Acoustics modelling of open-cell foam materials from microstructure and constitutive properties.

The dynamic relations for highly porous fibrous materials, having analytical expressions for dynamic viscous drag forces and oscillatory solid-to-fluid heat transfer, are now extended towards open-cell foam materials where the struts of the foam are considered to be primarily cylindrical except in the region of the joints. By also including analytical expressions for the stiffness of the foam cell, an entirely analytically-based model is presented for the acoustics of highly-porous, open-celled foam materials. This approach is extremely efficient, requiring only the mean cell size, mean strut diameter, and constitutive properties of the solid foam material and the surrounding viscous fluid as input. The acoustic performance prediction of not only isotropic foam cell designs, but also anisotropic ones may be performed rapidly and virtually, without the need for the determination of poroelastic material properties from existing material samples. The steps required for the development of the analytical foam-cell model are presented, along with the acoustic performance prediction of a typical Melamine foam cell, yielding very promising results in comparison against measurements. In order to understand the suitability of the cylindrical foam strut assumption, a viscous drag force comparison with foam struts having square and triangular cross-sectional profiles is also presented.

The use of panoramic images for identification of edentulous persons.

The aim of this study was to determine if edentulous persons could be identified using panoramic images by: I) investigating the possibility of matching two panoramic radiographs of the same person obtained on two different occasions, II) determining what anatomical features are used as the base for matching, III) investigating if oral and maxillofacial radiologists (OMR) and dentists who were not oral and maxillofacial radiologists (NOMR) differed in their ability to match the images, and IV) determining if the time elapsed between the images affected the results or the confidence of the match. Panoramic image pairs from 19 patients obtained on two different occasions were included, plus 10 images from other edentulous patients. The time elapsed between the image pairs varied between 4 months and 6 years. Four OMR and four NOMR were asked to match the image pairs depicting the same patient. The participants marked each match as "certain", "likely", or "possible" and what anatomical structure they used for matching. The OMR group correctly matched 100% of the images and the NOMR group correctly matched 96%. The anatomy of the mandible was most often used for matching. The OMR group was more certain in their decisions than the NOMR group. The time elapsed between the examinations did not affect the result. In conclusion, panoramic images can be used to identify edentulous patients. Both OMR and NOMR could identify edentulous individuals when only panoramic radiographic images were available and the OMR were especially confident in the identification process.

Mutations in FLVCR2 associated with Fowler syndrome and survival beyond infancy.

Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (PVHH, OMIM 225790), also known as Fowler syndrome, is a rare autosomal recessive disorder, caused by mutations in FLVCR2. Hallmarks of the syndrome are glomerular vasculopathy in the central nervous system, severe hydrocephaly, hypokinesia and arthrogryphosis. The disorder is considered prenatally lethal. We report the first patients, a brother and a sister, with Fowler syndrome and survival beyond infancy. The patients present a phenotype of severe intellectual and neurologic disability with seizures, absence of functional movements, and no means of communication. Imaging of the brain showed calcifications, profound ventriculomegaly with only a thin edging of the cerebral cortex and hypoplastic cerebellum. Investigation with whole-exome sequencing (WES) revealed, in both patients, a homozygous pathogenic mutation in FLVCR2, c.1289C>T, compatible with a diagnosis of Fowler syndrome. The results highlight the power of combining WES with a thorough clinical examination in order to identify disease-causing mutations in patients whose clinical presentation differs from previously described cases. Specifically, the findings demonstrate that Fowler syndrome is a diagnosis to consider, not only prenatally but also in severely affected children with gross ventriculomegaly on brain imaging.

Autocrine growth factors in human periodontal ligament cells cultured on enamel matrix derivative.

