Mechanics and electrostatics of the interactions between osteoblasts and titanium surface.

Due to oxidation and adsorption of chloride and hydroxyl anions, the surface of titanium (Ti) implants is negatively charged. A possible mechanism of the attractive interaction between the negatively charged Ti surface and the negatively charged osteoblasts is described theoretically. It is shown that adhesion of positively charged proteins with internal charge distribution may give rise to attractive interaction between the Ti surface and the osteoblast membrane. A dynamic model of the osteoblast attachment is presented in order to study the impact of geometrically structured Ti surfaces on the osteoblasts attachment. It is indicated that membrane-bound protein complexes (PCs) may increase the membrane protrusion growth between the osteoblast and the grooves on titanium (Ti) surface and thereby facilitate the adhesion of osteoblasts to the Ti surface. On the other hand, strong local adhesion due to electrostatic forces may locally trap the osteoblast membrane and hinder the further spreading of osteointegration boundary. We suggest that the synergy between these two processes is responsible for successful osteointegration along the titanium surface implant.

Mathematical correlation between biomaterial and cellular parameters--critical reflection of statistics.

For mathematical modelling of the biomaterial-cell contact, it is necessary to find both parameters characterizing physical and chemical properties of the material surface and also such describing the reaction of the adhering cells. Only those material and cell parameters that correlate with each other are applicable to model this contact mathematically. Only few papers are dealing with this special problem. The aim of this paper is to present results of physical/chemical and biological investigations made on differently modified rough titanium implant surfaces in order to find out only the correlating parameters. Furthermore we discuss several ways to apply statistical methods to the correlation problem. Only few ones of all investigated parameters both on material and on cellular side were applicable for correlation. For example we found in our studies that fractal structure parameter topothesy has influence on the spreading behaviour of the osteoblastic cells. However the value of the correlation coefficient and its statistical significance heavily depend on the method of averaging the available data. Especially the biological data (spreading area) were afflicted with relatively high error up to 30%. Averaging of this data masks the true facts. That is why the correlation coefficient considerably decreases if the biological parameters are not averaged. On the other hand, the statistical reliability increases due to the higher number of investigated cases. Critical error discussion is necessary in statistical correlation between material and biological parameters. Often the results are heavily influenced by the statistical handling of data, especially if only few data are available. May be that new unconventional methods like bootstrap method can show a way out of this dilemma.

Micro-plasma textured Ti-implant surfaces.

The surface state of titanium implants modulates bone response and implant anchorage. This evidence brought implant manufacturers to switch from the standard surface refinements and implement new surface treatments for more bone apposition and enhanced interfacial strength measured by removal torque or push-out tests. Anodic plasma-chemical treatment of implant surfaces is a cost-effective process to modify surface topography and chemistry. This technique is used for structuring connected with a coating of implant surfaces. The aim of our investigations, here, is to texture the implant surface in the nanoscale without coating. Ti disks with different mechanical pre-treatment (grinded, glass blasted) were used as substrate. Micro-plasma texturing was carried out in an aqueous electrolyte. By applying a pulsed DC voltage to the specimen, micro-plasma discharge was generated in the thin steam film between immersed specimen and electrolyte. The electrical process parameter current density was varied. The micro-plasma textured Ti surfaces were characterised optically by SEM and electrochemically by CV- (for testing the corrosion parameters), CA- (to give the enlargement of the real surface) and EIS-measurement in range of 100 kHz-100 microHz. We found that the initial structure of the material surface has small or no influence on the results of the micro-plasma treatment. The properties of the thick oxide layer resulting from the plasma process are influenced by electrical process parameters. After removal of the thick oxide layer a fine, micro- and nanoscaled surface structure of the titanium remains.

Cell-extracellular matrix interaction and physico-chemical characteristics of titanium surfaces depend on the roughness of the material.

