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D D Davey

Publications and source records attributed to D D Davey.

72 records · Page 4Linked to original sources
PubMed1987

Synthesis and antiarrhythmic activity of novel 3-alkyl-1-[omega-[4-[(alkylsulfonyl)amino]phenyl]-omega- hydroxyalkyl]-1H-imidazolium salts and related compounds. 2.

Novel analogues of the class III antiarrhythmic agent 1-[2-hydroxy-2-[4-[(methylsulfonyl)amino]phenyl]ethyl]-3-methyl-1H- imidazolium chloride, 1 (CK-1649), were prepared and investigated for their class III electrophysiological activity on isolated canine cardiac Purkinje fibers and ventricular muscle tissue. Structure-activity relationships are discussed for a series of 11 compounds. One compound, N-[4-[1-hydroxy-2-(4,5-dihydro-2-methyl-1H-imidazol-1- yl)ethyl]phenyl]methanesulfonamide hydrochloride, 9, was comparable in activity to 1 in vitro and prolonged the functional refractory period in anesthetized dogs when given intraduodenally. Unlike 1, compound 9 was ineffective at preventing ventricular tachycardia induced by programmed electrical stimulation in anesthetized dogs 24 h after an acute myocardial infarction.

Action Potentials↗
PubMed1986

Acute myelocytic leukemia manifested by prominent generalized lymphadenopathy: report of two cases with immunological, ultrastructural, and cytochemical studies.

Although it is well recognized that granulocytic sarcoma can cause localized lymphadenopathy, widespread nodal involvement by acute myelocytic leukemia (AML), clinically mimicking non-Hodgkin's lymphoma, has only been previously described twice. We report the clinicopathological, immunological, and cytochemical features of two patients who had widespread, prominent lymphadenopathy secondary to AML as well as concurrent marrow leukemia (M1 and M2). For one patient the lymphadenopathy was the predominant abnormality prompting him to seek medical attention, while the second patient had symptoms of infection following a 9-month history of myelodysplasia. The disease in both patients was aggressive; one patient survived only 1 week and the other survived only 5 weeks after diagnosis. In both cases the granulocytic sarcoma was confirmed by cytochemistry studies (naphthol ASD-chloroacetate esterase on tissue sections and myeloperoxidase on imprint smears), and electron microscopy, including morphology (both cases) or ultrastructural localization of myeloperoxidase (case 2). Non-specific esterase activity was not detected in either patient's blasts, although serum lysozyme was elevated in both cases. Immunological studies revealed reactivity of both patients' cells with panleukocyte, MY4, MY7, OKM-1, and Leu-M1 monoclonal antibodies and with alpha-1-antitrypsin and muramidase antibodies. The cells of one of these patients also reacted with anti-S-100 protein. Although the cytochemical studies indicated that both cases exhibited only myeloid differentiation, the immunological markers suggested that the tumor cells possessed some features of monocytes, perhaps explaining their propensity for widespread tumor formation. Morphological, immunological, cytochemical, and ultrastructural methods of diagnosing granulocytic sarcoma are presented.

Aged↗
PubMed1986

Synthesis and class III antiarrhythmic activity of (phenylbut-2-enyl)ammonium salts. Effect of conformation on activity.

The syntheses of seven 4-(substituted phenyl)but-2-en(or yn)yl quaternary ammonium salts and four related tertiary amines are described. The Meerwein arylation reaction was the preferred synthetic method for the required intermediate 1-aryl-4-halo-2-butenes (15a-c, 18). In the case of 18, the trans stereochemistry of the Meerwein adduct of 2,3-dimethylbutadiene was established unambiguously by 2D NMR and X-ray studies. The title compounds represent conformationally restricted analogues of the class III antiarrhythmic agent clofilium (1) and exhibit comparable potency and efficacy in the in vitro evaluation using isolated canine Purkinje fibers. These results suggest that the alkylene chain in 1 is extended in the active conformation. Computer-aided conformational analysis (MM2) supports this conclusion. Selective catalytic hydrogen conditions were developed for the conversion of the unsaturated analogue 2 to clofilium (1) with minimal hydrogenolysis of the allylic quaternary ammonium moiety, thus completing a novel and efficient synthesis of this substance.

