Nontransmural versus transmural myocardial infarction: A morphologic study

Although “nontransmural” and “transmural” are morphologic terms used widely to distinguish patients with myocardial infarction, controversy exists as to their meaning regarding clinical course. For this study, a transmural infarct was defined as one that involves essentially the full thickness of the ventricular wall, and nontransmural was defined as something less. The purpose of this study was to identify true morphologic nontransmural acute (less than 21 days old) infarcts at autopsy and compare them with transmural (full-thickness) infarcts in age-matched subjects, for clinical and pathologic similarities and differences. Among the autopsy subjects, comparing 35 nontransmural and 35 transmural infarcts, there was no significant difference with regard to subjects' race or sex, chest pain, arrhythmias, heart block, or cause of death; transmural myocardial infarctions did have a higher frequency of new Q waves (30 of 35 versus six of 35, p < 0.001) and presented more often with increasing dyspnea. At autopsy, there were no significant differences regarding heart weight, location of infarcts, severity of coronary disease, age of acute infarct, or total size of infarct (18 percent of left ventricle for nontransmural versus 22 percent for transmural). There was, however, a significantly greater tendency for those with nontransmural infarct to have evidence of prior infarction at autopsy (27 of 35 versus 19 of 35, p < 0.05). Acute coronary thrombi in the distribution of the infarct were significantly more common among transmural myocardial infarcts (32 of 35 versus 18 of 35, p < 0.001). Morphologically, the nontransmural infarcts showed mural involvement ranging from 20 to 90 percent of the left ventricle, and histologically showed more contraction band (i.e., reflow) injury (57 percent with more than 30 percent contraction band necrosis) compared with transmural infarcts (32 percent with more than 30 percent contraction band necrosis) (p < 0.05). Fatal nontransmural and transmural infarcts have major clinical and pathologic similarities, but differences in number of prior infarcts, type of necrosis, and occurrence of coronary thrombi suggest differing pathophysiology. The heterogeneity of both transmural and nontransmural infarcts likely accounts for existing differences among clinical studies regarding prognosis. Although this classification system has value in the clinical setting, that at times it represents an imprecise oversimplification of infarct type should be recognized in assessing individual patients.     

Subepicardial aneurysms: a rare complication of myocardial infarction

Delayed rupture of myocardial infarcts, more than 10 days after infarction, is only rarely observed at autopsy. Of 1,814 hearts examined after postmortem arteriography from autopsy subjects at the Johns Hopkins Hospital, 704 had 1,140 infarcts. Three (0.2 percent) infarcts were complicated by subepicardial aneurysms, and two of these had ruptured. The infarcts were 21 to 60 days old and had an abrupt dissection of the inferior left ventricular myocardium with a narrow fibrous lined channel comprising the mouth and neck of the aneurysm. The components of the aneurysm wall differed in all three cases. In two, epicardium prevented acute ventricular rupture. In the third case, myocardial fibers were present in the fibrous wall proximally. Adherent parietal pericardium was absent. Previous authors have required the lack of myocardium within the wall to define those lesions, often called pseudoaneurysms. Aneurysms with myocardium have been labeled true aneurysms or pseudo-false aneurysms. A more unifying concept of this lesion is proposed. The unique constellation of features consisting of an abrupt interruption of the myocardium, a narrow neck, and a propensity to rupture spontaneously distinguishes the subepicardial aneurysm regardless of its wall's components. The ability to surgically correct the potentially lethal subepicardial aneurysms necessitates a more accurate categorization of and familiarity with the lesion.     

Ehlers-Danlos syndrome with abnormal collagen fibrils,sinus of Valsalva aneurysms,myocardial infarction,panacinar emphysema and cerebral heterotopias

A 30 year old woman with marked joint hypermobility had severe, progressive lung disease, seizures, aneurysms of the sinuses of Valsalva and myocardial infarction documented during life. She died of intractable ventricular fibrillation, and postmortem examination showed myocardial injury in the distribution of the left coronary artery but no occlusive coronary artery disease. Severe panacinar emphysema was found in the lungs. Cerebral heterotopias with peculiar vascularization were present and were a likely cause of the seizure disorder. Electron microscopy showed dermal collagen fibrils to be heterogeneous in size, reduced in number, and irregular and frayed in appearance. This patient had a form of the Ehlers-Danlos syndrome, different from the 10 distinct variants described thus far, associated with lethal internal manifestations.     

