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Biomedical subjects

H Mitchell

Publications and source records attributed to H Mitchell.

At least 145 records · Page 8Linked to original sources

The SCM test for cancer. an evaluation in terms of lymphocytes from healthy donors and cancer patients.

The SCM test was established as originally described, and an attempt was made to evaluate it using myelin basic proteins. Various later modifications described by the original authors were incorporated as they were communicated to us. In separate studies attempts were also made to overcome some of the problems which seemed inherent in the technique. In the small series for which valid results were obtained we were unable to confirm the original claim that the method discriminates between cancer patient lymphocytes and those from non-cancer subjects with almost 99% reliability. Indeed, although differences were found between the mean SCM values of cancer patients and of healthy controls, these differences were not significant.

Cells, Cultured↗

Particulate emboli retained by the Intersept (R) transfusion filter; a sem study.

The Intersept (R) transfusion filter is the transfusion filter developed by Johnson and Johnson. Filtration is performed by both adsorption and mechanical retention. Not only microaggregates, but damaged and injured cells are likely to be trapped and/or adsorbed. Such a filter is not injurious to the blood components, but thrombotic material accumulation can occur with fresh blood.

Animals↗

The Aberdeen formula.

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Nursing Service, Hospital↗

The Aberdeen formula.

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Nursing Service, Hospital↗

Influences on the risk of recurrent high grade cervical abnormality.

The objective of this study is to determine the risk of recurrent abnormality after a first episode of high-grade epithelial abnormality and its evolution over time in a population setting. Two cohorts were established from a statewide registry. The cervical intraepithelial neoplasia (CIN) cohort comprised 6849 women with a biopsy of CIN 2, 2/3 or 3 (squamous or glandular) during 1990-92. A cohort of 6857 women with negative cytology during 1990-92 was used for comparison. The CIN cohort had a significantly greater rate of subsequent high-grade epithelial abnormality than the negative cohort. The risk increased with age. For women over 50 years at the incident biopsy, the rate ratio for subsequent high-grade epithelial abnormality was 24.45 (95% CI, 7.2, 84.3). The rate of subsequent high-grade epithelial abnormality was greater if the incident biopsy was CIN 3 (rate 13.50 per 1000 person years [95% CI, 12.5, 14.6]) rather than CIN 2 or 2/3 (rate 7.83 per 1000 person years [95% CI, 7.1, 8.7]). The rate ratio for subsequent invasive cancer was 9.46 (95% CI, 2.5, 35.3) when the CIN cohort was compared with the negative cohort. We conclude the risk of recurrent high-grade epithelial abnormality is related to the age and degree of abnormality on the incident biopsy. Screening policies should acknowledge the risk does not diminish with time.

Adult↗

Design and SAR study of a novel class of nucleotide analogues as potent anti-HCMV agents.

We have developed a novel class of 2-phosphonate 1,3-dioxolane nucleotide analogues, from which the guanine derivative displayed weak anti-HCMV activity. Further SAR studies led to the identification of both cis and trans guanine derivatives of tetrahydrofuran analogues as potent anti-HCMV agents, both in vitro and in vivo, compared to ganciclovir and HPMPC.

