) whether serum IgE and IgE-mediated reactions against various mould, mite and pollen extracts are associated with RAO. IDT reactions were evaluated at different times in order to detect IgE-mediated immediate type reactions (type I hypersensitivity reactions, 0.5-1 h), immune complex-mediated late type reactions (type III reactions, 4-10 h) and cell-mediated delayed type reactions (type IV hypersensitivity reactions 24-48 h). In the serological test, overall the control horses displayed more positive reactions than the RAO-affected horses but the difference was not significant. Comparison of the measured IgE levels showed that the RAO-affected horses had slightly higher IgE levels against Aspergillus fumigatus than controls (35 and 16 AU, respectively, p<0.05), but all values were below the cut off (150 AU) of the test. In the sLT release assay, seven positive reactions were observed in the RAO-affected horses and four in the controls but this difference was not significant. A significantly higher proportion of late type IDT reactions was observed in RAO-affected horses compared to controls (25 of 238 possible reactions versus 12 of 238 possible reactions, respectively, p<0.05). Interestingly, four RAO-affected but none of the control horses reacted with the recombinant mould allergen A. fumigatus 8 (rAsp f 8, p<0.05), but only late phase and delayed type reactions were observed. In all three tests the majority of the positive reactions was observed with the mite extracts (64%, 74% and 88% of all positive reactions, respectively) but none of the tests showed a significant difference between RAO-affected and control animals. Our findings do not support that IgE-mediated reactions are important in the pathogenesis of RAO. Further studies are needed to investigate whether sensitisation to mite allergens is of clinical relevance in the horse and to understand the role of immune reactions against rAsp f 8.

Development of two real-time PCR assays for the detection of Mycoplasma hyopneumoniae in clinical samples

In order to improve the diagnosis of enzootic pneumonia (EP) in pigs two real-time polymerase chain reaction (rtPCR) assays for the detection of Mycoplasma hyopneumoniae in bronchial swabs from lung necropsies were established and validated in parallel. As a gold standard, the current "mosaic diagnosis" was taken, including epidemiological tracing, clinical signs, macro- and histopathological lesions of the lungs and immunofluorescence. One rtPCR is targeting a repeated DNA element of the M. hyopneumoniae genome (REP assay), the other a putative ABC transporter gene (ABC assay). Both assays were shown to be specific for M. hyopneumoniae and did not cross react with other bacteria and mollicutes from pig. With material from pigs of defined EP-negative farms the two assays showed to be 100% specific. When testing lungs from pig farms with EP, the REP assay detected 50% and the ABC assay 90% of the farms as positive. Both tests together detected all positive farms. Within a positive herd the two assays tested similarly with on average over 90% of the lung samples analysed from a single farm showing positive scores. A series of samples with suspicion of EP and samples from pigs with diseases other than respiratory taken from current routine diagnostic was assayed. None of the assays showed false positive results. The sensitivities in this sample group were 50% for the REP and 70% for the ABC assays and for both assays together 85%. The two assays run in parallel are therefore a valuable tool for the improvement of the current diagnosis of EP.

Anti-eosinophil activity and clinical efficacy of the CRTH2 antagonist OC000459 in eosinophilic esophagitis

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic, Th2-type inflammatory disease. Chemoattractant receptor-homologous molecule on Th2 cells (CRTH2) is a prostaglandin D(2) (PGD(2)) receptor, expressed by Th2 cells and other inflammatory cells, including eosinophils and basophils, that mediates chemotaxis and activation. OC000459 is a selective CRTH2 antagonist and would be expected to suppress eosinophilic tissue inflammation. The purpose of this study was to evaluate the efficacy and safety of an OC000459 monotherapy in adult patients with active, corticosteroid-dependent or corticosteroid-refractory EoE. METHODS: In this randomized, double-blind, placebo-controlled trial, 26 adult patients (m/f = 22/4; mean age 41 years, range 22-69 years) with active EoE, dependent or resistant to corticosteroids, were treated either with 100 mg OC000459 (n = 14) or placebo (n = 12) twice daily. Pre- and post-treatment disease activity was assessed clinically, endoscopically, histologically, and via biomarkers. The primary end point was the reduction in esophageal eosinophil infiltration. RESULTS: After an 8-week OC000459 treatment, the esophageal eosinophil load decreased significantly, from 114.83 to 73.26 eosinophils per high-power field [(eos/hpf), P = 0.0256], whereas no reduction was observed with placebo (102.80-99.47 eos/hpf, P = 0.870). With OC000459, the physician's global assessment of disease activity improved from 7.13 to 5.18 (P = 0.035). OC000459 likewise reduced extracellular deposits of eosinophil peroxidase and tenascin C, the effects not seen with placebo. No serious adverse events were observed. CONCLUSIONS: An 8-week treatment with the CRTH2-antagonist, OC000459, exerts modest, but significant, anti-eosinophil and beneficial clinical effects in adult patients with active, corticosteroid-dependent or corticosteroid-refractory EoE and is well tolerated.

Gingival recessions and the change of inclination of mandibular incisors during orthodontic treatment

SUMMARY A recent systematic review demonstrated that, overall, orthodontic treatment might result in a small worsening of periodontal status. The aim of this retrospective study was to test the hypothesis that a change of mandibular incisor inclination promotes development of labial gingival recessions. One hundred and seventy-nine subjects who met the following inclusion criteria were selected: age 11-14 years at start of orthodontic treatment (TS), bonded retainer placed immediately after treatment (T₀), dental casts and lateral cephalograms available pre-treatment (TS), post-treatment (T₀), 2 years post-treatment (T₂), and 5 years post-treatment (T₅). Depending on the change of lower incisor inclination during treatment (ΔInc_Incl), the sample was divided into three groups: Retro (N = 34; ΔInc_Incl ≤ -1 degree), Stable (N = 22; ΔInc_Incl > -1 degree and ≤1 degree), and Pro (N = 123; ΔInc_Incl > 1 degree). Clinical crown heights of mandibular incisors and the presence of gingival recessions in this region were assessed on plaster models. Fisher's exact tests, one-way analysis of variance, and regression models were used for analysis of inter-group differences. The mean increase of clinical crown heights (T₀ to T₅) of mandibular incisors ranged from 0.6 to 0.91 mm in the Retro, Stable, and Pro groups, respectively; the difference was not significant (P = 0.534). At T₅, gingival recessions were present in 8.8, 4.5, and 16.3 per cent patients from the Retro, Stable, and Pro groups, respectively. The difference was not significant (P = 0.265). The change of lower incisors inclination during treatment did not affect development of labial gingival recessions in this patient group.