G. William Moore

The lung in systemic lupus erythematosus. Analysis of the pathologic changes in 120 patients.

The nature and frequency of pulmonary involvement in systemic lupus erythematosus (SLE) is controversial. We reviewed the clinical and pathologic features of 120 patients with SLE described in autopsy records at The Johns Hopkins Hospital to determine the pulmonary parenchymal changes that could be attributed directly to SLE. Each case was reviewed to determine the extent of extrapulmonic SLE and possible alternative explanations for the observed lung pathology. Moderate or severe pulmonary parenchymal alterations that were attributed to SLE were found in 22 patients (18 percent). Five patients with interstitial fibrosis, two with pulmonary vasculitis, and one with pulmonary hematoxylin bodies were attributable only to SLE, as were 11 of 15 (73 percent) patients with interstitial pneumonitis. Alternative explanations for findings previously attributed to SLE included congestive heart failure, renal failure, infection, aspiration, oxygen toxicity and increased intracranial pressure. Alveolar hemorrhage, thought to be a feature of acute lupus pneumonitis, was unexplained in only two of 29 (7 percent) patients, alveolar wall necrosis was unexplained in one of seven (14 percent) and edema was unexplained in three of 70 (4 percent). Hyaline membranes, present in four patients, were always explained. Pleuritis and pleural effusions were attributed to SLE in 22 of 36 (61 percent) and three of 28 (11 percent) patients, respectively. The findings suggest that many nonspecific pulmonary lesions previously attributed to SLE, such as alveolar hemorrhage, alveolar wall necrosis, edema and hyaline membranes, are probably secondary to intercurrent infection, congestive heart failure, renal failure or oxygen toxicity.

Infarct expansion: Pathologic analysis of 204 patients with a single myocardial infarct

The reasons for the marked variability in expansion of myocardial infarcts are unknown. To examine this question, the hearts in 204 patients with a single myocardial infarct, autopsied at The Johns Hopkins Hospital and studied after coronary arteriography and fixation in distension, were reviewed. There were 58 (28%) hearts with marked infarct expansion, 34 (17%) with moderate expansion and 112 (55%) with no or minimal expansion. The degree of expansion was greater in larger, more transmural infarcts (p less than 0.001). Infarcts with greater expansion had significantly more endocardial thrombus (p less than 0.001) and endocardial fibroelastosis (p less than 0.01). Larger heart weight and degree of left ventricular hypertrophy had a significant negative correlation with infarct expansion (p less than 0.05). A markedly greater degree of expansion was noted in the 101 infarcts (50%) caused by lesions in the distribution of the left anterior descending coronary artery as compared with the 57 infarcts (28%) secondary to right coronary lesions and the 46 infarcts (23%) in the distribution of the left circumflex coronary artery (p less than 0.001). The results show that expansion is associated with large infarcts but is less marked in hearts with ventricular hypertrophy. Expansion occurs predominantly in infarcts in the left anterior descending coronary artery distribution, that is, regions of the left ventricular myocardium with the greatest curvature. These results suggest that the degree to which an infarct expands may be influenced by the preinfarction thickness of the ventricular wall.

Pathogenesis of Persistent Left Superior Vena Cava with a Coronary Sinus Connection

The basis for persistence of the left superior vena cava (LSVC), usually associated with cardiac malformations, is poorly understood. We examined 351 staged, serially sectioned human embryos in the Carnegie Embryological Collection and 1208 specimens with congenital cardiovascular malformations in the Pathology Collection of the Johns Hopkins Hospital. A standardized questionnaire was answered for each embryo and autopsy case and a computer program was employed to tabulate concurrent anatomic features. In the normal embryos a symmetric venous system appeared with the heart tube at Carnegie stage 9; the sinoatrial junction translocated to the right and the relationship of the coronary sinus to the LSVC was established by stage 12. The LSVC was patent through stage 20 and subsequently underwent luminal obliteration by compression between the left atrium and the hilum of the left lung. Among the 1208 hearts with a congenital abnormality, 104 (9%) had a persistent LSVC with a coronary sinus connection. Statistically, significantly more frequent associations were found between persistent LSVC and atrioventricular canal defects, cor triatriatum, and mitral atresia and a significantly less frequent association was observed between persistent LSVC and atrial septal defect or patent foramen ovale as a primary defect. The normally late embryonic obliteration of the LSVC suggests that its persistence would be secondary to reduce cardiac compression or to blood flow redistribution at an early stage, and the malformations associated with persistent LSVC support that view. Identification of a persistent left superior vena cava with coronary sinus connection should suggest an associated malformation, especially atrioventricular canal, cor triatriatum, or mitral atresia.

