Biomedical subjects
R V Pierre
Publications and source records attributed to R V Pierre.
Giant cell arteritis detected by bone marrow biopsy.
A case of giant cell arteritis is reported that was detected by bone marrow biopsy. The histopathologic features of the bone marrow lesion included an enlarged artery, whose wall showed intimal thickening, fibrinoid necrosis, destruction of the internal elastic lamina, and multinucleated giant cells. The demonstration of involvement of bone marrow vessels by giant cell arteritis reaffirms the systemic nature of the disease. Bone marrow biopsy is not the method of choice for establishment of the diagnosis of giant cell arteritis, but it may lead to the diagnosis in rare instances.
Automation of blood film preparation and staining utilizing the technicon autoslide.
Evaluation of a prototype Technicon Autoslide, which automatically prepares, fixes, stains, dries labels, and "coverslips" blood films, attached to a Technicon Hemalog D-90 revealed that the instrument prepares high-quality wedge blood smears with uniform distribution of leukocytes, excellent red blood cell and platelet morphology, and adequate staining of normal types of leukocytes. The fixation-staining characteristics did not enable reliable identification of some immature cell types. An additional 200 microliters of blood samples is requred above that required for the Hemalog D-90 in order to prepare a smear. The throughput time of the instrument, from sample aspirate to completion of the blood smear, is 14 min. One sample is completed every 45s. The final glass-slide specimen contains the blood smear sample and its identification and date, embedded in acrylic plastic, which also serves as a coverslip. The instrument can be operated by the D-90 operator with negligible additional effort. The approximate cost of each sample was 8.25 cents. The Autoslide in combination with the Hemalog D-90 should reduce technician time required to prepare, stain, and label blood smears. Its use should reduce the frequency of sample misidentification and provide more uniform quality to slide preparation and staining than is available by current manual techniques. Preliminary studies suggest that Autoslide smears are suitable for use on an image-processing type of automated differential system, and this therefore makes their use possible in a tiered screening system for detection of platelet or red cell abnormalities not recognized by the high-volume cell-counting instruments.
Malignant histiocytosis as a terminal condition in chronic lymphocytic leukemia.
Chronic lymphocytic leukemia rarely develops an acute blastic phase as a terminal complication. When it does, the blastic phase is characterized by the appearance of large, immature cells with the same immunologic markers as the cells in the chronic phase of chronic lymphocytic leukemia; this coexistence of mature lymphocytes and blastic forms in chronic lymphocytic leukemia has been termed "Richter's syndrome." In a patient of ours with chronic lymphocytic leukemia, the development of a presumed large cell lymphoma was recognized on both bone marrow aspiration and biopsy examination, but later the condition was proved to be a true histiocytic neoplasm (malignant histiocytosis) by cytochemical and immunohistochemical techniques. We are unaware of another reported instance of malignant histiocytosis as a terminal complication of chronic lymphocytic leukemia and mimicking Richter's syndrome.
Acute lymphoblastic leukemia in children: immunologic, cytochemical, morphologic, and cytogenetic studies in relation to pretreatment risk factors.
Thirty children with previously untreated acute lymphoblastic leukemia were studied prior to therapy to determine whether sheep erythrocyte (E)-receptor status correlated with clinical factors, cytochemical staining characteristics, FAB morphologic classification, and karyotype. Five patients (17%) with more than 50% E+ blasts had intense focal acid phosphatase staining and distinct clinical characteristics, including high leukocyte counts, mediastinal masses, and involvement of the central nervous system at diagnosis. Focal acid phosphatase activity was present in blasts of patients with greater than 20% E+ blasts, but this group had fewer poor risk factors. Morphologic and karyotypic features were not related to erythrocyte-receptor status, but the L2 morphologic appearance occurred more frequently in older patients (P less than 0.05). Erythrocyte receptors have both qualitative and quantitative clinical correlations in childhood acute lymphoblastic leukemia; however, E+ and E- groups are heterogeneous and E+ groups must be analyzed for other risk factors and relapse rates determined before firm conclusions can be made about erythrocyte rosetting as an independent risk variable.
Preleukemic syndromes.
Acute nonlymphocytic leukemia (ANLL) is preceded by a hematologic illness representing the "preclinical" stages of the disease in many patients. This "preclinical stage" or preleukemic stage is difficult to recognize by conventional hematologic morphologic techniques. A prospective study was carried out to determine whether cytogenetic studies would be helpful in the recognition of preleukemic states and whether the presence of cytogenetic abnormalities would have prognostic significance. A study of 284 patients with suspected preleukemia has yielded 62 patients with progression to overt ANLL. Cytogenetic abnormalities were found in 30% of suspected preleukemic patients, whereas 53% of the patients progressing to acute leukemia had cytogenetic abnormalities. These studies show that the presence of cytogenetic abnormalities aid in the recognition of preleukemia but are not specific for early leukemia. Patients with cytogenetic abnormalities are more likely to develop overt ANLL. Banded chromosome studies demonstrated cytogenetic abnormalities in the preleukemic phase in 13 of 26 patients. A variety of clonal chromosomal abnormalities were observed.
