Multiple myeloma presenting as extramedullary plasmacytoma of the thyroid, advanced grade II-III plasmablastic type.
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Aged↗
Biomedical subjects
R R Turner
Publications and source records attributed to R R Turner.
Form of mercury in stream fish exposed to high concentrations of dissolved inorganic mercury.
The form of mercury predominating in mercury-contaminated fish from both pristine and industrialized waters in North America and Europe has almost universally been methylmercury. Sunfish (Lepomis auritus) living in a stream contaminated with 0.5-1 micrograms/L dissolved inorganic mercury accumulated greater concentrations of total mercury at headwater sites, where the dissolved mercury concentrations were greatest, than they did at downstream sites. However, despite evidence from laboratory studies that dissolved inorganic mercury is rapidly accumulated by fish without transformation to methylmercury, methylmercury constituted 85% or more of the total mercury concentration in fish at all sites.
Animals↗
Improved axillary staging of breast cancer with sentinel lymphadenectomy.
OBJECTIVE: The authors evaluated the effect of intraoperative lymphatic mapping and sentinel lymphadenectomy (SLND) on the axillary staging of patients with carcinoma of the breast. SUMMARY BACKGROUND DATA: The accurate staging of patients with breast cancer is essential to guide management and determine prognosis. The authors previously reported the feasibility and accuracy of SLND in breast carcinoma. Sentinel lymphadenectomy identifies the first ("sentinel") axillary lymph node draining the site of a primary tumor; because this node is the most likely site of axillary metastasis, histopathologic examination of the sentinel node correlates well with examination of the entire axillary contents. The current study compares SLND with standard axillary lymphadenectomy (ALND) for the staging of breast carcinoma. METHODS: The incidence of axillary node metastasis and micrometastasis in SLND and ALND specimens from patients undergoing operative treatment of a primary breast carcinoma was compared prospectively. Multiple sections of each sentinel lymph node in SLND specimens were examined by hematoxylin and eosin (H&E) staining and by immunohistochemical techniques using antibodies to cytokeratin. One or two sections of each nonsentinel lymph node in ALND specimens were examined by routine H&E staining. RESULTS: One hundred thirty-four patients underwent ALND (ALND group), and 162 underwent successful SLND followed by completion ALND (SLND group). Both groups were similar with respect to age (median, 55 and 54 years, respectively), palpable primary tumors (54.5% and 59.3%, respectively), palpable axillary nodes (5.2% and 7.4%, respectively), size of primary tumor (median, 1.5 cm in each group), and total number of axillary lymph nodes examined (median, 19 and 21, respectively). The number of patients with axillary metastasis was 39 (29.1%) in the ALND group and 68 (42.0%) in the SLND group (p < 0.03). Of these, 4 of 39 (10.3%) ALND patients (3.0% of all ALND patients) and 26 of 68 (38.2%) SLND patients (16.0% of all SLND patients) had micrometastasis (< or = 2 mm), a highly significant difference (p < 0.0005) CONCLUSIONS: Sentinel lymphadenectomy with multiple sectioning and immunohistochemical staining of sentinel nodes increases the accuracy of axillary staging in breast cancer and can identify significantly more patients with lymph nodes metastases, especially micrometastases, than can ALND with routine histopathologic processing of lymph nodes.
Adult↗
Evaluation and quality-of-life assessment of amlodipine and enalapril in patients with hypertension.
In this multicentre, double-blind trial in 461 patients with essential hypertension, amlodipine (5-10 mg once daily) and enalapril (10-40 mg once daily) were compared in terms of quality of life, efficacy and tolerability after 1 year of treatment (part 1). In part 2, 177 patients successfully treated with amlodipine in part 1 continued in an open evaluation of efficacy and safety of antihypertensive treatment with amlodipine for a further 2 years. In part 1, both drugs were similarly effective in lowering blood pressure (BP) (although significantly more enalapril patients required a diuretic) while maintaining quality of life. Apart from class-typical effects, such as oedema for calcium antagonists and cough for angiotensin-converting enzyme inhibitors, both drugs were equally well tolerated, with few adverse effects of clinical significance. Only a few patients (eight amlodipine (4%), nine enalapril (4%)) were withdrawn from the trial because of drug-related adverse events, demonstrating that the tolerability was good. Neutral to slightly beneficial effects were found in blood lipid concentrations after treatment with amlodipine. The BP reduction seen in the amlodipine patients after part 1 was maintained during part 2. Also, blood lipids and safety variables remained virtually constant. It is concluded that, at similar BP reduction, quality of life is equally well maintained on amlodipine and enalapril therapy. Thus, amlodipine compares favourably with enalapril as an effective and well-tolerated anti-hypertensive agent over the first year. Additionally, amlodipine patients evaluated over a 2-year extension maintained good BP control and the drug was well tolerated.
