A combined experimental and computational approach to evaluate microclimate control at the support surface interface.

Temperature and humidity conditions at the interface between a support surface and the skin, termed microclimate, has been implicated in the development of pressure ulcers. Support surface technologies have been developed to control microclimate conditions, although only a few standard test methods exist to evaluate their performance. This study describes a combined experimental-computational approach to analyzing microclimate control systems. The study used a modified physical model protocol to evaluate two specific support surface systems involving a spacer fabric cover with i) no air flow and ii) an active fan. The physical model deposited moisture at a controlled rate for 25 min, and the microclimate conditions under the model and the surrounding area were monitored for 24 h. Using the experimental data as boundary conditions, a finite element model was developed using mass transport principles, which was calibrated using experimental results. Model inputs included mass density and mass diffusivity, resulting in an estimated absolute humidity change over time. The physical model tests revealed distinct differences between the support surfaces with and without active airflow, with the former having little effect on local humidity levels (RH>75% for 24hr). By contrast, there was a spatial and temporal change in microclimate with the active fan, with sensors positioned towards the source of airflow reaching ambient conditions within 24hr. The computational model was refined to produce comparable results with respect to both the spatial distribution of microclimate and the change in values over time. The combined experimental and computation approach was able to distinguish distinct difference in microclimate change between two support surface designs. The approach could enable the efficient evaluation of different mattress design principles to aid decision making for personalized support surface solutions, for the prevention of pressure ulcers.

Radiological imaging of teratological fetuses: what can we learn?

OBJECTIVES: To determine the advantages of radiological imaging of a collection of full-term teratological fetuses in order to increase their scientific and educational value. BACKGROUND : Anatomical museums around the world exhibit full-term teratological fetuses. Unfortunately, these museums are regularly considered as "morbid cabinets". Detailed dysmorphological information concerning the exhibited specimens is often lacking. Moreover, fetuses with severe and complex congenital anomalies are frequently diagnosed incompletely, incorrectly or not at all. METHODS: In order to verify diagnoses and to enrich their educational and scientific value, we imaged 41 out of the 72 teratological specimens present in the collection of our Anatomy and Pathology Museum in Nijmegen (The Netherlands) by means of magnetic resonance imaging (MRI) and computed tomography (CT). Additionally, contemporary dysmorphological insights and 3D models are implemented in the teratology education of medical students and residents. CONCLUSIONS: Full-term teratological fetuses have become increasingly rare and deserve a prominent place in every anatomical museum; they are suitable for contemporary teratological research and education. Modern radiological techniques markedly enhance their scientific and didactic value. TEACHING POINTS: • To explore the scientific and educational potential of institutionalised teratological collections • To understand the additional value of radiological imaging in diagnosing teratological specimens • To learn about the specific settings of MRI parameters when scanning fixed specimens • To recognise specific internal dysmorphology in several congenital anomalies.

Multi-center reproducibility of neurochemical profiles in the human brain at 7 T.

The purpose of this work was to harmonize data acquisition and post-processing of single voxel proton MRS ((1) H-MRS) at 7 T, and to determine metabolite concentrations and the accuracy and reproducibility of metabolite levels in the adult human brain. This study was performed in compliance with local institutional human ethics committees. The same seven subjects were each examined twice using four different 7 T MR systems from two different vendors using an identical semi-localization by adiabatic selective refocusing spectroscopy sequence. Neurochemical profiles were obtained from the posterior cingulate cortex (gray matter, GM) and the corona radiata (white matter, WM). Spectra were analyzed with LCModel, and sources of variation in concentrations ('subject', 'institute' and 'random') were identified with a variance component analysis. Concentrations of 10-11 metabolites, which were corrected for T1 , T2 , magnetization transfer effects and partial volume effects, were obtained with mean Cramér-Rao lower bounds below 20%. Data variances and mean concentrations in GM and WM were comparable for all institutions. The primary source of variance for glutamate, myo-inositol, scyllo-inositol, total creatine and total choline was between subjects. Variance sources for all other metabolites were associated with within-subject and system noise, except for total N-acetylaspartate, glutamine and glutathione, which were related to differences in signal-to-noise ratio and in shimming performance between vendors. After multi-center harmonization of acquisition and post-processing protocols, metabolite concentrations and the sizes and sources of their variations were established for neurochemical profiles in the healthy brain at 7 T, which can be used as guidance in future studies quantifying metabolite and neurotransmitter concentrations with (1) H-MRS at ultra-high magnetic field.

