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Objective: The aim of this multicentric cross‐sectional study was to examine the permanency of Montgomery thyroplasty (MTIS) results from a patient's perspective. Design: The study consisted of collecting Voice Handicap Index (VHI‐30) questionnaires from patients who had previously been operated with MTIS between 2 and 12 years before. Very long‐term (>2 years) postoperative data were compared with the previously acquired preoperative and early postoperative VHI results. Influence of factors such as age, gender, size/side of the prosthesis and length of the follow‐up were also analysed. Setting: Multicentric study involving three tertiary European voice centres. Participants: Forty‐nine unilateral vocal fold paralysis (UVFP) patients, treated by MTIS, were included in the study. Main outcome measures: The Voice Handicap Index‐30 score. Results & Conclusions: The median VHI was significantly different over time‐points (Friedman's test P < .001), with a significant difference between preoperative and early postoperative time‐points (median VHI: 70 vs 21, respectively; P < .001) and between preoperative and very long‐term postoperative time‐points (median VHI: 70 vs 16, respectively; P < .001). The median VHI did not differ for the early and very long‐term postoperative time‐points (median VHI: 21 vs 16; P = .470). Age differences, gender differences and size/side differences of the prostheses, centres where surgery took place and length of the follow‐up showed no significant influence. Medialisation thyroplasty (MT) overall and MTIS, in particular, should be considered as a possible standard of care for UVFP when permanency of voice results is sought. [ABSTRACT FROM AUTHOR]

Background: Laryngeal re-innervation in paediatric unilateral vocal fold paralysis is a relatively new treatment option, of which there has been little reported experience in Europe. Methods: In this European case report of a 13-year-old boy with dysphonia secondary to left-sided unilateral vocal fold paralysis after cardiac surgery, the patient underwent re-innervation using an ansa cervicalis to recurrent laryngeal nerve transfer, in combination with fat augmentation, after 12 years of nerve denervation. Perceptual analysis data, and acoustic and laryngoscopy recordings were acquired pre-operatively, and at one and two years post-operatively. Results: The patient's perceptual voice quality was improved. He experienced subjective improvement and is very satisfied with the result. As expected, laryngoscopy at one and two years after surgery showed no physiological mobility of the vocal fold concerned, but improved closure during phonation was achieved. Electromyography showed evidence of re-innervation. Conclusion: Laryngeal re-innervation could be considered as a treatment option for unilateral vocal fold paralysis in children and adolescents, even after a long-term delay. [ABSTRACT FROM AUTHOR]

Introduction: There is no consensus on which voice outcome indicators (VOIs) should be used to compare the merits of the various surgical treatments for unilateral vocal fold paralysis (UVFP). Authors performed a literature review to identify which VOIs are most frequently used and most relevant, in terms of significant change in pre- and post-operative measurements, to assess UVFP surgical treatments.Method: A Medline/Pubmed literature review was performed and the most frequently used VOIs were identified using a Pareto diagram. For these most frequently used VOI’s, the number of studies that showed a statistically significant change in pre- and post-operative results were compared to the total number of studies found using that same VOI, this portion was expressed in percent. This percentage was defined as the “percentage of significance” and used to assess changes of each VOI.Results: Eleven VOIs were identified using the Pareto analysis. These were, in decreasing order of frequency of citation: maximum phonation time (MPT), jitter, Shimmer, video-stroboscopic examination, noise to harmonic ratio (NHR/HNR), mean air flow (MeAF), fundamental frequency (F0), “Infrequent Perceptional Scales”, GRBAS scale, mean subglottic pressure (MSGP). MPT, MeAF, factor G of GRBAS-I, Jitter, shimmer and VHI-30 had respective “percentage of significance” of 90, 86, 85, 74, 68 and 64%, respectively.Conclusion: The results indicate that MPT, MeAF and GRBAS-I, represent the top-three most frequently used and the most relevant VOIs in terms of “percentage of significance”. VHI-30 showed a relatively low rate of use and low “percentage of significance”. The role of Jitter and Shimmer remains unclear. Finally, MSGP and the F0 appear to be less relevant VOIs for the evaluation of UFVP surgical treatments in terms of significant change in pre- and post-operative measurements. [ABSTRACT FROM AUTHOR]

