Role of tumour necrosis factor-alpha receptor p75 in cigarette smoke-induced pulmonary inflammation and emphysema.

Chronic obstructive pulmonary disease (COPD) is characterised by a local pulmonary inflammatory response to respiratory pollutants and by systemic inflammation. Tumour necrosis factor (TNF)-alpha has been implicated in systemic effects of COPD and operates by binding the p55 (R1) and p75 (R2) TNF-alpha receptors. To investigate the contribution of each TNF-alpha receptor in the pathogenesis of COPD, the present study examined the effects of chronic air or cigarette smoke (CS) exposure in TNF-alpha R1 knockout (KO) mice, TNF-alpha R2 KO mice and wild type (WT) mice. CS was found to significantly increase the protein levels of soluble TNF-alpha R1 (by four-fold) and TNF-alpha R2 (by 10-fold) in the bronchoalveolar lavage of WT mice. After 3 months, CS induced a prominent pulmonary inflammatory cell influx in WT and TNF-alpha R1 KO mice. In TNF-alpha R2 KO mice, CS-induced pulmonary inflammation was clearly attenuated. After 6 months, no emphysema was observed in CS-exposed TNF-alpha R2 KO mice in contrast to WT and TNF-alpha R1 KO mice. CS-exposed WT and TNF-alpha R1 KO mice failed to gain weight, whereas the body mass of TNF-alpha R2 KO mice was not affected. These current findings suggest that both tumour necrosis factor-alpha receptors contribute to the pathogenesis of chronic obstructive pulmonary disease, but tumour necrosis factor-alpha receptor-2 is the most active receptor in the development of inflammation, emphysema and systemic weight loss in this murine model of chronic obstructive pulmonary disease.     

Estimating Potency for the E max-Model Without Attaining Maximal Effects

The most widely applied model relating drug concentrations to effects is the E_max model. In practice, concentration–effect relationships often deviate from a simple linear relationship but without reaching a clear maximum because a further increase in concentration might be associated with unacceptable or distorting side effects. The parameters for the E_max model can only be estimated with reasonable precision if the curve shows sign of reaching a maximum, otherwise both EC₅₀ and E_max estimates may be extremely imprecise. This paper provides a solution by introducing a new parameter (S₀ ) equal to E_max/EC₅₀ that can be used to characterize potency adequately even if there are no signs of a clear maximum. Simulations are presented to investigate the nature of the new parameter and published examples are used as illustration.     

Stemmed femoral knee prostheses: Effects of prosthetic design and fixation on bone loss

Although the revision rates for modern knee prostheses have decreased drastically, the total number of revisions a year is increasing because many more primary knee replacements are being done. At the time of revision, bone loss is common, which compromises prosthetic stability. To improve stability, intramedullary stems are often used. The aim of this study was to estimate the effects of a stem, its diameter and the interface bonding conditions on patterns of the bone remodeling in the distal femur.

We created finite element models of the distal half of a femur in which 4 types of knee prostheses were placed. The bone remodeling process was simulated using a strain-adaptive bone remodeling theory. The amount of such remodeling was determined by calculating the changes in bone mineral density in 9 regions of interest from simulated DEXA scans.

The computer simulation model showed that revision prostheses tend to cause more bone resorption than primary ones, especially in the most distal regions. Predicted long-term bone loss due to a revision prosthesis with a thin stem equalled that around a prosthesis with an intercondylar box. However, strong regional differences were found- the stemmed prostheses having more bone loss in the most distal areas and some bone gain in the more proximal ones. A prosthesis with a thick stem led to an increase in bone loss. When the prosthesis-cement interface was bonded, more bone loss was predicted than with an unbonded interface. These results suggest that a stem which increases stability initially may reduce stability in the long term. This is due to an increase in stress shielding and bone resorption.     

Scalp electrical recording during paralysis: quantitative evidence that EEG frequencies above 20 Hz are contaminated by EMG.

