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OBJECTIVE: To compare the AutoCyte SCREEN (AutoCyte, Burlington, North Carolina, U.S.A.) system with manual screening by experienced cytotechnologists using thin-layer preparations that had been previously extensively studied and their cytologic abnormalities well defined. STUDY DESIGN: AutoCyte PREP (AutoCyte) samples prepared for a previous split-sample study comparing thin-layer preparations to conventional smears were used. These 1,992 AutoCyte PREP samples were in a cohort the abnormal findings of which had been confirmed via independent review by two sets of pathologists. For the current study, these samples were remasked and evaluated by the AutoCyte SCREEN system in a clinical laboratory. The instrument scanned each slide and selected six overview fields and 120 single objects for storage and display. The computer classified each slide in one of the following categories: abnormal, uncertain, normal or unsatisfactory. Independently for each case, a cytotechnologist evaluated the six fields and 120 objects selected by the instrument as abnormal, normal or unsatisfactory. For those cases classified as uncertain by AutoCyte, the technologist then reexamined the cellular displays and entered a consensus classification. These results were then compared to those of an independent review by cytotechnologists of the identical set of slides using routine manual screening. RESULTS: The AutoCyte SCREEN selected 35% of slides for manual review. Technologist and computer rendered equivalent classifications in 79%. Of the total slides screened by the AutoCyte SCREEN, 57% were classified as "uncertain," and 88% of these were subsequently classified as normal by consensus. Using the well-defined abnormal values of the cellular sample as a basis for calculation, the AutoCyte SCREEN-assisted practice had a diagnostic sensitivity of 85% and diagnostic specificity of 97.6%. Comparable values for manual screening of the identical cellular sample were a diagnostic sensitivity of 80% and specificity of 97.4%. CONCLUSION: The AutoCyte SCREEN achieves comparable or greater sensitivity in detecting cervical abnormalities in comparison with manual screening. When combined with the substantial advantage of thin-layer preparations over conventional smears, the AutoCyte SCREEN provides a screening system of superior sensitivity over conventionally prepared and examined cervical smears.

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Transfusion of ABO-incompatible platelets to a cardiac surgery patients resulted in acute intravascular hemolysis complicated by ventricular tachycardia. Nine similar cases with significant morbidity or mortality have been reported in similar settings. Five fatalities caused by transfusion of ABO-incompatible platelet products have been reported to the US Food and Drug Administration during the last 4 years. Non-group O patients, particularly those with small plasma volumes, receiving multiple non-group specific platelets in a short time are at risk for intravascular hemolysis caused by passively infused anti-A1 or anti-B. To prevent intravascular hemolysis in such at-risk patients, the indications for platelet transfusion must be continually assessed. If transfusion of ABO-incompatible platelet products is necessary, consideration should be given to minimizing the accompanying plasma via further concentration of the platelets or by saline washing of platelet products.

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This report details the histopathologic findings in a woman who acquired the human papillomavirus 6/11 in her late teens and developed papilloma/condyloma of the nasopharynx, oropharynx, anogenital region, urethra, and urinary bladder. General evaluations of immune function reveal no defect, and there was no evidence of HIV infection. The morphologic expression of HPV 6/11 infection appears to be completely dependent on the mucosal epithelium affected. The complete spectrum of benign and premalignant epithelial changes induced by the human papillomavirus family-papilloma, verrucae, condyloma acuminatum, epithelial hyperplasia, and dysplasia-were present in this patient with a single papillomavirus infection. We postulate that this patient has a specific immune deficiency that limits her ability to control local infection and spread of the papillomavirus.

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OBJECTIVE: To compare the diagnostic efficacy of a thin-layer technique with that of a membrane filter technique using a wide variety of fresh cytologic specimens. STUDY DESIGN: Paired samples from 272 nongynecologic cytology specimens were processed for microscopy using thin-layer and membrane filter preparation techniques. Specimens included 162 body fluids and urines, 32 bronchial aspirates and 78 fine needle aspiration biopsies. The two techniques were compared for diagnostic efficacy, cell density/specimen, cell types recovered, qualitative cytomorphology, ease of interpretation and long-term stability of the final preparations. RESULTS: Diagnoses supported by filter preparations were also supported by their matched thin-layer preparations. The same cell types were recovered by both techniques, and the slide cell density was slightly greater using membrane filters. Qualitative morphology and ease of use were superior with the thin-layer samples. After two years, all thin-layer slides were stable and readable, whereas only 43% of the membrane filter slides were usable. CONCLUSION: Thin-layer techniques are morphologically comparable and, in some ways, superior to membrane filter techniques for processing a wide variety of nongynecologic cytology specimens.