Action Potentials↗
PubMed1986

Millipore filter vs cytocentrifuge for detection of childhood central nervous system leukemia.

To evaluate the relative merits and deficiencies of Millipore filter and cytocentrifuge preparations in the detection of central nervous system (CNS) acute leukemia in pediatric patients, 300 cerebrospinal fluid (CSF) specimens from 17 patients were prepared by both methods. The 17 patients studied were all diagnosed and treated for CNS leukemia. Leukemic blast cells were found by at least one method in 91 CSF specimens, and the results of both techniques were positive in 77 (85%) of 91 specimens. Of the 14 specimens in which the results of only one method were positive, seven yielded positive results only by the cytocentrifuge method, and seven yielded positive results only by the Millipore filter method. In 12 of the 14 discrepant specimens, the paired specimen whose results were not interpreted as positive was technically unsatisfactory (nine specimens) or had cells suspicious for blast cells rather than unequivocal blast cells (three specimens). Blast cells were identified in specimens with low nucleated cell counts (less than or equal to 5/mm3) by both methods and usually were immediately preceded or followed by CSF specimens showing florid disease. We conclude that performance of both methods is unnecessary for routine surveillance if processing techniques yield quality preparations. Cytocentrifuge preparations stained by Wright's method allow better morphologic correlation with bone marrow blast cells and allow easier identification of blood or bone marrow contamination.

Adolescent↗
PubMed1984

Inhibition of cholesterol oxidase in a patient with Cushing's syndrome.

Serum from a patient with Cushing's syndrome who was being treated with mitotane contained components that interfered with determination of cholesterol in the Du Pont aca. A measured concentration of cholesterol of 4.19 g/L in the undiluted serum increased to a calculated concentration of 9.50 g/L in diluted serum. Adding additional cholesterol oxidase (EC 1.1.3.6) overcame the reaction inhibition in the undiluted sample; adding additional cholesterol esterase (EC 3.1.1.13) had no effect. There is the potential for clinically significant underestimation of cholesterol with the aca in such patients, because the interference may remain undetected. On the other hand, the aca accurately quantified undiluted specimens containing as much as 10 g of cholesterol per liter when mitotane was not present.

3-Hydroxysteroid Dehydrogenases↗
PubMed1983

Evaluation of a solid-phase enzyme immunoassay for human choriogonadotropin beta subunit.

We evaluated a quantitative solid-phase enzyme immunoassay for human choriogonadotropin beta subunit (beta-HCG) with anti-beta-HCG:horseradish peroxidase conjugate, recently marketed by Abbott Laboratories. We compared results on 56 patients' serum specimens, obtained mostly for followup of neoplastic disease, with those by a competitive radioimmunoassay kit. The correlation was good, the differences being of little clinical significance. Linear regression in the low and intermediate ranges gave a slope of 0.93, a y-intercept of 0.34, and a correlation coefficient of 0.97. Precision studies yielded an interassay CV of 6.4% in the intermediate range and 13% in the low range. Sensitivity was 0.69 int. unit/L. Cross reactivity was 1 to 2% with specimens fortified with lutropin or follitropin. The only substantial problem was with linearity in the upper part of the standard curve, especially in the interval, 100-200 int. units/L. This problem is obviated by adequate sample dilution.

Chorionic Gonadotropin↗
PubMedDate not supplied

Parathyroid cytopathology.

