Gastric emptying in chronic renal failure.
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Biomedical subjects
Publications and source records attributed to G W Moore.
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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.
Electromechanical dissociation (EMD), defined as electrocardiographically adequate ventricular systolic complexes in the absence of detectable pulse or blood pressure, may occur in the terminal course of patients and is frequently unexplained. The 50 cases in the autopsy files of The Johns Hopkins Hospital in which the patients had died after documented episodes of EMD were reviewed. Four major categories of patients were identified: In 22 of 50 cases (44 per cent) myocardial ischemia appeared to precipitate EMD; in 14 of these 22 cases (64 per cent) myocardial ischemia was global in extent, while in eight (36 per cent) myocardial ischemia was regional, occurring in the distribution of an occluded coronary artery. A subset of ten patients with ischemia had terminal ventricular tachycardia or fibrillation, which was converted to EMD following resuscitation maneuvers. In 12 of 50 cases (24 per cent) systemic shock preceded the development of EMD; in nine of these 12 (75 per cent) hypotension was due to myocardial or arterial rupture, while in three (25 per cent) hypotension was secondary to sepsis. In ten of 50 cases (20 per cent) pulmonary vascular compromise was the apparent cause of EMD. Of these ten cases, eight (80 per cent) were secondary to pulmonary embolization, and two (20 per cent) were due to pneumothorax. In six of 50 cases (12 per cent) the precise cause of EMD could not be determined. The results of this study indicate that in the dying patient with electromechanical dissociation the differential diagnosis should include myocardial ischemia, systemic shock, and pulmonary vascular compromise.
A catenoidal, or saddle-shaped, configuration of the interventricular septum, concave toward the left ventricular cavity in the transverse plane, but convex toward the left ventricular cavity in the apex to base plane, occurs in idiopathic hypertrophic subaortic stenosis and possibly may lead to septal hypertrophy and immobility. The authors also have observed catenoidal shape of the interventricular septum in hearts with myocardial infarcts. They reviewed 1,415 hearts examined after postmortem arteriography and fixation in distention from patients autopsied at The Johns Hopkins Hospital. Among 586 hearts with myocardial infarcts, there were 54 (9%) with a catenoidal shape of the interventricular septum. The infarcts, 45 anterior septal and 9 inferior and lateral, appeared to account for the reversal of normal apex to base curvature, although coexistent idiopathic hypertrophic subaortic stenosis could not be excluded in 3 patients. There was moderate or marked infarct expansion in 25/54 (46%) and septal or free wall rupture in 8 (15%) hearts. Reduced average net septal curvature in the 54 hearts, highly significant compared with that in 80 hearts without infarcts (P less than 0.001), would reduce the septum's contribution to left ventricular function and may contribute to the observed postinfarct congestive failure, 30/54 (56%), and hypoperfusion, 7/54 (13%). The results suggest that some myocardial infarcts may produce a catenoidal shape of the interventricular septum that could reduce the functional activity of the surviving uninfarcted basilar portion of the septum and thereby contribute to postinfarction cardiac dysfunction.
Peripheral neuroblastic tumors (PNT), including neuroblastomas, pheochromocytomas, ganglioneuromas, and paragangliomas, have been reported in association with congenital heart disease (CHD). If a significant correlation between PNT and CHD could be demonstrated, it would suggest that peripheral neuroblastic tumors might represent reactive, secondary phenomena rather than independent or incidental events. We examined this question by reviewing the autopsy files of The Johns Hopkins Hospital and found that the frequency of congenital cardiovascular problems among patients with PNT was significantly greater than the frequency of CHD in the general autopsy population (p less than 0.001). There was no correlation between CHD and central neuroblastic tumors (CNT), i.e., medulloblastomas, retinoblastomas, or pinealoblastomas, or between CHD and metastatic malignant melanoma. We examined the hypothesis that erythropoietic activity, as might be stimulated by hypoxia, was correlated with the presence of peripheral neuroblastic tumors. We found that most (87%) cardiac malformations associated with PNT produced cyanosis, and histologic assessment of hematopoiesis revealed greater activity in patients with PNT (with or without CHD) compared to those with CNT (p less than 0.05) or malignant melanoma (p less than 0.05). In addition, patients with PNT and CHD had higher frequencies of extramedullary hematopoiesis compared to age-matched controls with similar congenital heart defects (p less than 0.05), and compared to patients with CNT or metastatic malignant melanoma (p less than 0.01). These results suggest that peripheral neuroblastic tumors may arise in a setting of chronic hypoxia produced by congenital heart disease.