[Thrombosis in ovarian hyperstimulation syndrome]. / Trombose bij ovarieel hyperstimulatiesyndroom.

BACKGROUND: Ovarian hyperstimulation syndrome is a rare complication of IVF treatment. In severe ovarian hyperstimulation syndrome there is an increased risk of thrombo-embolic events. Venous thrombotic complications tend to occur several weeks after the resolution of ovarian hyperstimulation syndrome. Predominant sites of venous thrombosis in OHSS are the upper extremities. CASE DESCRIPTION: A 34-year old woman presented to the emergency department with complaints about a painful swelling in the neck and a bluish discoloration of the right arm. She had been admitted to the hospital six weeks before, because of shortness of breath from pleural effusion due to ovarian hyperstimulation syndrome. The diagnosis of jugular vein and subclavian vein thrombosis was made. She was treated with therapeutic doses of low-molecular-weight heparin. CONCLUSION: Venous thrombosis is a rare but serious complication of ovarian hyperstimulation syndrome. For patients who require admission because of severe ovarian hyperstimulation syndrome, thromboprophylaxis should be continued several weeks after discharge.

Functional MRI techniques demonstrate early vascular changes in renal cell cancer patients treated with sunitinib: a pilot study.

OBJECTIVE: To assess the early vascular effects of sunitinib in patients with renal cell carcinoma (RCC) with diffusion-weighted magnetic resonance imaging (DWI), dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and T2* perfusion MRI. PATIENTS AND METHODS: In 10 patients with abdominal RCC lesions, DWI, DCE-MRI and T2* perfusion MRI measurements at 3 Tesla were performed at baseline, 3 and 10 days after start of sunitinib. VEGF-A plasma levels were measured on days 0, 3 and 10. RESULTS: DWI showed a significant increase in the apparent diffusion coefficient (×10(-6) s/mm(2)) from baseline (mean 1158, range 814-2003) to day 3 (mean 1306, range 1008-2097, P = 0.015) followed by a decrease to baseline levels at day 10 (mean 1132, range 719-2005, P = 0.001). No significant changes were found in mean DCE-MRI parameters. T2* perfusion MRI showed a significant decrease in relative tumor blood volume (rBV) and relative tumor blood flow (rBF) at day 3 (rBV P = 0.037, rBF P = 0.018) and day 10 (rBV P = 0.006, rBF P = 0.009). VEGF-A plasma levels significantly increased after 10 days, but did not correlate with MRI parameters. CONCLUSIONS: Sunitinib induces antiangiogenic effects as measured by DWI and T2*-perfusion MRI, 3 and 10 days after the start of the initial treatment. DCE-MRI did not show significant changes. In the near future, early functional MRI-based evaluation can play an important role in tailoring treatment to the individual patient with RCC. Further investigation is warranted.

Detection of fully refocused polyamine spins in prostate cancer at 7 T.

(1)H MRSI is often used at 1.5 or 3 T to study prostate cancer, where the ratio of choline + creatine to citrate is taken as a marker for tumour presence. Recently, the level of polyamines (mainly spermine) has been shown to improve specificity even further. However, the in vivo detection of these polyamines (at 3.1 ppm) is hampered by signal cancellation as a result of J-coupling effects and signal overlap with choline (3.2 ppm) and creatine (3.0 ppm) resonances. At higher magnetic field strengths, the chemical shift dispersion will increase, which allows the use of very selective radiofrequency pulses to refocus J-coupled spins. In this work, we added selective refocusing pulses to a semi-LASER (localisation based on adiabatic selective refocusing) sequence at 7 T, and optimised the inter-pulse timings of the sequence for fully refocused detection of spermine spins, whilst maintaining optimised detection of choline, creatine and the strongly coupled spin system of citrate.