OBJECTIVE: Enamel extracellular matrix proteins in the form of the enamel matrix derivative EMDOGAIN (EMD) have been successfully employed to mimic natural cementogenesis to restore fully functional periodontal ligament, cementum and alveolar bone in patients with severe periodontitis. When applied to denuded root surfaces EMD forms a matrix that locally facilitates regenerative responses in the adjacent periodontal tissues. The cellular mechanism(s), e.g. autocrine growth factors, extracellular matrix synthesis and cell growth, underlying PDL regeneration with EMD is however poorly investigated. MATERIAL AND METHODS: Human periodontal ligament (PDL) cells were cultured on EMD and monitored for cellular attachment rate, proliferation, DNA replication and metabolism. Furthermore, intracellular cyclic-AMP levels and autocrine production of selected growth factors were monitored by immunological assays. Controls included PDL and epithelial cells in parallel cultures. RESULTS: PDL cell attachment rate, growth and metabolism were all significantly increased when EMD was present in cultures. Also, cells exposed to EMD showed increased intracellular cAMP signalling and autocrine production of TGF-beta1, IL-6 and PDGF AB when compared to controls. Epithelial cells increased cAMP and PDGF AB secretion when EMD was present, but proliferation and growth were inhibited. CONCLUSION: Cultured PDL cells exposed to EMD increase attachment rate, growth rate and metabolism, and subsequently release several growth factors into the medium. The cellular interaction with EMD generates an intracellular cAMP signal, after which cells secrete TGF-beta1, IL-6 and PDGF AB. Epithelial cell growth however, is inhibited by the same signal. This suggest that EMD favours mesenchymal cell growth over epithelium, and that autocrine growth factors released by PDL cells exposed to EMD contribute to periodontal healing and regeneration in a process mimicking natural root development.

Enamel matrix derivative promotes reparative processes in the dental pulp.

During odontogenesis, amelogenins from the preameloblasts are translocated to differentiating odontoblasts in the dental papilla, suggesting that amelogenins may be associated with odontoblast changes during development. In the present study, we have explored the effects of enamel matrix derivative (EMD) on the healing of a pulpal wound. Coronal pulp tissue of permanent maxillary premolars of miniature swine were exposed through buccal class V cavities. The exposed pulp was capped with EMD. The contralateral teeth served as controls and were capped with a calcium hydroxide paste (Dycal). The cavities were sealed with glass-ionomer cement. After 2 and 4 weeks, the histology of the teeth was analyzed. In the EMD-treated teeth, large amounts of newly formed dentin-like hard tissue with associated formative cells outlined the pulpal wound separating the cavity area from the remaining pulp tissue. Inflammatory cells were present in the wound area but not subjacent to the newly formed hard tissue. Morphometric analysis showed that the amount of hard tissue formed in EMD-treated teeth was more than twice that of the calcium-hydroxide-treated control teeth (p < 0.001), suggesting that EMD is capable of promoting reparative processes in the wounded pulp more strongly than is calcium hydroxide.

Reversal of meconium inhibition of pulmonary surfactant by ferric chloride, copper chloride, and acetic acid.

Meconium inhibits pulmonary surfactant function. We investigated the in vitro effect of meconium on three different commercial surfactants. The dynamic surface properties of these surfactants were evaluated at the concentration of 5 mg/ml with a pulsating bubble system. The inhibitory effect of 2.75 mg/ml meconium was significantly less on Alveofact than on Curosurf and Survanta. Ferric chloride and copper chloride completely reversed the inhibitory effect of meconium. Meconium also prevented effective spreading of surfactant in a Wilhelmy balance system, and this inhibitory effect was counteracted by addition of ferric chloride. Image analysis of Curosurf demonstrated that meconium reduced the total number of microbubbles in 15 light-microscopic fields (4.35 mm(2)) from 1,748 +/- 481 to 180 +/- 166. Ferric chloride restored the number of microbubbles. Addition of ferric chloride or copper chloride to surfactant/meconium lowers pH, and pH adjustment by acetic acid also reversed the inhibitory effect of meconium. Together with the fact that the iron-chelator deferoxamine did not attenuate the effect of ferric chloride this suggests that the observed contrainhibition is caused by lowering of pH, and that meconium inhibition of surfactant is pH-dependent. Lowering pH from 6.2 to 5-5.5 abolished the inhibitory effects of meconium on surfactant. Inhibition of 2.5 mg/ml of Curosurf with plasma could also be reversed by increasing amounts of ferric chloride. We conclude that the inhibitory effect of meconium on surfactant in vitro can be abolished by addition of ferric chloride, copper chloride, or acetic acid.

