Influence of low amounts of zinc or magnesium substitution on ion release and apatite formation of Bioglass 45S5.

Magnesium and zinc ions play various key roles in the human body, being involved, among others, in skeletal development and wound healing. Zinc is also known to have antimicrobial properties. While low concentrations can stimulate cells in vitro, high concentrations of magnesium or zinc introduced into bioactive glasses significantly reduce glass degradation and ion release and inhibit apatite precipitation. On the other hand, magnesium and zinc ions improve the high temperature processing of bioactive glasses, even when present at low concentrations only. Results here show that by substituting small amounts of Mg or Zn for Ca, ion release remains high enough to allow for apatite precipitation. In addition, magnesium and zinc containing bioactive glasses are shown to be very susceptible to changes in particle size and relative surface area. For a given magnesium or zinc content in the glass, ion release and apatite formation can be enhanced dramatically by reducing the particle size, reaching comparable levels as Bioglass 45S5 of the same particle size range. Taken together, these findings suggest that when introducing these ions into bioactive glasses, ideally low Mg or Zn for Ca substitution as well as small particle sizes are used. This way, bioactive glasses combining good high temperature processing with fast ion release and apatite precipitation can be obtained, providing the potential additional benefit of releasing magnesium or zinc ions in therapeutic concentrations.

Mg or Zn for Ca substitution improves the sintering of bioglass 45S5.

Bioglass 45S5 is well-known for its bioactivity, but it possesses poor sintering behaviour owing to viscous flow being inhibited by the crystallisation of sodium calcium silicate phases. Mg or Zn were partially (0, 25, 50, 75%) or fully (100%) substituted for Ca on a molar base, and thermal properties (differential scanning calorimetry, dilatometry) and sintering (heating microscopy, SEM and X-ray diffraction) were investigated. Here we show that sintering can be improved significantly by partial or complete substitution of Mg or Zn for Ca, owing to a pronounced decrease in crystallisation tendency. Glass transition temperature and dilatometric softening point went through minima for mixed compositions, with random mixing of Mg/Ca or Zn/Ca ions in the glass structure and the resulting effect on configurational entropy being a likely explanation. As the onset of crystallisation did not vary much with substitution, substituted glasses possessed a wider temperature range for sintering, resulting in up to 57% and 27% sample height reduction for Mg and Zn substituted glasses, respectively, compared to only 3% height reduction for Bioglass 45S5. Taken together, these results suggest that using a combination of modifiers, particularly alkaline earths or zinc, may be a promising approach for improving the sintering of Bioglass 45S5.

Effect of poly(acrylic acid) architecture on setting and mechanical properties of glass ionomer cements.

OBJECTIVE: This work focuses on the influence of poly(acrylic acid) (PAA) architecture (linear or branched) on setting behavior and compressive strength of glass ionomer cements (GICs). METHODS: Branched and linear poly(acrylic acid)s were synthesized according to the Strathclyde methodology or by free radical polymerization. They were characterized by 1H-NMR spectroscopy and size exclusion chromatography to determine their molecular weight and size distribution. GIC setting was characterized by oscillating rheometry and time-dependent FTIR spectroscopy. In addition, compressive strength was tested on cylindrical samples (6 × 4 mm; n = 8/cement composition) after storage in deionized water at 37 °C for one day. RESULTS: We used two different routes to prepare PAA. One direct route in order to provide straightforward access to branched PAA and a two-step approach in order to get more control about the PAA molecular weight using tert-butyl acrylate (tBA) for polymerization with subsequent deprotection. Using the second approach we obtained several linear PAA of which a mixture was used in order to mimic the molecular weight and size distribution of branched PAA. This allowed the direct comparison of properties relying only on the polymer architecture. Comparing linear PAA to branched samples in general led to faster setting but at the same time decreased the compressive strength. Increasing molecular weight of branched PAA resulted in even faster GIC setting while increasing compressive strength and this correlates well with the trends reported for linear PAA in literature. Mixing of branched and linear PAA, however, turned out to be an effective way of tailoring GIC properties. SIGNIFICANCE: our results suggest that both molecular weight and dispersity need to be considered when choosing suitable PAA architecture for obtaining specific GIC properties.