The nature of the changes occurring in the border zone of myocardial infarcts is uncertain. To study this question, the authors analyzed a number of morphologic features in hearts studied after postmortem arteriography and fixation in distention from 204 patients with single myocardial infarcts autopsied at The Johns Hopkins Hospital. Vacuolization of myocytes was observed in 53 (26%) cases, predominantly in surviving subendocardium and trabecular myocardium within the infarct. Lateral myocardium seldom and subepicardial myocardium almost never showed vacuolar change. Myocyte vacuolization progressively developed and then decreased with time: 1/20 (5%) hearts with infarcts less than 2 days old, 17/48 (35%) infarcts 2-14 days old, 13/27 (48%) infarcts 15-60 days old, 4/12 (33%) infarcts 61-365 days old, and 18/97 (19%) infarcts greater than 365 days old. Reduction in vacuolization with time was not explained by necrosis of vacuolated cells; rather, the myocardium showed normal morphology. Presence of vacuolization in old infarcts was associated with severe multivessel coronary artery disease and endocardial fibroelastosis. The results suggest that infarct border zone myocyte vacuolization may be correctable by reversal of regional ischemia; however, only a trivial amount of myocardium, relative to infarct size, undergoes vacuolar change.
The sequence of events in the development of the brain in staged human embryos was investigated in much greater detail than in previous studies by listing 100 features in 165 embryos of the first 5 weeks. Using a computerized bubble-sort algorithm, individual embryos were ranked in ascending order of the features present. This procedure made feasible an appreciation of the slight variation found in the developmental features. The vast majority of features appeared during either one or two stages (about 2 or 3 days). In general, the soundness of the Carnegie system of embryonic staging was amply confirmed. The rhombencephalon was found to show increasing complexity around stage 13, and the postoptic portion of the diencephalon underwent considerable differentiation by stage 15. The need for similar investigations of other systems of the body is emphasized, and the importance of such studies in assessing the timing of congenital malformations and in clarifying syndromic clusters is suggested.
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Serious late sequelae including chronic active hepatitis, cirrhosis, massive necrosis, and hepatocellular carcinoma may develop in patients infected with hepatitis B virus. Clinical and epidemiologic risk factors for such complications have not been identified. To examine this question, the clinical and pathologic features of the 60 patients with documented hepatitis B virus infection who underwent postmortem examination at the Johns Hopkins Hospital were reviewed. In 27 patients (45 percent), the outcome of hepatitis B infection was nonlethal, i.e., at autopsy, the liver showed either no histopathologic lesions attributable to hepatitis B infection, acute viral hepatitis, or chronic persistent hepatitis. Lethal outcomes of hepatitis B infection, i.e., chronic active hepatitis, cirrhosis, hepatocellular carcinoma, and/or massive hepatic necrosis, were present in the remaining 33 (55 percent) patients. Chronic active hepatitis was observed more frequently in whites (p less than 0.05) and males (p less than 0.05). Lethal outcomes of hepatitis B infection were correlated with recent or concomitant exposure to known hepatotoxic agents (p less than 0.05), including heavy ethanol abuse, isoniazide, hydrocarbon exposure, methyldopa, and the chemotherapeutic agents busulfan and methotrexate. In addition, a lethal outcome of hepatitis B virus, particularly massive hepatic necrosis, was positively correlated with a history of nephrolithiasis (p less than 0.005). Recent, concomitant treatment with immunosuppressive agents, given in 24 patients (40 percent), was correlated with the absence of lethal sequelae (p less than 0.005). These data suggest that patients with recent exposure to hepatotoxic agents have an increased risk of lethal sequelae following hepatitis B infection. Furthermore, the results suggest that immunosuppressive or antiinflammatory therapy may be beneficial in reducing morbidity and mortality from hepatitis B virus infection.
