Areas Of Coagulative Necrosis Research Articles

Herpes simplex hepatitis in apparently immunocompetent adults.

A study of eight cases of herpes simplex hepatitis in apparently immunocompetent adults is presented. The clinical features were nonspecific and were usually those of a severe systemic infection, mimicking septic shock. However, the histologic features were distinctive, with randomly distributed patchy areas of coagulative necrosis surrounded by hepatocytes containing viral inclusions. Viral particles could be identified by electron microscopy and Herpes simplex antigens by immunohistochemistry, but these were not necessary for diagnosis. The light microscopic morphologic features are so distinctive that if these are recognized in a biopsy, the diagnosis of herpetic hepatitis can be made and anti-viral therapy may be instituted.

Effects at the periphery of the laser lesion in human brain and its tumors after CO2, Nd:YAG, and CO2 high-peak pulsed radiation.

The histological changes in various tissues irradiated with lasers are well known. Our own previous observations with the optical microscope confirm those already reported in the laser literature. If tissue is treated with various laser sources, the results are similar, with the characteristic three layers from the outside toward the inside of carbonization, coagulative necrosis, and edema. Otherwise, only the shapes and sizes of the lesions differ, with craters of different depths. In this paper, we report an ultrastructural study of the changes occurring in the periphery of the laser lesions in both normal human brain and neoplastic tissues (gliomas and meningiomas). Continuous-wave CO2 and Nd:YAG lasers were used at different exposure times and powers and the effects of high-peak pulsed CO2 laser radiation has also been investigated. The study, performed during neurosurgical procedures was mostly focused on microcirculation at 1.5-3 mm outside the area of coagulative necrosis, at the level of the edema zone. Only lesions of the blood brain barrier are produced in normal brain by CO2 radiation (power ranging from 40 to 80 W; exposure time from 3 to 10 seconds). The same results were achieved by Nd:YAG radiation of short duration (3 seconds) regardless of the power used (40 and 80 W). Long-duration Nd:YAG radiation (10 sec; power: 40-80 W) produces endoluminal phenomena leading to the complete occlusion of the capillaries. In neoplastic brain tissues, microcirculation does not seem to be impaired by CO2 radiation. More marked lesions are produced in tumors even after Nd:YAG short-time radiation. Endoluminal obliteration is observed in meningiomas and perivascular hemorrhage occurs in highly vascularized gliomas. According to these results, the risk of delayed post-operative hemorrhages, noticed in some patients with glioblastoma operated on by Nd:YAG lasers, suggests that residual tumor in the cavity should be treated by CO2 laser because of its minimal damage of microcirculation.

Milliwatt carbon dioxide laser and hepatic surgery in mice: surgical technique and pathology.

The milliwatt carbon dioxide laser was used to induce focal lesions and to perform wedge resections in the livers of 75 strain A mice. The procedures were feasible and well tolerated by the mice, with only one postoperative death in the wedge resection group in an early experiment. The hepatic lesions produced by the laser were characterized histologically by an inner area of vaporization, an intermediate area of coagulation necrosis, and an outer rim of cells with variable damage. The lesions healed by fibroblastic proliferation and scar formation with no hepatocytic contribution. The small vessel and bile ductule sealing effect of CO2 laser, together with the sound healing of laser-induced wounds, highlights the usefulness of this modality in liver surgery in general, and suggests its particular application in the treatment of liver trauma and a variety of hepatic focal lesions, neoplastic or otherwise.

Early myocardial infarction. A feasible histologic diagnostic procedure.