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OBJECTIVE: To determine the feasibility and utility of thin-layer cytology preparations for morphometric analysis of nuclear and cytoplasmic area in cells from nongynecologic cytology specimens. STUDY DESIGN: Identical paired samples from nongynecologic specimens (bronchial aspirate, urine, pleural and peritoneal fluid) were used to prepare thin-layer preparations and corresponding traditional membrane filter preparations. The paired preparations were analyzed by static image morphometry measuring eight nuclear and cytoplasmic parameters that allowed calculation of nuclear area, cytoplasmic area and total cell size. Hepatocytes and bronchial columnar, mesothelial, squamous and transitional cells were studied, as was a single case of high grade transitional cell carcinoma. Sufficient numbers of each cell type were measured to allow statistical analysis. RESULTS: Both thin-layer and membrane filter preparation techniques yielded individual cells suitable for morphometric analysis, and there were no consistent morphologic measurement differences between the two methods. The thin-layer preparation had the following significant technical advantages: more numerous easily measured single cells, lack of interfering background and superior specimen stability. Benign oval to round nuclei from a variety of cell types have a mean nuclear area in a narrow range from 29 to 55 microns 2. The mean nuclear area of malignant cells studied was significantly larger (78 microns 2), and there was a significant decrease in absolute cytoplasmic profile area in the malignant population studied. CONCLUSION: Thin-layer cytology preparations have significant advantages for morphometric studies over traditional membrane filter cytologic preparations. The morphometric measurement of nuclear area in benign and malignant cell populations has great potential as a generic screening tool for malignancy in cytologic specimens. Simultaneous measurement of cytoplasmic area adds a powerful dimension. The subsequent calculation of a true nuclear/cytoplasmic ratio may yield a sensitive and specific discriminator for detecting malignant cell populations in human nongynecologic cytology specimens.

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This article traces the development of pathology practice from its origins in autopsy pathology to its current practice in the United States. The American model of practice differs markedly from that in continental European countries because of the extensive incorporation of "Clinical Pathology" with the traditional disciplines of anatomic pathology under the auspices of the Pathology Department. "Clinical Pathology" as it is now defined includes the laboratory testing disciplines of Chemistry, Hematology, Immunology, Medical Microbiology, and Transfusion Medicine. The increasing importance of computers and information management, DNA diagnostic techniques, and the multiple roles of the pathologist as a researcher and consultant in pathology practice in the United States is discussed.

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OBJECTIVE: To assess the efficacy of 10% formalin perfusion fixation as a method of rapid fixation to examine the human brain immediately following autopsy. DESIGN: Compare the histology and immunohistochemistry from human brains in which one hemisphere undergoes perfusion fixation using 10% buffered formalin, and the contralateral nonperfused hemisphere undergoes standard 14-day immersion fixation in 8 L of 10% buffered formalin. SETTING: Autopsy material in a general medical-surgical university hospital. PARTICIPANTS: Pathologists, neuropathologists, resident pathologists, and pathology assistants. INTERVENTION: Immediately following brain removal, a single hemisphere was perfused with 1 L 10% buffered formalin over a 15- to 20-minute period. The contralateral nonperfused hemisphere served as a control, undergoing standard immersion fixation for 2 weeks in 10% formalin. The perfusion-fixation hemisphere was immediately available for neuropathologic examination, and histologic sections of the brain were processed immediately with the other necropsy tissue sections. This allows completion of a final autopsy neuropathology report within 3 to 5 days in concert with the systemic section of the report. MAIN OUTCOME MEASURE: Perfusion-fixation brain sections were compared with immersion-fixation brain sections from the same brain. The effects on hematoxylin-eosin, Bielschowsky's silver, and immunohistochemical staining were evaluated by an experienced neuropathologist and a general pathologist with no prior knowledge of the fixation technique. RESULTS: Perfusion fixation revealed equal and occasionally superior histologic sections compared with traditional immersion fixation in terms of (1) technical preparation of section, (2) quality and intensity of staining with both hematoxylin-eosin and silver, and (3) immunoreactivity localization with a variety of immunohistochemical reactions. CONCLUSIONS: Immediate perfusion of the brain is an easily performed fixation technique that yields comparable or superior fixation to prolonged immersion fixation and allows an immediate complete neuropathologic examination and report within 3 to 5 days of performance of the autopsy.

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Leadership and management skills are increasingly critical to the success of pathologists in and outside of academic centers. We describe a leadership and management curriculum in a combined anatomic and clinical pathology residency program. The mentor-based approach incorporates leadership and management skills throughout the residency with a dedicated 2-month rotation during the final year of training. This 2-month rotation is led by a senior faculty pathologist mentor and includes active participation in management activities, small group discussions, reading, and a management process project. The topics for the small group discussions, reading list, mentor-based activities, and completed management process projects are described. Outcomes and evaluations are reported for residents who have completed this curriculum in leadership and management.