Type and distribution of pulmonary parenchymal and vascular amyloid: Correlation with cardiac amyloidosis☆

Abstract The spectrum of amyloidosis was studied in 223 patients examined at autopsy at The Johns Hopkins Hospital since 1889. Of these patients, pulmonary involvement with amyloid was found in 68 patients including 31 with senile cardiac amyloidosis, 23 with primary amyloidosis, eight with myeloma associated amyloidosis, two with familial amyloidosis with polyneuropathy, three with isolated nodular pulmonary parenchymal amyloidosis and only one patient with secondary amyloidosis. The degree of pulmonary involvement ranged from either focal parenchymal or vascular amyloid to severe diffuse parenchymal and vascular amyloid. In general, cardiac amyloid involvement tended to parallel the pulmonary involvement and usually was more severe. Correlations between pulmonary amyloidosis and cardiac amyloidosis were statistically significant. Patients with primary amyloidosis, senile cardiac amyloidosis, myeloma associated amyloidosis, nodular pulmonary amyloidosis and familial amyloidosis with polyneuropathy had potassium permanganate-resistant amyloid. These findings suggest that the amyloid in these types of amyloidosis, in which pulmonary involvement is frequent, is a protein of either immunoglobulin origin or of a similar structure.

Risk Factors for the Development and Rupture of Intracranial Berry Aneurysms

Risk factors for the development and rupture of intracranial saccular (berry) aneurysms were identified in a case-control study of autopsy subjects. The development of berry aneurysms was positively correlated with increased frequencies of systemic arterial hypertension (p less than 0.001), cerebral artery atherosclerosis (p less than 0.05), and marked asymmetry of the cerebral vessels comprising the circle of Willis (p less than 0.005). In addition, patients with berry aneurysms more frequently had histories of persistent headache (p less than 0.001), pregnancy-induced hypertension (p less than 0.01), long-term use of analgesics (p less than 0.001), especially aspirin (p less than 0.05), and a family history of stroke (p less than 0.05). Factors associated with a decreased risk of berry aneurysms included treatment with insulin to control diabetes mellitus (p less than 0.005), leanness (p less than 0.05), chronic pancreatitis (p less than 0.001), malignant tumors (p less than 0.001), and moderate or severe coronary or renal atherosclerosis (p less than 0.05). Rupture of berry aneurysms was positively correlated with size (p less than 0.05) and the presence of multiple aneurysms (p less than 0.005), but also with long-term analgesic usage (p less than 0.05), excessive ethanol consumption (p less than 0.01), and fatty metamorphosis of the liver (p less than 0.01). The factors that predispose to rupture of berry aneurysms are interrelated in the sense that several of them are known to cause a decrease in the synthesis of prostaglandin E, whereas one of the factors that appears to be protective has the opposite effect. Marked and abrupt lowering of serum prostaglandin levels would cause dilatation of cerebral vasculature and increased cerebral blood flow; in the setting of hypertension, focal defects in cerebral arteries could develop, leading to the formation and subsequent rupture of berry aneurysms.

The liver in sickle cell disease: A clinicopathologic study of 70 patients

In clinical studies, frequent hepatic dysfunction associated with crises in sickle cell disease has been noted, but whether irreversible morphologic changes arise from these transient episodes is uncertain. We studied 70 patients with sickle cell disease (57 SS, 12 SC and one S-thalassemia (S-thal) hemoglobin) autopsied at The Johns Hopkins Hospital. They ranged in age from five months to 75 years (average 21 years) and 35 (50 percent) were female, In 64 patients (91 percent), livers were enlarged and had distention of Kupffer cells with phagocytized sickled red cells; this was massive in 10. In 19 patients (27 percent) the sinusoids were markedly distended with sickled red cells and appeared obstructed. Focal parenchymal necroses were present in 24 patients (34 percent) and were explained in 12, eight by cardiac dysfunction and four by sepsis. Reparative changes, portal fibrosis and regenerative nodules were each found in 14 patients (20 percent), only one of whom had a known history of viral hepatitis despite the frequency of transfusions. Cirrhosis of unknown cause was present in seven patients and cardiac cirrhosis in one. Cirrhosis with hemochromatosis was present in three patients and 30 others had parenchymal iron accumulation. Thus, unexplained hepatic necroses, portal fibrosis, regenerative nodules and cirrhosis were frequently encountered in these patients. This spectrum of liver disease appears to be best understood as a consequence of recurrent vascular obstruction, necrosis and repair arising as a component of sickle cell disease.