Cytogenetics in malignant lymphoma.
There appear to be four primary areas of interest in the application of cytogenetic techniques to the study of malignant lymphomas: (1) the role of cytogenetics in the diagnosis of lymphoma in problem cases, (2) as an aid to the classification of malignant lymphomas, (3) whether specific chromosomal patterns will have prognostic significance for response to therapy or survival, and (4) the role of cytogenetics in staging of malignant lymphomas. A case of reactive lymphoid hyperplasia is reported in which cytogenetic studies demonstrated an aneuploid clone suggesting that cytogenetic abnormalities of lymphoma may precede the diagnostic histopathologic picture. The occurrence of 14q+ marker chromosomes in plasmacytic myeloma, plasma cell leukemia, malignant lymphomas, Burkitt's lymphoma, and ataxia-telangiectasia suggest that a common etiologic or pathogenetic mechanism may be present in some of these disorders. A preliminary pilot study of spleens removed at staging laparotomy for Hdgkin's disease suggests that cytogenetic studies may be able to detect Hodgkin's disease that is not apparent histologically. Further studies are required to provide answers to these areas of interest in cytogenetics in malignant lymphoma.
Investigation of statistical decision rules for sequential hematologic laboratory tests.
A statistical data processing program for identifying patients who are likely to have abnormalities on various hematologic laboratory tests is described. The prediction of abnormal levels of serum vitamin B12, serum folate, transferrin saturation, and reticulocyte counts is based on a statistical analysis of the patient's age, sex, and routine blood cell measurements. The program was developed using data from normal-value studies and data from patients who had these laboratory abnormalities. The sensitivity and specificity of the program were evaluated in a controlled prospective study of about 5,000 ambulatory adult patients. The program's predictions also were compared with the laboratory tests requested by the patients' attending physicians. The program was most sensitive for predicting low serum vitamin B12 (74%) and low transferrin saturation (78%). In the prospective evaluation, the predictive values varied from 11% for predicting low serum folate to 65% for predicting low transferrin saturation.
Atypical lymphoid leukemia in ataxia telangiectasia.
We observed two sisters with ataxia telangiectasia, one of whom developed an atypical subacute lymphocytic leukemia characterized by atypical lymphocytes and absence of palpable lymphadenopathy or hepatosplenomegaly. The lack of organomegaly in this patient may have been due to the underlying ataxia telangiectasia, which was associated with lymphoid hypoplasia. Cytogenetic studies showed a marker chromosome 14 [t(14q11:14q34)] in both patients. The sister with leukemia had other complex chromosomal aberrations in addition to the marker chromosome 14 that were stable for more than 14 mo before the patient's death from complicating infection. The development of atypical T cell leukemia has not been previously described in ataxia telangiectasia. This case further illustrates the interesting interrelationships amoung immunosuppressed states, development of lymphoid malignancy, and an emerging pattern of a propensity to chromosome 14 abnormalities in various lymphoid malignancies.
Rapid identification of monocytes in a mixed mononuclear cell preparation.
A method for identifying monocytes by the "non-specific esterase" stain is described. This method is particularly applicable to mononuclear cell suspensions obtained by Ficoll--Hypaque density gradient separations and allows rapid as well as accurate determinations.
Platelet satellitism as a cause of abnormal hemalog D differential results.
Platelet satellitosis resulted in an elevated high-peroxidase-activity value (9.9% versus normal range 0 to 3.65%) of the automated leukocyte differential count performed by the Technicon Hemalog D. Platelet satellitism occurred in Wright-stained smears of EDTA-anticoagulated blood, as well as in the effluent of the peroxidase channel of the Hemalog D. All platelets took up the perosidase stain. The rosette-like clusters of platelets and neutrophils were interpreted as single, large, intensely stained leukocytes resulting in the elevated high-peroxidase-activity value.
Effect of Surgery on the Quantity of Lymphocyte Subpopulations.
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Routine erythrocyte measurements in diagnosis of iron-deficiency anemia and thalassemia minor.