[Influence of asthma severity and asthma-specific knowledge on participation in physical education among children and young people with bronchial asthma]. / Kinder und Jugendliche mit Asthma bronchiale im Schulsport: Teilnahmehäufigkeit abhängig vom Schweregrad oder vom asthmaspezifischen Wissen durch Schulung?

BACKGROUND: Physical activity is an important part of the therapy of bronchial asthma. Even if there is exercise-induced bronchoconstriction in more or less all children with bronchial asthma, the goal is an almost complete participation in physical education lessons in school. The present study investigates their participation rate. In addition, the influence of the knowledge about asthma and the severity of the disease were studied. METHODS: A questionnaire on asthma knowledge and severity, participation rate and exercise-induced symptoms was used in 217 school children suffering from asthma (9 - 16 years). RESULTS: 80 % of the patients showed a regular participation in physical education. No correlation between participation and asthma severity was found. In contrast, a significant correlation between participation and knowledge about asthma could be demonstrated (r = 0.35, p < 0.01). The knowledge about asthma was better in school children who had completed any asthma education program in the past (19 %). However, there was generally an insufficient knowledge about asthma and exercise in the investigated group. 58 subjects were not familiar with pursed lip breathing and 112 participated in physical education lessons in spite of forgotten asthma medication. CONCLUSION: Our study demonstrates a moderate increase of participation in physical education lessons in school children with bronchial asthma during the last ten years. The participation rate correlated with asthma-specific knowledge, but not with asthma severity underlining the importance of education programs on asthma and exercise.

[Total ankle arthroplasty for rheumatoid arthritis]. / Endoprothetik des Oberen Sprunggelenks Beim Rheumatiker.

Modern second generation total ankle arthroplasty is now a serious alternative to ankle fusion in patients with rheumatoid arthritis after careful assessment of the indications. The midterm results with 10-year survival rates between 70% and 90% and the possible revision for implant exchange or arthrodesis are the reasons for the increasing importance of ankle arthroplasty. Patients with rheumatoid arthritis in particular with generally lower physical requirements can expect a pain-free function of the operated ankle for 8-10 years. In comparison to fusion ankle arthroplasty allows a significantly faster remobilization and reserves the correction capabilities of the ankle. Arthrodesis remains a valuable therapeutic alternative for severe bony destruction and instability as well as a possible fallback for failure of arthroplasty.

[Minimally invasive approach to implantation of a hip endoprosthesis]. / Der minimal-invasive Zugang zur Implantation der Hüftendoprothese.

Early experiences with the two-incision approach at the hip joint are reported. We started in July 2002 and until now 272 procedures have been performed. Blood loss (292 ml) and the need for rehabilitation are reduced, the patients will achieve a Harris Hip Score of more than 90 points within 6 or 8 weeks. Complications related to the approach primarily include irritation of the lateral femoral cutaneous nerve. During the learning curve when the initial shaft model was used, shaft fractures or fissures occurred in 4% of the cases. This complication was no longer observed with the ML Taper shaft model now employed (n=102). The development and establishment of minimally invasive approaches constitute a valuable and seminal option for implantation of hip endoprostheses. In the medium term, the time spent in rehabilitation could conceivably be reduced. Conventional approaches still represent the gold standard.

Altruistic living donors: evaluation for nondirected kidney or liver donation.

A program was established within our regional procurement organization to permit evaluation of altruistic living donors (LD) interested in nondirected kidney or liver segment donation prior to transplant center referral. During the initial 30 months of program operations, 731 donor inquiries were received of which 131 individuals called back after review of mailed information materials. Forty-seven candidates initiated and 19 completed the evaluation process. Seven underwent donation to include six kidneys and one liver segment, five are actively pending donation, five were excluded from donation following transplant center evaluation and two took no further action after their intended liver recipients received deceased donor (DD) transplants. Psychological evaluation of these 19 candidates found them to be free of psychopathology, highly cooperative and self-directed. They did not exhibit attention-seeking or religious motivations for their actions. All seven donors and recipients continue to do well postoperatively. This evaluation program has made possible large-scale screening and education of prospective altruistic LD within the general population and also provides a unique opportunity to further our understanding of those individuals interested in living-nondirected donation.

