Preoperative ultraviolet B inflammation in skin: Modelling individual differences in acute postoperative pain and neuro-immune interactions.

BACKGROUND: Neuroimmune interactions play a vital role in many of the most common pain conditions, such as arthritis. There have been many attempts to derive clinically predictive information from an individual's inflammatory response in order to gauge subsequent pain perception. OBJECTIVES: Here, we wanted to test whether this effort could be enhanced and complemented by the use of a model system which takes into account the function of not just circulating, but also tissue-resident immune cells: ultraviolet B (UVB) irradiation of the skin. METHODS: We conducted psychophysical and transcriptional analysis of hyperalgesia arising as a result of UVB-induced inflammation in patients before total knee arthroplasty (TKA, n = 23). Levels of acute postoperative pain were assessed and correlated with preoperative data. RESULTS: Cytokine and chemokine responses after UVB irradiation were found to be inversely correlated with the level of pain experienced after surgery (Spearman's ρ = -0.498). CONCLUSION: It may be possible to use this simple model to study and predict the nature of neuro-immune responses at more remote, clinically relevant sites. SIGNIFICANCE: A simple model of UVB inflammation in the skin might predict the degree of a patient's neuro-immune response and the extent of their postoperative pain after total knee arthroplasty.

[All-polyethylene tibial component in Walter-Motorlet total knee arthroplasty. Long-term outcomes]. / ALL-POlY standardní tibiální komponenta náhrady kolenního kloubu Walter-Motorlet v dlouhodobém hodnocení

PURPOSE OF THE STUDY: An analysis of long-term results of the all-polyethylene tibial component in Walter-Motorlet cemented condylar knee arthroplasty, with a standard tibial plateau (STP) of our own design. MATERIAL AND METHODS: A total of 49 patients underwent knee replacement; of them, 35 (71.4%) with 38 Walter-Motorlet implants using the STP were evaluated. The average age at the time of evaluation was 87.3 years. The follow-up ranged from 18 to 27 years (average, 24.6 years). Mechanical properties of the STP were tested by experimental measurements and in a photoelasticimetric study. The clinical results were evaluated according to the EULAR Knee Assessment Chart (EKACH). Twenty-four patients (26 knees; 49%) had osteoarthritis (OA) and 11 (12 knees; 23%) had rheumatoid arthritis (RA). Of the 14 (28.6%) patients not included in evaluation, seven (14.3%), with seven knees, required revision arthroplasty and seven (14.3%), with 10 knees, were lost to follow-up. RESULTS: Of the 38 implants evaluated by the EKACH at an average of 24.6 years, subjectively, 14 (36.8%) knees were free from pain and 14 (36.8%) were mildly painful. The remaining 10 (26.4%) joints were acutely painful on walking up or down the hill. In 14 (36.8%) cases the patients experienced their knees as stable. Light domestic chores were routinely performed by 17 patients (10 OA and 7 RA; 48.6%). One (2.9%) OA patient had a full-time job, and nine (25.7%) patients were socially independent. The functional outcome was significantly related to the patient's age at the time of evaluation. Complications included STP aseptic loosening in five (13.1%) and late infection in two (5.2%) knees. Radiography showed translucent zones below an all-polyethylene component in 14 (36.8%) knees. DISCUSSION The five cases of aseptic loosening may have been due to insufficient hardness of a U-shaped polyethylene component and long-term stress at the bone-implant interface. In the majority of knees the anterior cruciate ligament was defective or missing completely. Maintenance of the posterior cruciate ligament facilitates absorption of the greater part of forces at the cement-bone interface, as also reported by other authors. The high incidence of complications associated with patellar components, as described in the literature of the late 1970s and the early 1980s, led us to avoid the primary use of a patellar implant. CONCLUSIONS: Our evaluation showed that, in 73% of the cases, the all-polyethylene tibial component was a suitable and inexpensive implant with very good or good long-term results on average at 24.6 years of follow-up. Since the quality of currently produced polyethylene is high, we recommend the use of all-polyethylene tibial components in all indicated cases.

[Clinical evaluation of the ceramic femoral component used for reconstruction of total knee replacement]. / Klinické zhodnocení pouzití keramické femorální komponenty v konstrukci náhrady kolenního kloubu.

PURPOSE OF THE STUDY: The study evaluates mid-term results of total knee replacement with a zirconia ceramic (ZrO2) femoral component. MATERIAL: The evaluated group comprised 20 knees in 19 patients (4 men and 15 women). In one patient the replacement was performed bilaterally. Two patients had in the contralateral knee the same type of prosthesis with a femoral chrome-cobalt component.The mean age at the time of operation was 65.2 years (range, 38-81 years).The primary indication was 14 times osteoarthritis and 5 times rheumatoid arthritis. The average follow-up period was 6.5 years (range, 2.1-8.5 years). METHODS: Patients included in the study regardless of age, body mass and the basic diagnosis, agreed with the use of the ceramic femoral component. The evaluation covered a range of motion, mechanical axis, joint stability, pain, swelling, ability to walk on level ground and on stairs, subjective satisfaction (EULAR Knee Chart). Radiograph were assessed at one year intervals in two projections to identify the incidence of radiolucency around the implant. The Kaplan-Meier survival curve was used and compared with the survival curve in identical chrome-cobalt implants. RESULTS: At he final follow-up, 14 knees were evaluated, because 3 patients died without any connection with the implant, in one case the tibial component migrated due to necrosis of the tibial condyle in a patient with RA and two implants had to be revised and replaced due to polyethylene wear. No infection or negative tissue reaction was recorded in the evaluated group. The average flexion range was 109 degrees. All knees were stable and without swelling, in two cases there occurred slight femoropatellar pain. Twelve patients were fully satisfied, 2 patients were satisfied with a certain reservation. The differences in the course of the survival curves of chrome-cobalt and ceramic implants were statistically insignificant. DISCUSSION: Although the use of zirconia ceramics in vitro reduces the amount of polyethylene wear, the clinical outcomes of total knee replacements as compared to the hip are not convincing. One of the causes may be the substantially different and more complex biomechanics of the knee. Tribology improvement of the femoral ceramic component cannot compensate the deficiencies in the joint balancing in flexion and extension. The economically and technologically demanding production of these implants may be justified in patients with allergies caused by chrome-cobalt components. CONCLUSIONS: The results of mid-term follow-up of the use of zirconia ceramic femoral components proved no impact on the improvement of the period of survival of the knee implant. No adverse response to the material or mechanical failure of the ceramic components was encountered. Key words: total knee replacement, zirconia ceramic femoral component, TKR mid-term results, ceramic knee survival curve.

