Adenosine A2A receptor gene expression in the normal striatum and after 6-OH-dopamine lesion

Summary. Adenosine A_2A receptors are present on enkephalinergic medium sized striatal neurons in the rat and have an important function in the modulation of striatal output. In order to establish more accurately whether adenosine transmission is a generalized phenomenon in mammalian striatum we compared the A_2A R expression in the mouse, rat, cat and human striatum. Secondly we compared the modulation of enkephalin gene expression and A_2A receptor gene expression in rat striatal neurons after 6-OH-dopamine lesion of the substantia nigra. Hybridization histochemistry was performed with a ³⁵S-labelled radioactive oligonucleotide probe. The results showed high expression of A_2A adenosine receptor genes only in the medium-sized cells of the striatum in all examined species. In the rat striatum, expression of A_2A receptors was not significantly altered after lesion of the dopaminergic pathways with 6-OH-dopamine even though enkephalin gene expression was up-regulated. The absence of a change in A_2A receptor gene expression after 6-OH-dopamine treatment speaks against a dependency on dopaminergic innervation. The maintained inhibitory function of A_2A R on motor activity in spite of dopamine depletion could be partly responsible for the depression of locomotor activity observed in basal ganglia disorders such as Parkinson's disease. Received May 10, 1999; accepted November 24, 1999     

Bedeutung der intraoperativ registrierten elektrischen Stapediusreflexschwelle für die Cochlear-implant-Anpassung bei Kindern

The programming of a cochlear implant speech processor used by young children is often difficult, especially when the stimulus level associated with maximum auditory loudness (MAL) needs to be determined. Excessively high stimulation should be avoided as this can have a traumatic effect. The aim of this study was to determine if a relationship exists between the intraoperatively determined electrical stapedius reflex threshold (ESRT) and the postoperatively determined MAL and hearing threshold for 27 patients, each having one of three implant types. The question of whether the ESRT provides a practical technique to simplify, improve and accelerate speech processor programming was investigated. For the monopolar stimulation mode used for the Med-El and Clarion implant systems, the average MAL and threshold was expressed as a percentage of the average ESRT across all electrodes. For the "common ground" stimulation mode used for the Nucleus implant system, a parabolic transformation was used to relate MAL and ESRT to one another. These transformations between MAL values calculated from the ESRT and the actual MAL values, determined psychoacoustically, diverged considerably from one another. Therefore, it was not possible to determine the MAL from the ESRT with certainty. The ESRT does, however, provide a means to estimate an approximate upper boundary for the MAL, apart from its use to control implant function. The determination of the exact MAL will still need to be determined using behavioural techniques.     

Secondary reconstruction of flexor tendon function in the fingers

Summary Among the various procedures to restore flexor tendon function after failed or omitted primary suture flexor tendon grafting is the most frequently applied technique. It can be performed in an one-stage procedure using a palmaris- or plantaris graft in cases with less scarring or in a two-stage procedure for cases in unsuitable conditions. The main purpose for using silicone rods is to prepare an artificial tendon sheath to avoid adhesions of the tendon graft. The disadvantage of two operations seems to be justified by better results. We performed this technique in 168 zone-II-lesions. According to the Buck-Gramcko score we achieved excellent results in 30,9 % and good results in 25,6 %. In 76 fingers we applied the combination of the Paneva-Holevich technique of using a pedicled superficialis tendon with Hunters method without obtaining better results (22,4 % and 32,9 % respectively). The various techniques of grafting are described as well as indication and technique of tenodesis and alternatively staged procedure for isolated profunda lesions.      

Secondary effects of femoral instrumentation on pulmonary physiology in a standardised sheep model: what is the effect of lung contusion and reaming?

