A requirement of serotonergic p38α mitogen-activated protein kinase for peripheral immune system activation of CNS serotonin uptake and serotonin-linked behaviors.

Alterations in central serotonin (5-hydroxytryptamine, 5-HT) neurotransmission and peripheral immune activation have been linked to multiple neuropsychiatric disorders, including depression, schizophrenia and autism. The antidepressant-sensitive 5-HT transporter (SERT, SLC6A4), a critical determinant of synaptic 5-HT inactivation, can be regulated by pro-inflammatory cytokine signaling. Systemic innate immune system activation via intraperitoneal lipopolysaccharide (LPS) injection rapidly elevates brain SERT activity and 5-HT clearance. Moreover, the pro-inflammatory cytokine interleukin (IL)-1ß rapidly stimulates SERT activity in raphe nerve terminal preparations ex vivo, effects that are attenuated by pharmacological p38 MAPK inhibition. To establish a role of serotonergic p38α MAPK signaling in LPS/IL-1ß-induced SERT regulation and attendant behavioral responses, we pursued studies in mice that afford conditional elimination of p38α MAPK in 5-HT neurons (p38α(5HT-)). We found p38α(5HT-) and control (p38α(5HT+)) littermates to be indistinguishable in viability and growth and to express equivalent levels of SERT protein and synaptosomal 5-HT transport activity. Consistent with pharmacological studies, however, IL-1ß fails to increase SERT activity in midbrain synaptosomes prepared from p38α(5HT-) animals. Moreover, although LPS elevated plasma corticosterone and central/peripheral pro-inflammatory cytokines in p38α(5HT-) animals, elevations in midbrain SERT activity were absent nor were changes in depressive and anxiety-like behaviors observed. Our studies support an obligate role of p38α MAPK signaling in 5-HT neurons for the translation of immune activation to SERT regulation and 5-HT-modulated behaviors.

Jugular bulb oxyhemoglobin desaturation, S100beta, and neurologic and cognitive outcomes after coronary artery surgery.

UNLABELLED: We reported that a decline in cognitive performance 3 mo after coronary artery bypass grafting surgery is associated with palpable aortic atheroma, but not postoperative jugular bulb oxyhemoglobin saturation (SjO2) <50%. However, the effect of SjO2 on clinical neurologic findings is not known. S100beta is a possible surrogate biochemical marker of brain injury, and we report here the scored clinical neurologic findings in 98 patients from our previous study in relation to SjO2, cognitive performance, aortic atheroma, and S100beta. Patients underwent a scored neurologic examination and cognitive assessment the day before and 3 mo after coronary artery bypass grafting surgery. Intraoperatively, intermittent blood sampling was performed, and postoperatively, the area under the curve describing SjO2 <50% in relation to time was calculated from continuous jugular bulb reflectance oximetry. Palpation was used to assess the ascending aorta for the presence of atheroma. The jugular bulb concentration of S100beta was measured 6 h after completion of surgery. The neurologic score 3 mo after surgery did not correlate with either intra- or postoperative SjO2 (r = 0.111, P = 0.278; and r = -0.074, P = 0.467, respectively). The main determinant of neurologic score at 3 mo was the preoperative neurologic score (r(2) = 0.63, P < 0.001), whereas palpable atheroma of the ascending aorta made a small but significant contribution (r(2) = 0.034, P = 0.004). Neurologic and cognitive scores correlated before surgery (r = 0.226, P = 0.022) and at 3 mo after surgery (r = 0.348, P < 0.001). A preoperative neurologic deficit of two or more had a small but significant negative effect on cognitive performance at 3 mo (standardized beta = -0.097, P = 0.018). There was a significant univariate correlation between S100beta and the 3-mo neurologic score (r = -0.232, P < 0.05), but not a multivariate correlation (beta = -0.090, P = 0.156). IMPLICATIONS: Intraoperative jugular bulb oxyhemoglobin saturation (SjO2) and postoperative SjO2 <50% do not have an important influence on long-term neurologic outcome after coronary artery bypass graft surgery. Subtle preoperative neurology is associated with long-term cognitive decline, and aortic atheroma is a risk factor for both cognitive and neurologic decline.

Pigmented villonodular synovitis of lumbar facet joint: a rare cause of nerve root entrapment.

STUDY DESIGN: A case report of nerve root entrapment due to pigmented villonodular synovitis of lumbar facet joint is reported for which excision was performed. OBJECTIVE: To report a rare cause for nerve root claudication. SUMMARY OF BACKGROUND DATA: Pigmented villonodular synovitis is an uncommon synovial abnormality with an estimated incidence of 1.8 cases per million. Large joints, such as knee and hip, are commonly affected. Involvement of the facet joint is very rare. In our case a high index of suspicion from CT and MRI helped us in the appropriate management. METHODS: A 71-year-old man presented with severe back pain and right-sided L5 sciatica. CT and MRI scans showed a cystic lesion arising from the L5-S1 facet joint. Excision and adequate decompression in the form of undercutting facetectomy were done. RESULTS: The patient had symptomatic improvement with surgery, and at the 3-year follow-up he showed no signs of recurrence. CONCLUSION: Unless pigmented villonodular synovitis is considered in the differential diagnosis of tumors of the vertebral column causing nerve root claudication, it may be overlooked.