Chimeric transcription factor E2A-PBX1 induces the development of acute lymphoblastic B-cell leukemia in children. Using a transgenic mouse model, we previously demonstrated that homeobox ( HOX) gene HOXA9 genetically interact with E2A-PBX1 gene in the development of B-cell leukemia in mice. HOXA9 itself is a potent oncogene resulting in myeloid leukemia when overexpressed, which is strongly accelerated by its collaborator Meis1. HOX, PBX1 and MEIS1 proteins have been shown to form hetero dimeric or trimeric complexes in different combinations. Cooperative interaction between PBX1 and HOX proteins enhances their DNA binding specificity, essential for HOX dependent developmental programs. PBX1 is retained in E2A-PBX1, and thus the strong transcriptional activator properties of E2A-PBX1 may lead to aberrant activation of normally repressed targets of HOX-PBX complexes. However, although there is evidence that E2A-PBX1 could bind to HOX and MEIS1 proteins it is still unclear whether such complexes are actually required for leukemic transformation or whether E2A-PBX1 and HOXA9 are each part of larger protein complexes acting in independent complementing oncogenic pathways. In this study we aim to search for other HOXA9 and E2A-PBX1 interacting proteins. To identify novel proteins interacting with human E2A-PBX1 or HOXA9 we used tandem affinity purification (TAP) of protein complexes from 697 pre-B leukemic and HeLa cell lines transduced to express E2A-PBX1 or HOXA9, respectively, with covalently attached FLAG/HA peptides. The protein composition of each complex was determined using tandem mass-spectrometry. In the E2A-PBX1 containing complex we identified lymphoid transcription factor IKAROS, chromatin remodeling factors of SWI/SNF family while multiple subunits of translation initiation factor eIF3, E3 ubiquitin ligase UBR5 emerged from the HOXA9 complex as potential critical protein partners. This is the first time the protein partners of either E2A-PBX1 or HOXA9 oncoproteins were identified using an unbiased biochemical approach. The identification of translation initiation factors associated with HOXA9 might indicate a novel function for HOX proteins independent of their transcriptional activity. [ABSTRACT FROM AUTHOR]

In the last decade it has become clear that homeobox containing genes (HOX genes) not only play a significant role in regulating body formation, but in addition, they are contributing to organization and regulation of hematopoiesis. Modern molecular technologies showed that deregulated expression or disruption of Hox genes can lead to altered characteristics of blood cells or disturbance of blood cell development. In this paper we review the role of HOX proteins in hematopoiesis and leukemogenesis and speculate about their possible target genes and involvement in lymphomagenesis. [ABSTRACT FROM AUTHOR]

Background: The optimal treatment of desmoid tumours is controversial. We evaluated desmoid management in Dutch familial adenomatous polyposis (FAP) patients.Methods: Seventy-eight FAP patients with desmoids were identified from the Dutch Polyposis Registry. Data on desmoid morphology, management, and outcome were analysed retrospectively. Progression-free survival (PFS) rates and final outcome were compared for surgical vs non-surgical treatment, for intra-abdominal and extra-abdominal desmoids separately. Also, pharmacological treatment was evaluated for all desmoids.Results: Median follow-up was 8 years. For intra-abdominal desmoids (n=62), PFS rates at 10 years of follow-up were comparable after surgical and non-surgical treatment (33% and 49%, respectively, P=0.163). None of these desmoids could be removed entirely. Eventually, one fifth died from desmoid disease. Most extra-abdominal and abdominal wall desmoids were treated surgically with a PFS rate of 63% and no deaths from desmoid disease. Comparison between NSAID and anti-estrogen treatment showed comparable outcomes. Four of the 10 patients who received chemotherapy had stabilisation of tumour growth, all after doxorubicin combination therapy.Conclusion: For intra-abdominal desmoids, a conservative approach and surgery showed comparable outcomes. For extra-abdominal and abdominal wall desmoids, surgery seemed appropriate. Different pharmacological therapies showed comparable outcomes. If chemotherapy was given for progressively growing intra-abdominal desmoids, most favourable outcomes occurred after combinations including doxorubicin. [ABSTRACT FROM AUTHOR]

