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Biomedical subjects

P Kidd

Publications and source records attributed to P Kidd.

At least 37 records · Page 2Linked to original sources

Familial occurrence of LGL leukaemia.

The aetiology of LGL leukaemia is now known; however, we recently detected HTLV-II from such a patient. We describe here the occurrence of LGL leukaemia in a mother and her son. Serum from the son reacted to HTLV-I/II gag proteins, but not a recombinant HTLV-I env protein p21e; serum from the mother was negative. PCR analyses in both patients were negative for pX and pol sequences shared by HTLV-I/II and also for specific gag sequences of HTLV-I and HTLV-II. These data show that familial cases of LGL leukaemia are not associated with prototypical HTLV-I or HTLV-II infection.

Adult↗

Assessment of the effects of instrumentation, monoclonal antibody, and fluorochrome on flow cytometric immunophenotyping: a report based on 2 years of the NIAID DAIDS flow cytometry quality assessment program.

This study of the effect on CD4%, CD8%, CD3+8+%, and CD3% of flow cytometer, monoclonal antibody, and fluorochrome was based on 71 whole-blood samples, each evaluated by 42 to 59 laboratories during 2 years of a flow cytometry quality assessment program. For the 24 HIV-positive specimens, FACScans produced significantly lower CD4% values than EPICS-Cs or EPICS Profiles, and for the 47 HIV-negative specimens, FITC was associated with significantly lower CD4% values than PE or RD1, but differences were never larger than 2% and regressions accounted for only 3-12% of the variability. The labs using the most common CD4 technique had significantly higher between-laboratory variability than all other labs grouped together. For both CD8 and CD3+8+, measurements on FACScans were significantly higher than measurements on EPICS, and measurements using Leu2 were significantly higher than measurements using T8, with regressions accounting for 12-31% of the variability. The machine differences in medians were 3-7% for labs using Leu2-FITC. It might be worthwhile to discourage the use of Leu2-FITC for measuring CD8% but no change in instrument, monoclonal antibody, or fluorochrome would greatly improve interlaboratory agreement on CD4%.

Antibodies, Monoclonal↗

Clinical applications of cytometry: 5th annual meeting.

The 5th annual Clinical Applications of Cytometry meeting was held September 12-15, 1990 in charleston, SC. The theme which emerged repeatedly throughout the meeting was the need to take full advantage of the quantitative power of cytometry to provide the most useful clinically relevant diagnostic and prognostic information. Greater quantitative power is based on careful and reproducible standards and quality control. The same principles, albeit with somewhat different approaches, apply to cell surface immunofluorescence analysis, DNA measurements, and image cytometry assessments. Monoclonal antibody probes against oncogenes, others against lymphokines within the Golgi, and a novel fluorogenic substrate designed to quantitate the activity of a mitochondrial enzyme were exciting developments described at the meeting.

Autoimmune Diseases↗

Reversed helper/suppressor T-lymphocyte ratio in bronchoalveolar lavage fluid from patients with breast cancer and Pneumocystis carinii pneumonia.

Pneumocystis pneumonia (PCP) usually occurs in patients with hematologic malignancies and acquired immunodeficiency syndrome (AIDS). Patients with solid tumors represent a very small fraction of the reported cases of PCP. Over an 18-month period, PCP was diagnosed in three patients who had received radiation and chemotherapy for breast cancer. In all three patients, there was no serologic or clinical evidence of AIDS. Direct staining of bronchoalveolar lavage fluid (BAL) revealed Pneumocystis carinii, and cellular analysis of BAL revealed an increased percentage of lymphocytes with reversed helper/inducer:suppressor/cytotoxic T-cell (CD4:CD8) ratio. Because decreased CD4:CD8 ratio in BAL is commonly accepted as findings consistent with hypersensitivity pneumonitis and AIDS, we conclude that similar findings in patients without AIDS are not specific for hypersensitivity pneumonitis, and P. carinii should be ruled out in the appropriate clinical setting.

Adult↗

Oligoclonal immunoglobulin heavy chain gene rearrangement in a childhood immunoblastic lymphoma. Presentation as a polyphenotypic atypical lymphoproliferative reaction.

