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Biomedical subjects

J W Parker

Publications and source records attributed to J W Parker.

At least 19 recordsLinked to original sources

Successful short-segment instrumentation and fusion for thoracolumbar spine fractures: a consecutive 41/2-year series.

STUDY DESIGN: A retrospective review of all the surgically managed spinal fractures at the University of Missouri Medical Center during the 41/2-year period from January 1989 to July 1993 was performed. Of the 51 surgically managed patients, 46 were instrumented by short-segment technique (attachment of one level above the fracture to one level below the fracture). The other 5 patients in this consecutive series had multiple trauma. These patients were included in the review because this was a consecutive series. However, they were grouped separately because they were instrumented by long-segment technique because of their multiple organ system injuries. OBJECTIVES: The choice of the anterior or posterior approach for short-segment instrumentation was based on the Load-Sharing Classification published in a 1994 issue of Spine. The purpose of this review was to demonstrate that grading comminution by use of the Load-Sharing Classification for approach selection and the choice of patients with isolated fractures who are cooperative with spinal bracing for 4 months provide the keys to successful short-segment treatment of isolated spinal fractures. SUMMARY OF BACKGROUND DATA: The current literature implies that the use of pedicle screws for short-segment instrumentation of spinal fracture is dangerous and inappropriate because of the high screw fracture rate. METHODS: Charts, operative notes, preoperative and postoperative radiographs, computed tomography scans, and follow-up records of all patients were reviewed carefully from the time of surgery until final follow-up assessment. The Load-Sharing Classification had been used prospectively for all patients before their surgery to determine the approach for short-segment instrumentation. Denis' Pain Scale and Work Scales were obtained during follow-up evaluation for all patients. RESULTS: All patients were observed over 40 months except for 1 patient who died of unrelated causes after 35 months. The mean follow-up period was 66 months (51/2 years). No patient was lost to follow-up evaluation. Prospective application of the Load-Sharing Classification to the patients' injury and restriction of the short-segment approach to cooperative patients with isolated spinal fractures (excluding multisystem trauma patients) allowed 45 of 46 patients instrumented by the short-segment technique to proceed to successful healing in virtual anatomic alignment. CONCLUSIONS: The Load-Sharing Classification is a straightforward way to describe the amount of bony comminution in a spinal fracture. When applied to patients with isolated spine fractures who are cooperative with 3 to 4 months of spinal bracing, it can help the surgeon select short-segment pedicle-screw-based fixation using the posterior approach for less comminuted injuries and the anterior approach for those more comminuted. The choice of which fracture-dislocations should be strut grafted anteriorly and which need only posterior short-segment pedicle-screw-based instrumentation also can be made using the Load-Sharing Classification.

Adolescent↗

Endobronchial disease and racial differences in pulmonary sarcoidosis.

In a retrospective review of 7 years of Walter Reed Army Medical Center fiberoptic bronchoscopy records, 154 patients with biopsy specimen proved (122) and clinically diagnosed (32) sarcoidosis were identified. Endobronchial mucosal appearance was normal in only 70 (45%). Abnormal mucosal findings included erythema (29 patients), nodules (13), plaques (13), and cobblestoning (29). Fifty-nine patients were evaluated with endobronchial biopsies (EBBX), and non-necrotizing granulomata diagnostic of sarcoidosis were found in 42 (71%). The diagnostic yield from endobronchial biopsies was similar regardless of the type of mucosal abnormality. EBBX specimens were diagnostic in 85% of black patients and 38% of white patients (p = 0.00081), but diagnostic yield did not correlate with patient's sex, symptoms, radiographic stage of disease, or extent of physiologic abnormalities. Four patients with normal-appearing bronchial mucosa underwent EBBX, and sarcoidosis was diagnosed in two. Transbronchial lung biopsy (TBBX) specimens were diagnostic of sarcoidosis in 61 of 82 (74%) black and 28 of 56 (50%) white patients (p = 0.0038). We conclude that the bronchial mucosa appears abnormal in the majority (55%) of patients with sarcoidosis. EBBX specimens will diagnose sarcoidosis in a high percentage of such patients and should be performed routinely. EBBX may be preferable to TBBX because of its greater safety profile. In our patients, the yield of both EBBX and TBBX was significantly greater in African-Americans than white Americans.