Diabet. Med. 27, 85–91 (2010) Objective To assess the preferences of patients with Type 2 diabetes regarding self-care activities and diabetes education. Research design and methods Questionnaire survey carried out in general practices and outpatient clinics across the Netherlands. Outcomes: preferred setting for education, preferred educator, and preferred and most burdensome self-care activity. Multinomial logistic regression analysis assessed associations between outcomes and patient characteristics, preferences and opinions. Results Data of 994 consecutive individuals were analysed (mean 65 years; 54% male; 97% Caucasian; 21% low education level; 80% primary care). Of these, 19% thought they had poor to average glycaemic control, 61% thought they were over-weight and 32% thought they took too little exercise. Eighty per cent of respondents preferred diabetes education during regular diabetes check-ups. Patients taking insulin preferred education to be given by nurses [odds ratio (OR) 2.45; 95% confidence interval (CI) 1.21–4.96]. Individuals who thought their health to be poor/average preferred education to be given by doctors (OR 1.65; 95% CI 1.08–2.53). Physical exercise was the preferred self-care activity of those who thought they took too little exercise (OR 1.97; 95% CI 1.32–2.93) but was preferred less by patients with mobility problems (OR 0.65; 95% CI 0.43–0.97). Patients with eating disinhibition reported keeping to a healthy diet (OR 4.63; 3.00–7.16) and taking medication (OR 1.66; 95% CI 1.09–2.52) as the most burdensome self-care activities. Age was not an independent determinant of any preference. Conclusions When providing education for patients with newly diagnosed Type 2 diabetes, healthcare providers should consider making a tailored education plan, irrespective of the patient’s age. [ABSTRACT FROM AUTHOR]

Using murine Moloney leukemia virus (MMLV)-based proviral insertional mutagenesis, we previously showed a preferential targeting of a small region in the Hoxa gene locus in E2A–PBX1-induced lymphoid leukemia resulting in the overexpression of several Hoxa genes including Hoxa10, Hoxa9 and Hoxa7. This observation suggested a functional interaction between Hox gene overexpression and E2A–PBX1 in lymphoid tumors. To further explore this possibility, we generated a series of compound E2A–PBX1 × Hox transgenic mice and tested the genetic interaction between these genes in the generation of lymphoid leukemia in vivo. Results presented in this report show that the onset of T-cell leukemia is significantly accelerated in E2A–PBX1 × Hoxb4 compound transgenic animals when compared with control E2A–PBX1 or Hoxb4 littermates. Hoxa9 appears less potent than Hoxb4 to accelerate E2A–PBX1-induced T-cell leukemia in mice. E2A–PBX1-induced T-cell leukemias express much higher levels of Hoxa genes than MMLV-induced counterparts, possibly suggesting a contribution of these genes to T-cell transformation by E2A–PBX1. Collectively, these data provide the first genetic evidence showing oncogenic collaboration between E2A–PBX1 and a Hox gene in lymphoid malignancies in vivo and document the specific deregulation of a subgroup of Hoxa genes in these leukemias.Oncogene (2008) 27, 6356–6364; doi:10.1038/onc.2008.233; published online 4 August 2008 [ABSTRACT FROM AUTHOR]