Adult↗
A double-blind, long-term, comparative study on quality of life, safety, and efficacy during treatment with amlodipine or enalapril in mild or moderate hypertensive patients: a multicenter study.
Amlodipine (5-10 mg, once daily) and enalapril (10-40 mg, once daily) were compared in terms of quality of life, efficacy, and tolerability, in a multicenter, double-blind trial lasting for 50 weeks in 461 mild or moderate hypertensive patients. Both drugs were similarly effective in lowering blood pressure while maintaining quality of life. Apart from class-typical effects, such as edema for calcium antagonists, and cough for angiotensin-converting enzyme inhibitors, both drugs were equally well tolerated, with few adverse effects of clinical significance. Only a few patients [eight amlodipine (4%); nine enalapril (4%)] were withdrawn from the trial due to drug-related adverse events, demonstrating that tolerability was good. Neutral to slightly beneficial effects were found in blood lipid concentrations after treatment with amlodipine. Both drugs reduced the calculated risk of coronary heart disease over the next 10 years. It was concluded that amlodipine compared favorably with enalapril as an effective and well-tolerated antihypertensive drug.
Adult↗
Role of quality of life in hypertension therapy: implication for patient compliance.
Although the cardiovascular risk factors associated with hypertension are well established, the effects of the disease are usually transparent to the patient. However, the impact of diagnosis and treatment are often overt and usually negative. Because of high rates of non-compliance following adverse experiences with treatment, patients are exposed to the kind of risk for which therapeutic intervention was originally intended. The nature of the impact of hypertension therapy has become more clearly defined as well-controlled, quality-of-life studies have been reported across a variety of therapeutic classes. These studies may be used to address the problem of patient compliance by (1) informing the physician about the likely effects a class of, or particular, compound might have, and (2) by providing a means by which the physician can monitor and intervene in the treatment process. By using quality-of-life information, the clinician can directly influence the impact of therapy on the patient, improve compliance with the therapeutic regimen, and reduce that patient's risk for cardiovascular events.
Humans↗
Cost implications of alternative treatments for AIDS patients with cryptococcal meningitis. Comparison of fluconazole and amphotericin B-based therapies.
The extra demands placed upon health care resources by management of AIDS patients have increased the focus on cost implications of therapeutic alternatives. Cryptococcal meningitis is a common life-threatening infection in AIDS patients, usually treated with amphotericin B, often in combination with flucytosine. Administered intravenously, this therapy is associated with frequent and often severe side effects. Fluconazole is a new alternative which can be given orally once daily and has fewer such side effects. The purpose of this study was to examine the cost implications of these different therapies for both primary and maintenance treatment of cryptococcal meningitis. Comparison of these two therapies in recent clinical trials has indicated that fluconazole is at least as effective as amphotericin B, and therefore cost-minimisation analysis is an appropriate method to study the economic consequences of the alternative treatments. Patient management and resource-use information for both treatments was obtained using a modified Delphi technique with a panel of European physicians experienced in the treatment of this disease, and three models were developed to reflect the variability of practice evident among the panel members. U.K. health care costs were used to value these resources. The results indicated that, despite the higher cost of the drug itself, the costs associated with fluconazole were likely to be markedly less than those for amphotericin B for primary treatment, and similar or slightly cheaper for maintenance treatment. Over 1 year of treatment, the saving from the use of fluconazole would be in the range of 4000-14,000 pounds.
Acquired Immunodeficiency Syndrome↗
Immunophenotypic analysis of peripheral blood leukocytes at different stages of HIV infection. An analysis of asymptomatic, ARC, and AIDS populations.
