An acute pain service improves postoperative pain management for children undergoing selective dorsal rhizotomy

Background: A continuous epidural infusion of morphine is the pain treatment modality for children undergoing selective dorsal rhizotomy (SDR) in our institution. The aim of the study was to evaluate the impact of having an organized acute pain service (APS) on postoperative pain management of these children. Methods: We conducted a retrospective cohort study using anesthetic records and the APS database to compare the postoperative pain management of children undergoing SDR before and after the introduction of the APS at the Montreal Children’s Hospital in April 2001. Ninety‐two consecutive children who had their surgery between January 1997 and July 2006 were included. We collected data regarding postoperative pain, opioid‐induced side effects, complications (sedation, desaturations < 92%), and hospital length of stay. Results: Pain scores were documented more frequently after the implementation of the APS (61% vs 48.5%). Sedation scores were documented only after the implementation of the APS. Postoperative desaturation was significantly more frequent in the pre‐APS group compared to the APS group (45.5% vs 6.8%, P < 0.001). Despite the fact that the epidural catheter was in place for the same duration for both groups [median of 3 days (3–3 25–75%ile)], the duration of hospitalization was 1 day shorter in the APS group compared to the pre‐APS group [median of 5 (5–5 25–75%ile) vs 6 (5–6 25–75%ile) days, P < 0.001]. Conclusions: Although we recognize that it is possible that there were changes in care not related specifically to the introduction of a dedicated APS that occurred in our institution that resulted in improvements in general postoperative care and in length of stay, our study did show that having an organized APS allowed to significantly decrease the incidence of postoperative oxygen desaturation and to decrease the hospital length of stay by 1 day.     

Week-Long High-Maintenance Dose Clopidogrel Regimen Achieves Better Platelet Aggregation Inhibition than a Standard Loading Dose before Percutaneous Coronary Intervention: Results of a Double-Blind, Randomized Clinical Trial

Background: Adequate platelet inhibition before percutaneous coronary intervention (PCI) reduces periprocedural and long-term ischemic complications. Reduced response to clopidogrel has been associated with subsequent major adverse cardiovascular events. Strategies to optimize platelet inhibition pre-PCI are under investigation. This study evaluated the effect on platelet aggregation of four different dosing regimens of clopidogrel given before elective PCI in a randomized, prospective, double-blind, and placebo-controlled design.
Methods: One hundred twenty participants were randomized to one of four groups of clopidogrel: (a) 300 mg on the day prior to angiography; (b) 600 mg on the day prior to angiography; (c) 300 mg followed by 75 mg daily started 1 week prior to angiography; and (d) 300 mg followed by 150 mg daily started 1 week prior to angiography. Platelet aggregation was assessed by light transmission aggregometry (LTA) after stimulation with adenosine diphosphate 20 μM at baseline and at the time of diagnostic coronary angiography. The absolute change in platelet aggregation between these two time points was considered the main outcome measure.
Results: At the time of diagnostic coronary angiography, the 300-mg/150-mg daily regimen achieved the greatest decrease in platelet aggregation (37 ± 19%), while the 300 mg regimen provided the smallest (20 ± 22%), an absolute difference between the two groups of 17.2 ± 5.1% (P = 0.005).
Conclusions: A 300-mg loading dose of clopidogrel followed by 150 mg daily for 1 week prior to coronary angiography provides more effective platelet inhibition, as defined by LTA, compared to the standard 300-mg loading dose regimen at the time of coronary intervention.     

VJ REARRANGEMENTS OF THE TCRγ LOCUS IN PERIPHERAL T-CELL LYMPHOMAS: ANALYSIS BY POLYMERASE CHAIN REACTION AND DENATURING GRADIENT GEL ELECTROPHORESIS

