Effect of etanercept therapy on psoriasis symptoms in patients from Latin America, Central Europe, and Asia: a subset analysis of the PRISTINE trial.

BACKGROUND: Psoriasis prevalence and characteristics in Asia, Central Europe, and Latin America have not been thoroughly investigated and there are no large trials for biologic treatments for patients from these regions. The goal of this analysis was to report clinical response to anti-tumor necrosis factor-alpha treatment in these patients. METHODS: Patients from Argentina, Czech Republic, Hungary, Mexico, Taiwan, and Thailand (N=171) were included in this subset analysis of the PRISTINE trial. Patients with stable moderate-to-severe plaque psoriasis were blinded and randomized to receive etanercept 50 mg once weekly (QW) or biweekly (BIW) for 12 weeks, followed by 12 weeks of open-label QW treatment with etanercept 50 mg through week 24 (QW/QW vs. BIW/QW). Concomitant methotrexate (≤20 mg/week) and mild topical corticosteroids or other agents were permitted at the physician's discretion, in accordance with therapeutic practice. RESULTS: As early as week 8, 26.7 % in the etanercept QW group and 44.0 % in the BIW group achieved Psoriasis Area and Severity Index (PASI) 75. At weeks 12 and 24, respectively, PASI 75 increased to 39.5 % and 62.8 % in the QW/QW group and 66.7 % and 83.3 % in the BIW/QW group. PASI 75 was significantly different between treatment groups from week 8 through the end of study (p<0.05). The Kaplan-Meier estimate of the proportions achieving PASI 75 in QW/QW and BIW/QW groups, respectively, was 27.4 % and 45.8 % through week 8; 41.9 % and 68.7 % through week 12; and 72.5 % and 95.2 % through week 24. CONCLUSIONS: Treatment with etanercept 50 mg provided rapid relief of psoriasis symptoms in patients from Asia, Central Europe, and Latin America. A more rapid response was observed in patients who received BIW treatment for the first 12 weeks which was sustained after reducing to QW dosing for the subsequent 12 weeks. Response rates were similar to those observed in the overall PRISTINE population. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00663052 .

Effects of hypercapnea and of hypercapnea in combination with hypoxia on midbrain-induced cardiac dysrhythmias.

Stimulation of the midbrain during acute combined arterial hypoxia and hypercapnea produces serious cardiac dysrhythmias which are not evoked when stimulation is elicited either with normal arterial blood gas tensions or with isolated mild hypercapnea. The cardiac dysrhythmias are mediated by both enhanced sympathetic and parasympathetic efferent discharge. The results support the concept that increased autonomic activity in combination with acute arterial hypoxia and hypercapnea contribute significantly to the exhibition of serious cardiac rhythm disturbances. Acute hypoxia appears to be the major determinant of such dysrhythmias.

Intracellular autogenetic effects of muscular contration on extensor motoneurones. The silent period.

1. Intracellular records have been taken from cat motoneurones belonging to gastrocnemius and soleus or to popliteal synergists during contractions of gastrocnemius and soleus, acting separately or jointly. Such contractions were elicited by brief tetani or single shocks to the peripheral end of the cut ventral roots L7 or S1.2. Hyperpolarization of the motoneurone accompanies rise of tension in contraction. The amount of it increases when at constant extension the contraction of the muscle is increased by increasing stimulus strength, as well as when it is increased by augmenting extension at constant stimulus strength. It is therefore tension-sensitive.3. The duration of the hyperpolarization induced in this manner reflects the duration of the contraction itself, being considerably longer in the slow soleus than in the faster gastrocnemius. It is often preceded by a brief wavelet of depolarization ascribed to the so-called back-response.4. Early in relaxation there occurs a transient ;hump' of membrane depolarization. This corresponds to the moment characterized by phasic bursts from the spindle primaries. The ;hump' terminates hyperpolarization.5. When the cell is stimulated by injected current to maintained repetitive firing, the ;silent period' in contraction begins with the phase of hyperpolarization and ends with the hump of depolarization as described above.6. Later during relaxation, delayed inhibition, may or may not follow often accompanied by hyperpolarizing activation noise and sometimes also visible as an extension of the silent period of a firing cell. There is, however, no marked hyperpolarization of the motoneurone in delayed inhibition.7. In the Discussion the events described above are related to previous studies employing monosynaptic testing or electromyography for the analysis of the variations of excitability caused in extensor motoneurones by autogenetic contractions as well as to known properties of stretch receptors.