Animals↗

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↗

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

ISSUES: Increasing litigation over alleged false negative cervical cytologic (CC) smears threatens the viability of this test for cervical cancer detection. The problem appears to be largely American but is beginning to appear in some other countries. In the vast majority of cases there is either a settlement or jury verdict for the plaintiff based largely on the testimony of expert witnesses. Cases are judged on an individual basis without significant consideration of the general performance of the CC smear in laboratories operating in compliance with a wide array of laboratory regulations and with documented and comprehensive quality control practices in place. It is acknowledged that there are problem laboratories and cytology practitioners. There is an emerging issue of automated preparation and screening devices and issues of informed patient consent. CONSENSUS POSITION: Cytology professionals have done an extraordinary and commendable job of educating the public about the benefits of the CC smear. We have been less successful and conscientious about explaining and defining the limitations of the CC test. There is a need for public and professional education as to the benefits and limitations of the CC smear for cervical cancer detection. The process suggested is to work with women's groups, public health agencies, government agencies, and state and national legislatures and to coordinate professional committees working on liability issues. Contextual information could be included with the CC smear report to indicate that a negative report confers a low probability of developing cervical cancer. It is suggested that appropriate language and a menu of statements be developed. Increased efforts should be directed to physician education with respect to informed consent concerning the benefits and limitations of CC smear testing and the application of new technology to improve smear accuracy. The process should include development of appropriate statements on the use of alternative technology. The profession should develop "process guidelines" for review of CC smears in the context of possible litigation, including standardized methods for blind slide review of smears that reduce or eliminate context and outcome bias. It is suggested that review panels be anonymous, that the process be standardized and that there be limitations on liability for participating organizations. Professional cytopathology and pathology societies should formulate acceptable guidelines for expert witnesses. The standards should be applicable to both defendant and plaintiff experts. All materials to the extent practical, including consultant opinions, should be available for peer review. Professional cytopathology and pathology societies should monitor expert testimony for objectivity and scientific accuracy. ONGOING ISSUES: For the near future, litigation will continue to focus on false negative CC smears on a case-by-case basis. Laboratories and individuals can reduce the risk of malpractice liability by directing their attention to proactive quality control and quality assurance methods. In the final analysis, consumer education about the benefits and limitations of the test is key to limiting malpractice claims. To stem the tide of continued medicolegal challenges to the integrity of cytology practice, the cytology community has now focused its efforts on developing and utilizing standards that convey to patients, attorneys and cytologists the contemporary status of and reasonable expectations for the practice of cytology. Guidelines such as those for uniform reporting terminology and clinical management of cervical abnormalities form the basis of cytology practice standards on which legal standards of practice can be based. Consensus conference reports, clinical management trials and scientifically valid studies of false negative rates that analyze the type, frequency and cause of missed cases represent sounder methods of establishing defensible

Cell Biology↗

Detection of unsuspected abnormalities by PAPNET-assisted review.

OBJECTIVE: To determine the positive predictive value of abnormalities detected by PAPNET-assisted review of slides considered to show no abnormality on two manual screenings and to evaluate the repeatability of technical codes assigned by the PAPNET scanner. STUDY DESIGN: PAPNET-assisted review was performed on 19,805 slides that had been assessed as showing no abnormality on two occasions by manual screening plus 195 slides with abnormal cells seeded at random. Abnormalities detected by cytotechnologists were graded by cytopathologists and compared with the findings of later histology/cytology. RESULTS: On PAPNET-assisted review, the cytotechnologists identified 212 slides as containing unsuspected abnormalities; cytopathologists agreed with 76% (162/212) of these predictions. Later histology/cytology confirmed 54% (14/26) and 32% (33/102) of the predictions of high and low grade abnormality, respectively. The PAPNET scanner gave concordant technical codes for 94.8% of 2,690 slides that were submitted twice for scanning. CONCLUSION: Some additional abnormalities will be detected by a PAPNET-assisted review, even among slides considered negative on two manual screenings. However, many of these abnormalities will not be confirmed on later investigation and will thus appear to represent false positive cytology. The assigning of technical codes by the PAPNET machine is subject to a degree of variation on repeat evaluation of the same slides.

Artifacts↗

Detection of laboratory false negative smears by the PAPNET cytologic screening system.

OBJECTIVE: To evaluate the ability of PAPNET-assisted screening to identify abnormal slides that had originally been reported as negative on manual screening. STUDY DESIGN: One hundred ninety-five abnormal slides were seeded into 20,000 slides that had been assessed as showing no abnormality on two occasions by manual screening. All slides were submitted for PAPNET review and the tiles assessed by trained cytotechnologists. RESULTS: With a single assessment of the PAPNET tiles and when the prevalence of seeded abnormality was around 1%, only 44% of the seeded abnormal slides were recognized as abnormal. With multiple independent assessments and by increasing the prevalence of abnormality to 81%, 83% of the seeded abnormalities were recognized by at least one of three reviewing cytotechnologists. This increase in sensitivity appeared to be associated with a state of relative hyperalertness in the reviewing cytotechnologists. CONCLUSION: The sensitivity of a PAPNET-assisted review was < 100% for the detection of seeded abnormal slides. Altering the format of presentation of information to the cytotechnologist may result in improved sensitivity.

Algorithms↗