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Objective: The enzyme phosphoinositide-specific phospholipase C (PI-PLC) is a component of the phosphoinositide signal transduction system. Other components of this system have been found to be abnormal in adults and adolescents who have committed suicide, and so the authors examined whether PI-PLC activity and protein expression of PLC isozymes are abnormal in postmortem brains of teenage suicide subjects., Method: PI-PLC activity and protein expression of the PLC beta1, delta1, and gamma1 isozymes were examined in Brodmann's areas 8 and 9 of postmortem brains obtained from 18 teenage suicide subjects and 18 matched comparison subjects. PI-PLC activity was determined by enzymatic assay, and protein expression of the PLC isozymes was determined by the Western blot technique., Results: Compared with the normal subjects, the teenage suicide subjects had significantly lower PI-PLC activity and immunolabeling of the specific PLC beta1 isozyme in both membrane and cytosol fractions of Brodmann's areas 8 and 9 combined (prefrontal cortex). There was also a significant correlation between PI-PLC activity and protein levels of the PLC beta1 isozyme in the brains of the teenage suicide subjects. There was no significant difference in PI-PLC activity or level of PLC beta1 protein between the suicide subjects with a history of mental disorders and those with no history of mental disorders; however, both groups had significantly lower PI-PLC activity and expression of PLC beta1 protein than the normal subjects., Conclusions: Low PI-PLC activity and expressed levels of the PLC beta1 isozyme in postmortem brains of suicide subjects may have clinical relevance in the pathophysiology of suicidal behavior.

Two venlafaxine (Effexor)-related deaths are reported with comparison of results from the analysis of specimens using capillary gas chromatography with a nitrogen-phosphorous detector (GC-NPD) and high-performance liquid chromatography (HPLC) using a UV-vis detector. Blood concentrations in Case 1 were 7.27 micrograms/mL venlafaxine and 5.03 micrograms/mL O-desmethylvenlafaxine, and Case 2 had 89.67 micrograms/mL venlafaxine with 3.44 micrograms/mL of the desmethyl metabolite. A comparison of analytical methods and specimen concentration is presented.

Sudden unexpected deaths in epileptic persons are not rare events, most commonly encountered by the forensic pathologist rather than the clinician. Such deaths may represent 1-1.5% of all "natural" deaths certified by the medical examiner or coroner. The typical victim is a black male about 30 years of age who tends to abuse alcohol, with a history of generalized epilepsy for more than 1 year and likely for more than 10 years. There are a lack of obvious anatomic causes for the death at autopsy, but 60-70% of cases will have a lesion in the brain (most commonly old trauma) to explain the epilepsy. Most victims have no blood levels of anticonvulsant medications at the time of death. We have evolved a form for use by medical examiner/coroner's investigators at the scene to collect relevant information which will be of assistance to the pathologist in interpreting the case. Estimated prevalence of sudden epilepsy death, mechanisms, and other features of such cases are reviewed briefly.

We have analyzed 66 cases of sudden unexpected death (SUD) in persons with seizure disorders, which were examined by the Office of the Medical Examiner, Cook County (Chicago), Illinois. The individuals ranged in age from 10 months to 60 years (mean age, 28 years). Autopsy findings were insufficient to explain death, and there was no evidence of major systemic pathology. Approximately 40% of victims were found dead in bed, and the remainder in some other room at home, apparently having been engaged in normal activity. Several died in an emergency room following a seizure at home. Cardiopulmonary resuscitation was attempted but was ineffective. Neuropathological examination revealed brain lesions, which probably caused the seizures, in 60% of the cases. In 68% the anticonvulsant blood level was subtherapeutic or below detectable levels. The prevalence of seizure-associated SUD may be between 1:525 and 1:2,100 among epileptics. The mechanism of death in these cases probably involves cardiac arrhythmias mediated by sympathetic autonomic events occurring during the seizure.

Sudden unexpected death accounts for a substantial portion of deaths among epileptics. The incidence of this phenomenon is probably 1 in 370 to 1 in 1,110 in the general epileptic population but may be even higher in the 20- to 40-year age group, and still higher if epileptics with symptomatic epilepsy are selected. Sudden unexpected death in epileptics has been observed at least once weekly by the Office of the Medical Examiner of Cook County (Chicago), Illinois, for many years. A year-long prospective study revealed that victims of this complication of epilepsy are most commonly black males averaging 35 years of age who have infrequent generalized seizures and usually have some structural lesion in the brain responsible for their seizures. They tend to abuse alcohol and have poor compliance with anticonvulsant medication. The electroencephalograms display considerable variability from record to record. At autopsy the heart, lung, and liver weights were heavier and the brain weights were lighter than expected. The mechanisms involved in sudden unexpected death in epileptics may include autonomically mediated cardiac arrhythmia alone or in combination with sudden "neurogenic" pulmonary edema and "backward" cardiac failure.

Atypical gunshot wounds of entrance occur when bullets deviate from their stable nose-on trajectory before entering the body. When this occurs, the resulting wound may have an atypical D-shaped appearance. Ray-like abrasions or bruises may radiate from the corners of the wound. Unstable nonaxial flight may be caused by intermediate targets, ricochets , inappropriate weapon/ ammunition combinations, poor weapon construction, or use of misaligned silencers . If a bullet is deformed before entrance the configuration of the resulting wound may be bizarre, and the wound configuration may closely resemble the configuration of the striking bullet. Nine cases are presented showing the effects of various intermediate targets. A number of methods for the investigation of atypical wounds are discussed.