Small cell carcinoma of the lung is frequently associated with a paraneoplastic syndrome or constitutional symptoms. To examine correlations between paraneoplastic syndromes or constitutional symptoms and tumor behavior, the clinical and pathologic features were reviewed in 85 patients with small cell carcinoma of the lung who underwent complete autopsy at The Johns Hopkins Hospital between 1962 and 1983. The 28 (33 percent) subjects with a paraneoplastic syndrome survived significantly longer (10.5 +/- 1.5 months) than those without a paraneoplastic syndrome (7.4 +/- 0.7 months) (p less than 0.05), and they had significantly higher frequencies of tumor invasion into major bronchi (p less than 0.01) and more extensive metastases to bone marrow (p less than 0.05), but significantly lower frequencies of and less extensive metastases to the central nervous system (p less than 0.005). The 35 (41 percent) subjects with constitutional symptoms had markedly increased tumor burdens (p less than 0.005) with significantly more extensive metastases to bone marrow, liver, and lungs (all p less than 0.05). The findings suggest that subjects with small cell carcinoma of the lung associated with a paraneoplastic syndrome tend to have a more benign clinical course with prolonged survival; in addition, the significantly lower frequency of central nervous system metastases in these patients may be due to a paucity of the subpopulations of tumor cells that have the propensity to metastasize to the brain. In contrast, it appears that constitutional symptoms develop in patients with small cell carcinoma of the lung because of rapid tumor growth, coupled with impairment of synthetic activity in the liver due to extensive infiltration of tumor into hepatic parenchyma.
The relation between estrogen- and progesterone-binding receptors and the metastatic behavior of breast carcinoma was examined by reviewing autopsy findings in 25 subjects with metastatic breast cancer at Johns Hopkins Hospital for whom the results of estrogen- and/or progesterone-binding assays were available. Regardless of receptor status, patients treated with hormone therapy had prolonged survival (p less than 0.05), but had greater tumor burden at autopsy (p less than 0.05). The distributions of metastases differed for receptor-positive versus receptor-negative tumors. Estrogen-positive tumors metastasized more frequently to thyroid and/or parathyroid glands (p less than 0.01). Estrogen-negative tumors metastasized more extensively to the leptomeninges (p less than 0.01). Progesterone-positive tumors metastasized more frequently to myocardium (p less than 0.01), small bowel (p less than 0.01), urothelial structures (p less than 0.05), and thyroid and/or parathyroid glands (p less than 0.05). These differences in the distributions of metastases may reflect different tissue preferences in metastasizing breast carcinoma cells with estrogen- and/or progesterone-binding receptors. In this regard, perhaps patients with estrogen-negative tumors should be monitored closely for the development of carcinomatous meningitis, because this form of central nervous system involvement is a frequent cause of death among patients with breast carcinoma.
The gross pathological, microscopic, and clinical features of 173 Stage I and Stage II primary nonsmall cell carcinomas resected for cure by segmental resection, lobectomy, or pneumonectomy at the Johns Hopkins Hospital were analyzed to determine which provided useful independent prognostic information. The tumors studied included 79 squamous carcinomas (56%); 74 adenocarcinomas (44%), including 15 undifferentiated tumors which contained intracellular mucin; 18 large-cell undifferentiated carcinomas (10%); one giant cell carcinoma (less than 1%); and one adenosquamous carcinoma (less than 1%). Clinical features evaluated for each case included age, sex, race, and history of previous or subsequent malignancy; and pathologic features evaluated included tumor size, lymph node metastases, tumor location, cellular anaplasia, desmoplastic response, inflammatory response, preexisting scar, tumor necrosis, and degree of tumor differentiation. Multivariate analysis using the Cox life table regression model indicated that five features had a significant (p less than 0.05) independent association with subsequent death due to the tumor, and that the final set was highly significant (p = 0.001). These features were the following: large-cell undifferentiated histology, lymph node metastases expressed as N classification, tumor size expressed as T classification, tumor giant cells in any histologic type, and absent or minimal plasma cell infiltration. No additional prognostic information was obtained from any of the other features analyzed.
