Health-related quality of life in oropharyngeal cancer survivors - a population-based study.

OBJECTIVE: The aim of this study was to compare QoL of oropharyngeal cancer survivors who had received different treatments. SUBJECTS AND METHODS: We contacted 954 survivors. Each survivor received the QoL questionnaires EORTC QLQ-C30 and EORTC QLQ-H&N35. RESULTS: A total of 263 survivors completed the questionnaires (28% responses). Forty-five of them had undergone surgery, 20 had received definitive radiotherapy or chemo-radiotherapy, 85 surgery plus adjuvant radiotherapy, and 111 surgery plus adjuvant chemo-radiotherapy. Survivors who had received adjuvant radiotherapy and surgery reported significantly more problems with swallowing (B=13.43 [95% Confidence Interval (CI) 1.83-25.03]), senses (B=24,91 [CI 11.86-37.97]), eating (B=16.91 [CI 3.46-30.36]), dry mouth (B=26.42 [CI 12.17-40.67]), sticky saliva (B=22.37 [CI 6.23-38.50]) and nutritional supplements (B=18.59 [CI 0.62-36.56]) than those who had received surgery only. Survivors who had received adjuvant chemo-radiotherapy and surgery reported significantly many more problems with dry mouth (B=34.15 [CI 18.91-49.39]) and sticky saliva (B=22.90 [CI 5.65-40.16]), and fewer problems with physical functioning (B=-12.07 [CI 0.49-23-64]). CONCLUSION: Survivors who participated in this survey and who had undergone surgery alone reported in some head- and neck-specific domains a better health-related quality of life than patients who had undergone multi-modal treatment or adjuvant radiotherapy.

[Management of spinal metastases, strategies and surgical indications]. / Management der Wirbelsäulenmetastasen, Strategien und operative Indikationen.

The number of bone metastases increases with prolonged survival of primary tumors of kidney, breast, prostate and other tumors. The spine is the most frequent site of bone metastases. This leads to high number of patients where the decision has to be made what kind of treatment should be the best. Several scores have been developed to solve this problem. The decision has to include the biology of the metastatic disease according to primary tumor and dissemination of the disease, the general condition of the patient, the residual stability of the spine, the neurologic status and most important the quality of life of the patient. Treatment options range from conservative treatment up to en bloc resection of the metastatic lesion. Therefore, the strategy of treatment always has to be decided on an individual base.

[Radiological diagnostics of inflammatory spinal diseases: what is the state of the art?]. / Radiologische Diagnostik entzündlicher Wirbelkörpererkrankungen : Was ist "state of the art"?

Back pain is nonspecific and allows a broad range of differential diagnoses. In the early phase of infectious or neoplastic processes conventional diagnostic radiology rarely shows groundbreaking findings. Magnetic resonance imaging (MRI) is the method of choice to detect early changes in the vertebral bodies, intervertebral discs and surrounding tissues. Fluid-sensitive, fat-suppressed sequences (STIR) and contrast media are used to distinguish infections from other diseases. Due to the typical signal intensity in T1 and T2 sequences, infections of degenerative, rheumatic, and neoplastic processes can be defined and allow the initiation of appropriate therapy.

[Pyogenic spondylodiscitis: therapy algorithm and a new classification for therapeutic decision-making]. / Pyogene Spondylodiszitis : Therapiealgorithmus und neue Klassifikation zur therapeutischen Entscheidungsfindung.

The incidence of pyogenic spondylodiscitis is low but has been steadily increasing in recent years. To date there has been no consensus concerning selection of the appropriate treatment, management and strategies and the recommendations for an operative strategy are still a highly controversial issue. In the literature a few statements have been published concerning therapeutic decision-making in pyogenic spondylodiscitis. The classification given in this article is based on clinical experience and retrospective data analysis considering the degree of segmental bony destruction, grade of kyphosis and instability, epidural involvement of the disease and neurological deficits, which are pivotal for therapeutic decision-making. The therapeutic procedure can be defined based on this classification.

[Role and limitations of vertebroplasty and kyphoplasty in the management of spinal metastases]. / Rolle und Grenzen der Vertebro-/Kyphoplastie im Metastasenmanagement der Wirbelsäule.

The spine is the most common site for skeletal metastases. Tumor-induced osteolysis may lead to pain, dysfunction and ultimately vertebral fracture. In some patients conventional surgery is not suitable because of the palliative therapy approach. Just for this patient population it was shown that cement augmentation of the vertebra is an effective therapy option and plays an important role. Nevertheless, cement augmentation of the vertebra has its limitations and should only be applied by appropriate indications.