The Barbeito-López trichrome stain (BLTS) was compared with hematoxylin and eosin (HE), the basic fuchsin picric acid (BFP) and nitro-blue tetrazolium (NBT) dye tests. Two types of hearts were studied: myocardial necrosis induced by isoproterenol (ISP) in rats and human hearts with early coagulation necrosis (Early CN). The BLTS was much more sensitive than HE for diagnosis of Early CN in rats. By 24 hours, both BLTS and HE showed established coagulation necrosis (Established CN) although BLTS did so more clearly. In human material BLTS was a useful indicator of Early CN. It showed patchy areas of coagulation necrosis in the cytoplasm of damaged myocardial cells which were not visualized with HE. Normal myocardium remained green or pale blue. Early CN appears as patchy yellow areas while the remainder of the cytoplasm stains green. Established CN appears "golden yellow" or "orange yellow".

Toxicity of the mycotoxin, cyclopiazonic acid, to Sprague-Dawley rats

Groups of male Sprague-Dawley rats received po doses of cyclopiazonic acid (CPA) on four consecutive days at 0.0, 0.2, 2.0, 4.0, or 8.0 mg kg −1 days −1. Clinical signs of toxicity were observed only in the two highest dose groups. Rats in the highest dose group exhibited abnormal behavior, diarrhea, and other signs of toxicity after several days of dosing, and most were moribund before the last scheduled dose was administered. Liver and spleen were more severely affected than other organs in the two highest dose groups. Livers contained diffuse pycnotic nuclei and, in some high-dose rats, focal areas of coagulative necrosis. In the highdose group aspartate and alanine aminotransferase activities were elevated, cytochrome P-450 concentration was decreased, and glutathione S-transferase activity was unchanged. Spleens were hemorrhagic and white pulp contained necrotic lymphocytes. White cell counts were decreased in a dose-related manner in the two highest dose groups. The gastrointestinal tract of high-dose rats contained pycnotic nuclei, and sites of necrosis were observed in stomach, but these lesions were limited to several animals, and were generally mild. Pathologic changes in conjunction with decreased feed and water intake probably contributed to the general deterioration of high-dose rats that resulted in death.

Myocytolysis (vacuolar degeneration) of myocardium: Immunohistochemical evidence of viability

Human myocardium with focal myocytolysis (vacuolar degeneration, colliquative myocytolysis) was examined by routine light microscopy and by immunoperoxidase staining techniques for creatine kinase (CK) M and B, myoglobin, lactate dehydrogenase (H4)(LDH-1), and aspartate aminotransferase (AST, GOT). Sections of myocardium were selected from autopsy and surgical specimens from patients with and without clinical morphologic evidence of ischemic heart disease. Areas of coagulation necrosis showed loss of enzyme staining, while both normal and myocytolytic cells stained darkly. These results indicate that fibers with myocytolysis retain enzymes and other proteins, indicating sarcolemmal integrity, which is not present in fibers with coagulation necrosis. The implication of these findings is that fibers with myocytolysis are viable; thus, myocytolysis may be a reversible form of myocardial alteration that does not necessarily lead to cell death and eventual myocardial fibrosis.

Quaternary Ammonium Compound Toxicity in Chickens

Two commercial White Leghorn flocks of 41,000 and 57,000 25-week-old hens experienced death losses of 676 and 1,089 birds in a week. Six birds from each flock were presented for necropsy to the Animal Disease Diagnostic Laboratory at Purdue University with a clinical history of excessive deaths, unsatisfactory production, and dehydration. Gross lesions were present on the tongue and on oral and pharyngeal mucosa as uniformly pale or white areas with interspersed multifocal sites of ulceration. Other changes were cyanotic, shriveled combs and wattles and ruptured ovarian follicles with concurrent egg yolk peritonitis. Microscopic examination revealed large areas of coagulative necrosis with multifocal epithelial ulceration of the oral and pharyngeal mucosae. There was an intense inflammatory, heterophilic response at the periphery of affected areas. Alterations in the abdominal viscera were limited to egg yolk peritonitis. The high death rate and oral lesions were attributed to accidental use of excessive levels of a quaternary ammonium disinfectant in the drinking water.