We have described a 77-year-old woman with a 14 x 15 cm cystic mass arising from the head of pancreas. The serum glucagon level was elevated, and electron microscopy revealed large numbers of alpha granules within the tumor cells. Glucagonoma syndrome should be considered in the differential diagnosis of a large abdominal mass even if skin rash is minimal.
Breast carcinoma frequently metastasizes to endocrine organs, a behavior which may have prognostic or therapeutic relevance. Whether endocrine organ involvement represents a trophic influence on some carcinomas or is simply a "mass effect" of tumor dissemination is uncertain. To investigate this question, the authors reviewed the clinical and pathologic features of 187 subjects with metastatic breast carcinoma, all of whom had been subjected to complete autopsy at The Johns Hopkins Hospital. Metastases to primary endocrine organs, ie, the anterior pituitary, thyroid, parathyroid, or adrenal cortex, occurred in 57%, and metastases to secondary endocrine organs, ie, the pineal, posterior pituitary, thymus, adrenal medulla, or pancreas, occurred in 62% of patients. In general, patients with endocrine organ metastases were significantly younger and had significantly greater numbers of metastases and greater overall tumor burden than those without endocrine organ metastases (all P less than 0.001). There was no correlation between endocrine organ metastases and survival, therapy, histologic type of tumor, or grade of anaplasia or desmoplasia. Metastases to primary endocrine organs were correlated with one another and with metastases in secondary endocrine organs. Metastases in secondary endocrine organs were intercorrelated and also correlated with several nonendocrine organs, chiefly the heart, liver, and gut (all P less than 0.005). These findings indicate that metastases of breast carcinoma to endocrine organs occur in a setting of widely disseminated tumor. However, the observed correlations among metastatic sites suggest that the distributions are nonrandom; these distributions may reflect fundamental properties of some breast carcinomas with respect to hormone receptors, biologic behavior, or environmental growth requirements.
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Computerized indexing and retrieval of medical records is increasingly important; but the use of natural language versus coded languages (SNOP, SNOMED) for this purpose remains controversial. In an effort to develop search strategies for natural language text, the authors examined the anatomic diagnosis reports by computer for 7000 consecutive autopsy subjects spanning a 13-year period at The Johns Hopkins Hospital. There were 923,657 words, 11,642 of them distinct. The authors observed an average of 1052 keystrokes, 28 lines, and 131 words per autopsy report, with an average 4.6 words per line and 7.0 letters per word. The entire text file represented 921 hours of secretarial effort. Words ranged in frequency from 33,959 occurrences of "and" to one occurrence for each of 3398 different words. Searches for rare diseases with unique names or for representative examples of common diseases were most readily performed with the use of computer-printed key word in context (KWIC) books. For uncommon diseases designated by commonly used terms (such as "cystic fibrosis"), needs were best served by a computerized search for logical combinations of key words. In an unbalanced word distribution, each conjunction (logical and) search should be performed in ascending order of word frequency; but each alternation (logical inclusive or) search should be performed in descending order of word frequency. Natural language text searches will assume a larger role in medical records analysis as the labor-intensive procedure of translation into a coded language becomes more costly, compared with the computer-intensive procedure of text searching.
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.
In order to aid in the identification of a group of breast cancer patients at high risk of recurrence in whom the possible value of adjuvant chemotherapy might be most readily demonstrable, the authors reviewed the clinicopathologic features of 74 women with infiltrating, Stage I, estrogen receptor-negative breast carcinoma. They found significant correlations between short-term recurrence (within 2 years) and extensive necrosis (P less than 0.005), anaplastic tumor nuclear morphology (P less than 0.01), a positive family history of breast carcinoma (P less than 0.05), diffuse hyperplasia of axillary lymph nodes (P less than 0.05), and young age (P less than 0.05). Twenty percent of all patients experienced recurrence within 2 years, while recurrence was noted in 32% of patients with highly pleomorphic nuclei, 38% of those with extensive necrosis, and 45% of those with a positive family history. Recurrence was noted in 55% of the small number of patients with both anaplastic nuclear morphology and a positive family history. These apparent risk factors for early recurrence may be helpful in prospectively selecting patients most eligible to receive adjuvant chemotherapy.