This literature review was carried out to examine the effects of user involvement in shared decision-making processes and the methods/tools available to psychiatric nurses to measure and encourage user involvement. A systematic literature review was then used in this study. Many studies indicate that an increased involvement of service users leads to better care, better treatment compliance, improved health outcomes and higher levels of patient satisfaction. The tools and methods described are designed to measure the ability to participate, the process of implementation and the evaluation of healthcare services. An adequate instrument to measure user involvement will be necessary to underpin the positive effects. Although care providers have a statutory duty to help shape user involvement, and the tools required are available, care providers are still insufficiently inclined to take up this duty. [ABSTRACT FROM AUTHOR]

Abstract Aim: To review the safety and efficacy of percutaneous closure of patent foramen ovale (PFO) in symptomatic patients without the use of general anaesthesia or echocardiographic guidance. Method: All patients accepted for percutaneous PFO closure by our service from August 2002 to August 2004 were included. Patient demographics and clinical information were obtained from clinical records and by telephone interview. Follow-up outcomes recorded were recurrence of systemic thromboembolism, residual shunt, and change in pattern of migraines. Results: Forty consecutive adult patients, of whom 19 (48%) had an atrial septal aneurysm (ASA), underwent PFO closure using the Amplatzer occluder device with fluoroscopic guidance alone. Their mean age was 45 ± 10 years (range 23–63 years) and 24 (60%) were male. The indications for closure were ischaemic stroke ( n = 26), transient ischaemic attack (TIA) ( n = 8), both stroke and TIA ( n = 2), refractory hypoxia ( n = 2), platypnoea-orthodeoxia ( n = 1) and severe migraine with seizures ( n = 1). Twenty patients suffered a single neurological event and 16 suffered >1 event, including six with only radiographic evidence of >1 event. Mean procedure time was 17.7 ± 9.6 min and fluoroscopy time was 6.7 ± 7.3 min. Implanted device sizes were 18 mm ( n = 1), 25 mm ( n = 37) and 35 mm ( n = 2). In 33 patients, the procedure was performed as a day-case. No complications were encountered. No further neurological events occurred in 39 patients at a mean follow-up time of 11 ± 7 months (3–25 months) nor was a significant shunt detected in the 34 who underwent follow-up echocardiography. Conclusions: Percutaneous closure of PFO with or without ASA, under local anaesthesia and without echocardiographic guidance, is a safe and effective procedure which can be performed as a day-case. This has now become our standard clinical practice. (Intern Med J 2005; 35: 706–710) [ABSTRACT FROM AUTHOR]

This article summarizes the development and validation of a scale to measure the level of self-efficacy of patients with type 2 diabetes mellitus. Self-efficacy is described as people's belief in their capability to organize and execute the course of action required to deal with prospective situations. This self-efficacy scale was developed based on the self-care activities these patients have to carry out in order to manage their diabetes. The following psychometric properties of this scale were established: content validity, construct validity, internal consistency and stability. The original scale contained 42 items. A panel of five experts in diabetes and four self-efficacy experts evaluated the original scale two times for relevance and clarity. This content validity procedure resulted in a final scale which consisted of 20 items. Subsequently, patients with type 2 diabetes were asked to complete this 20-item scale and further tests were done with the 94 usable responses. Factor analysis identified four factors, all of which were related to clusters of self-care activities used to manage diabetes which comprised this scale. The internal consistency of the total scale was alpha=0.81 and the test-retest reliability with a 5-week time interval was r=0.79 (P < 0.001). [ABSTRACT FROM AUTHOR]