Experimental cobalt cardiomyopathy in the dog: A model for cardiomyopathy in dogs and man

The effect of cobalt cardiomyopathy was studied in 21 mongrel dogs. The dogs were divided into four groups; Group A (5 dogs) contained the normal controls, Group B (5 dogs) was fed a protein- and thiamine-deficient diet, Group C (5 dogs) was fed a normal diet and given cobalt by iv infusion, and Group D (6 dogs) was fed a protein-and thiamine-deficient diet and given cobalt by iv infusion. Cobalt (500 mg) dissolved in saline was given iv through a chronic indwelling venous catheter in the femoral vein for a 10-week period. No changes were seen in the control groups. The primary clinical findings in dogs in Groups C and D were dyspnea, exercise intolerance, and mild systolic murmurs with a prominent gallop rhythm. Abnormal electrocardiograms illustrating sinus tachycardia and lowered QRS complexes in limb leads were characteristic as was microcardia as visualized in thoracic radiographs, elevated left ventricular end diastolic pressure, lowered systolic pressures, angiographic evidence of a small end systolic volume, and slightly enlarged left diastolic volume. The dogs were necropsied in the 10th week, 24 hr after the last infusion and the heart was fixed in formalin, processed, and examined by light microscopy. The principle gross lesions in dogs in both Groups C and D were marked right ventricular dilatation, slight hypertrophy of the left ventricle, uniform paleness of the myocardium and dilatation of both atria. Histologic lesions included vacuolation of myofibers, loss of myofibers with hypertrophy of remaining fibers, and randomly scattered areas of coagulation necrosis. These findings suggest that experimental cobalt-induced cardiomyopathy in the dog is similar to alcoholic cardiomyopathy in man.

Tissue alterations induced by radio- and chemotherapy in brain with malignant gliomas.

35 brains with malignant gliomas treated by surgery, radiotherapy and chemotherapy and processed by means of the "complete study" technique have been studied. The preliminary results are reported. Many types of changes have been observed. Areas of coagulative necrosis with vessel alterations and teleangectasias are present around the tumor in many cases. Different pathologic aspects are observed distant from the tumor. Edema both in the homo - and contralateral hemisphere is constantly present. Severe edema with demyelination, axon disappearance and loss of cells is frequently found associated with prolonged survival. Often it is accompanied by wide or small areas filled with macrophages. Spongio-necrosis in the white matter of contralateral temporal lobe has been observed in two cases and telangiectasias areas have been found in another one. The relation between changes and treatment is discussed.

Effect of CO2 laser on skin lymphatics

The effects of a CO2 laser on lymphatics and small blood vessels were studied by electron microscopy. Laser incisions were made on white rats at different sites of the skin and of the mucous membranes. Electron microscopically, three zones of the lased tissue were observed: the first superficial layer consisted of a carbonized skeletal rest; the second layer was an area of coagulative necrosis; the third and deepest layer was characterized by edema of varying degrees. Small blood vessels were completely filled with erythrocyte fragments leading to an apparent occlusion of the vessels. On the other hand, lymphatic vessels of comparable size seemed to be less damaged and their lumina appeared to be open and not occluded. Our results indicate that in tumor surgery with the laser scalpel, the propagation of cellular material, e.g. tumor cells, cannot be excluded with certainty.

Legionnaires' disease. Postmortem pathologic findings of 20 cases.

From March 1977 to December 1978, postmortem examination was performed at Wadsworth Veterans Administration Medical Center for 20 patients who had had nosocomially acquired Legionnaires' disease. Seventeen patients died during the acute illness due to Legionnaires' disease, and three patients died after clinical resolution of the acute process. The only consistent postmortem findings were limited to the lungs. Confluent bronchopneumonia, and less frequently lobar pneumonia, was present in most cases. Although a spectrum of microscopic pulmonary findings was observed, the characteristic histologic features of acute Legionnaires' disease were an extensive intra-alveolar exudation of macrophages and neutrophils in varying proportions, erythrocytes, and fibrin. Lysis of the inflammatory cells was frequently found. Areas of coagulative necrosis of the lung parenchyma and edematous thickening of the alveolar septa were typically seen. Microscopy of lung tissue from the three patients who died after clinical resolution of the acute process revealed organized pneumonia, with patchy organization of the intra-alveolar exudate and focal obliteration of the alveolar septal framework. Associated postmortem findings were fibrinous endocarditis in one case and hemorrhagic infarction of the adrenal glands in two cases. Electron-microscopic examination of the lungs revealed as many as 23 separate bacillary profiles within a single macrophage. Septate binary fission or spore-like structures were not observed.