The role of inflammation on atherosclerosis, intermediate and clinical cardiovascular endpoints in type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with increased cardiovascular morbidity and mortality. Sub-clinical systemic inflammation is often present in T2DM patients. Systemic inflammation has also been implicated in the pathophysiology of atherosclerosis. This review investigates the direct evidence present in literature for the effect of inflammation on atherosclerosis, specifically in the setting of T2DM. Special emphasis is given to the pathogenesis of atherosclerosis as well as intermediate and clinical cardiovascular endpoints. The important role of deteriorated endothelial function in T2DM was excluded from the analysis. METHODS: Extensive literature searches were performed using the PubMed and Web of Science databases. Articles were identified, retrieved and accepted or excluded based on predefined criteria. RESULTS: Substantial evidence was found for an important inflammatory component in the pathogenesis of atherosclerosis in T2DM, demonstrated by inflammatory changes in plaque characteristics and macrophage infiltration. Most epidemiologic studies found a correlation between inflammation markers and intermediate cardiovascular endpoints, especially intima-media thickness. Several, but not all clinical trials in T2DM found that reducing sub-clinical inflammation had a beneficial effect on intermediate endpoints. When regarding cardiovascular events however, current literature consistently indicates a strong relationship between inflammation and clinical endpoints in subjects with T2DM. CONCLUSION: Current literature provides direct evidence for a contribution of inflammatory responses to the pathogenesis of atherosclerosis in T2DM. The most consistent relation was observed between inflammation and clinical endpoints.

Cowpoxvirus infection in the Patagonian cavy (Dolichotis patagonum) emerging disease in an educational animal park the first reported case.

Generalized cowpox infection in the Patagonian cavy may represent a threat to the health of immunocompromised persons. We report the first case of cowpoxvirus infection in the Patagonian cavy in an educational animal park. The mara developed extensive pox lesions, shedding large amounts of viral particles. The ending of vaccination programmes against smallpox in the late 1970's may lead to an increase in susceptibility of humans to zoonotic poxviruses.

Biological monitoring the exposure to polycyclic aromatic hydrocarbons of coke oven workers in relation to smoking and genetic polymorphisms for GSTM1 and GSTT1.

UNLABELLED: Occupational exposure to polycyclic aromatic hydrocarbons (PAH) increases the risk of developing lung cancer. Human exposure is often demonstrated by increased internal levels of PAH metabolites and of markers for early biological effects, like DNA adducts and cytogenetic aberrations. OBJECTIVE: This study aimed to assess whether the current exposure to PAH of coke oven workers in a Dutch plant induced biological effects, and to determine if these effects are influenced by tobacco smoking and by genetic polymorphisms for the glutathione S-transferase genes GSTM1 and GSTT1. METHODS: Urinary 1-hydroxypyrene (1-OHpyr) levels were used to monitor the internal dose, while the internal effective dose was assessed by monitoring PAH-DNA adducts, DNA strand breaks (Comet assay), sister-chromatid exchanges (SCE) and cells with a high frequency of SCE (HFC) in lymphocytes together with micronuclei (MN) in exfoliated urothelial cells. RESULTS: Occupational exposure to PAH resulted in statistically significant increased 1-OHpyr levels (P<0.001), but it did not cause a significant induction of SCE, HFC, MN, DNA strand breaks or DNA adducts. Smoking caused a significant increase of 1-OHpyr (P<0.05), SCE (P<0.001), HFC (P<0.001) and DNA adducts (P<0.05), but not of MN or DNA strand breaks. Following correction for the smoking-related effects, no occupational induction of the effect biomarkers could be discerned. Multi-variate analysis did not show a significant influence of GSTM1 and GSTT1 polymorphisms on any biomarker. Also no significant interactions were observed between the various biomarkers. CONCLUSION: This study shows that in the examined plant, the occupational exposure to PAH does not result in measurable early biological effects

Studies on the efficacy of hyperbaric rendering procedures in inactivating bovine spongiform encephalopathy (BSE) and scrapie agents.

