If platelet counts are problematic despite dose modifications, then splenectomy, either surgical 9 or by endovascular means using an embolic approach 10, can help in selected patients.
Further, although grandmothers were the primary caregiver, other household members also administered medication to the child, which became problematic when doses were changed.
If focusing on poorly-known substances, the risk is greater that the detection method is problematic, the doses used are inappropriate, or that some other, unexpected problem will render the results invalid or uninformative.
In both cases, extrapolations to human populations are problematic because doses studied may have little or no relevance to environmental exposure levels (Schneider et al. 2006; Tran et al. 2002).
Results of the Carvedilol Or Metoprolol European Trial (COMET), suggested that overall tolerability of carvedilol vs. metoprolol tartrate does not differ, but it has been suggested that this interpretation is problematic because doses were not equivalent.
Palmar plantar erythrodysesthesia is the usual dose-limiting toxicity of Doxil®, and it renders problematic any substantial dose escalation that liposome delivery might otherwise provide.
However as long term administration of 6TG is problematic due to dose related toxicities, such as veno- occlusive disease, this study will assess the activity of 6-mercaptopurine (6MP), which is converted to the same active moiety, 6-thioguanine nucleotide, prior to incorporation into DNA.
This suggests that PONV may be less problematic within this dose range, and is in agreement with our previous finding that 50 – 200 μg of IT morphine does not contribute to the incidence of PONV in the setting of elective hip arthroplasty under spinal anaesthesia [ 17].
In AKI, metabolites that are normally renally eliminated may be retained [ 37- 42], and accumulation is more likely to be problematic with repeated dosing.
