QUANTITATIVE MORPHOLOGICAL AND MOLECULAR PATHOLOGY OF THE HUMAN THYMUS CORRELATE WITH INFANT CAUSE OF DEATH.

The objective of this study was to investigate and quantify the morphological and molecular changes in the thymus for common causes of human infant death. Thymic architecture and molecular changes apparent in human infant head trauma victims were assessed by microscopy and quantified by image analysis of digital whole slide images. Thymuses from victims of SIDS and suffocated infants displaying normal thymus architecture were used for comparison. Molecular expression of proliferation and serotonin receptor and transporter protein markers was evaluated. Duplicate morphological and molecular studies of rodent thymuses were completed with both mouse and rat models. Quantification of novel parameters of digital images of thymuses from human infants suffering mortal head trauma revealed a disruption of the corticomedullary organization of the thymus, particularly involving dissolution of the corticomedullary border. A similar result was obtained for related mouse and rat models. The human thymuses from head trauma cases also displayed a higher percentage of Ki-67-positive thymocytes. Finally, we determined that thymus expression of the human serotonin receptor, and the serotonin transporter, occur almost exclusively in the thymic medulla. Head trauma leads to a disruption of the thymic, corticomedullary border, and molecular expression patterns in a robust and quantifiable manner.

Sudden death after exercise in an adolescent with hemoglobin SE.

Hemoglobin (Hb) S and Hb E are the most common variant hemoglobins, but because of the geographical separation of the areas where they are prevalent, the combination of the 2 is uncommon. Approximately 46 cases of hemoglobin SE compound heterozygosity have been reported. No deaths from the condition have been reported previously, whereas death after vigorous physical activity in individuals with sickle cell trait (hemoglobin AS) has been described in a few case reports. Here we report previously undiagnosed hemoglobinopathy SE in a 12-year-old American boy who collapsed during football practice and had a cardiac arrest on the field after a brief lucid interval. The autopsy was significant only for postmortem intravascular sickling. A postmortem hemoglobin electrophoresis test revealed 57% S, 34% E, and 1% F hemoglobins. The death is attributed to cardiac ischemia from functional vaso-occlusion by sickled erythrocytes.

Suffocation in motor vehicle crashes.

Because death from suffocation in traffic fatalities has not been well described, we delineated the clinical, circumstantial, and autopsy findings associated with suffocation in a series of motor vehicle crashes. Medical examiner case files from a 5-year period were reviewed. Scene investigation, autopsy, toxicology, and first-responder reports were examined. Crash descriptions were reviewed, including vehicle type, mechanism of crash, response time, restraint use, occupant ejection, and victim position in cabins of vehicles. Mechanisms of suffocation, including torso compression, inversion, neck flexion, facial occlusion, and blood aspiration, were determined for each case. The files were searched for factors relevant to the diagnosis of suffocation, namely, cerebral concussion, alcohol intoxication, obesity, petechiae, lung weights as a proxy for livor, natural disease, and impact wounds. Twenty-nine traffic fatality cases were identified in which suffocation caused death. In 26, suffocation mechanisms were solely responsible for death. In 3, death was caused by suffocation in combination with other mechanisms. Twenty-five subjects were occupants of vehicles with cabins and 4 were motorcycle riders. The most common mechanism of suffocation was torso compression. Most subjects had either multiple mechanisms of suffocation or a single mechanism acting in concert with concussion or alcohol intoxication. Concussion and intoxication were common, with one or both present in 20 subjects, including all of those with blood aspiration. Petechiae were frequent but were found consistently only among those with inversion. Cutaneous chest petechiae were associated with inversion and torso compression. Lung weights were highest among those with blood aspiration and lowest among those with inversion. Body mass index was highest among those with inversion, suggesting that obesity could be a risk factor for this mechanism.

Decreased activity of brain phospholipid metabolic enzymes in human users of cocaine and methamphetamine.

Phospholipids are essential components of cell membranes which may also function to mediate some of the behavioural effects of dopamine receptor stimulation caused by psychostimulant drugs. Neuroimaging and pharmacological data suggest that abnormal brain metabolism of phospholipids might explain some of the consequences of chronic exposure to drugs of abuse including drug craving. We previously reported decreased activity of calcium-stimulated phospholipase A(2) (Ca-PLA(2)) in autopsied putamen of human cocaine users. To establish the specificity of this change in phospholipid metabolism and whether decreased Ca-PLA(2) might be a general feature of all abused drugs which enhance dopaminergic neurotransmission, we measured activity of 11 major phospholipid metabolic enzymes in dopamine-rich (putamen) and poor brain areas of chronic users of cocaine and of methamphetamine. Enzyme changes were restricted to the putamen which showed decreased (-21%, as compared with the control subjects) Ca-PLA(2) activity in users of methamphetamine and reduced (-31%) activity of phosphocholine cytidylyltransferase (PCCT), the rate-limiting enzyme of phosphatidylcholine synthesis, in the cocaine users. We suggest that chronic exposure to psychostimulant drugs might cause a compensatory downregulation of Ca-PLA(2) in dopamine-rich brain areas due to excessive dopamine-related stimulation of the enzyme. Decreased striatal Ca-PLA(2) and/or PCCT activity in cocaine users might also help to explain why CDP choline, which enhances phospholipid synthesis, reduces craving in some users of the drug cocaine.