[Assessment of health-related quality of life with the German SF-8. A comparison of telephone and postal survey modes]. / Erfassung der gesundheitsbezogenen Lebensqualität mit dem deutschen SF-8. Ein Vergleich der telefonischen und postalischen Befragungsmethode.

Within a comprehensive comparison of telephone and postal survey methods the SF-8 was applied to assess adult's health-related quality of life. The 1690 subjects were randomly assigned to a telephone survey and a postal survey. Comparisons across the different modes of administration addressed the response rates, central tendency, deviation, ceiling and floor effects observed in the SF-8 scores as well as the inter-item correlation. The importance of age and gender as moderating factors was investigated. Results indicate no or small statistically significant differences in the responses to the SF-8 depending on the actual mode of administration and the health aspect questioned. It was concluded that further investigations should focus on the exact nature of these deviations and try to generate correction factors.

[Initial stability of press-fit acetabular cups--an in-vitro study]. / Primärstabilität von Press-fit Hüftpfannen--eine in-vitro Studie.

AIM OF THE STUDY: Mechanical lever-out tests were performed in vitro to investigate the initial stability of press fit acetabular cups. METHOD: Five different uncemented, hemispherical press-fit cups were implanted in a standardized manner into Sawbones, Polyurethane foam blocks. Each cup was levered-out by using a 250 mm stainless steel rod, which was connected to the acetabular cup. Loads were then applied to the rod causing the cup to be diplaced. Lever-out forces were recorded by a computer. RESULTS: The results of the lever-out forces ranged between 39,2 and 50,8 Nm. The highest initial stability was achieved by two Titanium cups with a Titanium plasmaspray coating, a flattened pole and a sharp equatorial edge. According to our trials the equatorial rim of the polyurethane cavity is the crucial area for the implant's initial stabilty. There the highest amount of attrition was observed. CONCLUSION: To guarantee a high reproducibilty of the tests it is essential to pay particular attention to the quality of the polyurethane foam blocks, to the exactness of the reaming procedure and to a defined cup insertion. However as our trials were carried out under optimized labaratory conditions one must be careful not to over-interpret its results. Intraoperatively primary stability is also influenced by the quality of the bone.

Functional MRI reveals an interhemispheric dissociation of frontal and temporal language regions in a patient with focal epilepsy.

We report the case of a patient with frontal lobe epilepsy in whom the Wada test failed to lateralize representation of language (fluent speech was observed after amobarbital injection on both the right and left side). Functional magnetic resonance imaging (fMRI) during a lexical processing task revealed an atypical organization of language represented by an interhemispheric dissociation of language regions with a right frontal dominance and a left temporal dominance. Consistent with the fMRI results, the patient's ability to name pictures was not reliably impaired by electrocortical stimulation (ECS) of left frontal cortex. The findings from Wada, fMRI, and ECS were confirmed by a lack of language impairment after left frontal lobectomy for seizures. This case illustrates that fMRI can precisely map cortical language networks in epileptic patients and that fMRI may be used to help interpret laterality results provided by the Wada procedure.

Competition between Fe(III)-reducing and methanogenic bacteria for acetate in iron-rich freshwater sediments.

