The antinociception induced by the intraperitoneal coadministration of combinations of paracetamol with the nonsteroidal anti-inflammatory drugs (NSAIDs) diclofenac, ibuprofen, ketoprofen, meloxicam, metamizol, naproxen, nimesulide, parecoxib and piroxicam was studied by isobolographic analysis in the acetic acid abdominal constriction test of mice (writhing test). The effective dose that produced 50% antinociception (ED50) was calculated from the log dose-response curves of fixed ratio combinations of paracetamol with each NSAID. By isobolographic analysis, this ED50 was compared to the theoretical additive ED50 calculated from the ED(50) of paracetamol and of each NSAID alone obtained from ED50 dose-response curves. As shown by isobolographic analysis, all the combinations were synergistic, the experimental ED50s being significantly smaller than the theoretically calculated ED50s. The results of this study demonstrate potent interactions between paracetamol and NSAIDs and validate the clinical use of combinations of these drugs in the treatment of pain conditions.
and the Italian Acute Stroke Study GroupWe compared 211 consecutive patients who had acute ischemic hemispheric stroke and atrial fibrillation with 837 consecutive patients who had stroke without atrial fibrillation. The atrial fibrillation group included a higher frequency of women, older subjects, and those with a severe neurologic deficit, abnormal computed tomogram, and elevated heart rate. The 1-month casefatality rate in the atrial fibrillation group was 27% while that in the group without atrial fibrillation was 14%. The 6-month case-fatality rates in the two groups were 40% and 20%, respectively. The risk of death attributable to atrial fibrillation, adjusted for the effect of other prognostic factors, was significant at 1 month (relative risk=1.55) and at 6 months (relative risk=1.74). The causes of death were equally distributed in the two groups during both the acute and subacute phases. We conclude that atrial fibrillation is a negative prognostic factor in patients hospitalized for acute stroke. Nevertheless, cerebral embolism alone does not completely explain the increase in mortality for stroke patients with atrial fibrillation. Other associated pathogenetic mechanisms must also be taken into account [Stroke 1991^22:169-174) A trial fibrillation (AF) is a common cardiac condition in the older population 1 -4 and L has an even higher prevalence in hospitalized stroke patients.5 " 8 The presence of AF is associated with higher stroke recurrence and mortality rates.2 -8 -11 While the association between AF and short-term mortality has been proved, an association with long-term mortality remains to be confirmed. 812 ' 13 To determine the contribution of AF to stroke mortality, we undertook a retrospective case-control study of 211 stroke patients with AF and 837 stroke patients without AF, all of whom were enrolled in the Italian Hemodilution Trial.
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Subjects and MethodsWe studied 211 consecutive stroke patients with AF (mean±SD age 73.6±9.5 years, 40% men) and 837 stroke patients without AF (mean±SD age 66.5±11.2 years, 64% men), all of whom were hospitalized for a first hemispheric stroke. We excluded those with symptoms lasting >12 hours or severe coma. Patients with cerebral hemorrhage (22 with
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