Fever with dissecting aneurysm of the aorta

Following acute aortic dissection, in two of the four cases we describe the patients experienced a prolonged febrile syndrome which spontaneously resolved five and 11 weeks later. Because of fever and a murmur of aortic regurgitation, the two other patients with aortic dissection were initially treated for acute bacterial endocarditis. These four cases serve to re-emphasize fever as an important clinical manifestation of dissecting aneurysm of the aorta.     

Hemorrhagic diathesis in a carrier of hemophilia B.

A carrier of hemophilia B was found to have an unusually low factor IX level of 13 per cent. Her history of previous bleeding and the hospital course following elective dental extractions were consistent with a mild hemorrhagic diathesis. The patient is a member of a rare kindred of hemophiliacs. The mean level of factor IX in 12 carriers in this kindred was 42 per cent, with a range of 13 to 100 per cent. This patient represents the sixth reported case in which a female carrier of factor IX deficiency was symptomatic.     

Arizona hinshawii osteomyelitis with antecedent enteric fever and sepsis. A case report with a review of the literature.

A case of Arizona osteomyelitis of the spine which occurred 11 months after an episode of gastroenteritis and enteric fever is presented. As close biochemical and antigenic relative of Salmonella, Arizona infection produces a similar clinical course with gastrointestinal manifestations frequently preceding localized infections by several months. The boney lesion in the present case and in three of the four other cases of Arizona osteomyelitis described in the literature was a chronic inflammation which may have a xanthomatous component. The bone destruction caused by Arizona infection is less severe than that of tuberculosis or pyogenic osteomyelitis. Proposed treatment of Arizona osteomyelitis consists of debridement of the localized infection and long term antimicrobial therapy.     

Venous thrombosis and splenic rupture in paroxysmal nocturnal hemoglobinuria

A patient with an 11 year history of paroxysmal nocturnal hemoglobinuria presented with severe abdominal pain. On admission, the hematocrit value was 30 per cent and unchanged from repeated measurements during the previous three years. Abdominal angiography identified extensive thromboses of the splenic and portal venous systems. After initial improvement on heparin therapy, the patient experienced additional abdominal crises. A ruptured and multifragmented spleen was removed at the time of exploratory laparotomy. Postoperatively, after a several days' interval of improvement, the patient experienced additional thrombotic episodes of the abdomen, upper extremities and cerebral cortex. The latter was associated with disabling nerve paralysis. With continuous intravenous heparin plus steroid therapy, the patient's condition improved progressively. Despite the numerous thrombotic episodes during the prolonged hospital course, no hemolytic episodes were observed. This is the first report of documented splenic rupture in a patient with paroxysmal nocturnal hemoglobinuria.     

Genetic factors predisposing to autoimmune diseases. Autoimmune hemolytic anemia, chronic thrombocytopenic purpura, and systemic lupus erythematosus

Genetic factors predisposing to autoimmune diseases were investigated in 10 families having more than one affected member. Seventy relatives and 23 spouses from two large kindreds (one in whom the proband had autoimmune hemolytic anemia and the other immune thrombocytopenic purpura) were examined for immunologically mediated disorders, autoantibodies, immunoglobulin abnormalities, and HLA genotypes. Significant differences between relatives and spouses were found for immune diseases (21 percent versus 0 percent; p = 0.02), antinuclear antibody titer of 1:80 or more (18 percent versus 0 percent; p = 0.04), single-strand DNA antibodies (18 percent versus 0 percent; p = 0.04), high-titer antinuclear antibody or antibodies to single-strand DNA or both (33 percent versus 0 percent; p = 0.001), and the combined frequencies of immune diseases and serologic abnormalities (44 percent versus 4 percent; p = 0.0004). Similar frequencies were found in 41 relatives from eight families in whom the proband had SLE. Segregation analyses using these abnormalities as genetic traits were most compatible with a Mendelian dominant model. Impressive odds (100:1) against linkage to HLA were calculated.     

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

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.     

