Periglacial fires and trees in a continental setting of Central Canada, Upper Pleistocene.

Fire is a key factor controlling global vegetation patterns and carbon cycling. It mostly occurs under warm periods during which fuel builds up with sufficient moisture, whereas such conditions stimulate fire ignition and spread. Biomass burning increased globally with warming periods since the last glacial era. Data confirming periglacial fires during glacial periods are very sparse because such climates are likely too cold to favour fires. Here, tree occurrence and fires during the Upper Pleistocene glacial periods in Central Canada are inferred from botanical identification and calibrated radiocarbon dates of charcoal fragments. Charcoal fragments were archived in sandy dunes of central Saskatchewan and were dated >50000-26600 cal BP. Fragments were mostly gymnosperms. Parallels between radiocarbon dates and GISP2-δ¹8O records deciphered relationships between fire and climate. Fires occurred either hundreds to thousands of years after Dansgaard-Oeschger (DO) interstadial warming events (i.e., the time needed to build enough fuel for fire ignition and spread) or at the onset of the DO event. The chronological uncertainties result from the dated material not precisely matching the fires and from the low residual ¹4C associated with old sample material. Dominance of high-pressure systems and low effective moisture during post-DO coolings likely triggered flammable periglacial ecosystems, while lower moisture and the relative abundance of fuel overshadowed lower temperatures for fire spread. Laurentide ice sheet (LIS) limits during DO events are difficult to assess in Central Canada due to sparse radiocarbon dates. Our radiocarbon data set constrains the extent of LIS. Central Saskatchewan was not covered by LIS throughout the Upper Pleistocene and was not a continental desert. Instead, our results suggest long-lasting periods where fluctuations of the northern tree limits and fires after interstadials occurred persistently.

Promising early outcomes with a novel, complete steroid avoidance immunosuppression protocol in pediatric renal transplantation.

BACKGROUND: Corticosteroids have been a cornerstone of immunosuppression for four decades despite their adverse side effects. Past attempts at steroid withdrawal in pediatric renal transplantation have had little success. This study tests the hypothesis that a complete steroid-free immunosuppressive protocol avoids steroid dependency for suppression of the immune response with its accompanying risk of acute rejection on steroid withdrawal. METHODS: An open labeled prospective study of complete steroid avoidance immunosuppressive protocol was undertaken in 10 unsensitized pediatric recipients (ages 5-21 years; mean 14.4 years) of first renal allografts. Steroids were substituted with extended daclizumab use, in combination with tacrolimus and mycophenolate mofetil. Protocol biopsies were performed in the steroid-free group at 0, 1, 3, 6, and 12 months posttransplantation. Clinical outcomes were compared to a steroid-based group of 37 matched historical controls. RESULTS: Graft and patient survival was 100% in both groups. Clinical acute rejection was absent in the steroid-free group at a mean follow-up time of 9 months (range 3-13.7 months). Protocol biopsies in the steroid-free group (includes 10 patients at 3 months, 7 at 6 months, and 4 at 12 months) revealed only two instances of mild (Banff 1A) subclinical rejection (reversed by only a nominal increase in immunosuppression) and no chronic rejection. At 6 months the steroid-free group had no hypertension requiring treatment (P=0.003), no hypercholesterolemia (P=0.007), and essentially no body disfigurement (P=0.0001). Serum creatinines, Schwartz GFR, and mean delta height Z scores trended better in the steroid-free group. In the steroid-free group, one patient had cytomegalovirus disease at 1 month and three had easily treated herpes simplex stomatitis, but with no significant increase in bacterial infections or rehospitalizations over the steroid-based group. The steroid-free group was more anemic early posttransplantation (P=0.004), suggesting an early role of steroids in erythrogenesis; erythropoietin use normalized hematocrits by 6 months. CONCLUSIONS: Complete steroid-free immunosuppression is efficacious and safe in this selected group of children with no early clinical acute rejection episodes. This protocol avoids the morbid side effects of steroids without increasing infection, and may play a future critical role in avoiding noncompliance, although optimizing renal function and growth.