Cytologic criteria for diagnosing parathyroid adenomas and hyperplasia have not been elucidated. This report will present the cytomorphology of parathyroid tissue in the spectrum of normal, hyperplastic, and neoplastic states. We examined clinical needle aspirates from three patients with parathyroid lesions as well as 15 needle aspirations or touch preparations from surgical specimens. The series included three with hyperparathyroidism secondary to chronic renal failure, four with primary chief cell hyperplasia, nine with typical adenomas, and two with atypical adenomas. Normal parathyroid glands were also studied. Most parathyroid lesions could be distinguished from thyroid lesions by frequent thick fragments of cohesive cells with frayed edges and typical nuclear features. In general, the nuclei were small (6-8 mu) and round with regular coarse granular chromatin. Occasional larger nuclei (10-30 mu) with similar chromatin were observed in some cases. Oxyphil cells with abundant granular cytoplasm were present in some cases; one case with mostly oxyphil cells was difficult to differentiate from a thyroid neoplasm. Pseudocolloid was found in seven cases. Criteria for the differentiation between parathyroid hyperplasia and adenomas were not discovered. In addition, the cytology and differential diagnosis of atypical parathyroid adenomas are described and illustrated.

Adenoma↗
PubMedDate not supplied

Quality assurance and risk reduction guidelines.

Cervical cancer continues to be a major cause of death in women worldwide. The major problem facing most women is the unavailability of screening Pap tests in poor and underdeveloped countries. While rates of cancer deaths have decreased 60-80% in developed countries since the Pap test became available, the accuracy of Paps was challenged recently. In order to instill public confidence and promote optimal patient care, measures to improve the quality of the entire screening process should be undertaken. Continuous quality improvement processes are more appropriate than traditional quality assurance monitors. Although no standards can be defined that are applicable to all laboratory settings and nations, this document provides current views on universal quality procedures and risk reduction. Procedure/policy manuals, workload assessment, hierarchic/peer review, discrepancy analysis, rescreening studies and cytohistologic correlation are examples of universally applicable quality tools. The variability in practices in different parts of the world is also discussed.

Female↗
PubMedDate not supplied

Competency assessment and proficiency testing.

Competency assessment is an ongoing, continuous process of monitoring individuals' abilities to perform their specific job functions. A variety of methods are useful in monitoring cytology competency, including rescreening studies, descriptive monitors (abnormality rates), discrepancy rates, workload patterns, competency-based educational programs and programs using unknown slide challenges. The goal of proficiency testing (PT) is to ascertain and assess the ability of individuals beyond the particular items or challenges presented. However, cytology PT faces many challenges for implementation as it cannot duplicate normal working conditions, and there is often no gold standard to define the truth. PT is just one measure of performance and should be considered in conjunction with other quality assessment monitors. There is no consensus on the value or validity of a large-scale regulatory PT program. Any regulatory PT program should be field tested prior to implementation, and the grading system should be scientifically defensible. Scoring of performance on PT should occur in a timely fashion, and there should be an opportunity for educational feedback. The ultimate aim of both competency assessment and PT is to positively affect laboratory procedures and improve the cervical cancer screening process.