Factor analysis of the Zung Self-Rating Depression Scale in a large ambulatory oncology sample.

Screening cancer patients for depression with self-report inventories presents clinical and methodological challenges. Many investigators separate "somatic" from "cognitive" symptoms when adapting such measures to oncology settings. However, this practice has rarely been empirically validated through factor-analytic studies. The following study describes a factor analysis of the Zung Self-Rating Depression Scale (ZSDS) from a large ambulatory sample of cancer patients (N = 1,109). A four-factor solution emerged, consisting of a cognitive symptom factor, a manifest depressed mood factor, and two somatic factors (eating and non-eating related). These factors accounted for 20% (cognitive), 13% (mood), 8% (non-eating), and 7% (eating) of the variance on the Zung, respectively. The authors discuss the implications of these results as they pertain to screening cancer patients for depression.

The effect of immediate-hypersensitivity reactions on the level of SLPI, granulocyte elastase, alpha1-antitrypsin, and albumin in nasal secretions, by the method of unilateral antigen challenge.

BACKGROUND: The aim of this paper was to investigate the role of SLPI in patients with allergic rhinitis. From this point of view, we also examined leukocyte elastase, alpha1-antitrypsin, and albumin. SLPI is an inhibitor of serine proteases such as leukocyte elastase, cathepsin G, and mast-cell chymase. Since chymase is considered to participate in mast-cell degranulation and histamine release, SLPI might act as a regulator of allergic reactions. Recent interest has been focused on leukocytes and allergy. Since SLPI is a strong inhibitor of leukocyte elastase, we also focused on the function of elastase in allergic rhinitis. METHODS: We used the method of nasal lavage after unilateral nasal antigen challenge in atopic and healthy subjects. The ELISA quantified SLPI and elastase. Albumin and alpha1-antitrypsin were quantified by electroimmunoassay. Gel filtration was used to separate native SLPI from its complex with elastase. RESULTS: There was a higher level of SLPI in lavage fluid from healthy subjects than from atopic patients. SLPI was increased on the contralateral side in atopic subjects after allergen challenge. The absence of increase in SLPI on the challenged side may be attributed to the increase in elastase and its binding to SLPI, which might have an effect on the immunoreactivity and interfere with the ELISA. It may then be assumed that there is an augmentation of SLPI on the challenged side as well. No increase was seen in healthy subjects. There was a higher concentration of elastase, alpha1-antitrypsin, and albumin before antigen challenge in atopic patients outside the pollen season than in healthy subjects. As expected, an increase was also seen in the challenged side exclusively in atopic subjects. CONCLUSIONS: The lower concentration of SLPI in nasal lavage fluid among the atopic patients than the healthy subjects indicates damaged mucosa. Neural reflexes are involved in SLPI release since there was an increase even in the contralateral nostril. A higher level of elastase and albumin before allergen challenge suggests chronic inflammation in nasal mucosa outside the pollen season. Leukocyte recruitment takes place in response to IgE-mediated reactions, which are reflected in an increase in elastase in response to allergen challenge.

Deposition and disposition of [11C]zanamivir following administration as an intranasal spray. Evaluation with positron emission tomography.