Formation and photocatalytic decomposition of a pellicle on anatase surfaces.

The acquired dental pellicle plays a critical role in the adhesion and detachment of dental plaque bacteria. It has been reported that titanium dioxide biomaterials decompose single-protein films by photocatalysis. However, it is not known whether this can also be achieved with complex structured pellicle films. This in vitro study investigated in real-time the formation and photocatalytic decomposition of human pellicle at anatase-saliva interfaces. Nanostructured polycrystalline anatase layers were deposited on titanium-coated quartz crystals by magnetron-sputtering, serving as a model for titanium implant surfaces. The quartz crystals were used as acoustic sensors in a quartz-crystal microbalance (QCM) system with dissipation. In situ UV irradiation of pellicle-covered anatase caused a statistically significant decrease of the adsorbed salivary mass. In contrast, photocatalytic decomposition of pellicle could not be observed on reference titanium surfaces. Wettability characterization revealed superhydrophilicity of anatase upon UV irradiation, whereas titanium was unaffected. XPS measurements provide further information concerning the decomposition of the salivary films. The results suggest that the photocatalytic activity of polycrystalline anatase-modified biomaterial surfaces is able to decompose complex structured macromolecular pellicle films. Therefore, this study opens the way to surface modifications supporting therapeutic approaches of biofilm removal.

Not all biologics are equal!

BACKGROUND: Although the efficacy of various biologic meshes in the abdominal reconstruction of complex ventral hernia has been shown, the performance profile of various biologic mesh scaffolds in terms of hernia-specific outcomes such as recurrence, mesh explantation, and mesh infections has not been examined. AIM: To evaluate the clinical outcomes of patients who underwent complex ventral hernia repair with bioprosthetic material. METHODS: This study is a retrospective analysis of the use of bioprosthetic material in complex ventral hernia at an academic institution from January 2002 to December 2007. RESULTS: A total of 58 patients with a mean age of 57.2 years and mean body mass index (BMI) of 33.8 who underwent reconstruction of ventral abdominal defects with a bioprosthetic from January 2002 to February 2009 were included in the study. The study patients had about 4.8 previous surgeries and 43.1% of patients had reconstruction in a setting of enterocutaneous fistula, while 46.6% had a previous mesh infection. Complex ventral hernia was seen in 50 patients, while eight patients had ventral and parastomal hernia. The type of biologic used for reconstruction was human-derived (AlloDerm, 29), porcine cross-linked (CollaMend, 3; Permacol, 2), and non-cross-linked porcine (Surgisis, 16; Strattice, 8). At least one complication was seen in 72.4% of patients. Major complications noted were surgical wound infections (19.0%), seroma (8.6%), and abscess formation (5.2%). The one-year hernia recurrence rate was 27.9% and mesh explantation was needed in 17.2% of patients. AlloDerm was less likely to be explanted (13.8%) or become infected (37.9%) but more likely to recur (28.6%) compared to porcine cross-linked bioprosthesis. Porcine cross-linked biologics were more likely to become infected (60%) and explanted (40%) but less likely to recur (20%) compared to AlloDerm. Non-cross-linked porcine biologics were less likely to be explanted (16.7%) but had higher recurrence (29.4%) compared to cross-linked porcine biologics and a higher infection rate (54.2%) compared to AlloDerm. CONCLUSIONS: The results from this study underscore the difficulty of repairing complex abdominal wall defects in contaminated fields. Cross-linked porcine biologics showed relatively higher infection and explantation rates. Equivalent recurrence and explantation rates were observed for the non-cross-linked porcine biologics and AlloDerm. These data indicate that there is currently no ideal biologic for complex ventral hernia repair.

Multifunctional nature of UV-irradiated nanocrystalline anatase thin films for biomedical applications.

Anatase is known to decompose organic material by photocatalysis and to enhance surface wettability once irradiated by ultraviolet (UV) light. In this study, pulse magnetron-sputtered anatase thin films were investigated for their suitability with respect to specific biomedical applications, namely superhydrophilic and biofilm degrading implant surfaces. UV-induced hydrophilicity was quantified by static and dynamic contact angle analysis. Photocatalytic protein decomposition was analyzed by quartz crystal microbalance with dissipation. The surfaces were characterized by X-ray diffraction, atomic force microscopy, scanning electron microscopy and X-ray photoelectron spectroscopy. The radical formation on anatase, responsible for photocatalytic effects, was analyzed by electron spin resonance spectroscopy. Results have shown that the nanocrystalline anatase films, in contrast to reference titanium surfaces, were sensitive to UV irradiation and showed rapid switching towards superhydrophilicity. The observed decrease in carbon adsorbents and the increase in the fraction of surface hydroxyl groups upon UV irradiation might contribute to this hydrophilic behavior. UV irradiation of anatase pre-conditioned with albumin protein layers induces the photocatalytic decomposition of these model biofilms. The observed degradation is mainly caused by hydroxyl radicals. It is concluded that nanocrystalline anatase films offer different functions at implant interfaces, e.g. bedside hydrophilization of anatase-coated implants for improved osseointegration or the in situ decomposition of conditioning films forming the basal layer of biofilms in the oral cavity.

