Proteins and peptides in parotid saliva of irradiated patients compared to that of healthy controls using SELDI-TOF-MS.

BACKGROUND: Radiotherapy to the head and neck area damages the salivary glands. As a consequence hyposalivation may occur, but also the protein composition of saliva may be affected possibly compromising oral health. The aim of our study was to compare the relative abundance of proteins and peptides in parotid saliva of irradiated patients to that of healthy controls. METHODS: Using Lashley cups and citric acid, saliva from the parotid glands was collected from nine irradiated patients and ten healthy controls. The samples were analyzed with SELDI-TOF-MS using a NP20 and IMAC-30 chip in the molecular weight range of 1-30 kDa. RESULTS: On the NP20 chip 61 (out of 217) and on the IMAC-30 chip 32 (out of 218) peaks differed significantly in intensity between the saliva of the irradiated patients and healthy controls. 55 % of the significant peaks showed higher intensity and 45 % showed lower intensity in the saliva of irradiated patients. The peaks may represent, amongst others, the salivary proteins lysozyme, histatins, cystatin, protein S100 and PRP's. CONCLUSIONS: Large differences were found in the relative abundance of a wide range of proteins and peptides in the parotid saliva of irradiated patients compared to healthy controls.

Activity and mechanism of action of HDVD, a novel pyrimidine nucleoside derivative with high levels of selectivity and potency against gammaherpesviruses.

A novel nucleoside analogue, 1-[(2S,4S-2-(hydroxymethyl)-1,3-dioxolan-4-yl]5-vinylpyrimidine-2,4(1H,3H)-dione, or HDVD, was evaluated against a wide variety of herpesviruses and was found to be a highly selective inhibitor of replication of the gammaherpesviruses Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). HDVD had also a pronounced inhibitory activity against murine herpesvirus 68 (MHV-68) and herpes simplex virus 1 (HSV-1). In contrast, replication of herpesvirus saimiri (HVS), HSV-2, and varicella-zoster virus (VZV) was weakly inhibited by the compound, and no antiviral activity was determined against human cytomegalovirus (HCMV) and rhesus rhadinovirus (RRV). The HDVD-resistant virus phenotype contained point mutations in the viral thymidine kinase (TK) of HSV-1, MHV-68, and HVS isolates. These mutations conferred cross-resistance to other TK-dependent drugs, with the exception of an MHV-68 mutant (E358D) that exhibited resistance only to HDVD. HSV-1 and HVS TK-mutants isolated under selective pressure with bromovinyldeoxyuridine (BVDU) also showed reduced sensitivity to HDVD. Oral treatment with HDVD and BVDU was assessed in an intranasal model of MHV-68 infection in BALB/c mice. In contrast to BVDU treatment, HDVD-treated animals showed a reduction in viral DNA loads and diminished viral gene expression during acute viral replication in the lungs in comparison to levels in untreated controls. The valyl ester prodrug of HDVD (USS-02-71-44) suppressed the latent infection in the spleen to a greater extent than HDVD. In the present study, HDVD emerged as a highly potent antiviral with a unique spectrum of activity against herpesviruses, in particular, gammaherpesviruses, and may be of interest in the treatment of virus-associated diseases.

Antihypertensive effectiveness of aliskiren for the 'real-world' management of hypertension: multilevel modelling of 180-day blood pressure outcomes (the Belgian DRIVER Study).

AIMS: The 'DRIVER' study was designed to investigate the 'real-world' effectiveness of aliskiren-based treatment of hypertension. This article reports the 180-day blood pressure (BP) outcomes, and the multilevel (physician- and patient-level) determinants thereof. METHODS AND RESULTS: DRIVER was a prospective, observational, open-label, multi-centre, pharmaco-epidemiologic study of hypertensive patients treated with aliskiren in whom prior treatment failed or was not tolerated. 2070 patients (enrolled by 426 physicians) were enrolled; 1695 patients (81.9%) completed the 180-day aliskiren treatment period. Mean patient age was 64.2 ± 12.1 years; 53.7% were men, 25.3% diabetic and 40.7% had a high or very high cardiovascular (CV) risk. At 180 days, the mean ± SD reductions in systolic and diastolic BP were -22.9 ± 16.7 mmHg and -10.5 ± 10.9 mmHg respectively (both p < .001). 2007 and 2009 guideline-defined BP control was achieved in 36.4% and 56.3% of patients, respectively (both p < .001). 64.2% of eligible patients had a reduction in CV risk (p < .001). A physician-level class effect was responsible for 22.8% and 28.1% of variability in systolic and diastolic BP, respectively, for 20.1% of variability in BP control, and for 16.1% of variability in the reduction of CV risk. Both patient- (e.g. adherence) and physician-related factors (e.g. age and knowledge) were significant in profiling best response to treatment with aliskiren. Adverse events reported in this article were consistent with the aliskiren scientific leaflet. CONCLUSION: Aliskiren is safe and effective in reducing BP, improving BP control and reducing global CV risk in a 'real-world' setting and for patients in whom prior treatment failed or was not tolerated. Optimising treatment adherence and strategic medical education may be ways of improving BP outcomes in patients with hypertension.

