[Therapy relevant imaging in modern surgical treatment of arthrosis of the shoulder: interesting facts for orthopedic surgeons]. / Therapierelevante Bildgebung in der modernen Arthrosebehandlung am Beispiel des Schultergelenks: Wissenswertes für den Orthopäden.

CLINICAL/METHODICAL ISSUE: Imaging for shoulder surgery varies a lot nowadays. Advantages and disadvantages of possible imaging methods according to the pathology and treatment options are described. STANDARD RADIOLOGICAL METHODS: Digital projection radiography in 3 planes, ultrasonography, MRI, CT scanning and scintigrams. METHODICAL INNOVATIONS: Special axial view to visualize the glenoid situation, as well as 3-D CT scanning for larger defects and classification. PERFORMANCE: Imaging of the glenoid situation, the version and erosion in axial view x-ray is mandatory to plan and control glenoid replacement. ACHIEVEMENTS: Useful application of imaging methods for the daily routine of orthopedic surgeons. PRACTICAL RECOMMENDATIONS: Digital 3 plane x-ray imaging in arthroplasty surgery is the minimum requirement. For rotator cuff lesions ultrasonography is good. In order to gain information on fatty infiltration of rotator muscles MRI is needed as well as for intra-articular lesions. For bony defects CT and reconstruction 3-D are recommended.

Effect of a haloperidol challenge on regional brain metabolism in neuroleptic-responsive and nonresponsive schizophrenic patients.

OBJECTIVE: The CNS metabolic response to a neuroleptic challenge in treatment-responsive and nonresponsive schizophrenic patients was measured in order to examine the relation between treatment outcome and the capacity to alter neurochemical function in response to acute receptor blockade. METHOD: Positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG) were used to measure regional cerebral metabolism in seven schizophrenic patients judged to have been responsive to drug treatment previously and seven nonresponsive schizophrenic patients after a drug-free period of at least 3 weeks (baseline) and again 12 hours after administration of 5.0 mg of haloperidol. RESULTS: The haloperidol challenge caused widespread decreases in absolute metabolism in the nonresponsive patients but not the responsive patients. These group differences reflect the findings on the second (challenge) scans, since metabolic values at baseline were not statistically different in the two groups. The pattern of decreased metabolic activity in the nonresponders after the haloperidol challenge is similar to that previously observed in normal subjects. CONCLUSIONS: The metabolic response to drug challenge separates treatment responders from nonresponders and normal subjects. The results suggest that subtyping of schizophrenia (and other psychiatric disorders) can be achieved by measuring the physiologic response to a pharmacologic challenge in vivo with chemical brain-imaging techniques.

Gamma vinyl-GABA differentially modulates NMDA antagonist-induced increases in mesocortical versus mesolimbic DA transmission.

To explore the role of endogenous GABA in NMDA antagonist induced dopamine (DA) release, we used in vivo microdialysis to study the effects of pretreatment with gamma-vinyl GABA (GVG) on phencyclidine (PCP)-induced DA release in terminal regions of midbrain DA neurons. GVG, an irreversible inhibitor of the GABA catabolizing enzyme GABA-AT, significantly reduced the DA response to PCP (7.0 mg/kg) in freely moving animals. Preferential increases in PCP-induced DA release in the PFC (four-fold those of NAcc) were dose-dependently inhibited by acute pretreatment with GVG at doses of 150 (51% inhibition), 300 (68% inhibition), and 500 (82% inhibition) mg/kg, whereas NAcc PCP-induced DA activity was unresponsive to 150 mg/kg and only partially inhibited by 300 and 500 mg/kg. Subchronic treatment with GVG did not enhance the inhibitory capacity of the GABAergic system. While GVG evidently modulates PCP-induced increases in mesocorticolimbic DA transmission, the character of this modulation is regionally specific, with cortical NMDA-antagonist induced increases appearing more sensitive to inhibition by endogenous GABA than subcortical areas.

gamma-aminobutyric acid mimetic drugs differentially inhibit the dopaminergic response to cocaine.