In vivo evidence that 5-HT(2C) receptors inhibit 5-HT neuronal activity via a GABAergic mechanism.

BACKGROUND AND PURPOSE: Recent evidence suggests that 5-HT(2C) receptor activation may inhibit midbrain 5-HT neurones by activating neighbouring GABA neurones. This hypothesis was tested using the putative selective 5-HT(2C) receptor agonist, WAY 161503. EXPERIMENTAL APPROACH: The effect of WAY 161503 on 5-HT cell firing in the dorsal raphe nucleus (DRN) was investigated in anaesthetised rats using single unit extracellular recordings. The effect of WAY 161503 on DRN GABA neurones was investigated using double label immunohistochemical measurements of Fos, glutamate decarboxylase (GAD) and 5-HT(2C) receptors. Finally, drug occupancy at 5-HT(2A) receptors was investigated using rat positron emission tomography and ex vivo binding studies with the 5-HT(2A) receptor radioligand [(11)C]MDL 100907. KEY RESULTS: WAY 161503 caused a dose-related inhibition of 5-HT cell firing which was reversed by the 5-HT(2) receptor antagonist ritanserin and the 5-HT(2C) receptor antagonist SB 242084 but not by the 5-HT(1A) receptor antagonist WAY 100635. SB 242084 pretreatment also prevented the response to WAY 161503. The blocking effects of SB 242084 likely involved 5-HT(2C) receptors because the drug did not demonstrate 5-HT(2A) receptor occupancy in vivo or ex vivo. The inhibition of 5-HT cell firing induced by WAY 161503 was partially reversed by the GABA(A) receptor antagonist picrotoxin. Also, WAY 161503 increased Fos expression in GAD positive DRN neurones and DRN GAD positive neurones expressed 5-HT(2C) receptor immunoreactivity. CONCLUSIONS AND IMPLICATIONS: These findings indicate that WAY 161503 inhibits 5-HT cell firing in the DRN in vivo, and support a mechanism involving 5-HT(2C) receptor-mediated activation of DRN GABA neurones.

Differential involvement of serotonin and dopamine systems in cost-benefit decisions about delay or effort.

RATIONALE: Although tasks assessing the role of dopamine in effort-reward decisions are similar to those concerned with the role of serotonin in impulsive choice in that both require analysis of the costs and benefits of possible actions, they have never been directly compared. OBJECTIVES: This study investigated the involvement of serotonin and dopamine in two cost-benefit paradigms, one in which the cost was delay and the other in which it was physical effort. METHODS: Sixteen rats were trained on a T-maze task in which they chose between high and low reward arms. In one version, the high reward arm was obstructed by a barrier, in the other, delivery of the high reward was delayed by 15 s. Serotonin and dopamine function were manipulated using systemic pCPA and haloperidol injections, respectively. RESULTS: Haloperidol-treated rats were less inclined either to exert more effort or to countenance a delay for a higher reward. pCPA had no effect on the performance of the rats on the effortful task, but significantly increased the rats' preference for an immediate but smaller reward. All animals (drug treated and controls) chose the high reward arm on the majority of trials when the delay or effort costs were matched in both high and low reward arms. CONCLUSION: A dissociation was found between the neurotransmitter systems involved in different types of cost-benefit decision making. While dopaminergic systems were required for decisions about both effort and delay, serotonergic systems were only needed for the latter.

[CNS-active pyrans: amine- and aryl- substituted dioxabicyclooctanes]. / ZNS-wirksame Pyrane: Amin- und arylsubstituierte Dioxabicyclooctane.

The amin- and phenyl substituted 6,8-dioxabicyclooctanes 10 and 11 show distinct CNS-activities. Intensity and profile depend on the type of amine and the stereochemistry of the products. Therefore, we have synthesized 6,8-dioxabicyclooctanes with different amine-phenyl distances and examined their CNS-activities on mice as well as by receptor binding studies with the PCP-binding site which is part of the NMDA-receptor-complex.

[Synthesis of CNS-activity of pyran derivatives: 6,8-dioxabicyclo(3,2,1)octane]. / Synthese und ZNS-Wirkung von Pyranderivaten: 6,8-Dioxabicyclo[3,2,1]octane.

The amino nitriles 4a,b and 5a,b, prepared from (1S,5R)-6,8-dioxabicyclo[3,2,1]octan-4-one (2), react with phenylmagnesium bromide to afford the diastereomeric 4-amino-4-phenyl derivatives 7a,b and 8a,b, respectively. The diastereomeric piperidine derivatives 7b and 8b show different CNS-activity.