The authors describe a diagnostically difficult case of childhood lymphoma that presented as an atypical polyphenotypic lymphoproliferative reaction. Initial immunophenotyping revealed the presence of IgG, IgA, kappa, and lambda within the neoplastic lymphocytes. The patient had circulating plasmacytoid lymphocytes and a polyclonal hypergammaglobulinemia. The patient died of widespread immunoblastic lymphoma in two months. Postmortem tumor DNA showed a oligoclonal pattern of immunoglobulin heavy chain gene rearrangement. Blots for T-cell receptor beta-chain rearrangement showed germline bands. Epstein-Barr virus DNA was present within tumor cells, but there was no history of prior immunosuppression or serologic evidence of Epstein-Barr virus infection. The apparent polyclonal nature of the immunoproliferation delayed the institution of chemotherapy.

Blotting, Southern↗

Very low dose alpha-2b interferon for the treatment of hairy cell leukemia.

Alpha-2b interferon (alpha-2b IFN), administered at 2 x 10(6) U/m2 three times per week is highly effective in the treatment of progressive hairy cell leukemia (HCL) and in the retreatment of patients who have relapsed after previous IFN therapy. To determine if a lower interferon dose would induce a comparable antileukemic effect with less toxicity, a-2b IFN was administered at 2 x 10(5) U/m2 subcutaneously three times per week to 17 patients with progressive HCL. Thirteen patients had HCL in relapse after a previous response to alpha-2b IFN; four patients were previously untreated. The median duration of treatment was 9 months. Toxicity consisted only of transient, mild flu-like symptoms in two patients. Of the 13 previously IFN-treated patients, four had a minimal response, one had no response, and eight had progressive disease. Of four previously untreated patients, one had a partial response, two had a minimal response, and one had no response. In seven of eight patients whose disease progressed on low-dose IFN, the dose was escalated to 2 x 10(6) U/m2 three times per week, and all seven patients demonstrated hematologic response within 3 months to the dose escalation. We conclude that alpha-2b IFN at 2 x 10(5) U/m2 three times per week is relatively ineffective for the treatment of relapse after previous IFN therapy.

Dose-Response Relationship, Immunologic↗

Results of the flow cytometry ACTG quality control program: analysis and findings.

The AIDS Clinical Trial Group's (ACTG) Immunology Committee was charged with initiating a quality control program for all laboratories participating in the ACTG program reporting flow cytometry data. Forty-one laboratories were evaluated. This report defines the goals of this program and the subsequent findings after 19 send-outs were made. Both HIV positive volunteer donors and normal age-matched donors were used. Sample sets included both heparin and EDTA anticoagulated bloods. Laboratories were asked to report hematologic parameters as well as flow cytometry data both in percentages and absolute numbers. Results were evaluated using nonparametric statistical analysis. Robust CVs and interquartile ranges were used to define the performance of individual laboratories for each CD subset analyzed. Intralaboratory reproducibility was analyzed by paired sample sets. All laboratories were found to be able to define normal samples as normal. Seventy-five percent of the laboratories were able to define abnormal samples as abnormal. Twenty-five percent could not identify two abnormal samples as abnormal. Forty percent of the labs were found unable to reproduce paired samples within an absolute of +/- 5%. EDTA was found slightly superior to heparin in bloods evaluated by flow cytometry within 30 hr of collection. The analysis of specific histograms, questionnaires, and data analysis led to a specific set of recommendations for performance of flow cytometry studies.

Acquired Immunodeficiency Syndrome↗

Subcutaneous granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndrome: toxicity, pharmacokinetics, and hematological effects.

The toxicity, pharmacokinetics, and hematologic effects of granulocyte-macrophage colony-stimulating (GM-CSF) were studied in a phase I/II trial of 16 patients with myelodysplastic syndrome (MDS). The GM-CSF was administered subcutaneously (SC) daily so as to achieve prolonged blood levels and to establish an outpatient treatment regimen. Four dose levels were administered for ten days: 0.3 microgram/kg/d (three patients), 1.0 microgram/kg/d (three), 3.0 micrograms/kg/d (four), and 10.0 micrograms/kg/d (six). The most common toxicities were fever and a flu-like syndrome, which were dose-dependent. The maximum-tolerated dose was 10.0 micrograms/kg/d, which induced severe rigors (two patients), fever greater than 40 degrees C (one), severe bronchospasm (one), and WBC 60,000 (one). In one patient, refractory anemia with excess blasts in transformation (RAEB-T) progressed to acute nonlymphocytic leukemia after two doses of GM-CSF, and the patient died of leukemia that did not respond to chemotherapy. After doses of 3.0 and 10.0 micrograms/kg, serum GM-CSF levels peaked at 3.8 to 6.3 hours, and persisted for 14 and 24 hours, respectively. Circulating granulocytes (neutrophils and bands) increased in a dose-dependent manner, as 11 of 13 patients who received greater than or equal to 1.0 microgram/kg/d responded with a two- to 194-fold increase. Although the neutrophils usually returned to pretreatment levels shortly after stopping GM-CSF, two patients continue to exhibit an elevation of neutrophils for 6 months. Dose-related increases in circulating monocytes and eosinophils were also noted. Transient increases in platelet and reticulocyte counts were observed in two and three patients, respectively. Five of the 16 patients later received maintenance GM-CSF at 3 micrograms/kg/d for 2 to 9 weeks. All showed a dramatic increase in neutrophils after 2 weeks. Thereafter, despite continued therapy, the neutrophil count in four patients declined markedly. In conclusion, GM-CSF is well tolerated by the SC route and induces striking, but usually temporary, improvement in the neutropenia of MDS. Larger prospective phase III trials will determine the duration of hematologic responses and the impact on infection, morbidity, and mortality.

