James P. Crowley

A Paucity of Thalassemia Trait in Italian Men with Myocardial Infarction

We studied the prevalence of thalassemia trait in a group of Italian male myocardial infarction (MI) patients and an ethnically similar group of men admitted for other conditions. Italian men constituted approximately 13% of each group. Of 359 Italian men with a MI, only 2 had thalassemia trait. In contrast, of 330 adult Italian males in the non-MI group (mean age 59.6 years), 11 had thalassemia trait. Because the frequency of thalassemia trait was significantly (p less than 0.01) lower in the myocardial infarct group, we conclude that thalassemia trait may be a protective attribute as regards MI. A prospective study of individuals with thalassemia minor is indicated to elucidate the mechanism for the observed protective effect and to determine what risk factors may offset the protective effect in those that do experience MI.

Splenic Artery Ligation for Splenic Salvage: Clinical Experience and Immune Function

Documentation of overwhelming post-splenectomy sepsis, characterized by infection from encapsulated organisms, has led to development of surgical techniques for preservation of the injured spleen to maintain splenic clearance of encapsulated, opsonized organisms from the circulation. In this study splenic artery ligation (SAL) was performed as an adjunct to successful splenorrhaphy in 20 adults suffering blunt splenic injury. There were no deaths and no reoperations. Twenty units of blood were transfused in ten patients. Splenic removal of blood-borne opsonized particles was measured as the clearance of anti-Rh-antibody-coated 51Cr-radiolabeled autologous red blood cells from the circulation in five SAL patients and nine normal volunteers. The clearance of opsonized red cells 120 minutes after injection was not different (40 +/- 7% of injected dose in controls, 40 +/- 4% in SAL patients). These results demonstrate that SAL can safely be applied as an adjunct to splenorrhaphy and that SAL does not diminish splenic clearance of opsonized particles from the circulation.

Lectin binding patterns in diffuse large cell lymphoma

The staining reaction of a panel of lectins in paraffin embedded lymph node specimens of diffuse large cell lymphoma was studied in relation to survival. In 47 of 49 patients, varying degrees of lectin binding were observed with Ricinus communis agglutinin (RCA), crude extract of Arachis hypogaea (c‐PNA), Concanavalin ensiformis A (Con A), Triticum vulgaris A (WGA) and Phaseolus vulgaris A (PHA). Binding was either absent or only minimal with Pisum sativum A (PSA) and Lens culinaris A (LCA). Two categories of binding were observed: cell surface and cytoplasmic. Cell surface binding was seen in tumor cells, while cytoplasmic binding was observed in macrophage–histiocytes. Varying numbers of tumor cells were stained with RCA, WGA, c‐PNA or PHA; but with Con A virtually no tumor cells were stained. Stromal macrophage–histiocytes were stained with RCA, WGA, or Con A in all but one case, frequently with all three lectins; c‐PNA binding macrophage–histiocytes were absent in one third of the cases. With PHA the staining of stromal macrophage–histiocytes was extremely rare. Tumor cells that stained with RCA but not with c‐PNA were observed in 9 of 15 patients who survived more than 2 years after diagnosis. In all 15 long‐term survivors, stromal macrophage–histiocytes were positive for c‐PNA. Tumor cells that reacted with c‐PNA but not with RCA were seen in five patients who survived less than two years. All 16 patients whose tumors lacked c‐PNA binding stromal macrophage–histiocytes in the presence of RCA binding macrophage–histiocytes were short‐term survivors. These observations suggest the heterogeneity of stromal macrophage–histiocytes as well as that of tumor cells. Furthermore, the variation of lectin binding might be useful in assessing prognosis. Cancer 52:2089‐2099, 1983.

