Chronic lymphocytic leukemia with localized extranodal prolymphocytic transformation.
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Biomedical subjects
Publications and source records attributed to J D Bessman.
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Unstimulated whole saliva was collected from 21 HIV-positive men and women before and after dental treatment. The frequency of HIV detection did not increase after dental treatment. Infectious HIV was recovered from only one patient. Study findings raise the possibility that, in most cases, salivary inhibitors render the virus non-infectious.
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Presumptive distinction between iron deficiency and heterozygous thalassemia by analysis of the automated blood count and differential continues to be a challenge. We compared two proposed numerical discriminants (MCV2 x MCH, and MCV2 x RDW/100 x Hb) with an analytic microcomputer program (BCDE2 Lea & Febiger). In 7114 subjects, the numerical discriminants and the BCDE2 program correctly identified greater than 90% of thalassemia. In subjects with iron deficiency, the BCDE program was greater than 90% sensitive and specific for positive identification, while the numerical discriminants were less than 75% sensitive and specific at inferential identification. The numerical discriminants, BCDE2, and 17 experts in blood counting were asked to interpret the blood-count data in 7 fully-defined actual cases. The mean experts' score was 5.65 cases correct out of 7. The BCDE program was correct in all cases. The numerical discriminants could not analyze all cases, and both were incorrect in at least one case. We conclude that for the task of analyzing blood counts for microcytic disorders, microcomputer analysis by BCDE outperforms both numerical discriminant functions and analysis by expert hematologists.
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Increasingly, all automated blood counts are not accompanied by a microscopic white blood cell differential. A popular strategy is to obtain a manual differential if any part of the automated blood count and differential is outside specified limits (the "diff-if" strategy). The authors compared two sets of criteria to triage blood counts for manual differentials: previously recommended numeric values, and the analysis of a microcomputer program. In a population of subjects with a high percentage of hematologic disorders, the microcomputer program and the numeric criteria were equally specific (excluding normal blood smears); the program was more sensitive for bands, immature granulocytes, monocytes, nucleated red blood cells, reticulocytosis, teardrops, red blood cell fragments, and hypersegmented neutrophils. The numeric criteria were more sensitive for eosinophilia (less than 1.0 X 10(9)/L) and mandated fewer manual differentials. In a population of predominantly normal subjects, the program was more sensitive for increased bands and equally sensitive for eosinophilia, the only abnormalities observed on the smear. In a population of subjects with predominantly abnormal blood counts, but excluding most primary hematologic disorders, there were few blood smears with abnormalities beyond eosinophilia or increased bands. In both of these groups, the computer program mandated more manual differentials than did the numeric criteria. The authors conclude that microcomputer analysis by the program tested was more sensitive than numeric criteria to identify specimens with abnormal blood smears. Specificity depended on the patient population. The choice of a triage strategy should be based on the individual laboratory's patient population.
The peripheral blood film and the red blood cell size distribution histogram were examined for evidence of red blood cell fragments in 2,350 subjects. To distinguish subjects with greater than or equal to 10 fragments/1,000 red blood cells (abnormal) from normal, examination of the blood film was 0.83 sensitive and 0.30 specific, whereas examination of the histogram was 0.97 sensitive and 0.87 specific. The most common causes of abnormal fragmentation were malignancy with cytotoxic chemotherapy and severe iron deficiency. In two subjects, an abnormal red blood cell fragmentation pattern was the clue to a spectrin mutant in subjects with an automated blood count previously evaluated as normal. The data suggest two conclusions: the red blood cell volume histogram appears more accurate than the peripheral blood film for routine identification of red blood cell fragments; and asymptomatic spectrin abnormality identifiable by abnormal histogram may be a relatively common disorder.
A microcomputer program (BCDE) has been developed to analyze automated blood cell counts and differentials' similarity to normal values or to 36 disease categories. In 50 normal subjects, the analytic program listed the correct diagnosis as the first diagnosis in 49 cases (the only diagnosis in 44) and second of two diagnoses in one case. In 182 subjects with known hematologic disorders, the correct diagnosis was listed first in 134 and second or third in an additional 40. Subjects with iron deficiency, heterozygous thalassemia, immune thrombocytopenia, anemia of chronic disease, reactive thrombocytosis, acute infection, and chronic leukemia had the disorder identified as the most likely one by the analytic program with both sensitivity greater than 80% and specificity greater than 98%. Subjects with acute leukemia, folate deficiency, sickle cell anemia, cytotoxic chemotherapy, and chronic liver disease had the disorder identified as most likely by the program with a sensitivity less than 80%. In a different 11 cases with known hematologic status, a panel of 37 physicians identified the disorder(s) or normality only 72% of the time, whereas the analytic program listed the correct diagnosis first in 10 of 11 (91%). The analytic program appears useful for both triage of normal from abnormal data and for the initial differential analysis of abnormal data.
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New methods for determination of specific concentration and molecular activity of monoamine oxidase (MAO) in platelets are described and evaluated in parallel with specific activity measures, performed in whole platelets and platelet extracts. Platelet MAO specific concentration is determined in platelet extracts by a radioimmunoassay, using a monoclonal antibody that recognizes human MAO B, the form that occurs in platelets, but not MAO A. All four platelet MAO measures are found to be reliable and stable, and thus are suitable for long-term comparisons of normal and clinical populations, such as those reported in Part II of this report. The new measures of enzyme concentration and molecular activity make available important information about the state of MAO B molecules in a given individual that reflects the genetic expression and control of the enzyme.
Platelet monoamine oxidase (MAO B) in 59 normal and 57 RDC-diagnosed medicated and unmedicated schizophrenic subjects was analyzed for whole platelet and extracted activities, specific concentration, and molecular activity. A novel radioimmunoassay using a monoclonal antibody elicited to human platelet MAO was used. Female schizophrenics showed no differences from female normals in MAO measures; however, these data could not be clearly evaluated because of confounding effects of age and drugs. Male schizophrenics treated with neuroleptics expressed significantly reduced whole platelet MAO activity, compared to untreated male patients. Compared with normal males, male schizophrenics showed significantly lowered molecular activities, along with elevated specific concentrations, which did not appear to be explained solely by drug usage. Additional mechanisms explaining the diminished molecular activity in male schizophrenics may be the presence of an endogenous irreversible inhibitor or a genetically determined, possibly structural, variant of MAO B.
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We measured the complete blood cell count, including the index of RBC size heterogeneity (RBC distribution width [RDW]), in 181 subjects without anemia to determine whether RDW became abnormal earlier in the development of iron deficiency than did other variables. In 163 subjects selected only for otherwise normal blood cell counts, an increased RDW was 66% specific (48/73) and 100% sensitive (48/48) for decreased serum iron saturation. Stool guaiac testing was equally specific but less sensitive. In 13 subjects with polycythemia, as iron deficiency developed, RDW increased a minimum of four weeks before mean cell volume changed. In one apparently normal young woman, an abrupt isolated rise in RDW revealed a newly developed low serum transferrin saturation; all values remained normal during serial testing of four other normal subjects. We conclude that RDW is the part of the routine blood cell count that first becomes abnormal during the development of iron deficiency.
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