Mechanical heart valve cavitation: valve specific parameters.

Several aspects of mechanical heart valve cavitation, in particular of "severe" vapor cavitation, have been investigated in order to describe the phenomenon of cavitation itself and to classify various mechanical heart valves with respect to their tendency to cavitation. Furthermore, following the results of the measurements, a model for determination of time-dependent physical properties and dynamics of cavitation bubbles, such as size, pressure and temperature was developed. In order to classify the cavitation tendency of mechanical valves, a pulsatile hydraulic-driven circularly mock loop was used. Besides measurements of the relevant hemodynamic parameters, the leaflet velocities of the valves were also determined. In addition, numerous high-resolution pressure measurements, in particular the pressure drops necessary for the initiation of cavitation (local atrial pressure drop), were performed. For the investigation of bubble dynamics, a second pulsatile electro-magnetically-driven tester was used. The influence of density, viscosity and temperature of the fluid on the onset of cavitation was investigated. Cavitation events were recorded with a digital high-speed video camera (up to 40,500 frames/sec) for all investigated heart valves and under different conditions. A critical local upstream pressure drop (located within the model atrium after valve closure) of 450 mmHg was found for all valves as well as a valve specific correlation between left ventricular pressure gradient and local upstream pressure drop. Also, a valve dependent correlation between left ventricular pressure gradient and the local upstream pressure drop was provided. Finally, valve specific parameters were found to predict the cavitation tendency for a specific heart valve. The implementation of a suitable theoretical model allowed conclusions on bubble physics. High pressures (up to 800 bar) and temperatures (up to 1,300 degrees C) at bubble collapse have been determined. The influence of fluid parameters such as density, viscosity and temperature on the onset of cavitation is negligible within physiological range. Critical regions for cavitation for all mechanical heart valves were detected. All mechanical heart valves investigated show cavitation under different conditions (dp/dt) associated with high pressures and temperatures at bubble collapse. Cavitation bubble occurrence depends on valve design and location.

A general strategy for site-specific double labeling of globular proteins for kinetic FRET studies.

Site-directed mutagenesis provides a straightforward means of creating specific targets for chemical modifications of proteins. This capability enhanced the applications of spectroscopic methods adapted for addressing specific structural questions such as the characterization of partially folded and transient intermediate structures of globular proteins. Some applications such as the steady state or time-resolved fluorescence resonance energy transfer (FRET) detection of the kinetics of protein folding require relatively large quantities (approximately 10-100 mg) of site-specific doubly labeled protein samples. Engineered cysteine residues are common targets for labeling of proteins. The challenge here is to develop methods for selective modification of one of two reactive sulfhydryl groups in a protein molecule. A general systematic procedure for selective labeling of each of two cysteine residues in a protein molecule was developed, using Escherichia coli adenylate kinase (AKe) as a model protein. Potential sites for insertion of cysteine residues were selected by examination of the crystal structure of the protein. A series of single-cysteine mutants was prepared, and the rates of the reaction of each engineered cysteine residue with a reference reagent [5,5'-dithiobis(2-nitrobenzoic acid) (DTNB)] were determined. Two-cysteine mutants were prepared by selection of pairs of sites for which the ratio of this reaction rate constant was high (>80). The conditions for the selective labeling reaction were optimized. In a first cycle of labeling, the more reactive cysteine residue was labeled with a fluorescent probe (donor). The second probe was attached to the less reactive site under unfolding conditions in the second cycle of labeling. The doubly and singly labeled mutants retained full enzymatic activity and the capacity for a reversible folding-unfolding transition. High yields (70-90%) of the preparation of the pure, site-specific doubly labeled AK mutant were obtained. The procedure described herein is a general outline of procedures, which can meet the double challenge of both site specificity and large-scale preparation of doubly labeled proteins.

Phase I clinical trial on adjuvant active immunotherapy of human gliomas with GD2-conjugate.