OBJECTIVE: This study used positron emission tomography (PET) to investigate the deposition and disposition of zanamivir administered as a nasal spray. DESIGN: This was an open-label single-dose study in healthy volunteers. STUDY PARTICIPANTS: Six healthy male volunteers, aged 19 to 33 years (mean age 25 years) with a bodyweight of 65 to 94 kg (mean bodyweight 76 kg), took part in the study. INTERVENTIONS: Each participant received by nasal spray zanamivir 6.4 mg mixed with, on average, 2.5 MBq of [11C]zanamivir. The amount of radioactivity was recorded sequentially in 5 different sectors of the body, starting with a short dynamic sequence over the nasal passage. Each of the regions was examined 1 to 4 times at different times after inhalation. The duration of the examination was 90 minutes. During this time, multiple blood samples were taken for analysis of radioactivity in whole blood. Serum samples for pharmacokinetic determinations were collected for 8 hours after administration. RESULTS: Immediately after administration, about 90% of the drug was deposited in the nasal passage, decreasing to 48% at 90 minutes after administration. Less than 2% was detected in the lower respiratory tract. The major elimination route was via the oesophagus to the stomach. Approximately 2% of the dose was absorbed; the median maximum drug concentration in serum was 15 micrograms/L, and occurred around 1.75 hours after inhalation. CONCLUSIONS: The major deposition site for zanamivir administered by nasal inhalation is the nasal passage; half of the drug remains there for at least 1.5 hours after administration. PET seems to be an excellent tool for this type of kinetic study, allowing imaging and measurements of inhaled drugs with high quantitative accuracy and good spacial resolution.

The subacromial impingement syndrome. A study of results of treatment with special emphasis on predictive factors and pain-generating mechanisms.

Forty-two patients with subacromial impingement syndrome entered a randomized prospective study comparing open anterior acromioplasty with a physiotherapy regime. The criterion for a successful outcome of treatment was a reduction of the initial pain score of more than 50% using the visual analogue scale (VAS) technique. The evaluation was performed by an independent observer. At the 6-month follow-up, treatment in the surgical group had been successful in 12/21 (57%) patients versus 6/18 (33%) in the physiotherapy group. A one-year evaluation revealed 16/21 (76%) "successes" in the surgical group. A direct and unbiased comparison with the physiotherapy group was not possible at one year, since 13 patients chose surgery after initial physiotherapy. However, in "an intention to treat" analysis outcome at one year was significantly better in those randomized to surgery. We found two standardized, composite, active movements--the "Pour out of a Pot" manoeuvre requiring the emptying of a pot of water, and the "Hand in Neck" manoeuvre--to be of predictive value for the outcome of surgery. When combining three pain-related variables into a criterion for prediction of success, a sensitivity of 78% (p < 0.02) and a specificity of 90% (p < 0.03) were attained. We advance the hypothesis that pain in the impingement syndrome is mainly elicited by comparison of the subacromial bursa. In some patients a traction-responsive pain generator in the supraspinatus tendon may be present as well.

IgE-mediated histamine release from nasal mucosa is inhibited by SLPI (secretory leukocyte protease inhibitor) to the level of spontaneous release.

The secretory leukocyte protease inhibitor (SLPI) is a low-molecular-weight inhibitor of proteases, such as elastase and cathepsin G which are released from leukocytes during phagocytosis. The purpose of this study was to determine whether or not SLPI is able to inhibit IgE-mediated histamine release. Nasal mucosa from 11 test subjects without atopic disposition was used for this in vitro study. We found that SLPI inhibited histamine release in a dose-dependent way but was without influence on the spontaneous release.

Production and secretion of pancreatic secretory trypsin inhibitor in normal human small intestine.

The aim of this study was to prove the production and secretion of pancreatic secretory trypsin inhibitor (PSTI) in human small intestine. To achieve this we analyzed the content of immunoreactive PSTI (irPSTI) in rinsing fluid from isolated small intestine, using the urea method to estimate the volume of epithelial lining fluid recovered. IrPSTI, measured by an enzyme-linked, immunosorbent assay (ELISA), was present in both free and complexed form. The free PSTI showed intact biologic activity, binding trypsin in stable complexes. The complexed PSTI was dissociated on acidification. With the reverse transcriptase polymerase chain reaction (RT-PCR) and Southern blot hybridization, PSTI mRNA was demonstrated in the mucosa of the ileum. These findings indicate that PSTI is produced and secreted in the small intestinal epithelium and may be part of defence system in intestinal mucosa.

