Postmortem screening

Acylcarnitine analysis for the diagnosis of organic acidemias and particularly of FAO disorders plays an increasingly prominent role in all venues of clinical biochemical genetics prenatal diagnosis, newborn screening, evaluation of symptomatic patients, and postmortem screening. Almost exclusively performed by tandem... 

Figure 55-3 Protocol for the postmortem screening of FAO disorders. (From Rinaldo Matern D, Bennett MJ. Fatty add oxidation disorders. Ann Rev Physiol 2002 64 477-502.)...

MS/MS analysis of DBS is one model of clinical analysis that has been utilized on millions of infants for 15 years. Each year since its first clinical use in the mid-1990s, there have been substantial improvements such as improved ionization, more sensitive instruments, and a reduction of the actual size of instruments. The profile has expanded to include T4, succinylacetone, and in a few labs, LSD metabolites and steroids. Many of these analyses can be used in other clinical applications and research such as nutrition studies in premature infants or postmortem screening on sudden unexplained deaths in infants or carnitine status in dialysis patients with end-stage renal disease. As additional clinical assays are developed and used, it might be wise for these labs to consider the models of MS/MS, NBS, and the DBS as a reference. 

Herrin, G., McCurdy, H.H.H. and Wall, W.H. (2005) Investigation of an LCMSMS (QTrap) Method for the Rapid Screening and Identification of Drugs in Postmortem Toxicology Whole Blood Samples. J Anal Toxicol, 29, 599. 

The authors recommended including vitreous glucose and gammahydroxybutyrate analysis as part of postmortem toxicology work-up when the drug screen reveals either olanzapine or clozapine. 

Figure 55-3 shows a flow chart for the postmortem evaluation of sudden and unexpected death that is centered on the analysis of acylcarnitines in blood and bile spots. Blood and bile could be conveniently collected on a single filter paper card, one identical to those used for newborn screening, which can be shipped at room temperature once properly dried. Both specimens should be collected to detect patients who may have only mild blood abnormalities when carnitine is depleted (Figure 55-4). In cases with a higher level of suspicion, an effort should be made to collect and freeze a specimen of liver and a skin biopsy, which could be analyzed only if needed to reduce cell culture workload. ...

R. G. Boles, E. A. Buck, M. G. Blitzer, et al. Retrospective biochemical screening of fatty acid oxidation disorders in postmortem livers of 418 cases of sudden death in the first year of life. Journal of Pediatrics 132, 924(1998). 

D.J. Tranthim-Fryer, R.C. Hansson, K.W. Norman, Headspace/solid-phase microexlraction/gas chromatography-mass spectrometry a screening technique for the recovery and identification of volatile organic compounds (VOC s) in postmortem blood and viscera samples, J. Forensic Sci., 46, 934-946 (2001). 

In pig stomach smooth muscle, PMCAlb was the only isoform detected either by screening of a cDNA library or by analysis of mRNA by Northern blotting and by the polymerase chain reaction (PCR) (De Jae-gere et al., 1990). This finding contrasts with the presence of at least three different PMCA-related polypeptide bands on Western blots. Since there was no evidence for artefactual postmortem proteolysis, De Jaegere et al. (1990) concluded that the PMCAlb protein is post-translationally modified in smooth muscle. In rabbit stomach and aorta, Khan and Grover (1991) found by PCR that 83 to 86% of the PMCAl message is accounted for by PMCAlb, the remainder represent-... 

Lambert, W.E. Meyer, E. Xue-Ping, Y. De Leenheer, AP. Screening, identification, and quantitation of benzodiazepines in postmortem samples by HPLC with photodiode array detection. JAnal.ToxicoL, 1995, 19, 35-40... 

Herrin GL, McCurdy HH, Wall WH. Investigation of an LC-MS-MS (QTrap) method for the rapid screening and identification of drugs in postmortem toxicology whole blood samples. J Anal Toxicol 2005 29 599-606. 

CE is also useful in forensic toxicology laboratories to screen urine for drugs of abuse such as opiates, barbiturates, benzodiazepines, amphetamines, morphine, etc. and also for screening postmortem fluids for illicit drugs or elevated levels of legal drugs. When coupled to MS, CE is a powerful tool in the confirmation of positive results. 

Another area where an imbalance in neuropeptide levels has been implicated in illness is that of schizophrenia. In collaboration with Dr. T. Crow (Northwick Park Hospital), we are currently studying both the CSF and postmortem brain extracts from schizophrenic and control patients. Peptides screened by the HPLC-bio/radioimmunoassay approach include the enkephalins and endorphins, CCKg, VIP, LH-RH, TRH, and substance P. 

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