Background: To determine the knowledge, attitudes and practices regarding organ donation in a selected adult population in Pakistan.

No abstract

The MTD of cis-RA given on this intermittent schedule was 160 mg/m2/d. Serum levels known to be effective against neuroblastoma in vitro were achieved at this dose. The DLT included hypercalcemia, and may be predicted by serum cis-RA levels. Monitoring of serum calcium and cis-RA levels is indicated in future trials.

Serum uric acid (sUA) level may be associated with cognitive impairment/dementia. It is possible this relationship varies with dementia subtype, particularly between vascular dementias (VaD) and Alzheimer's (AD) or Parkinson's disease (PDD)-related dementia. We aimed to present a synthesis of all published data on sUA and relationship with dementia/cognition through systematic review and meta-analysis. We included studies that assessed the association between sUA and any measure of cognitive function or a clinical diagnosis of dementia. We pre-defined subgroup analyses for patients with AD, VaD, PDD, mild cognitive impairment (MCI), and mixed or undifferentiated. We assessed risk of bias/generalizability, and where data allowed, we performed meta-analysis to describe pooled measures of association across studies. From 4811 titles, 46 papers (n = 16,688 participants) met our selection criteria. Compared to controls, sUA was lower in dementia (SDM -0.33 (95%CI)). There were differences in association by dementia type with apparent association for AD (SDM -0.33 (95%CI)) and PDD (SDM -0.67 (95%CI)) but not in cases of mixed dementia (SDM 0.19 (95%CI)) or VaD (SDM -0.05 (95%CI)). There was no correlation between scores on Mini-Mental State Examination and sUA level (summary r 0.08, p = 0.27), except in patients with PDD (r 0.16, p = 0.003). Our conclusions are limited by clinical heterogeneity and risk of bias in studies. Accepting this caveat, the relationship between sUA and dementia/cognitive impairment is not consistent across all dementia groups and in particular may differ in patients with VaD compared to other dementia subtypes.

A phase I clinical trial of 13-cis-retinoic acid (cis-RA) was undertaken to determine the maximally tolerated dose (MTD) and pharmacokinetics (PK) of cis-RA following bone marrow transplantation (BMT) in children with high-risk neuroblastoma. Mean peak serum levels of cis-RA in 31 pediatric patients ranged from 4.9 to 8.9 microM following doses of 100-200 mg/m2 per day, divided into two doses every 12 h administered orally. The PK of cis-RA obeyed a single-compartment model following first-order absorption in the majority of patients. A linear increase in the mean peak serum levels and area under the time-concentration curve (AUC) with increasing dose was observed. The average half-lives of absorption and elimination were 1.0 and 5.8 h, respectively. At the MTD of 160 mg/m2 per day, the mean cis-RA peak serum concentration was 7.2 +/- 5.3 microM. AUC values were not altered significantly during a 2-week course of treatment or over a long period of multiple courses. Levels of trans-retinoic acid, a metabolite of cis-RA, remained low but were similar on days 1 and 14, whereas the 4-oxo-13-cis-RA metabolite had increased in 64% of patients by day 14. Peak serum cis-RA concentrations correlated with clinical toxicity as grade 3 to 4 toxicity was seen in 44% of patient-courses (8/18) with peak serum levels > 10 microM, but only 13% (12/96) with peak serum levels < 10 microM. These results show that cis-RA given at 160 mg/m2 to children achieved serum concentrations known to be effective against neuroblastoma in vitro, and the PK for cis-RA differs from that reported for trans-retinoic acid in children.