Leukocyte activation detected by increased plasma levels of inflammatory mediators in patients with ischemic cerebrovascular diseases.

BACKGROUND AND PURPOSE: Leukocytes have been implicated in the development of ischemic atherosclerotic vascular diseases. In a prospective study we investigated whether the plasma concentrations of inflammatory mediators, ie, proteases and cytokines, as markers for systemic leukocyte activation, are increased in patients with acute ischemic cerebrovascular diseases. METHODS: Using enzyme-linked immunosorbent assays, we measured the plasma levels of neutrophil gelatinase-associated lipocalin (NGAL), neutrophil proteinase 4 (NP4), tumor necrosis factor-alpha (TNF), and soluble TNF receptor protein-1 p55 (sTNFR-1) in 120 patients with acute ischemic cerebrovascular insult (72 with stroke and 48 with transient ischemic attack [TIA]) and in 35 age- and sex-matched healthy subjects. RESULTS: Compared with the control group, plasma NGAL levels were higher in the stroke group (P < .0001) and the TIA group (P < .01); plasma NP4 levels were higher in the stroke group (P < .0001) and the TIA group (P < .01); and plasma sTNFR-1 levels were higher in the stroke group (P < .04). There was significant correlation between the plasma levels of fibrinogen and those of both sTNFR-1 (r = .32; P = .005) and NGAL (r = .40; P = .0001) and between the erythrocyte sedimentation rate and the plasma levels of both sTNFR-1 (r = .35; P = .001) and NGAL (r = .34; P = .002). CONCLUSIONS: Our study demonstrated that markers for systemic leukocyte activation, ie, plasma levels of cytokines and proteases, were higher in patients with acute ischemic cerebrovascular disease than in healthy control subjects. Activated leukocytes and leukocytic mediators may have an important role in acute cerebrovascular ischemia and its consequences.

Release of cytokines and proteases from human peripheral blood mononuclear and polymorphonuclear cells following phagocytosis and LPS stimulation.

Release and cellular contents of pro- and anti-inflammatory cytokines, neutrophilic elastase and secretory leukocyte proteinase inhibitor (SLPI) were measured with enzyme-linked immunosorbent assay in peripheral blood mono- and polymorphonuclear cells stimulated with preopsonized yeast cells or lipopolysaccharide. Tumour necrosis factor alpha (TNF alpha) was also measured with a bioassay. TNF alpha production and soluble TNF alpha receptor I (sTNF RI) were demonstrated in the environment of both cell populations. The bioassay indicated levels of TNF alpha far below those detected by ELISA. The overall secretion of cytokines and their inhibitors was found to favour an anti-inflammatory balance in the environment of the stimulated cells. The interleukin-1 receptor antagonist (IL1-ra), compared with interleukin-1 beta (IL-1 beta), dominated the secretions from both cell types with a 100- to 1000-fold excess respectively. Most of the translated IL-1 beta was not secreted but found associated with the cellular compartments. In contrast to lipopolysaccharide (LPS) stimulation, preopsonized yeast cells stimulated a massive release of elastase from neutrophil cells.

Release of bacterial DNA by marine nanoflagellates, an intermediate step in phosphorus regeneration.

The concentrations of dissolved DNA and nanoflagellates were found to covary during a study of diel dynamics of the microbial food web in the Adriatic Sea. This observation was further investigated in a continuous seawater culture when nanoflagellates were fed bacteria grown in filtered seawater. Analysis of dissolved organic phosphorus and dissolved DNA showed a sixfold increase of dissolved DNA in the presence of the nanoflagellates (Ochromonas sp.). The amount of DNA released suggested that the majority of the consumed bacterial DNA was ejected. Phagotrophic nanoflagellates thus represent an important source of origin for dissolved DNA. The rate of breakdown of dissolved DNA and release of inorganic phosphorus in the pelagic ecosystem is suggested to be dependent on the ambient phosphate pool. In the P-limited northern Adriatic Sea, rapid degradation of the labelled DNA could be demonstrated, whereas the N-limited southern California bight water showed a much lower rate. Phosphorus originating from dissolved DNA was shown to be transferred mainly to organisms in the <3-mum-size fractions. On the basis of the C/P ratios, we suggest that a significant fraction of the phosphorus demand by the autotrophs may be sustained by the released DNA during stratified conditions. Thus, the nucleic acid-rich bacterial biomass grazed by protozoa plays an important role in the biogeochemical cycling of phosphorus in the marine environment.