Dopaminergic activity in the mesocorticolimbic system is associated with reinforcing properties of psychostimulant drugs. We previously demonstrated that increased gamma-aminobutyric acid (GABA)-ergic activity produced by gamma-vinyl GABA [D,L-4-amino-hex-5-enoic acid (Vigabatrin(R))], an irreversible inhibitor of GABA-transaminase, attenuated cocaine, nicotine, heroin, alcohol, and methamphetamine-induced increases in extracellular nucleus accumbens dopamine as well as behaviors associated with these biochemical changes. In the present study, using in vivo microdialysis techniques, we compared three different strategies to increase GABAergic activity in order to modulate cocaine-induced increase in extracellular dopamine. Our data demonstrate that the anticonvulsant 1-(2-(((diphenylmethylene)amino)oxy)ethyl)-1,2,5, 6-tetrahydro-3-pyridinecarboxylic acid hydrochloride (NNC-711), a GABA uptake inhibitor, dose and time dependently diminished increases in extracellular dopamine following acute cocaine challenge. Furthermore, we demonstrated that cyclized analogue of vigabatrin, a competitive reversible GABA-transaminase inhibitor, is a more potent inhibitor of cocaine-induced dopamine increase than vigabatrin. Our data suggest that in addition to irreversible inhibition of GABA transaminase, inhibition of GABA uptake represent another potentially effective, indirect strategy for the treatment of cocaine abuse.

GABAergic blockade of cocaine-associated cue-induced increases in nucleus accumbens dopamine.

Environments previously associated with drug use can become one of the most common factors triggering relapse to drug-seeking behavior. To better understand the neurochemical mechanisms potentially mediating these cues, we measured nucleus accumbens dopamine levels in animals exposed to environmental cues previously paired with cocaine administration. In animals exposed to a cocaine-paired environment nucleus accumbens dopamine increased by 25%. When administered 2.5 h prior to presentation of the environmental trigger, racemic vigabatrin (an irreversible inhibitor of gamma-aminobutyric acid (GABA)-transaminase) abolished this cue-induced increase. Conversely, R-(-)-vigabatrin, the inactive enantiomer, had no effect. Combined with our earlier findings, these studies support the potential therapeutic benefit of this enzyme-based GABAergic strategy to modulate brain dopamine and the subsequent treatment of drug addiction.

Stereoselective inhibition of dopaminergic activity by gamma vinyl-GABA following a nicotine or cocaine challenge: a PET/microdialysis study.

Elevation of endogenous GABA by the racemic mixture of gamma vinyl-GABA (GVG, Vigabatrin) decreases extracellular nucleus accumbens (NAc) dopamine (DA) levels and diminishes the response to many drugs of abuse known to elevate DA in the mesocorticolimbic system. We investigated the effects of the individual enantiomers (S(+)-GVG, R(-)-GVG) on cocaine-induced NAc DA in rodents as well as the effects of nicotine-induced increases in primates. In a series of microdialysis experiments in freely moving animals, S(+)-GVG (150 mg/kg), R(-)-GVG (150 mg/kg) or racemic (R, S) GVG (300 mg/kg) was administered 2.5 hours prior to cocaine (20 mg/kg) administration. When compared with cocaine alone, the R(-) enantiomer did not significantly inhibit cocaine induced NAc DA release. S(+)-GVG, at half the dose of the racemic mixture (150 mg/kg), inhibited cocaine-induced DA elevation by 40%, while the racemic mixture (300 mg/kg) inhibited cocaine-induced DA release by 31%. In addition, our PET studies in primates demonstrated that S(+)-GVG completely inhibits nicotine-induced increases in the corpus striatum, again at half the dose of the racemic mixture. The R(-) enantiomer was ineffective. Although the S(+) enantiomer has been well established as the active compound in the treatment of epilepsy, the efficacy of this enantiomer with regard to mesolimbic DA inhibition generates a complex series of clinical and neurochemical issues. Further investigations will determine the locus of action and physiologic properties of each enantiomer.

Study of brain uptake and biodistribution of [11C]toluene in non-human primates and mice.

