SummaryFactor H (fH), a key alternative complement pathway regulator, is a cofactor for factor I-mediated cleavage of C3b. fH consists of 20 short consensus repeat (SCR) domains. Sialic acid binding domains have previously been localized to fH SCRs 6-10 and 13. To examine fH binding on a sialylated microbial surface, we grew Neisseria gonorrhoeae in the presence of 5 Ј -cytidinemonophospho-N -acetylneuraminic acid, which sialylates lipooligosaccharide and converts to serum resistance gonococci previously sensitive to nonimmune serum killing. fH domains necessary for binding sialylated gonococci were determined by incubating organisms with recombinant human fH (rH) and nine mutant rH molecules (deletions spanning the entire fH molecule). rH and all mutant rH molecules that contained SCRs 16-20 bound to the sialylated strain; no mutant molecule bound to serum-sensitive nonsialylated organisms. Sialic acid was demonstrated to be the fH target by flow cytometry that showed a fourfold increase in fH binding that was reversed by neuraminidase-mediated cleavage of sialic acid off gonococci. Functional specificity of fH was confirmed by decreased total C3 binding and almost complete conversion to iC3b on sialylated gonococci. Sialic acid can therefore bind fH uniquely through SCRs 16-20. This blocks complement pathway activation for N. gonorrhoeae at the level of C3.

T lymphocytes from a majority of patients with urogenital gonococcal disease (67%-80%) proliferated on incubation with gonococcal porin (Por), compared with minimal induced proliferation of T lymphocytes from normal volunteers. A significant increase in Por-specific interleukin (IL)-4-producing CD4+ T helper lymphocytes was seen in patients with mucosal gonococcal disease and not in normal controls. Similar results were observed in CD8+ T lymphocytes from these patients. There was no measured increase in IL-2, IL-10, IL-12, interferon-gamma, or tumor necrosis factor-alpha production by T lymphocytes from infected subjects on incubation with Por. Concomitant increases in IL-4 production in T lymphocytes from infected subjects expressing the mucosal addresin VLAalpha4/beta7 on their surface were also observed on Por incubation, but the increases were similar in T lymphocytes that were VLAalpha4/beta7 negative. In conclusion, mucosal gonococcal disease can induce Por-specific circulating T lymphocytes with a Th2 phenotype, and a portion of these Por-specific T lymphocytes can potentially traffic to mucosal surfaces.

Migraine is a common neurological disorder that is characterized by episodic headaches associated with symptoms such as nausea, visual disturbances, photophobia, and phonophobia. In Canada, approximately 7% of adult males and 22% of adult females suffer from migraine. 1 Migraine symptoms result in a considerable burden with regard to health care utilization, health care costs, and work/productivity loss due to disability and decreased functional status. [2][3][4][5][6] Clinical trials have demonstrated that sumatriptan (Imitrex®, GlaxoSmithKline) is effective in relieving migraine pain. These studies have established the efficacy of sumatriptan among patients who treated their migraines at a point in which their headache pain was classified as moderate or severe. 7-11 However, ABSTRACT: Background: There is evidence that headache response rates may be higher if triptans are used early when a migraine attack is still mild, as compared to when it is treated after pain has reached moderate or severe intensity. Methods: In this randomized, double blind, placebo controlled, parallel group clinical trial, 361 patients took either placebo, sumatriptan 50 mg, or sumatriptan 100 mg in a single attack study. The primary outcome measure was pain-free status at two hours. Results: In the intention to treat group, two hour pain free rates were 16%, 40%, and 50% in the placebo group, sumatriptan 50 mg group, and the sumatriptan 100 mg group respectively (p<0.001, active treatment groups vs. placebo). Conclusions: Both sumatriptan 50 mg and 100 mg were significantly superior to placebo for the pain-free end point at two hours. The pain-free response rates in this trial where sumatriptan was taken while the headache was still mild were generally higher than in older clinical trials where headache was treated after reaching a moderate or severe intensity. RÉSUMÉ: Absence de douleur comme mesure de l'efficacité du sumatriptan pour le traitement précoce de la migraine. Contexte: Le taux de réponse serait plus élevé si les triptans sont utilisés tôt au cours d'une crise de migraine alors que les symptômes sont légers plutôt que quand la douleur est devenue modérée ou sévère. Méthodes: Il s'agit d'une étude de pharmacologie clinique randomisée, à double insu, avec placebo et groupes parallèles. 361 patients ont pris soit le placebo, le sumatriptan 50 mg ou le sumatriptan 100 mg au cours d'une seule crise migraineuse. Le critère d'évaluation primaire était l'absence de douleur 2 heures après la prise du médicament. Résultats: À l'analyse selon l'intention de traitement, le taux de patients sans douleur était de 16%, 40% et 50% pour le groupe placebo, le groupe sumatriptan 50 mg et le groupe sumatriptan 100 mg respectivement (groupes traitement actif versus placebo, p > 0,001). Conclusions: Le sumatriptan 50 mg et 100 mg étaient significativement supérieurs au placebo quant au critère d'évaluation primaire, soit l'absence de douleur 2 heures après la prise du médicament. Le taux de réponse, soit l'absence de douleur, dans cette étude ...

Flupirtine maleate 100 mg was compared with dihydrocodeine 60 mg when given by mouth to 50 women on the first 3 days following abdominal hysterectomy in a double-blind parallel-group trial. The analgesia produced was similar for both preparations, and the consumption of active drug was the same in both groups. The only significant differences in side-effects were an increased frequency of depression in patients receiving flupirtine and of sleepiness in those receiving dihydrocodeine.

BackgroundThromboelastography (TEG) has been utilized for the guidance of blood component therapy (BCT). We aimed to investigate the association between emergent TEG-guided BCT and clinical outcomes in patients with traumatic abdominal solid organ (liver and/or spleen) injuries.MethodsA single center retrospective study of patients who sustained traumatic liver and/or spleen injuries receiving emergent BCT was conducted. TEG was ordered in all these patients. Patient demographics, general injury information, outcomes, BCT, and TEG parameters were analyzed and compared in patients receiving TEG-guided BCT versus those without.ResultsA total of 166 patients were enrolled, of whom 52% (86/166) received TEG-guided BCT. A mortality of 12% was noted among patients with TEG-guided BCT when compared with 19% of mortality in patients with non-TEG-guided BCT (P > 0.05). An average of 4 units of packed red blood cell (PRBC) was received in patients with TEG-guided BCT when compared to an average of 9 units of PRBC received in non-TEG-guided BCT patients (P < 0.01). A longer hospital length of stay (LOS, 19 ± 16 days) was found among non-TEG-guided BCT patients when compared to the TEG-guided BCT group (14 ± 12 days, P < 0.05). TEG-guided BCT showed as an independent factor associated with hospital LOS after other variables were adjusted (coefficiency: 5.44, 95% confidence interval: 0.69 - 10.18).ConclusionsTraumatic abdominal solid organ injury patients receiving blood transfusions might benefit from TEG-guided BCT as indicated by less blood products needed and less hospitalization stay among the cohort.

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