The kinetics of acetate uptake and the depth distribution of [2-14C]acetate metabolism were examined in iron-rich sediments from a beaver impoundment in northcentral Alabama. The half-saturation constant (Km) determined for acetate uptake in slurries of Fe(III)-reducing sediment (0.8 mM) was more than 10-fold lower than that measured in methanogenic slurries (12 mM) which supported comparable rates of bulk organic carbon metabolism and Vmax values for acetate uptake. The endogenous acetate concentration (Sn) was also substantially lower (1.7 mM) in Fe(III)-reducing vs methanogenic (9.0 mM) slurries. The proportion of [2-14C]acetate converted to 14CH4 increased with depth from ca 0.1 in the upper 0.5 cm to ca 0.8 below 2 cm and was inversely correlated (r2 = 0.99) to a decline in amorphous Fe(III) oxide concentration. The results of the acetate uptake kinetics experiments suggest that differences in the affinity of Fe(III)-reducing bacteria vs methanogens for acetate can account for the preferential conversion of [2-14C]acetate to 14CO2 in Fe(III) oxide-rich surface sediments, and that the downcore increase in conversion of [2-14C]acetate to 14CH4 can be attributed to progressive liberation of methanogens from competition with Fe(III) reducers as Fe(III) oxides are depleted with depth.

Wada testing reveals frontal lateralization for the memorization of words and faces.

Neuroimaging studies have suggested that specific regions of the frontal and medial temporal cortex are engaged during memory formation. Further, there is specialization across these regions such that verbal materials appear to preferentially engage the left regions while nonverbal materials primarily engage the right regions. An open question, however, has been to what extent frontal regions contribute to successful memory formation. The present study investigates this question using a reversible lesion technique known as the Wada test. Patients memorized words and unfamiliar faces while portions of their left and right hemispheres were temporarily anesthetized with sodium amytal. Subsequent memory tests revealed that faces were remembered better than words following left-hemisphere anesthesia, whereas words were remembered better than faces following right-hemisphere anesthesia. Importantly, inspection of the circulation affected by the amytal further suggests that these memory impairments did not result from direct anesthetization of the medial temporal regions. Taken in the context of the imaging findings, these results suggest that frontal regions may also contribute to memory formation in normal performance.

Structural features of the Abeta amyloid fibril elucidated by limited proteolysis.

Although the gross morphology of amyloid fibrils is fairly well understood, very little is known about how the constituent polypeptides fold within the amyloid folding motif. In the experiments reported here, we used trypsin and chymotrypsin to conduct limited proteolysis studies on synthetic amyloid fibrils composed of the Alzheimer's disease peptide Abeta(1-40). In both reactions, the extreme N-terminal proteolytic fragment is released from fibrils as rapidly as it is from the Abeta monomer, while other proteolytic fragments are generated much more slowly. Furthermore, aggregated material isolated by centrifugation of intermediate digestion time points from both proteases contains, in addition to full-length material, peptides that possess mature C-termini but truncated N-termini. These data strongly suggest that the N-terminal region of Abeta is not involved in the beta-sheet network of the amyloid fibril, while the C-terminus is essentially completely engaged in protective-presumably beta-sheet-structure. In both digests, release of the extreme N-terminal fragments of Abeta(1-40) reaches plateau values corresponding to about 80% of the total available Abeta. This suggests that there are two classes of peptides in the fibril: while the majority of Abeta molecules have an exposed N-terminus, about 20% of the peptides have an N-terminus that is protected from proteolysis within the fibril structure. The most likely cause of this heterogeneity is the lateral association of protofilaments into the fibril structure, which would be expected to generate a unique environment for those Abeta N-termini located at protofilament packing interfaces and/or in the interior core region between the packed protofilaments. This suggests that the N-terminal region of Abeta, while not directly involved in the beta-sheet network of the fibril, may contribute to fibril stability by participating in protofilament packing.

Immunocytochemical localization of Na-K-ATPase alpha- and gamma-subunits in rat kidney.