Adolescent↗

Myasthenia gravis and lymphoblastic lymphoma antiacetylcholine receptor antibody as a tumor marker--a case report.

This report documents an association between lymphoblastic lymphoma and myasthenia gravis. Elevation of acetylcholine receptor antibody titer was an unusual marker for the lymphoblastic lymphoma. Following chemotherapy all symptoms of myasthenia gravis resolved and the acetylcholine receptor antibody titer normalized. The patient remains in complete remission off all therapy 20 months since the diagnosis of myasthenia gravis was made and 12 months after chemotherapy for her lymphoma.

Antigens, Neoplasm↗

Interactive computer-video modules for health sciences education.

Advances in electronic image recording and computer technology have resulted in a remarkable increase in the power and flexibility of interactive computer-video teaching systems. The University of Washington Health Science Videodisc Development Group first demonstrated a laser videodisc controlled by a remote central computer in 1980. Even this rudimentary unit highlighted basic medical informatics principles including: rapid accessibility; a "generic" or multi-purposed format; ease of computer control; and large collections of valid, rigorously reviewed images. Advances in medical informatics have led to the development of the following previously undescribed series of teaching units: 1. The hypertext programs Hypercard, Linkway, and Guide have been used with videodiscs to develop easy-to-use instructional and reference materials. These materials demonstrate the ease with which a computer-naive instructor may develop new programs and the advantages that the intuitive nature of these programs brings to student users. 2. Patient simulations using single and double screens plus pre-defined knowledge structures; 3. Interactive single topic tutorials using preset knowledge structures; 4. A key-word-based disc searching system; 5. Electronic video microscopy; 6. A series of programs developed independently by health science faculty who have purchased multi-purpose videodiscs that demonstrate the flexibility of the multi-purpose or "generic": collection concept.

Computer Simulation↗

Clonal proliferation of large granular lymphocytes in rheumatoid arthritis.

Some patients with chronically elevated large granular lymphocyte (LGL) numbers have rheumatoid arthritis (RA). Since these patients also may have neutropenia and splenomegaly, their symptoms resemble those of patients diagnosed as having Felty's syndrome (FS). We studied the immunophenotypic and genotypic characteristics of mononuclear cells from patients with RA and neutropenia to better determine the extent of heterogeneity in this condition. Four patients had markedly increased numbers of LGLs, which expressed HNK-1 antigen and IgG Fc receptors. In contrast, the remaining 8 patients, who had FS, had normal LGL counts, and surface marker studies showed normal numbers of HNK-1 and IgG Fc receptor positive cells. Clonal rearrangement of the T cell receptor beta chain gene was demonstrated in all 4 patients with excess LGLs, whereas a germline configuration of this gene was present in all 6 FS patients in whom this was studied. These results suggest that there are diverse groups among patients with RA and neutropenia. Since prognosis may differ, it is important to recognize that some patients who are considered to have Felty's syndrome may have a clonal proliferation of LGLs.

Antigens, Surface↗

Idiopathic myelofibrosis in blast transformation with 4;12 and 5;12 translocations and a 7q deletion.

A case of a patient who developed a leukemic transformation following an 8.5-year history of idiopathic myelofibrosis (IMF) with myeloid metaplasia is presented. Surface marker analysis identified the blast cells as myeloid in lineage. The karyotype of unstimulated peripheral blood cells was 46,XY,t(4;12)(q26;15),t(5;12)(q13;q24),del(7)(q22). In the literature, the 7q- has a minor association with IMF, and the t(5;12) translocation has been reported in one case of acute nonlymphocytic leukemia, but neither the t(4;12) nor the combination of these three abnormalities has been reported in IMF.

