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Biomedical subjects

C Hauke

Publications and source records attributed to C Hauke.

12 recordsLinked to original sources

Polylactide implants and bacterial contamination: an animal study.

Although bioresorbable aliphatic polyesters derived from lactic acid are now used clinically as sutures, bone-fracture fixation devices and sustained-release drug-delivery systems, very little is known about their behavior in the infected environment. The aim of the present study was to compare the resistance to infection of two polylactide implants with different degradation characteristics, and to evaluate the influence of a bacterial challenge on their mechanical and physicochemical properties. Various quantities of a beta-haemolyzing strain of Staphylococus aureus (V 8189-94) were inoculated into the medullary cavity of rabbit tibiae, and an extruded polylactide rod composed of either P(L)LA (Poly(L-Lactide)) or P(L/DL)LA (Poly(L/DL-Lactide)) was then inserted. Animals were sacrificed four weeks after surgery. The tibiae and implants were removed under sterile conditions and evaluated microbiologically by culturing. The severity of infection was graded according to positive colony-forming units in the bone. The mechanical properties of the retrieved implants were assessed by 4-point bending and shear tests, performed in compliance with the ASTM D790 standard and their physicochemical characteristics also were characterized. P(L)LA and P(L/DL)LA implants were equally resistant to local infection, their mechanical and physicochemical properties being unaffected by bacterial challenge. Hence, once an infection has become established, the release of bactericidal/bacteriostatic by-products during implant degradation does not appear to affect its natural course. The release of bactericidal/bacteriostatic degradation products at the implantation site is unlikely to affect the natural course of an established infection.

Animals↗

Biomechanical and biological considerations relating to the clinical use of the Point Contact-Fixator--evaluation of the device handling test in the treatment of diaphyseal fractures of the radius and/or ulna.

The Point Contact-Fixator (PC-Fix) was designed as part of the developmental evolution of more biological devices for internal fixations. It is a device characterized by minimal contact to the underlying periosteum and bone, hereby minimizing potential damage to perfusion. A multicentre handling test was conducted in 1993 and 1994 in six hospitals to assess its performance. A total of 83 fractured forearm bones (34 radii and 49 ulnae) in 52 patients were stabilized with a PC-Fix. The mean age of the patients was 37 years. There were 24 AO type A, 24 type B and 5 type C fractures. Nine fractures were open. Mean follow-up was 15.6 months; follow-up was 100%. All 21 surgeons involved considered the use of the PC-Fix self-explanatory and relatively easy. Handling difficulties were mainly related to insertion of the monocortical screws. In particular, the precision required for insertion, the inability to incline the screw and the inability to pull the plate to the bone using the screw were considered hard to deal with. Stripping of the hexagonal slot was a problem at removal of the implant, possibly related to overtightening of the screws at insertion. In 76 of 83 bones (49 of 53 forearms), the fractures united without additional surgery. The healing pattern typically showed early callus formation bridging the fracture, followed by progressive mineralization of the central radiolucent line. Complications included one infection, one late displacement and four delayed unions, all requiring revision surgery. In 8 forearms, plate removal was performed after a mean of 10.3 months. Two refractures occurred after removal of the implant 6 and 7 months postoperatively. In conclusion, the practical handling of the new implant was straightforward and easily learnt. The treatment failures observed were related to technical and strategic errors. We consider that, when using devices with a locking compression principle, a minimum number of three screws should be placed on each side of the fracture, that interfragmentary compression of simple fractures is desirable in order to increase stability and that, contrary to in vivo animal studies, early plate removal is not indicated. The trend in fracture fixation is to improve the biomechanical and biological properties of operating technique and the devices used. The PC-Fix has proven a useful step in the right direction in this evolutionary process.

Adolescent↗

Methodology of clinical trials focusing on the PC-Fix clinical trials.