The interaction of cells with the extracellular matrix at the interface of an implant determines the biology of cells and tissues. We analysed components of cell adhesion and measured physico-chemical characteristics of structural modifications of titanium surfaces: polished, machined, glass particle-blasted, corundum-blasted, vacuum plasma-sprayed. Scanning electron microscopy and profilometry revealed a differentiated topography from smooth to rough surfaces, respectively. Osteoblastic MG-63 cells showed an increased spreading on surfaces with low roughness, although without a straight correlation with the surface topography. Integrin expression was increased on structured surfaces compared with polished material, and the organization of the actin cytoskeleton and fibronectin was impaired on extremely rough surfaces. Electrochemical methods, especially the electrochemical impedance spectroscopy (EIS) was used to evaluate physico-chemical characteristics, and the impedance curves revealed a dependence on the roughness of the material surfaces. Further analyses of the EIS results were performed using equivalent circuits which model the electrical flow through the interface. First indications for a correlation between parameters from the equivalent circuits with surface properties were obtained which promise a relevance for the biological response of the cells.

Stoma care nurses: good value for money?

Decreasing financial resources in health services often lead to wholesale budget reducing in hospitals. Enterostomal therapists are more and more concerned by this situation. Data on the cost-effectiveness of stoma therapy have not existed, a gap filled by the present study. From January to December 1996 data from 94 patients about therapy-related costs, outcome, and evaluation of stoma therapy from the patient's point of view were ascertained prospectively. For an average (SD) of 14.6 (7.1) patient contacts for stoma planning, advice, care, and so on the average duration was 12.9 (9.1) minutes per contact. At an average exchange rate of 1.50 German marks (DM) per US dollar in 1996 the enterostomal therapist's part of the total staff costs was US$15,212 (2.7%), the cost of stoma products was US$7750 (4.5% of the total costs of medical supplies). About 89.3% of the patients classified the enterostomal therapist necessary and indispensable; 70.3% of the patients said they could cope with their stoma very well to well at the time of questioning. In contrast, 69.2% of those questioned declared that without the care by the enterostomal therapist in hospital they would be able to cope with their stoma only poorly to very poorly. We conclude that from the patient's point of view the costs of our stoma therapy are justifiably low. Therefore we see no reason for a discussion about rationalization measures regarding our stoma therapy staff.

The effects of S- and R-flurbiprofen on the inflammation-evoked intraspinal release of immunoreactive substance P--a study with antibody microprobes.

Using antibody coated microprobes in anesthetized rats, we studied the intraspinal release of immunoreactive substance P during development of kaolin/carrageenan-induced inflammation in the knee joint, and the effects of S- and R-flurbiprofen on inflammation-evoked intraspinal release of immunoreactive substance P once inflammation was established. During the first 6 h after induction of acute inflammation, the basal release and the release of immunoreactive substance P evoked by innocuous pressure applied to the knee showed increases (n=4 rats). An intravenous dose of 9 mg/kg S-flurbiprofen (a potent inhibitor of cyclooxygenases that is anti-inflammatory and antinociceptive) did not significantly alter the pattern of inflammation-evoked release of immunoreactive substance P within 2 h although this dose reduced the responses of spinal cord neurons to pressure applied to the inflamed knee joint within 15 min to about 15% of the predrug value (Neugebauer et al., J. Pharmacol. Exp. Ther. 275 (1995) 618-628). The subsequent i.v. injection of 27 mg/kg S-flurbiprofen significantly changed the pattern of release of immunoreactive substance P showing a reduction of the level of immunoreactive substance P in the dorsal horn within 1 h (n=4 rats). The release of immunoreactive substance P was also reduced after the i.v. injection of 27 mg/kg R-flurbiprofen that is also antinociceptive but less anti-inflammatory (n=5 rats). These data show that both S- and R-flurbiprofen reduce the inflammation-evoked intraspinal release of immunoreactive substance P within hours. However, the reduction of release of immunoreactive substance P does not seem to be a prerequisite for the initial antinociceptive action of non-steroidal anti-inflammatory drugs. It may be rather important in the long term range.

Release of immunoreactive substance P in the trigeminal brain stem nuclear complex evoked by chemical stimulation of the nasal mucosa and the dura mater encephali--a study with antibody microprobes.

