Skin sealant InteguSeal® has no impact on prevention of postoperative mediastinitis after cardiac surgery.

BACKGROUND: Surgical site infections (SSIs) after median sternotomy represent a serious complication and a high potential risk for adverse clinical outcome after cardiac surgery. The antimicrobial skin sealant InteguSeal® was introduced as a novel tool in preventing development of SSI. AIM: This single-centre investigation used two prospective registries to evaluate the prophylactic effect of a cyanoacrylate-based antimicrobial skin sealant (InteguSeal®) on the incidence of postoperative mediastinitis or any other form of chest skin incision SSI after elective cardiac surgery. METHODS: Between October 2010 and April 2011 a total of 998 patients underwent elective cardiac surgical procedures with median sternotomy in our centre. In 496 patients InteguSeal® was included in standard preoperative preparation procedures before chest skin incision (group 1). In 502 patients standard preoperative skin preparation procedures were used without InteguSeal® (group 2). Freedom from mediastinitis and from any other form of SSI within 30 postoperative days were the primary and secondary endpoints, respectively. FINDINGS: A total of 983 patients were eligible for inclusion in per-protocol analysis (488 vs 495 patients). The incidence of postoperative mediastinitis was 2.3% in group 1 vs 3.2% in group 2 (not significant). The incidence of any form of SSI was 10.9% in group 1 vs 11.5% in group 2 (not significant). Perioperative patient characteristics, complexity of surgical procedures performed and length of hospitalization were similar in both groups. CONCLUSION: The use of InteguSeal® has no influence on the incidence of postoperative SSI and mediastinitis after cardiac surgery with median sternotomy.

Exposure to client aggression and burnout among community staff who support adults with intellectual disabilities in Ontario, Canada.

BACKGROUND: Studies have shown that staff who support adults with intellectual disabilities (ID) are exposed to challenging behaviour in their work including client aggression. Exposure to aggressive behaviour has been associated with staff stress and burnout. Study samples have been small however, and there has been very little data exploring this issue among North American staff. METHODS: A cross-sectional survey which included demographics, measures of frequency and severity (including perceived severity and a standardised severity score) of exposure to client aggression and the Maslach Burnout Inventory - Human Services Survey (MBI-HSS) was completed by 926 community staff who support adults with ID in Ontario, Canada. Relationships between demographic variables and exposure to aggression were examined with descriptive statistics. Pearson correlations were used to analyse exposure variables and MBI-HSS scores. RESULTS: Nearly all staff reported being exposed to client aggression in the prior 6 months. Mean MBI-HSS scores were comparable to previously published data in similar populations with the exception of a higher score in the personal accomplishment domain. All measures of exposure to aggression were significantly positively correlated with MBI-HSS scores in the emotional exhaustion and depersonalisation dimensions of burnout. CONCLUSIONS: The prevalence of burnout in this North American sample is comparable to what has been reported in similar populations in other locations, although these staff may have a higher sense of accomplishment with regard to their work. Findings from this large sample support the evidence that exposure to client aggression affects staff emotional well-being but is by no means the only important factor. Further study is needed to explore the differences and similarities reported here as well as other contributing factors which will guide the implementation of effective strategies to improve staff well-being.

A descriptive study of a specialized worker's psychological trauma program.

BACKGROUND: Psychological trauma in the workplace is gaining recognition as an important cause of workplace disability but little is known about the workers who are affected. The Psychological Trauma Program (PTP) in Toronto (Canada) is a specialized provincial worker's compensation board assessment program for workers with psychological sequelae of workplace trauma. AIMS: To characterize workers presenting to the PTP in terms of demographic, occupational, traumatic exposure and diagnostic variables. METHODS: A retrospective secondary analysis of all workers referred to the PTP for assessment within 1 year of traumatic event between 1999 and 2006. RESULTS: Five hundred and thiry-one referred workers were included in the study. Most workers were working-age male (76%), married (65%) and labourers (43%). Nearly half were born outside Canada. Post-traumatic stress disorder was the primary diagnosis in 44%. Fifty-eight percent had one or more secondary diagnoses. For just over half of the workers, the traumatic event resulted in a permanent physical impairment. CONCLUSIONS: Specialist referral may be indicated for workers experiencing prolonged recovery following workplace trauma. Male workers and those with co-morbidities or permanent injuries may be more likely to require referral. Individualized treatment approaches are likely important; however, more research is needed to guide future interventions.