Cell Biology↗
PubMedDate not supplied

ASCUS and AGUS criteria. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: The conference participants addressed the following issues: (1) reporting of equivocal diagnoses, (2) strategies to minimize the use of such diagnoses, (3) morphologic criteria, and (4) management of women with equivocal diagnoses. CONSENSUS POSITION: Equivocal diagnoses should be minimized, to the extent possible, by emphasizing cytologist education and training, improved specimen collection and quality assurance monitoring of individual and laboratory diagnosis rates. Cases fulfilling criteria for other diagnostic entities should not be included in the equivocal category. Regardless of the term utilized, an equivocal diagnosis should be qualified in some manner to indicate that the diagnosis defines a patient at increased risk of a lesion, particularly for those cases which raise concern about a possible high grade lesion. Qualification of an equivocal diagnosis can also be accomplished by appending laboratory statistics of the likelihood of various clinical outcomes or recommendations for patient follow-up. In contrast to favoring a reactive process versus squamous intraepithelial lesion (SIL), a more rationale approach to qualification of atypical squamous cells of undetermined significance may be to separate cases equivocal for low grade SIL from those suspicious for high grade SIL. With regard to glandular lesions, the conference participants expressed unanimous support for the separation of adenocarcinoma in situ (AIS) from atypical endocervical cells of undetermined significance when sufficient criteria are present. However, the diagnosis of a precursor lesion to AIS, endocervical glandular dysplasia, was controversial. The majority of conference participants discourage the use of such terms as mild glandular dysplasia and low grade glandular dysplasia for cytologic diagnoses. ONGOING ISSUES: Conference participants agreed that a term reflecting diagnostic uncertainty is necessary to communicate findings that are equivocal. However, participants could not agree on the wording of such a term. Opinions differed as to: (1) use of atypical, abnormal or morphologic changes to describe cell changes, (2) whether the diagnosis should indicate a squamous or glandular origin of the cells in question when this determination can be made, and (3) the value of defining morphologic criteria for such a diagnosis. The debate over terminology, as well as morphologic criteria, is ongoing, and the readership is invited to communicate opinions to Acta Cytologica. Management of women with equivocal diagnoses varies widely from locale to locale and may differ based on how the equivocal diagnosis is qualified. Findings insufficient for the diagnosis of a high grade lesion may warrant more aggressive follow-up than cases equivocal for a low grade lesion. Where sensitivity of detection of lesions is of paramount importance, follow-up will generally consist of more frequent cytology screening or colposcopy and biopsy. However, in some countries it is considered unethical to have a high percentage of false positive diagnoses, which result in overtreatment and an unnecessary burden for women participating in cervical screening. Future studies may provide a morphologic, or perhaps molecular, basis for distinguishing true precursors of neoplasia from minor lesions of no significant clinical import; this would allow a more coherent and rational approach to diagnosis and management of women with equivocal cytologic findings.

Adenocarcinoma↗
PubMedDate not supplied

Cell preparation methods and criteria for sample adequacy. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Cell Preparation Methods Standardized fixation and optimal staining Sampling of cervix, sampling error, homogenization of sample, subsampling Assessment of liquid-based preparations: efficacy and economic impact Training and transitional procedures before full implementation of new technologies Criteria for Sample Adequacy Clinician responsibility for collecting and providing representative sample to laboratory Collection instruments, number of slides Cellular content of samples: evidence of transformation zone (TZ) sampling, number of squamous cells present, obscuring factors Screening issues CONSENSUS POSITION The conventional cervical smear remains the standard method of cervical cancer screening but has limitations in individual test sensitivity and specificity. Sample takers should: (1) receive appropriate training in sample collection, (2) be held responsible for providing the laboratory with appropriate samples, and (3) have their performance monitored. The instruments used for sampling should collect cells from both the ectocervix and endocervix; optimally, TZ sampling, represented by the presence of endocervical or squamous metaplastic cells, should be identifiable in samples other than atrophic specimens. The adequacy of a specimen (as judged microscopically) does not guarantee that it is representative of the cervix. Each cytology report should include a comment on cellular content/adequacy of the specimen. Liquid-based preparations may overcome many of the inherent problems with the conventional cervical smear. ONGOING ISSUES: We need further data on the cost-effectiveness of making two slides from cervical specimens and/or using two samplers rather than a single one. Do we have enough information to make recommendations as to the appropriate type of sampler to be used in particular situations, such as routine screening? What is the best method of screening for/detecting endocervical glandular neoplasia? How are such terms as unsatisfactory and inadequate defined in cervical cytology classifications other than the Bethesda System? What number and types of epithelial cells should be present (visualized) in a cervical smear or liquid-based preparation for it to be considered adequate? Do we need to have evidence of TZ sampling in specimens taken during the follow-up period after treatment of squamous intraepithelial lesion or after detection of endocervical glandular neoplasia? What criteria for obscuring factors, such as blood and inflammation, should be used in assessing adequacy? Cost-benefit analyses of utilizing liquid-based preparations are needed. Should we inform women about the technical details of the test methods available or chosen by the laboratory? Are women in a position to decide which method is the most appropriate to assess their cervical scrape sample? We need to obtain more information about the properties of proprietary liquid fixative/transport media with respect to inactivation of viral pathogens, tuberculosis and other bacterial pathogens and suitability for immunobiologic and molecular tests, etc. We need to obtain more information on the use of stoichiometric stains and the limitations of Papanicolaou stain for image analysis systems. The use of liquid-based preparations for nongynecologic cytopathology and ancillary tests must be considered, including criteria for adequacy. We need to obtain more information on the time required for and best methods of training experienced cytotechnologists to become competent at assessing liquid-based cervical preparations.