Cognition after coronary artery surgery is not related to postoperative jugular bulb oxyhemoglobin desaturation.

During the early postoperative period after coronary artery bypass grafting (CABG) surgery, many patients experience jugular bulb oxyhemoglobin desaturation (SjO(2) < 50%). We sought to determine whether SjO(2) during cardiopulmonary bypass and the early postoperative period influenced long-term cognitive performance after CABG surgery. One hundred two patients completed a battery of cognitive tests the day before and 3 mo after CABG surgery. A General Cognitive Score was generated from these tests as an overall measure of cognitive function. Intraoperatively, SjO(2) was determined by intermittent blood sampling, and postoperatively, the area under the curve of SjO(2) < 50% and time was calculated from continuous reflectance oximetry. No significant correlations between cognitive performance and either intra- or postoperative SjO(2) were found. Preoperative cognitive performance was the main determinant of cognition at 3 mo (r(2) = 0.83, P<0.001), and palpable atheroma of the ascending aorta made a small, but significant, contribution to a decline in cognition (r(2) = 0.018, P = 0.001).

Hydroxyapatite-coated hip prostheses: difficulties with revision in 4 cases.

The introduction of hydroxyapatite ceramic (HAC) coating on hip implants in 1985 (Furlong and Osborn 1991) was hailed as a major advancement for fixation of uncemented protheses. A problem that is now becoming evident is the extraction of these securely fixed prostheses for purposes of revision. We report on 4 patients who have had HAC-coated protheses implanted (2 as revision procedures and 2 at primary hip replacement) who had either continuing pain or a proven infection, so that it became necessary to carry out a revision hip arthroplasty. The prostheses were well-fixed and difficult to remove. A transfemoral, longitudinal osteotomy was used in 3 cases.

Ultrasound guided aspiration of symptomatic supraspinatus calcific deposits.

11 consecutive patients with shoulder pain were referred from the shoulder clinic for plain radiography. Supraspinatus calcific deposits were suspected after other causes of shoulder pain had been eliminated by clinical examination and local anaesthetic tests. Radiographs confirmed calcific deposits in all 11 shoulders and all deposits were shown by ultrasound to be lying in the supraspinatus tendon. Using a free-hand ultrasound guidance technique, a 19 G needle was passed percutaneously into all 11 shoulders in an attempt to aspirate the deposit. Six patients experienced immediate pain relief or relief on the same day, whilst four others were pain free at the 2 weeks follow-up clinic. One patient who was though to have a co-existing supraspinatus tear diagnosed by the scan was symptomatically unchanged.

Physiological integration in the clonal perennial herb Trifolium repens L.

Translocation of 14C-labelled carbohydrates between the parent stolon and branches, and among branches, of Trifolium repens plants was investigated in two glasshouse experiments to determine patterns of physiological organisation in this clonal species. Differential defoliation treatments were applied to the parent stolon and/or branches to test the sensitivity of translocation to the short-term carbon needs of defoliated sinks. Strong reciprocal exchange of carbohydrate between the parent stolon and branches was observed, with 18 41% of the 14C exported from leaves on the parent stolon moving to branches, while branches simulta-neously exported 25% (for old source branches) to 54% (for young source branches) of the 14C they assimilated to the parent plant, including translocation to other branches. Branch-to-branch translocation occurred both acropetally and basipetally. Parent-to-branch, branch-to-parent and branch-to-branch carbon fluxes all increased in response to defoliation of the sink, at the expense of carbon supply to stolon tissue or roots of the source module. Reduced export to stolon tissue of the parent axis played a major role in facilitating C reallocation from leaves on the parent stolon to defoliated branches. The observed patterns of C allocation and translocation could be adequately explained by accepted source-sink theory, and are consistent with a high degree of intra-plant physiological integration in resource supply and utilisation. This information provides mechanistic explanations for aspects of the growth dynamics and ecological interactions of T. repens in the patchy environment of a grazed pasture.

The physiological role of old stolon material in white clover (Trifolium repens L.).