Auditory cortex stimulation by low-frequency tones-an fMRI study.

BACKGROUND AND PURPOSE: Low-frequency tones (LFT) and infrasound (IS) are looked upon as potentially hazardous to human health. We aimed at assessing LFT/IS-induced activation of the auditory cortex by using fMRI. MATERIALS AND METHODS: fMRI was used to investigate LFT/IS perception in 17 healthy volunteers. Short tone bursts of 12, 36, 48 and 500 Hz were delivered directly into the right external ear canal through a 12-m long silicone tube and an ear plug. Sound pressure levels (SPL) and spectral analysis of the stimuli and scanner noise were measured in situ by using a metal-free optical microphone and a fiber-optic cable. RESULTS: SPL-dependent activation of the superior temporal gyrus, i.e. Brodmann areas (BA) 41 and 42 as well as BA 22, was delineated subsequent to acoustic stimulation with 12-, 48- and 500-Hz stimuli. Thresholds for LFT/IS-induced brain activation were between 110 and 90 dB SPL in normal hearing subjects. Spectral analysis revealed the occurrence of harmonics together with LFT, of which 36-Hz harmonics interfered with IS exposure at 12 Hz as well as scanner noise. CONCLUSION: Our results provide evidence that auditory cortex activation may be induced by LFT/IS exposure, depending on sound pressure levels applied. Clinical implications of our findings will have to be addressed by subsequent studies involving patients presumptively suffering from LFT-dependent disorders.

Low-frequency distortion product otoacoustic emission test compared to ECoG in diagnosing endolymphatic hydrops.

Previous studies assumed that specific audiometric measures like low-frequency biasing were noninvasive and inexpensive techniques for diagnosing endolymphatic hydrops (EH). The aim of this study was to compare the results of low-frequency DPOAE (LF-DPOAE) with those of transtympanic electrocochleography (ECoG) in patients with Menière's disease (MD). The prospective study included 50 patients, 22 to 72 years old, who were diagnosed with Menière's disease according to the criteria laid down by the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) in 1995. LF-DPOAE and ECoG were performed on the same day after standard audiometry. Enlarged amplitude of summation potential to action potential ratio was used as the diagnostic criterion for EH. The results were compared to those of LF-DPOAE. In this audiometric examination we used the modulation index (MI) to detect EH if MI < 0.5. ECoG yielded a result in 46 of the 50 patients examined. An enlarged SP/AP ratio was found in 23 patients (50%). The results of 33 patients could be compared, i.e. assessable results in both tests. The two tests yielded the same results in 13 patients and different ones in 20 patients. ROC analysis and Mann-Whitney statistics showed no significant correlation between the two tests. With ECoG as the gold standard for verifying EH, we found that LF-DPOAE is not yet a suitable method for diagnosing EH.

[Bipolar affective and schizoaffective disorders of older age -- classification, symptoms and course]. / Bipolare affektive und schizoaffektive Störungen des höheren Lebensalters.

Bipolar affective and schizoaffective disorders of older age are underdiagnosed, although they are of growing importance for psychiatric services. In this review article, we present and discuss results concerning classification, psychopathology, epidemiology, course, prognosis, neuroimaging, family studies and therapy. Bipolar (schizo)affective disorders of older age are a diagnostic heterogeneous group, especially as secondary manias must be separated from "endogenous" bipolar disorders nosologically. Bipolar (schizo)affective disorders of older age show some peculiarities: Gender ratio, age at onset, mortality and comorbidity with neurological disease are amongst them. Nevertheless, in many other aspects bipolar (schizo)affective disorders of older age do not differ from bipolar disorders of younger patients. For the acute and maintenance treatment there is a dearth of controlled studies. Lithium is of great importance. Other substances, as well as psychoeducation and ECT may be used analogously as in younger patients, if age specific factors are taken into account (as for example the danger of falls).

[Diagnosis of endolymphatic hydrops using low frequency modulated distortion product otoacoustic emissions]. / Diagnostik des endolymphatischen Hydrops mit tieftonmodulierten DPOAE.

