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Biomedical subjects

D W Ross

Publications and source records attributed to D W Ross.

At least 73 records · Page 4Linked to original sources

White blood cell differential: a call for standards.

The technology available to count and classify white blood cells has rapidly evolved from 1974 to the present. Two previous conferences, the College of American Pathologists Aspen Conference (1977) and Blood Cells in Paris (1980) have considered the technical and medical questions raised by these new technologies. The National Committee for Clinical Laboratory Standards (NCCLS) met in November 1984 to continue this debate and to provide a forum for manufacturers, laboratory directors, and government regulatory agencies to establish standards for the performance of the white blood cell differential. The development and clinical evaluation of the current commercially available white cell differential counters is reviewed as background for this meeting.

Automation↗

Differentiation versus cytoreduction during remission induction in acute nonlymphoblastic leukemia treated with sequential high-dose ara-C and asparaginase.

Patients with acute nonlymphoblastic leukemia (ANLL) treated with sequential high-dose ara-C and asparaginase (HiDAC----ASNase) have occasionally exhibited an unusual morphologic picture during induction therapy with a transition period in which large numbers of blasts coexist with returning mature hemopoietic elements. In 2 of 11 adult patients with ANLL treated during a 6-month period using a new protocol of HiDAC----ASNase, the hypoplastic phase typically seen after intense induction never developed. Serial marrow examinations performed 7 to 35 days after treatment showed equal admixtures of blasts and mature elements. Despite these findings, both patients subsequently entered complete remission with morphologically normal bone marrow examinations. The possibility for diagnostic error in interpreting these transition marrows as failed inductions is great and could lead to cessation of supportive therapy or to an unnecessary further course of cytotoxic therapy. This phenomenon raises the biological question, does remission represent leukemia killed or leukemia matured?

Acute Disease↗

Cl- permeabilities in red blood cells and peripheral blood lymphocytes from cystic fibrosis and control subjects.

Recent studies have identified abnormalities in Cl- permeation across two target cystic fibrosis (CF) epithelia (sweat duct and respiratory epithelium). In the present study, anion conductances of red blood cells (RBCs) and peripheral blood lymphocytes (PBLs) from CF and normal subjects were estimated and compared. For RBCs, the valinomycin-induced rate constant for K+ loss (PK+) was taken as an index of PCl-. For PBLs, the secondary volume increase after gramicidin pretreatment and hypotonic (0.67 X isotonic) stress was used to estimate PCl-. The Cl- permeabilities of RBCs and PBLs from CF and control subjects were comparable. These findings suggest that the abnormality in PCl- reported for CF sweat ductal and respiratory epithelia is not expressed in circulating blood elements.

Adult↗

Leukemoid blood reaction to tetracycline.

A pronounced leukemoid reaction consisting of WBC as high as 82,300/microliters was observed coexistent with a clinical picture of hepatitis in a young man taking oral minocycline. No etiologic source for the hepatitis was found. After complete recovery, an erroneous ingestion of a single dose of tetracycline reproduced his initial symptoms and a leukemoid reaction.

Adult↗

Unbalanced cell growth and increased protein synthesis induced by chemotherapeutic agents.

Unbalanced cell growth as manifested by an increase in cellular volume and in cellular dry mass following exposure to a variety of chemotherapeutic agents has been shown for neoplastic cells in vitro and human leukemic cells in vivo. The purpose of the present investigation was to test the hypothesis that unbalanced cell growth results from a disassociation of cell growth and cell division due to the blocking effect of chemotherapeutic agents. Monolayer cultures of CHO fibroblasts were studied in terms of their response to two chemotherapeutic agents that differ significantly in their mode of action, adriamycin and chlorambucil. Following exposure to these drugs, cell volume increased at a rate of from 1% to 4% per h; the total cell protein increased at a rate of from 4% to 7% per h. These changes were observed in both log and stationary phase cultures. Thus exposure to adriamycin and chlorambucil was followed by a more rapid rate of protein synthesis relative to the rate of degradation, resulting in larger cells with more protein whether or not the cells were actively in the division cycle. This is inconsistent with the hypothesis that unbalanced growth results simply from a disassociation of the cell division cycle from cell growth. These observations suggest that a final common pathway in the mode of action of chemotherapeutic agents may be the induction of unscheduled protein synthesis resulting in unbalanced cell growth.

Animals↗

The effect of cell hydration on the deformability of normal and sickle erythrocytes.

