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R L Katz

Publications and source records attributed to R L Katz.

At least 73 records · Page 4Linked to original sources

Proliferation markers in non-Hodgkin's lymphoma. A comparative study between cytophotometric quantitation of Ki-67 and flow cytometric proliferation index on fine needle aspirates.

Proliferation markers appear to predict biologic behavior and responses to therapy in non-Hodgkin's lymphoma (NHL). We examined the value of the antibody against Ki-67, a marker for cycling cells, in 73 fine needle aspirates and compared these results with parameters of ploidy, DNA, RNA and proliferative index (PI) derived from acridine orange flow cytometry. NHLs were classified into three grades according to the Working Formulation. A fourth miscellaneous group, consisting of atypical lymphoid hyperplasia, was also analyzed. Ki-67 expression was quantitated on a single Cytospin sample from each FNA specimen using an image analysis quantitation software program based on measurement of optical density in the labeled structures. An average of 680 cells distributed through 10 random files was digitized per specimen. The mean Ki-67 positivity and PI calculated for each lymphoma grade were significantly different between grades (P < .0001), while the overall correlation between Ki-67 positivity and PI was high (r = .8). There was no correlation between grade and mean optical density of Ki-67, DNA and RNA, but Ki-67 positivity strongly correlated with PI (r = .8). These results are similar to those of previous studies performed on histologic sections of NHL in which the Ki-67-positive labeling index, measured by either visual scoring or image analysis, correlated positively with increasing grade of lymphoma according to both the Kiel classification and the Working Formulation. We conclude that Ki-67 staining of NHL provides information equivalent to that of PI and is useful for small specimens, such as fine needle aspirates.

Biomarkers↗

Quantitation of immunocytochemical estrogen and progesterone receptor content in fine needle aspirates of breast carcinoma using the SAMBA 4000 image analysis system.

Evaluation of estrogen receptors (ER) and progesterone receptors (PR) in breast carcinoma using ER and PR immunocytochemical assays (ER-ICA and PR-ICA) has traditionally been semiquantitative at best. We investigated the use of the SAMBA 4000 image analysis system for quantitation of immunocytochemical ER content in 23 cases and PR content in 20 cases of breast carcinoma after obtaining cytology specimens by fine needle aspiration (FNA). We compared the quantitative assessment obtained by image analysis, the quick score (QS), to the biochemical assay as well as to the ER-ICA and PR-ICA semiquantitative visual histochemical score (H-score). Using Pearson's linear correlation coefficient, we demonstrated that for both ER and PR, the QS obtained by the "area" or "nuclear" programs correlated significantly with the H-scores. However, while the QS obtained on the area program for both ER and PR correlated significantly with the biochemical assay, the QS obtained on the nuclear program did not. The discrepancy might reflect the smaller number of cells evaluated with the nuclear program as compared to the area one. These results show that the SAMBA 4000 system provides an objective means of quantitating ER and PR content by immunocytochemical methods.

Biopsy, Needle↗

Two AgNOR counts in fine-needle aspirates of lymphoproliferative disorders compared with acridine orange flow cytometry.

Studies have shown that argyrophilic nucleolar organizer region-associated proteins (AgNORs) may correlate with DNA ploidy and/or proliferative activity in neoplastic and non-neoplastic conditions. However, studies have estimated only the mean AgNOR counts. Here we used two AgNOR counts, one of which may correlate with DNA ploidy and the other with proliferative activity. The mean AgNOR count (mAgNOR) was defined as the mean number of AgNORs/nucleus in 100 cells and may represent DNA or RNA index. The percentage of nuclei exhibiting 5 or more AgNORs/nucleus (pAgNOR) may reflect proliferative activity. These two AgNOR counts were correlated with results from acridine orange flow cytometry in 50 fine-needle aspirate (FNA) smears of nodal and extranodal sites, including three cases of reactive lymphadenopathy and 47 cases of non-Hodgkin's lymphoma. The mean mAgNOR count in the diploid specimens was 2.03 (+/- 0.74 SD) and 2.62 (+/- 0.73 SD) in the aneuploid tumors (P less than 0.0001). Samples with a low RNA index had mean mAgNOR of 1.80 (+/- 0.41 SD), whereas those with high RNA had a mean mAgNOR of 2.93 (+/- 0.86 SD) (P less than 0.0001). Lesions with low proliferative index, determined by flow cytometry, had a mean pAgNOR of 4%, whereas those with intermediate and high proliferative indices had a mean pAgNOR of 16% (P less than 0.0001). A similar but less significant correlation existed between RI and pAgNOR (P less than 0.005). We conclude that the two AgNOR counting methods may reliably reflect cell kinetics and distinguish ploidy from proliferative activity, making them useful adjuncts to flow cytometry in limited cytology specimens and small biopsy samples.