BACKGROUND: The low frequency modulation of distortion product otoacoustic emissions (DPOAEs) is an objective audiometric method that appears to be a useful tool for the diagnosis of endolymphatic hydrops (EH), e.g. in patients with Menière's disease, or in those who present only some of the symptoms of the disease. METHOD: Low-frequency modulated DPOAEs were registered in 20 patients with unilateral Menière's disease (13 women and 7 men, aged 40-66 years) and were compared to a control group matched in age and gender. As a diagnostic parameter, the 'modulation index' MI=1/2 MS/DM was used (MS or modulation span, being the difference between the maximal and the minimal DPOAE-amplitude, and DM, being the mean of the suppressed stationary DPOAE-amplitude). RESULTS: In the patients with unilateral Menière's disease, MI was lower than in the control group. This difference was highly significant. In 56% of the patients' contralateral ears MI was lower than the cut off-value and significantly lower than in the control group, but did not differ significantly from the patients' ipsilateral ears. CONCLUSION: The registration of low-frequency modulated DPOAEs is comparable to the generally applied transtympanic electrocochleography in its diagnostic validity. The method is fast and non-invasive and could be applied to monitor the course of the disease.

Prevalence of fungal foot infections in patients with diabetes mellitus type 1 - underestimation of moccasin-type tinea.

In diabetic patients, mycotic infections may increase the risk of developing diabetic foot syndrome. However, few data are available on the prevalence of fungal foot infections in patients with diabetes. During a conference attended by patients with long-term diabetes, 95 individuals with type 1 diabetes mellitus (52 men, 43 women, mean disease duration 35.8 years) were examined for fungal infections of the feet. As well as frequency of infection and risk profiles, the level of patient awareness and preventive measures taken were assessed by means of a questionnaire. Clinically, 78 patients (82.1 %) showed probable pedal fungal infections, of which 84.6 % (66/78) were mycologically confirmed by direct microscopy and/or culture. Skin mycoses were found in 9 patients (toe webs 5, soles 4), onychomycosis in 29 patients and simultaneous infection of nails and skin in 28 patients (toe webs 8, soles 20). Thirty-seven (47.4 %) of these patients had positive cultures, particularly for the dermatophyte Trichophyton rubrum (69.2 % of isolates). A significant correlation was found between infection and gender (men more frequently affected) and the age of the patients. The actual frequency of mycoses was underestimated by the patients. This correlated with the assessment of their own knowledge level concerning fungal infections: 83.2 % of patients with skin mycoses and 88.4 % of those with onychomycosis of the feet felt that they needed more information about their disease. Marked mycoses on the soles were often considered to be dry skin by the patients. The high number of infections detected is especially remarkable in that this group of patients were highly motivated. It therefore appears that diabetics require more diagnostic, therapeutic and preventive care in terms of mycotic diseases than has been previously thought.

Breakpoints of t(4;11) translocations in the human MLL and AF4 genes in ALL patients are preferentially clustered outside of high-affinity matrix attachment regions.

Chromosomal translocations t(4;11) are based on illegitimate recombinations between the human MLL and AF4 genes, and are associated with high-risk acute leukemias of infants and young children. Here, the question was asked, whether a correlation exists between the location of translocation breakpoints within both genes and the location of S/MARs. In "halo mapping experiments" (to define SARs), about 20 kb of MLL DNA was found to be attached to the nuclear matrix. Similar experiments performed for the translocation partner gene AF4 revealed that SARs are spanning nearly the complete breakpoint cluster region of the AF4 gene. By using short DNA fragments in "scaffold reassociation experiments" (to define MARs), similar results were obtained for both genes. However, Distamycin A competition experiments in combination with "scaffold reassociation experiments" revealed specific differences in the affinity of each tested DNA fragment to bind the isolated nuclear matrix proteins. When the latter data were compared with the known location of chromosomal breakpoints for both genes, an unexpected correlation was observed. DNA areas with strong MAR affinity contained fewer translocation breakpoints, while areas with weak or absent MAR affinity showed a higher density of chromosomal breakpoints.

Biased distribution of chromosomal breakpoints involving the MLL gene in infants versus children and adults with t(4;11) ALL.

Derivative chromosomes of 40 patients diagnosed with t(4;11) acute lymphoblastic leukemia (ALL) were analysed on the genomic DNA level. Chromosomal breakpoints were identified in most cases within the known breakpoint cluster regions of the involved MLL and AF4 genes. Due to our current knowledge of the primary DNA sequences of both breakpoint cluster regions, specific features were identified at the chromosomal fusion sites, including deletions, inversions and duplications of parental DNA sequences. After separation of all t(4;11) leukemia patients into two age classes (below and above 1 year of age), the analysis of chromosomal fusion sites revealed significant differences in the distribution of chromosomal breakpoints and led to the definition of two hotspot areas within the MLL breakpoint cluster region. This may point to the possibility of different age-linked mechanisms that were leading to t(4;11) chromosomal translocations.