The efficacy of the procedures in use at the two rendering plants in the Netherlands was assessed on a laboratory-scale using procedures that simulated the pressure cooking part of the rendering process. A pool of bovine spongiform encephalopathy (BSE)-infected brainstem from the United Kingdom and a pool of scrapie-infected brainstem from Dutch sheep were used to spike the rendering materials. The mixtures were subjected to various time-temperature combinations of hyperbaric heat treatment related to the conditions used in Dutch rendering plants in the early 1990s, and to the combination of 20 minutes at 133 degrees C required by the EU Directive on rendering of 1996. The efficacy of the procedures in inactivating BSE or scrapie infectivity was measured by titrating the materials before and after heat treatment in inbred mice, by combined intracerebral and intraperitoneal inoculations at limiting dilutions. Two independent series of experiments were carried out. The design of the study allowed for minimum inactivations of up to 2.2 log (2.0 in the second series) to be measured in the diluted infective material and 3.1 log in the undiluted material. After 20 minutes at 133 degrees C there was a reduction of BSE infectivity of about 2.2 log in the first series (with some residual infectivity detected), and in the second series more than 2.0 log (with no residual infectivity detected). With undiluted brain material there was an inactivation of about 3.0 log (with some residual infectivity detected). With the same procedure, scrapie infectivity was reduced by more than 1.7 log in the first series and by more than 2.2 log in the second series. With undiluted brain material there was an inactivation of more than 3.1 log. In each case no residual scrapie infectivity was detected. The BSE agent consistently appeared to be more resistant to heat inactivation procedures than the scrapie agent, particularly at lower temperatures and shorter times.

Monitoring of occupational exposure to polycyclic aromatic hydrocarbons in a carbon-electrode manufacturing plant.

An investigation is presented of occupational exposure to polycyclic aromatic hydrocarbons (PAH) in a carbon-electrode manufacturing plant, as assessed by three monitoring methods, viz. environmental monitoring of the external dose by analysis of personal air samples, biological monitoring of the internal dose by analysis of urinary 1-hydroxypyrene (1-OHpyrene), and biological effect monitoring by dosimetry of PAH-DNA adducts in blood lymphocytes. On the basis of job conditions, workers at the plant were divided into three groups with presumed low, intermediate and high exposure to air-borne PAH, respectively. All air samples showed levels of total PAH below the current MAC-value in the Netherlands, which is 200 micrograms/m3, whereas the benzo[a]pyrene level was occasionally higher than the recommended concentration of 2 micrograms/m3. The values of 1-OHpyrene in urine from the intermediate and high exposure groups were significantly higher than those of the low exposure group, namely 3.6- and 8.2-fold, respectively. Clear external and internal exposure was thus demonstrated for workers of the high and intermediate exposure groups, but this did not result in a measurable effect at the DNA level in blood lymphocytes. Tobacco smoking, on the other hand, caused a significant increase of the levels of PAH-DNA adducts but did not affect 1-OHpyrene values. These data suggest that smoking is a more important risk factor for adverse health effects, i.e. cancer, than occupational exposure to PAH in this plant.

8OHdG levels in brain do not indicate oxidative DNA damage in Alzheimer's disease.