Using Southern blotting for the diagnosis of clonality in peripheral T-cell lymphomas (PTCLs), analysis of the T-cell receptor (TCR) γ gene rearrangement was shown to be more informative than that of the TCR β gene rearrangement. In order to amplify every VJγ rearrangement, a polymerase chain reaction (PCR) procedure using newly designed GC-clamp primers has been developed. All primers can be mixed in a single multiplex PCR. PCR products are analysed by denaturing gradient gel electrophoresis (DGGE), providing tumour-specific imprints inasmuch as the procedure characterizes N sequence polymorphism at the VJ junctions. In a series of 30 PTCL cases, the PCR procedure demonstrated 27 cases to be clonally rearranged and failed in three cases. PCR was more accurate than Southern blotting, showing 47 rearranged γ alleles, four of which were undetectable on the Southern blot. When lymphomas were studied at different sites and at relapse, the DGGE pattern remained unchanged. In PTCL, the proposed PCR is helpful for the diagnosis and staging of the disease and should improve the follow-up monitoring. The undetectability of clonal rearrangements in a few cases is discussed in the light of concepts of lymphomagenesis and T-cell differentiation.     

A study of allergens in celery with cross-sensitivity to mugwort and birch pollens

Sixty-one sera with positive RAST to mugwort pollen ( Artemisiae vulgaris ) were submitted to RASTs for birch pollen ( Betula verrucosa) and celery ( Apium graveolens ). In 36 cases RAST results were positive for celery. In addition, 23 sera presented specific IgE to birch pollen. The binding of specific IgE to individual allergens in celery, mugwort pollen and birch pollen was studied by the immunoblotting technique. This involved electrophoretic separation of allergenic extracts, electrotransfer of proteins onto nitrocellulose sheets and sensitive immunoenzymatic detection. Eighteen sera had specific IgE binding to two celery components of molecular weight around 15 kD. All these sera also detected a 15 kD allergen in mugwort and two allergens in birch of 14 kD and 16 kD molecular weight. The sera that did not detect the 15 kD bands in celery failed to react with both the 15 kD mugwort component and the 14 and 16 kD birch components. Specific cross-inhibitions of the detection of these allergens on immunoblots were obtained by pre-incubation of the sera with crude extract of the three species. These results strongly suggest that such allergens display some structural identity and that they could be at the origin of some cases of crossed hypersensitivity to celery, mugwort pollen and birch pollen.     

Transformation of slow- or fast-twitch rabbit muscles after cross-reinne rvation or low frequency stimulation does not alter the in vitro properties of their satellite cells

We previously showed that satellite cells isolated from rabbit fast-twitch and slow-twitch muscles presented different behaviours in culture; cells from slow muscle differentiated more quickly and fused into more numerous myotubes than those from fast muscle. Moreover, only slow-muscle derived satellite cells expressed in vitro the slow type I myosin heavy chain isoform (MyHC). We wanted to investigate whether the properties of satellite cells originating from different muscles were under the influence of the adult fibre type on which they were located. For this purpose, we transformed the properties of the adult rabbit fast-twitch semimembranosus accessorius (SMa; ∼100% type II fibres) and the slow-twitch semimembranosus proprius (SMp; 100% type I fibre) muscles by (1) cross-reinnervating the SMp with the main branch of the fast SMa nerve; or (2) electrical stimulation at 10 Hz of the SMa muscle. We studied their satellite cells in vitro. Five-month cross-reinnervation of the SMp induced a large shift of its MyHC type characteristics towards those of a fast muscle, and three-month electrical stimulation at low frequency transformed the fast-twitch SMa into a slow-twitch muscle, as shown by SDS--PAGE of MyHC. In spite of the transformation of their muscle characteristics, satellite cells in culture kept their original properties. Indeed, as shown by MyoD and myogenin gene expression as markers of fusion, satellite cells isolated from cross-reinnervated and from control SMp began to fuse by eight days of culture, and expressed MyoD and myogenin at that stage. Later they differentiated into numerous myotubes. Satellite cells isolated from electrically stimulated and control SMa presented a similar behaviour in culture: they did not express MyoD and myogenin at eight days, and fused by ten days into only a few myotubes. Moreover, MyHC gene expression showed that, in contrast with slow-muscle derived satellite cells, the type I MyHC gene was not expressed by satellite cells isolated from the stimulated SMa in spite of its homogeneous type I fibre composition. Taken together, these data support the idea that once constituted, muscle fibre types per se do not influence the properties of their associated satellite cellsThis revised version was published online in July 2005 with corrections to the Cover Date.     