Adolescent↗

Initial studies on active immunization of HIV-infected subjects using a gp120-depleted HIV-1 Immunogen: long-term follow-up.

In 1987, exploratory clinical studies were initiated to determine whether the development of AIDS in HIV-infected individuals might be delayed or prevented by immunization with an inactivated HIV preparation. Preclinical studies had shown the preparation to be safe and immunogenic. Twenty-three patients with biopsy-confirmed persistent generalized lymphadenopathy (CDC III) and two with asymptomatic HIV infection and CD4 lymphocyte counts between 135 and 769/mm3 were studied, of whom eight (32%) had additional HIV-related symptoms. Over a 3-year period, they received a median of eight open-label inoculations of 100 micrograms of inactivated gp 120-depleted HIV-1 Immunogen in incomplete Freund's adjuvant (IFA). Clinical, general laboratory, immunologic, and virologic parameters were followed for up to 6 years. No serious treatment-related adverse experiences were reported, nor was accelerated HIV disease progression seen. Twelve patients developed a delayed-type hypersensitivity response (HIV-DTH) to the immunogen and nine showed fourfold or greater increases in anti-p24 antibody titers. In the follow-up period, 10 of the 25 patients developed AIDS and one with Kaposi's sarcoma (KS) at baseline progressed. Of the 12 patients who became HIV-DTH-responsive, one developed an opportunistic infection (OI), occurring approximately 5 years from study onset, and subsequently died. One additional HIV-DTH responder developed KS. Of the 13 patients who remained HIV-DTH-nonresponsive, nine (69%) progressed to AIDS and seven of these have died. Differences were also observed in terms of HIV-DNA copy number, CD4 percentages, and anti-p24 antibody patterns between the HIV-DTH-responsive and -nonresponsive groups, suggesting a more favorable clinical course in the former. HIV-1 Immunogen in IFA appears to be safe and immunogenic. Further studies are indicated to determine clinical efficacy of the HIV Immunogen as well as the significance of the apparent correlation between HIV-DTH responsivity and a more favorable clinical course.

AIDS Vaccines↗

Standardization of absolute CD4+ lymphocyte counts across laboratories: an evaluation of the Ortho CytoronAbsolute flow cytometry system on normal donors.

The Ortho CytoronAbsolute is a flow cytometer designed to provide direct absolute counts of lymphocytes and their subsets from a single instrument. This study was designed to determine the performance of four geographically separated CytoronAbsolute instruments using 24-h-old, shipped, whole blood samples and to compare the results obtained on the CytoronAbsolute to those obtained using combinations of hematology instruments and other flow cytometers. The absolute count feature of the CytoronAbsolutes located at the four sites were cross calibrated and gave across-site coefficients of variation (CVs) of <4.0% for absolute count and 8.2% for absolute lymphocyte count. The calibration was stable for at least 2 months. Absolute lymphocyte counts and lymphocyte percentage immunophenotypes were determined on blood from 50 healthy human immunodeficiency virus (HIV)-seronegative donors. There were no significant site-to-site differences (each P > .05) in CD3+/CD4+ absolute lymphocyte counts determined on the CytoronAbsolute. In contrast, there was a significant site-to-site difference (P < .001) between sites 2 and 3 and sites 3 and 4 in the absolute CD3+/CD4+ lymphocyte counts determined via the conventional method of combining a flow cytometry-derived percentage with a hematology instrument-derived lymphocyte count. There was no significant difference (P = .388) in CD3+/CD4+ lymphocyte percent determinations between the CytoronAbsolute and the FACScan or Profile II flow cytometers used in this study. These results demonstrate that different operators can cross calibrate CytoronAbsolutes for absolute CD3+/CD4+ lymphocyte subset determinations, even over large geographic distances.

