Interleukin-6 exacerbates early atherosclerosis in mice.

Acute-phase proteins, which respond to systemic proinflammatory cytokines such as interleuken-6, are elevated in cardiovascular disease and are predictive markers of future ischemic events, even over decades. This suggests a role for proinflammatory cytokines and/or acute phase proteins in early lesion development. To explore this issue, we fed C57Bl/6 and nonobese diabetic male mice high-fat (20% total fat, 1.5% cholesterol) diets and ApoE-deficient male mice both high-fat and normal chow diets for 6 to 21 weeks, injecting them weekly with either 5000 U recombinant interleukin-6 (rIL-6) or saline buffer. Blood was collected when animals were euthanized and assayed for cytokines, acute-phase proteins, and cholesterol. Across all mice, IL-6 injection resulted in significant increases in proinflammatory cytokines (IL-6, 4.6-fold; IL-1beta, 1.6-fold; and tissue necrosis factor-alpha, 1.7-fold) and fibrinogen (1.2-fold) and with decreased concentrations of albumin (0.9-fold) in plasma. Total cholesterol levels were unchanged between rIL-6-treated and nontreated groups. Serial sections through the aortic sinus were stained with oil red O to detect fatty streaks, and area of the lesions was determined by image analysis. Although no fatty streaks were detected in the nonobese diabetic mice with or without rIL-6 treatment, rIL-6 treatment increased lesion size in C57Bl/6 and ApoE-deficient mice 1.9- to 5.1-fold over lesions in saline-treated animals. These results suggest that under the appropriate circumstances changes in circulating proinflammatory cytokines and acute-phase proteins may be more than just markers of atherosclerosis but actual participants in early lesion development.

Angiogenesis as a prognostic marker in early head and neck cancer.

Experimental evidence suggests that tumor growth beyond the earliest stages is dependent on angiogenesis, or neovascularization, and that angiogenesis may also promote metastasis. Recent clinical studies demonstrate that angiogenesis is a prognostic marker in breast, lung, and prostate cancer. To investigate whether tumor angiogenesis also correlates with metastasis and survival in early head and neck carcinoma, we quantified the microvascularity of 106 primary carcinomas prior to treatment and correlated the counts with eventual outcome after 3 to 15 years of follow-up. Microvessels were stained immunocytochemically for von Willebrand factor and then counted by light microscopy. Microvessels were counted per 200x and 400x fields, and their density was graded from 1 to 4, in the area of most intense neovascularization. We found that neither microvessel counts nor density grades correlated with metastatic disease, local recurrence, or survival in early head and neck carcinoma. These results are in contradistinction to those recently reported for other tumor sites.

Fatal hemorrhage caused by varicose veins.

Varicose veins are a common, worldwide medical problem, but are generally considered non-life-threatening. We report three cases of fatal hemorrhage resulting from varicose veins and review the literature. The pathology of acute perforations onto the skin surface in varicose venous disease is described.

The nasogastric tube syndrome.

The nasogastric tube can produce sudden, life-threatening bilateral vocal cord paralysis and is often an unrecognized cause of this clinical entity. The pathophysiologic mechanism is thought to be paresis of the posterior cricoarytenoid muscles secondary to ulceration and infection over the posterior lamina of the cricoid. Since our initial report of this entity in 1981, several cases have been photo-documented. Study of whole organ sections of an involved larynx have demonstrated the histopathology. Diabetic renal transplant patients appear to be particularly susceptible to the condition, due to prolonged gastroparesis and requirement for nasogastric tube drainage. Esophagoscopy should be performed promptly in these patients when pharyngodynia, hoarseness, or evolving stridor present in the postoperative period.

Hypersensitivity myocarditis and hepatitis associated with imipramine and its metabolite, desipramine.

We present two cases of myocarditis and hepatitis with histologic characteristics of hypersensitivity-mediated drug reactions associated with imipramine and its metabolite, desipramine. In one case, death was directly attributed to myocarditis; in the second case, the patient died of an acute myocardial infarct, but myocarditis may have played a contributory role. One patient was taking imipramine, and therapeutic concentrations of imipramine and desipramine were documented in postmortem blood. The other patient was receiving desipramine documented by in-patient hospital medication records. Both cases had liver lesions associated in the medical literature with adverse drug reaction to imipramine. Although myocarditis has been previously associated with amitriptyline, these cases appear to be the first reported in association with imipramine/desipramine. The fact that one patient was taking only desipramine suggests that it may be the offending agent.

Method for estimating right ventricular volume by planes applicable to cross-sectional echocardiography: correlation with angiographic formulas.

Right ventricular (RV) volumes determined by echocardiography were compared with those measured using established angiographic formulas. RV cast displacement volumes were first correlated with data derived from radiographic images of the casts corresponding to standard angiographic RV views. Four established angiographic formulas (Ferlinz, Boak, Fisher and Thilenius) correlated well with cast volume, with the corrected prism method of Fisher showing a best fit (r = 0.98, y = 1.1 + 0.9 x, standard error of the estimate = 3.6). Cast volumes calculated using our echocardiographic formula were then examined relative to the volumes derived from radiographic images of the RV casts. Volumes calculated using the corrected area-length Thilenius formula correlated best with those obtained using our derived 2-dimensional echocardiographic formula (r = 0.96, y = 4.6 + 1.0 x, standard error of the estimate = 6.8). These data confirm that volume calculated using the suggested optimal echocardiographic formula correlates well with volume obtained using derived angiographic data. Accordingly, confirmation in humans by the use of angiography is a rational step.

Pathoanatomic correlates of regional left ventricular wall motion assessed by equilibrium radionuclide angiocardiography: a postmortem correlation.