Sclerosis in diffuse histiocytic lymphoma: A clinicopathologic study of 25 cases

Sclerosis was observed in the lymph node specimens of 26 of 57 (46%) patients with diffuse histiocytic lymphoma. Two major types of sclerosis were observed: “compartmentalizing” (56%), in which the tumor was divided into many small compartments by anastomosing, hyalinized stroma; and “diffuse” (44%), in which the sclerosis occurred without evident partitioning of the tumor. The hyalinized stroma of the compartmentalizing sclerosis was frequently continuous with small vessels accompanied by aggregates of small lymphocytes, suggesting that the sclerosis was related to the occurrence of small lymphocyte‐associated postcapillary venules. Compartmentalizing sclerosis was further divided into two groups: The first group (even pattern) was characterized by an orderly occurrence of the stromal network with no evidence of distortion, evenly spaced tumor cells showing no axis in their arrangement, and a sharp demarcation of tumor cells from the stroma. The second group (uneven pattern) was marked by either a disorderly occurrence of the stromal network with distortion of the overall pattern, tumor cells arranged along an axis, or poor demarcation of tumor cells from the stroma with individual envelopment of tumor cells by the stroma. Approximately two‐thirds of the patients (9/14) with the compartmentalizing sclerosis survived two years or more after diagnosis; most patients (10/11) with diffuse sclerosis died within two years. Compartmentalizing sclerosis, even pattern, was associated with a consistently favorable prognosis; the uneven pattern was not. This study indicates a marked variation in the survival of patients with diffuse histiocytic lymphoma with sclerosis and demonstrates that prognostic subgroups may be delineated by additional morphologic features.

Perioperative paraplegia and multiorgan failure from heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia and thrombosis syndrome is a rare but devastating complication. We report a patient with heparin-induced thrombocytopenia in whom heparin-induced thrombocytopenia and thrombosis syndrome developed after a cardiac operation, complicated by acute thrombosis of the aorta followed by renal failure, paralysis, and ischemic necrosis of the lower extremities. The literature suggests aspirin, dipyridamole, and iloprost as effective prophylactic agents for perioperative heparin-induced thrombocytopenia and thrombosis syndrome. This unfortunate complication underscores the importance of close platelet count monitoring in all preoperative patients undergoing prolonged heparin therapy.

Occurrence and patterns of muramidase containing cells in Hodgkin's disease, non-Hodgkin's lymphomas, and reactive hyperplasia

The occurrence and pattern of cytoplasmic muramidase containing histiocytes were studied by the unlabeled antibody peroxidase-antiperoxidase method in biopsy material from patients with Hodgkins disease, non-Hodgkins lymphomas, and reactive hyperplasia. The majority of lymph nodes from patients with Hodgkins disease, nodular lymphoma, and reactive hyperplasia gave positive staining reactions when tested in this manner. Differences in the staining pattern were observed for the different conditions studied. In general, stain positive cells occurred in one of the following four patterns: nodular, dispersed, aggregating without background stain, or aggregating with background stain (mottling pattern). The nodular and aggregating without background stain patterns were not specific and were seen in various conditions. The dispersed pattern, however, was observed only in some cases of non-Hodgkins diffuse lymphomas, suggesting a subgroup of tumors characterized by active participation of reactive histiocytes. The mottling pattern was virtually limited to Hodgkins disease. Since the mottling pattern appeared to be produced by virtue of a large amount of extracellular muramidase, the elevation of the serum muramidase level in Hodgkins disease may be related to enzymatically active secretory histiocytes. Moreover, the mottling staining pattern was observed frequently in the lymphocytic predominance and nodular sclerosis type of Hodgkins disease, but relatively infrequently in the mixed cellularity or lymphocytic depletion types, suggesting that the variation in histiocytic activity may be related to the course of the disease. The decreased staining reaction observed in the latter two categories could not be accounted for by a decrease in the numbers of histiocytic cells in hematoxylin and eosin stained sections, suggesting that release or synthesis may be defective in those unfavorable types of Hodgkins disease.

Anti-interleukin-1 reactive cells in Hodgkin's disease.

Constitutional symptoms (or B‐symptoms) of Hodgkins disease may be mediated by interleukin 1 (IL‐1), a product of macrophage‐histiocytes. To further study this relation, the authors examined the cells that reacted with anti‐human IL‐1 antibody in biopsy specimens from 140 untreated patients with Hodgkins disease (72 asymptomatic patients and 68 with B‐symptoms). Fever was the most common symptom, present in 57 of the 68 patients. Anti‐IL‐1 reactive cells were observed in 62 cases. A positive staining reaction was observed in three types of cells: Reed‐Sternberg and related (R‐S) cells (33 cases); small to medium cells of undetermined origin (18); and granulocytes (11). The staining was negative in 78 cases, including 42 with B‐symptoms. The majority of tumors (27/33) with positively stained R‐S cells were from asymptomatic patients. Most tumors (14/18) with positively stained small to medium sized cells were from patients with B‐symptoms. Large numbers of granulocytes were positively stained in five asymptomatic patients and six with B‐symptoms. The immunohistochemical demonstration of IL‐1‐bearing cells in tumors does not correlate with the manifestation of constitutional symptoms in Hodgkins disease.