CD4 Lymphocyte Count↗

Blood transfusions and immunophenotypic alterations of lymphocyte subsets in sickle cell anemia. The Transfusion Safety Study Group.

Transfusions purportedly induce dysfunction of cell-mediated immunity in sickle cell anemia (SCA). We studied hematologic and lymphocytic indices in 173 human immunodeficiency virus (HIV)-negative subjects with SCA and 131 black controls. Children aged 1 to 7 years with SCA had leukocyte counts and percentages of granulocytes, monocytes, natural killer cells, and T-cell markers (CD2+CD11b+, CD4+CD26+, CD4+CD29+) that were significantly higher than those for control children. Percent total lymphocytes was decreased for this age group, but the total number of lymphocytes and T and B cell counts were similar to controls. Platelets were not increased. Adolescents (aged 8 to 17 years) and adults (aged > or = 18 years) with SCA had increased total leukocytes and monocytes and lymphocytes counts that remained level instead of decreasing, as did comparably aged controls. Lymphocyte subsets typically increased in count, but their percentage remained similar to children. The exception was CD56+ cell counts, which were increased in adolescents and adults. No lymphocytic subset change suggested impaired cellular immunity, and none could be related to transfusion. Prophylactically transfused patients had higher granulocyte counts, but these may arise from the complications of SCA itself.

Adolescent↗

Immunologic differentiation of absolute lymphocyte count with an integrated flow cytometric system: a new concept for absolute T cell subset determinations.

We describe a method to obtain results for immune status monitoring that uses a three-test panel, comprised of isotype control and 2 specific Mab tests (CD4/CD8/CD3 and CD16/CD19/CD3), in conjunction with a flow cytometer that directly measures absolute counts. Automated software is used for lineage-specific gating of three-color immunofluorescence to determine lymphocyte and lymphocyte subset counts. The autogating function of this software is shown to yield equivalent results to manual analysis by an expert user, and to be effective when as few as 25 target cells are present. The software is also shown to perform automatic quality control checks of the sample preparation, reagent, and automated analysis. We demonstrate that the sum of T (CD3+), B (CD19+), and natural killer (NK, CD16 + CD3-) cells, as a determination of all lymphocytes, correlates well with lymphocytes measured using a light scatter differential. Moreover, T + B + NK lymphocyte count is shown to be less error-prone than lymphocyte count from light scatter differential, and to minimize errors that arise from between-technician variation in sample preparation. Our data suggest that the new approach that we describe could offer an alternative to the traditional two-stage methods for measuring absolute counts of lymphocyte subsets for immune status monitoring. As such this method could reduce, through objective automated analysis, testing cost and complexity, without sacrificing the quality of results.

Algorithms↗

Long-term intravenous therapy with use of peripherally inserted silicone-elastomer catheters in orthopaedic patients.

We studied the results of prolonged intravenous therapy with antibiotics through a central venous silicone-elastomer catheter that had been peripherally inserted in thirty-five orthopaedic patients. The catheters remained in place for an average of twenty-nine days (range, five to seventy-four days). The 20-gauge (one-millimeter-diameter) catheters used in our study were smaller in diameter than the triple-lumen catheters or the double-lumen Hickman catheters used in previous studies. The catheters in our study were left indwelling for as long as, or for longer than, those in other studies. Our patients had no serious complications related to the insertion or use of the catheter. However, three (8 per cent) of thirty-eight inserted catheters failed mechanically and had to be removed. Two additional catheters (5 per cent) were removed because the lumen became plugged. One catheter in each of these groups was not replaced, because a catheter was no longer necessary. We believe that the problems with the catheters were related to the small diameter of the tubing that was used in our series. Use of the small-diameter catheter reduces the risk of cardiac tamponade and other complications associated with catheters that have larger diameters, and small-diameter catheters can remain indwelling for a long time. The peripheral route of insertion eliminates the risk of pneumothorax associated with the subclavian route of placement and allows for greater ease of insertion. In addition, the use of catheters made of silicone elastomer reduces the risk of thrombosis and infection, which are associated with catheters made of polyethylene.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of low- and intermediate-purity clotting factor therapy on progression of human immunodeficiency virus infection in congenital clotting disorders. Transfusion Safety Study Group.