The objective of this study was to determine the feasibility, toxicity, and potential therapeutic benefits of an adjuvant active immunotherapy using a tumour specific ganglioside (GD2) conjugate for the adjuvant treatment of recurrent or progressive gliomas. Seven patients with proven GD2 expression in surgical specimens underwent a vaccination course with GD2-KLH/MPL-A conjugate. The follow-up was performed according to WHO guidelines regarding common toxicity criteria. Antibody titres against the ganglioside and the adjuvants were analysed. All patients developed a local type 4 reaction. Anti-GD2-antibody titres could not be detected, despite high titres against the immunoadjuvants. No tumour regression was observed. The disease remained stable for a median of 21.5 weeks (6-34 weeks). The median survival time after the first immunization was 47 weeks. The medial total survival time was 76 weeks. Adverse effects have not been observed. Active GD2-KLH/MPL-A immunization was technically feasible, but did not elicit anti-GD2 antibody generation.

Measurement of parenting self-efficacy and outcome expectancy related to discussions about sex.

The purpose of this study was to evaluate the psychometric properties of two scales--one to measure the self-efficacy of parents to discuss sexual health issues with their adolescents and the other to measure parents' outcome expectancy associated with such discussions. Understanding how parents feel about their confidence in talking with their children about important sexual health issues and the outcomes they expect as a result of such discussions can be useful in guiding both the development and refinement of educational programs to promote parent-child discussions. The responses of 491 mothers who participated in an HIV prevention intervention with their adolescents were used for the present analysis. Mothers ranged in age from 25 to 68 years with a mean of 37.9 years (SD = 6.9). Of mother participants, 33% were married, 96.7% were African American, and 89.2% had completed high school. Their adolescents ranged in age from 11 to 14 years, and 61.5% were male. Assessment of reliability for both scales showed that internal consistency reliability was acceptable for the total scales as well as three of the five subscales. With the exception of one item on the outcome expectancy scale, the inter-item correlations, the mean inter-item correlations, and the item-to-total correlations meet the standard criteria for scale development for both scales. Factor analysis was used to identify the underlying structure of the scales, and hypothesis testing was used to assess construct validity. The results of these analyses provide support for the construct validity of the scales.

Origin and appearance of HITS induced by prosthetic heart valves: an in vitro study.

Patients with mechanical heart valve prostheses show significantly enhanced numbers of HITS detected by transcranial Doppler ultrasound. In order to assess the origin of HITS formation, an in vitro study was set out to quantify valve induced microemboli for mechanical and bioprosthetic valves under various circulatory conditions by means of Ultrasound-Doppler-Sonography. At the same time the influence of CO2 partial pressure on HITS rate vas investigated. It can be summarised that for mechanical heart valve prostheses a strong correlation exists between left ventricular dp/dtmax and the detected HITS rates. It was also demonstrated that a bioprosthesis generates significantly less HITS than a mechanical valve. The origin of HITS is gaseous since the tests were carried out using a cell-free filtered water-glycerol test fluid. The HITS rate could be increased by increasing the amount of dissolved gas within the test fluid. The results support the hypothesis that cavitation is the key factor in the appearance of gaseous microemboli at heart valve prostheses.

Can vortices in the flow across mechanical heart valves contribute to cavitation?

Cavitation in mechanical heart valves is traditionally attributed to the hammer effect and to squeeze and clearance flow occurring at the moment of valve closure. In the present study, an additional factor is considered--the contribution of vortex flow. Using a computational fluid dynamics analysis of a 2D model of a tilting disk mitral valve, we demonstrate that vortices may form in the vicinity of the inflow side of the valve. These vortices roll up from shear layers emanating from the valve tips during regurgitation. A significant decrease in the pressure at the centre of the vortices is found. The contribution of the vortex to the total pressure drop at the instant of closure is of the order of 70 mmHg. Adding this figure to the other pressure drop sources that reach 670 mmHg, it might be that this is the deciding factor that causes the drop in blood pressure below vapour pressure. The total pressure drop near the upper tip (750 mmHg) is larger than near the lower tip (670 mmHg), indicating a preferential location for cavitation inception, in agreement with existing experimental findings.

A library of atmospheric pressure ionization daughter ion mass spectra based on wideband excitation in an ion trap mass spectrometer.

A searchable library of MS/MS spectra obtained using a quadrupole ion trap mass spectrometer and electrospray or atmospheric pressure chemical ionization is presented. The application of wideband excitation (activation) and normalized collision energy leads to highly reproducible mass spectra which are searched using the NIST algorithm. Flow injection and LC/MS/MS applications of this powerful technique in the biomedical (diastereoisomeric steroids, morphine glucuronides, isovalerylcarnitine) and environmental (pirimicarb and desmethyl-pirimicarb) areas are described.