The gamma-subunit of the Na-K-ATPase is a single-span membrane protein that alters the kinetic properties of the enzyme. It is expressed in the kidney, but our initial observations indicated that it is not present in all nephron segments (Arystarkhova E, Wetzel RK, Asinovski NK, and Sweadner KJ. J Biol Chem 274: 33183-33185, 1999). Here we used triple-label confocal immunofluorescence microscopy in rat kidney with antibodies to Na-K-ATPase alpha1- and gamma-subunits and nephron segment-specific markers. Na-K-ATPase alpha1-subunit stain was low but unambiguous in proximal segments, moderate in macula densa, connecting tubules, and cortical collecting ducts, high in thick ascending limb and distal convoluted tubules, and nearly undetectable in glomeruli, descending and ascending thin limb, and medullary collecting ducts. The gamma-subunit colocalized at staining levels similar to alpha1-subunit in basolateral membranes in all segments except cortical thick ascending limb and cortical collecting ducts, which had alpha1-subunit but no detectable gamma-subunit stain. Selective gamma-subunit expression may contribute to the variations in Na-K-ATPase properties in different renal segments.

New spatially explicit method for detecting extracellular protease activity in biofilms.

A novel method of detecting extracellular protease activity at biofilm-substratum interfaces was developed. This method utilizes fluorescent molecules bound to cellulose substrata with a lectin. Extracellular proteases degrade the lectin and release the fluorochrome into solution. This new technique and a standard dissolved-substrate assay detected similar responses of biofilm extracellular protease activity to experimental manipulation of N supply. Combination of this technique with confocal scanning laser microscopy allowed direct visualization of microspatial patterns of bacterial distribution and extracellular protease activity at the biofilm-substratum interface.

A microtiter plate assay for polyglutamine aggregate extension.

Polyglutamine (polyGln) aggregates are neuropathological markers of expanded CAG repeat disorders, and may also play a critical role in the development of these diseases. We have established a highly sensitive, fast, reproducible, and specific assay capable of monitoring aggregate-dependent deposition of polyglutamine peptides. This assay allows detailed studies on various aspects of aggregation kinetics, and also makes possible the detection and quantitation of low levels of "extension-competent" aggregates. In the simplest form of this assay, polyGln aggregates are made from chemically synthesized peptides and immobilized onto microplate wells. These wells are incubated for different times with low concentrations of a soluble biotinylated polyGln peptide. Europium-streptavidin complexation of the immobilized biotin, followed by time-resolved fluorescence detection of the deposited europium, allows us to calculate the rate (fmol/h) of incorporation of polyGln peptides into polyGln aggregates. This assay will make possible basic studies on the assembly mechanism of polyGln aggregates and on critical features of the reaction, such as polyGln length dependence. The assay also will be a valuable tool for screening and characterizing anti-aggregation inhibitors. It will also be useful for detection and quantitation of aggregation-competent polyGln aggregates in biological materials, which may prove to be of critical importance in understanding the disease mechanism.

Polyglutamine aggregation behavior in vitro supports a recruitment mechanism of cytotoxicity.

In expanded CAG repeat diseases such as Huntington's disease, proteins containing polyglutamine (poly(Gln)) sequences with repeat lengths of about 37 residues or more are associated with development of both disease symptoms and neuronal intranuclear inclusions (NIIs). Disease physiology in animal and cellular models does not always correlate with NII formation, however, and the mechanism by which aggregate formation might lead to cytotoxicity is unknown. To help evaluate various possible mechanisms, we determined the biophysical properties of a series of simple poly(Gln) peptides. The circular dichroism spectra of poly(Gln) peptides with repeat lengths of five, 15, 28 and 44 residues are all nearly identical and are consistent with a high degree of random coil structure, suggesting that the length-dependence of disease is not related to a conformational change in the monomeric states of expanded poly(Gln) sequences. In contrast, there is a dramatic increase in both the kinetics and the thermodynamic favorability of the spontaneous formation of ordered, amyloid-like aggregates for poly(Gln) peptides with repeat lengths of greater than 37 residues. At the same time, poly(Gln) peptides with repeat lengths in the 15-20 residue range, despite their poor abilities to support spontaneous, self-nucleated aggregation, are capable of efficiently adding to an already-formed aggregate. We also find that morphologically small, finely divided aggregates are much more efficient at recruiting poly(Gln) peptides than are large aggregates, suggesting a possible explanation for why disease pathology does not always correlate with the observable NII burden. Together, these data are consistent with a model for disease pathology in which critical cellular proteins possessing poly(Gln) sequences of modest length become inactivated when they are recruited into aggregates of an expanded poly(Gln) protein.