Blood leukocytes from 51 patients with acquired immune deficiency syndrome (AIDS) or AIDS-related syndrome (ARC) were immunophenotyped with the use of monoclonal antibodies and flow cytometry. The patients were placed into four clinically defined groups: HIV-positive asymptomatic (HIV+/A, 8); persistent generalized adenopathy (14); Kaposi's sarcoma (12); and opportunistic infections (17). Immunophenotypes were compared between groups. Statistically significant differences were seen in absolute lymphocyte counts, total T-cells, helper/inducer T-cells, the helper inducer subset of CD4+ lymphocytes, the suppressor inducer subset of CD4+ lymphocytes, activated helper T-cells, and natural killer cells. CD8+ cells and subsets were not statistically different between groups, possibly obscured by large ranges, but median values suggested differences. Results indicate a pattern of increasing or decreasing numbers of certain subpopulations as HIV infection progresses.
AIDS-Related Complex↗
Flow cytometric measurements of proliferation-associated nuclear antigen p105 and DNA content in non-Hodgkin's lymphomas.
Non-Hodgkin's lymphomas are characterized by heterogeneity in cell kinetics, which may be related to differential expression of proliferation-associated nuclear antigens. We have performed two-color flow cytometric quantitation of nuclear antigen p105 and DNA content in nuclear suspensions from 80 paraffin-embedded lymphomas. High-grade lymphomas with diploid DNA histograms tended to express high levels of p105 in all phases of the cell cycle. Aneuploid populations, observed in 14 of 80 cases, showed high p105 expression compared with diploid cells of the same case, with the highest aneuploid:diploid p105 ratios in the high-grade group. We conclude that high-grade or DNA aneuploid lymphomas tend to have increased expression of p105; but considerable variations within each histologic subtype were observed, and the differences between histologic grades were not statistically significant. Further studies that correlate p105 expression and clinical outcome will help to determine the prognostic value of this marker.
Antigens, Neoplasm↗
Flow cytometric analysis of pituitary tumors. Correlation of nuclear antigen p105 and DNA content with clinical behavior.
Flow cytometric quantitation of the proliferation-associated nuclear antigen p105 and DNA content was performed on nuclear suspensions from 12 paraffin-embedded pituitary macroadenomas and one pituitary carcinoma and correlated with clinical outcome. Median follow-up was 41 months (range, 33 to 48 months). Three of the 13 tumors (23%) had an identifiable aneuploid peak. Of the four tumors that recurred or metastasized, only one was aneuploid. Nuclear antigen analysis of all diploid tumors showed enhanced p105 expression in G2M phase cells compared to G0G1 cells. The G2M/G0G1 fluorescence ratio for p105 was consistently higher (P less than 0.05) for the three diploid tumors that recurred (median, 1.32 arbitrary fluorescence units; range, 1.27 to 1.80) than for the seven nonrecurrent diploid tumors (median, 1.20 arbitrary fluorescent units; range 1.14 to 1.22). These findings indicate a low incidence of DNA aneuploidy among pituitary tumors and suggest that for diploid adenomas, measurement of p105 may provide information useful in predicting prognosis and directing postoperative adjuvant therapy.
Adolescent↗
Lymphocyte immunophenotyping of B-cell lymphomas: a flow cytometric analysis of neoplastic and nonneoplastic cells in 271 cases.
We have reviewed our experience with 271 B-cell lymphomas to determine the effectiveness of flow cytometry in the characterization of these malignancies. Flow cytometric immunophenotyping of the total lymphocyte and/or large lymphocyte populations confirmed the morphologic diagnosis of B-cell lymphoma in 92% of cases, which included 79% monoclonal and 13% surface immunoglobulin (SIg)-negative lymphomas. Light chain monoclonality was most frequent in low grade and follicular center cell (FCC) lymphomas, while SIg-negative cases were most common in high grade and non-FCC types. Low grade lymphomas of all histologic types had high median percentages of neoplastic cells and low T-cell percentages. Conversely, high grade lymphomas exhibited lower and less uniform median percentages of B-cells, with higher numbers of T-cells and lower CD4/CD8 ratios than low grade lymphomas. Several differences in B- and T-cells were observed between specific high grade histologic types. FCC lymphomas with a diffuse pattern had lower percentages of CD4+ cells and lower CD4/CD8 ratios than cases with a follicular pattern. Thus, immunophenotypic differences were observed between histologic types or groups with known differences in clinical course and prognosis. We conclude that flow cytometry provides reliable information on neoplastic and nonneoplastic cells in lymph nodes involved by B-cell lymphomas.
Antigens, Differentiation↗
Peripheral blood mononuclear cell abnormalities and their relationship to clinical course in homosexual men with HIV infection.