Antidyskinetic effect of JL-18, a clozapine analog, in parkinsonian monkeys.

Clozapine reduces L-3,4-dihydroxyphenylalanine (L-Dopa)-induced dyskinesias in parkinsonian patients. To test if the antidyskinetic effect of clozapine is related to antagonism at the dopamine D(4) receptor, we investigated the effect of 8-methyl-6-(4-methyl-1-piperazinyl)-11H-pyrido[2,3-b][1, 4]benzodiazepine (JL-18), a structural analog of clozapine which is more selective for this receptor. Four 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP)-treated cynomolgus monkeys with a stable parkinsonian syndrome and reproducible dyskinesias to L-Dopa were used in this study. They were injected subcutaneously (s.c.) with L-Dopa methyl ester (125 mg per animal) plus benserazide (50 mg per animal; L-Dopa/benserazide) alone or in combination with JL-18 (at the doses of 0.1, 0.3, or 0.9 mg/kg, s.c.). Subcutaneous injection of sterile saline was used as control. L-Dopa/benserazide increased locomotion and improved parkinsonism but also induced dyskinesias. Co-administration of JL-18, at low doses (0.1, 0.3 mg/kg) with L-Dopa/benserazide, produced a dose-dependent reduction in L-Dopa-induced dyskinesias without a parallel return to parkinsonism. The present results suggest that novel selective dopamine D(4) receptor antagonists may represent a useful tool to reduce L-Dopa-induced dyskinesias.

[Rally-resources. The integration of community principles]. / Le rallye-ressources. L'intégration des principes communautaires.

PROBLEM BEING ADDRESSED: Family medicine training programs are required to teach the four principles of family medicine, two of which deal with community responsibilities. Teachers in the Family Practice Unit at the Centre hospitalier de Québec, pavillon St-François d'Assise (UMF-SFA) have developed a learning activity that introduces residents to community agencies in the area. OBJECTIVE OF PROGRAM: To introduce family medicine residents to community aspects of the principles of family medicine, to help them identify community resources in the area served by UMF-SFA, to discuss these services so that they can use them effectively, and to offer new residents an opportunity to become better acquainted with these services and with the UMF-SFA team. MAIN COMPONENTS OF PROGRAM: In early September, a half-day is set aside for a rally during which mixed teams of supervisors and residents (four to eight to a team) visit about 10 community agencies in the vicinity of UMF-SFA. Walking from place to place, the teams spend 15 to 20 minutes with staff or users of each agency. The informal tone of the rally makes it easier for residents to understand these agencies. CONCLUSION: Each year for the past 10 years, all UMF-SFA members have taken part in a rally that introduces residents to the community-based resources of family medicine.

Opioidergic and adrenergic modulation of formalin-evoked spinal c-fos mRNA expression and nocifensive behavior in the rat.

Fos protein expression has been used to reflect neuronal activation in pain processing pathways although analgesics may uncouple behavioral and Fos responses. We determine whether formalin-induced spinal c-fos mRNA expression (Northern blotting) correlates with nocifensive behavior following pretreatment with morphine, the alpha2-adrenoceptor agonist dexmedetomidine, or their respective antagonists naloxone and atipamezole. Both opiate and alpha2-adrenoceptor agonists reduced formalin-induced c-fos gene transcription and nocifensive behavior via their cognate receptors. Unexpectedly, blockade of either the opiate or alpha2-adrenergic receptors, alone, caused an increase in formalin-evoked c-fos mRNA; while blocking the opiate receptor had no effect on formalin-induced behavior, alpha2-adrenoceptor block had an analgesic effect, indicating discordance between c-fos message transcription and nocifensive behavior. We concluded that the formalin-induced spinal c-fos signal was a poor predictor of the behavioral response to pharmacological manipulation of pain processing pathways.