Intramedullary nailing is the treatment of choice for patients with femoral shaft fractures. However, there is an ongoing debate in multiple trauma patients with associated lung contusion when primary or secondary definitive stabilisation of the long bone fracture should be performed, as nailing is thought to play an important role in the pathogenesis of adult respiratory distress syndrome (ARDS). In a standardised sheep model, this study aimed to quantify the development of acute pulmonary endothelial changes, to assess the activation of polymorphonuclear leucocytes (PMNL) and to observe the effects on the coagulation system associated with the reamed nailing procedure. Furthermore, the effect of coexisting lung contusion in an experimental model was evaluated. The animals were randomly assigned to one of four different groups (6 animals/group). In control groups, only a sham operation (thoracotomy) was performed, whereas in study groups, lung contusion was induced prior to femoral stabilisation either by external fixation or reamed femoral nailing. Using bronchoalveolar lavage (BAL) pulmonary permeability changes were quantified and PMNL activation was assessed by chemiluminescence. Additionally PMNL diapedesis and interstitial lung oedema were determined by histological analysis. All animals were sacrificed 4 h after the start of the femoral instrumentation. Without an associated lung injury, instrumentation of the femoral canal with the reamed nailing technique induced a transient increase in pulmonary permeability. In the face of an induced lung contusion, reamed femoral nailing resulted in significant increases in PMNL activation, pulmonary permeability and interstitial lung oedema, compared with external fixation. Without pulmonary contusion, reaming of the femoral canal was associated with a transient increase in pulmonary permeability. This was exacerbated in the presence of lung contusion along with increased PMNL activation. External fixation did not provoke similar changes. The findings of this study support the view that reaming of the femoral canal should be avoided in polytrauma patients with severe chest trauma as it could act as an additional stimulus for adverse outcome. Temporary external fixation appears to be a safe method for fracture stabilisation until inflammatory and coagulatory disturbances after trauma have been normalized.     

Adrenomyeloneuropathy

Summary Histopathological, immunocytochemical, and electron microscopical investigations were carried out in a man with a protracted history of spastic paraparesis, adrenal insufficiency and hypogonadism. Pathological findings were identical with those of the few previously reported cases of adrenomyeloneuropathy (AMN) including cytoplasmic lamellar inclusions consisting of two parallel 2.5 nm leaflets separated by a clear space of variable extent, in the brain, spinal roots, adrenal gland, and interstitial cells of the testis. No inclusions could be found in oligodendrocytes. In brain macrophages they are thought to represent breakdown products of pathological myelin stored in lysosomes, whereas in other localizations they might be an expression of the primary metabolic defect of the cell.Special attention was paid to the pseudosystematic type of fiber tract degeneration in the spinal cord. The dying-back pattern of axonal destruction was interpreted as a possible result of the multisegmental demyelination observed in these tracts.All known hormones could be localized in the pituitary by immunocytochemistry. Corticotrophs and gonadotrophs were numerous. The structural damage of the adrenal cortex and the interstitial cells of the testis is, therefore, considered to result from the inborn error of metabolism on the one hand and from an enhanced stimulation exerted by ACTH and gonadotrophins on the other.This work was supported in part by Grant No. 3.419.78 of the Swiss National Science Fundation     

Otoacoustic emissions and extended high-frequency hearing sensitivity in young adults

The relationship between hearing sensitivity in the extended high-frequency region (8-16 kHz) and (1) the presence of synchronized spontaneous otoacoustic emissions (SSOAEs) and (2) the strength of click-evoked and distortion product otoacoustic emissions (CEOAEs and DPOAEs) was investigated in 104 ears of 57 young adults. The age range was confined to 16 to 19 years. All subjects had normal hearing in the conventional audiometric frequency range (0.5-8 kHz). Ears with detected SSOAEs had better hearing sensitivity in the extended high-frequency region and also higher levels of CEOAEs and DPOAEs than ears with undetected SSOAEs. The results support the hypothesis that the presence of SSOAEs is indicative of an ear with highly normal cochlear function over a broad frequency range.     

C5a negatively regulates toll-like receptor 4-induced immune responses

The complement system and the Toll-like receptors (TLRs) are two central arms of innate immunity that are critical to host defense as well as the development of adaptive immunity. Most pathogens activate both complement and TLRs, suggesting the potential for crosstalk between the two systems. We show here that the complement-derived C5a anaphylatoxin negatively regulates TLR4- and CD40-induced synthesis of IL-12 family cytokines (IL-12, IL-23, and IL-27) from inflammatory macrophages (M phi s) by extracellular signal-regulated kinase- and phosphoinositide 3 kinase-dependent pathways. This decreased cytokine response translates into a decreased T helper type 1 (Th1) response in vitro and in vivo. Accordingly, we found enhanced Th1 immunity in C5a receptor-deficient mice, something that conferred protection from Leishmania major infection. Our findings identify the negative impact of C5a on IL-12 family cytokines as an important mechanism for regulating Th1 polarization in response to innate and adaptive immune network activation.