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One hundred seventy-six United States and Canadian pathology residency programs were surveyed to assess the status of management training for residents. Specific questions in the survey concerned approaches to management, instructional methods used, topics covered, and length of management rotations. Eighty-four programs (48%) responded to the survey. This group represented a cross section of all programs as to location, size, and type of program. Of the 84 programs, 81 (96%) offered management training, while 54 programs (64%) offered a management course. Management training usually occurred in combination with other rotations, most frequently clinical pathology subspecialties. A dedicated management rotation was reported in 19 programs (23%). The most common method of instruction was apprenticeship/mentor followed by didactic lecture. A majority of programs used multiple instructional methods. The five most frequently covered topics were budgets, personnel issues, quality assurance, utilization, and instrument evaluation, but a wide variety of topics were included in management curricula surveyed. There was an emphasis on clinical laboratory administration. Nonpathologist instructors, such as medical technologists, hospital administrators, and business executives, were used for formal didactic exercises, while teaching by pathologists occurred predominantly by mentoring during clinical pathology rotations.

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BACKGROUND: Most of the literature dealing with the surgical management of acute cholecystitis bases patient selection on pathological diagnosis, either exclusively or using it as a major selection criteria or as a confirmation of diagnosis. The purpose of this study was to examine the correlation between preoperative clinical findings, intraoperative gross findings, and postoperative pathological findings. METHODS: A retrospective review of 493 consecutive laparoscopic cholecystectomies performed by a single surgeon (RJF) in a single institution was done. Four different sets of criteria were used to define four groups of patients as having acute cholecystitis: (1) preoperative acute cholecystitis based on defined criteria (PA); (2) intraoperative gross findings of acute or subacute cholecystitis based on surgeon assessment of inflammation (IA); (3) initial pathological evaluation by a staff pathologist (IP); and (4) expert pathological (EP) review using strictly defined histological criteria. RESULTS: Of 41 patients, 40 (97.6%) were classified as having acute cholecystitis by IA, 21 (51.2%) by IP, and 17 (41.5%) by EP. Of the 75 patients classified as having acute cholecystitis by IA, 40 (53.0%) were classified acute by PA, 34 (45. 0%) by IP, and 17 (22.7%) by EP. Of the 72 IP patients, 34 (47.2%) were classified as acute by IA, 15 (20.8%) by EP, and 24 (33.3%) were PA. Of the 32 EP patients, 21 (65.6%) were classified as acute by IA, 14 (43.8%) by IP, and 18 (56.3%) were PA. CONCLUSION: The correlation between the pathological diagnosis and intraoperative findings is poor. Preoperative clinical findings of acute cholecystitis are highly reliable for predicting intraoperative gross findings. However, intraoperative findings of acute cholecystitis are commonly found in the absence of preoperative clinical signs. Recommendations for surgical therapy should be based on studies which use either operative findings or the preoperative clinical findings as the basis for patient selection.

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Cryptococcus neoformans is an encapsulated yeast that infects patients who have defective cell-mediated immunity, including AIDS, but rarely infects individuals who have intact cell-mediated immunity. Studies of the immune response to C. neoformans have been hampered by a paucity of defined T-lymphocyte antigens, and hence, the understanding of the T-cell response is incomplete. The goal of this study was to separate C. neoformans into its component parts, determine whether those components stimulate lymphocyte proliferation, perform preliminary characterization of the proteins, and establish the potential mechanism of lymphocyte proliferation. The lymphocyte response to fungal culture medium, whole organisms, disrupted organisms, and the yeast intracellular fraction or cell wall and membrane was studied by determining thymidine incorporation and by determining the number of lymphocytes at various times after stimulation. The cell wall and membrane of C. neoformans stimulated lymphocyte proliferation, while the intracellular fraction and culture filtrate did not. The optimal response occurred on day 7 of incubation, with 4 x 10(5) peripheral blood mononuclear cells per well and with 13 microg of cryptococcal protein per ml. The number of lymphocytes increased with time in culture, indicating that thymidine incorporation was accompanied by proliferation. Proteinase K treatment of the cell wall and membrane abrogated lymphocyte proliferation, indicating that the molecule was a protein. [35S]methionine labeling, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and fluorography were performed to analyze the proteins contained in the cell wall and membrane, intracellular fraction, and culture filtrate. At least 18 discrete bands were resolved from the cell wall and membrane. Since a large percentage of healthy adults responded to the cryptococcal cell wall and membrane, a mitogenic effect was investigated by testing proliferation of fetal cord blood lymphocytes. The percentage of fetal samples that proliferated in response to the cell wall and membrane was similar to the percentage of fetal samples that proliferated in response to Staphylococcus enterotoxin B, a microbial mitogen. Thus, a protein in the cell wall and membrane of C. neoformans is a potent stimulant of lymphocyte proliferation and has mitogenic properties, which may have important implications for cell-mediated immunity to C. neoformans.

