Standardized counting of circulating platelet microparticles using currently available flow cytometers and scatter-based triggering: Forward or side scatter?

Clinical determination of MP counts using flow cytometry has not been fully accepted yet due to the lack of standardization protocols. In the past 5 years, we have proposed two versions of a method with reproducible PMP counts in plasma samples. Both methods use forward scatter (FSC)-based threshold set with reference beads of appropriate sizes; first using 0.5 µm beads and later with 0.3 µm beads. Both systems provide reproducible PMP counts. However, this technique works only with some of currently used commercial flow cytometers. Instruments with limited resolution or generating heterogeneous FSC signals are excluded. Such performances are incompatible with the required interinstrument standardization. Here we show that (i) flow cytometers with sub-optimal FSC capabilities generally have higher SSC resolution and background rejection capacity, and (ii) that the same biological entities, "dim and bright PMP," both can be counted using alternative strategies, either as previously described, based on FSC measurements, or as presented here, based on SSC detection. The critical element in the standardization protocol is the use of different sizes of reference beads. This study was designed to permit simultaneous access to both FSC- and SSC-optimized platforms. A new range of about 0.17-0.6 µm eq. (µm-equivalents) is proposed for an alternative SSC-based MP gate generating the same PMP counts as those obtained in the previously proposed 0.3-1 µm eq. FSC-based MP gate. The two equivalent standardization options reconcile intrinsically different scattering behaviors between SSC- and FCS--triggered instruments and open the opportunity for multicenter studies in the future.

Influence of levothyroxine in augmentation therapy for bipolar depression on central serotonergic function.

INTRODUCTION: Adjunctive treatment with supraphysiological doses of levothyroxine (L-T4) in bipolar depression shows promise, but the neurobiological mechanisms underlying clinical improvement are unknown. It has been postulated from animal studies that exogenous thyroid hormones may exert their modulatory effects in patients with affective disorders via an increase in serotonergic neurotransmission. Therefore, we investigated the loudness dependence of auditory evoked potentials (LDAEP) as a measure of central serotonergic activity and response to L-T4. METHODS: This 6-week, double-blind, randomized, placebo-controlled study assessed the efficacy of L-T4 adjunctive to continuing treatment with mood stabilizer and/or antidepressant medication in 20 patients with bipolar depression. LDAEP was assessed before and after treatment with L-T4. RESULTS: Scores of the Hamilton Depression Rating Scale and Montgomery Asberg Depression Rating Scale decreased significantly during the study. There was no difference in pre- and post-treatment LDAEP between the groups, and no correlation between LDAEP and psychometric measures in the course of the study. DISCUSSION: The hypothesis of a relationship between response of augmentation therapy with levothyroxine in bipolar depression and serotonergic activity could not be confirmed.

Opiate maintenance with buprenorphine in ambulatory care: a 24-week follow-up study of new users.

BACKGROUND: Many studies suggest that buprenorphine, a long acting partial opioid agonist, may be comparable to methadone in efficacy, with fewer withdrawal symptoms and a lower risk of overdose. The aim of this study was to assess the patterns of buprenorphine prescription use in ambulatory care and retention rate under treatment during a 24-week follow-up period. METHODS: This observational cohort study included buprenorphine users identified from the French Health System prescription database in an area of 1 million inhabitants and followed for 24 weeks. RESULTS: We selected 282 users of buprenorphine defined as "new users" (74% male, mean age 32.4+/-6.2 years). Three groups were defined: 50% of "rational users" (141 subjects, no more than 2 prescribers), 24% of "occasional users" (67 subjects, less than 2 buprenorphine prescriptions) and 26% of "non-rational users" (74 subjects, 3 or more prescribers). The overall 24-week treatment retention rate was 37%. Misuse of buprenorphine or benzodiazepines was significantly more frequent in "non-rational" than "rational users". CONCLUSION: The retention rate with buprenorphine estimated in this observational study was very similar to that obtained in controlled trials. A majority of regular users of buprenorphine could be regarded as "rational users" in this area of France.