Accumulation of oxidative DNA damage has been proposed to underlie aging and neurodegenerative diseases such as Alzheimer's Disease (AD). The DNA adduct 8-hydroxy-2'-deoxyguanosine (8OHdG) is considered a good indicator of oxidative DNA damage. To investigate whether this type of DNA damage is involved in AD etiology, 8OHdG levels were determined in postmortem human brain tissue of controls and AD patients (in frontal, occipital, and temporal cortex and in hippocampal tissue). Parametric studies in rat revealed no influences of postmortem delay, repeated freezing/thawing or storage time. In human brain, approximately two 8OHdG molecules were present per 10(5) 2'-deoxyguanosines. In AD patients and controls, 8OHdG-levels were not related to age, sex, or brain region. Also, no differences were found between controls and AD patients. It was concluded that 8OHdG in nuclear DNA, although present throughout the brain in fairly high amounts, does not accumulate with age, nor does it appear to be involved in AD. More detailed studies are required to extend this conclusion to other types of oxidative damage.

Effect of eugenol on the mutagenicity of benzo[a]pyrene and the formation of benzo[a]pyrene-DNA adducts in the lambda-lacZ-transgenic mouse.

To study the possible reduction by eugenol of the mutagenicity and genotoxicity of benzo[a]pyrene (B[a]P) in vivo, the lambda-lacZ-transgenic mouse strain 40.6 (Muta Mouse) was used. Male mice were fed a diet containing 0.4% (w/w) eugenol or a control diet for 58 days. On day 10, half of the mice received an i.p. dose of 100 mg/kg b.w. B[a]P. The lacZ mutants were recovered by packaging of DNA isolated from liver into lambda phage, and expressed in E. coli C lacZ-recA-galE- bacteria. In both control mice and mice fed the eugenol diet, B[a]P treatment resulted in a similar, significant increase in lacZ mutant frequency. Eugenol was not mutagenic by itself. By 32P-postlabelling analysis of the liver DNA using an analysis method with chromatographic conditions for B[a]P-DNA adducts, no effect of eugenol on the formation of B[a]P-DNA adducts in the lambda-lacZ-transgenic mouse was found. By 32P-postlabelling analysis using an alkenylbenzene solvent system the amount of B[a]P-DNA adducts was lower in mice fed the eugenol diet than in mice fed the control diet but the decrease was not statistically significant. However, one spot indicative of an eugenol-associated DNA adduct was detected. The present data provide no evidence for antimutagenic or antigenotoxic potential of eugenol in vivo. Furthermore, they suggest genotoxicity in vivo of eugenol per se.

The influence of aging on dimethylnitrosamine-demethylase enzyme kinetics in rat liver microsomes.

To investigate the observed age-related increased susceptibility to chemically-induced carcinogenesis, liver microsomes from 12- or 36-month-old rats either untreated or maximally induced with phenobarbital or isoniazid were used to determine the Vmax and Km for dimethylnitrosamine-demethylase (DMNA-d). A decrease in cytochrome P450 content between young and old animals was observed in the untreated group, but no change was seen in the treated animals. Inducer-related increases were observed after phenobarbital treatment and in the 36-month-old isoniazid-treated group. The Vmax for DMNA-d did not change between 12 and 36 months of age in all experimental groups, but significant changes between the young and old age-group and inducer-related differences were observed in the Km,app for DMNA-d. A high correlation was found between the Cl(int) (= Vmax/Km,app) of DMNA-d and the Vmax of p-nitrophenol-hydroxylation, indicating a major role for CYP2E1 in the metabolism of DMNA-d. The observed changes in the cytochrome-P450 levels and the reduced affinity in DMNA-d metabolism in the untreated group in this study is another indication that aging predominately affects the activity of some constitutive cytochrome P450 enzymes but not the activity of the inducible types of P450.

The effect of age on inducibility of various types of rat liver cytochrome P-450.