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OBJECTIVE: To develop a system for enhancing the performance and reporting of autopsies in an effective and clinically useful manner. DESIGN: Twelve steps were defined as essential for the completion of the autopsy. Each step of the process was evaluated for usefulness and effectiveness. SETTING: Autopsies performed in a university hospital from 1992 through 1994. PARTICIPANTS: Pathology residents and staff, clinicians, and clinical team house staff. INTERVENTION: Participants followed the 12-step process, with emphasis on involving the clinical team in the interview, prosection, and final rounds. The final rounds conference was designated a working conference, where the perfused-fixed brain was cut, histologic sections of the case were submitted, and the provisional diagnosis was written with the clinicians. A next-day microscopic slide review session was scheduled to "sign out" the case. Establishing a philosophy of status equal to all other department functions facilitated implementation. MAIN OUTCOME MEASURE: All autopsies performed for a period of 3 years (2 retrospective and 1 prospective) were included. RESULTS: The autopsy completion time was reduced from a mean of 57 days (range 7 to 174) in 1992 to 4.8 days (range 1 to 16) in 1994. CONCLUSION: The autopsy completion time was reduced, increasing its usefulness for teaching and quality assurance. Relationships with the clinical staff were enhanced with consultation-style final reports. Enthusiasm for, and satisfaction with, the new process was expressed by clinicians, pathology staff, residents, and technical support staff.

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Quality assurance (QA) in surgical pathology has focused primarily on retrospective audits of randomly selected cases. The authors describe an effective method of prospective audit for a selected class of surgical specimens--diagnostic biopsies--and document the benefits, additional staff time required and impact on turnaround time. Additionally, these results were compared with a retrospective review. During a 6-month period, all diagnostic surgical pathology biopsies (n = 2,694, 55% of all cases) were reviewed by a second pathologist before release of the final report. Errors detected were subdivided into four categories: (1) major: errors in diagnosis that could directly affect patient care; (2) diagnostic discrepancies: errors in diagnosis that should not affect patient care; (3) minor: correct diagnosis rendered, but report correction required to add supportive information; (4) clerical: typographical and grammatical errors. Thirty-two major errors were found, involving 1.2% of cases reviewed. This manner of review caused an increase in overall turnaround time from 1.62 days to 1.79 days, and an increase in turnaround time for diagnostic biopsies from 1.44 days to 1.50 days. Time spent in performing prospective peer review averaged 4 hours per day. For comparison, results were included from a retrospective review performed on 480 of the 5,556 cases accessioned in a 6-month period before the institution of prospective quality assurance. This retrospective review revealed eight major errors (1.7%). In conclusion, the prospective peer review of diagnostic biopsies yields sufficient benefits in increased accuracy of diagnostic reports to justify the slight increase in additional work by pathologists.

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Frozen red cells have been field-tested at the Mobile Fleet Hospital deployed at 29 Palms, Calif., and at Bridgeport, Calif., and at the PACOM Blood Program Office, Okinawa, Japan, to evaluate the feasibility of using these products to support the US Navy and Marines in combat areas. We studied both nonrejuvenated and rejuvenated cryopreserved red cell concentrates. Red cells stored at 4 degrees C in CPD or CPDA-1 for 3-6 days (nonrejuvenated), and red cells stored at 4 degrees C in CPD for 22-26 days or in CPDA-1 for 36-38 days before biochemical modification (rejuvenated), were frozen with 40% w/v glycerol at -80 degrees C. A multiple-bag collection system with a 600 or 800 ml primary bag was used for blood collection, and the primary bag was used for processing from preparation of the red cell concentrate through prewash dilution. The thawed red cells were washed with 1.5 liters of a sodium chloride-glucose-phosphate solution. As part of this feasibility study, frozen red cells were shipped by air in dry ice (-79 degrees C), and previously frozen washed red cells were shipped in wet ice (4 degrees C). In vitro red cell recovery values were at least 90%. After postwash storage at 4 degrees C for as long as 3 days, the red cells had 24-hour posttransfusion survivals of at least 70%, normal or slightly impaired oxygen transport function, and minimal hemolysis.

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The long-term effectiveness of a four-week comprehensive dietary-behavioral weight control program was evaluated. Program components included a 700 kcal diet, nutritional education, medical and health education, behavior modification, and physical activity and exercise. Mean weight loss 12 months after treatment was 29.2 lb (13.2 kg) with 66 percent of patients losing 20 lb (9.1 kg) or more, 45 percent losing 30 lb (13.6 kg) or more and 29 percent losing 40 lb (18.1 kg) or more. These weight losses are higher than those generally reported for either behavioral or non-behavioral treatments. Comparison of successful versus unsuccessful patients revealed that exercise, cognitive restructuring, eating style, and social skills were most related to success.

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