Acridine Orange↗

Accuracy of diagnosis of malignant lymphoma by combining fine-needle aspiration cytomorphology with immunocytochemistry and in selected cases, Southern blotting of aspirated cells: a tissue-controlled study of 86 patients.

Fine-needle aspiration (FNA) cytology of lymph nodes in malignant lymphoma is fraught with difficulty. In certain clinical situations, cytology has been documented to be useful in patients with malignant lymphoma. The intent of our investigation was to determine the accuracy of a multiparameter approach in diagnosing lymphoma. We reviewed the results of FNA cytology combined with the immunocytochemistry and, in some cases, the Southern blots of aspirated cell suspensions obtained from 86 suspected lymphoma patients who subsequently underwent surgical biopsy of the aspirated site. In four cases, in which FNA was unable to retrieve sufficient material for diagnosis, the histology showed extensive fibrosis. When the FNA diagnoses were compared with the histologic diagnoses, the diagnosis concurred in 69 cases (56 malignant lymphomas, 12 reactive, 1 atypical lymphoid proliferation). There was one false-positive, six false-negatives, and eight cases diagnosed as atypical lymphoid proliferation. Overall accuracy was 91%. There were two types of false-negative cases: those in which a diagnosis of another malignancy or unspecified malignant neoplasm was made and those that were diagnosed as reactive when the histology showed lymphoma. In seven cases, the DNA rearrangement studies of the antigen receptor genes were successfully performed on the aspirated cells and were useful in establishing lineage and clonality of both B and T lymphoid cells. Our study indicated that the use of a multiparameter approach in the diagnosis of malignant lymphoma by FNA enhanced the accuracy of diagnosis of the non-Hodgkin's lymphomas. In Hodgkin's disease, no benefit was derived from the approach.

Biopsy, Needle↗

Total hip arthroplasty in patients with avascular necrosis of the hip. Follow-up observations on cementless and cemented operations.

Thirty-one patients with avascular necrosis of the hip were treated by 34 total hip arthroplasties (THAs). All patients were observed prospectively with a minimum two-year follow-up evaluation (average, 46 months; range, 24-84 months). Twenty had cemented arthroplasties using contemporary cementing techniques. This included insertion of a medullary plug, cleansing of the canal with a medullary brush, pulsatile lavage irrigation, and insertion of the cement with a cement gun. In 14 hips, a cementless prosthesis was used. Patients were rated using a modified Harris hip score. Sequential postoperative roentgenograms were analyzed in each patient. The overall Harris hip score ratings were 88 in the cemented and 84 in the noncemented groups. Mechanical failure with loosening of the femoral component occurred in one patient who developed deep sepsis. Significant thigh pain occurred in four patients in the noncemented group. Previous studies in the literature have generally reported unfavorable results in patients with avascular necrosis of the hip treated with THA. Using cementless and cemented fixation with contemporary cementing techniques, improved results can be expected. A high incidence of thigh pain (29%) in the cementless group remains a problem.

Adult↗

Comparison of visual and CAS-200 quantitation of immunocytochemical staining in breast carcinoma samples.

Using the CAS-200 image analysis system, we compared the relationship between semiautomated computer measurements (QIC score) and visual scoring (H score) on 30 breast cancer fine needle aspirates (FNAs) and corresponding tissue specimens stained by the estrogen receptor immunocytochemical assay. These results were compared to the corresponding biochemistry assays for ER. We also investigated whether the computerized system could decrease false-negative staining for ER in 32 cryostat sections. QIC scores were generated using fixed nuclear and antibody thresholds after standardizing the illumination. Computer quantitation was essentially as precise as visual semiquantitation for FNAs: a small but significant correlation was found between tumor ER content and QIC score (r = .504, P less than .02) as compared with H score and ER content (rs = .55, P less than .005). The computerized system did not decrease the false-negative rate in cryostat sections. In all, computerized quantitation was no better than visual analysis of ER staining in these breast carcinomas.

