Coronary Artery Complicated Lesion Area Is Related to Functional Polymorphism of Matrix Metalloproteinase 9 Gene: An Autopsy Study.
Arteriosclerosis, Thrombosis & Vascular Biology.
21(9):1446-1450, September 2001.
Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Department of Forensic Medicine, Department of Human Molecular Genetics
Helsinki, Finland and Los Angeles, CA, USA

Abstract: Matrix metalloproteinase 9 (MMP9) is expressed in human atherosclerotic plaques, and the protein is localized in human coronary atherosclerotic lesions. The MMP9 gene has a C-to-T promoter polymorphism at position -1562, which affects transcription and leads to promoter low-activity (C/C) and high-activity (C/T, T/T) genotypes. To determine whether these genotypes exert an influence on the atherosclerotic lesion area, we investigated their association with different types of coronary lesions in an autopsy cohort of 276 men aged 33 to 69 years. Areas of the coronary wall covered with fatty streaks and fibrotic, calcified, and complicated lesions were measured, and the percentage of coronary narrowing was determined. MMP9 genotypes were determined by polymerase chain reaction and restriction enzyme digestion. In men aged >=53 years, the mean area of complicated lesions in 3 coronaries was significantly associated with the MMP9 genotype (P =0.008). Subjects with high promoter activity genotypes had, on average, larger complicated lesion areas than did those with the low-activity genotype. The MMP9 genotype persisted as an independent predictor of complicated lesion area after adjustment for age, body mass index, hypertension, diabetes, and smoking (P =0.012). These data provide evidence that the proposed effect of MMP9 in the process of atherosclerotic lesion development may be modified by the MMP9 genotype.

Cholesterol and neuropathologic markers of Alzheimer's Disease (AD):
A population-based autopsy study.
Neurology. 57(8):1447-1452, October 23, 2001.
Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, NIH
Pacific Health Research Institute and Honolulu Heart Program, Honolulu, HI.

Objective: To examine the association of plasma cholesterol (total and high-density [HDL] and low-density lipoprotein) levels with neuritic plaques (NP) and neurofibrillary tangles (NFT) in a population-based autopsy series of 218 Japanese American men followed as a part of the Honolulu-Asia Aging Study.

Methods: Cholesterol levels were measured in late life (average age at death 84.6 years) in all subjects (n = 218) and in midlife (20 years before late life) in a subsample (n= 89); for the analyses, levels were categorized into quintiles, with the lowest quintile serving as the reference. Tissue from four areas of neocortex and two areas of hippocampus was prepared with Bielschowsky silver-stained sections and evaluated by one of three neuropathologists who were blinded to clinical information. Diffuse and neuritic plaques and NFT were counted in field areas standardized to 1 mm2. Fields were selected from areas with the highest numbers of lesions, and the field withthe highest count was taken to represent the brain area.

Results: After adjusting for age at death, education, APOE allele, dementia, neuropathologic infarction, and blood pressure, a strong linear association was found for increasing late-life HDL cholesterol (HDL-C) levels and an increasing number of neocortical NP and hippocampal and neocortical NFT.

Conclusions: The constituents of HDL-C may play a role in the formation of AD pathology, and these processes are reflected in peripheral measures.

Lack of Evidence for an Association Between Neurofibromatosis Type I and Intracranial Aneurysms: Autopsy Study and Review of the Literature.
Stroke. 32(11):2481-2485, November 2001.
Department of Neurosurgery, Department of Pathology
Johns Hopkins Medical Institutions, Baltimore, Md.

Background and Purpose-: Neurofibromatosis type I (NF1) is an autosomal dominant, hereditary, neurocutaneous syndrome purported to be associated with intracranial aneurysms. To study the relationship between NF1 and intracranial aneurysms, we analyzed all intracranial autopsies of NF1 patients performed at our institution from 1889 to 1999 and analyzed all intracranial aneurysm cases at our institution from 1990 to 1999 in an attempt to identify patients with NF1.

Methods-: The autopsy database at our institution, which contains 50,000 cases from 1889 to 1999, was searched to identify NF1 patients, and the results of these autopsies were reviewed. The prevalence of intracranial aneurysms in these NF1 patients was compared with the prevalence of intracranial aneurysms in our hospital's autopsy population and with the published prevalence of intracranial aneurysms in the general population.

Conclusions-: The autopsy prevalence of no NF1 patients with intracranial aneurysms out of 25 is not different from the prevalence of intracranial aneurysms in the general autopsy population. These findings are supported by the observation that an association between NF1 and intracranial aneurysms has never been identified in 8 large clinical studies of NF1 patients. We conclude that there is a lack of evidence for any association between NF1 and intracranial aneurysms.

Postoperative Death and Malpractice Suits: Is Autopsy Useful?
Anesthesia & Analgesia. 91(2):344-346, August 2000.
France

This report demonstrates the extremely high yield of autopsies performed in the case of postoperative death with suspicion of malpractice. They frequently identified undetected complications. They could also suggest faulty or negligent practice that would otherwise go unrecognized. This report supports the widespread use of autopsies to investigate perioperative death.