Cell Biology↗
PubMedDate not supplied

Quality assurance/control issues. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: General definitions of quality assurance and quality control (QA/C) have existed in many forms for decades, and a new discipline guides their application to diverse industrial and recently medical processes without much fanfare. However, in the field of cervical cytology screening, the range of QA/C options has recently broadened and become controversial. With the advent of new systems of terminology, larger-scale laboratories and new technologies--plus strong governmental and legal pressures in some nations--the range of extremely difficult and sometimes expensive QA/C choices our community faces is greater than ever. CONSENSUS POSITION: At our conference, the basic definitions of QA/C posed little difficulty. Presentation of the range of methods in use today and of those based on new technologies where use is proposed or has just begun also was achieved with little or no dispute. However, there was lack of consensus on exactly how QA/C methods are to be assessed. Indeed, there was little consistency in the use of different outcome measures with which we can judge success or failure of specific QA/C options. In addition, the tension between pressure to adopt sometimes uncertain or expensive method enhancements and pressure to maintain affordability and the widest possible access for populations that most need cervical cytology screening is greater than ever. ONGOING ISSUES: More data are required that would enable assessment of QA/C options with the clearest possible understanding of cost/benefits and current or new assumptions of risk. Other task forces, such as medicolegal, cost/benefit and those devoted to new technologies, are our essential partners in meeting the challenges described above.

Centers for Medicare and Medicaid Services, U.S.↗
PubMedDate not supplied

Computerized training and proficiency testing. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Computerized technologies probably will revolutionize the field of gynecologic cytology in the next century. Such technologies will be useful in both training and evaluating proficiency. However, manual screening/review of gynecologic cytology preparations is the current "gold standard" for both training and assessment of proficiency. CONSENSUS POSITION: Training programs for cytotechnologists and pathologists should provide instruction and experience in new technologies, but their introduction may depend on the availability of equipment and staff. Advantages of digital images for training include standardization of teaching sets and interactive capabilities, allowing educational feedback. Computerized support/assistance devices aid in complete screening of the slide during training and provide feedback to cytologists on screening techniques. Liquid-based cytopreparatory instruments facilitate multiple glass slides for teaching or testing. Proficiency testing (PT) in cytology has similar quality assurance goals as in other areas of the laboratory, but the subjective nature of cytologic analysis poses many challenges for implementation. There is consensus that all cytology practitioners would like to know the proficiency of the laboratory. However, the majority question the value and validity of any large-scale formal testing programs. Locator and diagnostic skills are both critical in cytology, but assessment of each skill may occur in different ways using computerized technologies. Any type of assessment should provide educational feedback to participants. Psychometric issues in PT include the consideration of different types of validity, including face, content, construct and criterion related. The reliability or consistency of the testing event is also critical. A valid and reliable correlation between work performance and performance on a PT needs to be established. The goal is to ensure that PT will identify submarginal practitioners and that persons successful on PT are in fact competent. Any cytology PT program should also be considered in the context of other laboratory quality assurance tools and the entire cervical cancer screening program. Regulatory agencies should evaluate entire laboratory performance, while each laboratory director should assume primary responsibility for evaluating and documenting the competency and daily performance of each practicing cytologist. Professional scientific organizations should take the lead in recommending methods and standards of performance assessment. ONGOING ISSUES: A reliable method of correlating daily competency with results on PT is not yet established. Methods may evolve ever time using new technologies. The use of computerized techniques and images for assessment will require careful deliberation by experts as well as validation by practicing cytologists. Variables include diagnostic categories for testing, numbers of challenges per testing event, types of slide preparations and characteristics of the digital images. Availability of equipment and staff will affect the introduction of new technologies in different regions.