The pathoanatomic correlates of qualitative assessment of regional wall motion (RWM) on routine equilibrium radionuclide angiocardiography (ERNA) were evaluated in 62 patients who had ERNA within 3 months before they died. Of 51 patients with abnormal RWM, 46 (90%) had gross myocardial lesions at autopsy. Of 11 patients with normal RWM, 9 (82%) had normal myocardium. Complete agreement of RWM with postmortem findings in all left ventricular segments occurred in 32% of the patients. Compared with postmortem findings, abnormal RWM on ERNA overestimated the number of macroscopically abnormal segments in 21% of the patients and underestimated in 47%. Of 372 segments analyzed, the overall sensitivity, specificity and predictive value of abnormal RWM on ERNA for detecting gross myocardial infarction or fibrosis was 73%, 75% and 83%, respectively. There were 35 false-positive segments (9%) (15 patients). In 27 of these segments (77%), severe stenosis of the coronary artery supplying the segment or electrocardiographic left bundle branch block could explain these findings. There were 61 false-negative segments (16%) (30 patients). In 55 of these segments (90%), either nontransmural infarction or masking by severe adjacent asynergy provided a potential explanation. Thus, qualitative analysis of RWM on routine ERNA correlates well with postmortem findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Iatrogenic cardiac herniation: post mortem case.

A case is presented in which sudden cardiac death was caused by herniation of the heart through a pericardial incision following a gunshot wound to the chest, resulting in acute compression of the coronary arteries. At autopsy the heart protruded through the pericardial incision, which appeared to have elongated, and the cause of death was thought to be acute myocardial infarction secondary to coronary artery constriction.

Sudden unexpected death due to asymptomatic cardiac rhabdomyoma.

A case of cardiac rhabdomyoma producing sudden unexpected death in an asymptomatic six-year-old boy is reported. Cardiac rhabdomyoma is a rare tumor, and its ability to cause sudden unexpected death in children beyond infancy is not generally known. The great majority of afflicted patients die in the early infancy; few survive beyond five years of age. The signs and symptoms present in most cases are said to be due to interference of interaction blood flow or to interruption of the cardiac conduction system. Numerous cases have been clinically misdiagnosed because of this tumor's ability to mimic other cardiac disease.

Coronary artery dissection secondary to coronary arteriography: presentation of three cases and review of the literature.

Three cases of coronary artery dissection secondary to coronary arteriography are presented. Two of these include autopsy material demonstrating medial degeneration in the coronary arteries, which may have predisposed these arteries to dissect. The literature on catheter-induced coronary artery dissection is reviewed and an analysis is presented.

Pyelonephritis associated with Legionella pneumophila, serogroup 4.

A patient with bladder carcinoma metastatic to lung and brain died of pneumonia. Autopsy examination showed a confluent bronchopneumonia with several small abscesses and acute pyelonephritis with abscess formation. Legionella pneumophila, serogroup 4, was isolated in pure culture from lung tissue postmortem and was also shown by direct immunofluorescence in the kidney and spleen. In the kidney, the organism was noted in areas of acute pyelonephritis. This represents the first case of an extrathoracic inflammatory lesion associated with L. pneumophila.

Stability of aflatoxin M in milk.

This three-part study was designed to determine aflatoxin M recovery from pasteurized and/or stored cow's milk. (a) Aflatoxin M was added to samples of raw Holstein milk at a concentration of 2.0 mug/liter. Half of each sample then was pasteurized at 63 C for 30 min, and both raw and pasteurized portions were stored at 4 C up to 17 days. (b) Samples of raw milk, pasteurized (77 C, 16 s) skim milk, dry cottage cheese curd, and cottage cheese whey were taken from a commercial operation in an area in which natural contamination had been encountered. (c) Milk from a cow dosed with aflatoxin B1 was stored frozen (-18 C) in bulk and in assay-size sample containers for 120 days. Aflatoxin M was recovered completely after either storage or pasteurization in (a) and (b). In (c), a recovery deficiency was detectable after 68 days of storage, which increased to 45% of the original value by 120 days. These observations differ from those of others in that loss of aflatoxin M was significant after pasteurization or storage of raw milk, totaling 87% loss after 120 days of frozen storage. Aflatoxin M partitioning between curd and whey in the preparation of cottage cheese agrees with more recent studies, but differs from previous reports. Three possible explanations for the differences are offered.

Experimental induction of atheroarteriosclerosis by the synergy of allergic injury to arteries and lipid-rich diet. 3. The role of earlier acquired fibromuscular intimal thickening in the pathogenesis of later developing atherosclerosis.

Clinicopathologic evidence suggests that diffuse intimal thickening, a type of arteriosclerosis without manifest lipid deposit, may predispose to later developing atherosclerosis in man. This hypothesis was tested in the following experiments. Injury to coronary arteries of rabbits was induced by immunologic means, and arterial lesions were allowed to heal for many weeks. One group of animals was then sacrificed, and in their coronary arteries were found numerous fibromuscular intimal lesions closely resembling diffuse intimal thickening in man. The remaining rabbits were fed a cholesterol-supplemented diet for 80 days and then sacrificed. Fibromuscular intimal lesions of coronary arteries were found in these rabbits also. However, approximately two-thirds of these lesions were found to contain lipid, and many closely resembled coronary atherosclerosis in man. Further analysis of the data indicates that the atherosclerotic lesions in the rabbits evolved from immunologically induced fibromuscular intimal lesions which later and preferentially accumulated lipid in the presence of hypercholesterolemia. Results of these experiments suggest that in man fibromuscular intimal lesions, and in particular diffuse intimal thickening, acquired earlier in life can later accumulate lipid preferentially and thus redispose to atherosclerosis.