Shape of the human cardiac ventricles

Abstract Previous studies suggest that intramural myocardial architecture is arranged to maximize the efficiency of contraction. To examine the topography of the cardiac ventricles for a possible similar functional economy, measurements were made of the heart weight and ventricular wall curvature, thickness, chamber volumes and axial diameters in 80 hearts, with and without ventricular dilatation or hypertrophy, or both, that had normal coronary arteries and no myocardial lesions. Hearts in various positions of contraction were studied after postmortem arteriography and fixation in distension. Indexes of curvature-thickness were calculated from the measurements using the Laplace relation. The ventricles consist of three mutually intersecting curved partitions, right and left free walls and interventricular septum, which are segments of prolate spheroids. The septum usually curves so as to function as part of the left ventricle but is thinner and flatter than the free wall. Indexes of curvature-thickness showed that in the distended position ventricles are more globular and thin-walled; in the contracted position they are more cylindrical and thicker. The left ventricular free wall index showed greater change between distension and contraction than the other components. The results suggest that ventricular configuration is a compromise between a spherical shape that would need the least energy for diastolic ventricular filling and a tubular shape that would permit maximal conversion of systolic myocardial muscle cell tension into cavitary pressure increase. Ventricular topography probably develops as that geometry that requires the minimal energy expenditure in the overall economy of the circulation. Clinical determination of curvature-thickness indexes, similar to the postmortem indexes studied here, may find practical implementation in the assessment of cardiac diseases with two dimensional echocardiography and radionuclide imaging.

Absence of correlation between coronary arteria atherosclerosis and severity or duration of diabetes mellitus of adult onset

The relation between the severity and duration of diabetes mellitus and the severity of ischemic heart disease is uncertain. The clinical findings and the findings at autopsy were studied in 185 patients with diabetes mellitus of adult onset who ranged in age from 37 to 91 years and had a clinical diagnosis of diabetes established for a few days to 50 years before death. No statistically significant association was demonstrated either by simple correlation or by multivariate regression analysis between the clinically diagnosed severity or duration of diabetes and either the overall coronary disease, the number of diseased vessels or the number of myocardial infarctions. The presence of other expected correlations in the multivariate analysis suggested that the results of this study were not spurious. However, comparison with 185 age- and sex-matched control patients revealed that on the average, diabetic patients have more overall coronary disease (p < 0.002), more diffuseness of coronary disease (p < 0.005), more coronary collateralization (p < 0.001), more vessels involved by atherosclerosis (p < 0.001) and more myocardial infarcts (p < 0.001). The results suggest that although diabetes mellitus of adult onset is a condition in which the larger coronary arteries are subject to more atherosclerosis than are those in nondiabetic subjects, the progression of the atherosclerotic disease is unrelated to the duration or severity of the diabetes mellitus.

Midzonal Necrosis as a Pattern of Hepatocellular Injury After Shock

Midzonal necrosis is rarely observed in human liver, except in patients with yellow fever. In a retrospective analysis of livers from 1000 consecutively autopsied adult patients, we observed midzonal necrosis in 1.8% of the cases, and in 8% of patients with centrilobular necrosis. All of the affected patients had a history of one or more episodes of hypotension several days before death, and most patients (72%) had a history of congestive heart failure. Although the midzonal pattern of necrosis was always accompanied by centrilobular necrosis, the two patterns were not uniformly observed in the same microscopic fields. In 11 of 18 cases (61%), the midzonal pattern of necrosis appeared to be partially a consequence of centrilobular regeneration of hepatocytes. In 28% of the cases, however, the midzonal pattern of necrosis was primary and associated with selective survival of centrilobular and periportal hepatocytes. We conclude that midzonal hepatocellular necrosis may be observed after hypotension, and toxin- or drug-induced injury need not be implicated in the pathogenesis. This information may be useful in the interpretation of needle biopsy specimens of the liver.

Liver cell dysplasia:A DNA aneuploid lesion with distinct morphologic features.

Liver cell dysplasia is characterized by hepatocellular foci with nuclear atypia. It is often seen in cirrhosis and may be a precursor of hepatocellular carcinoma (HCC). To determine whether liver cell dysplasia is DNA aneuploid, 72 sections of 33 cirrhotic livers from the autopsy files of The Johns Hopkins Hospital were studied, and 14 foci of dysplasia from 13 cirrhotic livers were selected. Patients ranged in age from 32 to 70 years. Histologically, there were 10 foci of low-grade dysplasia and four foci of high-grade dysplasia. Nine HCCs served as positive controls; seven autopsy livers with no morphologic or clinical evidence of primary liver disease served as negative controls. One focus of HCC and one focus of dysplasia were unsatisfactory for analysis. Flow cytometric examination demonstrated subpopulations with DNA abnormality in four of nine (44%) foci of low-grade dysplasia, of which three were aneuploid. Three of four (75%) foci of high-grade dysplasia were aneuploid. Six of eight (75%) HCCs showed DNA abnormality, of which five were aneuploid. DNA aneuploidy was not present in the seven control livers; however, one showed DNA abnormality. We conclude that liver cell dysplasia is a morphologic entity that contains DNA aneuploid cells, a feature that supports the role of liver cell dysplasia in the evolution of HCC.