Antibodies, Monoclonal↗

Malignant lymphoma of the thyroid: a report of two cases diagnosed by fine-needle aspiration.

Two cases of primary malignant lymphoma of the thyroid were diagnosed by fine-needle aspiration biopsy. In addition to morphologic evaluation performed on direct smears, immunophenotyping, flow cytometry, and molecular studies were performed on the aspirated material. These additional studies made a clear distinction between lymphoma and Hashimoto's thyroiditis, which may present a similar cytologic picture.

Biopsy, Needle↗

The role of gene rearrangements for antigen receptors in the diagnosis of lymphoma obtained by fine-needle aspiration. A study of 63 cases with concomitant immunophenotyping.

To assess the efficacy of performing genotyping in addition to immunophenotyping as an adjunct to cytologic diagnosis, 63 consecutive patients with fine-needle aspirates of lymphoproliferative lesions who had concurrent immunophenotyping and genotyping performed on fine-needle aspirate cell suspensions were studied. Thirty-nine of 63 specimens (62%) that appeared to contain non-Hodgkin's lymphoma and that proved to be of B-cell lineage by genotyping were accurately phenotyped and shown to be monotypic for immunoglobulin light chains by cell suspension immunocytochemistry. Genotyping facilitated lineage assignment and/or confirmed clonality in 17 of 63 specimens (27%) that were difficult to determine based on morphologic data. These include cases of atypical lymphoid proliferations with polyclonal or inconclusive markers (n = 6), peripheral T-cell lymphoma (n = 3), extracutaneous mycosis fungoides (n = 1), lymphoblastic lymphoma (n = 4), null cell lymphoma (n = 1), and specimens with equivocal or technically unsatisfactory markers (n = 2). Based on these results, it is proposed that genotyping for lineage assignment and/or clonality be performed to include cases of atypical lymphoid proliferations, T-cell malignant neoplasms, lymphoid malignant neoplasms with equivocal markers, and differentiation of lymphoid from nonlymphoid neoplasms. Genotyping by antigen-receptor gene rearrangement appears to be redundant in cases with mature B-cell phenotypes that demonstrate monoclonality by immunophenotyping.

Adult↗

Uvulopalatopharyngoplasty in obstructive apnea. Value of preoperative localization of site of upper airway narrowing during sleep.

We hypothesized that those obstructive sleep apnea (OSA) patients with upper airway collapse during sleep within the transpalatal airway would have a more favorable response to uvulopalatopharyngoplasty (UPP) than those patients with obstruction within the hypopharyngeal airway. We tested this hypothesis in seven OSA patients with transpalatal and seven with hypopharyngeal obstruction undergoing UPP. Preoperatively the apnea/hypopnea index (AHI) was different between palatal and hypopharyngeal obstructors, 37.8 +/- 6.0 (+/- SEM) and 63.9 +/- 6.3, respectively (p less than 0.05), but the apnea-associated arterial oxygen desaturation and the lowest sleep saturation level were not different between the two groups. Postoperatively the AHI was 17.6 +/- 7.2 in the palatal obstructors and 40.3 +/- 15.6 in the hypopharyngeal obstructors (both p less than 0.05 from preoperative AHI). The palatal obstructors had a significant decrease in the percentage of sleep time spent apneic and the hypopharyngeal obstructors had a significant decrease in the hypopnea, but not apnea, time following surgery. The palatal obstructors had a significantly higher postoperative arterial oxygen saturation than the hypopharyngeal obstructors. Two hypopharyngeal obstructors worsened postoperatively. In addition we found that regardless of the site of the obstruction preoperatively, all obstructions occurred at the level of the palate postoperatively. We conclude that patients with preoperative transpalatal obstruction had diminution in obstructive apneas and those with hypopharyngeal obstruction had diminution in hypopneas but not apneas. Oxygenation was better postoperatively in the palatal obstructors, and none worsened postoperatively. These results suggest that identification of the site of upper airway obstruction in OSA may be beneficial.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Anesthetic and hemodynamic effects of dexmedetomidine during isoflurane anesthesia in a canine model.

