Atypical Post-Injection Reactions with Delayed Onset Following Glatiramer Acetate 40 mg: Need for Titration?

BACKGROUND: Glatiramer acetate (GA) 20 mg/day (GA20) is associated with immediate post-injection reactions (PIRs). For convenience of use, approved GA 40 mg three times weekly (GA40) delivers a similar weekly dose. The dose and concentration of a single GA40 injection are, however, twice as high as for GA20, and post-injection adverse events may differ. Cases of atypical PIRs to GA40 prompted us to systematically monitor such events. OBJECTIVE: The aim was to characterize atypical PIRs in multiple sclerosis (MS) patients treated with GA40. METHODS: Clinical practice data were prospectively collected in consecutive relapsing-remitting MS patients. Descriptive statistics for categorical and continuous variables, Mann-Whitney and Chi-squared tests for baseline comparisons, and Cox regression models for association of variables to first atypical PIRs were applied. RESULTS: Forty-six out of 173 patients (26.6%) given GA40 experienced any PIRs. Of those, 38 (22.0%) had atypical, 14 (8.1%) had combined typical and atypical, and 26 (15.0%) had recurrent atypical PIRs, most frequently shivering (13.3%) and nausea/vomiting (8.1%). Compared to typical PIRs, onset of atypical PIRs was significantly delayed (median 30 vs 1 min, p < 0.0001), and their median duration longer (median 120 vs 6 min, p = 0.00013). Previous exposure to GA20 was associated with a lower risk of atypical PIRs [hazard ratio (HR) = 0.35, 95% confidence interval (CI) 0.17-0.72, p = 0.0039]. Patients experiencing PIRs with GA20 were at elevated risk for atypical PIRs with GA40 (HR = 5.75, 95% CI 1.66-19.94, p = 0.0059). CONCLUSIONS: Atypical PIRs with GA40, especially gastrointestinal symptoms and/or fever/shivering, had a delayed onset and occurred in a significant proportion of our patients. Their real prevalence should be assessed in appropriately designed studies accounting for  nocebo responses. Initial dose titration might reduce PIR frequency.

Analgesia pós-operatória com morfina peridural em pacientes submetidos a cirurgia ortopédica de membros inferiores / Postoperative analgesia with extradural morphine in patients submitted to orthopedic surgeries of the lower limbs

Foram estudados 43 pacientes, de 16 a 68 anos de idade, de ambos os sexos, que se submeteram à anestesia peridural para cirurgias ortopédicas de membros inferiores. Na realizaçäo do bloqueio anestésico foram adicionados 2 ou 4 mg de morfina sem preservativo. A intensidade da dor foi avaliada pela escala análoga-visual e a incidência de prurido, náuseas e vômitos, retençäo urinária e depressäo respiratória foram registradas. Embora näo se tenha registrado nenhum caso de depressäo respiratória nesse estudo, observou-se uma incidência mais elevada de paraefeitos no grupo de pacientes que recebeu 4 mg de morfina. A analgesia assim obtida foi satisfatória, porém näo foi suficiente para aliviar a dor originada do movimento, mesmo no grupo de pacientes que recebeu o dobro da dose. O aumento da dose de morfina näo aumentou a eficácia de sua analgesia, nem a tornou eficaz no alívio da dor originado do movimento

Comparative study of the analgesic effect of transcutaneous nerve stimulation (TNS); electroacupuncture (EA) and meperidine in the treatment of postoperative pain.

Seventy two patients, from 15 to 60 years old, in good physical status and submitted to surgery in the upper or lower abdominal, rectal or lumbar areas were studied. In the immediate postoperative period, they were randomly divided in three groups and each group was submitted to one of the following treatments: intravenous meperidine, transcutaneous nerve stimulation (TNS) or electroacupuncture (EA). Each treatment was divided in two phases with one hour interval between them. Each phase was constituted of 30 minutes of stimulation in case of TNS and EA and fractionated administration of meperidine in all groups. The pain level was evaluated through a visual analogue scale before and after each phase of treatment. The results were compared among groups and, on each group, between the phases of treatment. In all surgery types, the postoperative pain relief presented by TNS and EA groups of patients was greater than that of meperidine treated group. But, the analgesia presented by the EA treated group of patients lasted longer and increased with the repetition of treatment. The differences of behaviour of TNS and EA analgesia suggest that their neurochemical mechanisms may not be the same.

Hemodialise e hepatite a virus B. / Hemodialysis and virus B hepatitis

Realizou-se um levantamento do grau de exposicao ao virus da hepatite B, observada entre pacientes e funcionarios de algumas unidades de hemodialise e fez-se um estudo comparativo com o que ocorre na populacao geral e em alguns grupos de pessoal tecnico hospitalar. A pesquisa, que empregou marcadores da hepatite B (HBsAg e anti-HBs), indicou maior exposicao ao virus entre os pacientes em hemodialise cronica (61%) e, em menor proporcao, entre os funcionarios hospitalares, com maior contato com sangue humano

Determination of the range of control limits in radioimmunoassay measurements.

Una tecnica grupal para control de limite en radioinmunoensayo es propuesta por los autores. Tiene la ventaja de permitir controles limites del 99.7% sin los inconvenientes que se presentan al utilizar intervalos de confianza. El metodo es practico y simple permitiendo flexibilizacion del proceso. Su definicion mejora al aumentar el numero de muestras

Determination of the range of control limits in radioimmunoassay measurements.

Una tecnica grupal para control de limite en radioinmunoensayo es propuesta por los autores. Tiene la ventaja de permitir controles limites del 99.7% sin los inconvenientes que se presentan al utilizar intervalos de confianza. El metodo es practico y simple permitiendo flexibilizacion del proceso. Su definicion mejora al aumentar el numero de muestras

The marginal band and its role in the ellipsoidal shape of Geochelone carbonaria erythrocytes.

Erythrocytes from a chelonian (Geochelone carbonaria) were submitted to physical and chemical treatments. Observations of their change in shape from ellipsoidal to spherical were made by means of light microscopy. A 100% change to the spherical shape was attained with erythrocytes under high temperature treatment (42 degrees C) for 45 min., and at room temperature (29 degrees C) plus colchicine, for 60 min. Erythrocytes kept at room temperature present changes in shape while those kept at low temperature (10 degrees C) did not exhibit significant changes in their original ellipsoidal shape, but displayed an intact marginal band (MB). By direct examination the diameter of microtubules was found to be nearly 300 A in the dissociated form and 0.70 mu when bundled. In cross section the value found for microtubule diameter was up to 210 A. These measures are compatible with those found by several other authors. Counting of microtubules by ultrathin sectioning indicated approximately 70 tubules per cell, a value that is higher than that found in other species. By means of electron microscopy the marginal band can be observed intact or dissociated into several dense rings formed by parallel microtubules running nearly or accompanying the periphery of the stroma. Temperature and colchicine are responsible for the depolymerization of the microtubules. In the stroma of spherical erythrocytes a dense peripheric fold can be observed but microtubules were never found. It is suggested therefore that the role of the marginal band is essential to maintain the ellipsoidal shape of chelonian erythrocytes.