Quantitative abnormalities of leukocyte subpopulations have been shown to correlate with clinical status in human immunodeficiency virus (HIV) infection. We have performed peripheral blood leukocyte phenotyping in 23 HIV-seropositive homosexual men, and correlated the results with clinical follow-up information. Individuals with CD4+ greater than 400/mm3 (Group 1) had less severe abnormalities in other mononuclear cell subpopulations than patients with CD4+ less than 400/mm3 (Group 2). Group 1 had decreased CD4+CDw29+ (B-cell inducer) cells, compared to HIV-seronegative homosexual controls, with normal CD4+CD45R+ (suppressor-inducer) cells, suggesting that CD4+ subpopulations are reduced at different rates. Group 2 had decreased counts for both CD4+CDw29+ and CD4+CD45R+ cells. Both groups had increased cytotoxic T cells (CD8+CD11b-), with decreased B cells and CD4+/CD8+ ratios, compared to HIV-seronegative homosexual controls. The Group 2 patients with subsequent clinical deterioration had particularly low CD4+ cells, CD4+CD45R+ cells, CD2+Ta1+ cells, and CD4+/CD8+ ratios and high CD8+CD11b- cells, compared to those with clinically stable illness. Our findings suggest that specific leukocyte subpopulations are altered differentially at various stages of HIV infection. However, the study involved only quantitative measurements of specific T- and B-cell subsets with no attempt to measure in vitro function. It is of course possible that normal numbers of cells in these subpopulations might be functionally deficient.
Antigens, Differentiation↗
Flow cytometric DNA and nuclear antigen content in astrocytic neoplasms.
Simultaneous flow cytometric DNA content and proliferation-associated nuclear antigen (p105) quantitation was performed on 23 astrocytic tumors and the results correlated with histologic subtype. Three of nine anaplastic astrocytomas and one of ten glioblastomas had an identifiable aneuploid peak, while all four well differentiated astrocytomas were diploid. Cell cycle analysis of malignant gliomas revealed a higher mean percentage of S and G2M cells compared to well differentiated astrocytomas but there was considerable overlap between histologic subtypes. Nuclear antigen analysis of diploid tumors showed a higher mean p105 fluorescence of S + G2M cells than G0G1 cells from the same case but there were no apparent differences in p105 expression by histologic subtype. Aneuploid tumors showed enhanced expression of p105 relative to diploid cells. The findings suggest that the aggressive course of high grade glial tumors may be related to an abnormal DNA stemline or an increase in proliferative activity.
Antigens, Neoplasm↗
Smooth muscle tumors of the gastrointestinal tract. Flow cytometric quantitation of DNA and nuclear antigen content and correlation with histologic grade.
Simultaneous flow cytometric quantitation of DNA content and the proliferation-associated nuclear antigen p105 was performed on 41 gastrointestinal smooth muscle neoplasms and the results were correlated with histologic features. Aneuploid DNA stemlines were found in 17 cases (41%), including four of 15 (21%) tumors of unknown malignant potential, eight of 17 (47%) low-grade leiomyosarcomas, and five of seven (71%) high-grade leiomyosarcomas. In 10 of the 17 aneuploid tumors, an aneuploid peak was clearly identified on the single parameter DNA histogram, with a mean DNA index of 1.36. In the other seven aneuploid cases, a near-diploid, aneuploid population (mean DNA index, 1.08) was identified only by simultaneous immunofluorescence for p105. Clinical follow-up information was available for 14 patients. Mean survival of 10 patients with aneuploid tumors was 32 months, whereas mean survival of four patients with diploid tumors was 51 months. Of the seven patients who died within 1 year of diagnosis, six had aneuploid leiomyosarcomas. These findings demonstrate that DNA aneuploidy is common in high-grade gastrointestinal leiomyosarcomas and may be associated with shortened survival.
Antigens, Neoplasm↗
Immunohistochemical characterization of two new monoclonal antibodies (LN-4, LN-5) reactive with human macrophage subsets and derived malignancies in B5-fixed, paraffin-embedded tissues.