Tissue damage from electrosurgical power output variations in hamster tongues

An investigation was designed to determine the differences in the amount of tissue damage produced by variations in the amount of cutting power delivered to the hamster tongue with electrosurgery. By dividing the power of an electrosurgical instrument into 5 W intervals, from the lowest setting which would produce a cut up to the 50 W setting, histometric comparisons were made in the hamster tongue. Histologic analysis showed the following: 1. The 30 W power interval produced less tissue damage than any other power interval. 2. The 25 and 35 W intervals produced significantly greater damage than the intervals from 40 thorugh 50 W. 3. Histologically the experimental defect showed an area of coagulation necrosis approximately 50 mu wide along the margin of the incision. Tissue damage decreased laterally and inferiorly from the surface of the defect except at the 30 W setting, where the damage in the epithelium and the damage in the connective tissue were essentially equal. 4. There is some validity to the sparking-dragging test for setting the power interval of an electrosurgical instrument. 5. Higher power values which produce excessive sparking should be avoided by the clinician during electrosurgery due to the imprecise nature of the clinical incision.

Methotrexate encephalopathy: A neuropathologic study

The present report is a neuropathologic study of three patients who died from a severe form of necrotizing encephalopathy following intrathecal methotrexate therapy and craniospinal irradiation for acute lymphoblastic leukemia. During the early phase the lesion presented as multifocal coalescing areas of coagulation necrosis in the deep white matter. In the diseased areas the myelin was lost and the axons were severely swollen and fragmented. During the late stage the white matter was reduced to a thin gliotic calcified layer. The pathogenesis of this lesion is unclear, but the preferential involvement of the white matter with sparing of the cortical gray matter and basal ganglia makes it unlikely that direct chemical injury is the cause. The distribution of the lesion suggests a vascular disturbance due to endothelial injury caused by interaction of the methotrexate with tissue infiltrated by leukemic cells and altered by irradiation.

A histologic comparison of effects of electrosurgical resection using different electrodes

Electrosurgery is a helpful adjunct to restorative dentistry, yet there often is damage to underlying connective tissue. In this study, small loop electrodes demonstrated a wider area of coagulation necrosis than was found with needle electrodes. In all instances, coagulation necrosis as a result of heat was noted. To help minimize tissue damage, very fine wire electrodes should be used, and entry into deep tissue layers should be avoided.

Necrotizing encephalopathy following intraventricular instillation of methotrexate.

Three children with posterior fossa tumors and evidence of ventricular obstruction were treated by instillation into the lateral cerebral ventricle of methotrexate in total doses ranging from 86 to 190 mg given over 3 to 13 months. All three patients developed neurological signs of bilateral cerebral or upper brainstem dysfunction. In two, unusual lesions consisting of areas of coagulation necrosis with fibrinoid degeneration and thrombosis of blood vessels and reactive astrocytosis involved the periventricular white matter. The third patient died a year later; his brain showed periventricular necrosis without blood vessel changes. Other patients without ventricular obstruction were treated with comparable intraventricular doses of methotrexate without incident. The most likely cause of the necrotizing encephalopathy was absorption of toxic doses of methotrexate through the lateral ventricular wall in patients with ventricular obstruction.