Low- and intermediate-purity clotting-factor therapies are believed to accelerate human immunodeficiency virus (HIV) progression in hemophiliacs through adverse immune effects of the other plasma proteins in the preparations. To investigate this postulate, we evaluated data from six clinical centers that observed persons with congenital factor deficiencies at 6-month intervals. The present analysis is based on HIV-infected subjects who received intermediate purity factor VIII or factor IX concentrates, or cryoprecipitate. For long-term outcome, we classified 374 subjects by the type and amount of treatment during our first year of observation, and determined the subsequent rate of progression to a CD4 count less than 200 cells/microL. A second analysis of this group used a repeated-measures, random-effect model that allowed for individual differences in CD4 decline. Finally, we compared short-term rates of change in CD4 count in each treatment interval of 525 subjects with the type and amount of factor therapy received in the same interval. There was no overall or dose-related deleterious effect of any form of treatment on CD4 trend. The CD4 decrease was less when cryoprecipitate was administered alone or combined with concentrate, but not significantly so. Our results counter the assertion that low- and intermediate-purity products accelerate the rate of CD4 decrease in HIV-1-infected hemophiliacs.

Acquired Immunodeficiency Syndrome↗

Effect on lymphocyte subsets of clotting factor therapy in human immunodeficiency virus-1-negative congenital clotting disorders. The Transfusion Safety Study Group.

Patients with hemophilia A without human immunodeficiency virus type 1 (HIV-1) infection have lower CD4+ counts and CD4+/CD8+ ratios than controls. This is usually interpreted as a therapy-induced immunodeficiency. Our data re-examine the effect of therapy on peripheral blood mononuclear cell immunophenotypic subpopulations in all congenital clotting disorders. Since late 1985 we have prospectively observed HIV-1 uninfected persons with all types and severity of disorder. Controls were household members without clotting disorders or HIV-1 infection. Analyses of immunophenotype and treatment included a longitudinal random effects model. Compared with controls, age-adjusted CD4+ counts were significantly lower in treated patients (P < .0001) and in patients with all types of clotting disorders who were seldom or never treated (P = .0005). Significantly lower values among both treated and untreated clotting disorder subjects (P < .05) were likewise found for total lymphocytes, several other T-cell subsets, and the CD4+/CD8+ ratio. For most indexes, including the CD4+ count and CD4+/CD8+ ratio, the type of clotting deficiency was not a significant variable. Comparing persons who had no or minimal therapy with those having the most showed increases in CD8+ (P = .0017) and CD20+ CD21- counts (P = .0255), and a lower CD20+ CD21+/CD20+ ratio (P = .0106) in the latter. Controls and persons with clotting disorders differ in CD4+ count. Among those with clotting factor disorders, there is no difference attributable to type of clotting disorder or factor therapy. Large amounts of treatment increased CD8+ and CD20+ CD21- counts, but were not associated with a change in CD4+ count.

Antigens, CD↗

Inhibition of human immunodeficiency virus infection by the lectin jacalin and by a derived peptide showing a sequence similarity with gp120.

