Nucleic acids. 11. Synthesis of 5'-esters of 1-beta-D-arabinofuranosylcytosine possessing antileukemic and immunosuppressive activity.
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Animals↗
Biomedical subjects
R C Kelly
Publications and source records attributed to R C Kelly.
Longitudinal changes in cognitive function and regional cerebral function in Alzheimer's disease: a SPECT blood flow study.
In Alzheimer's disease (AD), SPECT imagining of regional cerebral blood flow (rCBF) has emphasized deficits in the posterior association cortex. Previous studies have shown an association between these deficits and cognitive performance, both on overall cognitive tests and more specific tests such as praxis and language. Frontal deficits have been reported in more severe patients. This has led to the conclusion that the deficit in AD, at least with functional neuroimaging, starts in the posterior association cortex, and later in the disease process "spreads" to involve the frontal cortex. This study set out to measure, in a group of AD patients, the change over time of cognitive performance and the pattern of functional deficit measured by neuroimaging. Change in function was measured using 99TCm-HMPAO and SPECT and change in cognitive function using the CAMCOG. Two time points were used, 0 and 2 years. Twenty-four patients satisfying the DSM-III R criteria for probable AD were studied, nine of whom were subsequently diagnosed as having AD at post-mortem. The most striking finding was the effect that decreases in frontal lobe function had on cognitive function. A similar study by the same group, using the same techniques and many of the same patients but at only one time point, showed a correlation between cognitive function and rCBF in the parietal and posterior temporal lobes. This suggests that as AD patients deteriorate from unaffected to mild or moderately affected, the posterior association cortex exerts the greatest effect on cognitive deficit. In this longitudinal study, we found, using a MANOVA, that there were significant decreases over time for all the cortical regions studied, but that no region decreased significantly more than any other. In addition we found a correlation between change in frontal rCBF and change in cognitive function (both overall cognitive function and the CAMCOG sub tests of language and praxis). These data suggest, in contrast to the previous study, that as the disease progresses from mild or moderate to moderate or severe, the frontal cortex exerts the greatest effect on cognitive decline. These data support the concept of the deficit in functional imaging spreading from posterior to anterior as the disease progresses. However, both the initial pattern of deficit and the change over time were very heterogeneous when examined qualitatively. A posterior to anterior spread is the predominant pattern for the group as a whole, but individual patients, and possibly groups of patients, may well show alternative patterns.
Aged↗
123Iodo-MK-801: a spect agent for imaging the pattern and extent of glutamate (NMDA) receptor activation in Alzheimer's disease.
Glutamate, and the NMDA glutamate receptor, may be involved in Alzheimer's Disease (AD). Reductions in NMDA receptors are found in AD, possibly contributing to memory deficits. However the NMDA receptor is involved in excitotoxicity, which may play a role in cell death and the production of neurofibrillary tangles in AD; although with lower levels of glutamate than occur in cerebral ischaemia. Therefore reductions in the NMDA receptor may worsen memory deficit in AD, but increased stimulation of the receptor may contribute to the progress of the disease. MK-801 has been used to image excessive glutamate activation following ischaemia in rats. However, it is unclear how effective MK-801 is in conditions with lower levels of glutamate release. This study attempts to gain insight into the utility of the tracer in these conditions, exploring glutamatergic mechanisms in AD. It describes the retention and elimination of 123iodo-MK-801 in five AD and five control subjects, comparing this to regional cerebral blood flow (rCBF). The initial uptake of 123I-MK-801 is dominated by delivery of the ligand. However, despite significant reductions in rCBF in the AD patients, there is no significant difference in the uptake of 123I-MK-801. This suggests increased retention of 123I-MK-801 in the AD patients. In addition the washout of 123I-MK-801 was less in the AD patients, again suggesting increased retention, although this only reached significance in one region. Theses data hint at possible increases in NMDA activation in AD but ultimately 123I-MK-801 does not provide a sufficiently accurate measurement to demonstrate this conclusively. Further NMDA ligands are now at a late stage of development and may provide more conclusive answers to the role of glutamate in AD.
Aged↗
A novel GC/MS derivatization method for amphetamines.
Many widely used methods for derivatizing drugs of the amphetamine group for GC/MS are problematic. The difficulties with these methods include incompatibility with other derivatizing agents, short column life, lack of abundant high molecular weight ions, and the potential for interference from other drugs. The present procedure is an effort to reduce some of these problems by the use of a novel derivatizing agent, N-methyl-N-t-butyldimethylsilyl trifluoroacetamide (MTBSTFA). We describe here an MTBSTFA derivatization method for amphetamine (AMP) and methamphetamine (MAMP) that leads to stable derivatives that are well-separated from potential interferences and features high molecular weight fragments suitable for selected ion monitoring. The procedure is linear to approximately 3000 ng/mL for both AMP and MAMP and appears to be both precise and sensitive. Furthermore, it seems to have no adverse effect on column life.
Acetamides↗
Association of benzodiazepines with death in a major metropolitan area.
Death has been examined as a possible adverse consequence of the use of benzodiazepine drugs. Rather than limit ourselves to drug overdose cases, we have analyzed unselected blood specimens by a technique sensitive enough to detect therapeutic use as well. The subpopulation thus identified was found to have a number of interesting characteristics not shared by typical coroners' cases. These features are described and discussed in detail in the text.
Adolescent↗
A convenient thin-layer chromatographic screening method for acetaminophen in serum.
A thin-layer chromatographic screening procedure for acetaminophen in serum was developed that meets the clinical need to identify candidates for antidotal therapy within the critical first 24 hr after ingestion. The key feature of this approach is the use of a detection reagent containing Fe(III) and 2,4,6-tris-(2'-pyridyl)-s-triazine (TPTZ). Acetaminophen on the plate reduces the Fe(III) to Fe(II), which then forms an intensely blue-colored complex with the TPTZ. Concentrations as low as 3 to 4 mg/L can be detected and the procedure is free of interference from 38 other common drugs and metabolites.
Acetaminophen↗