Clonal plants of white clover (Trifolium repens L.), consisting of a single stolon plus roots and either three fully unfolded leaves or one fully unfolded leaf at the stolon apex, were grown in a controlled environment and sampled three times (after 7, 49 and 85 d growth) to examine the effects of increasing respiratory demand imposed by an increasing mass of old stolon material upon carbon allocation patterns and plant morphology. Where the total pool of available carbohydrate remained more-or-less constant over time, greater C allocation to stolon tissue was associated with reduced allocation to new leaf growth between d 7 and d 49. Rapid death of old stolon material began about d 70, perhaps as the result of withdrawal of C previously supplied to stolon tissue by leaves at the apex. Current assimilate no longer needed to maintain this old stolon material was, in part, reallocated to the apex region. Stolon death was greater when stolons were covered rather than fully illuminated, reflecting the elimination of direct CO2 assimilation by stolon tissue (estimated to be 12-22% as efficient as leaves in assimilating CO2 , on a surface area basis) and accentuation of the carbohydrate deficit. Respiration accounted for an estimated 32% of C fixed by leaves on d 85 when stolons were covered, compared to 25 % when stolons were fully illuminated. The relevance of these results to the seasonal changes in plant morphology in pastures, and the effects of stolon burial, are discussed.

The conformation of pyrethroids bound to lipid bilayers.

A number of pyrethroids have been synthesised containing bromine or iodine atoms in the acid and alcohol moieties. Quenching of the fluorescence of a pyrene-containing fatty acid in phospholipid bilayers has been used to measure the partitioning of the pyrethroids into the bilayers. Comparison of the intensity of the fluorescence of the 3-phenoxybenzyl moiety of the pyrethroids in lipid bilayers with that in organic solvents shows that the 3-phenoxybenzyl moiety is located in a hydrophobic environment; this was confirmed by fluorescence quenching by spin-labelled fatty acids. Self-quenching of the fluorescence of pyrethroids which contain both a bromine-containing acid and a 3-phenoxybenzyl moiety is consistent with a 'horseshoe' conformation for the bound pyrethroid, with the ester group located at the lipid/water interface and the acid and alcohol moieties folded back with both penetrating into the lipid bilayer.

Fluorescence and kinetic studies of the interactions of pyrethroids with the (Ca2(+) + Mg2+)-ATPase.

The fluorescence quenching properties of a series of brominated and iodinated pyrethroids have been used to study the binding of pyrethroids to the (Ca2(+) + Mg2+)-ATPase purified from skeletal muscle sarcoplasmic reticulum. It is suggested that binding at the lipid/protein interface of the ATPase is weak but that binding can occur at other (non-annular sites) on the ATPase. Pyrethroids containing either a brominated fatty acyl or iodinated alcohol moiety quench the tryptophan fluorescence of the ATPase, suggesting that the pyrethroids bound to the ATPase adopt a folded conformation with both the acid and alcohol moieties in contact with hydrophobic regions of the ATPase. Whereas effects of the pyrethroids on the activity of the ATPase in bilayers of dioleoylphosphatidylcholine are small, large increases are observed in the activity of the ATPase reconstituted into bilayers of the short-chain phospholipid, dimyristoleoylphosphatidylcholine (DMPC). The rate of phosphorylation of DMPC-ATPase by ATP is slow, but is increased on addition of pyrethroid. The level of phosphorylation of the ATPase by Pi is reduced on reconstitution into bilayers of DMPC, and this is also increased by addition of pyrethroid.

Social and psychological determinants of recovery from industrial injuries.

Social and psychological determinants of the time taken to return to work were investigated in a sample of male manual workers referred to an accident clinic with mostly minor industrial injuries. Patients who showed a rapid recovery relative to the severity of their injuries were more often married, had greater job satisfaction, were less likely to be receiving an income supplement from their employers, and blamed themselves more for their accidents. The findings also indicated that a poor recovery rate could be expected when the accident was due to some environmental fault or failure, and the implications for studies of compensation are discussed.

The treatment of fibrous non-union of fractures by pulsing electromagnetic stimulation.

Fifty-three ununited fractures with a median time since injury of 28 months were treated by electrical stimulation using pulsing electromagnetic fields. Union was achieved in 38 cases (71.7 per cent) in a median time of six months. For ununited fractures of the tibia the success rate was higher at 86.7 per cent. Previous or active sepsis, the presence of plates or nails, the age of the patient or the time since the injury did not affect the results. Analysis of the failures suggests that inadequate immobilisation, a fracture gap of more than five millimetres or the presence of a screw in the fracture gap was responsible. In four patients no cause of failure could be determined.

The pathophysiology of arthrogryposis multiplex congenita neurologica.

Eleven patients with arthrogryposis multiplex congenita neurologica have been reviewed. Distinct patterns of deformity and muscle activity were identified which have been correlated with specific levels of segmental neurological motor deficit without sensory loss. The clinical picture was consistent with localised lesions of the anterior horn cell cell columns. This finding agreed with the recorded pathological lesions. Orthopaedic treatment should take account of the paralytic nature of the deformities.

Cervical spondylolisthesis and other skeletal abnormalities in Rubinstein-Taybi syndrome.

A patient with Rubinstein-Taybi syndrome complicated by tetraplegia secondary to cervical spondylolisthesis is reported. The abnormalities presenting in this condition are reviewed.