Jacalin is a plant lectin known to specifically induce the proliferation of CD4+ T lymphocytes in human. We demonstrate here that jacalin completely blocks human immunodeficiency virus type 1 (HIV-1) in vitro infection of lymphoid cells. Jacalin does not bind the viral envelope glycoprotein gp120. Besides other T cell surface molecules, it interacts with CD4, the high-affinity receptor to HIV. Binding of jacalin to CD4 does not prevent gp120-CD4 interaction and does not inhibit virus binding and syncytia formation. The anti-HIV effect of the native lectin can be reproduced by its separated alpha-subunits. More importantly, we have defined in the alpha-chain of jacalin a 14-amino acid sequence which shows high similarities with a peptide of the second conserved domain of gp120. A synthetic peptide corresponding to this similar stretch also exerts a potent anti-HIV effect. This peptide is not mitogenic for peripheral blood mononuclear cells and does not inhibit anti-CD3-induced lymphocyte proliferation. These results make jacalin alpha chain-derived peptide a potentially valuable therapeutic agent for acquired immunodeficiency syndrome.

Amino Acid Sequence↗

Clonal analysis of in vivo activated CD8+ cytotoxic T lymphocytes from a melanoma patient responsive to active specific immunotherapy.

To study in vivo activated cytolytic T cells, CD8+ T cells clones were isolated from a melanoma patient (HLA A2, A11) treated with active specific immunotherapy for 5 years. CD8+ T lymphocytes, purified by fluorescence-activated cell sorting, were cloned directly from the peripheral blood without antigen-presenting cells in the presence of irradiated autologous melanoma cells and recombinant interleukin-2 (IL-2) and IL-4. These conditions were inhibitory to de novo in vitro immunization. Of the 28 cytolytic CD8+ T cell clones, 21 lysed the autologous melanoma cell line (M7) but not the autologous lymphoblastoid cell line (LCL-7) nor the two melanoma cell line, M1 (HLA A28) and M2 (HLA A28, A31), used to immunize the patient. The remaining 7 clones were also melanoma-specific, although their reactivities were broader, lysing several melanoma cell lines but not HLA-matched lymphoblastoid cells. Eight clones from the first group, ostensibly self-MHC-restricted, were expanded for further analysis. All expressed cluster determinants characteristic of mature, activated T cells, but not those of thymocytes, naive T cells, B cells or natural killer (NK) cells. They also expressed CD13, a myeloid marker. Of the 8 clones, 3 expressed both CD4 and CD8, but dual expression was not correlated with specificity of lysis. Two CD8+ and 2 CD4+ CD8+ clones were specific for the autologous melanoma cells, the other 4 were also reactive against other HLA-A2-positive melanomas. Cytotoxicity for both singly and doubly positive clones was restricted by HLA class I but not class II antigens. Analysis of the RNA expression of the T cell receptor (TCR) V alpha and V beta gene segments revealed heterogeneous usage by the A2-restricted clones and, perhaps, also by the broadly melanoma-specific clones. Apparent TCR-restricted usage was noted for the self-MHC-restricted clones; 2 of the 4 expressed the V alpha 17/V beta 7 dimer. Since the T cell clones were derived from separate precursors of circulating cytotoxic T lymphocytes (CTL), the V alpha 17/V beta 7 TCR was well represented in the peripheral blood lymphocytes of this patient. In summary, we show that melanoma cells presented their own antigens to stimulate the proliferation of melanoma-reactive CD8+ CTL. CTL with a range of melanoma specificities and different TCR alpha beta dimers were encountered in this patient, perhaps as a result of hyperimmunization.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Effect of age on human immunodeficiency virus type 1-induced changes in lymphocyte populations among persons with congenital clotting disorders. Transfusion Safety Study Group.