Unusual cardiac, renal and pulmonary involvement in Gaucher's disease. Intersitial glucocerebroside accumulation, pulmonary hypertension and fatal bone marrow embolization

A 25 year old black woman who had manifestations of Gaucher's disease since one year of age is described. This patient had clinically significant cardiac, renal and pulmonary involvement with Gaucher's disease. Interstitial infiltration of the myocardium by Gaucher cells caused decreased left ventricular compliance and decreased cardiac output. In the kidney, Gaucher cells were present in the mesangium of the glomeruli and the interstitium of the cortex. Also, electron dense, intramembranous granular deposits were seen in glomeruli on electron microscopy. The pulmonary findings included pulmonary arterial hypertension, accentuated basilar deposition of glucocerebroside in the interstitium of alveolar septums and fatal bone marrow embolization.     

Thrombocytopenia,hemolytic anemia and transient neurologic deficits

More than 350 genes have been assigned to specific chromosomes. These include more than 110 assigned to the X chromosome, more than 240 assigned to specific autosomes, and at least one assigned to the Y chromosome. (Even man's 25th chromosome, that of the mitochondrion, is being mapped.) Almost all the assignments to specific autosomes were made in the last decade. About half of these were made by study of clones derived from interspecific (e.g., man-mouse) somatic cell hybrids. Over a fifth were made by family linkage studies. Chromosomes 1 and 6 are rather extensively mapped. The genes of over 40 autosomal disorders have been specifically localized. The comparative anatomy, functional anatomy, developmental anatomy and even applied anatomy of the human genome is becoming better known.     

Clinical features in enteritis due to Vibrio parahemolyticus

Clinical features of a case of enteritis due to Vibrio parahemolyticus are presented. Superficial ulcerations of colonic mucosa were observed directly by sigmoidoscopy. Previously such damage had not been documented but inferred from the presence of red cells and leukocytes in the stools. The literature pertinent to V. parahemolyticus and its recent presence in the United States is reviewed.     

Reversed septal curvature: Association with primary pulmonary hypertension and Shone syndrome

In the normal heart the interventricular septum is curved concave to the left and functions as a component of the left ventricular wall. We have studied the hearts of five patients at autopsy, after postmortem angiography and fixation in distention, in which the septum was concave to the right ventricle. These patients ranged in age from eight months to 25 years (average, 16 years); three had primary pulmonary hypertension, and two had coarctation of the aorta and congenital aortic stenosis. Catheterization studies in the latter two patients had demonstrated subaortic stenosis. At autopsy there was no evidence of asymmetric septal hypertrophy or of abnormal septal myocardial fiber disarray. The right ventricles were markedly hypertrophied. In each, the septal curvature was reversed leading to protrusion of septal muscle into the left ventricular outflow tract with marked narrowing of the outflow tract. Since the septal configuration is determined early in life, this abnormality of ventricular topography may develop primarily or it may develop in hearts subject to early as well as long-standing right ventricular overload.     

Acute pancreatitis with hyperlipemia. Evidence for a persistent defect in lipid metabolism

Hyperlipemia has been recognized with increasing frequency in patients with acute pancreatitis. The significance of this association is unknown. Twenty-two such patients were electively readmitted to a metabolic ward for study of their lipid metabolism during a quiescent period. Persistent fasting hypertriglyceridemia was found in 16 and abnormal lipoprotein electrophoretic patterns in 17. In addition, response to a lipid load was abnormal; in 20 of the 22 patients triglyceride levels rose over 500 mg/100 ml, and in 10 over 1,000 mg/100 ml. It is concluded that the lipid abnormalities detected during the acute attack of pancreatitis were not secondary but persisted long after the patient had recovered. Such underlying lipid abnormalities may play an intermediary role in the pathogenesis of pancreatitis.     

Paraneoplastic syndromes and constitutional symptoms in prediction of metastatic behavior of small cell carcinoma of the lung

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.     

Estrogen and progesterone receptors in prediction of metastatic behavior of breast carcinoma

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 estrogenand/or progesterone-binding assays were available. Regardless of receptor status, patients treated with hormone therapy had prolonged survival (p < 0.05), but had greater tumor burden at autopsy (p < 0.05). The distributions of metastases differed for receptorpositive versus receptor-negative tumors. Estrogen-positive tumors metastasized more frequently to thyroid and/or parathyroid glands (p < 0.01). Estrogen-negative tumors metastasized more extensively to the leptomeninges (p < 0.01). Progesterone-positive tumors metastasized more frequently to myocardium (p < 0.01), small bowel (p < 0.01), urothelial structures (p < 0.05), and thyroid and/or parathyroid glands (p < 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.     