Although restoration of laryngeal function after laryngeal transplantation depends on appropriate reinnervation, non-selective reinnervation procedures result in synkinesis and poor function restoration. This study was performed to test the feasibility of selective reinnervation procedures to restore laryngeal function. Three surgical reinnervation procedures were studied each in a group of ten cats: in group 1 a non-selective procedure in which the recurrent laryngeal nerve (RLN) was cut and reanastomosed; in group 2 selective abductor reinnervation was performed with the phrenic nerve; in group 3 selective abductor reinnervation with the phrenic nerve (PN) was combined with selective adductor reinnervation with the ansa cervicalis. Ten weeks after surgical reinnervation abductor and reflex adductor functions were evaluated with videolaryngoscopy and electromyography. Findings demonstrated that non-selective reinnervation not only gave poor abduction during inspiration but even resulted in paradoxical movement during reflex adduction. Selective abductor reinnervation resulted in good abductor function. Selective adductor reinnervation with the ansa cervicalis brought about muscle tonus in the animals studied but no restoration of reflex adduction. Enhanced activity during respiratory distress gave only slight compromise to the abductor function. In all, selective laryngeal reinnervation with the PN and ansa cervicalis produced good restoration of respiratory laryngeal function. However, deglutition following laryngeal motor and sensory reinnervation with protection of the respiratory tract is probably not sufficient, as in the present group of animals no reflex glottic closure was achieved. More research is required. [ABSTRACT FROM AUTHOR]

To investigate the mechanisms of action underlying the therapeutic effect of CD4 monoclonal antibody therapy in rheumatoid arthritis (RA), clinical responses were compared with several laboratory parameters. Twenty-nine RA patients received either 10 mg, 50 mg or 100 mg of cM-T412, a chimeric CD4 MoAb, for 7 days. The CD4 binding sites on circulating lymphocytes were saturated directly with cM-T412 and serum levels of unbound cM-T412 accumulated towards day 7 of treatment only in the patients treated with 50 and 100 mg. The treatment induced an instant and prolonged depression of the number of circulating CD4+ cells, similar for all dosages. Clinical improvement was observed predominantly in the patients treated with 50 or 100 mg cM -T412 daily and did not correlate with changes in counts of circulating leucocyte subsets nor with changes in serum cytokine levels. An antiglobulin response against cM-T412 developed in a majority of the patients. Side effects on the first day of treatment were correlated with an increase of serum IL-6 levels. This study indicates that a favourable clinical effect of cM-T412 administration was associated with the presence of unbound cM-T412 in the circulation of RA patients. Therefore penetration of unbound cM-T412 into the site of inflammation might determine the therapeutic effect in RA. [ABSTRACT FROM AUTHOR]

Laryngeal reinnervation surgery is a difficult subject due to the fact that the recurrent laryngeal nerve (RLN) is responsible for both adductor and abductor laryngeal activity. Non-selective reinnervation procedures will result in laryngeal synkinesis with restoration of tonicity. Restoration of mobility requires selective reinnervation of the adductor and abductor branches with nerves with similar activity patterns as the initial abductor and adductor branches of the RLN. [ABSTRACT FROM AUTHOR]

For reliable detection of mRNA by non-radioactive in situ hybridization, calibration and standardization of the individual steps involved are essential. We describe a method that allows determination of the size and integrity as well as quantification of biotinylated RNA probes in a single experiment. Serial dilutions of biotinylated RNA probes generated by promotor-mediated in vitro transcription were size-separated by gel electrophoresis in the presence of known amounts of 5′-biotinylated oligomers which served as internal standard. Following immobilization onto nylon membranes and visualization by chemiluminescence, optical densities of probes and internal standards were measured by densitometry and analysed by linear regression. RNA probes complementary to the human homeobox genes HOX-C6, -C8 and -C9 were quantified. Four different 5′-biotinylated oligomers (20, 35, 50 and 75 bases) were tested as internal standards. Concerning the separation of probe and oligomer in the gel, transfer properties and efficiency of binding to the membrane, the oligomer of 35 bases was found to be the best internal standard with highest reproducibility. Comparison of probe concentration by spectrophotometry and the described method showed a good correlation, indicating that our method is a reliable assay for quantitative and qualitative control of biotin-labelled probes. [ABSTRACT FROM AUTHOR]