An outcomes analysis and satisfaction survey of 199 consecutive abdominoplasties.

Abdominoplasty is a popular body-contouring procedure. In this study the authors review retrospectively 199 abdominoplasty patients during a 15-year period to identify factors that affect overall outcome. Patients included 190 women and 9 men. The complication rate was 32% with few major complications (1.4%). The revision rate was 43%, and was related to fine-tuning the aesthetic appearance. Patients were divided into four groups based on tobacco use and history of diabetes and hypertension. There was no significant difference in revision rates or major complications between the subgroups. Minor complication rates, however, were significantly higher in smokers and patients with diabetes and/or hypertension. Complication and revision rates in patients undergoing intra-abdominal procedures combined with abdominoplasty were not significantly different from those patients undergoing abdominoplasty alone. A patient survey revealed symptom improvement in 95% of patients. Eighty-six percent of patients were satisfied with their result, and 86% would recommend abdominoplasty to a friend. The authors conclude that abdominoplasty is a safe and satisfying procedure, whether performed alone or in conjunction with another procedure. Patients are pleased with the outcome and have improvement in their symptoms, with minimal health risk. There is, however, a significant incidence of minor complications, related primarily to wound healing. These complications are increased significantly in smokers and patients with diabetes and/or hypertension. Revision rates are not different significantly between the subgroups. When complications do occur or revisions are required, they are minor and managed easily in an office setting.

Agonist-regulated Interaction between alpha2-adrenergic receptors and spinophilin.

Previously, we demonstrated that the third intracellular (3i) loop of the heptahelical alpha2A-adrenergic receptor (alpha2A AR) is critical for retention at the basolateral surface of polarized Madin-Darby canine kidney II (MDCKII) cells following their direct targeting to this surface. Findings that the 3i loops of the D2 dopamine receptors interact with spinophilin (Smith, F. D., Oxford, G. S., and Milgram, S. L. (1999) J. Biol. Chem. 274, 19894-19900) and that spinophilin is enriched beneath the basolateral surface of polarized MDCK cells prompted us to assess whether alpha(2)AR subtypes might also interact with spinophilin. [35S]Met-labeled 3i loops of the alpha2A AR (Val(217)-Ala(377)), alpha2BAR (Lys(210)-Trp(354)), and alpha2CAR (Arg(248)-Val(363)) subtypes interacted with glutathione S-transferase-spinophilin fusion proteins. These interactions could be refined to spinophilin amino acid residues 169-255, in a region between spinophilin's F-actin binding and phosphatase 1 regulatory domains. Furthermore, these interactions occur in intact cells in an agonist-regulated fashion, because alpha2A AR and spinophilin coimmunoprecipitation from cells is enhanced by prior treatment with agonist. These findings suggest that spinophilin may contribute not only to alpha2 AR localization but also to agonist modulation of alpha2AR signaling.

Phase-dependent suppression of transient evoked and distortion product otoacoustic emissions by a low-frequency tone.

The subjective recording of the masked threshold of short acoustical stimuli with a loud tone of 30 Hz (phase audiogram) has been used for the clinical diagnosis of endolymphatic hydrops (EH). In normally-hearing subjects, a marked modulation of the threshold was found, depending on the phase of the low-frequency tone. A very small dependence was found in patients with Menière's disease, due to the micromechanical changes in the basilar membrane (BM). The same phase relationship becomes apparent in low-frequency suppression of otoacoustic emissions. The amplitudes of TEOAEs are controlled by the phase-dependent displacement of the BM. The suppressed TEOAEs have to be measured separately in each phase relationship. During recording of suppressed DPOAEs, the low-frequency suppressor is permanently superimposed on the pair of primary tones. After time averaging and a moving short-time FFT, the spectral values of the DPOAEs are obtained depending on the phase of the low-frequency tone. Modulation depends also on the masker level, the levels of the primary tones, and on their frequency range. The method of low-frequency suppressed DPOAEs is an objective method to diagnose EH and could be a useful tool in human inner ear research.

Low-frequency modulation of the 2f1-f2 distortion product otoacoustic emissions in the human ear.