1. The content and specific activities of inducible cytochrome P-450 enzymes were determined in liver microsomes of rats of various ages after maximal induction with phenobarbital, isosafrole of 3-methylcholanthrene, and in untreated animals. 2. With age an increase in liver weight was observed both in untreated rats and in maximally induced ones; the microsomal protein content/g of liver decreased with age in untreated animals but not in induced ones. Total cytochrome P-450 content/mg microsomal protein remained unchanged with age in all experimental groups. 3. Immunologically detectable levels of cytochrome P4501A1/1A2 and 2B1/2B2 remain unchanged with age both in untreated animals and in maximally induced ones. 4. Several cytochrome P-450 activities showed an age-related decrease in untreated animals, but no change with age was observed in the activities of cytochrome P4501A1, 2A2 and 2B1/2B2 in rat liver microsomes. This indicates that ageing affects only the activity of some constitutive forms of cytochrome P-450 in male rats, but not the activity of inducible types of P-450. 5. Although previous results indicated decreased inducibility of the cytochrome P-450 mRNA levels with age, the present study clearly demonstrates that this is not reflected in decreased enzyme levels or activities after maximal induction. From this it is concluded that the decreased mRNA levels might rather be reflected in a decreased rate at which maximal induction can be achieved.

The effects of different steam-sterilization programs on material properties of poly(L-lactide).

As-polymerized poly(L-lactide) test rods were sterilized by seven different specially designed computer-operated autoclaving programs. As a control, common hospital sterilization was performed. In all cases, the molecular weight decreased after sterilization. A short time high-temperature sterilization led to less molecular weight decrease than a low sterilization temperature cycle with a longer sterilization time. Regular hospital sterilization significantly reduced the elongation at break and also resulted in a decrease of 35% in tensile strength. The program causing minimal damage to the material properties was studied in detail. This program, with a sterilization period of 60 s and 129 degrees C, was effective for PLLA sterilization and also looks very promising for sterilization of other thermo- and moisture-labile polymers.

The influence of ageing on the induction of the mRNAs of rat liver cytochromes P450IIB1 and P450IIB2.

To investigate the influence of age on the regulation of the cytochromes P450IIB1 and P450IIB2 the levels of the messenger RNAs for these two cytochromes were determined in liver cytoplasmic RNA of rats of various ages after maximal induction with either phenobarbital or isosafrole and in untreated rats. The levels of these mRNAs were determined by solution hybridization with a RNA-probe (riboprobe system) complementary to both mRNAs. This study showed a marked decrease in the maximal induction levels of these mRNAs between the ages of 12 and 36 months irrespective of the type of inducer used. To assess whether this age-related decrease could be found for both individual mRNAs also solution hybridization experiments were performed with deoxyoligonucleotide probes of a defined sequence. The data presented in this paper show that ageing influences the levels of both the cytochrome P450IIB1 and P450IIB2 mRNA in a similar way. After induction the amount of mRNA for P450IIB1 was in all age groups measured four- to five-fold higher than that of P450IIB2. These data indicate that previously observed age-related changes in the cytochrome P450 system could be related to a lower accumulation of its mRNAs.

The influence of age on the inducibility of rat liver cytochrome P450IA1 (CYPIA1) and P450IA2 (CYPIA2) mRNAs.

The levels of the messenger RNAs for the cytochromes P450IA1 (CYPIA1) and P450IA2 (CYPIA2) were determined in liver cytoplasmic RNA of rats of various ages after maximal induction with either 3-methylcholanthrene or isosafrole and in untreated rats. An increase in the CYPIA1 mRNA levels was observed only after treatment with 3-methylcholanthrene, whereas both 3-methylcholanthrene and isosafrole were able to induce the levels of CYPIA2 mRNA. The study presented here shows that the maximal induction of these 2 mRNAs did not change with age when 3-methylcholanthrene was used as the inducing agent. Isosafrole induction did not yield higher CYPIA1 mRNA levels in young rats but reduced the amount of this mRNA in old animals to levels below the detection limit of our assay. After induction with isosafrole the levels of the CYPIA2 mRNAs in the older age groups were lower than those observed in young rats. It is concluded that with age the responsiveness to cytochrome P450 inducers may change. This change is different for the various cytochrome P450 enzymes and depends on which inducer is used.