Concanavalin A binding histiocytes in Hodgkin's disease and their relation to clinicopathologic features of the disease

The occurrence and staining patterns of Concanavalin A (Con A) binding histiocytes were studied in diagnostic lymph node specimens of 133 patients with Hodgkins disease. Varying numbers of Con A binding histiocytes were present in all tumors. Two distinct cytoplasmic staining patterns of the Con A binding histiocytes were noted: diffuse, and a pattern termed “globular” which represents a dense, solitary paranuclear aggregate of binding sites. The diffuse binding pattern was seen in the majority of histiocytes with no apparent nuclear atypia, but was also occasionally seen in Reed‐Sternberg cells. Globular binding was present in both benign and malignant‐looking histiocytes, including rare Reed‐Sternberg cells. Based on the number of histiocytes in which globular binding of Con A (G‐cells) was observed, tumors were grouped in the following three categories: Group 1: tumors with large numbers of G‐cells (42 cases); Group 2: tumors with a small number of G‐cells (16); and Group 3: tumors with rare or no G‐cells (75). Tumors with large numbers of G‐cells were seen more frequently in patients with disseminated disease than in those with localized (69.0% versus 31.0%; P ⩽ 0.002), and more often in patients with B‐symptoms than in those without (73.8% versus 26.2%; P ⩽ 0.001). Large numbers of G‐cells were present in most tumors of the lymphocyte depletion type (14/16), whereas rare or no G‐cells were seen in the majority of the nodular sclerosis type (46/59). These observations suggest that the G‐cells may represent an abnormal variant of histiocytes, the occurrence of which is associated with unfavorable clinical and pathologic features of Hodgkins disease. Cancer 52:252‐257, 1983.

Macrophage‐histiocyte lysozyme activity in relation to the clinical presentation of Hodgkin's disease: An immunohistochemical study

The clinical presentation of 71 untreated patients with Hodgkins disease was studied in relation to immunohistochemically demonstrable lysozyme in the lymph node biopsy material. Sixty‐one patients (86%) showed a positive staining reaction of varying degree, while ten (14%) showed no demonstrable lysozyme. The clinical features of lysozyme‐positive patients differed markedly from those of lysozyme‐negative patients. Stain‐positive patients were younger (29 vs. 46), were more often in clinical Stage I or II disease (69% vs. 10%, P< 0.001), and less frequently had constitutional symptoms (34% vs. 70%, P< 0.02). Moreover, within the stain‐positive group, patients who had the most intense staining reaction (mottling pattern) also had the most favorable clinical and histopathologic features at the time of diagnosis. The observations suggest that in Hodgkins disease the lysozyme secretory activity of macrophage‐histiocytes may be an important element of host resistance to neoplasia and that a depression of this secretory activity corresponds with disseminated disease.

Lymphocyte subpopulations in long-term dialysis patients : a case-controlled study of the effects of blood transfusion

Lymphocyte subsets in a group of intensely transfused (> 10 units/year) patients on long‐term hemodialysis were compared with those in a carefully controlled population of lightly transfused (1–10 units/year, no units during study period) long‐term dialysis patients. The data confirm previous reports of lymphopenia and a symmetrical reduction of both T‐ and B‐cell subpopulations in patients on long‐term dialysis. Eleven (36.7%) of 30 intensely transfused dialysis (ITD) patients had a low T8 population when expressed as a percentage value, while 0 of 25 lightly transfused dialysis (LTD) control patients exhibited a low percentage of T8 cells. There were no significant absolute differences between the lymphocyte subsets in the ITD and LTD patients. These data contrast with previous reports of other groups of ITD patients in whom there was an observed increase in T8 cytotoxic suppressor cells. Our findings suggest that the immunologic effects of renal failure and long‐term dialysis largely override the increase in T8 lymphocyte subsets observed in other groups of transfused patients. There is little difference between ITD and LTD patients, but both groups are significantly different from nontransfused controls. Further longitudinal studies are needed in completely untransfused patients to resolve the contribution of minimal transfusion therapy to the immunologic deficits observed in long‐term dialysis patients.