Anti-circumsporozoite protein antibodies measure age related exposure to malaria in Kataragama, Sri Lanka

Antibodies to two peptides DDAAD and (NANP)40 representing the repetitive sequence of circumsporozoite antigens (CS protein) of P. vivax and P. falciparum respectively were measured in a cohort of 149 and 107 individuals respectively at four, 6 monthly blood surveys performed on residents of Kataragama, a P. vivax malaria endemic region in southern Sri Lanka. The prevalence of antibodies to the CS protein of both species was relatively low being less than 20% to either peptide in the population as a whole, this being consistent with the low entomological inoculation rates in the area. A marked age related prevalence pattern was evident, with the prevalence of antibodies increasing with age to reach between 25 to 30% in the 25-50 year age group in both P. vivax and P. falciparum. The population had had a life long exposure to P. vivax malaria but not to P. falciparum, an epidemic of which occurred in this region a few months prior to the beginning of this study. Nevertheless, the age-related prevalence of these antibodies was identical with respect to the two species. This suggests that the age-related prevalence pattern reflected differences in inoculation rates between the age groups due to differences in exposure to inoculation rather than an age acquired response resulting from a cumulative experience over several years. An analysis of antibody prevalence in individuals showed first, that sporozoite inoculations must have been clustered rather than homogeneously distributed in the population and secondly, that sero-conversion did not correlate with malaria infections in these individuals.     

Involvement of NK1 and NK2 Receptors in Pulmonary Responses Elicited by Non-adrenergic,Non-cholinergic Vagal Stimulation in Guinea-pigs

Previous studies from our laboratory using exogenously administered neurokinin (NK) agonists have shown that both NK₁- and NK₂-receptor subtypes are involved in plasma extravasation in the guinea-pig airways. In the present study, we have extended these observations using antidromic vagal stimulation to stimulate sensory c-fibres as a means of eliciting the release of endogenous tachykinins in propranolol- and atropine-treated guinea-pigs. Antidromic vagal stimulation (5 ms, 30 s) induced frequency-dependent (1–10 Hz) bronchoconstriction that was completely abolished by co-administration of the NK₁-selective antagonist CP-99,994 ((2s-methoxy-benzyl)-(2-phenyl-piperidin-3s-yl)-amine), and the NK₂-selective antagonist SR-48,968 ((S)-N-methyl-N-[4-(4-acetylamino-4-phenyl piperidino)-2-(3,4-dichlorophenyl) butyl]benzamide), each at a dose sufficient to block NK₁ and NK₂ receptors, respectively (each at 0.3 mg kg^?1, i.v.). In contrast, SR-48,968 when given alone only partially blocked the vagal stimulation-induced bronchospasm, whereas CP-99,994 had no effect. Significant increases (2–3-fold) in plasma extravasation of [¹²⁵I]fibrinogen in the trachea, main bronchi, distal airways and oesophagus following vagal stimulation (5 Hz, 5 min, 10 V, 5 ms) were observed. Pretreatment with the neutral endopeptidase inhibitor, thiorphan (1 mg kg^?1, i.v.), and the angiotensin-converting enzyme inhibitor, enalapril (1 mg kg^?1, i.v.), potentiated both vagal stimulation-induced bronchoconstriction and plasma leakage in all tissues examined. This potentiation was due to reduced metabolism of endogenously released tachykinins since enhanced plasma overflow of immuno-reactive substance P was observed following vagal stimulation in thiorphan- and enalapril-treated guinea-pigs. CP-99,994 substantially blocked plasma leakage in all parts of the airways and in the oesophagus. In comparison, SR-48,968 had no significant effect in the trachea and the oesophagus but partially inhibited plasma leakage in the main bronchi and distal airways. Co-administration of both CP-99,994 and SR-48,968 abolished the residual plasma leakage in these two regions. These results support the hypothesis that both NK₁ and NK₂ receptors are involved in tachykinin-induced pulmonary responses in the airways.