Pathogenesis of bile-induced acute pancreatitis in the dog

A series of recent observations on different aspects of the chemistry and metabolic actions of bile have led us to investigate the possibility that bile may induce pancreatitis through the physicochemical detergent properties of its salts. To determine the relative importance of proteolytic enzymes on the one hand, and the detergent action of bile on the other, in the pathogenesis of bile-induced experimental pancreatitis in the dog, the early morphologic changes (1–30 min) produced by the intraductal injection of the following substances were investigated: (1) autogenous bile; (2) bile salt; (3) an anionic detergent, sodium lauryl sulfate (SLS); (4) trypsin; (5) a cationic detergent, cetrimide; (6) a neutralized mixture of SLS and cetrimide; and (7) saline solution. Autogenous bile, bile salts and SLS produce pancreatitis of similar morphologic appearance, characterized by punched-out areas of coagulation necrosis. Trypsin-induced pancreatitis was distinctly different from that produced by bile, bile salts and SLS. In trypsin pancreatitis, irregular areas of necrosis and hemorrhage were seen. Inactivation of the detergent activity of SLS by mixing it with the cationic detergent, cetrimide, reduced the capacity of SLS to induce pancreatitis similar to that induced by bile and bile salts. These data seem to indicate that the early phases of bile-induced pancreatitis in our experiments are unlikely to result from the liberation of trypsin, but are related instead to the detergent activity of bile salts.

Pseudotumor resulting from a fresh renal infarct.

The angiographic appearance of a typical hypernephroma is characteristic. However, while hypernephromas with atypical vascularity, as well as other malignant and benign renal tumors containing only a few abnormal vessels, are easily differentiated from renal cysts, they are sometimes confused with so-called pseudotumors (1). In a pseudotumor, normal renal parenchyma shows localized contrast material staining which might be mistaken for a true tumor (6, 10, 14). Most frequently, normal variations such as hypertrophy of the renal parenchyma and lobulation of the kidneys or scar formation in the vicinity of normally functioning parenchyma result in this misleading appearance. Recently, we encountered a case in which a lesion diagnosed angiographically as an atypical renal tumor was found at surgery to be a fresh renal infarct. Case Report A 55-year-old Caucasian male with a 20-pound weight loss during the previous year complained of right upper quadrant pain. At physical examination, the only abnormal finding was slight hepatomegaly. A radioisotope liver scan was compatible with multiple metastases throughout the liver. An attempt to perform selective celiac axis arteriography in order to confirm the findings of the liver scan was unsuccessful, so contrast material was injected into the abdominal aorta. The angiogram showed a normal celiac axis and no evidence for significant hepatomegaly or for hepatic masses. It did, however, raise the question of a tumor stain in the midportion of the right kidney, and twenty-four hours later selective right renal arteriography was performed. This study showed a mass in the midportion of the right kidney which had displaced several intrarenal branches of the renal artery. Irregular small vessels in the periphery of the lesion were interpreted as tumor vessels. During the parenchymal phase, there was prolonged diffuse contrast material retention in this mass (Fig. 1). These findings were thought to represent an atypical tumor which had possibly produced liver metastases. At laparotomy, a radical right nephrectomy was performed. There was no evidence of liver metastases. Macroscopic and microscopic examination of the kidney showed a wedge-shape area of ischemic coagulation necrosis in its midportion in exactly the same area as had been stained with contrast material on the angiogram (Fig. 2). Slight fibroblastic proliferation at the margin of the infarct was noted. It was estimated that the infarct had occurred approximately two to six days prior to the aortography. No gross thrombi or arteriosclerotic changes were noted in the renal arteries. Histologically, the medium-size arteries showed arteriosclerotic thickening with slight-to-moderate intimal proliferation. A marginally organizing thromboembolus was observed within a hilar artery. Discussion This is a case of a recent renal infarct which angiographically resembled a renal tumor.

Pulmonary lesions in dogs with experimental and naturally occurring toxoplasmosis.