Low-frequency masking is a recent clinical procedure for the differential diagnosis of sensory hearing loss. Currently this requires the recording of the phase-dependent masked subjective threshold, which is time consuming and not always accurate. As an objective method, the recording of modulated distortion product otoacoustic emissions (DPOAEs) can be performed continuously, and with better frequency specificity. Results of measurements of the low-frequency modulated two-tone DPOAE 2f1-f2 in the human ear, and its dependence on various acoustic parameters, are presented here for the first time. Similar to the masked hearing threshold, the pattern of the phase-dependent modulated DPOAEs displayed two minima, at the phases of maximal rarefaction and condensation, respectively, with a latency of about 4 ms (suppressor frequency 32.8 Hz). The smaller dip, at maximal condensation, appeared only for a high suppressor level, and for a low level of the primary tone f2. The modulating effect measured for the primary frequencies f1 = 2.5 kHz and f2 = 3 kHz, decreased for 4 and 4.8 kHz, and vanished for 5 and 6 kHz. The results are discussed using a cubic distortion model based on the Boltzmann function for mechano-electrical transduction of the hair cells. The saturation behavior of the increase of the DPOAE level at different phases is compared with the growth rates of the DPOAE level in normal hearing and in sensory hearing loss.

Platelet-activating factor induction of activator protein-1 signaling in bronchial epithelial cells.

Platelet-activating factor (PAF) has been implicated in the pathogenesis of allergic and inflammatory events in the airway. In the present study, we sought to determine if PAF receptors are present on human bronchial epithelial cells and whether PAF binding to these receptors leads to activation of activator protein-1 (AP-1)-mediated transcription. Radioligand binding studies demonstrated specific binding sites for the PAF antagonist [3H]WEB 2086 (3-[4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f]-[1,2,4]triazolo[4,3- a][1,4]diazepine-2-yl]-1-(4-morpholinyl)-1-propanone) on primary bronchial epithelial cells with an equilibrium dissociation constant (Kd) = 9.8 nM and maximal density of binding sites (Bmax) = 42.4 fmol/mg of protein. The expression of PAF receptors in these cells was further confirmed by reverse transcriptase-polymerase chain reaction, which revealed amplification products derived from PAF receptor mRNA corresponding to transcripts 1 and 2. In the bronchial epithelial cell line BEAS-2B transfected with an expression plasmid for the human PAF receptor, PAF stimulation increased AP-1 DNA binding activity as determined by electrophoretic mobility shift assays. The Fos and Jun family proteins were identified as components of the DNA-protein complexes by anti-peptide antibodies in gel supershift assays. Additionally, PAF significantly induced AP-1 mediated transcription which was dependent on the expression of PAF receptors. The PAF antagonist WEB 2086 blocked the PAF effect but not that induced by 12-O-tetradecanoyl phorbol-13-acetate, indicating the specificity of the PAF response. These results indicate that activation of airway epithelial cells through stimulation of PAF receptors includes up-regulation of the nuclear transcription factor AP-1 and AP-1 transcriptional activity.

Alteration of Kupffer cell function and morphology by low melt point paraffin wax in female Fischer-344 but not Sprague-Dawley rats.

This study was conducted to compare the effects of 60-day dietary exposure (2%) to low melt point paraffin wax (LMPW) on both general liver morphology and Kupffer cell (KC) function and morphology in female F-344 and Sprague-Dawley (SD) rats. Livers from only F-344 rats fed LMPW had granuloma formation/lymphoid cell aggregates with small areas of necrosis. Significant increases in serum alanine and aspartate aminotransferase as well as gamma-glutamyltransferase activities were detected only in treated F-344 rats. Additionally, detectable amounts of LMPW were present only in livers of treated F-344 rats. Because KC can be involved in granuloma formation, their morphology and function were examined. Electron microscopy revealed the presence of large, irregularly shaped, membrane-associated vacuoles in cells isolated from F-344 rats exposed to LMPW. These vacuoles were not seen in KC from control rats and rarely detected in KC isolated from LMPW-exposed SD rats. Moreover, indices of KC function including phagocytic activity and nitric oxide and superoxide anion production were significantly increased by KC isolated from F-344 rats exposed to LMPW (1.6-, 36-, and 2.2-fold increases, respectively) over untreated controls. In contrast, LPS-stimulated production of TNF and LTB4 was significantly decreased only in KC of LMPW-fed F-344 rats. No significant changes in these functions were observed in KC isolated from SD rats exposed to LMPW or from KC isolated from control F-344 or SD rats. These data provide evidence that dietary LMPW alters the morphology and functional capacity of KC of F-344 but not SD rats and these changes may ultimately lead to granuloma formation.