Two monoclonal antibodies (LN-4, LN-5) reactive to human macrophages in B5 formalin-fixed, paraffin-embedded tissue sections have been produced by using deparaffinized cell extracts of peripheral blood mononuclear cells. Both monoclonal antibodies were initially identified on paraffin-embedded sections of hyperplastic lymph nodes by using the immunoperoxidase staining procedure. Specificity screens on normal human tissues show that LN-4 and LN-5 stain the cytoplasm of macrophages and histiocytes in hematopoietic organs including Kupffer's cells of the liver and Langerhans' cells of the skin. LN-4 also showed strong positivity with acini of the stomach, whereas LN-5 was positive with mantle zone B lymphocytes of the lymph node and spleen, spermatogonia, and chief cells of the stomach. Both antibodies were strongly reactive with cases of true histiocytic lymphoma but, except for infiltrating macrophages, were entirely negative in Hodgkin's disease and non-Hodgkin's lymphomas. In all cases of nodular sclerosis Hodgkin's disease, LN-4 was positive in macrophagelike cells present in the collagen bands surrounding the Hodgkin's lesions. Both monoclonal antibodies were also positive in macrophages and histiocytes present in a variety of benign lymphoid lesions including persistent generalized lymphadenopathy, Gaucher's disease, sinus histiocytosis, and dermatopathic lymphadenopathy. Because of their specificity for human macrophages, and their ability to stain B5-fixed, paraffin-embedded tissues, LN-4 and LN-5 are important new reagents for the diagnosis and classification of malignant and benign histiocytic lesions.
Animals↗
High-grade mantle zone lymphoma.
A 66-year-old man with a 6-month history of sweating at night, generalized lymphadenopathy, hepatosplenomegaly, and paraproteinemia was diagnosed to have a Stage IV mantle zone lymphoma (MZL), which behaved aggressively. The neoplasm rapidly disseminated to extranodal sites--the skin, lungs, pleural cavity, and the central nervous system. The neoplasm did not respond to initial double-agent chemotherapy, but it did partially respond to multi-agent chemotherapy. In addition, the neoplasm had histopathologic features not reported previously in MZL--vascular invasion, massive extranodal infiltration, high mitotic count, and convoluted nuclei.
Aged↗
Mitotic counts in follicular lymphomas.
Increased mitotic activity is associated with significantly shorter patient survival in some of the subtypes of diffuse non-Hodgkin's lymphomas. This study on 105 cases of follicular lymphoma was undertaken to determine the clinical significance of mitotic activity in follicular lymphomas. For each case, two pathologists independently counted mitotic figures in 20 random high-power fields. The difference of the average mitotic counts over 20 high-power fields for the two pathologists showed a Gaussian distribution with a median difference of -0.26 counts per high-power field and a standard error of 0.10 per cent. In 94 cases (91 per cent), the difference was less than two mitotic counts per high-power field, indicating good interobserver agreement. There was a statistically significant difference in mitotic counts between subtypes of follicular lymphoma as well as a gradient among subtypes, with the lowest mitotic activity in the poorly differentiated lymphocytic subtype and highest in the undifferentiated subtype. A multivariate statistical analysis of clinical and pathologic variables showed that mitotic figures were not of prognostic significance.
Humans↗
Endothelial cell phenotypic diversity. In situ demonstration of immunologic and enzymatic heterogeneity that correlates with specific morphologic subtypes.
Some endothelial cells share functional and phenotypic properties with cells of monocyte/macrophage lineage. The authors have performed frozen-section immunologic stains and plastic section enzyme histochemical stains on various human tissues to examine endothelial cell phenotypic properties in situ. They found that endothelial cells express heterogeneous phenotypes that correlate with vessel type. Several endothelial cell subsets were identified. These included arterioles, capillaries, and venules (HLA-ABC+, HLA-DR+, Factor VIII RA+, monocyte-, alkaline phosphatase+, ATPase+); high endothelial venules of lymphoid tissues and hepatic sinusoidal lining cells (HLA-ABC+, HLA-DR+, Factor VIII RA+, monocyte+); lymphatics and glomerular capillaries (HLA-ABC+, HLA-DR+/-, Factor VIII RA-, monocyte-, 5'nucleotidase+); splenic sinusoidal lining cells (HLA-ABC+, Leu-2+, HLA-DR+, Factor VIII RAweak+, monocyte-, alpha naphthyl acetate esterase+); umbilical cord vessels (Factor VIII RA+, HLA-ABCweak+, HLA-DR-, monocyte-). The expression of monocyte-related antigens by some endothelial cells appears to be acquired in extranodal inflammatory infiltrates and is probably modulated by lymphokines.
Blood Vessels↗