The lungs of 92 dogs with confirmed toxoplasmosis were studied. Focal areas of coagulation necrosis, adjacent to and involving small vessels and bronchioles, and exudation of fibrin were the characteristic lesions produced by T. gondii in the lungs of dogs with both experimentally induced and naturally occurring infections. The inflammatory response to the areas of necrosis was minimal. Dogs inoculated intratracheally developed more extensive pulmonary lesions with greater numbers of T. gondii than dogs inoculated by the intravenous or subcutaneous route. Toxoplasma were not demonstrated in the pulmonary lesions after the 16th day following inoculation. Distemper was a concurrent infection in 20 cases of naturally occurring toxoplasmosis. The lesions produced by the two etiologic agents were distinctly different. Based on the severity of pulmonary lesions the dogs appeared to be primarily infected with toxoplasma.

The Histopathology of Experimental Schistosomiasis

Summary and Conclusion 1. Histological sections of livers from white mice infected with male or female Schistosoma mansoni, S. japonicum or S. haematobium, and with both sexes of S. mansoni or S. japonicum prior to egg deposition, were examined to study lesions associated with the presence of worms in the portal-mesenteric vessels in the absence of lesions produced by eggs. Most of this material came from S. mansoni infections. 2. In unisexual S. mansoni infections periportal infiltration of mononuclear and polymorphonuclear leucocytes appeared after 3 to 4 weeks in the majority of unisexual infections and increased in intensity in infections up to about 12 weeks in duration, after which it tended to become less intense and was predominantly mononuclear. 3. Cellular infiltration in the parenchyma of the liver, predominantly polymorphonuclear, occurred in some animals, apparently independent of extensions from the periportal infiltrations. These increased in frequency and intensity in infections up to about 12 weeks in duration, but were rare in infections 20 weeks or more in duration. 4. Areas of coagulative necrosis in the parenchyma of the liver were found in a considerable number of animals. They became invaded by polymorphonuclear leucocytes with later disappearance of liver cells and invasion of mononuclear and multinuclear cells. Worms were sometimes present in venules immediately adjacent to these lesions, giving the impression that they may have been infarcts initiated by temporary obstruction of the blood supply by the worms. 5. No evidence of development of cirrhosis of the liver was found in unisexual infections up to 95 weeks in duration. 6. Some of the unisexual infections with S. japonicum or S. haematobium showed the same types of lesions as those infected with S. mansoni. In general the lesions were less intense, but accurate comparison is not warranted. 7. In bisexual S. mansoni infections up to 5 weeks in duration periportal and parenchymal cellular infiltration and coagulative necrosis appeared earlier and were more frequent and intense than in unisexual infections of the same duration. Occasional mural thrombi were found in portal venules. 8. Some uninfected mice had mild degrees of periportal and parenchymal cellular infiltration, but areas of coagulative necrosis were not seen. 9. Although some infected mice failed to show any lesions in the liver, it seems possible that the intense cellular infiltrations and areas of necrosis were causally related to the presence of worms in the mesenteric-portal blood vessels.

BUBONIC PLAGUE IN SAN FRANCISCO.

The following three cases of bubonic plague have occurred in San Francisco since the last report on this subject byThe Journal: <h3>Case 16.</h3> —Lea Do Hen, aged 50, Mongolian, cigarmaker, had lived in California 28 years. His residence was 710½ Dupont street. Patient died Oct. 5, at 10 p. m. Examination of the body revealed a large bubo in the right inguino-femoral region. Incision disclosed a lymph node about the size of an egg, surrounding which the tissues were filled with a chocolate-colored fluid. The cut surface of the gland was very dark, purple and mottled, but substance fairly firm. A microscopical examination showed numerous bipolar-staining bacilli, decolorizing by Gram's method. Two guinea-pigs were inoculated with a glandular emulsion on Oct. 7. One of the pigs lived four and one-half days after inoculation. On examination there was found a large area of coagulation necrosis surrounding the point of inoculation