Once development and mechanical and biological laboratory testing have been completed, new technologies to be used in orthopaedic and trauma surgery must be investigated in humans before they can be used routinely. Prospective clinical investigations with or without randomization to standard treatments conducted according to the current standards and guidelines for Good Clinical Practice must be performed to prove the safety and efficacy of the new device. Furthermore, these tests serve to determine the specific indications, contraindications, tips and tricks as well as the pitfalls and how to avoid them. Last, but not least, the study must result in improved teaching of the use of the device and in improved follow-up of patients. The basis of every conclusion drawn from such a study is the complete documentation of each single use of the new device. We present the modalities and methodology for conducting a prospective clinical multicentre investigation in trauma surgery, focusing on the clinical trials carried out on the Point Contact Fixator (PC-Fix), a device for the internal fixation of long bone fractures developed as part of the scientific evolution towards the Less Invasive Stabilization Systems (LISS) now being introduced into clinical practice. Four prospective multicentre clinical investigations with an overall number of 1,229 PC-Fixators implanted from October 1993 to May 1998 were performed. To our knowledge this is the largest prospective series ever reported in orthopaedic trauma surgery to test a new device before market introduction. Due to a special documentation and implant replacement procedure, every PC-Fix implantation was documented. Very few patients were lost to long-term follow-up due to the personal commitment of the study monitors. Regular personal visits of the study monitor to the investigating hospitals and close communication between the surgeons, the engineers responsible for development, the study monitor, and the study sponsor meant that problems were identified and dealt with professionally without compromising the health of the patient. Case report forms were concise and had to be transmitted without delay. Handling of radiographs has become easier thanks to the transmission of digital images to the study centre via the internet. There are some aspects specific to trauma surgery which require special consideration and planning is essential, but clinical trials can be performed effectively.

Clinical Trials as Topic↗

PC-Fix and local infection resistance--influence of implant design on postoperative infection development, clinical and experimental results.

Bacterial infection is still one of the main complications after internal fixation of fractures. The design of implants influences local infection resistance. To reduce the development of infections around implants after internal fixation, the vitality of the bone should be preserved to optimize cellular and humoral host defence mechanisms. For extramedullary fracture fixation, two implant designs are currently in routine use: the Dynamic Compression Plate (DCP) and the Limited Contact Dynamic Compression Plate (LC-DCP). The Point-Contact-Fixator (PC-Fix) is a new design concept based on the philosophy of the LC-DCP and the external fixator. Its function relies on splinting the fragments of a fracture internally with locking bolts rather than with screws that compress the plate to the bone. In this way, the blood supply is not compromised by compression of the periosteum. We investigated the effect of this new design on the incidence of postoperative infection rates in a clinical and an experimental setting. In a prospective multicentre study 1,229 PC-Fixators were used in 896 patients. Of these, 1,172 were available for assessment of infection development. The overall infection rate was 1.1% (13/1,172). The infection rate after open fractures was 1.6% (4/256) and after closed procedures (including closed fractures, osteotomies and non-unions) 1.0% (9/916). These rates are low in comparison to published rates using DCP and LC-DCP. In an experimental study, we compared the infection rates across two groups of rabbits four weeks after fixing either a bacterially contaminated DCP or a PC-Fix to the tibia. Infection rates in the DCP group were significantly higher than in the PC-Fix group: Of the 38 evaluated animals, 12 with a DCP and 5 with a PC-Fix developed local infection (p=0.022). The new PC-Fix design shows low postoperative infection rates in the clinical setting and lower infection rates than the DCP in the experimental setting. The design is an important step in the process of reducing postoperative infection rates.

Adolescent↗

Treatment of diaphyseal fractures of the forearm using the Point Contact Fixator (PC-Fix): results of 387 fractures of a prospective multicentric study (PC-Fix II).

Fractures of the forearm are considered to be a very good indication for plating. Conventional plating is still technically demanding. Extensive animal studies show that there is potential for improvement. The method consists of using an internal fixator that minimizes implant contact to the bone to reduce biological damage. Furthermore, foregoing the need for precise reduction and interfragmental compression makes it easier to use and, therefore, it should be safer. The goal of the study was to observe handling qualities, healing, and complications. For this purpose the study was designed to yield a very high follow-up in clinics with adequate experience and with a number of different surgeons performing the internal fixation. The study was designed as a prospective multicentre investigation in 16 trauma centres worldwide. To test the new approach to internal fixation, diaphyseal fractures of the forearm were stabilized surgically with the PC-Fix (Point-Contact Fixator) system, namely, 387 fractured bones involving 277 forearms in 272 patients. Internal fixation was performed using 387 PC-Fixators. 21% of the fractures were open and 25% occurred in polytraumatized patients. The rate of follow-up was 97%. 355 fractured bones healed uneventfully within four months. Overall, there were 32 complications before bone union occurred; 27 of these bones required re-operation (27 of 387, 7%). All of them subsequently healed without further complications. There were 15 delayed or non-unions and seven implant loosenings, two of which were associated with infection. Two superficial (0.6%) and two deep infections (0.6%) occurred in 306 closed fractures. Deep infection developed in one of 81 osteosyntheses of open fractures (1.2%). Other complications included one synostosis, fractures with the implant in situ with adequate trauma involving three bones, and two secondary correction procedures for postoperative malalignment. There were seven refractures occurring at a mean of three weeks after the removal of 150 PC-Fixators (4.7%). This study demonstrated that the technique of using an internal fixator is a simple one for the fixation of forearm fractures, resulting in shorter duration of surgery with a low rate of complications compared with the data reported in the literature on conventional techniques for forearm fracture stabilization.