A study was made of the routine electronic measurements of erythrocyte size and hemoglobin concentration in blood samples from 122 patients with decreased transferrin saturation and 66 patients with elevated levels of hemoglobin A2 or F. The medical histories of these patients were reviewed to identify 52 cases of uncomplicated iron-deficiency anemia and 39 cases of uncomplicated thalassemia minor. Four decision functions were compared for separating these two disorders. The functions evaluated were: D.F'. = MCV--[5 X Hb]-RBC; ratio MCV/RBC; ratio MCH/RBC, and RBC. The rules performed better in the uncomplicated cases than in the routine laboratory defined cases. Only minor differences in the performances of the various decision functions were observed. None was sufficiently accurate for final diagnosis, but they should have value in screening patients and in determining which additional test should be considered.
Lymphocyte-epithelial cell interactions in oral mucosal inflammatory diseases.
Lymphocyte cytotoxicity for target cells is a method for evaluating specific lymphocyte stimulation. In vitro lymphocytotoxicity has been demonstrated in chronic ulcerative colitis and granulomatous colitis, polymyositis and dermatomyositis, systemic scleroderma, recurrent aphthous stomatitis, and periodontal disease. We have investigated lymphocytotoxicity in 36 patients with various oral inflammatory diseases using an automated cell-counting system. This investigation demonstrated in vitro lymphocytotoxicity for gingival epithelial target cells by aggressor lymphocytes harvested from patients with recurrent aphthous stomatitis and periodontal disease. This effect was not seen when the lymphocytes were harvested from normal subjects or from patients with other oral mucosal inflammatory diseases. The automated cell-counting system corresponded very well with the assay technique of exclusion of supravital dye.
Endomyocardiopathy with eosinophilia.
Five patients were seen at the Mayo Clinic over an 8-year period with the following complex of clinical and morphologic features; striking eosinophilia, cardiomyopathy, hepatosplenomegaly, and either a rapidly fatal or a prolonged, debilitating illness. In recent years, controversy has raged over the precise designation of this syndrome, with proposals ranging from eosinophilic leukemia to hypereosinophilic syndromes. To focus on the major target organ of the disease, we have favored the term endomyocardiopathy with eosinophilia. Experience with these five patients showed that (1) eosinophilia can persist for many years before symptoms appear; (2) progressive restrictive cardiac disease was the major cause of death and debility; (3) osmiophilic cytoplasmic inclusions are present in eosinophils of these patients and also in cells from other patients with marked eosinophilia; and (4) echocardiography may prove to be a useful noninvasive tool to diagnose and follow the progress of cardiac involvement. Although none of these patients was thought to have leukemia, intensive therapy with steroids or cytotoxic agents, or both, is considered necessary to control the progression of the disease.
Multiple myeloma and acute leukemia associated with alkylating agents.
Rapidly fatal acute myelomonocytic leukemia developed in five patients with multiple myeloma who were treated with melphalan for 28 to 54 months. In each patient, multiple myeloma responded to therapy and progress was satisfactory until the development of acute leukemia. At postmortem examination, leukemic infiltration of organs was seen, and there was little or no evidence of myeloma. Consideration of these cases and a review of the literature suggest that these circumstances represent the development of acute myelomonocytic leukemia rather than plasma cell leukemia; there also appears to be an increased incidence of acute leukemia in multiple myeloma, probably related to the alkylating agent.
The platelets in preleukemia and myelomonocytic leukemia. Ultrastructural cytochemistry and cytogenetics.
Light and electron microscopic studies of platelets from 16 patients with myelomonocytic leukemia or "preleukemia" revealed major morphologic alterations in 15 and minor ones in 1. Although variable in severity from case to case, the changes present followed a distinct pattern. In most cases there were two platelet populations, one morphologically normal and one morpholigically abnormal. The most salient changes pertained to size (giant forms), shape (the platelets being rounded and probably spheroidal), decrease or absence of the microtubules, and increase in immature elements. A striking feature was the variation in size and shape of the granules, with truly giant forms (up to 2.5 mum) being present. In cytogenetic studies in 14 cases, there was no correlation between the chromosomal changes and the various types of platelet anomalies.
The value of cells in the pleural fluid in the differential diagnosis.
Fifty samples of pleural fluid, collected from consecutive patients in a thoracic clinic who had diagnostic thoracentesis, were studied prospectively. Pleural fluid protein was of value in differentiating transudates from exudates. Pleural fluid red cell counts, white blood cell counts, and differential white blood cell counts have no specificity and no usefulness in the differential diagnosis of the origin of the effusion. Pleural fluid cytology was positive in 60% of all the malignancies studied in this series; for the group with metastatic breast carcinoma, there was a 78% positive pleural fluid cytology. Differential white cell counts revealed tumor cells in 45% of malignant effusions. In our experience, the finding of tumor cells is the only useful finding in differential cell counts of the pleural fluid.