Multicenter study of whole-blood creatinine, total carbon dioxide content, and chemistry profiling for laboratory and point-of-care testing in critical care in the United States.

OBJECTIVES: To introduce a creatinine biosensor and a total carbon dioxide content (TCO2) method for whole-blood measurements, to evaluate the clinical performance of a new transportable analyzer that simultaneously performs these two and six other tests (Na+, K+, Cl-, glucose, urea nitrogen, and hematocrit), and to assess the potential of the new analyzer for point-of-care testing in critical care by comparing results obtained by nonlaboratory personnel and by medical technologists. DESIGN: Multicenter sites compared whole-blood measurements with the transportable analyzer to plasma measurements from the same specimens with local reference instruments. One site compared whole-blood results produced by nonlaboratory personnel vs. medical technologists and evaluated day-to-day and within-day precision at the point of care. SETTINGS AND PATIENTS: Four medical centers in the United States. Venous and arterial specimens from 710 critically ill patients with a variety of diagnoses. Point-of-care testing in the emergency room and operating room. RESULTS: The linear regression analyses at the four medical centers showed the following: creatinine (a) slope, 0.91 to 1.22, (b) y intercept, -0.07 to 0.15 mg/dL, and (c) r2, 0.77 to 1.00; and TCO2: (a) slope, 0.64 to 1.00, (b) y intercept, 1.36 to 9.6 mmol/L, and (c) r2, 0.52 to 0.72 (yi, whole-blood analyses; xi, plasma reference measurements). Bland-Altman plots also were used to assess multicenter creatinine and TCO2 results. Of the other analytes, K+, glucose, and urea nitrogen had the highest r2-values. For the eight chemistry profile tests performed at the point of care (yi, nonlaboratory personnel results; xi, medical technologist results), the average value of r2 was 0.96 (SD 0.08) in the operating room and 0.96 (SD 0.06) in the emergency room, and mean paired differences (yi - xi) were not statistically or clinically significant. Precision was acceptable. CONCLUSIONS: The performance of the creatinine biosensor and the TCO2 method was acceptable for whole-blood samples. Comparisons of whole-blood results from the transportable analyzer and plasma results from the local reference instruments revealed analyte biases that may be attributed to differences between direct whole-blood analyses and indirect-diluted plasma measurements and other factors. Performance of nonlaboratory personnel and medical technologists was equivalent for point-of-care testing in critical care settings. The whole-blood analyzer should be useful when patient care demands immediate results.

Partial molar transformation of the placenta of presumably monozygotic twins.

A pregnancy with one normal female fetus and a placenta that was divided into halves, one normal the other molar, is described. Genetic analysis shows the molar component to be hyperdiploid/tetraploid but having an identical DNA composition as the normal twin. Because there was no trophoblastic proliferation and the hyperdiploid cells were confined to the villous stroma, and because the molar component was still being perfused by diploid vessels from the normal twin, we believe the mole is derived from polyploidization of the mesenchymal epiblast in a monozygotic twin pregnancy.

New perspectives on the approach to chronic lymphocytic leukemia.

Investigation of the biological actions of loxoribine in chronic lymphocytic leukemia (CLL) was undertaken because of the pervasive immunostimulatory effects of the nucleoside on normal B cells. In vitro studies with cells from a spectrum of CLL patients demonstrate that loxoribine induces B-CLL cells to enter and traverse the cell cycle. This is reflected by marked increases in DNA synthesis, by standard morphological criteria, and by flow cytometric evaluation of cell cycle status and of cell surface activation markers. Cells from about 75% of patients studied evince this response. Analysis of a variety of biological parameters indicate that only the ratio of T cells (CD4+ or CD8+) to B-CLL cells correlates with induction and degree of proliferative response. Co-stimulation with loxoribine and IL-2 results in modest proliferative synergy, presumably due to upregulation of IL-2R alpha expression on B-CLL cells by loxoribine. Prolonged exposure of B-CLL cells to stimulatory concentrations of loxoribine frequently culminates in progression of the responsive cells to apoptosis. The capacity of loxoribine to transiently approximate the reversible transformation of a low grade B cell malignancy to one of a higher grade presents the opportunity for evaluation of cycle-active drugs under these conditions. Recent studies indicate that pre-treatment of B-CLL cells with loxoribine results in synergistic killing of leukemic cells with cycle-active drugs. The ability to induce B-CLL cells into cell cycle entry and/or into either activation-induced apoptosis or into phases of the cell cycle sensitive to cytotoxic therapy opens up new perspectives for the development of potentially curative strategies for this chronic leukemia.

Immunomorphologic analysis of bone marrow biopsies after treatment with 2-chlorodeoxyadenosine for hairy cell leukemia.

Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA) induces complete remissions in 85% of patients. Complete remission has been defined as the absence of hairy cells in the bone marrow after routine morphologic examination. To determine if hairy cells could be detected in complete remission bone marrows using immunohistochemical techniques with antibodies L26 (CD20) and DBA.44, 154 bone marrow biopsies performed between 3 months and 25 months after therapy were studied. Of the biopsies, 50% exhibited staining with L26 and/or DBA.44 in five or more cells with morphologic features of hairy cells. Minimal residual disease was usually less than 1% of the total cellular population. DBA.44-positive cells were demonstrated in 91% of the biopsies, although in 48% of these the morphologic features of the positive cells were not sufficiently distinctive for hairy cells. The proportion of biopsies with residual hairy cells was similar over the 25 months of follow up, indicating a relatively stable amount of residual disease. Immunomorphologic analysis is a more sensitive method for detecting residual hairy cells than morphology alone. Although further follow up is necessary to determine the clinical significance of the L26/DBA.44-positive staining in cells with and without distinctive morphologic features of hairy cells, we conclude that many patients in a stable clinical remission may have residual hairy cells.

Loxoribine induces chronic lymphocytic leukemia B cells to traverse the cell cycle.

Leukemic B cells from a majority of patients with chronic lymphocytic leukemia (CLL) enter the cell cycle upon stimulation in vitro with loxoribine, a potent 7,8-disubstituted guanine ribonucleoside immunostimulant. In the absence of added costimulants, a proportion of these cells become activated and undergo DNA synthesis and mitosis accompanied by a marked increase in expression of an array of cell surface activation antigens. The resultant activated B-CLL cells exhibit greatly enhanced sensitivity to cycle-active cytotoxic drugs. This approach may be of potential value in the therapy of CLL.

Diagnostic application of two-color flow cytometry in 161 cases of hairy cell leukemia.

Recent immunophenotypic studies of hairy cell leukemia (HCL) have suggested specific patterns of immunoreactivity that may aid in diagnosis. We studied peripheral blood (PB) from 161 cases of HCL using two-color direct immunofluorescence flow cytometry and an extended panel of antibody combinations. Circulating hairy cells were identified by immunophenotypic features in 92% of the cases and could be detected even when representing < or = 1% of circulating lymphocytes. The 133 cases with > or = 2% detectable hairy cells were analyzed in detail. HCL showed a uniform and unique B-cell phenotype, with each of the following features identified in 99% to 100% of cases: (1) positive staining for B-ly7, coexpressed with CD19; (2) very intense, uniform expression of CD11c, with CD19; (3) moderately intense staining for CD25, with CD19; (4) very intense staining for CD22; (5) moderate to very intense staining for CD20; and (6) moderately intense monoclonal surface Ig. Phenotypic variability existed in expression of CD10 (26%) and CD5 (4%). Based on these features, HCL was easily distinguished from 50 cases of chronic lymphocytic leukemia (CLL). Although CLL exhibited frequent expression of CD11c (74%) and CD25 (68%), the intensity of staining was significantly less than HCL. Furthermore, CLL was uniformly positive for CD5 and showed weak staining for CD20, CD22, and surface Ig. B-ly7 proved to be the most specific marker, reacting with 100% of HCL cases, but absent in all cases of CLL. We conclude that two-color flow cytometry with specific antibody combinations is an efficacious method for characterization and sensitive detection of hairy cells in PB. Application of the phenotypic criteria described should help to increase accuracy in diagnosis of HCL.

Acute effects of topical methyl tert-butyl ether or ethyl propionate on gallbladder histology in animals: a comparison of two solvents for contact dissolution of cholesterol gallstones.

Experiments were performed in anesthetized rabbits and piglets to assess gallbladder mucosal injury during irrigation with methyl tert-butyl ether, a C5 ether, or ethyl propionate, a C5 ester--two organic solvents used in the contact dissolution of cholesterol gallstones. In 44 New Zealand White rabbits, the gallbladder was exposed to individual solvents or saline solution through a transhepatic catheter for 2 hr. Gallbladders were then harvested and fixed immediately or after a recovery period of 1, 4 or 8 days. Tissue sections were examined under light microscopy, and severity of injury was graded with predefined criteria by two pathologists blinded to the animals' treatment regimens. Histological assessment showed severe mucosal injury such as necrosis of the cells at the villus tips immediately after 2 hr of exposure to either solvent. After 4 days, injury had decreased significantly; after 8 days, complete mucosal healing had taken place. A similar study was performed in 32 piglets. Solvent or saline solution was oscillated in and out of the gallbladders of these piglets with a computer-controlled syringe pump at a pressure less than the leakage pressure of the gallbladder. Histological assessment was performed on tissue samples obtained immediately after the procedure or 8 days later. Both solvents caused severe mucosal injury; however, after 8 days complete mucosal healing had occurred, so that gallbladders exposed to solvent were indistinguishable from gallbladders exposed to saline solution, which was used as control. We conclude that both methyl tert-butyl ether and ethyl propionate cause moderate to severe epithelial injury but that the gallbladder epithelium regenerates within a few days.(ABSTRACT TRUNCATED AT 250 WORDS)