The additive contribution from inflammatory genetic markers on the severity of cardiovascular disease.

Inflammation plays a key role in the development of atherosclerosis. Genetic differences in molecules related to inflammation have therefore been linked to the susceptibility for and severity of atherosclerosis. We hypothesized that the additive contribution from different genes of importance for inflammation would enhance the severity of cardiovascular disease. Blood samples were collected from 230 adults admitted for elective coronary angiography. A total of 130 patients had significant (>50%) stenosis in at least one main coronary artery branch and 100 had not. Six polymorphisms in five different genes were analysed: myeloperoxidase (MPO) -129G/A and -463G/A, toll-like receptor 4 (TLR4) Asp299Gly, interleukin-6 (IL6) -174G/C, surfactant protein D (SFTPD) Met11Thr and regulated upon normal T-cell expressed and secreted (CCL5) -403G/A. The IL6 polymorphism was significantly associated (P = 0.017) to angiographic significant coronary artery disease, and this relation remained after adjustment for age, gender, smoking and hypercholesterolaemia (P = 0.007). The TLR4 (P = 0.050) and SFTPD (P = 0.058) polymorphisms were also associated with the presence of coronary stenosis in univariate but not in multivariate analyses. For MPO and CCL5 no associations were found. There was a significant linear association between the number of high-risk gene variants (IL6-174CC, SFTPD 11CC and TLR4 299AA) and the proportion of patients with coronary artery disease (P < 0.0005). Inherited factors related to inflammation may increase susceptibility for severe coronary artery disease. Furthermore, the additive contribution from different inflammatory genetic markers strongly enhances the individual severity of cardiovascular disease.

Polyclonal systemic immunoblast proliferation: an unusual hematologic entity presenting as a medical examiner case.

A 43-year-old woman who was receiving oral antibiotics for several days for a superficial foot infection developed a persistent rash, fever, and lymphadenopathy, despite discontinuation of the antibiotic and administration of steroids for a presumed drug reaction. Hours after a subsequent visit to the emergency room for worsening symptoms, she died at home. At autopsy, there was a florid, systemic proliferation of polyclonal plasma cells and immunoblasts infiltrating nearly every organ and tissue of the body, most notably the lymph nodes and spleen. The polyclonal nature of the process was confirmed by immunofixation electrophoresis and immunohistochemistry. Cases of fatal polyclonal systemic immunoblast proliferations are extremely rare, and the trigger for such proliferations is not always known. We review the literature on this unusual entity and discuss the clinical and pathologic findings.

Trophoblastic microemboli as a marker for preeclampsia-eclampsia in sudden unexpected maternal death: a case report and review of the literature.

The authors report the case of a 25-year-old white woman at 7 months' gestation who died suddenly and unexpectedly at home. Anatomic findings at autopsy included a tongue contusion, glomerulonephritis, changes indicative of systemic hypertension, and trophoblastic microemboli in the lungs. Review of the prenatal care record disclosed 3+ proteinuria 2 days before death. The features of the postmortem examination were consistent with clinically undiagnosed preeclampsia-eclampsia and glomerulonephritis. The authors discuss the rarity of fatal preeclampsia-eclampsia, the contribution of concomitant glomerulonephritis, and the significance of trophoblastic microemboli in the lungs.

Homicidal cardiac lacerations in children.

We report six cases of intentionally inflicted cardiac laceration. The victims ranged in age from 9 weeks to 2 1/2 years. Five victims were girls and in five cases the right atrium was lacerated. The left ventricle was lacerated in the other case. In the three cases with a confession, one victim each was struck with a fist, stomped, and kicked. Four patients had rib fractures, with at least two fractures in each case. Cardiac rupture from blunt trauma most commonly results from compression of the heart between the sternum and vertebral column, but may also occur from compression of the abdomen or legs, deceleration, blast injury, puncture of the heart by a fractured rib, and rupture through a resolving contusion. Accidentally acquired cardiac lacerations usually result from motor vehicle accidents or similarly severe forces. In children there are neither well documented cases of cardiac laceration nor of rib fractures from cardiopulmonary resuscitation. Cardiac lacerations, as with other types of severe trauma acquired at home, are almost never accidental.