The association of irritable bowel syndrome and somatization disorder.

BACKGROUND AND OBJECTIVE: Irritable bowel syndrome (IBS) and somatization disorder (SD) are defined by nonobjective symptoms that overlap considerably. Psychiatric symptoms associated with IBS may originate from SD in IBS patients. Previous studies of IBS have not considered SD separately from IBS. METHODS: This study explored psychiatric symptoms and illness behavior in IBS in relation to SD. A total of 50 outpatients with IBS or ulcerative colitis (UC) were evaluated with the Diagnostic Interview Schedule and Illness Behavior Questionnaire. RESULTS: Definite or probable SD was diagnosed in no UC patients and in 42% of IBS patients (confirmed in 25% and lacking one symptom in another 17%). IBS patients with probable or definite SD, but not those without SD, reported more psychiatric symptoms and abnormal illness behaviors than did UC patients. SD accounted for the association of psychiatric symptoms with IBS. CONCLUSIONS: In this university-based office setting, the association of psychiatric features with IBS appears heterogeneous predicated on whether SD is present. Future studies of functional bowel diseases should distinguish between patients with and without SD to clarify its relationship to these disorders. Clinicians should consider whether patients with functional disorders have SD, a diagnosis that indicates specific clinical management strategies.

The virtual pediatric intensive care unit. Practice in the new millennium.

Patients and their families meet with health care providers in a complex marketplace. The information revolution is providing access to vast amounts of information and new ways to understand it. More important, perhaps, is that it also is providing new ways of communicating information not only about health but also about the health care delivery process. This occurrence makes it possible for patients not only to diagnosis and treat themselves but also see how well the professionals do it. Like all marketplaces, asymmetries in information define the value of the interaction. Patients see physicians because they have no way of overcoming this knowledge barrier, and health care is a highly regulated market because of these asymmetries in information. New information technologies in general and telemedicine (which, in this broad sense, include distance learning for patients) can address and erode these information asymmetries. This technology threatens to have a profound effect on health care. Telemedicine offers to increase greatly the reach (connectivity) and richness (bandwidth, customization, and interactivity) of the health care information marketplace. This radically will change the way in which physicians practice critical care. Intensivists must ensure that patients continue to receive high-quality critical care. This practice will require embracing these new technologies. Resisting them will be catastrophic. What is the VPICU? It is a committed group of pediatric intensivits who are dedicated to supporting pediatric critical care medicine in the enhancement of knowledge about pediatric critical care. It includes application of information technologies to support the practice of pediatric critical care. It primarily is focused on understanding the health care delivery process and providing the tools for pediatric intensive care practitioners to better understand the care they deliver. It is the desire of the VPICU to create a virtual community in which pediatric critical care practitioners work together to understand the way they practice and to identify and implement better ways to deliver pediatric critical care. This virtual community will be responsible for clinical and economic performance in the practice of pediatric critical care. The VPICU realizes that this requires the tools to make high-quality decisions and that these decisions depend on data and communication. The author invites all pediatric intensivists to participate in the VPICU to achieve the goals of better practice through the application of information technologies in pediatric critical care.

Solubilization and disaggregation of polyglutamine peptides.

A method is described for dissolving and disaggregating chemically synthesized polyglutamine peptides. Polyglutamine peptides longer than about Q20 have been reported to be insoluble in water, but dissolution in--and evaporation from--a mixture of trifluoroacetic acid and hexafluoroisopropanol converts polyglutamine peptides up to at least Q44 to a form readily soluble in aqueous buffers. This procedure also has a dramatic effect on peptides which appear to be completely soluble in water, by removing traces of aggregate that seed aggregation. The protocol makes possible solution studies-including in vitro aggregation experiments--on polyglutamine peptides with repeat lengths associated with increased risk of Huntington's Disease and other expanded CAG repeat diseases. It may also be useful in conducting reproducible, quantitative aggregation studies on other polypeptides.