Adolescent↗

Infection after intramedullary nailing: an experimental investigation on rabbits.

The purpose of this study was to investigate three relevant aspects of intramedullary nailing in terms of their effect on the occurrence of local infection. In an infection model on the rabbit tibia, the following were compared: a hollow and a solid nail (Experiment I), a reamed with an unreamed technique (Experiment II), and a steel with a titanium nail (Experiment III). In order to minimize the number of animals required, a grouped sequential procedure combined with an "up and down" dosage technique was applied. Microbiological evaluation was both qualitative and quantitative. The results in Experiment 1 (n = 44) indicated an infection rate for the hollow nail (59%) almost double that of the solid nail (27%) (P < or = 0.05). Experiment II (n = 44) produced an infection rate of 50% for the unreamed technique compared to 64% for the reamed technique, a difference which, on the basis of the number of bacteria present, was also statistically significant (P < or = 0.05). In Experiment III (n = 44) an infection rate of 82% was recorded for the steel nail compared to 59% for the titanium nail (P < or = 0.05). The results of the three experiments are only partially comparable with each other because of the grouped sequential procedure and the different inocula used. Nonetheless it would seem that the dead space inherent in the design of the hollow nail represents a considerable risk with regard to the occurrence of local infection. Reaming the medullary cavity with the attendant reduction in local vascularity and necrosis and the lesser biocompatibility of steel compared to titanium may be additional risk factors which should not be overlooked.

Animals↗

Cell proliferation in the subependymal layer of the adult mouse in vivo and in vitro.

Pulse labelling experiments with [3H] thymidine (dT) and double labelling experiments with [3H]dT and bromodeoxyuridine (BrdUrd) were carried out on cells of the subependymal layer in the brain of adult normal mice in vivo, in vivo/in vitro and in vitro. The results should (i) lead to information about cell cycle parameters of these cells in the brain of adult mice, since these cells have been studied mostly in the rat brain up to now and (ii) answer the question whether results concerning cell proliferation obtained in vivo correspond with those from brain slices incubated in vitro with or without prelabelling in vivo. In vivo an LI of 20.2 +/- 2.7% (mean +/- SEM) and Ts = 7.2 +/- 0.7 h were found. Furthermore, grain count halving experiments led to a surprisingly short cycle time (Tc) of 11.2-14.2 h. The longer Tc values (18-20 h) reported in the literature for subependymal cells in the rat brain seem to be due to evaluations of different areas around the lateral ventricle without considering the migrating behaviour of these cells which is quite different regionally. The in vitro studies (with or without prelabelling in vivo) showed a significantly reduced LI due to the fact that about 20% of the S phase cells, possibly lying in the middle of S, stopped further DNA synthesis after transfer to culture. This was shown by comparing the cell fluxes at the G1/S and S/G2 borders of in vivo vs. in vitro studies.

Animals↗

Fragmentation and narcissism. A revaluation.

The paper focuses on the articulation of two areas of theory: that of development of the self through fragmentation and differentiation and that of narcissism in early psychological development, and its pathology later in life. Jungian ideas concerning the self and individuation (including those developed by Fordham) are linked with psychoanalytic ideas, notably Kohut's, and related to the concepts of narcissism and ego-development. In this the focus is on a revaluation of the negative overtones of 'fragmentation' and 'narcissism' and an indication of their place in the process of individuation. It is pointed out that a varying emphasis in the analyst on what are called the biological and ethological aspects of these theories will have important implications for the treatment of patients. The theoretical position is illustrated by a lengthy clinical example involving a case of early injury to the self which suggests the pathology of narcissistic character disorder. But the case also illustrates the contribution to development of fragmentation and narcissism, which are revalued here as the 'part-for-the-whole' and as one of the 'motors' of individuation. Working within a perspective that prioritizes the importance of the drive towards relationship, it is recommended that the analyst learns to respect and value phenomenologically the contribution of fragmentation and narcissism to normal development, if true healing is to occur.

Adult↗

RCA-I lectin histochemistry after trypsinisation enables the identification of microglial cells in thin paraffin sections of the mouse brain.