Pituitary adenomas that produce adrenocorticotropic hormone and alpha-subunit: clinicopathological, immunohistochemical, ultrastructural, and immunoelectron microscopic studies in nine cases.

Eight surgical and one autopsy specimen of pituitary adenomas (six cases of Cushing's disease, two of Nelson's syndrome, and one of hypopituitarism) were studied by histochemical, immunohistocytological, and ultrastructural methods. Eight tumors showed the characteristic histochemical profile of corticotroph adenoma--amphophilic to basophilic, and periodic acid-Schiff-positive to some extent. In all tumors, immunohistochemical studies revealed adrenocorticotropic hormone (ACTH) and alpha-subunit in the cytoplasm of some adenoma cells. By electron microscopy, seven tumors were found to be monomorphous; six were typical corticotroph adenomas and one was a subtype II silent corticotroph adenoma. One unique lesion was bimorphous--i.e., composed of corticotrophs as well as cells resembling glycoprotein cells. Immunoelectron microscopy by the double-labeling immunogold technique, performed on one corticotroph adenoma, demonstrated the presence of ACTH and alpha-subunit not only within the same adenoma cells but also within the same secretory granules. The cytogenesis of ACTH alpha-subunit tumors, a rare form of plurihormonal adenoma, remains to be elucidated. The duration of disease associated with these tumors exceeded the duration in patients with ordinary corticotroph adenomas. Given the low frequency with which increases in serum alpha-subunit are detectable in patients with such tumors--13% in this series--hormone production is not recognized at preoperative evaluation.

Postoperative adjuvant therapy of rectal cancer: an analysis of disease control, survival, and prognostic factors.

Between 1976 and 1984, 139 patients with rectal cancer were treated with complete surgical resection and postoperative adjuvant pelvic radiation therapy with or without chemotherapy. In this group, tumor extended beyond the bowel wall or involved lymph nodes or both. Irradiation was begun between 15 and 182 days postoperatively (median delay, 42 days). The radiation was delivered with 4-, 6-, or 10-MV photons given 5 days per week at 1.8 to 2.0 Gy per fraction. Total doses ranged from 3.8 to 64.4 Gy (median, 50 Gy). The fields were AP:PA in 49 and AP:PA plus laterals in 90. Forty-four received concurrent chemotherapy: 5-fluorouracil and semustine in 37, and 5-fluorouracil alone in seven. Follow-up in survivors ranged from 2 to 10 years (median, 4.2 years). This analysis includes all failures, both initial and subsequent sites of failure. Local failure occurred in 30 (22%) of the 139 patients overall, 6 (18%) of 33 in Stage B-2, 1 of 3 in Stage B-3, 2 (10%) of 20 in Stage C-1, 20 (26%) of 76 in Stage C-2, and 1 (14%) of 7 in Stage C-3. Five-year actuarial survival was 59% overall, 82% in Stage B-2, 79% in Stages B-2 and B-3, 89% in Stage C-1, 41% in Stage C-2, and 42% in Stages C-2 C-3. The following prognostic factors were independently associated with poorer survival and increasing distant failure: lymph node involvement, tumor extension beyond the bowel wall, and high histologic grade. Use of chemotherapy was associated with a significant improvement in survival and decrease in distant failure. No single factor was significantly associated with local failure. Adequate perineal coverage after combined abdominoperineal resection yielded significantly fewer perineal failures. Overall, serious complications developed in 7%, but none was fatal. Treatment recommendations and optimal treatment techniques are discussed.

Isolated fibromuscular dysplasia of the coronary arteries with spontaneous dissection and myocardial infarction.

Fibromuscular dysplasia (FMD) is a segmental, nonatherosclerotic vascular disease of unknown etiology. Both the renal and extrarenal arterial FMD may have focally deficient or absent muscular media, and spontaneous dissection is a serious complication of this arterial wall abnormality. Although FMD may be found in virtually any small and medium-sized arteries, to our knowledge, FMD of the coronary arteries previously has not been documented convincingly in the literature. This article describes one such unusual occurrence of FMD in the coronary arteries with spontaneous dissection and myocardial infarction.