OBJECTIVE: To identify the possible contribution of electromyogram (EMG) to scalp electroencephalogram (EEG) rhythms at rest and induced or evoked by cognitive tasks. METHODS: Scalp EEG recordings were made on two subjects in presence and absence of complete neuromuscular blockade, sparing the dominant arm. The subjects undertook cognitive tasks in both states to allow direct comparison of electrical recordings. RESULTS: EEG rhythms in the paralysed state differed significantly compared with the unparalysed state, with 10- to 200-fold differences in the power of frequencies above 20 Hz during paralysis. CONCLUSIONS: Most of the scalp EEG recording above 20 Hz is of EMG origin. Previous studies measuring gamma EEG need to be re-evaluated. SIGNIFICANCE: This has a significant impact on measurements of gamma rhythms from the scalp EEG in unparalysed humans. It is to be hoped that signal separation methods will be able to rectify this situation.     

Experimentelle und klinische Studie zur Stabilit?t einer Osteosyntheseplatte für den atrophen Unterkiefer

ZusammenfassungHintergrund Der Anteil an älteren Patienten steigt ständig und damit auch die Zahl traumatischer altersbedingter Verletzungen wie Frakturen des Unterkiefers. Die Frakturversorgung bei älteren Menschen stellt spezielle Anforderungen. Durch das Design einer neu entwickelten Osteosyntheseplatte sollte versucht werden, diese speziellen Gesichtspunkte zu erfüllen.Material und Methoden Im Gegensatz zu den 2.0-Miniplatten (Medartis AG, Basel) besitzt die Pencilbone-2.0-Platte, die aus diesen Miniplatten entwickelt wurde, einen oval geformten Mittelsteg zur Stabilisierung des frakturnahen Knochens und zwei sphärische Gleitlöcher jenseits der Fraktur. An den verstärkten Teil der Osteosyntheseplatte schließen sich jeweils 2 bzw. 3 normale unverstärkte Löcher an, die sich sehr leicht an den frakturfernen Knochen adaptieren lassen. Dies ermöglicht dem Operateur den intraoralen Zugangsweg und eine Handhabung, welche er von der Miniplattenosteosynthese gewohnt ist, bietet aber gleichzeitig eine höhere Stabilität im Vergleich mit den Standard-2.0.-Miniplatten.Ergebnisse und Diskussion Nach experimentellen und biomechanischen Untersuchungen, die alle positive Ergebnisse zeigten, wurde die neue Platte zwischen Oktober 2000 und November 2001 in zwei Kliniken an 16 Frakturen des atrophischen Unterkiefers bei 14 Patienten erfolgreich angewendet. 15 Frakturen heilten primär, lediglich bei einer Fraktur wurde eine neue operative Versorgung wegen Knochendislokation nach erneutem Sturz notwendig.     

Sulfasalazine treatment in juvenile chronic arthritis: an open study.

In an open study, the effect of sulfasalazine was evaluated in the treatment of juvenile chronic arthritis (JCA). Forty-one patients, i.e., 27 boys and 14 girls with JCA under 16 years of age, were included in the study. In all of them, treatment with nonsteroidal antiinflammatory drugs (NSAID) had been unable to control the disease. The patients were divided in 4 subgroups depending on the mode of onset and evolution (Type I = systemic onset, Type II = polyarticular form. Type IIIa and Type IIIb = pauciarticular form). Remission was achieved in 21 patients, significant improvement in 12. Status was unchanged in 4 patients and worsened in 3. In 5 patients side effects were observed, which forced interruption of treatment in 4. Sulfasalazine was stopped in 7 patients: for toxicity in 4 and for inefficacy in 3. In 7 other patients the treatment was terminated after a prolonged remission. These promising results must be confirmed in a double blind versus placebo study, preferably restricted to type III JCA.     

Effects of preparation techniques on the porosity of acrylic cements

We investigated four acrylic cement preparation techniques for their effects on cement porosity: hand mixing, pressurization in a pneumatic pistol, centrifugation, and vacuum mixing. All the techniques were tested on three types of cement with different viscosity characteristics. The best results were obtained with vacuum mixing using a newly designed experimental system, yielding porosity reductions of 60-80 percent relative to hand mixing. Vacuum mixing with a commercial system was also effective, but to a somewhat lesser extent.

Pressurization and centrifugation had no substantial effect on the overall porosity. Centrifugation led to considerable nonuniformity in the distribution of pores and additives.