A biotinylated lectin from Ricinus communis (RCA-I) and avidin-biotin-horseradish peroxidase complex (ABC) were used to identify microglial cells in 3-microns-thick sections of formalin-fixed paraffin-embedded brains of adult mice required for quantitative cell kinetic studies. In 3-microns-thick sections of the mouse brain the staining intensity of RCA-I-positive cells compared to background staining was too low for evaluation, quite in contrast to rat brain. However, perikarya and cytoplasmic processes of microglial cells were clearly stained in 10- and 20-microns-thick sections. The low contrast characteristic of thin mouse brain sections could be enhanced by pre-incubating the sections with trypsin before application of the lectin. We assume that different densities of RCA-I binding sites among microglial cells of rats and mice, respectively, are responsible for the different staining intensities observed. Our protocol of lectin staining did not influence subsequent autoradiography for studies of cell proliferation after [3H]thymidine application.

Animals↗

Identification of endogenous sugar-binding proteins in the accessory sex glands of NMRI mice. A histochemical and biochemical study.

In the present study we report on the histotopographical distribution of carbohydrate-binding proteins in the prostate and seminal vesicle of sexually mature NMRI mice using a panel of fluorescein-isothiocyanate labelled neoglycoproteins and asialoglycoproteins. Additionally, biochemical analysis using affinity chromatography and SDS-gel electrophoresis was performed to purify and characterize the respective proteins from the tissue. Our histochemical results clearly demonstrate the presence of endogenous receptors for the carbohydrate part of glycoconjugates in both glands. In the prostate a distinct staining was seen after incubation with melibiose-BSA-FTC, glucuronic acid-BSA-FTC and asialofetuin-FTC (only in the ventral prostate). In the epithelium of the seminal vesicle a weak staining occurred after incubation with asialofetuin-FTC and maltose-FTC. In the stroma of both accessory sex glands a distinct binding of several (neo)glycoproteins specific for beta-galactoside-binding proteins was observed which could be attributed to a beta-galactoside-binding lectin. Indeed biochemical analysis ascertained presence of such a histochemically detectable activity. We assume that the carbohydrate-binding proteins of the stroma, which were obviously linked to the elastic fibers, could play a role in the organisation of the extracellular matrix in the interstitium of the glands.

Animals↗

[Lymph follicle formation and development of intestinal metaplasia in antrum mucosa as a reaction to Helicobacter pylori infection].

We examined 171 patients (76 females and 95 males) with definite type B-Gastritis. Antrum specimens were taken from all participants for histological examination. We studied the correlations between the formation of lymphoid follicles, the severity of gastritis, the degree of activity of gastritis and the density of Helicobacter pylori colonization. In addition we noted the distribution and extent of the intestinal metaplasia. In patients with high degree HP-colonization we found formation of lymphoid follicles in 59.8%, in patients with low degree HP-colonization in 35% and in patients without colonization only in 10.2% (high degree vs. low degree colonization p less than 0.05, low degree vs. absent colonization p less than 0.025, high degree vs. absent colonization p less than 0.0005). In patients with high grade type B-Gastritis we detected formation of lymphoid folliclesin 58%. There was no case of formation of lymphoid follicles in patients with low grade type B-Gastritis. Patients with a high grade activity of the type B-Gastritis displayed a formation of lymphoid follicles in a higher percentage as patients with a low grade activity of the gastritis (66% vs. 33%, p less than 0.0005). In the antrum intestinal metaplasia of the types I and II could be found significantly more frequent in patients with high grade Type B-Gastritis than in patients with low grade Type B-Gastritis (34.1% vs. 8.8%, p less than 0.005). Intestinal metaplasia was found more frequently in connection with high and low activity of type B-Gastritis than without activity (p less than 0.005 and p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Postnatal development of lectin binding sites in the rat ventral prostate.

Five Fluorescein-isothiocyanate (FITC)-labelled lectins were used to study the postnatal development of carbohydrate constituents in the rat ventral prostate: Concanavalin A (Con A), wheat germ agglutinin (WGA), peanut agglutinin (PNA), Dolichos biflorus agglutinin (DBA) and Ricinus communis agglutinin I (RCA-I). With all the lectins tested, except RCA-I, specific binding sites could be shown for every stage of differentiation in the glandular epithelium. Binding sites for Con A, WGA, PNA and DBA were found from day 10 to 13 post partum onwards. Each lectin showed a characteristic localization. Binding sites for the lectins used changed to different extents during the following two weeks. After the 24th day post partum no further changes in the lectin binding pattern could be found. The development of the lectin binding properties showed that the changes in carbohydrate-containing constituents of the prostate correlate with the beginning of prostatic secretion and to prostatic epithelial differentiation. In the periacinar stroma the development of the lectin binding pattern was similar to that in the glandular epithelium. The changes of stromal binding sites for Con A and WGA during epithelial differentiation may reflect the changes of epithelial-stromal interactions in the prostate.

Animals↗