Children other than neonates infected with human immunodeficiency virus type 1 (HIV-1) have low rates of progression to acquired immunodeficiency syndrome (AIDS). Through 1989, 5.3% of 95 infected hemophiliacs aged 5 to 13 years developed AIDS, compared with 20.3% of 364 aged greater than or equal to 25 years. We asked whether the HIV-1 impact on peripheral blood mononuclear cell subpopulations differed with age using pairwise comparisons of uninfected and infected male children and adult hemophiliacs. Infected children had lesser reductions of total lymphocytes than adults, but proportionately lower numbers of CD2+, CD4+, CD2+CD26+, and CD4+CD29+ counts. CD4+CD45RA+ cell counts were greater than twofold higher in uninfected and infected children than adults; with infection, the CD4+CD45RA+/CD4+ proportion increased by 1.4-fold in adults, but was unchanged in children. Infected adults had highly significantly increased total CD8+ counts; both age groups had elevated CD8+HLA-DR+ counts. Infected children had significantly higher total B-cell counts than infected adults, with a disproportionately lower number of resting B cells (CD20+CD21+). During 2 years of follow-up, infected children and adults had lymphocyte changes in the same directions and these were proportionately equal. The lower rate of HIV-1 progression in children may be partly associated with differences in lymphocyte populations compared with adults; functional properties of immune cells may be equally or more important.

Acquired Immunodeficiency Syndrome↗

Clinical applications of cytometry: 6th annual meeting.

The Sixth Annual Clinical Applications of Cytometry Meeting was held September 11-14, 1991, in Charleston, SC. Attendance reached a record 470. The meeting provides a forum for interactions among investigators who utilize cytometry as a tool in their clinical immunology, cell biology, hematology, and cancer investigations. Clinical laboratory directors and their technical staff find the meeting of practical value because of the presentation of new applications that they can take home to their own laboratories. The emphasis of the meeting is on advances in the application of cytometry to clinical problems. Often, advances result from new dyes or reagents or improved instrumentation. Sometimes they result from advances in biology that make the studies possible. Occasionally a new way of looking at the same data provides a useful answer. In every case, the effort is to provide a reliable, straightforward way to quantitate biologic information in order to provide improved diagnosis or treatment of human disease.

Acquired Immunodeficiency Syndrome↗

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↗

Lymphocyte immunophenotypes among anti-HTLV-I/II-positive blood donors and recipients. The Transfusion Safety Study Group.

The Transfusion Safety Study retrospectively screened a repository of serum specimens collected in late 1984-early 1985 to identify blood donors with antibody to human T-cell lymphotropic virus (HTLV) at that time. They and their recipients have been traced for additional HTLV studies. Immunophenotypic analyses of peripheral blood lymphocytes from nine anti-HTLV-positive recipients, assumed to be infected during or since late 1984, showed no significant changes from healthy controls. Evaluation of the immunophenotypes of the 48 donors, however, showed significant elevations in the absolute counts of the T-cell (CD2) and natural killer (CD56) populations, the T helper/inducer and suppressor/inducer subsets (CD4+ CD29+ and CD4+ CD45RA+), and changes in T-cell activation markers. Long-term but not recent HTLV infection appears to alter the T-cell immunophenotypic pattern. Both infection with HTLV and human immunodeficiency virus type 1 are associated with a decreased CD2+ CD26+ count.

Blood Donors↗

Leukocyte immunophenotyping by flow cytometry in a multisite study: standardization, quality control, and normal values in the Transfusion Safety Study. The Transfusion Safety Study Group.

The Transfusion Safety Study (TSS) is a multicenter, cooperative investigation of factors that may determine the occurrence and modify the expression of transfusion-transmitted infections. A flow cytometry laboratory was established in each of the six participating centers in order to avoid alterations in cell phenotypes which may be caused by shipping delays, temperature changes, and handling. As a consequence, in order to assure compatibility of results, stringent standardization, quality control, and proficiency testing procedures were developed. This paper documents (i) the effect of time from phlebotomy to specimen staining and then to analysis for the antibodies used in the study; (ii) the effects of variations in light scatter cursor location for certain antibodies; (iii) a quality control program and data management and analysis system, each specifically designed for the study; and (iv) presents extensive data on age- and sex-related reference (normal) ranges for the several individual and paired monoclonal antibodies used in the study. Problems encountered, including obtaining reliable absolute lymphocyte counts, interference by nucleated erythrocytes, and sources of variability in results, are discussed. This study is meant to serve as a reference for future TSS publications.

Blood Transfusion↗