Evaluation of voice control, touch panel control and assistant control during steering of an endoscope.

The increasing amount of equipment used in the Operating Room (OR) asks for ergonomical user interfaces. The aim of this study was to investigate in a pelvi-trainer setting the efficiency, reliability and user satisfaction of voice control, touch panel control and conventional manual control by an assistant. Ten subjects had to control the zoom and light intensity of an endoscope, using voice, a touch panel or an assistant. For each interface, the subject received nine tasks to control to a certain level, light, zoom or both. The experiment was repeated three times (three cycles) and the sequences of interfaces were varied per cycle. Experiments were recorded on video and off-line time needed per task and the number of wrongly interpreted tasks were measured. A questionnaire was used to investigate user satisfaction. Voice control was slower than assistant control and touch panel control (92.5 s, 80.2 s and 76.0 s, respectively, p<0.02). There was no significant difference between touch panel control and assistant control. With voice control, 3.1% of the commands were not interpreted and 1.7% were wrongly interpreted. 40% of the subjects experienced voice control as the quickest, 30% touch panel control and 30% assistant control. 48% of the subjects preferred voice control, 28% the touch panel and 24% assistant control. Voice control was less efficient than touch panel control and manual control by an assistant. The subjects experienced voice control as more efficient, however. In the future, voice control should be improved to overcome wrongly interpreted commands. Furthermore, experiments should be performed in a clinical setting in which the surgeon has to perform two-handed tasks to evaluate the effects on the surgeon's performance.

Particulate debris from a titanium metal prosthesis induces genomic instability in primary human fibroblast cells.

Previous studies detected both lethal and cumulative chromosomal aberrations in bone marrow and peripheral blood of patients with worn hip and knee replacements. This study shows that wear debris from a worn titanium metal on high-density polyethylene hip replacement also produces chromosomal instability and reproductive failure in cell culture. The progeny of these treated cells also displayed chromosomal instability, mainly consisting of chromatid breaks and minutes, and reproductive failure as determined by clonogenic survival many generations postexposure. These delayed effects are similar to those caused by the heavy metals cadmium and nickel and to those seen for low-dose radiation. These findings may have important implications with regard to the long-term risks of joint replacement surgery. This highlights the need for long-term epidemiological studies of patients with surgical implants.

Predictors for return to work in patients with median and ulnar nerve injuries.

PURPOSE: One of the consequences of median and ulnar nerve trauma is delayed return to work. The aim of this study was to determine return to work (RTW) and risk factors for delayed RTW in addition to time off work (TOW). Differences among median, ulnar, and combined median-ulnar nerve injuries were examined. METHOD: In this study 96 patients who were employed at the time of injury and who had undergone surgery for median, ulnar, or combined nerve injuries between 1990 and 1998 were evaluated. The response rate was 84% (n = 81). RESULTS: Within 1 year after injury, 59% (n = 48) returned to work. Mean TOW was 31.3 weeks. Return to work after combined nerve injuries was 24% versus after isolated median (80%) and ulnar (59%) nerve injuries. Level of education, type of job, and compliance to hand therapy were predictors for RTW. Furthermore, grip strength loss, tip pinch strength loss, and sensory recovery differed strongly between the RTW and no-RTW population. CONCLUSIONS: The predictors found in this study increase our understanding of delayed RTW after median and ulnar nerve injury and may be used to optimize postinjury rehabilitation.

Heavy metals of relevance to human health induce genomic instability.

Heavy metals used in medical prostheses or present in water supplies or tobacco can build up in tissues and blood and are well known to produce toxic effects. Normally, legislative controls on the levels of these substances are determined by reference to the acute toxicity data. This paper shows that cadmium and nickel can produce delayed effects in human cells in vitro, which are characteristic of genomic instability. The effects occur even at levels where no acute toxic effects can be demonstrated. Genomic instability can be demonstrated by persistent induction of cytogenetic abnormalities and delayed cell death in progeny of cells many generations after exposure. Formerly, this syndrome has only been definitively proven to occur following irradiation, but in these experiments cell populations exposed for only 1 or 24 hours were expanded over several months, involving eight passages, and the yield of chromosomal aberrations and cell loss due to lethal mutations did not decrease. The consequences of this genomic instability are not yet known but it is possible that many of the systemic symptoms associated with exposure to low concentrations of these metals could involve delayed expression of cellular damage. It is also clear that these effects cannot be predicted from acute toxicity data.