In order to study a possible involvement of substance P in the processing of chemonociceptive input from the nasal mucosa and the dura mater encephali in the spinal trigeminal, the release of immunoreactive substance P was measured in the trigeminal brain stem nuclear complex in anaesthetized rats. Microprobes coated with antibody to substance P were inserted into the lateral area of the brain stem up to 1 mm posterior to the obex corresponding to the trigeminal subnucleus caudalis. When the nasal mucosa was stimulated by topical administration of mustard oil (1% and 5%) into the nostrils, immunoreactive substance P was mainly detected in the dorsal region of the trigeminal brain stem nuclear complex with a maximum in the superficial gray matter. When the dura mater encephali was stimulated by topical administration of Tyrode's solution (pH 6.2), immunoreactive substance P was mainly released in the ventral region of the trigeminal brain stem nuclear complex; with pH 5.5 the release was more diffuse extending from the ventral to the dorsal part of the spinal trigeminal nucleus. Release was maximal rather after than during the administration of the stimuli, and it considerably outlasted the stimulation periods. These data suggest that substance P plays an important role in the processing of chemonociceptive inputs from the nasal mucosa and the dura mater encephali in the trigeminal brain stem nuclear complex. Substance P may be important, therefore, in the generation of those headaches that are caused by affections of the nasal mucosa and the dura mater encephali. Since enhanced levels of immunoreactive substance P were present for considerable time periods beyond the administration of the stimuli, substance P and neurokinin-1 receptors may be involved in long-lasting neuronal events following noxious stimulation.

Intracranial chondroma. Case report.

We present a rare case of intracranial chondroma originating from the falx cerebri. Diagnostic procedures and surgical management are discussed, with special reference to computed tomography, magnetic resonance imaging, and pathologic findings.

Ketogenic regulation by certain metabolites in rumen epithelium.

In experiments with rumen epithelium incubated in vitro in the presence of butyrate, the ketogenic effect of glucose was shared by epimeric monosaccharides but not by non-metabolizable analogues. 14C from glucose was not incorporated into ketone bodies. Malate increased ketogenesis from butyrate and decreased its oxidation, pyruvate and NH4+ had the opposite effect, and malonate inhibited both processes. The ketogenic effect of glucose was also effective with isovalerate maintaining the high proportion of acetoacetate which is characteristic of this substrate. Rumen epithelium transformed added acetoacetate into 3-hydroxybutyrate. It is concluded that reducing equivalents produced from glucose and other metabolizable substrates are responsible regulators of ketogenesis from butyrate. The results are discussed in view of the functional role of ruminal ketogenesis.

CT findings following diphenylhydantoin intoxication.

CT findings in three female epileptic patients are presented. The patients were treated with toxic doses of the anticonvulsant diphenylhydantoin, leading to irreversible ataxia of varying severity. CT shows cerebellar atrophy, including discernible sulci, a dilated 4th ventricle, basal cisterns, and subarachnoid space. These effects of severe DPH toxicity are relevant in the differential diagnosis of 'idiopathic' and other toxic and systemic atrophies, as well as dysontogenetic lesions of the cerebellum.

Cerebellar atrophy following diphenylhydantoin intoxication.

Seven epileptic patients with permanent ataxic dysfunction following DPH treatment are described. The ataxia correlates with cerebellar atrophy, though the extents of clinical and structural lesions are not necessarily proportional. Cerebellar atrophy is demonstrated by CT scans, the vermal region seems to be predominantly affected.--The tentatively increased susceptibility of female patients and of patients with pre-existing brain lesions, as well as the possible consequences pertaining to the course of the epilepsy are discussed.

The ketogenic effect of glucose in rumen epithelium of ovine (Ovis aries) and bovine (Bos taurus) origin.

In experiments with rumen epithelium incubated in vitro the ratio of 3-hydroxybutyrate: acetoacetate produced was similar to the ratio reported for portal blood, and the ratio ketogenesis: oxidized to CO2 of butyrate was also close to values reported in vivo. Ovine and bovine epithelium incubated with butyrate differed significantly by the values of about 12-17 and 4-7 obtained for the ratio of 3-hydroxybutyrate: acetoacetate. Increasing levels of butyrate in the incubation medium resulted in a decreasing proportion of butyrate oxidized to CO2 and an increasing proportion of ketogenesis. The addition of glucose to butyrate in the incubation medium significantly increased the rate of ketogenesis from butyrate by ovine and bovine tissues. The addition of glucose to butyrate in the incubation medium significantly decreased the rate of butyrate oxidation to CO2 by ovine and bovine tissues. The ketogenic effect of glucose was also apparent in perfused rumen epithelium with butyrate at the mucosal side and glucose at the serosal side.