Cell Biology↗
PubMedDate not supplied

Cytologic findings in posttransplant lymphoproliferative disease.

Transplant patients are at an increased risk of developing lymphoproliferative disorders (LPDs). To examine the role of cytology in diagnosing LPDs, the cytologic reports on all transplant patients seen at the University of Iowa from January 1983 to July 1988 were reviewed. Thirteen of 649 transplant patients developed LPD; 10 of those 13 patients had a total of 25 cytologic specimens obtained within two months of the diagnosis of LPD available for review. Ten specimens (four cerebrospinal fluids [CSFs], four effusions, one respiratory specimen and one liver aspirate) from six patients were positive for LPD. Immunophenotypic or immunogenotypic studies on cytologic specimens from four patients showed a clonal B-cell process. The cytologic features ranged from those of a plasmacytoid LPD to those of an immunoblastic or large-cell lymphoma. An additional seven specimens (five CSFs, one effusion and one liver aspirate) from four patients were suspicious for LPD, exhibiting rare atypical cells or cells with plasmacytoid features. Ten patients died with LPD within 12 months; three are alive. Cytologic specimens, especially body fluids, are frequently positive in LPD and may be useful diagnostically. Since the differential diagnosis includes reactive lymphocytosis, confirmatory immunophenotypic or immunogenotypic studies are recommended.

Follow-Up Studies↗
PubMedDate not supplied

Analysis of immunoglobulin and T-cell receptor gene rearrangement in cytologic specimens.

Recombinant DNA techniques to detect the rearrangement of genes encoding immunoglobulins and T-cell-antigen receptors have been used to identify clonality in lymphoid lesions. To determine the utility of such techniques in cytologic specimens, DNA was analyzed in 24 effusions and 6 fine needle aspirates. Immunophenotypic studies were also performed on the 19 specimens with suspected hematopoietic malignancies. Sufficient material for DNA analysis was present in 28 of the 30 specimens. Immunoglobulin or T-cell-receptor gene rearrangement was present in 13 specimens with atypical cytologic findings; DNA studies provided more information than did the immunologic studies in 3 cases. One T-cell malignancy showed T-cell receptor and heavy-chain gene rearrangement, and one B-cell malignancy showed immunoglobulin and T-cell receptor gene rearrangement. In all patients except one with no evidence of gene rearrangement, the morphologic and immunologic studies also favored a reactive process. Control specimens showed a germline configuration. This study demonstrated that DNA gene rearrangement studies are feasible on many cytologic specimens and may be useful in diagnostically difficult cases.

Biopsy, Needle↗
PubMedDate not supplied

Intranuclear cytoplasmic inclusions in aspirates of follicular neoplasms of the thyroid. A report of two cases.

Two cases are reviewed in which the presence of intranuclear cytoplasmic inclusions in fine needle aspiration biopsy specimens of the thyroid suggested a diagnosis of papillary carcinoma. Subsequent surgical specimens were consistent with diagnoses of microfollicular adenoma and follicular carcinoma. These cases suggest that the presence of intranuclear inclusions in epithelial thyroid cells is not limited to papillary and medullary carcinoma, as some authors have suggested.

Adenocarcinoma↗