Aged↗

Myasthenia gravis associated with T helper cell lymphoma.

A case of myasthenia gravis (MG) associated with a T helper cell lymphoma is reported. Treatment of the lymphoma led to resolution of the MG. This and other cases of hematologic tumors associated with MG suggest that immunoregulatory abnormalities may underlie the production of antibodies directed against the acetylcholine receptor.

Antigens, Surface↗

Induction of NK activity in large granular lymphocyte leukemia: activation with anti-CD3 monoclonal antibody and interleukin 2.

Large granular lymphocyte (LGL) leukemia is a rare disease characterized by clonal expansion of LGL associated with chronic neutropenia, multiple auto-antibodies, and occasionally polyarthritis. We studied cell surface antigen expression and functional activity of leukemic LGL from ten such patients. Using two-color flow cytometric analysis, we found that leukemic LGL from all ten patients expressed the CD3 and HNK-1 markers, while cells from only four patients expressed IgG Fc receptors (FcR). The LGL leukemic cells had little or no NK activity (defined as MHC-nonrestricted cytotoxicity against K562 target cells); however, NK activity could be induced in leukemic LGL by in vitro treatment with as little as 0.05 microgram/mL of anti-CD3 monoclonal antibody. Cell sorting experiments demonstrated that NK activity was induced in CD3+ leukemic LGL (either CD3+, HNK-1+ or CD3+, FcR+) with anti-CD3 monoclonal antibody but not in normal CD3+, FcR- T cells. Treatment with purified interleukin 2 (IL 2) also caused direct activation of some CD3+ leukemic LGL. Despite induction with anti-CD3 MAb or IL 2, activated leukemic LGL did not proliferate or express high density IL 2 receptors detectable by cell sorter analysis. Treatment with alpha interferon had minimal effect on NK activity of LGL leukemic cells. These results suggest that leukemic LGL may provide a useful model for examining the signals required for LGL maturation and activation.

Antibodies, Monoclonal↗

Monoclonal antibody 1F5 (anti-CD20) serotherapy of human B cell lymphomas.

Four patients with refractory malignant B cell lymphomas were treated with continuous intravenous (IV) infusions of murine monoclonal antibody (MoAb) 1F5 (anti-CD20) over five to ten days. Dose-dependent levels of free serum 1F5 were detected in all patients. Two patients had circulating tumor cells and in both cases 90% of malignant cells were eliminated from the blood stream within four hours of initiation of serotherapy. Antigenic modulation did not occur, and sustained reduction of circulating tumor cells was observed throughout the duration of the infusions. Serial bone marrow aspirations and lymph node biopsies were examined by immunoperoxidase and immunofluorescence techniques to ascertain MoAb penetration into extravascular sites. High doses (100 to 800 mg/m2/d and high serum 1F5 levels (13 to 190 micrograms/mL) were required to coat tumor cells in these compartments in contrast to the low doses that were adequate for depletion of circulating cells. Clinical response appeared to correlate with dose of MoAb administered with progressive disease (52 mg), stable disease (104 mg), minor response (1,032 mg), and partial response (2,380 mg) observed in consecutive patients. The patient treated with the highest 1F5 dose achieved a 90% reduction in evaluable lymph node disease, but the duration of this remission was brief (six weeks). This study demonstrates that high doses of 1F5 can be administered to patients with negligible toxicity by continuous infusion and that clinical responses can be obtained in patients given greater than 1 g of unmodified antibody over a ten-day period.

Adult↗

Magnetic resonance imaging of bone marrow in hairy cell leukemia: correlation with clinical response to alpha-interferon.

Five patients with progressive hairy cell leukemia were treated with recombinant alpha 2-interferon and examined prospectively at 3-month intervals using serial bone marrow biopsies and magnetic resonance (MR) imaging. Pretreatment iliac crest marrow biopsies demonstrated hairy cell infiltration involving 30-90% of marrow cellularity. Concurrent pretreatment coronal images of the proximal femurs and pelvis using MR revealed extensive marrow involvement that varied in distribution from patchy to diffuse. At 6 months, all patients had responded to alpha 2-interferon with improvement in peripheral blood counts and decrease in lymphoid infiltration on marrow biopsy to 15-40%. Six-month follow-up MR scans demonstrated decreasing marrow leukemia infiltration and increasing marrow fat. MR bone marrow imaging appears useful in the initial diagnosis of hairy cell leukemia, for monitoring the response to treatment, and possibly for predicting relapse.

Bone Marrow↗