Identification of synaptic connections in neural ensembles by graphical models.

A method for the identification of direct synaptic connections in a larger neural net is presented. It is based on a conditional correlation graph for multivariate point processes. The connections are identified via the partial spectral coherence of two neurons, given all others. It is shown how these coherences can be calculated by inversion of the spectral density matrix. In simulations with GENESIS, we discuss the relevance of the method for identifying different neural ensembles including an excitatory feedback loop and networks with lateral inhibitions.

Recognition of laparoscopic bile duct injuries by intraoperative ultrasonography.

BACKGROUND: The purpose of this study was to investigate the possibility of detecting bile duct injuries using laparoscopic intraoperative ultrasound (LIOU). METHODS: Fifty bile duct injuries were created using laparoscopic techniques in ten farmer pigs. The lesions created were: (1) partial occlusion, (2) complete occlusion (1 clip), (3) complete occlusion (2 clips), (4) transection between clips, (5) excision between clips. RESULTS: All injuries were easily visualized using LIOU. The relation of clips impinging upon or occluding the bile duct was readily visualized on LIOU in all cases. In some cases it was difficult to distinguish between partial and complete occlusion. It was also difficult to distinguish between transection and excision due to retraction of the severed bile duct. CONCLUSIONS: In cases of iatrogenic occlusion of the bile duct involving hemoclips (including transection or excision between clips), LIOU is a potentially useful modality that may allow earlier recognition and repair. Further studies are needed to evaluate the efficacy of LIOU in detection of bile duct injuries that do not involve hemoclips.

Stimulation of alpha 2 adrenoceptors dilates the rat middle cerebral artery.

BACKGROUND: Because alpha 2 adrenoceptor agonists are used as adjuncts to anesthetics, their effects on the cerebrovascular circulation are of prime importance. We studied changes in the diameter of rat middle cerebral arteries after stimulation of alpha 2 adrenoceptors with UK14,304. METHODS: Rat middle cerebral arteries were isolated, cannulated at each end with a glass micropipette, and pressurized to 85 mmHg. The middle cerebral arteries were immersed in a bath (37 degrees C) containing physiologic saline solution, and luminally perfused with physiologic saline solution (100 microliters/ min). Changes in vessel diameter were measured after magnification with a microscope. RESULTS: Resting diameter of the middle cerebral arteries was 239 +/- 13 microns (n = 8) for the first study. A dose-dependent dilation was produced by addition of UK14,304 to the extraluminal bath; a 10-15% increase in diameter occurred at a concentration of 10(-4)M. The dilations produced by UK14,304 were blocked with selective alpha 2-antagonists, idazoxan and rauwolscine, but not by the selective alpha 1-antagonist, prazosin. The dilations could be blocked by removal of the endothelium, or the nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (10(-5) M). The inhibitory effects of N-nitro-L-arginine methyl ester were reversed with the addition of 10(-3) M L-arginine, but not 10(-3) M D-arginine. Furthermore the dilation produced by UK14,304 was completely abolished with pertussis toxin (100 ng/ml). CONCLUSIONS: It was concluded that the stimulation of alpha 2 adrenoceptors with UK14,304 produced a dilation in the rat middle cerebral artery that (1) was dependent on intact endothelium, (2) involved nitric oxide, and (3) acted via a pertussis toxin-sensitive G protein.

In vitro testing of heart valve wear outside of the manufacturers laboratory--requirements and controversies.

BACKGROUND AND AIM OF THE STUDY: Currently, various national and international Standards regulate in vitro and in vivo testing as well as the clinical evaluation of heart valve prostheses. This study concentrates on a single aspect of these protocols: accelerated wear and fatigue testing. METHODS: The differences in the above Standards were appraised and an experimental study was designed to assess the validity of Standard testing conditions with respect to in vivo relevance. An instrumented BSCC tilting disc valve was tested in two different types of fatigue testers and in a separate study in a sheep model. RESULTS: By comparing the obtained results it could be clearly demonstrated that under the current Standard conditions (ISO, CEN, FDA) actual in vivo impact loading cannot be reproduced. Also, the two compared test devices, though operating under the same Standard conditions, generated totally different loading conditions on the test valve. CONCLUSIONS: Based on these findings it is suggested that the actual loading conditions of each valve type should be measured either in vivo in animal models or within a circulatory mock loop which provides physiologic loading conditions, and the test conditions for accelerated wear and fatigue testing should be modified accordingly. Cavitation effects which can be assumed to be associated with high frequency wear testing is another important issue which has to be addressed in future amendments to the Test Standards.