Release of immunoreactive human neutrophil proteinase 4, normally and in peritonitis.

A specific enzyme-linked immunoassay (ELISA) has been developed for the determination of neutrophil proteinase 4 (NP4) in human plasma/serum and tissue fluids. Comparison of the sequence for the first 20 N-terminal amino acids of NP4, neutrophil elastase and cathepsin G shows that NP4 is distinct from the other two proteases. However, all three show considerable homology. Neither elastase nor cathepsin G show any immunoreactivity when tested in the present ELISA. Normal human plasma contains about 38 micrograms/l of NP4, identified as alpha 1-proteinase inhibitor complexes. This represents about 50% of the total amount of NP4 released in plasma. The remaining 50% is bound by alpha 2-macroglobulin. Blood coagulation leads to a rapid release of NP4 from the leukocytes. Peritonitis is accompanied by a pronounced release of NP4, as shown by a three-to 10-fold increase of NP4 plasma levels and by the NP4 level in peritoneal exudates, which reaches about 40 mg/l in severe cases.

Immunochemical and immunohistochemical evaluation of lung permeability in ventilated newborn rabbits.

These experiments were designed to quantify the vascular-to-alveolar leakage albumin in the neonatal lung and to analyze the distribution of leaking airspaces in the lung parenchyma. Immediately after delivery, newborn rabbits with gestational age 27-29 days received an intravenous injection of human albumin as a marker and were ventilated for 15 min with standardized tidal volume (10 ml/kg). After the period of ventilation the lungs were either lavaged via the airways or fixed for histological studies. The median amount of albumin in lung lavage fluid, determined by immunodiffusion, was 4.8% of the injected dose after 27 days, 1.3% after 28 days, and 0.4% after 29 days of gestation; it was inversely correlated with the compliance of the respiratory system (r = -0.78; p less than .001). Immunohistochemical examination of lung section revealed that the leak was not diffuse; even in animals with gestational age 27 days it involved only a median of 48% of total alveoli. The median amount of alveoli containing the label fell to 6% after 28 days and to 0% after 29 days gestation, correlating inversely with the compliance of the respiratory system (r = -0.53; p less than 0.01). We suggest that our experimental model is useful for histological demonstration of serum proteins leaking into the airpaces under experimental conditions and for evaluating the effect of therapeutic regiments on neonatal lung permeability.

Persistence of antibody in healthcare workers vaccinated against hepatitis B.

A cross-sectional serological survey was undertaken in 82 randomly selected high-risk healthcare workers previously vaccinated with the hepatitis B vaccine. The study design allowed for the identification and testing for hepatitis B surface antibody in equal numbers of employees in six-month intervals up to five years after vaccination. The results showed a consistent decline in antibody level with time, and an increasing proportion of participants with antibody levels below the commonly accepted protective level of greater than or equal to 10 S/N (sample counts/negative control counts) radioimmunoassay units. The percent of vaccinees whose S/N ratio was greater than 10 fell from 10% at one year, to 25% at two years, to over 50% at four years. Based on these figures, as well as the financial costs of hepatitis B in employees and the predictability of booster immunization, it was possible to assess the cost benefit of a hospital policy for reimmunization. At our institution, a strategy of revaccination at fixed intervals could save up to $200,000 over a ten-year period if revaccination was not offered and vaccine efficacy declined. The information obtained should help determine the need for revaccination and the advantages and disadvantages of alternative revaccination strategies.