The deformability of the erythrocyte (RBC) is greatly influenced by its state of hydration. The purpose of this investigation is to quantitate this relationship by measuring the deformability of an RBC population over a broad range of cell water content. By manipulation of the ion content of the RBC, we performed all of the experiments in media which were isotonic with plasma. To raise ion and water content, RBC were incubated in a Li2CO3 medium. To lower cell ion and water content, RBC were exposed to the K ionophore, valinomycin. The range of cell water content achieved during the entire experiment was 900-3200 g/kg cell solid (normal in vivo cell water content being 1800-1950 g/kg cell solid). By using the Ektacytometer, an automated cylindrical viscometer, we were able to measure deformability of the RBC sampled at various points along this range of cell water content. We found that optimal rheologic behavior was exhibited by normal RBC when their water content was in the normal range. A rise or a fall in cell hydration resulted in a decrease in cell deformability. By contrast, the deformability of freshly drawn, well-oxygenated sickle RBC was well below that found for normal RBC. Upon volume expansion, however, the deformability of these sickle RBC improved markedly. This observation suggests that sickle RBC are suboptimally hydrated and that their abnormal rheology is at least in part a consequence of cell dehydration.

Anemia, Sickle Cell↗

Spuriously elevated platelet counts due to microspherocytosis.

A patient with an acute burn was noticed to have spuriously elevated platelet counts on an automated system. The major factor accounting for this discrepancy was the presence of numerous microspherocytes which were in the same size range of platelets. It is thus important to add microspherocytosis as an additional cause for a spuriously elevated platelet count. This has special clinical importance when dealing with an acute burn patient.

Aged↗

Automated cytochemical staining and inflammation. Further assessment of the "left shift".

Automated differential leukocyte counting devices identify neutrophils on the basis of size and peroxidase staining. Since no analysis of neutrophil subpopulations is provided, detection of the "left shift" as reflected by increased numbers of band neutrophils is not possible. It has been suggested that samples with increased numbers of high peroxidase neutrophils (HPX) correspond to conventional samples with increased band neutrophils. Using blood samples enriched by 700% in their band neutrophil concentration, no significant change in the number of HPX cells or mean peroxidase content was detected. Examination of Wright-stained smears with increased concentrations of HPX cells invariably revealed toxic neutrophils not seen in controls. The authors concluded that increases in HPX cells do reflect inflammation but that such increases correlate with the presence of toxic neutrophils and not band neutrophils.

Flow Cytometry↗

White cell differential: coupling of cell types in patients undergoing chemotherapy.

The peripheral white blood cell differential counts in patients undergoing chemotherapy showed an unexpected partial correlation between the various cell classes during wide swings in the absolute cell number. These observations were made using the technique of automated flow cytochemistry on a 10,000 cell count Hemalog-D, which increases the statistical precision and permits differential counts in leukopenic patients. The data demonstrated that the white cell types do not behave as independent variables and suggest that the white blood cell differential count in the peripheral blood during chemotherapy may be in part altered by factors unrelated to cell production or destruction kinetics.

Antineoplastic Agents↗

The nature of unbalanced cell growth caused by cytotoxic agents.

The volume of cells grown in tissue culture following exposure to a wide variety of cytotoxic drugs or x-rays increases at a rate of 1 to 10% of cell mass per hour. The same phenomenon is seen in animal neoplasias and human leukemias. This increase in cell volume is the result of unbalanced cell growth with a resulting disproportionate synthesis of proteins and possibly other macromolecules in the cytoplasm and nucleus. The dose response curve for a decrease in cell survival as measured by cloning efficiency in tissue culture is quantitatively correlated with the dose response curve for inducing an increase in cell volume. This quantitative relationship makes feasible the use of the phenomenon of unbalanced cell growth as a measure of cell death in screening for cytotoxic drugs or in monitoring response to therapy. An hypothesis to explain this increase in cell volume following chemotherapy is that cells are by the action of these drugs induced into an abortive or unbalanced pseudo-cycle which is characterized by synthesis of substantial amounts of protein without other preparative steps for cell division.

Animals↗

Automated platelet counts: accuracy, precision, and range.

The automation of platelet counting is essential in laboratories performing a large number of procedures with high precision. Maintaining this precision and establishing accuracy require an understanding of the special problems of counting platelets, including: (1) the large dynamic range of the measurement, (2) the variable size and aggregability of platelets, and (3) the specific requirements of a quality-control method. In evaluating these problems, we designed experiments that measured the linearity and precision of two types of platelet counters, light scattering and electronic aperture impedance, and that evaluated the suitability of commercially available reference materials. The results show that the instrumentation is excellent and the reference materials are good; such that, given a well-planned quality-control method as presented here, the automated platelet count gives a rapid result with precision and accuracy.

Calibration↗