Dexmedetomidine, an alpha 2-adrenergic agonist, was administered during isoflurane anesthesia to investigate its anesthetic sparing and hemodynamic effects in the canine model. Eleven healthy dogs were anesthetized with isoflurane, intubated, and allowed to breathe spontaneously. The animals were instrumented in order to measure or calculate mean arterial blood pressure (MABP), heart rate (HR), left ventricular end diastolic pressure (LVEDP), cardiac output (CO), and systemic vascular resistance (SVR). Isoflurane minimum alveolar concentration (MAC), baseline hemodynamic measurements, and plasma catecholamine levels were determined. A 20 micrograms/kg bolus of dexmedetomidine was injected intravenously (IV) and MAC and hemodynamic values were redetermined. When isoflurane requirements were 33% of baseline, isoflurane was returned to 90% MAC and the alpha 2-antagonist, atipamezole, was administered. All dogs were treated with 40 micrograms/kg glycopyrrolate throughout the experiment to prevent any bradycardic response. Dexmedetomidine reduced isoflurane MAC by 86%. SVR, MABP, and LVEDP were significantly increased while CO and catechloamine levels were reduced. Atipamezole fully reversed the reduction in anesthetic requirements. MABP and catecholamine levels returned to baseline. SVR and LVEDP increased while CO decreased. The dogs exhibited a profound reduction in anesthetic requirement, reduced catecholamine levels, and changes in hemodynamic parameters with dexmedetomidine administration. The anesthetic sparing effect appears to be mediated by the alpha 2-receptor, since atipamezole reversed the reduction in MAC. Hemodynamic changes may be species or dose related, or due to differences in existing sympathetic tone. The role of dexmedetomidine warrants further study as an adjunct anesthetic agent.

Adrenergic alpha-Agonists↗

Determination of the rate of DNA synthesis of human tumor cells obtained by fine needle aspiration. Comparison of flow cytometry and an immunoperoxidase method for the detection of thymidine analogue incorporation.

Two methods of detecting thymidine analogue incorporation by lymphoma, leukemia and myeloma cells obtained by fine needle aspiration (FNA) are described. In one method, cells which have been incubated with the thymidine analogue iododeoxyuridine (IDURD) were exposed to primary monoclonal anti-IDURD antibody and a fluorescein-labeled linking antibody. The fluorescence of the antibody-labeled cells, which had synthesized DNA and incorporated the analogue, was detected by flow cytometry (FCM). In a second method, the cells that incorporated the analogue were detected on glass slide Cytospin preparations by an immunoperoxidase (IP) technique. The IDURD labeling index (LI), as determined by both FCM and IP staining, was compared to the percentage of cycling (S + G2/M) cells as determined by acridine-orange FCM. The data indicate that the IP method is reliable and correlated strongly with FCM determination of LI, percentage S-phase and lymphoma grade. Given the low cost and wide availability of IP technology, the IP method may be desirable for laboratories wishing to supplement cytology reports with cell cycle data.

Biopsy, Needle↗

Cytologic diagnosis of leukemia and lymphoma. Values and limitations.

The value and limitations of the cytologic diagnosis of lymphoma and leukemia using a multiparameter approach, including cytomorphology, immunocytochemistry, and flow cytometry, are discussed. Using these diagnostic modalities, most subtypes of lymphoma and leukemia can be classified accurately. The differential diagnoses of the different disease entities also are presented.

Cytodiagnosis↗

Fine needle aspiration diagnosis of intraabdominal and retroperitoneal lymphomas by a morphologic and immunocytochemical approach.

We reviewed 238 fine needle aspiration biopsies (FNA) of intraabdominal or retroperitoneal (IA/RP) masses in 192 patients with known or suspected lymphoma. A limited battery of immunocytochemical stains, including kappa (k) and lambda (l) light chains and Leu-4, was performed in 104 aspirates. On hundred twenty-eight of the FNA were diagnostic of or consistent with lymphoma, and three were diagnostic of carcinoma. Twenty-eight were considered negative for malignancy and 79 were suspicious for lymphoma or were nondiagnostic. For 135 of the FNA, a histologic biopsy specimen was available for comparison purposes. Overall, only one false-positive result was seen in a specimen lacking immunocytochemical data. The sensitivity of FNA lymphoma diagnosis was 66%. False-negative results due to sampling error were not uncommon, giving a predictive value of a negative result as 42%. The classification of the lymphomas by FNA was identical to that of the surgical biopsy in 86% of specimens and concurrently discrepant in 6%. We conclude that the routine performance of immunocytochemical studies on FNA of IA/RP masses is a feasible and valuable technique. Whereas suboptimal sensitivity and sampling error may make a negative diagnosis unreliable, lymphoma marker studies (combined with morphology) allow for an accurate and confident diagnosis and subclassification of lymphoma in the majority of cases.