Inhalant abuse is a rapidly growing health problem particularly among adolescents. Yet we know little about the neural mechanisms underlying the abuse liability of inhalants, particularly when compared to other addictive drugs. Specifically, our understanding of the relationship between the regional brain phamacokinetics and features classically associated with drug reinforcement is lacking. Under the hypothesis that the abuse liability of toluene can be related to its pharmacokinetic properties and the pattern of regional brain uptake, we developed the methodology for radiolabeling and purifying [11C]toluene for use in PET studies. Here we report the regional brain distribution and kinetics of the widely abused solvent toluene in non-human primates and the whole body biodistribution in mice. To our knowledge, this is the first reported study of the in vivo brain pharmacokinetics of labeled toluene in non-human primates. Rapid uptake of radioactivity into striatal and frontal regions was followed by rapid clearance from the brain. Concurrent findings in rodents indicate similar radio-tracer kinetics, with excretion through kidneys and liver. Taken together, our data provides insight into pharmacokinetic features possibly associated with the abuse liability of toluene.

Task-specific deactivation patterns in functional magnetic resonance imaging.

In general, image analysis of cognitive experiments using functional magnetic resonance imaging techniques has emphasized those regions of the brain where increases in signal intensity, with regard to the reference state, are associated with activation. Nevertheless, a number of recent papers have shown that there are areas of deactivation as well. In this study, we have used a univariate analysis and echo-planar functional magnetic resonance imaging to address the relationship of the reference state to the deactivations. We employed two dichotomous covert tasks, orthographic lexical retrieval and pure visual retrieval, to contrast with the reference state (baseline) of silent counting. Our analysis yielded extensive, task-specific landscapes of regional incremental and decremental responses. We have specifically demonstrated that the decremental responses are not due to activation in the reference state. We have also demonstrated that they are not an artifact of a specific part of the image analysis, and propose that they represent a physiological, task specific signal that should be considered an integral component of neural networks representing brain function.

[Squatting cast for biomechanical treatment of decentred hip joints]. / Sitz-Hock-Gips zur biomechanischen Behandlung dezentrierter Hüftgelenke.

The so-called "congenital" luxation of the hip joint is endemic in Central Europe and occurs in about 1% of all newborn infants. By the means of ultrasonographic diagnosis according to the Graf method an early detection instantly after birth has become a good clinical routine in the German-speaking countries. Sonography-based conservative treatment has become the gold standard. The cast in squatting ("human") position is a standard procedure in order to retain the originally decentred or unstable hip joints in the reduced position: 100° flexion and 50° abduction are necessary to fix the hip joint in the reduced position without the risk of avascular necrosis. After the fixation in a squatting-cast, a period of functional bracing in flexed position enhances bony maturation. This two-phase functional conservative treatment can avoid later osteotomies or even early total hip replacement.

Therapeutic doses of amphetamine or methylphenidate differentially increase synaptic and extracellular dopamine.

Methylphenidate (MP) and amphetamine (AMP) are first-line treatments for attention-deficit hyperactivity disorder. Although both drugs have similar therapeutic potencies, the stimulatory effect of AMP on extracellular dopamine (ECF DA) is greater than that of MP. We compared extracellular effects directly against synaptic changes. ECF DA was assessed by microdialysis in freely moving rodents and synaptic dopamine (DA) was measured using PET and [11C]-raclopride displacement in rodents and baboons. Microdialysis data demonstrated that MP (5.0 mg/kg, i.p.) increased ECF DA 360% +/- 31% in striatum, which was significantly less than that by AMP (2.5 mg/kg, i.p.; 1398% +/- 272%). This fourfold difference was not reflected by changes in synaptic DA. In fact, rodent PET studies showed no difference in striatal [11C]-raclopride binding induced by AMP (2.5 mg/kg, i.p.; 25% +/- 4% reduction) compared with that by MP (5.0 mg/kg, i.p.; 21% +/- 4% reduction). Primate PET experiments also showed no differences between AMP (0.5 mg/kg, i.v.; 24% +/- 4% reduction) and MP (1.0 mg/kg, i.v.; 25% +/- 7% reduction) induced changes in [11C]-raclopride binding potential. The similar potencies of MP and AMP to alter synaptic DA, despite their different potencies in raising ECF DA, could reflect their different molecular mechanisms.