Relation between variations in the phenotypic expression of an unstable hemoglobin disorder (hemoglobin Zürich) and carboxyhemoglobin levels

Longitudinal studies in a group of 15 asymptomatic subjects with hemoglobin Zürich from two unrelated families indicated marked variation in the clinical and hematologic expression of the hemoglobinopathy, even within the same family. Carbon monoxide bound to normal hemoglobin stabilized the molecule when exposed to a variety of denaturing procedures. The marked increase in the affinity of hemoglobin Zürich for carbon monoxide, approximately 65 times that of normal hemoglobin, led to a study of carboxyhemoglobin levels in smoking and nonsmoking subjects with hemoglobin Zürich and their relation to the phenotypic expression of the hemoglobinopathy. The carboxyhemoglobin content in whole blood from persons with hemoglobin Zürich ranged from 3.9 to 6.7 percent in nine nonsmokers and from 9.8 to 19.7 percent in six smokers. Rates of hemolysis as determined by values for hematocrit, reticulocyte count, and haptoglobin and hemopexin levels were less in smokers than in nonsmokers. Also, rates of Heinz body formation in intact red cells and isopropanol-induced precipitation of the abnormal hemoglobin in hemolysates were less in smokers than in non-smokers. These observations suggest that variability in the phenotypic expression of hemoglobin Zürich is a post-translation event secondary to stabilization of the abnormal hemoglobin by carbon monoxide.     

Prospective randomized double-blind comparison of moxalactam and tobramycin in treatment of urinary tract infections

In a prospective, randomized, double-blind trial, a regimen of 250 mg of moxalactam every 12 hours was compared with 1.0 mg/kg of tobramycin every eight hours in the treatment of urinary tract infections. One hundred and eleven patients were entered into the study; results in 63 (18 men and 45 women) were evaluable for both efficacy and toxicity. Thirty evaluable patients received moxalactam, and 33 received tobramycin. The mean duration of therapy in each group was seven days. There were six treatment failures in the moxalactam group and 10 failures in the tobramycin group (p > 0.4). Nephrotoxicity, defined as an increase in serum creatinine levels to 0.5 mg/dl or more, did not occur in either group. Thirteen patients in the moxalactam group and one in the tobramycin group had enterococci isolated from a urine culture specimen during or after therapy. It is concluded that use of the moxalactam regimen Is as effective and safe as use of the tobramycin regimen in the treatment of urinary tract infections. The clinical significance of the enterococcal isolates associated with moxalactam therapy is yet to be determined.     

Hemoglobin Zürich: A third family presenting with hemolytic reactions to sulfonamides

Hemoglobin Zürich has been discovered in a second Caucasian family in Maryland, the members of which are unrelated to the families previously described. Three of the affected family members had severe hemolytic episodes during therapy with sulfonamides. A search for the etiology of the sulfonamide-induced hemolysis revealed that approximately one third of the hemoglobin in the circulating erythrocytes exhibited an electrophoretic mobility similar to that of hemoglobin S in usual electrophoretic systems. The sickling preparations were negative. Studies to define the structure of the abnormal hemoglobin showed that the nonheme-linked histidine (β 63) had been replaced by an arginine, thus identifying the abnormal hemoglobin as hemoglobin Zürich.Five other members of the family pedigree were heterozygous for hemoglobin Zürich. None had ever had hemolytic anemia, and, by history, none had ever been exposed to sulfonamides. Hematologic studies of these members as well as the three other affected members after recovery from sulfonamideinduced anemia, revealed no anemia, slight reticulocytosis, normal red cell morphology and a slight reduction of serum haptoglobin.Clinical expression of hemoglobin Zürich most often occurs when affected subjects are given sulfonamides. Sulfonamides also exacerbate hemolysis in patients with other types of unstable hemoglobins: hemoglobin H, hemoglobin Torino and hemoglobin Shepherds Bush. In defining the mechanism of drug-related hemolysis, several important possibilities should be considered: an immunologic reaction, impaired metabolism or excretion of the drug, an erythrocyte enzyme abnormality of the hexose monophosphate shunt pathway and the presence of an abnormal hemoglobin. This type of systematic approach for investigating mechanisms of drug-induced hemolysis may uncover other examples of hemoglobin Zürich, as well as other types of hemoglobin abnormalities.