Abdominal Neoplasms↗

Comparison of immunocytochemical and biochemical assays for estrogen receptor in fine needle aspirates and histologic sections from breast carcinomas.

An immunocytochemical assay using a monoclonal antibody specific for estrogen receptor (ER-ICA) was performed on needle aspirates and on histologic sections (mastectomy and biopsy specimens) from 55 patients with breast cancer. A total of 82 ER-ICAs were performed, with matched cytologic and histologic specimens in 27 patients, cytology alone in 15, and histology alone in 13. ER-ICA results were described by a histochemical score (H score) based on intensity-weighted percentages of staining cells. The H scores were compared with results of sucrose density gradient (SDG) analysis of histologic specimens (mastectomy, resection, or biopsy). An H score greater than or equal to 10 and an SDG value greater than or equal to 10 fmol/mg protein were considered positive. The sensitivity of cytologic ER-ICA was 94%, the specificity 100%. The sensitivity of histologic ER-ICA was 67%, the specificity 90%. Correlating cytologic H score with Black's nuclear grade showed that grade 1 (the most anaplastic) carcinomas demonstrated the lowest H scores (mean, 7.3 +/- 29.8), whereas the highest H scores were noted in grade 3 tumors (mean, 150.0 +/- 88.1). Both SDG and ER-ICA showed ER values to be lower in premenopausal than postmenopausal women. There was no correlation between H score and presence of axillary nodal metastases or tumor size. An overall good correlation was demonstrated between immunohistochemical methods and biochemical analysis.

Biopsy, Needle↗

Fine needle aspiration biopsy in lymphoma.

Patients with lymphoma undergo excisional biopsy of an affected lymph node for initial classification of their disease because accurate classification depends on the histologic characteristics of the neoplasm. However, fine needle aspiration cytology has a role in the management of lymphoma patients, particularly in those with recurrent or residual masses following treatment. Moreover, immunologic markers, nucleic acid flow cytometry, cytogenetics, and molecular genetics, which do not depend on histologic characteristics and can be performed on fine needle aspirates, are acquiring more importance in the management of patients with these diseases, particularly in those with non-Hodgkin's lymphoma. These latter tests add objectivity to the cytologic diagnosis of the B-cell lymphomas and increase its accuracy. In most series, the accuracy of fine needle aspiration in patients with lymphoma approaches 90%, with minimal complication rates.

Biopsy, Needle↗

Ductal carcinoma-in-situ of the breast: fine-needle aspiration cytology of 12 cases.

Aspiration specimens from 12 patients with histologically documented ductal carcinoma-in-situ (DCIS) of the breast (seven patients) or DCIS with minute foci of stromal invasion (five) were evaluated. Five patients presented with palpable masses, 1.5-4.0 cm, and four patients presented with localized thickening, associated with nipple erosion and discharge in two of them. One patient had nipple inversion, and one patient had bilateral nipple discharge. In one patient, no apparent abnormality of the breast was present. Mammography was either suspicious for or strongly suggestive of carcinoma in 10 patients and negative in two. Aspirates from all patients were composed of fragments of atypical ductal epithelium and numerous single epithelial cells. In nine cases, the smears were hypercellular and similar to aspirates of typical invasive ductal carcinoma. Calcifications were present in six cases. In four of these, associated tumor necrosis was evident. Cytologic features separating DCIS patients from those showing minimal stromal invasion or common types of invasive ductal carcinoma (IDC) were not identified. We conclude that fine-needle aspiration cytology of DCIS is identical to that of IDC. If preoperative radiotherapy or chemotherapy is considered in the management of invasive breast carcinoma, cutting-needle biopsy for confirmation of tumor invasion is necessary.

Adult↗