[Ultrasound examination of the shoulder joint]. / Die sonographische Untersuchung des Schultergelenkes.

The ultrasound examination of the shoulder is an effective, quick and painless diagnostic method. The skilled examiner has no problem to detect rotator cuff tears, bursitis, tendinitis and instabilities as well as arthrosis or hematoma of the acromioclavicular joint and biceps tendon rupture. In the literature the sensitivity of ultrasound examination of the shoulder depended from 91 to 100% and specificity from 83 to 100%. The dynamic examination gives a special view of gliding tendons, muscles and bony landmarks of the shoulder. With standardized pictures the orthopedic surgeon should be able to diagnose and document almost every shoulder soft tissue pathology.

[Studies on the degree of hypoxic and pharmacological coronary dilation (author's transl)]. / Untersuchungen zur Grösse der hypoxischen und pharmakologischen Coronardilation

On 11 isolated dog hearts, perfused with arterial blood of a donor dog, the degree of hypoxic dilatation and the maximum coronary blood flow achieved by adenosine were compared. The maximum coronary blood flow under adenosine infusion amounted to 455ml/minx100g, that means an increase of about 600% of the normal flow. If coronary venous pO2 was below 5mm Hg coronary blood flow was increased to 420ml/minx100g, which is 93% of the pharmacologically achieved maximum increase of the coronary blood flow. The difference between the maximum hypoxic and the maximum pharmacological dilatation is due to the method; it is caused by an increase of the extravascular component of coronary resistance under the influence of catecholamines in the case of hypoxic dilatation. It is pointed out that in order to achieve a maximum hypoxic dilatation oxygen pressure has to be below the critical value. It can be concluded that the intravascular component of coronary resistance is as low under hypoxic as under pharmacological dilatation.

[The effect of increased extracellular calcium concentration on the hypoxic and pharmacologic hyperemia of skeletal muscle]. / Der Einfluss erhöhter extrazellulärer Kalziumkonzentrationen auf die hypoxische und pharmakologische Mehrdurchblutung des Skelettmuskels

The influence of an increased Ca concentration on reactive hyperemia, work induced vasodilation and pharmacologically induced dilation (adenosine, nifedipine, verapamil) was studied in the blood perfused gastrocnemius of dogs. Reactive hyperemia, work induced vasodilation and increased blood flow by administration of adenosine could not be influenced by increased extracellular Ca concentrations. A Ca antagonism was demonstrated for nifedipine and verapamil, especially with regard to a diminution of the drug eff.

Synergistic interactions between nicotine and cocaine or methylphenidate depend on the dose of dopamine transporter inhibitor.

There is a greater prevalence of cigarette smoking among cocaine-dependent individuals and hyperactive children treated with stimulants (e.g., methylphenidate, MP). However, little is known about the neurochemical basis of the interaction between nicotine and cocaine or MP. It is thought that the reinforcing effects of cocaine and MP are due partly to increases in synaptic DA in the nucleus accumbens (NAc). These measurable increases are secondary to the blockade of the DA transporter. In contrast, nicotine stimulates acetylcholine receptors located presynaptically on dopaminergic projections from the ventral tegmental area (VTA) to the NAc and increases DA transmission. Here we investigate the effects of nicotine on NAc DA in animals simultaneously injected with cocaine or MP. Coadministration of nicotine (0.4 mg/kg s.c.) and cocaine (10 mg/kg i.p.) or MP (5 mg/kg i.p.) increased the extracellular NAc DA levels in an additive manner, while coadministration of nicotine (0. 4 mg/kg s.c.) and a higher dose of cocaine (20 mg/kg) or MP (10 mg/kg) clearly produced a synergistic elevation in NAc DA. These findings suggest that the degree of DA transporter (DAT) occupancy contributes to the synergistic interaction between nicotine and cocaine or MP.