The effect of rumen epithelial development on metabolic activities and ketogenesis by the tissue in vitro.

1. An investigation was made on oxygen consumption, glucose and lactate uptake and ketogenesis from butyrate by rumen epithelium in vitro from lambs at various stages of development. 2. Oxygen uptake was decreased by about 35% and glucose uptake by about 90% between 2 weeks and 1/2 year of age. 3. The uptake of L-lactate and the utilization of butyrate as a substrate for respiration were increased during epithelial development. 4. The production of D(-)-3-hydroxybutyrate and acetoacetate from butyrate by the epithelium was largely increased between 4 to 10 weeks of age, independently of rumen fermentation. 5. A synergistic effect of glucose on the production of D(-)-3-hydroxybutyrate and on total ketone bodies from butyrate by the epithelium was observed. It accounted to 40-80% over butyrate depending on the stage of epithelial development.

[Prosopagnosia and disturbance of color recognition during recovery from cortical blindness]. / Prosopagnosie und Farberkennungsstörung bei Rückbildung von Rindenblindheit.

Neuropsychologic findings during recovery from cortical blindness are described in four right-handed patients (two female, two male) aged 53 to 70 years. The lesions were due to occlusion of both posterior cerebral arteries (Case 1) and vascular spasm following subarachnoidal hemorrhage (Case 3) or angiography (Cases 2 and 4). Complete blindness lasted for 3 months until death in Case 1, 4 weeks in case 2, and 1 to 2 days in Cases 3 and 4. Confusional states and visual hallucinations were pronounced in three cases. Anosognosia (Anton's syndrome) was most pronounced in a patient with occlusion of both posterior cerebral arteries and less obvious in the remaining patients. During the recovery phase, symptoms of right hemisphere involvement were prominent with left-sided hemianopsia and diminished optokinetic nystagmus to the left, prosopagnosia in two cases, and dysmorphopsia with altered physiognomic recognition in one case. Transient disturbances of color recognition occurred in three patients. The observations are discussed with reference to clinical and neuropathologic findings of the literature.

Selective deprivation of sleep in pycnoleptic children. Effects of deprivation of slow-wave and REM sleep on the frequency and duration of petit mal attacks.

1. Selective deprivation of slow-wave and paradoxical sleep was performed in 10 children with pycnoleptic attacks (8 of them before anticonvulsive treatment, 2 of them while under medication). The frequency and duration of petit mal attacks were intraindividually compared during night sleep and after waking for a 5-h period. 2. After deprivation of slow-wave sleep with reduction of EEG stages 3 and 4 to about one-third of the baseline but normal duration of sleep, petit mal attacks are more frequent and long-lasting than after normal sleep or selective deprivation of REM sleep. 3. Although total sleep time is significantly diminished after selective deprivation of paradoxical sleep the frequency of attacks during the waking state was lower than after normal sleep and deprivation of slow wave sleep. This observation shows a clear i nfluence of the quality of sleep on the frequency of epileptic attacks. 4. During sleep petit mal seizures were mainly found during stages 2 and paradoxical sleep. Single spike and irregular spike were discharges, however, occurred more frequently during slow-wave sleep. Their frequency was not significantly different in the deprivation conditions. 5. In contrast to experimental data in animals, REM deprivation is less provoking to epileptic attacks outside sleep than deprivation of stages 3 and 4 sleep. Therefore a sufficient amount of slow-wave should be preserved for pycnoleptic children.

Paget's disease with spinal cord compression. Favourable course after decompression and calcitonin treatment in two cases.

Two cases with spinal cord compression due to Paget's disease (osteodystrophia deformans) are reported, which were treated with calcitonin (Salmon Calcitonin) during 12 and 24 months after decompressive laminectomy. Both presented a favourable clinical course with improvement of sensory and bladder disturbances, paraparesis and pain. Diagnostic criteria as X-ray investigation, scintigraphy of bones, biochemical parameters and the long-term treatment whith calcitonin, are discussed.